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1.
Int J Infect Dis ; 101: 326-333, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33017696

RESUMO

OBJECTIVES: This systematic review aims to qualitatively synthesize existing evidence on the efficacy of HIV interventions in African fishing communities. METHODS: Five databases (NCBI PubMed, EMBASE, Web of Science Core Collection, The Cochrane Library, and CABI Global Health Database) were searched in March 2019 for eligible studies. All peer-reviewed papers with a defined HIV intervention explicitly mentioning African fishing communities were included. Outcomes included any measure of the efficacy of HIV interventions. RESULTS: Of 22,289 search results, data was extracted from 25 eligible studies that passed critical appraisal; seven involved HIV prevention, six HIV testing and counseling, three treatment, and nine combinations of more than one intervention. Findings include a high coverage of safe male circumcision (SMC) but low condom use among fisher folk, and a preference for PrEP over other HIV prevention services. Uptake of HIV testing and ART coverage are below levels required to reach UNAIDS 90-90-90 targets, and there is a high demand for ART and HIV self-testing kits. CONCLUSIONS: Greater provision of services to combat HIV, specifically amongst fishing communities, is required; there is limited information on retaining fisher folk in care and achieving an undetectable viral load. Interventions tailored to individual fishing populations, offered in parallel to education or counseling services are likely to be most effective. Use of innovations, including mobile health and medical drones, could assist these hard-to-reach populations. Our findings will inform future HIV service provision in fishing communities.


Assuntos
Pesqueiros/estatística & dados numéricos , Infecções por HIV/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Aconselhamento , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Programas de Rastreamento , Carga Viral
2.
Biochem Pharmacol ; 174: 113823, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31987856

RESUMO

Supressed levels of intracellular cAMP have been associated with malignancy. Thus, elevating cAMP through activation of adenylyl cyclase (AC) or by inhibition of phosphodiesterase (PDE) may be therapeutically beneficial. Here, we demonstrate that elevated cAMP levels suppress growth in C6 cells (a model of glioma) through treatment with forskolin, an AC activator, or a range of small molecule PDE inhibitors with differing selectivity profiles. Forskolin suppressed cell growth in a PKA-dependent manner by inducing a G2/M phase cell cycle arrest. In contrast, trequinsin (a non-selective PDE2/3/7 inhibitor), not only inhibited cell growth via PKA, but also stimulated (independent of PKA) caspase-3/-7 and induced an aneuploidy phenotype. Interestingly, a cocktail of individual PDE 2,3,7 inhibitors suppressed cell growth in a manner analogous to forskolin but not trequinsin. Finally, we demonstrate that concomitant targeting of both AC and PDEs synergistically elevated intracellular cAMP levels thereby potentiating their antiproliferative actions.


Assuntos
Proliferação de Células/fisiologia , AMP Cíclico/metabolismo , Glioma/metabolismo , Inibidores do Crescimento/farmacologia , Líquido Intracelular/metabolismo , Adenilil Ciclases/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colforsina/farmacologia , Glioma/patologia , Humanos , Líquido Intracelular/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Ratos
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