Clozapine Promotes Glycolysis And Myelin Lipid Synthesis In Cultured Oligodendrocytes.

Clozapine displays stronger systemic metabolic side effects than haloperidol and it has been hypothesized that therapeutic antipsychotic and adverse metabolic effects of these drugs are related. Considering that cerebral disconnectivity through oligodendrocyte dysfunction has been implicated in schizophrenia, it is important to determine the effect of these drugs on oligodendrocyte energy metabolism and myelin lipid production. Effects of clozapine and haloperidol on glucose and myelin lipid metabolism were evaluated and compared in cultured OLN-93 oligodendrocytes. First, glycolytic activity was assessed by measurement of extra- and intracellular glucose and lactate levels. Next, the expression of glucose (GLUT) and monocarboxylate (MCT) transporters was determined after 6 and 24 h. And finally mitochondrial respiration, acetyl-CoA carboxylase, free fatty acids, and expression of the myelin lipid galactocerebroside were analyzed. Both drugs altered oligodendrocyte glucose metabolism, but in opposite directions. Clozapine improved the glucose uptake, production and release of lactate, without altering GLUT and MCT. In contrast, haloperidol led to higher extracellular levels of glucose and lower levels of lactate, suggesting reduced glycolysis. Antipsychotics did not alter significantly the number of functionally intact mitochondria, but clozapine enhanced the efficacy of oxidative phosphorylation and expression of galactocerebroside. Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

Energy of the first excited state of (43)Ar

Results of proton-proton-gamma coincidence measurements using the (36)S+(9)Be reaction revealed a gamma ray of 201.27 +/- 0.16 keV that most probably corresponds to the transition between the predicted 7/2(-) first excited state to the 5/2(-) ground state of (43)Ar.

Ethanol production by a new pentose-fermenting yeast strain, Scheffersomyces stipitis UFMG-IMH 43.2, isolated from the Brazilian forest

The ability of a recently isolated Scheffersomyces stipitis strain (UFMG-IMH 43.2) to produce ethanol from xylose was evaluated. For the assays, a hemicellulosic hydrolysate produced by dilute acid hydrolysis of sugarcane bagasse was used as the fermentation medium. Initially, the necessity of adding nutrients (MgSO(4).7H(2)O, yeast extract and/or urea) to this medium was verified, and the yeast extract supplementation favoured ethanol production by the yeast. Then, in a second stage, assays under different initial xylose and cell concentrations, supplemented or not with yeast extract, were performed. All these three variables showed significant (p < 0.05) influence on ethanol production. The best results (ethanol yield and productivity of 0.19 g/g and 0.13 g/l/h, respectively) were obtained using the hydrolysate containing an initial xylose concentration of 30 g/l, supplemented with 5.0 g/l yeast extract and inoculated with an initial cell concentration of 2.0 g/l. S. stipitis UFMG-IMH 43.2 was demonstrated to be a yeast strain with potential for use in xylose conversion to ethanol. The establishment of the best fermentation conditions was also proved to be of great importance to increasing the product formation by this yeast strain. These findings open up new perspectives for the establishment of a feasible technology for ethanol production from hemicellulosic hydrolysates. Copyright (C) 2011 John Wiley & Sons, Ltd.

Congenital Hyperinsulinism in Brazilian Neonates: A Study of Histology, KATP Channel Genes, and Proliferation of beta Cells

Congenital hyperinsulinism (CHI) is a rare pancreatic beta-cell disease of neonates, characterized by inappropriate insulin secretion with severe persistent hypoglycemia, with regard to which many questions remain to be answered, despite the important acquisition of its molecular mechanisms in the last decade. The aim of this study was to examine pancreatic histology, beta-cell proliferation (immunohistochemistry with double staining for Ki-67/insulin), and beta-cell adenosine triphosphate-sensitive potassium channels genes from 11 Brazilian patients with severe medically unresponsive CHI who underwent pancreatectomy. Pancreatic histology and beta-cell proliferation in CHI patients were compared to pancreatic samples from 19 age-matched controls. Ten cases were classified as diffuse form (D-CHI) and 1 as focal form (F-CHI). beta-cell nucleomegaly and abundant cytoplasm were absent in controls and were observed only in D-CHI patients. The Ki-67 labeling index (Ki-67-LI) was used to differentiate the adenomatous areas of the F-CHI case (10.15%) from the ""loose cluster of islets`` found in 2 D-CHI samples (2.29% and 2.43%) and 1 control (1.54%) sample. The Ki-67-LI was higher in the F-CHI adenomatous areas, but D-CHI patients also had significantly greater Ki-67-LI (mean value = 2.41%) than age-matched controls (mean value = 1.87%) (P = 0.009). In this 1st genetic study of CHI patients in Brazil, no mutations or new polymorphisms were found in the 33-37 exons of the ABCC8 gene (SUR1) or in the entire exon of the KCNJ11 gene (Kir 6.2) in 4 of 4 patients evaluated. On the other hand, enhanced beta-cell proliferation seems to be a constant feature in CHI patients, both in diffuse and focal forms.

Factors Related to the Selection of Surgical Versus Percutaneous Revascularization in Diabetic Patients With Multivessel Coronary Artery Disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) Trial

Objectives We evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial. Background Factors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined. Methods In the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005. Results Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis >= 70% (OR: 2.86), proximal left anterior descending stenosis >= 50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age >= 65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003). Conclusions The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305) (J Am Coll Cardiol Intv 2009;2:384-92) (C) 2009 by the American College of Cardiology Foundation

High prevalence of polycystic ovary syndrome in women born small for gestational age

There is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA). This was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirao Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS. The prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups. The prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

Texto para discuss??o 43:os especialistas em pol??ticas p??blicas e gest??o governamental: avalia????o de sua contribui????o para pol??ticas p??blicas e trajet??ria profissional

Este relat??rio apresenta os resultados de uma pesquisa piloto de avalia????o sobre a contribui????o dos Especialistas em Pol??ticas P??blicas e Gest??o Governamental (EPPGGs), doravante tamb??m denominados apenas gestores, para Administra????o P??blica Federal (APF). Uma das quest??es centrais da pesquisa consistiu na determina????o da exist??ncia ou n??o de uma atua????o t??pica dos gestores na APF que os singularize qua membros de uma carreira espec??fica. S?? se pode falar da contribui????o dos gestores enquanto tal, em contraposi????o ?? contribui????o de uma s??rie de indiv??duos isolada e desarticuladamente, se for poss??vel diferenciar institucionalmente as formas de atua????o caracter??sticas dos membros da carreira. Assim, o fio condutor da investiga????o, de acordo com a problem??tica exposta acima, foi pautado pela id??ia de institucionaliza????o da carreira de EPPGG

Potencial alelopático de plantas de cobertura verde de inverno sobre o crescimento do porta-enxerto VR043-43

Nos últimos anos, tem-se verificado aumento no uso da adubação verde de inverno na cultura da videira. Essa adubação proporciona ao vinhedo melhor controle da erosão e manutenção da fertilidade, aumento da macro e microporosidade do solo pela penetração e decomposição das raízes e aumento do teor de matéria orgânica, além da possibilidade de diminuição do uso de herbicidas. Algumas espécies vêm sendo utilizadas, mesmo sem se conhecerem os efeitos secundários para a videira, e poucos trabalhos têm sido realizados para avaliação desses efeitos. O objetivo deste trabalho foi verificar o efeito alelopático de diferentes espécies de plantas de cobertura verde de inverno sobre o desenvolvimento do porta-enxerto VR 043-43. O delineamento utilizado foi inteiramente casualizado, com 19 tratamentos e quatro repetições. Foram preparados extratos das partes aérea e radicular de nove espécies, utilizadas como cobertura verde de inverno. As estacas enraizadas foram colocadas em vasos com areia e, durante 45 dias, duas vezes por semana, foram regadas com solução aquosa de cada extrato e fertilizante. Após esse período, foi avaliado o comprimento das raízes, o número de raízes por estaca, a matéria fresca do sistema radicular e a matéria fresca das brotações. Os resultados obtidos permitiram concluir que, dentre os extratos das espécies estudadas, o que apresentou maior efeito alelopático foi o extrato da parte aérea da gorga (Spergula arvensis), seguido pelo extrato da parte aérea do dente-de-leão (Taraxacum officinale L.). O centeio (Secale cereale L.) e o nabo forrageiro (Raphanus sativus L.) não apresentaram efeito alelopático.

Portucorruptgal, SA e os 43

Bem, recordamos que, salvaguardando a presunção de inocência em relação a eventuais crimes como a fraude fiscal qualificada e/ou o branqueamento de capitais, entre outras especiarias, o art. 11º do Código Penal é claro (apesar da controversa constitucionalidade): “8 - A cisão e a fusão não determinam a extinção da responsabilidade criminal da pessoa colectiva ou entidade equiparada, respondendo pela prática do crime: § a) A pessoa colectiva ou entidade equiparada em que a fusão se tiver efectivado; e § b) As pessoas colectivas ou entidades equiparadas que resultaram da cisão; Abstract: Well, remember that, safeguarding the presumption of innocence in relation to possible crimes such as qualified tax fraud and / or money laundering, among other spices, art. 11 of the Criminal Code is clear (despite the controversial constitutionality): "8 - The split and the merger does not determine the extinction of criminal liability of the legal person or related entity, accounting for the crime: § a) The legal person or related entity where the merger has effected; and § b) A legal entity or related entities resulting from the split.