Hot-melt co-extrusion for the production of fixed-dose combination products with a controlled release ethylcellulose matrix core

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Squamous cell carcinoma of the dorsal hands and feet after repeated exposure to ultraviolet nail lamps

Gel nails are a common artificial nail option. Ultraviolet (UV) nail lamps are commonly used to cure gel nails. Ultraviolet A radiation is a known mutagen that penetrates into the nail bed. Although previously reported, the role of UV nail lamps in the carcinogenesis of both keratinocyte carcinoma and melanoma remains controversial. Herein, we report a patient taking the photosensitizing agent hydrochlorothiazide who developed numerous squamous cell carcinomas on the dorsal hands and feet with a 10-year history of UV nail light exposure every 2-3 weeks

Kidney function in the very elderly with hypertension: data from the hypertension in the very elderly (HYVET) trial.

BACKGROUND: numerous reports have linked impaired kidney function to a higher risk of cardiovascular events and mortality. There are relatively few data relating to kidney function in the very elderly. METHODS: the Hypertension in the Very Elderly Trial (HYVET) was a randomised placebo-controlled trial of indapamide slow release 1.5mg ± perindopril 2-4 mg in those aged ≥80 years with sitting systolic blood pressures of ≥160 mmHg and diastolic pressures of <110 mmHg. Kidney function was a secondary outcome. RESULTS: HYVET recruited 3,845 participants. The mean baseline estimated glomerular filtration rate (eGFR) was 61.7 ml/min/1.73 m(2). When categories of the eGFR were examined, there was a possible U-shaped relationship between eGFR, total mortality, cardiovascular mortality and events. The nadir of the U was the eGFR category ≥60 and <75 ml/min/1.73 m(2). Using this as a comparator, the U shape was clearest for cardiovascular mortality with the eGFR <45 ml/min/1.73 m(2) and ≥75 ml/min/1.73 m(2) showing hazard ratios of 1.88 (95% CI: 1.2-2.96) and 1.36 (0.94-1.98) by comparison. Proteinuria at baseline was also associated with an increased risk of later heart failure events and mortality. CONCLUSIONS: although these results should be interpreted with caution, it may be that in very elderly individuals with hypertension both low and high eGFR indicate increased risk

Contribution of the sympathetic nervous system to the pathogenesis of salt-sensitive hypertension

Dysregulation of the sodium-chloride cotransporter (NCC) is believed to significantly impact blood pressure. Recent studies have implicated overactivity of the sympathetic nervous system as a mechanism driving renal NCC dysregulation to evoke the development of salt-sensitive hypertension. It is proposed that the sympathetic nervous system accomplishes this by norepinephrine (NE)-mediated over-activation of the beta2-adrenergic receptors located in the distal tubules of the kidney. Beta2-adrenoreceptor activation is hypothesized to stimulate the protein kinases SPAK and OxSR1 to phosphorylate and thus activate NCC. This beta2-receptor-SPAK/OxSR1-NCC pathway was elucidated in studies that challenged salt-resistant mice with high-salt diets, bilateral adrenalectomies, and NE infusion. To expand the scope of these studies, we investigated the effects of elevated circulating NE on blood pressure, NCC activity, and expression of NCC proteins, SPAK, and OxSR1 in a different salt-resistant animal species (the Sprague-Dawley rat). In this study we implanted male Sprague-Dawley rats with osmotic minipumps delivering a subcutaneous infusion of either saline, NE, a 50:50 solution of DMSO/isotonic saline, a combination of NE and the NCC antagonist hydrochlorothiazide, or a combination of NE and the beta-adrenoreceptor antagonist propranolol. Following implantation of the pumps the rats were randomly assigned to either a standard diet (0.4% NaCl) or a high-salt diet (8% NaCl) for two weeks. After fourteen days all animals underwent acute femoral artery, vein, and bladder cannulation in order to monitor heart rate and blood pressure, administer drugs intravenously, and track renal function, respectively. Following surgical recovery, blood pressure and heart rate were measured continuously, and urine was collected in ten-minute intervals in order to assess peak natriuretic responses to amiloride and hydrochlorothiazide. Following this protocol the rats received an intravenous bolus of hexamethonium (30 mg/kg), and their peak drops in blood pressure were recorded. Afterwards both kidneys were harvested and frozen at -80 °C for measurement of NCC proteins, SPAK, and OxSR1 expression. This study demonstrates that increased circulating NE induces salt-sensitive hypertension in the naturally salt-resistant Sprague-Dawley rat. Chronic infusion of NE raised the blood pressure of the rats, and a high-salt diet exacerbated this effect. Furthermore, NE prevented salt-evoked suppression of NCC activity and NCC, SPAK, and OxSR1 protein expression. Co-infusion of hydrochlorothiazide with NE attenuated NE-mediated hypertension and caused no variance in the blood pressures between the standard salt and high-salt groups. This indicates that chronically antagonizing NCC eliminated the salt-sensitive component of NE-mediated hypertension. Beta-receptor antagonism combined with NE infusion completely eliminated the hypertensive influence of NE and downregulated the expression of NCC proteins, SPAK, and OxSR1. However, NCC activity still remained at a level comparable with that observed in the NE-infused rats, demonstrating dissociation between protein expression and function. These data, the first report in a rat model of an interaction of NE and a high salt intake that impairs NCC function, demonstrate that increased levels of NE in combination with a high dietary salt intake result in NCC dysregulation and the development of NE-mediated salt-sensitive hypertension. To an extent the data also support the proposition that NE activates the beta-adrenergic receptors to influence the activity of NCC and the expression of NCC proteins, SPAK, and OxSR1. Beta-antagonism combined with NE infusion attenuated the effects of NE on blood pressure and the expression of NCC proteins, SPAK, and OxSR1. However, the NE-mediated elevation of NCC activity still remained high. We propose that the beta-receptors are not the only adrenergic receptors that can influence NCC activity. The presence of alpha-adrenergic receptors in the distal tubules suggests that they may be able to keep NCC activity elevated through a pathway independent of the beta-receptors, SPAK, and OxSR1

Olmesartan-based monotherapy vs combination therapy in hypertension: A meta-analysis based on age and chronic kidney disease status.

Antihypertensive monotherapy is often insufficient to control blood pressure (BP). Several recent guidelines advocate for initial combination drug therapy in many patients. This meta-analysis of seven randomized, double-blind studies (N = 5888) evaluated 8 weeks of olmesartan medoxomil (OM)-based single-pill dual-combination therapy (OM+amlodipine/azelnidipine or hydrochlorothiazide) vs OM monotherapy in adults with hypertension. BP-lowering efficacy, goal achievement, and adverse events were assessed in the full cohort and subgroups (elderly/nonelderly and patients with and without chronic kidney disease). In the full cohort at week 8, for dual therapy vs monotherapy, seated BP was lower (137.5/86.1 mm Hg vs 144.4/89.9 mm Hg), and the mean change from baseline in BP and BP goal achievement (&lt;140/90 mm Hg) were greater (-22.7/-15.0 mm Hg vs -16.0/-11.3 mm Hg and 51.2% vs 34.7%, respectively). Adverse events were similar between groups. BP-lowering efficacy among subgroups mirrored the findings in the full cohort whereby changes were significantly greater following OM dual-combination therapy vs OM monotherapy

Is early and fast blood pressure control important in hypertension management?

Control of blood pressure (BP) in hypertension is recognized as a key measure in the management of cardiovascular (CV) risk and is a cornerstone of preventive strategies. It is not defined, however, whether an initiation of the antihypertensive treatment in the early stages of hypertension (such as prehypertension or high-normal BP), may bring benefits for the long-term prevention of CV events. In addition, it has not been thoroughly addressed the issue whether achievement of a prompt BP reduction in hypertensive patients may contribute to reduce CV damage and events. The aim of this article is to critically examine data from studies exploring these important questions. Our conclusion is that the available evidence, though not very extensive, supports the prevailing benefits associated with early BP control. We also discuss the therapeutic strategies to achieve early control of BP. Finally, we believe that this aspect deserves to be more thoroughly addressed in upcoming international guidelines

UV-Spectrophotometric Determination of Telmisartan and Hydrochlorothiazide in Combined Tablet Dosage Form Using Simultaneous Equation Method

A UV spectrophotometric method was developed for the estimation of Telmisartan and Hydrochlorothiazide in Combined Tablet Dosage Form Using Simultaneous Equation Method. The drug obeyed the Beers law and shows good correlation near to r 2 = 0.999 for Telmisartan and for Hydrochlorothiazide r 2 =0.999.Absorption maxima of Telmisartan 296.8 nm and Hydrochlorothiazide 271.2 nm. Beers law was obeyed in concentration rang of 5-30 g/ml for Telmisartan and 2-12 g/ml for Hydrochlorothiazide. The method has been validated for linearity, accuracy and precision. The recovery was 99.28 % for Telmisartan and 99.26% for Hydrochlorothiazide. The developed method was found to be accurate, simple, precise, economical, and selective for simultaneous estimation of Telmisartan and Hydrochlorothiazide in tablet formulations