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Product Description Common use Cleocin kills sensitive bacteria by stopping the production of essential bacterial proteins after binding a bacterial ribosome. Cleocin is close by its qualities to Lincomycin. Lincosamides are usually used to treat staphylococci and streptococci. Cleocin is administered to treat protozoal diseases such as malaria, infections of respiratory system, skin and soft tissures, bones and joints, abdominal organs, and others. It does not treat meningitis.

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Precautions This medication should be used only for treatment of serious bacterial infections due to its ability to cause severe and even fatal intestinal condition known as pseudomembranous colitis. This condition may appear during treatment or even weeks after treatment has stopped. So if you have persistent diarrhea, abdominal or stomach pain/cramping, or blood/mucus in your stool do not use anti-diarrhea drugs and inform your doctor about your condition.

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Ampicillin is the generic name of a drug that's prescribed to treat bacterial infections.

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Note: This page contains information about the side effects of betamethasone topical. Some of the dosage forms included on this document may not apply to the brand name Betacort.

For the Consumer

Applies to betamethasone topical: topical application cream, topical application foam, topical application gel/jelly, topical application lotion, topical application ointment

Other dosage forms:

In addition to its needed effects, some unwanted effects may be caused by betamethasone topical (the active ingredient contained in Betacort). In the event that any of these side effects do occur, they may require medical attention.

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thinning of the skin with easy bruising, especially when used on where the skin folds together (e. g. between the fingers)

Minor Side Effects

Some of the side effects that can occur with betamethasone topical may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common:

Acne or pimples

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

Incidence not known:

Burning and itching of the skin with pinhead-sized red blisters

burning, itching, and pain in hairy areas, or pus at the root of the hair

increased hair growth on the forehead, back, arms, and legs

lightening of normal skin color

lightening of treated areas of dark skin

reddish purple lines on the arms, face, legs, trunk, or groin

softening of the skin

For Healthcare Professionals

Applies to betamethasone topical: topical cream, topical foam, topical gel, topical lotion, topical ointment, topical spray

General

The most commonly reported side effects were pruritus, burning, itching, irritation.

Hypersensitivity

Rare (less than 0.1%): Hypersensitivity

Endocrine

Frequency not reported: Cushing's syndrome [Ref ]

Dermatologic

Common (1% to 10%): Pruritus Uncommon (0.1% to 1%): Folliculitis, skin infections (including bacterial, fungal and viral skin infections) Frequency not reported: Dryness, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infections, skin atrophy, striae, miliaria [Ref ]

Local

Uncommon (0.1% to 1%): Application site pain Frequency not reported: Burning, itching, irritation [Ref ]

Ocular

Rare (less than 0.1%): Eye disorder [Ref ]

Metabolic

Frequency not reported: Hyperglycemia

Renal

Frequency not reported: Glucosuria

Other

Rare (less than 0.1%): Rebound effect

References

1. Ruiz-Maldonado R, Zapata G, Lourdes T, Robles C "Cushing's syndrome after topical application of corticosteroids." Am J Dis Child 136 (1982): 274-5

2. "Product Information. Diprolene (betamethasone topical)." Schering Laboratories, Kenilworth, NJ.

3. Flynn MD, Beasley P, Tooke JE "Adrenal suppression with intranasal betamethasone drops." J Laryngol Otol 106 (1992): 827-8

4. Stoppoloni G, Prisco F, Santinelli R, Sicuranza G, Giordano C "Potential hazards of topical steroid therapy." Am J Dis Child 137 (1983): 1130-1

5. Stevens DJ "Cushing's syndrome due to the abuse of betamethasone nasal drops." J Laryngol Otol 102 (1988): 219-21

6. Walsh P, Aeling JL, Huff L, Weston WL "Hypothalamus-pituitary-adrenal axis suppression by superpotent topical steroids." J Am Acad Dermatol 29 (1993): 501-3

7. Reymann F, Kehlet H "Hypothalamic-pituitary-adrenocortical function. Association with topical application of betamethasone dipropionate." Arch Dermatol 115 (1979): 362-3

8. Salde L, Lassus A "Systemic side-effects of three topical steroids in diseased skin." Curr Med Res Opin 8 (1983): 475-80

9. Cunliffe WJ, Burton JL, Holti G, Wright V "Hazards of steroid therapy in hepatic failure." Br J Dermatol 93 (1975): 183-5

10. Macdonald A "Topical corticosteroid preparations. Hazards and side-effects." Br J Clin Pract 25 (1971): 421-5

11. Smith EB, Breneman DL, Griffith RF, Hebert AA, Hickman JG, Maloney JM, Millikan LE, Sulica VI, Dromgoole SH, Sefton J, et al "Double-blind comparison of naftifine cream and clotrimazole/betamethasone dipropionate cream in the treatment of tinea pedis." J Am Acad Dermatol 26 (1992): 125-7

12. Grice K "Tinea of the hand and forearm. Betamethasone valerate atrophy." Proc R Soc Med 59 (1966): 254-5

13. Hellgren L "Induction of generalized pustular psoriasis by topical use of betamethasone-dipropionate ointment in psoriasis." Ann Clin Res 8 (1976): 317-9

14. Ellis CN, Katz HI, Rex IH Jr, Shavin JS, Van Scott EJ, VanderPloeg D "A controlled clinical trial of a new formulation of betamethasone dipropionate cream in once-daily treatment of psoriasis." Clin Ther 11 (1989): 768-74

15. Sneddon I "Perioral dermatitis." Br J Dermatol 87 (1972): 430-4

16. Barkey WF "Striae and persistent tinea corporis related to prolonged use of betamethasone dipropionate 0.05% cream/clotrimazole 1% cream (Lotrisone cream)." J Am Acad Dermatol 17 (1987): 518-9

17. Butcher JM, Austin M, McGalliard J, Bourke RD "Bilateral cataracts and glaucoma induced by long term use of steroid eye drops." BMJ 309 (1994): 43

18. Eisenlohr JE "Glaucoma following the prolonged use of topical steroid medication to the eyelids." J Am Acad Dermatol 8 (1983): 878-81

19. Kitazawa Y "Increased intraocular pressure induced by corticosteroids." Am J Ophthalmol 82 (1976): 492-5

Not all side effects for Betacort may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here .



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Anzol Paint Factory, Anzol

Another place known to lots on the urban exploration circuit, the old Anzol Paint Factory looks set to disappear from the urbex radar fairly soon.

I had some trouble actually finding out any real information about Anzol Paints or this factory (if anyone knows more then I do please feel free to contact me as I would like to know) but all I could find on Anzol was that it was a paint company, and was known for its gutter paints and also suppling some paint (Army green) to the Australian Defence force to paint some of its tanks with.

Anzol by the sounds of it also had a bit of a tainted past and wasn't the most environmentally friendly company. Anzol was accused and from what I can gather, charged with some pretty horrendous pollution issues. Without reading through a scanned 84 page pdf I found online, I couldn't see exactly what they did, but their products contained some pretty horrid toxic ingredients and it sound's like they weren't disposing of it overly well.

Now for the construction of contamination…it looks like its days are numbered. The fences have been fenced in by new looking fences of a construction company, and a clean portaloo and a lunch table occupy some of the back area. These as well as finding a new and working oxy-welder upstairs, makes me think that the decommissioning of this paint playground in under way.

The far end of the property is a pile of rubble and not really worth venturing too unless you find piles of concrete and metal fascinating. There is one small building out that side but it has been overtaken by nature and now abused by falling debris, so not much to see there.

The main, multi-level building is where the majority of good stuff is at. The bottom floor has some graffiti splattered around and by the look of it may of been somewhere stocks were kept as signs for certain colours still hang from the roof. There was also an open area that looks up to the next level and has the bottoms of the vats/barrels there and some pipes and wheels and of course a few mattress formerly used by squatters.

Go up a level and there is some really interested stuff up here. Paint solvent taps, huge containers, rows of vats and mixers with drips of dried paint hanging from the lids. A huge conveyor belt style machine, some more clean rooms with graffiti and then over in the corners load of flat pack packed up furniture. This was probably my favourite level of the main building.

Head up another level and it looks like its the home of the former offices with old Anzol receipts from a 1980's printer littering the floor, and not far from the receipts, a very prehistoric looking printer. This floor has been punished, windows smashed, walls kicked in and only one decent piece of graffiti to be found, oh and not to mention some super rank soggy carpet on the floor.

Venture up some more and you reach the roof top, not much up here but it's still pretty cool! When it was first abandoned and no so thrashed, it probably would've been a sweet place for a beer in the afternoon.

Toward the front of the property (I consider the wall with Anzol painted on it to be the front) there are several small buildings that proved to be well worth a gander. The far one wasn't overly exciting, some graffiti and some huge containers that used to house flammable liquids. The middle one was in surprisingly good condition with not many windows smashed, and a few beautiful old machines lying around that have not fallen victim to the wrath of vandals. You could also get up onto the roof of this building, although the wooden boards and rusty handrails weren't overly inviting, but still they did the job of holding us up. And the final building turned out to have some goodies in there as well. Some more mixing vats, old wall mounted gauges, other pipes and knobs, minimal graffiti and we even found a lovely old litre measuring gauge. You could get onto the roof of this building to, but the rain had started falling and there was a tree guarding the entrance to the rooftop that I didn't have the energy to battle.

All in all, I was pretty impressed with the factory. We weren't bothered by anyone (although there were some weirdos running around in morph suits filming a video clip) and the place still has a lot of cool things to see. If I were you and you wanted to check this place out, I would get onto it pretty quickly as I think its going to join places like the Glebe Tram Shed and Dunlop Factories on the RIP list really soon.

WHAT: An abandoned paint factory previously owned by Anzol Paints. Apparently been abandoned for around 20 years.

ACCESS - EASY: We did a quick drive around the perimeter to see if there were any holes in fences or openings to grant us entry, but we could only find two access points, one was a climb over the wall using a vent in the brick wall, and the other was a dodgy corner section where fence met brick wall. During our time inside the complex though, we soon found out that the large door at the front was in fact open, but just pulled too, likewise with a little hatch door on another large door. Both unlocked but pulled too and hep closed with a stick or wire to stop it from swinging open.

SECURITY - LOW – MEDIUM: There is new developed and construction going on all around the factory, including the factory itself by the look of things. The residents around saw us and didn't seem to care (if you were being a dick and smashing things they probably would) so they pose no problem. We also went on a Sunday morning so worksites and factory workers weren't around. If you went on a weekday I think you would probably attract a bit more attention and possibly get kicked out or in trouble, or the workers could actually be on site as there was signs (portaloo and new oxy-welder) that people were starting to rip this place down. So it gets a mixed security rating, low for weekends and medium for weekdays.

INTEREST - 9/10: I was pleasantly surprised by this place. I have seen a few photos of it and nothing that really blew my mind, but we spent over two hours exploring and it was good. The place is super trashed, not sure if it is a result of vandal or it's future construction plans, but in saying that the main factory is in pretty decent condition. The calibre of graffiti is pretty shite, but there is some really cool old paint related things still to be found. Huge paint vat/storage things, taps and pipes, dials, containers, signs, mixing machines, papers and other cool stuff can be seen.

ALONE OR WITH A FRIEND: You could go alone easy enough, but it has got a little bit of a creepy feeling to it, so I opted to take a friend. The place in parts is in very bad condition, but like mentioned the main building and roof top are pretty solid, but still places that look like this, probably always best to take a friend just in case!

DANGERS: Just be careful. The main buildings floor and roof and stairs all seem solid. I didn't feel any soggy floors and there's no holes in the floor unless they are mean't to be there. There are some huge piles of rubble around, so would stay away from them. And the usual things like rusty metal and pipes and things sticking out from the walls and floors are around as well so just don't go running around with you're eyes closed and you should survive.



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Tallis - Dragon Age Wiki, Tallis

Tallis

Contents

Background Edit

Tallis was born in Tevinter. where slavery is legal. In Minrathous. she was sold into slavery by her parents so they could pay off their debts. She was on a slaver ship bound for the city of Carastes when the Qunari boarded and captured the ship. Everyone aboard was brought to the island fortress of Qunathras, to the east of Seheron. Tallis was initially deemed an unsuitable convert. and would have been rendered a mindless laborer if not for the intervention of Salit. a high-ranking Ben-Hassrath agent, who formally requested that the tammasrans turn the girl over to him so he could train her to become a Tallis, "those who solve". Her duties involved travelling to non-Qunari lands, primarily Orlais and Nevarra. where she was tasked with burglaries, heists, and assassinations. She always completed those missions successfully, though never to the complete specifications of her superiors. They would have preferred the mission be abandoned rather than completed imperfectly.

Tallis finally pushed them over the edge during a mission to retrieve a Qunari artifact in the possession of Count Alphonse Valmont in Arlesans. During the heist, Tallis found human and elven children being kept as sex slaves and set them free, killing the Count and several of his guards in the process. This set off a diplomatic incident that almost led to war between the Qunari and Orlais. Tallis had failed to steal the object without leaving any trace as she had been ordered and she was therefore demoted to the rank of "Athlok" - a laborer. She was assigned as a kitchen-hand on a boat docked in Kirkwall, during the Arishok 's stay in Kirkwall. She was offered a chance to redeem herself two years later. [1]

Involvement Edit

Dragon Age: Redemption Edit

“Victory is in the Qun.” — Tallis This article contains spoilers for Dragon Age Redemption . Click here to reveal them.

Tallis in Redemption

When she is first seen she is working as an Athlok in a ship moored in the docks of Kirkwall. A Qunari informs her that she has been reinstated as Tallis, and must track down a Tal-Vashoth Saarebas who escaped a Chantry prison. She harries an accomplice of the fugitive mage and encounters a Templar named Cairn. The two battle briefly before Tallis finally extracts the needed information from her captive mage, killing him shortly afterwards.

She attempts to intercept her target at a Dalish camp, only to discover that they have been decimated by the Saarebas. She discovers that the Saarebas and his accomplices stole a precious and dangerous elven artifact: Mask of Fen'Harel. Setting out again, she joins forces with Cairn the templar, who is also tracking the Qunari magi; they are joined by the First to the Keeper of the ravaged clan. Josmael.

Tallis locates the Saarebas in a cave, where he uses the blood of Josmael's love to complete part of the Mask of Fen'Harel. Saarebas then escapes and seals the group in the cave, alongside one of his cohorts: a reaver mercenary named Nyree.

Tallis hires Nyree using money she stole from Josmael's clan. The mercenary reveals that the mage is heading to Sundermount. and Josmael offers to show the party a shortcut through the mountains. On their way to the elven ruins, the group rests at an inn. There, they are confronted by a group of thugs hired by the rogue Saarebas.

After defeating the mercenaries, Tallis and Cairn accuse Josmael of leading the group into a trap, after which the templar attempts to kill the elven mage. Nyree rescues Josmael and reveals that Cairn is responsible for the Saarebas' escape in the first place. Tallis demands answers, and Cairn admits to trying to kill the mage for killing his family and destroying their village. Cairn's confession brings the two closer together. They no longer bear any ill will toward Josmael.

They manage to get to Sundermount and decide to wait for the Saarebas. Whilst they wait, Tallis has a conversation with Cairn about their purposes for hunting the mage. He insists that the Saarebas needs to die, and encourages Tallis to abandon the Qun and become a renegade within the Qunari society as he has become one within the Chantry. She then states that doing so would make her a Tal-Vashoth. but Cairn makes her realise that she may in fact already be one. Tallis is reluctant to think about the idea, but does not resist when Cairn kisses her.

After the Saarebas arrives, Fina, the elven prisoner of the mage, betrays Josmael by alerting the Saarebas of the group's presence. While the group battles, Josmael accidently stabs Fina, completing the ritual and tearing open the Veil. Before the power of The Fade can be completely unleashed however, Tallis shatters the Mask of Fen'Harel, sealing the Veil shut.

In his rage, the Saarebas unleashed a lightning bolt at the elven assassin, but Cairn saves her life by throwing himself in the bolt's path. Tallis collars the mage, and it makes the Qunari powerless. Tallis then spots Cairn's body. The elf decides to honour Cairn's wish and defies her orders and role in the Qun by killing the Saarebas to avenge Cairn.

The following day, she buries the dead along with Josmael and Nyree, before saying her farewells. Josmael gives her a broken phylactery that belonged to Cairn, as a keepsake. When Nyree inquires about how the Qunari will react when they discover the Saarebas was killed, Tallis hints that she might defect and become a Tal-Vashoth. Eventually however she returns to the Qun and regains her rank of Tallis.

Mark of the Assassin Edit

“There are men who embrace destiny; these are the ones that change the world forever.” — Flemeth This article contains spoilers for Dragon Age II . Click here to reveal them.

Tallis first encounters Hawke in Kirkwall at the Hightown market. Hawke is lured into an ambush set up by the Antivan Crows which Hawke narrowly survives with Tallis' assistance. Tallis manages to enlist Hawke's aid in stealing a jewel called the "Heart of the Many " from an Orlesian Duke named Prosper de Montfort. who she claims has no right to possess the jewel.

After arriving at the Duke's Free Marches resident, Chateau Haine. Tallis aids Hawke in the Duke's Wyvern hunt, successfully baiting and slaying one of the ferocious beasts. Upon finally breaching the Chateau's Vault, Duke Prosper and his Chevaliers capture Hawke and Tallis and reveal to Hawke that Tallis is a Qunari agent.

While locked in The Dungeons. Tallis confesses the truth to Hawke. She was actually trying to stop a Tal-Vashoth named Salit. who first recruited her into the Ben-Hassrath. from selling Qunari secrets to Orlais. Though the Ariqun did not feel it worth intervening, Tallis decided to stop Salit of her own volition, knowing that Salit's betrayal will harm many people, not just Qunari.

Whether Hawke decides to help Tallis or not, after escaping, Hawke eventually confronts both Prosper and Salit. While Hawke distracts Prosper, Tallis steals the scroll Salit was handing over to Prosper, which contains information on various Qunari sleeper agents throughout Thedas. even those who have left the Qun, the duke having not had a chance to be appraised of its true significance. Prosper and his troops kill Salit and his Tal-Vashoth but are slain after a grueling battle by Hawke and their companions. Tallis takes a moment to mourn her former mentor and reveals to Hawke that if the scroll fell into human hands, these agents and everyone they know would be persecuted and killed. Though the Ariqun believed they knew the risks, Tallis feared for the agents' families and friends. Tallis then passes Hawke an actual jewel called the Heart of the Many before departing from the Champion's company. It is likely that Tallis returned the scroll to the Qunari, as her name has surfaced in a number of reports of Ben-Hassrath activity along the northern coast, including in Minrathous.

Hawke mentions in their journal that they believe they spotted Tallis in a crowd a year later disguised as a servant but could not confirm it was her.

Dragon Age: Inquisition Edit

There are no upgrades for Tallis's armor in the DLC Where the Heart Lies .

Other Edit

Damage: 1.6 + 1.68 * LVL physical damage (2.9 + 3.11 * LVL per second) +X attack +Y% attack speed Improves with level-up – starting weapon

Quotes Edit

Early concept art of Tallis.

Main article: Tallis/Dialogue

"I may be Qunari, but I was raised an elf."

"He who wishes to walk on water must first learn to swim."

"You go elbow-deep in wyvern shit and I'm the weird one?"

"Don't look at me while I do this. (Ungodly cacophony)"

"It's not always meant to end in violence. There are other paths. They do not all need to lead to the same destination."

"Doubt is the path one walks to reach faith. To leave the path is to embrace blindness and abandon hope."

"Past the idea of right and wrong is a field. When the soul lies in that grass the world is in balance. I will meet you there."

Trivia Edit

Just like Sten. "Tallis" is not her name, but her rank. It means "to solve" in Qunlat.

Tallis is the first female qunari (of any race) introduced.

Despite using dual-wield daggers and talents, Tallis' default attack in Dragon Age II is ranged, involving her throwing her daggers.

If Isabela is in the party, during the final conversation with Tallis, Tallis will claim to have 6 toes on her left foot.

Back at the Hawke Estate after finishing the DLC, near the statue of Mark of the Assassin . there will be a journal filled by Hawke about their thoughts for Tallis. The content depends on their relationship.

While the player does have the option to flirt with Tallis (and receive a kiss, depending on the player's choices during the DLC), it will have no effect on any romance they currently have with another character (though if present, all except Sebastian express jealousy). Tallis will simply leave by the end of the quest.

Tallis has two unique daggers. One, Kathryn. is named after her voice actor (Kathryn Felicia Day); and the other one, Thane. is named after an alien assassin from the Mass Effect series whom Felicia romanced.

She seems to have some history with Leliana.

In spite of what she hints at the end of Redemption . Tallis, if she was telling the truth about her future, did not become a Tal-Vashoth. If she had, she would never have known about Salit's defection, let alone Ariqun's reaction to it.

In Dragon Age: Inquisition . Tallis is mentioned by Varric in banter with Iron Bull. Varric says that she used to cause all sorts of trouble.

Gallery Edit

See also Edit

Codex entry: Thoughts on Tallis Codex entry: Saarath

References Edit



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Kvinder > 62 mikromol/liter: 144 x (P-kreatinin/(0,7 x 88,4)) -1,209 x 0,993 Alder

M?nd ≤ 80 mikromol/liter: 141 x (P-kreatinin/(0,9 x 88,4)) -0,411 x 0,993 Alder

M?nd > 80 mikromol/liter: 141 x (P-kreatinin/(0,9 x 88,4)) -1,209 x 0,993 Alder

Reference . KDIGO: “Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease”.   Kidney International Supplements (2013) 3, viii, januar 2013.

Corodil®

Dosis skal neds?ttes ved darligt fungerende nyrer.

Midlet skal anvendes med forsigtighed ved

Forsn?vring i legemspulsaren og i pulsarerne til nyrerne

Sygdom i hjerteklapperne

Forstorret hjertemuskel

Bindev?vssygdomme

Oget tendens til blodninger pga. fald i antallet af blodplader

Tendens til allergisk h?velse i ansigtet, mundhulen og strubehovedet (angioodem).

Brug af anden medicin

Det er vigtigt at informere l?gen om alle de l?gemidler, du tager.

NSAID (midler mod gigt og smerter) kan neds?tte virkningen af Corodil® og samtidig oge risikoen for nyreskade, is?r hos ?ldre.

Corodil® oger risikoen for forgiftning med lithium (middel mod manier).

Ved samtidig behandling med Corodil® og kalium eller kaliumbesparende diuretika (vanddrivende) oges blodets indhold af kalium.

Samtidig behandling med allopurinol (middel mod urinsyregigt) kan give alvorlige overfolsomhedsreaktioner.

Ved samtidig brug af midler mod diabetes, skal du j?vnligt kontrollere dit blodsukker, is?r i den forste maned af behandlingen.

Hvis du har diabetes eller nedsat nyrefunktion, ma du ikke behandles med aliskiren (et andet middel mod forhojet blodtryk).

Samtidig behandling med angiotensin II-h?mmere eller aliskiren (andre midler mod forhojet blodtryk) oger risikoen for lavt blodtryk, forhojet kalium i blodet og pavirkning af nyrerne.

Ved samtidig brug af midler mod diabetes (sukkersyge) skal du j?vnligt kontrollere dit blodsukker.

Graviditet

Revisionsdato

2016-06-30. Priserne er dog g?ldende pr. mandag den 12. september 2016

Der kan forekomme forskelle mellem pr?paratbeskrivelsen og oplysningerne i indl?gssedlen. Det skyldes, at min. medicin. dk kan have suppleret L?gemiddelstyrelsens og producentens produktinformationer med andre kilder. Min. medicin. dk har det fulde ansvar for pr?paratbeskrivelserne. Indholdet pa min. medicin. dk kan ikke erstatte radgivning eller behandling af en sundhedsprofessionel (fx l?ge, farmaceut, sygeplejerske eller farmakonom).

Kon: Kvinde Mand

Estimeret glomerul?r filtrationsrate (eGFR) beregnes ud fra CKD-EPI krea - formlen uden racekorrektion:

Kvinder ≤ 62 mikromol/liter: 144 x (P-kreatinin/(0,7 x 88,4)) -0,329 x 0,993 Alder

Kvinder > 62 mikromol/liter: 144 x (P-kreatinin/(0,7 x 88,4)) -1,209 x 0,993 Alder

M?nd ≤ 80 mikromol/liter: 141 x (P-kreatinin/(0,9 x 88,4)) -0,411 x 0,993 Alder

M?nd > 80 mikromol/liter: 141 x (P-kreatinin/(0,9 x 88,4)) -1,209 x 0,993 Alder

Reference . KDIGO: “Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease”.   Kidney International Supplements (2013) 3, viii, januar 2013.



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Alercina

Medication guide about Alercina (Cetirizine)

Brand name: Alercina Generic name: Cetirizine

What is the most important information I should know about Alercina? Use caution when driving, operating machinery, or performing other hazardous activities. Alercina may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking Alercina. While you are taking Alercina, do not take other prescription or over-the-counter cough, cold, or allergy medications without first talking to your doctor or pharmacist.

What is Alercina? Alercina is an antihistamine. Alercina blocks the actions of the naturally occurring chemical histamine in the body. Alercina is less likely than some other antihistamines to cause side effects such as drowsiness and dizziness. Alercina is used to treat the symptoms of allergies such as sneezing; runny nose; itching, tearing, and redness of the eyes; and hives. Alercina may also be used for purposes other than those listed in this medication guide.

What should I discuss with my healthcare provider before taking Alercina? Do not take Alercina without first talking to your doctor if you have had an allergic reaction to it or to the medication hydroxyzine (Atarax, Vistaril). Before taking Alercina, tell your doctor if you have kidney or liver disease. You may need a dosage adjustment or special monitoring during treatment. Alercina is in the FDA pregnancy category B. This means that it is not expected to be harmful to an unborn baby. Do not take Alercina without first talking to your doctor if you are pregnant or could become pregnant during treatment. Alercina passes into breast milk and may affect a nursing baby. Do not take Alercina without first talking to your doctor if you are breast-feeding a baby. If you are over 65 years of age, you may be more likely to experience side effects from Alercina. Your doctor may prescribe a lower dose of this medication.

How should I take Alercina? Take Alercina exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you. Take the tablets with a full glass of water. Chew the chewable tablets thoroughly before swallowing. To ensure you get the correct dose, measure the liquid form of Alercina with a dose-measuring spoon, cup, or dropper, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one. Alercina can be taken with or without food. Store Alercina at room temperature away from moisture and heat.

What happens if I miss a dose? If you are taking Alercina on a regular schedule, take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose. If you are taking Alercina as needed, take the missed dose if it is needed, then wait the recommended or prescribed amount of time before taking another dose.

What happens if I overdose? Seek emergency medical attention if an overdose is suspected. Symptoms of a Alercina overdose are not well known but may include drowsiness.

What should I avoid while taking Alercina? Use caution when driving, operating machinery, or performing other hazardous activities. Alercina may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities. Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while taking Alercina. Alercina may increase the effects of other drugs that cause drowsiness or dizziness, including antidepressants, alcohol, sedatives (used to treat insomnia), pain relievers, anxiety medicines, muscle relaxants, and other antihistamines. Tell your doctor about all medicines that you are taking, and do not take any medicine without first talking to your doctor. While you are taking Alercina, do not take other prescription or over-the-counter cough, cold, or allergy medications without first talking to your doctor or pharmacist.

What are the possible side effects of Alercina? Stop taking Alercina and seek emergency medical attention if you experience a rare but serious allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives). Other, less serious side effects may be more likely to occur. Continue to take Alercina and talk to your doctor if you experience drowsiness; dizziness; headache; or dry mouth. Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Alercina? Alercina may increase the effects of other drugs that cause drowsiness or dizziness, including antidepressants, alcohol, sedatives (used to treat insomnia), pain relievers, anxiety medicines, muscle relaxants, and other antihistamines. Tell your doctor about all medicines that you are taking, and do not take any medicine without first talking to your doctor. While you are taking Alercina, do not take other prescription or over-the-counter cough, cold, or allergy medications without first talking to your doctor or pharmacist. Drugs other than those listed here may also interact with Alercina. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

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Nebilox 5mg Tablets, Nebilox

NEBILOX 5MG TABLETS

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

FDA Consumer Updates

Latest Drug Information Updates

Yosprala Yosprala (aspirin and omeprazole) is a platelet aggregation inhibitor and proton pump inhibitor combination.

Troxyca ER Troxyca ER (oxycodone hydrochloride and naltrexone hydrochloride) is an extended-release, abuse-deterrent.

Adlyxin Adlyxin (lixisenatide) is a once-daily prandial glucagon-like peptide-1 (GLP-1) receptor agonist indicated.

Xiidra Xiidra (lifitegrast) is a lymphocyte function-associated antigen-1 (LFA-1) antagonist indicated for the.

Epclusa Epclusa (sofosbuvir and velpatasvir) is a nucleotide analog polymerase inhibitor and pan-genotypic NS5A.

Byvalson Byvalson (nebivolol and valsartan) is a beta adrenergic blocker and an angiotensin II receptor blocker (ARB).

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Interactions, Usage, Facts, And Information On Azupamil, Azupamil

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Azupamil (Verapamil)

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DISCLAIMER: MediGuard is not intended to be a substitute for professional medical advice. MediGuard cannot and does not take into consideration every possible interaction or account for individual responses to medicine. Different individuals may respond to medication in different ways. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective, or appropriate for any given patient. Always seek the advice of a qualified health provider with any questions you may have before making any changes to your treatment. The use of the MediGuard site and its content is at your own risk. The MediGuard site and the information contained in it is intended for users in the United States and information in other countries may be different.

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Danazol - Woman S Health, Estolmon

Danazol is used to treat a number of different medical problems. These include:

Endometriosis;

Fibrocystic breast disease (cysts in the breasts);

Hereditary angioedema (swelling of the different parts of the body, such as abdomen or stomach, arms, legs, throat, skin, or sexual organs.

It is very important that you use danazol only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects.

You must start taking danazol while you are having your monthly period.

In order for danazol to help you, it must be taken regularly for the full time of treatment as ordered by your doctor.

If you miss a dose of danazol, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

The dose of danazol will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of danazol. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine. For oral dosage form (capsules): For treatment of mild endometriosis: Adults—At first, 200 to 400 milligrams (mg), divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of moderate to severe endometriosis: Adults—At first, 800 milligrams (mg) per day, divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of fibrocystic breast disease: Adults—100 to 400 milligrams (mg) per day, divided in two doses. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For prevention of hereditary angioedema: Adults—At first, 200 milligrams (mg) two or three times a day. Your doctor may adjust your dose as needed and depending upon your condition. Children—Use and dose must be determined by your doctor.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing. Keep out of the reach of children. Do not keep outdated medicine or medicine no longer needed.

It is very important that your doctor check your progress at regular visits to make sure that danazol does not cause unwanted effects. Blood tests may be needed to check for unwanted effects.

Using danazol while you are pregnant can harm your unborn baby. If you are a woman who can bear children, your doctor may give you a pregnancy test before you start using danazol to make sure you are not pregnant. Your birth control pills may not work as well while you are using danazol. You must use an effective form of birth control (e. g. a condom, a diaphragm, spermicide) to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using danazol may cause irregular monthly periods or absence of menstrual period. If your regular monthly period does not begin within 60 to 90 days after you stop taking danazol, check with your doctor right away.

Check with your doctor right away if you are a female and have a larger clitoris (sexual organ), deepening of your voice, or unusual hair growth after taking danazol. Your doctor may advise you to stop taking the medicine so these side effects do not get worse.

Stop using danazol and check with your doctor if you have the following symptoms while taking danazol: blurred vision; change in the ability to see colors, especially blue or yellow; headache; nausea; or vomiting.

For patients with diabetes: danazol may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, check with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you are taking danazol. The results of some tests may be affected by danazol.

Danazol may rarely cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness, or other discoloration of the skin, or a severe sunburn. Check with your doctor if this occurs.

Do not take other medicines unless they have been discussed with your doctor.

Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.

Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with Danazol, persistent amenorrhea has occasionally been reported.

Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.

Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of Danazol of 400 mg or more. It is recommended that patients receiving Danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.

Danazol is used to treat a number of different medical problems. These include:

Endometriosis;

Fibrocystic breast disease (cysts in the breasts);

Hereditary angioedema (swelling of the different parts of the body, such as abdomen or stomach, arms, legs, throat, skin, or sexual organs.

It is very important that you use danazol only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects.

You must start taking danazol while you are having your monthly period.

In order for danazol to help you, it must be taken regularly for the full time of treatment as ordered by your doctor.

If you miss a dose of danazol, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

The dose of danazol will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of danazol. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine. For oral dosage form (capsules): For treatment of mild endometriosis: Adults—At first, 200 to 400 milligrams (mg), divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of moderate to severe endometriosis: Adults—At first, 800 milligrams (mg) per day, divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of fibrocystic breast disease: Adults—100 to 400 milligrams (mg) per day, divided in two doses. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For prevention of hereditary angioedema: Adults—At first, 200 milligrams (mg) two or three times a day. Your doctor may adjust your dose as needed and depending upon your condition. Children—Use and dose must be determined by your doctor.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing. Keep out of the reach of children. Do not keep outdated medicine or medicine no longer needed.

It is very important that your doctor check your progress at regular visits to make sure that danazol does not cause unwanted effects. Blood tests may be needed to check for unwanted effects.

Using danazol while you are pregnant can harm your unborn baby. If you are a woman who can bear children, your doctor may give you a pregnancy test before you start using danazol to make sure you are not pregnant. Your birth control pills may not work as well while you are using danazol. You must use an effective form of birth control (e. g. a condom, a diaphragm, spermicide) to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using danazol may cause irregular monthly periods or absence of menstrual period. If your regular monthly period does not begin within 60 to 90 days after you stop taking danazol, check with your doctor right away.

Check with your doctor right away if you are a female and have a larger clitoris (sexual organ), deepening of your voice, or unusual hair growth after taking danazol. Your doctor may advise you to stop taking the medicine so these side effects do not get worse.

Stop using danazol and check with your doctor if you have the following symptoms while taking danazol: blurred vision; change in the ability to see colors, especially blue or yellow; headache; nausea; or vomiting.

For patients with diabetes: danazol may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, check with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you are taking danazol. The results of some tests may be affected by danazol.

Danazol may rarely cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness, or other discoloration of the skin, or a severe sunburn. Check with your doctor if this occurs.

Do not take other medicines unless they have been discussed with your doctor.

Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.

Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with Danazol, persistent amenorrhea has occasionally been reported.

Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.

Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of Danazol of 400 mg or more. It is recommended that patients receiving Danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.

Danazol is used to treat a number of different medical problems. These include:

Endometriosis;

Fibrocystic breast disease (cysts in the breasts);

Hereditary angioedema (swelling of the different parts of the body, such as abdomen or stomach, arms, legs, throat, skin, or sexual organs.

It is very important that you use danazol only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects.

You must start taking danazol while you are having your monthly period.

In order for danazol to help you, it must be taken regularly for the full time of treatment as ordered by your doctor.

If you miss a dose of danazol, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

The dose of danazol will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of danazol. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine. For oral dosage form (capsules): For treatment of mild endometriosis: Adults—At first, 200 to 400 milligrams (mg), divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of moderate to severe endometriosis: Adults—At first, 800 milligrams (mg) per day, divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of fibrocystic breast disease: Adults—100 to 400 milligrams (mg) per day, divided in two doses. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For prevention of hereditary angioedema: Adults—At first, 200 milligrams (mg) two or three times a day. Your doctor may adjust your dose as needed and depending upon your condition. Children—Use and dose must be determined by your doctor.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing. Keep out of the reach of children. Do not keep outdated medicine or medicine no longer needed.

It is very important that your doctor check your progress at regular visits to make sure that danazol does not cause unwanted effects. Blood tests may be needed to check for unwanted effects.

Using danazol while you are pregnant can harm your unborn baby. If you are a woman who can bear children, your doctor may give you a pregnancy test before you start using danazol to make sure you are not pregnant. Your birth control pills may not work as well while you are using danazol. You must use an effective form of birth control (e. g. a condom, a diaphragm, spermicide) to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using danazol may cause irregular monthly periods or absence of menstrual period. If your regular monthly period does not begin within 60 to 90 days after you stop taking danazol, check with your doctor right away.

Check with your doctor right away if you are a female and have a larger clitoris (sexual organ), deepening of your voice, or unusual hair growth after taking danazol. Your doctor may advise you to stop taking the medicine so these side effects do not get worse.

Stop using danazol and check with your doctor if you have the following symptoms while taking danazol: blurred vision; change in the ability to see colors, especially blue or yellow; headache; nausea; or vomiting.

For patients with diabetes: danazol may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, check with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you are taking danazol. The results of some tests may be affected by danazol.

Danazol may rarely cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness, or other discoloration of the skin, or a severe sunburn. Check with your doctor if this occurs.

Do not take other medicines unless they have been discussed with your doctor.

Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.

Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with Danazol, persistent amenorrhea has occasionally been reported.

Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.

Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of Danazol of 400 mg or more. It is recommended that patients receiving Danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.

Danazol is used to treat a number of different medical problems. These include:

Endometriosis;

Fibrocystic breast disease (cysts in the breasts);

Hereditary angioedema (swelling of the different parts of the body, such as abdomen or stomach, arms, legs, throat, skin, or sexual organs.

It is very important that you use danazol only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects.

You must start taking danazol while you are having your monthly period.

In order for danazol to help you, it must be taken regularly for the full time of treatment as ordered by your doctor.

If you miss a dose of danazol, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

The dose of danazol will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of danazol. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine. For oral dosage form (capsules): For treatment of mild endometriosis: Adults—At first, 200 to 400 milligrams (mg), divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of moderate to severe endometriosis: Adults—At first, 800 milligrams (mg) per day, divided in two doses, for at least 3 to 6 months and up to 9 months. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For treatment of fibrocystic breast disease: Adults—100 to 400 milligrams (mg) per day, divided in two doses. Your doctor may adjust your dose as needed and tolerated. Children—Use and dose must be determined by your doctor. For prevention of hereditary angioedema: Adults—At first, 200 milligrams (mg) two or three times a day. Your doctor may adjust your dose as needed and depending upon your condition. Children—Use and dose must be determined by your doctor.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing. Keep out of the reach of children. Do not keep outdated medicine or medicine no longer needed.

It is very important that your doctor check your progress at regular visits to make sure that danazol does not cause unwanted effects. Blood tests may be needed to check for unwanted effects.

Using danazol while you are pregnant can harm your unborn baby. If you are a woman who can bear children, your doctor may give you a pregnancy test before you start using danazol to make sure you are not pregnant. Your birth control pills may not work as well while you are using danazol. You must use an effective form of birth control (e. g. a condom, a diaphragm, spermicide) to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Using danazol may cause irregular monthly periods or absence of menstrual period. If your regular monthly period does not begin within 60 to 90 days after you stop taking danazol, check with your doctor right away.

Check with your doctor right away if you are a female and have a larger clitoris (sexual organ), deepening of your voice, or unusual hair growth after taking danazol. Your doctor may advise you to stop taking the medicine so these side effects do not get worse.

Stop using danazol and check with your doctor if you have the following symptoms while taking danazol: blurred vision; change in the ability to see colors, especially blue or yellow; headache; nausea; or vomiting.

For patients with diabetes: danazol may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, check with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you are taking danazol. The results of some tests may be affected by danazol.

Danazol may rarely cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness, or other discoloration of the skin, or a severe sunburn. Check with your doctor if this occurs.

Do not take other medicines unless they have been discussed with your doctor.

Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.

Other possible endocrine effects include menstrual disturbances in the form of spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with Danazol, persistent amenorrhea has occasionally been reported.

Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.

Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of Danazol of 400 mg or more. It is recommended that patients receiving Danazol be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported.



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Paracetamol Uses, Dosage - Side Effects, Paracetol

Paracetamol

Paracetamol (acetaminophen) is a pain reliever and a fever reducer. The exact mechanism of action of is not known.

Paracetamol is used to treat many conditions such as headache, muscle aches, arthritis, backache, toothaches, colds, and fevers. It relieves pain in mild arthritis but has no effect on the underlying inflammation and swelling of the joint.

Paracetamol may also be used for other purposes not listed in this medication guide.

Important information

There are many brands and forms of paracetamol available and not all brands are listed on this leaflet.

Do not use more of this medication than is recommended. An overdose of paracetamol can cause serious harm. The maximum amount of paracetamol for adults is 1 gram (1000 mg) per dose and 4 grams (4000 mg) per day. Taking more paracetamol could cause damage to your liver. If you drink more than three alcoholic beverages per day, talk to your doctor before taking paracetamol and never use more than 2 grams (2000 mg) per day.

Do not use this medication without first talking to your doctor if you drink more than three alcoholic beverages per day or if you have had alcoholic liver disease (cirrhosis). You may not be able to use paracetamol .

Before using paracetamol. tell your doctor if you have liver disease or a history of alcoholism.

Do not use any other over-the-counter cough, cold, allergy, or pain medication without first asking your doctor or pharmacist. Paracetamol is contained in many combination medicines. If you use certain products together you may accidentally use too much paracetamol. Read the label of any other medicine you are using to see if it contains paracetamol, acetaminophen or APAP. Avoid drinking alcohol while taking this medication. Alcohol may increase your risk of liver damage while taking paracetamol .

Before taking this medicine

Do not use this medication if you are allergic to acetaminophen or paracetamol.

Ask a doctor or pharmacist if it is safe for you to take paracetamol if you have:

a history of alcoholism;

It is not known whether paracetamol will harm an unborn baby. Before using paracetamol. tell your doctor if you are pregnant. This medication can pass into breast milk and may harm a nursing baby. Do not use paracetamol without telling your doctor if you are breast-feeding a baby.

How should I use paracetamol ?

Use paracetamol exactly as directed on the label, or as prescribed by your doctor.

Do not use more of this medication than is recommended. An overdose of paracetamol can cause serious harm. The maximum amount for adults is 1 gram (1000 mg) per dose and 4 grams (4000 mg) per day. Using more paracetamol could cause damage to your liver. If you drink more than three alcoholic beverages per day, talk to your doctor before taking paracetamol and never use more than 2 grams (2000 mg) per day. If you are treating a child, use a pediatric form of paracetamol. Carefully follow the dosing directions on the medicine label. Do not give the medication to a child younger than 2 years old without the advice of a doctor.

Measure the liquid form of paracetamol with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. You may need to shake the liquid before each use. Follow the directions on the medicine label.

The paracetamol chewable tablet must be chewed thoroughly before you swallow it.

Make sure your hands are dry when handling the paracetamol disintegrating tablet. Place the tablet on your tongue. It will begin to dissolve right away. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing.

To use the paracetamol effervescent granules, dissolve one packet of the granules in at least 4 ounces of water. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

Do not take a paracetamol rectal suppository by mouth. It is for use only in your rectum. Wash your hands before and after inserting the suppository.

Try to empty your bowel and bladder just before using the paracetamol suppository. Remove the outer wrapper from the suppository before inserting it. Avoid handling the suppository too long or it will melt in your hands.

For best results from the suppository, lie down and insert the suppository pointed tip first into the rectum. Hold in the suppository for a few minutes. It will melt quickly once inserted and you should feel little or no discomfort while holding it in. Avoid using the bathroom just after inserting the suppository.

Stop using paracetamol and call your doctor if:

you still have a fever after 3 days of use;

you still have pain after 7 days of use (or 5 days if treating a child);

you have a skin rash, ongoing headache, or any redness or swelling; or

if your symptoms get worse, or if you have any new symptoms.

Urine glucose tests may produce false results while you are taking paracetamol. Talk to your doctor if you are diabetic and you notice changes in your glucose levels during treatment.

Store paracetamol at room temperature away from heat and moisture. The rectal suppositories can be stored at room temperature or in the refrigerator.

What happens if I miss a dose?

Since paracetamol is often used only when needed, you may not be on a dosing schedule. If you are using the medication regularly, use the missed dose as soon as you remember. If it is almost time for your next regularly scheduled dose, skip the missed dose and use your next dose as directed. Do not use extra medicine to make up for a missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

The first signs of an paracetamol overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

What should I avoid?

Do not use any other over-the-counter cough, cold, allergy, or pain medication without first asking your doctor or pharmacist. Paracetamol is contained in many combination medicines. If you use certain products together you may accidentally use too much paracetamol. Read the label of any other medicine you are using to see if it contains paracetamol, acetaminophen or APAP. Avoid drinking alcohol while taking this medication. Alcohol may increase your risk of liver damage while taking paracetamol .

Paracetamol side effects

Get emergency medical help if you have any of these signs of an allergic reaction to paracetamol: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

low fever with nausea, stomach pain, and loss of appetite;

dark urine, clay-colored stools; or

jaundice (yellowing of the skin or eyes).

This is not a complete list of paracetamol side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Paracetamol dosing information

Usual Adult Paracetamol Dose for Fever:

General Dosing Guidelines: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours orally or rectally.

Paracetamol 500mg tablets: Two 500 mg tablets orally every 4 to 6 hours

Usual Adult Paracetamol Dose for Pain:

General Dosing Guidelines: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours orally or rectally.

Paracetamol 500mg tablets: Two 500 mg tablets orally every 4 to 6 hours

Usual Pediatric Dose for Fever:

<=1 month: 10 to 15 mg/kg/dose every 6 to 8 hours as needed.

>1 month to 12 years: 10 to 15 mg/kg/dose every 4 to 6 hours as needed (Maximum: 5 doses in 24 hours)

Fever: 4 months to 9 years: Initial Dose: 30 mg/kg (Reported by one study (n=121) to be more effective in reducing fever than a 15 mg/kg maintenance dose with no difference regarding clinical tolerance.)

>=12 years: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours.

Usual Pediatric Dose for Pain:

<=1 month: 10 to 15 mg/kg/dose every 6 to 8 hours as needed.

>1 month to 12 years: 10 to 15 mg/kg/dose every 4 to 6 hours as needed (Maximum: 5 doses in 24 hours)

Fever: 4 months to 9 years: Initial Dose: 30 mg/kg (Reported by one study (n=121) to be more effective in reducing fever than a 15 mg/kg maintenance dose with no difference regarding clinical tolerance.)

>=12 years: 325 to 650 mg every 4 to 6 hours or 1000 mg every 6 to 8 hours.

What other drugs will affect paracetamol ?

There may be other drugs that can interact with paracetamol. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More about Paracetamol (acetaminophen)

Consumer resources

Professional resources

Related treatment guides

Where can I get more information?

Your pharmacist can provide more information about paracetamol .

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2014 Version: 11.01. 12/07/2009



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Valsartan Medical Facts From, Valsartanum

valsartan

Valsartan is an angiotensin II receptor antagonist. Valsartan keeps blood vessels from narrowing, which lowers blood pressure and improves blood flow.

Valsartan is used to treat high blood pressure (hypertension) in adults and children who are at least 6 years old. Valsartan is also used in adults to treat heart failure, and to lower the risk of death after a heart attack.

Valsartan is sometimes given together with other blood pressure medications.

Valsartan may also be used for purposes not listed in this medication guide.

What is the most important information I should know about valsartan?

Do not use if you are pregnant. Stop using and tell your doctor right away if you become pregnant. Valsartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

If you have diabetes, do not use valsartan together with any medication that contains aliskiren (Amturnide, Tekturna, Tekamlo, Valturna).

What should I discuss with my healthcare provider before taking valsartan?

You should not use valsartan if you are allergic to it.

To make sure valsartan is safe for you, tell your doctor if you have:

kidney disease (or if you are on dialysis);

a heart condition other than one being treated with valsartan;

if you are on a low-salt-diet;

if you are dehydrated; or

if you have ever had a severe allergic reaction to any blood pressure medication.

Do not use if you are pregnant. Stop using and tell your doctor right away if you become pregnant. Valsartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester. Use effective birth control.

It is not known whether valsartan passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Valsartan should not be given to a child younger than 6 years old.

How should I take valsartan?

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take valsartan with or without food. Take the medicine at the same time each day.

If a child taking valsartan cannot swallow a capsule whole, your pharmacist can mix the medicine into a liquid. Shake this liquid well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

You may have very low blood pressure while taking valsartan. Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual.

Your blood pressure will need to be checked often. Your kidney function may also need to be checked.

It may take 2 to 4 weeks of using this medicine before your blood pressure is under control. Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life.

Talk with your doctor if your symptoms do not improve after 4 weeks of treatment.

Store at room temperature away from moisture and heat.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking valsartan?

Drinking alcohol can further lower your blood pressure and may increase certain side effects of valsartan.

Do not use potassium supplements or salt substitutes while you are taking valsartan, unless your doctor has told you to.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Valsartan side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

In rare cases, valsartan can cause a condition that results in the breakdown of skeletal muscle tissue, leading to kidney failure. Call your doctor right away if you have unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine.

Also call your doctor at once if you have:

shortness of breath (even with mild exertion);

little or no urinating, swelling, rapid weight gain;

weakness, confusion, increased thirst, loss of appetite, vomiting;

pounding heartbeats or fluttering in your chest;

a light-headed feeling, like you might pass out; or

high potassium--slow heart rate, weak pulse, muscle weakness, tingly feeling.

Common side effects may include:

headache, dizziness, tired feeling;

stomach pain, diarrhea;

back pain, joint pain; or

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Valsartan dosing information

Usual Adult Dose for Congestive Heart Failure:

Initial dose: 40 mg orally twice a day Maintenance dose: 80 to 160 mg twice a day. The dose should be increased to the highest dose tolerated by the patient.

Usual Adult Dose for Hypertension:

Initial dose: 80 to 160 mg orally once a day. Maintenance dose: 80 to 320 mg orally once a day

Usual Adult Dose for Myocardial Infarction:

Initial dose: 20 mg orally twice a day Maintenance dose: The initial dosage may be titrated upward within 7 days to 40 mg twice daily, with subsequent titrations to a target maintenance dose of 160 mg twice a day as tolerated by the patient. If symptomatic hypotension or renal dysfunction occurs, consideration should be given to a dosage reduction.

Comment: Valsartan may be initiated as early as 12 hours after a myocardial infarction, and may be given with other standard postmyocardial infarction treatment, including thrombolytics, aspirin, beta blockers, and statins.

Usual Pediatric Dose for Hypertension:

6 to 16 years: Initial dose: 1.3 mg/kg once a day (up to 40 mg) Maintenance dose: up to 2.7 mg/kg (up to 160 mg) once a day titrated according to patient response

Comments: - If the calculated dosage does not correspond to the available tablet strengths, or if children are unable to swallow tablets, the use of a suspension (which can be prepared from the tablets) is recommended. The valsartan dose may need to be increased if the suspension is replaced by a tablet. - No data are available in pediatric patients either undergoing dialysis or with a glomerular filtration rate less than 30 mL/min.

What other drugs will affect valsartan?

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with valsartan, especially:

a diuretic (water pill);

NSAIDs (nonsteroidal anti-inflammatory drugs)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with valsartan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

More about valsartan

Consumer resources

Professional resources

Related treatment guides

Where can I get more information?

Your pharmacist can provide more information about valsartan.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Disclaimer: Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 16.04. Revision Date: 2015-08-31, 4:23:04 PM.

Drug Status



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Fortilut

Generic/rINN (Recommended International Nonproprietary Name)

ATC (Anatomical Therapeutic Chemical Classification)

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19-Norpregn-4-en-20-yn-3-one, 17-hydroxy-, (17α)-

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Prazosin - Side Effects, Dosage, Interactions, Perazodin

Prazosin

Prazosin, sold under the brand name Minipress, is a prescription medication used to treat high blood pressure.

The drug may also be used to treat patients with an enlarged prostate, congestive heart failure, Raynaud's disease, pheochromocytoma, and Ergot alkaloid poisoning. Some doctors prescribe prazosin to people with post-traumatic stress disorder, as it blocks the body's release of the hormone adrenaline.

Prazosin is one drug in the class of alpha-adrenergic blockers, which work by relaxing the blood vessels so that blood can pass through more easily. Prazosin comes in a tablet and capsule form and is manufactured by Pfizer, Inc.

Prazosin (Minipress) Warnings

You may feel dizzy when you first start prazosin, since it lowers blood pressure. This effect usually stops once your body gets used to the medication. Try not to stand up too quickly.

Older patients may be more sensitive to the side effects of prazosin, especially dizziness and fainting, which can increase the risk of falling.

Before taking this drug, you should tell your doctor if you have a history of the following conditions:

Heart problems

Low blood pressure

Kidney disease

Narcolepsy

Prostate cancer

You should tell your doctor that you are taking this medication before having surgery, including eye surgery.

Don't stop taking prazosin without first consulting your physician. Because some conditions may worsen when the medication is stopped abruptly, your dose may need to be gradually decreased.

Pregnancy and Prazosin (Minipress)

Prazosin should only be used during pregnancy if absolutely necessary. The drug passes through breast milk.

Prazosin (Minipress) and Other Drug Interactions

Some drugs that may interact with prazosin include:

Beta blockers, such as atenolol (Tenormin), metoprolol (Toprol-XL), propranolol (Inderal)

Verapamil (Calan)

Erectile dysfunction or pulmonary hypertension meds

Antihistamines, such as diphenhydramine (llermax, Banophen, Benadryl)

Anti-seizure drugs, such as carbamazepine (Carbatrol, Epitol, Equetro, Tegretol)

Drugs for sleep or anxiety, such as alprazolam (Niravam, Xanax, Xanax XR), diazepam (Valium), zolpidem (Ambien)

Muscle relaxants

Narcotic pain relievers (such as codeine)

Psychiatric meds, such as chlorpromazine (Thorazine), risperidone (Risperdal), amitriptyline (Elavil), trazodone (Desyrel)

Check the labels on all of your medications because they may contain ingredients that can increase your blood pressure or cause a fast heartbeat. This drug may also interfere with certain lab tests, so you should tell laboratory personnel you are taking prazosin.

You should also discuss all prescription, non-prescription, illegal, recreational, herbal, nutritional or dietary drugs you are taking with your doctor.

Prazosin (Minipress) and Other Interactions

This drug may impair your vision and make you dizzy or drowsy. Do not drive, use machinery, or perform any other activity that requires alertness until you are sure you can do so safely. You should also limit your alcohol intake while taking prazosin.

Prazosin (Minipress) Dosage

The amount of prazosin you take will depend on your doctor's instructions. A typical dosing schedule may look like this:

For high blood pressure:

Adults: Start with 0.5-1 milligrams (mg), two or three times a day. Then, your doctor will slowly increase your dose to 6-15 mg, divided into two or three doses a day. However, the total daily dose is usually not more than 20 mg.

Children: The dose will be based on body weight. The usual dose is 50-400 micrograms per kilogram of body weight a day. This is typically divided into two or three doses.

Prazosin (Minipress) Overdose

If you suspect an overdose, contact a poison control center at (800) 222-1222 or an emergency room immediately.

Missed Prazosin (Minipress)

If you miss a dose of prazosin, take it as soon as you remember. If it is close to the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not "double up" and take more than one dose at a time.

Prazosin Pictures

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Prazosin 2 mg-MYL, brown, capsule,

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By Julie Marks | Medically Reviewed by Mona Khanna, MD

Latest Update: 2014-09-25 Copyright © 2014 Everyday Health Media, LLC

About Drugs A-Z

Drugs A-Z provides drug information from Everyday Health and our partners, as well as ratings from our members, all in one place. Cerner Multum™ provides the data within some of the Basics, Side Effects, Interactions, and Dosage tabs. The information within the Reviews and FAQ tabs is proprietary to Everyday Health.

You can browse Drugs A-Z for a specific prescription or over-the-counter drug or look up drugs based on your specific condition. This information is for educational purposes only, and not meant to provide medical advice, treatment, or diagnosis. Remember to always consult your physician or health care provider before starting, stopping, or altering a treatment or health care regimen.

Every effort has been made to ensure that the information provided by on this page is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. The information on this page has been compiled for use by healthcare practitioners and consumers in the United States and therefore neither Everyday Health or its licensor warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Neither Everyday Health nor its licensors endorse drugs, diagnose patients or recommend therapy. The drug information above is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. Neither Everyday Health nor its licensor assume any responsibility for any aspect of healthcare administered with the aid of the information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have any questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Daily Dose Omega-3, Omega-3

Daily Dose: Omega-3

It's good for your joints, skin, vision, brain, heart, helps lower bad cholesterol levels and even boosts fertility. It's an anti-ager and an anti-inflammatory. It's found naturally in a variety of delicious foods including walnuts, salmon, tuna, olive oil and avocados. It's omega-3 – and it's time you got to know the daily dose that's good for just about every single part of your body.

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The Truth About Omegas, Pt 1 (4:04)

Omega-3 fatty acids are the brain-boosting, cholesterol-clearing good fats. Dr. Oz lists them as 1 of the 5 critical supplements every woman should take, 1 of 5 daily nutrition needs and as one of the most important steps expecting mother's can take to promote their baby's healthy development.

There are 3 basic forms of omega-3:

Alpha-linolenic acid (ALA) found in English walnuts and vegetable oils like flaxseed, soybean and olive which the body eventually, but in small quantities, converts to DHA.

Docosahexaenoic acid (DHA) found primarily in fish oil, this is the ultimate form of fatty acid in humans. Most people get far too little of this all-important fatty acid, especially since the conversion of ALA to DHA is slow and minimally yielding. Getting a daily dose of of DHA (600 to 1000 mg) from supplements is preferable to reap the health benefits. You have a choice of taking a fish oil supplement or one derived from algae or krill, a shrimp-like crustacean.

Eicosapentaenoic acid (EPA) is also found in fish oil, so it's absorbed if you're taking a daily dose of DHA omega-3.

What to look for when buying fish-oil supplements:

Fish oil supplements vary in the amounts and ratios of DHA and EPA they contain. For example, salmon oil naturally contains more DHA than EPA; a supplement derived from algae may only contain DHA. Krill oil contains significant amounts of both EPA and DHA. Read the labels and remember whatever supplement you buy, it must have at least 600 mg of DHA.

Be aware that only about one-third of the oil from fish is rich in EPA and DHA. Many supplements also contain vitamin E or other antioxidants to stabilize the oils and prevent them from becoming rancid. If you choose to buy a fish-oil supplement, check the label carefully to see if it recommends refrigeration to prevent spoiling.

Most brands of fish oil have been proven safe, free of detectable traces of mercury, and do not contain unsafe levels of PCBs (polychlorinated biphenyls), a toxin and pollutant believed to pose various health threats. To avoid contaminants in an unrefined supplement, it's best to choose a fish-oil supplement made from small, oily fish like anchovy, sardines or menhaden.

Here's how a daily dose of omega-3 fatty acids can improve and protect vital aspects of your body's daily functioning:

Lubricates joints Helps provide the lubrication joints need to function at an effective level. By keeping joints lubed, you experience less grinding and less overall wear and tear – and thereby – less pain as you age.

Decreases inflammation in inflamed joints.



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Buy Doxysina Online Without Prescriptions, Doxysina

Doxycycline is used for treating infections caused by certain bacteria. It may be used in combination with other medicines to treat certain amoeba infections. It may also be used to prevent or slow the progression of anthrax after exposure. Doxycycline is a tetracycline antibiotic. It works by slowing the growth of bacteria. Slowing bacteria's growth allows the body's immune system to destroy the bacteria.

Take Doxycycline exactly as it was prescribed for you.

Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Take Doxycycline with a full glass of water (8 ounces).

Do not take the medication with milk or other dairy products, unless your doctor has told you to. Dairy products can make it harder for your body to absorb the medicine.

Do not crush, break, or open a capsule. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking or opening the pill would cause too much of the drug to be released at one time.

Take Doxycycline for the entire length of time prescribed by your doctor. Your symptoms may get better before the infection is completely treated.

Doxycycline will not treat a viral infection such as the common cold or flu.

Do not give this medicine to another person, even if they have the same condition you have.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking Doxycycline. You may need to stop using the medicine for a short time.

Do not take any Doxycycline after the expiration date printed on the label. Using expired Doxycycline can cause damage to your kidneys.

Do not give Doxycycline to a child younger 8 years. It can cause permanent yellowing or graying of the teeth, and it can affect a child's growth.

If you miss a dose of Doxycycline, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Doxycycline.

Store Doxycycline at room temperature between 68 and 77 degrees F (20 and 25 degrees C) in a tightly closed container. Brief periods at temperatures of 59 to 86 degrees F (15 to 30 degrees C) are permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Doxycycline out of the reach of children and away from pets.

Do NOT use Doxycycline if:

you are allergic to any ingredient in Doxycycline, or to similar medicines such as demeclocycline (Declomycin), minocycline (Dynacin, Minocin, Solodyn, Vectrin), or tetracycline (Brodspec, Panmycin, Sumycin, Tetracap)

you are taking acitretin, isotretinoin, or a penicillin (eg, amoxicillin)

you have recently received or will be receiving a live oral typhoid vaccine.

Contact your doctor or health care provider right away if any of these apply to you.

Some medical conditions may interact with Doxycycline. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have diarrhea, a stomach or intestinal infection, a history of lupus, or the blood disease porphyria

if you have liver or kidney disease, you may need a dose adjustment or special tests to safely take Doxycycline.

Some medicines may interact with Doxycycline. Tell your health care provider if you are taking any other medicines, especially any of the following:

Barbiturates (eg, phenobarbital), carbamazepine, or hydantoins (eg, phenytoin) because they may decrease Doxycycline's effectiveness

Acitretin or isotretinoin because side effects, such as increased pressure inside the skull (resulting in severe headaches and vision problems) may occur

Anticoagulants (eg, warfarin), digoxin, methotrexate, or methoxyflurane because the risk of their side effects may be increased by Doxycycline

Live oral typhoid vaccine, hormonal birth control (eg, birth control pills), or penicillins (eg, amoxicillin) because their effectiveness may be decreased by Doxycycline.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Doxycycline may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Important safety information:

Be sure to use Doxycycline for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.

Long-term or repeated use of Doxycycline may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.

Mild diarrhea is common with antibiotic use. However, a more serious form of diarrhea (pseudomembranous colitis) may rarely occur. This may develop while you use the antibiotic or within several months after you stop using it. Contact your doctor right away if stomach pain or cramps, severe diarrhea, or blood stools occur. Do not treat diarrhea without first checking with your doctor.

Doxycycline may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Doxycycline. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.

Tell your doctor or dentist that you take Doxycycline before you receive any medical or dental care, emergency care, or surgery.

Hormonal birth control (eg, birth control pills) may not work as well while you are using Doxycycline. To prevent pregnancy, use an extra form of birth control (eg, condoms).

Doxycycline may interfere with certain lab tests. Be sure your doctor and lab personnel know you are using Doxycycline.

Pregnancy and breast-feeding: Doxycycline has been shown to cause harm to the fetus. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Doxycycline while you are pregnant. Doxycycline is found in breast milk. Do not breastfeed while taking Doxycycline.

All medicines may cause side effects, but many people have no, or minor, side effects.

Check with your doctor if any of these most common side effects persist or become bothersome:

Loss of appetite; nausea; sensitivity to sunlight; vomiting.

Seek medical attention right away if any of these severe side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); bloody stools; chest pain; dark urine; decreased urination; fever, chills, or sore throat; moderate to severe sunburn; severe diarrhea; severe or persistent headache; stomach pain or cramps; throat irritation; trouble swallowing; unusual bruising or bleeding; unusual joint pain; unusual tiredness; vaginal irritation or discharge; vision changes; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider.

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Ulzol Generic Name Omeprazole Online, Ulzol

Ulzol General Information

Ulzol - Pharmacology:

Ulzol is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H + /K + - ATPase in the gastric parietal cell. By acting specifically on the proton pump, omeprazole blocks the final step in acid production, thus reducing gastric acidity.

Ulzol for patients

PRILOSEC Delayed-Release Capsules should be taken before eating. Patients should be cautioned that the PRILOSEC Delayed-Release Capsule should not be opened, chewed or crushed, and should be swallowed whole.

For patients who have difficulty swallowing capsules, the contents of a PRILOSEC Delayed-Release Capsule can be added to applesauce. One tablespoon of applesauce should be added to an empty bowl and the capsule should be opened. All of the pellets inside the capsule should be carefully emptied on the applesauce. The pellets should be mixed with the applesauce and then swallowed immediately with a glass of cool water to ensure complete swallowing of the pellets. The applesauce used should not be hot and should be soft enough to be swallowed without chewing. The pellets should not be chewed or crushed. The pellets/applesauce mixture should not be stored for future use.

This description is suitable for active ingredient Omeprazole

Ulzol Interactions

Ulzol can prolong the elimination of diazepam, warfarin and phenytoin, drugs that are metabolized by oxidation in the liver. Although in normal subjects no interaction with theophylline or propranolol was found, there have been clinical reports of interaction with other drugs metabolized via the cytochrome P-450 system ( e. g., cyclosporine, disulfiram, benzodiazepines). Patients should be monitored to determine if it is necessary to adjust the dosage of these drugs when taken concomitantly with omeprazole.

Because of its profound and long lasting inhibition of gastric acid secretion, it is theoretically possible that omeprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability ( e. g., ketoconazole, ampicillin esters, and iron salts). In the clinical trials, antacids were used concomitantly with the administration of omeprazole.

Combination Therapy with Clarithromycin

Co-administration of omeprazole and clarithromycin may result in increases in plasma levels of ompeprazole, clarithromycin, and 14-hydroxy-clarithromycin.

Concomitant administration of clarithromycin with cisapride, pimozide, or terfenadine is contraindicated.

There have been reports of an intereaction between erythromycin and astemizole resulting in QT prolongation and torsades de points. Concomitant administration of erythromycin and astemizole is contraindicated. Because clarithromycin is also metabolized by cytochrome P450, concomitant administration of clarithromycin with astemizole is not recommended.

Ulzol Contraindications



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Ventamol Expectorant - Hovid, Ventamol

The drug brand named Ventamol Expectorant contains generic salt – Albuterol Sulfate and is manufactured by Hovid. Ventamol Expectorant is mainly associated with symptoms and indications – The International Classification of Diseases (ICD) – R03AK04 – Salbutamol and other drugs for obstructive airway diseases.

Generic Salts

Available types of drugs

Medical categories

Human Drug Antiasthmatic and COPD preparations Cough and cold preparations Usage – Diseases R03AK04 – Salbutamol and other drugs for obstructive airway diseases Manufacturers Hovid Pinewood Laboratories

Ventamol Expectorant – Hovid related drugs

The drug brand named Ventamol Expectorant contains generic salt – Albuterol Sulfate and is manufactured by Hovid. Ventamol Expectorant is mainly associated with symptoms and indications – The International Classification of Diseases (ICD) – R03AK04 – Salbutamol and other drugs for obstructive airway diseases.

Generic Salts

Available types of drugs

Medical categories

Human Drug Antiasthmatic and COPD preparations Cough and cold preparations Usage – Diseases R03AK04 – Salbutamol and other drugs for obstructive airway diseases Manufacturers Hovid Pinewood Laboratories

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Xylocard - Side Effects, Uses, Dosage, Overdose, Pregnancy, Alcohol, Xylocard

Xylocard

Updated: January 9, 2015

Lidocaine is a prescription medication used to prevent pain before procedures or to relieve pain due to certain conditions. Lidocaine belongs to a group of drugs called local anesthetics. These stop nerves from sending pain signals to the brain.

This medication comes in several topical forms, including a patch to be applied to the skin (transdermal), ointment, cream, and oral solution. Lidocaine is an ingredient in some over-the-counter topical pain relievers. This page refers to the prescription forms of lidocaine.

This medication is also available in an injectable form to be given directly into a vein (IV) or for infiltration and nerve block by a healthcare professional.

Common side effects of topical lidocaine include irritation at site of application. Common side effects of injectable lidocaine include confusion, nervousness, and numbness. Lidocaine may also cause dizziness and drowsiness. Do not drive or operate heavy machinery until you know how this medication affects you.

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Xylocard Cautionary Labels

Uses of Xylocard

Lidocaine is a prescription medication used to prevent pain before procedures or to relieve pain due to certain conditions. Lidocaine patches may be used to treat pain due to post-herpetic neuralgia. Lidocaine ointment, gel, and cream are used to prevent and control pain during procedures, such as intubation and eye surgery, and relieve pain due to conditions such as inflammation of the urethra and sore throat. Lidocaine oral solution is used to treat pain in the mouth.

Injectable lidocaine is used as an anesthetic during surgical procedures.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with lidocaine. See the “Lidocaine Precautions” section.

Common side effects of topical lidocaine include irritation at site of application, including burning, blisters, bruising, redness, or swelling at the site of application. Lidocaine ointment, gel, and cream, as well as the oral solution, may also cause vomiting, seizures, ringing in the ears, and irregular heartbeat. Lidocaine ophthalmic gel may cause headache or bloodshot eyes.

Lidocaine may also cause dizziness and drowsiness. Do not drive or operate heavy machinery until you know how this medication affects you.

Common side effects of injectable lidocaine include confusion, nervousness, numbness, blurred vision, irregular heartbeat, vomiting, seizures, ringing in the ears, headache, and shivering.

This is not a complete list of lidocaine side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Xylocard Interactions

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

disopyramide (Norpace)

flecainide (Tambocor)

medications applied to the skin or mouth to treat pain

mexiletine (Mexitil)

moricizine (Ethmozine)

procainamide (Procanabid, Pronestyl)

propafenone (Rhythmol)

quinidine (Quinidex)

tocainide (Tonocard)

This is not a complete list of lidocaine drug interactions. Ask your doctor or pharmacist for more information.

Xylocard Precautions

Serious side effects have been reported with topical lidocaine including the following:

Allergic reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of an allergic reaction.

Difficulty breathing or swallowing

Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs

Hives or skin rash

Fast heartbeat

Fast breathing

Nausea or vomiting

Confusion

Weakness

Fainting

Seizures or convulsions

Serious side effects have been reported with injectable lidocaine including the following:

Allergic reactions. Tell your healthcare provider right away if you have some or all of the following symptoms of an allergic reaction.

Difficulty breathing or swallowing

Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs

Hives or skin rash

Fast pulse

Fast breathing

Nausea or vomiting

Confusion

Weakness

Fainting

Seizures or convulsions

Injectable lidocaine may also affect the central nervous system, including lightheadedness, nervousness, blurred or double vision, altered sensations, and changes in respiration.

Injectable lidocaine may also affect the cardiovascular system, including changes in heartbeat, decreased blood pressure, and cardiac arrest.

Lidocaine can cause drowsiness and dizziness. Do not drive or operate heavy machinery until you know how lidocaine affects you.

Do not take lidocaine if you:

are allergic to lidocaine or to any of its ingredients

are allergic to other local anesthetics, including bupivacaine (Marcaine), etidocaine (Duranest), mepivacaine (Carbocaine, Prolocaine), or prilocaine (Citanest)

Additionally, do not take injectable lidocaine if you:

have Stokes-Adams syndrome or Wolff-Parkinson-White syndrome

have sinoatrial, atrioventricular, or intraventricular block

Xylocard Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of lidocaine. there are no specific foods that you must exclude from your diet when receiving this medication.

Inform MD

Before taking lidocaine. tell your doctor about all of your medical conditions. Especially tell your doctor if you:

are allergic to lidocaine or to any of its ingredients

are allergic to other local anesthetics, including bupivacaine (Marcaine), etidocaine (Duranest), mepivacaine (Carbocaine, Prolocaine), or prilocaine (Citanest)

have Stokes-Adams syndrome or Wolff-Parkinson-White syndrome

have sinoatrial, atrioventricular, or intraventricular block

have or have had liver disease

are having surgery, including dental surgery

are pregnant or breastfeeding

Xylocard and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Lidocaine falls into category B.

There are no well-done studies that have been done in humans with lidocaine. In animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

Xylocard and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if lidocaine crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using lidocaine.

Xylocard Usage

Use lidocaine exactly as prescribed.

This medication comes in several topical forms, including a transdermal patch, ointment, cream, and oral solution. The dose and frequency of use of lidocaine will depend on the condition being treated.

This medication is also available in an injectable form to be given directly into a vein (IV) or for infiltration and nerve block by a healthcare professional.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of lidocaine at the same time.

Xylocard Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The dose and frequency of use of lidocaine will depend on the condition being treated or the procedure you will undergo.

The dose your doctor recommends may be based on the following:

other medical conditions you have

other medications you are taking

how you respond to this medication

Do not use topical forms of lidocaine on broken or blistered skin.

Do not swallow the oral solution of lidocaine. Swish and/or gargle in your mouth and/or throat and spit out the solution.

Xylocard Overdose

If you take too much lidocaine. call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If lidocaine is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

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Diclofenac (Professional Patient Advice), Dyclo

Diclofenac

Trade Names

Cambia - Powder for solution, oral 50 mg (as potassium)

Cataflam - Tablets, oral 50 mg (as potassium)

Diclofenac - Tablets, delayed-release, oral 25 mg (as sodium) - Tablets, delayed-release, oral 50 mg (as sodium)

Flector - Patch, transdermal 180 mg (as epolamine)

Pennsaid - Solution, topical 1.5% (as sodium)

Solaraze - Gel, topical 3% (as sodium)

Voltaren - Gel, topical 1% (as sodium) - Tablets, delayed-release, oral 75 mg (as sodium) - Solution, ophthalmic 0.1% (as sodium)

Voltaren-XR - Tablets, ER, oral 100 mg (as sodium)

Zipsor - Capsules, oral 25 mg (as potassium)

Apo-Diclo (Canada) Apo-Diclo Rapide (Canada) Apo-Diclo SR (Canada) Novo-Difenac (Canada) Novo-Difenac K (Canada) Novo-Difenac SR (Canada) Nu-Diclo (Canada) Nu-Diclo-SR (Canada) PMS-Diclofenac (Canada) PMS-Diclofenac SR (Canada) Sandoz Diclofenac (Canada) Sandoz Diclofenac Rapide (Canada) Sandoz Diclofenac SR (Canada) Voltaren Ophtha (Canada) Voltaren Rapide (Canada)

Pharmacology

Decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis.

Pharmacokinetics

Absorption

Bioavailability is approximately 50% because of first-pass metabolism (oral doseforms). Food decreases T max and C max .

Immediate-release capsules and tablets

T max is approximately 0.5 to 1 h.

T max is approximately 5.3 h.

Delayed-release tablets (50 mg dose)

T max is approximately 2.3 h.

Following a single application of the patch on the upper inner arm, C max of 0.7 to 6 ng/mL was noted between 10 and 20 h of application. With twice-daily application of patch, plasma concentrations ranged from 1.3 to 8.8 ng/mL after 5 days.

Following application of 40 drops 4 times daily for 7 days, mean AUC is 695.4 ng•h/mL, mean C max is 19.4 ng/mL, and mean T max is 4 h.

Following application of 2 g 3 times daily for 6 days, mean AUC is 9 ng•h/mL, mean C max is 4 ng/mL, and mean T max is 4.5 h.

C max with application of 160 mg/day is 15 ng/mL and with application of 480 mg/day is 54 ng/mL. T max is 14 h with the application of 160 mg/day and 10 h with the application of 480 mg/day. The amount reaching the systemic circulation is 158 times lower with 160 mg/day compared with oral treatment.

Distribution

More than 99% protein bound (albumin). Vd is approximately 1.4 L/kg (oral).

Metabolism

Undergoes hepatic metabolism. Five metabolites have been identified.

Elimination

Approximately 65% is excreted in the urine and 35% in the bile as conjugates of unchanged diclofenac plus metabolites. The half-life is 1 to 2 h. Plasma elimination half-life after application of Flector is approximately 12 h.

Special Populations

Renal Function Impairment

No differences in pharmacokinetics have been detected in studies in patients with renal impairment.

Hepatic Function Impairment

Because hepatic metabolism accounts for almost 100% of diclofenac elimination, patients with hepatic disease may require reduced doses.

Pharmacokinetics have not been studied.

Pharmacokinetic differences because of race have not been identified.

Indications and Usage

Acute and long-term use in the relief of signs and symptoms of ankylosing spondylitis (delayed-release tablets); acute treatment of migraine attacks with or without aura in adults (oral solution); relief of mild to moderate pain (immediate-release capsules and tablets); relief of signs and symptoms of osteoarthritis and rheumatoid arthritis (immediate-release, ER, and delayed-release tablets); treatment of primary dysmenorrhea (immediate-release tablets).

Treatment of postoperative inflammation after cataract removal; temporary relief of pain and photophobia following corneal refractive surgery.

Treatment of acute pain because of minor strains, sprains, and contusions.

For the treatment of signs and symptoms of osteoarthritis of the knee(s) only.

Treatment of actinic keratosis.

Treatment of pain of osteoarthritis or joint pain amenable to topical treatment (eg, knees, hands).

Unlabeled Uses

Treatment of juvenile idiopathic arthritis; treatment of postherpetic neuralgia.

Contraindications

Treatment of perioperative pain in the setting of coronary artery bypass graft surgery; patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or another NSAID; hypersensitivity to diclofenac or any component of the product. Do not apply topical patch to nonintact or damaged skin regardless of the cause (eg, burns or wounds, eczema, exudative dermatitis, infected lesion).

Dosage and Administration

Different tablet formulations of diclofenac are not necessarily bioequivalent.

Actinic Keratosis Adults

Solaraze Apply gel to lesions twice daily. The recommended duration of treatment is 60 to 90 days.

Analgesia Adults Immediate-release capsules

PO 25 mg 4 times daily.

PO 50 mg 3 times daily; may give initial dose of 100 mg if needed.

Ankylosing Spondylitis Adults

PO Delayed-release tablets 100 to 125 mg/day administered as 25 mg 4 times daily, with additional 25 mg at bedtime, if necessary.

PO Oral solution 50 mg as a one-time dose.

Minor Strains, Sprains, and Contusions Adults

Topical patch Apply 1 patch to most painful area twice daily.

Osteoarthritis Adults Immediate-release, delayed-release tablets

PO 100 to 150 mg/day in divided doses.

PO 100 mg daily.

40 drops per knee 4 times per day.

Using the dosing card supplied in the product carton, apply up to the 2 or 4 g line (2 g for elbows, wrist, or hand; 4 g for each knee, ankle, or foot). Apply 4 times daily by gently massaging gel into the skin, ensuring application to the entire affected area. Do not apply more than 8 g/day to any single joint of the upper extremities or more than 16 g/day to any single joint of the lower extremities. Do not apply more than 32 g/day over all affected joints.

Primary dysmenorrhea Adults

PO Immediate-release tablets 50 mg 3 times daily; may give initial dose of 100 mg if needed.

Rheumatoid Arthritis Adults Immediate-release, delayed-release tablets

PO 150 to 200 mg/day in divided doses.

PO 100 mg daily. If response is unsatisfactory, the dosage may be increased to 100 mg twice daily.

Ophthalmic Cataract Surgery

1 drop in affected eye 4 times daily beginning 24 h after cataract surgery and continuing during the first 2 wk of postoperative period.

Corneal Refractive Surgery

1 or 2 drops within 1 h prior to corneal refractive surgery; then, within 15 min after surgery, apply 1 or 2 drops to the operative eye and continue 4 times daily for up to 3 days.

General Advice

ER and delayed-release tablets

Advise patient to swallow whole. Do not break, cut, crush, or chew tablet.

Flector

Do not apply to damaged or nonintact skin.

Do not wear when bathing or showering.

Wash hands after applying, handling, or removing the patch.

Avoid contact with eyes.

Ophthalmic solution

For ophthalmic use only.

If using other topical ophthalmic drugs, separate each medication by at least 5 min. Instill ophthalmic ointment last.

Oral solution

Empty contents of 1 packet into a cup with 1 to 2 oz (30 to 60 mL) of water and mix well. The solution should be used immediately. Liquids other than water should not be used.

Administration with food may cause a reduction in effectiveness.

Pennsaid

Apply to clean, dry skin. Avoid showering or bathing for at least 30 min after application. Wash and dry hands after use.

Do not apply to open wounds. Avoid contact with eyes and mucous membranes.

Do not apply external heat and/or occlusive dressings to treated knees. Avoid wearing clothing over the treated knees or applying sunscreen, insect repellant, lotion, moisturizer, cosmetics, or other topical medications until the area is dry.

Protect the treated area from sunlight.

Solaraze

For dermatological use only.

Using gloves, gently smooth onto affected skin. Apply gel to adequately cover each lesion. Do not apply to open skin wounds, infections, or exfoliative dermatitis.

Avoid contact with the eyes, mouth, and other mucous membranes.

The safety of the concomitant use of sunscreens, cosmetics, or other topical medications is unknown.

Voltaren topical gel

Do not apply to open wounds.

Avoid contact with eyes and mucous membranes.

Do not apply heat or occlusive dressing to treated joint.

Avoid exposure of treated joint to sunlight.

Do not use sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medications on the same site.

Avoid wearing clothing or gloves for at least 10 min after application.

Avoid showering for at least 1 h after application.

If used on the hand(s) for treatment, do not wash the treated hand(s) for at least 1 h after the application.

Storage/Stability

Immediate-release, delayed-release, and ER tablets

Do not store at temperatures higher than 86°F. Protect from moisture.

Immediate-release capsules, oral solution

Store between 59° and 86°F. Protect capsules from moisture.

Store between 59° and 77°F. Protect from light.

Store between 59° and 86°F.

Pennsaid. Solaraze. and Voltaren gel

Store between 59° and 86°F. Do not freeze. Protect from heat.

Drug Interactions

Antihypertensive effect of ACE inhibitors may be diminished. In addition, the risk of nephrotoxicity associated with ACE inhibitors or diclofenac may be increased. Closely monitor BP. If BP control decreases, it may be necessary to discontinue diclofenac. Periodic measurement of renal function may be necessary.

The risk of GI bleeding may be increased. Use with caution.

Aminoglycosides (eg, gentamicin)

Aminoglycoside concentrations may be elevated, increasing the risk of adverse reactions (eg, acute renal insufficiency). If coadministration cannot be avoided, reduce the aminoglycoside dose before starting diclofenac. Monitor renal function and aminoglycoside serum concentrations and adjust the dose as needed.

Antiplatelet agents (eg, clopidogrel)

The risk of bleeding may be increased. Use with caution. Closely monitor for signs of bleeding.

Protein binding of diclofenac may be reduced; in addition, the risk of gastric erosion and bleeding may be increased. The clinical importance of this interaction is not known; however, as with other NSAIDs, coadministration is not generally recommended because of the potential of increased adverse effects.

Azole antifungal agents (eg, fluconazole)

Diclofenac plasma concentrations may be elevated, increasing the risk of adverse reactions. Observe the clinical response of the patient and adjust the diclofenac dose as needed.

Corticosteroids (eg, prednisone)

The risk of GI bleeding may be increased. Use with caution. Advise patients about the signs and symptoms of GI bleeding.

The nephrotoxicity of both agents may be increased. Use with caution and closely monitor for nephrotoxicity.

Food Diclofenac potassium

The extent of diclofenac potassium absorption is not affected when diclofenac potassium is taken with food; however, the rate of absorption is reduced by food, as indicated by a delay in onset and a decrease in C max .

Food has no effect on the extent of diclofenac absorption; however, there usually is a 1- to 4.5-hour delay in the onset of absorption and a reduction in C max of less than 20%.

High-fat food had no effect on the extent of diclofenac potassium absorption; however, there was a reduction in C max of approximately 70% after a high-fat meal. Decreased C max may be associated with decreased effectiveness. Taking diclofenac potassium oral solution with food may cause a reduction in effectiveness compared with taking it on an empty stomach.

Furosemide, thiazide diuretics

May inhibit diuretic and antihypertensive effects. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, closely observe the patient for signs of renal failure, as well as to ensure diuretic efficacy.

Risk of hemorrhagic adverse reactions may be increased. Closely monitor coagulation status and adjust the heparin dosage accordingly.

Hepatotoxic agents (eg, acetaminophen, certain antibiotics [eg, aminoglycosides (eg, gentamicin)], antiepileptic agents)

The risk of hepatotoxicity may be increased. Use with caution. Closely monitor for signs and symptoms of hepatotoxicity.

Diclofenac urinary excretion may be reduced, increasing diclofenac concentrations and risk of adverse reactions. Patients taking diclofenac should avoid beverages made from Hibiscus sabdariffa flowers.

May decrease lithium Cl, increasing lithium concentrations and risk of toxicity. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Closely monitor for signs of lithium toxicity.

May increase methotrexate levels. Use with caution.

Quinolones (eg, levofloxacin)

Risk of CNS stimulation and seizures from quinolones may be increased. In addition, quinolone plasma concentrations may be increased. Use with caution.

Serotonin norepinephrine reuptake inhibitors (eg, venlafaxine), SSRIs (eg, fluoxetine)

Risk of upper GI bleeding may be increased. Use with caution. Closely monitor for signs of GI bleeding. Advise patients about the signs and symptoms of GI bleeding.

The risk of GI bleeding may be increased. Use with caution.

Pharmacologic and toxic effects (eg, nephrotoxicity) of tenofovir may be increased. Use with caution. Consider use of an analgesic other than an NSAID.

Coadministration of diclofenac and triamterene may cause a sudden onset of nephrotoxicity. If renal function deteriorates during coadministration of these agents, consider stopping one or both drugs.

May increase risk of gastric erosion and bleeding. Closely monitor coagulation status and adjust the warfarin dosage accordingly. Monitor for signs of GI bleeding. Advise patients about the signs and symptoms of GI bleeding.

Adverse Reactions

Cardiovascular

Arrhythmia, CHF, hypertension, hypotension, MI, syncope, tachycardia.

CNS

Dizziness, headache (1% to 10%); somnolence (3%); coma, hallucinations, meningitis.

Dizziness, headache, insomnia (3% or less).

Headache (7%); asthenia, hypokinesia (2%); migraine (1%).

Dermatologic

Pruritus, rash (1% to 10%); increased sweating (1%); angioedema, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, TEN.

Application-site dryness, atrophy, discoloration, erythema, hyperhidrosis, irritation, vesicles (4%); dermatitis (2%).

Rash (3%); dry skin, ecchymosis, pruritus (2%).

Pruritus, rash (4%); dry skin (3%); contact dermatitis, skin ulcer (2%); pain (1%).

EENT

Lacrimation complaints (30%); keratitis (28%); elevated IOP, transient ocular burning and stinging (15%); abnormal vision, acute elevated IOP, blurred vision, conjunctivitis, corneal deposits, corneal edema, corneal lesions, corneal opacity, discharge, eyelid swelling, injection, iritis, irritation, itching, lacrimation disorder, ocular allergy, redness (5% or less); rhinitis (3% or less); corneal erosion, corneal infiltrates, corneal perforation, corneal thinning, corneal ulceration, epithelial breakdown, superficial punctuate keratitis (postmarketing).

Tinnitus (1% to 10%).

Conjunctivitis (4%); eye pain (2%).

GI

Abdominal pain, nausea, vomiting (3% or less).

Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, GI ulcers (gastric/duodenal), gross bleeding/perforation, heartburn, nausea, vomiting (1% to 10%); hematemesis, hepatitis, jaundice.

Nausea, constipation, diarrhea, dry mouth, gastritis, upper abdominal pain, vomiting (3%); dysgeusia (2%).

Dyspepsia (8%); abdominal pain (6%); diarrhea, flatulence, nausea (4%); constipation (3%).

Abdominal pain, diarrhea, dyspepsia (2%).

Genitourinary

Interstitial nephritis, renal failure.

Hematologic-Lymphatic

Anemia, increased bleeding time (1% to 10%); agranulocytosis, aplastic anemia, hemolytic anemia, lymphadenopathy, pancytopenia, thrombocytopenia.

Hepatic

Elevated liver enzymes (1% to 10%); liver failure.

Local

Dry skin (32%); contact dermatitis (9%); pruritus (4%); contact dermatitis with vesicles (2%).

Application-site reaction (84%); pruritus (52%); rash (46%); contact dermatitis (33%); pain (30%); dry skin (27%); exfoliation (24%); paresthesia (20%); edema, vesiculobullous rash (4%); hyperesthesia, photosensitivity reaction (3%); alopecia (2%); acne (1%).

Application-site reaction (7%); application-site dermatitis (4%).

Metabolic-Nutritional

Increased CPK (4%); increased AST (3%); increased ALT (2%); hypercholesterolemia, hyperglycemia (1%).

Musculoskeletal

Back pain (4%); myalgia (3%); arthralgia, arthrosis, neck pain (2%).

Renal

Abnormal renal function (1% to 10%).

Precautions

Warnings

NSAIDs may cause an increased risk of serious CV thrombotic events, MI, and stroke, which can be fatal. This risk may increase with length of therapy. Patients with CV disease or risk factors for CV disease may be at greater risk. Diclofenac is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft surgery.

NSAIDs cause an increased risk of serious GI adverse reactions, including bleeding, inflammation, perforation of the stomach or intestines, and ulceration, which can be fatal. These events can occur any time during use and without warning symptoms. Elderly patients are at greater risk of serious GI events.

Monitor

Monitor for signs and symptoms of GI bleeding. Closely monitor BP during initiation of treatment and throughout the course of therapy. Carefully monitor patients who may be adversely affected by alterations in platelet function (eg, patients with coagulation disorders, patients receiving anticoagulant therapy). Obtain baseline assessments of pain and ability to perform activities of daily living. Ensure CBC, serum electrolytes, and serum transaminases are evaluated periodically during prolonged therapy. Monitor patient for signs and symptoms of hepatic function impairment. If noted, discontinue therapy immediately. Note dark, tarry stools; epigastric pain; indigestion; or unusual bleeding or bruising. If used in patients with advanced renal disease, monitor renal function. Monitor refractive stability for 1 year following corneal refractive procedures in patients treated with the ophthalmic solution.

Check hemoglobin or hematocrit in patients on long-term treatment if they exhibit signs or symptoms of anemia.

Pregnancy

Category C (immediate-release capsules and tablets, ER tablets, oral solution, ophthalmic solution, topical patch, delayed-release tablets, Pennsaid. Voltaren gel). Category B ( Solaraze topical gel). Can cause premature closure of the ductus arteriosus; avoid in late pregnancy.

Lactation

Children



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Retrovir (Zidovudine) Side Effects, Interactions, Warning, Dosage & Uses, Retrovir-Azt

RISK OF HEMATOLOGICAL TOXICITY, MYOPATHY, LACTIC ACIDOSIS

Hematologic Toxicity

RETROVIR® (zidovudine) tablets, capsules, syrup, and injection have been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV-1 disease [see WARNINGS AND PRECAUTIONS ].

Myopathy

Prolonged use of RETROVIR has been associated with symptomatic myopathy [see WARNINGS AND PRECAUTIONS ].

Lactic Acidosis and Severe Hepatomegaly

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including RETROVIR and other antiretrovirals. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see WARNINGS AND PRECAUTIONS ].

DRUG DESCRIPTION

RETROVIR is the brand name for zidovudine (formerly called azidothymidine [AZT ]), a pyrimidine nucleoside analogue active against HIV -1. The chemical name of zidovudine is 3'-azido-3'-deoxythymidine; it has the following structural formula:

Zidovudine is a white to beige, odorless, crystalline solid with a molecular weight of 267.24 and a solubility of 20.1 mg per mL in water at 25°C. The molecular formula is C 10 H 13 N 5 O 4 .

RETROVIR tablets are for oral administration. Each film-coated tablet contains 300 mg of zidovudine and the inactive ingredients hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, and titanium dioxide.

RETROVIR capsules are for oral administration. Each capsule contains 100 mg of zidovudine and the inactive ingredients corn starch, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The 100-mg empty hard gelatin capsule, printed with edible black ink, consists of black iron oxide, dimethylpolysiloxane, gelatin, pharmaceutical shellac, soya lecithin, and titanium dioxide.

RETROVIR syrup is for oral administration. Each mL of RETROVIR syrup contains 10 mg of zidovudine and the inactive ingredients sodium benzoate 0.2% (added as a preservative), citric acid, flavors, glycerin, and liquid sucrose. Sodium hydroxide may be added to adjust pH.

RETROVIR injection is a sterile solution for IV infusion only. Each mL contains 10 mg zidovudine in water for injection. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH to approximately 5.5. RETROVIR injection contains no preservatives. The vial stoppers for RETROVIR injection contain natural rubber latex.

What are the possible side effects of zidovudine (Retrovir)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

This medication may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or.

What are the precautions when taking zidovudine (Retrovir)?

Before taking zidovudine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, liver problems (such as hepatitis B or C, cirrhosis), alcohol use, low red/white blood cells.

Liquid products may contain sugar. Caution is advised if you have diabetes or any other condition that requires you to limit sugar in your diet. Ask your doctor or pharmacist about using this product safely.

Before having surgery, tell your doctors or dentist about all the products you use (including.

Last reviewed on RxList: 1/20/2015 This monograph has been modified to include the generic and brand name in many instances.



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Galantamine Oral Uses, Side Effects, Interactions, Pictures, Warnings - Dosing, Galantamin

galantamine

Uses

Galantamine is used to treat mild to moderate confusion (dementia ) related to Alzheimer's disease. It does not cure Alzheimer's disease. but it may improve memory, awareness, and the ability to perform daily functions. This medication works by restoring the balance of certain natural substances (neurotransmitters) in the brain .

How to use galantamine

Take this medication by mouth with food, usually twice daily with the morning and evening meals, or as directed by your doctor. Drink plenty of fluids with this medication unless instructed otherwise. To lower your risk of side effects, your dosage will be gradually increased to your target dose. Your dosage is based on your medical condition and response to therapy. Do not take more than the maximum recommended dose of 24 milligrams per day.

If you are using the liquid form of this drug, read the manufacturer's instruction sheet that comes with the bottle. Follow the directions exactly. Use the measuring device that comes with the product to measure out your dose. Mix your dose of medication in about 4 ounces (120 milliliters) of nonalcoholic beverage, stir, and drink the entire mixture. Ask your pharmacist about any information that is unclear.

If you stop taking galantamine for longer than 3 days, your doctor may direct you to restart this medication at a low dose and gradually increase your dose to reduce your risk of side effects. Carefully follow your doctor's instructions.

Use this medication regularly in order to get the most benefit from it. Do not stop taking it or increase the dosage unless your doctor instructs you to do so.

It may take at least 4 weeks of continued use before the full benefit of this drug takes effect.

Inform your doctor if your condition worsens.

Side Effects

Nausea. vomiting. diarrhea. dizziness. drowsiness, loss of appetite, and weight loss may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: fainting. unusually slow heartbeat, difficult urination.

Get medical help right away if you have any very serious side effects, including: seizures. black/bloody stools, vomit that looks bloody or like coffee grounds, severe stomach /abdominal pain. irregular heartbeat .

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction. including: rash. itching /swelling (especially of the face/tongue /throat), severe dizziness, trouble breathing .

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www. fda. gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking galantamine, tell your doctor or pharmacist if you are allergic to it; or to daffodil plants; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe liver disease, severe kidney disease .

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems, kidney problems, stomach /intestinal problems (e. g. ulcers, bleeding), heart problems (e. g. sick sinus syndrome. bradycardia. AV block, arrhythmias), breathing/lung problems (e. g. severe asthma. COPD - chronic obstructive pulmonary disease ), seizures, problems urinating (e. g. due to enlarged prostate ).

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Before having surgery, tell your doctor or dentist that you are taking this medication.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is unknown if this drug passes into breast milk. Consult your doctor before breast - feeding.

Interactions

Your healthcare professionals (e. g. doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anticholinergic drugs (e. g. atropine, diphenhydramine. scopolamine, tolterodine), aspirin (high doses used for arthritis), cholinergic drugs (e. g. bethanechol), cholinesterase inhibitors (e. g. neostigmine), long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, naproxen), drugs affecting liver enzymes that remove galantamine from your body (such as azole antifungals including ketoconazole. amitriptyline. SSRI antidepressants including paroxetine, quinidine ).

Also report the use of heart drugs (those that decrease heart rate or block AV impulse conduction) such as: beta-blockers (e. g. metoprolol, propranolol), calcium channel blockers (e. g. diltiazem, verapamil), digoxin.

Check all prescription and nonprescription medicine labels carefully since many medications contain pain relievers/fever reducers (NSAIDs such as aspirin, ibuprofen, or naproxen) which, if taken together with galantamine, may increase your risk for stomach/intestinal bleeding. Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day), should be continued. Consult your doctor or pharmacist for more details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

Overdose

If overdose is suspected, contact a poison control center or emergency room right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include muscle weakness or twitching, severe stomach cramping, slow or shallow breathing, slow/fast/irregular heartbeat, fainting, and seizures.

Notes

Do not share this medication with others.

Since galantamine may cause loss of appetite and weight loss, your doctor should monitor your weight before and during treatment with this medication.

Missed Dose

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Storage

Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised October 2015. Copyright(c) 2015 First Databank, Inc.

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Celius, Celius

Celius

Fantasy Grade 6, Herbert Fadeley Collection

Celius started around 1959/60 at Suhr's Pibemageri in Copenhagen, where he learned the craft of pipemaking from Poul Rasmussen (†), but presumeably even more from Sven Knudsen. Rasmussen's foreman. Young Celius was obviously a bright boy being one of the very first Danes who sensed the beginning boom for Danish fancy pipes looming first of all in the huge US market. And so he went off for self-employment founding a pipe manufacture in the former dairy building of Bogo By on the small island Bogo in 1963.

So he definitely improved the shining hour, because he was one of the first, who was able to supply these innovative Danish freehands in considerable large numbers to the States. Smaller quantities went to Germany. Here however he didn't become as famous as in the USA, where especially his better pieces gained cult status. In other respects Celius' business developed well, too. For instance he was contracted by W. O. Larsen of Copenhagen to supply pipes as Hans Jonny Nielsen (> Former ), at that time master of Larsen's workshop, confirmed. Anyhow, in it's best times Celius’ manufacture employed close to 20 co-workers.

But all the same, Celius wasn't able to make this periodically big success an enduring success. If this depended on mercantilistic deficiencies or if the often claimed minor quality of the bulk of his pipes caused the decline, will presumeably remain an unanswered question. As well it mustn't be disregarded that there were mighty - if not superior - concurrents in the field of mainly machine-made semi-freehands like the manufactures of Erik Nording. Karl Erik (†), Preben Holm (†), Soren and others more. Celius moved away from Bogo around 1970 and sold his shop and the Celius name to a man named Randsborg who continued with the business until 1975-76, when he closed the shop. Durring this period some of the Celius pipes were also stamped "Randsborg" .

Courtesy, Stig Andersen . These these pipes have no stamps but the bottom right pipe was made for him by his father, Henning, and is not a Celius model. The finish of the pipe in the upper left and was made with a drill and then sandblasted, the same finish as the Grade 2 Fantasy pipe in the gallery bellow

CELIUS KING 17 a shape one sees in other CELIUS pipes in the chess series, Courtesy David Cuneo

CELIUS KING 17, Courtesy David Cuneo

Shortly after Randsorg closed the shop, Celius returned to see if he could make another go of it. One of Celius's original employees was a pipemaker by the name of Henning Andersen who worked part time with Celius during his second run in the business. Andersen's son, Stig related an account that his father helped with the Celius pipes as well as a small production of handmade pipes for Stanwell. Anderson also worked along side Celius from the beginning on Bogo and later for Randsborg, making many of the fantasy pipes and other handmades. Many thanks to Stig for his help with this information.

The second period was characterized by many ups and downs, and his success remained inconstant and changeable. He never managed to match the top quality of his teacher Rasmussen or the students of Rasmussen's workshop like Sven Knudsen, Former Nielsen or Tom Eltang. Svend Axel Celius moved to Fyn in the late 1980's and lived there until his death around 1999/2000

Essentially three lines of Celius pipes can be described:

Fantasy line: these are those well-known "wild to slightly crazy" shaped fancy freehands. Predominantly stamped "Fantasy" . there are however also pipes Celius stamped "Fancy" . Today it is sheerly impossible to decide whether "Fantasy" and "Fancy" were temporarily made in coexistence, or whether the "Fancy" functioned more or less as a successor of the "Fantasy" in one of Celius' new starts. "Fantasy" and "Fancy" both have a grading by number from 1 - 6 (although 5 is unconfirmed). Chip Fadeley, who has owned a grade 2 and 6 has recently acquired a grade 1. Chip reports the following: " I own a Celius Fantasy stamped #6. I also own another which is a rusticated sitter, and it's stamped #2. I've not met anyone who has heard of or seen a Celius rusticated pipe. The #6 is a smooth pipe with nothing fancy about the straight grain, and plateau briar top and partial on the shank's end. The shape is somewhat unusual because it has a long pointed front; and it has two separate flat spots on one side to perfectly accommodate the pairs of fingers made next to the index finger and pinky finger of a right-handed person. The stamping Celius Fantasy Denmark appear exactly the same in slant and font style and height on both pipes. The #6 appears to have a rounded bottom when viewing it from the front and back; however, it appears pointed on either side. The index and ring finger can also be used singly with the thumb overtop the shank depending on how you want to hold this pipe.

Zenia line: pipes in classical forms. They are named for his daughter Zenia, Celius delivered this line for a limited time only.

Chess line: the most important group of Celius pipes. The grading of these typical Danish freehands is borrowed from the chess pieces: Pawn (sand-blasted), Rook, Knight, Bishop, Queen to King. Pipes, where the natural bark of the briar was left at the rim of the bowl, were called and additionally stamped "Root". Furthermore these pipes had numbers from 1 to 31 (as far as known today). The numbers, we can take that for certain, denominate the shape. But please note that they surely have not the same binding character as the shape numbers of other manufacturers-- they rather stand for a basic form, that was modified often.

Remaining a mystery is why some Queen pipes are stamped with additional capital letters and why other (= few) pipes of the Chess line are stamped with "by hand".

Result: The quality of Celius' pipes is widely disputed. Lovers of the typical Danish Fancy pipes will however enjoy Celius' shapes - many of them later appeared again elsewhere. In the Chess line, that is also credited with very independent forms, one may find pipes of partly excellent wood quality from the Knight grade upwards. What tempers delight is the fact that many nice Celius pipe is only good but surely far away from excellent concerning the overall craftsmanship.

Celius Fantasy Pipes, Courtesy Herbert Fadeley Collection

Fantasy Grade 1



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Elocon Cream Uses, Side Effects - Warnings, Ecural

Elocon

What is Elocon?

Elocon (mometasone) is a topical steroid. It reduces the actions of chemicals in the body that cause inflammation.

Elocon is used to treat the inflammation and itching caused by a number of skin conditions such as allergic reactions, eczema. and psoriasis .

Elocon may also be used for other purposes not listed in this medication guide.

Important information

Use Elocon exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger amounts or for longer than recommended. Topical steroid medicine can be absorbed through the skin, which may cause steroid side effects throughout the body.

Do not cover treated skin areas with a bandage or other covering unless your doctor has told you to. If you are treating the diaper area of a baby, do not use plastic pants or tight-fitting diapers. Covering the skin that is treated with Elocon can increase the amount of medicine your skin absorbs, which may lead to unwanted side effects. Follow your doctor's instructions. Do not use Elocon on a child without a doctor's advice. Children are more likely to absorb large amounts of a topical steroid through the skin. Steroid absorption in children may cause unwanted side effects, or a delay in growth with long-term use. Talk with your doctor if you think your child is not growing at a normal rate while using Elocon over a long treatment period. Contact your doctor if your condition does not improve within 2 weeks of using this medicine, or if you develop signs of a bacterial, fungal, or viral skin infection.

Before taking this medicine

You should not use Elocon if you are allergic to mometasone.

Do not use Elocon to treat diaper rash.

To make sure Elocon is safe for you, tell your doctor if you have:

any type of skin infection.

Also tell your doctor if you have diabetes. Topical steroid medicines absorbed through the skin may increase the glucose (sugar) levels in your blood or urine.

FDA pregnancy category C. It is not known whether Elocon will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether mometasone topical passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not use this medicine on any child without a doctor's advice. Children can absorb larger amounts of this medication through the skin and may be more likely to have side effects.

How should I use Elocon?

Use Elocon exactly as directed on the label, or as it has been prescribed by your doctor. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Wash your hands before and after using Elocon, unless you are using the medicine to treat the skin on your hands.

Apply a small amount to the affected area and rub it gently into the skin. Do not apply Elocon over a large area of skin.

Do not cover the treated skin area unless your doctor tells you to.

Call your doctor if your symptoms do not improve after 2 weeks of treatment, or if they get worse while using Elocon.

If you use this medicine long-term, you may need frequent medical tests at your doctor's office.

Store at room temperature away from moisture and heat. Keep from freezing.

Elocon dosing information

Usual Adult Dose for Dermatitis:

Apply a thin layer to the affected area once a day.

Usual Adult Dose for Eczema:

Apply a thin layer to the affected area once a day.

Usual Adult Dose for Psoriasis:

Apply a thin layer to the affected area once a day.

Usual Pediatric Dose for Dermatitis:

Cream and ointment: 2 years or older: Apply a thin layer to the affected area once a day. Elocon should not be applied in the diaper areas if the child still requires diapers or plastic pants.

Lotion: 12 years or older: Apply a thin layer to the affected area once a day.

Safety and efficacy of Elocon in pediatric patients for more than 3 weeks of use have not established.

What happens if I miss a dose?

Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and use the medicine at the next regularly scheduled time. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of Elocon is not expected to produce life threatening symptoms. However, long term use of high steroid doses can lead to symptoms such as thinning skin, easy bruising, changes in the shape or location of body fat (especially in your face, neck, back, and waist), increased acne or facial hair, menstrual problems, impotence, or loss of interest in sex.

What should I avoid while using Elocon?

Avoid getting this medication in your eyes. If contact does occur, rinse with water. Do not use Elocon on broken or infected skin. Also avoid using this medication in open wounds.

Avoid applying Elocon to the skin of your face, underarms, or groin area without your doctor's instruction.

Do not use Elocon to treat any condition that has not been checked by your doctor.

Elocon side effects

Get emergency medical help if you have any of these signs of an allergic reaction to Elocon: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Topical steroid medicine can be absorbed through the skin, which may cause steroid side effects throughout the body. Stop using Elocon and call your doctor if you have:

blurred vision, or seeing halos around lights;

sleep problems (insomnia);

weight gain, puffiness in your face; or



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Melogen An Est Database For Melon Functional Genomics, Melogen

MELOGEN: an EST database for melon functional genomics

Abstract

Background

Melon ( Cucumis melo L.) is one of the most important fleshy fruits for fresh consumption. Despite this, few genomic resources exist for this species. To facilitate the discovery of genes involved in essential traits, such as fruit development, fruit maturation and disease resistance, and to speed up the process of breeding new and better adapted melon varieties, we have produced a large collection of expressed sequence tags (ESTs) from eight normalized cDNA libraries from different tissues in different physiological conditions.

Results

We determined over 30,000 ESTs that were clustered into 16,637 non-redundant sequences or unigenes, comprising 6,023 tentative consensus sequences (contigs) and 10,614 unclustered sequences (singletons). Many potential molecular markers were identified in the melon dataset: 1,052 potential simple sequence repeats (SSRs) and 356 single nucleotide polymorphisms (SNPs) were found. Sixty-nine percent of the melon unigenes showed a significant similarity with proteins in databases. Functional classification of the unigenes was carried out following the Gene Ontology scheme. In total, 9,402 unigenes were mapped to one or more ontology. Remarkably, the distributions of melon and Arabidopsis unigenes followed similar tendencies, suggesting that the melon dataset is representative of the whole melon transcriptome. Bioinformatic analyses primarily focused on potential precursors of melon micro RNAs (miRNAs) in the melon dataset, but many other genes potentially controlling disease resistance and fruit quality traits were also identified. Patterns of transcript accumulation were characterised by Real-Time-qPCR for 20 of these genes.

Conclusion

The collection of ESTs characterised here represents a substantial increase on the genetic information available for melon. A database (MELOGEN) which contains all EST sequences, contig images and several tools for analysis and data mining has been created. This set of sequences constitutes also the basis for an oligo-based microarray for melon that is being used in experiments to further analyse the melon transcriptome.

Background

Melon ( Cucumis melo L.) is an important horticultural crop grown in temperate, subtropical and tropical regions worldwide. Melon is among the most important fleshy fruits for fresh consumption, its total production in 2004 exceeding 874 million metric tons, of which 72.5% are produced in Asia, 11.7% in Europe, 8.4% in America and 6.1% in Africa, being a significant component of fresh fruit traded internationally [ 1 ]. Melon belongs to the Cucurbitaceae family, which comprises up to 750 different species distributed in 90 genera. Species in this family include watermelon, cucumber, squash and marrow, all of them cultivated essentially because of their fruits, but this family also includes species of interest for other reasons, as, for example, their contents in potentially therapeutic compounds (e. g. Momordica charantia ) [ 2 ]. Melon is a diploid species, with a basic number of chromosomes x = 12 (2x = 2n = 24) and an estimated genome size of 450 to 500 Mb [ 3 ], similar in size to the rice genome (419 Mb) [ 4. 5 ] and about three times the size of the Arabidopsis genome (125 Mb) [ 6 ]. Melon has been classified into two subspecies, C. melo ssp. agrestis and C. melo ssp. melo with India and Africa being their centres of origin, respectively [ 7. 8 ].

Melon has a great potential for becoming a model for understanding important traits in fruiting crops. Melon fruits have wide morphological, physiological and biochemical diversity [ 7. 9 ] which can be exploited to dissect biological processes of great technological importance, among them flavour development and textural changes that occur during fruit ripening. The contemporary melon cultivars can be divided into two groups, climacteric and nonclimacteric, according to their ripening patterns [ 10 ]. Climacteric fruits are characterized by rapid and profound changes during ripening associated to increased levels of respiration and release of ethylene, whereas the nonclimacteric varieties do not produce ethylene and have long shelf-life. Analyses of climacteric and nonclimacteric melons have illustrated the process of aroma formation [ 11 – 14 ] and the temporal sequence of cell wall disassembly [ 15 – 17 ]. Melon can be also a very useful experimental system to analyse other aspects of fundamental plant biology. For example, melon and other cucurbits have been used to analyse the development of the plant vasculature and the transportation of macromolecules through it [ 18 – 20 ], and different interactions between melon and pests and pathogens have been characterised with varying depths [ 21 – 27 ].

Important genetic tools have been described for melon, as for example linkage genetic maps [ 28. 29 ] and the development of a genomic library of near isogenic lines (NILs) from an exotic accession [ 30 ]; also, biotechnology is feasible in melon [ 31 – 33 ]. However, the great majority of genes involved in the aforementioned traits are yet to be identified in melon. Partial sequencing of cDNA inserts of expressed sequence tags (ESTs) have been used as an effective method for gene discovery. By sequencing clones derived from RNA from different sources, and/or by normalizing cDNA libraries, the total set of genes sampled can be maximized. Bioinformatic analysis, annotation and clustering of sequences could yield databases which mining can be used to select candidate genes implicated in traits of interest. EST collections can also serve to construct microarrays useful for identifying sets of plant genes expressed during different developmental stages and/or responding to environmental stimuli [ 34. 35 ]. In addition, EST collections are good sources of simple sequence repeats (SSRs) and single-nucleotide polymorphisms (SNPs) that can be used for creating saturated genetic maps [ 36. 37 ]. Thus, EST collections have been generated for many plant species, being the most comprehensive those of Arabidopsis[ 6 ] and rice [ 38 ]. Fruit crops have been less extensively surveyed, but important collections are publicly available for several species, including tomato [ 39 ], apple [ 40 ], grape [ 41 ] and citrus [ 42 ].

Despite the importance of the family Cucurbitaceae . relatively little EST information is currently available: only 16,039 nucleotide sequences have been annotated from the whole Cucurbitaceae family in the publicly accessible GenBank database as of November 2006; out of these, 12,180 correspond to the Cucumis genus and 6,061 to melon. These numbers are in sharp contrast with the data available for families composed of other important food crops like Solanaceae (1,020,102 sequences), Fabaceae (1,466,518 sequences), Brassicaceae (1,010,148 sequences excluding Arabidopsis), Vitaceae (449,478) and Rosaceae (390,066 sequences). Here we describe a public EST sequencing project in melon. We report the determination and analysis of 30,675 high-quality melon ESTs, sequenced from eight normalized cDNA libraries corresponding to different tissues in different physiological conditions. We have classified the sequences into functional categories and described SSRs and SNPs of potential use in genetic maps and marker-assisted breeding programs. A database which contains all EST sequences, contig images and several tools for analysis and data mining has been created. In addition, we have analyzed the EST melon dataset to identify candidate genes potentially coding microRNAs or involved in fruit maturation processes and pathogen defence. The pattern of transcript accumulation in different physiological conditions has been characterised by Real-Time-qPCR for 20 of these candidate genes.

Results

EST Sequencing and Clustering

Eight cDNA libraries were constructed using material from "Piel de Sapo" Spanish cultivars, the C-35 cantaloupe line (both belonging to Cucumis melo L. ssp. melo ) and the accession pat81 of C. melo L. ssp. agrestis (Naud.) Pangalo. The sources of RNA to construct each library were fruits of 15 and 46 days after pollination (dap), leaves, photosynthetic cotyledons inoculated with Cucumber mosaic virus (CMV), healthy roots and Monosporascus cannonballus Pollack et Uecker (the causal agent of melon vine decline) infected roots (Table 1 ). Approximately 3,700 sequences were determined from each library by single-pass 5' sequencing, except for the library prepared from CMV infected cotyledons for which approximately 6,600 sequences were determined, yielding a total of 33,292 raw sequences. Processing to eliminate vector sequences, low quality chromatograms and sequences of less than 100 base pairs (bp) gave rise to 29,604 good quality expressed sequence tags (ESTs) (Table 2 ) implying a cloning success of approximately 89%. The average edited length was 674 bp, and only a 6.4% of the sequences had less than 350 bp.

Description of cDNA libraries

Clustering of the sequences using default parameters of the EST analysis pipeline EST2uni [ 43 ] yielded 6,023 tentative consensus sequences (also called contigs) and 10,614 unclustered sequences (also called singletons), with a total of 16,637 non-redundant sequences or unigenes (Table 2 ). All good quality ESTs were used for clustering, independently of the melon genotype of origin, because single nucleotide polymorphisms (SNPs) were expected among genotypes. The number of ESTs per unigene was between 1 and 44 (1 case), with an average of 1.8 ESTs per contig, as a high proportion of contigs (4,886 out of 6,023) contained less than 5 ESTs and contigs with more than 8 ESTs were scarce (Fig. 1A ). Therefore, redundancy values were notably low (around 16%). The unigene length varied between 101 bp and 2,664 bp, averaging 751 bp (Fig. 1B ). Library specific unigenes were about one third of the total for each library (Table 2 ). A second round of clustering yielded 14,480 unigene clusters, referred to as superunigenes. A web integrated database that contains all EST sequences, contig images and several tools for analysis and data mining has been created and named MELOGEN [ 44 ]. Codon usage was estimated using this EST collection. As expected, the codon usage of melon was very similar to that of Arabidopsis and other dicots. The preferred stop codon was UGA occurring in the 48% of the sequences. Suppression of the CG dinucleotide in the last two codon positions is very frequent in dicots, possibly as a consequence of methylation of C in the CG dinucleotide, resulting in an increased mutation rate [ 45 ]; in agreement with these data, the ratio XCG/XCC for melon was 0.52, very similar to the corresponding figure for tomato (0.58), pea (0.51), potato (0.48) and other dicots [ 45 ].

Unigenes statistics . (A) Distribution of melon ESTs among unigenes (contigs and singletons). (B) Size distribution of melon unigenes.

Libraries obtained from tissues inoculated with M. cannonballus were expected to contain sequences from the fungus. To estimate the proportion of sequences of fungal origin in these libraries, BLAST analyses against a database with plant and fungal sequences were carried out [ 46 ]. Only 56 sequences from these libraries were found to have a more significant similarity with fungal sequences than with plant sequences (Table 3 ). Consequently, these sequences were considered of fungal origin [ 46 ].

ESTs showing significant similarity with fungal sequences

SSRs and SNPs

We have analysed the nature and frequency of microsatellites or simple sequence repeats (SSRs) in the melon sequence dataset. A search for repeats of two, three or four nucleotides in the dataset yielded 1,052 potential SSRs. Approximately, 6% of the unigenes contained at least one of the considered SSRs motifs, with repeats of three nucleotides being prevalent (Table 4 ). The maximum and minimum lengths of the repeats were 68 and 17 nucleotides, respectively, and the average length was 26 nucleotides. The most common repeat among dinucleotides was, by far, the AG repeat, constituting the 83% (Table 4 ). Repeats of AT and AC dinucleotides followed, with approximately 9% and 7%, respectively. Among the trinucleotide repeats, the most frequent was AAG (66%, Table 4 ), and the least frequent was ACT (0.6%, Table 4 ). Among tetranucleotide repeats, the most frequent was AAAG (51%, Table 4 ). A high proportion of SSRs (29.5%) were found in open reading frames (ORFs), though an analysis of the localization of di-, tri - and tetranucleotides separately showed that di - and tetranucleotides localised preferentially in untranslated regions (UTRs), whereas trinucleotides localised in both, UTRs and ORFs (Table 5 ).

Simple sequence repeats (SSRs) statistics*

Number of di-pSSR

Number of tri-pSSR

Number of tetra-pSSR

*The number of di-, tri - and tetranucleotide repeats identified in the melon database is shown for the complete set of putative SSRs (pSSRs).

Localization of simple sequence repeats (SSRs) with respect to putative initiation and termination codons in the melon sequence dataset*

All SSRs analyzed

*Only full length melon unigenes were used for this analysis. Full length unigenes were automatically selected by checking the presence of the start codon by comparison of the 5'-terminal region of the unigene with the corresponding Arabidopsis gene used for annotation. † Imprecise localization of the SSR with respect to putative initiation or termination codons.

Single nucleotide polymorphisms (SNPs) are the most abundant variations in genomes and, therefore, constitute a powerful tool for mapping and marker-assisted breeding. We initially identified in the melon sequence dataset 14,074 single nucleotide sequence variations and therefore potential SNPs (pSCH; Table 6 ) distributed in 4,663 contigs; however, these variations would include high-quality SNPs (pSNP) but also sequencing errors and mutations introduced during the cDNA synthesis step. Using more stringent criteria, these figures were substantially reduced: Putative SNPs were annotated only when the least represented allele was present in at least two EST sequences from the same genotype in a given contig and showing the same base change. Two accessions of the same cultivar (cv. "Piel de sapo") represented 47.3% of the sequences, but more than one half of the sequences were from two other more distant genotypes, the C-35 cantaloupe accession (29.3%) and the pat81 agrestis accession (23.4%). Thus, a total of 356 high-quality SNPs were found in 292 contigs, averaging 1.2 SNPs per contig. Transitions were much more common than transversions. There were 117 AG and 112 CT transitions compared with 28 AC, 37 AT and 33 GT transversions (Table 6 ). CG transversions were not detected. The MELOGEN database [ 44 ] includes a tool for designing oligonucleotide primers to amplify the region containing the polymorphism to generate the corresponding molecular marker.

Single nucleotide polymorphisms (SNPs) statistics*

*Type and number of transition and transversions are shown for putative single nucleotide variations in sequence (pSCH) and for putative high-quality single nucleotide polymorphism (pSNP) identified in the melon database.

Functional annotation

In order to identify melon unigenes potentially encoding proteins with known function, we carried out a BLASTX analysis [ 47 ] of the sequence dataset against the databases listed in Table 7. Out of the 13,019 unigenes with a hit with proteins in databases, 11,431 (68.7%) unigenes showing an E value of ? 1e-10 were annotated. On the other hand, 31.3% of the unigenes did not show significant similarity to any protein in the databases and, therefore, were not annotated.

Functional annotation statistics

A. Number of unigenes with BLAST hits

* Databases searched were: Arabidopsis [6,109]; Uniref90 [110,115]; Cucurbitaceae: all cucurbitaceae sequences available in the National Center for Biotechnology Information (NCBI); any database: results using Arabidopsis, cucurbitaceae and Uniref90 databases all together; Pfam [49,112].

Additionally, we performed a functional classification of the unigenes following the Gene Ontology scheme. Gene Ontology provides a structured and controlled vocabulary to describe gene products according to three ontologies: molecular function, biological process and cellular component [ 48 ]. To do that, we added GO terms based on the automated annotation of each unigene using the Arabidopsis database [ 6 ]. A summary of the results with the percentage of unigenes annotated in representative categories corresponding to the GO slim terms [ 48 ] is shown, as well as a comparison of the distribution of melon and Arabidopsis unigenes (Fig. 2 ). The distributions of melon and Arabidopsis unigenes follow similar tendencies, suggesting that the melon dataset is representative of the whole melon transcriptome. In total, 9,402 unigenes could be mapped to one or more ontologies, with multiple assignments possible for a given protein within a single ontology. A high percentage of unigenes in both species was classified as "unknown function". Out of the 9,791 assignments made to the cellular component category, 25.8% corresponded to membrane proteins and 17.8% to plastidial proteins (Fig. 2A ). Under the molecular function category, assignments were mainly to catalytic activity (23.0%) and to hydrolase activity (14.7%) (Fig. 2B ). The distribution of unigenes under the biological process category was more uniform, with 19.9% of assignments to cellular process and 12.7% to biosynthesis (Fig. 2C ).

Distribution of melon and Arabidopsis unigenes according to the Gene Ontology scheme for functional classification of gene products.

We have also identified 6,673 (40.1%) melon unigenes with an ortholog in the Arabidopsis database, and a HMMER motif has been assigned to 4,655 (28.0%) unigenes by comparisons with the Pfam database [ 49 ] (Table 7 ). All these results are compiled in the MELOGEN database, which also contains direct links to the databases used to carry out analyses.

Genes potentially encoding microRNAs

Central to RNA silencing are small RNA molecules (sRNAs) that can arise from endogenous or exogenous sources from precursors with double-stranded RNA (dsRNA) pairing. One class of such sRNAs are microRNAs (miRNAs), which originate from endogenous long self-complementary precursors that mature in a multi-step process involving many enzymes [ 50. 51 ]. Recently, a comprehensive strategy to identify new miRNA homologs in EST databases has been developed [ 52. 53 ]. We have followed this strategy to identify potential melon miRNAs. A total of 20 ESTs that contained homologs to miRNAs in the microRNA Registry database [ 54 ] were identified and grouped into 12 contigs and, after manual inspection of secondary foldback hairpin structure, 5 unigenes were selected (Table 8 ). Contig sequences varied between 536 and 840 nucleotides long, and had negative folding free energies of -206.8 to -160.8 kcal mol -1 (Table 8 ) according to MFOLD [ 55 ], which are in the range of the computational values of Arabidopsis miRNA precursors [ 52 ]. Their predicted secondary structures showed that there were at least 16 nucleotides paired between the sequence of the potential mature miRNA and its opposite arm (miRNA*) in the corresponding hairpin structure (Fig. 3 ). The location of the potential miRNAs varied among ESTs, 4 were found in the sense orientation of the EST, 1 was found in the antisense orientation. We have also searched for potential targets of the potential miRNAs in the melon EST dataset, identifying 3 of them (Table 8 ). However, minimal folding free energy indexes (MFEIs) [ 53 ] were below the -0.85 cut-off value proposed by Zhang et al. [ 53 ] only for m12 (Table 8 ). Potential melon miRNA m12 has a precursor of 536 nt in length and codes for a melon ortholog of the Arabidopsis miR319. miR319 targets a transcription factor of the TCP family [ 56. 57 ]; in the melon dataset, an ortholog of this Arabidopsis gene has been found in a unigene annotated as a TCP transcription factor. In this case, the melon miRNA and its potential target have a pattern of paired/non-paired bases between the target and the miRNA identical to the corresponding target-miRNA pattern in Arabidopsis (data not shown).

Potential melon miRNAs

*Nucleotide sequences correspond to potential mature miRNA sequences as deduced from BLAST searches using known plant miRNA sequences [54] and analysis of secondary structure predictions [52]. † Accession numbers (MELOGEN database) of potential precursors of melon miRNAs are given. § Computational values of folding free energies have been calculated using MFOLD 3.1 [55]. ? Minimal folding free energy indexes (MFEIs) have been calculated as described by Zhang et al. [53].

Potential precursors of melon microRNAs . (A) Stem loop sequence of putative precursor miRNA corresponding to unigene bCI_04-H02-M13R_c. (B) Stem loop sequence of putative precursor miRNA corresponding to unigene b15d_24-H05-M13R_c. The mature miRNA sequences are shown in bold.

Genes potentially encoding pathogen resistance and fruit quality traits

Pathogens affect severely the productivity of melon crops. Three of the cDNA libraries sequenced here correspond to pathogen-infected tissues and, thus, should contain transcripts from genes whose expression is induced in response infection. We have carried out a bioinformatics search for homologs of genes involved in pathogen resistance response (see [ 58 ] for a review) and virus susceptibility [ 59 – 61 ], finding among them at least one melon ortholog to the Arabidopsis FLS2 receptor [ 62 ], several unigenes potentially encoding disease resistance proteins as well as mitogen-activated protein kinases, homologs to translation initiation factors constituting potential virus susceptibility factors, etc. [see Additional file 1 ].

Fruit development and ripening are the most important processes determining the fruit quality traits of fleshy fruits like melon. At present most of the molecular and genetic data available about fruit development and ripening come from tomato [ 63. 64 ] and Arabidopsis [ 65. 66 ]. In recent years, several genes and quantitative trait loci controlling fruit quality traits have been described in melon [ 67. 68 ]. As for developmental processes, homologs to genes involved in melon fruit development, ripening and quality have been found in the melon dataset. These include several MADS-box genes, homologs to the fw2.2 and ovate QTLs [ 69. 70 ], several homologs to members of the SBP-box gene family to which the major tomato ripening gene COLORLESS NON-RIPENING belongs [ 71 ], several ACC synthase and ACC oxidase genes, unigenes from several cell wall-metabolism enzymes, etc [see Additional file 1 ].

Expression analysis of selected ESTs by Real-Time-qPCR

The accumulation of transcripts for 20 selected genes was analyzed by reverse transcription Real-Time-qPCR. ESTs for this analysis were preferentially chosen among those showing significant similarity with genes related to response to infection and fruit quality characteristics in melon and other species, and included CTL1, EIF4A-2, EIF4E, EIN4, GA2OX1, HSP101, HSP70, IAA9, LSM1, LUT2, NCBP, SVP, HIR, TCH4, TIP4, TOM1, TOM2A, TOM3, UGE5 and WRKY70 (Table 9 ). Preliminary experiments were carried out to choose between GAPDH and CYCLOPHILIN ( CYP7 ) RNAs as endogenous controls; results showed that the CYP7 RNA levels varied the least among treatments (data not shown) and, therefore, transcript accumulation levels were expressed relative to CYP7 RNA levels.

Transcripts selected from the database for gene expression analysis by Real Time qPCR

Figure 4A illustrates the alteration of the RNA accumulation levels of selected genes that occurred in photosynthetic cotyledons after CMV infection. A significant increase in the level of transcripts from HSP101, HSP70, HIR, TOM2A, WRKY70 and EIN4 was observed; for HSP101, HSP70, WRKY70 and EIN4 . transcript accumulation levels in inoculated cotyledons were up to five times greater than in uninoculated controls (Fig. 4A ). All of these genes, except TOM2A . have been shown to be responsive to virus infection in other hosts [ 72 – 74 ]. Notably, the expression of EIF4E . known to be required for MNSV multiplication [ 27 ], remained unaltered. A shutoff of host gene expression also occurs in association with virus infection [ 75 ]; for the set of genes analysed here, only GA2OX1 and NCBP responded to CMV infection with a reduction in the accumulation of their transcripts.

Transcripts analyzed by Real Time qPCR . (A) Pattern of transcripts accumulation in CMV-infected melon cotyledons (CI) relative to that of healthy cotyledons (CS). (B) Pattern of transcripts accumulation in M. cannonballus infected roots of C. melo L. cv. "Piel de sapo" (PSI) relative to that of healthy roots (PS). (C) Pattern of transcripts accumulation in M. cannonballus infected roots of C. melo L. ssp. agrestis (AI) relative to that of healthy roots (A). (D) Pattern of transcripts accumulation in fruits of 15 days after pollination of C. melo L. cv. "Piel de sapo" (15d) relative to that of fruits of 46 days after pollination (46d). cy: cyclophilin endogenous control; see Table 9 for the rest of genes.

The response of selected genes in roots inoculated with M. cannonballus was analysed in melon genotypes known to be susceptible (cultivar "Piel de sapo"; Fig. 4B ) and partially resistant (accession pat81 of C. melo L. ssp. agrestis ; Fig. 4C ) to the infection by this fungus. The patterns of transcript accumulation resulted clearly different for both genotypes. For pat81 (resistant), transcription factors WRKY70 and SVP increased their expression between 2 and 3 times after inoculation; other stress-inducible genes ( HSP101, HSP70 ) showed only a moderate increase (Fig. 4C ). For "Piel de sapo" (susceptible), accumulation of WRKY70 and SVP transcripts only increased about 1.5 times after inoculation whereas the expression of HSP101 showed a marked increase (Fig. 4B ). It is also worth noting the differential response of the GA2OX1 gene in the two genotypes. Expression of GA2OX1 increased about 1.5 times in pat81 roots after the M. cannonballus attack, whereas it decreased in "Piel de sapo" roots after fungal infection (compare Figs. 4B and 4C ).

Comparison of patterns of transcript accumulation at two stages of fruit development showed increased levels of gene expression for 9 of the analysed genes. This was particularly evident for HSP70, TOM2A, TOM3, EIN4 and IAA9 . In contrast, decreased levels of transcript accumulation were observed for the other 11 genes.

Discussion

In this paper we provide an initial platform for functional genomics of melon by the identification of more than 16,000 unigenes assembled from almost 30,000 ESTs sequenced from 8 melon cDNA libraries. It is probably premature to estimate the proportion of melon genes represented in this dataset, but based on available data for other plant species (i. e. Arabidopsis and rice), it is likely that the melon unigene set characterised here represents approximately between half and one-third of the number of expressed, protein coding genes of melon. Libraries were constructed from various tissue types, but with a bias towards fruit development and pathogen-infected tissues. Data from these libraries will become a useful resource of genes for experiments aimed at understanding important processes involved in fruit development and resistance to viral and fungal pathogens. Also, data presented here provide an important tool for generating markers to saturate melon genetic maps.

In contrast to typical EST gene-sampling strategies reported previously, we have found a low degree of redundancy in the sequences determined. The process of clustering reduced the number of sequences to 56%, from 29,604 good quality ESTs to 6,023 contigs and 10,614 singletons. Contigs with more than 8 ESTs were scarce, the majority of them being formed by 3 or 2 ESTs. Redundancy of the sequences derived from each library ranged from 13% to 20%, with singletons constituting approximately one third of the unigenes determined per library. This low redundancy is probably due to the success of the normalization process, responsible for the suppression of superabundant transcripts specific for a given tissue or condition. Normalization precludes in silico analysis of gene expression, but greatly increases the number of unigenes that can be determined by reducing redundancy [ 76 ]. Here we have used a recently described normalization protocol which is based on the cleavage of DNA or DNA-RNA duplexes by a specific DNase [ 77 ]; this process, in our hands, has proven simple, reproducible and efficient. Another factor that has contributed to the low redundancy values obtained has been the sequencing of libraries from very distinct tissues. Thus, the number of library specific unigenes was about one half of the total number of unigenes contributed by each library, suggesting that further sequencing of the libraries still has the potential to provide a good number of new, non-redundant sequences.

cDNA sequences are a useful source of SSRs, which are excellent molecular markers due to their high degree of polymorphism. A common feature of cDNA sequences obtained from plants is the high frequency of SSRs that they contain [ 36 ]. We have identified more than 1,000 potential SSRs in the melon dataset, with approximately 6% of the melon unigenes containing di-, tri - or tetranucleotide repeats. A clear bias toward AG and AAG repeats existed, that account for 67% of the SSRs. In contrast, the GC repeat was not found in the melon dataset. A similar bias toward AG and against CG repeats has been identified in Arabidopsis and other plant species [ 40. 78 ]. As proposed at least in one other instance [ 40 ], this may be due to the tendency of CpG sequences to be methylated [ 79 ], which potentially might inhibit transcription. Another interesting feature of melon SSRs relates to their pattern of localization with respect to putative initiation and termination codons. It is known that the UTRs of transcribed sequences are richer in SSRs than coding regions, particularly at the 5'-UTRs [ 36. 40 ]. However, in the melon dataset, a high proportion of SSRs (29.5%) were found in ORFs. An analysis of the localization of di-, tri - and tetranucleotide repeats separately showed that di - and tetranucleotides were preferentially located in UTRs, whereas trinucleotides localised in both, UTRs and ORFs, consistently with maintenance of the ORFs coding capacity. Thus, the prevalence of trinucleotide repeats in the melon dataset (71%) explains this result.

We identified in the melon sequence dataset 356 high-quality SNPs. Since non-redundant sequences analysed here encompassed 4.5 Mb, one SNP was found every 12,000 pb of sequence. This small figure is probably due to the limited number of melon genotypes used and the low redundancy found among libraries. In fact, when the frequency of SNPs is computed in relation to the length and number of contigs containing SNPs, the corresponding value (one SNP in every 616 bp of sequence) is of the same order of magnitude as values previously calculated for melon (441 bp; [ 80 ]) and other plant species [ 40 ]. With the advent of high-throughput detection systems, the SSRs and SNPs identified here will constitute an important resource for mapping and marker-assisted breeding in melon and closely related crops.

As an approach to the function of melon unigenes, we carried out a bioinformatics analysis based on BLASTX and matches with the Pfam database [ 49 ]. The proportion of melon unigenes with no similar sequences in databases was quite high, suggesting that the melon dataset may encompass an important number of melon-specific sequences. However, the proportion specific sequences might be overestimated because blasting has been made with unigene sequences, which in many cases do not cover the complete length of the transcript. We performed a functional classification of the unigenes following the Gene Ontology scheme, which is one of the more versatile and complete systems for functional classification [ 48 ]. A comparison of the distributions of melon and Arabidopsis unigenes in GO categories showed that both followed similar tendencies, suggesting that the melon dataset is representative of the whole melon transcriptome. This is remarkable, as the number of different libraries sequenced has been relatively small; again, this is probably due to the success of the normalization process. We have also carried out specific searches for genes involved in pathways of particular relevance in melon, such are resistance response and fruit development, identifying a remarkable number of melon candidates. For example, an ortholog of the flagellin receptor FLS2 from Arabidopsis [ 62 ] has been identified, together with 163 candidate RLKs that may have critical roles in pathogen recognition or diverse signalling processes. Similarly, up to 8 MADS-box gene homologs with potential roles in development have been found in the melon dataset. Moreover, a bioinformatics approach [ 52. 53 ] allowed the identification of potential precursors of melon miRNAs together with several potential targets in the melon dataset. This finding opens the door to biotechnology approaches based on the use of artificial miRNAs to specifically silence melon genes [ 81. 82 ].

The transcript accumulation analysis for the 20 selected genes revealed important changes in gene expression associated with pathogen infection and fruit development. For virus infection, the accumulation of transcripts remained unaltered for 12 genes, but showed a significant increase for 6 genes and a decrease for 2. Among the set of genes analysed, TOM2A and EIF4E were known to code for virus susceptibility factors [ 27. 83 ]; the expression of TOM2A was increased after CMV infection, consistently with its requirement by the virus, but this was not the case for EIF4E . Different hypotheses can explain this result: since EIF4E is an abundant, housekeeping protein, increased expression may not be essential for virus multiplication; alternatively, CMV may not use EIF4E in melon or may use a factor coded by a different member of the 4E family; it may also be that timing of the sampling for this experiment was not appropriate to detect such an effect, as requirement of EIF4E might occur very early during virus multiplication. In the cases of infection of susceptible ("Piel de sapo") and resistant (pat81) melons by M. cannonballus . more extensive alterations in gene expression seemed to occur in the susceptible than in the resistant accession. Significantly, for the susceptible accession, stress responsive genes (e. g. HSP101 ) appeared to be maximally induced, whereas for the resistant accession, a gene encoding a WRKY70 transcription factor, potentially involved in resistance response, was induced to high levels. Significantly, expression of GA2OX1 increased about 1.5 times in pat81 after the M. cannonballus attack, whereas it decreased in "Piel de sapo". GA2ox is a major gibberellin (GA) catabolic enzyme, with an important role in controlling GA levels in plants. Hormones control many plant developmental processes, and strong evidence indicates that hormone signalling is involved in the regulation of root growth and architecture [ 84. 85 ]. The differential response of the GA2OX1 gene in the two melon genotypes is consistent with an enhanced root growth in pat81 after infection [ 86 ]. Notably, other genes involved in hormone-mediated signalling pathways, such as the IAA9 gene, did not show such differential response to M. cannonballus infection in both genotypes. In the case of fruit development, differences in the expression of selected genes between immature and ripening fruits appeared to be even sharper than in the cases of healthy and pathogen-infected tissues. Specific roles during fruit development for HSP70, TOM2A and TOM3 have not been identified, though an increased expression has been shown at least in the case of TOM2A in tomato [ 87 ]. The ethylene receptor gene EIN4 showed a two-fold increase in expression. EIN4 is the ortholog of Arabidopsis EIN4 and tomato LeETR4 [ 88. 89 ]. In tomato, LeETR4 is also highly expressed in ripening fruit, suggesting that it responds by modulating ethylene signalling during ripening [ 63 ]. The MADS-box gene ( SVP ) showed about a four-fold decrease in expression. This gene is the ortholog of tomato JOINTLESS . which specifies the abscission zone in tomato. In tomato fruit microarray hybridizations, the expression of JOINTLESS also decreased from 7 to 57 DAP [ 87 ], in agreement with our data for melon. The lycopene epsilon cyclase ( LUT2 ) and xyloglucan endotransglycosylase ( TCH4 ) genes showed an approximately four-fold decrease in expression during melon fruit development. These findings fit with the patterns of expression of these genes in tomato, where their transcript levels decrease to a non-detectable level in the ripe fruits [ 90. 91 ].

Conclusion

In summary, this collection of ESTs represents a substantial increase on the information available for melon. The dataset contains SSR and SNP markers that can be used for breeding, as well as a significant number of candidate genes that can be experimentally tested for their roles in various important processes. This set of genes constitutes also the basis for a microarray for melon that is being used in experiments to further analyse fruit development and maturation and responses to pathogen infections.

Methods

Plant material

The cDNA libraries were prepared using material from four different melon genotypes: the line T-111 (Semillas Fito, Barcelona, Spain), which corresponds to a Piel de Sapo breeding line, the Piel de Sapo cultivar "Pinonet torpedo" (Semillas Batlle, Barcelona, Spain), the accession C-35 of the germplasm collection of La Mayora-CSIC (EELM-CSIC, Malaga, Spain), which corresponds to a cantaloupe-type of melon, and the accession pat81 of C. melo L. ssp. agrestis (Naud.) Pangalo maintained at the germplasm bank of COMAV (COMAV-UPV, Valencia, Spain) (Table 1 ). Seeds of line T-111 were germinated at 30°C for two days and plants were grown in a greenhouse in peat bags, drip irrigated, with 0.25-m spacing between plants. Fruits of 15 and 46 days after pollination were collected and mesocarp tissues were recovered and used for RNA extractions. Root samples were from Piel de sapo and pat81 plants, both healthy and inoculated with M. cannonballus . Piel de sapo is fully susceptible to the infection by this fungus whereas pat81 has been shown to be partially resistant [ 92. 93 ]. Seeds were pre-germinated in Petri dishes. After 4 days, seedlings were transplanted to 0.5-l pots filled with sterile soil substrate and grown in a greenhouse (20–35°C, 60–85% relative humidity). Inoculations were carried out by adding 50 colony-forming units (CFU) of M. cannonballus per gram of sterile soil as described by Iglesias et al. [ 94 ]. Fourteen days after inoculation, healthy and inoculated roots were collected for RNA extraction. The presence of the fungus and the infection levels were assessed by real-time quantitative PCR as described by Pico et al. [ 95 ]. CMV infected cotyledons were collected from plants of the C-35 accession. In this case, seeds were pregerminated in Petri dishes for 24 h at 28°C in the dark, planted in 0.5-l pots and maintained in an insect-proof green house (20–28°C, 45 to 85% relative humidity) for 6 to 7 days, until the first true leaf started emerging. At this stage, cotyledons were mechanically inoculated with CMV following standard procedures [ 96 ]. Inoculated cotyledons were harvested 4 days after inoculation and used for RNA extractions. Dot-blot hybridisation [ 97 ] was used to check infection by CMV. Plants of the C-35 accession were also used for collecting healthy leaves. Plants were maintained in the greenhouse for 21 days, and second and third leaves above cotyledons were harvested for RNA extractions.

Construction of cDNA libraries and EST sequencing

Total RNA was prepared as described by Aranda et al. [ 98 ]. Poly(A + ) RNA from total RNA was purified using MicroPoly(A + ) Purist (Ambion, Austin, TX, USA), a cellulose-oligo(dT)-based method. Integrity and quality of both total and poly(A + ) RNA were tested by gel electrophoresis. cDNA libraries were constructed with the SMART cDNA Library Construction kit (Clontech, Mountain View, CA, USA), using a modified primer to include a Sfi I enzyme restriction site. A normalization step was carried out with TRIMMER kit (Evrogen, Moscow, Russia). After normalization, a cDNA fractionation step was performed with SizeSep 400 Spun Columns (Amersham Biosciences, Buckinghamshire, England). cDNA was digested with Sfi I, generating Sfi IA - Sfi IB cohesive ends for directional cloning into a modified version of BlueScript SK plasmid vector (Stratagene, La Jolla, CA, USA). Ligation products were transformed into E. coli electrocompetent cells DH10B (Invitrogen, Carlsbad, CA, USA) by electroporation. The titer of the libraries was evaluated by plating an aliquot on LB agar plates with ampicillin at 100 ?g ml -1. Only libraries of 10 5 cfu ml -1 or more were considered as acceptable. Prior to large scale sequencing, the average insert size was estimated by restriction analyses of 24 plasmid DNA minipreps per library from randomly picked colonies.

Sequencing was carried out from the 5'-end of the inserts without library amplification using the universal M13 reverse primer. An external custom service was contracted for this task (Macrogen Inc. Seoul, Korea). Approximately 6,000 clones were sequenced from the CI library, and 3,500 clones were sequenced from each of the other libraries (Table 2 ). Sequences obtained in this work can be found in GenBank [accession numbers AM713476 to AM743079] and MELOGEN [ 44 ].

Bioinformatics

EST sequences were automatically trimmed, clustered and annotated using the EST2uni analysis pipeline [ 43 ]. EST2uni compromises the analysis pipeline written in PERL [ 99 ], a database (MySQL) [ 100 ] and a web site to browse the results coded in PHP [ 101 ]. Thus, for the EST pre-processing step, base calling was performed with Phred [ 102 ], low quality regions and vector sequences were trimmed with Lucy [ 103 ], and repeats and low complexity regions were masked with RepeatMasker [ 104 ] and Seqclean [ 105 ]. Further vector contamination was also eliminated with Seqclean using NCBI's UniVec [ 106 ]. High-quality EST sequences were then assembled to obtain the unigene set using Tgicl [ 105 ].

Detection of SSRs was performed using Sputnik [ 107 ]. Putative SNPs were annotated when the least represented allele was present in two EST sequences or more. ORFs were predicted in the ESTs with the aid of the ESTScan software [ 108 ].

For functional annotation, comparisons against the Arabidopsis (TAIR) [ 109 ] and Uniref [ 110 ] databases were carried out using BLASTN or BLASTX for nucleotide or protein sequences, respectively. Functional domains were searched with HMMPFAM [ 111 ] using the Pfam database [ 112 ]. The Gene Ontology (GO) classification [ 48 ] was derived from the BLASTN results against the Arabidopsis proteome. Also, a bi-directional BLASTN comparison was performed in order to obtain a set of putative orthologs with Arabidopsis. Finally, a set of superunigenes was obtained grouping different unigenes with the same expected mRNA target, as judged by extensive sequence overlapping.

To assess codon usage, we generated a set of melon sequences predicted to contain full-length coding regions. These sequences were subjected to BLASTX and, after manual inspection, sequences showing a high similarity to Arabidopsis proteins were selected to ensure that no sequences containing frame-shift errors were included in the analysis. From this smaller dataset, which included 588 sequences, ORFs were defined and a codon usage table was created. Codon usage was calculated from sequences using the GCUA program [ 113 ]. All codons were found in the dataset, with the least frequent codon represented 134 times.

To identify potential melon miRNAs, the 33,292 melon ESTs were subjected to a BLAST search against mature sequences of known miRNAs from the miRNA Registry Database (released January 2007) [ 54 ] using BLASTN [ 47 ]. ESTs with only 0–1 mismatched nucleotides with known miRNAs were considered. Selected ESTs were subjected to a BLAST search against protein databases in order to remove potential protein-coding sequences. ESTs pertaining to the same melon unigene of the MELOGEN database were grouped. The secondary structures of the unigenes encoding potential miRNA precursors were predicted with the web-based tool MFOLD [ 55 ], using default parameters. In each case, only the lower energy structure was selected for visual inspection, as previously described [ 52. 114 ]. In order to select unigenes with perfect or near-perfect secondary foldback hairpin structures, only sequences with a maximum size of 3 nucleotides for a bulge in the miRNA sequence and with at least 16 paired nucleotides between the mature sequence and the opposite arm were considered as potential miRNA candidates. In addition, the minimal folding free energy index (MFEI) for each sequence was calculated following Zhang et al. [ 53 ].

Gene expression analyses

Real time quantitative PCR was performed with an AB 7500 System (Applied Biosystems, Foster City, CA, U. S.A) to quantify mRNA corresponding to some transcripts of interest, in the tissues and physiological conditions used for library construction. Twenty ESTs representing these transcripts were chosen from the database and used to generate gene-specific primers (Table 10 ) with Primer Express Software (Applied Biosystems). The chemistry used for PCR product detection was the Power SYBR green dye (Applied Biosystems) and ROX as passive reference. CYCLOPHILIN served as endogenous control (sequence extracted from the database), ??Ct was the method of calculation to perform relative quantification, and three technical replicates were carried out and considered for statistical analysis. Melting curves analyses at the end of the process and No Template Controls (NTC) were carried out to ensure product-specific amplification and no primer-dimer quantification. A control reaction as for reverse transcription but without the enzyme was performed to evaluate genomic DNA contamination.

Primer sequences for Real Time-qPCR analysis of transcript accumulation

Declarations

Acknowledgements

This work was supported by grants from Ministerio de Educacion y Ciencia (Spain) (GEN2003-20237-C06) and Consejeria de Educacion y Cultura (Region de Murcia, Spain) (BIO2005/04-6436). Wim Deleu, Cristina Roig and Daniel Gonzalez-Ibeas are recipient of a postdoctoral fellowship from the Centre de Recerca en Agrigenomica CSIC-IRTA (Spain), a Juan de la Cierva grant from Ministerio de Educacion y Ciencia (Spain) and a predoctoral fellowship from Ministerio de Educacion y Ciencia (Spain), respectively.

Electronic supplementary material

12864_2007_1019_MOESM1_ESM. pdf Additional file 1: Genes potentially encoding pathogen resistance and fruit quality traits. Genes were identified in the melon data set by comparison with the Arabidopsis database [ 6. 109 ]. A brief description, the corresponding Arabidopsis locus and the HMMR domain identified are given for each unigene. (PDF 111 KB)

Below are the links to the authors’ original submitted files for images.



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Nibelheim - Final Fantasy Wiki, Nibel

Nibelheim

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Crisis Core location maps

Dirge of Cerberus location maps .

Nibelheim ( ??????. Niburuheimu ? ) is a small mountain village located at the base of Mt. Nibel across the river from Cosmo Canyon in Final Fantasy VII . It is the hometown of both Cloud Strife and Tifa Lockhart. Years before the start of the game, a devastating incident occurred in the town that was never revealed to the public. Shinra Electric Power Company owns a Mako Reactor on the nearby Mt. Nibel, providing the town with power, as well as a manor on the outskirts of town that was the base for the company's scientific research for many years before it was left abandoned.

Contents

Story Edit

Shinra Mansion Edit

Shinra Mansion in Nibelheim.

The Shinra Mansion on the outskirts of Nibelheim was the first structure built years before the town was established, and it holds many secrets of Professor Hojo 's experiments. The mansion, having been in the Shinra Electric Power Company's possession for a long time, was the setting for the experiments that would become the Jenova Project. It is a derelict house of grandeur with a walk leading from the town outskirts to the entrance.

Many years ago the basement was used for experiments by the head of Shinra's Science Division, Hojo. In competition with his rival, Hollander. he tried to create a human with the powers of an Ancient. He injected Jenova 's cells into his colleague and lover Lucrecia Crescent while she was in early stages of pregnancy, which led to the birth of Sephiroth, a child born fused with Jenova cells. Although Sephiroth did not possess the powers of an Ancient, he was raised to be the ultimate SOLDIER while Lucrecia was unable to have a role in his life.

Vincent inside his coffin.

The Turk Vincent Valentine. whose assignment was to monitor the scientists during their experiments, fell in love with Lucrecia. When he heard of the ghastly things being done to her and her unborn child, Vincent confronted Hojo who shot Vincent. Lucrecia, realizing Vincent had been trying to protect her, tried to save his life.

She discovered a way to use Chaos. the servant of the Omega. to save Vincent, giving him the ability to transfigure. Hojo, seeing the use of this ability, implanted more and more monsters within him, but Vincent began to see himself as a monster, and as a failure for failing to save Lucrecia. He repented by resigning to a coffin in the mansion's basement, where he slept almost undisturbed for 23 years.

Cloud and Tifa's Childhood Edit

Cloud and Tifa under the moonlight.

Nibelheim remained a peaceful town and Cloud Strife and Tifa Lockhart grew up there. While Tifa played with her friends, Cloud isolated himself. His mother was his only family, as his father had died while he was young. He considered the other children childish and himself superior.

Tifa's mother died and she believed she could find her again by climbing Mt. Nibel. She injured herself during the trek and fell into a coma and Cloud, who had followed her, was blamed for the incident and forbidden from getting close to Tifa by her father. Cloud idolized Sephiroth, the hero SOLDIER of the Wutai War. and thought if he became a hero like him people would accept him, and he would win Tifa's attention. Before leaving for Midgar he met up with Tifa and told her his plans to become a SOLDIER, promising he would come to her rescue whenever she needed protection. Cloud departed and Tifa began training with Zangan. a martial arts expert, and worked as a guide on Mt. Nibel for tourists and visitors.

The Nibelheim Incident Edit

A photo of Zack, Tifa, and Sephiroth.

Cloud meets his idol Sephiroth, but never attains his goal of becoming SOLDIER First Class, becoming a mere Shinra infantryman who follows Zack Fair on missions. Sephiroth and Zack and their guards head to Nibelheim to investigate a broken section of the Nibelheim Reactor. Cloud is too ashamed to show his failure to his hometown, and keeps his helmet on when they meet with Tifa, their guide. When a picture is taken of the party before heading out, Cloud stays out of it.

As the group makes its way to the reactor a bridge collapses and a Shinra infantryman goes missing. Upon arriving at the reactor Sephiroth and Zack fix a broken valve, but find the hideous by-products of Hojo's experiments: makonoids within pods who once were humans. The back of the reactor has a sealed door, inscribed with the name Sephiroth had come to associate with the mother he had never met: Jenova. Sephiroth wonders if he is no different from the monsters, and his former friend, Genesis Rhapsodos. who had earlier deserted Shinra, appears to confirm his suspicions. Wanting to learn more, Sephiroth locks himself away in the Shinra Mansion basement and reads about the Jenova Project. The answers drive him insane.

The razing of Nibelheim.

Believing himself to be the heir to the Cetra legacy, due to a misconception that Jenova was an Ancient, Sephiroth slaughters most of the townsfolk and burns the town to the ground. Zack, Tifa, Zangan, and Cloud try to help, but their efforts are in vain. Cloud's mother and Tifa's father are killed. Sephiroth climbs Mt. Nibel to find his mother, Jenova, inside the reactor. He breaks into the sealed room and speaks with an angelic effigy that masks Jenova from view about finding the Promised Land. He tears the effigy off the machine, revealing an alien monster in a tank whom he refers to as "mother".

Tifa and Zack confront Sephiroth in the reactor. Tifa picks up the discarded Masamune and rushes at Sephiroth, but is disarmed and incapacitated. Zack fights Sephiroth but is defeated and cast aside. Finally Cloud charges at Sephiroth, impaling him with Zack's Buster Sword. Cloud leaves to check on Tifa and Zack, but Sephiroth staggers out of Jenova's chamber, holding her severed head. Cloud attacks Sephiroth again, but is disarmed and impaled through the chest. Using the sword as a lever Cloud picks up Sephiroth, and throws him into the Lifestream below the reactor.

Zack and Cloud escape their confinement.

Zangan rescues Tifa, but Cloud and Zack are captured by the player Turks of Before Crisis - Final Fantasy VII - . In Episodes 12 and 13, the player, along with the Turk leader, Veld. help Hojo start his new experiment and hide the incidence. Cloud and Zack are used as test subjects in Hojo's Jenova Reunion Theory. They, and the survivors of Sephiroth's rampage, are injected with Jenova cells and kept in tanks of Mako. Zack escapes with the help of his old mentor, Angeal Hewley. who aids him from the Lifestream.

Zack frees Cloud, who is suffering from Mako poisoning, and the two escape Nibelheim. Zack is unaffected by the experiments, possibly due to having already been exposed to Mako by way of becoming a SOLDIER. The town is rebuilt and repopulated with actors hired by Shinra to ensure word of the incident never gets out. Shinra seals up Sephiroth's records and he is presumed dead. Zangan had brought Tifa to Midgar where she recovers and sets out to get revenge on Shinra, joining the resistance group AVALANCHE and running its headquarters, the 7th Heaven bar in the Sector 7 slums.

Hunting for Sephiroth Edit

Five years later, Cloud and Tifa have reunited and search for the resurfaced Sephiroth across the Planet. Their search leads them to their hometown of Nibelheim, now rebuilt and infested with Sephiroth Clones who chant on about Sephiroth and Reunion. Not one of the town's inhabitants recognizes either of them, since they are fakes put in place by Shinra. In Tifa's old house Cloud finds a letter detailing what has happened in Nibelheim since they have been gone.

In the Shinra Mansion basement they find Vincent Valentine locked in a coffin, who can be coaxed to join the party. They encounter Jenova in Sephiroth's disguise who tells Cloud to follow across the mountains.

During the events Dirge of Cerberus - Final Fantasy VII - . Vincent Valentine returns to the Shinra Mansion.

Locations Edit

Location of Nibelheim, indicated by crosshair.

Nibelheim is located to the West on Gaia's Western continent, specifically in the Nibel Area.

Nibelheim is comprised of five accessible buildings and the mansion at the end. There is also a route next to the mansion which exits Nibelheim and leads up to Mt. Nibel. There are two times the player enters Nibelheim during the story and takes full control of where they go. The first time is Cloud and Sephiroth during the flashback told at Kalm before Nibelheim was razed, and the second time is with the party is in the restored Nibelheim.

Town Edit

Town, current day

The exit at the south of the town leads to the World Map. The exit at the north also leads to the World Map tough it leads to the small portion of World Map between the entrance to Mt. Nibel and Nibelheim, surrounded by mountain on either side. During the interactive flashback neither exit takes the player to the World Map: they can't exit from the south and the north takes the player straight to the Mt. Nibel.

Surrounding a well there are five accessible buildings. The most south-westerly building is the Inn. the more north-westerly is the Item Store. On the right, from the top-right down is Cloud's House. Tifa's House. and the Siblings' House.

At the back of the town is Shinra Mansion. a mansion owned by Shinra though long abandoned.

The town is visited with three different appearances, the first is the Nibelheim of five years ago, the second is Nibelheim aflame, and the third is a re-built Nibelheim which is notably different in its paving of the town.

The town is seen on various occasions in flashbacks and illusions. The well is a point of focus on the promise Cloud and Tifa made. Sephiroth uses illusions of Nibelheim when the party is in Whirlwind Maze to try to prove that Cloud was never present five years ago and instead constructed by Hojo after the events.

Inn Edit

The inn is found in the bottom-left of the town. During the first visit in the flashback, Cloud must enter the inn to talk to Sephiroth to continue with the events on Mt. Nibel after having visited the places around town.

During the first visit with the party, the innkeeper charges 100 gil for a room. There is also a second selectable option, " What's your story? ". Selecting this option prompts Cloud to question what is going on with the town not being destroyed; to which he replies saying he grew up in in Nibelheim and that it never burned down, to which prompts Tifa if she is present, or Cloud if she is not, to say he is lying. The innkeeper refutes this.

There is a man in a black cape in the back room only before the Reunion shortly into the start of disc 2. From him the player can receive a Luck Source.

Sephiroth is found on the second floor during the flashback, and talking to him continues the Mt. Nibel events.

Item Store Edit

During the flashback visit, nothing occurs here. During the second visit, the man in the black cape standing next to the fire gives an Elixir only before the Reunion shortly into the start of disc 2. The woman at the desk sells items.

Siblings' House Edit

Siblings' House 1f.

A two-story house in the bottom right of the town. This area is known as "Nibelheim House" in the menu in English versions of the game, though in the Japanese version it is "The house with the small older sister and younger brother" ( ?????????. chiisana shitei ga ita ie ? ). The siblings are seen on the first floor during the flashback. When the party visit the town for the first time, two black cloaked figures appear on the second floor, sharing their speech patterns with the siblings.

During the flashback there is a lady and two children on the first. During the visit with the party, there is nothing on the first floor.

During the flashback there is nothing on the second floor. During the visit with the party before the Reunion shortly into the start of Part 2, two cloaks can be found here. From these the player can get a Luck Source.

Tifa's House Edit

In the flashback, if the player enters Tifa's house and does certain things Tifa will question whether Cloud actually did such things. Replying "No" will take the player outside the room.

"P. S. Write me back, okay?"

The events done here directly change the script later on in the game. In the Whirlwind Maze. Sephiroth creates an illusion of a burning Nibelheim, and makes Cloud question what he did while in-town. "Yeah, I went to Tifa's room. There, I. " "I played the piano!" "I looked in the drawers!" "I read the letter addressed to Tifa!".

Tifa's house has more interactions the seconds time the player goes there with the party. The back room on the first floor a man in a black cape will relinquish a Turbo Ether. Upstairs, another black caped man gives another Turbo Ether.

On the table in Tifa's bedroom a note is found.

"Periodic Report to Professor Hojo"

1 Clone Activity Report

Unfortunately, no 'CLONES' have left this town this quarter. As previously reported, the 'CLONES' seem to be sensing something. But all they say is, 'reunion' or 'Sephiroth' and show no other signs of activity.

2 Confidentiality Report

A total of eight people have visited this town this quarter. Fortunately, none knew about the incident five years ago. Therefore, no one knows the town was restored exactly as it was five years ago. Our staff, disguised as townspeople have improved their acting skills, and we do not report any problems at this time. That is all.

If the piano is repeatedly played on, the player can discover 1 gil. When Tifa is the party leader in disc 2, playing the game's main theme gives the player an Elemental Materia. but only if the player made Cloud jam on the piano during the Kalm flashback. Doing this again when Cloud returns as party leader with Tifa in the party will get her Limit Break manual, Final Heaven.

Cloud's House Edit

During the flashback, if the player goes into Cloud's House, they can choose whether to watch clips of the events showing Cloud's conversations with his mother.

During the visit with Cloud and the party, Cloud's house has only a lady that refutes the fact Cloud grew up there.

Shinra Mansion Edit

Nibelheim is accessed in Chapter 5 of Dirge of Cerberus - Final Fantasy VII - . Vincent attempts to enter Shinra Manor through the town sewers. Nibelheim had been compromised by Deepground at the time.

Nibelheim Sewers Edit

The Nibelheim sewers is a large man-made sewer-system that stretches from the Reactor upon Mt. Nibel to the town of Nibelheim beneath Shinra Manor. Sahagin infest the sewers.

Following the path, the player will find a Potion on the right-side, and a Handgun Bullet x72 on the left. Further down on the left is a Phoenix Down. Further on, a Cardkey gate will block the way, on the right is a ladder for the player to climb. Here is a Mako point. From here the player can jump into the water to initiate a Sahagin attack, one of which having the Cardkey. After opening the Cardkey gate, the player should head to the red dot as seen on the map.

Back in the water, through the southern tunnel, and up the stairs is a Rifle Bullets x52 behind the player on their right. Heading left and forwards takes the player to an 1,000 gil pick-up. In the tunnel is a Limit Breaker. Back out and on the opposite side of the room is another room with boxes containing Machine Gun Bullets x70, and 900 gil. Back out there, and following the sewer going down the left leads to an end where the player can turn left again to get a Blizzard Materia. Back out and on the opposite side is a tunnel.

Down the tunnel and then out on the left will lead the player to a Potion on their right. Further down on the left is Rifle Bullets x40. A Cardkey barrier is opened by a nearby Sahagin's Cardkey. After getting the Handgun Bullets x72 pick-up in the center, the Cardkey gates will appear, keeping the player in. A subsequent Sahagin will have a Cardkey. Heading forwards in their original direction will get them 2,500 gil. Turning back east up the ladder is a Mako Point, and further on is a switch. The player can jump in the water to pick up a Potion and 500 gil. The red dot on the map takes the player to the sewer's exit.

The sewers exit out into a storage unit occupied by Deepground soldiers. In here the player will find an elevator taking them to the second and third floor. A smaller room has a small entrance where the player can crouch and move underneath. In here is a line of items, being a 100 gil pick-up, a 400 gil pick-up, and a Power Booster. An infinite DG Soldier respawn also occurs in here.

On the second floor there is a pathway taking them downstairs to a vending machine. On the third floor, the player finds Machine Gun Bullets x45, Handgun Bullets x90. This eventually links up to the library of Shinra Manor.

The main town area of Nibelheim.

The player enters Nibelheim in Chapter 9. From the main area of town, the player can access the outskirts and the inn. Here the player can talk to a boy, who is at the heart of the Seven Wonders sidequest.

Later in Chapter 9, when the town is burning, a chest containing a Fire Ring sits outside the building. The player can talk to the boy to save his mother from the building as part of the Seven Wonders sidequest.

In Chapter 10, when the player discovers a restored Nibelheim, they are attacked by Shinra infantrymen. After returning to and exiting the Shinra Manor, a final fight with some infantrymen takes place in a lit-up nighttime Nibelheim.

Inn Edit

Inn second floor.

The inn can be entered from the main area of Nibelheim, and has three rooms. The first is the room on the first floor that has a Save point. Upstairs is where Sephiroth stands, and in the room with the beds.

Outskirts Edit

The Nibelheim outskirts can be accessed through the town's main area. The outskirts lead off into two more places, Mt. Nibel's trail, and the Shinra Manor. There is a chest containing an Ether here.

Shinra Manor Edit

Shinra Manor can be reached from the outskirts.

The path of Mt. Nibel can be accessed through the Nibelheim outskirts.

Nibel Plains Edit

The player enters the Nibel Plains after leaving Nibelheim in Chapter 10. Here a minigame takes place involving using a sniper to shoot robots. After the minigame is a save point. Turk Cissnei also discovers Zack here.

Guides and quests Edit

Enemies Edit

The Bahba Velamyu is the only enemy in the forest area that can inflict negative status effectes. Silence and Slow which both cannot be avoided through the use of accessories except the Ribbon which is not available at this stage of the game. The Crown Lance is the only enemy fought on the beaches in the Nibel Area. They can inflict the Sleep and Petrify statuses but these cannot be avoided through the use of accessories in this stage of the game.

The Dazers item can be stolen from Battery Caps in their first slot with an average steal rate. The item inflicts Paralyze and can serve multiple purposes in the game including stopping enemies with high evasion, and stopping certain enemies from using their strong attacks.

The Nibel Wolf enemy fought on the grass areas can use the Howling ability to revive all fallen Nibel Wolf enemies defeated in the battle. Each one can use the ability three times. Allowing the Howling ability to be used allows for more EXP and Gil to be won from the battle.

The Valron enemy can be fought in grass areas, and can be manipulated to use the Dive Kick command which is a Gravity-elemental ability. This means it can't kill the player, and can be exploited to help increase the player's Limit gauge to help learn additional Limit Breaks.

Yuffie Edit

The Mystery Ninja can be fought in the forests in the Nibel Area.

Piano Edit

The piano in Tifa's house can be used to acquire a number of items.

During the flashback to Nibelheim, Cloud can go into Tifa's House and into Tifa's room, and play on the piano. If the player makes Cloud say "Yeah, I jammed on it", followed by "I forgot", a tutorial is shown.

Going up to the piano again and choosing "Just a little". The message gives the notes to the the Main Theme of Final Fantasy VII .

"Do. Re. Mi. Ti. La. Do. Re. Mi. So. Fa. Do. Re. Do. Forget it. "

On the first visit to Nibelheim with the party, playing anything on the piano repeatedly will eventually earn the player Tifa's secret savings, 1 gil.

Returning to Nibelheim on Disc 2 with Tifa as the party leader can earn the player an Elemental Materia. but only if Cloud "jammed on" the piano in the Kalm flashback. To attain the Materia, the "Main Theme of Final Fantasy VII " must be played on the piano.

The tune is as follows:

. . . + . + , . . . + . , . .

[CANCEL], [SWITCH], [MENU], [PAGEUP]+[MENU], [PAGEUP]+[SWITCH], [CANCEL], [SWITCH], [MENU], [PAGE UP]+[CANCEL], [OK], [CANCEL], [SWITCH], [CANCEL]

On Disc 2, after Cloud rejoins the party as party-leader, with Tifa in the party, and regardless of if the player played the piano on the previous Disc, playing the "Main Theme of Final Fantasy VII" tune again will reveal a letter to Tifa from Zangan, containing her ultimate Limit Break, Final Heaven.

"Tifa, what's happened to our town? Was it all an illusion‚ or just a dream? No‚ it was neither. I remember trying to get people out of the flames‚ but not having the strength. Burning with anger‚ I went to the reactor to kill Sephiroth."

"But he was nowhere to be found. Instead‚ I found you‚ collapsed inside. I felt saving you was far more important than going after Sephiroth. There were several others that were still alive inside, but I was only able to save you."

"As I was coming out of the reactor, Shinra troops were just arriving. I recall a scientist named Hojo was in charge. He ordered the troops to gather up everyone still alive for the experiment. I didn't know what type of experiment he was talking about, but I wasn't about to let them have my dearest student."

"Putting you on my back‚ I headed down the mountain to the village. I used the Cure spell on you many times."

"And started to head for Midgar to look for a doctor for you. I didn't like that city, and my Cure spells weren't helping."

"I decided to go to Midgar to find a doctor I could trust. I'm worried about you‚ but I can't settle down in one place for very long. Have you recovered fully? Are you well?"

"I wonder how many years have passed since then? I just got into town again, but I can't believe it. The whole town is back to normal, except for the strange people with black clothes all around."

"The town reeks of Shinra, but I won't go after them. You may think I'm running from them, but it's just that I don't want anything to do with Shinra anymore. Feels like time is running out."

"I'm sure you'll find this letter. And this gift for you. It should come in handy. I can't even jump anymore. But I hope you continue to sharpen your skills and remember what I taught you."

"To my most precious student‚ From Zangan"

Ultimate Weapon Edit

After defeating Diamond Weapon. and then after defeating Ultimate Weapon above the waterfall next to Junon, one of the places Ultimate Weapon stops above and can be fought at is above Mt. Nibel.

Eliminate the Sahagin Edit

This article or section is a stub about a location in Dirge of Cerberus - Final Fantasy VII-. You can help the Final Fantasy Wiki by expanding it.

Seven Wonders Edit

The Seven Wonders is a sidequest that allows the player to obtain another items. When the player enters Nibelheim, there is a boy who stays around the town. The first four wonders can be done at this point in the game. The remaining three can only be done after returning from Mt. Nibel's reactor.

Lately, the town's drinking water has been coming out red. Could it be. blood?

If the player goes to the water tower in the center and goes up, they will discover a red materia is the cause of the problem, and they'll obtain the Phoenix materia.

The boy will tell you about the painting of a girl. In the upstairs of the Inn. through the doors in the room, there is a painting of a girl in the corner of the room. If the player talks to him again, and says he has seen it, he tells you about the second wonder.

That girl sometimes leaves the painting and wanders around in our world.

When the player returns to the room, the painting on the wall will be gone, instead replaced with a version without the girl. After going up and down the stairs a few times until the clerk walks up the stairs. If the player follows him into the room, the clerk explains the wonder and the player receives 2,000 gil. After this, the player can get a smaller amount of gil (between 3 and 108) by going up and down the stairs until the picture in the room has the girl there.

You know Mt. Nibel, right? The dangerous mountain will all the monsters?

Well the most dangerous monsters there are the bombs.

Now, rumor has it one of the bombs is different from all the others.

No one has seen it yet, but they say that it has a different face.

The third wonder requires the player to head to the outskirts. and then on into Mt. Nibel. If the player heads east at the intersection, they'll eventually come into contact with three Bomb-type enemies: a Touchy Bomb. a Remedy Bomb. and a Gray Bomb. Defeating them without any of them blowing up earns the player a Gold Shard. After solving this wonder, the boy gives the player a Safety Bit. and then tells the player about the fourth wonder. The Gold Shard can either be kept or sold afterwards. If the Gold Shard is kept, the player can show it to the boy early, saving them the time to go up Mt. Nibel to get one.

Do you know about Shinra Manor? It's an old mansion in the back of the town.

We call it the haunted mansion.

Anyway, they say there's a safe in the mansion, and every night, you can hear laughter coming out of it.

But no one knows the code to open the safe, so we can't check what's inside.

The player can find Shinra Manor by heading through the outskirts. It is worth noting that the safe code is not the same as in Final Fantasy VII . and it changes every time.

From the first floor, the player can head up to the second floor and into the northeast room and look through the keyhole. The amount of books not on the shelf, that are on top of the shelf, on the floor, or on the chair, is the first number.

On the first floor, the player must look-through the keyhole on the east of the room and count the Dorky Faces. Some disappear for a short time, and others hide on the edge of the room which are hard to spot.

The third number is found on the western section of the second floor. The player must add the combined amount of blue Banora apples and blue cans, ignoring the green Potions.

The fourth number is found through the keyhole of the west room on the first floor. The player must count the chairs.

The safe is found on the western section of the second floor. Enter the digits into the safe, and a Cactuar will jump out the safe and run out the room. From the safe the player obtains a mastered Vital Slash materia. After this, the player can return to the boy to be told about the fifth wonder. However, the player cannot complete the wonder at this point in the game.

Did you know there are caverns underneath Shinra Manor?

Well, you can hear these bloodcurdling moans coming from deep within.

To get down there, you have to use these secret stairs from the second floor of the mansion.

They say a SOLDIER guy called Sephiroth has the key.

Later in the game, when the player has to access the Underground Caves area, a number of single Sahagins can be fought. After winning each battle, the player will get one Coffin Key. The player can repeatedly fight the Sahagin for more Coffin Keys. At the bottom of the ladder, the player can go through the door in the south eastern room, and open the coffin on the right unveiling a sleeping man. After this, head back out to the boy who will start the sixth wonder.

It's a legend that talks about a "treasure within flames."

The sixth wonder plays out when the town is in flames. The player talks to the boy who tells Zack to save his mother. The player has a minute to do this and he is watched as from a third-person view outside the house. The boy gives the player ATK Up++ for this.

If the player did the previous six wonders, in Chapter 10, they can head to the northeast area of the Nibelheim outskirts, and check the fence near the south side of the houses for a Wall Materia.

Sniper minigame Edit

The sniper minigame involves sniping a number of Shinra's robots in the Nibel Plains. Either side of the road, robots appear that the player has to snipe with the sniper rifles on the ground. Missing causes the enemy to escape, and a unit is added to the "FLED" counter. For every kill, a unit is added to the "KILL" counter. Points on the KILL counter can be used to purchase upgrades.

There are four types of upgrade. Attack Power Up, Steady Aim, and Wide Target all cost three points per upgrade, with a max level of ten. Smart Bomb is six points, but only one can be bought per sniper rifle.

Eighteen different robots exist in the minigame, sixteen with 2,000 HP, two with more. GH-WEDGE has 7,777 HP, and GH-BIGGS has 9,999 HP.

Where an enemy is hit changes the damage done. A headshot is 2,000 HP, the body is 400, legs are 150, and shield is 10.

The first sniper rifle is used to take out GH-77D. The second sniper rifle is used to take out GH-R2.

Between the second and third sniper there is a battle against Alert Heads. Each one counts as an extra KILL point. If the player backs out of the area and then re-enters, another battle will spawn, and the player can get more points. This is a quick way to max-out the sniper rifle early on in the minigame. If an enemy escapes from the battle however, it counts as an extra FLED point.

The third sniper rifle is used to take out GH-PIET on the left, and GH-MOD7 on the right. Another enemy encounter is also between the third and forth. On the forth, the easiest method for the player is to take out GH-GROBE on the right first, then GH-AMBUS on the left, then the remaining GH-BISCN in the center. Between the forth and the fifth is another encounter. If the player shoots the barrel with the next sniper rifle, they will destroy GH-999, GH-66DH, and GH-1138D.

The enemies on the sixth sniper are GH-BIGGS and GH-WEDGE. Three headshots will defeat GH-WEDGE on the left, and launching a Smart Bomb on GH-BIGGS will clear this area. There are a number of encounters between the two snipers. On the seventh sniper, quickly shoot GH-NOMA6 and GH-RACAM. On the final sniper, shoot the barrel next to GH-DATTO, then quickly take out GH-LETTY and GH-JASH.

In the area with the save point will be a number of chests with the player's prize. If eleven or more escaped, the player receives nothing. If ten or less, the player gets a Thundaga. If five or less, the player also gets a Dash. If two or less, the player gets a Gravity. If none escaped, the player gets all the aforementioned materia and a Dragon Armlet.

Shops Edit

Trouble with the audio sample?

When Nibelheim is first visited in Cloud's flashback, the song "On That Day, 5 Years Ago" ( 5??????. Gonen Mae no ano Hi ? ) plays. When the party later visits the town, the background music changes to "Heart of Anxiety" ( ????. Fuan na Kokoro ? ). Inside the Shinra Mansion, the background music switches to "Those Chosen by the Planet" ( ???????. Hoshi ni Erabareshi Mono ? ). Inside the basement the music turns to "The Nightmare Begins" ( ??????. Akumu no Hajimari ? ).

In Dirge of Cerberus - Final Fantasy VII - . the only piece that plays through the sewers and Shinra Manor is "Uneasy Feelings". "Memories with Lucrecia" plays in Vincent's flashback cutscene upon exiting of the sewers, and this also plays in the scenes after entry to the mansion in addition to "Lifestream", itself based upon "Memories with Lucrecia". In the two scenes with Rosso the Crimson. "Rosso the Crimson" plays. "Arms of Shinra" plays against the Black Widow.

In Crisis Core - Final Fantasy VII - . the track that plays in Nibelheim including its outskirts during Chapter 9 is called "A Closed Off Village", a rendition of "Heart of Anxiety". In Shinra Manor, "The Gloomy Mansion" plays, which is an eerie version of one of the recurring melodies, notable in "Burden of Truth". During a Nibelheim in flames, the piece played in the background is "March on the Frontier". In Chapter 10, "The Gloomy Mansion" plays in the Shinra Manor including through battles. In the outskirts "A Closed Off Village" plays, and into the main part of town until it switches to "Chaotic Battlefield". Beyond this the "Night of Seclusion" piece is the only music to play except for Zack's flashback to Aerith where "A Flower Blooming in the Slums" plays. In the Nibel plains where "Moonlight Wandering" is the background music.

Gallery Edit

Etymology Edit

The name Nibelheim is based on Niflheim. [view   · edit   · purge ] Niflheim. also called Niflheimr, is a location in Norse Mythology meaning "mist world". In the story of Gylfaginning . Odin explains that creation began when the ice of Niflheimr met the flames of Muspelheim. Nibelheim is literally translated as "fog-home" in German. "Nibel" is an old-fashioned way to pronounce "Nebel", the German word for "fog", but can also be translated as "cloud" resulting in "cloud home". This is implicitly suggested by being the home of the protagonist, Cloud.

Trivia Edit



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