The Epidermal Growth Factor Receptor Is Involved in Angiotensin II But Not Aldosterone/Salt-Induced Cardiac Remodelling

Experimental and clinical studies have shown that aldosterone/mineralocorticoid receptor (MR) activation has deleterious effects in the cardiovascular system; however, the signalling pathways involved in the pathophysiological effects of aldosterone/MR in vivo are not fully understood. Several in vitro studies suggest that Epidermal Growth Factor Receptor (EGFR) plays a role in the cardiovascular effects of aldosterone. This hypothesis remains to be demonstrated in vivo. To investigate this question, we analyzed the molecular and functional consequences of aldosterone exposure in a transgenic mouse model with constitutive cardiomyocyte-specific overexpression of a mutant EGFR acting as a dominant negative protein (DN-EGFR). As previously reported, Angiotensin II-mediated cardiac remodelling was prevented in DN-EGFR mice. However, when chronic MR activation was induced by aldosterone-salt-uninephrectomy, cardiac hypertrophy was similar between control littermates and DN-EGFR. In the same way, mRNA expression of markers of cardiac remodelling such as ANF, BNF or β-Myosin Heavy Chain as well as Collagen 1a and 3a was similarly induced in DN-EGFR mice and their CT littermates. Our findings confirm the role of EGFR in AngII mediated cardiac hypertrophy, and highlight that EGFR is not involved in vivo in the damaging effects of aldosterone on cardiac function and remodelling

The Making of a Monster: Postnatal Ontogenetic Changes in Craniomandibular Shape in the Great Sabercat Smilodon

Derived sabercats had craniomandibular morphologies that in many respects were highly different from those of extant felids, and this has often been interpreted functionally as adaptations for predation at extreme gape angles with hypertrophied upper canines. It is unknown how much of this was a result of intraspecific postnatal ontogeny, since juveniles of sabercats are rare and no quantitative study has been made of craniomandibular ontogeny. Postnatal ontogenetic craniomandibular shape changes in two morphologically derived sabercats, Smilodon fatalis and S. populator, were analysed using geometric morphometrics and compared to three species of extant pantherines, the jaguar, tiger, and Sunda clouded leopard. Ontogenetic shape changes in Smilodon usually involved the same areas of the cranium and mandible as in extant pantherines, and large-scale modularization was similar, suggesting that such may have been the case for all felids, since it followed the same trends previously observed in other mammals. However, in other respects Smilodon differed from extant pantherines. Their crania underwent much greater and more localised ontogenetic shape changes than did the mandibles, whereas crania and mandibles of extant pantherines underwent smaller, fewer and less localised shape changes. Ontogenetic shape changes in the two species of Smilodon are largely similar, but differences are also present, notably those which may be tied to the presence of larger upper canines in S. populator. Several of the specialized cranial characters differentiating adult Smilodon from extant felids in a functional context, which are usually regarded as evolutionary adaptations for achieving high gape angles, are ontogenetic, and in several instances ontogeny appears to recapitulate phylogeny to some extent. No such ontogenetic evolutionary adaptive changes were found in the extant pantherines. Evolution in morphologically derived sabercats involved greater cranial ontogenetic changes than among extant felids, resulting in greatly modified adult craniomandibular morphologies

Acompanhamento de pacientes submetidos à cirurgia bariátrica : aspectos laboratoriais nos períodos pré e pós-operatório

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde, Programa de Pós-Graduação em Farmácia, Florianópolis, 2017A obesidade é uma doença crônica e endócrino-metabólica caracterizada pelo acúmulo excessivo de triacilgliceróis no tecido adiposo, capaz de ser revertida ou amenizada através de intervenção cirúrgica. Epidemiologicamente têm sido descritas associações entre o excesso de peso, resistência à insulina e processo inflamatório crônico. Além disso, nas últimas décadas o sistema complemento foi associado a doenças metabólicas e cardiovasculares e intimamente relacionado com a obesidade e resistência à insulina. Sendo assim, a melhora do estado metabólico e a remissão da inflamação em pacientes obesos submetidos à cirurgia bariátrica foram avaliadas, bem como a associação dos fatores 3 e 4 (C3 e C4) do sistema complemento com a sensibilidade à insulina e a perda de peso após a cirurgia bariátrica. Para isso, a presença de comorbidades e as concentrações séricas de leptina, adiponectina, resistina e grelina foram avaliados em pacientes obesos mórbidos antes, 1, 3 e 6 meses após a cirurgia bariátrica. Também foram medidas as concentrações de IL-1ß, IL-6, TNF-a, proteína amiloide sérica A (SAA), proteína quimiotática de monócitos 1 (MCP-1), C3, C4, glicose, insulina, colesterol total, triacilglicerol, LDL- colesterol, HDL-colesterol e foi realizado o cálculo do modelo de avaliação da homeostase da resistência à insulina (HOMA-IR) durante o seguimento da cirurgia, bem como em comparação com um grupo de indivíduos não-obesos. Como resultado, observou-se uma redução significativa de peso acompanhada de melhora do perfil lipídico, da sensibilidade à insulina e das comorbidades. Ainda, houve diminuição de leptina e aumento de adiponectina no período pós-cirúrgico. IL-1ß, IL-6, TNF-a, MCP-1 e SAA não mostraram diferença no acompanhamento da cirurgia, porém SAA correlacionou-se com o IMC e apresentou-se muito mais alto no grupo de pacientes obesos. Além disso, C3 e C4 foram significativamente maiores em indivíduos obesos quando comparados aos indivíduos não-obesos e C3 e C4 foram positivamente correlacionados com HOMA-IR e as concentrações de C3 foram significativamente diminuídas após a cirurgia. Com base nesses resultados, a cirurgia bariátrica mostrou melhorar o estado metabólico melhorando as comorbidades associadas à obesidade e os biomarcadores de adiposidade leptina e adiponectina, mas não os demais hormônios e citocinas inflamatórias e C3 e C4 foram fortemente associados à sensibilidade à insulina.Abstract: Obesity is a chronic and endocrine-metabolic disease characterized by triacylglycerol accumulation in the adipose tissue, which can be reversed or improved through surgical intervention. Epidemiologically, associations between overweight, insulin resistance and chronic inflammatory process have been described. Furthermore, in the last decades the complement system was associated with metabolic and cardiovascular diseases and related to obesity and insulin resistance. Thus, metabolic status improvement and inflammation remission in obese patients undergoing bariatric surgery were evaluated, as well as the association of complement system factors 3 and 4 (C3 and C4) with insulin sensitivity and weight loss after bariatric surgery. For this, comorbidities and leptin, adiponectin, resistin and ghrelin serum concentrations were evaluated in morbidly obese patients before, 1, 3 and 6 months after bariatric surgery. IL-1ß, IL-6, TNF-a, serum amyloid A protein (SAA), monocyte chemotactic protein 1 (MCP-1), C3, C4, glucose, insulin, total cholesterol, triacylglycerol, LDL-cholesterol, HDL-cholesterol concentrations and the calculation of the homeostasis model of insulin resistance (HOMA-IR) were performed during the surgery follow-up, as well in a group of non-obese individuals. As a result, significant weight loss followed by improvement in lipid profile, insulin sensitivity and comorbidities were observed. Still, there was a decrease in leptin and an increase in adiponectin in the postoperative period. IL-1ß, IL-6, TNF-a, MCP-1 and SAA showed no difference after surgery, but SAA correlated with BMI and was much higher in obese patients. In addition, both C3 and C4 were significantly higher in obese individuals when compared to lean individuals and positively correlated with HOMA-IR. C3 concentrations were significantly decreased after surgery. Based on these results, bariatric surgery has been shown to improve metabolic status by improving obesity-associated comorbidities and adiposity biomarkers leptin and adiponectin but not the other hormones and inflammatory cytokines and C3 and C4 were strongly associated with insulin sensitivity

A comment on the proposed preservation of the generic name Panthera Oken, 1816 (Mammalia, Carnivora). Z.N.(s.) 482

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Cardiac hypertrophy and fibrosis in chronic L-NAME-treated AT2 receptor-deficient mice

Background: The role of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in cardiac hypertrophy and fibrosis is incompletely understood. The availability of AT2 receptor-deficient mice (AT 2 -/y) makes it possible to study the effects of AT1 receptors without the confounding influence of AT2 receptor activity. Objective: To test the hypothesis that the AT2 receptor affords protection from left ventricular hypertrophy and fibrosis in chronic hypertension induced by Nω-nitro-L-arginine methyl ester (L-NAME). Design: Four groups of mice were studied over a period of 3 weeks: AT2 -/y mice with and without L-NAME, and AT2 +/y mice with and without L-NAME. Methods: Blood pressure and heart rate were monitored by telemetry in groups of AT2 +/y and AT2 -/y mice for 4 weeks. L-NAME groups received the compound in drinking water for the last 3 weeks. We determined left ventricular AT1 receptor expression, cardiac hypertrophy and fibrosis, with and without L-NAME treatment. We used a miniaturized conductance-manometer system to measure pressure-volume loops at the time when the animals were killed. Results: AT2 -/y mice treated with L-NAME showed worse left ventricular hypertrophy, more perivascular fibrosis and greater concentrations of brain natriuretic peptide than did AT2 +/y mice treated with L-NAME. The end-systolic pressure-volume relationship, an index of left ventricular contractility, was decreased in AT2 -/y mice treated with L-NAME. Conclusions: The AT2 receptor is not essential for development of L-NAME-induced cardiac hypertrophy, fibrosis and concomitant changes in left ventricular performance. In contrast, the AT2 receptor offers a protective effect