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Journal of Toxicologic Pathology

Etsuko Fujii, Masaki Yamazaki, Shigeto Kawai, Yoshimi Ohtani, Takeshi Watanabe, Atsuhiko Kato, Masami Suzuki
In vitro -cultured 3D structures called organoids have become important tools for biological research, but there is little information concerning simple and efficient methods to evaluate organoid morphology. To address this issue, we attempted to establish a simple method by applying conventional histopathology that enables observation of multiple organoids on a single cross section, maintains good morphology, and is applicable to various histopathological stains. By centrifugation in unsolidified agarose solution, we were able to accumulate the organoids onto a single plane...
January 2018: Journal of Toxicologic Pathology
Young-Man Cho, Yasuko Mizuta, Jun-Ichi Akagi, Takeshi Toyoda, Mizuki Sone, Kumiko Ogawa
In this study, we aimed to evaluate changes in the acute toxicity of intraperitoneally administered silver nanoparticles (AgNPs) of varying sizes in BALB/c mice. Seven-week-old female BALB/c mice were intraperitoneally administered AgNPs measuring 10, 60, or 100 nm in diameter (0.2 mg/mouse) and then sacrificed 1, 3, or 6 h after treatment. In mice administered 10 nm AgNPs, reduced activity and piloerection were observed at 5 h post administration, and lowered body temperature was observed at 6 h post administration, with histopathological changes of congestion, vacuolation, single cell necrosis, and focal necrosis in the liver; congestion in the spleen; and apoptosis in the thymus cortex...
January 2018: Journal of Toxicologic Pathology
Shin-Ichi Chisada, Ayano Hirako, Akihiko Sugiyama
Ocular lesions in leptin receptor-deficient medaka were examined histopathologically at 10, 28, and 37 weeks post hatching. Leptin receptor-deficient medaka at 28 and 37 weeks old showed hyperglycemia and hypoinsulinemia. Histopathologically, vacuolation, swelling, fragmentation, and liquefaction of the lens fibers and dilatation of the retinal central veins, retinal capillaries, iridal veins and capillaries, and choroidal veins were observed in leptin receptor-deficient medaka at 28 and 37 weeks old. Thinning of the total retina, pigment epithelial layer, layer of rods and cones, outer granular layer, outer plexiform layer, inner granular layer, and inner plexiform layer was observed in leptin receptor-deficient medaka at 28 and 37 weeks compared with in control medaka...
January 2018: Journal of Toxicologic Pathology
Yuko Ono, Hiroko Sato, Toshiko Miyazaki, Katsuya Fujiki, Eisuke Kume, Masaharu Tanaka
Histopathological examination of formalin-fixed paraffin-embedded (FFPE) tissues that had been stored for 30 years was conducted, and reconstructivity of the results was verified. These FFPE tissues, which were from all organs of male and female rats, were re-sectioned and histopathologically examined using hematoxylin and eosin (HE) staining. In particular, the stainability and morphology of HE sections and reproducibility of microscopic findings in the liver and kidney demonstrated in the original final reports were evaluated...
January 2018: Journal of Toxicologic Pathology
Kyohei Yasuno, Kumi Honda, Shinobu Hakamata, Kiyonori Kai, Kazuhiko Mori
Minimal change disease (MCD) can be experimentally induced in rats, but spontaneous cases have not been reported. Herein, we present a case of MCD in rats that resembled the phenotypes of human MCD. A 9-week-old male Sprague Dawley rat developed continuous albuminuria for 2 weeks and was sacrificed at 11 weeks of age. Histological testing revealed no glomerular or renal tubular abnormalities on light microscopy. Immunofluorescence revealed absence of immunoglobulin G or immunoglobulin M deposition in the glomerulus...
January 2018: Journal of Toxicologic Pathology
Shizuka Konishi, Takashi Kotera, Masaaki Koga, Makoto Ueda
The term cardiomyopathy is used to describe heart disease resulting from an abnormality in the myocardium. It is rare in cynomolgus macaques ( Macaca fascicularis ). Here, we report a case of hypertrophic cardiomyopathy in an 11-year-old male cynomolgus macaque. Macroscopically, the interventricular septum (IVS) and the left ventricular (LV) and right ventricular (RV) walls of the heart were thickened. Histologically, cardiomyocytes showed hypertrophy and disarray with interstitial fibrosis, and some myocytes showed karyomegaly and vacuoles...
January 2018: Journal of Toxicologic Pathology
Riki Toita, Takahito Kawano, Satoshi Fujita, Masaharu Murata, Jeong-Hun Kang
Among five C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks, one mouse showed a body weight (BW) similar to normal diet (ND)-fed mice. We compared obesity-related parameters of three groups (ND-fed mice, one HFD-fed normal-weight mouse, and HFD-fed overweight mice), including visceral fat weight, serum levels of total cholesterol (TC), glucose, and aminotransferases (AST and ALT), adipocyte size, percentage of crown-like structures, severity of hepatic steatosis, and number of inflammatory foci. Compared to ND-fed mice, the HFD-fed normal-weight mouse exhibited a similar visceral fat weight, similar serum levels of glucose and aminotransferases, and a similar percentage of crown-like structures...
January 2018: Journal of Toxicologic Pathology
Hiroyuki Kuroda, Toshiko Kinomoto, Shuji Ogawa, Mayumi Kawabe, Mayuko Suguro, Hitoshi Naraoka, Kazuhiko Takamatsu, Yuji Oishi
Although acotiamide hydrochloride hydrate (acotiamide-HH) has not been reported to have genotoxic findings in any of the genotoxicity studies or treatment-related toxicological findings in reproductive and developmental studies, suspicious uterine tumorigenesis was observed in the results of a long-term rat carcinogenicity study. To clarify the uterine tumorigenesis of acotiamide-HH, we performed a 2-stage uterine carcinogenicity model in the transgenic rasH2 mouse initiated by N-Ethyl-N-nitrosourea (ENU). This model facilitated the short-term detection of uterine carcinogenic potential, and it appears to be a very useful testing method for assessing the safety of chemicals that may affect uterine tumorigenesis...
January 2018: Journal of Toxicologic Pathology
Osamu Ichii, Taro Horino
Mature microRNAs (miRNAs) are single-stranded RNAs with approximately 18-25 bases, and their sequences are highly conserved among animals. miRNAs act as posttranscriptional regulators by binding mRNAs, and their main function involves the degradation of their target mRNAs. Recent studies revealed altered expression of miRNAs in the kidneys during the progression of acute kidney injury (AKI) and chronic kidney disease (CKD) in humans and experimental rodent models by using high-throughput screening techniques including microarray and small RNA sequencing...
January 2018: Journal of Toxicologic Pathology
Chikuma Hamada
Generally, multiple statistical analysis methods can be applied for certain kind of data, and conclusion could differ, depending on the selected statistical method. Therefore, it is necessary to fully understand the performance of each statistical method and to examine which method is appropriate to use and to standardize statistical methods for toxicity studies to be carried out routinely. Several viewpoints for selecting appropriate statistical methods are discussed in this review paper. According to the distribution form, i...
January 2018: Journal of Toxicologic Pathology
Takuma Iguchi, Ken Sakurai, Satoshi Tamai, Kazuhiko Mori
Circulating microRNAs (miRNAs) can potentially be used as sensitive and specific biomarkers for tissue injury. However, the usefulness of circulating miRNAs as safety biomarkers in nonclinical toxicological studies using nonhuman primates is debatable owing to the limited information on organ-specific miRNAs. Therefore, a systematic investigation was performed to address this point. We identified organ-specific miRNAs from cynomolgus monkeys by next-generation sequencing analysis, which revealed that miR-122 was only abundant in the liver, whereas miR-192 was abundant in the liver, stomach, intestines, and kidney...
January 2018: Journal of Toxicologic Pathology
Yasushi Horai, Tetsuhiro Kakimoto, Kana Takemoto, Masaharu Tanaka
In evaluating pathological changes in drug efficacy and toxicity studies, morphometric analysis can be quite robust. In this experiment, we examined whether morphometric changes of major pathological findings in various tissue specimens stained with hematoxylin and eosin could be recognized and quantified using image processing software. Using Tissue Studio, hypertrophy of hepatocytes and adrenocortical cells could be quantified based on the method of a previous report, but the regions of red pulp, white pulp, and marginal zones in the spleen could not be recognized when using one setting condition...
October 2017: Journal of Toxicologic Pathology
Ayano Hirako, Yuki Takeoka, Toshinori Hayashi, Takashi Takeuchi, Satoshi Furukawa, Akihiko Sugiyama
To characterize the histomorphologic effects of cadmium on adult newt testes, male Iberian ribbed newts (6 months post-hatching) were intraperitoneally exposed to a single dose of 50 mg/kg of cadmium, with histologic analysis of the testes at 24, 48, 72, and 96 h. Beginning 24 h after cadmium exposure, apoptosis of spermatogonia and spermatocytes was observed, and congestion was observed in the interstitial vessels of the testes. Throughout the experimental period, the rates of pyknotic cells and TUNEL and cleaved caspase-3 positivity were significantly higher in the spermatogonia and spermatocytes of cadmium-treated newts compared with control newts...
October 2017: Journal of Toxicologic Pathology
Kaori Isobe, James Baily, Sydney Mukaratirwa, Claudio Petterino, Alys Bradley
The aim of this study was to determine the range and incidences of spontaneous microscopic lesions of the pituitary gland 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 pituitary gland were generally uncommon, excluding cysts/pseudocysts (6.42% in Han-Wistar rats, 5.85% in Sprague-Dawley rats, and 2.08% in CD-1 mice). Primary proliferative lesions were most frequently found in the pars distalis of the pituitary gland...
October 2017: Journal of Toxicologic Pathology
Ryo Watanabe, Kana Unuma, Kanako Noritake, Takeshi Funakoshi, Toshihiko Aki, Koichi Uemura
To examine the in vivo responses of promyelocytic leukemia protein (PML) to arsenic, rats (male, 6 weeks old, Sprague Dawley) were administered a single intraperitoneal dose of 5 mg/kg arsenic trioxide (ATO). The protein was examined in the heart, lung, liver, and brain 6 and 48 hours after administration: a significant response of PML was observed in the brain. Oxidative DNA modification was also observed in the brain as revealed by increased immunoreactivity to anti-8-hydroxy-2'-deoxyguanosine (8-OHdG) antibody...
October 2017: Journal of Toxicologic Pathology
Tetsuro Kurotaki, Yuki Tomonari, Junko Sato, Takeshi Kanno, Minoru Tsuchitani
A 20-week-old male Sprague Dawley rat noted with decreased body weight, dyspnea, and anorexia beginning 2 days before death was necropsied in the recovery period of a sub-chronic toxicity study. The heart was severely enlarged (30 × 20 × 20 mm), 3-4 times larger than normal, with an approximately 6 mm wide defect in the upper, membranous portion of the ventricular septum. Both ventricles measured 4 mm in thickness, and the right ventricle was 4 times thicker than normal. According to a microscopic examination, the myocardial fibers were severely hypertrophic in the right ventricle and mildly hypertrophic in the left ventricle and septum...
October 2017: Journal of Toxicologic Pathology
Asami Urashima, Kinji Kobayashi, Yuji Sasaki, Kimiaki Hirakawa, Hiroshi Maeda
To our knowledge, this is the first report on basal cell carcinoma with lung metastasis in a rat. A 6-week-old male Sprague-Dawley rat presented ulceration of the oral mucosa with surrounding tumor growth and white nodules in the lung. Microscopically, the mass showed solid, sheet-like growth with a partially lobular pattern and invaded the gingival mucosa, maxilla, and nasal submucosa. The nuclei of tumor cells were round to oval in shape with basophilic cytoplasm and a large number of mitotic figures. The pulmonary nodules were almost identical to the maxillary tumor in histopathological characteristics...
October 2017: Journal of Toxicologic Pathology
Tomoko Ishihara, Haruhiro Yamashita, Takanobu Sakurai, Junya Morita, Kouji Sakamoto, Aiko Ishii, Minoru Sasaki
Patchy thickening and reddish discoloration of active hair growth areas of skin in rabbits are occasionally found, and this gross feature could affect precise evaluation when conducting a dermal irritation test. Since little is known about the mechanism of this phenomenon, we examined the dorsal skin of New Zealand White rabbits morphologically and immunohistochemically in order to identify the possible mechanism responsible for developing these skin changes in relation to the hair cycle. Skin samples from 4 rabbits were divided into three groups (5 samples/group) based on their macroscopic characteristics: a thickened skin, erythematous skin, and smooth skin group...
October 2017: Journal of Toxicologic Pathology
Chu-Chun Chien, Yuan-Horng Yan, Hung-Tzu Juan, Tsun-Jen Cheng, Jia-Bin Liao, Huai-Pao Lee, Jyh-Seng Wang
Exposure to zinc oxide (ZnO) has been linked to adverse health effects, but the renal effects of ZnO nanoparticles (ZnONPs) remain unclear. The objective of this study was to determine the renal toxicity of inhaled ZnONPs. Sprague Dawley (SD) rats were exposed to occupationally relevant levels of 1.1 (low dose) and 4.9 mg/m(3) (high dose) ZnONPs or high-efficiency particulate arresting-filtered air (HEPA-FA) via inhalation for 2 weeks. Histopathological examinations of rat kidneys were performed at 24 hours, 7 days, and 1 month after exposure...
October 2017: Journal of Toxicologic Pathology
Eun Kyoung Koh, Ji Eun Kim, Sung Hwa Song, Ji Eun Sung, Hyun Ah Lee, Kil Soo Kim, Jin Tae Hong, Dae Youn Hwang
The Styela clava tunic (SCT) is known as a good raw material for preparing anti-inflammatory compounds, wound healing films, guided bone regeneration, and food additives. To investigate whether ethanol extracts of the SCT (EtSCT) could protect against hepatic injury induced by carbon tetrachloride (CCl4) in ICR mice, alterations in serum biochemical indicators, histopathology, hepatic apoptosis, inflammation, and fibrosis were observed in ICR mice pretreated with EtSCT for 5 days before CCl4 injection. EtSCT contained 15...
October 2017: Journal of Toxicologic Pathology
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