621: NOVEL ROLE OF ZONULIN IN THE PATHOPHYSIOLOGY OF GASTRIC MOTILITY: A CLINICAL-TRANSLATIONAL STUDY

AbstractWe examined the relationship between zonulin and gastric motility in critical care patients and a translational mouse model of systemic inflammation. Gastric motility and haptoglobin (HP) 2 isoform quantification, proxy for zonulin, were examined in patients. Inflammation was triggered by lipopolysaccharide (LPS) injection in C57Bl/6 zonulin transgenic mouse (Ztm) and wildtype (WT) mice as controls, and gastro-duodenal transit was examined by fluorescein-isothiocyanate, 6 and 12 h after LPS-injection. Serum cytokines and zonulin protein levels, and zonulin gastric-duodenal mRNA expression were examined. Eight of 20 patients [14 years, IQR (12.25, 18)] developed gastric dysmotility and were HP2 isoform-producing. HP2 correlated with gastric dysmotility (r = − 0.51, CI − 0.81 to 0.003, p = 0.048). LPS injection induced a time-dependent increase in IL-6 and KC-Gro levels in all mice (p < 0.0001). Gastric dysmotility was reduced similarly in Ztm and WT mice in a time-dependent manner. Ztm had 16% faster duodenal motility than WT mice 6H post-LPS, p = 0.01. Zonulin mRNA expression by delta cycle threshold (dCT) was higher in the stomach (9.7, SD 1.4) than the duodenum (13.9, SD 1.4) 6H post-LPS, p = 0.04. Serum zonulin protein levels were higher in LPS-injected mice compared to vehicle-injected animals in a time-dependent manner. Zonulin correlated with gastric dysmotility in patients. A mouse model had time-dependent gastro-duodenal dysmotility after LPS-injection that paralleled zonulin mRNA expression and protein levels.

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NMDA Receptor-Dependent Synaptic Activity in Dorsal Motor Nucleus of Vagus Mediates the Enhancement of Gastric Motility by Stimulating ST36

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/438460 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Xinyan Gao ◽

Yongfa Qiao ◽

Baohui Jia ◽

Xianghong Jing ◽

Bin Cheng ◽

...

Keyword(s):

Synaptic Transmission ◽

Gastric Motility ◽

Low Frequency ◽

Synaptic Activity ◽

Motor Nucleus ◽

Dorsal Motor Nucleus ◽

Vagal Reflex ◽

Precise Molecular Mechanism ◽

Lines Of Evidence

Previous studies have demonstrated the efficacy of electroacupuncture at ST36 for patients with gastrointestinal motility disorders. While several lines of evidence suggest that the effect may involve vagal reflex, the precise molecular mechanism underlying this process still remains unclear. Here we report that the intragastric pressure increase induced by low frequency electric stimulation at ST36 was blocked by AP-5, an antagonist of N-methyl-D-aspartate receptors (NMDARs). Indeed, stimulating ST36 enhanced NMDAR-mediated, but not 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic-acid-(AMPA-) receptor-(AMPAR-) mediated synaptic transmission in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). We also identified that suppression of presynapticμ-opioid receptors may contribute to upregulation of NMDAR-mediated synaptic transmission induced by electroacupuncture at ST36. Furthermore, we determined that the glutamate-receptor-2a-(NR2A-) containing NMDARs are essential for NMDAR-mediated enhancement of gastric motility caused by stimulating ST36. Taken together, our results reveal an important role of NMDA receptors in mediating enhancement of gastric motility induced by stimulating ST36.

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Role of enteric glial cells in gastric motility in diabetic rats at different stages

Journal of Huazhong University of Science and Technology [Medical Sciences] ◽

10.1007/s11596-013-1148-1 ◽

2013 ◽

Vol 33 (4) ◽

pp. 496-500 ◽

Cited By ~ 8

Author(s):

Ran Qi ◽

Wei Yang ◽

Jie Chen

Keyword(s):

Glial Cells ◽

Gastric Motility ◽

Diabetic Rats ◽

Enteric Glial Cells

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Erratum to: Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study

European Heart Journal ◽

10.1093/eurheartj/ehab868 ◽

2021 ◽

Keyword(s):

Right Ventricular ◽

Arrhythmogenic Right Ventricular Cardiomyopathy ◽

Ventricular Cardiomyopathy ◽

Translational Study ◽

Plakophilin 2

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Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.279.5.g925 ◽

2000 ◽

Vol 279 (5) ◽

pp. G925-G930 ◽

Cited By ~ 76

Author(s):

G. Cuche ◽

J. C. Cuber ◽

C. H. Malbert

Keyword(s):

Gastric Motility ◽

Short Chain Fatty Acid ◽

Peptide Yy ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Maximal Amplitude ◽

Inhibiting Factor ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

The aim of this study was to evaluate the nervous and humoral pathways involved in short-chain fatty acid (SCFA)-induced ileal brake in conscious pigs. The role of extrinsic ileal innervation was evaluated after SCFA infusion in innervated and denervated Babkin's ileal loops, and gastric motility was measured with strain gauges. Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) concentrations were evaluated in both situations. The possible involvement of absorbed SCFA was tested by using intravenous infusion of acetate. Ileal SCFA infusion in the intact terminal ileum decreased the amplitude of distal and terminal antral contractions (33 ± 1.2 vs. 49 ± 1.2% of the maximal amplitude recorded before infusion) and increased their frequency (1.5 ± 0.11 vs. 1.3 ± 0.10/min). Similar effects were observed during SCFA infusion in ileal innervated and denervated loops (amplitude, 35 ± 1.0 and 34 ± 0.8 vs. 47 ± 1.3 and 43 ± 1.2%; frequency, 1.4 ± 0.07 and 1.6 ± 0.06 vs. 1.1 ± 0.14 and 1.0 ± 0.12/min). Intravenous acetate did not modify the amplitude and frequency of antral contractions. PYY but not GLP-1 concentrations were increased during SCFA infusion in innervated and denervated loops. In conclusion, ileal SCFA inhibit distal gastric motility by a humoral pathway involving the release of an inhibiting factor, which is likely PYY.

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Bilateral but not unilateral subthalamic stimulation promotes apathy: a translational study in rodents and Parkinson’s disease patients

10.1101/2020.06.11.147116 ◽

2020 ◽

Author(s):

Yvan Vachez ◽

Marie Bahout ◽

Robin Magnard ◽

Pierre-Maxime David ◽

Carole Carcenac ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Acute Effect ◽

Recent Experimental Data ◽

Translational Study ◽

Clinical Center ◽

Subthalamic Stimulation ◽

Operative Assessment ◽

Stn Dbs

ABSTRACTApathy is frequently reported in Parkinson’s disease (PD) patients under subthalamic nucleus deep brain stimulation (STN-DBS). The prevailing clinical view for apathy following STN-DBS is the reduction of dopaminergic medication. However, few clinical reports and recent experimental data suggested the pathogenicity of bilateral STN-DBS on motivation, challenging the leading opinion. Here, we investigate whether bilateralism of STN-DBS influences apathy outcome after STN-DBS, combining pre-clinical and clinical approaches. We assess the motivational effects of chronic unilateral STN-DBS in rats in the exact same conditions having highlighted a loss of motivation under bilateral STN-DBS. Clinical data are obtained by the follow-up of a cohort of parkinsonian patients undergoing unilateral STN-DBS and coming from the clinical center that described apathy related to bilateral STN-DBS itself. Despite an acute effect, which fades rapidly, unilateral STN-DBS did not induce a loss of motivation reminiscent to apathy in rats. In patients, apathy did not increase between the preoperative and the post-operative assessment. Together, those data demonstrate that bilateral but not unilateral STN-DBS can induce a loss of motivation in both rats and patients. This constitutes another evidence of the role of STN-DBS itself for apathy in PD.

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Prognostic role of microRNA polymorphisms in advanced gastric cancer: a translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO)

Annals of Oncology ◽

10.1093/annonc/mdt330 ◽

2013 ◽

Vol 24 (10) ◽

pp. 2581-2588 ◽

Cited By ~ 27

Author(s):

L. Stenholm ◽

J. Stoehlmacher-Williams ◽

S.E. Al-Batran ◽

N. Heussen ◽

S. Akin ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Prognostic Role ◽

Translational Study

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Role of prostaglandins in regulating gastric motility

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.247.2.g117 ◽

1984 ◽

Vol 247 (2) ◽

pp. G117-G126 ◽

Cited By ~ 12

Author(s):

K. M. Sanders

Keyword(s):

Gastric Emptying ◽

Gastric Motility ◽

Motor Performance ◽

Tonic Contraction ◽

Frequency Effect ◽

Dominant Effect ◽

Proximal Stomach ◽

Distal Stomach ◽

Endogenous Prostaglandins

Muscles of the stomach possess the ability to synthesize several prostaglandins. These compounds function as local regulatory agents by influencing the motor performance of the muscle cells. In the distal stomach the dominant effect of endogenous prostaglandins is to decrease the amplitude of contractions and decrease the ability of the muscles to respond to excitatory stimuli. Prostaglandins also have a chronotropic role in the distal stomach, and they are responsible for the frequency effect of gastrin pentapeptide. In the proximal stomach prostaglandins have an opposite role; they promote tonic contraction. Because of the diverse effects of prostaglandins, they probably have complicated effects on gastric motility. In general, emptying of solids should be retarded by endogenous prostaglandins, whereas emptying of fluids may be facilitated by these compounds. Overproduction of prostaglandins may produce abnormal motility patterns and affect gastric emptying. A case of gastric pseudoobstruction apparently involving prostaglandins is discussed.

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