Analysis on the healing of gastrointestinal ulceration by using Hemospray.

Healing of gastrointestinal ulcers after Hemospray application was reported in literature. The pathophysiological mechanism of action of hemostatic powders is not elucidated so far. A prospective animal model was performed to evaluate the effect of Hemospray application on the healing process of artificially induced ulcers of the upper and lower gastrointestinal tract. In 10 pigs, 20 ulcers were created in each the upper and the lower gastrointestinal tract by endoscopic mucosal resection. 50% of the pigs were immediately treated with Hemospray application, the others were not treated. Ulcer size was measured endoscopically on day 0, 2, and 7. On day 7 the ulcers were histopathological evaluated for capillary ingrowth and the thickness of the collagen layer. After 7 days the sizes of the ulcers decreased significantly (stomach: - 22.8% with Hemospray application, - 19% without Hemospray application; rectum: - 50.8% with Hemospray application, - 49.5% without Hemospray application; p = 0.005-0.037), but without significant difference between both groups. This study shows no significant effect of the hemostatic powder Hemospray on ulcer healing in the upper and lower gastrointestinal tract compared with untreated controls, neither harmful nor beneficial. However, some trends merit further trials in patients and may indicate a possible mechanism of accelerated mucosal healing.

Interleukin- 17agene Polymorphism, Serum Level and Its Tissue Expression in Iraqi Patients Gastric Lesions.

BACKGROUND: T-helper 17 plays a novel role in inflammation in gastritis by producing IL-17A, IL-17A gene polymorphisms that might be responsible for disease susceptibility and development of different gastric lesions. OBJECTIVE: The aims of study was to determine the association of IL-17A (G197A) genotype and allele frequency with disease phenotype and risk with different gastric lesions. METHODS: Case controlled study involved 30 gastroduodenal ulcer, 30 chronic gastritis and 30 subjects as a control group with negative endoscopic findings. After genomic DNA extraction, IL-17A (G197A)ARMS-PCR genotyping were done for all cases. Serum IL-17A was measured using ELISA method and tissue expression was visualized using immunohistochemistry staining method. RESULTS: The results showed that allele A was significantly frequent in gastroduodenal ulcer more than that in healthy control odd ratio= 4 (1.42-10.46), and none significantly with chronic gastritis p=0.071. Serum IL-17A was significantly higher in gastroduodenal ulcer (116.45±48.09 pg/ml), chronic gastritis (78.02±30.17pg/ml) and healthy control 19.36±9.28 pg/ml).However, the serum IL-17A level is not related to the allele pattern of each group. The tissue expression was expressed as dense granular cytoplasmic and membranous of inflammatory cells. Interestingly, the percentage of IL-17A protein expression was significantly higher in gastroduodenal ulcer (38.2±16.55%), chronic gastritis (30.89±14.02%) and normal mucosa (2.8±3.02%). Furthermore, patients with strong intensity of IL-17A stained mucosa were frequently carrier for mutant allele (68%). CONCLUSION: IL-17A might predispose for aggressive inflammation of advanced lesions in stomach like ulcer.

Activation of transient receptor potential vanilloid channel 4 contributes to the development of ethanol-induced gastric injury in mice.

The transient receptor potential vanilloid channel 4 (TRPV4) is associated with the development of several pathologies, particularly gastric disorders. However, there are no studies associating this receptor with the pathophysiology of gastric erosions. The aim of this study was to investigate the role of TRPV4 in the development of ethanol-induced gastric damage in vivo. Gastric lesions were induced by ethanol in Swiss mice pretreated with TRPV4 antagonists, GSK2193874 (0.1; 0.3 and 0.9 mg/kg) or Ruthenium red (0.03; 0.1 or 0.3 mg/kg) or its agonist, GSK1016790A (0.9 mg/kg). Gastric mucosal samples were taken for histopathology, immunohistochemistry, atomic force microscopy and evaluation of antioxidant parameters. The gastric mucus content and TRPV4 mRNA expression were analyzed. Ethanol exposure induced upregulation of gastric mRNA and protein expression of TRPV4. TRPV4 blockade promoted gastroprotection against ethanol-induced injury on macro- and microscopic levels, leading to reduced hemorrhage, cell loss and edema and enhanced gastric mucosal integrity. Moreover, an increase in superoxide dismutase (SOD) and glutathione (GSH) activity was observed, followed by a decrease in malondialdehyde (MDA) levels. TRPV4 blockade during alcohol challenge reestablished gastric mucus content. The combination of TRPV4 agonist and ethanol revealed macroscopic exacerbation of gastric damage area. Our results confirmed the association of TRPV4 with the development of gastric injury, showing the importance of this receptor for further investigations in the field of gastrointestinal pathophysiology and pharmacology.

The pathophysiology of acute gastric ulcer development in normotensive and hypertensive rats: A comparative study.

Although gastric ulcers and hypertension are diseases that affect a large part of the population, the association of these comorbidities is still poorly studied. Therefore, the present study investigated the response of normotensive (NTR) and spontaneously hypertensive (SHR) rats to gastric ulcers induced by indomethacin or ethanol. For that, adult male and female NTR and SHR received indomethacin (100 mg/kg, p.o) or ethanol P.A (5 ml/kg, p.o) to induce gastric ulcer, after the pre-treatment with prostaglandin E2 (PGE2) and carbenoxolone (CBX), respectively. The results revealed that, when compared to NTR, the SHR, both male and female, showed lower lesion area indexes when exposed to indomethacin. On the other hand, ethanol caused an area of lesion approximately 60% larger in the male and female SHR in comparison with the NTR. Significantly, the pre-treatment with PGE2 or CBX prevented the gastric ulcer damage promoted by indomethacin or ethanol, respectively. The histological analyses of the gastric mucosa from ethanol-induced ulcer revealed severe disruption of gastric architecture and bleeding points, that have been exacerbated in the SHR group. The gastric tissue from the SHR group also showed high levels of nitrite, a marker of nitric oxide production, which was accompanied by an increase in lipid hydroperoxide levels, an important biomarker of oxidative damage, in comparison with NTR. Taking together, the results of the present study showed important differences in the development of gastric ulcer between NTR and SHR. Further studies are needed for an in-depth analysis of the pathophysiological mechanisms involved in these responses.

Immunohistochemical Studies of Age-Related Changes in Cell Proliferation and Angiogenesis during the Healing of Acetic Acid-Induced Gastric Ulcers in Rats.

Cell proliferation and angiogenesis are of utmost importance for healing to take place. The KI67 and EGFR proteins are markers of cell proliferation, while CD31 and factor VIII are markers of angiogenesis. To elucidate the mechanism responsible for delayed healing of the gastric injury in old age, we analyzed the expression of these markers in rats of different months during the healing of an acetic acid-induced gastric ulcer. Male Wistar rats (aged 3, 6, 12, and 18 months) divided into four groups, according to their ages, formed the experimental animals. Stomach tissue samples were collected on days 3, 7, 14, and 21 after induction for assessment of ulcer healing. The area of gastric mucosa healed was inversely proportional to age. The expression of markers of proliferation (KI67 and EGFR) and angiogenesis (factor VIII and CD31) decreased significantly (p < 0.05) in older rats when compared with younger ones (3 months > six months > 12 months > 18 months) on days 7, 14, and 21 after induction of gastric ulcer. This study revealed that the slower gastric ulcer healing rate in older rats might be due to reduced epithelial cell proliferation and angiogenic activities.

Nervous mechanisms of restraint water-immersion stress-induced gastric mucosal lesion.

Stress-induced gastric mucosal lesion (SGML) is one of the most common visceral complications after trauma. Exploring the nervous mechanisms of SGML has become a research hotspot. Restraint water-immersion stress (RWIS) can induce GML and has been widely used to elucidate the nervous mechanisms of SGML. It is believed that RWIS-induced GML is mainly caused by the enhanced activity of vagal parasympathetic nerves. Many central nuclei, such as the dorsal motor nucleus of the vagus, nucleus of the solitary tract, supraoptic nucleus and paraventricular nucleus of the hypothalamus, mediodorsal nucleus of the thalamus, central nucleus of the amygdala and medial prefrontal cortex, are involved in the formation of SGML in varying degrees. Neurotransmitters/neuromodulators, such as nitric oxide, hydrogen sulfide, vasoactive intestinal peptide, calcitonin gene-related peptide, substance P, enkephalin, 5-hydroxytryptamine, acetylcholine, catecholamine, glutamate, γ-aminobutyric acid, oxytocin and arginine vasopressin, can participate in the regulation of stress. However, inconsistent and even contradictory results have been obtained regarding the actual roles of each nucleus in the nervous mechanism of RWIS-induced GML, such as the involvement of different nuclei with the time of RWIS, the different levels of involvement of the sub-regions of the same nucleus, and the diverse signalling molecules, remain to be further elucidated.

Effect and mechanism of ethanol extracts of muxiang (Radix Aucklandiae) on gastric ulcers in rats.

OBJECTIVE: To investigate the effect of ethanol extracts of Muxiang (Radix Aucklandiae) (RA) on gastric ulcers in rats and explore the potential mechanisms. METHODS: A model was established by ethanol (0.75 mL/kg). According to body weight, rats were pretreated with RA extracts (2.5 or 5 g/kg). The rats were administered 95% ethanol orally after 1 h. The effects of ethanol were evaluated by measuring the gastric secretion volume, pH, pepsin activity, and ulcer area. Histological analysis and immunohistochemistry were also conducted. Furthermore, the effect of the ethanol extract of RA on transiting activity of the gastrointestinal tract was observed in mice. RESULTS: Intragastric administration of RA extracts protected the gastric mucosa from ethanol-induced gastric ulcers, while reducing submucosal edema and preventing hemorrhagic damage. Moreover, the extracts increased the production of gastric mucus, upregulated Bcl-2, and downregulated Bax expression. Importantly, pretreated rats exhibited no significant change in the gastric secretion volume, gastric juice acidity, or pepsin. Furthermore, pretreatment prominently (P < 0.05) enhanced propulsive movement of the gastrointestinal tract in normal mice and mice with gastrointestinal motility disorders. CONCLUSION: Ethanol extracts of RA ameliorated gastric lesions in the gastric ulcer rat model. The mechanisms of action were related to improvement of gastrointestinal dynamics, maintenance of mucus integrity, and inhibition of apoptosis by downregulating proapoptotic Bax protein and upregulating anti-apoptotic Bcl-2 protein.

Proton Pump Inhibitors Prevent Gastric Antral Ulcers Induced by NSAIDs via Activation of Capsaicin-Sensitive Afferent Nerves in Mice.

BACKGROUND/AIMS: We examined the effects of proton pump inhibitors (PPIs) on gastric antral ulcers induced by non-steroidal anti-inflammatory drugs in re-fed mice and the role of capsaicin-sensitive afferent nerves (CSANs) in the protective effects of PPIs on the antral mucosa. METHODS: Male mice were administered indomethacin after 2 h of re-feeding of diet after a 24-h fast, and gastric lesions were examined 24 h after indomethacin dosing. The effects of PPIs (lansoprazole and omeprazole), histamine H2-receptor antagonists (H2-RAs, famotidine, ranitidine), capsaicin and misoprostol on the formation of antral ulcers induced by indomethacin were examined. Functional ablation of CSANs was caused by pretreatment of mice with a high dose of capsaicin. RESULTS: Indomethacin produced lesions selectively in the gastric antrum in re-fed conditions. Formation of antral ulcers was not affected by H2-RAs, but inhibited by PPIs, capsaicin and misoprostol. The anti-ulcer effect of lansoprazole was 30 times stronger than that of omeprazole. Antral ulcers induced by indomethacin were markedly aggravated in mice with ablated CSANs. The effects of PPIs and capsaicin on ulcer formation were inhibited by ablation of CSANs, pretreatment with a capsaicin receptor antagonist (capsazepine/ruthenium red) and an inhibitor of nitric oxide synthesis (L-NAME). However, the inhibitory effect of misoprostol was not prevented by the ablation of CSANs or drugs. CONCLUSIONS: The results suggested that CSANs play an important role in protection of the antral mucosa and that both lansoprazole and omeprazole are capable of preventing NSAID-induced antral ulcers by activating CSANs.

Effects of transportation on gastric pH and gastric ulceration in mares.

BACKGROUND: Transportation has been suggested as a risk factor for gastric ulceration in horses, but limited evidence supports this assumption. ANIMALS: Twenty-six Standardbred, Thoroughbred, and Warmblood mares from a university teaching herd. METHODS: Twelve mares were confined for 12 hours, overnight, in reproductive stocks with indwelling nasogastric tubes (NGTs) to assess pH of gastric fluid (GF). Gastric ulceration was assessed endoscopically before and after confinement. Subsequently, 26 horses were transported for 12 hours, overnight, in 2 consignments. During transportation, GF was aspirated from indwelling NGT placed in the same 12 mares used in the confinement study, and gastric ulceration was assessed endoscopically before and after transportation in all horses. RESULTS: The median pH of GF in confined horses was 1.70-2.49 at each sampling point, and there was no apparent effect on gastric squamous ulcer scores. The median pH of GF from the same 12 horses at corresponding sampling times during transportation was 6.82-7.22. Transportation was associated with increased gastric squamous ulcer scores, particularly in horses fasted for gastroscopy and NGT placement immediately before departure. Gastric emptying appeared delayed after transportation in horses fed before departure. CONCLUSIONS AND CLINICAL IMPORTANCE: Transportation is associated with increased gastric squamous ulceration and with increased pH of GF. These findings may be a consequence of impaired gastric emptying and reflux of alkaline small intestinal content, with factors such as duodenal bile salts and short-chain fatty acids mediating mucosal injury.

Total triterpenoids from the fruits of Chaenomeles speciosa exerted gastroprotective activities on indomethacin-induced gastric damage via modulating microRNA-423-5p-mediated TFF/NAG-1 and apoptotic pathways.

Our previous studies have demonstrated that the total triterpenes from the fruits of Chaenomeles speciosa (CSTT) exhibit effective therapeutic effects on gastric ulcer patients and animals. The present aim is to further investigate the mechanisms involved. The results indicated that CSTT could ameliorate IND-induced gastric injury, which was related to promoting IND-damaged GES-1 cell proliferation and migration, improving the IND-damaged rat GBF, ulcer area, inhibition rate and pathologic changes of gastric mucous tissue, increasing the amount of adhered gastric mucus, attenuating the volume and total acidity of the gastric effluents, and augmenting the gastric pH; further studies showed that CSTT obviously downregulated miR-423-5p mRNA, NAG-1 mRNA and protein expression, Bax, Bad, cytosol cytochrome C, Apaf-1, cleaved-caspase-3, and cleaved-caspase-9 protein expression and cytosol cytochrome C concentration, and upregulated TFF1, TFF2 and TFF3 mRNA and protein expression, Bcl-2, Bcl-xl, pro-caspase-3, and pro-caspase-9 protein expression, mitochondrial viability, mitochondrial cytochrome C concentration and Bcl-2/Bax, Bcl-xl/Bad ratios. These findings demonstrated that CSTT protected against IND-induced gastric damage by depressing miR-423-5p expression and modulating the TFF/NAG-1 pathway, which in turn restrained mitochondrion-mediated apoptosis.

Medial prefrontal cortex exacerbates gastric dysfunction of rats upon restraint water­immersion stress.

Restraint water­immersion stress (RWIS) can induce a gastric mucosal lesions within a few hours. The medial prefrontal cortex (mPFC) is involved in the RWIS process. The present study investigated the modulatory effects and molecular mechanisms of the mPFC on gastric function under an RWIS state. Male Wistar rats were divided into four groups; namely, the control, RWIS 4 h (RWIS for 4 h only), sham­operated and bilateral­lesioned (bilateral­lesioned mPFC) groups. The gastric erosion index (EI) and gastric motility (GM) were determined, and the proteomic profiles of the mPFC were assessed by isobaric tags for relative and absolute quantitation (iTRAQ) coupled with two­dimensional liquid chromatography and tandem mass spectrometry. Additionally, iTRAQ results were verified by western blot analysis. Compared with the RWIS 4 h group and the sham­control group, the bilateral­lesioned group exhibited a significantly lower EI (P<0.01). In the bilateral­lesioned group, RWIS led to a significant decrease in EI and GM. When comparing the control and RWIS 4 h groups, 129 dysregulated proteins were identified, of which 88 were upregulated and 41 were downregulated. Gene Ontology functional analysis demonstrated that 29 dysregulated proteins, including postsynaptic density protein 95, were directly associated with axon morphology, axon growth and synaptic plasticity. Ingenuity pathway analysis revealed that the dysregulated proteins were mainly involved in neurological disease signaling pathways, including the NF­κB and ERK signaling pathways. These data indicated that the presence of the mPFC exacerbates gastric mucosal injury in awake rats during RWIS. Although the quantitative proteomic analysis elucidated the nervous system molecular targets associated with the production of gastric mucosal lesions, such as the role of PSD95. The underlying molecular mechanisms of synaptic plasticity need to be further elucidated.

A Differential Approach to Form and Site of Peptic Ulcer.

The structural organization of intestinal blood flow is such as to allow for intramural collateral flow. Redistribution phenomena due to different local metabolic demands may lead to an impaired perfusion of parts of the intestinal wall which will display a characteristic pattern. Based on Ohm's and Kirchhoff's laws, a differential analysis of the gastric vascular bed bridges the gap between basic physiological concepts and traditional anatomical, pathological and clinical knowledge. An ulcer of the intestinal wall becomes understandable as a non-occlusive infarct based on a supply/demand conflict in an anisotropic structure as it can be found in the upper and lower gastrointestinal tract of man.

(-)-Myrtenol accelerates healing of acetic acid-induced gastric ulcers in rats and in human gastric adenocarcinoma cells.

The gastroprotective property of (-)-myrtenol, a monoterpenoid, has been demonstrated previously against acute gastric ulceration induced by ethanol. However, the healing property of (-)-myrtenol in a chronic gastric ulcer model remains to be verified. This study evaluated its healing efficacy and the mechanism involved using the rat model of chronic gastric ulcer induced by serosal injection of 80% acetic acid in vivo, and human gastric adenocarcinoma cells (AGS) in vitro. The results showed that compared to vehicle-treated ulcer controls, oral administration of (-)-myrtenol (50 and 100 mg/kg/day) for 7 days promoted ulcer healing, as indicated by significant decreases in ulcer area and volume. The macroscopic and microscopic findings confirmed the healing potential of (-)-myrtenol. The ulcer healing activity was also associated with significant increases in gastric mucin content, collagen deposition, number of cells with positive marking for proliferating cell nuclear antigen (PCNA), and by changes in the expression of the inflammatory parameters tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and cyclooxygenase (COX)-2, as well as a decrease of metalloproteinases (MMP-9 and MMP-2) activity. Furthermore, in vitro assays using the AGS cultures revealed that (-)-myrtenol favors wound healing activity via stimulation of cell proliferation and migration without altering the cell viability. Taken together, these findings indicate that (-)-myrtenol has gastro-cytoprotective and ulcer healing properties that can be further explored to develop a new therapeutic agent from a natural source for the treatment of gastric ulcer.

Chronic intermittent stress exposure and access to grass silage interact differently in their effect on behaviour, gastric health and stress physiology of entire or castrated male growing-finishing pigs.

Entire male pigs display more aggressive and sexual behaviour. This might cause a condition of chronic stress and impair their welfare. In order to assess chronic stress in entire and castrated male pigs, as well as effects of providing grass silage as occupational and feed material on behaviour and health, we carried out a 2 × 2 × 2-factorial experiment with 147 growing-finishing pigs. Factors investigated were castration (entire/castrated), chronic intermittent social stress exposure (yes/no) and access to grass silage (yes/no), as well as their interactions. The stress exposure treatment consisted of repeated short-term confrontations and separations. We recorded different behavioural variables, circadian rhythm of salivary cortisol, response to an ACTH (adrenocorticotropic hormone) challenge test, pathological changes in the gastric mucosa and morphology of the intestinal epithelium. Stress exposure caused a decrease in posture changes and head knocks/bites in the home pen. Reference indicators affected by stress exposure did not differ between entire and castrated male pigs, indicating that there is no permanently increased baseline level of stress in entire male pigs. However, entire males responded more pronouncedly to the stress exposure compared to castrated males in terms of posture changes and play behaviour. Pigs provided with grass silage showed more play behaviour and less manipulative behaviours than pigs not receiving grass silage. Stress treated pigs had more hyperkeratosis in the gastric mucosa and gastric ulcers, while offering grass silage reduced such changes. In conclusion, our results indicate that the increased behavioural stress response of entire male pigs might require some adaptations in housing and management of entire male pigs. Gastric ulceration scoring turned out to be a potential post mortem indicator for chronic stress. Finally, providing roughages like grass silage could be a means to positively affect behaviour and gastric health in pigs.

Galaninergic intramural nerve and tissue reaction to antral ulcerations.

BACKGROUND: Well-developed galaninergic gastric intramural nerve system is known to regulate multiple stomach functions in physiological and pathological conditions. Stomach ulcer, a disorder commonly occurring in humans and animals, is accompanied by inflammatory reaction. Inflammation can cause intramural neurons to change their neurochemical profile. Galanin and its receptors are involved in inflammation of many organs, however, their direct participation in stomach reaction to ulcer is not known. Therefore, the aim of the study was to investigate adaptive changes in the chemical coding of galaninergic intramural neurons and mRNA expression encoding Gal, GalR1, GalR2, GalR3 receptors in the region of the porcine stomach directly adjacent to the ulcer location. METHODS: The experiment was performed on 24 pigs, divided into control and experimental groups. In 12 experimental animals, stomach antrum ulcers were experimentally induced by submucosal injection of acetic acid solution. Stomach wall directly adjacent to the ulcer was examined by: (1) double immunohistochemistry-to verify the changes in the number of galaninergic neurons (submucosal, myenteric) and fibers; (2) real-time PCR to verify changes in mRNA expression encoding galanin, GalR1, GalR2, GalR3 receptors. KEY RESULTS: In the experimental animals, the number of Gal-immunoreactive submucosal perikarya was increased, while the number of galaninergic myenteric neurons and fibers (in all the stomach wall layers) remained unchanged. The expression of mRNA encoding all galanin receptors was increased. CONCLUSIONS & INTERFERENCES: The results obtained unveiled the participation of galanin and galanin receptors in the stomach tissue response to antral ulcerations.

Accelerated gastric ulcer healing in thyroxine-treated rats: roles of gastric acid, mucus, and inflammatory response.

The roles of gastric acid, mucus, and inflammation on the pro-ulcer-healing effect of thyroid hormone were investigated. Male Wistar rats were randomly divided into four groups: control, thyroidectomised, thyroidectomised with thyroxine treatment (100 µg·kg-1·day-1), and sham-operated animals treated with thyroxine. Thirty-five days after thyroidectomy, sham surgery, or thyroxine treatment, an ulcer was experimentally induced. Healing was assessed 3, 7, and 10 days post-ulceration by measurement of the ulcer area, gastric mucus and acid secretion, and neutrophil lymphocyte ratio (NLR) as an index of inflammation. By day 10, the ulcer area had decreased in all groups. Recovery was significantly greater (P < 0.05) in thyroxine-treated rats (78.5% ± 1.6% reduction in ulcer area) than in controls (72.3% ± 1.2% reduction) or thyroidectomised rats (63.3% ± 1.9% reduction). Thyroxine-treated animals also had the highest reduction in NLR (65.0% ± 2.5%). Mucus secretion was significantly lower (P < 0.05) in thyroidectomised rats by days 3 and 7. Furthermore, by day 10, the concentration of basal acid decreased by 77.4% ± 2.6% in thyroxine-treated, 65.0% ± 0.0% in control, and 51.5% ± 3.3% in thyroidectomised rats. We conclude that thyroxine accelerates gastric ulcer healing by altering mucus and acid secretion and reducing NLR.

In vivo cellular and molecular gastroprotective mechanisms of chrysin; Emphasis on oxidative stress, inflammation and angiogenesis.

Gastric ulcer is one of the major gastrointestinal disorders affecting people worldwide. Despite medical advances, management of gastric ulcer and its complications remains a challenge facing medicine nowadays. In addition, currently available medicines exhibit limited efficacy and several side effects. In the current study, the potential protective effects of chrysin -naturally occurring flavonoid - were tested against indomethacin-induced gastric ulcer model in rats. It was found that chrysin in both doses; 50 and 100mg/kg were effective in promoting mucus secretion and preventing the rise in ulcer and lesion indices, acid production and histologic changes induced by indomethacin. During investigation of the possible underlying mechanisms, chrysin significantly attenuated indomethacin-induced oxidative injury and inflammatory response. Also, chrysin activated peroxisome proliferator activated receptor-É£ (PPAR-É£) leading to a phenotypic switch from pro-inflammatory M1 macrophages to the anti-inflammatory M2 macrophages that evidenced by the upregulated mRNA expression levels of PPAR-É£ and M2 marker genes (Arg-1 and CD206) and down regulation of M1 marker genes (IL-6 and CCL3). Furthermore, chrysin promoted angiogenesis via increasing expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and cluster of differentiation-31 (CD31). Collectively, these findings indicate that chrysin possesses a potential protective effect against indomethacin-induced gastric ulcer.

Risk Factors for Delayed Ulcer Healing after Endoscopic Submucosal Dissection of Gastric Neoplasms.

BACKGROUND AND AIMS: With improved technology, the size of artificial ulcers after endoscopic submucosal dissection (ESD) has increased. The aim of our study was to examine the risk factors for delayed gastric ulcer healing after ESD, including the possible benefit of potassium-competitive acid blocker (P-CAB) treatment. METHODS: The primary outcome was the rate of healing of the artificial ulcers induced by ESD at 8 weeks post intervention. Design - retrospective case series. Setting - Aichi Medical University Hospital. Patients - patients who underwent ESD for gastric neoplasm, between April 2015 and March 2017. Intervention - ESD, with a follow-up endoscopic examination at 8 weeks post-ESD. Univariate and multivariate analyses were used to identify the independent risk factors for delayed healing. RESULTS: Of the 73 gastric neoplasms included in the analysis, delayed ulcer healing was identified in 21.9%. Dyslipidemia (p=0.04), ESD procedure time (p=0.003) and artificial ulcer size (p<0.001) were identified as risk factors for delayed healing, with location in the lower third of the stomach [Odds ratio (OR) 6.76; p=0.016] and artificial ulcer size (OR, 1.18; p=0.024) retained as independent risk factors. A cut-off ulcer size of 854 mm2 was predictive of delayed healing, with a sensitivity of 29.8% and specificity of 87.5%. For large ulcers, the rate of healing of 70% with vonoprazan was higher than the rate of 47.6% with proton pump inhibitors (PPIs), although this difference was not significant. CONCLUSION: For artificial ulcers after ESD with a resection diameter >35 mm, it might be desirable to use PPIs for >8 weeks or P-CAB.