RESUMEN
Trovafloxacin, a new trifluoroquinolone, was evaluated for its therapeutic efficacy against Klebsiella pneumoniae lung infection in tumour (P388 murine leukaemia cells)-bearing mice, treated with or without a chemotherapeutic agent, daunorubicin (DNR) and in mice without tumour. Its activity was compared with ciprofloxacin and cephazolin. The effect on therapeutic efficacy of the addition of recombinant granulocyte colony stimulating factor (rGCSF) was also examined. Our study showed that both quinolones successfully cured pneumonia owing to infection with K. pneumoniae in mice without tumours but that all antibiotics failed in tumour-bearing mice if DNR was withheld. Substantial differences were noted in DNR-treated tumour-bearing mice with infection-the cure rate with trovafloxacin was 91% whereas the cure rate with ciprofloxacin or cephazolin was 57%. Addition of rGCSF to ciprofloxacin did not substantially improve its efficacy (when assessed by protection against death owing to infection; the survival rate was 41%). Trovafloxacin cure rates ranged from 80 to 90% whether or not rGCSF was added to the treatment regimen. Our results suggest that prior cancer chemotherapy had no adverse effect on the therapeutic efficacy of trovafloxacin, and that trovafloxacin may be a promising therapeutic agent for treatment of bacterial infections in the presence of leucopenia.
Asunto(s)
Antiinfecciosos/uso terapéutico , Fluoroquinolonas , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacos , Leucemia P388/complicaciones , Naftiridinas/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Animales , Antiinfecciosos/farmacocinética , Antibióticos Antineoplásicos/uso terapéutico , Ciprofloxacina/uso terapéutico , Daunorrubicina/uso terapéutico , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/metabolismo , Klebsiella pneumoniae/metabolismo , Leucemia P388/tratamiento farmacológico , Leucemia P388/metabolismo , Recuento de Leucocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos DBA , Naftiridinas/farmacocinética , Trasplante de Neoplasias , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/metabolismo , Proteínas RecombinantesRESUMEN
Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2 mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.
Asunto(s)
Aclarubicina/administración & dosificación , Leucemia P388/tratamiento farmacológico , Metástasis Linfática/prevención & control , Aclarubicina/farmacocinética , Aclarubicina/uso terapéutico , Animales , Carbón Orgánico , Leucemia P388/complicaciones , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Masculino , Ratones , Ratones EndogámicosRESUMEN
Two dosage forms of etoposide diluted by saline solution (Etp-sol) and etoposide particles suspended in oil (Etp-oil) were examined for the toxicity and therapeutic effects when injected intraperitoneally (ip) in mice. The 50% lethal dose (LD50) values for two weeks observation were 135 mg/kg in Etp-oil and 108 mg/kg in Etp-sol. Two days after intraperitoneal transplantation of 10(6) cells/mouse of P388 leukemia to CDF1 male mice, etoposide was injected intraperitoneally in the form of Etp-oil or Etp-sol. In the mice receiving 20mg/kg of etoposide, 11 of 19 mice given Etp-oil and 3 of 20 given Etp-sol survived to day 60. In the mice receiving 80 mg/kg of etoposide, 1 in 20 treated with Etp-oil and 8 of 20 treated with Etp-sol died from by the toxicity.
Asunto(s)
Etopósido/administración & dosificación , Aceite Yodado/administración & dosificación , Leucemia P388/complicaciones , Peritonitis/tratamiento farmacológico , Animales , Peso Corporal/efectos de los fármacos , Preparaciones de Acción Retardada , Etopósido/uso terapéutico , Etopósido/toxicidad , Infusiones Parenterales , Dosificación Letal Mediana , Leucemia P388/patología , Masculino , Ratones , Ratones Endogámicos ICR , Peritonitis/etiología , Peritonitis/patologíaRESUMEN
We studied the effect of antibody on the growth of reovirus, serotypes 1 and 3, in P388D1, a continuous mouse macrophage-like cell line. Enhanced growth of virus was observed when cells were infected in the presence of nonneutralizing monoclonal antibodies or subneutralizing concentrations of either immune ascitic fluids or neutralizing monoclonal antibodies. Both enhancement of viral growth and neutralization were accompanied by an antibody-mediated increase in binding of radiolabeled virus to P388D1 cells. Although neutralization was seen only with monoclonal antibodies directed toward the sigma-1 surface protein of the virus, enhancement was observed with two monoclonal antibodies directed toward other surface proteins. Trypsin treatment of P388D1 cells abrogated enhanced growth of virus mediated by a mouse IgG2a antibody; preincubation with P388D1 with human IgG1 but not IgG2 myeloma proteins also abrogated enhancement by immune ascitic fluid or monoclonal antibody. These observations are compatible with known properties of P388D1 Fc receptors and support the role of the Fc receptor in antibody-mediated infection.