Journal of Toxicologic Pathology最新文献_第3页

Polyorchidism in a young Sprague-Dawley rat 幼年 Sprague-Dawley 大鼠的多睾丸症

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-04-09 DOI: 10.1293/tox.2024-0005

Ryo D. OBARA, Yuki KATO, Yoshiji ASAOKA, Kae FUJISAWA, Emi KASHIWAGI, Kenji KOYAMA, Miho MUKAI, Minako TAJIRI, Mikinori TORII

{"title":"Polyorchidism in a young Sprague-Dawley rat","authors":"Ryo D. OBARA, Yuki KATO, Yoshiji ASAOKA, Kae FUJISAWA, Emi KASHIWAGI, Kenji KOYAMA, Miho MUKAI, Minako TAJIRI, Mikinori TORII","doi":"10.1293/tox.2024-0005","DOIUrl":"https://doi.org/10.1293/tox.2024-0005","url":null,"abstract":"Duplicate testes lined in series were observed in the right scrotum of a 6-week-old Sprague-Dawley rat in a single-dose toxicity study. Of the two right testicles, one was spherical and less than half the size of a normal testis. The other was oval-shaped, slightly smaller than a normal testis, and possessed clear, tortuous blood vessels similar to those of a normal testis. Each right testis was grossly separated but faced the intertesticular adipose tissue and was sparsely joined by thin cord-like structures. Only one epididymis covered or encompassed the two right testes. The caput epididymis was attached to the smaller spherical testis, whereas the cauda epididymis was attached to the oval testis. Histopathological examination revealed that the smaller spherical testis on the right side and the testis on the left side were normal. The oval-shaped testis on the right exhibited markedly dilated degenerative seminiferous tubules with one to two layers of Sertoli or germ cells, and almost no spermatogenesis was observed. Multinucleated germ cells were observed in the lumen of the degenerated seminiferous tubules. The right epididymis was morphologically normal and contained few sperm in the epididymal duct of the tail. The cord-like structures between duplicate testes comprised fibrous and adipose tissues. Single efferent ductules, ectopic cartilage, and skeletal muscle tissues were buried in the adipose tissue. To our knowledge, this is the first report of spontaneous polyorchidism in a rodent.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"39 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induction of lung lesions by bronchial administration using bronchoscope technique in mice 利用支气管镜技术通过支气管给药诱导小鼠肺部病变

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-02-23 DOI: 10.1293/tox.2023-0123

Takako HIYOSHI, Chiyoko NISHIME, Eiko NISHINAKA, Fumiko SEKI, Kenji KAWAI, Misa MOCHIZUKI, Koji URANO, Toshio IMAI, Taichi YAMAMOTO, Masami SUZUKI

{"title":"Induction of lung lesions by bronchial administration using bronchoscope technique in mice","authors":"Takako HIYOSHI, Chiyoko NISHIME, Eiko NISHINAKA, Fumiko SEKI, Kenji KAWAI, Misa MOCHIZUKI, Koji URANO, Toshio IMAI, Taichi YAMAMOTO, Masami SUZUKI","doi":"10.1293/tox.2023-0123","DOIUrl":"https://doi.org/10.1293/tox.2023-0123","url":null,"abstract":"This study aimed to establish an exposure method that can induce homogeneous lesions with minimal inter-individual variability. The distribution of lesions induced by bleomycin (BLM) administration was also analyzed. C57BL mice were intrabronchially administered 20 µL of BLM (3 mg/mL) using a bronchoscope in the left or right bronchus. The mice were sacrificed 14 days after administration, and their lungs were evaluated histopathologically. BLM-induced inflammatory lesions were widely observed in the lungs. In the left bronchus-treated group, lesions were uniformly observed throughout the lobe, and no individual differences were noted. Meanwhile, in the right bronchus-treated group, individual differences in the distribution of the pulmonary lesions were observed. The distribution of lesions differed among the four lobes of the right lung owing to their anatomical features. Administration into the left bronchus is recommended for highly homogeneous lung exposure and for establishing models that contribute to highly accurate toxicity and efficacy evaluations.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"56 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139921081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neural tissue tolerance to synthetic dural mater graft implantation in a rabbit durotomy model 兔硬脑膜切口模型中神经组织对合成硬脑膜移植物植入的耐受性

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-02-12 DOI: 10.1293/tox.2023-0121

Yuval RAMOT, Noam KRONFELD, Michal STEINER, Nora Nseir MANASSA, Amir BAHAR, Abraham NYSKA

{"title":"Neural tissue tolerance to synthetic dural mater graft implantation in a rabbit durotomy model","authors":"Yuval RAMOT, Noam KRONFELD, Michal STEINER, Nora Nseir MANASSA, Amir BAHAR, Abraham NYSKA","doi":"10.1293/tox.2023-0121","DOIUrl":"https://doi.org/10.1293/tox.2023-0121","url":null,"abstract":"In neurosurgical interventions, effective closure of the dura mater is essential to prevent cerebrospinal fluid leakage and minimize post-operative complications. Biodegradable synthetic materials have the potential to be used as dura mater grafts owing to their regenerative properties and low immunogenicity. This study evaluated the safety of ArtiFascia, a synthetic dura mater graft composed of poly(l-lactic-co-caprolactone acid) and poly(d-lactic-co-caprolactone acid), in a rabbit durotomy model. Previously, ArtiFascia demonstrated positive local tolerance and biodegradability in a 12-month preclinical trial. Here, specialized stains were used to evaluate potential brain damage associated with ArtiFascia use. Histochemical and immunohistochemical assessments included Luxol Fast Blue, cresyl Violet, Masson’s Trichrome, neuronal nuclei,, Glial Fibrillary Acidic Protein, and ionized calcium-binding adaptor molecule 1 stains. The stained slides were graded based on the brain-specific reactions. The results showed no damage to the underlying brain tissue for either the ArtiFascia or control implants. Neither inflammation nor neuronal loss was evident, corroborating the safety of the ArtiFascia. This approach, combined with previous histopathological analyses, strengthens the safety profile of ArtiFascia and sets a benchmark for biodegradable material assessment in dura graft applications. This study aligns with the Food and Drug Administration guidelines and offers a comprehensive evaluation of the potential neural tissue effects of synthetic dura mater grafts.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"189 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular autopsy for sudden death in Japan. 日本猝死的分子解剖。

IF 0.9 4区医学

Journal of Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2023-08-30 DOI: 10.1293/tox.2023-0080

Takuma Yamamoto, Yuko Emoto, Takehiko Murase, Takahiro Umehara, Aya Miura, Minori Nishiguchi, Kazuya Ikematsu, Hajime Nishio

{"title":"Molecular autopsy for sudden death in Japan.","authors":"Takuma Yamamoto, Yuko Emoto, Takehiko Murase, Takahiro Umehara, Aya Miura, Minori Nishiguchi, Kazuya Ikematsu, Hajime Nishio","doi":"10.1293/tox.2023-0080","DOIUrl":"10.1293/tox.2023-0080","url":null,"abstract":"Japan has various death investigation systems; however, external examinations, postmortem computed tomography, macroscopic examinations, and microscopic examinations are performed regardless of the system used. These examinations can reveal morphological abnormalities, whereas the cause of death in cases with non-morphological abnormalities can be detected through additional examinations. Molecular autopsy and postmortem genetic analyses are important additional examinations. They are capable of detecting inherited arrhythmias or inherited metabolic diseases, which are representative non-morphological disorders that cause sudden death, especially in infants and young people. In this review, we introduce molecular autopsy reports from Japan and describe our experience with representative cases. The relationships between drug-related deaths and genetic variants are also reviewed. Based on the presented information, molecular autopsy is expected to be used as routine examinations in death investigations because they can provide information to save new lives.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"1 1","pages":"1-10"},"PeriodicalIF":0.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10811381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66318311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats 结合病理、生化和行为评估，评估异烟肼治疗大鼠的外周神经毒性

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-12-29 DOI: 10.1293/tox.2023-0094

Akane KASHIMURA, Satomi NISHIKAWA, Yuhei OZAWA, Yui HIBINO, Takashi TATEOKA, Mao MIZUKAWA, Hironobu NISHINA, Tetsuya SAKAIRI, Takanori SHIGA, Naoyuki AIHARA, Junichi KAMIIE

{"title":"Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats","authors":"Akane KASHIMURA, Satomi NISHIKAWA, Yuhei OZAWA, Yui HIBINO, Takashi TATEOKA, Mao MIZUKAWA, Hironobu NISHINA, Tetsuya SAKAIRI, Takanori SHIGA, Naoyuki AIHARA, Junichi KAMIIE","doi":"10.1293/tox.2023-0094","DOIUrl":"https://doi.org/10.1293/tox.2023-0094","url":null,"abstract":"In drug development, assessment of non-clinical peripheral neurotoxicity is important to ensure human safety. Clarifying the pathological features and mechanisms of toxicity enables the management of safety risks in humans by estimating the degree of risk and proposing monitoring strategies. Published guidelines for peripheral neurotoxicity assessment do not provide detailed information on which endpoints should be monitored preferentially and how the results should be integrated and discussed. To identify an optimal assessment method for the characterization of peripheral neurotoxicity, we conducted pathological, biochemical (biomaterials contributing to mechanistic considerations and biomarkers), and behavioral evaluations of isoniazid-treated rats. We found a discrepancy between the days on which marked pathological changes were noted and those on which biochemical and behavioral changes were noted, suggesting the importance of combining these evaluations. Although pathological evaluation is essential for pathological characterization, the results of biochemical and behavioral assessments at the same time points as the pathological evaluation are also important for discussion. In this study, since the measurement of serum neurofilament light chain could detect changes earlier than pathological examination, it could be useful as a biomarker for peripheral neurotoxicity. Moreover, examination of semi-thin specimens and choline acetyltransferase immunostaining were useful for characterizing morphological neurotoxicity, and image analysis of semi-thin specimens enabled us to objectively show the pathological features.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"80 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139053869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease 环孢素诱发慢性肾病大鼠肾小管上皮细胞中 CD44 的表达

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-12-18 DOI: 10.1293/tox.2023-0111

Kohei MATSUSHITA, Takeshi TOYODA, Hirotoshi AKANE, Tomomi MORIKAWA, Kumiko OGAWA

{"title":"CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease","authors":"Kohei MATSUSHITA, Takeshi TOYODA, Hirotoshi AKANE, Tomomi MORIKAWA, Kumiko OGAWA","doi":"10.1293/tox.2023-0111","DOIUrl":"https://doi.org/10.1293/tox.2023-0111","url":null,"abstract":"Renal tubular epithelial cell (TEC) injury is the most common cause of drug-induced kidney injury (DIKI). Although TEC regeneration facilitates renal function and structural recovery following DIKI, maladaptive repair of TECs leads to irreversible fibrosis, resulting in chronic kidney disease (CKD). CD44 is specifically expressed in TECs during maladaptive repair in several types of rat CKD models. In this study, we investigated CD44 expression and its role in renal fibrogenesis in a cyclosporine (CyA) rat model of CKD. Seven-week-old male Sprague–Dawley rats fed a low-salt diet were subcutaneously administered CyA (0, 15, or 30 mg/kg) for 28 days. CD44 was expressed in atrophic, dilated, and hypertrophic TECs in the fibrotic lesions of the CyA groups. These TECs were collected by laser microdissection and evaluated by microarray analysis. Gene ontology analysis suggested that these TECs have a mesenchymal phenotype, and pathway analysis identified CD44 as an upstream regulator of fibrosis-related genes, including fibronectin 1 (Fn1). Immunohistochemistry revealed that epithelial and mesenchymal markers of TECs of fibrotic lesions were downregulated and upregulated, respectively, and that these TECs were surrounded by a thickened basement membrane. In situ hybridization revealed an increase in Fn1 mRNA in the cytoplasm of TECs of fibrotic lesions, whereas fibronectin protein was localized in the stroma surrounding these tubules. Enzyme-linked immunosorbent assay revealed increased serum CD44 levels in CyA-treated rats. Collectively, these findings suggest that CD44 contributes to renal fibrosis by inducing fibronectin secretion in TECs exhibiting partial epithelial-mesenchymal transition and highlight the potential of CD44 as a biomarker of renal fibrosis. \u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"69 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138824096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug review process advancement and required manufacturer and contract research organization responses 药品审评过程的进展和要求生产商和合同研究组织的回应

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-11-22 DOI: 10.1293/tox.2023-0106

Takayuki ANZAI, Glenn J. MYATT, Frances HALL, Brenda FINNEY, Kenshi NAKAGAWA, Hijiri IWATA, Reo ANZAI, Anne DICKINSON, Matthew FREER, Dai NAKAE, Hiroshi ONODERA, Takaaki MATSUYAMA

{"title":"Drug review process advancement and required manufacturer and contract research organization responses","authors":"Takayuki ANZAI, Glenn J. MYATT, Frances HALL, Brenda FINNEY, Kenshi NAKAGAWA, Hijiri IWATA, Reo ANZAI, Anne DICKINSON, Matthew FREER, Dai NAKAE, Hiroshi ONODERA, Takaaki MATSUYAMA","doi":"10.1293/tox.2023-0106","DOIUrl":"https://doi.org/10.1293/tox.2023-0106","url":null,"abstract":"The United States Senate passed the “FDA Modernization Act 2.0.” on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient safety. Nonetheless, society is becoming increasingly opposed to animal testing, and efforts will be made to use fewer animals and conduct fewer animal tests as a natural and reasonable response. These changes eventually alter the shape of new drug applications. Based on the assumption that fewer animal tests will be conducted or fewer animals will be used in testing, this study explored bioinformatics and new technologies as alternatives to compensate for reduced information and provide a picture of how future new drug applications may look. The authors also discuss the directions that pharmaceutical companies and nonclinical contract research organizations should adopt to promote the replacement, reduction, and refinement of animals used in research, teaching, testing, and exhibitions.\u0000","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"15 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138518799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying the dataset to define the optimal timing of histopathological examination for central nervous system toxicity in MPTP-induced Parkinson's disease monkey model. 确定数据集，以确定MPTP诱导的帕金森病猴模型中枢神经系统毒性的最佳组织病理学检查时间。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-05-24 DOI: 10.1293/tox.2023-0010

YasunoHironobu, MasudaYasushi, OzakiHarushige, SanoTomoya, ShinozawaTadahiro, WatanabeTakeshi

{"title":"Identifying the dataset to define the optimal timing of histopathological examination for central nervous system toxicity in MPTP-induced Parkinson's disease monkey model.","authors":"YasunoHironobu, MasudaYasushi, OzakiHarushige, SanoTomoya, ShinozawaTadahiro, WatanabeTakeshi","doi":"10.1293/tox.2023-0010","DOIUrl":"10.1293/tox.2023-0010","url":null,"abstract":"Determining the optimal timing for histopathological examination following exposure to a test article is crucial for assessing neurotoxicity. However, no study has focused on identifying an ideal dataset to define the optimal timing for histopathological examination of central nervous system (CNS) toxicity in monkeys. Therefore, this study aimed to define a predictive endpoint that would guide us in selecting the optimal timing for histopathological examination of CNS toxicity in monkeys. Four cynomolgus monkeys were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intravenously at a dosage of 0.6 mg/kg twice at 1-week intervals. Necropsies were performed 1 week after the final dose. The Parkinsonian rating (PR) score and temporal changes in neurofilament light chain and glial fibrillary acidic protein concentrations in the cerebrospinal fluid (CSF) and serum were evaluated and compared with the histopathological findings in the brain. The PR score of all animals administered MPTP increased from days 10 to 11, with some degree of individual variability. Microscopically, all animals showed axonal swelling and vacuolation, with or without microgliosis in the nigrostriatal bundle. However, substantial neurodegenerative findings were observed only in animals with high PR scores at necropsy. A slight increase in CSF biomarker levels at necropsy was also observed in animals with high PR scores. However, their correlation with microscopic findings in these animals was unclear. These data suggest that comprehensive clinical observations, such as PR score alone or combined with other CSF biomarkers, could be further evaluated as potential indicators for triggering anatomic CNS evaluations in monkeys following toxic insults.","PeriodicalId":17437,"journal":{"name":"Journal of Toxicologic Pathology","volume":"36 1","pages":"199-204"},"PeriodicalIF":1.2,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66318039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Retraction: Nuclear Morphometric Analysis of Leydig Cells of Male Pubertal Rats Exposed In Utero to Di(n-butyl) Phthalate. 收缩：暴露于邻苯二甲酸二正丁酯的雄性青春期大鼠睾丸间质细胞的核形态计量学分析。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-10-06 DOI: 10.1293/tox.36.R1

Shin Wakui, Masaya Motohashi, Takemi Satoh, Masaru Shirai, Tomoko Mutou, Hiroyuki Takahashi, Michael F Wempe, Hitoshi Endou, Tomoo Inomata, Masao Asari

引用次数: 0

Pathological analysis of lesions in the exocrine pancreas of rats induced by Zinc Maltol. 麦芽酚锌致大鼠外分泌胰腺损伤的病理学分析。

IF 1.2 4区医学

Journal of Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-07-13 DOI: 10.1293/tox.2023-0063

FujiwaraSakura, MorokiTakayasu, HitomiMasaya, SatoMakoto, TerayamaYui, YoshikawaTsuyoshi

引用次数: 0