Toxicologic Pathology最新文献

{"title":"Results of the European Society of Toxicologic Pathology Survey on the Use of Artificial Intelligence in Toxicologic Pathology.","authors":"Xavier Palazzi,&nbsp;Erio Barale-Thomas,&nbsp;Bhupinder Bawa,&nbsp;Jonathan Carter,&nbsp;Kyathanahalli Janardhan,&nbsp;Heike Marxfeld,&nbsp;Abraham Nyska,&nbsp;Chandrassegar Saravanan,&nbsp;Dirk Schaudien,&nbsp;Vanessa L Schumacher,&nbsp;Robert H Spaet,&nbsp;Simone Tangermann,&nbsp;Oliver C Turner,&nbsp;Enrico Vezzali","doi":"10.1177/01926233231182115","DOIUrl":"10.1177/01926233231182115","url":null,"abstract":"<p><p>The European Society of Toxicologic Pathology (ESTP) initiated a survey through its Pathology 2.0 workstream in partnership with sister professional societies in Europe and North America to generate a snapshot of artificial intelligence (AI) usage in the field of toxicologic pathology. In addition to demographic information, some general questions explored AI relative to (1) the current status of adoption across organizations; (2) technical and methodological aspects; (3) perceived business value and finally; and (4) roadblocks and perspectives. AI has become increasingly established in toxicologic pathology with most pathologists being supportive of its development despite some areas of uncertainty. A salient feature consisted of the variability of AI awareness and adoption among the responders, as the spectrum extended from pathologists having developed familiarity and technical skills in AI, to colleagues who had no interest in AI as a tool in toxicologic pathology. Despite a general enthusiasm for these techniques, the overall understanding and trust in AI algorithms as well as their added value in toxicologic pathology were generally low, suggesting room for the need for increased awareness and education. This survey will serve as a basis to evaluate the evolution of AI penetration and acceptance in this domain.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 4","pages":"216-224"},"PeriodicalIF":1.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41140510","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}

{"title":"European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development.","authors":"Josep M Monné Rodríguez,&nbsp;Anna-Lena Frisk,&nbsp;Robert Kreutzer,&nbsp;Thomas Lemarchand,&nbsp;Stephane Lezmi,&nbsp;Chandrassegar Saravanan,&nbsp;Birgit Stierstorfer,&nbsp;Céline Thuilliez,&nbsp;Enrico Vezzali,&nbsp;Grazyna Wieczorek,&nbsp;Seong-Wook Yun,&nbsp;Dirk Schaudien","doi":"10.1177/01926233231178282","DOIUrl":"https://doi.org/10.1177/01926233231178282","url":null,"abstract":"<p><p>In situ hybridization (ISH) is used for the localization of specific nucleic acid sequences in cells or tissues by complementary binding of a nucleotide probe to a specific target nucleic acid sequence. In the last years, the specificity and sensitivity of ISH assays were improved by innovative techniques like synthetic nucleic acids and tandem oligonucleotide probes combined with signal amplification methods like branched DNA, hybridization chain reaction and tyramide signal amplification. These improvements increased the application spectrum for ISH on formalin-fixed paraffin-embedded tissues. ISH is a powerful tool to investigate DNA, mRNA transcripts, regulatory noncoding RNA, and therapeutic oligonucleotides. ISH can be used to obtain spatial information of a cell type, subcellular localization, or expression levels of targets. Since immunohistochemistry and ISH share similar workflows, their combination can address simultaneous transcriptomics and proteomics questions. The goal of this review paper is to revisit the current state of the scientific approaches in ISH and its application in drug research and development.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 3","pages":"92-111"},"PeriodicalIF":1.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f0/7f/10.1177_01926233231178282.PMC10467011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182601","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}

{"title":"Absence of Increased Susceptibility to Acetaminophen-Induced Liver Injury in a Diet-Induced NAFLD Mouse Model.","authors":"Takeshi Izawa,&nbsp;Gregory S Travlos,&nbsp;Ricardo A Cortes,&nbsp;Natasha P Clayton,&nbsp;Robert C Sills,&nbsp;Arun R Pandiri","doi":"10.1177/01926233231171101","DOIUrl":"10.1177/01926233231171101","url":null,"abstract":"<p><p>Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence acetaminophen (APAP [N-acetyl-p-aminophenol])-induced hepatotoxicity in a diet-induced obese (DIO) mouse model of NAFLD. The male C57BL/6NTac DIO mice, fed a high-fat diet for more than 12 weeks, developed obesity, hyperinsulinemia, impaired glucose tolerance, and hepatomegaly with hepatic steatosis, similar to human NAFLD. In the acute toxicity study after a single dose of APAP (150 mg/kg), compared with control lean mice, the DIO mice had decreased serum transaminase levels and less severe hepatocellular injury. The DIO mice also had altered expression of genes related to APAP metabolism. Chronic APAP exposure for 26 weeks did not predispose the DIO mice with NAFLD to more severe hepatotoxicity compared with the lean mice. These results suggested that the C57BL/6NTac DIO mouse model appears to be more tolerant to APAP-induced hepatotoxicity than lean mice, potentially related to altered xenobiotic metabolizing capacity in the fatty liver. Further mechanistic studies with APAP and other drugs in NAFLD animal models are necessary to investigate the mechanism of altered susceptibility to intrinsic DILI in some human NAFLD patients.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 3","pages":"112-125"},"PeriodicalIF":1.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10523943/pdf/nihms-1889671.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182042","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}

{"title":"Retinal and Systemic Toxicity of Vigabatrin Is Driven by the S-Enantiomer in the Long Evans Rat.","authors":"Allan D Rasmussen,&nbsp;Nathalie Truchot,&nbsp;Agnete Dyssegaard,&nbsp;Pierluigi Fant","doi":"10.1177/01926233231179147","DOIUrl":"https://doi.org/10.1177/01926233231179147","url":null,"abstract":"<p><p>In this study, we assessed the toxicity and toxicokinetics of racemic vigabatrin and its S- and R-enantiomers (vigabatrin consists of 50:50% of the two enantiomers) by administering doses of the three test articles to male Long Evans rats via oral gavage. The animals were housed under high-intensity light conditions and the study consisted of an escalating dose phase and a 21-day fixed-dose phase. Systemic toxicity of vigabatrin appears to be due to the Vig-S-enantiomer only, as increasing doses of Vig-S or Vig-RS caused body weight loss, decreased food consumption, and affected activity. Administration of the Vig-R-enantiomer did not cause any such effects. Systemic exposure to R- and S-enantiomers was approximately linear with dose. Compared to administration of the racemate, there appeared to be a tendency for animals to take up higher amounts of Vig-R and lower amounts of Vig-S when administered as enantiomer. Bilateral retinal atrophy was observed in the fixed-dose phase in rats receiving Vig-S (either alone or as part of Vig-RS) and was characterized by irregular thinning and disorganization of the outer nuclear layer and thinning of the photoreceptor layer. The administration of the R-enantiomer alone did not cause any microscopic retinal change.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 3","pages":"126-134"},"PeriodicalIF":1.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182589","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}

{"title":"Neurofilament Light Chain: A Translational Safety Biomarker for Drug-Induced Peripheral Neurotoxicity.","authors":"Diethilde Theil,&nbsp;Jens Kuhle,&nbsp;Dominique Brees,&nbsp;Elaine Tritto,&nbsp;François Pognan,&nbsp;Wilfried Frieauff,&nbsp;Kelley Penraat,&nbsp;Emily Meseck,&nbsp;Reginald Valdez,&nbsp;Andreas Hartmann","doi":"10.1177/01926233231180179","DOIUrl":"https://doi.org/10.1177/01926233231180179","url":null,"abstract":"<p><p>Branaplam is a splicing modulator previously under development as a therapeutic agent for Spinal Muscular Atrophy Type 1 and Huntington's disease. Branaplam increased the levels of survival motor neuron protein in preclinical studies and was well tolerated in early clinical studies; however, peripheral neurotoxicity was observed in a preclinical safety study in juvenile dogs. The aim of this study was to determine whether serum neurofilament light chain (NfL) concentrations in dogs could serve as a monitoring biomarker for branaplam-induced peripheral neurotoxicity. A 30-week time-course investigative study in dogs treated with vehicle control (negative control), neurotoxic pyridoxine (positive control), or branaplam was conducted to assess neuropathology, nerve morphometry, electrophysiological measurements, gene expression profiles, and correlation to NfL serum concentrations. In branaplam-treated animals, a mild to moderate nerve fiber degeneration was observed in peripheral nerves correlating with increased serum NfL concentrations, but there were no observed signs or changes in electrophysiological parameters. Dogs with pyridoxine-induced peripheral axonal degeneration displayed clinical signs and electrophysiological changes in addition to elevated serum NfL. This study suggests that NfL may be useful as an exploratory biomarker to assist in detecting and monitoring treatment-related peripheral nerve injury, with or without clinical signs, associated with administration of branaplam and other compounds bearing a neurotoxic risk.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 3","pages":"135-147"},"PeriodicalIF":1.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10240919","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}

{"title":"Toxicologic Pathology Forum: Opinion on Performing Good Laboratory Practice Histopathology Evaluation for Nonclinical Toxicity Studies in a Remote Location.","authors":"Renee R Hukkanen,&nbsp;Michelle Trapani,&nbsp;Tana Derringer,&nbsp;Victoria Laast,&nbsp;Zbigniew W Wojcinski,&nbsp;Rosa Anna Manno,&nbsp;Matthias Rinke,&nbsp;Eric van Esch,&nbsp;Alys E Bradley,&nbsp;Patrizia Cristofori,&nbsp;Roger Alison,&nbsp;Barb Munch","doi":"10.1177/01926233231168133","DOIUrl":"https://doi.org/10.1177/01926233231168133","url":null,"abstract":"<p><p>Toxicologic/veterinary pathologists are working remotely from Good Laboratory Practice (GLP) test facilities (TFs) in increasing numbers, most commonly in home-office settings. A study pathologist (SP) generating data on GLP-compliant nonclinical studies must be keenly aware of applicable national GLP regulations and comply with TF and protocol requirements. This Toxicological Pathology Forum Opinion Piece will summarize primary areas of emphasis for the SP generating GLP data using glass slides. Peer review and digital review of whole slide images are out of scope for this opinion piece. Key GLP considerations for primary pathology on glass slides are discussed with respect to SP location and employment status, including pathologist qualifications, specimen management, facilities, equipment, archive, and quality assurance. Notable differences between national GLP regulations of the United States, the United Kingdom, Germany, the Netherlands, France, Ireland, Switzerland, Italy, and Israel are presented. With the understanding that each combination of location and employment is unique, the authors provide a general overview of considerations for successful remote GLP work.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 3","pages":"148-152"},"PeriodicalIF":1.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187235","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}

{"title":"Corrigendum to Histology Atlas of the Developing Mouse Placenta.","authors":"","doi":"10.1177/01926233231175051","DOIUrl":"https://doi.org/10.1177/01926233231175051","url":null,"abstract":"Figure 45. Example of twinning with a fused placenta at E15.5. A, Gross image of twin embryos sharing a fused placenta. The embryo shown on the right is slightly smaller and paler than its counterpart on the left. B, Low magnification of twin embryos sharing a fused placenta supporting two sets of umbilical arteries (UA). C, Higher magnification of fused placenta and separate uterine arteries with a clear border (arrows) between the two placentas where there is junctional zone fusion. Note the disorganization of the placenta associated with the right embryo. Intertwin growth discrepancy is a common finding and is likely due to differential nutrient exchange, oxygen supply, and waste removal within the respective placentas.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 3","pages":"153"},"PeriodicalIF":1.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10385552","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}

{"title":"Toxicologic Pathology Forum: Tissue Evaluation in Nonclinical Toxicity Studies for Prophylactic Vaccines.","authors":"Rani S Sellers","doi":"10.1177/01926233231163474","DOIUrl":"10.1177/01926233231163474","url":null,"abstract":"<p><p>Nonclinical toxicity testing (GLP) of prophylactic vaccines to support human clinical trials is outlined in the World Health Organization nonclinical vaccine-development guidelines, which are followed by most regulatory agencies globally. Vaccine GLP toxicity studies include at least two groups: a buffer control (often phosphate-buffered saline) group and a highest anticipated clinical dose formulation group. However, studies may include additional groups, including lower-dose formulation groups and adjuvant-containing formulation control groups. World Health Organization guidelines touch upon expectations for dose group and tissue selection for microscopic evaluation, but there is variation in the interpretation of this aspect of these guidelines between vaccine developers. This opinion piece proposes a scientifically based approach for defining appropriate groups to evaluate in the dosing and recovery phases in nonclinical vaccine toxicity studies, as well as suggestions on selecting tissues for microscopic evaluation at the recovery phase of studies to promote alignment between vaccine manufacturers.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"77-80"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/e2/10.1177_01926233231163474.PMC10278378.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9670396","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}

{"title":"Book Review: Toxicologic Pathology for Non-Pathologists","authors":"B. Bolon","doi":"10.1177/01926233231156614","DOIUrl":"https://doi.org/10.1177/01926233231156614","url":null,"abstract":"At first glance, publication of a book review on a tome dedicated to introducing major toxicologic pathology concepts to non-pathologists in a journal focused on the professional practice of toxicologic pathology would seem to be a pointless endeavor. Nothing could be further from the truth. This concise volume (892 pp [plus 27 pp for index] for the hardcover offering) offers a succinct introduction to many key topics in the field. While designed to edify toxicologists, regulatory reviewers, and basic investigators, Toxicologic Pathology for Non-Pathologists harbors much of value for toxicologic pathologists at all levels, from novice to expert. The text is framed in 20 chapters arranged to provide an orderly tutorial in the field. Each chapter has been written by one or more recognized subject matter experts for that topic, most of whom built their toxicologic pathology careers through long stints in contract research organizations, industry, research laboratories (academic or government), and/or consulting. Chapters possess a wealth of fundamental information, images, and tables as well as bibliographies designed to provide a relevant set of additional readings on that topic. The scope is broad, covering basic pathology practices (4 chapters), key organ systems (13 chapters), and several special problems (3 chapters). A thorough reading of this book will greatly speed the professional development of entry-level toxicologic pathologists while the numerous figures and tables will allow more experienced practitioners to better communicate with non-pathologist team members. The 4 chapters on basic pathology practices afford a masterful introduction to the field. Chapter 1 (“Introduction to Toxicologic Pathology”) paired with Chapter 3 (“Routine and Special Techniques in Toxicologic Pathology”) ably define expected qualifications of toxicologic pathologists, the tools they employ in tissue collection and analysis (focusing on structural [anatomic pathology] methods including in situ chemical and molecular procedures), and principal challenges in data generation (e.g., severity grading) and interpretation (e.g., adversity decisions). Chapter 17 (“Principles of Toxicologic Clinical Pathology”) covers similar considerations as they apply to analysis of cell and fluid samples, emphasizing the impact of such factors as animal species, husbandry, and study design parameters on the quality of the final data set. Chapter 2 (“The Pathology Report, Peer Review, and Pathology Working Group”) effectively addresses the elements that need to be included, or at least pondered, in preparing an accurate, brief, and clear pathology report. Such documents are the raison d'être for the toxicologic pathology role on a study team, and Chapter 2 readily outlines basic findings, their implications, and means of producing the best possible report. The 13 organ system chapters are abridged but nevertheless valuable synopses of major toxicologic pathology information for each","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"75 1","pages":"87 - 88"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74183820","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}

{"title":"Cardiac Rhabdomyoma in Four Göttingen Minipigs.","authors":"Laine E Feller, Aaron Sargeant, E J Ehrhart, Bethany Balmer, Keith Nelson, Jennifer Lamoureux","doi":"10.1177/01926233221148393","DOIUrl":"10.1177/01926233221148393","url":null,"abstract":"<p><p>Göttingen minipigs are increasingly used as an alternative large animal model in nonclinical toxicology studies, and proliferative lesions in this species are rare. Here, we report four cases of cardiac rhabdomyoma in Göttingen minipigs, an incidental and benign mass in the heart. Three cases lacked gross observations and had a microscopic nodule in either the left ventricle or interventricular septum. The last case had a large, firm, raised nodule on a left ventricular papillary muscle noted at necropsy, with additional microscopic intramural masses in the left ventricular wall. In all cases, microscopic evaluation revealed well-circumscribed, expansile nodules composed of bundles of large, highly vacuolated, ovoid to polygonal cells with variable cytoplasmic processes radiating from a centrally located nucleus. Cells displayed patchy accumulation of intracytoplasmic, PAS-positive material and haphazardly arranged cytoplasmic cross-striations. There was no evidence of cardiac insufficiency or other data to suggest the masses were clinically meaningful. Cardiac rhabdomyomas have been reported in meat-hybrid swine, with a breed predisposition in red wattle. This lesion is well established in guinea pigs, but documentation in other laboratory species used in toxicologic studies is limited to two beagle dogs. To our knowledge, this is the first report of spontaneous cardiac rhabdomyoma in Göttingen minipigs.</p>","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"51 1-2","pages":"61-66"},"PeriodicalIF":1.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9645411","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}