Recent PubMed Articles on Gut Motility

Microstructural White Matter Abnormalities in the Dorsal Cingulum of Adolescents with IBS.

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Microstructural White Matter Abnormalities in the Dorsal Cingulum of Adolescents with IBS.

eNeuro. 2018 Jul-Aug;5(4):

Authors: Hubbard CS, Becerra L, Heinz N, Ludwick A, Rasooly T, Yendiki A, Wu R, Schechter NL, Nurko S, Borsook D

Abstract
Alterations in fractional anisotropy (FA) have been considered to reflect microstructural white matter (WM) changes in disease conditions; however, no study to date has examined WM changes using diffusion tensor imaging (DTI) in adolescents with irritable bowel syndrome (IBS). The objective of the present study was two-fold: (1) to determine whether differences in FA, and other non-FA metrics, were present in adolescents with IBS compared to healthy controls using whole-brain, region of interest (ROI)-restricted tract-based spatial statistics (TBSS) and canonical ROI DTI analyses for the cingulum bundle, and (2) to determine whether these metrics were related to clinical measures of disease duration and pain intensity in the IBS group. A total of 16 adolescents with a Rome III diagnosis of IBS (females = 12; mean age = 16.29, age range: 11.96-18.5 years) and 16 age- and gender-matched healthy controls (females = 12; mean age = 16.24; age range: 11.71-20.32 years) participated in this study. Diffusion-weighted images were acquired using a Siemens 3-T Trio Tim Syngo MRI scanner with a 32-channel head coil. The ROI-restricted TBSS and canonical ROI-based DTI analyses revealed that adolescents with IBS showed decreased FA in the right dorsal cingulum bundle compared to controls. No relationship between FA and disease severity measures was found. Microstructural WM alterations in the right dorsal cingulum bundle in adolescents with IBS may reflect a premorbid brain state or the emergence of a disease-driven process that results from complex changes in pain- and affect-related processing via spinothalamic and corticolimbic pathways.

PMID: 30109260 [PubMed - in process]

F-box protein 11 promotes the growth and metastasis of gastric cancer via PI3K/AKT pathway-mediated EMT.

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F-box protein 11 promotes the growth and metastasis of gastric cancer via PI3K/AKT pathway-mediated EMT.

Biomed Pharmacother. 2018 Feb;98:416-423

Authors: Sun C, Tao Y, Gao Y, Xia Y, Liu Y, Wang G, Gu Y

Abstract
F-box protein 11 (FBXO11) has both the E3 ubiquitin ligase activity and the methyltrasferase activity, and regulates metastasis, apoptosis and chemosensitivity in human cancer. However, the clinical significance and biological function of FBXO11 in gastric cancer (GC) are rarely known. Here, we demonstrated up-regulated expression of FBXO11 in GC tissues in comparison with that in tumor-adjacent tissues. Clinical analysis based on our specimens and the TCGA database revealed that FBXO11 overexpression was associated with large tumor size, lymph node metastasis and advanced TNM stage. Notably, GC patients with high FBXO11 expression showed a significant shorter overall survival. Cell proliferation and mobility were measured by CCK-8 and Transwell assays. FBXO11 silencing by transfection with two specific shRNAs attenuated proliferation, migration and invasion of MGC-803 cells. In accordance, FBXO11 overexpression promoted these cellular processes in SGC-7901 cells. Mechanistically, FBXO11 obviously facilitated epithelial-mesenchymal transition (EMT) process as suggested by immunoblotting and immunofluorescence data. Moreover, we found that FBXO11 promoted the activation of AKT pathway with increased phosphorylated AKT level in SGC-7901 cells. LY294002 and Wortmannin, phosphotidylinsitol-3-kinase (PI3K) inhibitors, blocked FBXO11 induced EMT, proliferation, migration and invasion of SGC-7901 cells. Phosphatase and tensin homolog (PTEN), which played a crucial role in regulating PI3K/AKT pathway, was negatively modulated by FBXO11 in GC cells. Taken together, our findings contribute to current understanding of the functions of FBXO11 and suggest a mechanism by which FBXO11 plays an oncogenic role in the development of GC possibly by inhibiting PTEN and subsequently promoting PI3K/AKT pathway activation.

PMID: 29278851 [PubMed - indexed for MEDLINE]

Perceived medication adherence barriers mediating effects between gastrointestinal symptoms and health-related quality of life in pediatric inflammatory bowel disease.

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Perceived medication adherence barriers mediating effects between gastrointestinal symptoms and health-related quality of life in pediatric inflammatory bowel disease.

Qual Life Res. 2018 01;27(1):195-204

Authors: Varni JW, Shulman RJ, Self MM, Saeed SA, Zacur GM, Patel AS, Nurko S, Neigut DA, Franciosi JP, Saps M, Denham JM, Dark CV, Bendo CB, Pohl JF, Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms Module Testing Study Consortium

Abstract
OBJECTIVES: The primary objective was to investigate the mediating effects of patient-perceived medication adherence barriers in the relationship between gastrointestinal symptoms and generic health-related quality of life (HRQOL) in adolescents with inflammatory bowel disease (IBD). The secondary objective explored patient health communication and gastrointestinal worry as additional mediators with medication adherence barriers in a serial multiple mediator model.
METHODS: The Pediatric Quality of Life Inventory™ Gastrointestinal Symptoms, Medicines, Communication, Gastrointestinal Worry, and Generic Core Scales were completed in a 9-site study by 172 adolescents with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and perceived medication adherence barriers were tested for bivariate and multivariate linear associations with HRQOL. Mediational analyses were conducted to test the hypothesized mediating effects of perceived medication adherence barriers as an intervening variable between gastrointestinal symptoms and HRQOL.
RESULTS: The predictive effects of gastrointestinal symptoms on HRQOL were mediated in part by perceived medication adherence barriers. Patient health communication was a significant additional mediator. In predictive analytics models utilizing multiple regression analyses, demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and perceived medication adherence barriers significantly accounted for 45, 38, and 29 percent of the variance in HRQOL (all Ps < 0.001), respectively, demonstrating large effect sizes.
CONCLUSIONS: Perceived medication adherence barriers explain in part the effects of gastrointestinal symptoms on HRQOL in adolescents with IBD. Patient health communication to healthcare providers and significant others further explain the mechanism in the relationship between gastrointestinal symptoms, perceived medication adherence barriers, and HRQOL.

PMID: 28887749 [PubMed - indexed for MEDLINE]

Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease.

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Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease.

World J Gastroenterol. 2017 Nov 14;23(42):7505-7518

Authors: Cukrowska B, Sowińska A, Bierła JB, Czarnowska E, Rybak A, Grzybowska-Chlebowczyk U

Abstract
Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive (specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiota homeostasis, epithelial layer integrity, and the gut-associated lymphoid tissue with its intraepithelial lymphocytes (IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

PMID: 29204051 [PubMed - indexed for MEDLINE]

ISPAD Clinical Practice Consensus Guidelines 2018 Compendium Management of cystic fibrosis related diabetes in children and adolescents.

ISPAD Clinical Practice Consensus Guidelines 2018 Compendium Management of cystic fibrosis related diabetes in children and adolescents.

Pediatr Diabetes. 2018 Aug 09;:

Authors: Moran A, Pillay K, Becker D, Granados A, Hameed S, Acerini CL

Abstract
Cystic fibrosis (CF) is the most common lethal genetic autosomal recessive disease in Caucasians, with a worldwide prevalence of 1 in ~2500 live births. Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity in CF. There are important pathophysiologic differences between CFRD and type 1 and type 2 diabetes Table 1, which necessitate a unique approach to diagnosis and management. Factors specific to CF which impact glucose metabolism include the loss of total islets leading to both insulin and glucagon deficiency, chronic and acute inflammation and infection which cause fluctuating insulin resistance, a requirement for high caloric intake because of increased energy expenditure and malabsorption, risk of life-threatening malnutrition, and gut abnormalities including delayed gastric emptying, altered intestinal motility, and liver disease. This article is protected by copyright. All rights reserved.

PMID: 30094886 [PubMed - as supplied by publisher]

Transcription factor GATA4 associates with mesenchymal-like gene expression in human hepatoblastoma cells.

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Transcription factor GATA4 associates with mesenchymal-like gene expression in human hepatoblastoma cells.

Tumour Biol. 2018 Jul;40(7):1010428318785498

Authors: Soini T, Eloranta K, Pihlajoki M, Kyrönlahti A, Akinrinade O, Andersson N, Lohi J, Pakarinen MP, Wilson DB, Heikinheimo M

Abstract
GATA4, a transcription factor crucial for early liver development, has been implicated in the pathophysiology of hepatoblastoma, an embryonal tumor of childhood. However, the molecular and phenotypic consequences of GATA4 expression in hepatoblastoma are not fully understood. We surveyed GATA4 expression in 24 hepatoblastomas using RNA in situ hybridization and immunohistochemistry. RNA interference was used to inhibit GATA4 in human HUH6 hepatoblastoma cells, and changes in cell migration were measured with wound healing and transwell assays. RNA microarray hybridization was performed on control and GATA4 knockdown HUH6 cells, and differentially expressed genes were validated by quantitative polymerase chain reaction or immunostaining. Plasmid transfection was used to overexpress GATA4 in primary human hepatocytes and ensuring changes in gene expression were measured by quantitative polymerase chain reaction. We found that GATA4 expression was high in most hepatoblastomas but weak or negligible in normal hepatocytes. GATA4 gene silencing impaired HUH6 cell migration. We identified 106 differentially expressed genes (72 downregulated, 34 upregulated) in knockdown versus control HUH6 cells. GATA4 silencing altered the expression of genes associated with cytoskeleton organization, cell-to-cell adhesion, and extracellular matrix dynamics (e.g. ADD3, AHNAK, DOCK8, RHOU, MSF, IGFBP1, COL4A2). These changes in gene expression reflected a more epithelial (less malignant) phenotype. Consistent with this notion, there was reduced F-actin stress fiber formation in knockdown HUH6 cells. Forced expression of GATA4 in primary human hepatocytes triggered opposite changes in the expression of genes identified by GATA4 silencing in HUH6 cells. In conclusion, GATA4 is highly expressed in most hepatoblastomas and correlates with a mesenchymal, migratory phenotype of hepatoblastoma cells.

PMID: 30074440 [PubMed - indexed for MEDLINE]

[COMPARISON OF CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF ARAB AND JEWISH CHILDREN LIVING IN THE GALILEE WHO HAVE SUFFERED FROM AN INTESTINAL INFECTION CAUSED BY CAMPYLOBACTER].

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[COMPARISON OF CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF ARAB AND JEWISH CHILDREN LIVING IN THE GALILEE WHO HAVE SUFFERED FROM AN INTESTINAL INFECTION CAUSED BY CAMPYLOBACTER].

Harefuah. 2017 Oct;156(10):631-634

Authors: Arian A, Abozaid S, On A, Nasser W, Pastukh N, Peretz A

Abstract
INTRODUCTION: Among all infectious agents that cause gastrointestinal infection in children, the most common is the Campylobacter bacterium. The bacterium has multiple virulence factors such as motility, adhesion and invasion of the human intestinal lining, and enzyme secretion. In recent years, there has been a worldwide increase in Campylobacter resistance to antibiotics.
AIMS: To examine the frequency of Campylobacter among children who were hospitalized at the Poriya Medical Center during 2012-2014 and suffered from an intestinal infection caused by Campylobacter; to compare the demographic, clinical, and laboratory data of Jewish and Arab children; to examine the resistance rate of the bacterium to antibiotics.
METHODS: The data on Campylobacter frequency in children who suffered from an intestinal infection was extracted from the medical records: age, sex, hospitalization duration, hemoglobin and leukocyte values in blood chemistry, the residential environment, and antibiotic treatment during hospitalization. In addition, antibiotic susceptibility tests were performed for Erythromycin and Ciprofloxacin for all Campylobacter cultures that were isolated from patients' stool samples and kept frozen.
RESULTS: Campylobacter is the most prevalent bacterial factor among children who were hospitalized following enteritis. There are differences in the bacterium frequency among Jewish children in comparison to frequency in Arab children in the following aspects: Campylobacter is more frequent in Arab children, more common among children living in rural areas, and especially those of Arab origin. Arab children were hospitalized for longer durations than Jewish children. The mean age of Jewish children who suffered from infection caused by Campylobacter was higher compared to the mean age of Arab children. No difference was found in leukocyte values in the cell count. Hemoglobin values were lower among Jewish children compared to Arab children. There was a high percentage of children treated with antibiotics due to intestinal infection caused by Campylobacter, especially among Arab children. Resistance to Erythromycin was not found; however the rate of resistance to Ciprofloxacin was 10.7%.
CONCLUSIONS: There are significant differences in intestinal infection caused by Campylobacter among Jewish and Arab children in parameters such as: mean age, hospitalization duration, and residential area. The antibiotic resistance rate that was found is low; however, presently, it still exists.

PMID: 29072380 [PubMed - indexed for MEDLINE]

Untreated Congenital Hypothyroidism Mimicking Hirschsprung Disease: A Puzzling Case in a One-Year-Old Child.

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Untreated Congenital Hypothyroidism Mimicking Hirschsprung Disease: A Puzzling Case in a One-Year-Old Child.

Case Rep Pediatr. 2018;2018:9209873

Authors: Tahan S, Siviero-Miachon AA, de Faria Soares MF, Soares Martins-Moura EC, Peterlini FL, Batista de Morais M, Spinola-Castro AM

Abstract
Congenital hypothyroidism is a clinical emergency due to its potential risk of mental retardation. Constipation might be present in hypothyroid children. However, Hirschsprung disease is rarely associated with congenital hypothyroidism. Herein, a case of congenital hypothyroidism in a one-year-old child mimicking Hirschsprung disease is described. Adequate treatment with levothyroxine sodium tablets controlled intestinal dysmotility that mimicked congenital intestinal aganglionosis due to the critical influence of thyroid hormones on bowel motility.

PMID: 30050717 [PubMed]

miR-205 regulation of ICT1 has an oncogenic potential via promoting the migration and invasion of gastric cancer cells.

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miR-205 regulation of ICT1 has an oncogenic potential via promoting the migration and invasion of gastric cancer cells.

Biomed Pharmacother. 2017 Dec;96:191-197

Authors: Tao Y, Song Y, Han T, Wang C, Zhao T, Gu Y

Abstract
Immature colon carcinoma transcript-1 (ICT1) is a newly identified oncogene, which regulates mobility, apoptosis, cell cycle progression and proliferation of cancer cells. Nevertheless, the role of ICT1 and its clinical significance in gastric cancer (GC) is largely uncovered. Here, we found that ICT1 displayed higher expression in GC tissues compared to corresponding tumor-adjacent tissues. Further investigation confirmed ICT1 overexpression in GC cell lines. Clinical data disclosed that high ICT1 expression correlated with distant metastasis and advanced tumor-node-metastasis (TNM) stage. The Cancer Genome Atlas (TCGA) data further demonstrated that GC tissues with metastasis showed a significant higher level of ICT1 compared to those without metastasis. Furthermore, ICT1 overexpression notably predicted poor prognosis of GC patients. Functionally, we demonstrated that ICT1 knockdown suppressed invasion and migration of MGC-803 and BGC-823 cells in vitro. ICT1 overexpression promoted the mobility of SGC-7901 cells. Mechanistically, microRNA-205 (miR-205) was recognized as a direct down-regulator and inversely modulated ICT1 abundance in GC cells. miR-205 expression was down-regulated and negatively associated with ICT1 level in GC tissues. Underexpression of miR-205 indicated an obvious shorter survival of GC patients. miR-205 overexpression inhibited migration and invasion of MGC-803 cells, while these inhibitory effects were reversed by ICT1 restoration. Taken together, we have the earliest evidence that miR-205 regulation of ICT1 functions as an oncogene and prognostic biomarker in GC.

PMID: 28987942 [PubMed - indexed for MEDLINE]

Pharmacological management of gastroesophageal reflux disease in infants: current opinions.

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Pharmacological management of gastroesophageal reflux disease in infants: current opinions.

Curr Opin Pharmacol. 2017 12;37:112-117

Authors: El-Mahdy MA, Mansoor FA, Jadcherla SR

Abstract
Gastroesophageal reflux disease (GERD) constitutes a troublesome symptom complex resulting from retrograde passage of gastric contents into the esophagus or extra-esophageal regions. Premature-born, high-risk infants and those with neuro-aero-digestive pathologies are at increased risk. Critical review over the last 3 years was conducted, and current opinions on pharmacological targets include agents aimed at prevention of transient lower esophageal sphincter relaxation, modification of the physico-chemical composition of gastric contents, modification of gut motility, or altering sensory thresholds to ameliorate the troublesome symptoms. As data from well-designed studies is limited in the infant population, information from adult studies has been cited where potential application may be helpful.

PMID: 29128854 [PubMed - indexed for MEDLINE]

Evaluation of intestinal injury, inflammatory response and oxidative stress following intracerebral hemorrhage in mice.

Evaluation of intestinal injury, inflammatory response and oxidative stress following intracerebral hemorrhage in mice.

Int J Mol Med. 2018 Jul 04;:

Authors: Cheng Y, Zan J, Song Y, Yang G, Shang H, Zhao W

Abstract
Intestinal injury is a common complication following intracerebral hemorrhage (ICH), which leads to malnutrition, impaired immunity and unsatisfactory prognosis. Previous studies have revealed the pathogenesis of intestinal injury following traumatic brain injury using ischemic stroke models. However, the effects of ICH on intestinal injury remain unknown. The present study aimed to investigate the pathological alterations and molecular mechanism, as well as the time course of intestinal injury following ICH in mice. Male C57BL/6 mice were randomly divided into the following seven groups (n=6 mice/group): Control group, which underwent a sham operation, and six ICH groups (2, 6, 12 and 24 h, and days 3 and 7). The ICH model was induced by stereotactically injecting autologous blood in two stages into the brain. Subsequently, intestinal tissue was stained with hematoxylin and eosin for histopathological examination. Small intestinal motility was measured by charcoal meal test, and gut barrier dysfunction was evaluated by detecting the plasma levels of endotoxin. Quantitative polymerase chain reaction (qPCR), immunohistochemistry and ELISA analysis were performed to evaluate the mRNA and protein expression levels of inflammatory cytokines [interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α, intercellular adhesion molecule 1, monocyte chemotactic protein 1 and chemokine (C‑C motif) ligand‑5] in intestinal tissue and serum. Furthermore, intestinal leukocyte infiltration was detected by measuring myeloperoxidase activity. Oxidative stress was indirectly detected by measuring reactive oxygen species‑associated markers (malondialdehyde content and superoxide dismutase activity assays) and the mRNA and protein expression levels of antioxidant genes [nuclear factor (erythroid‑derived 2)‑like 2, manganese superoxide dismutase and heme oxygenase 1] by qPCR and western blot analysis. The results demonstrated that significant destruction of the gut mucosa, delayed small intestinal motility, intestinal barrier dysfunction, and increased inflammatory responses and oxidative stress occurred rapidly in response to ICH. These symptoms occurred as early as 2 h after ICH and persisted for 7 days. These findings suggested that ICH may induce immediate and persistent damage to gut structure and barrier function, which may be associated with upregulation of inflammation and oxidative stress markers.

PMID: 30015849 [PubMed - as supplied by publisher]

Segmental colonic dilation is associated with premature termination of high-amplitude propagating contractions in children with intractable functional constipation.

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Segmental colonic dilation is associated with premature termination of high-amplitude propagating contractions in children with intractable functional constipation.

Neurogastroenterol Motil. 2017 Oct;29(10):1-9

Authors: Koppen IJN, Thompson BP, Ambeba EJ, Lane VA, Bates DG, Minneci PC, Deans KJ, Levitt MA, Wood RJ, Benninga MA, Di Lorenzo C, Yacob D

Abstract
BACKGROUND: Colonic dilation is common in children with intractable functional constipation (FC). Our aim was to describe the association between segmental colonic dilation and colonic dysmotility in children with FC.
METHODS: We performed a retrospective study on 30 children with intractable FC (according to the Rome III criteria) who had undergone colonic manometry and contrast enema within a 12-month time period. Colonic diameter was measured at 5 cm intervals from the anal verge up to the splenic flexure. Moreover, the distance between the lateral margins of the pedicles of vertebra L2 was measured to provide a ratio (colonic diameter or length/distance between the lateral margins; "standardized colon size" [SCS]). All manometry recordings were visually inspected for the presence of high-amplitude propagating contractions (HAPCs); a parameter for colonic motility integrity. The intracolonic location of the manometry catheter sensors was assessed using an abdominal X-ray.
KEY RESULTS: Colonic segments with HAPCs had a significantly smaller median diameter than colonic segments without HAPCs (4.08 cm vs 5.48 cm, P<.001; SCS 1.14 vs 1.66, P=.001). Children with prematurely terminating HAPCs had significantly larger SCS ratios for colonic diameter than children with fully propagating HAPCs (P=.008). SCS ratios for the length of the rectosigmoid and the descending colon and the SCS ratio for sigmoid colon diameter were significantly larger in children with FC compared to a previously described normative population (P<.0001, P<.0001 and P=.0007 respectively).
CONCLUSIONS & INFERENCES: Segmental colonic dilation was associated with prematurely terminating HAPCs and may be a useful indicator of colonic dysmotility.

PMID: 28524640 [PubMed - indexed for MEDLINE]

Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference.

Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference.

Gastroenterology. 2018 Jul 12;:

Authors: Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ

Abstract
BACKGROUND AND AIMS: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE in order to develop updated international consensus criteria for EoE diagnosis.
METHODS: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries utilized on-line communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences.
RESULTS: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement.
CONCLUSIONS: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or ∼60 eosinophils per mm2) on esophageal biopsy, and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change.

PMID: 30009819 [PubMed - as supplied by publisher]

The role of intermediate filaments in maintaining integrity and function of intestinal epithelial cells after massive bowel resection in a rat.

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The role of intermediate filaments in maintaining integrity and function of intestinal epithelial cells after massive bowel resection in a rat.

Pediatr Surg Int. 2018 Feb;34(2):217-225

Authors: Sukhotnik I, Shahar YB, Pollak Y, Dorfman T, Shefer HK, Assi ZE, Mor-Vaknin N, Coran AG

Abstract
PURPOSE: Intermediate filaments (IFs) are a part of the cytoskeleton that extend throughout the cytoplasm of all cells and function in the maintenance of cell-shape by bearing tension and serving as structural components of the nuclear lamina. In normal intestine, IFs provide a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. The purpose of this study was to evaluate the role of IFs during intestinal adaptation in a rat model of short bowel syndrome (SBS).
MATERIALS AND METHODS: Male rats were divided into two groups: Sham rats underwent bowel transection and SBS rats underwent a 75% bowel resection. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined 2 weeks after operation. Illumina's Digital Gene Expression (DGE) analysis was used to determine the cytoskeleton-related gene expression profiling. IF-related genes and protein expression were determined using real-time PCR, Western blotting and immunohistochemistry.
RESULTS: Massive small bowel resection resulted in a significant increase in enterocyte proliferation and concomitant increase in cell apoptosis. From the total number of 20,000 probes, 16 cytoskeleton-related genes were investigated. Between these genes, only myosin and tubulin levels were upregulated in SBS compared to sham animals. Between IF-related genes, desmin, vimentin and lamin levels were down-regulated and keratin and neurofilament remain unchanged. The levels of TGF-β, vimentin and desmin gene and protein were down-regulated in resected rats (vs sham animals).
CONCLUSIONS: Two weeks following massive bowel resection in rats, the accelerated cell turnover was accompanied by a stimulated microfilaments and microtubules, and by inhibited intermediate filaments. Resistance to cell compression rather that maintenance of cell-shape by bearing tension are responsible for contraction, motility and postmitotic cell separation in a late stage of intestinal adaptation.

PMID: 29043445 [PubMed - indexed for MEDLINE]

The effect of laminin-1 on enteric neural crest-derived cell migration in the Hirschsprung's disease mouse model.

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The effect of laminin-1 on enteric neural crest-derived cell migration in the Hirschsprung's disease mouse model.

Pediatr Surg Int. 2018 Feb;34(2):143-147

Authors: Nakazawa-Tanaka N, Fujiwara N, Miyahara K, Nakada S, Arikawa-Hirasawa E, Akazawa C, Urao M, Yamataka A

Abstract
BACKGROUND/AIM: Laminin-1 regulates neurite outgrowth in various neuronal cells. We have previously demonstrated that laminin-1 promotes enteric neural crest-derived cell (ENCC) migration by using Sox10-VENUS transgenic mice, in which ENCCs are labeled with a green fluorescent protein, Venus. Mice lacking the endothelin-B receptor gene, Ednrb -/- mice, are widely used as a model for Hirschsprung's disease (HD). The aim of this study was to investigate the effects of laminin-1on ENCC migration in Sox10-VENUS+/Ednrb -/- mice, a newly created HD mice model.
METHODS: Fetal guts were dissected on embryonic day 12.5 (E12.5). Specimens were incubated either with, or without laminin-1 for 24 h and images were taken under a stereoscopic microscope. The length from the stomach to the wavefront of ENCC migration (L-E) and the total length of the gut (L-G) were measured. Changes in the ratio of L-E to L-G (L-E/L-G) after 24 h were calculated.
RESULTS: On E12.5, the wavefront of ENCC migration in the HD gut samples was located in the midgut, whereas the wavefront of ENCC in Sox10-VENUS+/Ednrb +/+ (WT) samples had reached the hindgut. After 24 h, L-E/L-G had increased by 1.49%, from 34.97 to 36.46%, in HD gut and had increased by 1.07%, from 48.08 to 49.15%, in HD with laminin-1, suggesting there was no positive effect of laminin-1 administration on ENCC migration in HD.
CONCLUSIONS: Our results suggest that laminin-1 does not have a positive effect on ENCC migration in HD mice on E12.5, in contrast to the phenomenon seen in normal mice gut specimens, where laminin-1 promotes ENCC migration during the same period. This suggests that there is an impairment in the interaction between ENCC and extracellular environmental factors, which are required for normal development of the enteric nervous system, resulting in an aganglionic colon in HD.

PMID: 29018955 [PubMed - indexed for MEDLINE]

Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung's disease.

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Altered expression of laminin alpha1 in aganglionic colon of endothelin receptor-B null mouse model of Hirschsprung's disease.

Pediatr Surg Int. 2018 Feb;34(2):137-141

Authors: Fujiwara N, Nakazawa-Tanaka N, Miyahara K, Arikawa-Hirasawa E, Akazawa C, Yamataka A

Abstract
PURPOSE: Laminin, an extracellular matrix molecule, is essential for normal development of the nervous system. The alpha1 subunit of laminin-1 (LAMA1) has been reported to promote neurites and outgrowth and is expressed only during embryogenesis. Previously, we developed a Sox10 transgenic version of the Endothelin receptor-B (Ednrb) mouse to visualize Enteric neural crest-derived cell (ENCC)s with a green fluorescent protein, Venus. We designed this study to investigate the expression of LAMA1 using Sox10-VENUS mice gut.
METHODS: We harvested the gut on days 13.5 (E13.5) and 15.5 (E15.5) of gestation. Sox10-VENUS+/Ednrb -/- mice (n = 8) were compared with Sox10-VENUS+/Ednrb +/+ mice (n = 8) as controls. Gene expression of LAMA1 was analysed by real-time RT-PCR. Fluorescent immunohistochemistry was performed to assess protein distribution.
RESULTS: The relative mRNA expression levels of LAMA1 were significantly increased in HD in the proximal and distal colon on E15.5 compared to controls (p < 0.05), whereas there were no significant differences on E13.5. LAMA1 was expressed in the serosa, submucosa and basal lamina in the gut, and was markedly increased in the proximal and distal colon of HD on E15.5.
CONCLUSIONS: Altered LAMA1 expression in the aganglionic region may contribute to impaired ENCC migration, resulting in HD. These data could help in understanding the pathophysiologic interactions between LAMA1 and ENCC migration.

PMID: 28983681 [PubMed - indexed for MEDLINE]

Enteric Neural Stem Cells Expressing Insulin-Like Growth Factor 1: A Novel Cellular Therapy for Hirschsprung's Disease in Mouse Model.

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Enteric Neural Stem Cells Expressing Insulin-Like Growth Factor 1: A Novel Cellular Therapy for Hirschsprung's Disease in Mouse Model.

DNA Cell Biol. 2018 Jul;37(7):642-648

Authors: Liu W, Zhang L, Wu R

Abstract
Transplanting enteric neural stem cells (ENSCs) is an innovative approach for replacing enteric neurons in Hirschsprung's disease (HSCR). However, posttransplantation cell survival and differentiation limit efficacy. We aimed to investigate whether transplantation of ENSCs engineered with insulin-like growth factor 1 (IGF-1) could improve survival and differentiation of the engrafted cells and promote functional recovery of the aganglionic colon. ENSCs were isolated from the intestine of neonatal mice and genetically modified to express IGF-1. After implantation into the mice aganglionic colon induced by benzalkonium chloride, survival and differentiation of engrafted cells were assessed by immunohistochemistry for GFP, neuronal, and glial cell markers. Colonic motility was quantified by colonic bead expulsion time and response to electrical field stimulation (EFS). Expression of the neural marker nNOS and the glial cell marker (glial fibrillary acidic protein [GFAP]) was increased in IGF-1-ENSCs. IGF-1 had also improved neuroglial differentiation of ENSCs following transplantation in vivo. Colonic motility was significantly improved after IGF-1-ENSC transplantation, as demonstrated by reduction of colonic bead expulsion time and recovery of EFS-induced relaxation. IGF-1 has enhanced neurogenesis and function of ENSCs upon transplantation for enteric nervous system replacement, which may provide a potential novel therapy for the treatment of HSCR.

PMID: 29792527 [PubMed - indexed for MEDLINE]

Gastrointestinal dysmotility and pancreatic insufficiency in 2 siblings with Donohue syndrome.

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Gastrointestinal dysmotility and pancreatic insufficiency in 2 siblings with Donohue syndrome.

Pediatr Diabetes. 2017 Dec;18(8):839-843

Authors: Kostopoulou E, Shah P, Ahmad N, Semple R, Hussain K

Abstract
Donohue syndrome is a rare congenital syndrome of insulin-resistance and abnormal glucose homeostasis, caused by mutations in the insulin receptor (INSR) gene. It is characterized by specific phenotypic and clinical features and the diagnosis is based on clinical, biochemical and genetic criteria. We report 2 siblings with Donohue syndrome (cases 1, 2) with multiple clinical and biochemical characteristics. Both patients shared the same mutation and presented with intra-uterine growth restriction, failure to thrive, fasting hyperinsulinaemic hypoglycaemia and episodic post-prandial hyperglycaemia. Less common clinical features were also present, such as atrial septal defect and biventricular hypertrophy, clotting disorders, abnormal liver function tests and nephrocalcinosis. Interestingly, 2 previously unrecognized manifestations of the syndrome were also identified: severe gastrointestinal dysmotility (case 1) and exocrine pancreatic insufficiency (case 2). The co-existence of all the above clinical features makes these cases extremely rare. Gastrointestinal dysmotility should always be considered as a potentially fatal feature in patients with the syndrome, due to the complexity of the possible co-morbidities. In addition, our clinical experience for the first time suggests that pancreatic exocrine insufficiency may offer a possible explanation for the growth retardation observed in some patients with this syndrome. Our finding that replacement treatment with pancreatic enzymes improved weight gain (case 2) implies that all patients with Donohue syndrome should be investigated for exocrine pancreatic insufficiency.

PMID: 28004474 [PubMed - indexed for MEDLINE]

Platelet-derived growth factor receptor alpha-positive cells: a new cell type in the human ureteropelvic junction.

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Platelet-derived growth factor receptor alpha-positive cells: a new cell type in the human ureteropelvic junction.

Pediatr Res. 2017 Dec;82(6):1080-1087

Authors: Hunziker M, O'Donnell AM, Puri P

Abstract
BACKGROUND: Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis. Normal ureteral motility requires coordinated interaction between neurons, smooth muscle cells (SMCs), and interstitial Cajal-like cells (IC-LCs). Recently, a new type of interstitial cell, platelet-derived growth factor receptor α-positive (PDGFRα+) cells, was discovered in the gastrointestinal tract and bladder.MethodsWe used immunohistochemistry to study PDGFRα protein distribution in normal human UPJ and congenital UPJ obstruction. Western blot and real-time PCR (RT-PCR) were used to study PDGFRα protein and gene expression levels. In addition, closely associated cells and small conductance Ca2+-activated K+ (SK) channels were investigated.ResultsPDGFRα+ cells were distinct from IC-LCs and SMCs and were in close proximity to nerve fibers. PDGFRα+ cells expressed SK3 channels, which are thought to mediate purinergic inhibitory neurotransmission in SMCs. The distribution of PDGFRα+ cells was similar in UPJ obstruction vs.
CONTROLS: However, the expression of SK3 channels in PDGFRα+ cells was decreased in UPJ obstruction vs.
CONTROLS: ConclusionThis study shows, for the first time, the PDGFRα+ cell expression in the human UPJ. Altered SK3 channel expression observed in PDGFRα+ cells in UPJ obstruction suggests that the impairment of SK3 activity across the UPJ may perturb upper urinary tract peristalsis in this urological condition.

PMID: 28902181 [PubMed - indexed for MEDLINE]

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