Chemical and biological characterization and clinical evaluation of botanical dietary supplements: a phase I red clover extract as a model.

Botanical dietary supplements, as compared with nutritional supplements or single-component pharmaceutical drugs, are typically less-refined preparations derived from bulk plant material and, as such, require a modified approach to their development, production, and evaluation. An integrated, multidisciplinary team of scientific and clinical investigators is required in order to develop high quality phytomedicines and rigorously evaluate their safety and efficacy. Research on botanicals involves unique challenges as plant source materials frequently vary in chemical content and may contain unwanted pesticides, heavy metals, contaminant plant species, or other adulterants. Ideally, a botanical formulation should be standardized, both chemically and biologically, by a combination of analytical techniques and bioassays. This combination approach provides multiple measures by which reproducible quality and efficacy of botanical supplements may be achieved, and is particularly useful for botanical products for which the active compound(s) have not yet been identified. Safety and toxicity should be evaluated during the supplement development process in both in vitro and in vivo systems. A number of liquid chromatography-mass spectrometry methods can aid in the assessment of purity, bioavailability, toxicity, metabolism, and molecular target profiling of botanical extracts. Clinical investigators must appreciate the complexity of multi-component phytomedicines and adjust trial protocols accordingly. This review highlights practical considerations of value to basic science and clinical investigators engaged in the study of botanical supplements. Lessons and examples are drawn from the authors' experience in designing and developing a red clover (Trifolium pratense L.) standardized extract for evaluation in Phase I and Phase II clinical trials.

Aircraft and runway deicers at General Mitchell International Airport, Milwaukee, Wisconsin, USA. 1. Biochemical oxygen demand and dissolved oxygen in receiving streams.

Aircraft and runway deicers are used during cold weather at many of the world's airports to facilitate safe air travel. Propylene glycol-, ethylene glycol-, and urea-based deicers are known to have very high biochemical oxygen demand. At General Mitchell International Airport (GMIA) in Milwaukee, Wisconsin, USA, deicer application, water chemistry, and dissolved oxygen (DO) data were collected for two deicing seasons in order to evaluate and define premanagement water quality parameters prior to the implementation of a glycol management program. Calculations using stream-monitoring data during a controlled release of deicer provided an estimate of 0.8/d for the first-order decay rate constant, substantially higher than published laboratory test results. For eight precipitation events with deicing activities, between 2.4 and 99% of propylene and ethylene glycol applied to aircraft was delivered directly to receiving streams. The percentage of glycol runoff during an event increased with increasing storm-flow volume. Elevated concentrations of glycol and biochemical oxygen demand were measured downstream from the airport. However, the frequency of low DO concentrations in the receiving streams is comparable with that at an upstream reference site. This is possibly due to slowed bacteria metabolism at low water temperatures, short travel times, and dilution from downstream tributaries.