Pubertal hormones mediate sex differences in levels of myelin basic protein in the orbitofrontal cortex of adult rats.

Previous work from our lab revealed that adult female rats have increased levels of myelin basic protein (MBP), a marker for myelination, in the orbitofrontal cortex (OFC) as compared to adult males. The goal of the present study was to determine the role of gonadal hormones, acting either in adulthood or at puberty, in the development of an adult sex difference in OFC levels of MBP. In an initial experiment, we replicated our previous results demonstrating that gonadally intact female rats have increased levels of MBP in the OFC as compared to males. In a second experiment, gonadectomy in adulthood did not alter MBP levels in rats of either sex. In a third experiment, gonadectomy immediately prior to pubertal onset resulted in significant reduction of levels of MBP in adult females but not males. This reduction eliminated the sex difference in adult MBP levels in the OFC. These results reveal puberty to be an organizational time point for a sex difference in the OFC of adult rats in levels of a marker of myelination. This neuroanatomical difference may contribute to observed sex differences in OFC-associated behaviors including in inhibitory control.

Prevention of ßeta-adrenergic-induced Adverse Cardiac Remodeling by Gonadectomy in Male but Not Female Spontaneously Hypertensive Rats.

Chronic ß-adrenergic stimulation induces left ventricular (LV) remodeling in male but not in female spontaneously hypertensive rats (SHRs). However, the role of sex steroids in mediating these effects has not been determined. The aim of the present study was to assess the impact of gonadectomy on isoproterenol (ISO)-induced LV remodeling in SHR. Gonadectomy was performed on 9-month-old male and female SHR. LV remodeling was induced by daily ISO injection (0.04 mg/kg) for 6 months. LV dimensions and functions were determined in vivo by echocardiography and ex vivo using isolated perfused heart preparations. In males, ISO increased LV end diastolic (LVED) diameter in sham-operated (in millimeter, ISO: 8.12 ± 0.26 vs. Con: 6.67 ± 0.20, P = 0.0002) but not in castrated SHR (ISO: 6.97 ± 0.31 vs. Con: 6.53 ± 0.15, P = 0.66). Similarly, ISO increased the volume intercept of the LVED pressure-volume relationship in sham-operated (in milliliters, ISO: 0.26 ± 0.02 vs. Con: 0.19 ± 0.01, P = 0.01) but not in castrated SHR (ISO: 0.17 ± 0.02 vs. Con: 0.17 ± 0.01, P = 0.99). In females, ISO only increased LVED diameter (ISO: 6.43 ± 0.13 vs. Con: 6.07 ± 0.09, P = 0.027). However, ovariectomy did not modify any LV dimensions measured in vivo and ex vivo. In conclusion, testosterone may be responsible for the chronic ß-adrenergic-induced LV dilation and eccentric remodeling observed in male but not female SHR.

SEOM Clinical guidelines for the treatment of metastatic prostate cancer

Androgen deprivation treatment is the current standard first-line treatment for metastatic prostate cancer. For several years, docetaxel was the only treatment with a proven survival benefit for castration-resistant prostate cancer (CRPC). Since docetaxel became standard of care for men with symptomatic metastatic castration-resistant prostate cancer (CRPC), three treatment virtual spaces, for treatment and drug development in CPRC, have emerged: pre-docetaxel, docetaxel combinations and post-docetaxel. Sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 have been approved in the pre- or post-docetaxel setting in metastatic CRPC during the last few years. Patients are now living longer and experiencing better quality of life. Strategies for patient selection and treatment sequencing are therefore urgently require (AU)

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Adaptation or selection--mechanisms of castration-resistant prostate cancer.

Men with advanced prostate cancer are typically treated with hormonal therapy, which leads to tumour shrinkage. However, tumours relapse and develop into the lethal form of the disease, termed castration-resistant prostate cancer (CRPC). Two distinct, but not mutually exclusive, models have been proposed in the literature to describe the onset of CRPC: adaptation and selection. Although some studies indicate that tumour cells acquire new alterations that enable them to survive in the castrated state (adaptation), other research points to the outgrowth of rare, pre-existing cells capable of surviving hormonal therapy (selection). Targeting the cells that survive hormonal therapy--by either adaptation or selection--is necessary to prevent the development of CRPC. Current research is focused on not only understanding the cellular mechanisms of CRPC, but also defining critical pathways that can be targeted with combinatorial therapies in castration-resistant cancer cells.

Caracterização demográfica das populações de cães e gatos supervisionados do município de São Paulo / Demographic characterization of supervised dog and cat populations in Sao Paulo city, Brazil

A caracterização das populações canina e felina domiciliadas do município de São Paulo (SP) foi realizada utilizando-se amostragem complexa com seleção aleatória em dois estágios. Em cada distrito administrativo, foram visitados seis setores censitários e 20 domicílios em cada setor sorteado, de setembro de 2006 a setembro de 2009, totalizando 11.272 entrevistas. A razão homem:cão foi de 4,34, e a razão homem:gato de 19,33. A população canina foi estimada em 2.507.401, e a felina em 562.965. A população canina era composta por 52,7% de machos, e a felina por 45,1%. A proporção de fêmeas esterilizadas, 23,4% das cadelas e 46,1% das gatas, é maior que a de machos, 11,4% dos cães e 31,5% dos gatos. A idade média dos cães era de 4,99 anos e a dos gatos de 3,53 anos. A proporção de cães com restrição de acesso à rua, 64,4%, foi maior que a de gatos, 42,5%. A média de animais/domicílio foi estimada em 1,60 para cães e 1,69 para gatos. A guarda destes animais está associada a fatores culturais, assim a caracterização da população de animais é base da estruturação adequada de programas de controle populacional e de zoonoses.

This study aimed to estimate the owned dog and cat populations of São Paulo city using a complex sample with random selection in two stages. In each administrative district, six census sectors and 20 households in each sampled sector were visited from September 2006 to September 2009, totalizing 11,272 interviews. The human:dog ratio was 4.34 and the human:cat ratio was 19.33. The dog population was 2,507,401 and the cat population, 562,965. The dog population was composted of 52.7% males, while among the cat population it was 45.1%. The proportion of sterilized females (23.4% among dogs and 46.1% among cats) was higher than males (11.4% among dogs and 31.5% among cats). The mean age of dogs was 4.99 years, and for cats, 3.53 years. The proportion of restricted (without access to the street) dogs, 64.4%, was higher than restricted cats, 42.5%. The average number of animals/household was 1.60 for dogs and 1.69 for cats. The animal ownership is associated with cultural factors, therefore the characterization of canine and feline population is essential to implement an adequate animal population management program and zoonosis control.

Recomendaciones sobre el manejo de controversias en cáncer de próstata avanzado resistente a la castración / Recomendations on the Management of Controversies in Advanced Castrate-Resistant Prostate Cancer

Contexto: En el manejo integral del cáncer de próstata avanzado resistente a la castración siguen existiendo incertidumbres y controversias, a pesar de la existencia de numerosas guías de práctica clínica basadas en la evidencia, internacionalmente consensuadas. Objetivo: Elaborar un documento en el que se revise el manejo de controversias en el cáncer de próstata avanzado resistente a la castración, con recomendaciones desde su definición hasta el manejo de maniobras hormonales y el tratamiento de primera y segunda línea con nuevos fármacos como cabazitaxel y abiraterona, así como el abordaje multidisciplinario de la patología con el objetivo de buscar la alternativa más eficiente, el mejor momento de actuar y la mayor seguridad. Adquisición de la evidencia: Se realizaron 2 reuniones de un grupo de expertos multidisciplinarios implicados en el manejo de esta enfermedad (urólogos y oncólogos) donde se pusieron en común el análisis bibliográfico de artículos originales y se consensuó este documento de recomendaciones sobre el cáncer de próstata resistente a la castración, revisando e intentando dar respuesta a las actuales controversias de la enfermedad. Síntesis de la evidencia: Este documento está avalado por las principales sociedades científicas y grupos de trabajo implicados en el manejo actual de los tumores genitourinarios: la Asociación Española de Urología (AEU), el Grupo de Urología Oncológica (GUO) y el Grupo Español de Oncología Genitourinaria (SOGUG). Conclusiones: Con la adaptación e implementación de este documento de recomendaciones a la práctica clínica se dispone, por primera vez, de una verdadera hoja de ruta de calidad, eficiencia y seguridad del manejo de los pacientes con cáncer de próstata avanzado resistente a la castración (AU)

Context: Controversies and uncertainties among integral management of advanced castration resistant prostate cancer continue to exist despite the number of evidence based clinical practice guidelines published with high international consensus. Objective: To develop a document that reviews the management of controversies in advanced castration resistant prostate cancer, with recommendations from the definition, to the management in hormonal maneuvers, first-line treatment and second-line with new treatments as cabazitaxel or abirarerone and the multidisciplinary approach of the pathology with the goal of finding the most efficient, best time to act and safety. Evidence Acquisition: Two meetings of a multidisciplinary group of experts involved in the management of this disease (Oncologist and Urologist) where pooled analysis of original literature and reached consensus document of recommendations on castration resistant prostate cancer, reviewing and attempting to address the current controversies of the disease. Evidence Synthesis: This document is endorsed by the corresponding Scientific Associations and Working Groups involved in the current management of Genitourinary Tumours: the Spanish Association of Urology (AEU) with the Uro-Oncoloy Group (GUO) and the Spanish Oncology of Genitourinary Group (SOGUG). Conclusions: With the adaptation and implementation of this Document of Recommendations for clinical practice are available for the first time, a real road map for quality, efficiency and safety in the management of patients with CRPC (AU)