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1.
Mol Neurobiol ; 54(5): 3683-3694, 2017 07.
Article in English | MEDLINE | ID: mdl-27209189

ABSTRACT

MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate numerous signaling pathways involved in cerebral ischemia reperfusion injury. Recent finding demonstrated that miR-497 promotes ischemic neuronal death by negatively regulating anti-apoptotic proteins and therefore serves as a promising therapeutic target for cerebral ischemic injury. In this study, we present a systematic computational approach that includes 3D modeling, docking-based virtual screening, and molecular dynamics simulation to identify small-molecule inhibitors of pre-miR-497 maturation. The top hit, aminoglycosidic antibiotic, amikacin, formed a stable complex with pre-miR-497. Later, the protective efficacy of amikacin was evaluated against oxygen-glucose deprivation (OGD) and reoxygenation-induced neuronal cell death in SH-SY5Y cells and mouse organotypic hippocampal slice cultures. To confirm the inhibitory potential of amikacin on miR-497 maturation, quantitative real-time PCR was performed to check the expression of bcl-2, one of the primary anti-apoptotic targets of miR-497. Additionally, the expression level of mature miR-497 was quantified using TaqMan® MiRNA Assay Kit. Amikacin treatment effectively reduced OGD-induced cell death compared to control groups both in vitro and organotypic hippocampal slice cultures. Further, amikacin effectively increased the expression of bcl-2 in SH-SY5Y cells subjected to OGD. Interestingly, SH-SY5Y cells treated with amikacin displayed decreased expression of miR-497, probably due to inhibition of pre-miRic form. Our study provides strong evidence that amikacin inhibits miR-497 maturation and promotes ischemic neuronal survival by upregulating anti-apoptotic protein, bcl-2. Future studies directed at evaluating the neuroprotective efficacy and mechanism of amikacin animal models may lead to new therapeutic opportunities for preventing neuronal death after stroke.


Subject(s)
Amikacin/pharmacology , Brain Ischemia/genetics , Brain Ischemia/pathology , MicroRNAs/metabolism , Neuroprotection/drug effects , Animals , Base Sequence , Binding Sites , Cell Line, Tumor , Glucose/deficiency , Hippocampus/pathology , Humans , Mice , MicroRNAs/chemistry , MicroRNAs/genetics , Molecular Dynamics Simulation , Neuroprotective Agents/pharmacology , Oxygen , Proto-Oncogene Proteins c-bcl-2/metabolism , Up-Regulation/drug effects
2.
Int J Health Care Qual Assur ; 24(8): 601-10, 2011.
Article in English | MEDLINE | ID: mdl-22204265

ABSTRACT

PURPOSE: This paper aims to examine links between women's access to micro-finance and how they use maternal healthcare services in sub-Saharan Africa (SSA). DESIGN/METHODOLOGY/APPROACH: The authors use theoretical and empirical literature to propose a framework to sustain and improve women's access to maternal healthcare services through micro-financing. FINDINGS: It is found that improved access to micro-finance by women, combined with education may enhance maternal health service uptake. RESEARCH LIMITATIONS/IMPLICATIONS: The paper does not consider empirical data in the analysis. The authors advocate empirically testing the framework proposed in other SSA countries. SOCIAL IMPLICATIONS: It is important to empower women by facilitating their access to education and micro-finance. This has implications for improving maternal healthcare utilization in SSA. ORIGINALITY/VALUE: The paper moves beyond poor access to maternal health services in SSA and proposes a framework for providing sustainable solutions.


Subject(s)
Financial Support , Income/statistics & numerical data , Maternal Health Services/statistics & numerical data , Africa South of the Sahara , Female , Health Services Accessibility/economics , Health Services Accessibility/statistics & numerical data , Humans , Maternal Health Services/economics
3.
West Indian med. j ; 10(2): 133, June 1961.
Article in English | MedCarib | ID: med-7591

ABSTRACT

An attempt is made to compare the epidemics of poliomyelitis in Jamaica in 1954, 1957 and 1960. This includes the annual incidence, the infant mortality rate in relation to the poliomyelitis attack rate, the distribution of cases by age and parish, the fatality rate by age and the incidence of paralytic and non-paralytic disease. Prior to 1954 epidemic there was serological evidence of Types I, II, and III virus infections. During the epidemic of 1954 and 1957, and since that time, only Type I Poliomyelitis Virus has been isolated locally. There has, however, been serological evidence of Types I, II and III infections since 1957. An attempt has been made to estimate the effectiveness of Salk Immunization. It is suggested that a continued study of antibody levels in the population should be made, the failing of which would be indication for inauguration of further immunization, possible using Live Virus Vaccine (AU)


Subject(s)
Humans , Poliomyelitis/epidemiology , Age Factors , Poliovirus Vaccine, Inactivated
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