Transient Receptor Potential Ankyrin 1 and Substance P Mediate the Development of Gastric Mucosal Lesions in a Water Immersion Restraint Stress Rat Model.

BACKGROUND: Activation of substance P (SP) contributes to the development and maintenance of gastric lesions, but the mechanisms underlying the release of SP and SP-mediated damage to the gastric mucosa remain unknown. Transient receptor potential ankyrin 1 (TRPA1) is expressed in SP-positive neurons in the dorsal root ganglion (DRG) and stomach of rats. We hypothesized that water immersion restraint stress (WIRS) may activate and sensitize TRPA1 in DRG neurons, subsequently inducing the release of SP from DRG and stomach cells, causing the development of acute gastric mucosal lesions (AGML). METHODS: Changes in TRPA1 and SP expression in T8-11 DRG sensory neurons and the stomach in an AGML rat model were determined by reverse transcription polymerase chain reaction, western blotting and immunohistochemistry. The SP levels of serum and gastric mucosa were measured by using an enzyme-linked immunosorbent assay (ELISA). Gastric lesions were evaluated by histopathological changes. The TRPA1 antagonist HC-030031 and TRPA1 agonists allyl isothiocyanate were used to verify effect of TRPA1 and SP on AGML. RESULTS: SP and TRPA1 in the DRG and stomach were upregulated, and the serum and gastric mucosa levels of SP were increased after WIRS, which are closely associated with AGML. The release of SP was suppressed and AGML were alleviated following a selective TRPA1 antagonist HC-030031. TRPA1 agonists AITC increased release of SP and led to moderate gastric lesions. We confirmed that WIRS induced the release of SP in the DRG, stomach, serum and gastric mucosa, and in a TRPA1-dependent manner. CONCLUSIONS: Upregulated SP and TRPA1 in the DRG and stomach and increased serum and gastric mucosa SP levels may contribute to stress-induced AGML. TRPA1 is a potential drug target to reduce stress-induced AGML development in patients with acute critical illnesses. This study may contribute to the discovery of drugs for AGML treatment.

[Stress and the kynurenine pathway]. / A kinureninrendszer és a stressz.

The kynurenine pathway is the main route of tryptophan degradation which gives rise to several neuroactive metabolites. Kynurenic acid is an endogenous antagonist of excitatory receptors, which proved to be neuroprotective in the preclinical settings. Kynurenines have been implicated in the neuroendocrine regulatory processes. Stress induces several alterations in the kynurenine metabolism and this process may contribute to the development of stress-related pathological processes. Irritable bowel disease and gastric ulcer are well-known disorders which are related to psychiatric comorbidity and stress. In experimental conditions kynurenic acid proved to be beneficial by reducing inflammatory processes and normalizing microcirculation in the bowel. Further investigations are needed to better understand the relations of stress and the kynurenines, with the aim of developing novel therapeutic tools for stress-related pathologies.

Protective effects of oral administration of yeast thioredoxin against gastric mucosal injury.

Thioredoxin (TRX) is a redox regulating protein which has protective effects against oxidative stress-induced damage to cells and tissues. In this study, we investigated the effects of orally administered TRX derived from edible yeast, Saccharomyces cerevisiae, on gastric mucosa. First, we examined the digestibility of orally administered yeast TRX in mice, and detected yeast TRX in the stomach for 4 h after administration. Next, we investigated the mitigation of gastric mucosal injury after the oral administration of yeast TRX in water-immersion restraint stress and HCl/ethanol-induced gastric ulcer models. Furthermore, we conducted DNA microarray analysis, using the HCl/ethanol-induced model, which revealed that several groups of genes related to tissue repair were upregulated in ulcer regions in the stomachs of rats administered with yeast TRX. These results demonstrated the viability of the use of oral administrations of yeast TRX to protect the gastric mucosa.

[Psychoemotional status and "adaptation diseases" at patients with the peptic ulcer in Ural Federal Territory].

RESEARCH OBJECTIVE: To study the psycho-emotional status and prevalence of the coronary heart disease (CHD) and the idiopathic hypertensia (IH) at patients with the peptic ulcer of a stomach (PUS) and at patients with a peptic ulcer of a duodenum is (YaB DPK). MATERIALS AND METHODS: Examination of 226 patients with an exacerbation of a peptic ulcer was conducted. Patients were distributed in 3 groups of observation depending on localization of ulcerative process. At all surveyed questioning was carried out, data on heriditary burdeness, smoking, alcohol intake, existence of somatopathies were specified, clinic-morphological implications of a peptic ulcer were studied. RESULTS: Feeling of alarm was present at 109 (48.2%) patients with a peptic ulcer, from them at 92 (40.7%) the subclinical level of alarm is noted, and at 17 (7.5%) clinically expressed form is taped. At 39.3% of the examined patients the depression is defined, from them two thirds of patients had the subclinical level of a depression, and 13 people suffered from clinically expressed depression form. Communication of recurrence with a stress was noted at 86.0% of patients, professionally caused stress--at 44.4%. In our research at the time of the beginning of a disease prevalence of an ischemic heart disease among patients with an ulcer of a duodenum (DPK) made 18.2%. In group of patients with the combined localization of ulcerative defect in a stomach and in DPK which already had an ischemic heart disease before emergence of the second ulcerative defect there were 26.6% that statistically significantly doesn't differ. However that by the time of emergence of the combined lesion this category of patients made already 73.4% is indicative. In case of DPK ulcer prevalence of an ischemic heart disease increased from the moment of the beginning of a disease until carrying out research twice (to 36.4%), but patients with the combined ultserozny lesion nevertheless distinguished both larger initial prevalence of an ischemic heart disease, and more expressed its gain. At the time of the beginning of a disease of GB met in a group of persons with the isolated ulcerative defect authentically more often (36.4% against 18.7% in group of patients with the combined localization of an ulcer). At the time of carrying out research prevalence of GB among patients with DPK ulcer (47.7%) whereas in group of the combined lesion of a stomach and DPK of GB without ischemic heart disease there was only every fourth patient remained significant by 2,7 times (DI 1.2-6.3). The combination of associated diseases of an ischemic heart disease and GB at patients with the advent of an ulcer at the same time in a stomach and DPK practically always met at the persons abusing alcohol and tobacco smoking that in general enlarges risk of development of an ulcer of the second localization by 7,6 times CONCLUSION: At the peptic ulcer (PU) of any localization the previous stress conducting quite often to formation of alarm and a depression conducts to also education a stress--the induced conditions, for example, of an arterial hypertonia, and later--to an ischemic heart disease. As specific to every second patient with the combined form of a peptic ulcer of a stomach and a duodenum it is possible to consider a polisintropiya from such the comorbidity diseases as coronary heart disease and an idiopathic hypertensia. The combination of these associated diseases to alcohol intake and tobacco smoking progressively enlarges risk of development of a peptic ulcer of the combined localization by 7,6 times in comparison with the isolated duodenum canker. RESEARCH OBJECTIVE: To define influence of the comorbidity diseases and risk.

The association between reflux esophagitis and psychosocial stress.

BACKGROUND: The prevalence of reflux esophagitis is increasing in Korea. Reflux esophagitis aggravates the stress and fatigue level of daily life, but less is known about the association with stress and fatigue, which could be bi-directional. AIM: To evaluate the impact of reflux esophagitis on stress and fatigue and to compare the stress level of people with reflux esophagitis with that of controls with peptic ulcer disease and healthy controls. METHODS: Among a total of 9,033 subjects who underwent a comprehensive medical check-up including upper endoscopy, 6,834 subjects (75.7 %) were enrolled. Stress and fatigue scores were measured by a validated Korean version of the Brief Encounter Psychosocial Instrument and the Fatigue Severity Scale. RESULTS: Among 6,834 subjects, 13.2 % were in the high-stress group, and reflux esophagitis was found in 6.0 %. After adjustment for confounders, reflux esophagitis was significantly associated with high stress (odds ratio 1.94, 95 % confidence interval 1.25-3.02). Subjects with reflux esophagitis had significantly higher BEPSI-K scores compared with healthy controls (p = 0.027); and however, there was no significant difference in BEPSI-K scores between reflux esophagitis group and peptic ulcer disease controls. Fatigue severity scale was highly correlated with BEPSI-K (p < 0.001); however, there was no significant difference in fatigue severity scale level between the reflux esophagitis group and controls. The severity of reflux esophagitis was significantly correlated with BEPSI-K score (p = 0.008). CONCLUSIONS: Reflux esophagitis is significantly associated with psychosocial stress, and the severity of reflux esophagitis correlates with the degree of stress.

Proton pump inhibitors: are they overutilised in clinical practice and do they pose significant risk?

Proton pump inhibitors are highly effective acid suppressants with decades of use highlighting positive outcomes in millions of patients worldwide, and they offer minimal risk of adverse events. PPIs are considered overutilised when prescribed without an appropriate indication, when patients are left on them 'indefinitely' without appropriate indications and when they are continued after being utilised for most cases of hospital SUP. While several adverse outcomes have been linked to PPI therapy, most data are from retrospective observational studies that may be subject to confounding and bias.

Usefulness of a fast track list for anxious patients in a upper GI endoscopy.

BACKGROUND: To determine whether patients with no alarm signs who ask the endoscopist to shorten their waiting time due to test result anxiety, represent a risk category for a major organic pathology. METHODS: At our open-access endoscopy service, we set up an expedite list for six months for outpatients who complained that the waiting time for gastroscopy was too long. Over this period we studied 373 gastroscopy patients. In addition to personal details, we collected information on the presence of Hp infection and compliance with dyspepsia guideline indications for gastroscopy. RESULTS: Average waiting time was 38.2 days (SD 12.7). The 66 patients who considered the waiting time too long underwent gastroscopy within 15 days. We made 5 diagnoses of esophageal and gastric tumour and gastric ulcer (7.6%) among the expedite list patients and 14 (4.6%) among those on the normal list (p=0.31). On including duodenal peptic disease in the analysis, the total prevalence rate rose to 19.7% in the short-wait group and to 10.4% (p=0.036) in the longer-wait group. DISCUSSION AND CONCLUSIONS: Our data suggests that asking to be fast-tracked does not have prognostic impact on the diagnosis of a major (gastric ulcer and cancer) pathology.

[Factors affecting psychological reserves in the patients presenting with chronic somatic diseases].

The present study included 105 patients suffering chronic somatic diseases (CSD). Their health status was estimated based on the brief multifactor questionnaire for personality (BMQP) analysis; Spielberg state trait anxiety inventory (STAI); the Beck depression scale with the use of the "patient's quality of life" method; the well-being, activity, and mood (WAM) self-assessment test, and the stress-tolerance self-assistance test. The impairment of psychological reserve was documented in 85.7% of the patients with CSD. The degree of CSD deterioration was shown to be related to the frequency of exacerbation of clinical conditions, the severity of pain syndrome, the level of anxiety, depression, and hypochondriac mood. The impairment of psychological reserve was accompanied by the deterioration of the quality of life due to constraints imposed by the necessity to undergo medical treatment, avoid situations of emotional stress, restrict the scope of physical and social activities.

Knowledge, Attitudes and Practices of Adults in the United Arab Emirates Regarding Helicobacter pylori induced Gastric Ulcers and Cancers.

OBJECTIVE: The aim of this study is to assess the current level of knowledge, as well as the attitudes and practices (KAP) of the adult population in Sharjah, UAE with regards to H. pylori induced gastric ulcers and gastric cancers. METHODS: A cross sectional study of 500 participants was conducted in public venues in Sharjah, UAE through the distribution of a self-administered questionnaire English and Arabic speaking residents aged 18 years and above of both sexes were invited to participate in this study via convenience sampling. Responses were collected and analyzed using SPSS. RESULTS: General knowledge about H. pylori was poor, only 24.6% had heard of H. pylori. 61% of the participants did not know the link between H. pylori and gastric cancer. Only 3% of the participants associated psychological stress with gastric ulcer development. Females had higher knowledge scores (p = 0.008*). Participants with a medical background typically had higher knowledge scores than their peers in other fields of work (p < 0.0001*). Participants' attitudes towards H. pylori were suboptimal with only 33% willing to seek medical help If they get symptoms. Majority of participants with an approximate of 84% showed an overall average to excellent practices towards H. pylori. CONCLUSION: General awareness about H. pylori induced gastric ulcers and cancers is poor. The results of this study can be a starting point to devise new education programs and campaigns that raise awareness of this health issue which could be easily avoided with prevention, early detection, and intervention.
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Sodium R-lipoate and enzymatically-modified isoquercitrin suppressed IgE-independent anaphylactic reactions and stress-induced gastric ulceration in mice.

Anaphylaxis is a life-threatening allergic reaction, for which the worldwide prevalence is rapidly increasing. The currently used synthetic antiallergic drugs have a high tendency to cause adverse effects, like gastric ulcers, in long-term use. Therefore, a great deal of attention has been given to develop new safer and more effective antiallergic agents from natural compounds that are chemically/enzymatically-modified. Here, we evaluated/compared the efficacy of two different doses (50 and 100 mg/kg body weight "b.w", given orally) of sodium R-lipoate (NaRLA) and enzymatically-modified isoquercitrin (EMIQ) in alleviating both local/systemic non-immunological anaphylactic reactions and stress-induced gastric ulceration in mice, in comparison with sulfasalazine (SSZ) as a reference drug. The results indicated that the pre-treatment of animals with NaRLA or EMIQ (especially at 100 mg/kg b.w) completely succeeded, as SSZ, in alleviating the hind paw edema induced by either histamine or compound 48/80 (Cpd 48/80). Furthermore, NaRLA and EMIQ prevented the mast cell degranulation and anaphylactic shock caused by Cpd 48/80 (in a dose-dependent manner) and reduced significantly (P < 0.001) the histamine release from the mouse peritoneal mast cells, like SSZ. Moreover, their use was associated with alleviating both gastric histopathological and biochemical alterations in the water-restraint stress (WRS) mice model towards the control values. They also decreased the percentage of degranulated mesenteric mast cells in the WRS mice model. In conclusion, our findings provide possibility that both NaRLA and EMIQ may serve as an effective therapeutic agents for mast cells-dependent anaphylactic reactions without risks of inducing gastric ulcers.

Preventive effects of Chinese herb chai-hu-gui-zhi-tang extract on water immersion restraint stress-induced acute gastric ulceration in rats.

It is well known that maintenance therapy using Chai-hu-gui-zhi-tang (CHGZT), a traditional Chinese medicine, has been proven to prevent the recurrence of peptic ulcers. However, little is known as to whether or not it has protective effects against acute gastric injury. In the present study, we investigated the preventive effects of pretreatment with CHGZT extract on the development of water immersion restraint stress-induced acute gastric ulceration in male Wistar rats. The CHGZT extract (50, 250, 500 mg/kg b.w., p.o.) was given to rats before they were exposed to 2 or 4 hr of water immersion restraint stress; they were then were sacrificed immediately after stress exposure. Gastric mucosal lesions were evaluated macroscopically, and the gastric mucosal and hepatic non-protein sulfhydryls (NP-SH) were measured simultaneously. The results indicate that exposure to water immersion restraint stress resulted in the development of acute gastric stress erosions. Pretreatment with CHGZT extract caused a significant reduction of stress lesions and an increase in the gastric mucosal NP-SH and hepatic NP-SH concentrations. We conclude that the anti-ulcer response and extensive antioxidant effect of Chai-hu-gui-zhi-tang may be valuable in prevention of experimental gastric mucosal lesions in rats because it possesses preventive and gastroprotective effects.

[Indices of the responsiveness of system blood circulation as prognostic index of gastric ulcer development].

118 patients with gastric ulcer and 112 healthy people (control set) were examined. It is established that determination of connections between phenotype, responsiveness of general circulation, variability of cardiac rhythm, types of personality and levels of reactive anxiety allows to diagnose not only the prenosological and initial forms of gastric ulcer, but also to determine the tactics of conservative and surgical treatment of this disease.

DUOX2, a common modulator in preventive effects of monoamine-based antidepressants on water immersion restraint stress- and indomethacin- induced gastric mucosal damage.

Multiple kinds of monoamine-based antidepressants have been shown prophylactic effects in experimentally induced gastric ulcer. The loss of redox homeostasis plays a principle role in the development of peptic mucosal damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are one of the most important sources of reactive oxygen species within the gastrointestinal tract. It is unclear whether there are some common NADPH oxidases modulated by monoamine-based antidepressants in different gastric mucosal damage models. We explored the effects of selective serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine on the reactive oxygen species production and antioxidant capacity in the gastric mucosa of water immersion restraint (WIRS) or indomethacin treated rats, and examined the role of NADPH oxidases in the protective effects. Pretreated duloxetine prevented the increase of gastric mucosal NADPH oxidase activity and NADPH oxidase inhibitor apocynin dose-dependently protected gastric mucosa from damage by the two factors. Furthermore, dual oxidase 2 (DUOX2) and NADPH oxidase4 (NOX4) are involved in the protective effects of duloxetine in both models. We then examined NADPH oxidases expression modulated by the other monoamine-based antidepressants including selective serotonin reuptake inhibitor (SSRIs) fluoxetine, tricyclic agent (TCAs) amitriptyline and monoamine oxidase inhibitor (MAOs) moclobemide in the two models, and all the three antidepressants reduced the DUOX2 expression in the gastric mucosa. So DUOX2 was a common modulator in the preventive effects of all the monoamine-based antidepressants on WIRS- and indomethacin-induced gastric lesion. Our work provided a peripheral joint molecular target for monoamine modulatory antidepressants, which may be helpful to reveal the mechanisms of this kind of drugs more than monoamine regulation.

Association of comorbid mood disorders and chronic illness with disability and quality of life in Ontario, Canada.

Mood disorders are more prevalent in individuals with chronic physical illness compared to individuals with no such illness. These disorders amplify the disability associated with the physical condition and adversely affect its course, thus contributing to occupational impairment, disruption in interpersonal and family relationships, poor health and suicide. This study used data collected in the Canadian Community Health Survey, cycle 3.1 (2005) to examine factors associated with comorbid mood disorders and to assess their association with the quality of life of individuals living in Ontario. Results indicate that individuals with chronic fatigue syndrome, fibromyalgia, bowel disorder or stomach or intestinal ulcers had the highest rates of mood disorders. The odds of having a comorbid mood disorder were higher among women, the single, those living in poverty, the Canadian born and those between 30 and 69 years of age. The presence of comorbid mood disorders was significantly associated with short-term disability, requiring help with instrumental daily activities and suicidal ideation. Health care providers are urged to proactively screen chronically ill patients for mood disorders, particularly among the subgroups found to have elevated risk for these disorders.

Quality of life and emotional functioning in selected psychosomatic diseases.

BACKGROUND: Disease and its treatment may affect a patient not only in the physical, but also in the psychological and social spheres. Quality of life (QOL) is a global concept which should include mental and social actions, physical activities, and the beneficial aspects of a good physical and mental condition as well as negative ones caused by disease and infirmity. The aim of this study was to assess the relationships between emotional functioning and QOL among people diagnosed with coronary disease, hypertension, or gastric and/or duodenal ulcer. MATERIAL/METHODS: A group of 180 male patients hospitalized during 1999-2002 at the Military Medical Academy Hospital in Lódz was subjected to examinations. The Emotional Control Questionnaire by Brzezinski was applied together with the SF-36 Quality of Life Test. The psychometric techniques used in the examinations allowed determining statistically significant relationships between QOL level and emotional excitability, emotional expression control, and situation control. RESULTS: 1) The QOL level of the psychosomatic patients was essentially lower compared with that of healthy people. 2) QOL was strictly related to the emotional functioning of the subjects. 3) There was no essential diversity in the range of emotional functioning among the patients. 4) QOL of the patients suffering from gastric ulcer was on average a little higher than that of patients with coronary disease.

[Gastric and duodenal ulcer disease: morphofunctional, neuroendocrine and clinical parallels].

Morphofunctional state of gastric mucous tunic and neuroendocrine cells, and clinical indices at various stages of gastric and duodenal ulcer disease was studied. It was shown, that in clinico-endoscopic remission stage of disease intensity of pathogenetic mechanisms of some neuroimmune-endocrine and clinical indices remained.

Suicide and stomach ulcer mortality rate in Russia, 1965-2005.

BACKGROUND: Peptic ulcer disease is a common clinical problem. The relationship between stress and ulcer has been shown in a large series of methodologically sound studies. PURPOSE: To estimate the effect of psychosocial distress on stomach ulcer mortality rate at the aggregate level. METHODS: Trends in age-adjusted, sex-specific suicide (as an integral indicator for psychosocial distress) and stomach ulcer mortality rate in Russia from 1965 to 2005 were analyzed employing an ARIMA analysis in order to assess the bivariate relationship between the two time series. RESULTS: Time series analysis indicate the presence of a statistically significant association between the two time series for males (r=0.45; SE=0.16). The association between the two time series for females was also positive, however it was not statistically significant (r=0.25; SE=0.14). CONCLUSION: The results of the present study suggest a positive association between male suicide and stomach ulcer mortality rate at the aggregate level. This paper presents new epidemiological evidence that supports the psychosomatic concept of stomach ulcer disease.

[Gastric and duodenal peptic ulcer in automobile drivers: prevalence, clinical features and prophylaxis].

The authors first studied epidemiology of gastric and duodenal peptic ulcer, risk factors of gastro-duodenal diseases among automobile drivers; defined their real frequency and clinical features--presence of intensive boundary psychic disorders, combination with arterial hypertension and coronary heart disease, lower quality of occupational efficiency.

Comparison of the Hospital-Acquired Clostridium difficile Infection Risk of Using Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists for Prophylaxis and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Although proton pump inhibitors (PPIs) have been widely used for the prevention and treatment of stress gastric ulcers in hospital settings, there are concerns that PPIs increase the risk of Clostridium difficile infection (CDI). However, little is known about the risk of CDI following PPI and histamine-2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs. METHODS: A systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through August 19, 2016, identified 12 studies that reported the hospital-acquired CDI occurrence following H2RA and PPI use for the prevention and treatment of stress gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals were estimated. Heterogeneity was measured using I², and a meta-regression analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the overall quality of the evidence. RESULTS: A total of 74,132 patients from 12 observational studies were analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I²=42.81%). Subgroup analyses of the purpose of study medication use, study site, and study design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs. The overall quality of evidence was rated as low. CONCLUSIONS: The use of PPIs for both the prevention and treatment of stress ulcers was associated with a 38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.

The role of psychosocial factors in peptic ulcer disease: beyond Helicobacter pylori and NSAIDs.

A variety of organic etiologies are associated with peptic ulcer disease, and the most relevant of these are infection with Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs. Between 5% and 20% of patients with gastric or duodenal ulcer, however, lack an identifiable organic etiology. In these patients particularly and in all ulcer patients in general, psychosocial factors may play a significant role. At present, there is no definitive study proving a causal relationship between psychological stress and the development of ulcer disease. Studies to date suffer from significant methodological limitations and have not effectively addressed the poor correlation between ulcer craters and ulcer symptoms. A conservative application of available data would suggest that psychosocial factors play a significant role in symptom perception and reporting in patients with dyspeptic symptoms and may play a role in ulcer formation.