RESUMEN
BACKGROUND: Thymosin-alpha 1 is a biological response modifier that has been used clinically, alone and in combination with interferon-alpha for the treatment of chronic hepatitis B viral infection. Both immunomodulatory and immediate intracellular mechanisms have been postulated to explain the effect of these two agents on HBV-infected hepatocytes. METHODS: In this study, hepatitis B transfected HepG2 hepatoblastoma cells (HepG2-Nu2), derived from 2.2.15 cells, were used as an in vitro model to determine the efficacy of thymosin-alpha 1 and interferon-alpha, individually and combined, as proliferation inhibitors of HBV-infected cells. For comparison, parental HepG2 cells and an SV40-transfected HepG2 cell line (HepG2P9T2) were also evaluated. RESULTS: In a clonogenic soft agar assay, thymosin-alpha 1 inhibited the anchorage-independent growth of the HepG2-Nu2 cells by 40% compared with untreated controls, but did not inhibit parental HepG2 or HepG2P9T2 clonal growth. The response was dose dependent over concentrations spanning three log units. In comparison, 10000 units/ml of interferon-alpha inhibited parental HepG2, HepG2-N4Z and HepG2P9T2 by 33%, 41% and 87%, respectively. The combination of thymosin-alpha 1 and interferon-alpha consistently inhibited HepG2-Nu2 clonal growth more effectively than either treatment alone, reaching maximum inhibition levels of 51%. CONCLUSIONS: Thymosin-alpha 1 specifically inhibits the tumorigenic growth of HBV-transfected HepG2 cells in contrast to the general inhibition displayed by interferon-alpha. This panel of cell lines may be an important resource for dissecting the mechanism by which thymosin, alone or in combination with other drugs, influences HBV-infected hepatocytes and/or HBV-associated carcinoma.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Antivirales/farmacología , Virus de la Hepatitis B/efectos de los fármacos , Hepatoblastoma/tratamiento farmacológico , Interferón-alfa/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Timosina/análogos & derivados , Adyuvantes Inmunológicos/administración & dosificación , Antivirales/administración & dosificación , División Celular/efectos de los fármacos , Transformación Celular Viral , ADN Viral/biosíntesis , ADN Viral/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Ensayo de Inmunoadsorción Enzimática , Virus de la Hepatitis B/genética , Hepatoblastoma/virología , Humanos , Interferón-alfa/administración & dosificación , Neoplasias Hepáticas/virología , Timalfasina , Timosina/administración & dosificación , Timosina/farmacología , Transfección , Células Tumorales Cultivadas , Replicación Viral/efectos de los fármacosRESUMEN
From the histochemical studies of the mucus factor in normal controls and 10 cases with Hirschsprung's disease including 5 with enterocolitis, using Alcian blue-PAS method, we concluded that ganglionosis had no effect on the secretion of mucus. The presence of qualitative changes in the type of mucopolysaccharides, demonstrated as an increase in the sulphated group especially in cases with enterocolitis, was secondary to the chronic obstruction. These nonspecific changes might diminish the protecting mechanism of the mucous membrane. Quantitative changes were seen to be related to the severity of the enterocolitis.
Asunto(s)
Colon/metabolismo , Enterocolitis Seudomembranosa/complicaciones , Glicosaminoglicanos/metabolismo , Megacolon/metabolismo , Azul Alcián , Colon/patología , Humanos , Mucosa Intestinal/metabolismo , Megacolon/complicaciones , Megacolon/patología , Moco/metabolismo , Reacción del Ácido Peryódico de SchiffRESUMEN
A case of a 7-mo old male infant with a diverticulum of the left ventricle is reported. The diverticulum has been successfully resected and the defect of the diaphragm closed. Repair of the associated huge ventral hernia has been postponed to be done in stages.