Respect for human subject

Social value Scientific validity Fair subject selection Informed consent Favorable risk-benefit ratio Independent review Respect for human subjects... 

Regulatory authorities stipulate the need for ethical principles to be observed when conducting clinical trials. Clinical trials should never be conducted to gain knowledge per se. They should be based on risk-benefit considerations, informed consent, and respect for human individuals. Furthermore, subjects should be protected without being taken advantage of. 

In the United States it was as a direct result of the revelation of the Tuskegee Syphilis Study that the next U.S. medical ethics initiative emerged. The National Research Act of 1974 was passed (Public Law 93348), which required regulatory protection for human subjects and created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. In 1979 this commission produced the Belmont Report, named after the Smithsonian Institution s Conference Center, where the discussions were first held in 1976. The report established three ethical principles to allow problems to be solved in the area of ethics in clinical research (1) respect for persons, (2) beneficence, and (3) justice. In general terms, these categories were equivalent to informed consent, risk-benefit assessment, and an appropriate choice of subjects for the research. 

Since the main subject of this review is controversial, we hasten to emphasize that the views presented here are less than objective. The reader has the perfect right to weigh the evidence differently or invoke evidence unknown to this reviewer and reach a radically different point of view. After all, Nature has no respect for human intelligence. It should not surprise us if different interactions may play the dominant role in different, albeit very similar substances. What is also likely is that some new mechanism may be found some day that explains everything or produces more confusion. The only safe conclusion one can draw at this point is that the field is still wide open. 

The absolute quantity of an enzyme reflects the net balance between enzyme synthesis and enzyme degradation, where 4 and represent the rate constants for the overall processes of synthesis and degradation, respectively. Changes in both the 4 and of specific enzymes occur in human subjects. 

Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Some research populations are vulnerable and need special protection. The particular needs of the economically and medically disadvantaged must be recognized. Special attention is also required for those who cannot give or refuse consent for themselves, for those who may be subject to giving consent under duress, for those who will not benefit personally from the research, and for those for whom the research is combined with care. 

The pharmacokinetics of hypericin and pseudohypericin piasma have been studied as weii (Brockmoiier et ai. 1997). Human subjects receiving piacebo, or 900, 1800, or 3600 mg of a standardized hypericum extract (LI 160), which contained 0, 2.81, 5.62, and 11.25 mg of totai hypericin and pseudohypericin, achieved maximum total plasma concentrations at 4 hours (0.028, 0.061, and 0.159 mg/L, respectively). The half-lives of absorption, distribution, and elimination were 0.6, 6.0, and 43.1 hours, respectively, using 750 pg of hypericin, and are slightly different for 1578 pg of pseudohypericin (1.3, 1.4, and 24.8 hours, respectively) (Kerb et ai. 1996). The systemic availability of the hypericum extract LI 160 is between 14 and 21%. Comparable results are found in another study using LI 160 (Staffeldt et ai. 1994). Long-term dosing of 3 x 300 mg per day showed that steady-state levels of hypericin are reached after 4 days. 

Toxicokinetic studies in humans have demonstrated that coumarin is rapidly absorbed from the gastrointestinal tract after oral administration and extensively metabolized by the liver in the first pass, with only 2-6% reaching the systemic circulation intact (Ritschel etal., 1977, 1979 Ritschel Hofimann, 1981).The elimination of coumarin from the systemic circulation is rapid, the half-lives following intravenous doses of 0.125, 0.2 and 0.25 mg/kg bw being 1.82, 1.46 and 1.49 h [109, 88 and 89 min], respectively (Ritschel et a/., 1976). Coumarin is also extensively absorbed after dermal application. In one study with human subjects, some 60% of a 2.0-mg dose applied for 6 h was absorbed (reviewed in Lake, 1999). The percutaneous absorption of coumarin has also been demonstrated in vitro with human skin (Beckley-Kartey et al, 1997 Yourick Bronaugh, 1997). 

---