Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit
Toxicol Pathol. 2024 Feb 22:1926233241229808. doi: 10.1177/01926233241229808. Online ahead of print.ABSTRACTRecombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neuro...
Source: Toxicologic Pathology - February 22, 2024 Category: Pathology Authors: Eric Tien Branka Grubor Melissa Kirkland Su Jing Chan Nick van der Munnik Wenlong Xu Kate Henry Stefan Hamann Cong Wei Wan-Hung Lee Davide Gianni Ashton Brennecke Kalyani Nambiar Jeron Chen Bin Liu Shen Shen Claudine Tremblay Edward D Plowey Patrick Trapa Source Type: research
Adeno-Associated Virus-Mediated Dorsal Root Ganglion Toxicity in the New Zealand White Rabbit
Toxicol Pathol. 2024 Feb 22:1926233241229808. doi: 10.1177/01926233241229808. Online ahead of print.ABSTRACTRecombinant adeno-associated virus (AAV)-mediated degeneration of sensory neurons in the dorsal root ganglia (DRG) and trigeminal ganglia (TG) has been observed in non-human primates (NHPs) following intravenous (IV) and intrathecal (IT) delivery. Administration of recombinant AAV encoding a human protein transgene via a single intra-cisterna magna (ICM) injection in New Zealand white rabbits resulted in histopathology changes very similar to NHPs: mononuclear cell infiltration, degeneration/necrosis of sensory neuro...
Source: Toxicologic Pathology - February 22, 2024 Category: Pathology Authors: Eric Tien Branka Grubor Melissa Kirkland Su Jing Chan Nick van der Munnik Wenlong Xu Kate Henry Stefan Hamann Cong Wei Wan-Hung Lee Davide Gianni Ashton Brennecke Kalyani Nambiar Jeron Chen Bin Liu Shen Shen Claudine Tremblay Edward D Plowey Patrick Trapa Source Type: research
Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation
Toxicol Pathol. 2024 Feb 20:1926233241230536. doi: 10.1177/01926233241230536. Online ahead of print.ABSTRACTIn 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 ...
Source: Toxicologic Pathology - February 21, 2024 Category: Pathology Authors: Adeyemi O Adedeji Fiona Zhong Janice Corpuz Fangyao Hu Xiaofeng Zhao Dewakar Sangaraju Catherine F Ruff Noel Dybdal Source Type: research
Toxicologic Neuropathology of Novel Biotherapeutics
Toxicol Pathol. 2024 Feb 21:1926233241230542. doi: 10.1177/01926233241230542. Online ahead of print.ABSTRACTBiotherapeutic modalities such as cell therapies, gene therapies, nucleic acids, and proteins are increasingly investigated as disease-modifying treatments for severe and life-threatening neurodegenerative disorders. Such diverse bio-derived test articles are fraught with unique and often unpredictable biological consequences, while guidance regarding nonclinical experimental design, neuropathology evaluation, and interpretation is often limited. This paper summarizes key messages offered during a half-day continuing...
Source: Toxicologic Pathology - February 21, 2024 Category: Pathology Authors: Dinesh S Bangari Lisa G Lanigan Sarah D Cramer Jessica L Grieves Ren é Meisner Arlin B Rogers Elizabeth J Galbreath Brad Bolon Source Type: research
Comparative Impact of Various Fasting Periods on the Welfare of Sprague-Dawley Rats With or Without Supplementation
Toxicol Pathol. 2024 Feb 20:1926233241230536. doi: 10.1177/01926233241230536. Online ahead of print.ABSTRACTIn 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 ...
Source: Toxicologic Pathology - February 21, 2024 Category: Pathology Authors: Adeyemi O Adedeji Fiona Zhong Janice Corpuz Fangyao Hu Xiaofeng Zhao Dewakar Sangaraju Catherine F Ruff Noel Dybdal Source Type: research
Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective
Toxicol Pathol. 2023 Aug;51(6):390-396. doi: 10.1177/01926233231224805. Epub 2024 Jan 31.ABSTRACTIn the last decade, numerous initiatives have emerged worldwide to reduce the use of animals in drug development, including more recently the introduction of Virtual Control Groups (VCGs) concept for nonclinical toxicity studies. Although replacement of concurrent controls (CCs) by virtual controls (VCs) represents an exciting opportunity, there are associated challenges that will be discussed in this paper with a more specific focus on anatomic pathology. Coordinated efforts will be needed from toxicologists, clinical and anat...
Source: Toxicologic Pathology - January 31, 2024 Category: Pathology Authors: Armelle Grevot Julie Boisclair Magali Guffroy Peter Hall Gabriele Pohlmeyer-Esch Matt Jacobsen Ute Bach Anna Lena Frisk Noel Dybdal Xavier Palazzi Source Type: research
Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective
Toxicol Pathol. 2023 Aug;51(6):390-396. doi: 10.1177/01926233231224805. Epub 2024 Jan 31.ABSTRACTIn the last decade, numerous initiatives have emerged worldwide to reduce the use of animals in drug development, including more recently the introduction of Virtual Control Groups (VCGs) concept for nonclinical toxicity studies. Although replacement of concurrent controls (CCs) by virtual controls (VCs) represents an exciting opportunity, there are associated challenges that will be discussed in this paper with a more specific focus on anatomic pathology. Coordinated efforts will be needed from toxicologists, clinical and anat...
Source: Toxicologic Pathology - January 31, 2024 Category: Pathology Authors: Armelle Grevot Julie Boisclair Magali Guffroy Peter Hall Gabriele Pohlmeyer-Esch Matt Jacobsen Ute Bach Anna Lena Frisk Noel Dybdal Xavier Palazzi Source Type: research
Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective
Toxicol Pathol. 2023 Aug;51(6):390-396. doi: 10.1177/01926233231224805. Epub 2024 Jan 31.ABSTRACTIn the last decade, numerous initiatives have emerged worldwide to reduce the use of animals in drug development, including more recently the introduction of Virtual Control Groups (VCGs) concept for nonclinical toxicity studies. Although replacement of concurrent controls (CCs) by virtual controls (VCs) represents an exciting opportunity, there are associated challenges that will be discussed in this paper with a more specific focus on anatomic pathology. Coordinated efforts will be needed from toxicologists, clinical and anat...
Source: Toxicologic Pathology - January 31, 2024 Category: Pathology Authors: Armelle Grevot Julie Boisclair Magali Guffroy Peter Hall Gabriele Pohlmeyer-Esch Matt Jacobsen Ute Bach Anna Lena Frisk Noel Dybdal Xavier Palazzi Source Type: research
Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective
Toxicol Pathol. 2023 Aug;51(6):390-396. doi: 10.1177/01926233231224805. Epub 2024 Jan 31.ABSTRACTIn the last decade, numerous initiatives have emerged worldwide to reduce the use of animals in drug development, including more recently the introduction of Virtual Control Groups (VCGs) concept for nonclinical toxicity studies. Although replacement of concurrent controls (CCs) by virtual controls (VCs) represents an exciting opportunity, there are associated challenges that will be discussed in this paper with a more specific focus on anatomic pathology. Coordinated efforts will be needed from toxicologists, clinical and anat...
Source: Toxicologic Pathology - January 31, 2024 Category: Pathology Authors: Armelle Grevot Julie Boisclair Magali Guffroy Peter Hall Gabriele Pohlmeyer-Esch Matt Jacobsen Ute Bach Anna Lena Frisk Noel Dybdal Xavier Palazzi Source Type: research
Toxicologic Pathology Forum Opinion Piece: Use of Virtual Control Groups in Nonclinical Toxicity Studies: The Anatomic Pathology Perspective
Toxicol Pathol. 2024 Jan 31:1926233231224805. doi: 10.1177/01926233231224805. Online ahead of print.ABSTRACTIn the last decade, numerous initiatives have emerged worldwide to reduce the use of animals in drug development, including more recently the introduction of Virtual Control Groups (VCGs) concept for nonclinical toxicity studies. Although replacement of concurrent controls (CCs) by virtual controls (VCs) represents an exciting opportunity, there are associated challenges that will be discussed in this paper with a more specific focus on anatomic pathology. Coordinated efforts will be needed from toxicologists, clinic...
Source: Toxicologic Pathology - January 31, 2024 Category: Pathology Authors: Armelle Grevot Julie Boisclair Magali Guffroy Peter Hall Gabriele Pohlmeyer-Esch Matt Jacobsen Ute Bach Anna Lena Frisk Noel Dybdal Xavier Palazzi Source Type: research
Assessment of Color Reproducibility and Mitigation of Color Variation in Whole Slide Image Scanners for Toxicologic Pathology
Toxicol Pathol. 2024 Jan 30:1926233231224468. doi: 10.1177/01926233231224468. Online ahead of print.ABSTRACTDigital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology. In particular, co...
Source: Toxicologic Pathology - January 30, 2024 Category: Pathology Authors: Mei-Lan Chu Xing-Yue M Ge Jeffrey Eastham Trung Nguyen Reina N Fuji Ruth Sullivan Daniel Ruderman Source Type: research
Toxicologic Pathology Forum Opinion: Rational Approaches to Expanded Neurohistopathology Evaluation for Nonclinical General Toxicity Studies and Juvenile Animal Studies
Toxicol Pathol. 2024 Jan 30:1926233231225239. doi: 10.1177/01926233231225239. Online ahead of print.ABSTRACTExisting nervous system sampling and processing "best practices" for nonclinical general toxicity studies (GTS) were designed to assess test articles with unknown, no known, or well-known neurotoxic potential. Similar practices are applicable to juvenile animal studies (JAS). In GTS and JAS, the recommended baseline sampling for all species includes brain (7 sections), spinal cord (cervical and lumbar divisions [cross and longitudinal sections for each]), and 1 nerve (sciatic or tibial [cross and longitudinal section...
Source: Toxicologic Pathology - January 30, 2024 Category: Pathology Authors: Brad Bolon Source Type: research
Toxicogenomics Approaches to Address Toxicity and Carcinogenicity in the Liver
Toxicol Pathol. 2024 Jan 30:1926233241227942. doi: 10.1177/01926233241227942. Online ahead of print.ABSTRACTToxicogenomic 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 ident...
Source: Toxicologic Pathology - January 30, 2024 Category: Pathology Authors: Arun R Pandiri Scott S Auerbach Jim L Stevens Eric A G Blomme Source Type: research
Select Toxicologic Pathology Case Studies of the Hepatobiliary System
This article comprises several of the case studies that were presented during the session which included copper-associated hepatitis in a dog, sinusoidal obstruction syndrome in non-human primates, hepatic cytoplasmic alteration in mice and rats, and Kupffer cell hyperplasia/granulomatous inflammation in rats. Presenters, when applicable, provided case signalment, anatomic/clinical pathology data, and diagnoses and discussed potential pathogeneses.PMID:38281143 | DOI:10.1177/01926233231224464 (Source: Toxicologic Pathology)
Source: Toxicologic Pathology - January 28, 2024 Category: Pathology Authors: Allison C Boone Shakirat A Adetunji Rebecca Kohnken Kenji Koyama Source Type: research
Historical Control Background Incidence of Spontaneous Neoplastic Lesions of Sprague-Dawley Rats in 104-Week Toxicity Studies
Toxicol Pathol. 2024 Jan 28:1926233231224466. doi: 10.1177/01926233231224466. Online ahead of print.ABSTRACTData collected from approximately 1800 male and 1800 female Sprague-Dawley (SD) rats used in 104-week carcinogenicity studies were archived in a historical control database at Labcorp Early Development, Inc, and the neoplastic microscopic observation data from these rats were retrospectively evaluated. Historical control data can provide useful information on the range and incidence of spontaneously occurring background neoplasms in the species and strain of the test animal used in different types of toxicity studies...
Source: Toxicologic Pathology - January 28, 2024 Category: Pathology Authors: Amit Kumar Marie Bockenstedt Victoria Laast Alok Sharma Source Type: research
