Cocaine effects on mouse incentive-learning and human addiction are linked to alpha 2 subunit-containing GABA(A) receptors

Because GABA(A) receptors containing alpha 2 subunits are highly represented in areas of the brain, such as nucleus accumbens (NAcc), frontal cortex, and amygdala, regions intimately involved in signaling motivation and reward, we hypothesized that manipulations of this receptor subtype would influence processing of rewards. Voltage-clamp recordings from NAcc medium spiny neurons of mice with alpha 2 gene deletion showed reduced synaptic GABA(A) receptor-mediated responses. Behaviorally, the deletion abolished cocaine`s ability to potentiate behaviors conditioned to rewards (conditioned reinforcement), and to support behavioral sensitization. In mice with a point mutation in the benzodiazepine binding pocket of alpha 2-GABA(A) receptors (alpha 2H101R), GABAergic neurotransmission in medium spiny neurons was identical to that of WT (i.e., the mutation was silent), but importantly, receptor function was now facilitated by the atypical benzodiazepine Ro 15-4513 (ethyl 8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4] benzodiazepine-3-carboxylate). In alpha 2H101R, but not WT mice, Ro 15-4513 administered directly into the NAcc-stimulated locomotor activity, and when given systemically and repeatedly, induced behavioral sensitization. These data indicate that activation of alpha 2-GABA(A) receptors (most likely in NAcc) is both necessary and sufficient for behavioral sensitization. Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.

Estimation of lung vital capacity before and after coronary artery bypass grafting surgery: a comparison of incentive spirometer and ventilometry

Abstract Background Measurement of vital capacity (VC) by spirometry is the most widely used technique for lung function evaluation, however, this form of assessment is costly and further investigation of other reliable methods at lower cost is necessary. Objective: To analyze the correlation between direct vital capacity measured with ventilometer and with incentive inspirometer in patients in pre and post cardiac surgery. Methodology Cross-sectional comparative study with patients undergoing cardiac surgery. Respiratory parameters were evaluated through the measurement of VC performed by ventilometer and inspirometer. To analyze data normality the Kolmogorov-Smirnov test was applied, for correlation the Pearson correlation coefficient was used and for comparison of variables in pre and post operative period Student's t test was adopted. We established a level of ignificance of 5%. Data was presented as an average, standard deviation and relative frequency when needed. The significance level was set at 5%. Results We studied 52 patients undergoing cardiac surgery, 20 patients in preoperative with VC-ventilometer: 32.95 ± 11.4 ml/kg and VC-inspirometer: 28.9 ± 11 ml/Kg, r = 0.7 p < 0.001. In the post operatory, 32 patients were evaluated with VC-ventilometer: 28.27 ± 12.48 ml/kg and VC-inspirometer: 26.98 ± 11 ml/Kg, r = 0.95 p < 0.001. Presenting a very high correlation between the evaluation forms studied. Conclusion There was a high correlation between DVC measures with ventilometer and incentive spirometer in pre and post CABG surgery. Despite this, arises the necessity of further studies to evaluate the repercussion of this method in lowering costs at hospitals.

Associação entre sistema de incentivos gerenciais e práticas de contabilidade gerencial

O princípio da controlabilidade prevê que os gestores deveriam ser avaliados com base em fatores controláveis. Consequentemente, os incentivos gerenciais estariam relacionados a práticas de contabilidade gerencial capazes de evitar que os gestores sejam responsabilizados por resultados financeiros além do controle gerencial, tais como análise por centro de responsabilidade, custo padrão, preço de transferência, orçamento e avaliação de desempenho. Este artigo desenvolve um estudo de campo para investigar se há relação entre a presença de incentivos gerenciais e as práticas de contabilidade gerencial associadas ao princípio da controlabilidade. Entrevistas in loco foram realizadas para a coleta de dados em nível organizacional e testes estatísticos não paramétricos foram utilizados para a análise dos dados. Entre as práticas de contabilidade gerencial examinadas, os resultados sugerem que apenas orçamento anual, análise por centro de responsabilidade e avaliação de desempenho estão associados à presença de sistemas de incentivos nas empresas entrevistadas.

Maternal immune activation in late gestation enhances locomotor response to acute but not chronic amphetamine treatment in male mice offspring: Role of the D1 receptor

Exposure to elevated levels of maternal cytokines can lead to functional abnormalities of the dopaminergic system in the adult offspring, including enhanced amphetamine (AMPH)-induced locomotion. Therefore, it seems reasonable to consider that offspring of challenged mothers would behave differently in models of addictive behavior, such as behavioral sensitization. Thus, we sought to evaluate the effects of prenatal exposure to lipopolysaccharide (LPS) on the locomotor response to acute and chronic AMPH treatment in male mice offspring. For this purpose, LPS (Escherichia coli 0127:B8; 120 mu g/kg) was administered intraperitoneally to pregnant Swiss mice on gestational day 17. At adulthood, male offspring were studied under one of the following conditions: (1) locomotor response to acute AMPH treatment (2.5 or 5.0 mg/kg) in an open field test; (2) behavioral sensitization paradigm, which consists of a daily injection of AMPH (1.0 mg/kg) for 10 days and observation of locomotion in the open field on days 1, 5, 10 (development phase), 15 and 17 (expression phase). The LPS stimulated offspring showed enhancement of the locomotor-stimulant effect after an acute AMPH challenge in comparison to baseline and saline pre-treated mice. They also showed development of behavioral sensitization earlier than the saline pre-treated group, although no changes between saline and LPS pre-treated groups were observed on development or expression of locomotor behavioral sensitization to AMPH. Furthermore, there was up-regulation of D1 receptor protein level within striatum in the LPS-stimulated offspring which was strongly correlated with increased grooming behavior. Taken together, our results indicate that motor and dopaminergic alterations caused by maternal immune activation are restricted to the acute AMPH challenge, mostly due to up-regulation of the D1 receptor within the mesolimbic and nigrostriatal pathways, but no locomotor differences were observed for behavioral sensitization to AMPH. (C) 2012 Elsevier B.V. All rights reserved.

Involvement of the basolateral complex and central nucleus of amygdala in the omission effects of different magnitudes of reinforcement

Evidence from appetitive Pavlovian and instrumental conditioning studies suggest that the amygdala is involved in modulation of responses correlated with motivational states, and therefore, to the modulation of processes probably underlying reinforcement omission effects. The present study aimed to clarify whether or not the mechanisms related to reinforcement omission effects of different magnitudes depend on basolateral complex and central nucleus of amygdala. Rats were trained on a fixed-interval 12 s with limited hold 6 s signaled schedule in which correct responses were always followed by one of two reinforcement magnitudes. Bilateral lesions of the basolateral complex and central nucleus were made after acquisition of stable performance. After postoperative recovery, the training was changed from 100% to 50% reinforcement schedules. The results showed that lesions of the basolateral complex and central nucleus did not eliminate or reduce, but interfere with reinforcement omission effects. The response from rats of both the basolateral complex and central nucleus lesioned group was higher relative to that of the rats of their respective sham-lesioned groups after reinforcement omission. Thus, the lesioned rats were more sensitive to the omission effect. Moreover, the basolateral complex lesions prevented the magnitude effect on reinforcement omission effects. Basolateral complex lesioned rats showed no differential performance following omission of larger and smaller reinforcement magnitude. Thus, the basolateral complex is involved in incentive processes relative to omission of different reinforcement magnitudes. Therefore, it is possible that reinforcement omission effects are modulated by brain circuitry which involves amygdala. (C) 2012 Elsevier B.V. All rights reserved.

Metabolic engineering of beta-oxidation in Penicillium chrysogenum for improved semi-synthetic cephalosporin biosynthesis

Industrial production of semi-synthetic cephalosporins by Penicillium chrysogenum requires supplementation of the growth media with the side-chain precursor adipic acid. In glucose-limited chemostat cultures of P. chrysogenum, up to 88% of the consumed adipic acid was not recovered in cephalosporinrelated products, but used as an additional carbon and energy source for growth. This low efficiency of side-chain precursor incorporation provides an economic incentive for studying and engineering the metabolism of adipic acid in P. cluysogenum. Chemostat-based transcriptome analysis in the presence and absence of adipic acid confirmed that adipic acid metabolism in this fungus occurs via beta-oxidation. A set of 52 adipate-responsive genes included six putative genes for acyl-CoA oxidases and dehydrogenases, enzymes responsible for the first step of beta-oxidation. Subcellular localization of the differentially expressed acyl-CoA oxidases and dehydrogenases revealed that the oxidases were exclusively targeted to peroxisomes, while the dehydrogenases were found either in peroxisomes or in mitochondria. Deletion of the genes encoding the peroxisomal acyl-CoA oxidase Pc20g01800 and the mitochondrial acyl-CoA dehydrogenase Pc20g07920 resulted in a 1.6- and 3.7-fold increase in the production of the semi-synthetic cephalosporin intermediate adipoyl-6-APA, respectively. The deletion strains also showed reduced adipate consumption compared to the reference strain, indicating that engineering of the first step of beta-oxidation successfully redirected a larger fraction of adipic acid towards cephalosporin biosynthesis. (C) 2012 Elsevier Inc. All rights reserved.

Saphenofemoral arteriovenous fistula as hemodialysis access

Abstract Background An upper limb arteriovenous (AV) fistula is the access of choice for haemodialysis (HD). There have been few reports of saphenofemoral AV fistulas (SFAVF) over the last 10-20 years because of previous suggestions of poor patencies and needling difficulties. Here, we describe our clinical experience with SFAVF. Methods SFAVFs were evaluated using the following variables: immediate results, early and late complications, intraoperative and postoperative complications (up to day 30), efficiency of the fistula after the onset of needling and complications associated to its use. Results Fifty-six SFAVF fistulas were created in 48 patients. Eight patients had two fistulas: 8 patent (16%), 10 transplanted (20%), 12 deaths (24%), 1 low flow (2%) and 20 thrombosis (39%) (first two months of preparation). One patient had severe hypotension during surgery, which caused thrombosis of the fistula, which was successfully thrombectomised, four thrombosed fistulae were successfully thrombectomised and revised on the first postoperative day. After 59 months of follow-up, primary patency was 44%. Conclusion SFAVF is an adequate alternative for patients without the possibility for other access in the upper limbs, allowing efficient dialysis with good long-term patency with a low complication rate.

Associação entre sistema de incentivos gerenciais e práticas de contabilidade gerencial

O princípio da controlabilidade prevê que os gestores deveriam ser avaliados com base em fatores controláveis. Consequentemente, os incentivos gerenciais estariam relacionados a práticas de contabilidade gerencial capazes de evitar que os gestores sejam responsabilizados por resultados financeiros além do controle gerencial, tais como análise por centro de responsabilidade, custo padrão, preço de transferência, orçamento e avaliação de desempenho. Este artigo desenvolve um estudo de campo para investigar se há relação entre a presença de incentivos gerenciais e as práticas de contabilidade gerencial associadas ao princípio da controlabilidade. Entrevistas in loco foram realizadas para a coleta de dados em nível organizacional e testes estatísticos não paramétricos foram utilizados para a análise dos dados. Entre as práticas de contabilidade gerencial examinadas, os resultados sugerem que apenas orçamento anual, análise por centro de responsabilidade e avaliação de desempenho estão associados à presença de sistemas de incentivos nas empresas entrevistadas.

Roof modular system in wood and particle board (OSB) to rural construction

Wood is a material of great applicability in construction, with advantageous properties to form various structural systems, such as walls and roof. Most of the roof structural systems follow models that have remained unchanged for a long time. A roof modular system in distinguished materials is proposed: reforested wood (Pine), oriented strand board (OSB) and roof tiles made of recycled long-life packaging material in order to be applied in rural construction. In this alternative, besides the benefit of giving destination packages with long-life thermal comfort, it also highlights the use of reforestated wood being the cultivation of such species that provides incentive for agribusiness. The structural performance of this alternative was evaluated through computer modeling and test results of two modular panels. The analysis is based on the results of vertical displacements, deformations and stresses. A positive correlation between theoretical and experimental values was observed, indicating the model's feasibility for use in roof structures. Therefore, the modular system represents a solution to new architecture conceptions to rural construction, for example, storage construction, cattle handling and poultry, with benefits provided by prefabricated building systems.

Características da resposta à Aids de secretarias de saúde, no contexto da Política de Incentivo do Ministério da Saúde¹

OBJETIVOS: Analisar a cobertura da Política de Incentivo do Ministério da Saúde para Programas de Aids e as características das ações de prevenção, assistência, gestão e apoio às organizações da sociedade civil induzidas nos Estados e municípios. METODOLOGIA: Os Planos de Ações e Metas de 2006, das 27 Unidades Federadas e de 427 municípios incluídos na Política de Incentivo, foram analisados segundo indicadores estabelecidos para aferir a complexidade e a sustentabilidade das ações induzidas, a inclusão de populações prioritárias e a capacidade de intervenção na epidemia. Informações sobre população e casos de aids registrados foram utilizadas para mensurar a cobertura. RESULTADOS: Os municípios incluídos representaram uma cobertura de 85,2% dos casos de aids do País. Houve uma baixa proporção de secretarias estaduais (48,2%) e municipais (32,6%) de saúde que contemplaram, concomitantemente, ações de prevenção para a população geral e as de maior prevalência da doença, assim como ações para o diagnóstico do HIV, o tratamento de pessoas infectadas e a prevenção da transmissão vertical. Em relação às populações prioritárias, 51,9% dos Estados e 31,1% dos municípios propuseram ações específicas na prevenção e na assistência. Estados (44,4%) e municípios (27,9%) com Planos abrangentes estão mais concentrados no Sudeste e em cidades de grande porte, representando a maioria dos casos de aids do País. CONCLUSÃO: A Política de Incentivo do Ministério da Saúde compreende as regiões de maior ocorrência da aids no Brasil, porém, o perfil da resposta induzida encontra-se parcialmente dissociado das características epidemiológicas da doença no País.