Toxicologic Pathology最新文献_第10页

Scientific and Regulatory Policy Committee Points to Consider: Primary Digital Histopathology Evaluation and Peer Review for Good Laboratory Practice (GLP) Nonclinical Toxicology Studies 科学和监管政策委员会考虑的要点:良好实验室规范(GLP)非临床毒理学研究的初级数字组织病理学评估和同行评审

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-06-01 DOI: 10.1177/01926233221099273

T. Forest, F. Aeffner, D. Bangari, B. Bawa, Jonathan Carter, J. Fikes, Wanda High, S. Hayashi, M. Jacobsen, LuAnn Mckinney, D. Rudmann, T. Steinbach, V. Schumacher, Oliver C. Turner, J. Ward, C. Willson

{"title":"Scientific and Regulatory Policy Committee Points to Consider: Primary Digital Histopathology Evaluation and Peer Review for Good Laboratory Practice (GLP) Nonclinical Toxicology Studies","authors":"T. Forest, F. Aeffner, D. Bangari, B. Bawa, Jonathan Carter, J. Fikes, Wanda High, S. Hayashi, M. Jacobsen, LuAnn Mckinney, D. Rudmann, T. Steinbach, V. Schumacher, Oliver C. Turner, J. Ward, C. Willson","doi":"10.1177/01926233221099273","DOIUrl":"https://doi.org/10.1177/01926233221099273","url":null,"abstract":"The Society of Toxicologic Pathology’s Scientific and Regulatory Policy Committee formed a working group to consider the present and future use of digital pathology in toxicologic pathology in general and specifically its use in primary evaluation and peer review in Good Laboratory Practice (GLP) environments. Digital histopathology systems can save costs by reducing travel, enhancing organizational flexibility, decreasing slide handling, improving collaboration, increasing access to historical images, and improving quality and efficiency through integration with laboratory information management systems. However, the resources to implement and operate a digital pathology system can be significant. Given the magnitude and risks involved in the decision to adopt digital histopathology, this working group used pertinent previously published survey results and its members’ expertise to create a Points-to-Consider article to assist organizations with building and implementing digital pathology workflows. With the aim of providing a comprehensive perspective, the current publication summarizes aspects of digital whole-slide imaging relevant to nonclinical histopathology evaluations, and then presents points to consider applicable to both primary digital histopathology evaluation and digital peer review in GLP toxicology studies. The Supplemental Appendices provide additional tabulated resources.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"52 1","pages":"531 - 543"},"PeriodicalIF":1.5,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81771882","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: 1

Does Geographical Origin of Long-Tailed Macaques (Macaca fascicularis) Matter in Drug Safety Assessment?: A Literature Review and Proposed Conclusion 长尾猕猴(Macaca fascularis)的地理来源与药物安全性评估有关吗?:文献综述及建议结论

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-05-24 DOI: 10.1177/01926233221095443

G. Weinbauer, L. Mecklenburg

{"title":"Does Geographical Origin of Long-Tailed Macaques (Macaca fascicularis) Matter in Drug Safety Assessment?: A Literature Review and Proposed Conclusion","authors":"G. Weinbauer, L. Mecklenburg","doi":"10.1177/01926233221095443","DOIUrl":"https://doi.org/10.1177/01926233221095443","url":null,"abstract":"Long-tailed macaques are the predominant nonhuman primate species for the nonclinical safety testing of biopharmaceuticals. This species comprises 9 subspecies with Macaca fascicularis fascicularis naturally occurring in Southeast Asia. Since the 17th century, M. f. fascicularis also occurs on Mauritius. Cynomolgus macaques do not naturally occur in China, but are bred in many farms across the country. The current shortage in animal supply raises the question whether geographical animal origin matters and if animals from different geographical regions can be combined on a drug development program or even a single experiment. This article reviews geographical animal origin in relation to selected endpoints that are relevant in nonclinical drug safety testing. Animals from different countries within Asia mainland do not appear to show any meaningful difference. Very little data are available for animals from Asia island. Mauritian animals show consistent differences from Asian animals in several clinical and anatomical pathology parameters. For developmental parameters, animals from Mauritius and Asia are comparable with the exception that Mauritian animals mature faster. In the authors’ view, differences between the geographical clusters can be accounted for as long as baseline and reference data are available.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"93 1","pages":"552 - 559"},"PeriodicalIF":1.5,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90371410","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: 2

Comparison of ANP and BNP Granular Density in Atria of Rats After Physiological and Pathological Hypertrophy 生理性和病理性肥大大鼠心房ANP和BNP颗粒密度的比较

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-05-24 DOI: 10.1177/01926233221097970

Kevin Agostinucci, T. Manfredi, A. Cosmas, F. J. Vetter, S. Engle

{"title":"Comparison of ANP and BNP Granular Density in Atria of Rats After Physiological and Pathological Hypertrophy","authors":"Kevin Agostinucci, T. Manfredi, A. Cosmas, F. J. Vetter, S. Engle","doi":"10.1177/01926233221097970","DOIUrl":"https://doi.org/10.1177/01926233221097970","url":null,"abstract":"Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones located in atria granules. Both peptides respond to cardiac pressure and volume dynamics and accordingly serve as translation biomarkers for the clinical treatment of heart failure. Serum ANP and BNP play central secretary roles in blood pressure and cardiac output regulation and have proven utility as differential biomarkers of cardiovascular proficiency and drug-induced maladaptation, yet both peptides are impervious to exercise-induced hypertrophy. We employed immunoelectron microscopy to examine the effects of 28 days of chronic swim exercise or administration of a PPARγ agonist on atrial granules and their stored natriuretic peptides in Sprague Dawley rats. Chronic swimming and drug treatment both resulted in a 15% increase in heart weight compared with controls, with no treatment effects on perinuclear granule area in the left atria (LAs). Drug treatment resulted in larger size granules with greater BNP density in the right atria. Comparing swimming and PPARγ agonist treatment effects on ANP:BNP granule density ratios between atrial chambers revealed a shift toward a greater proportion of ANP than BNP in LAs of swim-trained rats. These data suggest a distinction in the population of ANP and BNP after chronic swim or PPARγ that makes it a novel metric for the differentiation of pathological and physiological hypertrophy.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"10 1","pages":"497 - 506"},"PeriodicalIF":1.5,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85293561","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: 2

Kidney Effects by Alternative Classes of Medicines in Patients and Relationship to Effects in Nonclinical Toxicity Studies 在非临床毒性研究中，替代药物对患者肾脏的影响及其与影响的关系

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-05-24 DOI: 10.1177/01926233221100414

Kendall S. Frazier

{"title":"Kidney Effects by Alternative Classes of Medicines in Patients and Relationship to Effects in Nonclinical Toxicity Studies","authors":"Kendall S. Frazier","doi":"10.1177/01926233221100414","DOIUrl":"https://doi.org/10.1177/01926233221100414","url":null,"abstract":"Drug-induced kidney injury has historically been associated with renal tubule injury related to small molecule pharmaceuticals such as nonsteroidal anti-inflammatory drugs, antineoplastic agents, or antibiotics, but as a greater number of alternative classes of medicines such as biotherapeutics, molecular-targeted antineoplastic drugs, chimeric antigen receptor T-cell therapies, antibody-drug conjugates, oligonucleotide therapies, or other immunomodulatory drugs come to market, the presentation of drug-induced nephrotoxicity is changing. This review article describes the potential rare clinical events in drug-induced kidney injury that might be noted with these new therapies and their potential impact on patients. Potential pathogenic mechanisms related to immunogenicity, immune complex formation, and stimulation of downstream proinflammatory pathways with some of these alternative medicine classes have resulted in the potential for glomerulonephritis, acute interstitial nephritis, renal vasculitis, and other immune-mediated renal disorders in humans. This contrasts with nonclinical toxicity studies, where biologic therapies more often result in vasculitis and glomerulonephritis associated with antidrug antibodies and immunomodulatory pharmacology, and which are not always predictive of clinical effects. While nonclinical antidrug antibody-related renal disease is generally not clinically relevant, other immune-mediated nephrotoxicities associated with immunomodulatory drugs may be predictive of clinical adverse events. Fortunately, these conditions are still rare and account for a small percentage of serious adverse events in kidneys of patients.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"7 1","pages":"408 - 414"},"PeriodicalIF":1.5,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83337754","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: 1

The Influence of Geographical Origin, Age, Sex, and Animal Husbandry on the Spontaneous Histopathology of Laboratory Cynomolgus Macaques (Macaca Fascicularis): A Contemporary Global and Multisite Review of Historical Control Data 地理来源、年龄、性别和畜牧业对实验室食蟹猕猴(Macaca Fascicularis)自发组织病理学的影响:对历史对照数据的当代全球和多地点回顾

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-05-10 DOI: 10.1177/01926233221096424

R. Chamanza, S. Naylor, M. Gregori, M. Boyle, Marcia E Pereira Bacares, E. Drevon-Gaillot, Annette Romeike, Cynthia Courtney, Kelsey Johnson, Julie Turner, Nadine Swierzawski, Alok K. Sharma

{"title":"The Influence of Geographical Origin, Age, Sex, and Animal Husbandry on the Spontaneous Histopathology of Laboratory Cynomolgus Macaques (Macaca Fascicularis): A Contemporary Global and Multisite Review of Historical Control Data","authors":"R. Chamanza, S. Naylor, M. Gregori, M. Boyle, Marcia E Pereira Bacares, E. Drevon-Gaillot, Annette Romeike, Cynthia Courtney, Kelsey Johnson, Julie Turner, Nadine Swierzawski, Alok K. Sharma","doi":"10.1177/01926233221096424","DOIUrl":"https://doi.org/10.1177/01926233221096424","url":null,"abstract":"To investigate the influence of geographical origin, age, and sex on toxicologically relevant spontaneous histopathology findings in cynomolgus macaques (Macaca fascicularis), we performed a comparative analysis of historical control data (HCD) from 13 test sites that included 3351 animals (1645 females and 1706 males) sourced from Mauritius, China, Vietnam, and Cambodia, aged from 2 to 9.5 years, and from 446 toxicology studies evaluated between 2016 and 2021. The most common findings were mononuclear infiltrates in the kidney, liver, brain, and lung, which showed highest incidences in Mauritian macaques, and heart, salivary glands, and gastrointestinal tract (GIT), which showed highest incidences of mononuclear infiltrates in mainland Asian macaques. Developmental and degenerative findings were more common in Mauritian macaques, while lymphoid hyperplasia and lung pigment showed higher incidences in Asian macaques. Various sex and age-related differences were also present. Despite origin-related differences, the similarities in the nature and distribution of background lesions indicate that macaques from all geographical regions are suitable for toxicity testing and show comparable lesion spectrum. However, in a toxicity study, it is strongly recommended to use animals from a single geographical origin and to follow published guidelines when using HCD to evaluate and interpretate commonly diagnosed spontaneous lesions.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"94 1","pages":"607 - 627"},"PeriodicalIF":1.5,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81530294","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: 5

Gastric Neuroendocrine Tumors With Parietal Cell Atrophy in a Long-term Carcinogenicity Study in Rats 大鼠胃神经内分泌肿瘤伴壁细胞萎缩的长期致癌性研究

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-05-05 DOI: 10.1177/01926233221095445

N. Shirai, S. Choudhary, C. Houle

引用次数: 1

Selected Resources for Pathology Evaluation of Nonhuman Primates in Nonclinical Safety Assessment 非临床安全性评估中非人灵长类动物病理评估的精选资源

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-04-28 DOI: 10.1177/01926233221091763

B. Bolon, J. Everitt

引用次数: 1

Comparison of Routine Hematology, Coagulation, and Clinical Chemistry Parameters of Cynomolgus Macaques of Mauritius Origin With Cynomolgus Macaques of Cambodia, China, and Vietnam Origin 毛里求斯原产食蟹猴与柬埔寨、中国、越南原产食蟹猴常规血液学、凝血和临床化学指标的比较

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-04-25 DOI: 10.1177/01926233221089843

Tara Arndt, Mandy J. Meindel, Joseph Clarke, Amanda Shaw, M. Gregori

{"title":"Comparison of Routine Hematology, Coagulation, and Clinical Chemistry Parameters of Cynomolgus Macaques of Mauritius Origin With Cynomolgus Macaques of Cambodia, China, and Vietnam Origin","authors":"Tara Arndt, Mandy J. Meindel, Joseph Clarke, Amanda Shaw, M. Gregori","doi":"10.1177/01926233221089843","DOIUrl":"https://doi.org/10.1177/01926233221089843","url":null,"abstract":"Cynomolgus macaques (Macaca fascicularis) are commonly used in safety assessment and as translational models for drug development. Recent supply chain pressures, exportation bans, and increased demand for drug safety assessment studies exacerbated by the COVID-19 pandemic have prompted the investigation of utilizing macaques of different geographic origin in preclinical toxicity studies. This study compares routine hematology, coagulation, and clinical chemistry endpoints of 3 distinct subpopulations of mainland Asia origin (Cambodia, China, and Vietnam) with Mauritius origin macaques compiling results of 3,225 animals from 123 regulatory toxicology studies conducted at North American and European Union contract research organization facilities between 2016 and 2019. Results were generally similar amongst the subpopulations compared in this study. Few notable differences in hematology test results and several minor differences in serum biochemistry and coagulation test results were identified when 3 distinct subpopulations of mainland Asia origin macaques were compared with Mauritius origin macaques. Our findings support the use of different origin macaques in drug development programs; however, emphasizes the importance of maintaining consistency in geographic origin of animals within a study.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"40 1","pages":"591 - 606"},"PeriodicalIF":1.5,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87337552","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: 1

Organ Weights in Relation to Age and Sex in Cynomolgus Monkeys (Macaca fascicularis) 食蟹猴(Macaca fascularis)器官重量与年龄和性别的关系

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-04-06 DOI: 10.1177/01926233221088283

Rachel Amato, J. F. Gardin, J. Tooze, J. Cline

{"title":"Organ Weights in Relation to Age and Sex in Cynomolgus Monkeys (Macaca fascicularis)","authors":"Rachel Amato, J. F. Gardin, J. Tooze, J. Cline","doi":"10.1177/01926233221088283","DOIUrl":"https://doi.org/10.1177/01926233221088283","url":null,"abstract":"Laboratory animal research is an important contributor to both human and animal medicine. Currently, there is extensive use of cynomolgus monkeys (Macaca fascicularis) in pathology and toxicology research. The purpose of this study was to define reference values for absolute and percentage organ weights in M fascicularis of different ages and sex. Organ weights were obtained from necropsies of 1022 cynomolgus monkeys at the Wake Forest School of Medicine from 1997 to 2018. Distributions of absolute and percentage weights for each organ were described; sex and age groups were compared using analysis of variance. Age effects on percentage of body weights for each organ were analyzed within each sex. Diet effects were also analyzed. This evaluation showed that male body weights and absolute organ weights were greater for all age groups; however, female organ to body weight percentages were greater for most organs. Percentage of organ weight to body weight declined for the adrenals, brain, lung, thyroid and thymus during maturation, whereas percentage weight of pancreas, prostate, testes, and uterus increased. Animals consuming a high-fat, Western-type diet had a lower body weight than animals consuming a carbohydrate-rich chow diet. This information will be useful for further toxicology and pathology studies concerning cynomolgus monkeys.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"140 1","pages":"574 - 590"},"PeriodicalIF":1.5,"publicationDate":"2022-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77025843","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: 5

Developing a Solution for Nasal and Olfactory Transport of Nanomaterials. 纳米材料鼻腔和嗅觉运输解决方案的开发。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-04-01 DOI: 10.1177/01926233221089209

Ryan C O'Connell, Tiana M Dodd, Sidney M Clingerman, Kara L Fluharty, Jayme Coyle, Todd A Stueckle, Dale W Porter, Lauren Bowers, Aleksandr B Stefaniak, Alycia K Knepp, Raymond Derk, Michael Wolfarth, Robert R Mercer, Theresa E Boots, Krishnan Sriram, Ann F Hubbs

{"title":"Developing a Solution for Nasal and Olfactory Transport of Nanomaterials.","authors":"Ryan C O'Connell, Tiana M Dodd, Sidney M Clingerman, Kara L Fluharty, Jayme Coyle, Todd A Stueckle, Dale W Porter, Lauren Bowers, Aleksandr B Stefaniak, Alycia K Knepp, Raymond Derk, Michael Wolfarth, Robert R Mercer, Theresa E Boots, Krishnan Sriram, Ann F Hubbs","doi":"10.1177/01926233221089209","DOIUrl":"https://doi.org/10.1177/01926233221089209","url":null,"abstract":"With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-Omptm3Mom/MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"50 3","pages":"329-343"},"PeriodicalIF":1.5,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872725/pdf/nihms-1861694.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9295913","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