Nutraceutical approaches to homocysteine lowering in hypertensive subjects at low cardiovascular risk: a multicenter, randomized clinical trial.

Although the role of homocysteine (HCys) in secondary cardiovascular prevention has been scaled down, hyper-homocysteinemia remains a risk factor for cerebrovascular events. The aim of this study was to investigate the efficacy of nutraceuticals in lowering HCys serum levels versus a conventional vitamin supplementation in hypertensive subjects at low cardiovascular risk. One-hundred and four patients (mean age 62.8±14.5 years, 63.5% males), 52 for each treatment group, were enrolled. The study recruited patients with stage 1 essential hypertension and hyper-homocysteinemia (HCys ≥15 µmol/L), without a history of cardiovascular and cerebrovascular disease. They were sequentially randomized to receive a combined nutraceutical containing 400 µg folate-6-5-methyltetrahydrofolate, 3 mg vitamin B6, 5 µg vitamin B12, 2.4 mg vitamin B2, 12.5 mg zinc and 250 mg betaine (Normocis400®) once daily for two months, or supplementation with highly dosed folic acid (5 mg/day) (control group). Differences in serum HCys values were compared by ANOVA for repeated measures. A significant HCys reduction in comparison to baseline was found in both groups at the end of the study treatment, from 21.5±8.7 to 10.0±1.7 µmol/L for Normocis400® subjects (p less than 0.0001), and from 22.6±6.2 to 14.3±2.8 µmol/L for controls (p less than 0.0001). HCys reduction was significantly higher among patients treated with Normocis400® (p less than 0.035). The ideal HCys level (i.e. less than 10 µmol/L) was reached in 55.8% of cases in theNormocis400® group, and it was significantly higher than in controls. No side effects were observed in either treatment group. Randomized clinical trials are ongoing to test the effect of folate, B6, and B12 supplementation in primary prevention of cardiovascular and cerebrovascular events. In the meantime, especially when the ideal HCys level is far from being reached, Normocis400® appears to be safe, well tolerated and effective in reducing HCys levels.

Rhodamine/Nanodiamond as a System Model for Drug Carrier.

In this paper we present some strategies that are being developed in our labs towards enabling nanodiamond-based applications for drug delivery. Rhodamine B (RhB) has been choosen as model molecule to study the loading of nanodiamonds with active moieties and the conditions for their controlled release. In order to test the chemical/physical interactions between functionalized detonation nanodiamond (DND) and complex molecules, we prepared and tested different RhB@DND systems, with RhB adsorbed or linked by ionic bonding to the DND surface. The chemical state of the DND surfaces before conjugation with the RhB molecules, and the chemical features of the DND-RhB interactions have been deeply analysed by coupling DND with Au nanoparticles and taking advantage of surface enhanced Raman spectroscopy SERS. The effects due to temperature and pH variations on the process of RhB release from the DND carrier have been also investigated. The amounts of released molecules are consistent with those required for effective drug action in conventional therapeutic applications, and this makes the DND promising nanostructured cargos for drug delivery applications.

Effects of the Antihypertensive Fixed-Dose Combinations on an Early Marker of Hypertensive Cardiac Damage in Subjects at Low Cardiovascular Risk.

BACKGROUND: In hypertensive subjects (HTs), isolated left ventricular diastolic dysfunction (LVDD) is an early marker of cardiac damage and is associated with poor prognosis. However, few intervention trials investigated the effects of antihypertensive therapy on isolated LVDD regression. This study investigates the blood pressure (BP)-lowering efficacy and the effect on LVDD of antihypertensive drugs administered as fixed-dose combinations in untreated HTs with isolated LVDD. METHODS: A total of 168 HTs (23% of them having impaired fasting glucose (IFG)) aged 48±4.2 years were randomized to receive open-label once-daily oral treatment of beta-blocker + diuretic, angiotensin-converting enzyme inhibitor (ACEI) + diuretic, angiotensin II receptor blocker (ARB) + diuretic, ARB + calcium channel blocker (CCB), or ACEI + CCB. Clinic and 24-hour ambulatory BP values were measured before randomization and at the follow-up. Regression of LVDD was defined as normalization of both the E/A (ratio of early-to-late ventricular filling wave velocity) and E/E' (mitral velocity to early diastolic velocity of the mitral annulus) ratios. Comparisons were made between categorical variables using the χ(2) test and between continuous variables by gender using analysis of variance for repeated measures. RESULTS: BP reduction did not differ between groups. LVDD regression was significantly more prevalent in the ARB + CCB or ACEI + CCB groups than with other combinations; in HTs with IFG, it was most prevalent (46%) with ACEI + CCB. CONCLUSIONS: Independently of BP reduction, the fixed-dose combinations ARB + CCB and ACEI + CCB led to regression of isolated LVDD. In those with an IFG, ACEI + CCB was most effective.

Aerobic exercise training fails to reduce blood pressure in nondipper-type hypertension.

To assess whether aerobic exercise training is an effective and an alternative method to control blood pressure (BP) in hypertension, 32 uncomplicated, never treated patients suffering from mild-to-moderate essential arterial hypertension (EAH) were included in an aerobic exercise training program using a regular standardized cycle ergometer exercise for 3 months. In all EAH patients, before and after the exercise training period, ambulatory BP monitoring (ABPM) was performed and several metabolic variables were assessed. Before exercise, in 20 EAH patients, a 48-h ABPM showed a normal day-night rhythm, with nocturnal BP decrease, according to a dipper-type hypertension, whereas in 12 EAH patients 48-h ABPM profile indicated a nondipper-type hypertension. After exercise, EAH dippers presented a significant decrease in the daytime systolic and diastolic BP, whereas EAH nondippers did not show any change in daytime and nighttime systolic and diastolic BP. Our study confirms the controversy about the postulated BP lowering effect of dynamic exercise in EAH patients, in the sense that only EAH dipper patients seem to obtain a beneficial diurnal lowering BP effect deriving from exercise, possibly through a reduction in sympathetic tone. On the contrary, physical activity seems to fail in reducing diurnal and nocturnal BP values in EAH nondippers, suggesting that in nondipper-type hypertension, other "masking" endogenous or exogenous factors could interfere with and prevail over the adrenergic-vagal balance that modulates the day-night BP synchronism.