Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate im... more Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell‑like cells. Using Reb‑treated LS174T cells, the level of mucin content was assessed by periodic acid‑Schiff (PAS) staining, and mucin 2, oligomeric mucus/gel‑forming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase 1 (Akt) path...
Water drop adhesions (WDA) impair endoscopic view during gastrointestinal endoscopy. We develope... more Water drop adhesions (WDA) impair endoscopic view during gastrointestinal endoscopy. We developed a novel lens cleaner designed using two types of harmLess surfactants and it is reported to be useful for preventing lens cloudiness during colorectal ESD. In the current study, we examined the ability of it for preventing and removing WDA. During laboratory experiments, the cleaner (Cleash; Fujifilm Co., Tokyo, Japan and Nagase Medicals Co., Hyogo, Japan) was applied to the endoscopic lens and an air/water device (AWD) (water 200 mL, dimethicone 1 mL, Cleash 1 mL). The endoscope was submerged in water 100 times for 5 cycles. Rates of WDA were calculated for various groups (lens and AWD with or without Cleash) and compared to a normal cleaner (SL cleaner). During clinical research, 30 colonoscopies and 30 esophagogastroduodenoscopies were analyzed. For the Cleash group, the cleaner was applied to both lens and AWD. The numbers of WDA and WDA with non-rapid removal were calculated, com...
Journal of gastroenterology and hepatology, Jan 5, 2017
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cel... more Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. Colitis was induced in wild-type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage, leukocyte infiltration, Tnf, Ifng, Il17a, and Il10 mRNA expression, and histology. Cytokine profiling of colonic lamina propria mononuclear cells (LPMCs) was performed by flow cytometry. Naïve CD4(+) T cells were isolated from WT and SPARC KO mouse spleens and the effect of SPARC on Th17 cell differentiation was examined. RAG1 KO mice reconstituted with T cells from either WT or SPARC KO mice was investigated. TNBS exposure significantly reduced body weight and increased mucosal inflammation, leukocyte infiltration, and Il17a mRNA expression in WT...
Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pa... more Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pancreatic cancer remains one of the most lethal malignancies. New-generation cancer immunotherapy methods, such as blocking of the PD-1/PD-L1 pathway, are consistently being investigated to improve the survival of pancreatic cancer patients. In the present study, we evaluated the influence of anticancer agents 5-fluorouracil, gemcitabine and paclitaxel on PD-L1 expression in human pancreatic cancer cell lines MIA PaCa-2 and AsPC-1 and in murine pancreatic cancer cell line Pan02. Additionally, we analyzed the molecular mechanisms that facilitated the regulation of PD-L1 expression in these cell lines. We observed that when AsPC-1, MIA PaCa-2 and Pan02 cells were stimulated by 5-fluorouracil, gemcitabine or paclitaxel, PD-L1 surface protein expression was enhanced. Similarly, the mRNA level of PD-L1 was upregulated in the AsPC-1 and Pan02 cells when stimulated by each of the three anticance...
Measuring trans-epithelial electrical resistance (TEER) in vitro is a method to evaluate barrier ... more Measuring trans-epithelial electrical resistance (TEER) in vitro is a method to evaluate barrier function. The first aim of this study is to verify a real-time TEER monitoring system in Caco-2 monolayer. The second aim is to investigate the therapeutic effect of partially hydrolyzed guar gum (PHGG), a dietary fiber, on interferon (IFN)-γ-induced intestinal barrier dysfunction using this monitoring system. We measured TEER using real-time monitoring system and evaluated epithelial paracellular permeability using fluorescein isothiocyanate-conjugated dextran (4 kDa; FD4) in Caco-2 monolayers treated by IFN-γ for 48 h. The expression and distribution of tight junction (TJ)-associated proteins, ZO-1 and occludin, were analyzed by Western blotting and immunocytochemistry respectively. In some experiments, PHGG was added prior to IFN-γ treatment in order to investigate its protective effect on barrier function. Using this system, we could evaluate the dynamic TEER change induced by IFN-γ ...
Rebamipide, a gastromucosal protective drug, suppresses indomethacin-induced gastropathy in human... more Rebamipide, a gastromucosal protective drug, suppresses indomethacin-induced gastropathy in humans and rodents. Effects of rebamipide on gene expression in indomethacin-treated gastric mucosal cells (RGM1) were investigated using high-density oligonucleotide arrays. Indomethacin induced apoptosis in RGM1 cells in a dose-dependent manner. Rebamipide pretreatment significantly reduced indomethacin-induced apoptosis. We used gene expression profiling on high-density oligonucleotide probe arrays to characterize the transcriptional response of RGM1 cells to indomethacin treatment for 6 hr. Of the 8,799 probes examined, 717 (8.1%) were induced (400 probes) or repressed (317 probes) at least 1.5-fold. Among the 158 genes that were induced by indomethacin at least 2.0-fold, four genes that were down-regulated by rebamipide at least 2.0-fold are listed: growth arrest and DNA-damageinducible 45α (GADD45α), golgi SNAP receptor complex member 1, iodothyronine deiodinases, and transcription factor 8. Real time-PCR confirmed GADD45α expression and its inhibition by rebamipide. Inhibition of apoptosis-related genes is possibly important for the cytoprotective effect of rebamipide against indomethacin-induced gastric mucosal cell injury.
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, Jan 13, 2016
Blue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light ... more Blue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light source developed for narrow-band light observation. The aim of this study was to evaluate the usefulness of BLI for the diagnosis of early gastric cancer. This single center prospective study analyzed 530 patients. The patients were examined with both conventional endoscopy with white-light imaging (C-WLI) and magnifying endoscopy with BLI (M-BLI) at Kyoto Prefectural University of Medicine between November 2012 and March 2015. The diagnostic criteria for gastric cancer using M-BLI included an irregular microvascular pattern and/or irregular microsurface pattern, with a demarcation line according to the vessel plus surface classification system. Biopsies of the lesions were taken after C-WLI and M-BLI observation. The primary end point of this study was to compare the diagnostic performance between C-WLI and M-BLI. We analyzed 127 detected lesions (32 cancers and 95 non-cancers). The acc...
Journal of Gastroenterology and Hepatology, Jul 1, 2010
Background and Aims: Ecabet sodium (ES) is a gastric mucosal protective and ulcerhealing agent. R... more Background and Aims: Ecabet sodium (ES) is a gastric mucosal protective and ulcerhealing agent. Recently enema therapy with ES was found to be effective for the treatment of human ulcerative colitis as well as experimental colitis in an animal model. Whereas ES possesses potential as a novel treatment for ulcerative colitis, its precise mechanism of action remains to be elucidated. In this study, we investigated the therapeutic efficacy of ES in an experimental rat model of colitis, and evaluated the restitution of intestinal epithelial cells treated with ES in vitro. Methods: Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal treatment with ES daily starting on day 7 and were sacrificed on day 14 after the administration of TNBS. The distal colon was removed to evaluate various parameters of inflammation. Moreover, wound-healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with ES. Results: Intracolonic administration of ES accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by ES treatment. The wound assay revealed ES enhancement of the migration of RIE cells migration through the phosphorylation of extracellular signal-regulated kinase. Conclusion: Daily administration of an ES enema promoted the healing of intestinal mucosal injury, in part by the enhanced restitution of intestinal epithelial cells via extracellular signal-regulated kinase activation. ES may thus represent a novel therapeutic approach for the treatment of inflammatory bowel disease.
Pyrroloquinoline quinone (PQQ), a putative essential nutrient, is a redox modulator in cell and a... more Pyrroloquinoline quinone (PQQ), a putative essential nutrient, is a redox modulator in cell and animal models. Here we characterized PQQ-induced protein oxidative modifications in a model peptide and protein, and we propose that the mechanism of protein modification by PQQ is redox cycling-mediated oxidation. PQQ may contribute to the regulation of intracellular protein functions through its prooxidant action.
Journal of clinical biochemistry and nutrition, 2016
Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes ris... more Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, on the occurrence of diabetes and its complications, fatty liver and nephropathy. We also identified predictive serum biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks. Body weight, food intake, oral glucose tolerance test, plasma insulin levels, and urine glucose and protein levels were regularly measured. Oral glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the...
The aim of the present study was to investigate the antioxidative effects of water-soluble vitami... more The aim of the present study was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(α-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on ischemiareperfusion (I/R)-induced gastric mucosal injury in rats. Gastric ischemia was induced by applying a small clamp to the celiac artery and reoxygenation was produced by removal of the clamp. The area of gastric mucosal erosion, the concentration of thiobarbituric acid-reactive substances, and the myeloperoxidase activity in gastric mucosa significantly increased in I/R groups compared with those of sham-operated groups. These increases were significantly inhibited by pretreatment with TMG. The contents of both mucosal TNF-α and CINC-2β in I/R groups were also increased compared with the levels of those in sham-operated groups. These increases of the inflammatory cytokines were significantly inhibited by the treatment with TMG. It is concluded that TMG inhibited lipid peroxidation and reduced development of the gastric mucosal inflammation induced by I/R in rats.
Your article is protected by copyright and all rights are held exclusively by Springer Japan. Thi... more Your article is protected by copyright and all rights are held exclusively by Springer Japan. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author's version for posting to your own website or your institution's repository. You may further deposit the accepted author's version on a funder's repository at a funder's request, provided it is not made publicly available until 12 months after publication.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical settings for a l... more Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical settings for a long time for their anti-inflammatory effects. With the number of NSAID users increasing, gastroenterological physicians and researchers have worked hard to prevent and treat NSAID-induced gastric mucosal injury, an effort that has for the large part being successful. However, the struggle against NSAID-induced mucosal damage has taken on a new urgency due to the discovery of NSAID-induced small intestinal mucosal injury. Although the main mechanism by which NSAIDs induce small intestinal mucosal injury has been thought to depend on the inhibitory effect of NSAIDs on cyclooxygenase (COX) activity, recent studies have revealed the importance of mitochondria-derived reactive oxygen species (ROS) production, which occurs independently of COX-inhibition. ROS production is an especially important factor in the increase of small intestinal epithelial cell permeability, an early stage in the pro...
Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate im... more Mucin is produced and secreted by epithelial goblet cells and is a key component of the innate immune system, acting as a barrier in the intestinal tract. However, no studies have been conducted investigating the increase in mucin secretion to enhance the intestinal barrier function. The present study investigated whether rebamipide (Reb) acts as a secretagogue of intestinal mucin and the underlying mechanisms involved, thereby focusing on the effect on goblet cells. The LS174T cell line was used as goblet cell‑like cells. Using Reb‑treated LS174T cells, the level of mucin content was assessed by periodic acid‑Schiff (PAS) staining, and mucin 2, oligomeric mucus/gel‑forming (MUC2) mRNA expression was assessed using quantitative polymerase chain reaction (PCR). Furthermore, MUC2 secretion in the supernatant was quantified by the dot blot method. The present study additionally investigated the involvement of the epidermal growth factor receptor/Akt serine/threonine kinase 1 (Akt) path...
Water drop adhesions (WDA) impair endoscopic view during gastrointestinal endoscopy. We develope... more Water drop adhesions (WDA) impair endoscopic view during gastrointestinal endoscopy. We developed a novel lens cleaner designed using two types of harmLess surfactants and it is reported to be useful for preventing lens cloudiness during colorectal ESD. In the current study, we examined the ability of it for preventing and removing WDA. During laboratory experiments, the cleaner (Cleash; Fujifilm Co., Tokyo, Japan and Nagase Medicals Co., Hyogo, Japan) was applied to the endoscopic lens and an air/water device (AWD) (water 200 mL, dimethicone 1 mL, Cleash 1 mL). The endoscope was submerged in water 100 times for 5 cycles. Rates of WDA were calculated for various groups (lens and AWD with or without Cleash) and compared to a normal cleaner (SL cleaner). During clinical research, 30 colonoscopies and 30 esophagogastroduodenoscopies were analyzed. For the Cleash group, the cleaner was applied to both lens and AWD. The numbers of WDA and WDA with non-rapid removal were calculated, com...
Journal of gastroenterology and hepatology, Jan 5, 2017
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cel... more Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. Colitis was induced in wild-type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage, leukocyte infiltration, Tnf, Ifng, Il17a, and Il10 mRNA expression, and histology. Cytokine profiling of colonic lamina propria mononuclear cells (LPMCs) was performed by flow cytometry. Naïve CD4(+) T cells were isolated from WT and SPARC KO mouse spleens and the effect of SPARC on Th17 cell differentiation was examined. RAG1 KO mice reconstituted with T cells from either WT or SPARC KO mice was investigated. TNBS exposure significantly reduced body weight and increased mucosal inflammation, leukocyte infiltration, and Il17a mRNA expression in WT...
Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pa... more Although improvements in the chemotherapy modalities for pancreatic cancer have been realized, pancreatic cancer remains one of the most lethal malignancies. New-generation cancer immunotherapy methods, such as blocking of the PD-1/PD-L1 pathway, are consistently being investigated to improve the survival of pancreatic cancer patients. In the present study, we evaluated the influence of anticancer agents 5-fluorouracil, gemcitabine and paclitaxel on PD-L1 expression in human pancreatic cancer cell lines MIA PaCa-2 and AsPC-1 and in murine pancreatic cancer cell line Pan02. Additionally, we analyzed the molecular mechanisms that facilitated the regulation of PD-L1 expression in these cell lines. We observed that when AsPC-1, MIA PaCa-2 and Pan02 cells were stimulated by 5-fluorouracil, gemcitabine or paclitaxel, PD-L1 surface protein expression was enhanced. Similarly, the mRNA level of PD-L1 was upregulated in the AsPC-1 and Pan02 cells when stimulated by each of the three anticance...
Measuring trans-epithelial electrical resistance (TEER) in vitro is a method to evaluate barrier ... more Measuring trans-epithelial electrical resistance (TEER) in vitro is a method to evaluate barrier function. The first aim of this study is to verify a real-time TEER monitoring system in Caco-2 monolayer. The second aim is to investigate the therapeutic effect of partially hydrolyzed guar gum (PHGG), a dietary fiber, on interferon (IFN)-γ-induced intestinal barrier dysfunction using this monitoring system. We measured TEER using real-time monitoring system and evaluated epithelial paracellular permeability using fluorescein isothiocyanate-conjugated dextran (4 kDa; FD4) in Caco-2 monolayers treated by IFN-γ for 48 h. The expression and distribution of tight junction (TJ)-associated proteins, ZO-1 and occludin, were analyzed by Western blotting and immunocytochemistry respectively. In some experiments, PHGG was added prior to IFN-γ treatment in order to investigate its protective effect on barrier function. Using this system, we could evaluate the dynamic TEER change induced by IFN-γ ...
Rebamipide, a gastromucosal protective drug, suppresses indomethacin-induced gastropathy in human... more Rebamipide, a gastromucosal protective drug, suppresses indomethacin-induced gastropathy in humans and rodents. Effects of rebamipide on gene expression in indomethacin-treated gastric mucosal cells (RGM1) were investigated using high-density oligonucleotide arrays. Indomethacin induced apoptosis in RGM1 cells in a dose-dependent manner. Rebamipide pretreatment significantly reduced indomethacin-induced apoptosis. We used gene expression profiling on high-density oligonucleotide probe arrays to characterize the transcriptional response of RGM1 cells to indomethacin treatment for 6 hr. Of the 8,799 probes examined, 717 (8.1%) were induced (400 probes) or repressed (317 probes) at least 1.5-fold. Among the 158 genes that were induced by indomethacin at least 2.0-fold, four genes that were down-regulated by rebamipide at least 2.0-fold are listed: growth arrest and DNA-damageinducible 45α (GADD45α), golgi SNAP receptor complex member 1, iodothyronine deiodinases, and transcription factor 8. Real time-PCR confirmed GADD45α expression and its inhibition by rebamipide. Inhibition of apoptosis-related genes is possibly important for the cytoprotective effect of rebamipide against indomethacin-induced gastric mucosal cell injury.
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, Jan 13, 2016
Blue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light ... more Blue laser imaging (BLI) is a new image-enhanced endoscopy technique that utilizes a laser light source developed for narrow-band light observation. The aim of this study was to evaluate the usefulness of BLI for the diagnosis of early gastric cancer. This single center prospective study analyzed 530 patients. The patients were examined with both conventional endoscopy with white-light imaging (C-WLI) and magnifying endoscopy with BLI (M-BLI) at Kyoto Prefectural University of Medicine between November 2012 and March 2015. The diagnostic criteria for gastric cancer using M-BLI included an irregular microvascular pattern and/or irregular microsurface pattern, with a demarcation line according to the vessel plus surface classification system. Biopsies of the lesions were taken after C-WLI and M-BLI observation. The primary end point of this study was to compare the diagnostic performance between C-WLI and M-BLI. We analyzed 127 detected lesions (32 cancers and 95 non-cancers). The acc...
Journal of Gastroenterology and Hepatology, Jul 1, 2010
Background and Aims: Ecabet sodium (ES) is a gastric mucosal protective and ulcerhealing agent. R... more Background and Aims: Ecabet sodium (ES) is a gastric mucosal protective and ulcerhealing agent. Recently enema therapy with ES was found to be effective for the treatment of human ulcerative colitis as well as experimental colitis in an animal model. Whereas ES possesses potential as a novel treatment for ulcerative colitis, its precise mechanism of action remains to be elucidated. In this study, we investigated the therapeutic efficacy of ES in an experimental rat model of colitis, and evaluated the restitution of intestinal epithelial cells treated with ES in vitro. Methods: Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. Rats received intrarectal treatment with ES daily starting on day 7 and were sacrificed on day 14 after the administration of TNBS. The distal colon was removed to evaluate various parameters of inflammation. Moreover, wound-healing assays were used to determine the enhanced restitution of rat intestinal epithelial (RIE) cells treated with ES. Results: Intracolonic administration of ES accelerated TNBS-induced ulcer healing. Increases in the wet weight of the colon after TNBS administration were significantly inhibited by ES treatment. The wound assay revealed ES enhancement of the migration of RIE cells migration through the phosphorylation of extracellular signal-regulated kinase. Conclusion: Daily administration of an ES enema promoted the healing of intestinal mucosal injury, in part by the enhanced restitution of intestinal epithelial cells via extracellular signal-regulated kinase activation. ES may thus represent a novel therapeutic approach for the treatment of inflammatory bowel disease.
Pyrroloquinoline quinone (PQQ), a putative essential nutrient, is a redox modulator in cell and a... more Pyrroloquinoline quinone (PQQ), a putative essential nutrient, is a redox modulator in cell and animal models. Here we characterized PQQ-induced protein oxidative modifications in a model peptide and protein, and we propose that the mechanism of protein modification by PQQ is redox cycling-mediated oxidation. PQQ may contribute to the regulation of intracellular protein functions through its prooxidant action.
Journal of clinical biochemistry and nutrition, 2016
Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes ris... more Recent evidence has indicated that total fiber intake is inversely related to type 2 diabetes risk. The present study aimed to investigate the effects of chronic administration of partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber, on the occurrence of diabetes and its complications, fatty liver and nephropathy. We also identified predictive serum biomarkers of treatment response to PHGG by mass spectroscopy-based proteomic analysis using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a good model of human non-insulin-dependent diabetes mellitus. In this study, at 5 weeks of age, OLETF rats and control strain Long-Evans Tokushima Otsuka (LETO) rats were fed a control diet or a high-fiber diet (5% PHGG) for 57 weeks. Body weight, food intake, oral glucose tolerance test, plasma insulin levels, and urine glucose and protein levels were regularly measured. Oral glucose tolerance tests (OGTT) and storage of serum in a deep freezer were conducted at the beginning of the...
The aim of the present study was to investigate the antioxidative effects of water-soluble vitami... more The aim of the present study was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(α-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on ischemiareperfusion (I/R)-induced gastric mucosal injury in rats. Gastric ischemia was induced by applying a small clamp to the celiac artery and reoxygenation was produced by removal of the clamp. The area of gastric mucosal erosion, the concentration of thiobarbituric acid-reactive substances, and the myeloperoxidase activity in gastric mucosa significantly increased in I/R groups compared with those of sham-operated groups. These increases were significantly inhibited by pretreatment with TMG. The contents of both mucosal TNF-α and CINC-2β in I/R groups were also increased compared with the levels of those in sham-operated groups. These increases of the inflammatory cytokines were significantly inhibited by the treatment with TMG. It is concluded that TMG inhibited lipid peroxidation and reduced development of the gastric mucosal inflammation induced by I/R in rats.
Your article is protected by copyright and all rights are held exclusively by Springer Japan. Thi... more Your article is protected by copyright and all rights are held exclusively by Springer Japan. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author's version for posting to your own website or your institution's repository. You may further deposit the accepted author's version on a funder's repository at a funder's request, provided it is not made publicly available until 12 months after publication.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical settings for a l... more Non-steroidal anti-inflammatory drugs (NSAIDs) have been implemented in clinical settings for a long time for their anti-inflammatory effects. With the number of NSAID users increasing, gastroenterological physicians and researchers have worked hard to prevent and treat NSAID-induced gastric mucosal injury, an effort that has for the large part being successful. However, the struggle against NSAID-induced mucosal damage has taken on a new urgency due to the discovery of NSAID-induced small intestinal mucosal injury. Although the main mechanism by which NSAIDs induce small intestinal mucosal injury has been thought to depend on the inhibitory effect of NSAIDs on cyclooxygenase (COX) activity, recent studies have revealed the importance of mitochondria-derived reactive oxygen species (ROS) production, which occurs independently of COX-inhibition. ROS production is an especially important factor in the increase of small intestinal epithelial cell permeability, an early stage in the pro...
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