Expression of AIF, PARP, and miRNAs MIR-145, MIR-210, and MIR-486 associated with apoptosis in the corpus cavernosum of rats subjected to chronic alcoholism model / Expresión de AIF, PARP y miRNAs MIR-145, MIR-210 y MIR-486 asociados con apoptosis en el cuerpo cavernoso de ratas sometidas a modelo de alcoholismo crónico

SUMMARY: Previous studies from our group described the consequences of using ethanol on penile erection. Nevertheless, the molecular mechanisms surrounding microRNAs, apoptosis process and their relationship with erectile dysfunction associated with alcohol consumption are still poorly understood. The objective of this analysis was to evaluate the mechanism of apoptosis by the expression of AIF and PARP, as well as their regulatory microRNAs: miR-145, miR-210 and miR-486, in the corpus cavernosum of rats submitted to a semivoluntary alcoholism model. For this study 24 Wistar rats were divided into two groups: control (C) and treated with 20 % ethanol (A) for seven weeks. The corpus cavernosum samples were prepared for immunohistochemical analysis of AIF and PARP protein expression, and microRNAs miR-145, miR-210, miR-486 gene expression in cavernous tissue was performed by real time PCR. The immunohistochemical analysis showed little nuclear positive labeling for the protein PARP and AIF in the corpus cavernosum of control and ethanol treated animals. After analysis of miR-145, -210 and -486 microRNA expression in the 12 animals studied, no results were found with significant statistical difference between the control and alcoholized groups. The expression of AIF and PARP and their regulatory microRNAs involved in apoptotic process (miR-145, miR-210 and miR-486) were not altered in the corpus cavernosum of rats submitted to semivoluntary alcoholism.

RESUMEN: Estudios previos de nuestro grupo describieron las consecuencias del uso de etanol en la erección del pene. Sin embargo, los mecanismos moleculares que rodean a los microARN, el proceso de apoptosis y su relación con la disfunción eréctil asociada con el consumo de alcohol aún no se conocen bien. El objetivo de este análisis fue evaluar el mecanismo de apoptosis mediante la expresión de AIF y PARP, así como sus microARN reguladores: miR-145, miR-210 y miR-486, en el cuerpo cavernoso de ratas sometidas a un modelo de alcoholismo semivoluntario. Se dividieron 24 ratas Wistar en dos grupos: control (C) grupo de ratas tratadas con etanol al 20 % (A) durante siete semanas. Las muestras del cuerpo cavernoso se prepararon para el análisis inmunohistoquímico de la expresión de la proteína AIF y PARP, y la expresión del gen microRNAs miR-145, miR-210, miR-486 en tejido cavernoso se realizó por PCR en tiempo real. El análisis inmunohistoquímico mostró escaso etiquetado nuclear positivo para la proteína PARP y AIF en el cuerpo cavernoso de los animales de control y tratados con etanol. Después del análisis de la expresión de microARN miR-145, -210 y -486 no se encontraron resultados con diferencias estadísticas significativas entre los grupos control y alcoholizados. La expresión de AIF y PARP y sus microARN reguladores involucrados en el proceso apoptótico (miR-145, miR-210 y miR-486) no se alteraron en el cuerpo cavernoso de las ratas sometidas a alcoholismo semivoluntario.

Losartan improves erectile function through suppression of corporal apoptosis and oxidative stress in rats with cavernous nerve injury / 亚洲男科学杂志(英文版)

This study aimed to investigate the functional and morphological changes in the corpus cavernosum after cavernous nerve (CN) injury or neurectomy and then reveal whether treatment with the angiotensin II Type 1 receptor antagonist losartan would improve erectile function as well as its potential mechanisms. A total of 48 10-week-old Sprague-Dawley male rats, weighing 300-350 g, were randomly divided into the following four groups (n = 12 per group): sham operation (Sham) group, bilateral cavernous nerve injury (BCNI) group, losartan-treated BCNI (BCNI + Losartan) group, and bilateral cavernous neurectomy (Neurectomy) group. Losartan was administered once daily by oral gavage at a dose of 30 mg kg-1 day-1 for 4 weeks starting on the day of surgery. The BCNI and the Neurectomy groups exhibited decreases in erectile response and increases in apoptosis and oxidative stress, compared with the Sham group. Treatment with losartan could have a modest effect on erectile function and significantly prevent corporal apoptosis and oxidative stress. The phospho-B-cell lymphoma 2 (Bcl-2)-associated death promoter (p-Bad)/Bad and phospho-the protein kinase B (p-AKT)/AKT ratios were substantially lower, while the Bcl-2-associated X protein (Bax)/Bcl-2 ratio, nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap-1), transforming growth factor-β 1 (TGF-β 1) and heme oxygenase-1 (HO-1) levels, and caspase-3 activity were higher in the BCNI and Neurectomy groups than in the Sham group. After 4 weeks of daily administration with losartan, these expression levels were remarkably attenuated compared with the BCNI group. Taken together, our results suggested that early administration of losartan after CN injury could slightly improve erectile function and significantly reduce corporal apoptosis and oxidative stress by inhibiting the Akt/Bad/Bax/caspase-3 and Nrf2/Keap-1 pathways.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study / Desequilíbrio na proporção salivar diurna de testosterona/cortisol em homens com apneia obstrutiva do sono grave: um estudo observacional

ABSTRACT INTRODUCTION: The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE: The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS: Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION: The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Resumo Introdução: A relação complexa entre os distúrbios do sono e os hormônios pode levar a alterações na produção de cortisol e testosterona em pacientes com Apneia obstrutiva do sono (AOS). Objetivo: O objetivo deste estudo foi determinar as curvas diurnas de testosterona e cortisol livres na saliva e sua proporção (razão T/C). Método: Dez indivíduos recém-diagnosticados com AOS com base na avaliação por polissonografia noturna e sonolência diurna excessiva e sete controles pareados foram recrutados, consecutivamente. Cortisol e testosterona foram medidos em amostras de saliva coletadas ao acordar, ao meio-dia e à noite. A avaliação psicométrica dos distúrbios de ansiedade/depressão e função sexual mencionados foi realizada para detectar a presença de comorbidades neuropsicológicas. Resultados: O achado principal foi que os indivíduos com AOS apresentam hipocortisolismo ao acordar e uma redução significante na concentração de testosterona à noite, em comparação com o grupo controle, que manteve a variação fisiológica diurna de testosterona e cortisol com concentrações hormonais mais elevadas pela manhã e concentrações mais baixas durante a noite. O uso de dados de várias mensurações diurnas, em vez de uma única mensuração, permitiu detectar as alterações na razão T/C de sinais opostos no início e no final do dia: os indivíduos com AOS apresentaram razão T/C maior que os controles na parte da manhã, enquanto que a razão T/C foi significantemente inferior à dos controles durante a noite. Conclusão: Os desequilíbrios no balanço anabólico-catabólico diurno sugerem que a AOS está associada a uma desregulação dos eixos hipotálamo-hipófise-adrenal e hipotálamo-hipófise-gonadal, potencialmente a causa subjacente de algumas das comorbidades neuropsicológicas observadas em pacientes com AOS.

Disfunción eréctil en portadores de diabetes mellitus tipo 2 en edad productiva / Erectile dysfunction among diabetic patients

Background: Diabetic microangiopathy is one of the main causes of erectile dysfunction. Aim: To study the prevalence of erectile dysfunction among diabetic patients. Material and Methods: The "international index of erectile function" survey was applied to 120 diabetic men aged 21 to 50years. Demographic data, evolution time of diabetes, a glycosilated hemoglobin measured in the last three months, weight, height and treatment received were also recorded. Results: Fifty five percent of patients had erectile dysfunction. Patients with an inadequate metabolic control had a significantly higher risk of having this condition (odds ratio 5.5; 95% confidence intervals 2.3-81). Conclusions: Erectile dysfunction is common among diabetic patients and closely associated with an inadequate metabolic control.

Clomiphene fails to revert hypogonadism in most male patients with conventionally treated nonfunctioning pituitary adenomas / Clomifeno não reverte o hipogonadismo na maioria dos homens com adenomas pituitários não funcionais tratados de forma convencional

OBJETIVE: To evaluate the effect of clomiphene in men with hypogonadism and conventionally treated nonfunctioning pituitary adenomas (NFPA). PATIENTS AND METHODS: Open label, single-arm, prospective trial. Nine hypogonadal men (testosterone < 300 ng/dL and low/normal LH) with previously treated NFPA. Clomiphene (50 mg/day orally) for 12 weeks. Testosterone, estradiol, LH, FSH, prolactin and erectile function were evaluated before and after 10 days, 4, 8 and 12 weeks of clomiphene treatment. RESULTS: After clomiphene treatment, testosterone and erectile function improved in only one patient. In the remaining eight patients, testosterone levels decreased whereas LH, FSH, and estradiol remained unchanged. Insulin sensitivity increased in unresponsive patients. CONCLUSIONS: Compared with hypogonadal men with prolactinomas under dopaminergic therapy, clomiphene treatment failed to restore normal testosterone levels in most patients with conventionally treated NFPA.

OBJETIVO: Avaliar o efeito do clomifeno em homens com hipogonadismo e adenoma hipofisário não funcionante (NFPA) previamente tratados. PACIENTES E MÉTODOS: Aberto, braço único, prospectivo. Nove homens hipogonádicos (testosterona < 300 ng/dL e LH normal/baixo) com NFPA previamente tratados. Clomifeno (50 mg/dia oral) por 12 semanas. Testosterona, estradiol, LH, FSH, prolactina e função erétil foram avaliados antes e após 10 dias, 4, 8 e 12 semanas de clomifeno. RESULTADOS: Após clomifeno, a testosterona e a função erétil melhoraram em um paciente. Em outros oito pacientes, os níveis de testosterona reduziram enquanto os níveis de LH, FSH, e estradiol permaneceram inalterados. A sensibilidade à insulina aumentou nos não respondedores. CONCLUSÕES: Em contraste com homens hipogonádicos com prolactinomas tratados com agonistas dopaminérgicos, a maioria dos hipogonádicos com NFPA falha em restaurar os níveis de testosterona durante o uso de clomifeno.