Public safety and dietary supplementation.

Approximately 6 in 10 Americans report regularly using some type of dietary supplement, and approximately 1 in 6 Americans reports using herbal remedies on a regular basis. The diversity of manufacturers, manufacturing processes, and quality control issues are enormous. As with all plant products, herbal products are complex mixtures of a variety of chemical constituents with considerable variation in the growth, harvesting, and storage conditions, including different extraction procedures. Furthermore, not only is there variation in batches, but also the potential for contamination. In addition, herbal products have the potential to interact with pharmaceuticals. These problems have led to consumer and physician confusion about the use of herbal products and have not been satisfactorily resolved, because the Food and Drug Administration has only very recently started to fulfill its mission of consumer protection in the realm of dietary supplements. More importantly, we provide a working plan for addressing this important issue.

The history and contemporary challenges of the US Food and Drug Administration.

BACKGROUND: The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. OBJECTIVE: The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. METHODS: Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. RESULTS: The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on pre-market control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. CONCLUSIONS: As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces currently are likely to be overcome only under strong and permanent leadership willing to redefine the role and procedures of the FDA with an open mind.

Thioredoxin-(dithiol-)linked inactivation of elastase.

Following inactivation by the alpha-1-antitrypsin (AAT) inhibitor, the protease elastase was reduced by thioredoxin, itself reduced by NADPH and NADP-thioredoxin reductase (NTR). Under these conditions, reduction of enzyme disulfide groups was accompanied by loss of more than 60% of the activity measured following dissociation of the enzyme-inhibitor complex with NaCl. The inhibitor was required (1) to prevent proteolysis of both reduced thioredoxin and NTR and (2) to assess the progress of the reduction reaction. At elevated temperature, elastase was also reduced by dithiols (dithiothreitol and lipoic acid) but not by monothiols (reduced glutathione, beta-mercaptoethanol). When reduced by dithiols under these conditions, the enzyme digested itself. Self-digestion was independent of the antitrypsin inhibitor and was proportional to temperature in the 37-50 degree C range. These findings open the door to a new mode of regulation of elastase and to possible new therapies for treating diseases associated with the enzyme.