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.

LTR point mutations in the Tax-responsive elements of HTLV-1 isolates from HIV/HTLV-1-coinfected patients

Background: In Virology Journal 2011, 8: 535, Neto et al. described point mutations into Tax-responsive elements (TRE) of the LTR region of HTLV-1 isolates from asymptomatic carriers from Sao Paulo, Brazil, and hypothesized that the presence of the G232A mutation in the TRE-1 increase viral proliferation and consequently the proviral load (PvL), while the A184G mutation in the TRE-2 do not have such effect. Findings: We performed the real-time PCR assay (pol) and sequenced LTR region of HTLV-1 isolates from 24 HIV/HTLV-1-coinfected patients without HTLV-1-associated diseases from the same geographic area. These sequences were classified as belonging to the transcontinental subgroup A of the Cosmopolitan subtype a. The frequency of G232A mutation (16/24, 66.7%) was high as much as 61.8% reported by Neto's in HTLV-1 asymptomatic carriers with high PvL. High frequency (13/24, 54.2%) of double mutations G232A and A184G was also detected in HIV/HTLV-1-coinfected patients. We did not quantify PvL, but comparative analyses of the cycle threshold (Ct) median values of the group of isolates presenting the mutated-types sequences (Ct 33.5, n = 16) versus the group of isolates with the wild-type sequences (Ct 32, n = 8) showed no statistical difference (p = 0.4220). Conclusion: The frequencies of mutated-type sequences in the TRE-1 and TRE-2 motifs were high in HIV/HTLV-1-coinfected patients from Sao Paulo, Brazil. If these LTR point mutations have predictive value for the development of HTLV-1-associated diseases or they correspond to the subtype of virus that circulate in this geographic area has to be determined.

Tax Gene Characterization of Human T-Lymphotropic Virus Type 1 Strains from Brazilian HIV-Coinfected Patients

The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil.

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.

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.

CD3e expression in HTLV-1-infected individuals is associated with proviral load and Tax expression

Financial support: FUNDHERP, CTC, INCTC, FAPESP, CNPq and CAPES.

Pacta sunt servanda versus the social role of contracts: the case of Brazilian agriculture contracts

This study explores the instability created by contradictory court decisions related with contract breaches. Forward marketing contracts represent an important source of resources to finance Brazilian agriculture, however a large number of contract breaches were observed during a period of marked increase in soy prices. The study analyzed 161 judicial appeal decisions and a survey was carried with 70 farmers. The results show the difference of judges' interpretation and the existence of second order effects. The effects of court decisions were more requirements of guarantees and the reduction in the number of contracts. Those soybean farmers who did not breach their contracts have also been negatively affected by the strategic reactions of trading and processing companies. The concept of "social function of the contract" introduced in Brazilian civil code led to a higher degree of instability in contracts, raising transaction costs and motivating private economic sanctions.