Drugs online research references
Prostate. 2001 Jul 1;48(2):71-8.
Reduction of human prostate tumor vascularity by the alpha1-adrenoceptor antagonist terazosin.
Keledjian K, Borkowski A, Kim G, Isaacs JT, Jacobs SC, Kyprianou N.
Division of Urology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
BACKGROUND: We previously demonstrated that the quinazoline-derived a1-adrenoceptor antagonists doxazosin and terazosin suppress prostate cancer growth via apoptosis induction. The aim of this study was to determine the potential effect of a1-adrenoceptor antagonists on tumor vascularity of the human prostate. METHODS: A total of 34 men with benign prostatic hyperplasia (BPH) who have been on terazosin treatment (for the obstructive symptoms) were pathologically diagnosed with prostate cancer following surgery. These patients were stratified according to the length of treatment periods with terazosin into two groups, 1 week-6 months, and 6-17 months. The control group consisted of prostatectomy specimens from 25 untreated prostate cancer patients undergoing surgery for localized disease. Formalin-fixed, paraffin-embedded prostate specimens were analyzed for apoptosis (TUNEL assay), cell proliferation (Ki-67), microvessel density (MVD) (von Willebrand factor/Factor VIII), vascular endothelial growth factor (VEGF) expression, and prostate specific antigen (PSA) immunoreactivity. RESULTS: A significant induction of apoptosis was observed among cancerous prostatic epithelial cells in the terazosin-treated, as compared to the untreated prostate cancer specimens, while there was no significant change in the proliferative index of the same tumor cell populations after treatment. Furthermore, terazosin resulted in a significant decrease in prostate tissue MVD compared with the untreated group (P < 0.01), that correlated with the increased apoptotic index of the cancerous areas. Tissue PSA expression in the prostatic tumor foci was also markedly reduced after terazosin treatment, while no significant changes in VEGF expression were detected. CONCLUSIONS: These findings provide the first evidence that terazosin, a quinazoline-based a1-blocker decreases prostate tumor vascularity. Our study has significant clinical implications in identifying selected alpha1-adrenoceptor antagonists as potential anti-tumor agents with apoptotic and anti-angiogenic effects in the human prostate that can be exploited for the treatment of advanced prostate cancer.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11433417&dopt=Abstract
Auton Neurosci. 2001 Jul 20;90(1-2):152-7.
Loss of nocturnal dipping of blood pressure and heart rate in obesity-induced hypertension in rabbits.
Antic V, Van Vliet BN, Montani JP.
Institute of Physiology, University of Fribourg, Switzerland.
We have investigated in rabbits whether overfeeding and weight gain, which lead to hypertension, are associated with changes in circadian rhythm of blood pressure (BP) and heart rate, and whether the sympathetic nervous system is involved in these changes. In adult male rabbits, mean arterial pressure (MAP) and heart rate (HR) were monitored by telemetry 22 h a day. Daily MAP and HR records were divided into four equal intervals and used to calculate day-night differences. After a 1-week control period, animals were switched to a high-fat (HFD) ad libitum diet for 8 weeks. HFD increased whole day MAP and HR, and rapidly abolished the normal diurnal rhythm of MAP and HR. Since HFD abolished the nocturnal dip in MAP, but had little effect on daytime values, the loss of dipping appears to account for most of the hypertension in this model of obesity. In a separate set of rabbits, alpha- and beta-adrenergic blockade (terazosin + propranolol) prevented HFD-induced hypertension and attenuated the increase in HR by more than half. Adrenergic blockade alone abolished the diurnal rhythm of MAP, chiefly by preventing daytime elevation of MAP. The addition of HFD ad libitum did not further modify daily MAP or its circadian pattern. The diurnal rhythm of HR was relatively unaffected by alpha + beta blockade alone, but was abolished after switching to HFD. In conclusion, rabbits fed an HFD ad libitum develop hypertension and tachycardia associated with a loss of the normal diurnal rhythm of MAP and HR. The hypertension appears to be sympathetically mediated.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11485285&dopt=Abstract
mersin.edu.tr
INTRODUCTION: To determine the changes in plasma lipid levels in symptomatic benign prostatic hyperplasia (BPH) patients receiving terazosin treatment. MATERIALS AND METHODS: The study included 99 patients with BPH aged 44-74 years. The patients were divided into 3 groups: in group 1 (n = 25) with baseline total cholesterol levels of >220 mg/dl, terazosin 5 mg/day was used; in group 2 (n = 56) with basal total cholesterol levels of < 220 mg/dl, terazosin 5 mg/day was used, and group 3 (n = 18) did not use terazosin and was defined as the control group. Plasma levels of total cholesterol, low-density lipoprotein, high-density lipoprotein and triglyceride were recorded, and the high-density lipoprotein to total cholesterol ratio was calculated at the beginning of the study and after 12 weeks. RESULTS: The total cholesterol level decreased from the baseline level by 10.88% after 12 weeks (p < 0.05) in group 1. The decrease was observed in 22 of 25 patients (88%). In group 1, the mean plasma total cholesterol level decreased significantly (p < 0.05), but the decrease was not significant in group 2 and no change was observed in group 3. The mean plasma low-density lipoprotein level decreased significantly in group 1 (p < 0.05), but no change was observed in the other 2 groups. The mean plasma high-density lipoprotein level increased in group 1, whereas no change was observed in the other 2 groups. The mean plasma triglyceride level decreased significantly in groups 1 and 2 (p < 0.05), but no change was observed in group 3. The high-density lipoprotein to total cholesterol ratio increased significantly in group 1, but no change was observed in the other 2 groups. CONCLUSION: We suggest that terazosin may be a reasonable choice because of the beneficial effect on the lipid profile in older symptomatic BPH patients with a higher ratio of dyslipidemia. Copyright 2001 S. Karger AG, Basel.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11490211&dopt=Abstract
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