RESUMO
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4(+)CD25(+)FoxP3(+)) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39(+)CD4(+)CD25(+)FoxP3(+) Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients.
Assuntos
Antígenos CD/metabolismo , Apirase/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Resistência a Medicamentos/imunologia , Metotrexato/uso terapêutico , Linfócitos T Reguladores/imunologia , 5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Biomarcadores/metabolismo , Resistência a Medicamentos/efeitos dos fármacos , Humanos , Contagem de Linfócitos , Metotrexato/farmacologia , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/efeitos dos fármacos , Células Th1/imunologia , Células Th17/imunologiaRESUMO
Ultraviolet-B radiation (UVBR) affects plants in many important ways, including reduction of growth rate and primary productivity, and changes in ultrastructures. Rice (Oryza sativa) is one of the most cultivated cereals in the world, along with corn and wheat, representing over 50% of agricultural production. In this study, we examined O. sativa plants exposed to ambient outdoor radiation and laboratory-controlled photosynthetically active radiation (PAR) and PAR + UVBR conditions for 2 h/day during 30 days of cultivation. The samples were studied for morphological and ultrastructural characteristics, and physiological parameters. PAR + UVBR caused changes in the ultrastructure of leaf of O. sativa and leaf morphology (leaf index, leaf area and specific leaf area, trichomes, and papillae), plant biomass (dry and fresh weight), photosynthetic pigments, phenolic compounds, and protein content. As a photoprotective acclimation strategy against PAR + UVBR damage, an increase of 66.24% in phenolic compounds was observed. Furthermore, PAR + UVBR treatment altering the levels of chlorophylls a and b, and total chlorophyll. In addition, total carotenoid contents decreased after PAR + UVBR treatment. The results strongly suggested that PAR + UVBR negatively affects the ultrastructure, morphology, photosynthetic pigments, and growth rates of leaf of O. sativa and, in the long term, it could affect the viability of this economically important plant.
Assuntos
Oryza/fisiologia , Oryza/ultraestrutura , Raios Ultravioleta , Oryza/efeitos da radiação , Fotossíntese/efeitos da radiação , Pigmentos Biológicos/metabolismo , Epiderme Vegetal/citologia , Epiderme Vegetal/efeitos da radiação , Epiderme Vegetal/ultraestrutura , Folhas de Planta/anatomia & histologia , Folhas de Planta/efeitos da radiação , Proteínas de Plantas/metabolismo , Polifenóis/metabolismo , SolubilidadeRESUMO
Este artigo tem como objetivos principais revisar os efeitos adversos da hiperglicemia entre os pacientes hospitalizados, informar os níveis glicêmicos atualmente recomendados e orientar o tratamento adequado desta condição.
Assuntos
Humanos , Masculino , Feminino , Índice Glicêmico , Hiperglicemia , Pacientes InternadosRESUMO
Relata-se um caso de cetoacidose diabética que apresentou edema cerebral no transcorrer do tratamento. O paciente era um menino de 5 anos de idade com história de diabetes mellitus há 3 anos, em tratamento com insulina NPH U-40 12 unidades, subcutâneo, antes do café da manhä, com antecedentes de uma internaçäo hospitalar por cetoacidose diabética e duas por hipoglicemia. O fator de descompensaçäo do diabetes foi uma sinusite maxilar esquerda, diagnosticada por raio-X de seus da face. O edema cerebral foi diagnosticado por tomografia computadorizada do crânio. Esta complicaçäo que levou o paciente ao óbito se atribuiu a queda brusca da glicemia pelo uso de insulina em infusäo. Os médicos devem ser alertados para as condiçöes exigidas quando se faz uso dessa técnica de terapêutica