Recent PubMed Articles on Gut Motility

Surgical options for the management of severe functional constipation in children.

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Surgical options for the management of severe functional constipation in children.

Curr Opin Pediatr. 2016 Jun;28(3):370-9

Authors: Wood RJ, Yacob D, Levitt MA

Abstract
PURPOSE OF REVIEW: Constipation is a very common problem in pediatrics with both the severity of presentations and treatments varying across a broad spectrum. The majority of children with functional constipation are managed successfully without the need for specialized testing and surgical intervention. Those who present with intractable constipation, with or without fecal soiling, require referrals for motility testing that helps determine both medical and surgical management, and interventions. The literature was reviewed for publications on surgical approaches to children with severe constipation, including assessing the quality and levels of evidence and the use of objective measures to determine outcomes.
RECENT FINDINGS: There is very little in the way of recent studies evaluating surgical indications or treatment approaches for functional constipation, apart from one systematic review and one recent expert review. Although the systematic review was published in the last year, most of the studies it analyzes are older. The vast majority of studies comprise level 4 and 5 evidence.
SUMMARY: The indication for most surgical procedures is 'failed' medical management, yet no standardized definition for this exists. Many surgical procedures are proposed with little evidence to show outcomes. We recommend that the surgical evaluation and treatment of children with constipation needs to be protocolized and studied in a prospective manner using validated outcomes measures. Our center's current protocol is described.

PMID: 26963948 [PubMed - indexed for MEDLINE]

Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration.

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Peroxiredoxin 6 (Prdx6) supports NADPH oxidase1 (Nox1)-based superoxide generation and cell migration.

Free Radic Biol Med. 2016 Jul;96:99-115

Authors: Kwon J, Wang A, Burke DJ, Boudreau HE, Lekstrom KJ, Korzeniowska A, Sugamata R, Kim YS, Yi L, Ersoy I, Jaeger S, Palaniappan K, Ambruso DR, Jackson SH, Leto TL

Abstract
Nox1 is an abundant source of reactive oxygen species (ROS) in colon epithelium recently shown to function in wound healing and epithelial homeostasis. We identified Peroxiredoxin 6 (Prdx6) as a novel binding partner of Nox activator 1 (Noxa1) in yeast two-hybrid screening experiments using the Noxa1 SH3 domain as bait. Prdx6 is a unique member of the Prdx antioxidant enzyme family exhibiting both glutathione peroxidase and phospholipase A2 activities. We confirmed this interaction in cells overexpressing both proteins, showing Prdx6 binds to and stabilizes wild type Noxa1, but not the SH3 domain mutant form, Noxa1 W436R. We demonstrated in several cell models that Prdx6 knockdown suppresses Nox1 activity, whereas enhanced Prdx6 expression supports higher Nox1-derived superoxide production. Both peroxidase- and lipase-deficient mutant forms of Prdx6 (Prdx6 C47S and S32A, respectively) failed to bind to or stabilize Nox1 components or support Nox1-mediated superoxide generation. Furthermore, the transition-state substrate analogue inhibitor of Prdx6 phospholipase A2 activity (MJ-33) was shown to suppress Nox1 activity, suggesting Nox1 activity is regulated by the phospholipase activity of Prdx6. Finally, wild type Prdx6, but not lipase or peroxidase mutant forms, supports Nox1-mediated cell migration in the HCT-116 colon epithelial cell model of wound closure. These findings highlight a novel pathway in which this antioxidant enzyme positively regulates an oxidant-generating system to support cell migration and wound healing.

PMID: 27094494 [PubMed - indexed for MEDLINE]

Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.

Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.

Auton Neurosci. 2017 Dec 20;:

Authors: Zizzo MG, Frinchi M, Nuzzo D, Jinnah HA, Mudò G, Condorelli DF, Caciagli F, Ciccarelli R, Di Iorio P, Mulè F, Belluardo N, Serio R

Abstract
Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt¯). Spontaneous and neurally evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips of distal colon. HGprt¯ tissues showed a lower in amplitude spontaneous activity and atropine-sensitivity neural contraction compared to control mice. The responses to carbachol and to high KCl were reduced, demonstrating a widespread impairment of contractility. L-NAME was not able in the HGprt¯ tissues to restore the large amplitude contractile activity typical of control. In HGprt¯ colon, a reduced expression of dopaminergic D1 receptor was observed together with the loss of its tonic inhibitory activity present in control-mice. The analysis of inflammatory and oxidative stress in colonic tissue of HGprt¯ mice revealed a significant increase of lipid peroxidation associated with over production of oxygen free radicals. In conclusion, HGprt deficiency in mice is associated with a decrease in colon contractility, not dependent upon reduction of acetylcholine release from the myenteric plexus or hyperactivity of inhibitory signalling. By contrast the increased levels of oxidative stress could partially explain the reduced colon motility in HGprt¯ mice. Colonic dysmotility observed in HGprt¯ mice may mimic the gastrointestinal dysfunctions symptoms of human syndrome, providing a useful animal model to elucidate the pathophysiology of this problem in the LND.

PMID: 29305058 [PubMed - as supplied by publisher]

Laparoscopic Adjustable Gastric Banding in Australian Adolescents: Should It Be Done?

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Laparoscopic Adjustable Gastric Banding in Australian Adolescents: Should It Be Done?

Obes Surg. 2017 Jul;27(7):1667-1673

Authors: Peña AS, Delko T, Couper R, Sutton K, Kritas S, Omari T, Chisholm J, Kow L, Khurana S

Abstract
OBJECTIVE: There are very few studies on laparoscopic adjustable gastric banding (LAGB) in obese adolescents with follow up for more than 36 months, let alone good prospective data beyond 24 months in Australian adolescents. We aimed to evaluate medium term (>36 months) safety and efficacy of LAGB in adolescents with severe obesity.
METHODS: This is a prospective cohort study (March 2009-December 2015) in one tertiary referral hospital including obese adolescents (14-18 years) with a body mass index (BMI) >40 (or ≥35 with comorbidities) who consented to have LAGB. Exclusion criteria were syndromal causes of obesity, depression and oesophageal motility disorders. Main outcome measures include change in weight and BMI at 6, 12, 24, 36 and 48 months post LAGB; postoperative complications; and admissions.
RESULTS: Twenty-one adolescents (median [interquartile range (IQR)] 17.4 [16.5-17.7] years, 9 males, mean ± SD BMI 47.3 ± 8.4 kg/m2) had a median follow up of 45.5 [32-50] months post LAGB. Follow up data were available for 16 adolescents. Weight and BMI improved significantly at all follow up times (all p < 0.01). The median maximum BMI loss was 10 [7.1-14.7] kg/m2. There were four minor early complications. Seven bands were removed due to weight loss failure/regain (two had also obstructive symptoms).
CONCLUSIONS: We have shown in the longest prospective LAGB postoperative follow up study of Australian adolescents that LAGB improves BMI in the majority of adolescents without significant comorbidities. LAGB is still a reasonable option to be considered as a temporary procedure to manage severe obesity during adolescence.

PMID: 28083846 [PubMed - indexed for MEDLINE]

Diagnostic Tests in Pediatric Constipation.

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Diagnostic Tests in Pediatric Constipation.

J Pediatr Gastroenterol Nutr. 2017 Dec 28;:

Authors: Tambucci R, Quitadamo P, Thapar N, Zenzeri L, Caldaro T, Staiano A, Verrotti A, Borrelli O

Abstract
Constipation is one of the most common gastrointestinal symptoms in children. With a median reported prevalence of 12%, it accounts for about 25% of all pediatric gastroenterology consultations. The majority of children suffers functional constipation and do not usually require any diagnostic testing. For those children not responding to conventional medical treatment or in the presence of a more significant clinical picture, however, an accurate instrumental assessment is usually recommended to evaluate either the underlying pathophysiologic mechanisms or a possible organic etiology. The present review analyzes the possible diagnostic investigations for severely constipated children, focusing on their actual indications and their utility in clinical practice. Over the last decade, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed and are discussed in this narrative review.

PMID: 29287015 [PubMed - as supplied by publisher]

Choline Alleviates Parenteral Nutrition-Associated Duodenal Motility Disorder in Infant Rats.

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Choline Alleviates Parenteral Nutrition-Associated Duodenal Motility Disorder in Infant Rats.

JPEN J Parenter Enteral Nutr. 2016 Sep;40(7):995-1005

Authors: Zhu J, Wu Y, Guo Y, Tang Q, Lu T, Cai W, Huang H

Abstract
BACKGROUND: Parenteral nutrition (PN) has been found to influence duodenal motility in animals. Choline is an essential nutrient, and its deficiency is related to PN-associated organ diseases. Therefore, this study was aimed to investigate the role of choline supplementation in an infant rat model of PN-associated duodenal motility disorder.
MATERIALS AND METHODS: Three-week-old Sprague-Dawley male rats were fed chow and water (controls), PN solution (PN), or PN plus intravenous choline (600 mg/kg) (PN + choline). Rats underwent jugular vein cannulation for infusion of PN solution or 0.9% saline (controls) for 7 days. Duodenal oxidative stress status, concentrations of plasma choline, phosphocholine, and betaine and serum tumor necrosis factor (TNF)-α were assayed. The messenger RNA (mRNA) and protein expression of c-Kit proto-oncogene protein (c-Kit) and membrane-bound stem cell factor (mSCF) together with the electrophysiological features of slow waves in the duodenum were also evaluated.
RESULTS: Rats on PN showed increased reactive oxygen species; decreased total antioxidant capacity in the duodenum; reduced plasma choline, phosphocholine, and betaine; and enhanced serum TNF-α concentrations, which were reversed by choline intervention. In addition, PN reduced mRNA and protein expression of mSCF and c-Kit, which were inversed under choline administration. Moreover, choline attenuated depolarized resting membrane potential and declined the frequency and amplitude of slow waves in duodenal smooth muscles of infant rats induced by PN, respectively.
CONCLUSION: The addition of choline to PN may alleviate the progression of duodenal motor disorder through protecting smooth muscle cells from injury, promoting mSCF/c-Kit signaling, and attenuating impairment of interstitial cells of Cajal in the duodenum during PN feeding.

PMID: 25904588 [PubMed - indexed for MEDLINE]

[Home and Ambulatory Artificial Nutrition (NADYA) Group Report - Home parenteral nutrition in Spain, 2016].

[Home and Ambulatory Artificial Nutrition (NADYA) Group Report - Home parenteral nutrition in Spain, 2016].

Nutr Hosp. 2017 Nov 24;34(5):1497-1501

Authors: Wanden-Berghe Lozano C, Virgili Casas N, Ramos Boluda E, Cuerda Compés C, Moreno Villares JM, Pereira Cunill JL, Gómez Candela C, Burgos Peláez R, Penacho Lázaro MÁ, Pérez de la Cruz A, Álvarez Hernández J, Gonzalo Marín M, Matía Martín P, Martínez Faedo C, Sánchez Martos EÁ, Sanz Paris A, Campos Martín C, Martín Folgueras T, Martín Palmero MÁ, Martín Fontalba MLÁ, Luengo Pérez LM, Zugasti Murillo A, Martínez Ramírez MJ, Carabaña Pérez F, Martínez Costa C, Díaz Guardiola P, Tejera Pérez C, Parés Marimón RM, Irles Rocamora JA, Garde Orbaiz C, Ponce González MÁ, García Zafra MV, Sánchez Sánchez R, Urgeles Planella JR, Apezetxea Celaya A, Sánchez-Vilar Burdiel O, Joaquín Ortiz C, Suárez Llanos JP, Pintor de la Maza B, Leyes García P, Gil Martínez MC, Mauri Roca S, Carrera Santaliestra MJ

Abstract
OBJECTIVE: To communicate HPN data obtained from the HPN registry of the NADYA-SENPE group (www.nadya-senpe.com) for the year 2016.
MATERIAL AND METHODS: Descriptive analysis of the data collected from adult and pediatric patients with HPN in the NADYA-SENPE group registry from January 1st, 2016 to December 31st, 2016.
RESULTS: There were 286 patients from 42 Spanish hospitals (54.2% women), 34 children and 252 adults, with 294 episodes, which represent a prevalence rate of 6.16 patients / million inhabitants / year 2016. The most frequent diagnosis in adults was "palliative cancer" (25.8%), followed by "others". In children it was "motility alterations" with 6 cases (17.6%), Hirschsprung's disease and necrotising enterocolitis, both with 5 children (14.7%). The first indication was short bowel syndrome in both children (64.7%) and adults (37.3%), followed by intestinal obstruction in 28.6% adults and 14.7% in children. The most frequently used type of catheter was tunnelled in both children (70.6%) and adults (37.9%). The most frequent complication in adults was infection related to the catheter, which presented a rate of 0.48 infections / 1,000 days of NPD. During this period, 71 episodes ended in adults and the main cause was death (57.7%) followed by resuming the oral route (31%).
CONCLUSIONS: There is a progressive increase of centers and professional collaborators in the registry who report patients receiving parenteral nutrition at home. The main indications of HPN and the motive for ending have remained stable.

PMID: 29280669 [PubMed - in process]

Gastroesophageal Reflux Burden, Even in Children That Aspirate, Does Not Increase Pediatric Hospitalization.

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Gastroesophageal Reflux Burden, Even in Children That Aspirate, Does Not Increase Pediatric Hospitalization.

J Pediatr Gastroenterol Nutr. 2016 Aug;63(2):210-7

Authors: Duncan DR, Amirault J, Johnston N, Mitchell P, Larson K, Rosen RL

Abstract
OBJECTIVES: Gastroesophageal reflux is common but remains a controversial disease to diagnose and treat and little is known about the role of reflux testing in predicting clinical outcomes, particularly in children at risk for extraesophageal reflux complications. The aim of this study was to determine if rates of hospitalization were affected by reflux burden even after adjusting for aspiration risk.
METHODS: We prospectively recruited, between 2009 and 2014, a cohort of pediatric patients with suspected extraesophageal reflux disease who were referred for reflux testing and underwent both multichannel intraluminal impedance with pH (pH-MII) and modified barium swallow studies. A subset of patients also underwent bronchoalveolar lavage with pepsin analysis. We determined their rates of hospitalization for a minimum of 1 year following pH-MII testing.
RESULTS: We prospectively enrolled 116 pediatric patients who presented for care at Boston Children's Hospital and underwent both pH-MII and modified barium swallow studies. There was no statistically significant relationship between reflux burden measured by pH-MII or bronchoalveolar pepsin and total number of admissions or number of admission nights even after adjusting for aspiration status (P > 0.2). There were no statistically significant relationships between reflux burden by any method and the number or nights of urgent pulmonary admissions before or after adjusting for aspiration risk (P > 0.08).
CONCLUSIONS: Even in aspirating children, reflux burden did not increase the risk of hospitalization. Based on these results, routine reflux testing cannot be recommended even in aspirating children, because the results do not impact clinically significant outcomes.

PMID: 26794490 [PubMed - indexed for MEDLINE]

Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.

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Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.

Schizophr Res. 2016 Sep;176(1):23-35

Authors: Severance EG, Yolken RH, Eaton WW

Abstract
Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders.

PMID: 25034760 [PubMed - indexed for MEDLINE]

Gastrointestinal Symptoms Predictors of Health-Related Quality of Life in Patients With Inflammatory Bowel Disease.

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Gastrointestinal Symptoms Predictors of Health-Related Quality of Life in Patients With Inflammatory Bowel Disease.

J Pediatr Gastroenterol Nutr. 2016 Dec;63(6):e186-e192

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

Abstract
OBJECTIVES: The aim of the study was to investigate the multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with inflammatory bowel disease from the perspectives of pediatric patients and parents.
METHODS: The Pediatric Quality of Life Inventory Gastrointestinal Symptoms Scales and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 260 families of patients with inflammatory bowel disease. Gastrointestinal Symptoms Scales measuring stomach pain, food and drink limits, gas and bloating, constipation, blood in stool, and diarrhea were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL (Generic Core Scales).
RESULTS: Stomach pain, food and drink limits, gas and bloating, constipation, blood in stool, and diarrhea were significantly associated with decreased HRQOL in bivariate analyses (P < 0.001). In predictive models utilizing hierarchical multiple regression analyses controlling for age, sex, and race/ethnicity, gastrointestinal symptoms accounted for an additional 40% of the variance in patient self-reported HRQOL (P < 0.001) and 37% of the variance in parent proxy-reported HRQOL (P < 0.001), reflecting large effect sizes. Stomach pain, food and drink limits, and constipation were significant individual patient-reported predictors after controlling for the other gastrointestinal symptoms in the predictive models.
CONCLUSIONS: Patient-reported gastrointestinal symptoms differentially predicted HRQOL. Identifying the specific gastrointestinal symptoms from a standardized multidimensional gastrointestinal symptoms profile that are the most important predictors from the patient perspective facilitates a patient-centered approach for interventions designed to ameliorate impaired HRQOL.

PMID: 27749610 [PubMed - indexed for MEDLINE]

Preoperative Evaluation is not Predictive of Transpyloric Feeding Conversion in Gastrostomy Dependent Pediatric Patients.

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Preoperative Evaluation is not Predictive of Transpyloric Feeding Conversion in Gastrostomy Dependent Pediatric Patients.

J Pediatr Gastroenterol Nutr. 2017 Dec 19;:

Authors: McSweeney M, Kerr J, Amirault J, Fishman E, Lurie M, Peinado-Fabregat MI, Mitchell PD, Rosen R

Abstract
OBJECTIVES: Limited literature exists as to whether preoperative gastrostomy (GT)evaluation may predict which patients will go onto require gastrojejunostomy tube (GJ) feeding. The goal of this study was to compare the preoperative evaluations between patients maintained on GT feeds versus patients who required conversion to GJ feeds.
METHODS: We identified patients at Boston Children's Hospital who underwent GT placement and required GJ feeding between 2006-2012. GT patients were matched according to age, neurologic, and cardiac status with GJ converted patients. Preoperative characteristics, rates of total hospitalizations, and respiratory related admissions were reviewed.
RESULTS: 79 GJ patients (median (IQR): age 15 (4.3, 55.7) months; weight 8.8 (4.6, 14.5) kg) were matched with 79 GT patients (median (IQR): age 14.6 (4.7, 55.7) months; weight 8.5 (5, 13.6) kg). Median time from GT to GJ conversion was 8 (IQR 3, 16) months. Both groups had similar rates of successful preoperative nasogastric feeding trials (GT (84.5%) vs GJ (83.1%), p = 1.0), upper GI series (GT (89.1%) vs GJ (93.2%), p = 0.73), abnormal videofluoroscopic swallow studies (GT (53.8%) vs GJ (62.2%), p = 0.4), and completion of gastric emptying studies (GT (10.1%) vs GJ (5.1%), p = 0.22). No differences were seen in preoperative hospitalization rates (p = 0.25), respiratory admissions (p = 0.36), although GJ patients had a mean reduction in the number of hospitalization of -1.5 ± 0.5 days, p < 0.001, after conversion.
CONCLUSIONS: No differences in preoperative patient characteristics or diagnostic evaluations were seen in GT fed versus GJ converted patients. GJ patients did experience an overall decrease in total admissions after GJ conversion.

PMID: 29261527 [PubMed - as supplied by publisher]

MnTE-2-PyP reduces prostate cancer growth and metastasis by suppressing p300 activity and p300/HIF-1/CREB binding to the promoter region of the PAI-1 gene.

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MnTE-2-PyP reduces prostate cancer growth and metastasis by suppressing p300 activity and p300/HIF-1/CREB binding to the promoter region of the PAI-1 gene.

Free Radic Biol Med. 2016 05;94:185-94

Authors: Tong Q, Weaver MR, Kosmacek EA, O'Connor BP, Harmacek L, Venkataraman S, Oberley-Deegan RE

Abstract
To improve radiation therapy-induced quality of life impairments for prostate cancer patients, the development of radio-protectors is needed. Our previous work has demonstrated that MnTE-2-PyP significantly protects urogenital tissues from radiation-induced damage. So, in order for MnTE-2-PyP to be used clinically as a radio-protector, it is fully necessary to explore the effect of MnTE-2-PyP on human prostate cancer progression. MnTE-2-PyP inhibited prostate cancer growth in the presence and absence of radiation and also inhibited prostate cancer migration and invasion. MnTE-2-PyP altered p300 DNA binding, which resulted in the inhibition of HIF-1β and CREB signaling pathways. Accordingly, we also found that MnTE-2-PyP reduced the expression of three genes regulated by HIF-1β and/or CREB: TGF-β2, FGF-1 and PAI-1. Specifically, MnTE-2-PyP decreased p300 complex binding to a specific HRE motif within the PAI-1 gene promoter region, suppressed H3K9 acetylation, and consequently, repressed PAI-1 expression. Mechanistically, less p300 transcriptional complex binding is not due to the reduction of binding between p300 and HIF-1/CREB transcription factors, but through inhibiting the binding of HIF-1/CREB transcription factors to DNA. Our data provide an in depth mechanism by which MnTE-2-PyP reduces prostate cancer growth and metastasis, which validates the clinical use of MnTE-2-PyP as a radio-protector to enhance treatment outcomes in prostate cancer radiotherapy.

PMID: 26944191 [PubMed - indexed for MEDLINE]

Application of Pyridostigmine in Pediatric Gastrointestinal Motility Disorders: A Case Series.

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Application of Pyridostigmine in Pediatric Gastrointestinal Motility Disorders: A Case Series.

Paediatr Drugs. 2017 Dec 14;:

Authors: Manini ML, Camilleri M, Grothe R, Di Lorenzo C

Abstract
BACKGROUND: Gastrointestinal (GI) motility disorders are common in children. Treatment is challenging with limited medical and surgical options. Pyridostigmine, an acetyl cholinesterase inhibitor, increases acetylcholine at the neuromuscular junction promoting intestinal contractions. Little is known about the role and dosing of pyridostigmine in pediatric GI motility disorders.
METHODS: We present a case series of children with GI dysmotility managed with oral pyridostigmine. Patients' diagnoses include chronic intestinal pseudo-obstruction, gastroparesis with delayed small bowel transit, chronic constipation with failure to thrive, and prolonged ileus after pelvic surgery with chronic opioid use.
RESULTS: Pyridostigmine was effective and safe in all cases. Pyridostigmine decreased abdominal distention, increased bowel movement frequency, and improved enteral feeding tolerance. Effective dosing ranged between 0.25-2.0 mg/kg/day. One patient experienced cramping abdominal pain while on pyridostigmine, but pain resolved after medication was discontinued.
CONCLUSION: We found oral pyridostigmine to be helpful in children with different GI motility problems. Pyridostigmine should be considered in such patients when other treatment interventions have not been beneficial.

PMID: 29243034 [PubMed - as supplied by publisher]

Effect of Medications for Gastric Acid-Related Symptoms on Total Motile Sperm Count and Concentration: A Case-Control Study in Men of Subfertile Couples from the Netherlands.

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Effect of Medications for Gastric Acid-Related Symptoms on Total Motile Sperm Count and Concentration: A Case-Control Study in Men of Subfertile Couples from the Netherlands.

Drug Saf. 2017 Mar;40(3):241-248

Authors: Huijgen NA, Goijen HJ, Twigt JM, Mulders AG, Lindemans J, Dohle GR, Laven JS, Steegers-Theunissen RP

Abstract
INTRODUCTION: Gastric acid-related symptoms are highly prevalent in the general population (21-40%), and more than 11% of individuals use medication for the treatment of these symptoms. The uptake of micronutrients is dependent on the gastrointestinal potential of hydrogen (pH).
OBJECTIVE: We hypothesized that medication affecting gastrointestinal pH reduces the availability of B vitamins, thereby deranging one-carbon metabolism and detrimentally affecting spermatogenesis.
METHODS: This explorative nested case-control study in men of subfertile couples investigated associations between medication used for gastric acid-related symptoms and semen parameters. We included 40 men using medication for gastric acid-related symptoms and 843 men not using medication. Semen analyses were performed between 70 days before and 21 days after the visit.
RESULTS: The use of medication was associated with a twofold higher risk of a low total motile sperm count [TMSC <1 × 106, odds ratio (OR) 2.090, p = 0.049] and negatively with sperm concentration (β -0.320, p = 0.028). Red blood cell folate was positively associated with TMSC (β 0.257, p = 0.026), sperm count (β 1.679, p = 0.013) and ejaculate volume (β 0.120, p = 0.023), and total homocysteine (tHcy) was negatively associated with sperm count (β -0.077, p = 0.021).
CONCLUSION: Here we delineate associations between the use of medication for gastric acid-related symptoms and poor semen quality in men of subfertile couples. The use of medication for gastric acid-related symptoms is associated with a twofold higher risk of a low TMSC and a decreased sperm concentration. Although these findings warrant further research on causality, the associations between folate, tHcy and semen quality emphasize the importance of preconception counselling in male subfertility.

PMID: 27995520 [PubMed - indexed for MEDLINE]

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

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

J Cell Physiol. 2017 Dec 11;:

Authors: 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. This article is protected by copyright. All rights reserved.

PMID: 29226325 [PubMed - as supplied by publisher]

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 - in process]

Collagen VI suppresses fibronectin-induced enteric neural crest cell migration by downregulation of focal adhesion proteins.

Collagen VI suppresses fibronectin-induced enteric neural crest cell migration by downregulation of focal adhesion proteins.

Biochem Biophys Res Commun. 2017 Nov 28;:

Authors: Nishida S, Yoshizaki H, Yasui Y, Kuwahara T, Kiyokawa E, Kohno M

Abstract
The enteric nervous system (ENS) is a network of neurons and glia that are derived from enteric neural crest cells (ENCCs) and essential for regulating peristaltic activity of the colon. ENCCs migrate along the gastrointestinal tract to form the ENS, and disruption of ENCC motility leads to ENS disorders, such as Hirschsprung's disease. Previous ENCC-transplant experiments show that ENCCs can invade into isolated mouse intestines by age E13.5, but not after E15.5. We hypothesized that altered age-specific micro-environments in the intestine are responsible for ENCC invasion/migration. Here, we compared gene expression in the intestine between at E11.5 and E15.5 and identified 1355 differentially expressed transcripts. Among these, we found that genes encoding extracellular matrix (ECM) proteins were enriched. Notably, collagen VI (ColVI) family members were upregulated in the E15.5 mouse intestine at the mRNA and protein levels, whereas fibronectin (FN) was downregulated; however, both proteins showed colocalization at E15.5. To understand the mechanisms of ColVI and FN in ENCC migration, we examined neurosphere or individual ENCC-adherence capabilities toward the ECM. ColVI suppressed FN-induced ENCC spreading/migration, whereas ColVI induced morphologically narrow ENCC spreading and weak stress-fiber formation as compared with those with FN. Additionally, in ENCCs cultured on plates containing ColVI, the expression and phosphorylation of p130Cas, a members of focal adhesion complexes, was reduced. These data indicated an inhibitory role of ColVI in ENCC migration and suggested that ColVI suppression in the intestine might represent a novel therapeutic strategy for aganglionic colonic diseases.

PMID: 29196262 [PubMed - as supplied by publisher]

Gastrointestinal disorders in Curry-Jones syndrome: Clinical and molecular insights from an affected newborn.

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Gastrointestinal disorders in Curry-Jones syndrome: Clinical and molecular insights from an affected newborn.

Am J Med Genet A. 2017 Jun;173(6):1586-1592

Authors: Wigby K, Twigg SRF, Broderick R, Davenport KP, Wilkie AOM, Bickler SW, Jones MC

Abstract
Curry-Jones syndrome (CJS) is a pattern of malformation that includes craniosynostosis, pre-axial polysyndactyly, agenesis of the corpus callosum, cutaneous and gastrointestinal abnormalities. A recurrent, mosaic mutation of SMO (c.1234 C>T; p.Leu412Phe) causes CJS. This report describes the gastrointestinal and surgical findings in a baby with CJS who presented with abdominal obstruction and reviews the spectrum of gastrointestinal malformations in this rare disorder. A 41-week, 4,165 g, female presented with craniosynostosis, pre-axial polysyndactyly, and cutaneous findings consistent with a clinical diagnosis of CJS. The infant developed abdominal distension beginning on the second day of life. Surgical exploration revealed an intestinal malrotation for which she underwent a Ladd procedure. Multiple small nodules were found on the surface of the small and large bowel in addition to an apparent intestinal duplication that seemed to originate posterior to the pancreas. Histopathology of serosal nodules revealed bundles of smooth muscle with associated ganglion cells. Molecular analysis demonstrated the SMO c.1234 C>T mutation in varying amounts in affected skin (up to 35%) and intestinal hamartoma (26%). Gastrointestinal features including structural malformations, motility disorders, and upper GI bleeding are major causes of morbidity in CJS. Smooth muscle hamartomas are a recognized feature of children with CJS typically presenting with abdominal obstruction requiring surgical intervention. A somatic mutation in SMO likely accounts for the structural malformations and predisposition to form bowel hamartomas and myofibromas. The mutation burden in the involved tissues likely accounts for the variable manifestations.

PMID: 28386950 [PubMed - indexed for MEDLINE]

Laparoscopic-Assisted Percutaneous Endoscopic Cecostomy (LAPEC) in Children and Young Adults.

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Laparoscopic-Assisted Percutaneous Endoscopic Cecostomy (LAPEC) in Children and Young Adults.

J Gastrointest Surg. 2017 Apr;21(4):676-683

Authors: Koyfman S, Swartz K, Goldstein AM, Staller K

Abstract
OBJECTIVE: We evaluated the safety and efficacy of the laparoscopic-assisted percutaneous endoscopic cecostomy (LAPEC) procedure both in children and young adults, along with review of their pre-operative motility profiles, antegrade continence enema (ACE) regimen, and postoperative complications.
METHODS: This retrospective review investigated 38 patients (32 children and 6 young adults) that underwent the LAPEC procedure. Primary outcomes evaluated were success versus failure of the procedure and post-operative complications. Success was defined as daily stool evacuation with minimal to no fecal incontinence per week.
RESULTS: Mean follow up time was 25.8 ± 22.4 months. Indications for LAPEC included slow transit constipation or colonic neuropathy (n = 22), other types of constipation (n = 5), and a variety of congenital disorders (n = 11). The overall success rate was 95% (36/38 patients) with the two failures in children, both attributed to inability to use the tube due to underlying behavioral disorders or severe anxiety. Five patients above age 18 had leakage compared to 6 in the under age 18 group (83% vs. 19, P = 0.003). There were no other significant complications.
CONCLUSION: LAPEC is a safe and effective means of addressing refractory constipation and fecal incontinence in children and young adults who have failed medical management with minimal post-operative complications.

PMID: 28097469 [PubMed - indexed for MEDLINE]

Use of bedside abdominal ultrasound to confirm intestinal motility in neonates with gastroschisis: A feasibility study.

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Use of bedside abdominal ultrasound to confirm intestinal motility in neonates with gastroschisis: A feasibility study.

J Pediatr Surg. 2017 May;52(5):715-717

Authors: Gurien LA, Wyrick DL, Dassinger MS, Burford JM, Mehl SC, Saylors ME, Smith SD

Abstract
BACKGROUND: Optimal timing to begin feeds in neonates with gastroschisis remains unclear. We examined if bedside abdominal ultrasound for intestinal motility is a feasible tool to detect return of bowel function in neonates with gastroschisis.
METHODS: Neonates born with uncomplicated gastroschisis who underwent closure received daily ultrasound exams. Full motility was defined as peristalsis seen in all quadrants. Average length of time between abdominal wall closure and start of enteral feeds, full ultrasound motility, and clinical characteristics was compared using Student's t-tests.
RESULTS: Seventeen patients were enrolled. No differences were found between motility on ultrasound and bowel movements, gastric residuals, or nonbilious residuals. Mean time to enteral feeds (11.82days) was significantly delayed compared to documentation of full motility on ultrasound (8.94days; p=0.012), consistent bowel movements (8.41days; p=0.006), low gastric residuals (9.47days; p<0.001), and nonbilious residuals (9.18days; p<0.001). In the single subject in which feeds were started before full motility was seen on ultrasound, feeds were subsequently discontinued because of emesis.
CONCLUSION: Bedside abdominal ultrasound provides real-time evidence regarding intestinal motility and is a feasible tool to detect return of bowel function in neonates with gastroschisis. Future studies are needed to determine if abdominal ultrasound can shorten time to start of enteral feeds.
LEVEL OF EVIDENCE: III (diagnosis: nonconsecutive study).

PMID: 28185628 [PubMed - indexed for MEDLINE]

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