Gut DYSBIOSIS and altered barrier function precedes the appearance of metabolic syndrome in a rat model of nutrient-induced catch-up growth.

Nutritional restriction early in life followed by catch-up growth has been associated with increased risk of metabolic syndrome in adulthood. To elucidate whether altered gut colonization underlies the mechanisms responsible of this predisposition gut microbiome was studied before or afterwards catch-up growth. Offspring of dams fed ad libitum (C) or undernourished during pregnancy and suckling (U), were weaned onto high-fat diet (HFD) for 22 weeks (CHF and UHF, respectively) or continued on their diet. HF-feeding induced glucose intolerance (P<.05), insulin resistance (P<.001), and white adipose tissue inflammation (P<.001) in UHF rats compared to CHF. Analyses of gut microbial composition before catch-up growth revealed reduced F/B ratio and significant expansion of the mucolytic genera Akkermansia (P<.05) and Desulfovibrio (P<.05) in U pups. Although relative abundance of Akkermansia remained elevated to adulthood in U rats, HFD normalized its levels to C and CHF. Food-restriction increased intestinal permeability causing disorganization on the tight-junction proteins of colonic epithelium, Zonula Occludens-1 (ZO-1) and occludin, and reducing the mucus thickness layer in U adult rats. The levels of ZO-1 and occludin were not recovered in U rats after HF-feeding. This event was correlated with increased circulating levels of bacterial lipopolysaccharides in both U and UHF adult rats. Even more, serum lipopolysaccharides were already elevated in U rats compared to C group (P<.001) at weaning. Thus, gut dysbiosis and chronic endotoxemia observed in U rats, even before catch-up growth, might anticipate a pro-inflammatory milieu promoting metabolic diseases when fed hyperlipidic diets.

¿Es el peso de las mochilas escolares lo que ocasiona dolor de espalda a los niños de 10-11 años de edad? / Does the weight of backpacks cause backache in 10-11 year-old children?

Introducción: El dolor de espalda es una patología cada vez más prevalente, produce un alto absentismo laboral, genera un alto coste tanto sanitario como económico y entraña una alta posibilidad de cronificación que, en muchos casos, se inicia en edades muy tempranas. Se ha relacionado con el uso y el peso de las mochilas que llevan los escolares, y se ha llegado a promover el uso de un determinado peso máximo para evitarlo. Objetivo: Conocer si es el peso de las mochilas escolares lo que realmente ocasiona dolor de espalda a los niños de 10-11años de edad y averiguar cuáles son los factores de riesgo que pueden estar relacionados con este dolor. Métodos: Estudio transversal realizado en 834 niños de 10-11 años de edad mediante entrevista, mediciones personales y cuestionarios; se determinó la talla de los niños y el peso de los niños y las mochilas; se hizo a los niños una serie de preguntas sobre hábitos de vida, antecedentes familiares, presencia y frecuencia de dolor de espalda y factores de posible origen psicosomático; se recogió un segundo cuestionario a los 6 meses del primero, analizando la presencia y la frecuencia de dolor de espalda y los mismos factores de posible origen psicosomático. Resultados: La prevalencia del dolor de espalda fue del 26,6%. Se ha encontrado una relación estadísticamente significativa entre el dolor de espalda y las siguientes variables: a) sexo, con más frecuencia entre las chicas (odds ratio [OR]=1,74; p <0,001); b) dolor de espalda de los progenitores (OR=2,90; p <0,001); c) dolor de espalda de los hermanos mayores (OR= 2,32; p <0,001); d) dolor de cabeza (OR= 2,49; p <0,001);e) dolor abdominal (OR= 2,29; p <0,001), y f) despertares nocturnos (OR= 1,85; p <0,005). La frecuencia del dolor de espalda se correlaciona con la combinación del peso de la mochila y el tiempo que tarda el sujeto en ir y volver andando al colegio (p <0,005). No hemos hallado ninguna relación con las variables talla, peso, pies planos, corrección de pies planos, forma de ir al colegio, forma de sentarse, sedentarismo, toma de medicamentos, tipo de mochila, forma de carga ni peso de la mochila. Conclusiones: Los factores de riesgo identificados en este estudio y relacionados con el dolor de espalda en la población estudiada son el sexo, los antecedentes familiares, otros factores de tipo psicosomático y la combinación del peso de la mochila con el tiempo que se lleva cargando (AU)

Introduction: The backaches are a more daily prevalent pathology, which produces a great absenteeism from work generating a high sanitary and economical cost, and with the possibility of becoming a frequent chronic pathology, that in many cases occurs at early ages. It has been related to the use and weight of the backpacks, which are used, by school children and the promotion of a determined weight to avoid problems are being used. The main goal of this study is to determine whether weight of schoolbags is actually causing backache in children aged 10 and 11, plus evaluating different risk factors that may influence the occurrence of these pains. Methods: A transversal study was conducted with 834 children, aged 10 to 11 years, through interviews and personal measurements through a questionnaire; children where measured and weighed Children were measured, and children and backpacks were weighted; a series of questions were done to them on life habits, familiar precedents, presence and frequency of backache and factors of possible psychosomatic origin; the second questionnaire was gathered 6 months after the first one, analyzing the presence and frequency of backache and the same factors of possible psychosomatic origin. Results: Backache prevalence was of 26.6%. Statistically significant relationships between backache and the following factors were found: a) gender, being this more frequent among females with an OR= 1.74 (p <0.001). b) Parents’ backache: it is more frequent among children having parents who have suffered backache (p <0.001), with an OR= 2.90. c) Older siblings’backache, with an OR= 2.32. d) Headache: (p <0.001), OR= 2.49.e) Abdominal pain: (p <0.001), OR= 2.29. f) Waking up at night: OR= 1.85 (p <0.005). Moreover, backache frequency was correlated to the combination of two factors: the weight of backpacks and the time it takes for the individual to walk back and forth to school (p <0.005). We have found no association between back pains and height, weight, flat feet, flat feet correction, means to get to school, ways of sitting, sedentariness, drug ingestion, types of backpacks, ways of carrying the backpacker the weight of backpacks. Conclusions: We have identified the following risk factors for back pain in school children: gender, family background, other psychosomatic factors and the combination between the weight of backpacks and the time it takes to carry them (AU)

MED and PSACH COMP mutations affect chondrogenesis in chicken limb bud micromass cultures.

Mutations in cartilage oligomeric matrix protein (COMP) cause pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). We studied the effects of over-expression of wild type and mutant COMP on early stages of chondrogenesis in chicken limb bud micromass cultures. Cells were transduced with RCAS virus harboring wild type or mutant (C328R, PSACH; T585R, MED) COMP cDNAs and cultured for 3, 4, and 5 days. The effect of COMP constructs on chondrogenesis was assessed by analyzing mRNA and protein expression of several COMP binding partners. Cell viability was assayed, and evaluation of apoptosis was performed by monitoring caspase 3 processing. Over-expression of COMP, and especially expression of COMP mutants, had a profound affect on the expression of syndecan 3 and tenascin C, early markers of chondrogenesis. Over-expression of COMP did not affect levels of type II collagen or matrilin-3; however, there were increases in type IX collagen expression and sulfated proteoglycan synthesis, particularly at day 5 of harvest. In contrast to cells over-expressing COMP, cells with mutant COMP showed reduction in type IX collagen expression and increased matrilin 3 expression. Finally, reduction in cell viability, and increased activity of caspase 3, at days 4 and 5, were observed in cultures expressing either wild type or mutant COMP. MED, and PSACH mutations, despite displaying phenotypic differences, demonstrated only subtle differences in their cellular viability and mRNA and protein expression of components of the extracellular matrix, including those that interact with COMP. These results suggest that COMP mutations, by disrupting normal interactions between COMP and its binding partners, significantly affect chondrogenesis.

Expression of prolactin gene and secretion of prolactin by rat retinal capillary endothelial cells.

PURPOSE: Prolactin fragments inhibit blood vessel formation, whereas anti-prolactin antibodies induce angiogenesis in the cornea. Endothelial cells from brain capillaries and the umbilical vein produce prolactin, and this study was undertaken to determine whether retinal capillary endothelial cells could be a source for prolactin in the eye. METHODS: Primary cultures of rat retinal endothelial cells were investigated for the expression of prolactin mRNA by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis and by in situ hybridization. The prolactin protein was analyzed by immunocytochemistry, enzyme-linked immunoabsorbent assay, Western blot analysis, and the Nb2-cell bioassay. The effect of prolactin and the 16-kDa prolactin fragment on retinal endothelial cell proliferation was investigated, and the expression of the cloned prolactin receptor was analyzed by RT-PCR and Southern blot analysis. RESULTS: Retinal endothelial cells expressed prolactin mRNA and full-length 23-kDa prolactin. Prolactin was observed in the cytoplasm of cells and in their conditioned medium at levels 300 times those described in endothelial cells from other vessels and species. Exogenous 16-kDa prolactin inhibited rat retinal endothelial cell proliferation, whereas 23-kDa prolactin was inactive. No evidence was obtained for the expression of the cloned prolactin receptor in these cells, but the prolactin receptor was amplified in whole rat retina. CONCLUSIONS: Endothelial cells from the microcirculation of rat retina produce and release prolactin. That the cloned prolactin receptor was not expressed in these cells argues against direct autocrine effects of prolactin. Possible paracrine effects are suggested by the expression of the prolactin receptor in retinal tissue.

[Detection of Mycobacterium tuberculosis by polymerase chain reaction in a selected population in northwestern Mexico]. / Detección de Mycobacterium tuberculosis mediante la reacción en cadena de la polimerasa en una población seleccionada del noroccidente de México.

This study compares the detection of Mycobacterium tuberculosis through bacilloscopy (Ziehl-Neelsen stain), growth in Lowenstein-Jensen medium, and polymerase chain reaction (PCR) carried out with DNA taken directly from various types of samples. A total of 252 samples were analyzed (114 sputum, 96 urine, 15 cerebrospinal fluid, and 27 of other types) from 160 patients with any form of suspected tuberculosis who came to the Clinical Pathology Laboratory of the Specialties Hospital of the Western National Medical Center of the Mexican Social Security Institute. In all cases Ziehl-Neelsen stains were done, as were also cultures with Lowenstein-Jensen medium and PCR amplification of a segment of 285 base pairs specific to the M. tuberculosis complex. Of the 252 samples, with the culture, 18 were positive for nontuberculous mycobacteria. Of the 234 others, 12 (5.1%) were positive with the PCR and the culture, 174 (74.4%) negative in both tests, 47 (20.1%) positive with the PCR and negative with the culture, and 1 (0.4%) negative with the PCR and positive with the culture. Using the culture as the reference test, the PCR provided a sensitivity of 92.3%, a specificity of 78.7%, a positive predictive value of 20.3%, and a negative predictive value of 99.4%. The PCR detection limit with DNA taken from culture was 10 fg, equivalent to four or five mycobacteria. Also in comparison with the culture, the PCR correctly identified the totality of the mycobacteria of the M. tuberculosis complex. Taking the culture as the reference test, when analyzing just the sputum samples, the direct PCR provided a sensitivity of 90.9%, a specificity of 89.5%, a positive predictive value of 52.6%, and a negative predictive value of 98.7%. The PCR is a sensitive and specific technique for detecting the M. tuberculosis complex in both positive and negative bacilloscopy samples. A controlled PCR procedure makes it possible to establish or to exclude the diagnosis of tuberculosis in a time that is reduced from more than three weeks to just 24 to 48 hours. This is particularly useful when an early diagnosis is needed to establish a patient's prognosis or in organ transplant cases.