RESUMO
Concurrent radiation and thermal injury (IRTI) was simulated in Wistar rats. For prevention of the autoinfectious complications sulacillin, a combination of ampicillin and sulbactam, was used. The use of sulacillin was started on the onset of IRTI and continued for 7 days. The drug was administered intramuscularly twice a day. It was observed that the 8-day survival of the animals increased by more than 40 per cent and the statistical levels of bacteremia and bacterial endotoxemia significantly decreased. The experiments showed that sulacillin had no side immunodepressive effect and did not aggravate the affection of the blood system. The drug was recommended for further studies to provide evidence for rational schemes of antibacterial therapy in IRTI.
Assuntos
Ampicilina/administração & dosagem , Infecções Bacterianas/prevenção & controle , Queimaduras/complicações , Lesões por Radiação/complicações , Sulbactam/administração & dosagem , Ampicilina/efeitos adversos , Animais , Combinação de Medicamentos , Masculino , Ratos , Ratos Wistar , Sulbactam/efeitos adversosRESUMO
Rats with altered microbial ecology and decreased colonization resistance due to neutropenia induced by cyclophosphamide were used as a model for estimating the effect of bacterial polysaccharides (lactulose and exopolysaccharide from Bacillus polymyxa) and fluoroquinolones (pefloxacin). Monotherapy with pefloxacin had a favourable effect both on normalization on the intestinal microflora in the rats and their hemopoiesis (decreased neutropenia). The highest correcting effect with respect to the lowered colonization resistance was observed when pefloxacin was used in combination with exopolysaccharide.
Assuntos
Bacillus , Aderência Bacteriana/fisiologia , Infecções Bacterianas/prevenção & controle , Colite/prevenção & controle , Colo/microbiologia , Ciclofosfamida , Modelos Animais de Doenças , Modelos Biológicos , Neutropenia/imunologia , Pefloxacina/administração & dosagem , Polissacarídeos Bacterianos/administração & dosagem , Adjuvantes Imunológicos , Animais , Aderência Bacteriana/efeitos dos fármacos , Infecções Bacterianas/etiologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Colite/etiologia , Colite/imunologia , Colite/microbiologia , Colo/efeitos dos fármacos , Colo/imunologia , Neutropenia/induzido quimicamente , Ratos , Ratos WistarRESUMO
The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting.
Assuntos
Aclarubicina/administração & dosagem , Crise Blástica/tratamento farmacológico , Citarabina/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Leucemia Monocítica Aguda/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de RemissãoRESUMO
Specific immunosuppressive activity of cyclosporine prepared at the National Research Centre of Antibiotics by using its original producing culture was studied. It inhibited basic cellular immune responses such as DTH and transplant vs. host and prolonged the lifespan of tumor xenografts under the kidney capsule. Cyclosporine also suppressed the humoral immunity. Its inhibitory effect on lymphocyte blast transformation induced by lectins and in mixed lymphocyte cultures was shown in vitro. Cyclosporine inhibited activity of natural killer cells and T-suppressor cells induced by concanavalin A. It was demonstrated on the models of skin allotransplantation in mice and heterotopic transplantation of the heart in rats that cyclosporine prolonged the transplant lifespan. By the main indices of the cellular immunity and in the models of the transplantation immunity, cyclosporine prepared at the National Research Centre of Antibiotics was shown to be similar to that manufactured by Sandoz.
Assuntos
Células Produtoras de Anticorpos/efeitos dos fármacos , Ciclosporina/administração & dosagem , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração/imunologia , Modelos Biológicos , Transplante de Pele/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Abdome , Animais , Células Produtoras de Anticorpos/imunologia , Sobrevivência de Enxerto/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Ratos , Linfócitos T Reguladores/imunologia , Transplante Heterotópico , Transplante HomólogoRESUMO
Novel biologically active substances were obtained from nonpathogenic for humans and free-living protozoa: Crithidia oncopelti, Trypanosoma lewisi, and Astasia longa. There were studied conditions of biosynthesis, composition and biological activity of the total lipid fraction from the protozoa species, sucrose ethers and fatty acids, the latter were isolated from A. longa--(astazilide preparation), reserve beta-1,3 glucan from A. longa (astazian preparation), and fraction of surface glycophospholipids and peptides from Crithidia oncopelti (GLP preparation). Two of three preparations studied (astazilide and GLP) are the complexes of natural substances with certain composition. Conditions of the protozoa cultivation were developed to provide standardization of the complex composition. Division of the complexes into separate components decreased or abolished the biological activity. It was established that the substances studied modify biological reactions, that is exert a systemic effect. They may be used for inhibiting the growth of experimental tumors and preventing the metastatic spreading in tumor-carrier animals. The substances obtained belong to the group of nonspecific stimulators for cellular immunity which can be used in medicine, veterinary medicine, food industry, pharmacologic industry and cosmetology.
Assuntos
Fatores Biológicos/farmacologia , Eucariotos , Lipídeos/farmacologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/toxicidade , Animais , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Fatores Biológicos/toxicidade , Crithidia , Glicoconjugados/farmacologia , Glicoconjugados/toxicidade , Humanos , Lipídeos/toxicidade , Polissacarídeos/farmacologia , Polissacarídeos/toxicidade , Trypanosoma lewisiRESUMO
Study on antitumor activity of free and liposomal anthracycline antibiotic aclarubicin in vitro and in vivo showed that liposomal aclarubicin was characterised by activity against ascitic Ehrlich carcinoma comparable to that of free aclarubicin when used in a dose of 25 mg/kg. Liposomal antibiotic had a more pronounced antimetastatic action and showed no toxicity (in a dose of 30 mg/kg). Liposomal aclarubicin had a higher activating capacity with respect to the macrophage tumoricidal properties.
Assuntos
Aclarubicina/administração & dosagem , Aclarubicina/toxicidade , Animais , Carcinoma de Ehrlich/tratamento farmacológico , Portadores de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Emulsões , Dose Letal Mediana , Leucemia P388/tratamento farmacológico , Lipossomos , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Metástase NeoplásicaRESUMO
Antisuppressant activity of aclarubicin, an anthracycline antibiotic, was studied on models of immunodepression induced in vivo by concanavalin A or associated with progressive tumor growth. In vivo in a dose of 2.5 mg/kg aclarubicin markedly lowered or completely eliminated the ability of concanavalin A to induce activity on the suppressor cells in the mouse spleen. In vitro in doses of 0.0001 to 0.01 micrograms/ml aclarubicin decreased the suppressing activity of the splenocytes from mice with solid tumors in regard to spontaneous proliferation of the lymphoid cells.
Assuntos
Aclarubicina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Divisão Celular/efeitos dos fármacos , Concanavalina A/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Neoplasias Experimentais/imunologia , Baço/citologia , Baço/efeitos dos fármacosAssuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Cuidados Críticos/métodos , Infecção Hospitalar/tratamento farmacológico , Aminoglicosídeos , Infecções Bacterianas/prevenção & controle , Congressos como Assunto , Infecção Hospitalar/prevenção & controle , Europa (Continente) , Humanos , Estados UnidosAssuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Neoplasias/tratamento farmacológico , Oncogenes/efeitos dos fármacos , Quinonas/uso terapêutico , Adjuvantes Imunológicos , Animais , Benzoquinonas , Bleomicina/uso terapêutico , Avaliação de Medicamentos , Humanos , Lactamas Macrocíclicas , Camundongos , Mitomicinas/uso terapêutico , Neoplasias/genética , Neoplasias/imunologia , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Rifabutina/análogos & derivadosAssuntos
Antibióticos Antineoplásicos/uso terapêutico , Micromonospora/metabolismo , Neoplasias Experimentais/tratamento farmacológico , Neoplasias/tratamento farmacológico , Nocardiaceae/metabolismo , Streptomyces/metabolismo , Animais , Antibióticos Antineoplásicos/biossíntese , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/classificação , Avaliação de Medicamentos , Humanos , CamundongosRESUMO
A membrane-bound glycoprotein with a molecular weight of 10000-12000 was isolated from Crithidia oncopelti and purified. The glycoprotein contained peptide, carbohydrate and lipid fragments and phosphorus. The peptide fragment was represented by 10 amino acids. The carbohydrate fragment was represented by 7 monosaccharides. The lipid part was mainly represented by stearic acid. The glycoprotein showed immunostimulating properties. It had a comitogenic effect on murine spleen cells in vitro and induced tumoricidal activity in murine peritoneal macrophages in vitro and in vivo.
Assuntos
Crithidia/metabolismo , Leucemia P388/imunologia , Leucemia Experimental/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Glicoproteínas de Membrana/imunologia , Adjuvantes Imunológicos , Aminoácidos/análise , Animais , Líquido Ascítico/citologia , Técnicas In Vitro , Glicoproteínas de Membrana/análise , Camundongos , Monossacarídeos/análise , Baço/citologia , Ácidos Esteáricos/análiseRESUMO
Platidiam, cyclophosphamide and adriamycin induced tumoricidal activity of peritoneal macrophages from patients with disseminated ovarian carcinoma when applied in the autologous tumor cells in vitro. This effect was not observed with 10 micrograms/ml concentration of 5-fluorouracil. The mice peritoneal macrophages after incubation in vitro with 0.01-1.0 micrograms/ml of aclarubicin showed cytostatic action on syngeneic and semisyngeneic P388 cells. The peritoneal macrophages from mice treated with 2.5 mu/kg of aclarubicin intraperitoneally 1-4 days before were cytotoxic for tumor cells too.
Assuntos
Antineoplásicos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Animais , Líquido Ascítico/patologia , Citotoxicidade Imunológica/efeitos dos fármacos , Citotoxicidade Imunológica/imunologia , Feminino , Humanos , Leucemia P388/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Neoplasias Ovarianas/imunologia , Cavidade Peritoneal/citologia , Células Tumorais CultivadasRESUMO
A significant decrease in resistance to infections caused by gramnegative pathogens was observed in mice with neutropenia induced by cytostatics. Efficacy of schemes for combined chemotherapy with beta-lactams, aminoglycosides and a novel peptide antibiotic was studied on model infections in mice with neutropenia. In the neutropenic mice with sepsis caused by Pseudomonas the peptide antibiotic administered parenterally in a single dose of 50 micrograms/kg provided high therapeutic activity. In combination with azlocillin, cefotaxime and amikacin the peptide antibiotic has a synergistic therapeutic action.
Assuntos
Agranulocitose/imunologia , Amicacina/administração & dosagem , Azlocilina/administração & dosagem , Cefotaxima/administração & dosagem , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Neutropenia/imunologia , Infecções por Pseudomonas/tratamento farmacológico , Animais , Sinergismo Farmacológico , Quimioterapia Combinada/administração & dosagem , Infecções por Escherichia coli/etiologia , Infecções por Escherichia coli/imunologia , Tolerância Imunológica/efeitos dos fármacos , Infecções por Klebsiella/etiologia , Infecções por Klebsiella/imunologia , Camundongos , Neutropenia/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/etiologia , Infecções Oportunistas/imunologia , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/imunologiaRESUMO
Stimulating effect of cyclosporine on growth and invasiveness of tumor xenographts was studied on a model of rat solid sarcoma M-1 transplanted under the kidney capsule in mice. Cyclosporine was administered subcutaneously in a dose of 25 or 75 mg/kg on days 1-7. The stimulating effect of cyclosporine was directly associated with the immunodepressant dose and accompanied by a decrease in the thymus weight. With using cyclosporine the model of xenographts under the kidney capsule can be of value in screening cytostatics and immunomodulators.
Assuntos
Ciclosporinas/farmacologia , Neoplasias Renais/patologia , Rim/cirurgia , Transplante de Neoplasias , Sarcoma Experimental/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Transplante Heterólogo , Animais , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Substâncias de Crescimento , Camundongos , Ratos , Sarcoma Experimental/patologia , Estimulação Química , Fatores de TempoRESUMO
The effect of different doses of aclarubicin, an anthracycline antitumor antibiotic and different regimens of its use on the cellular and humoral immune response in mice with semisyngeneic carcinoma 755 was studied with using multifactor experiments. The resulting quantitative data were computer processed and 2nd order polynomial equations reflecting regressive relationships between the indices being studied and expressed graphically were developed. The analysis indicated that it was possible to use multifactor experiments for studying relationships between various factors defining this or that effect and in particular for determining optimal interaction between therapeutic and immunological activity of antitumor drugs.
Assuntos
Aclarubicina/farmacologia , Adjuvantes Imunológicos/farmacologia , Neoplasias Mamárias Experimentais/terapia , Animais , Análise Fatorial , Feminino , Neoplasias Mamárias Experimentais/imunologia , Camundongos , Camundongos EndogâmicosRESUMO
Aclarubicin was established to be more active against murine mammary gland carcinoma Ca 755 after its intravenous injection as compared to oral administration. Pharmacokinetics of aclarubicin and its biologically active metabolites MA 144 N1, MA 144 T1 and MA 144 M1 was studied by HPLC in the tumour tissues. Not only quantitative but also qualitative differences in the ratios of the unchanged antibiotic and its metabolites in tumour Ca 755 were detected after aclarubicin administration by these methods. Diverse therapeutic activity was shown to be due to these differences.