The gains made by athletes in uncontrolled observations have been much more impressive. Weight gains of thirty or forty pounds, coupled with thirty percent increases in strength, are not unusual. Such case studies lack credibility because of the absence of scientific controls. However, it would be foolish to completely disregard such observations because the "subjects" have been highly trained and motivated see the articles on pharmacology of sport and sports medicine in the countries of the former Soviet Union for more information on anabolic steroids.
Contrary to ciclosporin and tacrolimus, drugs that affect the first phase of T lymphocyte activation, sirolimus affects the second phase, namely signal transduction and lymphocyte clonal proliferation. It binds to FKBP1A like tacrolimus, however the complex does not inhibit calcineurin but another protein, mTOR . Therefore, sirolimus acts synergistically with ciclosporin and, in combination with other immunosuppressants, has few side effects. Also, it indirectly inhibits several T lymphocyte-specific kinases and phosphatases, hence preventing their transition from G 1 to S phase of the cell cycle. In a similar manner, Sirolimus prevents B cell differentiation into plasma cells, reducing production of IgM, IgG, and IgA antibodies.
Transdermal patches (adhesive patches placed on the skin) may also be used to deliver a steady dose through the skin and into the bloodstream. Testosterone-containing creams and gels that are applied daily to the skin are also available, but absorption is inefficient (roughly 10%, varying between individuals) and these treatments tend to be more expensive. Individuals who are especially physically active and/or bathe often may not be good candidates, since the medication can be washed off and may take up to six hours to be fully absorbed. There is also the risk that an intimate partner or child may come in contact with the application site and inadvertently dose himself or herself; children and women are highly sensitive to testosterone and can suffer unintended masculinization and health effects, even from small doses. Injection is the most common method used by individuals administering AAS for non-medical purposes.