K. Wijarnpreecha, Pitchaphon Nissaisorakarn, Suthanya Sornprom, C. Thongprayoon, Natanong Thamcharoen, K. Maneenil, A. Podboy, W. Cheungpasitporn
AIM To investigate the association between hepatitis C virus (HCV) infection and risk of renal cell carcinoma (RCC). METHODS A literature search was performed from inception until February 2016. Studies that reported relative risks, odd ratios, hazard ratios or standardized incidence ratio comparing the risk of RCC among HCV-infected participants vs those without HCV infection were included. Participants without HCV infection were used as comparators. Pooled odds ratios and 95%CI were calculated using a random-effect, generic inverse variance method. RESULTS Seven observational studies were with 196826 patients were included in the analysis to assess the risk of RCC in patients with HCV. A significantly increased risk of RCC among participants with HCV infection was found with a pooled RR of 1.86 (95%CI: 1.11-3.11). The association between RCC and HCV was marginally insignificant after a sensitivity analysis limited only to studies with adjusted analysis, with a pooled RR of 1.50 (95%CI: 0.93-2.42). CONCLUSION Our study demonstrated a potential association between HCV infection and RCC. Further studies of RCC surveillance in patients with HCV are required.
{"title":"Hepatitis C infection and renal cell carcinoma: A systematic review and meta-analysis","authors":"K. Wijarnpreecha, Pitchaphon Nissaisorakarn, Suthanya Sornprom, C. Thongprayoon, Natanong Thamcharoen, K. Maneenil, A. Podboy, W. Cheungpasitporn","doi":"10.4291/wjgp.v7.i4.314","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i4.314","url":null,"abstract":"AIM To investigate the association between hepatitis C virus (HCV) infection and risk of renal cell carcinoma (RCC). METHODS A literature search was performed from inception until February 2016. Studies that reported relative risks, odd ratios, hazard ratios or standardized incidence ratio comparing the risk of RCC among HCV-infected participants vs those without HCV infection were included. Participants without HCV infection were used as comparators. Pooled odds ratios and 95%CI were calculated using a random-effect, generic inverse variance method. RESULTS Seven observational studies were with 196826 patients were included in the analysis to assess the risk of RCC in patients with HCV. A significantly increased risk of RCC among participants with HCV infection was found with a pooled RR of 1.86 (95%CI: 1.11-3.11). The association between RCC and HCV was marginally insignificant after a sensitivity analysis limited only to studies with adjusted analysis, with a pooled RR of 1.50 (95%CI: 0.93-2.42). CONCLUSION Our study demonstrated a potential association between HCV infection and RCC. Further studies of RCC surveillance in patients with HCV are required.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1","pages":"314 - 319"},"PeriodicalIF":0.0,"publicationDate":"2016-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71060328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Huan, Daniel Kim, Peiqi Ou, A. Alfonso, A. Stanek
Acute pancreatitis (AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin (IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly anti-inflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the anti-autophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy.
{"title":"Mechanisms of interleukin-22's beneficial effects in acute pancreatitis.","authors":"C. Huan, Daniel Kim, Peiqi Ou, A. Alfonso, A. Stanek","doi":"10.4291/wjgp.v7.i1.108","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.108","url":null,"abstract":"Acute pancreatitis (AP) is a disorder characterized by parenchymal injury of the pancreas controlled by immune cell-mediated inflammation. AP remains a significant challenge in the clinic due to a lack of specific and effective treatment. Knowledge of the complex mechanisms that regulate the inflammatory response in AP is needed for the development of new approaches to treatment, since immune cell-derived inflammatory cytokines have been recognized to play critical roles in the pathogenesis of the disease. Recent studies have shown that interleukin (IL)-22, a cytokine secreted by leukocytes, when applied in the severe animal models of AP, protects against the inflammation-mediated acinar injury. In contrast, in a mild AP model, endogenous IL-22 has been found to be a predominantly anti-inflammatory mediator that inhibits inflammatory cell infiltration via the induction of Reg3 proteins in acinar cells, but does not protect against acinar injury in the early stage of AP. However, constitutively over-expressed IL-22 can prevent the initial acinar injury caused by excessive autophagy through the induction of the anti-autophagic proteins Bcl-2 and Bcl-XL. Thus IL-22 plays different roles in AP depending on the severity of the AP model. This review focuses on these recently reported findings for the purpose of better understanding IL-22's regulatory roles in AP which could help to develop a novel therapeutic strategy.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1 1","pages":"108-16"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicole Y. Fatheree, Yuying Liu, M. Ferris, Melissa R. Van Arsdall, Valarie McMurtry, Marcela Zozaya, Chunyan C Cai, M. Rahbar, M. Hessabi, Ta Vu, Christine Wong, Juleen Min, D. Tran, F. Navarro, W. Gleason, Sara González, J. M. Rhoads
AIM To investigate recruitment, retention, and estimates for effects of formula supplementation with Lactobacillus rhamnosus GG (LGG) on inflammatory biomarkers and fecal microbial community in infants with colic. METHODS A prospective, double-blind, placebo-controlled trial was conducted in otherwise healthy infants with colic. We screened 74 infants and randomized and analyzed results in 20 infants [9 receiving LGG (LGG+) and 11 not receiving LGG (LGG-)]. LGG was incorporated in the formula (Nutramigen(®)) (minimum of 3 × 10(7) CFU/d) in the LGG+ group. Fecal microbiota and inflammatory biomarkers, including fecal calprotectin (FC), plasma cytokines, circulating regulatory T cells (Tregs), and crying + fussing time were analyzed to determine optimal time points and effect sizes for a larger trial. RESULTS Recruitment in this population was slow, with about 66% of eligible infants willing to enroll; subject retention was better (75%). These rates were influenced by parents' reluctance to volunteer their infant for a clinical trial and by their tendency to change formulas. The maximal difference of crying + fussing time was observed at day 14, comparing the 2 groups, with a mean difference of -91 (95%CI: -76, 259) min (P = NS). FC showed no significant difference, but the optimal time to determine a potential effect was at day 90 [with a mean difference of 121 (95%CI: -48, 291) μg/g stool], observing a lower level of FC in the LGG+ group. The fecal microbial communities were chaotic, as determined by Shannon's diversity index and not apparently influenced by the probiotic. No significant change was observed in plasma inflammatory cytokines or Tregs, comparing LGG+ to LGG- groups. CONCLUSION Designing future colic trials involving a probiotic-supplemented formula for infants in the United States will require consideration for difficult enrollment. Infants with colic have major variations in feal microbiota and calprotectin, both of which improve with time, with optimal time points for measurement at days 14 and 90 after treatment.
{"title":"Hypoallergenic formula with Lactobacillus rhamnosus GG for babies with colic: A pilot study of recruitment, retention, and fecal biomarkers.","authors":"Nicole Y. Fatheree, Yuying Liu, M. Ferris, Melissa R. Van Arsdall, Valarie McMurtry, Marcela Zozaya, Chunyan C Cai, M. Rahbar, M. Hessabi, Ta Vu, Christine Wong, Juleen Min, D. Tran, F. Navarro, W. Gleason, Sara González, J. M. Rhoads","doi":"10.4291/wjgp.v7.i1.160","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.160","url":null,"abstract":"AIM\u0000To investigate recruitment, retention, and estimates for effects of formula supplementation with Lactobacillus rhamnosus GG (LGG) on inflammatory biomarkers and fecal microbial community in infants with colic.\u0000\u0000\u0000METHODS\u0000A prospective, double-blind, placebo-controlled trial was conducted in otherwise healthy infants with colic. We screened 74 infants and randomized and analyzed results in 20 infants [9 receiving LGG (LGG+) and 11 not receiving LGG (LGG-)]. LGG was incorporated in the formula (Nutramigen(®)) (minimum of 3 × 10(7) CFU/d) in the LGG+ group. Fecal microbiota and inflammatory biomarkers, including fecal calprotectin (FC), plasma cytokines, circulating regulatory T cells (Tregs), and crying + fussing time were analyzed to determine optimal time points and effect sizes for a larger trial.\u0000\u0000\u0000RESULTS\u0000Recruitment in this population was slow, with about 66% of eligible infants willing to enroll; subject retention was better (75%). These rates were influenced by parents' reluctance to volunteer their infant for a clinical trial and by their tendency to change formulas. The maximal difference of crying + fussing time was observed at day 14, comparing the 2 groups, with a mean difference of -91 (95%CI: -76, 259) min (P = NS). FC showed no significant difference, but the optimal time to determine a potential effect was at day 90 [with a mean difference of 121 (95%CI: -48, 291) μg/g stool], observing a lower level of FC in the LGG+ group. The fecal microbial communities were chaotic, as determined by Shannon's diversity index and not apparently influenced by the probiotic. No significant change was observed in plasma inflammatory cytokines or Tregs, comparing LGG+ to LGG- groups.\u0000\u0000\u0000CONCLUSION\u0000Designing future colic trials involving a probiotic-supplemented formula for infants in the United States will require consideration for difficult enrollment. Infants with colic have major variations in feal microbiota and calprotectin, both of which improve with time, with optimal time points for measurement at days 14 and 90 after treatment.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1 1","pages":"160-70"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v7.i1.160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIM To investigate the efficacy and safety of mineral water with a high content of hydrogen carbonate in patients with heartburn. METHODS This open, single-center, single-arm clinical pilot study enrolled 50 patients, 18-64 years old, who had been suffering from heartburn at least twice a week for at least 3 mo before entering the study. Pharmacological treatment of heartburn was not permitted, and patients with severe organic diseases were excluded. After a run-in period of one week, the participants received 1.5 L of the test water for the following 6 wk; 300 mL with meals t.i.d., the remainder to be drunk throughout the day. During the trial, there were five visits at the study center (screening, baseline, two interim visits and the final visit). The efficacy endpoints included incidence and duration of heartburn episodes per week by patient's self-assessment (heartburn diary) as well as changes in symptom severity as per symptom specific questionnaires [Reflux Disease Questionnaire (RDQ); Quality of Life in Reflux and Dyspepsia (QOLRAD); Gastrointestinal Quality of Life Index] and overall health-related quality of life per SF-12 (12-question short form) at each visit. At the end of the study, patients and investigators independently rated the overall efficacy of the test water on a 4-point Likert scale. Safety was assessed by evaluation of adverse events (AEs), vital signs (heart rate, blood pressure) and laboratory parameters. Changes from initial to final examinations were assessed by the non-parametric Wilcoxon test; categorical variables were compared using the χ(2) test, and for more than 5 categories, by the U-test. RESULTS Twenty-eight participants were men, 22 women. The mean age of the patients in the full analysis set/intention-to treat population (FAS/ITT) was 40.6 years. Forty-two participants completed the study according to the study protocol and formed the per-protocol set (PP population); 48 participants drank the water at least once as requested and were analyzed as ITT population. The occurrence of heartburn was statistically significantly reduced at wk 6 in both the ITT and the PP populations. At wk 6, the mean number of heartburn episodes/week decreased by 5.1 episodes (P < 0.001) and the mean duration of heartburn symptoms by 19 min (ITT) (P = 0.002). The frequency of heartburn symptoms was reduced in 89.6% of the patients (P < 0.001), and the duration of symptoms in 79.2% of patients (ITT) (P < 0.001). All dimensions of the RDQ (heartburn, regurgitation, gastro-esophageal reflux disease symptoms, dyspepsia) showed a significant improvement at 6 wk. Likewise, disease-specific quality of life improved significantly (QOLRAD, GIQLI). Overall, 89.4% of patients rated the efficacy of the test water as "good" or "very good", as did the investigators for 91.5% of the patients. There were no serious AEs. After 6 wk, systolic and diastolic blood pressure values decreased slightly but significantly [-3.5 and -3.0 mmHg, respecti
{"title":"Efficacy and tolerability of hydrogen carbonate-rich water for heartburn.","authors":"A. Beer, R. Uebelhack, U. Pohl","doi":"10.4291/wjgp.v7.i1.171","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.171","url":null,"abstract":"AIM\u0000To investigate the efficacy and safety of mineral water with a high content of hydrogen carbonate in patients with heartburn.\u0000\u0000\u0000METHODS\u0000This open, single-center, single-arm clinical pilot study enrolled 50 patients, 18-64 years old, who had been suffering from heartburn at least twice a week for at least 3 mo before entering the study. Pharmacological treatment of heartburn was not permitted, and patients with severe organic diseases were excluded. After a run-in period of one week, the participants received 1.5 L of the test water for the following 6 wk; 300 mL with meals t.i.d., the remainder to be drunk throughout the day. During the trial, there were five visits at the study center (screening, baseline, two interim visits and the final visit). The efficacy endpoints included incidence and duration of heartburn episodes per week by patient's self-assessment (heartburn diary) as well as changes in symptom severity as per symptom specific questionnaires [Reflux Disease Questionnaire (RDQ); Quality of Life in Reflux and Dyspepsia (QOLRAD); Gastrointestinal Quality of Life Index] and overall health-related quality of life per SF-12 (12-question short form) at each visit. At the end of the study, patients and investigators independently rated the overall efficacy of the test water on a 4-point Likert scale. Safety was assessed by evaluation of adverse events (AEs), vital signs (heart rate, blood pressure) and laboratory parameters. Changes from initial to final examinations were assessed by the non-parametric Wilcoxon test; categorical variables were compared using the χ(2) test, and for more than 5 categories, by the U-test.\u0000\u0000\u0000RESULTS\u0000Twenty-eight participants were men, 22 women. The mean age of the patients in the full analysis set/intention-to treat population (FAS/ITT) was 40.6 years. Forty-two participants completed the study according to the study protocol and formed the per-protocol set (PP population); 48 participants drank the water at least once as requested and were analyzed as ITT population. The occurrence of heartburn was statistically significantly reduced at wk 6 in both the ITT and the PP populations. At wk 6, the mean number of heartburn episodes/week decreased by 5.1 episodes (P < 0.001) and the mean duration of heartburn symptoms by 19 min (ITT) (P = 0.002). The frequency of heartburn symptoms was reduced in 89.6% of the patients (P < 0.001), and the duration of symptoms in 79.2% of patients (ITT) (P < 0.001). All dimensions of the RDQ (heartburn, regurgitation, gastro-esophageal reflux disease symptoms, dyspepsia) showed a significant improvement at 6 wk. Likewise, disease-specific quality of life improved significantly (QOLRAD, GIQLI). Overall, 89.4% of patients rated the efficacy of the test water as \"good\" or \"very good\", as did the investigators for 91.5% of the patients. There were no serious AEs. After 6 wk, systolic and diastolic blood pressure values decreased slightly but significantly [-3.5 and -3.0 mmHg, respecti","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"69 1","pages":"171-80"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing (MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis (UC) and Crohn's disease (CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease.
{"title":"Mucosal healing in inflammatory bowel disease: Maintain or de-escalate therapy.","authors":"M. Cintolo, G. Costantino, S. Pallio, W. Fries","doi":"10.4291/wjgp.v7.i1.1","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.1","url":null,"abstract":"In the past decade, thanks to the introduction of biologic therapies, a new therapeutic goal, mucosal healing (MH), has been introduced. MH is the expression of an arrest of disease progression, resulting in minor hospitalizations, surgeries, and prolonged clinical remission. MH may be achieved with several therapeutic strategies reaching success rates up to 80% for both, ulcerative colitis (UC) and Crohn's disease (CD). Various scoring systems for UC and for the transmural CD, have been proposed to standardize the definition of MH. Several attempts have been undertaken to de-escalate therapy once MH is achieved, thus, reducing the risk of adverse events. In this review, we analysed the available studies regarding the achievement of MH and the subsequent treatment de-escalation according to disease type and administered therapy, together with non-invasive markers proposed as predictors for relapse. The available data are not encouraging since de-escalation after the achievement of MH is followed by a high number of clinical relapses reaching up to 50% within one year. Unclear is also another question, in case of combination therapies, which drug is more appropriate to stop, in order to guarantee a durable remission. Predictors of unfavourable outcome such as disease extension, perianal disease, or early onset disease appear to be inadequate to foresee behaviour of disease. Further studies are warranted to investigate the role of histologic healing for the further course of disease.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"34 1","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIM To investigate the intestinal functions of the NKCC1 Na(+)-K(+)-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed. METHODS Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed. RESULTS Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations. CONCLUSION The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors.
{"title":"Differential expression of pancreatic protein and chemosensing receptor mRNAs in NKCC1-null intestine.","authors":"Emily M. Bradford, Kanimozhi Vairamani, G. Shull","doi":"10.4291/wjgp.v7.i1.138","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.138","url":null,"abstract":"AIM\u0000To investigate the intestinal functions of the NKCC1 Na(+)-K(+)-2Cl cotransporter (SLC12a2 gene), differential mRNA expression changes in NKCC1-null intestine were analyzed.\u0000\u0000\u0000METHODS\u0000Microarray analysis of mRNA from intestines of adult wild-type mice and gene-targeted NKCC1-null mice (n = 6 of each genotype) was performed to identify patterns of differential gene expression changes. Differential expression patterns were further examined by Gene Ontology analysis using the online Gorilla program, and expression changes of selected genes were verified using northern blot analysis and quantitative real time-polymerase chain reaction. Histological staining and immunofluorescence were performed to identify cell types in which upregulated pancreatic digestive enzymes were expressed.\u0000\u0000\u0000RESULTS\u0000Genes typically associated with pancreatic function were upregulated. These included lipase, amylase, elastase, and serine proteases indicative of pancreatic exocrine function, as well as insulin and regenerating islet genes, representative of endocrine function. Northern blot analysis and immunohistochemistry showed that differential expression of exocrine pancreas mRNAs was specific to the duodenum and localized to a subset of goblet cells. In addition, a major pattern of changes involving differential expression of olfactory receptors that function in chemical sensing, as well as other chemosensing G-protein coupled receptors, was observed. These changes in chemosensory receptor expression may be related to the failure of intestinal function and dependency on parenteral nutrition observed in humans with SLC12a2 mutations.\u0000\u0000\u0000CONCLUSION\u0000The results suggest that loss of NKCC1 affects not only secretion, but also goblet cell function and chemosensing of intestinal contents via G-protein coupled chemosensory receptors.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1 1","pages":"138-49"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dahn L Clemens, K. J. Schneider, Christopher K Arkfeld, Jaclyn R Grode, Mark A Wells, Shailender Singh
Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.
{"title":"Alcoholic pancreatitis: New insights into the pathogenesis and treatment.","authors":"Dahn L Clemens, K. J. Schneider, Christopher K Arkfeld, Jaclyn R Grode, Mark A Wells, Shailender Singh","doi":"10.4291/wjgp.v7.i1.48","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.48","url":null,"abstract":"Acute pancreatitis is a necro-inflammatory disease of the exocrine pancreas that is characterized by inappropriate activation of zymogens, infiltration of the pancreas by inflammatory cells, and destruction of the pancreatic exocrine cells. Acute pancreatitis can progress to a severe life-threatening disease. Currently there is no pharmacotherapy to prevent or treat acute pancreatitis. One of the more common factors associated with acute pancreatitis is alcohol abuse. Although commonly associated with pancreatitis alcohol alone is unable to cause pancreatitis. Instead, it appears that alcohol and its metabolic by-products predispose the pancreas to damage from agents that normally do not cause pancreatitis, or to more severe disease from agents that normally cause mild pancreatic damage. Over the last 10 to 20 years, a tremendous amount of work has defined a number of alcohol-mediated biochemical changes in pancreatic cells. Among these changes are: Sustained levels of intracellular calcium, activation of the mitochondrial permeability transition pore, endoplasmic reticulum stress, impairment in autophagy, alteration in the activity of transcriptional activators, and colocalization of lysosomal and pancreatic digestive enzymes. Elucidation of these changes has led to a deeper understanding of the mechanisms by which ethanol predisposes acinar cells to damage. This greater understanding has revealed a number of promising targets for therapeutic intervention. It is hoped that further investigation of these targets will lead to the development of pharmacotherapy that is effective in treating and preventing the progression of acute pancreatitis.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1 1","pages":"48-58"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v7.i1.48","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AIM To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. METHODS Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). RESULTS Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. CONCLUSION The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.
{"title":"Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.","authors":"Mei-Hua Qu, Wan-Sheng Ji, Ting-kun Zhao, Chunyan Fang, Shu-Mei Mao, Zhiqin Gao","doi":"10.4291/wjgp.v7.i1.150","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.150","url":null,"abstract":"AIM\u0000To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion.\u0000\u0000\u0000METHODS\u0000Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA).\u0000\u0000\u0000RESULTS\u0000Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production.\u0000\u0000\u0000CONCLUSION\u0000The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1 1","pages":"150-9"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neuroendocrine tumors (NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging (NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.
{"title":"Small bowel neuroendocrine tumors: From pathophysiology to clinical approach.","authors":"S. Xavier, B. Rosa, J. Cotter","doi":"10.4291/wjgp.v7.i1.117","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.117","url":null,"abstract":"Neuroendocrine tumors (NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging (NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1 1","pages":"117-24"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v7.i1.117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barrett's esophagus (BE), a premalignant condition to Barrett's adenocarcinoma (BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2 (CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide (NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastro-esophageal junction (GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.
Barrett食管(BE)是Barrett腺癌(BAC)的一种癌前病变，与胃食管反流引起的慢性炎症密切相关。尾侧型同源盒2 (Caudal type homeobox 2, CDX2)是BE的代表性标志物，在BE的化生和肿瘤转化过程中增加。一氧化氮(NO)已被认为是巴雷特癌发生的重要介质。我们之前证明，在胃-食管交界处(GEJ)周围产生大量NO的刺激下，CDX2可能以不依赖配体的方式激活上皮生长因子受体，从而直接诱导CDX2。因此，我们回顾了NO在Barrett癌变中作用的最新进展。值得注意的是，最近的研究报道，在正常食管、反流性食管炎、BE或BAC组中，食管远端微生物群落存在显著差异，尽管细菌数量没有差异。考虑到微生物成分可能是大量NO的主要来源之一，这些研究提示食道远端细菌组成可能在致癌过程中调节NO的产生中发挥重要作用。控制由胃食管反流引起的炎症反应或GEJ周围的细菌组成可能有助于通过抑制NO的产生来防止巴雷特癌的进展。
{"title":"Role of nitric oxide in the pathogenesis of Barrett's-associated carcinogenesis.","authors":"G. Kusaka, K. Uno, K. Iijima, T. Shimosegawa","doi":"10.4291/wjgp.v7.i1.131","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i1.131","url":null,"abstract":"Barrett's esophagus (BE), a premalignant condition to Barrett's adenocarcinoma (BAC), is closely associated with chronic inflammation due to gastro-esophageal reflux. Caudal type homeobox 2 (CDX2), a representative marker of BE, is increased during the metaplastic and neoplastic transformation of BE. Nitric oxide (NO) has been proposed to be a crucial mediator of Barrett's carcinogenesis. We previously demonstrated that CDX2 might be induced directly under stimulation of large amounts of NO generated around the gastro-esophageal junction (GEJ) by activating epithelial growth factor receptor in a ligand-independent manner. Thus, we reviewed recent developments on the role of NO in Barrett's carcinogenesis. Notably, recent studies have reported that microbial communities in the distal esophagus are significantly different among groups with a normal esophagus, reflux esophagitis, BE or BAC, despite there being no difference in the bacterial quantity. Considering that microorganism components can be one of the major sources of large amounts of NO, these studies suggest that the bacterial composition in the distal esophagus might play an important role in regulating NO production during the carcinogenic process. Controlling an inflammatory reaction due to gastro-esophageal reflux or bacterial composition around the GEJ might help prevent the progression of Barrett's carcinogenesis by inhibiting NO production.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":"7 1 1","pages":"131-7"},"PeriodicalIF":0.0,"publicationDate":"2016-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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