F. A. Cimini, I. Barchetta, S. Carotti, S. Morini, M. Cavallo
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. NAFLD is known to be associated with obesity, type 2 diabetes, metabolic syndrome and increased cardiovascular events: for these reasons, it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment. The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled; consequently, at moment there are not effective treatments. In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation, inflammation and fibrosis, to the vitamin D/vitamin D receptor (VD/VDR) axis, showing a strong association between hypovitaminosis D and the diagnosis of NAFLD. However, the data currently available, including clinical trials with VD supplementation, still provides a contrasting picture. The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR. Based on recent data from literature, we focused in particular on the hypothesis that VDR itself, independently from its traditional ligand VD, may have a crucial function in promoting hepatic fat accumulation. This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.
{"title":"Overview of studies of the vitamin D/vitamin D receptor system in the development of non-alcoholic fatty liver disease","authors":"F. A. Cimini, I. Barchetta, S. Carotti, S. Morini, M. Cavallo","doi":"10.4291/wjgp.v10.i2.11","DOIUrl":"https://doi.org/10.4291/wjgp.v10.i2.11","url":null,"abstract":"Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. NAFLD is known to be associated with obesity, type 2 diabetes, metabolic syndrome and increased cardiovascular events: for these reasons, it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment. The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled; consequently, at moment there are not effective treatments. In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation, inflammation and fibrosis, to the vitamin D/vitamin D receptor (VD/VDR) axis, showing a strong association between hypovitaminosis D and the diagnosis of NAFLD. However, the data currently available, including clinical trials with VD supplementation, still provides a contrasting picture. The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR. Based on recent data from literature, we focused in particular on the hypothesis that VDR itself, independently from its traditional ligand VD, may have a crucial function in promoting hepatic fat accumulation. This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47489299","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}
G. Bonagura, D. Ribaldone, S. Fagoonee, N. Sapone, G. P. Caviglia, G. Saracco, M. Astegiano, R. Pellicano
AIM To evaluate the potential association between mild duodenal damage and microscopic colitis (MC). METHODS We retrospectively included 105 consecutive patients with type I Marsh-Oberhuber duodenal damage and negativity for immunoglobulin A anti-endomysium and anti-tissue transglutaminase. The following parameters were analyzed: Sex, age at execution of esophagogastroduodenoscopy, duodenal damage, and number of intraepithelial lymphocytes at biopsies, prevalence of Helicobacter pylori infection, age at execution of colonoscopy, macroscopic and microscopic features of colonoscopy, family history of gastrointestinal and autoimmune diseases, smoking habits, biochemical parameters of inflammation and autoimmunity, use of proton pump inhibitors or nonsteroidal anti-inflammatory drugs, adverse reactions to drugs or foods, pathologies known to be associated with celiac disease or MC, living on a gluten-free diet or on a gluten-low diet for at least 1 mo. RESULTS Colonoscopy was performed in 59 patients, but only in 48 of them biopsies were taken in the entire colon. Considering the latter cohort, the diagnosis of MC was met in 25 (52.1%) patients while in 18 patients other pathologic findings were reported: 13 (27%) cases of nonspecific inflammatory bowel disease, 2 (4.2%) cases of Crohn’s disease, 2 (4.2%) cases of eosinophilic gastroenteritis, and 1 (2.1%) case of autoimmune enteritis. Five (10.4%) patients had a normal colonoscopic result. Matching the groups by age, and considering only patients who underwent colonoscopy (42.7 ± 15.5 years) vs those who did not undergo colonoscopy (36.9 ± 10.6 years), a statistical difference was found (P = 0.039). Focusing on symptoms, diarrhea was statistically more prevalent in MC group than in patients who did not undergo colonoscopy (P = 0.03). CONCLUSION Mild duodenal damage is associated with MC in more than half of the cases. This association supports the hypothesis of a link between these two entities.
{"title":"Microscopic colitis in patients with mild duodenal damage: A new clinical and pathological entity (“lymphocytic enterocolitis”)?","authors":"G. Bonagura, D. Ribaldone, S. Fagoonee, N. Sapone, G. P. Caviglia, G. Saracco, M. Astegiano, R. Pellicano","doi":"10.4291/wjgp.v7.i4.307","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i4.307","url":null,"abstract":"AIM To evaluate the potential association between mild duodenal damage and microscopic colitis (MC). METHODS We retrospectively included 105 consecutive patients with type I Marsh-Oberhuber duodenal damage and negativity for immunoglobulin A anti-endomysium and anti-tissue transglutaminase. The following parameters were analyzed: Sex, age at execution of esophagogastroduodenoscopy, duodenal damage, and number of intraepithelial lymphocytes at biopsies, prevalence of Helicobacter pylori infection, age at execution of colonoscopy, macroscopic and microscopic features of colonoscopy, family history of gastrointestinal and autoimmune diseases, smoking habits, biochemical parameters of inflammation and autoimmunity, use of proton pump inhibitors or nonsteroidal anti-inflammatory drugs, adverse reactions to drugs or foods, pathologies known to be associated with celiac disease or MC, living on a gluten-free diet or on a gluten-low diet for at least 1 mo. RESULTS Colonoscopy was performed in 59 patients, but only in 48 of them biopsies were taken in the entire colon. Considering the latter cohort, the diagnosis of MC was met in 25 (52.1%) patients while in 18 patients other pathologic findings were reported: 13 (27%) cases of nonspecific inflammatory bowel disease, 2 (4.2%) cases of Crohn’s disease, 2 (4.2%) cases of eosinophilic gastroenteritis, and 1 (2.1%) case of autoimmune enteritis. Five (10.4%) patients had a normal colonoscopic result. Matching the groups by age, and considering only patients who underwent colonoscopy (42.7 ± 15.5 years) vs those who did not undergo colonoscopy (36.9 ± 10.6 years), a statistical difference was found (P = 0.039). Focusing on symptoms, diarrhea was statistically more prevalent in MC group than in patients who did not undergo colonoscopy (P = 0.03). CONCLUSION Mild duodenal damage is associated with MC in more than half of the cases. This association supports the hypothesis of a link between these two entities.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059896","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}
Y. Rhee, H. Ku, Hye-Ji Noh, Hyang-Hyun Cho, Hee-Kyong Kim, Jin-Chul Ahn
AIM To investigate the bactericidal effects of calcium chelated N-acetylneuraminic acid-glycomacropeptide (CaG-NANA) against Helicobacter pylori (H. pylori). METHODS For manufacture of CaG-NANA, calcium (Ca) was combined with glycomacropeptide (GMP) by chelating, and N-acetylneuraminic acid (NANA) was produced with Ca-GMP substrate by an enzymatic method. The final concentration of each component was 5% Ca, 7% NANA, 85% GMP, and 3% water. For in vitro study, various concentrations of CaG-NANA were investigated under the minimal inhibitory concentration (MIC). For in vivo study, CaG-NANA was administered orally for 3 wk after H. pylori infection. The levels of inflammatory cytokines in blood were analyzed by enzyme-linked immunosorbent assay and eradication of H. pylori was assessed by histological observation. RESULTS The time-kill curves showed a persistent decrease in cell numbers, which depended on the dose of CaG-NANA, and MIC of CaG-NANA against H. pylori was 0.5% in vitro. Histopathologic observation revealed no obvious inflammation or pathologic changes in the gastric mucosa in the CaG-NANA treatment group in vivo. The colonization of H. pylori was reduced after CaG-NANA treatment. The levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 were also decreased by CaG-NANA. CONCLUSION CaG-NANA demonstrates effective anti-bactericidal activity against H. pylori both in vitro and in vivo.
目的研究钙螯合n -乙酰神经氨酸糖大肽(CaG-NANA)对幽门螺杆菌的杀菌作用。方法将钙(Ca)与糖大肽(GMP)螯合结合，以Ca-GMP为底物酶法合成n -乙酰神经氨酸(NANA)。各组分的最终浓度为5% Ca, 7% NANA, 85% GMP, 3%水。体外实验采用最低抑菌浓度(MIC)对不同浓度的CaG-NANA进行研究。在体内研究中，幽门螺杆菌感染后口服CaG-NANA 3周。采用酶联免疫吸附法分析血中炎症因子水平，采用组织学观察观察幽门螺杆菌根除情况。结果时间杀伤曲线显示细胞数量持续下降，且与剂量有关，体外对幽门螺杆菌的杀伤MIC为0.5%。组织病理学观察显示，CaG-NANA治疗组胃黏膜在体内无明显炎症及病理改变。经CaG-NANA处理后，幽门螺杆菌的定植量减少。白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α和IL-10的水平也被CaG-NANA降低。结论CaG-NANA对幽门螺杆菌具有较强的体外和体内抑菌活性。
{"title":"Anti-Helicobacter pylori effect of CaG-NANA, a new sialic acid derivative","authors":"Y. Rhee, H. Ku, Hye-Ji Noh, Hyang-Hyun Cho, Hee-Kyong Kim, Jin-Chul Ahn","doi":"10.4291/wjgp.v7.i4.300","DOIUrl":"https://doi.org/10.4291/wjgp.v7.i4.300","url":null,"abstract":"AIM To investigate the bactericidal effects of calcium chelated N-acetylneuraminic acid-glycomacropeptide (CaG-NANA) against Helicobacter pylori (H. pylori). METHODS For manufacture of CaG-NANA, calcium (Ca) was combined with glycomacropeptide (GMP) by chelating, and N-acetylneuraminic acid (NANA) was produced with Ca-GMP substrate by an enzymatic method. The final concentration of each component was 5% Ca, 7% NANA, 85% GMP, and 3% water. For in vitro study, various concentrations of CaG-NANA were investigated under the minimal inhibitory concentration (MIC). For in vivo study, CaG-NANA was administered orally for 3 wk after H. pylori infection. The levels of inflammatory cytokines in blood were analyzed by enzyme-linked immunosorbent assay and eradication of H. pylori was assessed by histological observation. RESULTS The time-kill curves showed a persistent decrease in cell numbers, which depended on the dose of CaG-NANA, and MIC of CaG-NANA against H. pylori was 0.5% in vitro. Histopathologic observation revealed no obvious inflammation or pathologic changes in the gastric mucosa in the CaG-NANA treatment group in vivo. The colonization of H. pylori was reduced after CaG-NANA treatment. The levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 were also decreased by CaG-NANA. CONCLUSION CaG-NANA demonstrates effective anti-bactericidal activity against H. pylori both in vitro and in vivo.","PeriodicalId":68755,"journal":{"name":"世界胃肠病理生理学杂志(电子版)(英文版)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71059829","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}
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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
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