Effect of thyroxine on plasminogen activator and inhibitor activity in rat.

Thyroid hormones influence mineral metabolism, distribution of water and electrolytes and are therefore of great importance in the maintenance of homeostasis under normal and diseased conditions such as renal failure. The present study was carried out to determine the effect of thyroxine on fibrinolytic parameters such as plasminogen activators (PA) in rat kidney, levels of PA and plasminogen activator inhibitor (PAI), glucose in plasma and serum lipid profile injected with thyroxine (75 microg eltroxine/ 100 g(-1) body weight, ip for 7 days). Treatment increased PA activity significantly in rat kidneys. No changes were seen in PA, PAI and glucose in plasma of rats. There was significant decrease in total cholesterol and LDL-cholesterol levels in serum of treated group resulting in the decrease of HDL/LDL and total cholesterol/cholesterol ratios. However, triglycerides and VLDL showed significant higher activity in the serum of treated group as compared to controls. The results suggest beneficial effects of thyroxine treatment by increasing PA activity in kidney and reducing the cholesterol content in blood. It may be helpful to prevent hypercoagulable state by maintaining the normal homeostatic balance and restoring renal function.

Brothers of women with polycystic ovary syndrome: a new group with high risk for type 2 diabetes mellitus and cardiovascular disease

Polycystic ovary syndrome [PCOS] is common endocrinal disorder which is highly inherited and characterized by many metabolic abnormalities. We hypothesized that male relatives of PCOS women would also have metabolic abnormalities. Thus, our aim was to assess insulin sensitivity and metabolic parameters in brothers of women with PCOS and male control individuals. 30 brothers of women with PCOS and 20 male healthy control subjects were included in the study. Brothers and control were subjected to complete medical evaluation with stress on anthropometric measurements, fasting insulin, homeostasis assessment model [HOMA-IR], lipids, plasminogen activator inhibitor-1 [PAI-1], C-reactive protein [CRP] and androgens. Brothers and control individuals were similar as regard to age, MBI, WHR and blood pressure. However, brothers were insulin resistant and had dyslipidemia and dyscoagulability [HOMA-IR, P=0.043, TC P=0.001, LDL-C P=0.002, HDL-C P=0.03, TG P=0.048, PAI-1 P=0.002, CRP P=0.046]. Also HOMA-IR, was correlated significantly with BMI p<0.001, WHR P<0.001, PAI-1 P<0.001, CRP P<0.01, TG, P<0.001, LDL-C P=0.02, HDL-C P=0.019]. Brothers of women with PCOS have a metabolic phenotype consisting of dyslipidemia, insulin resistance, dysmgulability and carry an increased risk of cardiovascular disease [CVD] and type 2 diabetes mellitus [type 2 DM]. Given the high prevalence of PCOS, brothers may represent an important new risk factor for CVD in men and should be considered a well identified group for primary preventive measures

Renin angiotensin aldosterone system and fibrinolytic activity in experimentally induced diabetic and hypertensive rats

Many evidences pointed to certain relations between renin angiotensin aldosterone system [RAAS] and endogenous fibrinolytic system. To examine the effect of low salt supplement, as an activator to endogenous RAAS on plasma fibrinolytic function in alloxan diabetic L-NAME induced hypertensive ncphritic rats in the presence or absence of angiotensin converting enzyme inhibitor [ACEI] and/or aldosterone antagonist. Diabetes was induced in male Wistar rats by a single intraperitoneal [i.p] injection of alloxan [150 mg/kg]. Rats were received low salt supplement [0.08% NaCI] and N[G]-nitro-L-arginine methyl ester [L-NAME, 0.1 mg/ml] in the drinking water during the experimental periods. Treatment of diabetic hypertensive nephritic rats with ACEI [mocxipril hydrochloride, 7 mg/kg body weight daily and orally], aldosterone antagonist [spiranolactone, 25 mg/kg body weight daily and orally] or their combined administration for 6 weeks. Glucose, creatinine, sodium, potassium, aldosterone, ACE activity, transforming growth factor-beta 1 [TGF-beta] were determined in serum, whereas, renin, plasminogen activator inhibitors [PAI-1 were estimated in plasma. In urine nitric oxide [NO] concentration was evaluated and total. DNA and RNA were recorded in kidney tissues. During low salt intake, activation of the RAAS was monitored through observed significant Increase in serum alciosterone, sodium, potassium, and ACE activity. Impairment of renal function following diabetes and L-NAME administration was manifested By increase in serum glucose, mean arterial pressure [MAP] heart rate [HR]. serum creatinine and low urinary NO level, these data demonstrated that activation of RAAS in diabetic hypertensive nephritic rats significantly increased PAI-1 activity, TGF-beta1 and dry thrombus weight. It markedly decreased total DNA contents in kidney homogenate. Interruption of the RAAS with the ACEI, aldosterone antagonist or their combined administration lot 6 weeks significantly decreased PAl-1 activity TGF-beta1 and thrombus weight [fibrinolytic actvity]. However urinary NO, kidney content of total DNA showed significant increase. Combined form therapy has a better effect regarding PAI-1 TGF-beta 1 and NO than monotherapy. Data obtained provides an evidence of direct functional association between the RAAS and the fibrinolytic system in rats. This may help to elucidate possible mechanisms by which ACE inhibition and aldosterone antagonist exerts antagonist exerts vasculoprotective effects and reduce the risk of renal atherothromhotic events closely related to uncontrolled diabetes

Terapêutica de reposiçäo hormonal / Hormone replacement therapy

A mulher, no período pré-menopausa, está relativamente protegida de doença cardiovascular. Admite-se que essa proteção seja devida ao estrogênio e a seus efeitos sobre fatores de risco e mecanismos de aterogênese. A terapêutica de reposição hormonal, definida como tratamento com estrogênio ou a combinação estrogênio e protestógeno, representa, hoje, tema de permanente debate, considerando que sua indicação pode modificar o impacto de várias doenças que afetam a mulher na menopausa. A terapêutica de reposição pode reduzir o risco de osteoporose, câncer de cólon, doença de Alzheimer e doença isquêmica miocárdica, e, simultaneamente, aumentar a mortalidade devida a câncer de mama e de endométrio. Até que estejam disponíveis os resultados de ensaios clínicos aleatórios, com "endpoints" adequadamente definidos de doença cardiovascular, a decisão para o uso de reposição hormonal deverá ser individualizada, levando em conta os possíveis benefícios em mulheres de alto risco cardiovascular frente aos riscos de câncer de endométrio e câncer de mama.