Chloramphenicol-induced mitochondrial dysfunction is associated with decreased transferrin receptor expression and ferritin synthesis in K562 cells and is unrelated to IRE-IRP interactions.
For inclusion, subjects aged 6 to 17 years were required to have an average systolic blood pressure (SBP) or diastolic blood pressure (DBP) above the 95th percentile at the last of three visits during 2 weeks of single-blind placebo screening. Early study termination was defined as early termination for any reason. Screening termination was defined as normalization of blood pressure (BP) during the placebo screening phase.
Of 60 patients with a mean BP of 173.3 ± 1.7/98.4 ± 1.2 mmHg, 59 were randomized to losartan + HCTZ (n = 32) or bisoprolol + HCTZ (n = 27). Amlodipine was added if target BP was not achieved at 1 month, and doxazosin was added if target BP was not achieved after 3 months. Body mass index, office and 24-hour ambulatory BP, pulse wave velocity (carotid-femoral [PWVE] and radial [PWVM]), noninvasive central systolic BP, augmentation index (AIx), laboratory investigations, and electrocardiography were done at baseline and after 6 months of treatment.
The aim of this study was to compare the antihypertensive efficacy of losartan 100 mg + hydrochlorothiazide (HCTZ) 25 mg versus bisoprolol 10 mg + HCTZ 25 mg and their influence on arterial stiffness and central blood pressure (BP).
Sub-Saharan Africa experiences an epidemic surge in hypertension. Studies in African Americans led to the recommendation to initiate antihypertensive treatment in Blacks with a diuretic or a low-dose fixed combination including a diuretic. We mounted the Newer versus Older Antihypertensive Agents in African Hypertensive Patients (NOAAH) trial to compare in native African patients a fixed combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic.
Although both treatments decreased both office and 24-hour BP, losartan + HCTZ significantly decreased central systolic BP and had a more positive influence on pulse wave velocity, with a less negative effect of decreased heart rate on AIx and central systolic BP.
The association of an on-line circulation system with a chemometrics-assisted UV detection strategy is described as a useful system to continuously monitor the dissolution of a pharmaceutical preparation containing two active ingredients, and as a tool for the simultaneous determination of the dissolution curves and dissolution profiles of the latter. Multivariate curve resolution with alternating least squares (MCR-ALS) was used as the chemometric tool to quantitate the analytes, while the hydrochlorothiazide-bisoprolol fumarate (HCT-BIS) association was employed as a model for method development. The experiments were carried out with a dissolution tester configured as apparatus II (paddles), under USP 32 official conditions. The suitability of the calibration procedure for quantitating the dissolved drugs was assessed according to ICH guidelines, with regards to linearity in the working range, specificity, accuracy and precision. Figures of merit, including limits of detection and quantitation were also determined, as well as the method's robustness with regards to detection wavelength range. The system was able to consistently provide very reproducible dissolution curves of commercial tablets, which were statistically similar to those furnished by a manual sampling technique, followed by HPLC analysis. To demonstrate the usefulness of the proposed system, the dissolution profiles of different lots of HCT-BIS tablets were acquired and three of them were conveniently compared at a 31 data point level, employing the f(1) and f(2) ("difference" and "similarity") indexes. Use of multiple data points for comparison ensured reliability of the results.
Losartan + HCTZ was as effective as bisoprolol + HCTZ, with target office BP achieved in 96.9% and 92.6% of patients and target 24-hour BP in 75% and 66.7% of patients, respectively, after 6 months. Effective treatment of BP led to significant lowering of central systolic BP, but this was decreased to a significantly (P < 0.05) greater extent by losartan + HCTZ (-23.0 ± 2.3 mmHg) than by bisoprolol + HCTZ (-15.4 ± 2.9 mmHg) despite equal lowering of brachial BP. Factors correlated with central systolic BP and its lowering differed between the treatment groups. Losartan + HCTZ did not alter arterial stiffness patterns significantly, but bisoprolol + HCTZ significantly increased AIx. We noted differences in ΔPWVE, ΔPWVM, and ΔAIx between the groups in favor of losartan + HCTZ. Decreased heart rate was associated with higher central systolic BP and AIx in the bisoprolol + HCTZ group, but was not associated with increased AIx in the losartan + HCTZ group.
NOAAH (NCT01030458) is the first randomized multicenter trial of antihypertensive medications in hypertensive patients born and living in sub-Saharan Africa.
Patients aged 30-69 years with uncomplicated hypertension (140-179/90-109 mmHg) and two or fewer associated risk factors are eligible. After a 4-week run-in period off treatment, 180 patients will be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg or amlodipine/valsartan 5/160 mg. To attain and maintain blood pressure below 140/90 mmHg during 6 months of follow-up, the doses of bisoprolol and amlodipine in the combination tablets will be increased to 10 mg/day with the possible addition of α-methyldopa or hydralazine. NOAAH is powered to demonstrate a 5-mmHg between-group difference in sitting systolic pressure with a two-sided p-value of 0.01 and 90% power. NOAAH is investigator-led and complies with the Helsinki declaration.