Toxicologic Pathology最新文献_第3页

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

Characterization of Pulmonary Pathology in the Golden Syrian Hamster Model of COVID-19 Using Micro-Computed Tomography. 用显微计算机断层扫描表征金叙利亚仓鼠新冠肺炎模型的肺部病理。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-04-01 Epub Date: 2024-12-05 DOI: 10.1177/01926233241300451

Julita A Ramirez, Micah D Dunlap, Reyna Prosnitz, Anderson Watson, Mary K Montgomery, Matthew Gutman, Timothy M Coskran, Samantha L Levinson, Katharine Yang, Isis Kanevsky, Shambhunath Choudhary

{"title":"Characterization of Pulmonary Pathology in the Golden Syrian Hamster Model of COVID-19 Using Micro-Computed Tomography.","authors":"Julita A Ramirez, Micah D Dunlap, Reyna Prosnitz, Anderson Watson, Mary K Montgomery, Matthew Gutman, Timothy M Coskran, Samantha L Levinson, Katharine Yang, Isis Kanevsky, Shambhunath Choudhary","doi":"10.1177/01926233241300451","DOIUrl":"10.1177/01926233241300451","url":null,"abstract":"The Golden Syrian hamster is a well-characterized rodent model for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-associated pneumonia. We sought to characterize the pulmonary disease course during SARS-CoV-2 infection (strain USA-WA1/2020) in the hamster model using micro-computed tomography (micro-CT) and compare radiologic observations with histopathologic findings. We observed a range of radiologic abnormalities, including ground glass opacities (GGOs), consolidations, air bronchograms, and pneumomediastinum. The appearance, distribution, and progression of these abnormalities in hamsters were similar to those observed in the lungs of coronavirus disease 2019 (COVID-19) patients by clinical CT and chest X-rays, and correlated with clinical signs and weight loss during the course of disease. Histopathological analysis of infected hamsters revealed lung pathology characteristic of COVID-19 pneumonia, and we observed a strong association between CT and histopathologic scorings. We also analyzed accumulation of air in the thoracic cavity by both manual and automated threshold-based segmentation and found that automated analysis significantly decreases the time needed for data analysis. Data presented here demonstrate that micro-CT imaging can be a major tool in preclinical investigative studies using animal models by providing early and detailed assessment of disease severity and outcomes.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"267-277"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781005","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

Immunotoxicology From a Pathology Perspective: A Continuing Education Course Presented at the Annual STP Meeting in Baltimore, MD, Held June 16-19, 2024. 从病理学角度看免疫毒理学：在2024年6月16日至19日在马里兰州巴尔的摩举行的STP年度会议上提出的继续教育课程。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-03-31 DOI: 10.1177/01926233251328970

Tracey L Papenfuss, Ashwini Phadnis Moghe, Lauren E Himmel, Ana Goyos, Daniel Weinstock

引用次数: 0

Toxicologic Pathology Forum*: Opinion on New Technologies and Trends Disrupting Drug Discovery and Development: How Can the Next Generation of Toxicologic Pathologists Be Prepared for Evolving Roles? 毒理学病理学论坛*：新技术和趋势对药物发现和开发的影响：下一代毒理学病理学家如何为不断变化的角色做好准备？

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-03-31 DOI: 10.1177/01926233251321805

Rebecca Kohnken, Lauren Himmel, Magali Guffroy, Eric A G Blomme

{"title":"Toxicologic Pathology Forum*: Opinion on New Technologies and Trends Disrupting Drug Discovery and Development: How Can the Next Generation of Toxicologic Pathologists Be Prepared for Evolving Roles?","authors":"Rebecca Kohnken, Lauren Himmel, Magali Guffroy, Eric A G Blomme","doi":"10.1177/01926233251321805","DOIUrl":"https://doi.org/10.1177/01926233251321805","url":null,"abstract":"The pace of technological innovation in the pharmaceutical industry, like in many other sectors, is accelerating rapidly. This is not only reshaping how pharmaceutical Research and Development (R&D) is conducted (e.g., introduction of novel models, endpoints, and instrumentation) but also influencing the types of therapeutic modalities being developed. In addition, societal and regulatory expectations have evolved to emphasize approaches that align with the 4Rs principles (Replacement, Reduction, Refinement, and Responsibility) and to encourage the replacement of animal testing with new approach methods (NAMs) through the FDA Modernization Act 2.0. While innovation, societal changes, and regulatory evolution are not new, what stands out is the unprecedented speed and scale at which these transformations are occurring. This acceleration is fueled predominantly by groundbreaking technological advancements (e.g., artificial intelligence, deep learning, communication tools, and digital pathology) in the context of rapidly changing societal dynamics such as globalization, social networking, and the increase in remote working. Given these potentially disruptive changes, it is essential to consider how toxicologic pathologists need to adapt. More importantly, how can they leverage these advancements to contribute even more significantly to the discovery and development of novel, safe, and effective medicines? In essence, what types of toxicologic pathologists will the pharmaceutical industry require in the future?","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251321805"},"PeriodicalIF":1.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754580","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

Interpretative Challenges in Animal Studies: Review of Case Studies and Implications for Toxicologic Pathology. 动物研究中的解释性挑战：案例研究综述及其对毒理学病理学的影响。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2025-03-28 DOI: 10.1177/01926233251322767

Ruba Ibrahim, Abraham Nyska, Susan A Elmore, Molly Boyle, Yuval Ramot

{"title":"Interpretative Challenges in Animal Studies: Review of Case Studies and Implications for Toxicologic Pathology.","authors":"Ruba Ibrahim, Abraham Nyska, Susan A Elmore, Molly Boyle, Yuval Ramot","doi":"10.1177/01926233251322767","DOIUrl":"https://doi.org/10.1177/01926233251322767","url":null,"abstract":"Toxicologic pathologists play a crucial role in the evaluation of animal studies for drugs, environmental chemicals, medical devices, and other agents to determine their safety and potential toxic effects. A significant challenge in this domain is the differentiation between incidental or procedural changes and genuine treatment-related effects. Correct identification and interpretation of such findings are essential to ensure that safety assessments are accurate and reliable for subsequent approval for human use. This review presents several cases in which non-test item-related findings were encountered. By examining procedure-related findings and considering spontaneous background pathology, we underscore the need for meticulous pathological evaluation and proper contextual understanding to avoid misinterpretations that could lead to erroneous conclusions about a substance's safety profile. The insights shared in this review aim to enhance the proficiency of toxicologic pathologists in recognizing and managing various interpretative challenges, with the goal of ultimately improving the accuracy of toxicological assessments, thereby contributing to the safe development of new therapeutics and medical devices and sound characterization of potentially hazardous substances in our environment.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"1926233251322767"},"PeriodicalIF":1.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731190","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