“
“Metyrapone is a glucocorticoid synthesis inhibitor known to induce a stress-like biological syndrome, but also to limit stress-related behaviours. Since stress is usually associated to an increased locomotion, the aim of the study was to determine whether metyrapone will increase, decrease or respect locomotion. Forty rats were placed in infrared actimeters to study spontaneous locomotion before and after injecting 150 mg kg(-1) of either metyrapone (n = 20) or saline (n = 20). Two hours after injection, half of each treatment group animals were tested in an open field to study test-evoked locomotion. Stress-induced analgesia

was quantified using plantar test just before blood sampling. immediately after injection, metyrapone check details decreased drastically horizontal and vertical locomotion. During the open field test, metyrapone-treated rats remained less active with slower movement execution than saline-treated

rats. Metyrapone did not modify plantar test performances but blunted stress-induced corticosterone and ACTH increases. Mechanisms by which metyrapone induced these effects on locomotion are further discussed. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Transmission of human immunodeficiency virus (HIV) drug resistance is well-recognized and compromises response to first-line therapy. However, the population dynamics of transmitted resistance remains unclear, although previous models have assumed that such transmission reflects direct infection from treated individuals. We investigated whether population-based phylogenetic Dibutyryl-cAMP analyses would 4-Aminobutyrate aminotransferase uncover lineages of resistant viruses circulating in untreated individuals. Through the phylogenetic analysis of 14,061 HIV type 1 (HIV-1) pol gene sequences generated in the United Kingdom from both treatment-naive and -experienced individuals, we identified five treatment-independent viral clusters containing mutations conferring cross-resistance to antiretroviral drugs prescribed today in the United Kingdom.

These viral lineages represent sustainable reservoirs of resistance among new HIV infections, independent of treatment. Dated phylogenies reconstructed through Bayesian Markov chain Monte Carlo inference indicated that these reservoirs originated between 1997 and 2003 and have persisted in the HIV-infected population for up to 8 years. Since our cohort does not represent all infected individuals within the United Kingdom, our results are likely to underestimate the number and size of the resistant reservoirs circulating among drug-naive patients. The existence of sustained reservoirs of resistance in the absence of treatment has the capacity to threaten the long-term efficacy of antiretroviral therapy and suggests there is a limit to the decline of transmitted drug resistance.