RESUMO
Acute graft-versus-host diseases (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). T helper 1 (Th1)-type cytokines such as interferon-gamma or tumor necrosis factor-alpha have been implicated in the pathogenesis of acute GVHD. TAK-603 is a new quinoline derivative, which is now in clinical trials for use as a disease-modifying antirheumatic drug. In preclinical studies, it inhibited delayed-type hypersensitivity, but not Arthus-type reaction, in mice, and selectively suppressed Th1 cytokine production. Thus, the present study was designed to investigate whether the Th1 inhibitor (TAK-603) ameliorates lethal acute GVHD in a mouse model. Administration of TAK-603 into BALB/c mice given 10 Gy total body irradiation followed by transplantation of bone marrow and spleen cells from C57BL/6 mice markedly reduced the mortality in association with minimal signs of GVHD pathology in the liver, intestine, and skin. TAK-603 reduced not only the production of Th1-type cytokines, but also the proportion of Th1 cells in CD4(+) helper T cells in this GVHD mouse model. These results suggest that TAK-603 could be a potent therapeutic agent for acute lethal GVHD.
Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Quinolinas/uso terapêutico , Células Th1/efeitos dos fármacos , Triazóis/uso terapêutico , Doença Aguda , Administração Oral , Animais , Transplante de Medula Óssea/efeitos adversos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Intestinos/patologia , Fígado/patologia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Quinolinas/administração & dosagem , Quinolinas/farmacologia , Quimera por Radiação , Pele/patologia , Baço/transplante , Células Th1/metabolismo , Transplante Homólogo/efeitos adversos , Triazóis/administração & dosagem , Triazóis/farmacologiaRESUMO
A case of lead poisoning in a female art conservator is reported. The patient had experienced excessive lead exposure while restoring an antique Peruvian tapestry from the Chancay period (1000 to 1500 AD) using a powdered pigment (cinnabar), which had been recovered from the same tomb in which the tapestry was found. Over two months, prominent neurological, gastrointestinal, and diffuse muscular symptoms developed. Severe anemia accompanied by basophilic stippling of RBCs led to the diagnosis of lead poisoning, which was confirmed by markedly elevated blood lead levels (up to 130 micrograms/dL) and impairment of heme synthetic enzymes. The severity of the intoxication necessitated chelation therapy. Chemical analysis of the antique powdered pigment showed it to be the source of lead exposure, in that it contained about 1% lead.