Mechanisms mediating the inhibitory effects of quercetin against phthalates-induced testicular oxidative damage in rats / 南方医科大学学报

OBJECTIVE@#To explore the mechanism underlying the inhibitory effect of quercetin against testicular oxidative damage induced by a mixture of 3 commonly used phthalates (MPEs) in rats.@*METHODS@#Forty male Sprague-Dawley rats were randomly divided into control group, MPEs exposure group, and MPEs with low-, median- and high-dose quercetin treatment groups. For MPEs exposure, the rats were subjected to intragastric administration of MPEs at the daily dose of 900 mg/kg for 30 consecutive days; Quercetin treatments were administered in the same manner at the daily dose of 10, 30, and 90 mg/kg. After the treatments, serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testicular malondialdeyhde (MDA), catalase (CAT) and superoxide dismutase (SOD) were detected, and testicular pathologies of the rats were observed with HE staining. The expressions of nuclear factor-E2-related factor 2 (Nrf2), Kelch-like ECH2 associated protein 1 (Keap1) and heme oxygenase 1 (HO-1) in the testis were detected using immunofluorescence assay and Western blotting.@*RESULTS@#Compared with the control group, the rats with MPEs exposure showed significant reductions of the anogenital distance, weight of the testis and epididymis, and the coefficients of the testis and epididymis with lowered serum testosterone, LH and FSH levels (P < 0.05). Testicular histological examination revealed atrophy of the seminiferous tubules, spermatogenic arrest, and hyperplasia of the Leydig cells in MPEs-exposed rats. MPEs exposure also caused significant increments of testicular Nrf2, MDA, SOD, CAT and HO-1 expressions and lowered testicular Keap1 expression (P < 0.05). Treatment with quercetin at the median and high doses significantly ameliorated the pathological changes induced by MPEs exposure (P < 0.05).@*CONCLUSION@#Quercetin treatment inhibits MPEs-induced oxidative testicular damage in rats possibly by direct scavenging of free radicals to lower testicular oxidative stress and restore the regulation of the Nrf2 signaling pathway.

Cisplatin-induced azoospermia and testicular damage ameliorated by adipose-derived mesenchymal stem cells

BACKGROUND: The testes are highly susceptible to the adverse effects of chemotherapy and radiation at all stages of life. Exposure to these threats mainly occurs during cancer treatment and as an occupational hazard in radiation centers. The present study investigated the regenerative ability of adipose-derived mesenchymal stem cells (ADMSCs) against the adverse effects of cisplatin on the structure and function of the testes. METHODS: New Zealand white rabbits (N = 15) were divided into three groups of five: a negative control group (no treatment), a cisplatin group (single dose of cisplatin into each testis followed three days later by a PBS injection), and a cisplatin + ADMSCs group (cisplatin injection followed three days later by an ADMSC injection). On day 45 post-treatment, serum testosterone levels were evaluated, and the testes and epididymis were collected for histology, oxidative stress examination, and epididymal sperm analysis. RESULTS: Cisplatin caused damage to the testicular tissue and decreased serum testosterone levels, epididymal sperm counts, and oxidants. An antioxidant imbalance was detected due to increasing malondialdehyde (MDA) and reduced glutathione (GSH) levels in testicular tissue. The ADMSC-treated group displayed a moderate epididymal sperm count, adequate antioxidant protection, suitable hormone levels, and enhanced testicular tissue morphology. CONCLUSIONS: ADMSCs treatment repaired damaged testicular tissue, enhanced biochemical parameters, and modified pathological changes caused by cisplatin.

Unexpected effect of testosterone in hypergonadotropic hypogonadism and nodular Leydig cell hiperplasia. Report of one case / Efecto inesperado de la testosterona en un hipogonadismo hipergonadotrófico e hiperplasia de las células de Leydig. Informe de un caso

ABSTRACT We report a 27 -year-old male referred because of hypergonadotropic hypogonadism with low testosterone and azoospermia. At 23 years of age, he underwent an excision of a hypoechoic 0.7 cm nodule of the left testicle. The pathological diagnosis was a Leydig cell tumor. In the right testicle, there were three nodules at ultrasound, the biggest measuring 0.6 cm. Four years later, the nodules in the right testicle were still present and the larger nodule was excised. The biopsy showed tubules with only Sertoli cells in the perinodular zone. Diffuse and nodular hyperplasia of the Leydig cells was found in the interstitium. The pathological diagnosis was Sertoli syndrome with severe hyperplasia of the Leydig cells. With testosterone therapy, LH decreased, and the nodules disappeared. Thereafter, upon interrupting therapy, LH increased, and the nodules reappeared in two occasions. Resuming testosterone treatment, the nodules disappeared again, suggesting a Leydig cell hyperplasia dependent on chronic LH stimulation.

Presentamos un varón de 27 años referido por hipogonadismo hipergonadotrófico con testosterona baja y azoospermia. El paciente tenía el antecedente de un nódulo sólido hipoecogénico de 0,7 cm en el testículo izquierdo, extirpado los 23 años de edad en el año 2002 y diagnosticado patológicamente como tumor de células de Leydig. En ese año se encontraron tres nódulos en el testículo derecho por ultrasonografía, el mayor de 0,6 cm. Cuatro años después, en 2007, los micronódulos del testículo derecho seguían presentes. El mayor de ellos fue extirpado. En la biopsia, había túbulos con solo células de Sertoli en la zona perinodular. En el intersticio había hiperplasia difusa y nodular de las células de Leydig. El diagnóstico patológico fue un síndrome de Sertoli con severa hiperplasia de células de Leydig. La terapia con testosterona disminuyó la LH y los nódulos inesperadamente desaparecieron. En dos ocasiones, al interrumpir esta terapia, la LH aumentó y los nódulos reaparecieron. Este proceso revirtió nuevamente con el uso de testosterona, sugiriendo una hiperplasia de células de Leydig dependiente del estímulo crónico de LH.

Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake­via AMP-activated protein kinase (AMPK)­after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

The effect of testosterone replacement on intramedullary, inguinal and visceral fat in ovariectomized rats / Efeito da reposição de testosterona na gordura intramedular, inguinal e visceral em ratas ovariectomizadas

Abstract Objective The present article aims to evaluate the impact of testosterone treatment on the expansion of visceral, subcutaneous and intramedullary adipose tissue of ovariectomized rats and the visceral and subcutaneous fat expression of peroxisome proliferator-activated receptors (PPARs) gamma. Methods In total 48 female Wistar rats were castrated and randomly divided into 6 treatment groups: group E2 was submitted to estradiol 5 μg/day; group T, to testosterone 5 μg/day; group E2+ T, to estradiol 5 μg/day + testosterone 5 μg/day; group TT, to testosterone 30 μg/day; group E2+ TT, to estradiol 5 μg/day+ testosterone 30 μg/day; and placebo was administered to group P. After 5 weeks, the rats were euthanized, the inguinal and visceral adipose tissues were harvested, weighted, and had their PPAR gamma expression evaluated by reverse transcription quantitative polymerase chain reaction (RTqPCR). The right femurs were harvested and histologically prepared to performthe number count of the intramedullary adipocytes. Results The expansion of visceral fat tissue was much higher in the TT group when compared with other treated groups (p < 0.001). The TT group also showed a higher expansion of inguinal fat (p < 0.01), and groups E2 +T and E2+ TT presented lower growth compared to the P group (p < 0.01). The number of femur intramedullary adipocytes only showed significant differences between groups TT and E2 + TT (p < 0.05). The expression of PPAR gamma showed no differences among the groups. Conclusion The use of testosterone in high doses leads to an important expansion in both visceral and inguinal adipose tissues. Association with estradiol exerts an expansion-repressive effect on the visceral and inguinal adipose tissues.

Resumo Objetivo Este artigo tem como objetivo avaliar o impacto do tratamento com testosterona na expansão dos tecidos adiposos visceral, subcutâneo e intramedular de ratas ovariectomizadas e a expressão de receptores ativados por proliferadores de peroxissoma (RAPPs) gama nas gorduras visceral e subcutânea. Métodos No total, 48 ratas Wistar foram castradas e divididas aleatoriamente em 6 grupos de tratamento: o grupo E2 recebeu estradiol 5 μg/dia; o grupo T, testosterona 5 μg/dia; o grupo E2 + T, estradiol 5 μg/dia + testosterona 5 μg/dia; o grupo TT, testosterona 30 μg/dia; o grupo E2 + TT, estradiol 5 μg/dia + testosterona 30 μg/dia; e o grupo P recebeu placebo. Após 5 semanas, as ratas foram submetidas a eutanásia, o tecido adiposo inguinal e visceral foi coletado, pesado, e se avaliou a expressão dos RAPP gama por reação em cadeia da polimerase via transcriptase reversa quantitativa (RCP-TRq). Os ossos do fêmur direito foram colhidos e processados histologicamente para contagem de números de adipócitos intramedulares. Resultados A expansão do tecido adiposo visceral foi muito maior no grupo TT quando comparado a outros grupos tratados (p < 0,001). O grupo TT também apresentou maior expansão da gordura inguinal (p < 0,01), e os grupos E2 +T e E2 + TT apresentaram menor crescimento em relação ao grupo P (p < 0,01). O número de adipócitos intramedulares no fêmur mostrou apenas diferenças significativas entre os grupos TT e E2 + TT (p < 0,05). A expressão de RAPP gama não mostrou diferenças entre os grupos. Conclusão O uso de testosterona emaltas doses leva a uma importante expansão nos tecidos adiposos visceral e inguinal. A associação com o estradiol exerce um efeito repressivo de expansão nos tecidos adiposos visceral e inguinal.

Effect of testosterone on proliferation markers and apoptosis in breasts of ovariectomized rats / Efeito da testosterona em marcadores de proliferação e apoptose em mamas de ratas ovariectomizadas

Abstract Objective To investigate the action of testosterone (T), isolated or associated with estradiol benzoate (EB), on the proliferation markers and apoptosis of breasts of ovariectomized rats. Methods A total of 48 castrated female Wistar rats were divided into 6 groups, and each of them were submitted to one of the following treatments for 5 weeks: 1) control; 2) EB 50 mcg/day + T 50 mcg/day; 3) T 50mcg/day; 4) EB 50 mcg +T 300 mcg/day; 5) T 300 mcg/day; and 6) EB 50 mcg/day. After the treatment, the mammary tissue was submitted to a histological analysis and immunoexpression evaluation of proliferation markers (proliferating cell nuclear antigen, PCNA) and apoptosis (caspase-3). Results There was a statistically significant difference among the groups regarding microcalcifications and secretory activity, with higher prevalence in the groups treated with EB. There was no difference among the groups regarding atrophy, but a higher prevalence of atrophy was found in the groups that received T versus those that received EB +T. There was a difference among the groups regarding the PCNA (p = 0.028), with higher expression in the group submitted to EB +T 300 mcg/day. Regarding caspase-3, there was no difference among the groups; however, in the group submitted to EB +T 300 mcg/day, the expression was higher than in the isolated T group. Conclusion Isolated T did not have a proliferative effect on the mammary tissue, contrary to EB. Testosterone in combination with EB may or may not decrease the proliferation, depending on the dose of T.

Resumo Objetivo Investigar a ação da testosterona (T) isolada ou associada ao benzoato de estradiol (EB) na proliferação e apoptose de mamas de ratas ovariectomizadas. Métodos Um total de 48 ratas Wistar castradas foram divididas em 6 grupos, e cada um foi submetido a um dos seguintes tratamentos durante 5 semanas: 1) controle; 2) BE 50 mcg/dia + T 50mcg/dia; 3) T 50 mcg/dia; 4) BE 50 mcg + T 300mcg/dia; e) T 300 mcg/dia; e f) BE 50 mcg/dia. Após o tratamento, o tecido mamário foi submetido a análise histológica e avaliação de imunoexpressão de marcadores de proliferação (antígeno nuclear de células proliferantes, PCNA) e apoptose (caspase-3). Resultados Houve diferença estatisticamente significante entre os grupos com relação às microcalcificações e à atividade secretora, com maior prevalência nos grupos tratados com BE. Não houve diferença entre os grupos quanto à atrofia, mas houve maior prevalência de atrofia nos grupos que receberam T versus os que receberam BE+ T. Houve diferença entre os grupos quanto ao ANCP (p= 0,028), com maior expressão no grupo BE+ T 300 mcg/dia. Com relação à caspase-3, não houve diferença entre os grupos, mas, no grupo BE+ T 300 mcg/dia, a expressão foi maior do que no grupo de T isolada. Conclusão A T isolada não apresentou efeito proliferativo do tecido mamário, contrariamente ao EB. A T em associação ao EB pode diminuir ou não a proliferação, a depender da dose de T.

Testosterone and Voluntary Exercise, Alone or Together Increase Cardiac Activation of AKT and ERK1/2 in Diabetic Rats / Testosterona e Exercício Voluntário, Individualmente ou em Conjunto, Aumentam a Ativação Cardíaca de AKT e ERK1/2 em Ratos Diabéticos

Abstract Background: Impaired angiogenesis in cardiac tissue is a major complication of diabetes. Protein kinase B (AKT) and extracellular signal regulated kinase (ERK) signaling pathways play important role during capillary-like network formation in angiogenesis process. Objectives: To determine the effects of testosterone and voluntary exercise on levels of vascularity, phosphorylated Akt (P- AKT) and phosphorylated ERK (P-ERK) in heart tissue of diabetic and castrated diabetic rats. Methods: Type I diabetes was induced by i.p injection of 50 mg/kg of streptozotocin in animals. After 42 days of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, heart tissue samples were collected and used for histological evaluation and determination of P-AKT and P-ERK levels by ELISA method. Results: Our results showed that either testosterone or exercise increased capillarity, P-AKT, and P-ERK levels in the heart of diabetic rats. Treatment of diabetic rats with testosterone and exercise had a synergistic effect on capillarity, P-AKT, and P-ERK levels in heart. Furthermore, in the castrated diabetes group, capillarity, P-AKT, and P-ERK levels significantly decreased in the heart, whereas either testosterone treatment or exercise training reversed these effects. Also, simultaneous treatment of castrated diabetic rats with testosterone and exercise had an additive effect on P-AKT and P-ERK levels. Conclusion: Our findings suggest that testosterone and exercise alone or together can increase angiogenesis in the heart of diabetic and castrated diabetic rats. The proangiogenesis effects of testosterone and exercise are associated with the enhanced activation of AKT and ERK1/2 in heart tissue.

Resumo Fundamento: Angiogênese prejudicada em tecido cardíaco é uma das principais complicações das diabetes. As vias de sinalização da proteína-quinase B (AKT) e a quinase regulada por sinal extracelular (ERK) exercem um importante papel durante a formação de uma rede similar à capilar no processo de angiogênese. Objetivos: Determinar os efeitos da testosterona e exercícios voluntários sobre os níveis de vascularidade, AKT fosforilada (P- AKT) e ERK fosforilada (P-ERK) sobre o tecido cardíaco de ratos diabéticos e castrados diabéticos. Métodos: A diabetes tipo 1 foi induzida através de injeção intraperitoneal de 50 mg/kg de estreptozotocina em animais. Após 42 dias de tratamento com testosterona (2mg/kg/dia) ou exercícios voluntários, individualmente ou em conjunto, as amostras de tecidos cardíacos foram coletadas e usadas para avaliação histológica e determinação de níveis de P-AKT e P-ERK através do método ELISA. Resultados: Os nossos resultados mostraram que a testosterona ou os exercícios aumentaram a capilaridade, os níveis de P-AKT, e P-ERK nos corações de ratos diabéticos. O tratamento de ratos diabéticos com testosterona e exercícios obteve um efeito sinérgico sobre a capilaridade, níveis de P-AKT, e P-ERK no coração. Além disto, na capilaridade do grupo diabético castrado, os níveis de P-AKT e P-ERK diminuíram significativamente no coração, ao passo que o tratamento com testosterona ou o treinamento com exercícios reverteu tais efeitos. O tratamento simultâneo de ratos diabéticos castrados com testosterona e exercícios obteve um efeito aditivo sobre os níveis de P-AKT e P-ERK. Conclusão: Nossas descobertas sugerem que a testosterona e exercícios, em conjunto ou individualmente, podem aumentar a angiogênese nos corações de ratos diabéticos e castrados diabéticos. Os efeitos favoráveis à angiogênese da testosterona e dos exercícios estão associados à ativação reforçada de AKT e ERK1/2 no tecido cardíaco.

Effect of metformin on semen quality

ABSTRACT Various studies have linked metformin, a universally antidiabetic drug, with semen quality; however, such a direct link has not been established. This review systematically addresses and summarizes the effect of metformin on semen quality, particularly sperm function. We searched the MEDLINE electronic database for English articles and abstracts containing the key words 'metformin' and 'sperm', and relevant articles were reviewed. In summary, metformin appears to have improved and provided positive impact on sperm quality. This effect may be due to the ability of metformin to reduce oxidative stress and lipid peroxidation, enhance 5'-AMP activated protein kinase activity, and restore the normal levels of pituitary-gonadal hormones. However, further clinical research is still necessary to confirm such effect.

Os processos de hormonização e a produção do cuidado em saúde na transexualidade masculina / The hormonization process and the production of health care in male transexuality / Los procesos de hormonización y la producción del cuidado sanitario en la transexualidad masculina

Resumo O texto tem como proposta refletir sobre os usos do hormônio testosterona entre os homens transexuais, tendo como ponto central a relação com o cuidado em saúde. O objetivo é entender, a partir do uso de fármacos a base de testosterona, como eles transversalizam, interagem e reiteram os processos de construção do que se designa transexual masculino, suas diferentes experiências e narrativas e a relação com o cuidado em saúde, seja no âmbito do serviço de referência no atendimento aos transexuais, seja nas experiências em outros serviços privados, e/ou nas vivências cotidianas experimentadas pelos homens transexuais em diferentes espaços sociais. As discussões são baseadas em seis relatos de homens transexuais na cidade do Rio de Janeiro.

Abstract This paper discusses the uses of testosterone among transsexual men and its relation to healthcare. It addresses how the use of testosterone-based drugs crisscross, interact and reiterate the processes of construction of the subjects designated as transsexual men. It analyses trans men's experiences and narratives, as well as their view of healthcare, both in trans-specific healthcare clinics and in everyday experiences in other social realms. The discussion is based on interviews with six transsexual men in the city of Rio de Janeiro.

Resumen Este artículo se propone reflexionar sobre el uso de la hormona testosterona entre hombres transexuales, teniendo como punto central la relación con el cuidado sanitario. Tiene como objetivo entender, a partir del uso de fármacos a base de testosterona, cómo éstos transversalizan, interactúan y reiteran los procesos de construcción de lo que se designa como transexual masculino, sus diversas experiencias y narrativas, así como su relación con el cuidado sanitario, sea en el ámbito del servicio específico de referencia de atención a transexuales, sea en las experiencias en otros servicios privados, y /o en las vivencias cotidianas experimentadas por hombres transexuales en diferentes espacios sociales. Las discusiones se basan en seis relatos de hombres transexuales en la ciudad de Río de Janeiro.

Family care of people with severe mental disorders: an integrative review / Cuidado familiar de pessoas com doenças mentais graves: uma revisão integrativa / Cuidado familiar de la persona con trastorno mental grave: una revisión integradora

OBJECTIVE: to analyze the scientific literature on home-based family care of people with severe mental illness. METHOD: integrative review of 14 databases (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI COnNECT, LILACS, PsycINFO, PubMed, SciELO, and Scopus) searched with the key words "family caregivers", "severe mental illness", and "home" between 2003 and 2013. RESULTS: of 787 articles retrieved, only 85 met the inclusion criteria. The articles appeared in 61 journals from different areas and disciplines, mainly from nursing (36%). The countries producing the most scientific literature on nursing were Brazil, the UK, and the US, and authorship predominantly belonged to university centers. A total of 54.12% of the studies presented quantitative designs, with descriptive ones standing out. Work overload, subjective perspectives, and resources were the main topics of these papers. CONCLUSIONS: the international scientific literature on home-based, informal family care of people with severe mental disorder is limited. Nursing research stands out in this field. The prevalent topics coincide with the evolution of the mental health system. The expansion of the scientific approach to family care is promoted to create evidence-based guidelines for family caregivers and for the clinical practice of professional caregivers. .

OBJETIVO: analisar a produção científica sobre o cuidado familiar de pessoas com transtorno mental grave em casa. MÉTODO: revisão integrativa de 14 bases de dados (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI Connect, LILACS, PsycInfo e PubMed, SciELO, e Scopus), com as palavras-chave "cuidadores familiares", "TMG" (transtornos mentais graves ) e "casa", realizada entre 2003 e 2013. RESULTADOS: dos 787 artigos retornados, somente 85 atenderam os critérios de inclusão. Os artigos vieram de 61 periódicos de diferentes áreas e disciplinas, principalmente de enfermagem (36%). Os países com maior produção científica sobre enfermagem foram o Brasil, o Reino Unido e os Estados Unidos, e a autoria era predominantemente de centros universitários. Um total de 54,12% dos estudos apresentou delineamento quantitativo, e os descritivos se destacaram. Os principais temas desses trabalhos foram sobrecarga de trabalho, perspectivas subjetivas e recursos. CONCLUSÕES: a produção cientifica internacional sobre o cuidado familiar informal de pessoas com doenças mentais graves em casa é limitada. A pesquisa em enfermagem se destaca nesse campo. Os temas prevalentes coincidem com a evolução do sistema de saúde mental. Estimula-se a expansão da abordagem científica do cuidado familiar de modo a encontrar evidências para criar guias para cuidadores familiares e para a prática clínica de cuidadores profissionais. .

OBJETIVO: analizar la producción científica sobre el cuidado familiar de la persona con trastorno mental grave en el hogar familiar. MÉTODO: revisión integradora en 14 bases de datos (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, IME, ISOC, JBI ConNECT, LILACS, PsycInfo, PubMed, SciELO y Scopus), con las palabras clave "cuidadores familiares", "TMG" y "hogar"; realizada entre 2003 y 2013. RESULTADOS: de 787 artículos recuperados, sólo 85 cumplieron con los criterios de inclusión. Los artículos procedieron de 61 revistas de diferentes áreas y disciplinas destacando la disciplina de enfermería (36%). Los países con mayor producción científica sobre enfermería fueron Brasil, Reino Unido y EEUU. En la autoría predominaron los centros universitarios. El 54,12% de los estudios presentó diseño cuantitativo, sobresaliendo los descriptivos. Las temáticas destacadas fueron sobrecarga, perspectivas subjetivas y recursos. CONCLUSIONES: la producción científica internacional sobre el cuidado informal familiar de la persona con trastorno mental grave, en el contexto del hogar familiar, es limitada. En este campo, destaca la investigación de enfermería. Las temáticas prevalentes coinciden con la evolución del sistema de salud mental. Se estimula la ampliación del abordaje científico del cuidado familiar con el fin de encontrar evidencias para la elaboración de guías de cuidadores familiares y para la práctica clínica de cuidadores profesionales. .

Effect of exogenous testosterone, finasteride, and castration on serum level of thyroxin

The secretion of thyroxin [T4] as the main hormone of thyroid gland is regulated by androgens. The present study aimed to evaluate the effect of testosterone and finasteride administration and castration on serum levels of T4 and to show the effect of this regulation on total body weight, weight of testis, and the weight of prostate. Male adult rats [n = 32] were divided into 4 groups [n = 8]: Group 1 [control], Group 2 [castration], Group 3 [finasteride: 20 mg/kg/day] and Group 4 [testosterone: 5 mg/kg/day]. At the end of the study [35 days], serum level of thyroxin, body weight, weight of testis, and prostate were determined. The data showed that the body weight increased in castrated [P = 0.04] and decreased in testosterone [P = 0.00] groups but did not differ in finasteride [P>0.05] group. There were not any differences in the weight of testis among control, finasteride, and testosterone groups but the weight of prostate increased in testosterone group [P = 0.00] and decreased in castrated [P = 0.03] and finasteride groups [P = 0.04]. In addition, the serum level of T4 [nmo/ml] decreased in the three groups: finasteride [P = 0.03], testosterone [P = 0.04], and castrated [P = 0.00]. Testosterone in both high and low levels decreased the amount of T4 with a time-dependent manner

Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway

The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.

Effects of administering testosterone undecanoate in rats subjected to physical exercise: effects on the estrous cycle, motor behavior and morphology of the liver and kidney / Efeitos da administração de undecanoato de testosterona em ratos submetidos a exercício físico: efeitos sobre o ciclo estral, o comportamento motor e a morfologia do fígado e do rim

The aim of the work was evaluate the effects of testosterone undecanoate (TU) treatment combined with moderate physical training on: the estrous cycle, body weight (BW), motor behavior (MB), and the morphohistology of the reproductive system, the liver and kidney in rats. Female Wistar rats (180 g - 250 g) were divided as follows: sedentary + TU (S + TU), trained + TU (T + TU), sedentary + vehicle (S + V), trained + vehicle (T + V). The rats swam 50 min/Day, strapped with a 5 percent BW load, for 4 weeks. During this training, (BW) was monitored daily as well as the estrous cycle (EC) by vaginal smear. The TU (15 mg/kg s.c) was administered 3 times/week for 4 weeks. At the end of the study, data on MB, BW and morphohistopathological changes in viscera were compiled. The (T + TU) group had on average, a higher (BW) in the fourth week compared to the first week, and (BW) higher than (S + V) and (S + TU) groups. We noted an interruption in the EC and a decrease in weight of ovaries in animals treated with TU. In addition, there was an increase in the relative weight of the heart in groups (T + V) and (T+ TU), and kidneys in group (T + TU). Histopathological analysis showed periportal congestion and isolated foci of hepatic necrosis in rats with TU. Thus, TU combined with training abolished the EC, promoted ovarian atrophy, liver necrosis, cardiac hypertrophy and a decrease in motor activity.

O objetivo do trabalho foi avaliar o efeito do tratamento com undecanoato de testosterona (UT) combinado ao treinamento físico moderado sobre ciclo estral, peso corporal, estruturas do sistema reprodutor, comportamento motor e morfologia hepática e renal em ratas. Ratas Wistar (180 a 250 g) foram divididas em: sedentárias + UT (S+UT), treinadas + UT (T+UT), sedentárias + veículo (S+V), treinadas + veículo (T+V). As ratas nadaram 50 min/dia com sobrecarga de ~5 por cento do peso corporal por 4 semanas. Durante o período de treinamento foi realizado acompanhamento diário do peso corporal (PC) e do ciclo estral (CE) pelo esfregaço vaginal. O UT (15 mg/kg s.c.) foi administrado 3x/semana durante 4 semanas. Ao final foram avaliados comportamento motor, pesos e alterações histopatológicas de alguns órgãos. O grupo T+UT apresentou PC maior na quarta semana do que na primeira, com pesos corporais maiores que os grupos S+V e S+UT. Houve interrupção no CE e redução do peso dos ovários nos animais tratados com UT. Houve aumento do peso relativo do coração, nos grupos T+V e T+UT, e do peso relativo dos rins, no grupo T+UT. A análise histopatológica revelou congestão periportal e focos isolados de necrose hepática nas ratas com UT. O UT combinado com treinamento produziu supressão do ciclo estral, atrofia ovariana, necrose hepática, hipertrofia cardíaca e redução da atividade motora.

Efeitos dos esteroides anabólicos androgênicos sobre o útero e parâmetros reprodutivos de ratas adultas / Effects of androgenic anabolic steroids on the uterus and reproductive parameters of adult female rats

OBJETIVO: avaliar os efeitos da administração de dois esteroides sintéticos sobre a morfologia do útero e parâmetros reprodutivos de ratas adultas. MÉTODOS: quarenta ratas foram aleatoriamente distribuídas nos grupos experimentais: controle (C; solução fisiológica); tratados com decanoato de nandrolona (DN; 7,5 mg/kg de peso corpóreo); composto de ésteres de testosterona (T; 7,5 mg/kg de peso corpóreo); e, simultaneamente, com DN e T (7,5 mg/kg de peso corpóreo de cada esteroide), em uma única dose/semana, intraperitoneal, durante oito semanas. Cinco fêmeas de cada grupo foram sacrificadas e os cornos uterinos foram coletados, pesados e preparados para avaliação histológica e morfométrica. As ratas restantes foram acasaladas com machos normais para avaliação dos parâmetros reprodutivos, constituindo os grupos tratados durante o período pré-gestacional. Outro grupo de 20 ratas recebeu os tratamentos durante o período gestacional (7º-14º dias). Foi aplicada a análise de variância não paramétrica de Kruskal-Wallis, complementada com o teste de Dunn ou de Student-Newman-Kleus para análise dos dados (5 por cento de significância). RESULTADOS: houve aumento significativo no peso corpóreo das fêmeas androgenizadas (DN: 305±50; T: 280±35; DN+T: 275±30 versus C: 255±22 g) (p<0,05). O peso uterino não foi afetado pelos tratamentos esteroidais (DN: 0,6±0,2; T: 0,4±0,04; DN+T: 0,7±0,1 versus C: 0,4±0,09 g). Todas as fêmeas androgenizadas apresentaram aciclicidade estral e endométrio caracterizado pelo revestimento luminal papilífero, estroma edematoso com áreas hemorrágicas e atividade secretora. Houve alterações nos parâmetros morfométricos de espessura do epitélio luminal, miométrio e perimétrio, em função do grupo androgenizado. Nenhuma rata exibiu prenhez quando tratada com os esteroides no período pré-gestacional, e o tratamento durante a organogênese afetou negativamente os parâmetros reprodutivos. CONCLUSÕES: os agentes esteroidais alteram ...

PURPOSE: to evaluate the effects of the administration of two synthetic steroids in the uterus morphology and in the reproductive parameters of adult female rats. METHODS: divided into four experimental groups: control (C; physiological solution); treated with nandrolone decanoate (DN; 7.5 mg/kg of body weight); with a testosterone esters compound (T; 7.5 mg/kg); and simultaneously with DN and T (7.5 mg/kg of each steroid), in a single intraperitoneal weekly dose, for eight weeks. Five females of each group were sacrificed and the uterine horns were collected, weighted and prepared for histological and morphometrical evaluation. The remaining rats were mated with normal male rats for reproductive parameters evaluation, composing the groups treated during the pre-gestational period. Another group of 20 female rats were treated during the gestational period (7th-14th days). For data analysis, the Kruskal-Wallis non-parametric variance analysis was used, followed by the test of Dunn or of Student-Newman-Keus (5 percent significance level). RESULTS: there was a significant body weight increase in the androgenized females (ND: 305±50; T: 280±35; ND+T: 275±30 versus C: 255±22 g; p<0.05). Uterine weight was not affected by the steroidal treatment (ND: 0.6±0.2; T: 0.4±0.04; ND+T: 0.7±0.1 versus C: 0.4±0.09 g). All the androgenized females presented estral acyclicity and endometrium characterized by papilliferous luminal lining, oedematous stroma with hemorrhagic areas and secretory activity. There were changes in the morphometrical thickness parameters of the luminal epithelium, myometrium and perimetrium in the androgenized groups. None of the female rats got pregnant when treated with steroids in the pre-gestational period and the treatment during organogenesis affected negatively the reproductive parameters. CONCLUSIONS: steroidal agents alter the uterine structure and impair fertility and gestational outcome in female rats.

In vitro effects of steroid hormones on arylalkylamine N-acetyltransferase (AA-NAT) activity in the pineal of fish, Clarias gariepinus (Burchell, 1822) during different phases of breeding cycle.

In vitro effects of gonadal hormones (testosterone, 17beta-estradiol estriol and estrone) and corticosteroid hormones (corticosterone and cortisol) were studied on arylalklyamine N-acetyltransferase (AA-NAT) activity in the pineal organ of the fish, C. gariepinus during quiescent, progressive, breeding and regressive phases of its annual breeding cycle. The pineals were collected under dim red light, maintained in organ culture for 7 hr and incubated with three concentrations (10(-6), 10(-5) and 10(-4) M) of hormones for 6 hr. The treatments with gonadal hormones and corticosteroid hormones inhibited pineal AA-NAT activity in a dose-dependent manner during all the phases of the breeding cycle. AA-NAT activity was comparatively more sensitive to the inhibitory effects of the gonadal hormones during the regressive phase and less sensitive during the quiescent phase. Further, the enzyme activity was more sensitive to the inhibitory effects of corticosteroid hormones (corticosterone and cortisol) during the breeding phase and less sensitive during the quiescent phase. These findings seem to suggest that gonadal hormones and corticosteroid hormones have direct inhibitory influence on AA-NAT activity and, hence melatonin synthesis in the photoreceptive pineal organ of C. gariepinus.

Prenatal testosterone treatment alters LH and testosterone responsiveness to GnRH agonist in male sheep

Although evidence is accumulating that prenatal testosterone (T) compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 µg/kg), as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC) of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01). The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05). AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05). Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring.

Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

Phospholipid hydroperoxide glutathione peroxidase(PHGPx), an antioxidative selenoprotein, is modulated byestrogen in the testis and oviduct. To examine whetherpotential endocrine disrupting chemicals (EDCs) affectthe microenvironment of the testes, the expression patternsof PHGPx mRNA and histological changes were analyzedin 5-week-old Sprague-Dawley male rats exposed to severalEDCs such as an androgenic compound [testosterone (50,200, and 1,000microg/kg)], anti-androgenic compounds [flutamide(1, 5, and 25mg/kg), ketoconazole (0.2 and 1mg/kg), anddiethylhexyl phthalate (10, 50, and 250mg/kg)], andestrogenic compounds [nonylphenol (10, 50, 100, and 250mg/kg), octylphenol (10, 50, and 250mg/kg), and diethyl-stilbestrol (10, 20, and 40microg/kg)] daily for 3 weeks via oraladministration. Mild proliferation of germ cells andhyperplasia of interstitial cells were observed in the testesof the flutamide-treated group and deletion of thegerminal epithelium and sloughing of germ cells wereobserved in testes of the diethylstilbestrol-treated group.Treatment with testosterone was shown to slightly decreasePHGPx mRNA levels in testes by the reverse transcription-polymerase chain reaction. However, anti-androgeniccompounds (flutamide, ketoconazole, and diethylhexylphthalate) and estrogenic compounds (nonylphenol,octylphenol, and diethylstilbestrol) significantly up-regulated PHGPx mRNA in the testes (p<0.05). Thesefindings indicate that the EDCs might have a detrimentaleffect on spermatogenesis via abnormal enhancement ofPHGPx expression in testes and that PHGPx is useful as abiomarker for toxicity screening of estrogenic or anti-androgenic EDCs in testes.

Effect of testosterone on skeletal muscle of young and old male rats

The effects of testosterone on skeletal muscle were assessed in adult male Wistar rats aged 80 days and 1 year. The animals were divided into 4 groups: young testosterone (YT), old testosterone (OT), young control (YC), and old control (OC) groups. The YT and OT groups received 15 applications of testosterone cypionate (5 mg/kg) on alternate days and the controls received injections containing sterile oil alone. After 30 days the animals were sacrificed and the soleus (SOL) and extensor digitorum longus (EDL) muscles were analyzed using mATPase histochemistry. After treatment, YT group gained less body weight than YC group and OT group decreased body weight, differently from the body weight gain observed in the OC group. Testosterone treatment did not show significant changes in both relative muscle weight and muscle fiber composition profile. However, in the YT group we observed an increase in the cross-sectional area of type I fibers in the SOL muscle, and type I and IIAD fibers in the EDL muscle. In the OT group, the cross sectional area of type I was decreased in the EDL muscle. These results reveal that testosterone did not cause a shift in muscle fiber type, but the cross-sectional area had fiber type-specific changes.

La testosterona inhibe las respuestas contráctiles del agonista adrenérgico alpha1, fenilefrina, asociadas con la liberación de calcio intracelular en la aorta de rata / Testosterone inhibits the contractile responses to phenylephrine associated with the release of intracellular calcium in rat aorta

Utilizando segmentos de aorta de rata sin endotelio inmersos en solución sin Ca2+, evaluamos la capacidad de la testosterona para modificar el efecto contráctil del agonista adrenérgico fenilefrina, así como el incremento en el tono de reposo (ITR) asociado con la entrada capacitativa de calcio por el sarcoplasma. La testosterona [10-5–10- 4 M] inhibió significativamente la contracción activada por la fenilefrina [10-6 M] y el ITR. Estos efectos no fueron modificados con cicloheximida [10-5 M] (inhibidor de la síntesis protéica), flutamida [10-5 M] (antagonista de receptores androgénicos), o aminoglutetimida [10-5 M] (inhibidor de la citocromo P450 aromatasa). La testosterona también inhibió las respuestas contráctiles de la serotonina [10-5 M], pero no de la cafeína [10-2 M]. Además, la testosterona inhibió las contracciones del ácido ciclopiazónico [10-6 M] y de la ryanodina [10- 5 M] asociadas con el ingreso capacitativo de Ca2+ mediante canales de Ca2+ tipo no L. Estos datos sugieren que la testosterona interfiere con la vía de transducción de los receptores acoplados a proteínas Gq- 11, e inhibe la entrada capacitativa de Ca2+ a través de canales de Ca2+ tipo L y tipo no L; los efectos son no genómicos, independientes de receptores androgénicos, y de la conversión testosterona en estrógenos.

Using endothelium-denuded rat aortic rings incubated in Ca2+ -free solution, we assessed the ability of testosterone to influence the contractile effect of phenylephrine, and the increase in resting tone (IRT) associated with Ca2+ ability to cross the plasma membrane. The addition of testosterone [10(-5)-10(-4) 5 min before phenylephrine [10(-6) M], inhibited both phenylephrine-induced contraction and IRT. These changes were not affected by cycloheximide (10(-5) M; a protein synthesis inhibitor of), flutamide (10(-5) M; an androgenic receptor antagonist), or by adding aminoglutethimide (10(-5) M; an aromatase inhibitor). Testosterone also blocked the contractile response to serotonin [10(-5) M] but not to caffeine [10(-2) M]. On the other hand, testosterone inhibited the contractile responses to cyclopiazonic acid (10(-6) M; a selective Ca2+ -ATPase inhibitor) or ryanodine (10(-5 M; an activator of sarcoplasmic reticulum Ca2+ -release channels) associated with capacitative Ca2+ influx through non-L-type Ca2+ channels. These data suggest that by acting on the cellular membrane, testosterone interferes with the signal transduction pathway of G(q-11) protein-coupled receptors, and inhibits capacitative Ca2+ influx through both L-type and non-L-type Ca2+ channels. These effects are non-genomic, non-mediated by the intracellular androgen receptor, and not due to the conversion of testosterone to estrogens.