Recent PubMed Articles on Gut Motility

Associations between the severity of reflux esophagitis in children and changes in oxidative stress, serum inflammation, vasoactive intestinal peptide and motilin.

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Associations between the severity of reflux esophagitis in children and changes in oxidative stress, serum inflammation, vasoactive intestinal peptide and motilin.

Exp Ther Med. 2019 Nov;18(5):3509-3513

Authors: Deng Y, Pan L, Qian W

Abstract
Changes in the levels of serum oxidative stress indexes, gastrointestinal hormones and inflammatory factors in children with different severity of reflux esophagitis (RE) were detected. Sixty child patients diagnosed with gastroesophageal reflux disease (GERD) via gastroscopy were selected and divided into non-erosive reflux disease group (NERD group, n=12) and RE group (n=48) according to whether there was esophageal mucosal injury. In RE group, the patients were further divided into grade I RE group (n=15), grade II RE group (n=18) and grade III RE group (n=15) based on the severity of mucosal injury. None of the child patients took PPI and domperidone within 2 weeks before enrollment. The content of malondialdehyde (MDA) and total superoxide dismutase (T-SOD) in the esophageal mucosa was detected. The changes in the levels of serum vasoactive intestinal peptide (VIP), motilin, interleukin-1β (IL-1β), IL-8 and tumor necrosis factor-α (TNF-α) were determined. The DeMeester score was the highest in grade III RE group, followed by grade II RE group, grade I RE group and NERD group (P<0.05). The content of MDA in the esophageal mucosa was higher in RE group than that in NERD group, and the T-SOD activity declined with the increased severity of injury (P<0.05). In the three RE groups, the level of plasma VIP was significantly higher, while the motilin level was remarkably lower than those in NERD group (P<0.05). With the increased severity of disease, the expression levels of serum IL-1β, IL-8 and TNF-α in RE group were gradually raised (P<0.05). RE patients have strong oxidative stress and inflammatory response, an increased level of serum VIP, a regulator of gastrointestinal motility, and a decreased level of motilin. Controlling the changes in the above factors using effective treatment means can improve the development of GERD.

PMID: 31602227 [PubMed]

ERO1L promotes pancreatic cancer cell progression through activating the Wnt/catenin pathway.

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ERO1L promotes pancreatic cancer cell progression through activating the Wnt/catenin pathway.

J Cell Biochem. 2018 11;119(11):8996-9005

Authors: Han F, Xu Q, Zhao J, Xiong P, Liu J

Abstract
Pancreatic cancer is a lethal malignancy with an extremely poor prognosis. Although many genes and noncoding RNAs have been found to regulate its progression, more regulators are needed to be understood to resolve its high lethality. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) plays crucial roles in the progression of various tumors, but its role in pancreatic cancer progression has not been studied. In this study, we found that ERO1L was significantly upregulated in pancreatic cancer cells and patients; its overexpression significantly promoted pancreatic cancer migration, invasion, and growth, while its knockdown significantly inhibited pancreatic cancer migration, invasion, and growth. Mechanism analysis suggested that ERO1L promoted many tumor-associated signaling pathways, especially the Wnt/catenin pathway; it could activate the Wnt/catenin pathway and upregulate the targets of the Wnt/catenin pathway. We further analyzed the correlation between ERO1L expression and the prognosis of patients, suggesting that patients with high ERO1L expression had short survival time; it is an independent prognosis factor for patients' prognosis. Together, we found that ERO1L was an oncogene for pancreatic cancer.

PMID: 30076651 [PubMed - indexed for MEDLINE]

Aberrant expression of LncRNA-MIR31HG regulates cell migration and proliferation by affecting miR-31 and miR-31* in Hirschsprung's disease.

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Aberrant expression of LncRNA-MIR31HG regulates cell migration and proliferation by affecting miR-31 and miR-31* in Hirschsprung's disease.

J Cell Biochem. 2018 11;119(10):8195-8203

Authors: Cai P, Li H, Huo W, Zhu H, Xu C, Zang R, Lv W, Xia Y, Tang W

Abstract
Hirschsprung's disease (HSCR) is a birth defect that causes a failure of the enteric nervous system to cover the distal gut during early embryonic development. Evidence shows that long non-coding RNAs (lncRNA) play important roles in HSCR. The MIR31 host gene (MIR31HG), also known as Loc554202, is a long non-coding RNA (lncRNA), which acts as the host gene of (microRNA) miR-31 and miR-31*. There have been no studies regarding its function in early developmental defects during pregnancy, and its downstream genetic receptors. We report that downregulation of MIR31HG inhibited migration and proliferation in 293T and SH-SY5Y cell lines, by suppressing miR-31 and miR-31*. Moreover, the downregulation of miR-31 and miR-31* enhanced inter-α-trypsin inhibitor heavy chain 5 (ITIH5) and the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic gamma subunit (PIK3CG), respectively with reductions of cell migration and proliferation in 293T and SH-SY5Y cell lines. In addition, synergistic actions were observed between miR-31 and miR-31* in cell migration and proliferation. Our results demonstrated that the MIR31HG-miR-31/31*-ITIH5/PIK3CG pathway plays a role in the pathogenesis of HSCR.

PMID: 29626357 [PubMed - indexed for MEDLINE]

Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells.

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Colonic Dysmotility in Murine Partial Colonic Obstruction Due to Functional Changes in Interstitial Cells.

J Neurogastroenterol Motil. 2019 Oct 30;25(4):589-601

Authors: Wang Q, Zang J, Huang X, Lu H, Xu W, Chen J

Abstract
Background/Aims: Interstitial cells play important roles in gastrointestinal (GI) neuro-smooth muscle transmission. The underlying mechanisms of colonic dysmotility have not been well illustrated. We established a partial colon obstruction (PCO) mouse model to investigate the changes of interstitial cells and the correlation with colonic motility.
Methods: Western blot technique was employed to observe the protein expressions of Kit, platelet-derived growth factor receptor-α (Pdgfra), Ca2+-activated Cl- (Ano1) channels, and small conductance Ca2+- activated K+ (SK) channels. Colonic migrating motor complexes (CMMCs) and isometric force measurements were employed in control mice and PCO mice.
Results: PCO mice showed distended abdomen and feces excretion was significantly reduced. Anatomically, the colon above the obstructive silicone ring was obviously dilated. Kit and Ano1 proteins in the colonic smooth muscle layer of the PCO colons were significantly decreased, while the expression of Pdgfra and SK3 proteins were significantly increased. The effects of a nitric oxide synthase inhibitor (L-NAME) and an Ano1 channel inhibitor (NPPB) on CMMC and colonic spontaneous contractions were decreased in the proximal and distal colons of PCO mice. The SK agonist, CyPPA and antagonist, apamin in PCO mice showed more effect to the CMMCs and colonic smooth muscle contractions.
Conclusion: Colonic transit disorder may be due to the downregulation of the Kit and Ano1 channels and the upregulation of SK3 channels in platelet-derived growth factor receptor-α positive (PDGFRα+) cells. The imbalance between interstitial cells of Cajal-Ano1 and PDGFRαSK3 distribution might be a potential reason for the colonic dysmotility.

PMID: 31587550 [PubMed]

Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review.

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Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review.

J Neurogastroenterol Motil. 2019 10 30;25(4):508-514

Authors: Nardo GD, Viscogliosi F, Esposito F, Stanghellini V, Villa MP, Parisi P, Morlando A, Cal G, Giorgio R

Abstract
Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, longacting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility.

PMID: 31587541 [PubMed]

Upper Gastrointestinal Function in Morbidly Obese Adolescents Before and 6 Months After Gastric Banding.

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Upper Gastrointestinal Function in Morbidly Obese Adolescents Before and 6 Months After Gastric Banding.

Obes Surg. 2018 05;28(5):1277-1288

Authors: Singendonk M, Kritas S, Omari T, Feinle-Bisset C, Page AJ, Frisby CL, Kentish SJ, Ferris L, McCall L, Kow L, Chisholm J, Khurana S

Abstract
BACKGROUND: The effects of laparoscopic adjustable gastric band (LAGB) placement on upper gastrointestinal tract function in obese adolescents are unknown. Therefore, our aim was to determine the short-term effects of LAGB on esophageal motility, gastroesophageal reflux, gastric emptying, appetite-regulatory hormones, and perceptions of post-prandial hunger and fullness.
METHODS: This study was part of a prospective cohort study (March 2009-December 2015) in one tertiary referral hospital. The study included obese adolescents (14-18 years) with a body mass index (BMI) > 40 (or ≥ 35 with comorbidities). Gastric emptying was assessed by 13C-octanoic acid breath test, pharyngeal, and esophageal motor function by high-resolution manometry with impedance (HRIM), and appetite and other perceptions using 100-mm visual analogue scales. Dysphagia symptoms were scored using a Dakkak questionnaire. Data were compared pre- and post-LAGB placement and at a 6-month follow-up.
RESULTS: Based upon analysis of 15 adolescents, at the 6-month follow-up, LAGB placement: (i) led to a significant reduction in weight and BMI; (ii) increased fullness and decreased hunger post-meal; (iii) increased symptoms of dysphagia after solid food; and, despite these effects, (iv) caused little or no changes to appetite hormones, while (v) effects on gastric emptying, esophageal motility, esophageal bolus transport, and esophageal emptying were not significant.
CONCLUSION: In adolescents, LAGB improved BMI and altered the sensitivity to nutrients without significant effects on upper gastrointestinal tract physiology at the 6-month follow-up.

PMID: 29103072 [PubMed - indexed for MEDLINE]

Utility of Colon Manometry in Guiding Therapy and Predicting Need for Surgery in Children With Defecation Disorders.

Utility of Colon Manometry in Guiding Therapy and Predicting Need for Surgery in Children With Defecation Disorders.

J Pediatr Gastroenterol Nutr. 2019 Sep 17;:

Authors: Rodriguez L, Heinz N, Nurko S

Abstract
Colon manometry (CM) has emerged as a tool to evaluate children with defecation problems. Our aim was to evaluate the utility of CM in guiding therapy and predicting surgery in pediatric constipation.
METHODS: Retrospective review of children undergoing CM for 4 indications: constipation, fecal incontinence, post-surgical evaluation and chronic intestinal pseudo-obstruction. Variables included age, gender, follow up and CM parameters: gastrocolonic response (GC) and quality/quantity of high amplitude propagating contractions (HAPCs).
INTERVENTIONS: medical, surgical or no intervention.
OUTCOMES: response to change of therapy guided by CM, response to first intervention guided by CM (CMI) and CM predicting surgery (CMS). Response to therapy was classified according to study indication.
RESULTS: 555 studies (448 patients, 54.4% female; median age 8.9y;) were included, 24% of studies were normal. Change of therapy guided by CM was associated with a high response rate (p = 0.003). Overall response to stimulant laxatives was 48% and was not associated with CM findings. Surgical interventions had a higher response rate than medical or other interventions (p < 0.001). We found no association between the CM interpretation and CMI, but an abnormal CM was predictive of surgery (p < 0.01). GC and presence/number of HAPCs were not associated with CMI or CMS. We also found no association between HAPC quality and CMI but partially propagated HAPCs were predictive of surgery (p < 0.001). Logistic regression analysis showed no factors associated with CMI, however longer follow up and partially propagated HAPCs were predictive of surgery.
CONCLUSION: CM is useful in pediatric defecation disorders, although not predictive of successful medical intervention, an abnormal CM is predictive of surgery. CM should be performed only after medical interventions have failed and surgery is contemplated.

PMID: 31568156 [PubMed - as supplied by publisher]

A Distinct Esophageal mRNA Pattern Identifies Eosinophilic Esophagitis Patients With Food Impactions.

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A Distinct Esophageal mRNA Pattern Identifies Eosinophilic Esophagitis Patients With Food Impactions.

Front Immunol. 2018;9:2059

Authors: Sallis BF, Acar U, Hawthorne K, Babcock SJ, Kanagaratham C, Goldsmith JD, Rosen R, Vanderhoof JA, Nurko S, Fiebiger E

Abstract
Eosinophilic esophagitis (EoE), a Th2-type allergic immune disorder characterized by an eosinophil-rich esophageal immune infiltrate, is often associated with food impaction (FI) in pediatric patients but the molecular mechanisms underlying the development of this complication are not well understood. We aim to identify molecular pathways involved in the development of FI. Due to large variations in disease presentation, our analysis was further geared to find markers capable of distinguishing EoE patients that are prone to develop food impactions and thus expand an established medical algorithm for EoE by developing a secondary analysis that allows for the identification of patients with food impactions as a distinct patient population. To this end, mRNA patterns from esophageal biopsies of pediatric EoE patients presenting with and without food impactions were compared and machine learning techniques were employed to establish a diagnostic probability score to identify patients with food impactions (EoE+FI). Our analysis showed that EoE patients with food impaction were indistinguishable from other EoE patients based on their tissue eosinophil count, serum IgE levels, or the mRNA transcriptome-based p(EoE). Irrespectively, an additional analysis loop of the medical algorithm was able to separate EoE+FI patients and a composite FI-score was established that identified such patients with a sensitivity of 93% and a specificity of 100%. The esophageal mRNA pattern of EoE+FI patients was typified by lower expression levels of mast cell markers and Th2 associated transcripts, such as FCERIB, CPA3, CCL2, IL4, and IL5. Furthermore, lower expression levels of regulators of esophageal motility (NOS2 and HIF1A) were detected in EoE+FI. The EoE+FI -specific mRNA pattern indicates that impaired motility may be one underlying factor for the development of food impactions in pediatric patients. The availability of improved diagnostic tools such as a medical algorithm for EoE subpopulations will have a direct impact on clinical practice because such strategies can identify molecular inflammatory characteristics of individual EoE patients, which, in turn, will facilitate the development of individualized therapeutic approaches that target the relevant pathways affected in each patient.

PMID: 30455683 [PubMed - indexed for MEDLINE]

Mind the gut: probiotics in paediatric neurogastroenterology.

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Mind the gut: probiotics in paediatric neurogastroenterology.

Benef Microbes. 2018 Dec 07;9(6):883-898

Authors: Salvatore S, Pensabene L, Borrelli O, Saps M, Thapar N, Concolino D, Staiano A, Vandenplas Y

Abstract
The gut-brain axis has recently emerged as a key modulator of human health and the intestinal microbiome has a well-recognised pivotal role in this strong connection. The aim of this narrative review is to update and summarise the effect and clinical applicability of probiotics in paediatric neurogastroenterology. The Cochrane Database and PubMed were searched using keywords relating to different subtypes of functional gastrointestinal disorders (FGIDs) and their symptoms, those relating to the CNS and related neurological or behavioural dysfunction as well as 'probiotic' OR 'probiotics'. Included papers were limited to those including children (aged 0-18 years) and using English language. Although significant effects of specific strains have been reported in infants with FGIDs, heterogeneity amongst the studies (different products and concentrations used and FGID subtypes), has limited the ability to draw an overall conclusion on the clinical value of probiotics. According to different meta-analyses of randomised controlled trials, the use of Lactobacillus reuteri (DSM 17938) was associated with a significant decrease in average crying time in infantile colic. There is moderate evidence for this strain and LGG and limited evidence (based on one study each) for the beneficial effect of VSL#3 and a three-strain bifidobacteria mix in abdominal pain FGIDs, particularly in the irritable bowel disease subgroup of children, but not in functional dyspepsia. There is currently no clear evidence of positive effects of oral probiotics in autistic spectrum disorder. Efficacy and safety of other strains or beneficial effects in other conditions still need to be proven, as probiotic properties are strain-specific, and data cannot be extrapolated to other brain-gut or mood diseases or to other probiotics of the same or different species. To transform the use of probiotics from a tempting suggestion to a promising treatment modality in neurogastroenterological disorders more accurate differentiation of the efficacy-proven strains, clarification of dose, duration, and outcome and a careful selection of the target patients are still necessary.

PMID: 30198327 [PubMed - indexed for MEDLINE]

Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects.

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Artifact Rejection Methodology Enables Continuous, Noninvasive Measurement of Gastric Myoelectric Activity in Ambulatory Subjects.

Sci Rep. 2018 03 22;8(1):5019

Authors: Gharibans AA, Smarr BL, Kunkel DC, Kriegsfeld LJ, Mousa HM, Coleman TP

Abstract
The increasing prevalence of functional and motility gastrointestinal (GI) disorders is at odds with bottlenecks in their diagnosis, treatment, and follow-up. Lack of noninvasive approaches means that only specialized centers can perform objective assessment procedures. Abnormal GI muscular activity, which is coordinated by electrical slow-waves, may play a key role in symptoms. As such, the electrogastrogram (EGG), a noninvasive means to continuously monitor gastric electrical activity, can be used to inform diagnoses over broader populations. However, it is seldom used due to technical issues: inconsistent results from single-channel measurements and signal artifacts that make interpretation difficult and limit prolonged monitoring. Here, we overcome these limitations with a wearable multi-channel system and artifact removal signal processing methods. Our approach yields an increase of 0.56 in the mean correlation coefficient between EGG and the clinical "gold standard", gastric manometry, across 11 subjects (p < 0.001). We also demonstrate this system's usage for ambulatory monitoring, which reveals myoelectric dynamics in response to meals akin to gastric emptying patterns and circadian-related oscillations. Our approach is noninvasive, easy to administer, and has promise to widen the scope of populations with GI disorders for which clinicians can screen patients, diagnose disorders, and refine treatments objectively.

PMID: 29568042 [PubMed - indexed for MEDLINE]

Small Intestinal Bacterial Overgrowth in Children: A State-Of-The-Art Review.

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Small Intestinal Bacterial Overgrowth in Children: A State-Of-The-Art Review.

Front Pediatr. 2019;7:363

Authors: Avelar Rodriguez D, Ryan PM, Toro Monjaraz EM, Ramirez Mayans JA, Quigley EM

Abstract
Small intestinal bacterial overgrowth (SIBO) is a heterogenous and poorly understood entity characterised by an excessive growth of select microorganisms within the small intestine. This excessive bacterial biomass, in turn, disrupts host physiology in a myriad of ways, leading to gastrointestinal and non-gastrointestinal symptoms and complications. SIBO is a common cause of non-specific gastrointestinal symptoms in children, such as chronic abdominal pain, abdominal distention, diarrhoea, and flatulence, amongst others. In addition, it has recently been implicated in the pathophysiology of stunting, a disease that affects millions of children worldwide. Risk factors such as acid-suppressive therapies, alterations in gastrointestinal motility and anatomy, as well as impoverished conditions, have been shown to predispose children to SIBO. SIBO can be diagnosed via culture-dependant or culture-independent approaches. SIBO's epidemiology is limited due to the lack of uniformity and consensus of its diagnostic criteria, as well as the paucity of literature available. Antibiotics remain the first-line treatment option for SIBO, although emerging modalities such as probiotics and diet manipulation could also have a role. Herein, we present a state-of-the-art-review which aims to comprehensively outline the most current information on SIBO in children, with particular emphasis on the gut microbiota.

PMID: 31552207 [PubMed]

LncRNA MALAT1 induces colon cancer development by regulating miR-129-5p/HMGB1 axis.

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LncRNA MALAT1 induces colon cancer development by regulating miR-129-5p/HMGB1 axis.

J Cell Physiol. 2018 09;233(9):6750-6757

Authors: Wu Q, Meng WY, Jie Y, Zhao H

Abstract
Recent studies have exhibited significant roles of lncRNAs in various tumors' development, including colon cancer. Our study focused on the biological roles of lncRNA MALAT1 in colon cancer. In our study, it was demonstrated that MALAT1 was upregulated in human colon cancer cell lines including Lovo, HCT116, SW480, and HT29 cells compared to the normal human intestinal epithelial HIEC cells. Moreover, we observed that miR-129-5p was downregulated in colon cancer cells with a significant increase of HMGB1 expression. Inhibition of MALAT1 can inhibit the proliferation of colon cancer SW480 and HCT116 cells and next, bioinformatics analysis was used to predict the target microRNA of MALAT1. miR-129-5p was identified and confirmed as a direct regulator of MALAT1 and it was shown that miR-129-5p mimics were able to restrain the progression of colon cancer cells. In addition, high motility group box protein 1 (HMGB1), was predicted as a mRNA target of miR-129-5p. Furthermore, we found that MALAT1 exerted its biological functions through regulating HMGB1 by sponging miR-129-5p in vitro. Silencing MALAT1 greatly inhibited HMGB1 expression which can be reversed by miR-129-5p inhibitors. It was indicated in our investigation that MALAT1 may serve as a competing endogenous lncRNA (ceRNA) to mediate HMGB1 by sponging miR-129-5p in colon cancer. Taken together, our results indicated that MALAT1/miR-129-5p/HMGB1 axis could be provided as an important prognostic biomarker in colon cancer development.

PMID: 29226325 [PubMed - indexed for MEDLINE]

Pharmacokinetic considerations in pediatric pharmacotherapy.

Pharmacokinetic considerations in pediatric pharmacotherapy.

Am J Health Syst Pharm. 2019 Sep 16;76(19):1472-1480

Authors: Lim SY, Pettit RS

Abstract
PURPOSE: The changes in physiological functions as children grow and organ systems mature result in pharmacokinetic alterations throughout childhood. These alterations in children result in absorption, distribution, metabolism, and excretion of drugs that are different from those seen in the typical adult diseased population.
SUMMARY: Changes in gastrointestinal motility and gastric pH in neonates and infants affect the absorption rate and bioavailability of drugs. Skin absorption rate and extent can be altered by different skin structures and perfusion in young children. Intramuscular and rectal absorption become less predictable in children due to erratic absorption site perfusion and other factors. Children's body compositions also differ greatly from that in adults. Water-soluble drugs distribute more extensively in newborns due to larger water content than in older children and adults. Drug elimination and excretion are also affected in pediatric population due to differences in liver and renal function. Immature enzyme development and renal function result in reduced clearance of drugs in young children. There are limited pharmacokinetic data available for many drugs used in children.
CONCLUSION: Considering the changes in pharmacokinetics in children can help pharmacists optimize the dosing and monitoring of drugs and do the best they can to help this vulnerable population.

PMID: 31532503 [PubMed - in process]

Oesophageal atresia.

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Oesophageal atresia.

Nat Rev Dis Primers. 2019 04 18;5(1):26

Authors: van Lennep M, Singendonk MMJ, Dall'Oglio L, Gottrand F, Krishnan U, Terheggen-Lagro SWJ, Omari TI, Benninga MA, van Wijk MP

Abstract
Oesophageal atresia (EA) is a congenital abnormality of the oesophagus that is caused by incomplete embryonic compartmentalization of the foregut. EA commonly occurs with a tracheo-oesophageal fistula (TEF). Associated birth defects or anomalies, such as VACTERL association, trisomy 18 or 21 and CHARGE syndrome, occur in the majority of patients born with EA. Although several studies have revealed signalling pathways and genes potentially involved in the development of EA, our understanding of the pathophysiology of EA lags behind the improvements in surgical and clinical care of patients born with this anomaly. EA is treated surgically to restore the oesophageal interruption and, if present, ligate and divide the TEF. Survival is now ~90% in those born with EA with severe associated anomalies and even higher in those born with EA alone. Despite these achievements, long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common and lead to decreased quality of life. Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair and often underlie these complications and comorbidities. The implementation of several new diagnostic and screening tools in clinical care, including high-resolution impedance manometry, pH-multichannel intraluminal impedance testing and disease-specific quality of life questionnaires now provide better insight into these problems and may contribute to better long-term outcomes in the future.

PMID: 31000707 [PubMed - indexed for MEDLINE]

The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis.

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The EBI2-oxysterol axis promotes the development of intestinal lymphoid structures and colitis.

Mucosal Immunol. 2019 05;12(3):733-745

Authors: Wyss A, Raselli T, Perkins N, Ruiz F, Schmelczer G, Klinke G, Moncsek A, Roth R, Spalinger MR, Hering L, Atrott K, Lang S, Frey-Wagner I, Mertens JC, Scharl M, Sailer AW, Pabst O, Hersberger M, Pot C, Rogler G, Misselwitz B

Abstract
The gene encoding for Epstein-Barr virus-induced G-protein-coupled receptor 2 (EBI2) is a risk gene for inflammatory bowel disease (IBD). Together with its oxysterol ligand 7α,25-dihydroxycholesterol, EBI2 mediates migration and differentiation of immune cells. However, the role of EBI2 in the colonic immune system remains insufficiently studied. We found increased mRNA expression of EBI2 and oxysterol-synthesizing enzymes (CH25H, CYP7B1) in the inflamed colon of patients with ulcerative colitis and mice with acute or chronic dextran sulfate sodium (DSS) colitis. Accordingly, we detected elevated levels of 25-hydroxylated oxysterols, including 7α,25-dihydroxycholesterol in mice with acute colonic inflammation. Knockout of EBI2 or CH25H did not affect severity of DSS colitis; however, inflammation was decreased in male EBI2-/- mice in the IL-10 colitis model. The colonic immune system comprises mucosal lymphoid structures, which accumulate upon chronic inflammation in IL-10-deficient mice and in chronic DSS colitis. However, EBI2-/- mice formed significantly less colonic lymphoid structures at baseline and showed defects in inflammation-induced accumulation of lymphoid structures. In summary, we report induction of the EBI2-7α,25-dihydroxycholesterol axis in colitis and a role of EBI2 for the accumulation of lymphoid tissue during homeostasis and inflammation. These data implicate the EBI2-7α,25-dihydroxycholesterol axis in IBD pathogenesis.

PMID: 30742043 [PubMed - indexed for MEDLINE]

Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses.

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Intestinal Dysmotility Syndromes following Systemic Infection by Flaviviruses.

Cell. 2018 11 15;175(5):1198-1212.e12

Authors: White JP, Xiong S, Malvin NP, Khoury-Hanold W, Heuckeroth RO, Stappenbeck TS, Diamond MS

Abstract
Although chronic gastrointestinal dysmotility syndromes are a common worldwide health problem, underlying causes for these disorders are poorly understood. We show that flavivirus infection of enteric neurons leads to acute neuronal injury and cell death, inflammation, bowel dilation, and slowing of intestinal transit in mice. Flavivirus-primed CD8+ T cells promote these phenotypes, as their absence diminished enteric neuron injury and intestinal transit delays, and their adoptive transfer reestablished dysmotility after flavivirus infection. Remarkably, mice surviving acute flavivirus infection developed chronic gastrointestinal dysmotility that was exacerbated by immunization with an unrelated alphavirus vaccine or exposure to a non-infectious inflammatory stimulus. This model of chronic post-infectious gastrointestinal dysmotility in mice suggests that viral infections with tropism for enteric neurons and the ensuing immune response might contribute to the development of bowel motility disorders in humans. These results suggest an opportunity for unique approaches to diagnosis and therapy of gastrointestinal dysmotility syndromes.

PMID: 30293866 [PubMed - indexed for MEDLINE]

StatPearls

StatPearls

Book. 2019 01

Authors:

Abstract
Ketorolac is an FDA-approved medication used in the treatment of moderate to severe acute onset pain.[1] It is in the nonsteroidal anti-inflammatory drug (NSAID) drug class. Ketorolac is versatile, as it is available in multiple dose forms: oral, nasal spray, IV, or IM. It is commonly used postoperatively for pain management. Ketorolac, in combination with opioids, results in a significant decrease in opioid requirement and lowers the incidence of adverse effects such as vomiting and decreased gastrointestinal motility.[1] In children, ketorolac is as effective as major opioid analgesics.[2] Thus, it is a great pain management alternative or adjunct for pediatric (off label for acute moderate to severe pain) or adult individuals for whom there is concern regarding opioid dependence. In the emergency department setting, it is successful in treating musculoskeletal pain, migraines, and sickle cell crisis. Lastly, NSAIDs such as ketorolac are effective for pain associated with cancer that has metastasized to bones.[3] 


PMID: 31424756

A Wireless Implantable System for Facilitating Gastrointestinal Motility.

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A Wireless Implantable System for Facilitating Gastrointestinal Motility.

Micromachines (Basel). 2019 Aug 09;10(8):

Authors: Wang PM, Dubrovsky G, Dunn JCY, Lo YK, Liu W

Abstract
Gastrointestinal (GI) electrical stimulation has been shown in several studies to be a potential treatment option for GI motility disorders. Despite the promising preliminary research progress, however, its clinical applicability and usability are still unknown and limited due to the lack of a miniaturized versatile implantable stimulator supporting the investigation of effective stimulation patterns for facilitating GI dysmotility. In this paper, we present a wireless implantable GI modulation system to fill this technology gap. The system consists of a wireless extraluminal gastrointestinal modulation device (EGMD) performing GI electrical stimulation, and a rendezvous device (RD) and a custom-made graphical user interface (GUI) outside the body to wirelessly power and configure the EGMD to provide the desired stimuli for modulating GI smooth muscle activities. The system prototype was validated in bench-top and in vivo tests. The GI modulation system demonstrated its potential for facilitating intestinal transit in the preliminary in vivo chronic study using porcine models.

PMID: 31395845 [PubMed]

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