Drugs online research references
Circulation. 2003 Jan 7;107(1):127-31.
Doxazosin induces apoptosis in cardiomyocytes cultured in vitro by a mechanism that is independent of alpha1-adrenergic blockade.
Gonzalez-Juanatey JR, Iglesias MJ, Alcaide C, Pineiro R, Lago F.
Cardiology Research Unit, University Clinical Hospital, Santiago de Compostela, Spain.
BACKGROUND: The alpha1-adrenoceptor-blocking antihypertensive doxazosin has been associated with increased risk of heart failure and is known to induce prostate cell apoptosis. We hypothesized that it might also induce apoptosis in cardiomyocytes. METHODS AND RESULTS: Hoechst dye vital staining and flow cytometry provided evidence that doxazosin induced apoptosis time- and dose-dependently in cardiomyocytes of the HL-1 cell line. TUNEL assays and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) viability test confirmed that doxazosin induced DNA damage and cell death in these cells. MTT tests showed that doxazosin treatment decreased cell viability in primary cultures of neonatal rat cardiomyocytes, and Hoechst dye vital staining demonstrated doxazosin-induced apoptosis in primary cultures of human adult cardiomyocytes. The proapoptotic effect of doxazosin on cardiomyocytes seems not to depend on alpha1 blockade, because it was not modified by cotreatment with alpha- or beta-adrenergic agonists or with the irreversible alpha1-blocker phenoxybenzamine and because doxazosin also decreased the viability of NIH 3T3 cells, which lack alpha1-adrenoceptors. It also does not involve calcineurin, being unaffected by the presence of the calcineurin inhibitors cyclosporin A and FK506. Three other alpha1-blockers were also investigated; prazosin was proapoptotic, like doxazosin, but 5-methylurapidil and terazosin were not. CONCLUSIONS: The alpha1-blockers doxazosin and prazosin induce the apoptosis of cardiomyocytes cultured in vitro by a mechanism that is independent of alpha1 blockade and calcineurin.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12515754&dopt=Abstract
Urologiia. 2002 Sep-Oct;(5 Suppl):13-22.
[Urodynamic criteria of predicting efficacy of therapy with alpha1-adrenergic blockaders in patients with benign prostatic hyperplasia]
[Article in Russian]
Sivkov AV, Egorov AA, Romikh VV, Surikov VN.
AIM: As baseline urodynamic parameters do not correlate well with response to medical treatment for lower urinary tract symptoms (LUTS), this study was designed to asertain whether urodynamic parameters correlate better with response to alpha 1-adrenoblockers. METHODS: 23 men (mean age 64.6 +/- 9.3 years) with LUTS have undergone urodynamic examination prior to initiating therapy with terazosin titrated to 5 mg and followed for 2.5 months. Parameters of evaluation included IPSS symptom score, peak flow rate (Qmax), maximal detrusor pressure (Pmax), detrusor pressure at maximal flow (Pdet) and detrusor contraction duration (DCD). The correlation and predictive value of therapeutic response and baseline urodynamic parameters were assessed. RESULTS: For the entire group, IPSS decreased from 13.25 +/- 3.39 to 7.38 +/- 3.21 (44.6%), Qmax increased from 9.75 +/- 1.95 to 11.00 +/- 3.23 ml/s (21%), Pmax decreased from 109.75 +/- 35.72 to 93.88 +/- 20.91 cm. H2O (14.4%), Pdet decreased from 84.00 +/- 23.71 to 74.00 +/- 15.53 cm. H2O (16.8%), DCD increased from 127.63 +/- 53.99 to 130.13 +/- 45.41s (2.7%). There was a weak correlation between either Pmax or Pdet and therapeutic response (defined as a IPSS decrease of 40% and an increase in Qmax of 30%). There was a significant correlation with therapeutic response of DCD > 60 s (p < 0.05, r = 0.56). CONCLUSION: The pilot data suggest that DCD may be a useful urodynamic parameter to predict and optimize therapy with alpha 1-adrenoblockers.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12518669&dopt=Abstract
Urologiia. 2002 Sep-Oct;(5 Suppl):37-52.
[Results of monotherapy with terazosin (kornam) in chronic infectious prostatitis patients]
[Article in Russian]
Lopatkin NA, Apolikhin OI, Sivkov AV, Oshchepkov VN, Egorov AA.
AIM: To evaluate effectiveness of alpha 1-adrenoblockers (a1-AB) in patients with chronic non-infectious prostatitis (CP). MATERIAL AND METHODS: a1-AB effectiveness was studied in 28 volunteers with non-infectious CP (type IIIA). All the patients received terazosin (kornam, Slovenia) in a dose 5 mg/day after dose titration for 2-3 weeks (the initial dose was 1 mg/day). The assessment of the efficiency was standard with the use of frequency and severity of symptoms scales as well as questionnaire NIH CPSI. RESULTS: Symptomatic improvement was achieved in 27 patients (96%). Dysuria and intensity of pain diminished in 24 (82%) and 26 (93%) patients. Voiding disorders proved most sensitive to a1-AB. Quality of life rose 2-fold. Probability of the recurrence 1 month after terazosin therapy was 0.29, after 6 months--0.43. Recurrent dysuria occurred in 33%, pain--in 58%. CONCLUSION: Terazosin monotherapy in patients with non-infectious CP results in reduction of the symptoms severity and pollakiuria frequency, frequency of recurrences and in improvement of quality of life. a1-AB in CP do not prevent recurrence in half the cases but the symptoms severity in recurrent disease is much weaker.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12518671&dopt=Abstract
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