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1.
FASEB J ; 27(8): 3113-22, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23629861

RESUMO

Nonsegmental vitiligo (NSV) is characterized by loss of inherited skin color. The cause of the disease is still unknown despite accumulating in vivo and in vitro evidence of massive epidermal oxidative stress via H2O2 and peroxynitrite (ONOO(-)) in affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Strictly segmental vitiligo (SSV) with dermatomal distribution is a rare entity, often associated with stable outcome. Recently, it was documented that this form can be associated with NSV (mixed vitiligo). We here asked the question whether ROS and possibly ONOO(-) could be players in the pathogenesis of SSV. Our in situ results demonstrate for the first time epidermal biopterin accumulation together with significantly decreased epidermal catalase, thioredoxin/thioreoxin reductase, and MSRA/MSRB expression. Moreover, we show epidermal ONOO(-) accumulation. In vivo FT-Raman spectroscopy reveals the presence of H2O2, methionine sulfoxide, and tryptophan metabolites; i.e., N-formylkynurenine and kynurenine, implying Fenton chemistry in the cascade (n=10). Validation of the basic data stems from successful repigmentation of skin and eyelashes in affected individuals, regardless of SSV or segmental vitiligo in association with NSV after reduction of epidermal H2O2 (n=5). Taken together, our contribution strongly supports H2O2/ONOO-mediated stress in the pathogenesis of SSV. Our findings offer new treatment intervention for lost skin and hair color.


Assuntos
Catalase/metabolismo , Pestanas/metabolismo , Peróxido de Hidrogênio/metabolismo , Ácido Peroxinitroso/metabolismo , Pele/metabolismo , Vitiligo/metabolismo , Adolescente , Adulto , Biopterinas/metabolismo , Catalase/uso terapêutico , Criança , Pré-Escolar , Ativação Enzimática/efeitos da radiação , Epiderme/metabolismo , Epiderme/patologia , Pestanas/efeitos dos fármacos , Pestanas/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nitratos/metabolismo , Oxirredução/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia , Pigmentação da Pele/efeitos dos fármacos , Análise Espectral Raman , Raios Ultravioleta , Vitiligo/tratamento farmacológico , Vitiligo/patologia , Adulto Jovem
2.
Cell Biol Int ; 38(4): 412-25, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24155089

RESUMO

Modern non-thermal atmospheric pressure plasma sources enable controllable interaction with biological systems. Their future applications - e.g. wound management - are based on their unique mixture of reactive components sparking both stimulatory as well as inhibitory processes. To gain detailed understanding of plasma-cell interaction and with respect to risk awareness, key mechanisms need to be identified. This study focuses on the impact of an argon non-thermal atmospheric pressure plasma jet (kINPen 09) on human HaCaT keratinocytes. With increasing duration, cell viability decreased. In accordance, cells accumulated in G2/M phase within the following 24 h. DNA single-strand breaks were detected immediately after treatment and receded in the aftermath, returning to control levels after 24 h. No directly plasma-related DNA double-strand breaks were detected over the same time. Concurrently, DNA synthesis decreased. Coincident with treatment time, an increase in intracellular 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCFDA) conversion increased reactive oxygen species (ROS) levels. The radical scavenging activity of culture medium crucially influenced these effects. Thus, ROS changed DNA integrity, and the effectiveness of cellular defence mechanisms characterises the interaction of non-thermal plasma and eukaryotic cells. Effects were time-dependent, indicating an active response of the eukaryotic cells. Hence, a stimulation of eukaryotic cells using short-term non-thermal plasma treatment seems possible, eg in the context of chronic wound care. Long-term plasma treatments stopped in cell proliferation and apoptosis, which might be relevant in controlling neoplastic conditions.


Assuntos
Queratinócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Gases em Plasma/farmacologia , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Quebras de DNA de Cadeia Simples/efeitos dos fármacos , Fluoresceínas/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
3.
Psychon Bull Rev ; 19(3): 405-11, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22450570

RESUMO

In the present study we examined, first, whether voluntary and involuntary attention manifest differently in people who differ in impulsivity (measured with the Barratt Impulsivity Scale). For Experiment 1, we used the spatial cueing task with informative and noninformative spatial cues to probe voluntary and involuntary attention, respectively. We found that participants with high impulsivity scores exhibited larger involuntary attention effects, whereas participants with low impulsivity scores exhibited larger voluntary attention effects. For Experiment 2, we used the correlated-flanker task to determine whether the differences between groups in Experiment 1 were due to high-impulsive participants being less sensitive to the display contingencies or to high-impulsive participants having a greater spread of spatial attention. Surprisingly, high-impulsive participants showed a greater sensitivity to contingencies in the environment (correlated-flanker effect). Our results illustrate one situation in which involuntary attention associated with high impulsivity can play a useful role.


Assuntos
Atenção/fisiologia , Comportamento Impulsivo/psicologia , Percepção Espacial/fisiologia , Adolescente , Adulto , Sinais (Psicologia) , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Testes Neuropsicológicos , Adulto Jovem
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