Abstract:As a quarantine of biological materials, we tested 96 transplantable tumors and cell lines for contamination with microorganisms in a mouse antibody production (MAP) test, enzymatic assay and microbiological culture. Contamination with lactic dehydrogenase elevating virus (LDV), mycoplasmas and Pasteurella pneumotropica was detected. A considerable difference in the contamination rate was observed between in vivo-and in vitro-propagated tumors. LDV in the tumors could be eliminated by both in vitro subculture and subpassage in nude rats. Mycoplasmas were eliminated by means of the mycoplasmaremoval agent and P. pneumotropica by subpassage in mice. These results suggest that there is still a high risk of contamination in transplantable tumors and emphasizes the importance of adequate microbiological quality control. Key words: Contamination, Microorganisms, Transplantable tumor quarantined 907 human tumor samples by using 105 pairs of sentinel mice kept together with tumor-bearing mice, and found contamination with Staphylococcus aureus, Pseudomonas aeruginosa and mouse hepatitis virus, but as far as we know there is no report on the systematic search for contamination with murine pathogens in rodent tumors in Japan.In this report, we present our studies on the contamination of transplantable tumors and cell lines with murine pathogens and their successful elimination.The specimens tested were transplantable tumors and cell lines originating in various animal species. The tumors, which had been propagated either in vivo or in vitro, were obtained from commercial sources
A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II): cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin-ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg-1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg mL-1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.
Abstract:We encountered a case of nonsuppurative meningoencephalitis with neurologic signs of depression, tremor, and ataxic gait in a 15-month-old vaccinated male beagle dog. Hematologic and biochemical parameters indicated no significant changes except for some findings suggesting dehydration and anorexia. Microscopically, the main features consisted of nonsuppurative meningoencephalitis with disseminated foci of perivascular cuffing of mononuclear cell in the leptomeninges and gray matter of the cerebrum and cerebellum. Some glial nodules, which were characterized by accumulation of microglia, were seen in the molecular layer of the cerebellum. Demyelination and neuronal necrosis were not observed in the central nervous system. Although the dog had a slightly elevated serum antibody titer to canine distemper virus (CDV), neither viral inclusion bodies, nor CDV antigens were detected in the brain tissue. The cause of disease in this case remained unclear. (J Toxicol Pathol 2004; 17: 51-53)
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