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1.
Biochem Res Int ; 2021: 9542038, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881055

RESUMO

Alzheimer's disease manifests itself in brain tissue by neuronal death, due to aggregation of ß-amyloid, produced by senile plaques, and hyperphosphorylation of the tau protein, which produces neurofibrillary tangles. One of the genetic markers of the disease is the gene that translates the presenilin-2 protein, which has mutations that favor the appearance of the disease and has no reported crystallographic structure. In view of this, protein modeling is performed using prediction and structural refinement tools followed by an energetic and stereochemical characterization for its validation. For the simulation, four reported mutations are chosen, which are Met239Ile, Met239Val, Ser130Leu, and Thr122Arg, all associated with various functional responses. From a theoretical analysis, a preliminary bioinformatic study is made to find the phosphorylation patterns in the protein and the hydropathic index according to the polarity and chemical environment. Molecular visualization was carried out with the Chimera 1.14 software, and the theoretical calculation with the hybrid quantum mechanics/molecular mechanics system from the semi-empirical method, with Spartan18 software and an AustinModel1 basis. These relationships allow for studying the system from a structural approach with the determination of small distance changes, potential surfaces, electrostatic maps, and angle changes, which favor the comparison between wild-type and mutant systems. With the results obtained, it is expected to complement experimental data reported in the literature from models that would allow us to understand the effects of the selected mutations.

2.
Iatreia ; 23(2): 127-136, jun. 2010. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-599251

RESUMO

La sepsis, un síndrome de respuesta sistémica a la infección, es un problema de salud pública asociado a alta morbilidad y mortalidad alrededor del mundo. Entre los múltiples genes asociados a esta enfermedad se encuentra el gen que codifica para la caspasa-12 (csp-12), en el cual se ha identificado un polimorfismo de un sólo nucleótido (125T>C) en el exón 4 que predice una forma larga (L) de la proteína, que a su vez se ha asociado con riesgo de sepsis grave y alta mortalidad. Además, se ha demostrado que la frecuencia del alelo L es mucho mayor en poblaciones afroamericanas. Este estudio evalúa la presencia ó el polimorfismo 125T®C de la csp-12 en 128 individuos: 81 pacientes de Medellín con diagnóstico de sepsis, 23 individuos sanos de una población afroamericana del Chocó y24 individuos sanos provenientes de Medellín. En las tres poblaciones se encontraron 121 individuos homocigotos S/S (csp-12 corta) y 7 heterocigotos S/L discriminados así: 3 pacientes con diagnóstico de sepsis, 3 individuos afroamericanos y 1 de la población sana de Medellín. Nuestros resultados muestran que, a pesar de ser una muestra pequeña, en nuestra población existe el alelo L, encontrándose en mayor frecuencia en individuos afroamericanos y en una menor proporción en los mestizos, tanto pacientes como en los individuos sanos. Esto indica que la población afroamericana de Colombia podría tener mayor susceptibilidad a sepsis grave que las poblaciones mestizas, las cuales, se ha demostrado, son producto de mezcla europea, amerindia y africana, ésta última en una baja proporción. Por lo tanto, se deben efectuar estudios más amplios para un mejor entendimiento de las bases genéticas de la respuesta inmune de pacientes con sepsis, con el fin de diseñar terapias más racionales y personalizadas para prevenir este síndrome.


Sepsis, a syndrome of systemic response to infection is a major public health problem, because it is associated with high morbidity and mortality. Among the genes shown to be associated with this syndrome, there is one which encodes for caspase-12 (csp-12). Within this gene, the single nucleotide polymorphism 125T>C located in exon4, which predicts a long form of the protein, has been associated with severe sepsis and increased related mortality. On the other hand, higher frequency of allele L has been reported in African American populations. The present study evaluated the csp-12 polymorphism125T>C in 128 individuals: 81 patients with sepsis, 23 healthy African Colombian subjects and 24 healthy individuals from Medellin-Colombia. We found 121 individuals homozygous S/S (csp-12 short) in these three populations and 7 heterozygotes S/L, discriminated as follows: 3 septic patients, 3 African Colombians and 1 healthy subject from Medellin. This preliminary data suggest that the csp-12L allele is present in the Colombian population, both in African Colombians and Mestizo individuals (either septic patients or healthy individuals). Therefore, more comprehensive studies should be performed to better understand the genetic basis of the immune response of patients with sepsis in order to design more rational and personalized therapies to prevent this syndrome.


Assuntos
Humanos , Polimorfismo Genético , Saúde Pública , Sepse/mortalidade , Colômbia , Infecções
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