Cardiac Magnetic Resonance Assessment Of Interstitial Myocardial Fibrosis And Cardiomyocyte Hypertrophy In Hypertensive Mice Treated With Spironolactone.

Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Mice were randomized to l-nitro-ω-methyl ester (l-NAME, 3 mg/mL in water; n=22), or l-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l-NAME (l-NAME+S) showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 ± 0.09 for l-NAME versus 0.25 ± 0.03 for l-NAME+S, P<0.001; τic: 0.42 ± 0.11 for l-NAME groups versus 0.12 ± 0.05 for l-NAME+S group). Mice treated with a combination of l-NAME and spironolactone were similar to placebo-treated controls at 7 weeks. Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression.

Enhanced Endothelium-dependent Relaxation Of Rat Pulmonary Artery Following β-adrenergic Overstimulation: Involvement Of The No/cgmp/vasp Pathway.

The aim of this study was to investigate whether β-adrenoceptor (β-AR) overstimulation induced by in vivo treatment with isoproterenol (ISO) alters vascular reactivity and nitric oxide (NO) production and signaling in pulmonary arteries. Vehicle or ISO (0.3mgkg(-1)day(-1)) was administered daily to male Wistar rats. After 7days, the jugular vein was cannulated to assess right ventricular (RV) systolic pressure (SP) and end diastolic pressure (EDP). The extralobar pulmonary arteries were isolated to evaluate the relaxation responses, protein expression (Western blot), NO production (diaminofluorescein-2 fluorescence), and cyclic guanosine 3',5'-monophosphate (cGMP) levels (enzyme immunoassay kit). ISO treatment induced RV hypertrophy; however, no differences in RV-SP and EDP were observed. The pulmonary arteries from the ISO-treated group showed enhanced relaxation to acetylcholine that was abolished by the NO synthase (NOS) inhibitor N(ω)-nitro-l-arginine methyl ester (l-NAME); whereas relaxation elicited by sodium nitroprusside, ISO, metaproterenol, mirabegron, or KCl was not affected by ISO treatment. ISO-treated rats displayed enhanced endothelial NOS (eNOS) and vasodilator-stimulated phosphoprotein (VASP) expression in the pulmonary arteries, while phosphodiesterase-5 protein expression decreased. ISO treatment increased NO and cGMP levels and did not induce eNOS uncoupling. The present data indicate that β-AR overactivation enhances the endothelium-dependent relaxation of pulmonary arteries. This effect was linked to an increase in eNOS-derived NO production, cGMP formation and VASP content and to a decrease in phosphodiesterase-5 expression. Therefore, elevated NO bioactivity through cGMP/VASP signaling could represent a protective mechanism of β-AR overactivation on pulmonary circulation.

Pharmacological Characterization Of The Relaxation Induced By The Soluble Guanylate Cyclase Activator, Bay 60-2770 In Rabbit Corpus Cavernosum.

To characterize the relaxation induced by the soluble guanylate cyclase (sGC) activator, BAY 60-2770 in rabbit corpus cavernosum. Penis from male New Zealand rabbits were removed and fours strips of corpus cavernosum (CC) were obtained. Concentration-response curves to BAY 60-2770 were carried out in the absence and presence of inhibitors of nitric oxide synthase, L-NAME (100 μM), sGC, ODQ (10 μM) and phosphodiestarase type 5, tadalafil (0.1 μM). The potency (pEC50) and maximal response (Emax) values were determined. Second, electrical-field stimulation (EFS)-induced contraction or relaxation was realized in the absence and presence of BAY 60-2770 (0.1 or 1 μM) alone or in combination of ODQ (10 μM). In the case of EFS-induced relaxation two protocols were realized: 1) ODQ (10 μM) was first incubated for 20 min and then BAY 60-2770 (1 μM) was added for another 20 min (ODQ + BAY 60-2770). In different CC strips, BAY 60-2770 was incubated for 20 min followed by another 20 min with ODQ (BAY 60-2770 + ODQ). The intracellular levels of cyclic guanosine monophosphate (cGMP) were also determined. BAY 60-2770 potently relaxed rabbit CC with pEC50 and Emax values of 7.58 ± 0.19 and 81 ± 4%, respectively. The inhibitors ODQ (n=7) or tadalafil (n=7) produced 4.2- and 6.3-leftward shifts, respectively in BAY 60-2770-induced relaxation without interfering on the Emax values. The intracellular levels of cGMP were augmented after stimulation with BAY 60-2770 (1 μM) alone, whereas its co-incubation with ODQ produced even higher levels of cGMP. The EFS-induced contraction was reduced in the presence of BAY 60-2770 (1 μM) and this inhibition was even greater when BAY 60-2770 was co-incubated with ODQ. The nitrergic stimulation induced CC relaxation, which was abolished in the presence of ODQ. BAY 60-2770 alone increased the amplitude of relaxation. Co-incubation of ODQ and BAY 60-2770 did not alter the relaxation in comparison with ODQ alone. Interestingly, when BAY 60-2770 was incubated prior to ODQ, EFS-induced relaxation was partly restored in comparison with ODQ alone or ODQ + BAY 60-2770. Considering that the relaxation induced by the sGC activator, BAY 60-2770 was increased after sGC oxidation and unaltered in the absence of nitric oxide, these class of substances are advantageous over sGC stimulators or PDE5 inhibitors for the treatment in those patients with erectile dysfunction and high endothelial damage. This article is protected by copyright. All rights reserved.

Cromatografia líquida capilar: estado da arte e aplicações

This review describes the advantages and disadvantages of using capillary liquid chromatography (CLC), which is considered the newest member in the analytical separation science arsenal. Although CLC has tremendous potential for being the next major innovation in separatory analysis, it has not yet obtained great popularity compared to conventional high performance (and ultra-high performance) liquid chromatography. Comparisons are made between these techniques and some of the reasons that CLC has not yet reached its potential will be advanced.

Sistema MINUS® - técnica minimamente invasiva para o tratamento das fraturas transtrocanterianas do fêmur

The MINUS system was developed as a minimally invasive procedure that uses a diaphyseal cephalic extramedullary implant for the treatment of transtrochanteral fractures of the femur in elderly patients. The implant consists of a sliding screw coupled to a plate adapted to the minimally invasive technique. The surgical access is approximately three centimeters in length located on the lateral surface of the hip, below the projection of the small trochanter. A perfectly adapted instrument was used for the procedure, which also requires the use of an image intensifier, reducing surgery time and rate of bleeding. The objective of this study is to present a new instrument and implant, developed specifically for treatment with the minimally invasive technique, reducing the length of the conventional surgical access from 10 to three centimetres. This new implant was given the commercial name of MINUS System.

Programas de educação de jovens e adultos e pesquisa acadêmica: a contribuição dos estudos do letramento

The purpose of this article is to introduce elements that allow building an interface between the academic research and the programs of basic education for youngsters and adults. It discusses contributions to these programs that can be found in the results of qualitative research studies. To this end, results of a five-year long project on teacher education are used, which aim was that of analyzing the interaction between teacher and student in youngster and adult literacy classes. The research project was conducted in natural contexts with the purpose of understanding a given social reality, and not of establishing general laws. Therefore, the credibility of its results was built through the observation of multiple contexts, and the gathering of data was made through various methods, from the perspective of several participants observed during a prolonged period of time. This empirical basis was used to evaluate recommendations contained in the report commissioned by Unesco to the International Literacy Institute for presentation at the World Forum on Education held in 2000 in Dakar. This report proposed that the continuous attendance of students to basic education programs is one of the great challenges of the new millennium. With respect to the problem of adult evasion from courses and programs, the article discusses the motivation and accessibility factors, pointed out in official documents as relevant factors to the success or failure of the programs.

Lesões esportivas em atletas com deficiencia visual

Universidade Estadual de Campinas . Faculdade de Educação Física

Comportamento da ativação dos musculos : reto femoral, vasto lateral e vasto medial durante a realização do movimento de extensão do joelho

Universidade Estadual de Campinas . Faculdade de Educação Física

Desporto adaptado no Brasil : origem, institucionalização e atualidade

Universidade Estadual de Campinas. Faculdade de Educação Física

Entre o fogo e o vento : as praticas de batuques e o controle das emoções

Universidade Estadual de Campinas . Faculdade de Educação Física

Lazer e meio ambiente : percorrendo as trilhas de Ouro Preto (um estudo a partir das trilhas do Pico do Itacolomi)

Universidade Estadual de Campinas . Faculdade de Educação Física