Recent PubMed Articles on Gut Motility

Social Stress Affects Colonic Inflammation, the Gut Microbiome, and Short Chain Fatty Acid Levels and Receptors.

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Social Stress Affects Colonic Inflammation, the Gut Microbiome, and Short Chain Fatty Acid Levels and Receptors.

J Pediatr Gastroenterol Nutr. 2018 Dec 11;:

Authors: Maltz RM, Keirsey J, Kim SC, Mackos AR, Gharaibeh RZ, Moore CC, Xu J, Somogyi A, Bailey MT

Abstract
OBJECTIVES: Gastrointestinal disorders, such as inflammatory bowel diseases (IBD) and functional gastrointestinal disorders (FGID), involve disrupted homeostatic interactions between the microbiota and the host. Both disorders are worsened during stress, and in laboratory mice, stress exposure has been shown to change the composition of the gut microbiome. Stress-induced changes to the microbiome exacerbate intestinal inflammation and alter intestinal motility in mice. However, it is not yet known whether microbiota-derived short chain fatty acids (butyrate, propionate, and acetate) and their receptors contribute to this effect.
METHODS: Mice were exposed to a social disruption (SDR) stress, or left undisturbed as a control. After the first stress exposure, mice were orally challenged with Citrobacter rodentium or with vehicle. The levels of SCFAs were measured using gas chromatography-mass spectrometry. SCFA receptors were measured via real time PCR. Microbial community composition was assessed using 16S rRNA gene sequencing.
RESULTS: Stress exposure reduced colonic SCFA levels. However, stress exposure and C. rodentium significantly increased SCFA levels and changed the expression of SCFA receptors. The levels of SCFAs did not correlate with the severity of colonic inflammation, but the colonic expression of the SCFA receptor GPR41 was positively associated with inflammatory cytokines and colonic histopathology scores. The relative abundances of several taxa of colonic bacteria were significantly changed by stress exposure, including SCFA producers.
CONCLUSIONS: Social stress can have a significant effect on infection-induced colonic inflammation, and stress-induced changes in microbial-produced metabolites and their receptors may be involved.

PMID: 30540706 [PubMed - as supplied by publisher]

Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells.

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Colitis promotes neuronal differentiation of Sox2+ and PLP1+ enteric cells.

Sci Rep. 2017 05 31;7(1):2525

Authors: Belkind-Gerson J, Graham HK, Reynolds J, Hotta R, Nagy N, Cheng L, Kamionek M, Shi HN, Aherne CM, Goldstein AM

Abstract
Mechanisms mediating adult enteric neurogenesis are largely unknown. Using inflammation-associated neurogenesis models and a transgenic approach, we aimed to understand the cell-source for new neurons in infectious and inflammatory colitis. Dextran sodium sulfate (DSS) and Citrobacter rodentium colitis (CC) was induced in adult mice and colonic neurons were quantified. Sox2GFP and PLP1GFP mice confirmed the cell-type specificity of these markers. Sox2CreER:YFP and PLP1creER:tdT mice were used to determine the fate of these cells after colitis. Sox2 expression was investigated in colonic neurons of human patients with Clostridium difficile or ulcerative colitis. Both DSS and CC led to increased colonic neurons. Following colitis in adult Sox2CreER:YFP mice, YFP initially expressed predominantly by glia becomes expressed by neurons following colitis, without observable DNA replication. Similarly in PLP1CreER:tdT mice, PLP1 cells that co-express S100b but not RET also give rise to neurons following colitis. In human colitis, Sox2-expressing neurons increase from 1-2% to an average 14% in colitis. The new neurons predominantly express calretinin, thus appear to be excitatory. These results suggest that colitis promotes rapid enteric neurogenesis in adult mice and humans through differentiation of Sox2- and PLP1-expressing cells, which represent enteric glia and/or neural progenitors. Further defining neurogenesis will improve understanding and treatment of injury-associated intestinal motility/sensory disorders.

PMID: 28566702 [PubMed - indexed for MEDLINE]

Same day versus next day antroduodenal manometry results in children with upper gastrointestinal symptoms: A prospective study.

Same day versus next day antroduodenal manometry results in children with upper gastrointestinal symptoms: A prospective study.

Neurogastroenterol Motil. 2018 Dec 11;:e13521

Authors: Arbizu RA, Nurko S, Heinz N, Amicangelo M, Rodriguez L

Abstract
BACKGROUND: We evaluated the changes in antroduodenal manometry (ADM) parameters and interpretation when the test is performed the day of catheter placement and the following day.
METHODS: Catheter was placed endoscopically under anesthesia and recorded on day 1 and repeated on day 2. Study parameters including antrum and small bowel motility index (MI) during fasting, meal, postprandial, erythromycin (EES), and octreotide (OCT) challenge phases, the presence of the phase III of the migrating motor complex (MMC), visual postprandial response, and study interpretation were compared between both days.
KEY RESULTS: Twenty patients were studied. Antrum and small bowel MI during fasting, postprandial, and EES challenge phases were significantly higher on day 2 than on day 1 (P < 0.05). The proportion of patients having a phase III of the MMC was significantly higher on day 2 compared to day 1 (65% vs 15%; P = 0.006). Study interpretation changed from day 1 to day 2. On day 1, 70% of the patients had a normal study and 30% had an abnormal study. On day 2, 67% of the patients with an abnormal study on day 1 changed to normal and 33% remained abnormal. All patients with a normal study on day 1 remained normal on day 2.
CONCLUSIONS AND INFERENCES: ADM parameters are affected the day of catheter placement. The MI and presence of the phase III of the MMC were significantly higher on day 2 compared to day 1. Overall, ADM study interpretation changed from day 1 to day 2 in 20% of the patients.

PMID: 30537362 [PubMed - as supplied by publisher]

Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility.

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Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility.

Am J Hum Genet. 2018 03 01;102(3):364-374

Authors: Esteve C, Francescatto L, Tan PL, Bourchany A, De Leusse C, Marinier E, Blanchard A, Bourgeois P, Brochier-Armanet C, Bruel AL, Delarue A, Duffourd Y, Ecochard-Dugelay E, Hery G, Huet F, Gauchez P, Gonzales E, Guettier-Bouttier C, Komuta M, Lacoste C, Maudinas R, Mazodier K, Rimet Y, Rivière JB, Roquelaure B, Sigaudy S, Stephenne X, Thauvin-Robinet C, Thevenon J, Sarles J, Levy N, Badens C, Goulet O, Hugot JP, Katsanis N, Faivre L, Fabre A

Abstract
Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing, and bone fragility. Whole-exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A) as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss-of-function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.

PMID: 29429573 [PubMed - indexed for MEDLINE]

MicroRNA-204 Inhibits the Growth and Motility of Colorectal Cancer Cells by Downregulation of CXCL8.

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MicroRNA-204 Inhibits the Growth and Motility of Colorectal Cancer Cells by Downregulation of CXCL8.

Oncol Res. 2018 Sep 14;26(8):1295-1305

Authors: Shuai F, Wang B, Dong S

Abstract
Among all of the miRNAs, miR-204 has gained considerable attention in the field of cancer research. This study aimed to reveal the detailed functions and the underlying mechanism of miR-204 in colorectal cancer (CRC) cells. The expressions of miR-204 in CRC tumor tissues and cell lines were monitored. Expressions of miR-204 and CXCL8 in Caco-2 and HT-29 cells were altered by transfection, and then cell viability, apoptosis, migration, invasion, EMT-related protein expression, and PI3K/AKT/mTOR pathway protein expression were assessed. We found that miR-204 was expressed at low levels in CRC tumor tissues and cell lines when compared to their normal controls. miR-204 overexpression reduced the viability, migration, and invasion of Caco-2 and HT-29 cells while significantly inducing apoptosis. miR-204 overexpression upregulated E-cadherin expression and downregulated N-cadherin and vimentin expressions. CXCL8 was a target of miR-204, and miR-204 suppression could not increase cell viability, migration, invasion, and EMT procedure when CXCL8 was silenced. Moreover, miR-204 overexpression decreased the phosphorylated levels of PI3K, AKT, and mTOR. The increased phosphorylations of PI3K, AKT, and mTOR, and the upregulation of CXCL8 induced by miR-204 suppression were all abolished by the addition of LY294002 and AZD8055 (inhibitors of PI3K/AKT and mTOR, respectively). To conclude, we demonstrated a tumor-suppressive miRNA in CRC cell lines, miR-204, which is poorly expressed in CRC tissues and cell lines. miR-204 exerted antigrowth, antimigration, anti-invasion, and anti-EMT activities, which might be via deactivating the PI3K/AKT/mTOR pathway and repressing CXCL8 expression.

PMID: 29402343 [PubMed - indexed for MEDLINE]

Clinical and Cost Effectiveness of Online Cognitive Behavioral Therapy in Children with Functional Abdominal Pain Disorders.

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Clinical and Cost Effectiveness of Online Cognitive Behavioral Therapy in Children with Functional Abdominal Pain Disorders.

Clin Gastroenterol Hepatol. 2018 Nov 28;:

Authors: Lalouni M, Ljótsson B, Bonnert M, Ssegonja R, Benninga M, Bjureberg J, Högström J, Sahlin H, Simrén M, Feldman I, Hedman-Lagerlöf E, Serlachius E, Olén O

Abstract
BACKGROUND & AIMS: Scalable and effective treatments are needed for children with functional abdominal pain disorders (FAPDs). We performed a randomized controlled trial of the efficacy and cost effectiveness of cognitive behavioral therapy delivered online (internet CBT) compared to usual therapy.
METHODS: We studied children (8-12 years old) diagnosed with FAPDs, based on the Rome IV criteria, in Sweden from September 2016 through April 2017. The patients were randomly assigned to groups that received 10 weeks of therapist-guided, internet-delivered cognitive behavioral therapy (internet CBT, n=46) or usual treatment (treatments within the healthcare and school systems, including medications and visits to doctors and other healthcare professionals; n=44). The primary outcome was Global child-rated gastrointestinal symptom severity assessed using the Pediatric Quality of Life Gastrointestinal Symptom scale. All outcomes were collected from September 2016 through January 2018. Secondary outcomes included quality of life, gastrointestinal-specific anxiety, avoidance behaviors, and parental responses to children's symptoms. Societal costs and costs for healthcare consumption were collected during the treatment.
RESULTS: Children who received internet CBT had a significantly larger improvement in gastrointestinal symptom severity with a medium effect size (Cohen's d=0.46; 95% CI, 0.05-0.88; number needed to treat, 3.8) compared with children who received the usual treatment. The children's quality of life, gastrointestinal-specific anxiety, avoidance behaviors, and parental responses to children's symptoms also improved significantly in the internet CBT group compared with the usual treatment group. The effects of internet CBT persisted through 36 weeks of follow up. Children who received internet CBT had significantly less healthcare use than children who received usual treatment, with an average cost difference of US $137 (P=.011). We calculated a cost saving of US $1050 for every child treated with internet CBT compared with usual treatment.
CONCLUSION: In a randomized trial of pediatric patients with FAPDs, we found internet CBT to be clinically and cost effective compared with usual treatment. Internet CBT has the potential to increase the availability of treatment for a number of patients and reduce healthcare costs. ClinicalTrials.gov no.: NCT02873078.

PMID: 30502501 [PubMed - as supplied by publisher]

Retracing our STEPs: Four decades of progress in intestinal lengthening procedures for short bowel syndrome.

Retracing our STEPs: Four decades of progress in intestinal lengthening procedures for short bowel syndrome.

Am J Surg. 2018 Nov 27;:

Authors: Greig CJ, Oh PS, Gross ER, Cowles RA

Abstract
The surgical management of intestinal failure secondary to short bowel syndrome has undergone tremendous evolution in the last several decades. From the landmark description of an intestinal lengthening procedure by Bianchi in 1980 to the multidisciplinary modern care paradigm known as intestinal rehabilitation, innovative new treatments in this field have vastly improved patient outcomes. Initial attempts to treat short bowel syndrome surgically saw the birth of reversed intestinal segments, artificial valves and colonic transposition, all aimed at decreasing transit time and thus increasing absorption. In the long term, a common pitfall of these approaches, and intestinal adaptation itself, is bowel dilation and the associated poor motility, dysfunction and propensity for bacterial overgrowth. The development of techniques to mitigate these unfavorable conditions was a prelude to the birth of modern day operations aimed at increasing bowel length and improving function. This review examines the relevant historical approaches to short bowel syndrome and how they provided the foundation for the development of current intestinal lengthening surgery, followed by an in-depth discussion of surgical techniques and their outcomes.

PMID: 30514435 [PubMed - as supplied by publisher]

Peroral endoscopic myotomy in pediatric jackhammer esophagus.

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Peroral endoscopic myotomy in pediatric jackhammer esophagus.

Rev Esp Enferm Dig. 2018 07;110(7):464-465

Authors: Ramos RI, Guidi M, Kakisu MH, Rocca AM, Sakai P

Abstract
The jackhammer esophagus is a rare hypercontractile disorder and diagnosis is based on high-resolution manometry. Peroral endoscopic myotomy (POEM) of the spastic esophagus segments has been described. We report a pediatric patient with jackhammer esophagus that was treated endoscopically.

PMID: 29667413 [PubMed - indexed for MEDLINE]

Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography.

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Illuminating dynamic neutrophil trans-epithelial migration with micro-optical coherence tomography.

Sci Rep. 2017 04 03;8:45789

Authors: Chu KK, Kusek ME, Liu L, Som A, Yonker LM, Leung H, Cui D, Ryu J, Eaton AD, Tearney GJ, Hurley BP

Abstract
A model of neutrophil migration across epithelia is desirable to interrogate the underlying mechanisms of neutrophilic breach of mucosal barriers. A co-culture system consisting of a polarized mucosal epithelium and human neutrophils can provide a versatile model of trans-epithelial migration in vitro, but observations are typically limited to quantification of migrated neutrophils by myeloperoxidase correlation, a destructive assay that precludes direct longitudinal study. Our laboratory has recently developed a new isotropic 1-μm resolution optical imaging technique termed micro-optical coherence tomography (μOCT) that enables 4D (x,y,z,t) visualization of neutrophils in the co-culture environment. By applying μOCT to the trans-epithelial migration model, we can robustly monitor the spatial distribution as well as the quantity of neutrophils chemotactically crossing the epithelial boundary over time. Here, we demonstrate the imaging and quantitative migration results of our system as applied to neutrophils migrating across intestinal epithelia in response to a chemoattractant. We also demonstrate that perturbation of a key molecular event known to be critical for effective neutrophil trans-epithelial migration (CD18 engagement) substantially impacts this process both qualitatively and quantitatively.

PMID: 28368012 [PubMed - indexed for MEDLINE]

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 - in process]

Ophthalmoplegia in Mitochondrial Disease.

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Ophthalmoplegia in Mitochondrial Disease.

Yonsei Med J. 2018 Dec;59(10):1190-1196

Authors: Lee SJ, Na JH, Han J, Lee YM

Abstract
PURPOSE: To evaluate the classification, diagnosis, and natural course of ophthalmoplegia associated with mitochondrial disease.
MATERIALS AND METHODS: Among 372 patients with mitochondrial disease who visited our hospital between January 2006 and January 2016, 21 patients with ophthalmoplegia were retrospectively identified. Inclusion criteria included onset before 20 years of age, pigmentary retinopathy, and cardiac involvement. The 16 patients who were finally included in the study were divided into three groups according to disease type: Kearns-Sayre syndrome (KSS), KSS-like, and chronic progressive external ophthalmoplegia (CPEO).
RESULTS: The prevalences of clinical findings were as follows: ptosis and retinopathy, both over 80%; myopathy, including extraocular muscles, 75%; lactic acidosis, 71%; and elevated levels of serum creatine kinase, 47%. Half of the patients had normal magnetic resonance imaging findings. A biochemical enzyme assay revealed mitochondrial respiratory chain complex I defect as the most common (50%). The prevalence of abnormal muscle findings in light or electron microscopic examinations was 50% each, while that of large-scale mitochondrial DNA (mtDNA) deletions in a gene study was 25%. We compared the KSS and KSS-like groups with the CPEO patient group, which showed pigmentary retinopathy (p<0.001), cardiac conduction disease (p=0.013), and large-scale mtDNA deletions (p=0.038). KSS and KSS-like groups also had gastrointestinal tract disorders such as abnormal gastrointestinal motility (p=0.013) unlike the CPEO group.
CONCLUSION: Patients with KSS had gastrointestinal symptoms, which may indicate another aspect of systemic involvement. The presence of large-scale mtDNA deletions was an objective diagnostic factor for KSS and a gene study may be helpful for evaluating patients with KSS.

PMID: 30450853 [PubMed - in process]

Home-Based Transabdominal Interferential Electrical Stimulation for Six Months Improves Paediatric Slow Transit Constipation (STC).

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Home-Based Transabdominal Interferential Electrical Stimulation for Six Months Improves Paediatric Slow Transit Constipation (STC).

Neuromodulation. 2018 Oct;21(7):676-681

Authors: Yik YI, Hutson J, Southwell B

Abstract
BACKGROUND: Transcutaneous electrical stimulation (TES) for one to two months has produced some improvement in treatment-resistant slow-transit constipation (STC) in children. Optimal parameters for treatment are not known. It is possible that more improvement would occur with stimulation for longer. This study examined the effectiveness of stimulation for six months.
METHODS: Children with STC confirmed by nuclear transit study (NTS) were enrolled prospectively. All had chronic constipation for greater than two years and had failed medical treatment. TES was performed for one hour/day for six months using the INF 4160 (Fuji Dynamics) portable stimulator and 4 cm × 4 cm electrodes near the belly button and on the back. Families kept bowel diaries and completed PEDSQLCore QOL (4.0) questionnaires before and at end of treatment.
RESULTS: Sixty-two children (34 females; seven years, 2-16 year) with STC were studied. Defecation frequency increased in 57/62 (91%, mean ± SEM pre- 1.49 ± 0.20 vs. post- 3.25 ± 0.25 defecation/week, p < 0.0001) with the number with ≥3BA increasing from 6 to 37 (10-59%). Soiling frequency decreased from 4.8 to 1.1 days/week (p <0.001). Abdominal pain decreased from 1.7 to 0.3 days/week (<0.0001), and spontaneous urge to defecate improved. Quality of life (p < 0.01), mean transit index and gastric emptying on NTS improved (p < 0.005).
CONCLUSION: Treatment-resistant STC responds to TES using interferential current across the abdomen when given daily for many months. Battery operated stimulators allowed stimulation at home for an hour each day. Stimulation for six months produced clinically significant improvement in defecation frequency, soiling, abdominal pain, urge to defecate, and quality of life in half of these chronic patients.

PMID: 29164818 [PubMed - indexed for MEDLINE]

Tyrosine kinase Pyk2 is involved in colonic smooth muscle contraction via the RhoA/ROCK Pathway.

Tyrosine kinase Pyk2 is involved in colonic smooth muscle contraction via the RhoA/ROCK Pathway.

Physiol Res. 2018 Oct 23;

Authors: Tong L, Ao JP, Lu HL, Huang X, Zang JY, Liu SH, Song NN, Huang SQ, Lu C, Chen J, Xu WX

Abstract
The contraction of gastrointestinal (GI) smooth muscles is regulated by both Ca2+-dependent and Ca2+ sensitization mechanisms. Proline-rich tyrosine kinase 2 (Pyk2) is involved in the depolarization-induced contraction of vascular smooth muscle via a Ca2+ sensitization pathway. However, the role of Pyk2 in GI smooth muscle contraction is unclear. The spontaneous contraction of colonic smooth muscle was measured by using isometric force transducers. Protein and phosphorylation levels were determined by using western blotting. Pyk2 protein was expressed in colonic tissue, and spontaneous colonic contractions were inhibited by PF-431396, a Pyk2 inhibitor, in the presence of tetrodotoxin (TTX). In cultured colonic smooth muscle cells (CSMCs), PF-431396 decreased the levels of myosin light chain (MLC20) phosphorylated at Ser19 and ROCK2 protein expression, but myosin light chain kinase (MLCK) expression was not altered. However, Y-27632, a Rho kinase inhibitor, increased phosphorylation of Pyk2 at Tyr402 and concomitantly decreased ROCK2 levels; the expression of MLCK in CSMCs did not change. The expression of P(Tyr402)-Pyk2 and ROCK2 was increased when CSMCs were treated with Ach. Pyk2 is involved in the process of colonic smooth muscle contraction through the RhoA/ROCK pathway. These pathways may provide very important targets for investigating GI motility disorders.

PMID: 30433799 [PubMed - as supplied by publisher]

Azithromycin Induces Migrating Motor Complexes in Pediatric Patients Undergoing Antroduodenal Motility Studies.

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Azithromycin Induces Migrating Motor Complexes in Pediatric Patients Undergoing Antroduodenal Motility Studies.

J Pediatr Pharmacol Ther. 2018 Sep-Oct;23(5):390-394

Authors: Shakir AK, Altaf MA

Abstract
OBJECTIVE: Erythromycin (ERY) is used in the treatment of gastroparesis; however, this medication is associated with serious side effects, such as cardiac arrhythmias and consequent cardiorespiratory arrest. Azithromycin (AZM) has been suggested as an alternative to ERY as a result of its improved safety profile. Intravenous ERY (1 mg/kg) is administered during antroduodenal motility studies to induce migrating motor complexes (MMCs), the presence or absence of which helps diagnose motility disorders like gastroparesis and gastrointestinal dysmotility. However, there are no pediatric studies comparing the effects of AZM and ERY on antroduodenal pressure profiles. The goal of this study is to determine if AZM is comparable in inducing MMCs in pediatric patients undergoing antroduodenal motility studies.
METHODS: We performed a retrospective chart analysis of gastric and small bowel manometric data in 2 adolescent patients, both age 15 years, who were given AZM (1 mg/kg) during antroduodenal motility studies. The pressure profiles obtained during motility studies were compared to those of patients of similar age and symptomology who were given the standard intravenous ERY dose during motility studies. We then compared the total duration of effect, mean amplitude of contractions, number of cycles per minute, and duration of highest antral and duodenal contractions.
RESULTS: Intravenous AZM induces migrating motor contractions in the stomach followed by contractions in the small intestine. The mean amplitude of the stomach contractions was 259 mm Hg in patients who received AZM vs 241 mm Hg in patients who received ERY. The mean amplitude of small intestinal MMCs was 68 mm Hg in patients who received AZI and 72 mm Hg in patients who received ERY. Additionally, the frequency and duration of stomach and small intestinal contractions were also similar in the 2 groups.
CONCLUSIONS: Intravenous AZM has similar prokinetic effects to intravenous ERY. Our study suggests that AZM is a suitable alternative to ERY in inducing MMCs without the concerning side effects related to ERY and may potentially be used in the management of gastroparesis and other small bowel motility disorders. However, larger prospective studies are required to better understand the long-term efficacy of AZM.

PMID: 30429693 [PubMed]

Cow's Milk Protein Allergy in Infancy: A Risk Factor for Functional Gastrointestinal Disorders in Children?

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Cow's Milk Protein Allergy in Infancy: A Risk Factor for Functional Gastrointestinal Disorders in Children?

Nutrients. 2018 Nov 09;10(11):

Authors: Pensabene L, Salvatore S, D'Auria E, Parisi F, Concolino D, Borrelli O, Thapar N, Staiano A, Vandenplas Y, Saps M

Abstract
The role and prevalence of cow's milk protein allergy (CMA) in functional gastrointestinal disorders remains unclear. The aim of this review is to update knowledge on the relationship between CMA and functional abdominal pain disorders (FAPDs) in children. Cochrane Database and Pubmed were searched from inception using general and specific terms for CMA and functional gastrointestinal disorders. CMA is reported as a predisposing or coexisting factor in a wide range of functional gastrointestinal disorders in infants and children. Pathogenesis of both conditions is complex and multiple mechanisms including dysmotility and hypersensitivity might contribute to the clinical manifestations. Data supporting the possible role of food allergies in the pathogenesis of FAPDs are limited. CMA may predispose to early life inflammation and visceral hypersensitivity, which in turn might manifest as FAPDs. The diagnosis of either CMA or FAPDs and distinction between them is challenging because of nonspecific and overlapping symptoms. Lack of accurate allergy tests in non-IgE (immunoglobulin E) mediated cases is also problematic. Oral food challenge, following an elimination diet, should be performed to diagnose a suspected non-IgE CMA allergy in children with FAPDs. In the management of FAPDs, an elimination diet should be considered for a limited period to verify if the symptoms improve or resolve.

PMID: 30423934 [PubMed - in process]

Isolation and characterisation of mouse intestinal mesoangioblasts.

Isolation and characterisation of mouse intestinal mesoangioblasts.

Pediatr Surg Int. 2018 Nov 08;:

Authors: Perin S, McCann CJ, De Coppi P, Thapar N

Abstract
AIMS AND OBJECTIVES: Children suffering from intestinal failure (IF) endure considerable morbidity and overall have poor survival rates, complicated by the shortage of organs available for transplantation. Therefore, new therapeutic approaches are pivotal if outcomes are to be improved. Over the past years, tissue engineering (TE) has emerged as a possible alternative treatment for many congenital and acquired conditions. TE aims at creating bioengineered organs by means of combining scaffolds with appropriate cell types, which in the intestine are organised within a multilayer structure. In order to generate functional intestine, this cellular diversity and organisation will need to be recreated. While the cells for the epithelial, neural and vascular compartments have been well defined, so far, less attention has been put on the muscular compartment. More recently, mesoangioblasts (MABs) have been identified as a novel source for tissue regeneration since they are able to give rise to vascular and other mesodermal derivatives. To date MABs have not been successfully isolated from intestinal tissue. Therefore, our aim was to demonstrate the possibility of isolating MABs from adult mouse small intestine.
MATERIALS AND METHODS: All experiments were carried out using small intestinal tissues from C57BL/6J mice. We applied an established protocol for MAB isolation from the isolated neuromuscular layer of the small intestine. Cultured cells were stained for Ki67 to assess proliferation rates as well as for a panel of pericyte markers to determine their phenotype.
RESULTS: Cells were successfully isolated from gut biopsies. Cultured cells showed good proliferative capacity and positivity for at least three pericytes markers found in vessels of the gut neuromuscular wall: neuron-glial antigen 2, alkaline phosphatase and platelet-derived growth factor β.
CONCLUSION: This proof-of-principle study lays the foundation for further characterization of MABs as a possible cell source for intestinal smooth muscle regeneration and TE.

PMID: 30406837 [PubMed - as supplied by publisher]

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

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

Int J Mol Med. 2018 Oct;42(4):2120-2128

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 - indexed for MEDLINE]

miR-522-3p Promotes Tumorigenesis in Human Colorectal Cancer via Targeting Bloom Syndrome Protein.

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miR-522-3p Promotes Tumorigenesis in Human Colorectal Cancer via Targeting Bloom Syndrome Protein.

Oncol Res. 2018 Aug 23;26(7):1113-1121

Authors: Shuai F, Wang B, Dong S

Abstract
miR-522-3p is known to degrade bloom syndrome protein (BLM) and enhance expression of other proto-oncogenes, leading to tumorigenesis. This study aimed to investigate the molecular mechanisms of miR-522-3p in human colorectal cancer (CRC) cells. Expressions of miR-522-3p in CRC and adjacent tissues, as well as in normal human colon epithelial cell line (FHC) and five CRC cell lines, were detected. Human CRC cell lines, HCT-116 and HT29, were transfected with miR-522-3p mimic, inhibitor, or scrambled controls. Then cell viability, apoptosis, cell cycle progression, and the expressions of c-myc, cyclin E, CDK2, and BLM were assessed. It was found that miR-522-3p was highly expressed in CRC tissues when compared to adjacent nontumor tissues and was highly expressed in CRC cell lines when compared to FHC cells. miR-522-3p overexpression promoted cell viability, reduced apoptotic cell rate, arrested more cells in the S phase, and upregulated c-myc, cyclin E, and CDK2 expression. BLM was a target gene of miR-522-3p, and miR-522-3p suppression did not exert antiproliferative and proapoptotic activities when BLM was silenced. These findings demonstrate that miR-522-3p upregulation negatively regulates the expression of BLM, with upregulation of c-myc, CDK2, and cyclin E, and thereby promoting the proliferation of human CRC cells.

PMID: 29386092 [PubMed - indexed for MEDLINE]

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