Toxicologic Pathology最新文献_第9页

To Clot or Not to Clot: Deepening Our Understanding of Alterations in the Hemostatic System. 凝血还是不凝血:加深我们对止血系统改变的认识。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 DOI: 10.1177/01926233221125172

William J Reagan, Marjory B Brooks, Renata Grozovsky, Debra Pittman, Allison Vitsky, Karrie Brenneman

{"title":"To Clot or Not to Clot: Deepening Our Understanding of Alterations in the Hemostatic System.","authors":"William J Reagan, Marjory B Brooks, Renata Grozovsky, Debra Pittman, Allison Vitsky, Karrie Brenneman","doi":"10.1177/01926233221125172","DOIUrl":"https://doi.org/10.1177/01926233221125172","url":null,"abstract":"The session on the hemostatic system focused on new developments in coagulation and platelet biology as well as how therapeutic agents may affect hemostasis. The classic cascade model of coagulation was compared with the more recent models of cell-based and vascular-based coagulation, which may provide better insight on how the coagulation cascade works in vivo. A review of platelet biology highlighted that, as platelets age, desialylated platelets form and are recognized by Ashwell-Morell receptor (AMR), leading to hepatic uptake and subsequent increase in thrombopoietin (TPO) production. Administration of therapeutics that induce thrombocytopenia was also discussed, including Mylotarg, which is an antibody-drug conjugate that was shown to decrease human megakaryocyte development but had no effect on platelet aggregation. An acetyl co-A carboxylase inhibitor was shown to cause thrombocytopenia by inhibiting de novo lipogenesis, which is critical for the formation of the megakaryocyte demarcation membrane system responsible for platelet production. It was also illustrated how preclinical translation models have been very helpful in the development of adeno-associated virus (AAV) hemophilia B gene therapy and what old and new preclinical tools we have that can predict the risk of a prothrombotic state in people.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"50 7","pages":"890-894"},"PeriodicalIF":1.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10456523","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

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":"50 7","pages":"858-866"},"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

Black Cohosh Herbal Extract and Hematologic Alterations in B6C3F1/N Mice. 黑升麻草药提取物对B6C3F1/N小鼠血液学的影响。

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-10-01 DOI: 10.1177/01926233221133549

Michelle Cora

{"title":"Black Cohosh Herbal Extract and Hematologic Alterations in B6C3F1/N Mice.","authors":"Michelle Cora","doi":"10.1177/01926233221133549","DOIUrl":"https://doi.org/10.1177/01926233221133549","url":null,"abstract":"Black cohosh is a readily available dietary supplement currently marketed as a remedy for dysmenorrhea and menopausal symptoms and is one of the top-selling herbal supplements in the United States. Black cohosh extract (BCE) was nominated to the National Toxicology Program (NTP) by the National Cancer Institute and the National Institute of Environmental Health Sciences due to its widespread use and lack of animal toxicity studies. Results of the NTP BCE subchronic mouse toxicity study revealed a dose-dependent, non-regenerative decrease in the erythron with an increase in the mean corpuscular volume (macrocytosis). Howell-Jolly bodies, or micronuclei, were significantly increased. These particular changes indicated an ineffective erythropoiesis consistent with a condition known as megaloblastic anemia. Megaloblastic anemia is due to disruptions in DNA synthesis during hematopoiesis and can be a result of an inherited or drug-induced disorder or a consequence of folate or cobalamin deficiency. Subsequent mouse studies revealed hematological and biochemical changes that were consistent with a functional cobalamin deficiency. This article will review basic mechanisms and laboratory features of megaloblastic anemia. The results of our studies including morphological abnormalities of the erythron and biomarkers of folate and cobalamin deficiencies, as well as hepatic microarray gene changes, are also discussed.","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"50 7","pages":"886-889"},"PeriodicalIF":1.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396382","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

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":"50 7","pages":"871-880"},"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

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":"50 6","pages":"763-775"},"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

Society of Toxicologic Pathology Neuropathology Interest Group Article: Neuropathologic Findings in Nonhuman Primates Associated With Administration of Biomolecule-Based Test Articles 毒物病理学学会神经病理学兴趣小组文章:非人类灵长类动物的神经病理学发现与基于生物分子的试验品的管理有关

IF 1.5 4区医学

Toxicologic Pathology Pub Date : 2022-06-13 DOI: 10.1177/01926233221101314

D. Bangari, L. Lanigan, F. Goulet, S. Sisó, B. Bolon

{"title":"Society of Toxicologic Pathology Neuropathology Interest Group Article: Neuropathologic Findings in Nonhuman Primates Associated With Administration of Biomolecule-Based Test Articles","authors":"D. Bangari, L. Lanigan, F. Goulet, S. Sisó, B. Bolon","doi":"10.1177/01926233221101314","DOIUrl":"https://doi.org/10.1177/01926233221101314","url":null,"abstract":"The increasing specificity of novel druggable targets coupled with the complexity of emerging therapeutic modalities for treating human diseases has created a growing need for nonhuman primates (NHPs) as models for translational drug discovery and nonclinical safety assessment. In particular, NHPs are critical for investigating potential unexpected/undesired on-target and off-target liabilities associated with administration of candidate biotherapeutics (nucleic acids, proteins, viral gene therapy vectors, etc.) to treat nervous system disorders. Nervous system findings unique to or overrepresented in NHPs administered biomolecule-based (“biologic”) test articles include mononuclear cell infiltration in most neural tissues for all biomolecule classes as well as neuronal necrosis with glial cell proliferation in sensory ganglia for certain viral vectors. Such test article-related findings in NHPs often must be differentiated from procedural effects (e.g., local parenchymal or meningeal reactions associated with an injection site or implanted catheter to administer a test article directly into the central nervous system) or spontaneous background findings (e.g., neuronal autophagy in sensory ganglia).","PeriodicalId":23113,"journal":{"name":"Toxicologic Pathology","volume":"94 1","pages":"693 - 711"},"PeriodicalIF":1.5,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78704210","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