RESUMO
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). Pantothenate kinases catalyze the rate-limiting step of coenzyme A synthesis and Pank2 is the only pantothenate kinase isoform in humans that is localized to mitochondria. Acanthocytosis, the occurrence of spiculated erythrocytes, is observed in about 10% of the PKAN patients. Therefore PKAN is also classified together with other rare neurodegenerative diseases like Chorea Acanthocytosis (ChAc) and McLeod syndrome (MLS) into the Neuroacanthocytosis (NA) syndromes. It has not been investigated yet whether acanthocytosis in PKAN is associated with a specific subset of Pank2 mutations. In this study, we analyzed acanthocytosis of a cohort of 25 PKAN patients from the Dominican Republic that are homozygous for the c.680 A>G mutation in the PANK2 gene as compared to control donors that are heterozygous or wild-type with respect to this mutation. 3D modeling of this mutation indicated that the replacement of a tyrosine by a cysteine at position 227 in Pank2 disrupts a polar interaction within the A domain of the enzyme. Mean acanthocyte count was elevated in the cohort of patients, however, acanthocytosis varied among the patients with nearly half of them showing high (>20%) or elevated acanthocytosis and the rest showing mild (6-10%) or no (<6%) acanthocytosis. Heterozygous control donors revealed a tendency to mild acanthocytosis. Based on the insight that Pank2 is a normal constituent of red blood cells and de novo biosynthesis of coenzyme A is likely to take place in the erythrocyte cytosol we propose a hypothetical model that accounts for the variability in the occurrence of acanthocytic cells in PKAN.
Assuntos
Abetalipoproteinemia/diagnóstico , Acantócitos/patologia , Neurodegeneração Associada a Pantotenato-Quinase/complicações , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Polimorfismo de Nucleotídeo Único , Abetalipoproteinemia/genética , Abetalipoproteinemia/patologia , Adolescente , Adulto , Criança , Estudos de Coortes , República Dominicana , Estabilidade Enzimática , Homozigoto , Humanos , Modelos Moleculares , Neurodegeneração Associada a Pantotenato-Quinase/sangue , Neurodegeneração Associada a Pantotenato-Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/química , Adulto JovemRESUMO
In tropical spastic paraparesis, spinal cord atrophy is a well-known finding in magnetic resonance imaging. But in contrast to histological reports, focal lesions of the spinal cord have only been described in imaging reports in exceptional acute cases. Here, we looked for such focal lesions and for alterations of diffusion tensor imaging parameters of the long fibre tracts in the usual case of a long-standing and slowly progressive disease. We examined 10 symptomatic patients, 11 seropositive, but asymptomatic human T-lymphotrophic virus type 1 carriers and 18 seronegative volunteers as controls. Sagittal and transversal T2-weighted images were visually assessed for atrophy and focal cord lesions. The spinal cord cross-sectional areas and the segmental cord volumes were measured at all levels. High-resolution diffusion tensor imaging was performed in sagittal planes from the bregma down to the cervical spine. For tractography and calculation of fractional anisotropy and mean diffusivity, we used manufacturer-provided software. Two-thirds of patients showed focal lesions affecting the antero-lateral columns and in two cases also the dorsal columns. Compared to carriers and volunteers, patients presented a significant spinal cord atrophy and a reduction of fractional anisotropy (p < 0.05), correlating more to duration of symptoms than to clinical impairment. Because our carriers did not show a significant atrophy, focal lesions or a change of diffusion tensor imaging parameters, we need further long-term studies to see if these parameters at some stage may be used as early indicators of spinal cord affection in virus carriers.
Assuntos
Doenças Assintomáticas , Atrofia/patologia , Paraparesia Espástica Tropical/patologia , Medula Espinal/patologia , Adulto , Atrofia/diagnóstico , Portador Sadio , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/diagnóstico , Índice de Gravidade de DoençaRESUMO
Se investigó la concepción de violencia conyugal en las mujeres adheridas al Programa de "Planificación Familiar", del consultorio "Los Cstaños", perteneciente al S.M.S.S.O., durante los días 2 al 14 de enero de 1992. Se realizó un estudio de tipo descriptivo exploratorio. En el Programa de "Planificación Familiar", estan bajo control 2.800 mujeres. De este se extrajo una muestra seleccionada en forma intencionada, de 100 mujeres. En nuestra muestra en estudio, el 54% se encontraba dentro del rango de edad de 21 a 30 años, con un 43% de mujeres casadas. Se encontró un 1% de consumo de alcohol en las mujeres; y un 20% - 4% de consumo de alcohol y drogas, respectivamente en su pareja. Un 59% de las mujeres de la muestra tenia al momento del estudio menos de 3 años de vida en común con su pareja. En cuanto a los episodios de violencia conyugal, sólo un 29% de la mujeres reconoce haber experimentado algún tipo de violencia. Mientras que un 93% , realmente la recibe. Encontrándose un 92% de agresión psicológica, un 60% de agresión sexual y un 57% de agresión física. Siendo el grupo etario entre los 21 a 30 años en el cual se observó el mayor porcentaje de agresión. El propósito de este estudio fue determinar la concepción de violencia conyugal que tienen las mujeres. De los datos obtenidos de esta muestra podemos concluír que la mujer reconoce la violencia conyugal en una menor frecuencia de la que realmente recibe