Biophysical Characterization and Expression Analysis of Kv1.3 Potassium Channel in Primary Human Leukemic B Cells
Conclusion: Our results contribute to the characterization of B-CLL cells, as it shows that upregulation of Kv1.3 in pathologic B lymphocytes is linked to the oncogenic B-RAF signalling. We also conclude that Kv1.3 inhibitors represent a valuable tool to induce apoptosis of B-CLL cells even in the presence of MSC.Cell Physiol Biochem 2015;37:965-978 (Source: Cellular Physiology and Biochemistry)
Source: Cellular Physiology and Biochemistry - September 23, 2015 Category: Cytology Source Type: research
Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial
Publication date: Available online 20 September 2015 Source:The Lancet Author(s): Bryan Williams, Thomas M MacDonald, Steve Morant, David J Webb, Peter Sever, Gordon McInnes, Ian Ford, J Kennedy Cruickshank, Mark J Caulfield, Jackie Salsbury, Isla Mackenzie, Sandosh Padmanabhan, Morris J Brown Background Optimal drug treatment for patients with resistant hypertension is undefined. We aimed to test the hypotheses that resistant hypertension is most often caused by excessive sodium retention, and that spironolactone would therefore be superior to non-diuretic add-on drugs at lowering blood press...
Source: The Lancet - September 21, 2015 Category: Journals (General) Source Type: research
[Articles] Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial
Spironolactone was the most effective add-on drug for the treatment of resistant hypertension. The superiority of spironolactone supports a primary role of sodium retention in this condition. (Source: LANCET)
Source: LANCET - September 20, 2015 Category: Journals (General) Authors: Bryan Williams, Thomas M MacDonald, Steve Morant, David J Webb, Peter Sever, Gordon McInnes, Ian Ford, J Kennedy Cruickshank, Mark J Caulfield, Jackie Salsbury, Isla Mackenzie, Sandosh Padmanabhan, Morris J Brown, The British Hypertension Society's PATHWA Tags: Articles Source Type: research
Re: Comparison of the Efficacy of Isosorbide Mononitrate and Doxazosin in the Treatment of Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: A Randomized Clinical Trial
F. Tarhan, O. Çelik, Ç. Tosun, G. Faydacı and B. Eryıldırım (Source: The Journal of Urology)
Source: The Journal of Urology - September 18, 2015 Category: Urology & Nephrology Authors: Steven A. Kaplan Tags: Urological Survey Source Type: research
Targeting the Eph-ephrin system with protein-protein interaction (PPI) inhibitors.
Abstract
Eph-ephrin system is emerging as a new potential target in several diseases including cancer, diabetes, neurodegenerative diseases and inflammation. In the last decade, several efforts have been made to develop small molecule antagonists of Eph receptors. Both natural and synthetic compounds were discovered with (poly)phenol and steroidal derivatives on one side and the 1 agonist doxazosin, 2,5-dimethylpyrrol-1-yl-benzoic acids and amino acid conjugates of lithocholic acid on the other. In the present paper we critically present available data for these compounds and discuss their potential use...
Source: Current Drug Targets - August 25, 2015 Category: Drugs & Pharmacology Authors: Tognolini M, Lodola A Tags: Curr Drug Targets Source Type: research
Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014)
Conclusions: dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D). (Source: Age and Ageing)
Source: Age and Ageing - August 24, 2015 Category: Geriatrics Authors: Oelke, M., Becher, K., Castro-Diaz, D., Chartier-Kastler, E., Kirby, M., Wagg, A., Wehling, M. Tags: Systematic Reviews Source Type: research
Pharmacological modulation of ureteric peristalsis in a chronically instrumented conscious pig model: effect of adrenergic and nitrergic modulation
Conclusions
Activation of α- and β-adrenergic receptors, respectively, stimulates and inhibits ureteric peristalsis. The biological effect of NO on ureteric motility is regionally determined and corresponds to the distribution of NOS-positive nerves. Inhibition of NOS activity increases P
max in the distal ureter and tonic activity of the ureteric muscle resulting in higher hydrostatic pressure in the renal pelvis. (Source: World Journal of Urology)
Source: World Journal of Urology - August 15, 2015 Category: Urology & Nephrology Source Type: research
Abstract 2678: Targeting prostate cancer metastasis with novel small molecule agonists of EphA2
During tumor progression, EphA2 receptor can gain ligand-independent pro-oncogenic functions due to Akt activation and reduced ephrin-A ligand engagement. The effects can be reversed by ligand stimulation, which triggers the intrinsic tumor suppressive signaling pathways of EphA2 including inhibition of PI3/Akt and Ras/ERK pathways. These observations argue for development of small molecule agonists for EphA2 as potential tumor intervention agents. Through virtual screening and cell-based assays, we report here the identification and characterization of doxazosin as a novel small molecule agonist for EphA2 and EphA4, but n...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Wang, B., Petty, A. Tags: Experimental and Molecular Therapeutics Source Type: research
Comparative Effectiveness and Safety of Monodrug Therapies for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: A Network Meta-analysis
In conclusion, α-blockers, 5ARIs, and PDE5-Is are effective for BPH, with doxazosin and terazosin appearing to be the most effective agents. Drug therapies for BPH are generally safe and well-tolerated, with no major difference regarding the overall safety profile. (Source: Medicine)
Source: Medicine - July 1, 2015 Category: Internal Medicine Tags: Research Article: Systematic Review and Meta-Analysis Source Type: research
The truth about the lower plasma concentration of the (-)-isomer after racemic doxazosin administration in rats: Stereoselective inhibition of the (-)-isomer by the (+)-isomer at CYP3A.
In conclusion, although (-)-DOX is not depleted faster than (+)-DOX when only a single isomer of DOX is incubated with rat liver microsomes, it is depleted much faster than (+)-DOX when a mixture of the two isomers was used, suggesting a prominent and stereoselective inhibition of the (-)-isomer over the (+)-isomer at the CYP3A enzyme.
PMID: 26116989 [PubMed - as supplied by publisher] (Source: European Journal of Pharmaceutical Sciences)
Source: European Journal of Pharmaceutical Sciences - June 25, 2015 Category: Drugs & Pharmacology Authors: Kong D, Li Q, Zhang P, Zhang W, Zhen Y, Ren L Tags: Eur J Pharm Sci Source Type: research
The Role of Monitoring Arterial Stiffness with Cardio-Ankle Vascular Index in the Control of Lifestyle-Related Diseases
Arteriosclerosis is a major contributor to cardiovascular diseases. One of the difficulties in controlling those diseases is the lack of a suitable indicator of arteriosclerosis or arterial injury in routine clinical practice. Arterial stiffness was supposed to be one of the monitoring indexes of arteriosclerosis. Cardio-ankle vascular index (CAVI) is reflecting the stiffness of the arterial tree from the origin of the aorta to the ankle, and one of the features of CAVI is independency from blood pressure at a measuring time. When doxazosin, an α1-adrenergic blocker, was administered, CAVI decreased, indicating that arter...
Source: Pulse - June 19, 2015 Category: Cardiology Source Type: research
The VO(2)-on kinetics in constant load exercise sub-anaerobic threshold reflects endothelial function and dysfunction in muscle microcirculation.
In conclusion, the O(2) consumption kinetics during the on-transition of constant load exercise below the anaerobic threshold are highly sensitive to endothelial function in muscular microcirculation, and constitute a marker for the evaluation of endothelial dysfunction.
PMID: 26047383 [PubMed - as supplied by publisher] (Source: Physiological Research)
Source: Physiological Research - June 5, 2015 Category: Physiology Authors: Maione D, Cicero AF, Bacchelli S, Cosentino ER, Degli Esposti D, Manners DN, Rinaldi ER, Rosticci M, Senaldi R, Ambrosioni E, Borghi C Tags: Physiol Res Source Type: research
Role of the α1 blocker doxazosin in alcoholism: a proof‐of‐concept randomized controlled trial
This study provides preliminary evidence for personalized medicine using α1‐blockade to treat AD. However, confirmatory studies are required.
The α1 blocker doxazosin was tested in alcoholic patients. Drinks per week (DPW) and heavy drinking days (HDD) per week were the primary outcomes. While there was no main medication effect, when family history density of alcoholism (FHDA) was analyzed as a priori moderator, doxazosin significantly reduced DPW and HDD in patients with high FHDA and by contrast tended to increase drinking in those with low FHDA. This study provides preliminary evidence for personalized medicine us...
Source: Addiction Biology - June 2, 2015 Category: Addiction Authors: George A. Kenna, Carolina L. Haass‐Koffler, William H. Zywiak, Steven M. Edwards, Michael B. Brickley, Robert M. Swift, Lorenzo Leggio Tags: Original Article Source Type: research
Insights into cardio-oncology: Polypharmacology of quinazoline-based α1-adrenoceptor antagonists.
Abstract
New uses of cardiovascular drugs with proven experience are emerging, including for treating cancer. Quinazoline is a compound made up of two fused six member simple aromatic rings, benzene and pyrimidine rings, with several biological effects. Cardiologists first used quinazoline-based α1-adrenoceptor antagonists prazosin, doxazosin, and terazosin; currently available data support their use as safe, well tolerated, and effective add-on therapy in uncontrolled hypertension with additional favourable metabolic effects. Recent findings highlight the anticancer effects of quinazoline-based α1-adren...
Source: World Journal of Cardiology - May 26, 2015 Category: Cardiology Authors: Patanè S Tags: World J Cardiol Source Type: research
Adrenergic and serotonin receptors affect retinal superoxide generation in diabetic mice: relationship to capillary degeneration and permeability [Research Communication]
Reactive oxygen species play an important role in the pathogenesis of diabetic retinopathy. We studied the role of adrenergic and serotonin receptors in the generation of superoxide by retina and 661W retinal cells in high glucose and of the α1-adrenergic receptor (AR) on vascular lesions of the retinopathy in experimentally diabetic C57Bl/6J mice (and controls) after 2 and 8 months. Compared with 5 mM glucose, incubating cells or retinal explants in 30 mM glucose induced superoxide generation. This response was reduced or ablated by pharmacologic inhibition of the α1-AR (a Gq-coupled receptor) or Gs-coupled se...
Source: FASEB Journal - April 30, 2015 Category: Biology Authors: Du, Y., Cramer, M., Lee, C. A., Tang, J., Muthusamy, A., Antonetti, D. A., Jin, H., Palczewski, K., Kern, T. S. Tags: Research Communication Source Type: research
