Consideraciones en el manejo del adulto con Hiperplasia Suprarrenal congénita clásica por déficit de 21-Hidroxilasa / Management considerations for the adult with congenital adrenal hyperplasia due 21-hydroxylase deficiency

La Hiperplasia Suprarrenal Congénita (HSRC) corresponde a un grupo de defectos genéticos en la síntesis de cortisol. El 95% de ellas son debidas al déficit de 21-hidroxilasa por lo que nos referiremos solo a esta deficiencia. La hiperplasia suprarrenal congénita clásica (HSRC-C) debuta en recién nacidos o lactantes con insuficiencia suprarrenal primaria, diferentes grados de hiperandrogenismo clínico en mujeres y puede coexistir con hipotensión, hiperkalemia e hiponatremia si hay un déficit clínico de aldosterona. El objetivo de este artículo es actualizar el conocimiento y enfoques sugeridos para el manejo de la HSRC-C desde el inicio de sus controles en la etapa adulta. El diagnóstico diferencial en retrospectiva de la HSRC-C y la no clásica (HSRC-NC) a veces resulta difícil ya que esta enfermedad es un espectro fenotípico continuo. La insuficiencia suprarrenal y la dependencia a terapia corticoidal son los eventos principales para diferenciar estas dos patologías que tienen enfoques terapéuticos diferentes. El tratamiento de la HSRC-C en adultos abarca 2 objetivos primarios: la adecuada sustitución de la falla suprarrenal y el control de hiperandrogenismo mediante el uso de corticoides en sus dosis mínimas efectivas. En la mujer existen terapias complementarias para el control del hiperandrogenismo como anticonceptivos y otras que se encuentran en diferentes fases de investigación. Esto permite disminuir las dosis de corticoides en algunos casos. Es importante a la vez abordar tres objetivos secundarios: controlar el riesgo cardiometabólico propio de la enfermedad, evitar el sobre tratamiento corticoidal y manejar la infertilidad. La correcta monitorización del tratamiento en adultos tomando en cuenta los objetivos descritos permite una mejor calidad de vida en estos pacientes. Finalmente el consejo genético debe realizarse en todos los pacientes con HSRC que deseen fertilidad y en sus parejas. El estudio requiere de secuenciación del gen CYP21A2 y debe realizarse en un laboratorio de experiencia.

Congenital Adrenal Hyperplasia (CAH) are a group of genetic defects characterized by impaired cortisol synthesis. 95% of them are due to 21-hydroxylase deficiency. We will discuss only this enzyme's deficiency. Classic congenital adrenal hyperplasia (CAH-C) debuts in newborns or infants with primary adrenal insufficiency, some degree of clinical hyperandrogenism in newborn females, and can coexist with hypotension, hyperkalemia, and hyponatremia if there is a clinical aldosterone deficiency. The objective of this article is to update the knowledge and suggested approaches for the management of CAH-C from the beginning of its controls in the adult stage. The retrospective differential diagnosis of CAH-C and non-classical (CAH-NC) is sometimes difficult because this disease is a continuous phenotypic spectrum. Adrenal insufficiency and dependence on corticosteroid therapy are the main events to differentiate these two pathologies that have different therapeutic approaches. In adults, the treatment of CAH-C must include 2 primary objectives: adequate the replacement of adrenal failure and control of hyperandrogenism, through the use of corticosteroids in their minimum effective doses. In women there are complementary therapies for the control of hyperandrogenism, such as contraceptives and others that are in different phases of research. This makes it possible to reduce the doses of corticosteroids in some cases. It is important at the same time to address three secondary objectives: control the cardiometabolic risk of the disease secondary to corticosteroid treatment, avoid corticosteroid overtreatment and manage infertility. The correct monitoring of treatment in adults and taking in to account the objectives described, allows a better quality of life in these patients. Finally, genetic counseling must be carried out in all patients planning for children, with any type of CAH and in their partners. The study requires sequencing of the CYP21A2 gene and must be performed in a certified laboratory.

Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer: a real-world retrospective study / 亚洲男科学杂志(英文版)

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.

Preparation and physicochemical characterization of prazosin conjugated PLGA nanoparticles for drug delivery of flutamide

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using Poly(D,L-lactide-co-glycolide) (PLGA) decorated bypoly(ethylene glycol) (PEG) grafted prazosin (PLGA-PEG-Praz) as a targeting moiety. In a multi-step reaction, PLGA was linked to PEG and prazosin. The structure of the synthesized polymers was confirmed by FTIR and 1H-NMR. Flutamide-loaded nanoparticles were prepared by quasi-emulsion solvent diffusion technique. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency, and release properties. Also, the physicochemical properties of the nanoparticles were analyzed using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry, and Powder X-Ray Diffractometry (XRD). The particle size of nanoparticles was ranged between 191 and 249 nm. Loading efficiency of nanoparticles was about 43%-69%. Results showed a steady release rate for nanoparticles compared to that of a pure drug powder. SEM characterization confirmed that particles were in nanosize range. DSC and XRPD results verified a decrease in drug crystallinity in the prepared formulations. In conclusion, the results of this study showed that PLGA-PEG-Praz nanoparticles could be a good choice to improve the physicochemical properties of the drug and these formulations can increase Flutamide efficacy.

Protective effect of morin against flutamide-induced hepatotoxicity in mal wister rats

Aim of the work: The aim of this work was to investigate the protective role of morin against the hepatotoxic effect of flutamide [FLU] that is widely used drug for treatment of metastatic prostate adenocarcinoma. Administration of FLU to male rats in a dose of 100 mg/ kg b.w. daily for 4 weeks resulted in serious hepatic injury

Materials and Methods: Male Wistar rats were equally divided into six experimental groups [n = 10]: Group I [control group] received appropriate vehicle [carboxy methyl cellulose, CMC] for 8 weeks, Group II [CM group] received CMC for 4 weeks then morin for another 4 weeks, Group III [ M group] were treated with morin for 8 weeks, Group IV [CF group] received CMC for 4 weeks then FLU for another 4 weeks, Group V [CMF group] received CMC for 4 weeks then morin for another 4 weeks then received morin associated with FLU for additional4 weeks and Group VI [MMF group] was pretreated with morin for 4 weeks then treated with morin simultaneously with FLU for additional 4 weeks

Results: In FLU treated rats, highly significant increases in each of serum ALT, AST, direct and total bilirubin as well as hepatic MDA were observed relative to the control group. Moreover, highly significant decrease in hepatic SOD, GSH and GST activities were observed. On the other hand, administration of morin with FLU resulted in mild and marked reduction in the elevated serum ALT, AST, direct and total bilirubin and hepatic MDA levels induced by FLU intoxication, respectively [regardingco-treatment and pretreatment with FLU]

Conclusion: These data showed protective effect of morin against FLU-induced hepatic damage, especially when administered prior to and concomitantly with FLU

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 metformin and flutamide on anthropometric indices and laboratory tests in obese/overweight PCOS women under hypocaloric diet

This study was designed to investigate the effect of metformin and flutamide alone or in combination with anthropometric indices and laboratory tests of obese/overweight PCOS women under hypocaloric diet. This single blind clinical trial was performed on 120 PCOS women. At the beginning, hypocaloric diet was recommended for the patients. After one month while they were on the diet, the patients were randomly divided in 4 groups; metformin [500 mg, 3/day], flutamide [250 mg, 2/day], combined, metformin [500 mg, 3/day] with flutamide [250 mg, 2/day] and finally placebo group. The patients were treated for 6 months. Anthropometric indices and laboratory tests [fasting and glucose-stimulated insulin levels, lipid profile and androgens] were measured. A one-way ANOVA [Post Hoc] and paired t-test were performed to analyze data. A p

Expression of insulin-like factor 3 in the testis of flutamide-induced cryptorchidism mice and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the changes in the mRNA expression of insulin-like factor 3 (INSL-3) in the testis of mouse models of flutamide-induced cryptorchidism.</p><p><b>METHODS</b>We randomized pregnant BALB/c mice to groups A (control) , B, C, D and E to receive continuous gavage of flutamide at 0, 150, 300, 500 and 700 mg/kg body weight, respectively, from gestation day 12 to 21. We detected the expression of INSL-3 mRNA in the testis of the neonates by real-time PCR at 4 and 8 postnatal weeks.</p><p><b>RESULTS</b>No cryptorchidism was found in group A; unilateral cryptorchidism was seen in groups B (10.0%) and C (25.0%); and bilateral cryptorchidism was observed in groups D (21.1%) and E (40.0%). The expression of INSL-3 mRNA was reduced with the increased dose of flutamide, not significantly changed in groups B and C (P > 0.05) but remarkably decreased in D and E as compared with A (P < 0.05).</p><p><b>CONCLUSION</b>Administration of flutamide to pregnant mice can induce unilateral cryptorchidism at 150 and 300 mg/kg and bilateral cryptorchidism at 500 and 700 mg/kg in their male offspring, which may be related with its reducing effect on the expression of INSL-3 in the testis of the mice.</p>

effect of flutamide on ovulation induction in PCOS patients

Polycystic ovary syndrome [PCOS] is a disorder that affects various body organs and requires comprehensive long term evaluation and management. The aim of this study was to evaluate effect of Flutamide on ovulation induction in PCOS patients. This prospective study applied triple blind method, a simple convenience sampling method, to induce ovulations of the ninety six PCOS patients. Patients were divided into two groups; group A included 53 subjects [received Flutamide + Clomiphene Citrate] and group B included 43 subjects [received placebo + Clomiphene Citrate]. Ultrasound was carried to determine the size of follicles and growth rate of them during follicular phase of the menstrual cycle. Also, progesterone levels were measured on days 19 and 21 of the menstrual cycle. In this study, ninety six PCOS patients, in two treatment and control groups, were evaluated regarding to body mass index [BMI], cycle irregularity, age and number of dominant follicles, duration of stimulation, endocrine profile and score of hirsutism. The obtained results revealed no significant differences between two groups. Flutamide does not affect ovulation improvement in PCOS patients undergoing induction

Improvement of lower urinary tract symptoms in patients with prostate cancer treated with maximal androgen blockade / 中南大学学报(医学版)

OBJECTIVE@#To investigate the timing of reaching maximum improvement of the lower urinary tract symptoms (LUTS) in patients with advanced prostate cancer treated with maximal androgen blockade(MAB), and to provide guidelines for the treatment program.@*METHODS@#We collected the data of 45 advanced prostate cancer patients complicated with lower urinary tract symptoms who were treated by MAB. The international prostate symptom score (IPSS) and maximum urinary flow rate (Qmax) were selected as indicators reflecting the degree of lower urinary tract symptoms and were observed before the MAB, 3, 6, and 9 months after the patients received MAB. We also observed the changes of prostate volume and analyzed the role of MAB in improving LUTS in patients with prostate cancer.@*RESULTS@#The IPSS and Qmax had significant difference between the 3rd month after the patients received MAB and before the MAB (P0.05). The prostate volume had significant difference in the 3rd month and the 6th month (P0.05).@*CONCLUSION@#MAB for patients with advanced prostate cancer can improve their lower urinary tract symptoms, whose main effect is presented in the 3rd months after the androgen deprivation therapy.

Establishment of a rat model of flutamide-induced cryptorchidism with remaining gonocytes / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effects of flutamide (Flu) on the development of testicular germocytes in SD rats, and to establish a rat model for further researches on the maldevelopment of cryptorchidism gonocytes (Go).</p><p><b>METHODS</b>Pregnant SD rats were subcutaneously injected with Flu from gestational day (GD) 12 to 21 to establish a model of cryptorchidism. The testes of the newborns were harvested on postnatal day (PD) 1, 10, 20 and 80 for observation of their morphological and histological changes by HE staining and detection of the expression of neural cell adhesion molecules (NCAM) by immunohistochemistry and RT-PCR.</p><p><b>RESULTS</b>Flu induced 43.9% (29/66) of cryptorchidism in the exposed rats. Significant differences were found in the testicular weight and organ coefficient between the Flu and the control groups on PD 20 and 80. Gos remained in the center of seminiferous tubules of the Flu-induced testis on PD 10, and in the center of seminiferous tubules in the cryptorchids' testicular tissues on PD 20 and 80. Immunohistochemistry showed the expression of NCAM on the membrane of the remaining Gos, and RT-PCR revealed significantly up-regulated expression of NCAM mRNA in the Flu-induced testes on PD 10 and 20 as compared with the controls (P < 0.05).</p><p><b>CONCLUSION</b>A rat model of Flu-induced cryptorchidism with remaining Gos was successfully established, which could be used to study the mechanism and management of the maldevelopment of cryptorchidism gonocytes.</p>

Tratamento hormonal da acne baseado em evidências / Hormonal treatment of acne based on evidence

Este trabalho de revisão apresenta o tratamento hormonal da acne baseado em evidências. O trabalho resume a clínica, a classificação, a fisiopatologia e a etiologia da acne. A avaliação de estudos selecionados mostrou que o tratamento hormonal da acne deve ser complementado por tratamento cosmiátrico, e não está indicado para gestantes ou mulheres com planos de engravidar. A primeira escolha para esse tratamento são os contraceptivos hormonais orais, pois são efetivos e seguros para tratamento da acne e também para anticoncepção. Após tempo estabelecido, se o resultado for insatisfatório, outro medicamento, como acetato de ciproterona ou espironolactona, deve ser adicionado. A finasterida é o medicamento indicado para acne de origem idiopática, e a flutamida apresenta efeitos colaterais significativos, não constituindo indicação segura até o momento.

This review shows the hormonal treatment of acne. The review summarizes the clinical aspects, classification, physiopathology and etiology of the acne. The evaluation of selected papers showed that hormonal treatment of acne with hormones has to be complemented by esthetics treatment and is not prescribed for pregnant women or those who want to get pregnant. The first choice of treatment is the hormonal oral contraceptive one, because it is effective and safe for treatment of acne and also for contraception. After an established period with unsatisfactory results, other medicines, such as ciproterone acetate or spironolactone, can be added. The finasteride is prescribed for idiopathic acne and flutamide has many relevant side effects and is also not safe.

Tratamento hormonal do hirsutismo baseado em evidências / Evidence-based hormonal treatment of hirsutism

A revisão de estudos baseados em evidências mostra o melhor tratamento hormonal para o hirsutismo. Inicialmente, resumiu-se a fisiologia do pelo, caracterizou-se o hirsutismo, suas variantes e suas causas. Revelou-se que o tratamento hormonal do hirsutismo deve ser complementado pelo tratamento cosmético e não deve ser indicado para mulheres grávidas ou que desejam engravidar. A primeira opção é o contraceptivo hormonal oral, seguro para contracepção e eficaz para tratamento do hirsutismo. Após tempo estipulado, não ocorrendo resposta satisfatória, associar acetato de ciproterona ou espironolactona. A finasterida é indicada para hirsutismo idiopático e a flutamida, devido aos efeitos colaterais, ainda não é opção segura

An evidence-based review shows the best hormonal treatment of hirsutism. This paper summarized the physiology of the hair, characterized the hirsutism, its variants and etiologies. The study revealed that hormonal treatment of hirsutism has to be complemented by esthetic treatment, and it is not recommended for pregnant women or for those who want to get pregnant. The first option is hormonal oral contraceptive, which is safe for contraception and effective for treatment of hirsutism. After a established period of treatment, if good results do not occur, the association of cyproterone or spironolactone is recomended. Finasteride is the treatment of idiopathic hirsutism, and flutamide is not a safe option due to its side effects

Bicalutamide-induced Interstitial Lung Disease / 결핵및호흡기질환

Androgen deprivation therapy, which is the standard treatment for metastatic prostate cancer, includes nonsteroidal antiandrogenic drugs, such as flutamide, nilutamide and bicalutamide. Of them, bicalutamide rarely induces interstitial pneumonia. We report a case of bicalutamide-induced interstitial pneumonia. A 68-year old male diagnosed with prostate cancer and multiple bone metastases presented with dry cough and low grade fever for 3 days. He had taken bicalutamide (50 mg/day) for 13 months. High resolution computed tomography revealed ground glass opacity in his right upper lung. The laboratory studies showed no eosinophilia in the serum and bronchoalveolar lavage fluid. Despite the use of antimicrobial agents for 2 weeks, the extent of the lung lesions increased to the left upper and right lower lung. He had no environmental exposure, collagen vascular disease and microbiological causes. Under the suspicion of bicalutamide-induced interstitial pneumonia, bicalutamide was stopped and prednisolone (1 mg/kg/day) was initiated. The symptoms and radiologic abnormalities were resolved with residual minimal fibrosis.

Hepatitis colestásica inducida por flutamida. Presentación de un caso / Cholestatic hepatitis induced by flutamida. Presentation of a case

La flutamida es un antiandrógeno no esteroideo, utilizado como terapia a largo plazo para el cáncer de próstata. Entre los efectos secundarios se incluye toxicidad hepática, la cual es muy rara vez reportada. Se presenta el caso de un adulto de 71 años con cáncer de próstata que desarrolla episodio de hepatitis colestásica durante tratamiento con flutamida. Luego de suspender la flutamida el paciente recupera progresivamente su función hepática, pero presenta recurrencia más severa al reiniciar la droga.No se justifica el reinicio del tratamiento luego de un primer episodio de hepatitis tóxica y es necesario tener en cuenta la toxicidad hepática del fármaco, cuando se decide indicarlo como tratamiento.

Flutamide is a nonsteroidal antiandrogen, used like therapy a long term for the prostate cancer. Between the indirects effects the hepatic toxicity is included, which is very rarely reported. The case of an adult of 71 years old with prostate cancer appears that develops episode of cholestatic hepatitis during treatment with flutamide. After to suspend flutamide the patient it recovers progressively his hepatic function, but he presented a recurrence more severely upon reintroduction of the drug.The resumption of the treatment after a first episode of toxic hepatitis is not justified and is necessary to consider the hepatic toxicity of the drug, when it is decided to indicate it like treatment.

Actividad inducida por androsterona y hemisuccinato de androsterona sobre la presión de perfusión y la resistencia vascular / Activity induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance

Introducción. Existen pocos datos sobre los efectos de la androsterona y sus derivados a nivel cardiovascular. Además, el mecanismo molecular de estos andrógenos y su sitio de acción celular son poco claros. Objetivo. Evaluar el efecto inducido por la androsterona y el hemisuccinato de androsterona sobre la presión de perfusión y la resistencia vascular. Materiales y métodos. Los efectos de la androsterona y del derivado de androsterona sobre la presión de perfusión y la resistencia vascular fueron evaluados en un modelo de corazón aislado de rata (Langendorff). Resultados. Los resultados mostraron que: 1) el hemisuccinato de androsterona [10-9 M] incrementa la presión de perfusión y la resistencia vascular en comparación con la androsterona [10-9 M]; 2) los efectos del derivado de androsterona [10-9 M-10-5 M] sobre la presión de perfusión no fueron inhibidos por indometacina [10-6 M]; 3) la nifedipina [10-6M] bloquea los efectos ejercidos por el hemisuccinato de androsterona [10-9 M-10-5 M] sobre la presión de perfusión, y 4) el efecto del derivado de androsterona [10-9 M-10-5 M] sobre la presión de perfusión en presencia de flutamida [10-6 M] fue inhibido. Conclusiones. Los efectos inducidos por androsterona y hemisuccinato de androsterona sobre la presión de perfusión y la resistencia vascular pueden depender de su estructura química. En el caso de la actividad ejercida por el análogo de androsterona, podría involucrar la interacción del esteroide-receptor androgénico e, indirectamente, la activación del canal de calcio y, consecuentemente, inducir variaciones en la presión de perfusión.

Introduction. Few data exist with respect to the effects of androsterone and their derivatives at cardiovascular level. In addition, the molecular mechanisms and cellular site of action of these androgens are still unclear. Objective. An evaluation was conducted on the effects induced by androsterone and hemisuccinate of androsterone on perfusion pressure and vascular resistance. Materials and methods. The effects of both androsterone and hemisuccinate of androsterone on the perfusion pressure and vascular resistance in isolated rat hearts (Langendorff model) were evaluated. Results. The results showed that: (1) the hemisuccinate of androsterone [10-9 M] increases the perfusion pressure and vascular resistance in comparison with the androsterone [10-9 M]; (2) the effect of androsterone-derivative [10-9 M-10-5 M] on perfusion pressure not was inhibited by indometacin [10-6 M]; (3) nifedipine [10-6 M] blocks the effects exerted by hemisuccinate of androsterone [10-9 M-10-5 M] on perfusion pressure; and (4) the effect of androsterone-derivative [10-9 M-10-5 M] on perfusion pressure in presence of flutamide [10-6 M] was inhibited. Conclusions. The effects induced by androsterone and hemisuccinate of androsterone on the perfusion pressure and resistance vascular probably involve the interaction of steroid-receptor androgenic and, indirectly, activation of the calcium channel to induce variations in the perfusion pressure.

Increase in apoptosis and of the stress protein HSP70 in the mouse epididymis produced by the antiandrogen flutamide / El antiandrógeno flutamida produce un aumento de la apoptosis y de la proteína de stress HSP70 en el epidídimo del ratón

The general aim of this paper was to characterize some changes induced by androgen receptors blockage in the epithelial cells of the mouse epididymis. The antiandrogen flutamide was injected (10 mg/Kg b.w.) to adult male mice which were sacrificed 24h. and 72h. after. Controls injected with the vehicle (corn oil) were sacrificed at the same intervals. Cryosections were made of the epididymides and examined by the TUNEL method for quantification of apoptosis and also using immunocytochemistry to visualize the expression of the stress protein HSP70. The highest indexes of apoptosis were observed in the caput epididymis after 72 h. and were of 7.40 cells/1000 in contrast to controls (0.21 cells/1000). HSP70 appeared particularly increased in the caput and cauda epididymis after 72 h. treatment. Results indicated that the blockage of androgen receptors induces apoptosis and a HSP70 expression in the principal epithelial cells of the mouse epididymis, and that these changes occur in a region-specific fashion.

Este trabajo estudia los cambios inducidos por el bloqueador de receptores de andrógeno flutamida en el epitelio del epidídimo del ratón. Varios machos adultos fueron inyectados con flutamida (1Omg/Kg.b.w.) y se sacrificaron a las 24 y 72horas. Otros machos, que sirvieron de controles fueron inyectados sólo con el vehículo empleado para las inyecciones (aceite de maíz) y se sacrificaron a intervalos similares. Los epidídimos tratados y controles fueron examinados mediante el método TÚNEL para cuantificar la apoptosis y mediante procedimientos inmunocitoquímicos para localizar la proteína de stress HSP70. El índice apoptótico más alto fue observado en la cabeza del epidídimo después de 72 horas de tratamiento. HSP70 se observó también a las 72 horas en la cabeza y en la cauda epididimaria. Los resultados indican que el bloqueo de los receptores de andrógenos induce apoptosis y expresión de HSP70 en las células principales del epitelio epididimario, y que estos cambios ocurren afectando a regiones específicas del epidídimo.

Neoadjuvant hormonal deprivation for patients undergoing radical prostatectomy / 亚洲男科学杂志(英文版)

The purpose of this study is to evaluate the therapeutic effect of radical prostatectomy combined with preoperative neoadjuvant hormonal ablation therapy for prostate cancer (PCa). In this study, a total of 31 patients with local PCa underwent radical prostatectomy; of these, 12 patients underwent preoperative hormonal deprivation with a combination of goserelin and flutamide for a period of 5.6 months. Data regarding clinical characteristics were compared between the neoadjuvant therapy and radical prostatectomy groups. A total of 31 patients received pelvic lymph node clearance, and the rate of positive lymph nodes was 12.9% (4/31). Serum prostate-specific antigen (PSA) was 8.9 +/- 1.2 microg L(-1) after the neoadjuvant therapy and 0.4 +/- 0.3 microg L(-1) one month after the radical prostatectomy. There were significant differences in the positive surgical margins, seminal vesicle invasion and lymph node metastasis between the neoadjuvant therapy group (n = 12) and the radical prostatectomy group (n = 19, P < 0.01). The resulsts indicates that preoperative hormonal deprivation induced by goserelin and flutamide can decrease clinical and pathological staging, but assessment of its influence on long-term prognosis requires further study.

Changes in gene expression following androgen receptor blockade is not equivalent to androgen ablation by castration in the rat ventral prostate.

Involution of the rat ventral prostate and concomitant modulation of gene expression post-castration is a well- documented phenomenon. While the rat castration model has been extensively used to study androgen regulation of gene expression in the ventral prostate,it is not clear whether all the gene expression changes post-castration are due to androgen depletion alone. To obtain insights into this, we performed differential display reverse transcriptase polymerase chain reaction (DD-RT-PCR) which resulted in the identification of castration and/or flutamide-regulated genes in the rat ventral prostate. These include clusterin, methionine adenosyl transferase II alpha, and prostate-specific transcripts such as PBPC1BS, S100RVP and A7. While clusterin, PBPC1BS and methionine adenosyl transferase II alpha are regulated by both castration and flutamide, S100 RVP and A7 are regulated by castration alone. Interestingly, we show that flutamide, unlike castration, does not induce apoptosis in the rat ventral prostate epithelium, which could be an underlying cause for the differential effects of castration and flutamide treatment. We propose that castration leads to enrichment and depletion of stromal and epithelial cell types, respectively, resulting in erroneous conclusions on some of the cell type-specific transcripts as being androgen regulated.

Effect of testosterone on morphine withdrawal syndrome in rats / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To determine whether testosterone is involved in morphine withdrawal syndrome (WS).</p><p><b>METHODS</b>In order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg), and after the last dose of morphine (day 8) WS was induced by intraperitoneal injection of naloxone (1 mg/kg). Wet dog shake (WDS), abdomen writhing (AW), and jumps (J) were recorded as indicators of WS.</p><p><b>RESULTS</b>The severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated (10 mg/kg/day for 8 days, i.p.) male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy (10 mg/kg/day for 8 days, i.m.) in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats.</p><p><b>CONCLUSION</b>It can be concluded that testosterone might be effectively involved in morphine WS.</p>

Anticonvulsant Effect of Flutamide in vitro Seizure Model / 대한간질학회지

PURPOSE: Flutamide (4-nitro-3-t-trifluoromethyl-isobutyranilide) is an androgen-receptor antagonist with typical antiandrogenic effect, used to treat androgen-dependent disorders such as prostate cancer. However, some reports noted that flutamide has direct effects to neuronal cells. It has been shown to retard the development of electrical kindling in rats. METHODS: We used the chemoconvulsant 4-aminopyridine (4-AP) and picrotoxin (PTX) in the in vitro hippocampal slice model to determine of flutamide for the suppression of epileptiform discharges. Extracellular field potential recordings were obtained from the CA3 pyramidal layer of hippocampus. RESULTS: The concentration of 30 and 100 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 57.8% and 66.8% each compared with the 4-AP only slices. In 100 micrometer PTX, 10 and 30 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 56.6% and 82.5% each. Intermixed with flumazenil, the anticonvulsant effect of flutamide was decreased. CONCLUSIONS: Flutamide suppressed epileptiform discharges induced by 4-AP and PTX in vitro seizure model. It suggests that flutamide influence to anti-epileptic activity by benzodiazepine site of the GABAA receptor.