著者

Yuval RAMOT Michal STEINER Netanel AMOUYAL Yossi LAVIE Guy KLAIMAN Abraham J. DOMB Abraham NYSKA Tal HAGIGIT

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

pp.2020-0041, (Released:2020-08-31)

被引用文献数

3

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Fracture-related infections remain a leading cause of morbidity and mortality. We aimed to establish a simple contaminated radial osteotomy model to assess the efficacy of a biodegradable polymer poly(sebacic-co-ricinoleic acid) [p(SA-RA)] containing 20% w/w gentamicin. A unilateral transverse osteotomy was induced in Sprague-Dawley (SD) rats, followed by application of Staphylococcus aureus suspension over the fracture. After successfully establishing the contaminated open fracture model, we treated the rats either systemically (intraperitoneal cefuroxime), locally with p(SA-RA) containing gentamicin, or both. Control groups included non-contaminated group and contaminated groups that were either untreated or treated with the polymer alone. After 4 weeks, the bones were subjected to micro-CT scanning and microbiological and histopathology evaluations. Micro-CT analysis revealed similar changes in the group subjected to both local and systemic treatment as in the non-contaminated control group. Lack of detectable bacterial growth was noted in most animals of the group subjected to both local and systemic treatment, and all samples were negative for S. aureus. Histopathological evaluation revealed that all treatment modalities containing antibiotics were highly effective in reducing infection and promoting callus repair, resulting in early bone healing. While p(SA-RA) containing gentamicin treatment showed better results than cefuroxime, the combination of local and systemic treatment displayed the highest therapeutic potential in this model.

著者

Keiko Makita-Suzuki Chihaya Kakinuma Akira Inomata Yasuhiro Shimada Takefumi Hara Takashi Yao

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.33, no.1, pp.1-9, 2020 (Released:2020-01-24)

参考文献数

40

被引用文献数

2

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Although several liposomal drugs, including liposomal doxorubicin, have been approved, the etiology of the pathological responses caused by their physicochemical properties remains unknown. Herein, we investigated the pathological changes in the liver and the gallbladder of dogs following a single injection of liposomal doxorubicin (1 or 2.5 mg/kg) or an empty liposomal formulation (i.e., liposomal formulation without doxorubicin, ca. 21 mg/kg as lipid content). Injection of liposomal doxorubicin or the empty liposomal formulation induced hemorrhagic changes in the liver and the gallbladder. These changes were accompanied by minimal cellular infiltration with no obvious changes in the blood vessels. As there were no differences in the incidence and severity of hemorrhage between the groups administered comparable amounts of total lipid, the physicochemical properties of the liposomal formulation rather than an active pharmacological ingredient, doxorubicin, were associated with the hemorrhagic changes. Furthermore, decreased cytoplasmic granules with low electron density in mast cells beneath the endothelium of the hepatic vein were observed in the liver of dogs treated with liposomal doxorubicin or empty liposomal formulation. Injection of compound 48/80, a histamine releaser induced comparable hemorrhage in dogs, implying that hemorrhage caused by injection of liposomal doxorubicin or the empty liposomal formulation could be attributed to the histamine released from mast cells. The absence of similar hemorrhagic lesions in other species commonly used in toxicology studies (i.e., rats and monkeys), as well as humans, is due to the lack of mast cells beneath the endothelium of the hepatic vein in these species.

著者

Shin-ichi NAKAMURA Takamitsu TSUKAHARA

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

pp.2018-0060, (Released:2019-06-06)

被引用文献数

1

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Herein, we describe the case of a 6-year-old female ferret that died within a few days of the onset of anorexia and reduced spontaneous locomotor activity. Necropsy revealed a dark red abdominal mass of unknown origin between the right lobes of the pancreas and the proximal jejunum, with massive blood retention in the peritoneal cavity. Histopathologically, spindle-shaped or sometimes polygonal tumor cells were proliferating with irregularly shaped vascular spaces containing blood components and surrounding-tissue infiltration. In some areas, tumor cells formed distinctly dilated blood vessel-like structures. Immunohistochemically, most of the tumor cells were strongly positive for CD31, but factor VIII-related antigen immunoreactivity was confined to the area with dilated blood vessel-like structures. Based on these findings, the tumor was diagnosed as an abdominal hemangiosarcoma. Abdominal hemangiosarcoma excluding cases of the liver and spleen are rare in ferrets.

著者

Kazuo Hakoi Taiji Hayashi Kenji Irimura Shuji Hayashi Satoshi Suzuki Shuji Yamaguchi Noboru Konishi Shoji Fukushima

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.14, no.1, pp.13, 2001 (Released:2001-06-01)

参考文献数

35

被引用文献数

1 1

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DHG, a glycosaminoglycan extracted from the sea cucumber is known to show antithrombotic effects in animals and be a possible therapeutic agent for prevention of disseminated intravascular coagulation. In toxicology study, however, dose-dependent intracellular deposition of eosinophilic or basophilic droplets, and crystalloid substances were observed in the proximal tubular epithelial cells of the kidneys when male Sprague-Dawley rats were administered DHG daily for two weeks at the doses of 10, 100, and 200 mg/kg. In contrast to heparin, a glycosaminoglycan that has been reported to induced similar deposits which were identified to be composed of a hemoglobin-like substance using the alizarin red staining. The inclusions observed in rats given DHG were immunohistochemically positive for α2u-globulin. Moreover, the droplets showed metachromasia in toluidine blue staining, and negative for Hall's, Gmelin's, Schmol's tests, and alizarin red staining, but the crystalloids were positive for alizarin red staining. These results suggested that DHG-induced degeneration of proximal tubular epithelial cells in male rats is related to α2u-globulin accumulation.

著者

伊藤 明弘 後藤 孝彦 藤本 成明

出版者

JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

雑誌

Journal of toxicologic pathology (ISSN:09149198)

巻号頁・発行日

vol.11, no.2, pp.79-84, 1998-06-01

被引用文献数

2 5

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Cancer is a genetic disease and numerous genetic changes have been disclosed in its developmental stages. Corresponding to those endogenous events, environmental factors including chemicals, oncogenic viruses, and radiation participate in the initiation, promotion, and progression stages. Furthermore, development of cancer is greatly influenced by nutritional factors such as from daily food consumption and the additives in these foods. Retinoids, vitamins, essence of tea, and vegetables are believed to be highly effective in chemoprevention of cancer. In this mini review, miso, a fermented soy product, and the purported active chemopreventative component of soybeans, isoflavones, were examined for their biological activity; 1) during recovery from radiation induced damage, and 2) as a possible chemopreventor of cancers. Thus far, promising results have been obtained for prevention of liver tumors in mice, breast tumors in rats, and intestinal tract tumors in rats. Since chemopreventors derived from natural foods are not cytotoxic, they need not be given to the recipients intermittently. Furthermore, we have found that a combination of tamoxifen with miso greatly reduced occurrence of mammary tumors in rats and therefore might be applicable to human cancers.

著者

Ayako SAYAMA Keiko OKADO Masako IMAOKA Yusuke YOKOUCHI Toshimasa JINDO Wataru TAKASAKI

出版者

日本毒性病理学会

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

pp.2013-0044, (Released:2014-02-05)

被引用文献数

1 1

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A nine-year-old male beagle dog had a white spherical mass in the subcutis of the left lumbar region. Microscopically, spindle to oval cells diffusely proliferated in the fibrous and myxoid stroma. Many neoplastic cells showed rhabdoid features or vacuolated cytoplasm. Immunohistochemically, the neoplastic cells were positive for vimentin and S100 and partly positive for neuron-specific enolase and glial fibrillary acidic protein but were negative for von Willebrand factor, desmin and α-smooth muscle actin. Ultrastructurally, the neoplastic cells had abundant cytoplasmic processes and desmosome-like structures. Cytoplasmic inclusions of rhabdoid-featured cells in HE sections were composed of aggregates of intermediate filaments, and cytoplasmic vacuoles were identified as an invagination of cytoplasm. Although malignant peripheral nerve sheath tumor was suggested according to these results, the present case was diagnosed as a soft tissue sarcoma with rhabdoid features due to a lack of identification of the basal lamina under electron microscopy.

著者

Shinichiro Ikezaki Mizuho Takagi Kazutoshi Tamura

出版者

日本毒性病理学会

雑誌

Journal of Toxicologic Pathology (ISSN:09149198)

巻号頁・発行日

vol.24, no.1, pp.37-40, 2011 (Released:2011-04-17)

参考文献数

8

被引用文献数

8 32

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It is important for the assessment of toxicological effects of chemicals to know what kinds of neoplasms naturally occur in the early life of experimental animals. In the present study, we demonstrated spontaneous neoplasms in Sprague-Dawley rats used in 4-, 13- and 26-week toxicity studies conducted at Bozo Research Center in the last decade. The tumors, which were first observed in 19-week-old animals, included anterior adenoma of the pituitary, follicular cell adenocarcinoma and C cell adenoma of the thyroids, nephroblastoma of the kidneys, basal cell tumor of the skin and malignant lymphoma. Thereafter, hemangiosarcoma of the tongue, adenocarcinoma of the submandibular glands, histiocytic sarcoma of the spleen, oligodendroglioma of the brain and adenocarcinoma and fibroadenoma of the mammary glands were detected in 32-week-old animals. The incidences of mammary adenocarcinoma and pituitary anterior adenoma were higher than those of other tumors. The present results showed that the same tumors as reported in aged rats could also develop in younger rats.