Effect of fenfluramine on food intake, mood, and performance of humans living in a residential laboratory

Five male and four female normal weight research volunteers, participating in 13-day residential studies, received oral fenfluramine (20, 40 mg) or placebo at 09:30 and 17:00. Food intake, performance, and subjective ratings were measured throughout the day. Carbohydrate intake was manipulated by providing lunch meals high (males: 120 g; females: 80 g) or low (males: 25 g; females: 16 g) in carbohydrate on 8 days; on the remaining days subjects self-selected lunch. Total caloric intake (approximately 2800 Kcal) did not differ among the low- and high-carbohydrate, and self-selected lunch conditions when subjects received placebo, indicating caloric compensation. Total carbohydrate intake was significantly less, however, when subjects consumed the low-carbohydrate lunch compared to the other lunch conditions. Fenfluramine significantly decreased total caloric intake (approximately 500 kcal) by decreasing meal size, not number, only when subjects consumed the low-carbohydrate lunch. Fenfluramine was only an effective anorectic drug when subjects consumed a lunch with fewer calories and a lower carbohydrate:protein ratio than self-selected baseline. Also, fenfluramine improved performance on a range of computer tasks and increased ratings of "Alert," "Friendly," and "Talkative," while decreasing ratings of "Tired" and "Irritable."     

The angle between the anticodon and aminoacyl acceptor stems of yeast tRNA(Phe) is strongly modulated by magnesium ions

Many tRNAs undergo tertiary folding transitions at temperatures well below the main thermally induced (hyperchromic) transition. Such transitions are essentially isochromic and isoenthalpic and display an absolute requirement for divalent cations; however, the nature of the structural transition is not known for any tRNA. Using a combination of transient electric birefringence (TEB) and gel electrophoretic measurements, we have characterized the influence of magnesium ions on the apparent angle between the anticodon and acceptor stems of a yeast tRNA(Phe) construct. TEB is a particularly sensitive method for quantifying the bends introduced in RNA by various nonhelix elements. In the current instance, the tRNA construct comprises an unmodified tRNA(Phe) molecule in which the anticodon and acceptor stems have been extended by approximately 70 bp to more effectively "report" the interstem angles. Upon the addition of sub-millimolar concentrations of magnesium ions, the tRNA core undergoes a substantial rearrangement in tertiary structure, passing from an open form with an apparent interstem angle of approximately 150 degrees to a conformation with an interstem angle of approximately 70 degrees (200 microM Mg2+). Further addition of magnesium ions results in a minor adjustment of the apparent interstem angle to approximately 80-90 degrees, in line with earlier results. Finally, the magnesium-induced structural transition is essentially isochromic, in agreement with previous observations with native tRNAs. The current results suggest that changes in local divalent ion concentration in the ribosome could profoundly affect the global conformations of tRNAs during the translation cycle.     

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study

Normal women produce small amounts of active androgens. When androgen levels are elevated, such as for example in the polycystic ovary syndrome, this is followed by the development of male physical characteristics and muscle mass, structure and function as well as android adipose tissue distribution and function. Psychological features and stress reactions also seem similar to those of men. Such women have an increased risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular disease. Recent data have shown that these physical, and psychological characteristics, as well as risk of ill health, are also found in the population of women selected at random. Women in the lowest quintiles of levels of sex-hormone-binding globulin--an indicator inversely related to active androgens--are at risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular mortality. The mechanism probably includes muscular insulin resistance, following a relative androgen excess. It is thus apparent that androgens, even within the highest levels of the nonselected population of women, are powerful predictors of serious disease development. The population at risk might be as large as about 20% of middle-aged women. This is an area of female disease risk which requires more attention in screening and intervention procedures.     

Stereochemical influence on the stability of radio-metal complexes in vivo. Synthesis and evaluation of the four stereoisomers of 2-(p-nitrobenzyl)-trans-CyDTPA

Distinct differences in in vivo stability of the two diastereomeric C-Functionalized CyDTPA chelating agents, (CHX-A DTPA and CHX-B DTPA, both racemates), as recently reported prompted further investigation as to why differences in configuration produced striking effects on the in vivo stability of their yttrium complexes. To this end, the four individual component stereoisomers of CHX-A and CHX-B were synthesized and ability to bind yttrium was investigated both in vitro and in vivo.