RESUMO
BACKGROUND: The phytocannabinoid cannabidiol (CBD) exhibits antioxidant and antiinflammatory properties. The present study was designed to explore its effects in a mouse model of sepsis-related encephalitis by intravenous administration of lipopolysaccharide (LPS). METHODS: Vascular responses of pial vessels were analyzed by intravital microscopy and inflammatory parameters measured by qRT-PCR. RESULTS: CBD prevented LPS-induced arteriolar and venular vasodilation as well as leukocyte margination. In addition, CBD abolished LPS-induced increases in tumor necrosis factor-alpha and cyclooxygenase-2 expression as measured by quantitative real time PCR. The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD. CONCLUSIONS: These data highlight the antiinflammatory and vascular-stabilizing effects of CBD in endotoxic shock and suggest a possible beneficial effect of this natural cannabinoid.
Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Canabidiol , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Pia-Máter/irrigação sanguínea , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/fisiologia , Encéfalo , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Circulação Cerebrovascular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Inflamação/patologia , Leucócitos/citologia , Leucócitos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia/métodos , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: The prognosis of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) is very heterogeneous. PATIENTS AND METHODS: We analyzed the prognostic value of several genes in a cohort of 85 MDS and AML patients. RESULTS: Overexpression of glycogen synthase 1 and macrophage migration inhibitory factor genes had an adverse outcome in multivariate analysis (P = .003 and P < .001, respectively). Furthermore, the higher expression of myelocytomatosis oncogene was associated with a lower response to azacitidine (P = .03). CONCLUSION: In the current study we identified a specific gene expression profile as prognostic factors for response to azacitidine and survival in MDS and AML.