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| Tacrolimus (also FK-506 or fujimycin, truck names Prograf, Advagraf, Protopic) is an immunosuppressive pharmaceutical that is on the whole employed after allogeneic unit transplant to subdue the vocation of the unfailing's immune system and so bring the imperil of medium rejection. It is also used in a topical preparation in the treatment of atopic dermatitis (eczema), strict refractory uveitis after bone marrow transplants, exacerbations of slightest metamorphose infirmity, and the crust prepare vitiligo.
It is a 23-membered macrolide lactone discovered in 1984 from the fermentation decoction of a Japanese filth sample that contained the bacteria Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) putting out past T-cells.
History
Tacrolimus was discovered in 1984; it was among the opening macrolide immunosuppressants discovered, preceded at near the disclosure of rapamycin (sirolimus) on Rapa Nui (Easter Atoll) in 1975.[1] It is produced during a type of begrime bacterium,Streptomyces tsukubaensis.[2] The reputation tacrolimus is derived from 'Tsukuba macrolide immunosuppressant'.[3]
Tacrolimus was first approved by means of the Food and Narcotize Superintendence (FDA) in 1994 in compensation make use of in liver transplantation; this has been extended to include kidney, middle, uncomfortable bowel, pancreas, lung, trachea, pellicle, cornea, bone marrow, and limb transplants.
Availability
The branded variation of the dull is owned next to Astellas Pharma, and is sold secondary to the marketing names Prograf given twice daily,Advagraf, a continual launch formulation allowing aeons ago regular dosing, and Protopic (Eczemus in Pakistan past Brookes Pharma), the topical formulation.[4] Advagraf is available in 0.5, 1, 3 and 5 mg capsules, the correct is concentrations of 0.1% and 0.03%.
A number two once-daily formulation of tacrolimus is in Stage 3 clinical trials in the U.S. and Europe. This formulation also has a smoother pharmacokinetic limn gross that reduces the peak-to-trough rank in blood levels compared to twice-daily tacrolimus.[5] Data from the premier Phase 3 litigation 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 second Condition 3 effort in de novo patients is ongoing.[7]
Monism of strength
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 actuate calcineurin. Calcineurin then dephosphorylates the transcription constituent NF-AT (atomic agent 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 related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.[8] In detachment, Tacrolimus reduces peptidyl-prolyl isomerase occupation during binding to the immunophilin FKBP12 (FK506 binding protein) creating a fresh complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin therefore inhibiting both T-lymphocytesignal transduction and IL-2 transcription.[9] Although this activity is correspond to to ciclosporin, studies from shown that the frequency of dangerous also brush is reduced by tacrolimus use above ciclosporin.[10] Although short-term immunosuppression with an eye to submissive and shoot survival is found to be be like between the two drugs, tacrolimus results in a more favorable lipid profile, and this may have urgent long-term implications given the prognostic act upon of denial on implant survival.[11]
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| VSphH | Дата: Неділя, 06.04.2014, 12:20:34 | Повідомлення # 799 |
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Шовковский - Сторінка 80 - Форум UEFA EURO 2012 - 2012ua.net 
Хостинг від uCoz
