Evaluation of apoptosis indexes in currently used oral alpha-blockers in prostate: a pilot study

ABSTRACT Objectives: Apoptosis effect of oral alpha-blockers is known in the prostate. Apoptosis index of silodosin has not been proved, yet. Aims are to present apoptosis index of silodosin in prostate and to compare this with other currently used alpha-blocker's apoptosis indexes together with their clinical effects. Materials and Methods: Benign prostatic hyperplasia (BPH) patients were enrolled among those admitted to urology outpatient clinic between June 2014 and June 2015. Study groups were created according to randomly prescribed oral alpha-blocker drugs as silodosin 8mg (Group 1; n=24), tamsulosin 0.4mg (Group 2; n=30), alfuzosin 10mg (Group 3; n=25), doxazosin 8mg (Group 4; n=22), terazosin 5mg (Group 5; n=15). Pa- tients who refused to use any alpha-blocker drug were included into Group 6 as control group (n=16). We investigated apoptosis indexes of the drugs in prostatic tissues that were taken from patient's surgery (transurethral resection of prostate) and/or prostate biopsies. Immunochemical dyeing, light microscope, and Image Processing and Analy- sis in Java were used for evaluations. Statistical significant p was p<0.05. Results: There were 132 patients with mean follow-up of 4.2±2.1 months. Pathologist researched randomly selected 10 areas in each microscope set. Group 1 showed statisti- cal significant difference apoptosis index in immunochemical TUNEL dyeing and im- age software (p<0.001). Moreover, we determined superior significant development in parameters as uroflowmetry, quality of life scores, and international prostate symptom score in Group 1. Conclusions: Silodosin has higher apoptosis effect than other alpha-blockers in prostate. Thus, clinic improvement with silodosin was proved by histologic studies. Besides, static factor of BPH may be overcome with creating apoptosis.

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

Evaluation of the effect of sildenafil and/or doxazosin on Benign prostatic hyperplasia-related lower urinary tract symptoms and erectile dysfunction

To verify the association between lower urinary tract symptoms [LUTS] and erectile dysfunction [ED] and evaluate the influence of sildenafil and doxazosin either as single agents or combined on both symptoms. A prospective randomized study including 150 patients presented with LUTS caused by BPH in association with clinically diagnosed ED, with age equal or more than 45 years from April 2010 to April 20011. They were categorized into three comparative groups each one containing 50 patients. These groups were comparable regarding pretreatment international prostate symptoms score [IPSS] and international index of erectile function [IIEF]. The patients of the first group were given sildenafil 50 mg as monotherapy, those of the second group were given doxazosin 2 mg and those of the third group were given combination of both drugs for 4 months for each group. The main post-treatment parameters for assessment and comparison include assessment of patient's symptoms by repeated IPSS and IIEF, uroflowmetry and assessment of PVR. The statistics was done by use of the chi-square test Pre-treatment parameters were assessed and compared between the three groups. After 4 months of treatment, the comparative parameters were applied to all groups and the differences were measured post-treatment regarding IPSS, erectile function score, uroflowmetry, and post-void residual [PVR] urine. Sildenafil alone caused mild improvement in IPSS, more improvement in IIEF score, and little effect on flow rate and PVR urine. Doxazosin alone caused more improvement in IPSS, flow rate and PVR urine and less improvement in IIEF score. A combination of both sildenafil and doxazosin caused more improvement in all of the comparative parameters than when each drug was given alone. There is a strong relationship between LUTS and ED. Doxazosin or sidenafil as a single drug could be used in treating mild or mild to moderate symptoms but more severe symptoms may usually need a combination of both drugs

Proposta para o uso de doxozosina e dexametasona para facilitar a micçäo espontânea após cirurgia ginecológica e/ou uroginecológica / Proposal for the use of doxozosine and dexametasone to facilitate the spontaneous miction after gynecologic and/or urogynecologic surgery

Estamos mostrando nossa experiência com o uso de doxazosina e dexametasona no tratamento e na prevençäo da retençäo urinária após colpossuspensäo abdominal. Estamos propondo o uso destas drogas com a finalidade de facilitar a micçäo espontânea após cirurgia ginecológica e/ou uroginecológica

Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin

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.

Uso de doxazosin en la hiperplasia prostática benigna obstructiva: experiencia clínica / Use of doxazosin in the obstructive benign prostate hyperplasia: clinical experience

Mucho se ha publicado sobre farmacoterapia para el manejo de la hiperplasia prostática benigna, pero no está bien definido la existencia de influencia ambientales, genéticas o alimenticias sobre su desarrollo y la respuesta a los distintos medicamentos comercialmente disponibles. Un total de 24 pacientes son evaluados con un parámetro urodinámico (uroflujometría) a la administración de dosis creciente de doxazosin y se confirma su beneficio en mejoría de flujo, buena tolerancia y efectos positivos en bajas dosis, con efecto residual prolongada

Efecto inotropico negativo directo de la cocaina en ventriculo de rata / Direct negative inotropic effect of cocaine in rat ventricle strip

Cocaine, when used as a recreative drug, can induce cardiovascular toxic effects such as acute reduction of left ventricle ejection fraction, which indicates a negative inotropic effect of the drug. The purpose of this study was to clarify the direct negative inotropic effect of cocaine in in vitro conditions. Rat right ventricle strips were incubated in Krebs solution gassed with 95 percent O2 and 5 percent CO2 at 37 degrees, and electrically driven with 2 ms square pulses, 17 mA, at 110 systoles/min. Separate experiments were conducted to study cocaine effect at 210 and 310 systoles/min. The contractile force was recorded through a strain-gauge isometric transducer. Cocaine increased contractile force at doses of 0.3-10.0 micrograms/ml, up to 53 percent over basal contraction. In the presence of 4 x 10(-8) Matenolol, low doses of cocaine did not increase contractile force and at doses between 3.0-10.0 micrograms/ml revealed a depressant activity on heart muscle contractions. Doxazosin (1.0 microM) and yohimbine (0.1 microM) did not modify the positive inotropic effect of cocaine, showing that alpha 1 and alpha 2 adrenergic receptors were not involved in this cocaine ventricle action. Increasing ventricle strip stimulation rate to 210 and 310 systoles/min for 30 seconds, the contractile force was risen by 55 percent and 95 percent, respectively. Cocaine at doses 1.0-3.0 micrograms/ml did not modify the physiological increase of contractile force seen upon ventricle rate increase. The mechanism involved in the contractile force increment after ventricle rate increase is a transient rise of cytosolic Ca2+, mainly derived from the sarcoplasmic reticulum and from extracellular fluid. Atenolol (4 x 10(-8) M) exposure of the right ventricle strip intensified the negative inotropic effect of cocaine (3.0-10 micrograms/ml) seen by ventricle stimulation at 210 and 310 systoles/min. The miocardial direct depressant effect of cocaine, in the presence of atenolol, was gradually reversed by extracelular Ca2+ increase at 3.2 and 5.0 mM, respectively. In conclusion, the mechanism of myocardial direct depressant effect of cocaine is related to the beating frequency of the ventricle, which may be sociated to interference with the Ca2+ release process from the myocite sarcoplasmic reticulum, and not to calcium entry blockade from extracellular fluid...

Biochemical changes during a cross-over treatment of doxazosin, moduretic and amlodipine in hypertensive patients

A cross-over study was done to compare the effects of doxazosin, moduretic and amlodipine on biochemical values in 9 hypertensive Nigerians aged 35 to 65 years. Doxazosin therapy was characterized by significant increase in the levels of mean plasma total protein and albumin, while moduretic therapy showed significant reduction in the mean values of plasma creatinine and calcium. All other parameters did not show any significant variation during doxazosin and moduretic treatment phases; and amlodipine therapy did not have any effect on the biochemical values of the hypertensive patients