The role of AT1-receptor blockade on reactive oxygen species and cardiac autonomic drive in experimental hyperthyroidism.

The objective of this study was to explore the influence of the renin-angiotensin system on cardiac prooxidants and antioxidants levels and its association to autonomic imbalance induced by hyperthyroidism. Male Wistar rats were divided into four groups: control, losartan (10mg/kg/day by gavage, 28 day), thyroxine (T4) (12 mg/L in drinking water for 28 days), and T4+losartan. Spectral analysis (autonomic balance), angiotensin II receptor (AT1R), NADPH oxidase, Nrf2 and heme-oxygenase-1 (HO-1) myocardial protein expression, and hydrogen peroxide (H2O2) concentration were quantified. Autonomic imbalance induced by hyperthyroidism (~770%) was attenuated in the T4+losartan group (~32%) (P<0.05). AT1R, NADPH oxidase, H2O2, as well as concentration, Nrf2 and HO-1 protein expression were elevated (~172%, 43%, 40%, 133%, and 154%, respectively) in T4 group (P<0.05). H2O2 and HO-1 levels were returned to control values in the T4+losartan group (P<0.05). The overall results demonstrate a positive impact of RAS blockade in the autonomic control of heart rate, which was associated with an attenuation of H2O2 levels, as well as with a reduced counter-regulatory response of HO-1 in experimental hyperthyroidism.

Validation of a numerical code for the simulation of a short-term CO2 release in an open environment: effect of wind conditions and obstacles.

Carbon Capture and Storage (CCS) is one of the possible mitigation measures to reduce the CO(2) emissions produced from anthropogenic sources and thus help address the issue of global warming. Accidental CO(2) releases may occur at any of the CCS stages, having potentially harmful consequences on the people who work in the CCS facilities, the general public in their vicinity and the environment. CFD is an increasingly used tool to investigate the behavior of released substances and predict the consequences of hazardous scenarios. This information aids the development of mitigation methods to minimize the consequences of an accident. The validation of numerical codes and models is a necessary preliminary step before their application to safety and risk assessment analysis. In this context, numerical simulations of CO(2) release and dispersion field experiments were performed with a CFD code. The experimental data were taken from the Kit Fox CO(2) gas field experiments which were designed to investigate the effect of ground roughness of industrial process plants and of meteorological conditions on the formation and extent of the CO(2) gas cloud. This study presents a comparison between the simulation results and the experimental measurements in order to assess the accuracy of the code with different modeling approaches.

Terapia de reposição de testosterona: a polêmica / Testosterone replacement therapy

A terapia de reposição de testosterona (TRT) é uma opção de tratamento para a andropausa, porém é evitada por ser historicamente associada com o surgimento de câncer de próstata (PCa) clinicamente detectável. Esta crença, suportada por mais de meio século, tem sido muito contestada ultimamente por possuir lacunas científicas importantes. O presente trabalho faz uma revisão da literatura recente e aborda as evidências que sustentam a prática e aplicação clínica de TRT e os novos estudos que procuram esclarecer qual a verdadeira relação de dependência entre crescimento do PCa e hormônios andrógenos.

Synthesis and pharmacological characterisation of a conformationally restrained series of indole-2-carboxylates as in vivo potent glycine antagonists.

After the identification of GV150526, the indole-2-carboxylate template was further explored in order to identify novel potential anti-stroke agents. In particular, the SAR of the side chain present at the C-3 position of the indole nucleus was widely studied. In this paper, the synthesis and the pharmacological profile of a further class of conformationally restricted analogues of GV150526 as in vitro and in vivo potent glycine antagonists is reported. In particular, a pyrazolidinone derivative was identified as a potent neuroprotective agent in animal models of cerebral ischaemia.

Substituted indole-2-carboxylates as potent antagonists of the glycine binding site associated with the NMDA receptor.

A novel series of indole-2-carboxylate analogues of GV150526 (1) in which the propenoic double bond was substituted with different "probes" or replaced by a isosteric cyclopropyl moiety were synthesized and evaluated for their affinity profile in order to obtain further information on the pharmacophoric model of the glycine binding site associated to the NMDA receptor.

Unusual synthesis of new glycine antagonists via sequential aldol condensation-lactonization-elimination reaction.

Compounds 2 and 3 were designed in order to probe the North-East region of the strichnine-insensitive glycine binding site of the NMDA receptor. The two products were obtained readily by a tandem aldol condensation-lactonization-elimination step which affords the desired E isomer with complete regioselection.

[Sprout inhibition by radiation and chemical treatment in four potato cultivars (author's transl)]. / Inibizione della germinazione mediante irraggiamento e trattamento chimico in quattro cultivar di patate

Irradiated and chemically treated potatoes were then stored at 10 degrees C and 80-85% relative humidity. Radiations caused complete inhibition of sprouting and for up to 10 months after harvest the physical and chemical condition of the potatoes remained satisfactory. On the other hand chemical treatment controlled sprouting for up to 7-8 months only. Irradiation and chemical condition of the potatoes rotting. Weight loss was higher in the chemically treated samples. Treatment by radiation did not effect vitamin C and niacin content as compared with chemically treated samples. Irradiation did not cause any change in the sucrose and the total sugar content, as compared with chemical treatment. Total and soluble nitrogen contents were not affected by either treatment. The response to both irradiation and chemical treamtments was only slightly affected by varietal factors provided that the potatoes were healthy and mature at harvest time.