Neural tissue tolerance to synthetic dural mater graft implantation in a rabbit durotomy model
This study evaluated the safety of ArtiFascia, a synthetic dura mater graft composed of poly(l-lactic-co-caprolactone acid) and poly(d-lactic-co-caprolactone acid), in a rabbit durotomy model. Previously, ArtiFascia demonstrated positive local tolerance and biodegradability in a 12-month preclinical trial. Here, specialized stains were used to evaluate potential brain damage associated with ArtiFascia use. Histochemical and immunohistochemical assessments included Luxol Fast Blue, cresyl Violet, Masson's Trichrome, neuronal nuclei,, Glial Fibrillary Acidic Protein, and ionized calcium-binding adaptor molecule 1 stains. The...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Yuval Ramot Noam Kronfeld Michal Steiner Nora Nseir Manassa Amir Bahar Abraham Nyska Source Type: research

CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease
In this study, we investigated CD44 expression and its role in renal fibrogenesis in a cyclosporine (CyA) rat model of CKD. Seven-week-old male Sprague-Dawley rats fed a low-salt diet were subcutaneously administered CyA (0, 15, or 30 mg/kg) for 28 days. CD44 was expressed in atrophic, dilated, and hypertrophic TECs in the fibrotic lesions of the CyA groups. These TECs were collected by laser microdissection and evaluated by microarray analysis. Gene ontology analysis suggested that these TECs have a mesenchymal phenotype, and pathway analysis identified CD44 as an upstream regulator of fibrosis-related genes, including fi...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Kohei Matsushita Takeshi Toyoda Hirotoshi Akane Tomomi Morikawa Kumiko Ogawa Source Type: research

Induction of lung lesions by bronchial administration using bronchoscope technique in mice
This study aimed to establish an exposure method that can induce homogeneous lesions with minimal inter-individual variability. The distribution of lesions induced by bleomycin (BLM) administration was also analyzed. C57BL mice were intrabronchially administered 20 µL of BLM (3 mg/mL) using a bronchoscope in the left or right bronchus. The mice were sacrificed 14 days after administration, and their lungs were evaluated histopathologically. BLM-induced inflammatory lesions were widely observed in the lungs. In the left bronchus-treated group, lesions were uniformly observed throughout the lobe, and no individual differenc...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takako Hiyoshi Chiyoko Nishime Eiko Nishinaka Fumiko Seki Kenji Kawai Misa Mochizuki Koji Urano Toshio Imai Taichi Yamamoto Masami Suzuki Source Type: research

Drug review process advancement and required manufacturer and contract research oraganization responses
J Toxicol Pathol. 2024 Apr;37(2):45-53. doi: 10.1293/tox.2023-0106. Epub 2023 Nov 22.ABSTRACTThe United States Senate passed the "FDA Modernization Act 2.0." on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient sa...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takayuki Anzai Glenn J Myatt Frances Hall Brenda Finney Kenshi Nakagawa Hijiri Iwata Reo Anzai Anne Dickinson Matthew Freer Dai Nakae Hiroshi Onodera Takaaki Matsuyama Source Type: research

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats
In this study, since the measurement of serum neurofilament light chain could detect changes earlier than pathological examination, it could be useful as a biomarker for peripheral neurotoxicity. Moreover, examination of semi-thin specimens and choline acetyltransferase immunostaining were useful for characterizing morphological neurotoxicity, and image analysis of semi-thin specimens enabled us to objectively show the pathological features.PMID:38584972 | PMC:PMC10995436 | DOI:10.1293/tox.2023-0094 (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Akane Kashimura Satomi Nishikawa Yuhei Ozawa Yui Hibino Takashi Tateoka Mao Mizukawa Hironobu Nishina Tetsuya Sakairi Takanori Shiga Naoyuki Aihara Junichi Kamiie Source Type: research

Neural tissue tolerance to synthetic dural mater graft implantation in a rabbit durotomy model
This study evaluated the safety of ArtiFascia, a synthetic dura mater graft composed of poly(l-lactic-co-caprolactone acid) and poly(d-lactic-co-caprolactone acid), in a rabbit durotomy model. Previously, ArtiFascia demonstrated positive local tolerance and biodegradability in a 12-month preclinical trial. Here, specialized stains were used to evaluate potential brain damage associated with ArtiFascia use. Histochemical and immunohistochemical assessments included Luxol Fast Blue, cresyl Violet, Masson's Trichrome, neuronal nuclei,, Glial Fibrillary Acidic Protein, and ionized calcium-binding adaptor molecule 1 stains. The...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Yuval Ramot Noam Kronfeld Michal Steiner Nora Nseir Manassa Amir Bahar Abraham Nyska Source Type: research

CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease
In this study, we investigated CD44 expression and its role in renal fibrogenesis in a cyclosporine (CyA) rat model of CKD. Seven-week-old male Sprague-Dawley rats fed a low-salt diet were subcutaneously administered CyA (0, 15, or 30 mg/kg) for 28 days. CD44 was expressed in atrophic, dilated, and hypertrophic TECs in the fibrotic lesions of the CyA groups. These TECs were collected by laser microdissection and evaluated by microarray analysis. Gene ontology analysis suggested that these TECs have a mesenchymal phenotype, and pathway analysis identified CD44 as an upstream regulator of fibrosis-related genes, including fi...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Kohei Matsushita Takeshi Toyoda Hirotoshi Akane Tomomi Morikawa Kumiko Ogawa Source Type: research

Induction of lung lesions by bronchial administration using bronchoscope technique in mice
This study aimed to establish an exposure method that can induce homogeneous lesions with minimal inter-individual variability. The distribution of lesions induced by bleomycin (BLM) administration was also analyzed. C57BL mice were intrabronchially administered 20 µL of BLM (3 mg/mL) using a bronchoscope in the left or right bronchus. The mice were sacrificed 14 days after administration, and their lungs were evaluated histopathologically. BLM-induced inflammatory lesions were widely observed in the lungs. In the left bronchus-treated group, lesions were uniformly observed throughout the lobe, and no individual differenc...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takako Hiyoshi Chiyoko Nishime Eiko Nishinaka Fumiko Seki Kenji Kawai Misa Mochizuki Koji Urano Toshio Imai Taichi Yamamoto Masami Suzuki Source Type: research

Drug review process advancement and required manufacturer and contract research oraganization responses
J Toxicol Pathol. 2024 Apr;37(2):45-53. doi: 10.1293/tox.2023-0106. Epub 2023 Nov 22.ABSTRACTThe United States Senate passed the "FDA Modernization Act 2.0." on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient sa...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takayuki Anzai Glenn J Myatt Frances Hall Brenda Finney Kenshi Nakagawa Hijiri Iwata Reo Anzai Anne Dickinson Matthew Freer Dai Nakae Hiroshi Onodera Takaaki Matsuyama Source Type: research

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats
In this study, since the measurement of serum neurofilament light chain could detect changes earlier than pathological examination, it could be useful as a biomarker for peripheral neurotoxicity. Moreover, examination of semi-thin specimens and choline acetyltransferase immunostaining were useful for characterizing morphological neurotoxicity, and image analysis of semi-thin specimens enabled us to objectively show the pathological features.PMID:38584972 | PMC:PMC10995436 | DOI:10.1293/tox.2023-0094 (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Akane Kashimura Satomi Nishikawa Yuhei Ozawa Yui Hibino Takashi Tateoka Mao Mizukawa Hironobu Nishina Tetsuya Sakairi Takanori Shiga Naoyuki Aihara Junichi Kamiie Source Type: research

Neural tissue tolerance to synthetic dural mater graft implantation in a rabbit durotomy model
This study evaluated the safety of ArtiFascia, a synthetic dura mater graft composed of poly(l-lactic-co-caprolactone acid) and poly(d-lactic-co-caprolactone acid), in a rabbit durotomy model. Previously, ArtiFascia demonstrated positive local tolerance and biodegradability in a 12-month preclinical trial. Here, specialized stains were used to evaluate potential brain damage associated with ArtiFascia use. Histochemical and immunohistochemical assessments included Luxol Fast Blue, cresyl Violet, Masson's Trichrome, neuronal nuclei,, Glial Fibrillary Acidic Protein, and ionized calcium-binding adaptor molecule 1 stains. The...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Yuval Ramot Noam Kronfeld Michal Steiner Nora Nseir Manassa Amir Bahar Abraham Nyska Source Type: research

CD44 expression in renal tubular epithelial cells in the kidneys of rats with cyclosporine-induced chronic kidney disease
In this study, we investigated CD44 expression and its role in renal fibrogenesis in a cyclosporine (CyA) rat model of CKD. Seven-week-old male Sprague-Dawley rats fed a low-salt diet were subcutaneously administered CyA (0, 15, or 30 mg/kg) for 28 days. CD44 was expressed in atrophic, dilated, and hypertrophic TECs in the fibrotic lesions of the CyA groups. These TECs were collected by laser microdissection and evaluated by microarray analysis. Gene ontology analysis suggested that these TECs have a mesenchymal phenotype, and pathway analysis identified CD44 as an upstream regulator of fibrosis-related genes, including fi...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Kohei Matsushita Takeshi Toyoda Hirotoshi Akane Tomomi Morikawa Kumiko Ogawa Source Type: research

Induction of lung lesions by bronchial administration using bronchoscope technique in mice
This study aimed to establish an exposure method that can induce homogeneous lesions with minimal inter-individual variability. The distribution of lesions induced by bleomycin (BLM) administration was also analyzed. C57BL mice were intrabronchially administered 20 µL of BLM (3 mg/mL) using a bronchoscope in the left or right bronchus. The mice were sacrificed 14 days after administration, and their lungs were evaluated histopathologically. BLM-induced inflammatory lesions were widely observed in the lungs. In the left bronchus-treated group, lesions were uniformly observed throughout the lobe, and no individual differenc...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takako Hiyoshi Chiyoko Nishime Eiko Nishinaka Fumiko Seki Kenji Kawai Misa Mochizuki Koji Urano Toshio Imai Taichi Yamamoto Masami Suzuki Source Type: research

Drug review process advancement and required manufacturer and contract research oraganization responses
J Toxicol Pathol. 2024 Apr;37(2):45-53. doi: 10.1293/tox.2023-0106. Epub 2023 Nov 22.ABSTRACTThe United States Senate passed the "FDA Modernization Act 2.0." on September 29, 2022. Although the effectiveness of this Bill, which aims to eliminate the mandatory use of laboratory animals in new drug development, is limited, it represents a significant trend that will change the shape of drug applications in the United States and other countries. However, pharmaceutical companies have not taken major steps towards the complete elimination of animal testing from the standpoint of product safety, where they prioritize patient sa...
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Takayuki Anzai Glenn J Myatt Frances Hall Brenda Finney Kenshi Nakagawa Hijiri Iwata Reo Anzai Anne Dickinson Matthew Freer Dai Nakae Hiroshi Onodera Takaaki Matsuyama Source Type: research

Combination of pathological, biochemical and behavioral evaluations for peripheral neurotoxicity assessment in isoniazid-treated rats
In this study, since the measurement of serum neurofilament light chain could detect changes earlier than pathological examination, it could be useful as a biomarker for peripheral neurotoxicity. Moreover, examination of semi-thin specimens and choline acetyltransferase immunostaining were useful for characterizing morphological neurotoxicity, and image analysis of semi-thin specimens enabled us to objectively show the pathological features.PMID:38584972 | PMC:PMC10995436 | DOI:10.1293/tox.2023-0094 (Source: Journal of Toxicologic Pathology)
Source: Journal of Toxicologic Pathology - April 8, 2024 Category: Toxicology Authors: Akane Kashimura Satomi Nishikawa Yuhei Ozawa Yui Hibino Takashi Tateoka Mao Mizukawa Hironobu Nishina Tetsuya Sakairi Takanori Shiga Naoyuki Aihara Junichi Kamiie Source Type: research