Experimentally induced herpesvirus Sa 8 ? Encephalitis in Kenya baboons (Papio cynocephalus)

Herpesvirus SA 8 infections are occurring naturally in African green monkeys and baboons. Neither the clinical nor the morphological sequelae of SA 8 infections in homologous or heterologous hosts are sufficiently known. Therefore, colony-born baboons of three age groups were inoculated intravenously or intratracheally, using a SA 8 strain (strain 0430) isolated from fatally infected newborn baboons. Of all experimental animals, 63% developed focal encephalitis, characterized predominantly by glial nodule formation and necrosis of nerve and glial cells. Early stages of the infection (2–5 days after infection) were accompanied by inclusion body formation or by eosinophilic nerve cell degeneration. The distribution of the CNS lesions depended largely on the inoculation route. In intravenously inoculated newborn baboons, the inflammatory foci were scattered throughout the entire brain and spinal cord, including the leptomeninges, whereas these lesions were focused on the vagal root areas within the medulla oblongata in the intratracheally inoculated animals of all age groups. In the intratracheally infected animals corresponding herpetic lesions were also commonly found in pulmonary ganglia or pulmonary vagal branches. The possible vagal ascendance of herpesvirus SA 8 from the primarily affected lung to the brain in intratracheally inoculated animals is discussed

Novos sedativos hipnóticos The newer sedative-hypnotics

Nas últimas décadas houve um esforço para o desenvolvimento de hipnóticos mais seguros e eficazes. Zolpidem, zaleplona, zopiclona, eszopiclona (drogas-z) e indiplona são moduladores do receptor GABA-A, os quais agem de forma seletiva na subunidade &#945;1, exibindo, desta forma, mecanismos similares de ação, embora evidências recentes sugiram que a eszopiclona não seja tão seletiva para a subunidade &#945;1 quanto o zolpidem. Ramelteon e tasimelteon são novos agentes crono-hipnóticos seletivos para os receptores de melatonina MT1 e MT2. Por outro lado, nos últimos anos, o consumo de drogas antidepressivas sedativas tem aumentado significativamente no tratamento da insônia. Como droga experimental, a eplivanserina tem sido testada como um potente agonista inverso do subtipo 5-HT2A da serotonina, com um uso potencial na dificuldade da manutenção do sono. Outro agente farmacológico para o tratamento da insônia é o almorexant, o qual apresenta um novo mecanismo de ação envolvendo antagonismo do sistema hipocretinérgico, desta forma levando à indução do sono. Finalmente, também discutiremos o potencial papel de outras drogas gabaérgicas no tratamento da insônia.<br>There has been a search for more effective and safe hypnotic drugs in the last decades. Zolpidem, zaleplon, zopiclone, eszopiclone (the z-drugs) and indiplon are GABA-A modulators which bind selectively &#945;1 subunits, thus, exhibiting similar mechanisms of action, although recent evidence suggests that eszopiclone is not as selective for &#945;1 subunit as zolpidem is. Ramelteon and tasimelteon are new chrono-hypnotic agents, selective for melatonin MT1 and MT2 receptors. On the other hand, the consumption of sedative antidepressant drugs is significantly increasing for the treatment of insomnia, in the last years. As an experimental drug, eplivanserin is being tested as a potent antagonist of serotonin 2-A receptors (ASTAR) with a potential use in sleep maintenance difficulty. Another recent pharmacological agent for insomnia is almorexant, which new mechanism of action involves antagonism of hypocretinergic system, thus inducing sleep. Finally we also discuss the potential role of other gabaergic drugs for insomnia

Natural and laboratory mutations in kuzbanian are associated with zinc stress phenotypes in Drosophila melanogaster

Organisms must cope with altered environmental conditions such as high concentrations of heavy metals. Stress response to heavy metals is mediated by the metal-responsive transcription factor 1 (MTF-1), which is conserved from Drosophila to humans. MTF-1 binds to metal response elements (MREs) and changes the expression of target genes. kuzbanian (kuz), a metalloendopeptidase that activates the evolutionary conserved Notch signaling pathway, has been identified as an MTF-1 target gene. We have previously identified a putatively adaptive transposable element in the Drosophila melanogaster genome, named FBti0019170, inserted in a kuz intron. In this work, we investigated whether a laboratory mutant stock overexpressing kuz is associated with zinc stress phenotypes. We found that both embryos and adult flies overexpressing kuz are more tolerant to zinc compared with wild-type flies. On the other hand, we found that the effect of FBti0019170 on zinc stress tolerance depends on developmental stage and genetic background. Moreover, in the majority of the genetic backgrounds analyzed, FBti0019170 has a deleterious effect in unpolluted environments in pre-adult stages. These results highlight the complexity of natural mutations and suggest that besides laboratory mutations, natural mutations should be studied in order to accurately characterize gene function and evolution.H.L.M. was a VAST-CSIC fellow, L.G. was a FI/DGR fellow (2012FI-B-00676) and J.G. is a Ramón y Cajal fellow (RYC-2010-07306). This work was supported by grants from the European Community’s Seven Framework Programme (FP7-PEOPLE-2011-CIG-293860), from the Spanish Government (BFU2011-24397 and BFU2014-57779-P), and from the Generalitat de Catalunya (2014 SGR 201).EUR 1,305 APC fee funded by the EC FP7 Post-Grant Open Access PilotPeer reviewe