SummaryTo establish the diagnostic significance of canine C-reactive protein (CRP)in gastrointestinal disorders, the serum canine CRP concentration was measured in dogs with experimentallyinduced acute gastric mucosal injury.Gastric injury was induced in one male and one female beagle by a single dose oral administration of acetylsalicylic acid (200 mg/kg body weight I or indomethacin (60 mg/kg body weight), or sodium chloride (1000 mg/kg body weight). CRP was measured prior to dose, and I, 3, 7, and 14 days after the administration of the drugs, together with the total leucocyte counts and serum iron. Changes in the serum CRP in dogs with gastric injury were similar for the three test compounds, and reflected by the endoscopic findings. CRP values increased from 87 to 390 mg/l within 1 to 3 days after the compound administration but returned nearly to the predose levels within 14 days. Endoscopy revealed haemorrhagic erosion of the gastric mucosa in all dogs one day after dosing, with no evidence of the erosions observed after 7 days in many of the dogs. Changes of the total leucocyte and serum iron also occurred following gastric injury, but these changes were not as marked as those observed for CRP.The results of this study suggest that serum CRP level may be a useful indicator of a gastrointestinal mucosal injury in dogs.
Abstract:The cynomolgus macaque (Macaca fascicularis) has emerged as an important experimental animal model for biomedical research in various domains, necessitating the more extensive characterization of the genetic backgrounds influencing the macaque's response to drugs and sensitivity to experimental disease. The diversity of the variable mitochondrial DNA (mtDNA) D-loop region has been analyzed phylogenetically among geographically isolated populations or within subdivisions of the same regional population. However, the genetic differences among several substructures originating from a common population have not yet been investigated. By sequencing fragments of the mtDNA D-loop region from two subpopulations from the Indochinese region (Cambodian-Chinese and Vietnamese) along with two native Indonesian and Filipino populations, we identified 87 mtDNA D-loop haplotypes, of which 67 are new. The phylogenetic relationship suggests that the Indochinese haplotypes are intermingled in comparison to the distinct divergence of the Indonesian and Filipino lineages. The subpopulations were shown by estimation of evolutionary divergence and Wright's F-statistic (Fst) to have little genetic differentiation. Altogether, the subpopulations may be used in biomedical research, even though a slight difference is observed in haplotype frequencies among them. Therefore, genetic diversity analyses will be necessary for the elucidation of genetic differences among the populations, as well as to obtain a better understanding of genetic diversity for biomedical research. This will involve the selection of macaques and the monitoring of genetic heterogeneity among and within breeding facilities.
Pulmonary drug administration of most peptide/protein drugs is characterized by low bioavailability due to low permeability. Surface active agents have been tested as an absorption enhancer, but few studies have been carried out on the local toxicity of these additives. In the present study, to clarify the toxic effects of surface active agents on the lung, a relatively high concentration (1%) of polyoxyethylene 9 lauryl ether (Laureth-9) and sodium glycocholate (SGC) was given to rats in a single intratracheal instillation (100 microliters/rat), and the lung was evaluated histopathologically. In the rats treated with Laureth-9, lung lesions were observed in the bronchi to alveoli. At 1 day after administration, edema, hemorrhage and inflammatory cell infiltration due to degeneration and desquamation of epithelium were observed. At 3 and 7 days after administration, the wound healing process resulting from the lung injury, such as hyperplasia of epithelium and sporadic fibrosis, was noted. SGC also induced lung lesions with a similar histopathological nature, whereas the lesions were mostly confined to the alveoli. These results suggest that surface active agents induce acute inflammation of the lung by intratracheal instillation, that the distribution of lesions is different among surface active agents, and moreover that pathological examination is indispensable for clarifying local toxicity of absorption enhancers in pulmonary drug-delivery studies.
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