Sildenafil como tratamiento de la restricción de crecimiento intrauterino, revisión sistemática de la literatura / Sildenafil as a treatment for blood restriction fetal growth, systematic review of the literature

INTRODUCCIÓN Y OBJETIVO: La restricción del crecimiento intrauterino (RCIU), expresión insuficiente del potencial genético de crecimiento fetal, complica el 5-8% de los embarazos, con unas altas tasas de morbimortalidad perinatal. De origen multifactorial, puede ser causada por patologías maternas, fetales o placentarias. El tratamiento es limitado, optándose por un seguimiento riguroso con eventual interrupción del embarazo según la evolución. Se han utilizado diferentes estrategias terapéuticas para su prevención y manejo, surgiendo el citrato de sildenafil (CS), inhibidor de la fosfodiesterasa tipo 5, como fármaco que podría mejorar el flujo sanguíneo uteroplacentario y ofrecer mejores resultados perinatales en fetos con RCIU. Se propone realizar una revisión de la literatura disponible en relación al CS como tratamiento del RCIU. MÉTODO: Se realizó una búsqueda de literatura en inglés y español. De 105 artículos seleccionados, se excluyeron 94. La información obtenida fue clasificada y utilizada como soporte para la realización de esta revisión, siguiendo el modelo PRISMA. RESULTADOS: Se encontraron 11 estudios que contrastan el uso de placebo y CS en pacientes con RCIU. Respecto al aumento de peso al nacimiento, solo dos estudios demostraron evidencia significativa. Se reportaron 40 casos de muerte fetal/neonatal asociada al tratamiento con CS. CONCLUSIONES: No se encontró evidencia suficiente que justifique el uso sistemático de CS en casos de RCIU. Aún es necesario realizar estudios con muestras de mayor tamaño y posterior metaanálisis para confirmar el beneficio farmacológico en cuanto al aumento de peso de nacimiento, la prolongación del embarazo y los posibles efectos adversos a largo plazo.

INTRODUCTION AND OBJECTIVE: Intrauterine growth restriction (IUGR) is an insufficient expression of the genetic potential for fetal growth, complicates 5-8% of pregnancies and represents high rates of perinatal morbidity and mortality. Of multifactorial origin, it can be caused by pathologies at the maternal, fetal or placental level. The treatment is limited, opting for a rigorous follow-up with eventual interruption of the pregnancy according to evolution. Different therapeutic strategies have been used for its prevention and management, emerging sildenafil citrate (CS), inhibitor of phosphodiesterase type 5, as a drug that could improve the uteroplacental blood flow and offer better perinatal results in fetuses with IUGR. A review of the available literature on CS as a treatment for IUGR is proposed. METHOD: A search was conducted for literature in English and Spanish. Out of 105 selected articles, 94 were excluded. The information obtained was classified and used as support for this review, following the PRISMA model. RESULTS: We found 11 studies that contrast the use of placebo and CS in patients with IGR. Regarding birth weight gain, only two studies showed significant evidence. Forty cases of fetal/neonatal death associated with CS treatment were reported. CONCLUSIONS: Not enough evidence was found to justify the routine use of CS in IUGR cases. Studies with larger samples and subsequent meta-analysis are still necessary to confirm the benefit of this drug in terms of birth weight gain, prolongation of pregnancy and possible long-term adverse effects.

Enfermedad cardiovascular aterosclerótica y sexualidad / Atherosclerotic Cardiovascular Disease and Sexuality

La enfermedad cardiovascular aterosclerótica es la primera causa de muerte en todo el mundo, y la principal causa de años de vida perdidos por discapacidad (AVADs) en los adultos. Sus factores de riesgo son muy prevalentes en la población, y su ocurrencia se ha asociado con disfunción sexual tanto en hombres como en mujeres, debido a que comparten un mecanismo fisiopatológico similar en el caso de la disfunción eréctil en los hombres y potencialmente en la disfunción sexual femenina. Además, los trastornos mentales asociados (principalmente ansiedad y depresión) y los efectos adversos de los medicamentos antihipertensivos y antidepresivos también contribuyen a las disfunciones sexuales. Por otro lado, los inhibidores de la fosfodiesterasa 5 (iFDE5s) han demostrado seguridad y beneficios cardiovasculares en los hombres, y en las mujeres hay evidencia creciente de su utilidad en las disfunciones sexuales. En esta revisión, se presentan las implicaciones de la enfermedad cardiovascular aterosclerótica y su tratamiento en la vida sexual de hombres y mujeres, los efectos cardiovasculares de los tratamientos de las disfunciones sexuales, y la consejería a los pacientes.

Atherosclerotic cardiovascular disease is the leading cause of death worldwide and the leading cause of disability-adjusted life years (DALYs). Its risk factors are very prevalent in the population, and its occurrence has been associated with sexual dysfunction in both men and women, because they share a similar pathophysiological mechanism in the case of erectile dysfunction in men and potentially in female sexual dysfunction. Furthermore, associated mental disorders (mainly anxiety and depression) and the adverse effects of antihypertensive drugs and antidepressants also contribute to sexual dysfunction. On the other hand, phosphodiesterase 5 inhibitors (PDE5is) have shown safety and cardiovascular benefits in men, and in women there is growing evidence of their usefulness in female sexual dysfunctions. The present review describes the implications of atherosclerotic cardiovascular disease and its treatment on the sexual lives of men and women, the cardiovascular effects of the treatments for sexual dysfunctions, and patient counseling.

Cardioprotector effect of phosphodiesterase 5 inhibitors in experimental model for diabetes mellitus / Efeito cardioprotetor dos inibidores da fosfodiesterase 5 em modelo de diabetes mellitus experimental

Diabetes mellitus (DM) is considered a 21st century pandemic and is often associated with cardiovascular disease (CVD). The aim of this integrative review was to analyze the cardioprotective effects of phosdodiesterase-5 (PDE5i) inhibitors in experimental diabetes models. The articles were selected from the PubMed, SciELO and LILACS databases from 2014 to 2019. The following descriptors were used in combination with the Boolean operators: Diabetes mellitus experimental AND Phosphodiesterase 5 inhibitors; Diabetic cardiomyopathies AND Phosphodiesterase 5 inhibitors. An initial sample of 155 articles was obtained, of which six met the criteria for the synthesis of the review. The studies analyzed showed that treatment with PDE5i in experimental models, resulted in positive effects on cardiac function and metabolic parameters. Similar results have also been seen in humans. The reduction in cardiac hypertrophy, apoptosis of cardiomyocytes, pro-inflammatory factors and oxidative stress and the modulation of transcription factors involved in diabetes homeostasis, were prevalent among studies. The mechanisms of action involved in cardioprotection have not yet been fully elucidated, however the restoration of the activated cyclic guanosine monofate (cGMP) pathway by soluble guanylate cyclase (sGC) via nitric oxide (NO) was a common mechanism among the studies.

O Diabetes mellitus (DM) é considerado uma pandemia do século XXI e está frequentemente associado às doenças cardiovasculares (DCVs). O objetivo desta revisão integrativa foi analisar os efeitos cardioprotetores de inibidores da fosdodiesterase 5 (PDE5i) em modelos de diabetes experimental. Os artigos foram selecionados nas bases de dados PubMed, SciElo e LILACS no período de 2014 a 2019. Foram utilizados os seguintes descritores combinados com os operadores booleanos: Diabetes mellitus experimental AND Phosphodiesterase 5 inhibitors; Diabetic cardiomyopathies AND Phosphodiesterase 5 inhibitors. Foi obtida uma amostra inicial de 155 artigos, dos quais seis se enquadraram nos critérios para a síntese da revisão. Os estudos analisados evidenciaram que o tratamento com os PDEi5 em modelos experimentais, resultou em efeitos positivos sobre a função cardíaca e parâmetros metabólicos. Resultados semelhantes também foram observados em humanos. A redução da hipertrofia cardíaca, apoptose de cardiomiócitos, fatores pró-inflamatórios e estresse oxidativo e a modulação de fatores de transcrição envolvidos na homeostasia do diabetes, foram achados prevalentes entre os estudos. Os mecanismos de ação envolvidos na cardioproteção ainda não foram totalmente elucidados, contudo a restauração da via da guanosina monofato cíclica ativada (GMPc) pela Guanilato ciclase solúvel (GCs) via Óxido Nítrico (NO) foi um mecanismo comum entre os estudos.

Ressecção anterior do reto vs prostatectomia radical. Existem diferenças na reabilitação sexual? / Anterior resection of the rectum vs radical prostatectomy. Are there any differences in sexual rehabilitation?

RESUMO Objetivo: O objetivo deste estudo foi avaliar o impacto da reabilitação peniana na recuperação da função erétil em pacientes submetidos a ressecção anterior do reto (RAR) ou a prostatectomia radical (PR), comparando os resultados entre esses dois grupos. Materiais e Métodos: Foi realizado estudo de coorte retrospetivo unicêntrico, em pacientes avaliados na nossa consulta multidisciplinar de oncosexologia, entre janeiro de 2015 e janeiro de 2018, submetidos a PR ou RAR (homens) com disfunção sexual. Avaliamos as características oncológicas dos pacientes, idade, estado civil, tipo de disfunção sexual, Índice Internacional de Função Erétil (IIEF-5) na primeira e última consulta e terapêutica utilizada. Foi realizada análise estatística. Resultados: Foram incluídos 55 pacientes, 60% (33) realizaram RAR e 40% (22) PR. Em relação à disfunção sexual após a cirurgia, a disfunção erétil (DE) foi encontrada na maioria dos pacientes (> 95%). Na pontuação inicial do IIEF-5, os pacientes com RAR e PR apresentaram, com maior frequência, DE moderada ou grave (escore 5-11), em 78,8% e 59,1% dos casos, respetivamente. Ao reavaliar a pontuação do IIEF-5 de cada paciente durante o acompanhamento, verificou-se melhoria em 69,7% dos pacientes com RAR e 72,7% dos pacientes com PR (p = 0,81). Quanto à abordagem terapêutica, 84,8% dos pacientes com RAR foram medicados com inibidores da fosfodiesterase-5 (PDE5I) exclusivamente e 3% com injeção de Alprostadil. Os pacientes com PR foram medicados com PDE5I em 63,6% e com injeção de Alprostadil em 31,8% (p <0,05). Conclusões: Apesar das diferenças técnicas destas cirurgias, do ponto de vista sexual, os pacientes se beneficiaram com a reabilitação peniana.

ABSTRACT Purpose: The aim of this study was to evaluate the impact of penile rehabilitation in restoring erectile function in patients submitted to anterior resection of the rectum (ARR) or radical prostatectomy (RP), comparing the results between these two groups. Materials and Methods: We performed a unicenter retrospective cohort study, on patients evaluated in our multidisciplinary oncosexology consultation, between January 2015 and January 2018, submitted to RP or ARR (males) and presenting sexual dysfunction. We evaluate the patient and oncologic characteristics, the type of sexual dysfunction, marital status, assessed the International Index of Erectile Function (IIEF-5) on the first and last consultation and the therapeutic approach. A statistical analysis was performed. Results: A total of 55 patients were included, 60% (33) performed ARR and 40% (22) RP. Regarding the sexual dysfunction after surgery, erectile dysfunction (ED) was found in the majority of patients (>95%). On the initial IIEF-5 scoring, ARR and RP patients had, most frequently, severe or moderate ED (score 5-11), 78.8% and 59.1% respectively. When reassessed the IIEF-5 scoring of each patient during follow-up, there was an improvement in 69.7% of ARR patients and 72.7% of RP patients (p=0.81). Regarding the therapeutic approach, 84.8% of ARR patients used phosphodiesterase-5 inhibitors (PDE5I) exclusively, 3% used Alprostadil injection, while RP patients used 63.6% and 31.8%, respectively (p<0.05). Conclusions: Despite the technical differences of these surgeries, from the sexual point of view these patients benefit with a penile rehabilitation.

Medida computadorizada da evolução da área cicatricial tratada com ultrassom terapêutico e citrato de sildenafila / Computerized measurement of the evolution of cicatricial area treated with ultrasound and sildenafil citrate

Objetivou-se comparar a evolução da cicatrização de feridas cirúrgicas com cinco protocolos de tratamento através de análise planimétrica. Grupos de 12 ratos Wistar, foram alocados em cinco estudos experimentais: A- controle negativo; B- ferida cirúrgica, tratada com ultrassom terapêutico (UST) desligado ; C- ferida tratada somente com citrato de sildenafila ; D- ferida tratada com citrato de sildenafila e UST e grupo E-ferida tratada somente com UST. A evolução cicatricial foi acompanhada diariamente e avaliada por imagem fotográfica computadorizada aos sete, 14 e 21 dias. A aplicação do UST pulsado, com doses 1MHZ e 0,4Wcm2 reduziu o tempo de cicatrização epitelial em condições experimentais, favorecendo precocemente a reparação tecidual com efeitos qualitativos superiores ao tratamento com citrato de sildenafila (CS). A mensuração computacional para evolução da cicatrização de ferida dérmica mostrou-se um recurso de fácil aplicação sendo de baixo custo e eficiente para a aplicabilidade na rotina médica veterinária.

This study aimed at comparing the evolution of healing of surgical wounds with five treatment protocols through planimetric measurement. Groups of 12 Wistar rats were allocated in five experimental studies: A ­ negative control; B ­ surgical wound treated with therapeutic ultrasound turned off; C ­ surgical wound treated with sildenafil citrate; D ­ wound treated with sildenafil citrate and therapeutic ultrasound; and group E ­ wound treated only with therapeutic ultrasound. The healing progress was monitored daily and assessed by computed photographic image at seven, 14 and 21 days. It was concluded that the application of pulsated therapeutic ultrasound on surgical wounds at 1 MHz and 0.4Wcm2 doses reduces the epithelial healing time in experimental conditions, favoring the early repair of tissue with qualitative effects superior than the ones found in the treatment with sildenafil citrate (SC). The computational measurement for the evolution of the dermal wound healing proved to be an easy-to-apply resource, with a low cost and great efficiency for the applicability in the veterinary medical routine.

Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum

ABSTRACT Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.

Positive outcomes of phosphodiesterase type 5 inhibitor on histopathologic and biochemical changes induced by ureteral obstruction

SUMMARY OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

RESUMO OBJETIVOS: Examinamos os efeitos do tadalafil em um dos inibidores da fosfodiesterase tipo 5 (PDE5) em um modelo de rato com obstrução ureteral unilateral parcial e completa (UUO). MÉTODOS: Os ratos foram divididos em cinco grupos: sham (n = 6), obstrução ureteral unilateral parcial (PUUO, n = 6), PUUO com tadalafil (PUUO T; Cialis, 10 mg/72 h, intragástrica; Lilly, Indianapolis, Indiana, EUA), completa obstrução ureteral unilateral (CUUO, n = 6) e CUUO com tratamento com tadalafil (CUUO T). RESULTADOS: Quinze dias após a UUO, o ureter apresentou alterações nas camadas de urotélio e infiltração significativa de células inflamatórias nos grupos PUUO e CUUO. Em comparação com os grupos sham, PUUO e CUUO, houve um aumento grave da infiltração de células inflamatórias. O epitélio urotelial exibiu degeneração e perda celular devido às células epiteliais inchadas, atróficas e desnudas nos grupos PUUO e CUUO. Nos grupos PUUO T e CUUO T, o urotélio revelou menor degeneração e perda de células epiteliais. Nós mostramos que a expressão da actina do músculo liso-α (α-SMA) e do fator de crescimento transformador-β (TGF-β) foram exibidas como sub-regulação nos grupos PUUO e CUUO. A expressão do TGF-β foi diminuída positivamente correlacionada com a da α-SMA nos grupos de terapia com tadalafil, PUUO T e CUUO T. CONCLUSÃO: O tadalafil do inibidor da fosfodiesterase tipo 5 reduziu as expressões α-SMA e TGF-β nos ureteres obstruídos, medidos por exames bioquímicos. Além disso, o tadalafil diminuiu a degeneração do urotélio devido à diminuição da perda de células epiteliais e da infiltração de células inflamatórias. Nossos resultados mostram que o tadalafil previne ou retarda o início da inflamação do ureter e degeneração urotelial em ratos com UUO.

Effects of tadalafil to prevent injury on corpus cavernosum after vascular or nervous peri-prostatic bundle injury. Experimental model in rats

Abstract Purpose: To evaluate the effects of tadalafil (TD) in preventing histological alterations of the corpus cavernosum caused by isolated lesions of cavernous nerve (ILCN) and artery (ILCA) in rats. Methods: Fifty male Wistar rats were randomly assigned in five groups: G1: control; G2: bilateral ILCN; G3: bilateral ILCA; G4: ILCN+TD; G5: ILCA+TD. The cavernous bodies were submitted to histomorphometry, immunohistochemistry and biochemical analysis. Results: Nerve density was significantly higher in G2 and G4 compared to control (22.62±2.84 and 19.53±3.47 vs. 15.72±1.82; respectively, p<0.05). Smooth muscle density was significantly lower in G2 and G3 in comparison to G1 (12.87±1.90 and 18.93±1.51 vs. 21.78±1.81, respectively; p<0.05). A significant decrease in the sinusoidal lumen area was observed in G2 compared to controls (5.01±1.62 vs. 9.88±3.66, respectively; p<0.05) and the blood vessel density was increased in G2 and G3 (29.32±4.13 e 20.80±2.47 vs. 10.13±2.71, p<0.05). Collagen density was higher in G3 compared to G1 (93.76±15.81 vs. 64.59±19.25; p<0.05). Conclusions: Histomorphometric alterations caused by ILCN were more intense than those produced by vascular injury, but the collagen analyses showed more fibrosis in animals with ILCA. TD was effective in preventing the majority of the alterations induced by the periprostatic bundle injury.

Oxidative stress assessment in intestine of newborn rats submitted to hypoxia and reoxygenation with tadalafil

Abstract Purpose: To evaluate the functional and structural response of tadalafil effects in the intestinal mucosa, using an experimental model of hypoxia and reoxygenation injury in rats. Methods: The animals were divided into 4 groups: CTL, H/R, H/R+Td and M+Td. The newborn rats allocated in groups H/R, H/R+Td and M+Td were submitted twice a day, to a gas chamber with CO2 at 100% for 10 minutes and afterward reoxygenation with O2 at 98% for 10 minutes, in the three first days of life. Tadalafil dose was given to newborn of group H/R+Td and to the pregnant rat of group M+Td. Histological analysis was made with hematoxylin-eosin technique and oxidative stress through nitrite and nitrate levels and lipid peroxidation. Results: The histological analysis showed a reduction of mucosa alterations in the groups that received tadalafil. In the oxidative stress evaluation, occurred an increase of NO levels and less lipidic peroxidation in the ileum segments that received tadalafil. Conclusion: Tadalafil provides tissue protection when administered independently to both, pregnant or newborns.

Surdez súbita em paciente em uso de tadalafil: um relato de caso clínico / Sudden deafness in a patient with tadalafil use: a clinical case report

Introdução: a Surdez Súbita (SS) é uma emergência médica de baixa prevalência, porém com potencial de perda auditiva irreversível para o paciente. Possui diversos e ainda incertos mecanismos etiopatológicos. Recentemente a literatura vem trazendo a associação da SS com a classe dos inibidores da fosdodiesterase-5 (IPDE-5), a qual inclui medicamentos para tratamento de impotência sexual. Objetivo: relatar caso clínico de paciente idoso que apresentou SS após fazer uso de medicamento da classe dos IPDE-5, pesquisando na literatura qual a provável fisiopatologia. Metodologia: trata-se de estudo qualitativo, descritivo do tipo relato de caso clínico, realizado através da coleta de dados do prontuário médico, que foram comparados com literatura especializada. Resultado: paciente masculino, 72 anos, engenheiro, procurou atendimento referindo hipoacusia e plenitude aural à direita notados subitamente há três dias. Relata ter feito uso de Tadalafil 5mg, anteriormente aos sintomas. Anamnese e exame físico direcionaram para hipótese diagnóstica de SS, de modo que exames complementares foram solicitados. À audiometria evidenciou-se perda auditiva sensorioneural moderada a severa em orelha direita. Após tratamento com prednisolona oral e mesilato de codergocrina, paciente apresentou melhora, com audiometria evidenciando perda sensorioneural leve em orelha direita. Conclusão: a relação entre SS e o uso de IPDE-5 está cada vez mais evidente de acordo com a literatura. É provável que possa haver ativação de vias de estresse celular, contribuindo para patologia

Penile microvascular endothelial function in hypertensive patients: effects of acute type 5 phosphodiesterase inhibition

The primary aim of this study was to evaluate penile endothelial microvascular function in patients with primary arterial hypertension and age-matched normotensive subjects using laser speckle contrast imaging (LSCI). Additionally, we analyzed the acute penile microvascular effects induced by oral phosphodiesterase type 5 inhibitor (sildenafil; SIL) administration. Endothelium-dependent microvascular reactivity was evaluated in the penises and forearms of hypertensive patients (aged 58.8±6.6 years, n=34) and age-matched healthy volunteers (n=33) at rest and 60 min following oral SIL (100 mg) administration. LSCI was coupled with cutaneous acetylcholine (ACh) iontophoresis using increasing anodal currents. Basal penile cutaneous vascular conductance (CVC) values were not significantly different between control subjects and hypertensive individuals. Penile CVC values increased significantly after SIL administration in control (P<0.0001) and hypertensive (P<0.0001) subjects. Peak CVC values were not different between the two groups during penile ACh iontophoresis before SIL administration (P=0.2052). Peak CVC values were higher in control subjects than in hypertensive subjects after SIL administration (P=0.0427). Penile endothelium-dependent microvascular function is, to some extent, preserved in patients presenting with primary arterial hypertension under effective anti-hypertensive treatment. LSCI may be a valuable non-invasive tool for the evaluation of penile vascular responses to phosphodiesterase type 5 inhibitor.

Daily use of phosphodiesterase type 5 inhibitors as prevention for recurrent priapism / Prevenção do priapismo recorrente com a utilização diária de inibidores da fosfodiesterase tipo 5

Summary Objective: The pathogenesis of recurrent priapism is currently being investigated based on the regulation of the phosphodiesterase 5 (PDE5) enzyme. We explored the daily use of PDE5 inhibitors to treat and prevent priapism recurrences. Method: We administered PDE5 inhibitors using a long-term therapeutic regimen in seven men with recurrent priapism, with a mean age of 29.2 years (range 21 to 35 years). Six men (85.7%) had idiopathic priapism recurrences and one man (24.3%) had sickle cell disease-associated priapism recurrences. Tadalafil 5 mg was administered daily. The mean follow-up was 6.6 months (range 3 to 12 months). Results: Daily long-term oral PDE5 inhibitor therapy alleviated priapism recurrences in all patients. Five (71.4%) had no episodes of priapism and two (28.6%) referred decrease in their episodes of priapism. All patients referred improvement in erectile function. Conclusion: These findings suggest the hypothesis that PDE5 dysregulation exerts a pathogenic role for both sickle cell disease-associated priapism and for idiopathic priapism, and that it offers a molecular target for the therapeutic management of priapism. These preliminary observations suggest that continuous long-term oral PDE5 inhibitor therapy may treat and prevent recurrent priapism.

Resumo Objetivo: Uma das teorias propostas para explicar a etiologia do priapismo recorrente está baseada no mecanismo de regulação da fosfodiesterase tipo 5. Estudamos o uso diário dos inibidores de fosfodiesterase tipo 5 no tratamento e na prevenção do priapismo recorrente. Método: Sete homens com diagnóstico de priapismo recorrente, com idade média de 29,5 anos (21 a 35 anos), utilizaram inibidor de fosfodiesterase tipo 5 em dose diária (tadalafila 5 mg/dia) por período prolongado. Seis homens (85,7%) apresentavam priapismo recorrente de etiologia idiopática, e um homem (24,3%), de etiologia associada à anemia falciforme. O seguimento médio foi de 6,6 meses (3 a 12 meses). Resultados: Todos os pacientes se beneficiaram com a utilização de inibidores de fosfodiesterase tipo 5. Cinco (71,4%) não apresentaram nenhum episódio de priapismo e dois (28,6%) relataram diminuição dos episódios. Todos os pacientes relataram melhora da função erétil. Conclusão: Estes achados sugerem que a hipótese do mecanismo de regulação da fosfodiesterase tipo 5 exerce papel importante na patogenia do priapismo recorrente. O uso contínuo e diário de inibidores da fosfodiesterase tipo 5 pode ser uma opção no tratamento do priapismo recorrente.

Prevalence of erectile dysfunction oral drugs use in a city of southern Brazil / Prevalência do uso de drogas orais para disfunção erétil em uma cidade do sul do Brasil

Abstract The last decade has seen a breakthrough in the treatment of erectile dysfunction (ED) with the advent of phosphodiesterase-5 inhibitors. There are few population-based observational studies on the prevalence of use of these drugs. We conducted a cross-sectional population-based study in the city of Pelotas (Brazil). Our sample comprised 1,082 men aged 20 years or older who answered a confidential and self-administered questionnaire. Prevalence of EDD use was 5% (IC95% = 4%;7%). ED and advanced age were strongly associated with a higher prevalence of EDD use. ED prevalence in men who used EDD was 68%, which was much higher than the one found in the entire sample (27%). The use of EDD was more frequently reported among separated men, respondents with higher level of education and those without ED. A high proportion of respondents (68%) did not seek medical advice on the use of EDD. Sildenafil was the most commonly used drug (38%) but non-regulated and non-evidence-based drugs were also frequently used (14%). Prevalence of EDD use is higher among individuals with ED, opposing to the notion of recreational use of EDD.

Resumo Na última década houve um grande avanço no tratamento da disfunção erétil (DE), com o advento dos inibidores da fosfodiesterase-5. Existem poucos trabalhos sobre a prevalência de uso destas drogas. Foi realizado um estudo transversal de base populacional na cidade de Pelotas. A amostra foi composta por 1.082 homens com 20 anos ou mais de idade que responderam um questionário confidencial e auto-aplicado. A prevalência do uso de medicamentos estimulantes da ereção (MEE) foi de 5%(IC95% = 4%-7%). Idade avançada e DE foram fortemente associados a uma maior prevalência de uso de MEE. A prevalência foi também maior em indivíduos com ensino superior e aqueles separados. A prevalência de DE em homens que usaram MEE foi de 68%, sendo maior do que a prevalência encontrada em toda a amostra (27%). A maioria dos indivíduos não teve aconselhamento médico para o uso de MEE (68%). Sildenafil foi a droga mais utilizada (38%), seguida por aquelas não regulamentadas (14%). A prevalência do uso de MEE é maior em indivíduos com disfunção erétil, opondo-se à noção de uso "recreativo" de EDD.

Tadalafil: protective action against the development of multiple organ failure syndrome

Abstract Introduction: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. Methods: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. Results: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. Conclusion: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.

The effect of tadalafil therapy on kidney damage caused by sepsis in a polymicrobial septic model induced in rats: a biochemical and histopathological study

ABSTRACT Introduction Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). Materials and Methods Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. Results Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p<0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p<0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p<0.05). Conclusion In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.

Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction

ABSTRACT Objective To investigate the effect of a 5mg daily tadalafil treatment on the ejaculation time, erectile function and lower urinary tract symptoms (LUTS) in patients with erectile dysfunction. Materials and Methods A total of 60 patients diagnosed with erectile dysfunction were retrospectively evaluated using the international index of erectile function questionnaire-5 (IIEF-5), intravaginal ejaculatory latency time (IELT) and international prostate symptoms scores (IPSS). After the patients were treated with 5mg tadalafil once a day for three months, their erection, ejaculation and LUTS were assessed again. The fasting levels of blood glucose, total testosterone, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were measured. The independent-samples t-test was used to compare the pre- and post-treatment scores of the patients. Results The mean age of the 60 participants was 50.4±7.9 and the mean baseline serum total testosterone, total cholesterol, and fasting blood sugar were 444.6±178.6ng dL-1, 188.7±29.6mg/dL-1,104 (80-360) mg dL-1, respectively. The mean baseline scores were 2.2±1.4 min for IELT, 9.5±3.7 for IIEF-5 and 14.1±4.5 for IPSS. Following the three-month daily 5mg tadalafil treatment, the scores were found to be 3.4±1.9 min, 16.1±4.7, and 10.4±3.8 for IELT, IIEF and IPSS, respectively. When the baseline and post-treatment scores were compared, a statistically significant increase was observed in the IELTs and IIEF-5 values whereas there was a significant decrease in IPSS (p<0.01). Conclusion A daily dose of 5mg tadalafil can be safely used in the treatment of erectile dysfunction and LUTS, that prolongs the ejaculatory latency time.

Effects of sildenafil on dental pulp: immunohistochemical and ultrastructural evaluation / Efectos de sildenafil en la pulpa dental: evaluación inmunohistoquímica y ultraestructural

Sildenafil is a strong peripheral vasodilator and is used to treat cardiovascular and neurosurgery. The purpose of this study was to investigate the immunohistochemical and ultrastructural effects of sildenafil on dental pulp of rats. The study was performed with adult female Wistar-Albino rats. Control group (n= 7) were fed on standard laboratory diet until surgery. The study group (n= 7) were administered sildenafil orally with orogastric tube 10 mg·kg-1 once a day for 30 days. Each rat was anesthetized and incisor teeth were removed. This study examined the immunohistochemical and ultrastructural effects of sildenafil on the dental pulp in rats. The relaxation from the vessel, endothelial cell hyperplasia, moderate degeneration of collagen fibers were observed to cause degenerative changes in odontoblast with sildenafil. In the pulp tissue long-term use sildenafil is thought to cause degeneration and new vessel formation.

El sildenafil es un vasodilatador periférico importante y se utiliza para tratar enfermedades cardiovasculares y en neurocirugía. El propósito de este estudio fue investigar los efectos inmunohistoquímicos y ultraestructurales del sildenafil sobre la pulpa dental de ratas. El estudio se realizó con ratas Wistar albinas, hembras adultas. El grupo de control (n= 7) fue alimentado con una dieta estándar de laboratorio hasta que se realizó la cirugía. El grupo de estudio (n= 7) fue tratado con sildenafil por vía oral y sonda orogástrica 10 mg·kg-1 una vez al día durante 30 días. Cada rata fue anestesiada y se extrajeron los dientes incisivos. Se examinaron los efectos inmunohistoquímicos y ultraestructurales del sildenafil sobre la pulpa dentaria. Con la administración de sildenafil se observó la relajación de los vasos, la hiperplasia de las células endoteliales y una degeneración moderada de fibras colágenas causando cambios degenerativos en los odontoblastos. En el tejido pulpar, el uso de sildenafil a largo plazo puede causar la degeneración y neoformación de vasos.