Toxicologic Pathology最新文献_第9页

How Does Lifestyle Affect Hematopoiesis and the Bone Marrow Microenvironment? 生活方式如何影响造血和骨髓微环境？

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-09-16 DOI: 10.1177/01926233221123523

James J Vanhie, Michael De Lisio

{"title":"How Does Lifestyle Affect Hematopoiesis and the Bone Marrow Microenvironment?","authors":"James J Vanhie, Michael De Lisio","doi":"10.1177/01926233221123523","DOIUrl":"10.1177/01926233221123523","url":null,"abstract":"Lifestyle factors are modifiable behavioral factors that have a significant impact on health and longevity. Diet-induced obesity and physical activity/exercise are two prevalent lifestyle factors that have strong relationships to overall health. The mechanisms linking obesity to negative health outcomes and the mechanisms linking increased participation in physical activity/exercise to positive health outcomes are beginning to be elucidated. Chronic inflammation, due in part to overproduction of myeloid cells from hematopoietic stem cells (HSCs) in the bone marrow, is an established mechanism responsible for the negative health effects of obesity. Recent work has shown that exercise training can reverse the aberrant myelopoiesis present in obesity in part by restoring the bone marrow microenvironment. Specifically, exercise training reduces marrow adipose tissue, increases HSC retention factor expression, and reduces pro-inflammatory cytokine levels in the bone marrow. Other, novel mechanistic factors responsible for these exercise-induced effects, including intercellular communication using extracellular vesicles (EVs), is beginning to be explored. This review will summarize the recent literature describing the effects of exercise on hematopoiesis in individuals with obesity and introduce the potential contribution of EVs to this process.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/75/10.1177_01926233221123523.PMC9669729.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394778","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

Pathology of Bone: Changes Associated With Different Classes of Compounds. 骨病理:与不同种类化合物相关的变化。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 DOI: 10.1177/01926233221123778

Kathryn E Gropp

引用次数: 0

Overview of Session 3 Mechanisms of Decreased Erythropoiesis and Erythroid Cell Injury. 第三部分:红细胞生成减少和红细胞损伤的机制综述。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 DOI: 10.1177/01926233221120550

A Eric Schultze, Lila Ramaiah

引用次数: 0

Methodologies and Emerging Technologies for the Evaluation of the Hematopoietic System. 评估造血系统的方法和新兴技术。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 DOI: 10.1177/01926233221128755

Florence Poitout-Belissent, Allison Vitsky, Mark A Smith, Madhu P Sirivelu

引用次数: 0

Gemtuzumab Ozogamicin Treatment Results in Decreased Proliferation and Differentiation of Human Megakaryocytes but Does Not Inhibit Mature Platelet Function. 吉妥珠单抗Ozogamicin治疗导致人巨核细胞增殖和分化减少，但不抑制成熟血小板功能。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 DOI: 10.1177/01926233221129202

Allison Vitsky, Aida Sacaan, Wenyue Hu, Martin Finkelstein, William Reagan

{"title":"Gemtuzumab Ozogamicin Treatment Results in Decreased Proliferation and Differentiation of Human Megakaryocytes but Does Not Inhibit Mature Platelet Function.","authors":"Allison Vitsky, Aida Sacaan, Wenyue Hu, Martin Finkelstein, William Reagan","doi":"10.1177/01926233221129202","DOIUrl":"https://doi.org/10.1177/01926233221129202","url":null,"abstract":"Mylotarg (Gemtuzumab ozogamicin [GO]), an antibody drug conjugate comprising a CD33-directed antibody linked to calicheamicin, is approved for use in certain acute myeloid leukemia patients. Following reports of prolonged thrombocytopenia and hemorrhagic events in a subset of patients, a detailed series of in vitro and ex vivo studies was performed at the request of regulators, both to look at the effects of GO on platelet production and to determine whether treatment with GO was likely to affect platelet aggregation under a variety of conditions. Treatment with GO resulted in cellular cytotoxicity and/or decreased differentiation during human megakaryocyte development. However, GO did not impair platelet aggregation under the experimental conditions evaluated. Ultimately, the effect of GO on megakaryocyte development observed in our studies was determined to have no impact on the risk-benefit assessment in the intended patient population, as thrombocytopenia is a known side effect of GO, and monitoring of platelet counts in patients is already strongly recommended.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762701","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

Proceedings of the 2022 National Toxicology Program Satellite Symposium. 2022 年国家毒理学计划卫星研讨会论文集》。

IF 1.4 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 Epub Date: 2022-09-27 DOI: 10.1177/01926233221124825

Erin M Quist, Shambhunath Choudhary, Richard Lang, Debra A Tokarz, Mark Hoenerhoff, Jonathan Nagel, Jeffrey I Everitt

引用次数: 0

Morphologic Features and Deep Learning-Based Analysis of Canine Spermatogenic Stages. 犬生精阶段的形态特征及深度学习分析。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-08-01 Epub Date: 2022-08-24 DOI: 10.1177/01926233221117747

Shima Mehrvar, Takahito Kambara

{"title":"Morphologic Features and Deep Learning-Based Analysis of Canine Spermatogenic Stages.","authors":"Shima Mehrvar, Takahito Kambara","doi":"10.1177/01926233221117747","DOIUrl":"https://doi.org/10.1177/01926233221117747","url":null,"abstract":"In nonclinical toxicity studies, stage-aware evaluation is often expected to assess drug-induced testicular toxicity. Although stage-aware evaluation does not require identification of specific stages, it is important to understand microscopic features of spermatogenic staging. Staging of the spermatogenic cycle in dogs is a challenging and time-consuming process. In this study, we first defined morphologic features for the eight spermatogenic stages in standard histology sections (H&E slides) of dog testes. For image analysis, we defined the key morphologic features of five stages/pooled stage groups (I-II, III-IV, V, VI-VII, and VIII). These criteria were used to develop a deep learning (DL) algorithm for staging of the spermatogenic cycle of control dog testes using whole slide images. In addition, a DL-based nucleus segmentation model was trained to detect and quantify the number of different germ cells, including spermatogonia, spermatocytes, and spermatids. Identification of spermatogenic stages and quantification of germ cell populations were successfully automated by the DL models. Combining these two algorithms provided color-coding visual spermatogenic staging and quantitative information on germ cell populations at specific stages that would facilitate the stage-aware evaluation and detection of changes in germ cell populations in nonclinical toxicity studies.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40438024","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

Preclinical In Vivo Safety of Poly-Phosphorylated Superlubrication Vectors for the Treatment of Osteoarthritis. 多磷酸化超润滑载体治疗骨关节炎的临床前体内安全性研究。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-08-01 Epub Date: 2022-06-21 DOI: 10.1177/01926233221105393

Yuval Ramot, Oleg Dolkart, Michal Steiner, Sabrina Jahn, Ronit Goldberg, Orna Cacical, Yossi Lavie, Nati Ezov, Gabi Agar, Abraham Nyska

{"title":"Preclinical In Vivo Safety of Poly-Phosphorylated Superlubrication Vectors for the Treatment of Osteoarthritis.","authors":"Yuval Ramot, Oleg Dolkart, Michal Steiner, Sabrina Jahn, Ronit Goldberg, Orna Cacical, Yossi Lavie, Nati Ezov, Gabi Agar, Abraham Nyska","doi":"10.1177/01926233221105393","DOIUrl":"https://doi.org/10.1177/01926233221105393","url":null,"abstract":"Osteoarthritis (OA) can lead to a significant functional disability. Poly[2-(methacryloyloxy)ethyl phosphorylcholine] (pMPC) liposomes are a novel treatment modality for OA, intended to restore the natural lubrication properties of articular cartilage. Here, we report on two studies aimed to assess the local and systemic safety and toxicity of pMPCylated liposomes in comparison with physiological saline, in Sprague-Dawley (SD) rats and in sheep after a single intra-articular (IA) injection. The animals were sacrificed after 1 and 6 weeks (rats) and 3 and 6 weeks (sheep). No signs of toxicity or abnormal clinical findings were observed. Histopathological evaluation revealed no signs of reactivity or abnormal findings in the injected joints or in any other organs. In conclusion, a single IA injection of the pMPCylated liposomes demonstrated an excellent safety profile and did not result in local reactivity or systemic toxicity, thus supporting its further development for use in humans.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40122040","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

Inhalation of Silver Silicate Nanoparticles Leads to Transient and Differential Microglial Activation in the Rodent Olfactory Bulb. 吸入硅酸银纳米颗粒导致啮齿动物嗅球中瞬时和差异的小胶质细胞激活。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-08-01 DOI: 10.1177/01926233221107607

Huong Huynh, Priya Upadhyay, Cora H Lopez, Malia K Miyashiro, Laura S Van Winkle, Sara M Thomasy, Kent E Pinkerton

{"title":"Inhalation of Silver Silicate Nanoparticles Leads to Transient and Differential Microglial Activation in the Rodent Olfactory Bulb.","authors":"Huong Huynh, Priya Upadhyay, Cora H Lopez, Malia K Miyashiro, Laura S Van Winkle, Sara M Thomasy, Kent E Pinkerton","doi":"10.1177/01926233221107607","DOIUrl":"https://doi.org/10.1177/01926233221107607","url":null,"abstract":"Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO2 NPs), are used in a wide variety of medical and consumer applications. Inhaled AgNPs have been found to translocate to the olfactory bulb (OB) after inhalation and intranasal instillation. However, the biological effects of Ag-SiO2 NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO2 NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO2 NPs at a concentration of 1 mg/ml for 6 hours. On day 0, 1, 7, and 21 post-exposure, rats were necropsied and OB were harvested. Immunohistochemistry on OB tissues were performed with anti-ionized calcium-binding adapter molecule 1 and heme oxygenase-1 as markers of microglial activation and oxidative stress, respectively. Aerosol characterization indicated Ag-SiO2 NPs were sufficiently aerosolized with moderate agglomeration and high-efficiency deposition in the nasal cavity and olfactory epithelium. Findings suggested that acute inhalation of Ag-SiO2 NPs elicited transient and differential microglial activation in the OB without significant microglial recruitment or oxidative stress. The delayed and differential pattern of microglial activation in the OB implied that inhaled Ag-SiO2 may have translocated to the central nervous system via intra-neuronal pathways.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529873/pdf/nihms-1812245.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10744046","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: 1

IT/QA and Regulatory Aspects of Digital Pathology: Results of the 8th ESTP International Workshop. 数字病理学的IT/QA和监管方面:第八届ESTP国际研讨会的结果。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-08-01 Epub Date: 2022-08-11 DOI: 10.1177/01926233221113275

Julie Boisclair, Bhupinder Bawa, Erio Barale-Thomas, Lise Bertrand, Jonathan Carter, Richard Crossland, Celine Dorn, Thomas Forest, Sabine Grote, Anja Gilis, Deon Hildebrand, Brian Knight, Sébastien Laurent, Heike Antje Marxfeld, Steen Jørgen Østergaard, Thibault Roguet, Thorsten Schlueter, Vanessa Schumacher, Richard Spehar, William Varady, Christian Zeugin

{"title":"IT/QA and Regulatory Aspects of Digital Pathology: Results of the 8th ESTP International Workshop.","authors":"Julie Boisclair, Bhupinder Bawa, Erio Barale-Thomas, Lise Bertrand, Jonathan Carter, Richard Crossland, Celine Dorn, Thomas Forest, Sabine Grote, Anja Gilis, Deon Hildebrand, Brian Knight, Sébastien Laurent, Heike Antje Marxfeld, Steen Jørgen Østergaard, Thibault Roguet, Thorsten Schlueter, Vanessa Schumacher, Richard Spehar, William Varady, Christian Zeugin","doi":"10.1177/01926233221113275","DOIUrl":"https://doi.org/10.1177/01926233221113275","url":null,"abstract":"Digital toxicologic histopathology has been broadly adopted in preclinical compound development for informal consultation and peer review. There is now increased interest in implementing the technology for good laboratory practice-regulated study evaluations. However, the implementation is not straightforward because systems and work processes require qualification and validation, with consideration also given to security. As a result of the high-throughput, high-volume nature of safety evaluations, computer performance, ergonomics, efficiency, and integration with laboratory information management systems are further key considerations. The European Society of Toxicologic Pathology organized an international expert workshop with participation by toxicologic pathologists, quality assurance/regulatory experts, and information technology experts to discuss qualification and validation of digital histopathology systems in a good laboratory practice environment, and to share the resulting conclusions broadly in the toxicologic pathology community.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40698022","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