RESUMEN
BACKGROUND AND AIMS: Obesity and hypoadiponectinemia are often associated with high blood pressure. Moreover, microvascular dysfunction is reported to be an early event in patients with hypertension and may be involved in the pathogenesis of organ damage. METHODS AND RESULTS: We investigated the impact of 8-week moderate-intensity aerobic training on adiponectin plasma levels and skin microvascular reactivity in 24 overweight sedentary patients (18 men, age 44+/-6 years, body mass index 28+/-3 kg/m(2)) with never-treated grade 1 essential hypertension. Twenty-four age- and sex-matched hypertensive patients, who were examined twice at 8-week intervals in the absence of exercise training, served as controls. Exercise training was followed by a significant reduction in waist circumference (from 97+/-9 to 95+/-9 cm, p<0.05) and an increase in adiponectin plasma levels (from 11.9+/-3 to 12.5+/-4 mg/L, p<0.05). An inverse correlation was found between adiponectin change and waist circumference change (r=-0.43, p<0.05). The area under the curve after post-occlusive reactive hyperemia at skin laser-Doppler examination increased significantly after aerobic training (from 876+/-539 to 1468+/-925 PU/s, p<0.001). A positive correlation was found between exercise-induced variations of post-occlusive reactive hyperemia and adiponectin plasma levels (r=0.41, p<0.05). Office or 24-h blood pressure values did not change significantly. CONCLUSION: In sedentary overweight patients with mild hypertension, moderate aerobic training improves cutaneous microvascular reactivity and adiponectin plasma levels. These changes precede blood pressure reduction and may serve as biomarkers of the efficacy of non-drug treatment in hypertensive patients.
Asunto(s)
Terapia por Ejercicio , Hipertensión/terapia , Microcirculación , Sobrepeso/terapia , Conducta Sedentaria , Piel/irrigación sanguínea , Adiponectina/sangre , Adulto , Biomarcadores/sangre , Presión Sanguínea , Femenino , Humanos , Hiperemia/fisiopatología , Hipertensión/sangre , Hipertensión/complicaciones , Hipertensión/fisiopatología , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Sobrepeso/sangre , Sobrepeso/complicaciones , Sobrepeso/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Circunferencia de la CinturaRESUMEN
BACKGROUND: Patients with renal insufficiency tend to suffer from advanced atherosclerosis and exhibit a reduced life expectancy. OBJECTIVES AND DESIGN: This prospective study investigated the relation between renal dysfunction and long-term all-cause and cardiovascular mortality in a population of nonsurgical patients with lower extremity arterial disease (LEAD). SUBJECTS AND METHODS: A total of 357 patients with symptomatic LEAD underwent baseline glomerular filtration rate (GFR) estimation by the 4-variable Modification Diet in Renal Diseases equation, and were then followed for 4.2 years (range: 1-17). RESULTS: During follow-up, 131 patients died (8.6 deaths per 100 patient-years), 79 of whom (60%) from cardiovascular causes. All-cause death rates were 3.8, 6.6, and 15.5 per 100 patient-years, respectively, in the groups with normal GFR, mild reduction in GFR (60-89 mL min(-1) per 1.73 m2) and chronic kidney disease (CKD; <60 mL min(-1) per 1.73 m2; P < 0.001 by log-rank test). Compared to patients with normal renal function, the risk of all-cause and cardiovascular death was significantly higher in patients with CKD [hazard ratio, respectively, 2.23, 95% confidence interval (CI): 1.16-4.34, P = 0.017; 2.15, 95% CI: 1.05-4.43, P = 0.03]. The association of CKD with all-cause and cardiovascular mortality were independent of age, LEAD severity, cardiovascular risk factors and treatment with angiotensin-converting enzyme (ACE)-inhibitors, hypolipidaemic and antiplatelet drugs. The power of GFR in predicting all-cause death was higher than that of ankle-brachial pressure index (P = 0.029) and Framingham risk score (P < 0.0001). CONCLUSION: Chronic kidney disease strongly predicts long-term mortality in patients with symptomatic LEAD irrespective of disease severity, cardiovascular risk factors and concomitant treatments.
Asunto(s)
Enfermedades Vasculares Periféricas/complicaciones , Insuficiencia Renal/complicaciones , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Enfermedad Crónica , Creatinina/sangre , Electrocardiografía , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Riñón/fisiopatología , Extremidad Inferior , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/mortalidad , Enfermedades Vasculares Periféricas/fisiopatología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Insuficiencia Renal/mortalidad , Insuficiencia Renal/fisiopatología , Medición de Riesgo/métodos , Fumar/efectos adversos , Tasa de SupervivenciaRESUMEN
The p53 tumor suppressor controls multiple cell cycle checkpoints regulating the mammalian response to DNA damage. To identify the mechanism by which p53 regulates G2, we have derived a human ovarian cell that undergoes p53-dependent G2 arrest at 32 degrees C. We have found that p53 prevents G2/M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter. Cyclin B1 is the regulatory subunit of the cdc2 kinase and is a protein required for mitotic initiation. The ability of p53 to control mitotic initiation by regulating intracellular cyclin B1 levels suggests that the cyclin B-dependent G2 checkpoint has a role in preventing neoplastic transformation.
Asunto(s)
Ciclo Celular/fisiología , Ciclina B/fisiología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Animales , Proteína Quinasa CDC2/metabolismo , Línea Celular , Ciclina B/genética , Ciclina B1 , Femenino , Fase G2 , Regulación de la Expresión Génica , Genes Reporteros , Humanos , Ratones , Mitosis , Neoplasias Ováricas , Proteínas Quinasas/metabolismo , Proteínas Recombinantes/metabolismo , Transfección , Células Tumorales CultivadasRESUMEN
Raynaud's phenomenon is in most cases idiopathic, but it may appear as secondary to other diseases. Since clinical evaluation is often inadequate to distinguish between these two forms, simple noninvasive methods are needed for an early diagnosis of the secondary form. The authors used nailfold capillaroscopy to study 58 patients with Raynaud's phenomenon--44 apparently idiopathic and 14 secondary to connective tissue diseases. In all patients affected by secondary Raynaud's phenomenon nailfold capillaroscopy confirmed the presence of an abnormal pattern with typical systemic sclerosis alterations in 5 cases. Twenty-one (48%) of the other 44 patients presented a normal capillaroscopic pattern, 15 (34%) had alterations compatible with long-term idiopathic Raynaud's phenomenon, and 8 (18%) showed abnormal capillaroscopic patterns, 2 of which were identified as the sclerodermic pattern. Nailfold capillaroscopy distinguishes between primary and secondary Raynaud's phenomenon and may be used to identify patients presenting no evidence of underlying disease who could be at risk of developing connective tissue disease.
Asunto(s)
Enfermedad de Raynaud/diagnóstico , Piel/irrigación sanguínea , Adulto , Anciano , Capilares/patología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Uñas , Enfermedad de Raynaud/etiologíaRESUMEN
The efficacy of physical training alone or combined with antiplatelet therapy (dipyridamole and aspirin) was studied in 30 patients with stage II peripheral arterial occlusive disease (PAOD). Patients were randomly allocated to one of the following groups: Group A--dipyridamole 75 mg three times daily and aspirin 330 mg once daily: Group B--physical exercise; Group C--physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily. After six months' treatment the pain-free walking time (PFWT) and the maximum walking time (MWT) improved significantly (p less than 0.05) in all three groups. In group A the PFWT lengthened by 35% (from 101.00 +/- 34.56 to 137.32 +/- 40.50 s) and the MWT by 38% (from 150.34 +/- 55.60 to 207.26 +/- 60.67 s); in group B the PFWT lengthened by 90% (from 90.65 +/- 40.54 to 171.45 +/- 55.60 s) and the MWT by 86% (from 145.39 +/- 60.50 to 270.63 +/- 63.61 s). When physical exercise was associated with drugs as in group C, the PFWT lengthened by 120% (from 89.51 +/- 43.89 to 196.72 +/- 51.73 s) and the MWT by 105% (from 160.43 +/- 59.84 to 329.05 +/- 63.96 s). No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after standard treadmill exercise, in the plethysmographic rest and peak flows, or in the transcutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia. The results confirm the benefits of regular exercise in stage II PAOD patients but suggest they may be enhanced by antiplatelet therapy.
Asunto(s)
Aspirina/uso terapéutico , Dipiridamol/uso terapéutico , Terapia por Ejercicio , Claudicación Intermitente/terapia , Terapia Combinada , Femenino , Humanos , Claudicación Intermitente/rehabilitación , Masculino , Persona de Mediana Edad , Factores de Tiempo , CaminataRESUMEN
Treating chronic arterial occlusive disease with heparin is controversial because of the risks associated with long-term anticoagulant therapy. Low molecular weight (LMW) heparin (mw about 5000 Dalton), which selectively inhibits the Xa factor with minimal risk of hemorrhage, seems to offer new possibilities in the prevention and treatment of both venous and acute arterial thromboembolism. Therefore, 44 patients with intermittent claudication were recruited to a randomized, double-blind, controlled study. Twenty-two were treated for six months with a single daily subcutaneous dose (15,000 UaXa) of LMW heparin and 22 with placebo administered in the same way over the same period of time. After six months, LMW heparin treatment not only improved walking capacity (by lengthening the pain-free walking time by 25%) but also significantly modified the hemorrheologic pattern (by reducing fibrinogen concentrations and whole blood viscosity at low shear rates). LMW heparin also exerted an antithrombotic and profibrinolytic effect by significantly increasing both the anti-Xa factor and plasminogen activity without markedly modifying activated partial thromboplastin time (+20%). No LMW heparin-treated patient hemorrhaged or reported other noteworthy side effects. These results suggest LMW heparin might be a useful drug in the long-term treatment of chronic arterial occlusive disease of the limbs.