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WilliamMtДата: Пятница, 14.03.2014, 05:46 | Сообщение # 977
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StanleyvexДата: Пятница, 14.03.2014, 09:13 | Сообщение # 978
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ArmandmnДата: Пятница, 14.03.2014, 12:32 | Сообщение # 979
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EvangelinbqoДата: Пятница, 14.03.2014, 15:00 | Сообщение # 980
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tcsindustrywДата: Среда, 19.03.2014, 19:16 | Сообщение # 981
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It is a 23-membered macrolide lactone discovered in 1984 from the fermentation stock of a Japanese filth sample that contained the bacteria Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) making beside T-cells.
Olden days
Tacrolimus was discovered in 1984; it was among the first macrolide immunosuppressants discovered, preceded past the invention of rapamycin (sirolimus) on Rapa Nui (Easter Eyot) in 1975.[1] It is produced on a class of loam bacterium,Streptomyces tsukubaensis.[2] The handle tacrolimus is derived from 'Tsukuba macrolide immunosuppressant'.[3]
Tacrolimus was first approved via the Food and Cure-all Supplying (FDA) in 1994 for the benefit of utilization in liver transplantation; this has been extended to embrace kidney, middle, miniature bowel, pancreas, lung, trachea, skin, cornea, bone marrow, and limb transplants.
The branded manifestation of the medicate is owned by Astellas Pharma, and is sold below the marketing names Prograf noted twice daily,Advagraf, a unceasing releasing formulation allowing once daily dosing, and Protopic (Eczemus in Pakistan on Brookes Pharma), the topical formulation.[4] Advagraf is handy in 0.5, 1, 3 and 5 mg capsules, the ointment is concentrations of 0.1% and 0.03%.
A jiffy once-daily formulation of tacrolimus is in Stage 3 clinical trials in the U.S. and Europe. This formulation also has a smoother pharmacokinetic vigorish that reduces the peak-to-trough range in blood levels compared to twice-daily tacrolimus.[5] Statistics from the primary Configuration 3 contest in reasonable kidney move patients showed that this once-daily formulation was non-inferior in efficacy and sanctuary compared to twice-daily tacrolimus.[6] A aid Juncture 3 trial in de novo patients is ongoing.[7]
Mechanism of vigour
Tacrolimus is chemically known as a macrolide. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription constituent NF-AT (nuclear aspect of activated T-cells), which moves to the focus of the T-cell and increases the undertaking of genes coding in behalf of IL-2 and tied up cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.[8] In detachment, Tacrolimus reduces peptidyl-prolyl isomerase vocation by binding to the immunophilin FKBP12 (FK506 binding protein) creating a fresh complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin thus inhibiting both T-lymphocytesignal transduction and IL-2 transcription.[9] Although this liveliness is alike resemble to ciclosporin, studies have shown that the degree of acute rejection is reduced about tacrolimus utilization from ciclosporin.[10] Although short-term immunosuppression concerning acquiescent and extortion survival is develop to be similar between the two drugs, tacrolimus results in a more favorable lipid portrait, and this may have important long-term implications given the prognostic play of rejection on insert survival.[11]
AndrewMrДата: Вторник, 01.04.2014, 08:13 | Сообщение # 982
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