However, it is unknown how the circadian system including the suprachiasmatic nucleus

(SCN) and clock genes affects thermoregulation. Food deprivation in mice induces a greater reduction of T(b) particularly in the light phase. We examined the role of Clock, one of key clock genes and the SCN during induced hypothermia. At 20 degrees C with fasting, mice increased their metabolic heat production in the dark phase and maintained T(b), whereas in the light phase, heat production was less, resulting in hypothermia. Under these conditions, neuronal activity in the SCN, assessed by cFos expression, increased only in the light phase. this website However, such differences in thermoregulatory and neural responses between the phases in Clock mutant mice were less marked. The neural network between the SCN and paraventricular nucleus appeared to be important in hypothermia. These findings suggest that the circadian system per se is influenced

by both the feeding condition and environmental temperature and that it modulates thermoregulation. (C) 2009 IBRO. Published by ISRIB molecular weight Elsevier Ltd. All rights reserved.”
“T20 (generic name, enfuvirtide; brand name, Fuzeon) is a first-generation human immunodeficiency virus (HIV) fusion inhibitor approved for salvage therapy of HIV-infected patients refractory to current antiretroviral

drugs. However, its clinical use is limited because of rapid emergence of T20-resistant viruses in T20-treated patients. Therefore, T1249 and T1144 are being developed as the second- and third-generation HIV fusion inhibitors, respectively, with improved efficacy and drug resistance profiles. Here, we found that combinations of T20 with T1249 and/or T1144 resulted in exceptionally potent synergism (combination index, <0.01) against HIV-1-mediated membrane Interleukin-3 receptor fusion by 2 to 3 orders of magnitude in dose reduction. Highly potent synergistic antiviral efficacy was also achieved against infection by laboratory-adapted and primary HIV-1 strains, including T20-resistant variants. The mechanism underlying the synergistic effect could be attributed to the fact that T20, T1249, and T1144 all contain different functional domains and have different primary binding sites in gp41. As such, they may work cooperatively to inhibit gp41 six-helix bundle core formation, thereby suppressing virus-cell fusion. Therefore, these findings strongly imply that, rather than replacing T20, combining it with HIV fusion inhibitors of different generations might produce synergistic activity against both T20-sensitive and -resistant HIV-1 strains, suggesting a new therapeutic strategy for the treatment of HIV-1 infection/AIDS.