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Alonso-Galicia M.,Hypertension | Zhou X.,Hypertension | Pai L.-Y.,Hypertension | Xiao J.,Hypertension | And 6 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2014

The renal outer medullary potassium (ROMK) channel, which is located at the apical membrane of epithelial cells lining the thick ascending loop of Henle and cortical collecting duct, plays an important role in kidney physiology by regulating salt reabsorption. Loss-of-function mutations in the human ROMK channel are associated with antenatal type II Bartter's syndrome, an autosomal recessive life-threatening salt-wasting disorder with mild hypokalemia. Similar observations have been reported from studies with ROMK knockout mice and rats. It is noteworthy that heterozygous carriers of Kir1.1 mutations associated with antenatal Bartter's syndrome have reduced blood pressure and a decreased risk of developing hypertension by age 60. Although selective ROMK inhibitors would be expected to represent a new class of diuretics, this hypothesis has not been pharmacologically tested. Compound A [5-(2-(4-(2-(4-(1H-tetrazol-1-yl)phenyl) acetyl)piperazin-1-yl)ethyl) isobenzofuran-1(3H)-one)], a potent ROMK inhibitor with appropriate selectivity and characteristics for in vivo testing, has been identified. Compound A accesses the channel through the cytoplasmic side and binds to residues lining the pore within the transmembrane region below the selectivity filter. In normotensive rats and dogs, short-term oral administration of compound A caused concentration-dependent diuresis and natriuresis that were comparable to hydrochlorothiazide. Unlike hydrochlorothiazide, however, compound A did not cause any significant urinary potassium losses or changes in plasma electrolyte levels. These data indicate that pharmacologic inhibition of ROMK has the potential for affording diuretic/natriuretic efficacy similar to that of clinically used diuretics but without the dose-limiting hypokalemia associated with the use of loop and thiazide-like diuretics. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.


Premuzic V.,Hypertension | Gavranic B.B.,Hypertension | Tomasevic B.,University of Zagreb | Jelakovic B.,Hypertension
Therapeutic Apheresis and Dialysis | Year: 2016

There is a correlation between central venous cannulation and the development of central venous stenosis. Minor retrosternal vein lesions can be easily missed. Computerized tomographic (CT) venography is the diagnostic procedure of choice. The aim of this study was to examine the complications after catheter implantation in patients with prior permanent catheter placement and to evaluate present diagnostic procedures performed prior to choosing permanent access site in order to reduce possible complications after catheter placement. Complications of permanent CVC insertion in our department were analyzed between October 2011 and February 2015. We have implanted the Tesio twin catheter system and the Hickman Bard dual lumen catheter. All patients with prior permanent dialysis catheter were evaluated with color doppler, while patients with suspected central venous stenosis (CVS) or thrombosis were evaluated with phlebography or CT venography prior to catheter placement. One hundred and ninety-eight permanent dialysis catheters were placed (173 Tesio [87.4%] and 25 Hickman [12.6%]) in 163 patients. There were 125 patients (76.7%) with prior temporary catheter and 61 (48.8%) of them had more than one prior permanent catheter (1.92 catheter per person).There were 4/61 (6.5%) patients with catheter-related complications without prior phlebography and CT venography. Phlebography and CT venography were performed in 30 (24.0%) patients with suspected CVS/thrombosis and with dialysis vintage of 76.23 months (52.78–98.28). Phlebography and CT venography were more sensitive than color doppler in the detection of CVS/thrombosis in patients with prior permanent catheter placements (P < 0.001). Since this diagnostic algorithm was introduced prior to catheter placement there were no catheter insertion-related complications or dysfunctions (P < 0.001). All our procedures on patients with prior permanent catheters followed preliminary color doppler diagnostics. Nevertheless, in four cases, the vessel obstruction and abnormality led to catheter insertion-related complications. When phlebography and CT venography was performed before the procedure in patients with prior permanent catheters and one or more CVS or thrombosis, early and late catheter-related complications were avoided by careful selection of the least injured vein and planning of procedure. When planning a permanent dialysis catheter placement in patients with prior multiple CVC, phlebography and CT venography may be diagnostic procedures of choice for avoidance of early catheter dysfunction and CVC placement complications. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy


NEW HOPE, Pa., Oct. 31, 2016 /PRNewswire/ -- BackBeat Medical Inc. today announced the presentation of data demonstrating a continued significant reduction in blood pressure over a one year period with the company's patented Programmable Hypertension Control (PHC) therapy for the...


DUBLIN, Nov. 12, 2016 /PRNewswire/ -- Allergan plc (NYSE: AGN), a leading global pharmaceutical company today announced that data on nebivolol will be presented at the American Heart Association (AHA) Annual Scientific Meeting scheduled November 12-16th, 2016 in New Orleans, Louisiana, at...


News Article | October 31, 2016
Site: www.prnewswire.com

-Aralez Enters into Long-term Supply Agreement with AstraZeneca- -Transaction Expected to be EBITDA Accretive and to Move Profitability Forward to 2017 on an Adjusted Basis- MISSISSAUGA, Ontario, Oct. 31, 2016 /PRNewswire/ -- Aralez Pharmaceuticals Inc. (NASDAQ: ARLZ) (TSX: ARZ),...


PubMed | Hypertension
Type: Journal Article | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2012

Skin autofluorescence, a non-invasive measure of the accumulation for advanced glycation end products, has been reported to be a useful marker for diabetic vascular risks in the Caucasian population. The aim of this study was to evaluate associations between skin autofluorescence and vascular complications in non-Caucasian patients with Type 2 diabetes.Subjects in this cross-sectional study comprised 130 Japanese patients with Type 2 diabetes. Skin advanced glycation end products were assessed by skin autofluorescence using an autofluorescence reader. Association between skin autofluorescence and severity of vascular complications was evaluated.Of the 130 patients, 60 (46.2%) had microvascular complications such as diabetic retinopathy, neuropathy and nephropathy, 10 (7.7%) had macrovascular complications and 63 (48.5%) had micro- and/or macrovascular complications. Skin autofluorescence increased with severity of vascular complications. Independent determinants of skin autofluorescence were age ( = 0.24, P < 0.01), mean HbA(1c) in previous year ( = 0.17, P = 0.03), microvascular complications ( = 0.44, P < 0.01) and macrovascular complications ( = 0.27, P < 0.01). Multiple logistic regression analysis revealed that diabetes duration (odds ratio 1.15, P < 0.01), systolic blood pressure (odds ratio 1.04, P = 0.01), skin autofluorescence (odds ratio 3.62, P = 0.01) and serum albumin (odds ratio 0.84, P < 0.01) were independent factors for the presence of vascular complications in these patients.Skin autofluorescence had independent effects on vascular complications in Japanese patients with Type 2 diabetes. This indicates that skin advanced glycation end products are a surrogate marker for vascular risk and a non-invasive autofluorescence reader may be a useful tool to detect high-risk cases in non-Caucasian patients with diabetes.

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