Pub Date : 2022-10-01Epub Date: 2022-09-16DOI: 10.1177/01926233221123523
James J Vanhie, Michael De Lisio
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.
{"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":"<p><p>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.</p>","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}
Pub Date : 2022-10-01DOI: 10.1177/01926233221123778
Kathryn E Gropp
During this presentation, a variety of class effects were reviewed by their differing effects on bone, including inhibition of endochondral ossification, inhibition of the growth hormone-insulin-like growth factor 1 axis, promotion of bone formation, inhibition of bone formation, abnormal bone formation, promotion of bone resorption, inhibition of bone resorption, and bone necrosis.
{"title":"Pathology of Bone: Changes Associated With Different Classes of Compounds.","authors":"Kathryn E Gropp","doi":"10.1177/01926233221123778","DOIUrl":"https://doi.org/10.1177/01926233221123778","url":null,"abstract":"<p><p>During this presentation, a variety of class effects were reviewed by their differing effects on bone, including inhibition of endochondral ossification, inhibition of the growth hormone-insulin-like growth factor 1 axis, promotion of bone formation, inhibition of bone formation, abnormal bone formation, promotion of bone resorption, inhibition of bone resorption, and bone necrosis.</p>","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":"10401186","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}
Pub Date : 2022-10-01DOI: 10.1177/01926233221120550
A Eric Schultze, Lila Ramaiah
This session, held during the 41st Annual STP Symposium, focused on mechanisms of decreased erythropoiesis and erythroid cell injury. The speakers provided comprehensive overviews of physiologic and pathologic erythropoiesis, reviewed various mechanisms of erythroid cell injury, and shared innovative investigative research with the audience.
{"title":"Overview of Session 3 Mechanisms of Decreased Erythropoiesis and Erythroid Cell Injury.","authors":"A Eric Schultze, Lila Ramaiah","doi":"10.1177/01926233221120550","DOIUrl":"https://doi.org/10.1177/01926233221120550","url":null,"abstract":"<p><p>This session, held during the 41st Annual STP Symposium, focused on mechanisms of decreased erythropoiesis and erythroid cell injury. The speakers provided comprehensive overviews of physiologic and pathologic erythropoiesis, reviewed various mechanisms of erythroid cell injury, and shared innovative investigative research with the audience.</p>","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":"10396488","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}
Pub Date : 2022-10-01DOI: 10.1177/01926233221128755
Florence Poitout-Belissent, Allison Vitsky, Mark A Smith, Madhu P Sirivelu
Hematology and bone marrow analysis is central to our understanding of the hematopoietic system and how it responds to insults, and this session presented during the 2022 STP symposium provided a review of current and novel approaches for the evaluation of the hematopoietic system in the context of nonclinical investigations. This publication summarizes the information presented on novel approaches for evaluation of the hematopoietic system using automated hematology analyzers, including details around the quantitative assessment of bone marrow cell suspensions as well as introducing several newly available hematology parameters. It was followed by a discussion on intravital microscopy and live cell imaging and how these methods can assist with de-risking hematopoiesis-associated safety concerns, and a review of recent assays using artificial intelligence for the evaluation of bone marrow.
{"title":"Methodologies and Emerging Technologies for the Evaluation of the Hematopoietic System.","authors":"Florence Poitout-Belissent, Allison Vitsky, Mark A Smith, Madhu P Sirivelu","doi":"10.1177/01926233221128755","DOIUrl":"https://doi.org/10.1177/01926233221128755","url":null,"abstract":"<p><p>Hematology and bone marrow analysis is central to our understanding of the hematopoietic system and how it responds to insults, and this session presented during the 2022 STP symposium provided a review of current and novel approaches for the evaluation of the hematopoietic system in the context of nonclinical investigations. This publication summarizes the information presented on novel approaches for evaluation of the hematopoietic system using automated hematology analyzers, including details around the quantitative assessment of bone marrow cell suspensions as well as introducing several newly available hematology parameters. It was followed by a discussion on intravital microscopy and live cell imaging and how these methods can assist with de-risking hematopoiesis-associated safety concerns, and a review of recent assays using artificial intelligence for the evaluation of bone marrow.</p>","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":"10746590","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}
Pub Date : 2022-10-01DOI: 10.1177/01926233221129202
Allison Vitsky, Aida Sacaan, Wenyue Hu, Martin Finkelstein, William Reagan
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.
{"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":"<p><p>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.</p>","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}
Pub Date : 2022-10-01Epub Date: 2022-09-27DOI: 10.1177/01926233221124825
Erin M Quist, Shambhunath Choudhary, Richard Lang, Debra A Tokarz, Mark Hoenerhoff, Jonathan Nagel, Jeffrey I Everitt
The 2022 annual National Toxicology Program Satellite Symposium, entitled "Pathology Potpourri," was held in Austin, Texas at the Society of Toxicologic Pathology's 40th annual meeting during a half-day session on Sunday, June 19. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included induced and spontaneous neoplastic and nonneoplastic lesions in the mouse lung, spontaneous lesions in the reproductive tract of a female cynomolgus macaque, induced vascular lesions in a mouse asthma model and interesting case studies in a rhesus macaque, dog and genetically engineered mouse model.
{"title":"Proceedings of the 2022 National Toxicology Program Satellite Symposium.","authors":"Erin M Quist, Shambhunath Choudhary, Richard Lang, Debra A Tokarz, Mark Hoenerhoff, Jonathan Nagel, Jeffrey I Everitt","doi":"10.1177/01926233221124825","DOIUrl":"10.1177/01926233221124825","url":null,"abstract":"<p><p>The 2022 annual National Toxicology Program Satellite Symposium, entitled \"Pathology Potpourri,\" was held in Austin, Texas at the Society of Toxicologic Pathology's 40th annual meeting during a half-day session on Sunday, June 19. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers' talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included induced and spontaneous neoplastic and nonneoplastic lesions in the mouse lung, spontaneous lesions in the reproductive tract of a female cynomolgus macaque, induced vascular lesions in a mouse asthma model and interesting case studies in a rhesus macaque, dog and genetically engineered mouse model.</p>","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://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678128/pdf/nihms-1832450.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10745711","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}
Pub Date : 2022-08-01Epub Date: 2022-08-24DOI: 10.1177/01926233221117747
Shima Mehrvar, Takahito Kambara
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.
{"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":"<p><p>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.</p>","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}
Pub Date : 2022-08-01Epub Date: 2022-06-21DOI: 10.1177/01926233221105393
Yuval Ramot, Oleg Dolkart, Michal Steiner, Sabrina Jahn, Ronit Goldberg, Orna Cacical, Yossi Lavie, Nati Ezov, Gabi Agar, Abraham Nyska
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.
{"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":"<p><p>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.</p>","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}
Pub Date : 2022-08-01DOI: 10.1177/01926233221107607
Huong Huynh, Priya Upadhyay, Cora H Lopez, Malia K Miyashiro, Laura S Van Winkle, Sara M Thomasy, Kent E Pinkerton
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.
{"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":"<p><p>Engineered silver nanoparticles (AgNPs), including silver silicate nanoparticles (Ag-SiO<sub>2</sub> 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-SiO<sub>2</sub> NPs and their potential nose-to-brain transport have not been evaluated. The present study assessed whether inhaled Ag-SiO<sub>2</sub> NPs can elicit microglial activation in the OB. Adult Sprague-Dawley rats inhaled aerosolized Ag-SiO<sub>2</sub> 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-SiO<sub>2</sub> 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-SiO<sub>2</sub> 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-SiO<sub>2</sub> may have translocated to the central nervous system via intra-neuronal pathways.</p>","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}
Pub Date : 2022-08-01Epub Date: 2022-08-11DOI: 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
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.
{"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":"<p><p>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.</p>","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}