The effect of non-antihypertensive doses of angiotensin converting enzyme inhibitor on myocardial necrosis and hypertrophy in young rats with renovascular hypertension

In renovascular hypertensive rats, low doses of angiotensin converting enzyme (ACE) inhibitors have been found to prevent myocardial hypertrophy independent of blood pressure level. This finding would suggest humoral rather than mechanical control of myocyte growth. The aim of this study was to examine the effect of nonantihypertensive doses of ACE inhibitor on myocardial hypertrophy and necrosis in hypertensive rats. Renovascular hypertension (RHT) was induced in four-week-old Wistar rats. Twenty-eight animals were treated for four weeks with three doses of ramipril (0.01, 0.1 or 1.0 mg/kg/day, which are unable to lower blood pressure. Fourteen animals were not treated (RHT group). A sham operated, age/sex-matched group was used as control (n=10). Myocardial histology was analysed in 3 μm thick sections of the ventricle stained with either haematoxylin-eosin, reticulin silver stain or Masson's trichrome. There was a significant correlation between systolic blood pressure and left ventricular to body weight ratio in both sets of animals: untreated plus controls and ramipril-treated rats. ACE inhibition prevented myocyte and perivascular necrosis and fibrosis in a dose-dependent manner. We conclude that myocardial hypertrophy in rats with renovascular hypertension is directly related to arterial pressure, and that this relationship is not affected by nonantihypertensive doses of ACE inhibitor. Myocardial necrosis/fibrosis and coronary artery damage induced by angiotensin II are prevented by ACE inhibitor in a dose-dependent manner, despite the presence of arterial hypertension.

Evaluation of toxicity after one-months treatment with Bauhinia forficata decoction in streptozotocin-induced diabetic rats

Background: Previous experiments have shown that a decoction of Bauhinia forficata leaves reduces the changes in carbohydrate and protein metabolism that occur in rats with streptozotocin-induced diabetes. In the present investigation, the serum activities of enzymes known to be reliable toxicity markers were monitored in normal and streptozotocin-diabetic rats to discover whether the use of B. forficata decoction has toxic effects on liver, muscle or pancreas tissue or on renal microcirculation. Methods: An experimental group of normal and streptozotocin-diabetic rats received an aqueous decoction of fresh B. forficata leaves (150 g/L) by mouth for 33 days while a control group of normal and diabetic rats received water for the same length of time. The serum activity of the toxicity markers lactate dehydrogenase, creatine kinase, amylase, angiotensin-converting enzyme and bilirubin were assayed before receiving B. forficata decoction and on day 19 and 33 of treatment. Results: The toxicity markers in normal and diabetic rats were not altered by the diabetes itself nor by treatment with decoction. Whether or not they received B. forficata decoction the normal rats showed a significant increase in serum amylase activity during the experimental period while there was a tendency for the diabetic rats, both treated and untreated with decoction, to have lower serum amylase activities than the normal rats. Conclusions: Administration of an aqueous decoction of B. forficata is a potential treatment for diabetes and does not produce toxic effects measurable with the enzyme markers used in our study. © 2004 Pepato et al; licensee BioMed Central Ltd.

Treatment of atherosclerotic renovascular disease

Treatment of atherosclerotic renovascular disease is controversial and revascularization is not a beneficial approach to all patients. Conditions as progressive deterioration of renal function, refractory hypertension or accelerated cardiovascular disease, especially recurrent pulmonary edema, could profit from renal angioplasty with stent placement. Surgical revascularization is a good option for patients who will need concomitant surgical corrections of abdominal aortic lesions. Treatment of all other patients must be individualized. Medical therapy is indicated for all patients with atherosclerotic renovascular disease. Observational studies pointed out to the beneficial effect of controlling blood pressure (<130/80 mm Hg), glucose and lipids profile, lifestyle modifications, specific use of platelet antiaggregant therapy, Angiotensin Conversion Enzyme Inhibitors (ACEI) and statins. All others cardiovascular risk factors must be controlled. The evaluation and management of other systemic atherosclerotic vascular lesions is important, especially coronary, carotid and abdominal aortic. This paper presents a review of evidences to rationale the atherosclerotic renovascular disease treatment. © 2008 Bentham Science Publishers Ltd.

Anthracycline-induced cardiotoxicity

The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/ attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed. © 2008 Bentham Science Publishers Ltd.

Farmacología en la tercera edad: Medicamentos de uso continuo y peligros de la interacción medicamentosa

Introduction: It was observed a considerable growth of elderly people. They are who use more medicines. The physiological changes associated with the age advancing can make pharmacokinetic and pharmacodynamic alterations. The cognitive decline, physical limitations and associate chronic pathology affect the medications appropriately use ability. Aims: Based in a literature review, appoint the main pharmacological groups prescribed to the elderly and the drug-drug interaction risks. Conclusion: The most of elderly use continually at least 3 medicines, the most prescribed are to cardiovascular and psychic diseases treatment.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): Study protocol for a randomized double-blind controlled trial

Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted.Methods/design: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution.Discussion: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number: ClinicalTrials.gov: NCT00971165. © 2011 Fuchs et al; licensee BioMed Central Ltd.

Prevention of hypertension in patients with pre-hypertension: Protocol for the PREVER-prevention trial

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial Registration: Clinical Trials NCT00970931. © 2011 Fuchs et al; licensee BioMed Central Ltd.

Ausência de arteriosclerose na porção intramiocárdica das artérias coronárias: Um mistério a ser resolvido?

Several studies show that portions of intramyocardial coronary arteries are spared of arteriosclerosis, involving morphological, embryological, biochemical and pathophysiological aspects. Endothelial function is significantly affected in the segment of transition, as estimated by the vasoactive response to Ach. These findings suggest that myocardial bridge can provide protection against arteriosclerosis by counteracting the negative effects of endothelial dysfunction. The intramyocardial portion's protection phenomenon deserves further scientific research on all research fronts. Improved morphological, biomechanical and especially physiological and embryological knowledge may be the key to a future window of opportunity for chronic arterial disease therapy and prevention. In addition, this review discusses possible therapeutic approaches for symptomatic coronary ischemia caused by myocardial bridges.

Causes of resistant hypertension detected by a standardized algorithm

Resistant hypertension (RH) is characterized by blood pressure above 140 × 90 mm Hg, despite the use, in appropriate doses, of three antihypertensive drug classes, including a diuretic, or the need of four classes to control blood pressure. Resistant hypertension patients are under a greater risk of presenting secondary causes of hypertension and may be benefited by therapeutical approach for this diagnosis. However, the RH is currently little studied, and more knowledge of this clinical condition is necessary. In addition, few studies had evaluated this issue in emergent countries. Therefore, we proposed the analysis of specific causes of RH by using a standardized protocol in Brazilian patients diagnosed in a center for the evaluation and treatment of hypertension. The management of these patients was conducted with the application of a preformulated protocol which aimed at the identification of the causes of resistant hypertension in each patient through management standardization. The data obtained suggest that among patients with resistant hypertension there is a higher prevalence of secondary hypertension, than that observed in general hypertensive ones and a higher prevalence of sleep apnea as well. But there are a predominance of obesity, noncompliance with diet, and frequent use of hypertensive drugs. These latter factors are likely approachable at primary level health care, since that detailed anamneses directed to the causes of resistant hypertension are applied. © 2012 Livia Beatriz Santos Limonta et al.

Caracterização do soro de leite de búfala: identificação das proteínas e produção de hidrolisados com médio e alto grau de hidrólise

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Produção e aplicação de hidrolisado de proteínas do soro de queijo bovino no preparado de suplemento nutricional: minimização da sarcopenia em ratos idosos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Proteínas do soro de queijo: hidrólise e formulação de suplemento alimentar para ratos Wistar

Pós-graduação em Alimentos e Nutrição - FCFAR

Transport of amino acids from milk whey by Caco-2 cell monolayer after hydrolytic action of gastrointestinal enzymes

The bioavailability of amino adds from milk whey protein hydrolysates was evaluated using diffusion of the substances through semi-permeable membranes (dialyzability) and transport by Caco-2 cell cultures. The hydrolysates with low degree of hydrolysis (LDH) and high degree of hydrolysis (HDH) were obtained after 120 min of reaction time at 50 degrees C after the initial addition of pepsin, followed by the addition of trypsin, chymotrypsin and carboxypeptidase-A. The proteins and hydrolysates were further subjected to in vitro digestion with pepsin plus pancreatin. HPLC was used to determine the concentrations of dialyzable amino adds (48.4% of the non-hydrolyzed proteins, 63.2% of the LDH sample and 58.3% of the HDH sample), demonstrating the greater dialyzability of the hydrolysates. The LDH and HDH whey protein hydrolysates prepared with pepsin, trypsin, chymotrypsin and carboxypeptidase-A showed only 14.7% and 20.8% of dialyzable small peptides and amino acids, respectively. The efficiency of absorption was demonstrated by the preferential transport of Ile, Lou and Arg through a layer of cells. In the LDH hydrolysate, Tyr was also transported. Prior high- and low-degree hydrolysis of the whey provided transport by 5.7% and 6.6%, respectively, in comparison with 23% for non-hydrolyzed proteins, considering the total amount of these amino adds that was applied to the cells. (C) 2014 Elsevier Ltd. All rights reserved.

Buffalo cheese whey proteins, identification of a 24 kda protein and characterization of their hydrolysates: in vitro gastrointestinal digestion

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)