RESUMEN
Antioxidant capacity of several drug specialities containing as mean component acetylsalicylic acid were experimentally evaluated using an enzymatic electrode, recently developed by the present authors, based on superoxide dismutase (SOD) enzyme. The precision of this method of analysis was found to be good (for drug samples RSD < or = 5%). The results were also compared with those ones by a traditional spectrofluorimetric method and by two other methods, respectively, based on cyclic and pulsed voltammetry, recently trialled by the present authors.
Asunto(s)
Antioxidantes/análisis , Aspirina/análisis , Preparaciones Farmacéuticas/análisis , Tecnología Farmacéutica/métodos , Antioxidantes/normas , Aspirina/normas , Técnicas Biosensibles , Electroquímica , Preparaciones Farmacéuticas/normas , Sensibilidad y Especificidad , Espectrometría de Fluorescencia , Superóxido Dismutasa/química , Tecnología Farmacéutica/instrumentación , Xantina Oxidasa/químicaRESUMEN
Enzymatic electrodes based on superoxide dismutase (SOD) biosensors, working both in aqueous and non-aqueous solutions, recently developed by the present authors, were used to experimentally evaluate the antioxidant capacity of several phytotherapeutic diet integrators. The precision of this method of analysis was found to be reasonable (R. S. D. < or = 10%). The results were also compared with those obtained using a traditional spectrophotometric method as well as a spectrofluorimetric method described in literature. Lastly, the comparison was extended to another method based on cyclic voltammetry currently being trialled by the present authors.
Asunto(s)
Antioxidantes/análisis , Técnicas Biosensibles/métodos , Fitoterapia , Técnicas Biosensibles/instrumentación , Electroquímica/métodos , Espectrometría de Fluorescencia/métodosRESUMEN
Administration of rHuIFN-alpha A/D and rMuIFN-gamma as single agents to tumor-bearing mice resulted in a dose-related antitumor effect in each of the six models studied. When the IFNs were given in combination, the effects varied between the tumor systems. No increase in efficacy was seen in mice bearing B16-F10 melanoma or M5076 reticulum cell sarcoma while additive antitumor activity was shown in the KA31 fibrosarcoma and P388 leukemia systems. Mice inoculated with L1210 lymphoma or colon 38 carcinoma, however, revealed enhanced efficacy which was greater than additive. The data also reveal that combination of IFNs alpha and gamma administered to normal and tumor-bearing mice resulted in toxicity which was not predicted by the appropriate doses of the single agents. These studies suggest that combination of IFNs alpha and gamma may provide greater therapeutic utility than the single agents and underscore the need for additional, carefully designed preclinical and clinical efforts.
Asunto(s)
Interferón Tipo I/administración & dosificación , Interferón gamma/administración & dosificación , Neoplasias Experimentales/terapia , Animales , Ensayos de Selección de Medicamentos Antitumorales , Quimioterapia Combinada , Femenino , Interferón Tipo I/toxicidad , Interferón gamma/toxicidad , Ratones , Ratones Endogámicos , Proteínas RecombinantesRESUMEN
The in vivo anti-tumor effects of a recombinant human hybrid interferon alpha, rHuIFN-alpha A/D, and recombinant murine interferon gamma (rMuIFN-gamma) were evaluated against experimental hepatic metastases and s.c. tumor growth of the murine reticulum cell sarcoma M5076. The 2 interferons were equally active in preventing experimental hepatic metastases. However, the interferons differed in their relative ability to influence the growth of the same tumor when treatment was initiated following injection of tumor cells. Greater efficacy was obtained in the treatment of metastatic foci in the liver with rHuIFN-alpha A/D, while rMuIFN-gamma was more active in the therapy of an s.c. growing M5076 tumor. These results demonstrate that the same tumor growing at different sites can have different relative sensitivities to IFN-alpha and IFN-gamma.
Asunto(s)
Interferón Tipo I/uso terapéutico , Interferón gamma/uso terapéutico , Neoplasias Hepáticas Experimentales/secundario , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/secundario , Ratones , Ratones Endogámicos C57BL , Especificidad de Órganos , Proteínas Recombinantes/uso terapéuticoRESUMEN
The in vivo anti-tumor activity of 2 recombinant cytokines, interleukin-2 (rIL-2) and human hybrid interferon alpha (rHuIFN-alpha A/D), were tested using the murine reticulum cell sarcoma M5076. Experimental hepatic metastases, following i.v. injection of tumor cells, and tumor growth and spontaneous metastases, following s.c. injection of tumor cells, were inhibited to a greater extent in mice treated with a combination of these cytokines than in animals treated with either one alone. When used in conjunction with surgical removal of the s.c. tumor, treatment of mice with both cytokines significantly prolonged survival of tumor-bearing animals. Injection of normal mice with a combination of cytokines, but not with either cytokine alone, resulted in a marked increase in cytotoxic activity of hepatic effector cells. The effector cells in these mice appeared to be NK cells since this enhanced cytotoxicity was markedly reduced in animals treated in vivo with anti-asialo GM1 or in NK-deficient beige mice. Furthermore, no in vivo efficacy was observed in M5076-bearing beige mice treated with these cytokines. Thus, injection of mice with rIL-2 and rHuIFN-alpha A/D results in the induction of an NK-cell-like population in the liver with enhanced cytotoxic activity that correlates with the observed anti-tumor activity in vivo in this murine model. These results suggest that combinations of cytokines, in particular IFN-alpha and IL-2, can be effectively used in combination for the treatment of tumors and/or metastases.