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| Andreysito | Дата: Четверг, 06.03.2014, 06:22 | Сообщение # 3286 | |
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| tcsgroupk | Дата: Понедельник, 17.03.2014, 06:39 | Сообщение # 3287 | |
| GW501516 (also known as GW-501,516, GW1516, GSK-516 and Endurobol[2 - ) is a PPARδ receptor agonist that was previously investigated for tranquillizer use past GlaxoSmithKline. The narcotize was discovered to cause cancer in rats and GlaxoSmithKline has ceased development.[3 - [4 - It activates the same pathways activated including exercise, including PPARδ and AMP-activated protein kinase. It had been investigated as a developing treatment for bulk, diabetes, dyslipidemia and cardiovascular disease.[5 - [6 - GW501516 has a synergistic effect when combined with AICAR: the grouping has been shown to significantly multiply bring to bear stick-to-it-iveness in bestial studies more than either blend alone.[7 - [8 -
Report
GW501516 was initially discovered during a research collaboration between GSK and Ligand Pharmaceuticals that began in 1992.[9 - R & D Cynosure clear Medicine Expos?reported that GSK began step I trials of the formulate an eye to the treatment of hyperlipidemia in 2000[10 - followed by angle I/II in 2002.[11 - The finding of the blend was published in a 2001 issue of PNAS.[12 - Oliver et al. reported that they familiar "combinatorial chemistry and structure-based dope block out" to exploit it.[13 - Anecdote of the authors was the son of Leo Sternbachwho discovered benzodiazepines in the 1960s.[14 - In 2003, Ligand Pharmaceuticals earned a $1 million payment as a result of GSK continuing off I development.[15 -
GW501516 had completed two status II clinical studies but GSK reprobate remote circumstance of the benumb in 2007 in the interest reasons which where not disclosed as of 2008.[16 -
Ronald M. Evans from the Salk Institute wishes to create the "first-ever performance-enhancing poison that can radically boost medical man patience in humans". In 2004 he had showed that mice genetically engineered to disclose PPARδ in muscle cells had greater endurance. He called the mice "marathon mice".[17 - [18 - He purchased a representation of GW501516 and gave mice a much higher prescribe than had been in dig into beside GSK and create that the blend increased the tolerance of the mice. The up on culminated in a 2007 thesis inCell that was considerably reported in the predominating newspapermen including The Unfamiliar York Times and The Obstacle Street Journal.[17 -
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| fmyykjn | Дата: Пятница, 21.03.2014, 05:15 | Сообщение # 3288 | |
| Tacrolimus (also FK-506 or fujimycin, selling names Prograf, Advagraf, Protopic) is an immunosuppressive stimulant that is on the whole acclimatized after allogeneic unit transplant to reduce the vocation of the passive's exempt method and so lower the gamble of tool rejection. It is also occupied in a topical preparation in the treatment of atopic dermatitis (eczema), dictatorial refractory uveitis after bone marrow transplants, exacerbations of tiniest change complaint, and the skin condition vitiligo.
It is a 23-membered macrolide lactone discovered in 1984 from the fermentation consomm?of a Japanese befoul sampling that contained the bacteria Streptomyces tsukubaensis. It reduces interleukin-2 (IL-2) production beside T-cells.
Yesteryear
Tacrolimus was discovered in 1984; it was middle the prime macrolide immunosuppressants discovered, preceded at near the development of rapamycin (sirolimus) on Rapa Nui (Easter Island) in 1975.[1 - It is produced by a type of stain bacterium,Streptomyces tsukubaensis.[2 - The high regard tacrolimus is derived from 'Tsukuba macrolide immunosuppressant'.[3 -
Tacrolimus was first approved via the Comestibles and Downer Superintendence (FDA) in 1994 for utilization in liver transplantation; this has been extended to include kidney, middle, reduced bowel, pancreas, lung, trachea, pellicle, cornea, bone marrow, and limb transplants.
Availability
The branded variation of the medicate is owned next to Astellas Pharma, and is sold under the vocation names Prograf assumption twice ordinary,Advagraf, a unceasing launch formulation allowing once constantly dosing, and Protopic (Eczemus in Pakistan past Brookes Pharma), the timely formulation.[4 - Advagraf is handy in 0.5, 1, 3 and 5 mg capsules, the not bad 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 rank in blood levels compared to twice-daily tacrolimus.[5 - Statistics from the premier Configuration 3 contest in reasonable kidney shift patients showed that this once-daily formulation was non-inferior in efficacy and safety compared to twice-daily tacrolimus.[6 - A aid Condition 3 litigation in de novo patients is ongoing.[7 -
Mechanism of encounter
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 turn on calcineurin. Calcineurin then dephosphorylates the transcription constituent NF-AT (atomic part of activated T-cells), which moves to the core of the T-cell and increases the motion of genes coding for IL-2 and tied up cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.[8 - In charge, Tacrolimus reduces peptidyl-prolyl isomerase vocation by binding to the immunophilin FKBP12 (FK506 binding protein) creating a up to date complex. This FKBP12-FK506 complex interacts with and inhibits calcineurin and so inhibiting both T-lymphocytesignal transduction and IL-2 transcription.[9 - Although this activity is similar to ciclosporin, studies from shown that the degree of dangerous also brush is reduced about tacrolimus use done with ciclosporin.[10 - Although short-term immunosuppression anent acquiescent and shoot survival is found to be similar between the two drugs, tacrolimus results in a more favorable lipid good, and this may have substantial long-term implications foreordained the prognostic act upon of also brush on corruption survival.[11 -
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| vitaliikEi | Дата: Вторник, 08.04.2014, 14:26 | Сообщение # 3289 | |
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