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BACKGROUND: Benign prostate hyperplasia (BPH) and prostate cancer established that disruption of the molecular mechanisms that regulate apoptosis and cell proliferation among the stromal and epithelial cell populations, may underlie the neoplastic development that characterizes the aging gland. This work examined the effects of selected alpha(1)-adrenoceptor (alpha(1)-AR) antagonists (blockers) on cellular dynamics to determine whether induction of apoptosis or inhibition of proliferation could contribute to the overall clinical profile. METHODS: Our efforts were focused on investigating whether alpha(1)-AR antagonists of two different chemical classes affect prostate pathophysiology via mechanisms other than smooth muscle contraction. In in vitro experiments, the two clinically used quinazoline alpha(1)-adrenoceptor antagonists terazosin and doxazosin and the chemically-distinct sulphonamide, tamsulosin, were examined for effects on prostatic tumor growth, by inhibiting cell proliferation and'or inducing apoptosis. RESULTS: Our findings suggest that alpha(1)-AR antagonists, terazosin and doxazosin, suppress prostatic growth by inducing apoptosis in a dose-dependent manner and without affecting cell proliferation. Tamsulosin exerted no effect on prostate cancer cell growth. The apoptotic effect of terazosin and doxazosin appears to be independent of the alpha(1)-adrenoceptor block. CONCLUSIONS: Taken together, our findings demonstrate the ability of the quinazoline alpha-blockers, terazosin and doxazosin, but not the sulphonamide, tamsulosin, to suppress prostate growth by inducing apoptosis among the epithelial cells in the benign and malignant prostate. These studies underwrite the durability of the response seen in long-term studies with terazosin, and suggest the potential of this drug in the treatment of prostate carcinoma. Copyright 2000 Wiley-Liss, Inc.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11056502&dopt=Abstract
BJU Int. 2000 Oct;86(6):630-3.
The psychological effects of treatments for lower urinary tract symptoms.
Quek KF, Low WY, Razack AH, Loh CS.
Health Research Development Unit, Faculty of Medicine, University of Malaya, and Department of Surgery, University Hospital, Kuala Lumpur, Malaysia.
OBJECTIVE: To assess and evaluate the level of depression, anxiety and psychiatric status in patients with lower urinary tract symptoms (LUTS) before and after treatment by surgery or drugs. PATIENTS AND METHODS: The study included 123 patients (mean age 64.6 years, SD 7. 95) with LUTS who were treated medically (with alpha-blockers, i.e. terazosin, prazosin, doxazosin and alfuzosin), and 52 patients (mean age 69.6 years, SD 7.94) with LUTS and confirmed to have benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP). Both groups were assessed at baseline and 3 months after treatment using standardized questionnaires (the Beck Depression Inventory, the State-Trait Anxiety Inventory and the General Health Questionnaire-12). RESULTS: Patients before TURP were significantly more depressed, worried and psychiatrically morbid than were those before medical treatment. Three months after medical and surgical treatment, there was significantly less depression, anxiety and psychiatric morbidity in the TURP than in the medication group. CONCLUSIONS: TURP is a better treatment than medication for minimising anxiety, depression and psychiatric morbidity after treatment in patients with LUTS, but causes greater psychological stress before treatment.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11069367&dopt=Abstract
J Korean Med Sci. 1999 Feb;14(1):69-74.
Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.
Seo KK, Lee MY, Lim SW, Kim SC.
Department of Urology, College of Medicine, Chung-Ang University, Seoul, Korea.
Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10102527&dopt=Abstract
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