Effects of short-term supplementation with folic acid on different oxidative stress parameters in patients with hypertension.

Oxidative stress seems to play an important role in the pathophysiology of essential hypertension. Due to its antioxidant features, we studied the protective action of folic acid in hypertensive patients, their food supplemented for 2 weeks with this vitamin. Several oxidative stress parameters were measured in the serum of these patients. The results show that folic acid supplementation improves levels of oxidative stress markers in individuals with hypertension, overall in those patients whose initial parameter values were highest.

Glucose effectiveness is strongly related to left ventricular mass in subjects with stage I hypertension or high-normal blood pressure.

BACKGROUND: Evidence suggests that "glucose effectiveness," (SG) or the effect of glucose per se to enhance net glucose disposal, may be at least as important as the insulin sensitivity index (SI) in the assessment of glucose tolerance. Our objective was to study the relationship of SG and SI parameters to left ventricular mass in a group of untreated, nondiabetic, and nonobese subjects recently diagnosed with stage I or high-normal blood pressure (BP). METHODS: In this sample of subjects, among whom the expected prevalence of insulin resistance is low, we assessed SG and SI parameters using the intravenous glucose tolerance test and minimal model analysis. We also measured left ventricular mass (LVM) index and diastolic function by echocardiography. RESULTS: We observed a strong relationship between SG and LVM index (r = -0.61, P <.0001). Patients with left ventricular hypertrophy (LVH) had lower SG than those without LVH (0.1114 +/- 0.04 v 0.2088 +/- 0.08 x 10(-1). min(-1), P <.001). In contrast, patients below the lowest quartile of the SG parameter distribution had higher LVM index (126.4 +/- 23.1 v 94.8 +/- 22.3 g/m(2), P <.001) and also had higher prevalence of LVH than the other patients (P <.0001). The SI related only to diastolic dysfunction, suggesting that SG may be an earlier marker of LVH than SI in hypertension. CONCLUSION: In this sample of nonobese and glucose-tolerant subjects with an early stage of hypertension, SG but not SI was related to LVM.

Role of ketoconazole treatment in urinary-free cortisol-to-cortisone and tetrahydrocortisol-to-tetrahydrocortisone ratios in nonectopic Cushing's syndrome.

We hypothesized that in nonectopic Cushing syndrome there is an insufficient activity of type II (renal) 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) that is related to cortisol excess, rather than to corticotropin (adrenocorticotropic hormone [ACTH]) levels. We measured plasma ACTH and urinary-free cortisol (UFF), urinary-free cortisone (UFE), tetrahydrocortisol (UTHF), and tetrahydrocortisone (UTHE) in 24-h urine samples of 24 healthy subjects and 15 patients diagnosed with nonectopic Cushing syndrome. Then, in the group of patients, a new 24-h urine sample was collected after treatment with 800 mg daily of ketoconazole. The UFF/UFE and UTHF/UTHE ratios were calculated as an estimation of 11beta-HSD2 activity. The patients had an increase in both the UFF/UFE (19.95 +/- 10.3 vs 5.78 +/- 4.72 nmol/24 h; p < 0.0001) and UTHF/UTHE ratios (5.36 +/- 5.23 vs 1.39 +/- 0.95 nmol/24 h; p < 0.001). Both UFF/UFE and UTHF/UTHE ratios decreased after ketoconazole treatment (19.95 +/- 10.3 vs 12.2 +/- 6.9 nmol/24 h; p < 0.005; and 5.36 +/- 5.23 vs 1.62 vs 1.21 nmol/24 h; p < 0.001, respectively). The control subjects had a significant relationship between UFF and UFE (r = 0.70, p < 0.0001), and between UTHF and UTHE (r = 0.75, p < 0.0001) that did not exist in the patient group. After ketoconazole treatment, the decrease in cortisol excretion in the patient group allowed a positive and significant relation between UFF and UFE (r = 0.64, p < 0.01) and between UTHF and UTHE (r = 0.56, p < 0.05) to appear. There was not any significant relationship between either UFF/UFE or UTHF/UTHE ratios and plasma levels of ACTH.

Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect.

BACKGROUND: Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors have beneficial effects beyond their cholesterol-lowering properties. The antioxidant mechanism of HMGCoA reductase inhibitors is not completely understood. OBJECTIVES: To elucidate the antioxidant effect of simvastatin. METHODS: We studied the influence of simvastatin treatment on the development of hypertension, modification of antioxidant systems, and reactivity of aortic rings in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. RESULTS: Simvastatin had no effect on blood pressure (BP). Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats. Carbachol-induced relaxation of aortic rings was impaired in control SHR rats and was restored by simvastatin treatment. Addition of SOD improved the response in control SHR rats and did not have any effect in treated SHR rats. Addition of diethyldithiocarbamic acid, a selective inhibitor of SOD, produced a mild non-significant impairment in carbachol-induced relaxation in control SHR rats, suggesting a deficient antioxidant system in these animals. However, in treated SHR and in WKY rats, impairment of the relaxation was marked, implying that SOD activity in these animals was important to maintain endothelial function. In aortic rings without endothelium from SHR rats, contraction induced by free radicals was substantially higher than in WKY rats. This effect was attenuated in 1-mg-treated rats and abolished in 2-mg-treated rats. CONCLUSIONS: Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a major complication of intra-arterial (IA) thrombolytic therapy. Identifying significant predictors of hemorrhage after thrombolysis would be useful in guiding patient selection for IA treatment. METHODS: Data were collected retrospectively on consecutive patients with acute focal cerebral ischemia within the anterior or posterior circulation who were treated with combined intravenous (IV)-IA or pure IA thrombolysis over an 8-year period at the UCLA Medical Center. RESULTS: Eighty-nine patients were treated. Median baseline National Institutes of Health Stroke Scale (NIHSS) score was 16, and mean age was 69 years. Twenty-six patients received IA tissue plasminogen activator (tPA) only, 22 received IV-IA tPA, and 41 received IA urokinase only. Asymptomatic HT occurred in 29 patients (33%), minor symptomatic HT (1- to 3-point worsening in NIHSS score) occurred in 10 patients (11%), and major symptomatic HT (> or = 4-point worsening in NIHSS score) occurred in 6 patients (7%). The rate of any HT was similar in patients treated with pure IA thrombolysis (39%) versus combined IV-IA thrombolysis (41%). In pure IA cases, the rate of any HT was 50% with tPA versus 32% with urokinase (P=0.2). Eighty-six percent of the patients with HT versus 39% of the patients without HT were dead or disabled (modified Rankin score >2) at day 7 (P<0.0001). On multivariate analysis, independent predictors of any HT were higher NIHSS score, longer time to recanalization, lower platelet count, and higher glucose level. A model using these variables correctly predicted HT with positive predictive value 70% and overall accuracy 78%. CONCLUSIONS: In this large series of IA thrombolysis, rates of HT were similar to those demonstrated in prior series and clinical trials. Higher NIHSS score, longer time to recanalization, lower platelet count, and higher glucose level were independent predictors of any HT.

Disminución de la actividad de la 11- ß-hidroxiesteroide deshidrogenasa en pacientes con síndrome de Cushing / Decreased activity of 11-ß-hydroxysteroid dehydrogenase in patients with Cushing's syndrome

Fundamento: Análisis de la actividad de la 11-ß-hidroxiesteroide deshidrogenasa en el síndrome de Cushing. Pacientes y método: Determinación de la eliminación en orina de 24 h de cortisol, cortisona y sus tetrahidroderivados en 15 pacientes con síndrome de Cushing y 24 controles sanos. Resultados: Existía una relación lineal significativa entre cortisol y cortisona (r = 0,70; p < 0,0001) y entre sus tetrahidroderivados (r = 0,75; p < 0,0001) en los controles, pero no en los pacientes. Conclusiones: Los pacientes con síndrome de Cushing presentan un déficit de la actividad de la 11-ß-hidroxiesteroide deshidrogenasa (AU)