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1.
J R Soc Interface ; 11(95): 20140097, 2014 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-24647908

RESUMO

Previous observations suggest that static magnetic field (SMF)-exposure acts on living organisms partly through reactive oxygen species (ROS) reactions. In this study, we aimed to define the impact of SMF-exposure on ragweed pollen extract (RWPE)-induced allergic inflammation closely associated with oxidative stress. Inhomogeneous SMF was generated with an apparatus validated previously providing a peak-to-peak magnetic induction of the dominant SMF component 389 mT by 39 T m(-1) lateral gradient in the in vivo and in vitro experiments, and 192 mT by 19 T m(-1) in the human study at the 3 mm target distance. Effects of SMF-exposure were studied in a murine model of allergic inflammation and also in human provoked skin allergy. We found that even a single 30-min exposure of mice to SMF immediately following intranasal RWPE challenge significantly lowered the increase in the total antioxidant capacity of the airways and decreased allergic inflammation. Repeated (on 3 consecutive days) or prolonged (60 min) exposure to SMF after RWPE challenge decreased the severity of allergic responses more efficiently than a single 30-min treatment. SMF-exposure did not alter ROS production by RWPE under cell-free conditions, while diminished RWPE-induced increase in the ROS levels in A549 epithelial cells. Results of the human skin prick tests indicated that SMF-exposure had no significant direct effect on provoked mast cell degranulation. The observed beneficial effects of SMF are likely owing to the mobilization of cellular ROS-eliminating mechanisms rather than direct modulation of ROS production by pollen NAD(P)H oxidases.


Assuntos
Asma , Dermatite Atópica , Magnetoterapia/métodos , Campos Magnéticos , Rinite Alérgica Sazonal , Adulto , Animais , Asma/metabolismo , Asma/patologia , Asma/terapia , Linhagem Celular , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Dermatite Atópica/terapia , Modelos Animais de Doenças , Método Duplo-Cego , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/terapia , Magnetoterapia/instrumentação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio , Rinite Alérgica Sazonal/metabolismo , Rinite Alérgica Sazonal/patologia , Rinite Alérgica Sazonal/terapia
2.
Bioorg Med Chem Lett ; 23(12): 3576-9, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23659860

RESUMO

Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(ß-D-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC50 values ranging from 4 to 11 µM at 37 °C. The inhibitory activities were maintained, although somewhat lowered, at a temperature of 4 °C as well. Three further derivatives displayed similar activities against at least one of the three strains. Low cytotoxicities of the active compounds, tested on confluent HeLa, Vero and peritoneal macrophage cell cultures, resulted in significantly higher selectivity indices (SI) than that of the reference drug benznidazole. Remarkably, several molecules of the tested panel strongly inhibited the parasite release from T. cruzi infected HeLa cell cultures suggesting an effect against the intracellular development of T. cruzi amastigotes as well.


Assuntos
Antiprotozoários/farmacologia , Dissulfetos/farmacologia , Glicosídeos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Derivados de Benzeno/farmacologia , Doença de Chagas/tratamento farmacológico , Chlorocebus aethiops , Dissulfetos/química , Glicosídeos/química , Células HeLa , Humanos , Trypanosoma cruzi/crescimento & desenvolvimento , Células Vero
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