Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
J Biomol Struct Dyn ; 41(22): 13250-13259, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36718094

RESUMO

Glycogen synthase kinase 3 (GSK-3) is involved in different diseases, such as manic-depressive illness, Alzheimer's disease and cancer. Studies have shown that insulin inhibits GSK-3 to keep glycogen synthase active. Inhibiting GSK-3 may have an indirect pro-insulin effect by favouring glycogen synthesis. Therefore, the development of GSK-3 inhibitors can be a useful alternative for the treatment of type II diabetes. Aminopyrimidine derivatives already proved to be interesting GSK-3 inhibitors. In the current study, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) have been performed on a series of 122 aminopyrimidine derivatives in order to generate a robust model for the rational design of new compounds with promising antidiabetic activity. The q2 values obtained for the best CoMFA and CoMSIA models have been 0.563 and 0.598, respectively. In addition, the r2 values have been 0.823 and 0.925 for CoMFA and CoMSIA, respectively. The models were statistically validated, and from the contour maps analysis, a proposal of 10 new compounds has been generated, with predicted pIC50 higher than 9. The final contribution of our work is that: (a) we provide an extensive structure-activity relationship for GSK-3 inhibitory pyrimidines; and (b) these models may speed up the discovery of GSK-3 inhibitors based on the aminopyrimidine scaffold. Finally, we carried out docking and molecular dynamics studies of the two best candidates, which were shown to establish halogen-bond interactions with the enzyme.Communicated by Ramaswamy H. Sarma.


Assuntos
Diabetes Mellitus Tipo 2 , Insulinas , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Relação Quantitativa Estrutura-Atividade , Quinase 3 da Glicogênio Sintase , Ligação Proteica , Pirimidinas/farmacologia , Pirimidinas/química
2.
Rev. chil. obstet. ginecol. (En línea) ; 87(4): 273-278, ago. 2022. tab
Artigo em Espanhol | LILACS | ID: biblio-1407853

RESUMO

Resumen Introducción: Tanto a nivel sudamericano como mundial, el incremento de la tasa de cesáreas electivas ha sido abrumante. Esto se considera un problema de salud pública, ya que el parto vaginal es la vía más fisiológica para el nacimiento y trae beneficios de salud para la madre y el recién nacido, tanto inmediatos como a futuro. Objetivo: Evaluar la postura de mujeres nuligestas en edad fértil acerca de las vías del parto a través de sus conocimientos, percepciones y preferencias. Método: Estudio de corte transversal. Se aplicó una encuesta a estudiantes universitarias para la recopilación de datos mediante SPSS, y análisis con prueba de diferencias de proporciones y de χ2. Resultados: 210 mujeres encuestadas. Un 80% de ellas desconoce la menor morbilidad infantil asociada a un parto vaginal, más de la mitad estima una ventaja de la cesárea que evite el dolor y un gran porcentaje desconoce los riesgos médicos asociados a la cesárea. Conclusiones: Existe un alto nivel de desconocimiento respecto a beneficios, riesgos y consecuencias de las diferentes vías del parto.


Abstract Introduction: Both in South America and worldwide, the increase in the rate of elective caesarean sections has been overwhelming. This is considered a public health problem, since vaginal delivery is the most physiological route for birth and brings health benefits for the mother and the newborn, immediately and in the future. Objective: To evaluate the position of nulliparous women of childbearing age regarding the delivery pathways through their knowledge, perceptions, and preferences. Method: Cross-sectional study with an analytical component. A survey was applied to university students for data collection through SPSS, and analysis was made with the difference of proportions and χ2 test. Results: 210 women surveyed; 80% of them are unaware of the lower infant morbidity associated with a vaginal delivery, more than a half estimate an advantage of a cesarean section that it avoids pain, and a large percentage are unaware of the medical risks associated with cesarean sections. Conclusions: There is a high level of ignorance regarding the benefits, risks and consequences of the different delivery routes.


Assuntos
Humanos , Feminino , Adulto , Adulto Jovem , Estudantes/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Parto Obstétrico/psicologia , Comportamento Reprodutivo/psicologia , Paridade , Percepção , Universidades , Cesárea/psicologia , Estudos Transversais , Inquéritos e Questionários , Fatores Etários , Parto/psicologia , Período Fértil
3.
Proc Natl Acad Sci U S A ; 119(25): e2204620119, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35704760

RESUMO

In neurosecretion, allosteric communication between voltage sensors and Ca2+ binding in BK channels is crucially involved in damping excitatory stimuli. Nevertheless, the voltage-sensing mechanism of BK channels is still under debate. Here, based on gating current measurements, we demonstrate that two arginines in the transmembrane segment S4 (R210 and R213) function as the BK gating charges. Significantly, the energy landscape of the gating particles is electrostatically tuned by a network of salt bridges contained in the voltage sensor domain (VSD). Molecular dynamics simulations and proton transport experiments in the hyperpolarization-activated R210H mutant suggest that the electric field drops off within a narrow septum whose boundaries are defined by the gating charges. Unlike Kv channels, the charge movement in BK appears to be limited to a small displacement of the guanidinium moieties of R210 and R213, without significant movement of the S4.


Assuntos
Ativação do Canal Iônico , Canais de Potássio Ativados por Cálcio de Condutância Alta , Arginina/metabolismo , Ativação do Canal Iônico/genética , Simulação de Dinâmica Molecular , Mutação
4.
Membranes (Basel) ; 12(6)2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35736302

RESUMO

Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of the CaV2.3 subtype. Two mechanisms dominate the binding process of cysteine-rich peptides: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts in the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics guides membrane binding by incrementing and aligning the molecular dipole. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determining the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482.

5.
Med. fam. (Caracas) ; 13(2): 27-35, jul.-dic. 2005. tab
Artigo em Espanhol | LILACS | ID: lil-479044

RESUMO

El objetivo de este estudio fue establecer la prevalencia de A. lumbricoides y otros parásitos intestinales, en habitantes de doce comunidades rurales del Municipio Piar, Estado Monagas, diciembre de 2004 a julio de 2005. Fueron evaluados mediante examen directo de heces, 2.648 individuos, de ambos exos y todas las edades. Los resultados se analizaron mediante frecuencias relativas. La prevalencia de parasitosis intestinal fue de 91,10 por ciento . El patógeno más observado fue A. lumbricoides, con una prevalencia de 40,97 por ciento. Otros patógenos: G. lamblia (39,24 por ciento), E. histolytica/E. dispar (11,52 por ciento), H. nana (6,57 por ciento), B. hominis (2,83 por ciento), T. trichiuria (1,17 por ciento), E. vermicularis (0,98 por ciento), A. duodenale (0,64 por ciento), S. stercoralis (0,38 por ciento), T. solium (0,11 por ciento) y comensales en 12,72 por ciento. La alta prevalencia de parasitosis en las comunidades estudiadas, se ve justificada por inadecuado saneamiento ambiental presente en cada uno de los poblados y obliga a realizar futuras investigaciones tendientes a establecer los factores determinantes de estas infecciones, ya que esas altas tasas, aunado al gran poliparasitismo, reflejan una mayor frecuencia de exposición con heces humanas.


Assuntos
Masculino , Humanos , Feminino , Ascaris lumbricoides , Fezes/parasitologia , Enteropatias Parasitárias , Prevalência , Medicina de Família e Comunidade , Venezuela
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA