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Extraskeletal osteosarcoma is extremely rare in humans and animals, especially in rodents. This is the first case report on spontaneous extraskeletal osteosarcoma in the neck skeletal muscle of a Crlj:CD1 (ICR) mouse (36 weeks, dead). Necropsy revealed a solid white mass located in the neck skeletal muscle (scalenus muscle). Histological examination showed that the tumor consisted of atypical polygonal cells, a small osteoid clump, and bone tissue. Mitotic figures were observed. Serial sections showed that neoplastic cells lacked clear invasive proliferation to adjacent normal skeletal muscle and continuity with normal bone tissue. Immunohistochemical analysis showed that the neoplastic cells were positive for osteocalcin, osterix, vimentin, and S-100. Based on these results, the tumor was diagnosed as extraskeletal osteosarcoma in the neck skeletal muscle.

application/pdf, Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1β, resulting in reduced nitric oxide and prostaglandin E2 production. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment. © 2019 The Pharmaceutical Society of Japan.

Drug-induced lens opacity has the potential to cause blindness and is of concern in drug development. Inhibition of cholesterol biosynthesis is one of the causes of lens opacity. Lens opacity is only observed after chronic administration in in vivo nonclinical studies in drug development. Thus, to save resources (e.g., time and cost) and to reduce burden on animals, it is required to develop in vitro evaluation systems that can predict and avoid the risk of lens opacity earlier and easier. In this study, we investigated whether rat lens explant cultures could be useful for the evaluation of drug-induced lens opacity via inhibition of cholesterol biosynthesis. Nineteen drugs, including statins, allylamine, thiocarbamate, azole, and morpholine, which inhibit cholesterol biosynthesis, as well as a negative control (acetaminophen, rosiglitazone and troglitazone), were used. Rat lens explants were treated with drugs for 13 days at concentrations close to IC

Background In experimentally induced cases of AA amyloidosis, the development of disease is enhanced by the administration of homogenous or heterogeneous amyloid fibrils. In recent years, cross-species transmission of animal amyloidosis into human has become of particular concern. Methods Cynomolgus monkeys (Macaca fascicularis) and C3H/HeN mice were inoculated with bovine amyloid fibrils under acute inflammation. Results Amyloid A deposits were not detected in any of the monkeys, but mild-to-severe AA deposits were found in all mice. Conclusions These results suggest that unlike in rodents, cross-species transmission of AA amyloidosis is less likely to develop, at least during acute inflammation, in primates.

Historical control data from prenatal developmental toxicity studies in rats have been used to evaluate whether toxicology outcomes were induced by exposure to a chemical or were within the range of spontaneous variation. These data are also important for monitoring animal characteristics. As a follow-up to historical control data from 1998 to 2010, this study analyzed control data from prenatal developmental studies performed in rats from 2011 to 2015. Data were collected from studies performed by 24 Japanese laboratories, including 15 pharmaceutical and chemical companies and nine contract research organizations, in Sprague-Dawley and two-sub-strains of Wistar Hannover rats. The data included maternal reproductive findings at terminal cesarean section and fetal findings, including incidences of spontaneous external, visceral, and skeletal anomalies. No noticeable differences in maternal reproductive data were observed among laboratories. The inter-laboratory variations in the incidences of fetal anomalies seemed to be due to differences in the selection of observation parameters, observation criteria, and classification of the findings, as well as to differences in terminology of fetal alterations. These historical control data may be helpful for adequate interpretation of experimental results and for evaluating the reproductive and developmental toxicities of various chemicals.

Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid deposition with juvenile chickens obtained in our previous study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens, while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile chickens (88%). These results suggest that additional amyloid deposition in chickens previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition in chickens may tend to regress when causative factors, such as vaccinations and/or chronic inflammation, are absent.

Background Cross-species transmission of AA amyloidosis between primates and other animals has not been previously reported. Methods Eight geriatric squirrel monkeys were intravenously administered chimpanzee, bovine, or chicken amyloid fibrils and simultaneously received inflammatory stimulation. Results AA amyloid deposition was not detected in any of the monkeys histopathologically or immunohistochemically. Conclusions These results suggest that heterogeneous AA amyloidosis may not be easily transmitted into primates.