Toxicologic Pathology最新文献_第2页

A Fandango of Form and Function: The Interplay Between Clinical Neurology and Neuropathology Evaluation. 形式与功能的方丹戈：临床神经病学与神经病理学评估之间的相互作用。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-13 DOI: 10.1177/01926233251332210

Brad Bolon, Joe N Kornegay

{"title":"A Fandango of Form and Function: The Interplay Between Clinical Neurology and Neuropathology Evaluation.","authors":"Brad Bolon, Joe N Kornegay","doi":"10.1177/01926233251332210","DOIUrl":"https://doi.org/10.1177/01926233251332210","url":null,"abstract":"The central (CNS) and peripheral (PNS) nervous systems of vertebrates represent divisions of a continuous, body-wide communication grid based on conserved principles of structural organization. Discrete neuroanatomic regions within this grid are associated with specific neural functions, so distinct patterns of neurological dysfunction (\"problems\") can provide guidance regarding neural regions to evaluate beyond those in published sampling schemes or institutional standard operating procedures. Each neurological problem or syndrome (i.e., a group of in-life signs indicating that a given neuroanatomic region is damaged) is associated with a particular list of differential diagnoses and causes. Vulnerability of neural cells and tissues is influenced by intrinsic tissue properties (e.g., high metabolic rates of neurons, presence of blood:tissue barriers, degree of collateral vascular supply) and extrinsic factors (bone protuberances and connective tissue partitions impinging on neural surfaces, fluid flow patterns in the cerebroventricular system and meninges, etc.). In the toxicologic pathology setting, expansion (when warranted) of routine neural sampling protocols to collect additional anatomic regions correlated to a specific neurological problem improves the likelihood that a neuropathological evaluation will identify lesions and causes responsible for neurological conditions as well as detect findings related to potential test item-related neurotoxicity.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251332210"},"PeriodicalIF":1.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047931","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

Inaugural Special Issue Celebrating the 21st Annual Congress of the European Society of Toxicologic Pathology. 首期特刊庆祝第21届欧洲毒理学病理学会年会。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-06 DOI: 10.1177/01926233251337033

Dinesh S Bangari, Saravanan Kaliyaperumal

引用次数: 0

Bilateral Basal Nuclei Vacuolar Lesions: A Novel and Emerging Potential Background Finding in Beagle Dogs. 双侧基底核空泡病变：在比格犬中发现的一种新的潜在背景。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-06 DOI: 10.1177/01926233251335320

Stefanie Arms, Stephen D Cahalan, Felix Goulet, Katja Hempel, Giovanni Pellegrini, Sophie Rau, Julia Schlichtiger, Thomas Nolte

引用次数: 0

Neurobiomarkers: Basic Aspects and Their Relevance in Nonclinical Studies. 神经生物标志物：基本方面及其在非临床研究中的相关性。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-05-06 DOI: 10.1177/01926233251335849

Andrea Greiter-Wilke, Nicolau Beckmann, Warren E Glaab, Diethilde J Theil, Ingrid D Pardo

{"title":"Neurobiomarkers: Basic Aspects and Their Relevance in Nonclinical Studies.","authors":"Andrea Greiter-Wilke, Nicolau Beckmann, Warren E Glaab, Diethilde J Theil, Ingrid D Pardo","doi":"10.1177/01926233251335849","DOIUrl":"https://doi.org/10.1177/01926233251335849","url":null,"abstract":"The second session of the 2024 European Society of Toxicologic Pathology (ESTP) Congress highlighted the significance of neural biomarkers and functional endpoints in nonclinical studies for detecting acute or delayed peripheral (PNS) and central nervous system (CNS) alterations and /or injury caused by drugs during development. The session emphasized the potential clinical translation of these biomarkers and endpoints and critical role of pathologists in correlating these biomarkers with the microscopic findings. Key neural biomarkers discussed included fluid-based biomarkers such as Neurofilament Light Chain (NF-L), Nonspecific Enolase (NSE), Tubulin Associated Unit (TAU), and Glial Fibrillar Associated Protein (GFAP) in blood and/or cerebrospinal fluid (CSF). These were evaluated in 15 in-vivo studies conducted with CNS and PNS toxicants. Safety pharmacology evaluation, such as the Irwin screen/the functional observation battery (FOB), were presented for detecting drug effects on behavior, motor and sensory functions in both rodents and nonrodent species, with or without histopathological correlate. Follow-up tests like nerve conduction velocity assessment were also highlighted. The session underscored the usefulness of noninvasive imaging modalities, including magnetic resonance imaging (MRI), nuclear imaging techniques, X-ray computed tomography, and ultrasound in preclinical studies. Overall, integrating neural biomarkers, safety pharmacology endpoints, advanced imaging modalities, and detailed histopathological analysis aids in better predicting neurotoxicity.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251335849"},"PeriodicalIF":1.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033150","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

Toxicologic Pathology Forum: Opinion on Addressing Gaps in INHAND Terminology for Medical Devices-A Proposal to Add New Diagnostic Nomenclature. 毒理学病理学论坛：关于解决医疗器械INHAND术语差距的意见-增加新的诊断术语的建议。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-05 DOI: 10.1177/01926233251331580

JoAnn C L Schuh, Lyn M Wancket, Brad Bolon, Kathleen A Funk, Nicole Kirchhof, Joanna M Rybicka

{"title":"Toxicologic Pathology Forum: Opinion on Addressing Gaps in INHAND Terminology for Medical Devices-A Proposal to Add New Diagnostic Nomenclature.","authors":"JoAnn C L Schuh, Lyn M Wancket, Brad Bolon, Kathleen A Funk, Nicole Kirchhof, Joanna M Rybicka","doi":"10.1177/01926233251331580","DOIUrl":"https://doi.org/10.1177/01926233251331580","url":null,"abstract":"Historically, safety and efficacy assessment of medical devices began and has continued as standards under the International Organization for Standardization (ISO) rather than under regulatory agency guidelines applied to developing other biomedical product classes. These parallel and unequal pathways have led to multiple and substantive differences in methods and endpoints to determine adverse biological responses among therapeutic classes. Toxicologic pathologists with medical device experience consider standardized nomenclature and diagnostic criteria for medical devices and device-containing combination products as a critical unmet need for nonclinical pathology evaluations. The International Harmonization of Nomenclature and Diagnostic Criteria for Lesions (INHAND) initiative has established globally accepted terminology for proliferative and nonproliferative lesions in various laboratory animal species. Experienced pathologists have identified that some existing INHAND terms for rodents and particularly nonrodents are already used or can be modified for use in medical device studies, but new terms for diagnostic features unique to medical device studies are needed to close gaps in existing INHAND nomenclature. The best approach to establishing appropriate INHAND terms for medical devices (and by extension, device-containing combination products) will be to develop and implement suitable terminology (modified and new, as warranted) to address unmet needs for this distinctive therapeutic class.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251331580"},"PeriodicalIF":1.4,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789227","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

Comparisons of the Sensitivity of Histopathological and Immunohistochemical Analyses With Blood Hormone Levels for Early Detection of Antithyroid Effects in Rats Treated With Promoters of Thyroid Hormone Metabolism. 甲状腺激素代谢促进剂对大鼠抗甲状腺作用早期检测的组织病理学和免疫组化分析与血激素水平的敏感性比较

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-03-13 DOI: 10.1177/01926233251316880

Hirotoshi Akane, Takeshi Toyoda, Kohei Matsushita, Mizuho Uneyama, Tomomi Morikawa, Tadashi Kosaka, Hitoshi Tajima, Hiroaki Aoyama, Kumiko Ogawa

{"title":"Comparisons of the Sensitivity of Histopathological and Immunohistochemical Analyses With Blood Hormone Levels for Early Detection of Antithyroid Effects in Rats Treated With Promoters of Thyroid Hormone Metabolism.","authors":"Hirotoshi Akane, Takeshi Toyoda, Kohei Matsushita, Mizuho Uneyama, Tomomi Morikawa, Tadashi Kosaka, Hitoshi Tajima, Hiroaki Aoyama, Kumiko Ogawa","doi":"10.1177/01926233251316880","DOIUrl":"10.1177/01926233251316880","url":null,"abstract":"Although blood triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels are useful for detecting antithyroid compounds in rodent toxicity studies, there are challenges with high variability due to sampling conditions. Here, we compared histopathological and immunohistochemical findings with blood hormone levels in rats treated with promoters of thyroid hormone metabolism to explore useful markers for hypothyroidism. Six-week-old male and female Sprague-Dawley rats (5/group) were administered phenobarbital sodium salt (NaPB) or nicardipine hydrochloride (NCD) by gavage for 28 days. Decreased serum T4 and increased TSH levels were detected at 100 mg/kg NaPB and 150 mg/kg NCD, whereas follicular cell hypertrophy occurred at lower doses of ≥ 30 mg/kg NaPB and ≥ 50 mg/kg NCD. There was no obvious change in T3 or T4 immunostaining in the thyroid unlike thyroid peroxidase (TPO) inhibitors, and uridine diphosphate-glucuronosyltransferase 1A6-positive area in the liver increased at doses lower than those affecting the serum T4 levels and generally the same as those at which hepatocellular hypertrophy and follicular cell hypertrophy were observed, indicating its usefulness in detecting thyroid hormone metabolism promoters. These results indicate that histopathology is useful for sensitive detection of hormone metabolism promoters and can be distinguished from TPO inhibitors by immunohistochemistry.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"251-266"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626172","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

Corrigendum to Toxicologic Pathology Forum: Opinion on Performing Good Laboratory Practice Histopathology Evaluation for Nonclinical Toxicity Studies in a Remote Location. 毒理学病理学论坛的更正：关于在偏远地区进行非临床毒性研究的良好实验室规范组织病理学评估的意见。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-03-18 DOI: 10.1177/01926233251322124

引用次数: 0

Toxicologic Pathology Forum*: Opinion on Assessing and Communicating Adversity for Implantable Medical Devices. 毒理病理学论坛*：关于评估和通报植入式医疗器械不良反应的意见。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2024-11-27 DOI: 10.1177/01926233241300313

L M Wancket, B Bolon, K A Funk, J C L Schuh

{"title":"Toxicologic Pathology Forum*: Opinion on Assessing and Communicating Adversity for Implantable Medical Devices.","authors":"L M Wancket, B Bolon, K A Funk, J C L Schuh","doi":"10.1177/01926233241300313","DOIUrl":"10.1177/01926233241300313","url":null,"abstract":"Medical devices are a product class encompassing many materials and intended uses. While adversity determination is a key part of nonclinical safety assessments, relatively little has been published about the unique challenges encountered when determining adversity for implantable medical devices. The current paper uses the Society of Toxicologic Pathology (STP)'s \"Scientific and Regulatory Policy Committee Recommended ('Best') Practices for Determining, Communicating, and Using Adverse Effect Data from Nonclinical Studies,\" which were crafted for conventional bio/pharmaceutical products (small and large molecules, cell and gene therapies, etc), as a framework for making adversity decisions for medical devices. Some best principles are directly translatable to medical devices: (1) adversity indicates harm to the animal; (2) effects should be assessed on their merits without speculation regarding future or unmeasured implications; (3) adversity decisions apply only to the test species under the specific conditions of the nonclinical study; and (4) adversity decisions and supporting evidence should be clearly stated in reports. However, unique considerations also apply for evaluating implanted medical devices, including testing of multiple articles in the same animal and the unavoidable tissue trauma during device implantation. This opinion piece offers suggestions for applying previously published STP best practice recommendations for assigning adversity to implantable medical devices.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"278-286"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740628","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

Scientific and Regulatory Policy Committee Points to Consider: Proposal and Recommendations to Reduce Euthanasia of Control Nonhuman Primates in Nonclinical Toxicity Studies. 科学和监管政策委员会指出：在非临床毒性研究中减少控制非人类灵长类动物安乐死的提案和建议。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-01-29 DOI: 10.1177/01926233241309905

Magali Guffroy, Tara Arndt, Erio Barale-Thomas, Susan Bolin, Armelle Grevot, Joelle Ibanes, Steven T Laing, Michael W Leach, Mandy Meindel, Xavier Palazzi, Lila Ramaiah, Julie Schwartz, Robert L Johnson

{"title":"Scientific and Regulatory Policy Committee Points to Consider: Proposal and Recommendations to Reduce Euthanasia of Control Nonhuman Primates in Nonclinical Toxicity Studies.","authors":"Magali Guffroy, Tara Arndt, Erio Barale-Thomas, Susan Bolin, Armelle Grevot, Joelle Ibanes, Steven T Laing, Michael W Leach, Mandy Meindel, Xavier Palazzi, Lila Ramaiah, Julie Schwartz, Robert L Johnson","doi":"10.1177/01926233241309905","DOIUrl":"10.1177/01926233241309905","url":null,"abstract":"Nonhuman primates (NHPs) have been and remain a highly valuable animal model with an essential role in translational research and pharmaceutical drug development. Based on current regulatory guidelines, the nonclinical safety of novel therapeutics should be evaluated in relevant nonclinical species, which commonly includes NHPs for biotherapeutics. Given the practical and ethical limitations on availability and/or use of NHPs and in line with the widely accepted guiding \"3Rs\" (replace, reduce, and refine) principles, many approaches have been considered to optimize toxicity study designs to meaningfully reduce the number of NHPs used. Standard general toxicity studies usually include four groups of equal size, including one group of vehicle control animals. Here, we describe an approach to achieve an overall significant reduction in control animal use, while also resolving many of the issues that may limit application of fully virtual control animals. We propose in Good Laboratory Practice (GLP)-compliant toxicity studies to maintain concurrent control group animals for the in-life phase of the studies, but to limit euthanasia to a subset of control animals. The nonterminated control animals can then be returned to the facility colony for reuse in subsequent studies. The proposed study design could lead to a 15% to 20% reduction in NHP usage. The scientific, logistical, and animal welfare considerations associated with such an approach and suggested solutions are discussed in detail.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"287-296"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068139","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

Development of a Deep Learning Tool to Support the Assessment of Thyroid Follicular Cell Hypertrophy in the Rat. 一种支持大鼠甲状腺滤泡细胞肥大评估的深度学习工具的开发。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2025-01-17 DOI: 10.1177/01926233241309328

Stuart W Naylor, Elizabeth F McInnes, James Alibhai, Scott Burgess, James Baily

{"title":"Development of a Deep Learning Tool to Support the Assessment of Thyroid Follicular Cell Hypertrophy in the Rat.","authors":"Stuart W Naylor, Elizabeth F McInnes, James Alibhai, Scott Burgess, James Baily","doi":"10.1177/01926233241309328","DOIUrl":"10.1177/01926233241309328","url":null,"abstract":"Thyroid tissue is sensitive to the effects of endocrine disrupting substances, and this represents a significant health concern. Histopathological analysis of tissue sections of the rat thyroid gland remains the gold standard for the evaluation for agrochemical effects on the thyroid. However, there is a high degree of variability in the appearance of the rat thyroid gland, and toxicologic pathologists often struggle to decide on and consistently apply a threshold for recording low-grade thyroid follicular hypertrophy. This research project developed a deep learning image analysis solution that provides a quantitative score based on the morphological measurements of individual follicles that can be integrated into the standard pathology workflow. To achieve this, a U-Net convolutional deep learning neural network was used that not just identifies the various tissue components but also delineates individual follicles. Further steps to process the raw individual follicle data were developed using empirical models optimized to produce thyroid activity scores that were shown to be superior to the mean epithelial area approach when compared with pathologists' scores. These scores can be used for pathologist decision support using appropriate statistical methods to assess the presence or absence of low-grade thyroid hypertrophy at the group level.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"240-250"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143011957","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