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Métodos Terapéuticos y Terapias MTCI
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Antiviral Res ; 25(2): 105-22, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7847873


A major component of a US Army Medical Research and Development Command-supported program to discover and develop new drugs for the treatment of Rift Valley fever, sandfly fever, and Crimean-Congo hemorrhagic fever has been to study candidate test materials against hepatotropic infections of C57BL/6 mice induced by the related but less biohazardous Punta Toro virus (PTV). The effects of 75 compounds, some of which were considered immunomodulators in their primary mechanism of activity, were studied in the PTV infection model. Of these, ribavirin, ribamidine, ribavirin 2',3',5'-triacetate, tiazofurin, tiazofurin-5'-monophosphate, tiazofurin-2',3',5'-triacetate, selenazofurin, pyrazofurin, 3-deazaguanine, and 3-deazaguanosine were considered significantly inhibitory, acting against the infection by a direct antiviral (non-immunomodulatory) fashion. These compounds had therapeutic indices (TI) ranging from > or = 5 to 65, using increased survivors as the evaluation parameter. Immunomodulators considered significantly inhibitory to this infection were poly (ICLC), ampligen, human recombinant interferon-alpha-A/D, MVE-1, MVE-2, AM-3, AM-5, mannozym, bropirimine, CL246,738, phenyleneamine, and 7-thia-8-oxoguanosine. Utilizing increased survivor numbers as measure of activity, these inhibitors had TI ranging from > or = 16 to 1000. Other antiviral effects exerted by the active compounds included reduction of hepatic icterus, lowered serum glutamic oxaloacetic and pyruvic acid transaminases, and inhibition of recoverable serum and liver virus titers. The active immunomodulators were significantly effective when therapy was initiated as late as 48 h after virus inoculation, at a time when clinical signs of the PTV disease were being manifested in the animal.

Antivirales/uso terapéutico , Infecciones por Bunyaviridae/tratamiento farmacológico , Phlebovirus/efectos de los fármacos , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Alanina Transaminasa/sangre , Animales , Antivirales/farmacología , Aspartato Aminotransferasas/sangre , Infecciones por Bunyaviridae/enzimología , Infecciones por Bunyaviridae/terapia , Evaluación Preclínica de Medicamentos , Hígado/enzimología , Hígado/virología , Ratones , Ratones Endogámicos C57BL , Seguridad
Cancer Res ; 45(3): 1058-65, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3155990


In this report, we describe the immunomodulatory characteristics of poly(I,C)-LC, a synthetic, double-stranded nucleic acid polymer, polyinosinic-polycytidylic acid, that is complexed with poly-L-lysine and solubilized by the addition of carboxymethylcellulose. We consistently observed, both in vitro and in vivo, stimulation of macrophage cytotoxicity and augmentation of natural killer-cell activity by poly(I,C)-LC. This immunomodulator also increased the allogeneic mixed-lymphocyte response, without any blastogenic effect on responder cells cultured in the absence of allogeneic stimulator cells. Further, the addition of poly(I,C)-LC to an allogeneic mixed-lymphocyte tumor reaction did not stimulate the development of cytotoxic effector T-cells. Poly(I,C)-LC did, however, have adjuvant activity when admixed with irradiated tumor cells in the immunization of syngeneic mice. Unlike classic adjuvants, poly(I,C)-LC also enhanced the development of specific cytotoxic T-lymphocytes when it was injected either i.v. or i.p. in conjunction with a vaccine delivered at an intradermal site. The results indicate that poly(I,C)-LC has considerable potential as an immunotherapeutic agent, with the ability not only to induce macrophage and NK cell activation but also to stimulate specific cytotoxic T-lymphocytes.

Adyuvantes Inmunológicos/farmacología , Carboximetilcelulosa de Sodio/farmacología , Inductores de Interferón/farmacología , Metilcelulosa/análogos & derivados , Péptidos/farmacología , Poli I-C/farmacología , Polilisina/farmacología , Animales , Citotoxicidad Inmunológica/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Prueba de Cultivo Mixto de Linfocitos , Activación de Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Linfocitos T/efectos de los fármacos
Leuk Res ; 6(1): 89-95, 1982.
Artículo en Inglés | MEDLINE | ID: mdl-6803071


Studies on the chemotherapeutic potential of methyl-CCNU on experimental leukemias were undertaken. A number of murine transplantable in vivo lines (chemical carcinogen-induced T and B leukemias; radiation- and viral-induced T leukemias of C57BL/6, C3H/eb and SJL/J origin; radiation-induced myeloid leukemias and spontaneous reticulum cell neoplasms of SJL/J mine) were used in these studies. The optimal dose of methyl-CCNU and optimal timing of administration were extensively investigated on two sample lines of T cell leukemias of C57BL/6 mice. Leukemic cell eradication could be achieved in almost all of the different leukemias treated, irrespective of whether induction was brought about by chemical or physical means or due to a viral leukemogenic agent. Studies undertaken to elucidate the effect of methyl-CCNU on the establishment of preleukemic cells following induction of leukemia by the radiation leukemia virus (RadLV) or by total body irradiation, indicated the oncostatic effect of methyl-CCNU on early preleukemic cells.

Leucemia Experimental/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Lesiones Precancerosas/tratamiento farmacológico , Semustina/uso terapéutico , 9,10-Dimetil-1,2-benzantraceno , Animales , Recuento de Células Sanguíneas , Peso Corporal , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Femenino , Hematócrito , Leucemia Experimental/etiología , Leucemia Inducida por Radiación/tratamiento farmacológico , Ratones , Ratones Endogámicos , Lesiones Precancerosas/etiología , Retroviridae