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1.
Epidemiol Infect ; 146(13): 1642-1653, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29986778

RESUMO

Co-circulation of Chikungunya and Dengue viral infections (CHIKV and DENV) have been reported mainly due to transmission by common Aedes vector. The purpose of the study was to identify and characterise the circulating strains of CHIKV and DENV in DENV endemic region of New Delhi during 2016. CHIKV and DENV were identified in the blood samples (n = 130) collected from suspected patients by RT-PCR. CHIKV was identified in 26 of 65 samples (40%). Similarly, DENV was detected in 48 of 120 samples (40%). Co-infection with both the viruses was identified in five (9%) of the samples. Interestingly, concurrent infection with DENV, CHIKV and Plasmodium vivax was detected in two samples. CHIKV strains (n = 11) belonged to the ECSA genotype whereas DENV-3 sequences (n = eight) clustered in Genotype III by phylogenetic analysis. Selection pressure of E1 protein of CHIKV and CprM protein of DENV-3 revealed purifying selection with four and two positive sites, respectively. Four amino acids of the CHIKV were positively selected and had high entropy suggesting probable variations. Co-circulation of both viruses in DENV endemic regions warrants effective monitoring of these emerging pathogens via comprehensive surveillance for implementation of effective control measures.


Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya/isolamento & purificação , Coinfecção/epidemiologia , Vírus da Dengue/isolamento & purificação , Dengue/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Febre de Chikungunya/virologia , Criança , Pré-Escolar , Coinfecção/virologia , Dengue/virologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Filogenia , Adulto Jovem
2.
Hum Exp Toxicol ; 37(4): 399-411, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28441890

RESUMO

Amyloid beta (Aß) peptide aggregation and cholinergic neurodegeneration are involved in the development of cognitive impairment. Therefore, in this article, we examined rosuvastatin (RSV), an oral hypolipidemic drug, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aß peptide aggregation for the treatment of cognitive impairment. Molecular docking study was done to examine the affinity of RSV with Aß1-42 and AChE in silico. We also employed neurobehavioral activity tests, biochemical estimation, and histopathology to study the anti-Aß1-42 aggregation capability of RSV in vivo. Molecular docking study provided evidence that RSV has the best binding conformer at its receptor site or active site of an enzyme. The cognitive impairment in female Wistar rats was induced by high-salt and cholesterol diet (HSCD) ad libitum for 8 weeks. RSV ameliorated serum cholesterol level, AChE activity, and Aß1-42 peptide aggregations in HSCD induced cognitive impairment. In addition, RSV-treated rats showed greater scores in the open field (locomotor activity) test. Moreover, the histopathological studies in the hippocampus and cortex of rat brain also supported that RSV markedly reduced the cognitive impairment and preserved the normal histoarchitectural pattern of the hippocampus and cortex. Taken together, these data indicate that RSV may act as a dual inhibitor of AChE and Aß1-42 peptide aggregation, therefore suggesting a therapeutic strategy for cognitive impairment treatment.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Colesterol na Dieta , Inibidores da Colinesterase/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva/prevenção & controle , Fragmentos de Peptídeos/antagonistas & inibidores , Agregação Patológica de Proteínas , Rosuvastatina Cálcica/farmacologia , Cloreto de Sódio na Dieta , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Inibidores da Colinesterase/química , Disfunção Cognitiva/enzimologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Modelos Animais de Doenças , Feminino , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Locomoção/efeitos dos fármacos , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Conformação Proteica , Ratos Wistar , Rosuvastatina Cálcica/química , Relação Estrutura-Atividade
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