World Journal of Gastrointestinal Pathophysiology最新文献

{"title":"Gastro-oesophageal reflux disease and eosinophilic oesophagitis: What is the relationship?","authors":"Stephanie Wong,&nbsp;Andrew Ruszkiewicz,&nbsp;Richard H Holloway,&nbsp;Nam Q Nguyen","doi":"10.4291/wjgp.v9.i3.63","DOIUrl":"https://doi.org/10.4291/wjgp.v9.i3.63","url":null,"abstract":"<p><p>Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) are the most common causes of chronic oesophagitis and dysphagia associated with oesophageal mucosal eosinophilia. Distinguishing between the two is imperative but challenging due to overlapping clinical and histological features. A diagnosis of EoE requires clinical, histological and endoscopic correlation whereas a diagnosis of GORD is mainly clinical without the need for other investigations. Both entities may exhibit oesophageal eosinophilia at a similar level making a histological distinction between them difficult. Although the term proton-pump inhibitor responsive oesophageal eosinophilia has recently been retracted from the guidelines, a relationship between EoE and GORD still exists. This relationship is complex as they may coexist, either interacting bidirectionally or are unrelated. This review aims to outline the differences and potential relationship between the two conditions, with specific focus on histology, immunology, pathogenesis and treatment.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"9 3","pages":"63-72"},"PeriodicalIF":0.0,"publicationDate":"2018-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v9.i3.63","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36639697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acinar cell injury induced by inadequate unfolded protein response in acute pancreatitis.","authors":"Kaylene Barrera,&nbsp;Albert Stanek,&nbsp;Kei Okochi,&nbsp;Zuzanna Niewiadomska,&nbsp;Cathy Mueller,&nbsp;Peiqi Ou,&nbsp;Devon John,&nbsp;Antonio E Alfonso,&nbsp;Scott Tenner,&nbsp;Chongmin Huan","doi":"10.4291/wjgp.v9.i2.37","DOIUrl":"https://doi.org/10.4291/wjgp.v9.i2.37","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR's signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB's pro-inflammatory activity and impair autophagy's protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"9 2","pages":"37-46"},"PeriodicalIF":0.0,"publicationDate":"2018-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/eb/9b/WJGP-9-37.PMC6163129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36597878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiome profiling and colorectal cancer in African Americans and Caucasian Americans.","authors":"Lulu Farhana,&nbsp;Fadi Antaki,&nbsp;Farhan Murshed,&nbsp;Hamidah Mahmud,&nbsp;Stephanie L Judd,&nbsp;Pratima Nangia-Makker,&nbsp;Edi Levi,&nbsp;Yingjie Yu,&nbsp;Adhip Pn Majumdar","doi":"10.4291/wjgp.v9.i2.47","DOIUrl":"https://doi.org/10.4291/wjgp.v9.i2.47","url":null,"abstract":"<p><strong>Aim: </strong>To determine whether and to what extent the gut microbiome is involved in regulating racial disparity in colorectal cancer (CRC).</p><p><strong>Methods: </strong>All patients were recruited and experiments were performed in accordance with the relevant guidelines and regulations by the Institutional Review Boards (IRB), committees of the John D. Dingell VAMC and Wayne State University guidelines. African American (AA) and Caucasian American (CA) patients were scheduled for an outpatient screening for colonoscopy, and no active malignancy volunteer patients were doubly consented, initially by the gastroenterologist and later by the study coordinator, for participation in the study. The gut microbial communities in colonic effluents from AAs and CAs were examined using 16sRNA profiling, and bacterial identifications were validated by performing SYBR-based Real Time PCR. For metagenomic analysis to characterize the microbial communities, multiple software/tools were used, including Metastats and R statistical software.</p><p><strong>Results: </strong>It is generally accepted that the incidence and mortality of CRC is higher in AAs than in CAs. However, the reason for this disparity is not well understood. We hypothesize that the gut microbiome plays a role in regulating this disparity. Indeed, we found significant differences in species richness and diversity between AAs and CAs. <i>Bacteroidetes</i> was more abundant in AAs than in CAs. In particular, the pro-inflammatory bacteria <i>Fusobacterium nucleatum</i> and <i>Enterobacter</i> species were significantly higher in AAs, whereas probiotic <i>Akkermansia muciniphila</i> and <i>Bifidobacterium</i> were higher in CAs. The polyphyletic <i>Clostridia</i> class showed a divergent pattern, with <i>Clostridium XI</i> elevated in AAs, and <i>Clostridium IV</i>, known for its beneficial function, higher in CAs. Lastly, the AA group had decreased microbial diversity overall in comparison to the CA group. In summary, there were significant differences in pro-inflammatory bacteria and microbial diversity between AA and CA, which may help explain the CRC disparity between groups.</p><p><strong>Conclusion: </strong>Our current investigation, for the first time, demonstrates microbial dysbiosis between AAs and CAs, which could contribute to the racial disparity of CRC.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"9 2","pages":"47-58"},"PeriodicalIF":0.0,"publicationDate":"2018-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v9.i2.47","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36597877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute cholangitis - an update.","authors":"Monjur Ahmed","doi":"10.4291/wjgp.v9.i1.1","DOIUrl":"https://doi.org/10.4291/wjgp.v9.i1.1","url":null,"abstract":"<p><p>Acute cholangitis is bacterial infection of the extra-hepatic biliary system. As it is caused by gallstones blocking the common bile duct in most of the cases, its prevalence is greater in ethnicities with high prevalence of gallstones. Biliary obstruction of any cause is the main predisposing factor. Diagnosis is established by the presence of clinical features, laboratory results and imaging studies. The treatment modalities include administration of intravenous fluid, antibiotics, and drainage of the bile duct. The outcome is good if the treatment is started early, otherwise it could be grave.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"9 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2018-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v9.i1.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35867985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver cirrhosis-effect on QT interval and cardiac autonomic nervous system activity.","authors":"Elias Tsiompanidis, Spyros I Siakavellas, Anastasios Tentolouris, Ioanna Eleftheriadou, Stamatia Chorepsima, Anastasios Manolakis, Konstantinos Oikonomou, Nikolaos Tentolouris","doi":"10.4291/wjgp.v9.i1.28","DOIUrl":"10.4291/wjgp.v9.i1.28","url":null,"abstract":"<p><strong>Aim: </strong>To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy (CAN).</p><p><strong>Methods: </strong>A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval (QTc) and their dispersions (dQT, dQTc) were measured and calculated using a computer-based program. The diagnosis of CAN was based upon the battery of the tests proposed by Ewing and Clarke and the consensus statements of the American Diabetes Association. CAN was diagnosed when two out of the four classical Ewing tests were abnormal.</p><p><strong>Results: </strong>QT, QTc and their dispersions were significantly longer (<i>P</i> < 0.01) in patients with cirrhosis than in controls. No significant differences in QT interval were found among the subgroups according to the etiology of cirrhosis. Multivariate regression analysis after controlling for age, gender and duration of cirrhosis demonstrated significant association between QT and presence of diabetes mellitus [standardized regression coefficient (beta) = 0.45, <i>P</i> = 0.02] and treatment with diuretics (beta = 0.55, <i>P</i> = 0.03), but not with the Child-Pugh score (<i>P</i> = 0.54). Prevalence of CAN was common (54.9%) among patients with cirrhosis and its severity was associated with the Child-Pugh score (<i>r</i> = 0.33, <i>P</i> = 0.02). Moreover, patients with decompensated cirrhosis had more severe CAN that those with compensated cirrhosis (<i>P</i> = 0.03). No significant association was found between severity of CAN and QT interval duration.</p><p><strong>Conclusion: </strong>Patients with cirrhosis have QT prolongation. Treatment with diuretics is associated with longer QT. CAN is common in patients with cirrhosis and its severity is associated with severity of the disease.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"9 1","pages":"28-36"},"PeriodicalIF":0.0,"publicationDate":"2018-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/02/0d/WJGP-9-28.PMC5823700.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35868958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abundance of <i>Enterobacteriaceae</i> in the colon mucosa in diverticular disease.","authors":"Caroline Linninge,&nbsp;Bodil Roth,&nbsp;Charlotte Erlanson-Albertsson,&nbsp;Göran Molin,&nbsp;Ervin Toth,&nbsp;Bodil Ohlsson","doi":"10.4291/wjgp.v9.i1.18","DOIUrl":"https://doi.org/10.4291/wjgp.v9.i1.18","url":null,"abstract":"<p><strong>Aim: </strong>To compare gut bacterial diversity and amount of <i>Enterobacteriaceae</i> in colonic mucosa between patients with and without diverticular disease (DD).</p><p><strong>Methods: </strong>Patients in a stable clinical condition with planned elective colonoscopy were included. Blood samples and colon mucosa biopsies were collected at the colonoscopy. Study questionnaires including questions about gastrointestinal symptoms were completed by the patients and physicians. DNA from mucosa samples was isolated and the amount of <i>Enterobacteriaceae</i> was estimated using PCR assay. Terminal restriction fragment length polymorphism was applied to assess microbial diversity. Diversity was estimated by calculations of richness (number of terminal restriction fragments) and Shannon-Wiener and Simpson's indices.</p><p><strong>Results: </strong>A total of 51 patients were included, 16 patients with DD [68 (62-76) years] and 35 controls [62 (40-74) years] without any diverticula. Patients with DD had significantly higher levels of <i>Enterobacteriaceae</i> than those without DD (<i>P</i> = 0.043), and there was an inverse relationship between the amount of <i>Enterobacteriaceae</i> and the Simpson's index (rs = -0.361, <i>P</i> = 0.033) and the Shannon-Wiener index (rs = -0.299, <i>P</i> = 0.081). The Simpson's index (<i>P</i> = 0.383), Shannon-Wiener index (<i>P</i> = 0.401) or number of restrictions fragments (<i>P</i> = 0.776) did not differ between DD and controls. The majority of patients experienced gastrointestinal symptoms, and 22 patients (43.1%) fulfilled the criteria for irritable bowel syndrome, with no difference between the groups (<i>P</i> = 0.212). Demography, socioeconomic status, lifestyle habits, inflammatory biomarkers, or symptoms were not related to the amount of <i>Enterobacteriaceae</i> or bacterial diversity.</p><p><strong>Conclusion: </strong>Patients with DD had higher amount of <i>Enterobacteriaceae</i> in the colon mucosa compared to patients without diverticula.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"9 1","pages":"18-27"},"PeriodicalIF":0.0,"publicationDate":"2018-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v9.i1.18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35868957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergency resection surgery for colorectal cancer: Patterns of recurrent disease and survival.","authors":"Joe Littlechild,&nbsp;Muneer Junejo,&nbsp;Anne-Marie Simons,&nbsp;Finlay Curran,&nbsp;Darren Subar","doi":"10.4291/wjgp.v9.i1.8","DOIUrl":"https://doi.org/10.4291/wjgp.v9.i1.8","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate prognostic pathological factors associated with early metachronous disease and adverse long-term survival in these patients.</p><p><strong>Methods: </strong>Clinical and histological features were analysed retrospectively over an eight-year period for prognostic impact on recurrent disease and overall survival in patients undergoing curative resection of a primary colorectal cancer.</p><p><strong>Results: </strong>A total of 266 patients underwent curative surgery during the study period. The median age of the study cohort was 68 year (range 26 to 91) with a follow-up of 7.9 years (range 4.6 to 12.6). Resection was undertaken electively in 225 (84.6%) patients and emergency resection in 35 (13.2%). Data on timing of surgery was missing in 6 patients. Recurrence was noted in 67 (25.2%) during the study period and was predominantly early within 3 years (82.1%) and involved hepatic metastasis in 73.1%. Emergency resection (OR = 3.60, <i>P</i> = 0.001), T4 stage (OR = 4.33, <i>P</i> < 0.001) and lymphovascular invasion (LVI) (OR = 2.37, <i>P</i> = 0.032) were associated with higher risk of recurrent disease. Emergency resection, T4 disease and a high lymph node ratio (LNR) were strong independent predictors of adverse long-term survival.</p><p><strong>Conclusion: </strong>Emergency surgery is associated with adverse disease free and long-term survival. T4 disease, LVI and LNR provide strong independent predictive value of long-term outcome and can inform surveillance strategies to improve outcomes.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"9 1","pages":"8-17"},"PeriodicalIF":0.0,"publicationDate":"2018-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/8e/WJGP-9-8.PMC5823701.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35868955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paneth cells in intestinal physiology and pathophysiology.","authors":"Nikolaus Gassler","doi":"10.4291/wjgp.v8.i4.150","DOIUrl":"https://doi.org/10.4291/wjgp.v8.i4.150","url":null,"abstract":"<p><p>Small intestinal mucosa is characterised by villus forming connective tissues with highly specialised surface lining epithelial cells essentially contributing to the establishment of the intestinal border. In order to perform these diverse functions, spatially distinct compartments of epithelial differentiation are found along the crypt-villus axis, including Paneth cells as a highly specialised cell type. Paneth cells locate in crypts and assist undifferentiated columnar cells, called crypt base columnar cells, and rapidly amplifying cells in the regeneration of absorptive and secretory cell types. There is some evidence that Paneth cells are involved in the configuration and function of the stem cell zone as well as intestinal morphogenesis and crypt fission. However, the flow of Paneth cells to crypt bottoms requires strong Wnt signalling guided by EphB3 and partially antagonised by Notch. In addition, mature Paneth cells are essential for the production and secretion of antimicrobial peptides including α-defensins/cryptdins. These antimicrobials are physiologically involved in shaping the composition of the microbiome. The autophagy related 16-like 1 (ATG16L1) is a genetic risk factor and is involved in the exocytosis pathway of Paneth cells as well as a linker molecule to PPAR signalling and lipid metabolism. There is evidence that injuries of Paneth cells are involved in the etiopathogenesis of different intestinal diseases. The review provides an overview of the key points of Paneth cell activities in intestinal physiology and pathophysiology.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"8 4","pages":"150-160"},"PeriodicalIF":0.0,"publicationDate":"2017-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/69/WJGP-8-150.PMC5696613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35649429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological inhibition of diacylglycerol acyltransferase-1 and insights into postprandial gut peptide secretion.","authors":"Benjamin S Maciejewski,&nbsp;Tara B Manion,&nbsp;Claire M Steppan","doi":"10.4291/wjgp.v8.i4.161","DOIUrl":"https://doi.org/10.4291/wjgp.v8.i4.161","url":null,"abstract":"<p><strong>Aim: </strong>To examine the role that enzyme Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) plays in postprandial gut peptide secretion and signaling.</p><p><strong>Methods: </strong>The standard experimental paradigm utilized to evaluate the incretin response was a lipid challenge. Following a lipid challenge, plasma was collected <i>via</i> cardiac puncture at each time point from a cohort of 5-8 mice per group from baseline at time zero to 10 h. Incretin hormones [glucagon like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY) and glucose dependent insulinotropic polypeptide (GIP)] were then quantitated. The impact of pharmacological inhibition of DGAT1 on the incretin effect was evaluated in WT mice. Additionally, a comparison of loss of DGAT1 function either by genetic ablation or pharmacological inhibition. To further elucidate the pathways and mechanisms involved in the incretin response to DGAT1 inhibition, other interventions [inhibitors of dipeptidyl peptidase-IV (sitagliptin), pancreatic lipase (Orlistat), GPR119 knockout mice] were evaluated.</p><p><strong>Results: </strong>DGAT1 deficient mice and wildtype C57/BL6J mice were lipid challenged and levels of both active and total GLP-1 in the plasma were increased. This response was further augmented with DGAT1 inhibitor PF-04620110 treated wildtype mice. Furthermore, PF-04620110 was able to dose responsively increase GLP-1 and PYY, but blunt GIP at all doses of PF-04620110 during lipid challenge. Combination treatment of PF-04620110 and Sitagliptin in wildtype mice during a lipid challenge synergistically enhanced postprandial levels of active GLP-1. In contrast, in a combination study with Orlistat, the ability of PF-04620110 to elicit an enhanced incretin response was abrogated. To further explore this observation, GPR119 knockout mice were evaluated. In response to a lipid challenge, GPR119 knockout mice exhibited no increase in active or total GLP-1 and PYY. However, PF-04620110 was able to increase total GLP-1 and PYY in GPR119 knockout mice as compared to vehicle treated wildtype mice.</p><p><strong>Conclusion: </strong>Collectively, these data provide some insight into the mechanism by which inhibition of DGAT1 enhances intestinal hormone release.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"8 4","pages":"161-175"},"PeriodicalIF":0.0,"publicationDate":"2017-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/14/85/WJGP-8-161.PMC5696614.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35649430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats.","authors":"Alexandra L Whittaker,&nbsp;Ying Zhu,&nbsp;Gordon S Howarth,&nbsp;Chi S Loung,&nbsp;Susan E P Bastian,&nbsp;Michelle G Wirthensohn","doi":"10.4291/wjgp.v8.i4.176","DOIUrl":"https://doi.org/10.4291/wjgp.v8.i4.176","url":null,"abstract":"<p><strong>Aim: </strong>To determine if almond extracts reduce the severity of chemotherapy-induced mucositis as determined through biochemical, histological and behavioural markers.</p><p><strong>Methods: </strong>Intestinal mucositis is a debilitating condition characterized by inflammation and ulceration of the gastrointestinal mucosa experienced by cancer patients undergoing chemotherapy. Certain bioactive plant products have shown promise in accelerating mucosal repair and alleviating clinical symptoms. This study evaluated almond extracts for their potential to reduce the severity of chemotherapy-induced mucositis in Dark Agouti rats. Female Dark Agouti rats were gavaged (days 3-11) with either PBS, almond hull or almond blanched water extract at two doses, and were injected intraperitoneally with 5-fluorouracil (5-FU-150 mg/kg) or saline on day 9 to induce mucositis. Burrowing behavior, histological parameters and myeloperoxidase activity were assessed.</p><p><strong>Results: </strong>Bodyweight was significantly reduced in rats that received 5-FU compared to saline-treated controls (<i>P</i> < 0.05). Rats administered 5-FU significantly increased jejunal and ileal MPO levels (1048%; <i>P</i> < 0.001 and 409%; <i>P</i> < 0.001), compared to healthy controls. Almond hull extract caused a pro-inflammatory response in rats with mucositis as evidenced by increased myeloperoxidase activity in the jejunum when compared to 5-FU alone (rise 50%, 1088 ± 96 U/g <i>vs</i> 723 ± 135 U/g, <i>P</i> = 0.02). Other extract-related effects on inflammatory activity were minimal. 5-FU significantly increased histological severity score compared to healthy controls confirming the presence of mucositis (median of 9.75 <i>vs</i> 0; <i>P</i> < 0.001). The extracts had no ameliorating effect on histological severity score in the jejunum or ileum. Burrowing behavior was significantly reduced in all chemotherapy-treated groups (<i>P</i> = 0.001). The extracts failed to normalize burrowing activity to baseline levels.</p><p><strong>Conclusion: </strong>Almond extracts at these dosages offer little beneficial effect on mucositis severity. Burrowing provides a novel measure of affective state in studies of chemotherapy-induced mucositis.</p>","PeriodicalId":23760,"journal":{"name":"World Journal of Gastrointestinal Pathophysiology","volume":"8 4","pages":"176-187"},"PeriodicalIF":0.0,"publicationDate":"2017-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4291/wjgp.v8.i4.176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35649432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}