Efeitos cardiorrespiratórios da infusão contínua de amitraz ou de romifidina em equinos anestesiados com isofluorano. Determinação das concentrações plasmáticas do amitraz

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cetamina S(+) como adjuvante na anestesia e no tratamento da dor pós-operatória de pacientes queimados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Manipulation of the periovulatory sex steroidal milieu affects endometrial but not luteal gene expression in early diestrus Nelore cows

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

ANGIOTENSINERGIC AND CHOLINERGIC RECEPTORS OF THE SUBFORNICAL ORGAN MEDIATE SODIUM INTAKE INDUCED BY GABAergic ACTIVATION OF THE LATERAL PARABRACHIAL NUCLEUS

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

ATP in the locus coeruleus as a modulator of cardiorespiratory control in unanaesthetized male rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Increased Expression of Angiotensin II Type 2 Receptors in the Solitary-Vagal Complex Blunts Renovascular Hypertension

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of nemorosone, isolated from the plant Clusia rosea, on the cell cycle and gene expression in MCF-7 BUS breast cancer cell lines

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interação entre as vias de sinalização de receptores serotoninérgicos e Β-adrenérgicos em artéria femoral de ratos

Fundamento: A doença coronária tem sido amplamente estudada em pesquisas cardiovasculares. No entanto, pacientes com doença arterial periférica (DAP) têm piores resultados em comparação àqueles com doença arterial coronariana. Portanto, os estudos farmacológicos com artéria femoral são altamente relevantes para a melhor compreensão das respostas clínicas e fisiopatológicas da DAP. Objetivo: Avaliar as propriedades farmacológicas dos agentes contráteis e relaxantes na artéria femoral de ratos. Métodos: As curvas de resposta de concentração à fenilefrina contrátil (FC) e à serotonina (5-HT) e os agentes relaxantes isoproterenol (ISO) e forskolina foram obtidos na artéria femoral de ratos isolada. Para as respostas ao relaxamento, os tecidos foram contraídos com FC ou 5-HT. Resultados: A potência de classificação na artéria femoral foi de 5-HT > FC para as respostas contráteis. Em tecidos contraídos com 5-HT, as respostas de relaxamento ao isoproterenol foram praticamente abolidas em comparação aos tecidos contraídos com FC. A forskolina, um estimulante da adenilil ciclase, restaurou parcialmente a resposta de relaxamento ao ISO em tecidos contraídos com 5-HT. Conclusão: Ocorre uma interação entre as vias de sinalização dos receptores β-adrenérgicos e serotoninérgicos na artéria femoral. Além disso, esta pesquisa fornece um novo modelo para estudar as vias de sinalização serotoninérgicas em condições normais e patológicas que podem ajudar a compreender os resultados clínicos na DAP.

Adalimumab for maintenance therapy for one year in Crohn's disease: results of a Latin American single-center observational study

Adalimumab is a fully-human antibody that inhibits TNF alpha, with a significant efficacy for long-term maintenance of remission. Studies with this agent in Latin American Crohn's disease patients are scarce. The objective of this study was to outline clinical remission rates after 12 months of adalimumab therapy for Crohn's disease patients. Retrospective, single-center, observational study of a Brazilian case series of Crohn's disease patients under adalimumab therapy. Variables analyzed: demographic data, Montreal classification, concomitant medication, remission rates after 1, 4, 6 and 12 months. Remission was defined as Harvey-Bradshaw Index ≤ 4, and non-responder-imputation and last-observation-carried-forward analysis were used. The influence of infliximab on remission rates was analyzed by Fischer and Chi-square tests (P<0.05). Fifty patients, with median age of 35 years at therapy initiation, were included. Remission rates after 12 months of therapy were 54% under non-responder-imputation and 88% under last-observation-carried-forward analysis. After 12 months, remission on patients with previous infliximab occurred in 69.23% as compared to 94.59% in infliximab-naïve patients (P = 0.033). Adalimumab was effective in maintaining clinical remission after 12 months of therapy, with an adequate safety profile, and was also more effective in infliximab naïve patients.

Androgen receptors and experimental bone loss - an in vivo and in vitro study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fructose-Induced Hypothalamic AMPK Activation Stimulates Hepatic PEPCK and Gluconeogenesis due to Increased Corticosterone Levels

Fructose consumption causes insulin resistance and favors hepatic gluconeogenesis through mechanisms that are not completely understood. Recent studies demonstrated that the activation of hypothalamic 5'-AMP-activated protein kinase (AMPK) controls dynamic fluctuations in hepatic glucose production. Thus, the present study was designed to investigate whether hypothalamic AMPK activation by fructose would mediate increased gluconeogenesis. Both ip and intracerebroventricular (icv) fructose treatment stimulated hypothalamic AMPK and acetyl-CoA carboxylase phosphorylation, in parallel with increased hepatic phosphoenolpyruvate carboxy kinase (PEPCK) and gluconeogenesis. An increase in AMPK phosphorylation by icv fructose was observed in the lateral hypothalamus as well as in the paraventricular nucleus and the arcuate nucleus. These effects were mimicked by icv 5-amino-imidazole-4-carboxamide-1-beta-D-ribofuranoside treatment. Hypothalamic AMPK inhibition with icv injection of compound C or with injection of a small interfering RNA targeted to AMPK alpha 2 in the mediobasal hypothalamus (MBH) suppressed the hepatic effects of ip fructose. We also found that fructose increased corticosterone levels through a mechanism that is dependent on hypothalamic AMPK activation. Concomitantly, fructose-stimulated gluconeogenesis, hepatic PEPCK expression, and glucocorticoid receptor binding to the PEPCK gene were suppressed by pharmacological glucocorticoid receptor blockage. Altogether the data presented herein support the hypothesis that fructose-induced hypothalamic AMPK activation stimulates hepatic gluconeogenesis by increasing corticosterone levels. (Endocrinology 153: 3633-3645, 2012)

Disulfide Biochemistry in 2-Cys Peroxiredoxin: Requirement of Glu50 and Arg146 for the Reduction of Yeast Tsa1 by Thioredoxin

2-Cys peroxiredoxin (Prx) enzymes are ubiquitously distributed peroxidases that make use of a peroxidatic cysteine (Cys(P)) to decompose hydroperoxides. A disulfide bond is generated as a consequence of the partial unfolding of the alpha-helix that contains Cys(P). Therefore, during its catalytic cycle, 2-Cys Prx alternates between two states, locally unfolded and fully folded. Tsa1 (thiol-specific antioxidant protein 1 from yeast) is by far the most abundant Cys-based peroxidase in Saccharomyces cerevisiae. In this work, we present the crystallographic structure at 2.8 angstrom resolution of Tsa1(C47S) in the decameric form [(alpha(2))(5)] with a DTT molecule bound to the active site, representing one of the few available reports of a 2-Cys Prx (AhpC-Prx1 subfamily) (AhpC, alkyl hydroperoxide reductase subunit C) structure that incorporates a ligand. The analysis of the Tsa1(C47S) structure indicated that G1u50 and Arg146 participate in the stabilization of the Cys(P) alpha-helix. As a consequence, we raised the hypothesis that G1u50 and Arg146 might be relevant to the Cys(P) reactivity. Therefore, Tsa1(E50A) and Tsa1(R146Q) mutants were generated and were still able to decompose hydrogen peroxide, presenting a second-order rate constant in the range of 10(6) M-1 S-1. Remarkably, although Tsa1(E50A) and Tsa1(R146Q) were efficiently reduced by the low-molecular-weight reductant DTT, these mutants displayed only marginal thioredoxin (Trx)-dependent peroxidase activity, indicating that G1u50 and Arg146 are important for the Tsa1-Trx interaction. These results may impact the comprehension of downstream events of signaling pathways that are triggered by the oxidation of critical Cys residues, such as Trx. (C) 2012 Elsevier Ltd. All rights reserved.

Kinin B1 Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity

Background: Kinins participate in the pathophysiology of obesity and type 2 diabetes by mechanisms which are not fully understood. Kinin B-1 receptor knockout mice (B-1(-/-)) are leaner and exhibit improved insulin sensitivity. Methodology/Principal Findings: Here we show that kinin B-1 receptors in adipocytes play a role in controlling whole body insulin action and glucose homeostasis. Adipocytes isolated from mouse white adipose tissue (WAT) constitutively express kinin B-1 receptors. In these cells, treatment with the B-1 receptor agonist des-Arg(9)-bradykinin improved insulin signaling, GLUT4 translocation, and glucose uptake. Adipocytes from B-1(-/-) mice showed reduced GLUT4 expression and impaired glucose uptake at both basal and insulin-stimulated states. To investigate the consequences of these phenomena to whole body metabolism, we generated mice where the expression of the kinin B-1 receptor was limited to cells of the adipose tissue (aP2-B-1/B-1(-/-)). Similarly to B-1(-/-) mice, aP2-B-1/B-1(-/-) mice were leaner than wild type controls. However, exclusive expression of the kinin B1 receptor in adipose tissue completely rescued the improved systemic insulin sensitivity phenotype of B-1(-/-) mice. Adipose tissue gene expression analysis also revealed that genes involved in insulin signaling were significantly affected by the presence of the kinin B-1 receptor in adipose tissue. In agreement, GLUT4 expression and glucose uptake were increased in fat tissue of aP2-B-1/B-1(-/-) when compared to B-1(-/-) mice. When subjected to high fat diet, aP2-B-1/B-1(-/-) mice gained more weight than B-1(-/-) littermates, becoming as obese as the wild types. Conclusions/Significance: Thus, kinin B-1 receptor participates in the modulation of insulin action in adipocytes, contributing to systemic insulin sensitivity and predisposition to obesity.

A simple and precise conductometric method for the determination of losartan in pharmaceutical products

Losartan is an antihypertensive agent that lost its patent protection in 2010, and, consequently, it has been available in generic form. The latter motivated the search for a rapid and precise alternative method. Here, a simple conductometric titration in aqueous medium is described for the losartan analysis in pharmaceutical formulations. The first step of the titration occurs with the protonation of losartan producing a white precipitate and resulting in a slow increase in conductivity. When the protonation stage is complete, a sharp increase in conductivity occurs which was determined to be due to the presence of excess of acid. The titrimetric method was applied to the determination of losartan in pharmaceutical products and the results are comparable with values obtained using a chromatographic method recommended by the United States Pharmacopoeia. The relative standard deviation for successive measurements of a 125 mg L-1 (2.71x10(-4) mol L-1) losartan solution was approximately 2%. Recovery study in tablet samples ranged between 99 and 102.4%. The procedure is fast, simple, and represents an attractive alternative for losartan quantification in routine analysis. In addition, it avoids organic solvents, minimizes the risk of exposure to the operator, and the waste treatment is easier compared to classical chromatographic methods.