Assuntos
Macroglobulinemia de Waldenstrom/epidemiologia , Macroglobulinemia de Waldenstrom/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Programa de SEER , Análise de Sobrevida , Estados UnidosRESUMO
Lipoic acid is a disulfhydryl-containing compound used in clinical medicine and in experimental models as an antioxidant. We developed a stable isotope dilution capillary gas chromatography/mass spectrometry assay for lipoic acid. We assayed a panel of the metabolites of transmethylation and transsulfuration 30 min after injecting 100 mg/kg lipoic acid in a rat model. Lipoic acid values rose 1000-fold in serum and 10-fold in liver. A methylated metabolite of lipoic acid was also detected but not quantitated. Lipoic acid injection caused a massive increase in serum S-adenosylhomocysteine and marked depletion of liver S-adenosylmethionine. Serum total cysteine was depleted but liver cysteine and glutathione were maintained. Serum total homocysteine doubled, with increases also in cystathionine, N,N-dimethylglycine, and alpha-aminobutyric acid. In contrast, after injection of 2-mercaptoethane sulfonic acid, serum total cysteine and homocysteine were markedly depleted and there were no effects on serum S-adenosylmethionine or S-adenosylhomocysteine. We conclude that large doses of lipoic acid displace sulfhydryls from binding sites, resulting in depletion of serum cysteine, but also pose a methylation burden with severe depletion of liver S-adenosylmethionine and massive release of S-adenosylhomocysteine. These changes may have previously unrecognized deleterious effects that should be investigated in both human disease and experimental models.
Assuntos
Antioxidantes/farmacologia , Fígado/metabolismo , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Ácido Tióctico/farmacologia , Animais , Cisteína/sangue , Cisteína/deficiência , Cromatografia Gasosa-Espectrometria de Massas , Fígado/efeitos dos fármacos , Masculino , Metilação , Ratos , Ratos Sprague-Dawley , Ácido Tióctico/sangueRESUMO
The mean red blood cell volume (MCV) is usually increased in severe megaloblastic anemia due to pernicious anemia. However, during one year in a university hospital, three patients with life-threatening pancytopenia and normal MCV were proven to have severe vitamin B12 deficiency. The red blood cell distribution width was markedly increased (three times normal) and led to review of the blood smear and recognition of megaloblastosis as well as prominent red cell fragmentation. These three cases illustrate that vitamin B12 status should be evaluated in cases of pancytopenia, independent of the MCV value.
