Effects of chronic administration of tamsulosin and tadalafil, alone or in combination, in rats with bladder outlet obstruction induced by chronic nitric oxide deficiency

Purpose The aim of this study was to define if tadalafil causes detrusor muscle impairment and to observe the effect of combination of tadalafil with tamsulosin on the lower urinary tract of rats with bladder outlet obstruction (BOO) induced by chronic nitric oxide deficiency. Materials and Methods Thirty-one male rats were randomized to following groups: 1 - control; 2 - L-Nitroarginine methyl ester (L-NAME); 3 - Tamsulosin + L-NAME, 4 Tadalafil+L-NAME; and 5 - Tamsulosin + Tadalafil + L-NAME. At the end of the treatment period (30 days), all animals were submitted to urodynamic study. Results The administration of L-NAME increased the number of non-voiding contractions (NVC) (1.04 ± 0.22), volume threshold (VT) (1.86 ± 0.35), and micturition cycle (MC) (1.34 ± 0.11) compared with control (0.52 ± 0.06, 0.62 ± 0.06, and 0.67 ± 0.30), respectively. The administration of tamsulosin reduced the number of NVC (0.57 ± 0.42) and VT (0.76 ± 0.24 ) compared with L-NAME group. Co-treatment with tadalafil decreased the number of VT (0.85 ± 0.53) and MC (0.76 ± 0.22) compared with L-NAME group. The combination of tamsulosin with tadalafil improved the number of NVC (0.56 ± 0.18), VT (0.97 ± 0.52) and MC (0.68 ± 0.30) compared with L-NAME group. Conclusion In rats with BOO induced by chronic nitric oxide deficiency, tadalafil did not cause impairment in detrusor muscle and seems to have an addictive effect to tamsulosin because the combination decreased non voiding contractions as well the number of micturition cycles. .

Interacciones genotóxicas de mutágenos en mezclas binarias mediante ensayo cometa alcalino en linfocitos humanos / Interaction of mutagens in binary mixtures using the alkaline comet assay in human lymphocytes

Introducción. Los mutágenos contenidos en mezclas complejas presentan interacciones de sinergismo, aditivas o antagónicas. Se han desarrollado enfoques experimentales que permitan dilucidar el responsable de las interacciones en la mezcla. Objetivo. Desarrollar un diseño experimental para comprender los procesos que se llevan a cabo entre los compuestos presentes en las mezclas complejas. Materiales y métodos. Se expusieron linfocitos humanos a mezclas binarias de mutágenos B[a]P, DMBA, Trp-P-1 y MX durante una hora, con activación metabólica y sin ella. La viabilidad se evaluó con azul de tripano y, la genotoxicidad, con cometa alcalino. Resultados. Ningún hidrocarburo tuvo efecto con furanona. Con S9 y sin él, se observó que se presentaban interacciones tóxicas entre hidrocarburos. Se observó sinergismo sin S9 entre B[a]P y Trp-P-1 y, con actividad metabólica, entre DMBA y Trp-P-1. Sin S9 se observó interacción antagónica entre Trp-P-1 y DMBA y, con S9, entre Trp-P-1 y MX y entre MX y DMBA. Se observó un incremento dependiente de la dosis en la longitud de la cola. Hubo daño genotóxico medio y aumento de las células dañadas. Para todas las mezclas se pudo determinar la concentración mínima en la que se observaban efectos adversos y solo para algunas se determinó la concentración máxima en la cual no se observaron efectos adversos. Conclusión. Se hace un aporte para comprender los procesos que ocurren cuando en una mezcla hay presentes, al menos, dos mutágenos y se valida un modelo de análisis que permite dilucidar el compuesto que tiene efecto sobre otro. También, se demostró que según el tipo de compuestos en la mezcla, se tendrá o no un umbral de riesgo.

Introduction. Mutagens contained in complex mixtures can present synergistic interactions, either additive or antagonistic. Therefore, development of experimental approaches is necessary to elucidate which is the responsible agent for the effect in the mixtures. Objective. An experimental design was developed that allowed an understanding of the processes between the compounds of complex mixtures. Materials and methods. Human lymphocytes were exposed to binary mixtures of the mutagens B[a]P, DMBA, Trp-P-1 and MX for 1 hour with or without S9. Viability was assessed with trypan blue dye and the genotoxicity by the comet assay. Results. All of the hydrocarbon showed an effect with furanone. With and without S9, the most toxic interactions were observed between hydrocarbons. Synergistic interaction was observed without S9 between B [a] P and Trp-P-1 and between DMBA and Trp-P-1 with metabolic activity. Without S9 antagonistic interaction was observed only between Trp-P-1+DMBA, and with S9 between Trp-P-1+MX and MX+DMBA. It observed an increase dose dependent in tail length. Half the cultures showed genotoxic damage and increased cell damage. For each mixture, minimum concentrations were determined at which adverse effects are observed; for some only the maximum concentration was determined at which no adverse effects are observed. Conclusion. The processes between mutagens present in a mixture have become better understood, and the results validated an analytical model that determined which component had an effect on another. The results also showed that the type of compounds in the mixture determined whether or not a risk threshold was present.

Tratamiento médico de la fisura anal con tadafilo tópico como principio activo / Medical treatment of chronic anal fissure with topical tadalafil

Introducción: La fisura anal es una úlcera lineal dolorosa que generalmente, aparece en la línea media posterior del canal anal, extendiéndose desde la línea dentada hasta el margen del ano. Su persistencia se debe al espasmo anómalo del músculo del esfínter interno. Hasta hace poco, la curación definitiva de las fisuras solo se logró mediante procedimientos quirúrgicos dirigidos a la ablación del espasmo esfinteriano. Diseño: Estudio prospectivo, controlado y aleatorio para comprobar la hipótesis de que la aplicación tópica de una preparación de Tadalafilo es un método efectivo y seguro para relajar el músculo liso y promover la cicatrización de la fisura anal. Población y métodos: Se seleccionaron los pacientes que acudieron a la consulta de coloproctología del HCC con diagnóstico de fisura anal (726). Todos fueron sometidos a una historia clínica y examen físico, antes del comienzo del tratamiento y seguimiento por 1 año. Los pacientes fueron divididos en tres grupos: Grupo A: tratados de forma médica con AINES por via oral, sediluvios y pomadas tópicas de esteroides 3 veces al dia. Grupo B: tratados con nitroglicerina 0,25% locales crema 3 veces al día. Grupo C: tratados con toxina botulínica inyectada 1 sola dosis en el espesor del esfínter interno del ano. Grupo D: tratados con formula magistral crema tópica de Tadalafilo aplicada 3 veces al día. Grupo E: pacientes a quienes se les realiza la Esfinterotomía Lateral Interna una vez que se considera ha fracasado el manejo médico y tratamiento farmacológico. Resultados: Se encontró predominio del sexo femenino con 370 pacientes (50.97%). Las edades en las cual se agrupó mayor cantidad de individuos fue entre los 26 a 35 años con 218 pacientes (30,02%). Predominó el diagnóstico de fisura crónica con 382 casos (52,61 %). El tratamiento inicial que se utilizó más frecuentemente fue el quirúrgico con 270 pacientes (37,19%), seguido de Tadalafilo tópico con 196 pacientes (26,99%)...

Introduction: Anal fissure is a painful linear ulcer usually appears in the posterior midline of the anal canal, extending from the dentate line to the margin of the anus. Its persistence is due to spasm abnormal internal sphincter muscle. Until recently, a definitive cure was achieved only cracks by surgical procedures aimed at ablation of the sphincter spasm. Design: Prospective. controlled trial to test the hypothesis that topical application of a preparation of Tadalafil is a safe and effective method to relax the smooth muscle and promote healing of anal fissure. Population and methods: We selected patients who attended the consultation of Coloproctology of HCC diagnosed with anal fissure (726). AIl underwent a medical history and physical examination before starting treatment and followed for 1 year. The patients were divided into three groups: Group A: treated medical oral NSAlDs, topical ointments sediluvios and steroids 3 times a day. Group B: treated with local nitroglycerin cream 0.25% 3 times a day. Group C: treated with botulinum toxin injection 1 dose in the thickness of the internal anal sphincter. Group D: treated with topical cream formulation TadalafiI masterfully applied 3 times a day. Group E: patients who underwent lateral internal sphincterotomy is considered after failed medical management and pharmacological treatment. Results: There was a predominance of females with 370 patientes (50.97%). The ages at which more individuals grouped was between 26 to 35 years with 218 patients (30.02%). The predominant diagnosis of chronic fissure with 382 cases (52.61%). The initial treatment was most frequently used surgical treatment of 270 patients (37.19%), followed by topical Tadalafil 196 patients (26.99%). The initial treatment had less failure was the use of topical Tadalafil 10 cases (1.37%), which required surgery...

Oral tadalafil in pulmonary artery hypertension: a prospective study.

BACKGROUND: Pulmonary artery hypertension is a disorder with limited treatment options and poor prognosis. We studied the effect of tadalafil, a selective phosphodiesterase type 5 inhibitor, in patients with this disease. METHODS AND RESULTS: In thirteen patients (5 males, 8 females) aged 15-70 years, with pulmonary artery hypertension (7 with congenital heart disease, 4 with chronic pulmonary thromboembolism and 2 with primary pulmonary hypertension), tadalafil was added to their baseline therapy at 10 mg OD for two weeks and if tolerated well, increased to 20 mg OD for the next two weeks. After four weeks of therapy, all thirteen patients had subjective improvement in the form of overall well being and objective improvement as measured by duration of exercise on treadmill following Bruce protocol from a baseline of 350.54+/-255.06 seconds to 479.54+/-195.00 seconds (p<0.01). There was improvement in NYHA functional class in eleven patients. Two patients, though showed no improvement in functional class, had subjective improvement in effort tolerance and objective improvement as measured by duration of exercise on TMT. Hemodynamic parameters showed a trend towards improvement, mean pulmonary artery mean pressure decreased from 63.5+/-26.2 mmHg to 62.2+/-24.8 mmHg (p>0.05), mean pulmonary blood flow increased from 3.26+/-1.04 L/min to 3.44+/-1.26 L/min (p>0.05), mean total pulmonary vascular resistance decreased from 1858.6+/-1138.9 dyne-sec.cm-5 to 1737.3+/-1017.2 dyne-sec.cm-5 (p>0.05). CONCLUSION: Oral tadalafil was well tolerated and had a beneficial effect in patients with pulmonary artery hypertension irrespective of age, sex and underlying etiology. Patient had improved effort tolerance and a trend towards improved pulmonary hemodynamics.