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Journal of Toxicologic Pathology

Samak Sutjarit, Amnart Poapolathep
Fusarenon-X is a non-macrocyclic type B trichothecene mycotoxin. It occurs naturally in agricultural commodities, such as wheat and barley. We investigated fusarenon-X-induced apoptosis in the liver, kidney, and spleen of male and female mice after a single exposure. Thus, mice were orally administered fusarenon-X (4 mg/kg body weight) and were assessed at 0, 3, 9, 18, 24, and 48 hours after treatment. Apoptosis in the liver, kidney, and spleen was determined using hematoxylin and eosin staining, the terminal deoxynucleotidyl transferase dUTP nick end labeling method, immunohistochemistry for proliferating cell nuclear antigen, and electron microscopy...
July 2016: Journal of Toxicologic Pathology
Kaori Isobe, Sydney Mukaratirwa, Claudio Petterino, Alys Bradley
The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3...
July 2016: Journal of Toxicologic Pathology
Martin Heinrichs, Heinrich Ernst
Craniopharyngiomas are extremely rare epithelial tumors of the sellar region in human beings and domestic and laboratory animals. A craniopharyngioma, 0.6 cm in diameter, was observed grossly in the sellar and parasellar regions of an untreated 23-month-old male Wistar-derived rat sacrificed moribund. The tumor was composed of cords, columns, and nests of neoplastic stratified squamous epithelium with marked hyperkeratosis and parakeratosis. Neoplastic cells formed solid or cystic areas, infiltrating the base of the skull, brain, and pituitary gland...
July 2016: Journal of Toxicologic Pathology
Tetsuya Ide, Akiko Moriyama, Kazuyuki Uchida, James K Chambers, Takanobu Okazaki, Kinji Kobayashi, Shunji Nakatsuji, Masahiro Matsumoto
A male cynomolgus monkey (Macaca fascicularis) of 5 years and 11 months of age from the vehicle control group of a 4-week repeated oral dose toxicity study had a spontaneously occurring mass lesion directly attached to the proximal part of the left trigeminal nerve. Histologically, the mass was characterized by a multifocal nodular appearance. Nodular zones showed low to moderate cellularity and were composed of small round cells exhibiting nuclear uniformity. On the other hand, inter-nodular zones were composed of nerve fiber containing septa and closely aggregated highly pleomorphic cells...
July 2016: Journal of Toxicologic Pathology
Akira Inomata, Kazuhiro Hayakawa, Toyohiko Aoki, Satoru Hosokawa
Carcinosarcoma is a rare neoplasm composed of malignant epithelial and stromal elements, and, for rats, carcinosarcomas in the kidney have not been reported. In a long-term study to gather background data, we encountered a spontaneous carcinosarcoma originating from the renal pelvis with metastasis to the lung. At necropsy, a mass was observed in the abdominal cavity, and white nodules were scattered in lung lobes. Microscopically, there was polypoid hyperplasia of the urothelium accompanied by hyperplasia of spindle stromal cells in the pelvis...
July 2016: Journal of Toxicologic Pathology
Yoshika Yamakawa, Tetsuya Ide, Hikaru Mitori, Yuji Oishi, Masahiro Matsumoto
Accumulation of macrophages containing brown pigments in the lungs is a well-known spontaneous lesion found in cynomolgus monkey. However, its pathogenesis has not been clearly described. In our survey, brown pigment-laden macrophages were found in the lungs of 4 out of 43 cases. Brown pigments were mostly found in the macrophages of the perivascular interstitium, which proved to be hemosiderin. Some small- to medium-sized vessels that exhibited prominent accumulation of brown pigment-laden macrophages showed degeneration and necrosis of the smooth muscle cells of tunica media...
July 2016: Journal of Toxicologic Pathology
Cheng Zhe Zu, Masato Kuroki, Ayano Hirako, Takashi Takeuchi, Satoshi Furukawa, Akihiko Sugiyama
Pregnant rats were treated intraperitoneally with a single dose of methotrexate (MTX) 90 mg/kg on gestation day (GD) 13, and fetal eyeballs were examined time-dependently from GD 13.5 to 15.5. Throughout the experimental period, the inner plate of the ocular cup in the MTX group was significantly thinner than that in the control group. In the inner plate of the ocular cup on GD 15 and 15.5, whereas a developed ganglion cell layer was observed in the control group, the ganglion cell layer in the MTX group was undeveloped and indistinguishable...
July 2016: Journal of Toxicologic Pathology
Ryota Tochinai, Yuriko Nagata, Minoru Ando, Chie Hata, Tomo Suzuki, Naoyuki Asakawa, Kazuhiko Yoshizawa, Kazumi Uchida, Shoichi Kado, Toshihide Kobayashi, Kimiyuki Kaneko, Masayoshi Kuwahara
Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs)...
July 2016: Journal of Toxicologic Pathology
Junko Sato, Masahiro Nasu, Minoru Tsuchitani
Accurate analysis of female reproductive toxicity requires a thorough understanding the differences in and specifics of estrous or menstrual cycles between laboratory animals. There are some species differences such as the time of sex maturation, the length of the estrous or menstrual cycle, the length of the luteal phase, the number of dominant follicles or corpora lutea, the size of follicles, processes of luteinization, and hormonal changes during the estrous or menstrual cycle. Rodents have a short estrous cycle, and their ovarian cycling features are the same in both ovaries, which contain a large number of follicles and corpora lutea...
July 2016: Journal of Toxicologic Pathology
Minoru Tsuchitani, Junko Sato, Hiroko Kokoshima
As basic knowledge for evaluation of pancreatic toxicity, anatomical structures were compared among experimental animal species, including rats, dogs, monkeys, and minipigs. In terms of gross anatomy, the pancreases of dogs, monkeys, and minipigs are compact and similar to that of humans. The rat pancreas is relatively compact at the splenic segment, but the duodenal segment is dispersed within the mesentery. In terms of histology, the islet of each animal is characterized by a topographic distribution pattern of α- versus β-cells...
July 2016: Journal of Toxicologic Pathology
(no author information available yet)
[This corrects the article on p. 223 in vol. 24.].
April 2016: Journal of Toxicologic Pathology
Munmun Pervin, Hossain M Golbar, Alexandra Bondoc, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
Liposomes have been used as a vehicle for encapsulating chemicals or toxins in toxicological studies. We investigated the transient effects of empty liposomes on hepatic macrophages by applying a single intravenous injection at a dose of 10 ml/kg body weight in 6-week-old male F344 rats. One day after injection, the numbers of hepatic macrophages reacting to CD163, CD68, Iba-1, MHC class II, Gal-3 and CD204 were significantly increased in liposome-treated rats. CD163(+) Kupffer cells and CD68(+) macrophages with increased phagocytic activity in hepatic lobules were most sensitive...
April 2016: Journal of Toxicologic Pathology
Haruka Kimura-Kojima, Kana Unuma, Takeshi Funakoshi, Chizuru Kato, Ayumi Komatsu, Toshihiko Aki, Koichi Uemura
The aim of this study was to examine the possible involvement of smooth muscle cell remodeling and the induction of MFG-E8 (milk fat globule protein epidermal growth factor-VIII) in vascular pathophysiology during cocaine administration in cultured cells and rats. Cocaine exerts bifurcate effects on vascular cells; it stimulates vasoconstriction through enhancement of catecholamine release at low doses, while it suppresses cardiovascular functions through inhibition of ion channels at high doses. Short-term exposure to a high concentration of cocaine (3 mM, 24 hr) resulted in cell death of A7r5 rat aorta-derived smooth muscle cells...
April 2016: Journal of Toxicologic Pathology
Tomoaki Tochitani, Masaya Mori, Koichi Matsuda, Mami Kouchi, Yuta Fujii, Izumi Matsumoto
The human renin-angiotensinogen double transgenic rat (dTGR) is a model of hypertension. The aim of this short report was to describe the histopathological characteristics of the renal changes in this rat strain in detail. Seven to nine-week-old male dTGRs were euthanized, and their kidneys were histopathologically examined. At the time of sacrifice, the average systolic blood pressure of the dTGRs was 258 mmHg, while that of age-matched, normal Sprague-Dawley rats was 135 mmHg. In the kidney, histopathological changes were observed mainly in blood vessels, tubules and glomeruli...
April 2016: Journal of Toxicologic Pathology
Takashi Ogawa, Tomoya Onozato, Yuji Okuhara, Tatsuya Nagasawa, Toru Tamura, Morimichi Hayashi
A small mass with an ulcer was found in the skin of the dorsal cervix of a 7-month-old male Sprague-Dawley rat. Histologically, the central region of the tumor showed a high cellular density with oval-shaped tumor cells arranged in an alveolar pattern and thin collagen fiber bundles. The peripheral region of the tumor had a low cellular density with short spindle- or polygonal-shaped tumor cells surrounded by abundant collagen fiber bundles. Immunohistochemically, the tumor cells were strongly positive for vimentin and proliferating cell nuclear antigen, and a portion of the short spindle- or polygonal-shaped cells located in the peripheral region of the tumor were positive for S100A4...
April 2016: Journal of Toxicologic Pathology
Kota Irie, Yusuke Kuroda, Norihiko Mimori, Seigo Hayashi, Masayoshi Abe, Naho Tsuji, Akihiko Sugiyama, Satoshi Furukawa
Wavy medakas are medakas that exhibit spinal curvature characterized by dorsoventrally curved vertebrae. We found a spontaneous wavy medaka in our experimental stock and subjected it to a histopathological examination. Macroscopically, the wavy medaka's spine formed an M shape, and its vertebrae displayed a dorsoventral curvature that started at the third vertebral bone. Microscopically, the vertebral cavities were filled with fibrous tissue, which was similar to that seen in the central parts of the intervertebral discs of a normal medaka...
April 2016: Journal of Toxicologic Pathology
Yukie Abiko
A spontaneous tumor was observed in the maxillary gland of a 12-week-old male BALB/c F1 hybrid mouse. Histopathologically, the tumor invaded both the nasal cavity and maxillary sinus, and ethmoturbinates were destroyed. The majority of the tumor cells had oval nuclei with eosinophilic and vacuolar cytoplasm. Numerous mitotic figures and necrotic foci were also observed throughout the tumor. Immunohistochemically, almost all of the tumor cells were strongly positive for cytokeratin (WSS) and alpha-smooth muscle actin...
April 2016: Journal of Toxicologic Pathology
Masanao Kanitani, Nobuo Nishimura, Hiroshi Edamoto, Yoshio Kase
Keishibukuryogan is a traditional Japanese medicine widely administered to patients with menopausal symptoms. Because humans use it on a long-term basis, we believed that a carcinogenicity study was warranted. We orally administered keishibukuryogan (TJ-25) extract powder to 6-week-old Sprague-Dawley rats [Crl:CD(SD)], which were divided into four dosage groups-0 (water for injection), 100, 500 and 2,500 mg/kg/day for 24 months. We found that TJ-25 did not affect the survival rate of either sex. Furthermore, it did not affect the clinical condition of the rats, number of superficial tumors found by palpation, body weight, food consumption, hematology, or gross pathological findings...
April 2016: Journal of Toxicologic Pathology
Sang Jin Lee, Jong-Hwan Park, Jun-Young Lee, Yu-Jin Jeong, Jeong Ah Song, Kyuhong Lee, Dong-Jae Kim
Although several animal models have been developed to study human pulmonary fibrosis, lack of a perfect model has raised the need for various animal models of pulmonary fibrosis. In this study, we evaluated the pulmonary effect of polyhexamethyleneguanidine phosphate instillation into the lungs of mice to determine the potential of these mice as a murine model of pulmonary fibrosis. Intratracheal instillation of polyhexamethyleneguanidine phosphate induced severe lung inflammation manifested by the infiltration of mononuclear cells and neutrophils and increased production of IL-6, TNF-α, CCL2 and CXCL1...
April 2016: Journal of Toxicologic Pathology
Minoru Sasaki, Takanobu Sakurai, Aiko Ishii, Kenta Matsue, Yutaka Nakanishi, Shunsuke Tsutsumi, Yasushi Sato
The incidence of mesenteric lymph node vascular tumors can vary in rats, and appropriate assessment of potential risk of tumorigenicity is needed when the incidence is higher in treated groups than in a control group. In a 2-year rat carcinogenicity study of luseogliflozin, a selective sodium-dependent glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus, there was a slight but statistically significant increase in the total number of hemangiomas and hemangiosarcomas in the mesenteric lymph nodes in males at a high-dose...
April 2016: Journal of Toxicologic Pathology
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