Toxicologic Pathology最新文献_第8页

Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) Mice. 基于下一代测序的荷尔玛氏肠杆菌鉴定：NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) 小鼠高死亡率疾病的致病菌。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-13 DOI: 10.1177/01926233241231286

Catherine Si, Kourtney Nickerson, Taylor Simmons, Parker Denton, M Russell Nichols, Robert C Dysko, Mark Hoenerhoff, Rinosh Mani, Cheryl Woods, Kenneth S Henderson, Zachary T Freeman

{"title":"Next-Generation Sequencing-Based Identification of Enterobacter hormaechei as Causative Agent of High Mortality Disease in NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) Mice.","authors":"Catherine Si, Kourtney Nickerson, Taylor Simmons, Parker Denton, M Russell Nichols, Robert C Dysko, Mark Hoenerhoff, Rinosh Mani, Cheryl Woods, Kenneth S Henderson, Zachary T Freeman","doi":"10.1177/01926233241231286","DOIUrl":"10.1177/01926233241231286","url":null,"abstract":"NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice, lacking many components of a mature immune system, are at increased risk of disease. General understanding of potential pathogens of these mice is limited. We describe a high mortality disease outbreak caused by an opportunistic bacterial infection in NSG mice. Affected animals exhibited perianal fecal staining, dehydration, and wasting. Histopathologic lesions included a primary necrotizing enterocolitis, with inflammatory and necrotizing lesions also occurring in the liver, kidneys, heart, and brain of some mice. All affected individuals tested negative for known opportunistic pathogens of immunodeficient mice. We initially identified a member of Enterobacter cloacae complex (ECC) in association with the outbreak by traditional diagnostics. ECC was cultured from extraintestinal organs, both with and without histopathologic lesions, suggesting bacteremia. Infrared spectroscopy and MALDI-TOF mass spectrometry demonstrated that isolates from the outbreak shared molecular features and likely a common origin. We subsequently hypothesized that advanced sequencing methods would identify a single species of ECC associated with clinical disease. Using a novel targeted amplicon-based next-generation sequencing assay, we identified Enterobacter hormaechei in association with this outbreak. Knowledge of this organism as a potential opportunistic pathogen in NSG mice is critical for preclinical studies to prevent loss of animals and confounding of research.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"67-80"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140111506","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

Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation. 补充或不补充各种禁食期对 Sprague-Dawley 大鼠福利影响的比较

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-02-20 DOI: 10.1177/01926233241230536

Adeyemi O Adedeji, Fiona Zhong, Janice Corpuz, Fangyao Hu, Xiaofeng Zhao, Dewakar Sangaraju, Catherine F Ruff, Noel Dybdal

{"title":"Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation.","authors":"Adeyemi O Adedeji, Fiona Zhong, Janice Corpuz, Fangyao Hu, Xiaofeng Zhao, Dewakar Sangaraju, Catherine F Ruff, Noel Dybdal","doi":"10.1177/01926233241230536","DOIUrl":"10.1177/01926233241230536","url":null,"abstract":"In nonclinical toxicology studies, lab animals are fasted typically overnight, to reduce variability in some clinical pathology parameters. However, fasting adds undue stress, and this is particularly concerning in rodents given their fast metabolic rates. Furthermore, as rodents are nocturnal animals, an overnight fasting may cause a protracted negative metabolic state even when the fasting has technically ended, given their minimal activity and food consumption during the day. Therefore, to evaluate the impacts of different fasting durations (±DietGel supplementation) on rats' welfare, we assessed the traditional and ancillary clinical pathology parameters in Sprague-Dawley rats, along with body weight, organ weight, and histopathology. Although most endpoints were comparable between the different fasting durations (±DietGel supplementation), the long fasting times (≥8 hr) without DietGel supplementation caused significant decreases in body weight, liver weight, liver glycogen content, serum glucose, triglyceride, and creatinine concentrations-all findings suggestive of a negative energy balance that could impact animal welfare and consequently, data quality; while the short fasting time (4 hr) and DietGel supplementation were associated with higher triglycerides variability. Hence, we propose that short fasting time should be adequate for most toxicology studies in rats, and long fasting times should only be accommodated with scientific justification.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"21-34"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139913490","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

Expression of Concern. 表达关切。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2024-01-01 Epub Date: 2024-03-07 DOI: 10.1177/01926233241238763

引用次数: 0

Select Toxicologic Pathology Case Studies of the Hepatobiliary System. 肝胆系统毒物病理学病例研究精选》。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2024-01-28 DOI: 10.1177/01926233231224464

Allison C Boone, Shakirat A Adetunji, Rebecca Kohnken, Kenji Koyama

引用次数: 0

Toxicogenomics Approaches to Address Toxicity and Carcinogenicity in the Liver. 解决肝脏毒性和致癌性的毒物基因组学方法。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2024-01-30 DOI: 10.1177/01926233241227942

Arun R Pandiri, Scott S Auerbach, Jim L Stevens, Eric A G Blomme

{"title":"Toxicogenomics Approaches to Address Toxicity and Carcinogenicity in the Liver.","authors":"Arun R Pandiri, Scott S Auerbach, Jim L Stevens, Eric A G Blomme","doi":"10.1177/01926233241227942","DOIUrl":"10.1177/01926233241227942","url":null,"abstract":"Toxicogenomic technologies query the genome, transcriptome, proteome, and the epigenome in a variety of toxicological conditions. Due to practical considerations related to the dynamic range of the assays, sensitivity, cost, and technological limitations, transcriptomic approaches are predominantly used in toxicogenomics. Toxicogenomics is being used to understand the mechanisms of toxicity and carcinogenicity, evaluate the translational relevance of toxicological responses from in vivo and in vitro models, and identify predictive biomarkers of disease and exposure. In this session, a brief overview of various transcriptomic technologies and practical considerations related to experimental design was provided. The advantages of gene network analyses to define mechanisms were also discussed. An assessment of the utility of toxicogenomic technologies in the environmental and pharmaceutical space showed that these technologies are being increasingly used to gain mechanistic insights and determining the translational relevance of adverse findings. Within the environmental toxicology area, there is a broader regulatory consideration of benchmark doses derived from toxicogenomics data. In contrast, these approaches are mainly used for internal decision-making in pharmaceutical development. Finally, the development and application of toxicogenomic signatures for prediction of apical endpoints of regulatory concern continues to be area of intense research.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"470-481"},"PeriodicalIF":1.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11014763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139576463","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

An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy. AAV基因治疗相关的非临床和临床肝毒性综述。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-09-29 DOI: 10.1177/01926233231201408

Laurence O Whiteley

引用次数: 0

Translational Relevance of Rodent Models to Predict Human Liver Disease. 预测人类肝病的啮齿动物模型的转化意义

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2024-03-18 DOI: 10.1177/01926233241230543

Debabrata Mahapatra, Robert Maronpot

{"title":"Translational Relevance of Rodent Models to Predict Human Liver Disease.","authors":"Debabrata Mahapatra, Robert Maronpot","doi":"10.1177/01926233241230543","DOIUrl":"10.1177/01926233241230543","url":null,"abstract":"Animals models are essential to understand the complex pathobiology of human diseases. George Box's aphorism based on statistics \"All models are wrong, but some are useful\" certainly applies to animal models of disease. In this session, the translational relevance of various animal models applicable to human liver disease was explored starting with a historic overview of the rodent cancer bioassay with emphasis on hepatocarcinogenesis from early work at the National Cancer Institute, refinement by the National Toxicology Program and contemporary efforts to identify potential mechanisms and their relevance to human cancer risk. Subsequently, recently elucidated understanding of the molecular drivers and signaling mechanisms of liver pathophysiology and liver cancer, including factors associated with liver regeneration, metabolic hepatocellular zonation, and the role of macrophages and their crosstalk with stellate cells in understanding human liver disease was discussed. Next, our contemporary understanding of the role of nuclear receptors in hepatic homeostasis and drug response highlighting nuclear receptor activation and crosstalk in modulating biological responses associated with liver damage and neoplastic response were discussed. Finally, an overview and translational relevance of different drug-induced liver injury (DILI) rodent model systems focused on pathology and mechanisms with commentary on current relevant Food and Drug Administration (FDA) perspective were summarized with closing remarks.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"482-486"},"PeriodicalIF":1.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144117","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

Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity. 肝胆汁酸转运体与药物性肝毒性。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2023-11-20 DOI: 10.1177/01926233231212255

Chitra Saran, Kim L R Brouwer

{"title":"Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity.","authors":"Chitra Saran, Kim L R Brouwer","doi":"10.1177/01926233231212255","DOIUrl":"10.1177/01926233231212255","url":null,"abstract":"Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure. One mechanism of DILI is altered bile acid homeostasis and involves several hepatic bile acid transporters. Functional impairment of some hepatic bile acid transporters by drugs, disease, or genetic mutations may lead to toxic accumulation of bile acids within hepatocytes and increase DILI susceptibility. This review focuses on the role of hepatic bile acid transporters in DILI. Model systems, primarily in vitro and modeling tools, such as DILIsym, used in assessing transporter-mediated DILI are discussed. Due to species differences in bile acid homeostasis and drug-transporter interactions, key aspects and challenges associated with the use of preclinical animal models for DILI assessment are emphasized. Learnings are highlighted from three case studies of hepatotoxic drugs: troglitazone, tolvaptan, and tyrosine kinase inhibitors (dasatinib, pazopanib, and sorafenib). The development of advanced in vitro models and novel biomarkers that can reliably predict DILI is critical and remains an important focus of ongoing investigations to minimize patient risk for liver-related adverse reactions associated with medication use.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"405-413"},"PeriodicalIF":1.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11014762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138047997","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

Proceedings of the 2023 Division of Translational Toxicology Satellite Symposium. 2023 年转化毒理学分部卫星研讨会论文集》。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2024-03-06 DOI: 10.1177/01926233241231287

Erin M Quist, Ronnie Chamanza, Amanda J Martinot, Allison Boone, Gregory A Krane, Martha E Hensel, Shawn V Lennix

引用次数: 0

Risk Assessment for Hepatobiliary Toxicity Liabilities in Drug Development. 药物开发中的肝胆毒性责任风险评估。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2023-10-01 Epub Date: 2024-01-20 DOI: 10.1177/01926233231223751

Richard T Miller

{"title":"Risk Assessment for Hepatobiliary Toxicity Liabilities in Drug Development.","authors":"Richard T Miller","doi":"10.1177/01926233231223751","DOIUrl":"10.1177/01926233231223751","url":null,"abstract":"Risk assessment of hepatobiliary toxicities represents one of the greatest challenges and, more often than not, one of the most rewarding activities in which toxicologic pathologists can partake, and often times lead. This is in part because each liver toxicity picture is a bit different, informed by a broad range and diversity of relevant data, and also in part because the heavily relied upon animal models are imperfect regarding predictivity of hepatic effects in humans. Following identification and characterization of a hepatotoxicity hazard, typically in nonclinical toxicology studies, a holistic and integrated assessment of liver-relevant endpoints is conducted that typically incorporates ADME (absorption, distribution, metabolism, and excretion) information (ideally, including extensive transporter data, exposure margins, and possibly concentration of parent/metabolite at region of injury), target expression/function, in silico prediction data, in vitro hepatocyte data, liver/circulating biomarkers, and importantly, species specificity of any of these data. Of course, a thorough understanding, developed in close partnership with clinical colleagues, of the anticipated liver disease status of intended patient populations is paramount to hepatic risk assessment. This is particularly important since the likelihood of translatable determinant hepatic events observed in nonclinical models to occur in humans has been reasonably well established.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":" ","pages":"432-436"},"PeriodicalIF":1.5,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139502685","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