Drugs online research references
BJU Int. 2004 Feb;93(3):410-414.
Prostate apoptosis after doxazosin treatment in the spontaneous hypertensive rat model.
Lujan M, Ferruelo A, Paez A, Moreno A, Berenguer A.
Department of Urology, Hospital de Getafe and Basic Research Unit, Fundacion Urologica de Getafe, Madrid, Spain.
OBJECTIVE: To validate the spontaneous hypertensive rat (SHR) model for basic research into benign prostate hyperplasia (BPH), and to assess doxazosin-induced changes in prostatic structure and apoptotic status. MATERIALS AND METHODS: Four groups of rats were assessed: group 1, 15 SHRs treated with doxazosin; group 2, 14 SHRs with unilateral excision of the major pelvic ganglion; group 3, 14 untreated SHRs; and group 4, 16 intact Wistar-Kyoto (WKY) rats. The doxazosin mesylate (0.03 mg daily) was given compacted in rat food for 3 months. The prostatic ventral lobe (VL) was excised and weighed. Stereological light microscopy, multiplex reverse transcription-polymerase chain reaction of prostate caspases, and caspase-3 activity (cellular enzymatic assay) were assessed. RESULTS: There was more development of the glandular epithelium (P < 0.001) in SHR rats than in controls, which was even greater after doxazosin exposure (P = 0.027). SHR animals had higher caspase expression (P < 0.05) and activity (P = 0.008) than WKY rats, but both were reduced after doxazosin therapy (P < 0.01 and 0.028, respectively). CONCLUSIONS: This study confirmed prostate hyperplasia in the SHR model. Doxazosin exposure did not reduce the volume of glandular epithelium and contributed to protecting against caspase-induced apoptosis. The SHR model may be not a valid option to study doxazosin-induced apoptosis in BPH.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14764147&dopt=Abstract [PubMed - as supplied by publisher]
utsouthwestern.edu
PURPOSE: We provide a comprehensive overview of the role of alpha1-adrenergic receptors (alpha1ARs) as critical mediators of lower urinary tract symptoms (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH), and we review the pharmacological antagonists of alpha1ARs. MATERIALS AND METHODS: A review was performed of pertinent studies in the literature relating to the pathophysiology of LUTS and BPH, focusing on the role of alpha1ARs, and of clinical trial and practice data evaluating the different agents that inhibit these receptors. RESULTS: Further characterization of the alpha1AR gene family indicates that 3 receptor subtypes exist in humans. Their different distribution between urinary tract and cardiovascular tissues has provided a strategy for the development of improved therapeutic agents. Since excessive activity of the alpha1aAR and alpha1dAR subtypes appears to be a common feature in symptomatic BPH and alpha1aARs are enriched in prostatic tissue, drugs that demonstrate high alpha1aAR selectivity have attracted attention. Tamsulosin, which has high affinity for alpha1aAR and alpha1dAR subtypes but not for alpha1bAR, shows efficacy similar to the nonsubtype selective agents terazosin and doxazosin. It is associated with fewer cardiovascular side effects, although it has some ejaculatory side effects. The nonsubtype selective agent alfuzosin also demonstrates efficacy and offers an enhanced side effect profile, particularly minimizing hypotension. Other agents with super selective specificity for the alpha1aAR subtype are under investigation. CONCLUSIONS: Further advances in the treatment of LUTS associated with BPH may depend not only on receptor subtype selectivity, but also on other pharmacokinetic and pharmacodynamic factors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14767264&dopt=Abstract [PubMed - in process]
Br J Surg. 1992 Dec;79(12):1285-8.
Long-term reduction of intimal hyperplasia by the selective alpha-1 adrenergic antagonist doxazosin.
Vashisht R, Sian M, Franks PJ, O'Malley MK.
Department of Surgery, Charing Cross and Westminster Medical School, London, UK.
Studies have shown that alpha 1-adrenergic blockade reduces intimal hyperplasia in the rabbit aorta. In this study a selective alpha 1-adrenergic antagonist, doxazosin, has been used to examine whether this effect is persistent and dose dependent. Forty-eight New Zealand White rabbits underwent endothelial denudation of the abdominal aorta using a Fogarty balloon catheter. Test rabbits were given low-dose (2 mg) or high-dose (8 mg) doxazosin daily and all animals killed at either 1 or 12 weeks after the procedure. The aortas were harvested after fixation in situ with 4 per cent glutaraldehyde and neointimal hyperplasia was measured, using an x-y digitizer, as the percentage reduction in luminal cross-sectional area. At 1 week after surgery, rabbits receiving the low dose had a median area reduction of 7.7 per cent and those receiving the high dose a reduction of 8.2 per cent; both had significantly less intimal hyperplasia than control rabbits, which had a median area reduction of 14.8 per cent (P < 0.01). However, at 12 weeks, when compared with the 32.6 per cent reduction in the control group, only those rabbits receiving high-dose doxazosin had significantly less intimal hyperplasia, with a reduction of 5.5 per cent (P < 0.001). It is concluded that selective alpha 1-adrenergic blockade significantly reduces neointimal hyperplasia, that this effect is dose dependent, and that it persists for at least 3 months.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1486418&dopt=Abstract
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