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PloS One 2016Gastric antrum ulcerations are common disorders occurring in humans and animals. Such localization of ulcers disturbs the gastric emptying process, which is precisely...
The Influence of Gastric Antral Ulcerations on the Expression of Galanin and GalR1, GalR2, GalR3 Receptors in the Pylorus with Regard to Gastric Intrinsic Innervation of the Pyloric Sphincter.
Gastric antrum ulcerations are common disorders occurring in humans and animals. Such localization of ulcers disturbs the gastric emptying process, which is precisely controlled by the pylorus. Galanin (Gal) and its receptors are commonly accepted to participate in the regulation of inflammatory processes and neuronal plasticity. Their role in the regulation of gastrointestinal motility is also widely described. However, there is lack of data considering antral ulcerations in relation to changes in the expression of Gal and GalR1, GalR2, GalR3 receptors in the pyloric wall tissue and galaninergic intramural innervation of the pylorus. Two groups of pigs were used in the study: healthy gilts and gilts with experimentally induced antral ulcers. By double immunocytochemistry percentages of myenteric and submucosal neurons expressing Gal-immunoreactivity were determined in the pyloric wall tissue and in the population of gastric descending neurons supplying the pyloric sphincter (labelled by retrograde Fast Blue neuronal tracer). The percentage of Gal-immunoreactive neurons increased only in the myenteric plexus of the pyloric wall (from 16.14±2.06% in control to 25.5±2.07% in experimental animals), while no significant differences in other neuronal populations were observed between animals of both groups. Real-Time PCR revealed the increased expression of mRNA encoding Gal and GalR1 receptor in the pyloric wall tissue of the experimental animals, while the expression(s) of GalR2 and GalR3 were not significantly changed. The results obtained suggest the involvement of Gal, GalR1 and galaninergic pyloric myenteric neurons in the response of pyloric wall structures to antral ulcerations.
Topics: Animals; Galanin; Ganglia; Gastric Mucosa; Gene Expression Regulation; Myenteric Plexus; Pyloric Antrum; Pylorus; RNA, Messenger; Real-Time Polymerase Chain Reaction; Receptors, Galanin; Stomach Ulcer; Sus scrofa
PubMed: 27175780
DOI: 10.1371/journal.pone.0155658 -
World Journal of Gastroenterology Jun 2019Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options... (Review)
Review
Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.
Topics: Gastroparesis; Gastroscopy; Humans; Natural Orifice Endoscopic Surgery; Pyloromyotomy; Pylorus; Treatment Outcome
PubMed: 31210711
DOI: 10.3748/wjg.v25.i21.2581 -
Proceedings of the National Academy of... Nov 2022Neural circuits can produce similar activity patterns from vastly different combinations of channel and synaptic conductances. These conductances are tuned for specific...
Neural circuits can produce similar activity patterns from vastly different combinations of channel and synaptic conductances. These conductances are tuned for specific activity patterns but might also reflect additional constraints, such as metabolic cost or robustness to perturbations. How do such constraints influence the range of permissible conductances? Here we investigate how metabolic cost affects the parameters of neural circuits with similar activity in a model of the pyloric network of the crab . We present a machine learning method that can identify a range of network models that generate activity patterns matching experimental data and find that neural circuits can consume largely different amounts of energy despite similar circuit activity. Furthermore, a reduced but still significant range of circuit parameters gives rise to energy-efficient circuits. We then examine the space of parameters of energy-efficient circuits and identify potential tuning strategies for low metabolic cost. Finally, we investigate the interaction between metabolic cost and temperature robustness. We show that metabolic cost can vary across temperatures but that robustness to temperature changes does not necessarily incur an increased metabolic cost. Our analyses show that despite metabolic efficiency and temperature robustness constraining circuit parameters, neural systems can generate functional, efficient, and robust network activity with widely disparate sets of conductances.
Topics: Pylorus; Temperature
PubMed: 36279461
DOI: 10.1073/pnas.2207632119 -
American Journal of Physiology. Cell... May 2023The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel...
The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel the chyme through the pyloric sphincter at a rate in which the small intestine can process the chyme for optimal nutrient absorption. Mfge8 binding to α8β1 integrins helps regulate gastric emptying by reducing the force of antral smooth muscle contractions. The source of Mfge8 within gastric muscles is unclear. Since Mfge8 is a secreted protein, Mfge8 could be delivered via the circulation, or be locally secreted by cells within the muscle layers. In this study, we identify a source of Mfge8 within human gastric antrum muscles using spatial transcriptomic analysis. We show that Mfge8 is expressed in subpopulations of Mef2c perivascular cells within the submucosa layer of the gastric antrum. Mef2c is expressed in subpopulations of NG2 and PDGFRB pericytes. Mfge8 is expressed in NG2/Mef2c pericytes, but not in NG2/Mef2c, PDGFRB/Mef2c, or PDGFRB/Mef2c pericytes. Mfge8 is absent from CD34 endothelial cells but is expressed in a small population of perivascular ACTA2 cells. We also show that α8 integrin is not expressed by interstitial cells of Cajal (ICC), supporting the findings that Mfge8 attenuates gastric antrum smooth muscle contractions by binding to α8β1 integrins on enteric smooth muscle cells. These findings suggest a novel, supplementary mechanism of regulation of gastric antrum motility by cellular regulators of capillary blood flow, in addition to the regulation of gastric antrum motility by the enteric nervous system and the SMC, ICC, and PDGFRα cell (SIP) syncytium.
Topics: Humans; Pyloric Antrum; Pericytes; Endothelial Cells; Receptor, Platelet-Derived Growth Factor beta; Pylorus; Gastric Emptying; Integrins; Obesity; Antigens, Surface; Milk Proteins
PubMed: 36939201
DOI: 10.1152/ajpcell.00043.2023 -
Developmental Biology Mar 2005The organs of the digestive tract are specified by coordinated signaling between the endoderm and mesoderm during development. These epithelial-mesenchymal interactions...
The organs of the digestive tract are specified by coordinated signaling between the endoderm and mesoderm during development. These epithelial-mesenchymal interactions lead to the organ-specific morphogenesis and differentiation of regions along the gut tube. In this paper, we show that in the chick, the SRY-related transcription factor Sox9 is a marker for the posterior gizzard. Viral misexpression of Sox9 in the gizzard mesoderm is sufficient to specify epithelium characteristic of the pyloric sphincter. Sox9 expression is normally limited to the region of the posterior gizzard under the regulation of BMP signaling from the adjacent midgut. Misexpression of an activated form of BMPR1b in the gizzard upregulates Sox9 expression, while the BMP antagonist noggin down-regulates Sox9 expression in the gizzard mesoderm. Previously, Nkx2.5 was identified as a marker for the mesoderm of the pyloric sphincter. As with Sox9, BMP signaling appears to regulate Nkx2.5 and its ability to determine the pyloric epithelium. Despite these similarities, our evidence suggests that Sox9 and Nkx2.5 are regulated independently by BMP signaling, and act coordinately to specify the pyloric sphincter.
Topics: Animals; Biomarkers; Bone Morphogenetic Proteins; Chick Embryo; Epithelial Cells; Epithelium; Gene Expression Regulation, Developmental; Gizzard, Avian; High Mobility Group Proteins; Homeodomain Proteins; In Situ Hybridization; Pylorus; Retroviridae; SOX9 Transcription Factor; Signal Transduction; Transcription Factors
PubMed: 15733673
DOI: 10.1016/j.ydbio.2004.12.019 -
World Journal of Gastroenterology May 2015To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy (PPPD) and subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). (Meta-Analysis)
Meta-Analysis Review
AIM
To investigate the differences in outcome following pylorus preserving pancreaticoduodenectomy (PPPD) and subtotal stomach-preserving pancreaticoduodenectomy (SSPPD).
METHODS
Major databases including PubMed (Medline), EMBASE and Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched for comparative studies between patients with PPPD and SSPPD published between January 1978 and July 2014. Studies were selected based on specific inclusion and exclusion criteria. The primary outcome was delayed gastric emptying (DGE). Secondary outcomes included operation time, intraoperative blood loss, pancreatic fistula, postoperative hemorrhage, intraabdominal abscess, wound infection, time to starting liquid diet, time to starting solid diet, period of nasogastric intubation, reinsertion of nasogastric tube, mortality and hospital stay. The pooled odds ratios (OR) or weighted mean difference (WMD) with 95% confidence intervals (95%CI) were calculated using either a fixed-effects or random-effects model.
RESULTS
Eight comparative studies recruiting 650 patients were analyzed, which include two RCTs, one non-randomized prospective and 5 retrospective trial designs. Patients undergoing SSPPD experienced significantly lower rates of DGE (OR = 2.75; 95%CI: 1.75-4.30, P < 0.00001) and a shorter period of nasogastric intubation (OR = 2.68; 95%CI: 0.77-4.58, P < 0.00001), with a tendency towards shorter time to liquid (WMD = 2.97, 95%CI: -0.46-7.83; P = 0.09) and solid diets (WMD = 3.69, 95%CI: -0.46-7.83; P = 0.08) as well as shorter inpatient stay (WMD = 3.92, 95%CI: -0.37-8.22; P = 0.07), although these latter three did not reach statistical significance. PPPD, however, was associated with less intraoperative blood loss than SSPPD [WMD = -217.70, 95%CI: -429.77-(-5.63); P = 0.04]. There were no differences in other parameters between the two approaches, including operative time (WMD = -5.30, 95%CI: -43.44-32.84; P = 0.79), pancreatic fistula (OR = 0.91; 95%CI: 0.56-1.49; P = 0.70), postoperative hemorrhage (OR = 0.51; 95%CI: 0.15-1.74; P = 0.29), intraabdominal abscess (OR = 1.05; 95%CI: 0.54-2.05; P = 0.89), wound infection (OR = 0.88; 95%CI: 0.39-1.97; P = 0.75), reinsertion of nasogastric tube (OR = 1.90; 95%CI: 0.91-3.97; P = 0.09) and mortality (OR = 0.31; 95%CI: 0.05-2.01; P = 0.22).
CONCLUSION
SSPPD may improve intraoperative and short-term postoperative outcomes compared to PPPD, especially DGE. However, these findings need to be further ascertained by well-designed randomized controlled trials.
Topics: Ampulla of Vater; Chi-Square Distribution; Common Bile Duct Neoplasms; Gastric Emptying; Gastroparesis; Humans; Length of Stay; Odds Ratio; Organ Sparing Treatments; Pancreaticoduodenectomy; Pylorus; Recovery of Function; Risk Factors; Time Factors; Treatment Outcome
PubMed: 26034372
DOI: 10.3748/wjg.v21.i20.6361 -
Surgical Endoscopy Jan 2022Endoscopic per-oral pyloromyotomy (POP) has emerged as a safe and effective first line option in medically refractory gastroparesis. Determining the appropriate extent...
BACKGROUND
Endoscopic per-oral pyloromyotomy (POP) has emerged as a safe and effective first line option in medically refractory gastroparesis. Determining the appropriate extent of the pyloromyotomy continues to present a challenge as there are no standardized tools for measuring changes in pyloric distensibility during the procedure. The objective of this study was to evaluate the utility of using impedance planimetry with endoscopic functional luminal imaging probe (FLIP) to measure changes in pyloric distensibility after POP, and to compare these changes with improvement in symptoms and objective gastric emptying.
METHODS
Patients with medically refractory gastroparesis underwent POP with FLIP measurements of the pylorus (EndoFLIP®, Medtronic, Fridley MN). FLIP measurements, as well as changes in symptoms measured by the validated gastroparesis cardinal symptom index (GCSI) and scintigraphic gastric emptying studies (GES), were evaluated before and after POP.
RESULTS
A total of 14 patients underwent measurement with FLIP during POP, 12 of whom had pre- and post-POP measurements. Mean pyloric diameter increased by 1.4 mm, from 13.9 mm to 15.3 mm (p = 0.0012). Mean distensibility index increased from 6.2 mm/mmHg to 9.1 mm/mmHg (p = 0.0074). Successful division of the pylorus was achieved in 100% of patients with a mean operative time of 36 min and no perioperative complications. The mean length of stay was 0.7 days (0-3 days). Post-POP mean GCSI score improved from 2.97 to 2.28 at a mean follow-up time of 27 days (p < 0.001). Objective improvement in gastric emptying was observed in 80% of patients with scintigraphic GES, with mean four-hour retention decreasing from 46.3% to 32.4% (p < 0.007).
CONCLUSIONS
FLIP is a safe and feasible tool to provide objective measurements during POP. Larger cohorts with longer follow-up are required to determine if measured improvements in pyloric diameter and distensibility are predictive of sustained improvements in GCSI and GES.
Topics: Gastric Emptying; Gastroparesis; Humans; Pyloromyotomy; Pylorus; Treatment Outcome
PubMed: 33427911
DOI: 10.1007/s00464-020-08237-5 -
Gut Apr 1992The relation between pyloric motor activity, opening, and closure was examined in eight healthy men. Manometry was performed with an assembly combining 13 side holes and...
The relation between pyloric motor activity, opening, and closure was examined in eight healthy men. Manometry was performed with an assembly combining 13 side holes and a sleeve sensor positioned astride the pylorus. Simultaneous with manometry, pyloric opening and closure and antroduodenal contractions were observed fluoroscopically with the antrum filled with barium. During intraduodenal normal saline infusion, coordinated antral pressure waves swept over the pylorus and ejected barium into the duodenum. No localised pyloric motor pattern was observed under these conditions. In contrast, the intraduodenal triglyceride infusion was associated with the absence of antral pressure waves and virtual absence of antral wall movement. At the pylorus, there was a zone of luminal occlusion less than 1 cm long that persisted for the period of observation. This zone of luminal occlusion corresponded precisely with manometric recordings of a narrow zone of pyloric phasic and tonic activity. During the duodenal triglyceride infusion, the pylorus was closed for 98.5% of the measurement period when basal pyloric pressure was 4 mm Hg or more, and during this motor pattern, barium did not traverse the pylorus. Localised pyloric contractions cause sustained pyloric closure, whether these contractions are phasic or tonic. These contractions occur independently of antral or duodenal contractions and may interrupt gastric emptying.
Topics: Adult; Duodenum; Fluoroscopy; Gastric Emptying; Humans; Male; Manometry; Pyloric Antrum; Pylorus; Sodium Chloride; Triglycerides
PubMed: 1582588
DOI: 10.1136/gut.33.4.466 -
Annals of the Royal College of Surgeons... Mar 1979Before the First World War the treatment of gastroduodenal haemorrhage was predominantly medical, though the results, especially with recurrent haemorrhage, were far...
Before the First World War the treatment of gastroduodenal haemorrhage was predominantly medical, though the results, especially with recurrent haemorrhage, were far less satisfactory than was claimed by some physicians. It was not until Finsterer, in 1939, demonstrated the virtues of early operation that surgery began to take its place in the treatment of this condition, mainly by gastric resection. Results remained poor, however, until 1958 with the introduction of conservative treatment by vagotomy, pyloroplasty, and under-running of the bleeding point. Personal experience, both with partial gastrectomy in the 1950s and 1960s and with mainly conservative treatment between 1967 and 1970, is described and the results presented.
Topics: Adult; Duodenal Ulcer; England; Female; Gastrectomy; History, 20th Century; Humans; Male; Methods; Peptic Ulcer Hemorrhage; Pylorus; Stomach Ulcer; Vagotomy
PubMed: 373573
DOI: No ID Found -
Gastrointestinal Endoscopy Sep 2021The role of decreased pyloric distensibility in gastroparesis as measured by the endolumenal functional luminal imaging probe (EndoFLIP) has been receiving increasing...
BACKGROUND AND AIMS
The role of decreased pyloric distensibility in gastroparesis as measured by the endolumenal functional luminal imaging probe (EndoFLIP) has been receiving increasing attention. In this study, we present clinical outcomes to pyloric dilation with the esophageal FLIP (EsoFLIP) in regard to gastric emptying, symptom evolution, and FLIP metrics.
METHODS
Patients evaluated for gastroparesis (gastric emptying studies of t ≥180 minutes during C-octanoic acid breath test and/or gastric remnants during gastroscopy after a sufficient fasting period) were scheduled for EsoFLIP controlled pyloric dilation. Pre- and postprocedural gastric emptying studies, questionnaires (Patient Assessment of Upper GI Symptoms Severity Index [PAGI-SYM; including the Gastroparesis Cardinal Symptom Index] and Patient Assessment of Quality of Life Index [PAGI-QOL]), and FLIP metrics were documented. Dilation was conducted according to a self-developed algorithm.
RESULTS
Forty-six patients were analyzed (72% women; median age, 39 years [range, 18-88]). Etiologies of gastroparesis were diabetic in 10 patients (22%), idiopathic in 33 (72%), and postoperative in 3 (6%). Postprocedural gastric emptying time decreased from a median of 211 minutes to 179 minutes (P = .001). In accordance, pyloric distensibility, PAGI-SYM, PAGI-QOL, and Gastroparesis Cardinal Symptom Index values improved significantly. After a median follow-up of 3.9 months, 57% of all treated patients with returned questionnaires reported improved symptoms.
CONCLUSIONS
Pyloric EsoFLIP controlled dilation shows value in the treatment of gastroparesis, both subjectively and objectively. Long-term follow-up to assess efficacy and comparative trials are warranted.
Topics: Adult; Dilatation; Female; Gastric Emptying; Gastroparesis; Humans; Male; Pylorus; Quality of Life
PubMed: 33771556
DOI: 10.1016/j.gie.2021.03.022