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Medicinas Complementárias
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1.
J Infect Dis ; 214(1): 114-21, 2016 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-26984141

RESUMEN

BACKGROUND: Mucormycosis is a destructive invasive mold infection afflicting patients with diabetes and hematologic malignancies. Patients with diabetes are often treated with statins, which have been shown to have antifungal properties. We sought to examine the effects of statins on Rhizopus oryzae, a common cause of mucormycosis. METHODS: Clinical strains of R. oryzae were exposed to lovastatin, atorvastatin, and simvastatin and the minimum inhibitory concentrations (MICs) were determined. R. oryzae germination, DNA fragmentation, susceptibility to oxidative stress, and ability to damage endothelial cells were assessed. We further investigated the impact of exposure to lovastatin on the virulence of R. oryzae RESULTS: All statins had MICs of >64 µg/mL against R. oryzae Exposure of R. oryzae to statins decreased germling formation, induced DNA fragmentation, and attenuated damage to endothelial cells independently of the expression of GRP78 and CotH. Additionally, R. oryzae exposed to lovastatin showed macroscopic loss of melanin, yielded increased susceptibility to the oxidative agent peroxide, and had attenuated virulence in both fly and mouse models of mucormycosis. CONCLUSIONS: Exposure of R. oryzae to statins at concentrations below their MICs decreased virulence both in vitro and in vivo. Further investigation is warranted into the use of statins as adjunctive therapy in mucormycosis.


Asunto(s)
Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Mucormicosis/tratamiento farmacológico , Rhizopus/efectos de los fármacos , Virulencia/efectos de los fármacos , Animales , Atorvastatina/farmacología , Atorvastatina/uso terapéutico , Dípteros/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Femenino , Humanos , Lovastatina/farmacología , Lovastatina/uso terapéutico , Ratones , Pruebas de Sensibilidad Microbiana , Simvastatina/farmacología , Simvastatina/uso terapéutico , Esporas Fúngicas/efectos de los fármacos , Texas
2.
Biol Trace Elem Res ; 150(1-3): 391-5, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22895809

RESUMEN

A growing body of evidence suggests that interactions between pollen grains and environmental pollutants, especially air pollutants, could be of critical importance with regard to the increase in allergic responses observed in the past decades. Using birch pollen grains (BPG), a major allergy source in European countries, and lead (Pb), a highly toxic metal trace element (MTE) present in urban areas, the immune response of human epithelial cells exposed to BPG or to Pb-associated BPG was compared. The cellular response after exposure either to BPG, BPG exposed to 30 mg/L of Pb (BPG-30), or BPG exposed to 60 mg/L of Pb (BPG-60) was evaluated after two time lapses (2 and 6 h) by measuring mRNA levels of four mediators, including two inflammatory (interleukin-8 and interleukin-6) and two allergic (interleukin-5 [IL-5] and interleukin-13) cytokines. After 2 h of exposure, significant upregulation of the IL-5 gene was observed after exposure to BPG-60 in comparison with exposure to BPG and BPG-30 (N (IL-5) = 1.9, Mann-Whitney test, p = 0.003). After 6 h of exposure, significant upregulation of the IL-5 gene was observed after exposure to BPG-30 with N (IL-5) = 1.8 and to BPG-60 with N (IL-5) = 2.3 (Mann-Whitney test, p = 0.0029) in comparison with exposure to BPG. This first attempt to investigate the influence of pollution by MTE on pollen grain showed a dose-time-dependent increase in IL-5 gene expression after exposure to BPG combined to Pb.


Asunto(s)
Alérgenos/efectos adversos , Betula/efectos adversos , Plomo/toxicidad , Polen/efectos adversos , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Rinitis Alérgica Estacional/inmunología , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Alérgenos/química , Antígenos de Plantas/efectos adversos , Antígenos de Plantas/análisis , Betula/química , Línea Celular , Francia , Humanos , Interleucina-5/biosíntesis , Interleucina-5/genética , Interleucina-5/metabolismo , Cinética , Plomo/análisis , Polen/química , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/inmunología , Alveolos Pulmonares/metabolismo , ARN Mensajero/metabolismo , Mucosa Respiratoria/metabolismo , Rinitis Alérgica Estacional/inducido químicamente , Regulación hacia Arriba/efectos de los fármacos
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