Unexpected metabolites produced from clomethiazole

The heterocyclic drug clomethiazole is metabolized by body passage partly to small aliphatic molecules. The occurrence of such unexpected metabolites is usually overlooked. An appropriate method for their detection is the comparison of urine profiles during drug intake and after withdrawal of the drug.     

Effect of elevating serum lipids on luteinizing hormone response to gonadotrophin releasing hormone challenge in energy-deficient anestrous heifers

A study was conducted to evaluate the effect of feeding a bypass fat on luteinizing hormone (LH) response to gonadotrophin releasing hormone (GnRH) in noncyclic Holstein heifers. Twelve cyclic Holstein heifers were fed a complete diet at 40% net energy for maintenance (NE(m)) until cessation of ovarian activity. Based on weights and condition scores, heifers were assigned to either a control or treatment diet containing 0.45 kg bypass fat and fed at an energy level of 85% NE(m). Diet adjustments were made following weekly weighings. GnRH challenges were conducted at four periods: prior to initial energy deprivation, at termination of 40% NE(m) feeding, and twice more at 21-d intervals after 85% NE(m) feeding began. Blood was sampled via a jugular catheter every 15 min for 5 h, and GnRH was injected after the fourth sample. None of the heifers exhibited estrous activity after the initial energy deprivation. Heifers on the bypass fat diet continued to lose weight during the treatment period, while the control heifers gained a slight amount of weight. Baseline and peak concentrations of LH were not significantly affected by time or diet. Time to GnRH-induced LH peak was longer (53 vs 130 min, P < 0.01) after 40% NE(m) and remained greater at all times thereafter. Serum lipid levels increased 82.5% among heifers being fed the bypass fat. Energy restriction had no effect on the magnitude of LH response to GnRH but did delay response time.     

Differential response of stress fibers and myofibrils to gelsolin

The actin-severing activity of human platelet gelsolin was analyzed on embryonic skeletal and cardiac myofibrils, and on stress fibers in non-muscle cells. These subcellular structures, although in all three cell types composed of contractile proteins arranged in sarcomeric units, were found to respond differently to gelsolin. The myofibrils in permeabilized myotubes or cardiac cells, as well as in living, microinjected muscle cells proved resistant to a wide concentration range of gelsolin. The same was found for the "mini-sarcomeres" which are seen in developing muscle cells. In contrast, stress fibers in microinjected fibroblasts or epithelial cells, as well as in permeabilized cells, were broken down rapidly by the platelet gelsolin. We conclude from these results that the mini-sarcomeres in embryonic myotubes and cardiac myocytes are not identical with stress fibers.