RESUMO
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role.
Assuntos
Hormônios Hipotalâmicos/sangue , Melaninas/sangue , Hormônios Hipofisários/sangue , Adolescente , Adulto , Idoso , Glicemia , Índice de Massa Corporal , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Valores de Referência , Adulto JovemRESUMO
BACKGROUND: SPRED1 and 2 are key negative regulators of MAPK signalling in mammalian cells. Here, we investigate the expression and functional role of SPREDs in prostate cancer. METHODS: A transcriptome bank of microdissected grade-specific primary cancers was constructed and interrogated for transcript expression of prostate cancer genes, known negative signalling regulators as well as SPRED1 and 2. The effect of SPRED2 manipulation was tested in in vitro assays. RESULTS: In a panel of 5 benign glands and 15 tumours, we observed concomitant downregulation of the negative regulators SEF and DUSP1 in tumours with increasing Gleason grade. Profiling in the same cohorts revealed downregulation of SPRED2 mRNA in tumours compared with benign glands (P<0.05). By contrast, SPRED1 expression remained unchanged. This observation was further validated in two additional separate cohorts of microdissected tumours (total of n=10 benign and n=58 tumours) with specific downregulation of SPRED2 particularly in higher grade tumours. In functional assays, SPRED2 overexpression reduced ERK phosphorylation and inhibited prostate cancer cell proliferation and migration in response to different growth factors and full-media stimulation (P<0.001). Conversely, SPRED2 suppression by siRNA enhanced the mitogenic response to growth factors and full media (P<0.001). CONCLUSION: These data suggest first evidence that SPRED2 is downregulated in prostate cancer and warrants further investigation as a potential tumour-suppressor gene.
Assuntos
Fosfatase 1 de Especificidade Dupla/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Receptores de Interleucina/genética , Proteínas Repressoras/genética , Proteínas Adaptadoras de Transdução de Sinal , Western Blotting , Movimento Celular , Proliferação de Células , Estudos de Coortes , Regulação para Baixo , Fosfatase 1 de Especificidade Dupla/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Gradação de Tumores , Prognóstico , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais CultivadasRESUMO
El hallasgo de IIH, demuestra que no existe una linea matriz de acciones, dirigidas a solucionar problema. No se cuenta con instrmentos (matrices), que permitan detectar y corregir la presencia de IIH. No existe una correcta supervision de la medidas de bioseguridad. Los Comites de Historias Clinicas y Auditoria medica, Comite de Evaluacion en Salud y seguimiento a la Gestion y Comite de Bioseguridad y Vigilancia Epidemiologica; no existen o no son operativos. No se ha estructurado un Comite de Bioseguridad y Vigilancia Epidemiologica entre si. No se ha pensado en la creacion de un Comite Multidiciplinario, que incluya varias instancias con referencia a las IIH. Se constata una carencia de metodos y procedimientos para detectar, prevenir y controlar la aparicion de Infecciones Intrahospitalarias...
Assuntos
Assepsia , Departamentos Hospitalares , EpidemiologiaRESUMO
Recent work from this laboratory both in rat primary cardiomyocytes and in ventricular tissue of transgenic mouse models of induced hypertrophy has identified two Ca(2+)/calmodulin-dependent nuclear signaling cascades. The first involves the phosphatase calcineurin (CaN). The second is the CaM kinase kinase cascade which involves CaM kinase I and CaM kinase IV. Each of these signaling cascades strongly up-regulate transcription of hypertrophy-sensitive genes in the rat ventricular cardiomyocyte. We have documented that over-expression of an active form of CaM kinase II silenced transcriptional induction of hypertrophy-sensitive genes. The purpose of this study was to generate an inducible CaM kinase II expression system and correlate its expression with the silencing of hypertrophic-sensitive reporters. A truncated form of CaM KII, CaM KII (1-290) was subcloned downstream and proximal to a promoter under transcriptional control (induction) of the tetracycline-regulated transcription factor, tet-TransActivator (tTA). Hypertrophy-sensitive reporter activity in primary cardiomyocytes was silenced when tet-inducible CaM KII was co-expressed with plasmids harboring active forms of CaN, CaM KI or CaM KIV. For instance, induced CaM KII expression silenced CaN, CaM kinase I, or CaM kinase IV driven ANF reporter activity 4.9-, 2.9-, and 6.9-fold below their maximal values, respectively. Myocyte exposure to doxycycline (DOX) blocked tTA-driven CaM KII expression and restored CaN/CaM KI or CaN/CaM KIV driven reporter activation. This study demonstrates, for the first time, that active CaM KII silences Ca(2+)-sensitive nuclear signaling cascades for transcriptional up-regulation of cardiomyocyte hypertrophy.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/fisiologia , Miocárdio/metabolismo , Miocárdio/patologia , Inibidores da Síntese de Proteínas/farmacologia , Tetraciclina/farmacologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Tamanho Celular/fisiologia , Células Cultivadas , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Camundongos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
This paper is intended to offer a qualitative and quantitative diagnosis on publications concerned with human health impact of exposure to environmental chemical pollutants in Mexico. The review of these subjects included scientific papers on studies carried out in Mexico, published both in Mexican and international journals. The articles were analyzed according to the following criteria: chemical pollutants, type of study and institution that conducted it, study population, design, and analysis of data. The article concludes that publications in this field are scarce. Moreover, this review showed that there is little diversity, limited methodology and an unequal distribution of the human and material resources for research. All this indicates a rudimentary level of scientific knowledge in Mexico regarding public health implications of chemical pollutants.
Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Humanos , México , Publicações Periódicas como Assunto/estatística & dados numéricos , Análise de Regressão , Pesquisa/estatística & dados numéricos , Pesquisa/tendênciasRESUMO
Este informe relata los resultados de la visita realizada a La Paz por un asesor de la O.P.S. con el propósito de prestar asesoria en aspectos técnico administrativos en situaciones de Desastre, a la Unidad Coordinadora Nacional en Salud para Desastres del Ministerio de Salud de Bolivia. Incluye dos documentos elaborados por esta asesoria: El Programa Nacional para la Prevencion , Preparativos y Atencion de Salud en Emergencias y Desastres, que establece la estructura organizativa de la Unidad y define las estrategias a seguir y las funciones de cada uno de los niveles, de acuerdo a la estructura del Sistema Nacional de Salud; y el Plan de Emergencia para la ciudad de La Paz, que presenta dos fases, de planeacion y operativa. La primera establece elementos de diagnostico, direccion y control e identificacion de recursos necesarios. La segunda fase define la coordinacion inter-institucional y las actividades de las organizaciones de socorro para atención pre-hospitalaria y hospitalaria
