RESUMEN
OBJECTIVE: Aim of the study was to compare Connexin 43 (Cx43) in human bladder tissue of urodynamically proven idiopathic detrusor overactivity to those of urodynamically stable bladders. STUDY DESIGN: We compared bladder biopsies of patients with detrusor overactivity and those with stable bladder analysing Cx43 message by RNA extraction and PCR amplification. All patients had multichannel urodynamics prior to the biopsies. RESULTS: We investigated the bladder biopsies of 15 female patients with and 15 patients without detrusor overactivity. Cx43 could be detected in nine patients of the detrusor overactivity group and in eight patients of the control group which was not statistically significant. 42 cycles of PCR were necessary to demonstrate Cx43 presence in the positive specimen. The presence of Cx43 was not consistent in the samples from the bladder dome and the side walls meaning there were Cx43 positive results in the dome and negative ones in the side walls of the same patient and vice versa. CONCLUSION: In conclusion, Cx43 is present in human bladder tissue both of overactive bladders and those of controls. However, it is expressed in very small amounts and is not always detectable. The role of Cx43 for the origin of detrusor overactivity remains unclear.
Asunto(s)
Conexina 43/metabolismo , Vejiga Urinaria Hiperactiva/metabolismo , Vejiga Urinaria/metabolismo , Anciano , Anciano de 80 o más Años , Biopsia , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Proyectos PilotoRESUMEN
Poor prenatal nutrition is associated with a greater risk of adult glucose intolerance and insulin insensitivity in the offspring. Skeletal muscle is the primary tissue for glucose utilization, and insulin resistance in muscle is the earliest identifiable abnormality in the pre-diabetic patient. We investigated the effect of early and late gestation undernutrition on structure and markers of growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow- and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri-implantation (PI, n = 9; 40%, 1-31 days gestation (dGA) (term approximately 147)) or in late gestation (L, n = 6; 50%, 104-127 dGA). At 127 +/- 1 dGA we measured myofibre and capillary density in the fetal TB and soleus muscles, and mRNA levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary densities were lower in the TB, but not the soleus, of PI and L fetuses. The predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT-4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced myofibre density is consistent with a redistribution of resources at the expense of specific peripheral tissues by early and late gestation undernutrition which may be mediated by a decrease in capillary density. The increase in key regulatory components of glucose uptake following late gestation undernutrition may constitute a short-term compensation to maintain glucose homeostasis in the face of fewer type I (insulin-sensitive) myofibres. However, together these adaptations may influence the risk of later metabolic disease and thus our findings have implications for future strategies aimed at improving maternal diet.
Asunto(s)
Implantación del Embrión , Trastornos Nutricionales en el Feto/fisiopatología , Fenómenos Fisiologicos Nutricionales Maternos , Músculo Esquelético/embriología , Músculo Esquelético/fisiopatología , Complicaciones del Embarazo/fisiopatología , Animales , Femenino , Edad Gestacional , Embarazo , Preñez , OvinosRESUMEN
In our previous study, we have shown that maternal low protein diet (LPD, 9% casein vs 18% casein control) fed exclusively during the rat preimplantation period (0-4.25 day postcoitum) induced low birth weight, altered postnatal growth and hypertension in a gender-specific manner. In this study, we investigated the effect of maternal LPD restricted only to the preimplantation period (switched diet) or provided throughout gestation on fetal growth and imprinted gene expression in blastocyst and fetal stages of development. Male, but not female, blastocysts collected from LPD dams displayed a significant reduction (30%) in H19 mRNA level. A significant reduction in H19 (9.4%) and Igf2 (10.9%) mRNA was also observed in male, but not in female, fetal liver at day 20 postcoitum in response to maternal LPD restricted to the preimplantation period. No effect on the blastocyst expression of Igf2R was observed in relation to maternal diet. The reduction in H19 mRNA expression did not correlate with an observed alteration in DNA methylation at the H19 differentially methylated region in fetal liver. In contrast, maternal LPD throughout 20 days of gestation did not affect male or female H19 and Igf2 imprinted gene expression in fetal liver. Neither LPD nor switched diet treatments affected H19 and Igf2 imprinted gene expression in day 20 placenta. Our findings demonstrate that one contributor to the alteration in postnatal growth induced by periconceptional maternal LPD may derive from a gender-specific programming of imprinted gene expression originating within the preimplantation embryo itself.
Asunto(s)
Blastocisto/metabolismo , Dieta con Restricción de Proteínas , Regulación del Desarrollo de la Expresión Génica , Impresión Genómica , Fenómenos Fisiologicos Nutricionales Maternos , Animales , Secuencia de Bases , Islas de CpG , Metilación de ADN , Desarrollo Embrionario/fisiología , Estradiol/sangre , Femenino , Expresión Génica , Factor II del Crecimiento Similar a la Insulina/genética , Hígado/metabolismo , Masculino , Datos de Secuencia Molecular , Placenta/fisiología , Embarazo , Progesterona/sangre , ARN Largo no Codificante , ARN no Traducido/análisis , Ratas , Ratas Wistar , Receptor IGF Tipo 2/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores SexualesRESUMEN
OBJECTIVE: To compare tissue markers of collagen metabolism in the uterosacral ligaments with those in vaginal tissue in women with uterine prolapse. DESIGN: Prospective observational experimental study. SETTING: A tertiary urogynaecology unit. POPULATION: Women referred for hysterectomy for prolapse or benign gynaecological disease. METHODS: Matrix metalloproteinase (MMP)-2 and -9 expression, tissue inhibitors of metalloproteinase (TIMP)-2 expression and hydroxyproline content were measured in the uterosacral ligaments and vaginal tissue from 14 women with prolapse compared with 14 controls. MAIN OUTCOME MEASURES: Levels of MMP, TIMP and hydroxyproline in the uterosacral ligaments and vaginal tissue of women with prolapse and controls. RESULTS: Fourteen women with prolapse and 14 women without prolapse (controls) were included. A significant increase in pro MMP-2 expression was seen in vaginal tissue from women with prolapse (P < 0.05) but not activated MMP-2, MMP-9 and TIMP-2. For uterosacral ligaments, the differences were not statistically significant. No significant difference in hydroxyproline content was found between control and prolapse in either tissue. Significant correlations exist in expression of pro-MMP-2, activated MMP-2, MMP-9 and TIMP-2 in vaginal tissue with that in uterosacral ligaments. CONCLUSIONS: Correlations existed between markers of collagen metabolism in the vaginal and uterosacral tissues. This suggests vaginal tissue reflects the endopelvic fascia. The changes which are more pronounced in vaginal tissue may be as a result of prolapse rather than cause.
Asunto(s)
Colágeno/metabolismo , Piel/metabolismo , Prolapso Uterino/metabolismo , Vagina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Femenino , Humanos , Hidroxiprolina/metabolismo , Ligamentos/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Persona de Mediana Edad , Estudios Prospectivos , Sacro/metabolismo , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Útero/metabolismoRESUMEN
Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and leptin receptor isoforms were found in fetal mouse brain at embryonic day 12 (E12). Levels of expression for these genes were altered in brains of E12 fetuses from pregnant dams on a protein-restricted diet, suggesting that the fetal brain is responsive to changes in maternal nutrition prior to birth.