Lateralidad, perfil cognitivo y rendimiento escolar en pacientes con mielomeningocele / Laterality, cognitive profile, and school performance in children with myelomeningocele

El mielomeningocele (MMC) es la forma más grave de los disrafismos de la columna vertebral. Afecta a 1/1200 recién nacidos vivos. Su etiología es multifactorial. El 80% cursa con hidrocefalia (HC) asociada a malformación de Arnold Chiari. El coeficiente intelectual (CI) oscila en un rango entre fronterizo y normal promedio. La tasa mundial de la población general de zurdos es del 10% pero se describe un aumento de su presentación en niños con MMC. Además se evidencian déficits visoespaciales, grafomotores, atencionales, memorísticos, dificultades en aritmética y en la comprensión de textos. Materiales y métodos: Este es un trabajo analítico, descriptivo, transversal. Se evaluaron 179 pacientes derivados del Consultorio Interdisciplinario de MMC; edad: entre 5 años, 0 meses y 15 años, 11 meses. No se emplearon controles sanos. Instrumentos administrados: Stanford Binet IV, Prolec ­ Prolec-Se, Wrat3, TMT A y B, d2, Stroop y pruebas de lateralidad de Zazzo. Objetivo: Describir la lateralidad, el perfil cognitivo y el rendimiento escolar en pacientes pediátricos con patología de mielomeningocele, analizando también las funciones ejecutivas, los procesos atencionales, memorísticos y la modalidad escolar en la cual se encuentran inmersos. Resultados: El 20% (35/179 pacientes) con edades que oscilan entre los 5 años, 0 meses y 15 años, 11 meses han presentado lateralidad zurda, y de ellos presentaban antecedentes familiares de zurdera 26%. Se observó lateralidad cruzada en 6% y eran ambidiestros 11%. El perfil cognitivo de la muestra completa (N: 179) fue homogéneo en todas las áreas (verbal, abstracto/visual y memoria de corto plazo), arrojando puntuaciones fronterizas. En pruebas atencionales el 100% obtuvo niveles descendidos. Todos reportaron dificultades en el rendimiento escolar. Sólo el 14% tuvo plan de integración y el 11% accedió a algún tipo de tratamiento. Conclusiones: Los niños con MMC evidencian déficits neuropsicológicos y alta tasa de zurdera, siendo probablemente los problemas de lateralidad una de las causas que ocasionarían el bajo rendimiento escolar y afectando el rendimiento académico (AU)

Myelomeningocele (MMC) is the most severe form of spinal dysraphism, affecting 1/1200 live newborns. Its etiology is multifactorial. Overall, 80% develops hydrocephalus (HC) associated with an Arnold Chiari malformation. The intelligence quotient (IQ) ranges from borderline to average. The worldwide incidence in the general population of left-handedness is 10%; however, an increase is found among children MMC. Additionally, visuospatial, graphomotor, attention, memory deficits as well as difficulties in arithmetic and text comprehension is found. Material and methods: A cross-sectional, analytical, descriptive study was conducted. Overall, 179 patients aged between 5 years 0 months and 15 years 11 months referred from the interdisciplinary MMC clinic were evaluated. No healthy control group was used. Instruments administrated: Stanford Binet IV, Prolec ­ Prolec-Se, Wrat3, TMT A and B, d2, Stroop and Zazzo's laterality test. Aim: To describe laterality, cognitive profile, and school performance in pediatric patients with MMC, analyzing executive functions, attention and memory, and the school system the children were attending. Results: 20% (35/179 patients) aged between 5 years, 0 months and 15 years, 11 months were left-handed, 26% of whom had a family history of left-handedness. Cross dominance was observed in 6% and ambidexterity in 11%. Overall, the cognitive profile of the sample (N: 179) was homogeneous in all areas (verbal, abstract/visual, and short-term memory), with borderline scores. In attention tasks, levels were low in 100%. All children had difficulties in school performance. Only 14% had an integration program and 11% received some type of treatment. Conclusions: Children with MMC show neuropsychological deficits and a high rate of left-handedness, the latter of which may be one of the causes of poor school performance and affecting academic achievements (AU)

Mesenchymal cell precursors of peritubular smooth muscle cells of the mouse testis can be identified by the presence of the p75 neurotrophin receptor.

In the mouse embryo, at approximately 11.5 days postcoitum (dpc), cells migrate from the mesonephros into the developing testis to contribute to the somatic population of the interstitial compartment (i.e., peritubular myoid cells, Leydig cells, and endothelial cells). Studies from this laboratory have shown that the interstitial population of mesenchymal cells in fetal and newborn mouse testis express the p75 neurotrophin receptor (p75NTR, formerly known as the low-affinity nerve growth factor receptor); part of the cell population progressively congregates around testis cords, later to be replaced by contractile peritubular myoid cells, which express smooth muscle cell markers. In the present study, we show that the migrating cells and the p75NTR-expressing cells are the same population. We also show that the neurotrophin receptor is a useful endogenous marker to follow cell migration within the urogenital ridge and to identify and isolate mesenchymal precursors of myoid cells. A time-course immunolocalization study of the location of p75NTR-bearing cells within the urogenital ridge of mouse embryos between 10.5 and 12.5 dpc showed that the interstitium of the fetal testis was progressively occupied by p75NTR+ cells. The progressive increase of p75NTR expression within the developing testis was confirmed by immunoblot analysis of proteins isolated from the fetal gonads. Organ cultures of isolated testes or testis-mesonephros grafts confirmed that p75NTR+ cells do not appear in the testis unless a mesonephros is attached to it. Cells bearing the p75NTR receptor, purified from 12.5-dpc male mouse mesonephroi by immunomagnetic sorting, were able to differentiate in vitro into myoid cells. Immunofluorescence analysis of postnatal testis sections confirmed the presence around the tubules of cells coexpressing p75NTR and alpha-smooth muscle actin. The ability to identify and purify precursors of myoid cells may be of considerable help for studying the mechanisms regulating their differentiation.

Spatiotemporal patterns of expression of neurotrophins and neurotrophin receptors in mice suggest functional roles in testicular and epididymal morphogenesis.

Several reports have established that the action of neurotrophins is not restricted to the nervous system but can affect a broad range of non-neuronal cells. Nerve growth factor (NGF) is present in adult testis and has been suggested as a potential regulator of meiosis in rat seminiferous epithelium. Here we present an extensive immunohistochemical study on neurotrophins and their receptors (p75 and trk) in the developing mouse testis and epididymis, and in fetal human testis. During the early steps of testicular and epididymal organization in the mouse, strong p75 immunoreactivity is detectable in the gonadal ridge in the mesenchyme that is excluded from the evolving testicular cords, and in the mesenchymal cells of the mesonephros. Later in organogenesis, most of the p75-positive interstitial cells of the testis coexpress neurotrophin-3 (NT-3) and the truncated trk B receptor in a developmentally regulated pattern. Our Western blot data confirm the expression of these molecules. These findings suggest that neurotrophin receptors play a role in early inductive events during critical periods of testicular and epididymal development. During fetal and postnatal histogenesis, an increasing number of NT-3- and p75-positive mesenchymal cells start to express alpha-smooth muscle isoactin, suggesting a role for the so-called neurotrophic system in the differentiation of testicular myoid cells and epididymal smooth muscle cells. In the testis of an 18-wk gestational-age human fetus, immunohistochemical analysis has shown intense immunoreactivity of mesenchymal cells to antibodies for neurotrophin receptors p75, trk A, and trk C, and their ligands NGF and NT-3. In addition, we found that in the human fetal testis, the interstitial cells that are differentiating into peritubular myoid cells are associated with a dense network of nerve fibers. Our data suggest that neurotrophins and their receptors are involved in a multifunctional system that regulates cell differentiation and innervation in the developing testis and epididymis.

Retinoic acid treatment induces apoptosis or expression of a more differentiated phenotype on different fractions of cultured fetal rat hepatocytes.

The present study reports the effects of retinoic acid (RA) on cultured fetal rat hepatocytes. We show that RA treatment induces both differentiation and apoptosis. Hepatocytes cultured for 48 hours in the presence of 5 microl/L RA form junctional complexes in the areas of contact between neighboring cells and develop bile canaliculi, typical features of mature and well-differentiated cells. At the same time, about 20% of cells are induced to die by apoptosis, and the percentage of apoptotic cells increases according to the concentration of RA used and the duration of treatment. The induction of apoptosis, studied at the morphological and biochemical levels, revealed that, in our system, the classical compaction of chromatin occurs only during the final stages of the process; instead of the common marker of apoptosis, i.e., the "DNA ladder" pattern of fragmentation, megabase-sized fragments were found. These observations provide further evidence of the existence of fundamental differences in the mechanisms of apoptosis among cell types. To investigate the molecular mechanism of the effects of RA, we evaluated the expression of two proteins, c-myc and p53, which are known to be involved in both cell differentiation and apoptosis. The data obtained show that the amount of p53 remained unchanged after RA treatment. On the contrary, a dose-dependent reduction in c-myc levels was found, suggesting that RA action may be mediated by modulation of this oncogene. Our findings regarding the apoptosis-inducing effect of RA, which was not found in adult hepatocytes, suggest a possible relationship between this phenomenon and the proliferative capacity and/or differentiation state of hepatocytes.

The effect of retinoic acid on the re-establishment of differentiated hepatocyte phenotype in primary culture.

The usefulness of cultured hepatocytes is limited by the gradual loss of their typical physiological functions that occurs in vitro, mainly due to the absence of microenviromental conditions found in vivo. In this study we describe the effect of retinoic acid on the re-establishment of morphological characteristics and on the reorganization of the cytoskeletal network in cultured rat hepatocytes. Results obtained demonstrate that retinoic acid can influence hepatocyte differentiation, as regards the recovery of cell polarity, polyhedric shape and reformation of bile canaliculi and junctional complexes. The main target of this action appears to be the cytoarchitecture of cytoskeletal components, particularly cytokeratin filaments, which regain the configuration present in intact liver. The reorganization of the intermediate filaments does not seem to be dependent on the induction of higher levels of cytokeratin proteins, but rather appears to be due to post-translational regulation. The effect of retinoic acid on the cytoskeletal organization could determine the stabilization of intercellular contacts by means of junctions, leading to the appearance of morpho-functional characteristics typical of well-differentiated hepatocytes.

Role for differential cell proliferation in perforation and rupture of chick pharyngeal closing plates.

Patterns of cell proliferation show two distinct domains around avian pharyngeal closing plates as they form, perforate, and rupture. Pouch endoderm and groove ectoderm are in one domain showing 81-86% proliferation, which suggests relatively rapid growth. Cells in epithelia that comprise the pharyngeal closing plates contiguous with pouch and groove epithelia are vital but are dividing at a significantly lower percentage (62-64%). This phenomenon is similar to the lag in growth reported for cells in the oral membrane around the time of rupture (Miller and Olcott, 1989: Anat. Rec., 223:204-208), is consistent with Waterman's suggestion (1985: Anat. Rec., 211:450-457) that cellular reorganization, rather than massive degeneration, is a major mechanism of initial perforation, and suggests that differential growth is a contributor to performation and rupture of chick pharyngeal closing plates.