Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system.

Liddle syndrome is an autosomal dominant form of hypertension resulting from deletion or missense mutations of a PPPxY motif in the cytoplasmic COOH terminus of either the beta or gamma subunit of the epithelial Na channel (ENaC). These mutations lead to increased channel activity. In this study we show that wild-type ENaC is downregulated by intracellular Na+, and that Liddle mutants decrease the channel sensitivity to inhibition by intracellular Na+. This event results at high intracellular Na+ activity in 1.2-2.4-fold higher cell surface expression, and 2.8-3.5-fold higher average current per channel in Liddle mutants compared with the wild type. In addition, we show that a rapid increase in the intracellular Na+ activity induced downregulation of the activity of wild-type ENaC, but not Liddle mutants, on a time scale of minutes, which was directly correlated to the magnitude of the Na+ influx into the oocytes. Feedback inhibition of ENaC by intracellular Na+ likely represents an important cellular mechanism for controlling Na+ reabsorption in the distal nephron that has important implications for the pathogenesis of hypertension.

Estudio comparativo entre una escala de desarrollo y una prueba basada en la teoría de Piaget, aplicadas a un grupo de niños con síndrome de Down

Este trabajo pretende analizar la similitud entre algunos de los ítems de dos escalas utilizadas en el psicodiignóstico de la primera infancia y construidas a partir de marcos conceptuales divergentes: Brunet-Uzine de estructura psicométrica clásica y Casati-Uzine, adaptación de las pruebas de Piaget. Asimismo deseamos.verificar si ambas escalas proporcionan dliagnósticos equivalentes al aplicarlas a niños con sindrome de Down. El análisis sistemático del contenido de 10s ítems de las dos escalas evidencia una gran similitud de las pautas de conducta que algunos de los items solicitan al niño. El tratamiento estadístic0 de 10s datos indica que para el tipo de niños estudiado la escala Casati-Lézine tiende a acordar edades de desarrollo más altas que la de Brunet-Lézine. La muestra esta compuesta por 18 niños, entre 6 y 24 meses, con sindrome de Down.

Indicadores cognitivos del proceso de envejecimiento en las personas con síndrome de Down

Fundamentos: el aumento de la esperanza de vida en las personas con síndrome de Down plantea nuevos interrogantes sobre el proceso de su envejecimiento. La revisión bibliográfica sobre el tema muestra acuerdo sobre algunos aspectos diferenciales respecto a la población con discapacidad psíquica y la población general. Entre ellos, destacamos dos: a) la precocidad del inicio del proceso y b) el aumento de la probabilidad de desarrollar un envejecimiento patológico a causa de la demencia tipo Alzheimer. El objetivo del presente estudio se centra en la aportación de datos que ayuden a delimitar los posibles indicadores del declive cognitivo de las personas adultas con síndrome de Down relacionados con un posible deterioro propio de la demencia tipo Alzheimer. Método: el estudio se realiza en una muestra de 84 personas adultas con discapacidad psíquica, 42 de las cuales presentan el síndrome de Down. La media de edad se sitúa entorno a los 40 años y su nivel de retraso mental es medio. Se aplica de forma longitudinal en un período de dos años el test d’Aptituds Cognitives per a Deficiència del 65% (Castelló, Carrillo y Barnosell, 1996). Se utiliza un diseño factorial mixto de medidas repetidas controlando las variables etiología, edad cronológica, nivel de retraso mental y paso del tiempo. Resultados: se observa con el paso del tiempo, un declive cognitivo significativo de las personas con síndrome de Down de más de 38 años y nivel de retraso mental ligero respecto al grupo con discapacidad psíquica de referencia. Los indicadores cognitivos se sitúan preferentemente en las áreas de lenguaje y coordinación visomotora. Conclusiones: las personas con síndrome de Down de más de 38 años y nivel de retraso mental ligero manifiestan una probabilidad mayor de desarrollar un declive cognitivo relacionado con un probable deterioro propio de la demencia Alzheimer.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Caractérisation fonctionnelle du gène AP1S1 mutant associé au syndrome de MEDNIK

Dans les cellules eucaryotes, le trafic intracellulaire de nombreuses protéines est assuré par des vésicules de transport tapissées de clathrine. Les complexes adaptateurs de clathrine (AP) sont responsables de l’assemblage de ces vésicules et de la sélection des protéines qui seront transportées. Nous avons étudié cinq familles atteintes du syndrome neurocutané MEDNIK qui est caractérisé par un retard mental, une entéropathie, une surdité, une neuropathie périphérique, de l’icthyose et de la kératodermie. Tous les cas connus de cette maladie à transmission autosomique récessive sont originaires de la région de Kamouraska, dans la province de Québec. Par séquençage direct des gènes candidats, nous avons identifié une mutation impliquant le site accepteur de l’épissage de l’intron 2 du gène codant pour la sous-unité σ1 du complexe AP1 (AP1S1). Cette mutation fondatrice a été retrouvée chez tous les individus atteints du syndrome MEDNIK et altère l’épissage normal du gène, menant à un codon stop prématuré. Afin de valider l’effet pathogène de la mutation, nous avons bloqué la traduction de cette protéine chez le poisson zébré en injectant une séquence d’oligonucléotides antisenses spécifique à AP1S1. À 48 heures après la fertilisation, les larves knock down pour AP1S1 montrent une réduction de la pigmentation, une désorganisation de la structure de l’épiderme et une perturbation du développement moteur. Alors que la surexpression de l’AP1S1 humain dans ce modèle a permis la récupération du phénotype normal, l’expression de l’AP1S1 mutant fut sans effet sur les phénotypes moteurs et cutanés des larves knock down. Les résultats obtenus montrent que la mutation du AP1S1 responsable du syndrome de MEDNIK est associée à une perte de fonction et que la sous-unité σ1 du complexe AP1 joue un rôle crucial dans l’organisation de l’épiderme et le développement de la moelle épinière.

Création d'un modèle cellulaire des voies respiratoires du porc pour étudier les effets d'une co-infection virale au virus du syndrome reproducteur et respiratoire porcin et au circovirus porcin

Le circovirus porcin de type 2 (PCV2) est un pathogène majeur pour l’industrie porcine et est associé à une longue liste de maladies associées au circovirus porcin (MACVP). Les premières tentatives pour reproduire ces maladies ont montré que le virus doit être combiné à d’autres agents pathogènes du porc ou à différents stimulants du système immunitaire. De ces agents, le virus du syndrome reproducteur et respiratoire porcin (VSRRP) est celui qui est le plus souvent co-isolé avec le PCV dans les fermes. Une grande partie des efforts faits pour étudier les interactions entre ces deux virus ont été menés in vivo. Les interactions in vitro ont jusqu’à maintenant été peu étudiées du fait qu’il n’existe pas de modèle cellulaire permettant la réplication efficace des deux virus. L’objectif de ce projet était donc de développer un modèle cellulaire propice à la réplication des deux virus et d’étudier leur interaction en co-infection. Une lignée cellulaire provenant de la trachée d’un porcelet nouveau-né (NPTr), permissive au PCV, a été génétiquement modifiée pour exprimer la protéine CD163, un récepteur majeur du VSRRP. Ce projet a montré que cette nouvelle lignée cellulaire (NPTr-CD163) est permissive au VSRRP ainsi qu’à plusieurs génotypes de PCV (PCV1, PCV2a, PCV2b et PCV1/2a). De plus, les résultats obtenus lors d’infections mixtes suggèrent que la réplication du VSRRP et du PCV conditionne de façon génotype-dépendante celle du PCV puisque la réplication du PCV1 est inhibée en présence de VSRRP, alors que celle du PCV2b est significativement augmentée dans les mêmes conditions. Ni la mortalité cellulaire, ni la réponse cellulaire en cytokines n’a permis d’expliquer ces résultats. La modulation de la réplication du PCV par le VSRRP serait donc liée à un mécanisme spécifique qui demeure inconnu. De plus, cet effet varierait en fonction du génotype de PCV.

Down-regulation of cerebellar 5-HT2C receptors in pilocarpine-induced epilepsy in rats: Therapeutic role of Bacopa monnieri extract

Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory action on cerebellar function through 5HT2C receptors. 5-HT2C receptors are novel targets for developing anticonvulsant drugs. In the present study, we investigated the changes in the 5-HT2C receptors binding and gene expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a significant down regulation of the 5-HT content (pb0.001), 5-HT2C gene expression (pb0.001) and 5-HT2C receptor binding (pb0.001) with an increased affinity (pb0.001). Carbamazepine and B. monnieri treatments to epileptic rats reversed the down regulated 5-HT content (pb0.01), 5-HT2C receptor binding (pb0.001) and gene expression (pb0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the upregulation of 5-HT2C receptor in epileptic rats. This has clinical significance in the management of epilepsy

Correlación genotipo-fenotipo y análisis molecular en pacientes con síndrome Down

El síndrome Down (SD) es la trisomía más común en humanos, presentándose en 1 de cada 745 nacidos vivos y es la causa más frecuente de retardo mental. El origen más observado de la trisomíaes una no disyunción meiótica (95%), la cual generalmente es de origen materno, mientras un 5% se debe a errores post-cigóticos mitóticos. Objetivo: identificar el origen parental delcromosoma 21 extra, el momento del error no disyuncional y establecer una correlación entre estos eventos y las manifestaciones fenotípicas de los pacientes afectados. Materiales y métodos: se estudiaron cincuenta familias con un hijo con SD mediante el uso de cinco short tandem repeats (STR) a lo largo de 21q, se construyeron los haplotipos de cada paciente y sus padres, determinandoel origen parental y el momento en que surgió el error no disyuncional. Resultados:en 80% de las familias el error fue en meiosis I y 20% en la meiosis II; 98% de los cromosomasadicionales fue de origen materno y 2% paterno. Se encontró correlación genotipo-fenotipo en ocho características estudiadas: cuello corto y ancho, tercera fontanela, labio inferior prominente, paladar estrecho y corto, raíz del hélix cruzando la concha, alopecia, pliegue único palmar yotras anomalías como nevus y xeroderma y eventos de recombinación en 24,5% de las familias analizadas. Conclusiones: la edad materna y la variación en el número de recombinaciones está asociada con no disyunciones meióticas I y II; se encontró correlación entre el momento del errorno disyuncional y algunas variables clínicas.

C??mo hacer hablar al ni??o con s??ndrome de Down y mejorar su lenguaje : un programa de intervenci??n psico-ling????stica

En la port. adem??s : European Down Syndrome Association (EDSA)

(Com)passo a (com)passo com o síndrome de Down

RESUMO: O presente projecto surge como trabalho final de Mestrado em “Educação Especial: Domínio Cognitivo e Motor”, relatando a concepção, realização e avaliação de um Projecto de Intervenção/Acção, no qual a Expressão Musical configura a área primordial de intervenção. O trabalho intitula-se “(Com)passo a (com)passo com a Síndrome de Down”. Baseia-se num grupo de treze crianças de educação pré-escolar, no qual está incluída uma criança com Síndrome de Down. Neste contexto reflecte-se sobre essa síndrome, segundo a perspectiva de vários autores. Descrevem-se também as metodologias de investigação utilizadas para a recolha de dados, tendo por base autores de referência. Faz-se ainda a caracterização do contexto escolar onde se desenvolveu o Projecto de Intervenção/Acção e a apresentação do respectivo Plano de Acção. Relata-se a intervenção realizada, acrescida da interpretação e avaliação dos dados obtidos a partir das vinte e três sessões de actividade levadas a cabo. A análise dos resultados permitiu inferir que as sessões de Expressão Musical se revestiram de um carácter bastante positivo, dado que se constataram mudanças consideráveis no comportamento das crianças e do grupo. Tais mudanças tornaram-se mais evidentes na área da socialização, traduzidas num maior envolvimento das crianças dentro do grupo, que provocou um maior entusiasmo e interesse em participar nas actividades propostas. ABSTRACT: The present draft appears as Masters final work in “Special Education: Cognitive and Motor Domains”, reporting the idea, implementation and evaluation of an Intervention / Action Project, in which the Musical Expression configures the primary area of intervention. The work is entitled “(Com)passo a (com)passo com a Síndrome de Down”, based on a group of thirteen children of preschool, in which is included in a child with Down Syndrome. In this context this work reflects upon this syndrome from several authors‟ perspective. It also describes the research methodologies used for data collection having for base reference authors. It‟s done, also, the characterization of the school environment where the Intervention/ Action Project and the presentation of its Action Plan were developed. It is reported the intervention, together with the interpretation and evaluation of data obtained from the twenty-three sessions of activity carried out. The results allowed inferring that Musical Expression sessions assumed a very positive character, given that significant changes were observed in the behavior of the studied children and the rest of the group. These changes became more evident in the socialization area, translated into a greater involvement of children within the group, which led to a greater enthusiasm and interest in participating in the proposed activities.

Do children with Williams syndrome really have good vocabulary knowledge? Methods for comparing cognitive and linguistic abilities in developmental disorders

The comparison of cognitive and linguistic skills in individuals with developmental disorders is fraught with methodological and psychometric difficulties. In this paper, we illustrate some of these issues by comparing the receptive vocabulary knowledge and non-verbal reasoning abilities of 41 children with Williams syndrome, a genetic disorder in which language abilities are often claimed to be relatively strong. Data from this group were compared with data from typically developing children, children with Down syndrome, and children with non-specific learning difficulties using a number of approaches including comparison of age-equivalent scores, matching, analysis of covariance, and regression-based standardization. Across these analyses children with Williams syndrome consistently demonstrated relatively good receptive vocabulary knowledge, although this effect appeared strongest in the oldest children.

Obesity, diabetes and longevity in the Gulf: is there a Gulf Metabolic Syndrome?

The Gulf is experiencing a pandemic of lifestyle-induced obesity and type 2 diabetes mellitus (T2DM), with rates exceeding 50 and 30%, respectively. It is likely that T2DM represents the tip of a very large metabolic syndrome iceberg, which precedes T2DM by many years and is associated with abnormal/ectopic fat distribution, pathological systemic oxidative stress and inflammation. However, the definitions are still evolving with the role of different fat depots being critical. Hormetic stimuli, which include exercise, calorie restriction, temperature extremes, dehydration and even some dietary components (such as plant polyphenols), may well modulate fat deposition. All induce physiological levels of oxidative stress, which results in mitochondrial biogenesis and increased anti-oxidant capacity, improving metabolic flexibility and the ability to deal with lipids. We propose that the Gulf Metabolic Syndrome results from an unusually rapid loss of hormetic stimuli within an epigenetically important time frame of 2-3 generations. Epigenetics indicates that thriftiness can be programmed by the environment and passed down through several generations. Thus this loss of hormesis can result in continuation of metabolic inflexibility, with mothers exposing the foetus to a milieu that perpetuates a stressed epigenotype. As the metabolic syndrome increases oxidative stress and reduces life expectancy, a better descriptor may therefore be the Lifestyle-Induced Metabolic Inflexibility and accelerated AGEing syndrome – LIMIT-AGE. As life expectancy in the Gulf begins to fall, with perhaps a third of this life being unhealthy – including premature loss of sexual function, it is vital to detect evidence of this condition as early in life as possible. One effective way to do this is by detecting evidence of metabolic inflexibility by studying body fat content and distribution by magnetic resonance (MR). The Gulf Metabolic Syndrome thus represents an accelerated form of the metabolic syndrome induced by the unprecedented rapidity of lifestyle change in the region, the stress of which is being passed from generation to generation and may be accumulative. The fundamental cause is probably due to a rapid increase in countrywide wealth. This has benefited most socioeconomic groups, resulting in the development of an obesogenic environment as the result of the rapid adoption of Western labour saving and stress relieving devices (e.g. cars and air conditioning), as well as the associated high calorie diet.

O educando com síndrome de down: um estudo sobre a relação entre pais e profissionais na escola regular

This work makes a documental analise about the relationship between families of Down syndrome students and professionals of who teach them, in order to improve the process of developing teaching-learning, in an inclusive perspective. For this, we use a qualitative approach, because we believe that the object of research is not a passive and neutral knowledge, since it has meanings and relationships whose can be better interpreted and understood by the researcher in a real and active situation. For the development of this research, a bibliographical review was made about the subject, and a case studied in two regular education schools, both of them at the city of Natal/RN, one public and another one particular. We work on these educational institutions with professionals and parents of Down syndrome students. As an instrument of building information we used a semi-structured interview and to analise the results a qualitative method. Crossing the stages, we noticed: the pedagogical coordinators who made up both analyzed schools showed interest about doing an effective work with parents, regardless of Educational Policy Project of each school, predict or not the participation on educational undertaken process; On teachers discourses, reporting the relationship with the family, we realize that one of those teachers try to keep a good relationship with parents, permeated by learning exchanges, guidance and knowledge, in relation to another one, even existing an apparent openness to dialogue, when parents have any suggestions or criticism, that attitude is not always well coming. From the parents interviews, we can emphasize, first of all, that both of them recognize the benefits of inclusion, with regard to socialization - in general from the coexistence with pairs and the process of teaching and learning, as shown in a consistent way. Regarding school meetings with teachers, the studied parents agree about importance of such appointments and try to attend them, besides the other events organized by the school, beyond keeping individual touch with the teacher, when necessary. They are always present, looking for get envolved in everything that happens at school, in order to know better what is being done, listening and may suggest alternatives to improving the educational process. We perceive, from the study undertaken, that although the school inclusion is not an easy process to be built, is something that could be achieved. For this, is necessary that professionals of education and families recognize their functions in the educational process and act jointly on this direction

A escrita e a criança com síndrome de Down: uma relação possível na escola regular

The school inclusion is based on respect for diversity and the belief that everyone has the capacity to learn and develop, for this the school needs to prepare itself to meet the differences and provide a meaningful learning for everyone, including those with Down syndrome. It is in the interaction with others that children develop their skills and exchange substantial experiences to learn the school and non school knowledge. Among the knowledge the school must offer students, there is one that is indispensable to the present society; the writing, because writing is a way to Interact, to communicate and to build autonomy to relate in society. Before exposed, the research that started this study aimed to investigate the level of the writing conceptualization of children with Down syndrome during the literacy process in a regular school of the private school network in the city of Natal/RN. For carrying out this study, initially we conducted a qualitative research, using the bibliographical as a methodological recourse, seeking to the deepening of information, based on the literature about the subject, which allowed us to collect data about people with Down syndrome, their education and the process of the writing acquisition. Later, a case study was performed, involving free observation in the room and interviews with teachers and children, trying to verify how this writing acquisition process occurs by children with Down syndrome. The data analyzed and information recorded demonstrated that the school inclusion, when taken seriously, benefits the learning of writing for children who have intellectual deficit, and, mainly, they develop in this environment and are able to learn to write, as long as their own pace are respected