L-glutamine supplementation reduced morphological damage in the renal glomerulus of rats with Walker-256 tumor

ABSTRACT Purpose: To evaluate the effects of the experimental subcutaneous Walker-256 tumor and L-glutamine supplementation, an antioxidant, on the glomerular morphology of rats. Methods: Twenty Wistar rats were distributed into four groups (n = 5): control (C); control treated with 2% L-glutamine (CG); rats with Walker-256 tumor (WT); and rats with Walker-256 tumor treated with 2% L-glutamine (WTG). Renal histological samples were submitted to periodic acid-Schiff and Masson's Trichrome staining to analyze glomerular density, morphometry of glomerular components and glomerulosclerosis; and to immunohistochemistry for fibroblast growth factor-2 (FGF-2). Results: WT showed 50% reduction in body mass gain and cachexia index > 10%, while WTG demonstrated reduction in cachexia (p < 0.05). WT revealed reduction of glomerular density, increase in the glomerular tuft area, mesangial area, matrix in the glomerular tuft, decrease in the urinary space and synechia, and consequently higher glomerulosclerosis (p < 0.05). L-glutamine supplementation in the WTG improved glomerular density, and reduced glomerular tuft area, urinary space, mesangial area, and glomerulosclerosis compared to WT(p < 0.05). WT showed higher collagen area and FGF-2 expression compared to C (p < 0.05). WTG presented lower collagen fibers and FGF-2 expression compared to WT (p < 0.05). Conclusions: L-glutamine supplementation reduced cachexia and was beneficial for glomerular morphology of the rats, as well as it reduced kidney damage and improved the remaining glomeruli morphology.

Evolução temporal da proliferação neointimal após implante de dois tipos de stent farmacológico com polímeros biodegradáveis em modelo porcino: avaliação qualitativa por tomografia de coerência óptica sequencial / Temporal evolution of neointimal proliferation after implantation of two types of drug-eluting stents with biodegradable polymers in porcine model: qualitative assessment by sequential optical coherence tomography

INTRODUÇÃO: Baseados na hipótese de que a neoíntima encontrada em stents farmacológicos (SFs) com polímeros biodegradáveis aos 28 dias não é a neoíntima definitiva e de que a tomografia de coerência óptica (TCO) é um método eficaz para a avaliação sequencial da neoíntima, objetivamos, neste estudo experimental, comparar os achados da TCO aos 28 dias e aos 90 dias em dois tipos de SF com polímeros biodegradáveis: o stent liberador de sirolimus (Inspiron®, Scitech) e o stent liberador de biolimus A9 (Biomatrix®, Biosensors International). MÉTODOS: No total, 6 porcos não-ateroscleróticos foram submetidos a implante de 6 stents Inspiron® e de 6 stents Biomatrix®. Cada porco recebeu os dois tipos de stent, um em cada artéria coronária (descendente anterior e circunflexa) e após 28 dias e 90 dias foram realizadas avaliações qualitativas intrastent a cada milímetro com TCO. RESULTADOS: A avaliação qualitativa, feita por pareamento milímetro a milímetro intrastent, evidenciou neoíntima heterogênea em 39% aos 28 dias e em 0% aos 90 dias, presença de tecido intraluminal em 18% aos 28 dias e em 0% aos 90 dias, irregularidade luminal em 62% aos 28 dias e em 2% aos 90 dias (P < 0,005). Não houve diferença entre os grupos quanto à qualidade da neoíntima ao longo do tempo (P > 0,05). CONCLUSÕES: Os achados à TCO corroboram a hipótese de que a neoíntima encontrada em SFs com polímeros biodegradáveis aos 28 dias não é a neoíntima definitiva. A evidência experimental mais significativa é a mudança das características da neoíntima observada à TCO sequencial.

BACKGROUND: Based on the hypothesis that the neointima found in drug-eluting stents (DES) with biodegradable polymers at 28 days is not a definitive neointima and that optical coherence tomography (OCT) is an effective method for sequential neointimal evaluation, we aim, in this experimental study, to compare OCT findings at 28 and 90 days, in two different DES with biodegradable polymers: the sirolimus-eluting stent (Inspiron®, Scitech) and the biolimus A9-eluting stent (Biomatrix®, Biosensors International). METHODS: Overall, 6 non-atherosclerotic pigs were submitted to the implantation of 6 Inspiron® stents and 6 Biomatrix® stents. Each pig received both stent types, one in each coronary artery (left anterior descending artery and circumflex artery) and after 28 and 90 days qualitative in-stent OCT analyses were performed at 1-millimeter intervals. RESULTS: Qualitative assessment was performed in-stent pairing millimeter by millimeter. Heterogeneous neointimal tissue was evidenced in 39% at 28 days and in 0% at 90 days, the presence of intraluminal tissue in 18% at 28 days and in 0% at 90 days, luminal irregularity in 62% at 28 days and in 2% at 90 days (P < 0.005). There was no difference between groups regarding the quality of the neointima over time (P > 0.05). CONCLUSIONS: The OCT findings corroborate the hypothesis that the neointima found in DES with biodegradable polymers at 28 days is not a definitive neointima. The most significant experimental evidence is the change in the neointimal characteristics observed at sequential OCT.

Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles

OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility and diastolic relaxation and examined the distribution of phosphodiesterase-5 in the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or sildenafil for eight weeks. The Langendorff method was used to examine the effects of sildenafil on cardiac contractility and diastolic relaxation. The presence and location of phosphodiesterase-5 and phosphodiesterase-3 were assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA. RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5 immunoreactivity was localized in the intercalated discs between the myocardial cells. The staining intensity was reduced by L-NAME, and sildenafil treatment abolished this reduction. Consistent with these results, the plasma levels of cGMP were decreased in the L-NAME-treated rats but not in rats that were treated with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.

Hemodynamic, morphometric and autonomic patterns in hypertensive rats - renin-angiotensin system modulation

Background: Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system. AIMS: To investigate the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats. Methods: Male spontaneously hypertensive rats were randomized into two groups: young (n=13) and adult (n=12). Hemodynamic signals (blood pressure, heart rate), blood pressure variability (BPV) and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g), by myocyte diameter (ìm) and by relative fibrosis area (RFA, percent). ACE and ACE2 activities were measured by fluorometry (UF/min), and plasma renin activity (PRA) was assessed by a radioimmunoassay (ng/mL/h). Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU). Results: The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components. Conclusions: The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable...

Human saphenous vein organ culture under controlled hemodynamic conditions

INTRODUCTION: Saphenous vein grafting is still widely used to revascularize ischemic myocardium. The effectiveness of this procedure is limited by neointima formation and accelerated atherosclerosis, which frequently leads to graft occlusion. A better understanding of this process is important to clarify the mechanisms of vein graft disease and to aid in the formulation of strategies for prevention and/or therapeutics. OBJECTIVE: To develop an ex vivo flow system that allows for controlled hemodynamics in order to mimic arterial and venous conditions. METHODS: Human saphenous veins were cultured either under venous (flow: 5 ml/min) or arterial hemodynamic conditions (flow: 50 ml/min, pressure: 80 mmHg) for 1-, 2- and 4-day periods. Cell viability, cell density and apoptosis were compared before and after these intervals using MTT, Hoeschst 33258 stain, and TUNEL assays, respectively. RESULTS: Fresh excised tissue segments were well preserved prior to the study. Hoechst 33258 and MTT stains showed progressive losses in cell density and cell viability in veins cultured under arterial hemodynamic conditions from 1 to 4 days, while no alterations were observed in veins cultured under venous conditions. Although the cell density from 1-day cultured veins under arterial conditions was similar to that of freshly excised veins, the TUNEL assay indicated that most of these cells were undergoing apoptosis. CONCLUSION: The results observed resemble the events taking place during early in vivo arterial-vein grafting and provide evidence that an ex vivo perfusion system may be useful for the identification of new therapeutic targets that ameliorate vein graft remodeling and increase graft patency over time.

Fisiopatologia da hipertensão: o que avançamos? / Pathogenesis of hypertension: what is new?

A hipertensão arterial é uma doença poligênica, que resulta de anormalidades dos mecanismos de controle da pressão arterial. Grande número de substâncias biologicamente ativas pode interagir com diferentes sistemas fisiológicos de maneira complexa e com redundância para garantir a homeostasia cardiovascular. Nesta revisão é descrito o papel do sistema nervoso simpático na gênese e na manutenção da hipertensão e o papel dos pressorreceptores e quimiorreceptores arteriais e os receptores cardiopulmonares no controle da pressão arterial pela modulação da atividade simpática. Influências hormonais, como o sistema renina-angiotensina, e outros peptídeos vasoativos, como as cininas e a vasopressina, são também considerados. Além disso, destacam-se influência de substâncias vasodilatadoras e vasoconstritoras derivadas do endotélio e a disfunção endotelial na hipertensão, bem como as modificações associadas a outros fatores, como o conteúdo de sal na dieta, a obesidade e a inatividade física. Finalmente, com o advento das técnicas de biologia molecular e as abordagens da genética molecular, discute-se a possibilidade de se estabelecer estratégias para estudar e identificar os determinantes genéticos da hipertensão essencial. Além disso, comenta-se a abertura de novas oportunidades no estudo da fisiologia em que um novo campo, a genômica fisiológica, pode ser aplicado no entendimento da genética da hipertensão e das doenças cardiovasculares...