Orexin depolarizes rat hypothalamic paraventricular nucleus neurons

Orexins, also called hypocretins, are newly discovered hypothalamic peptides that are thought to be involved in various physiological functions. In spite of the fact that orexin receptors, especially orexin receptor 2, are abundant in the hypothalamic paraventricular nucleus (PVN), the effects of orexins on PVN neurons remain unknown. Using a whole cell patch-clamp recording technique, we investigated the effects of orexin-B on PVN neurons of rat brain slices. Bath application of orexin-B (0.01-1.0 microM) depolarized 80.8% of type 1 (n = 26) and 79.2% of type 2 neurons tested (n = 24) in the PVN in a concentration-dependent manner. The effects of orexin-B persisted in the presence of TTX (1 microM), indicating that these depolarizing effects were generated postsynaptically. Addition of Cd(2+) (1 mM) to artificial cerebrospinal fluid containing TTX (1 microM) significantly reduced the depolarizing effect in type 2 neurons. These results suggest that orexin-B has excitatory effects on the PVN neurons mediated via a depolarization of the membrane potential.     

Lipase-catalyzed synthesis of capsaicin analogs by transacylation of capsaicin with natural oils or fatty acid derivatives in n-hexane

Transacylation of capsaicin with triolein using a commercial lipase gave olvanil in an 85% yield at 70°C for 144 h. When olive oil was employed, the major product was olvanil (62%). Safflower oil gave a mixture of olvanil (39%) and linoleoyl vanillylamide (32%). Perilla oil gave linolenoyl vanillylamide (13%). Myristic acid and its methyl ester could be used as an acyl donor, and myristoyl vanillylamide was obtained in 20–78% using several lipases.     

Purification and characterization of an extremely thermostable cyclomaltodextrin glucanotransferase from a newly isolated hyperthermophilic archaeon, a Thermococcus sp

The extremely thermophilic anaerobic archaeon strain B1001 was isolated from a hot-spring environment in Japan. The cells were irregular cocci, 0.5 to 1.0 micrometers in diameter. The new isolate grew at temperatures between 60 and 95 degrees C (optimum, 85 degrees C), from pH 5.0 to 9.0 (optimum, pH 7.0), and from 1.0 to 6.0% NaCl (optimum, 2.0%). The G+C content of the genomic DNA was 43.0 mol%. The 16S rRNA gene sequencing of strain B1001 indicated that it belongs to the genus Thermococcus. During growth on starch, the strain produced a thermostable cyclomaltodextrin glucanotransferase (CGTase). The enzyme was purified 1,750-fold, and the molecular mass was determined to be 83 kDa by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Incubation at 120 degrees C with SDS and 2-mercaptoethanol was required for complete unfolding. The optimum temperatures for starch-degrading activity and cyclodextrin synthesis activity were 110 and 90 to 100 degrees C, respectively. The optimum pH for enzyme activity was pH 5.0 to 5.5. At pH 5.0, the half-life of the enzyme was 40 min at 110 degrees C. The enzyme formed mainly alpha-cyclodextrin with small amounts of beta- and gamma-cyclodextrins from starch. This is the first report on the presence of the extremely thermostable CGTase from hyperthermophilic archaea.     

Neuronal effects of orexins: relevant to sympathetic and cardiovascular functions

Orexin A and B, also called hypocretin 1 and 2, were recently discovered in the hypothalamus. This organ, in which a number of neuropeptides have been demonstrated to stimulate or suppress food intake, is considered important for the regulation of appetite and energy homeostasis. Orexins were initially reported as a regulator of food intake. More recent reports suggest their possible important roles in the multiple functions of neuronal systems, such as narcolepsy, a sleep disorder. Orexins and their receptors are distributed in neural tissue and brain regions involved in the autonomic and neuroendocrine control. Functional studies have shown that these peptides evoke changes in cardiovascular and sympathetic responses. The data from our in vivo and in vitro studies suggest that the peptide acting on neurons in the hypothalamic paraventricular nucleus increases the cardiovascular responses. This review will focus on the neural effects of orexins and how these peptides may participate in the regulation of cardiovascular and sympathetic functions.     

The effects of maternal mild protein restriction on stroke incidence and blood pressure in stroke-prone spontaneously hypertensive rats (SHRSP)

The effect of maternal protein restriction during pregnancy on the offspring's blood pressure was assessed in stroke-prone spontaneously hypertensive rats (SHRSP) which are genetically predisposed to hypertension and stroke. After the confirmation of pregnancy, the control group was given a 20% casein diet, and the low-protein group was fed a 9% casein diet. After the confirmation of delivery, commercial feed was given to both of the groups. No differences were seen between the control and low-protein offspring in regard to body weight, blood pressure elevation, or life span. One percent saline solution was put in the control and low-protein groups after the age of 11 weeks. Blood pressure increased markedly in the low-protein group, on the blood pressure level in the low-protein group on week 2 after salt loading (242+/-6 mmHg) was significantly higher than that in the control group (223+/-9 mmHg; p<0.05). The survival duration was significantly shorter in the low-protein group (113+/-4 days) than in the control group (135+/-22 days; p<0.05). These results suggest that maternal protein malnutrition in SHRSP exerted a high salt sensitivity and a malignant influence on stroke incidence on offspring.     

Effect of royal jelly on bisphenol A-induced proliferation of human breast cancer cells

Royal jelly is known as a functional food containing many useful minerals. In this study, we found an anti-environmental estrogen activity of royal jelly. Bisphenol A (BPA) is an environmental estrogen that stimulates proliferation of human breast cancer MCF-7 cells. Royal jelly inhibited the growth-promoting effect of BPA on MCF-7 cells, even though it did not affect the proliferation of cells in the absence of BPA. In addition, this inhibiting effect of royal jelly was heat-stable.     

Design and synthesis of highly potent and selective human peroxisome proliferator-activated receptor alpha agonists

A combination of benzoxazole, phenoxyalkyl side chain, and phenoxybutyric acids was identified as a highly potent and selective human peroxisome proliferator-activated receptor alpha (PPARalpha) agonist. The synthesis, structure-activity relationship (SAR) studies, and in vivo activities of the representative compounds are described.