Toxicologic Pathology最新文献

Exogenous Growth Hormone Exacerbates Post-Irradiation Atherosclerosis in Susceptible Epicardial Coronary Arteries 外源性生长激素加剧易受辐射影响的心外膜冠状动脉辐射后动脉粥样硬化

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-09-10 DOI: 10.1177/01926233241277454

Krystal J. Vail, J. Daniel Bourland, Gregory O. Dugan, Benny J. Chen, Thomas B. Clarkson, J. Mark Cline, Giselle C. Meléndez

{"title":"Exogenous Growth Hormone Exacerbates Post-Irradiation Atherosclerosis in Susceptible Epicardial Coronary Arteries","authors":"Krystal J. Vail, J. Daniel Bourland, Gregory O. Dugan, Benny J. Chen, Thomas B. Clarkson, J. Mark Cline, Giselle C. Meléndez","doi":"10.1177/01926233241277454","DOIUrl":"https://doi.org/10.1177/01926233241277454","url":null,"abstract":"Cardiac exposure to ionizing radiation can damage both the microvasculature and coronary arteries, as well as increase the long-term risk of heart disease, myocardial fibrosis, and conduction abnormalities. Therapeutic agents capable of promoting recovery from radiation injury to the heart are limited. Growth hormone is linked to improved cardiac function following injury. Here, we leveraged a cynomolgus macaque model to determine the long-term outcomes of recombinant human growth hormone (rhGH) therapy on the heart following low-dose ionizing radiation. Macaques were exposed to 2 Gy radiation, treated with rhGH for one month, and assessed after 2 years. Overall, plasma lipid profile, cardiac function, and coronary artery disease were similar between rhGH and placebo treated animals. However, a subgroup of rhGH-treated animals exhibited more extensive atherosclerotic plaques in the coronary arteries. Together, these findings indicate that transient human growth hormone therapy subsequent to a single low dose of ionizing radiation involving the heart does not result in long-term changes to plasma cholesterol but may promote exacerbated coronary artery disease in a subset of individuals.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177883","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*: mRNA Vaccine Safety–Separating Fact From Fiction 毒理病理学论坛*：mRNA 疫苗安全性--分清事实与虚构

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-09-10 DOI: 10.1177/01926233241278298

Rani S. Sellers, Philip R. Dormitzer

{"title":"Toxicologic Pathology Forum*: mRNA Vaccine Safety–Separating Fact From Fiction","authors":"Rani S. Sellers, Philip R. Dormitzer","doi":"10.1177/01926233241278298","DOIUrl":"https://doi.org/10.1177/01926233241278298","url":null,"abstract":"SARS-CoV-2 spread rapidly across the globe, contributing to the death of millions of individuals from 2019 to 2023, and has continued to be a major cause of morbidity and mortality after the pandemic. At the start of the pandemic, no vaccines or anti-viral treatments were available to reduce the burden of disease associated with this virus, as it was a novel SARS coronavirus. Because of the tremendous need, the development of vaccines to protect against COVID-19 was critically important. The flexibility and ease of manufacture of nucleic acid–based vaccines, specifically mRNA-based products, allowed the accelerated development of COVID-19 vaccines. Although mRNA-based vaccines and therapeutics had been in clinical trials for over a decade, there were no licensed mRNA vaccines on the market at the start of the pandemic. The rapid development of mRNA-based COVID-19 vaccines reduced serious complications and death from the virus but also engendered significant public concerns, which continue now, years after emergency-use authorization and subsequent licensure of these vaccines. This article summarizes and addresses some of the safety concerns that continue to be expressed about these vaccines and their underlying technology.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177884","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

Classic Lesions of the Biliary Tree. 胆管的典型病变

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-08-27 DOI: 10.1177/01926233241257912

John M Cullen, David Malarkey, John R Foster

引用次数: 0

A Minimal Approach to Demonstrate Concordance of Digital and Conventional Microscopy in Toxicologic Pathology. 在毒理病理学中展示数字显微镜和传统显微镜一致性的最低限度方法。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-07-01 Epub Date: 2024-06-03 DOI: 10.1177/01926233241255125

Charlotte Lempp, Stefanie Arms, Christof Albert Bertram, Robert Klopfleisch, Bernd-Wolfgang Igl, Leonie Hezler, Thomas Nolte, Gabriele Pohlmeyer-Esch

{"title":"A Minimal Approach to Demonstrate Concordance of Digital and Conventional Microscopy in Toxicologic Pathology.","authors":"Charlotte Lempp, Stefanie Arms, Christof Albert Bertram, Robert Klopfleisch, Bernd-Wolfgang Igl, Leonie Hezler, Thomas Nolte, Gabriele Pohlmeyer-Esch","doi":"10.1177/01926233241255125","DOIUrl":"10.1177/01926233241255125","url":null,"abstract":"Digitalization of pathology workflows has undergone a rapid evolution and has been widely established in the diagnostic field but remains a challenge in the nonclinical safety context due to lack of regulatory guidance and validation experience for good laboratory practice (GLP) use. One means to demonstrate that digital slides are fit for purpose, that is, provide sufficient quality for pathologists to reach a diagnosis, is conduction of comparison studies, which have been published both, for veterinary and human diagnostic pathology, but not for toxicologic pathology. Here, we present an approach that uses study material from nonclinical safety studies and that allows for the statistical comparison of concordance rates for glass and digital slide evaluation while minimizing time and effort for the involved personnel. Using a benchmark study design, we demonstrate that evaluation of digital slides fits the purpose of nonclinical safety evaluation. These results add to reports of successful workflow validations and support the full adaptation of digital pathology in the regulatory field.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200582","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

Biocompatible Solutions: Evaluating the Safety of Repeated Intra-Articular Injections of pMPCylated Liposomes for Knee Osteoarthritis Therapy in Rat Models. 生物相容性解决方案：评估在大鼠模型中重复关节内注射 pMPCylated 脂质体治疗膝骨关节炎的安全性。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-07-01 Epub Date: 2024-08-28 DOI: 10.1177/01926233241271400

Yuval Ramot, Noam Kronfeld, Michal Steiner, Eric D Lee, Ronit Goldberg, Sabrina Jahn, Abraham Nyska

{"title":"Biocompatible Solutions: Evaluating the Safety of Repeated Intra-Articular Injections of pMPCylated Liposomes for Knee Osteoarthritis Therapy in Rat Models.","authors":"Yuval Ramot, Noam Kronfeld, Michal Steiner, Eric D Lee, Ronit Goldberg, Sabrina Jahn, Abraham Nyska","doi":"10.1177/01926233241271400","DOIUrl":"10.1177/01926233241271400","url":null,"abstract":"Knee osteoarthritis (OA) poses a significant health care burden globally, necessitating innovative therapeutic approaches. CCoat, a novel poly(2-[methacryloyloxy]ethyl phosphorylcholine) (pMPC)ylated liposome device, protects the cartilage surface of the joint from mechanical wear through an entropy-favored process. Two preclinical studies were performed to explore the safety of CCoat following repeated intra-articular (IA) injections into the knee joint (i.e., femorotibial joint) in Sprague-Dawley rats. The studies involved 2 or 3 IA injections, at an interval of 2 or 3 weeks, and an observation period of 1 or 13 weeks after the last injection. Assessments included clinical, histopathological, and immunofluorescent evaluations. In study 1, no mortality or abnormal clinical signs occurred. At 1 week post last injection, histopathology revealed minimal vacuolated macrophages beneath the synovial membrane, predominantly M2-like, indicating a nonadverse response. Immunofluorescent staining supported M2-like macrophage predominance. Study 2 confirmed these findings with no systemic effects over 13 weeks. Statistical analyses indicated no significant differences in body weight, clinical pathology, or organ weights compared with controls. Results affirming the safety of pMPCylated liposomes following repeated IA injections in rat. This novel lubricant coating approach shows promise in OA therapy, with this safety assessment supporting its potential clinical application.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11414135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081559","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

Ginsenoside Rh2 Regulates the Calcium/ROS/CK1α/MLKL Pathway to Promote Premature Eryptosis and Hemolysis in Red Blood Cells. 人参皂苷 Rh2 调节钙/ROS/CK1α/MLKL 通路，促进红细胞过早嗜酸化和溶血

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-07-01 Epub Date: 2024-08-16 DOI: 10.1177/01926233241268846

Sumiah A Alghareeb, Jawaher Alsughayyir, Mohammad A Alfhili

{"title":"Ginsenoside Rh2 Regulates the Calcium/ROS/CK1α/MLKL Pathway to Promote Premature Eryptosis and Hemolysis in Red Blood Cells.","authors":"Sumiah A Alghareeb, Jawaher Alsughayyir, Mohammad A Alfhili","doi":"10.1177/01926233241268846","DOIUrl":"10.1177/01926233241268846","url":null,"abstract":"Ginsenoside Rh2 (GRh2) exhibits significant potential as an anticancer agent; however, progress in developing chemotherapeutic drugs is impeded by their toxicity toward off-target tissues. Specifically, anemia caused by chemotherapy is a debilitating side effect and can be caused by red blood cell (RBC) hemolysis and eryptosis. Cells were exposed to GRh2 in the antitumor range and hemolytic and eryptotic markers were examined under different experimental conditions using photometric and cytofluorimetric methods. GRh2 caused Ca2+-independent, concentration-responsive hemolysis in addition to disrupted ion trafficking with K+ and Cl- leakage. Significant increases in cells positive for annexin-V-fluorescein isothiocyanate, Fluo4, and 2,7-dichlorofluorescein were noted upon GRh2 treatment coupled with a decrease in forward scatter and acetylcholinesterase activity. Importantly, the cytotoxic effects of GRh2 were mitigated by ascorbic acid and by blocking casein kinase 1α (CK1α) and mixed lineage kinase domain-like (MLKL) signaling. In contrast, Ca2+ omission, inhibition of KCl efflux, and isosmotic sucrose aggravated GRh2-induced RBC death. In whole blood, GRh2 selectively targeted reticulocytes and lymphocytes. Altogether, this study identified novel mechanisms underlying GRh2-induced RBC death involving Ca2+ buildup, loss of membrane phospholipid asymmetry and cellular volume, anticholinesterase activity, and oxidative stress. These findings shed light on the hematologic toxicity of GRh2 which is crucial for optimizing its utilization in cancer treatment.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988978","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 an Uncommon Finding in the Basal Nuclei in Beagle Dogs: A Novel Potential Background Lesion in the Canine Brain. 比格犬基底核不常见发现的特征：犬脑中一种新的潜在背景病变。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-07-01 Epub Date: 2024-08-16 DOI: 10.1177/01926233241268849

Stefanie Arms, Katja Hempel, Sophie Rau, Julia Schlichtiger, Thomas Nolte

引用次数: 0

Inter-Rater and Intra-Rater Agreement in Scoring Severity of Rodent Cardiomyopathy and Relation to Artificial Intelligence-Based Scoring. 啮齿动物心肌病严重程度评分中评分者间和评分者内的一致性以及与基于人工智能的评分的关系。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-07-01 Epub Date: 2024-06-22 DOI: 10.1177/01926233241259998

Thomas J Steinbach, Debra A Tokarz, Caroll A Co, Shawn F Harris, Sandra J McBride, Keith R Shockley, Avinash Lokhande, Gargi Srivastava, Rajesh Ugalmugle, Arshad Kazi, Emily Singletary, Mark F Cesta, Heath C Thomas, Vivian S Chen, Kristen Hobbie, Torrie A Crabbs

{"title":"Inter-Rater and Intra-Rater Agreement in Scoring Severity of Rodent Cardiomyopathy and Relation to Artificial Intelligence-Based Scoring.","authors":"Thomas J Steinbach, Debra A Tokarz, Caroll A Co, Shawn F Harris, Sandra J McBride, Keith R Shockley, Avinash Lokhande, Gargi Srivastava, Rajesh Ugalmugle, Arshad Kazi, Emily Singletary, Mark F Cesta, Heath C Thomas, Vivian S Chen, Kristen Hobbie, Torrie A Crabbs","doi":"10.1177/01926233241259998","DOIUrl":"10.1177/01926233241259998","url":null,"abstract":"We previously developed a computer-assisted image analysis algorithm to detect and quantify the microscopic features of rodent progressive cardiomyopathy (PCM) in rat heart histologic sections and validated the results with a panel of five veterinary toxicologic pathologists using a multinomial logistic model. In this study, we assessed both the inter-rater and intra-rater agreement of the pathologists and compared pathologists' ratings to the artificial intelligence (AI)-predicted scores. Pathologists and the AI algorithm were presented with 500 slides of rodent heart. They quantified the amount of cardiomyopathy in each slide. A total of 200 of these slides were novel to this study, whereas 100 slides were intentionally selected for repetition from the previous study. After a washout period of more than six months, the repeated slides were examined to assess intra-rater agreement among pathologists. We found the intra-rater agreement to be substantial, with weighted Cohen's kappa values ranging from k = 0.64 to 0.80. Intra-rater variability is not a concern for the deterministic AI. The inter-rater agreement across pathologists was moderate (Cohen's kappa k = 0.56). These results demonstrate the utility of AI algorithms as a tool for pathologists to increase sensitivity and specificity for the histopathologic assessment of the heart in toxicology studies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440918","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

Immune-Mediated Liver Effects Associated With Administration of a Human Anti-IL-21 Receptor Antibody (ATR-107) in Rats. 在大鼠体内施用人源抗IL-21受体抗体（ATR-107）对肝脏产生的免疫效应

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-07-01 Epub Date: 2024-07-25 DOI: 10.1177/01926233241259011

Wenyue Hu, Bernard S Buetow, Karuna Sachdeva, Michael W Leach

{"title":"Immune-Mediated Liver Effects Associated With Administration of a Human Anti-IL-21 Receptor Antibody (ATR-107) in Rats.","authors":"Wenyue Hu, Bernard S Buetow, Karuna Sachdeva, Michael W Leach","doi":"10.1177/01926233241259011","DOIUrl":"10.1177/01926233241259011","url":null,"abstract":"The toxicity of ATR-107, a human anti-interleukin-21 receptor (IL-21R) monoclonal antibody (mAb), was evaluated in CD-1 mice and cynomolgus monkeys after single-dose intravenous (IV) administration, and in Sprague-Dawley (SD) rats and cynomolgus monkeys after weekly IV and subcutaneous (SC) administration in 13-week toxicity studies that included recovery. Adverse liver necrosis, diffuse bridging fibrosis, and higher liver enzymes occurred in rats in the low-dose IV group (10 mg/kg), but not at 50 or 250 mg/kg IV, and not following SC administration despite overlapping systemic ATR-107 exposures. Similar findings were not seen in mice or cynomolgus monkeys. A series of investigative rat toxicity studies showed liver findings only occurred after administration of at least 3 weekly doses, only occurred in rats that developed anti-drug antibodies (ADAs), and the incidence was associated with higher ADAs titers. However, the presence of ADAs did not always result in liver injury. Liver findings did not occur in nude rats, which had high ATR-107 exposures and no ADAs. These findings suggest an adaptive immune response with formation of ADAs was necessary for development of ATR-107-related liver findings, and that liver injury can occur in rats secondary to development of ADAs following repeated administration of a human therapeutic mAb.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761061","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

Histology Atlas of the Developing Mouse Respiratory System From Prenatal Day 9.0 Through Postnatal Day 30. 从出生前第 9.0 天到出生后第 30 天小鼠呼吸系统发育组织学图谱》（Histology Atlas of the Developing Mouse Respiratory System From Prenatal Day 9.0 Through Postnatal Day 30.

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2024-06-01 Epub Date: 2024-08-03 DOI: 10.1177/01926233241252114

Vanessa R Parslow, Susan A Elmore, Robert Z Cochran, Brad Bolon, Beth Mahler, David Sabio, Beth A Lubeck

{"title":"Histology Atlas of the Developing Mouse Respiratory System From Prenatal Day 9.0 Through Postnatal Day 30.","authors":"Vanessa R Parslow, Susan A Elmore, Robert Z Cochran, Brad Bolon, Beth Mahler, David Sabio, Beth A Lubeck","doi":"10.1177/01926233241252114","DOIUrl":"10.1177/01926233241252114","url":null,"abstract":"Respiratory diseases are one of the leading causes of death and disability around the world. Mice are commonly used as models of human respiratory disease. Phenotypic analysis of mice with spontaneous, congenital, inherited, or treatment-related respiratory tract abnormalities requires investigators to discriminate normal anatomic features of the respiratory system from those that have been altered by disease. Many publications describe individual aspects of normal respiratory tract development, primarily focusing on morphogenesis of the trachea and lung. However, a single reference providing detailed low- and high-magnification, high-resolution images of routine hematoxylin and eosin (H&E)-stained sections depicting all major structures of the entire developing murine respiratory system does not exist. The purpose of this atlas is to correct this deficiency by establishing one concise reference of high-resolution color photomicrographs from whole-slide scans of H&E-stained tissue sections. The atlas has detailed descriptions and well-annotated images of the developing mouse upper and lower respiratory tracts emphasizing embryonic days (E) 9.0 to 18.5 and major early postnatal events. The selected images illustrate the main structures and events at key developmental stages and thus should help investigators both confirm the chronological age of mouse embryos and distinguish normal morphology as well as structural (cellular and organ) abnormalities.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879464","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