Dyspepsia Research Articles

The Significant Association of the dupA and cagA genes of Helicobacter pylori with Peptic Ulcer

Background: Helicobacter pylori play a significant etiological role in various digestive diseases. Peptic ulcer is caused by H. pylori, which destroys the duodenum mucus and is often observed in the individuals consuming tobacco, spicy and heavy meals, alcohol, coffee, and tranquilizers. Several studies have indicated that duodenal ulcer promoting genes dupA and cagA are involved in H. pylori etiology. The present study aimed to evaluate the correlation between these genes and peptic ulcer. Methods: In this study, 500 stomach biopsy samples were assessed based on the rapid urease test and polymerase chain reaction (PCR) for H. pylori infection, followed by histological and microscopic examinations. Results: The dupA and cagA genes were subjected to PCR. Although dupA showed no significant correlation with peptic ulcer, the cagA genotype had a significant association with peptic ulcer (P less-than 0.05). Similar to the dupA gene, blood group was not observed to be correlated with H. pylori infection. Conclusion: According to the results, there are significant correlations between tobacco use (P less-than 0.05), tranquilizer use (P less-than 0.05), and meteorism (P less-than 0.05) with peptic ulcer. In addition, the expression of the cagA and dupA genes was investigated in patients with non-ulcer dyspepsia and peptic ulcer.

Electroacupuncture activates phosphorylated AMPKα to regulate the expression of the mTOR gene in rats with functional dyspepsia

Objective To investigate how electroacupuncture activates the AMPKα pathway in the treatment of functional dyspepsia (FD). Methods Tail clipping stimulation was combined with an irregular diet to induce FD in 20 Sprague-Dawley rats. They were randomly divided into a model group and an electroacupuncture group, each of 10. Ten others had no FD induced and formed a normal group. The rats in the electroacupuncture group were given 10 days of electroacupuncture treatment, while those in the normal and model groups were restrained and fixed like those in the electroacupuncture group, but not given electroacupuncture. The expression of phosphorylated adenosine monophosphate-activated protein kinase alpha (p-AMPKα), phosphorylated tuberin (p-TSC2) and Rheb protein in the stomachs and small intestines of each group were detected using the western blotting. Levels of mTOR mRNA were quantified using the reverse-transcription polymerase chain reaction (RT-PCR). Results The western blotting results showed that compared with the normal group, the expression levels of p-AMPKα and p-TSC2 in the stomachs and small intestines of the model group decreased significantly, while that of Rheb protein increased significantly. Compared with the model group, the expression of p-AMPKα and p-TSC2 increased significantly after the electroacupuncture treatment, while that of Rheb protein decreased significantly. According to the RT-PCR results, the expression of mTOR mRNA in the stomachs and small intestines of the model group was up-regulated significantly compared with the normal group. Compared with the model group, expression of mTOR mRNA in the electroacupuncture group was significantly down-regulated. Conclusion Electroacupuncture can activate the AMPKα pathway, up-regulate the expression of the related protein p-TSC2, and decrease the expression of Rheb protein, thereby down-regulating the transcription of the mTOR gene. That would serve to treat FD. Key words: Electroacupuncture; Functional dyspepsia; mTOR; AMPKα

Evidence for Local and Systemic Immune Activation in Functional Dyspepsia and the Irritable Bowel Syndrome: A Systematic Review.

Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and the irritable bowel syndrome (IBS). The mechanisms that drive recruitment of these cells to the gastrointestinal tract remain unexplained, largely due to the heterogeneity in phenotypes among patients diagnosed with such conditions. We aimed to systematically review the literature and collate the evidence for immune activation in FD and IBS, and where possible, detail the nature of activation. Seven literature databases were searched using the keywords: 'functional gastrointestinal disorder', FGID, 'functional dyspepsia', 'non-ulcer dyspepsia', 'idiopathic dyspepsia', 'irritable bowel syndrome', IBS and 'immun*'. Fifty-one papers reporting discordant immune features met the selection criteria for this review. Changes in lymphocyte populations, including B and T lymphocyte numbers and activation status were reported in IBS and FD, in conjunction with duodenal eosinophilia in FD and increased colonic mast cells in IBS. Increases in circulating α4+β7+ gut-homing T cells appear to be linked to the pathophysiology of both FD and IBS. Studies in the area are complicated by poor phenotyping of patients into subgroups and the subtle nature of the immune activity involved in FD and IBS. Alterations in proportions of gut-homing T lymphocytes in both FD and IBS indicate that a loss of mucosal homeostasis may drive the symptoms of FD and IBS. There is indirect evidence that Th17 responses may play a role in FGIDs, however the evidence for a Th2 immune phenotype in FD and IBS is limited. Although immune involvement is evident, large, well-characterised patient cohorts are required to elucidate the immune mechanisms driving the development of FGIDs.

Polymorphisms in the host CYP2C19 gene and antibiotic-resistance attributes ofHelicobacter pyloriisolates influence the outcome of triple therapy

Eradication of Helicobacter pylori is influenced by susceptibility to antimicrobial agents, elevated bacterial load and degree of acid inhibition, which can be affected by genotypes of drug-metabolizing enzymes [cytochrome P450 (CYP) 2C19 polymorphism]. Theoretically, the choice and dose of proton pump inhibitor may also influence the suppression of H. pylori infection. The CYP2C19 genotype has recently been found to have an impact on peptic ulcer healing, H. pylori eradication and therapeutic efficacy of proton pump inhibitors. Here, we investigated the impact of the CYP2C19 genotype polymorphism and the success of triple therapy (fluoroquinolones/metronidazole/clarithromycin) on antibiotic-resistant strains in eradicating H. pylori in human subjects with non-ulcer dyspepsia (NUD), in human subjects with peptic ulcer disease (PUD) and in asymptomatic human subjects (positive and negative for H. pylori infection). Based on the CYP2C19 genotypes, determined by Droplet Digital PCR (ddPCR) analysis, we found 11.2%, 62.5% and 26.3% corresponding to rapid metabolizers, intermediate metabolizers and poor metabolizers, respectively. However, we did not find any significant effect for homozygous ABCB1 or CYP2C19*2 and CYP2C19*3 alleles. We detected several participants heterozygous for both ABCB1 and CYP2C19*2, CYP2C19*3 and CYP2C19*17 loci. The participants heterozygous for both ABCB1 and CYP2C19*2 and *3 loci should be defined as intermediate and poor metabolizers according to the haplotype analysis in the NUD, PUD and asymptomatic subjects. Consequently, fluoroquinolones/metronidazole/clarithromycin-based triple therapies can be used to eradicate H. pylori infection, if one does not know the CYP2C19 genotype of the patient.

BabA-mediated adherence of pediatric ulcerogenic H. pylori strains to gastric mucins at neutral and acidic pH

ABSTRACT Helicobacter pylori infection can result in non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), adenocarcinoma, and gastric lymphoma. H. pylori reside within the gastric mucus layer, mainly composed of mucins carrying an array of glycan structures that can serve as bacterial adhesion epitopes. The aim of the present study was to characterize the binding ability, adhesion modes, and growth of H. pylori strains from pediatric patients with NUD and PUD to gastric mucins. Our results showed an increased adhesion capacity of pediatric PUD H. pylori strains to human and rhesus monkey gastric mucins compared to the NUD strains both at neutral and acidic pH, regardless if the mucins were positive for Lewis b (Leb), Sialyl-Lewis x (SLex) or LacdiNAc. In addition to babA positive strains being more common among PUD associated strains, H. pylori babA positive strains bound more avidly to gastric mucins than NUD babA positive strains at acidic pH. Binding to Leb was higher among babA positive PUD H. pylori strains compared to NUD strains at neutral, but not acidic, pH. PUD derived babA-knockout mutants had attenuated binding to mucins and Leb at acidic and neutral pH, and to SLex and DNA at acidic pH. The results highlight the role of BabA-mediated adherence of pediatric ulcerogenic H. pylori strains, and points to a role for BabA in adhesion to charged structures at acidic pH, separate from its specific blood group binding activity.

Camostat Mesilate, Pancrelipase, and Rabeprazole Combination Therapy Improves Epigastric Pain in Early Chronic Pancreatitis and Functional Dyspepsia with Pancreatic Enzyme Abnormalities

Background/Aims: The aims of the study are to clarify the pathophysiological differences among early chronic pancreatitis (ECP), functional dyspepsia with pancreatic (FD-P) enzyme abnormalities and FD patients and to determine whether camostat mesilate, pancrelipase, and rabeprazole triple therapy improve FD symptoms in the ECP patients and FD-P patients in cross-over way. Methods: We enrolled 84 consecutive patients presenting with typical symptoms of FD patients (n = 42), ECP patients (n = 15), and FD-P patients (n = 27). Gastric emptying was assessed by the ¹³C-acetate breath test. ECP was diagnosed based on the criteria recommended by the Japan Pancreatic Association. Results: The proportions of female in ECP patients and FD-P were significantly higher compared to that in FD patients. The early phase of gastric emptying in ECP and FD-P patients was significantly disturbed compared to that in FD patients. The primary outcome of this study is that 4 weeks of camostat mesilate, pancrelipase, and rabeprazole triple therapy significantly ameliorated epigastric pain in ECP patients compared to acotiamide and rabeprazole combination therapy. Conclusion: Although there were no significant differences in pathophysiology between ECP patients and FD-P patients, triple therapy can significantly ameliorate epigastric pain in ECP patients. Further studies will be needed to clarify why triple therapy can improve epigastric pain in ECP patients.

Chronic Urticaria Associated with Helicobacter pylori

Chronic urticaria (CU) is a common skin disease characterized by widespread, transient wheals occurring daily or almost daily for at least 6 weeks. Chronic urticaria caused by Helicobacter pylori can be cured after H. pylori quadruple regimen. A 31-year-old male with a past medical history of mild intermittent asthma presented with a complaint of chronic pruritus with diffuse urticarial wheals for the past seven months. Allergy history was unremarkable. He underwent an extensive work up including complete blood count, basic metabolic panel, HIV, thyroid stimulating hormone, thyroid peroxidase antibodies, serum IgE level, environmental allergy testing, and chest X- ray and all were negative. He was started on cetirizine and ranitidine with mild improvement, however his symptoms persisted. Four weeks later, he complained of epigastric pain and was subsequently tested for H.pylori by stool antigen which resulted as positive. He was treated with bismuth subsalicylate, metronidazole, tetracycline and omeprazole for two weeks. Pruritus and urticarial wheals disappeared in four weeks after therapy was started. Repeat stool H. pylori was done in eight weeks to confirm eradication. It was negative and no recurrence of urticaria was noticed. Chronic urticaria and dyspepsia are associated with H. pylori and its presence can be tested for by using an affordable, noninvasive, sensitive and specific test such as H. pylori stool antigen. The case demonstrates that H. pylori should be included in the diagnostic work-up of chronic urticaria, especially in patients without response to habitual treatment for chronic urticaria or those with concomitant gastrointestinal symptoms.

Can You See the Carcinoid Tumor? A Case of Autoimmune Metaplastic Atrophic Gastritis (AMAG) and Carcinoid Tumor

Atrophic gastritis is a known risk factor for the development of carcinoid tumor and gastric adenocarcinoma. In AMAG, there is destruction of parietal cells which leads to G-cell hyperplasia and elevated gastrin levels resulting in the proliferation of enterochrommaffin-like cells. These cells serve as precursors to carcinoid tumors, thus can be neoplastic in nature. A majority of carcinoid tumors appear on upper endoscopy (EGD) as polypoid lesions in the gastric body or fundus. We would like to present a unique case of carcinoid tumor in the context of AMAG, with grossly normal EGD. Our patient is a 25 year old female without significant past medical history with sole complaint of chronic dyspepsia and upper abdominal pain. She presented to clinic for a second opinion after a recent diagnosis of a neuroendocrine malignancy on EGD one month prior. The patient underwent repeat EGD with biopsies taken from the antrum, body, and fundus. An area of hypopigmented mucosa was identified in the antrum, prompting biopsies. The remainder of the stomach, duodenum, and esophagus were grossly normal. Pathology from the antrum and fundus all revealed chronic gastritis with mild enterochromaffin-like cell hyperplasia and severe reactive changes. The fundic biopsy showed chronic atrophic gastritis with antralized mucosa, suggestive of AMAG. The biopsies from the body of the stomach demonstrated well-differentiated neuroendocrine tumor (NET) grade 1, arising in the background of chronic atrophic gastritis. KI67 demonstrates proliferation index less than 2%. No lymphovascular invasion was seen. Her prior EGD showed well differentiated NET on antral biopsy. Patient underwent EGD/EUS with biopsies at a tertiary center, which was unremarkable, and biopsy showed atrophic gastritis. She was advised to repeat EGD every 6-12 months. This case raises concern for therapy modalities as minimal literature exists in regards to treatment of NET in the setting of AMAG with normal EGD. Given the lack of gross focality to the carcinoid lesion, does one resect or surveil? Although gastric carcinoid in the setting of atrophic gastritis is rarely malignant, one must ponder the malignancy potential given that we were unable to pinpoint the lesion despite multiple EGD's. Further cases must be studied to adequately manage such patients and better understand disease progression.3087_A Figure 1. EGD with normal appearing mucosa3087_B Figure 2. EGD with normal appearing mucosa and narrow band imaging

An Anatomical Explanation for a Chronic Gastrointestinal Complaint

Introduction: Median Arcuate Ligament Syndrome (MALS) is an anatomic abnormality causing vascular compression. Variation in the location of either the fibrous band of the median arcuate ligament or the origin of the celiac trunk results in stenosis. This causes ischemia and delayed gastric emptying. Our case demonstrates the extensive workup patients endure prior to being accurately diagnosed with MALS. Case: 75 yo female with a 20 year history of chronic dyspepsia, H. pylori, and C. difficile presented to the ED complaining of worsening nausea and two days of hematochezia. The patient stated new onset dysphagia to both solids and liquids. 2 months prior to presentation, she recalls frequent episodes of abdominal pain requiring multiple ED visits and weight loss of 15lbs. On initial examination, the patient was found afebrile, normotensive, with laboratory results showing a WBC count of 19.3x103 cells/μL, hemoglobin of 16.0 g/dL, and platelet count of 307 x 103 cells/ μL. Physical exam showed an abdomen mildly tender to palpation in the LUQ and LLQ without rebound or guarding. Patient was admitted and placed empirically on piperacillin / tazobactam. Abdominal CT demonstrated wall thickening, trace fluid, and adjacent fat stranding involving the distal transverse, descending, and proximal sigmoid colon likely representing an infectious or inflammatory colitis with a patent inferior mesenteric artery. EGD was only positive for mild antral erythema and few duodenal erosions with no ulcers and samples were obtained to test for H. pylori. During colonoscopy, biopsies obtained showed erythema and congestion consistent with ischemic colitis. A duplex ultrasound was performed, revealing a peak systolic velocity (PSV) within the celiac artery of 285 cm/s, correlating to >70% occlusion. The previous CT results were examined retrospectively and mild compression of the celiac trunk by the median arcuate ligament was noted. A diagnosis of median arcuate ligament syndrome (MALS) was made. Conclusions: We present a case of MALS which depicts a rare diagnosis, initially presenting with vague symptoms such as postprandial epigastric pain and weight loss. These non-specific complaints mimic more common conditions, delaying proper diagnosis and treatment.It is prudent to consider MALS as a cause of chronic mesenteric ischemia when evaluating patients with unresolved abdominal pain and weight loss to prevent delay in curative surgical treatment.

Helicobacter Pylori Infection and Lung Cancer: New Insights and Future Challenges.

Helicobacter pylori (H. pylori) is the causative agent of chronic gastritis and peptic ulcer diseases and is an important risk factor for the development functional dyspepsia, peptic ulceration, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. H. pylori has very high rates of infection in human populations, and it is estimated that over 50% of the world population is infected. Recently, certain extra-gastric manifestations, linked to H. pylori infection, have been widely investigated. Noteworthy, a growing body of evidences supports an association between H. pylori infection with lung cancer. The present review intend to highlight not only the most recent evidences supporting this association, but also some missed points, which must be considered to validate this emerging association.

Study on personality traits of patients with functional dyspepsia

Objective To explore the personality traits of patients with functional dyspepsia (FD). Methods From October 2016 to May 2017, 80 patients with FD who were admitted to the Department of Gastroenterology, Second Affiliated Hospital of Xi′an Jiaotong University were enrolled, among them 40 patients were in the depression and anxiety group and 40 patients were in the non depression or anxiety group. In addition, 40 healthy controls who underwent physical examination at the same period were included. Four dimensions including extroversion, neuroticism, psychoticism and masking of the subjects were analyzed by Eysenck personality questionnaire and their personality traits were evaluated. T-test and chi-square test were performed for statistical analysis. Results The extroversion scores of the depression and anxiety group, the non depression or anxiety group and the healthy control group were 8.18±3.80, 8.65±4.16 and 10.95±3.40, respectively; and the scores of the depression and anxiety group and the non depression or anxiety group were both lower than that of the healthy control group, and the differences were statistically significant (t=-3.443 and -2.708, both P 0.05). The psychoticism scores of the depression and anxiety group, the non depression or anxiety group and the healthy control group were 7.30±3.16, 5.93±2.50 and 4.93±1.87, respectively; the psychoticism score of the depression and anxiety group was higher than those of the non depression or anxiety group and the healthy controls, and the differences were statistically significant (t=2.158 and 4.086, both P<0.05); and the score of the non depression or anxiety group was higher than that of the healthy control group, and the difference was statistically significant (t=2.027, P=0.046). The masking scores of the depression and anxiety group, the non depression or anxiety group and the healthy control group were 13.48±4.24, 11.68±4.64 and 11.10±3.93, respectively, the score of the depression and anxiety group was higher than that of the healthy control group, and the difference was statistically significant (t=2.598, P=0.011). The percentages of introversional personality of the depression and anxiety group, the non depression or anxiety group and the healthy control group were 30.0% (12/40), 30.0% (12/40) and 7.5% (3/40), respectively; the percentages of the depression and anxiety group and the non depression or anxiety group were both higher than that of the healthy control group, and the differences were statistically significant (both χ2=5.251, P=0.022). The percentages of psychotic personality of the depression and anxiety group, the non depression or anxiety group and the healthy control group were 77.5% (31/40), 65.0% (26/40) and 45.0% (18/40), respectively; the percentage of the depression and anxiety group was higher than that of the healthy control group, and the difference was statistically significant (χ2=8.901, P=0.003). Conclusions The characteristics of personality traits of FD patients are introversion, neuroticism and psychoticism. Whether FD patients are associated with anxiety and depression is related to neuroticism and psychoticism. Psychological interventions can effectively improve the clinical symptoms of some FD patients. Key words: Introversion (psychology); Functional dyspepsia; Personality trait; Neuroticism; Psychoticism

A clinical investigation of patients with functional gastrointestinal disorders complicated with sleep disorders

Objective To analyze the status of sleep disorders in patients with functional gastrointestinal disease (FGID) and its relation with symptom characteristics. Methods From January to December 2014, questionnaire was carried out in FGID patients who met the Rome Ⅲ criteria and visited the outpatient department of gastroenterology at six third-level general hospitals in Tianjin City to assess the severity of symptoms, sleep quality (Pittsburgh sleep quality index, PSQI), and psychological state (anxiety and depression). Chi-square test and Mann-Whitney rank sum test were performed for statistical analysis. Results Among 931 patients with FGID, 651(69.92%) patients had sleep disorders and 280 (30.08%) patients had no sleep disorders. Among 828 patients with functional dyspepsia (FD), 360 (43.48%) patients had sleep disorders complicated with and depression. Among 292 patients with irritable bowel syndrome (IBS), 138 (47.26%) had sleep disorders complicated with anxiety and depression. Among 618 patients with FD complicated with sleep disorders, 70 (11.33%) patients overlapped with IBS; among 210 patients with FD, but without sleep disorder, 11 (5.24%) patients overlapped with IBS and the percentage of the former was higher than the latter, and the difference was statistically significant (χ2=6.580, P=0.01). The proportion of lower abdominal pain, sheep fecal or hard stool, laborious defecation or incomplete defecation in FGID patients without sleep disorder were 22.14% (62/280), 11.79% (33/280), 19.29% (54/280) and 27.86% (78/280), respectively; which were lower than those of FGID patients with sleep disorders (36.10%(235/651), 21.20%(138/651), 32.41%(211/651) and 44.39%(289/651)); and the differences were statistically significant (χ2=17.552, 11.569, 16.566 and 22.419; all P<0.01). FGID patients with sleep disorders have more severe symptoms such as lower abdominal pain, lower abdominal discomfort (non-pain), sheep fecal or hard stool, laborious defecation incomplete defecation, and urgency than FGID patients without sleep disorders; and the differences were statistically significant (Z=-4.423, -1.973, -3.360, -4.467, -4.550 and -2.420; all P<0.05). Conclusions Sleep disorders, anxiety and depression often coexist in patients with FGID. Sleep disorders are closely related with lower gastrointestinal symptoms in patients with FGID. Key words: Sleep disorders; Anxiety; Depression; Functional gastrointestinal disorders; Lower gastrointestinal symptoms

Helicobacter pylori and nonmalignant upper gastrointestinal diseases.

The review of the most important recent publications concerning the relation of Helicobacter pylori with peptic ulcer disease (PUD), noninvestigated and functional dyspepsia, and gastroesophageal reflux disease (GERD) is presented. H.pylori remains the main etiopathogenetic factor in complicated and uncomplicated PUD. Nevertheless, the role of nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin is increasing. The novel data did not confirm that PUD caused by NSAIDs and aspirin is less symptomatic. The role of glucocorticoids, immunosuppressants, and antidepressants seems to be of some importance. Although the involvement of H.pylori in functional dyspepsia is controversial, several data support the importance of H.pylori-induced gastritis in the pathogenesis of dyspeptic symptoms. Recent interventional studies have reported that H.pylori eradication improves dyspepsia mainly in areas with a high prevalence of this bacterium. Novel data regarding the relation of gastrointestinal peptides, ghrelin and obestatin, with H.pylori infection are also presented. Intriguing findings support the involvement of the gastric microbiota in the causation of chronic functional dyspepsia. Finally, some data concerning negative, positive, or neutral associations of H.pylori with gastroesophageal reflux disease (GERD) were published. In this context, today there is no evidence indicating that H.pylori eradication could worsen the symptoms or the course of GERD.

Characterization of clarithromycin heteroresistance among Helicobacter pylori strains isolated from the antrum and corpus of the stomach

Mixed infections and heteroresistance of Helicobacter pylori contribute to decreased efficacy of treatments. This study aimed to investigate frequency of clarithromycin heteroresistance and its link with mixed infections, medication history, and disease severity. A total of 40 pairs of H. pylori strains were isolated from the antrum and corpus of 97 patients. Susceptibility of the strains to clarithromycin was measured by agar dilution method. Site-specific mutations of 23S rRNA at A2143G, A2142G, and A2142C positions were analyzed by PCR and genomic relatedness of pairs of the strains was determined by random amplified polymorphic DNA (RAPD)-PCR. The results showed a prevalence of 35% (14/40) clarithromycin resistance. Diversity of the antrum and corpus isolates in resistance to clarithromycin was detected among 17.5% (7/40) of the patients. Similarly, diversity in MIC value was also detected in two patients infected with the sensitive strains. Significant difference in frequency of resistance was detected among patients with peptic ulcer disease (PUD) (MIC90 32μg/mL) and severe gastritis (MIC90 16μg/mL), compared with those who suffered from non-ulcer dyspepsia (NUD) (MIC90 8μg/mL) and chronic gastritis (MIC90 0.25μg/mL). MIC values showed 8-32 folds increased levels in the corpus. A2142G, A2143G, and A2142C mutations were detected in three, two, and two patients, respectively, but not observed in 46% of the resistant strains. RAPD-PCR fingerprints showed identical molecular patterns for the isolates of the corpus and antrum in each patient. In conclusion, microevolution of H. pylori strains during chronic infection, rather than mixed infection, and inappropriate medication appear to be main reasons of treatment failure in adults.

The importance of the association of cagL with cagA, vacAs/m and babA gene regions in patients with gastric cancer, duodenal ulcer and non-ulcer dyspepsia related to H. pylori: First in vitro study from Turkey

The importance of the association of cagL with cagA, vacAs/m and babA gene regions in patients with gastric cancer, duodenal ulcer and non-ulcer dyspepsia related to H. pylori: First in vitro study from Turkey

Expression of tryptophan hydroxylase in gastric mucosa in symptomatic and asymptomatic Helicobacter pylori infection.

IntroductionHelicobacter pylori infection induces clinical symptoms in 15–20% of subjects, and the reason for this variation is still not clear. The aim of the present study is to evaluate the expression of tryptophan hydroxylase (TpH-1) in gastric mucosa of patients with symptomatic and asymptomatic H. pylori infection in relation to the intensity of bacterial colonization and severity of dyspeptic symptoms.Material and methodsNinety subjects (aged 35–49 years) were enrolled in the study and separated into 3 groups of 30 subjects each. Group I – healthy volunteers without H. pylori infection, group II – subjects with asymptomatic H. pylori infection, group III – H. pylori-infected patients with dyspeptic symptoms, mainly fasting and nocturnal epigastric pain. To diagnose H. pylori infection the urea breath test (UBT-13C) and histological analysis were performed. The level of mRNA expression of tryptophan hydroxylase (TpH-1) was estimated in gastric mucosa with RT-PCR.ResultsThe expression of this enzyme in antral mucosa was 2.69 ±0.97 in group I, 2.28 ±0.69 in group II (p > 0.05) and 4.40 ±1.64 in group III (p < 0.001). The levels of expression of TpH-1 in gastric body mucosa were 2.16 ±0.70, 1.57 ±0.52 (p > 0.05) and 3.40 ±1.51 (p < 0.001), respectively. In group III a positive correlation was found between intensity of H. pylori colonization and TpH-1 expression as well as between TpH-1 expression and severity of dyspeptic symptoms.ConclusionsIncreased expression of TpH-1 in gastric mucosa plays a role in pathogenesis of chronic dyspepsia.

CagA and vacA allelic combination of Helicobacter pylori in gastroduodenal disorders

BackgroundAllelic variation of the virulence genes, vacA and cagA, as the most important virulence associated genes play an important role in the pathogenesis of severe gastrointestinal disease. ObjectiveThe aim of the present study was to identify the diversity of the virulence genes in patients with Gastric Cancer (GC), who were referred to the gastro-endoscopy unit of Imam Khomeini Hospital, Ahvaz Jundishapur University of medical science, Ahvaz, Iran. MethodsGastric biopsy specimens from 301 patients suspected to gastrointestinal disorders, were analyzed for H. pylori using molecular and phenotypical methods (culture, and biochemical test (catalase, oxidase and urease tests)). ResultsAmong 201 PCR positive for H. pylori, using histopathological methods, 22 (10.9%) patients had GC. Presence of vacA gene in our H. pylori strains was 100% (201/201), while the most virulent vacA s1 allele was detected in 82.6% isolates, and the mid region vacA m1 was found in 39.8% isolates. The vacA s1/m1 genotype was the most virulent allelic combination in GC and Peptic Ulcer Disease (PUD) in 68.2% and 50%, respectively. The cagA gene was detected in 66.7% isolates. Among the cagA positive isolates, EPIYA-ABC motif was the most common motif in the GC (66.7%), PUD (55.6%) and Erosive Gastroduodenitis (EG) samples (55.2%), while EPIYA-ABCC was the most common motif (58.7%) in the Non-Ulcer Dyspepsia (NUD) samples. The vacA s1m1/cagA+ combination was detected in GC (73.3%) and PUD (51.9%), while vacA s1m2/cagA+ presented in the NUD and EG samples in 77.8% and 62.1%, respectively. ConclusionIn this work, Western type (EPIYA-ABC and ABCC motifs) cagA, vacA s1m1 combinations have been demonstrated as the dominant genotype in the tested Ahvazian H. Pylori strains. Also the participation of cagA gene and vacA s1m1 genotype in development and severity of gastric disorder was well evident. Therefore, infection with H. pylori strain containing the cagA gene or the vacA s1m1 genotypes could be associated with increased risk of GC. This is the first study in our area that reports the high incidence and diversity of allelic combination of cagA and vacA genes in gastroduodenitis patients.

Association of Low Fecal Elastase-1 and Non-Ulcer Dyspepsia.

Non-ulcer dyspepsia (NUD) is a term used to define a set of symptoms that are believed to originate from the gastroduodenal region, and no underlying organic, systemic, or metabolic reason can be found. The majority of patients suffer from chronic symptoms although half of the patients report improvement in symptoms with time. The potential role exocrine pancreatic insufficiency in NUD patients has not been clarified yet. We aimed to identify exocrine pancreas function with pancreatic fecal elastase-1 in patients diagnosed with non-ulcer dyspepsia and no typical exocrine pancreatic insufficiency (EPI) symptoms. Thirty-five patients referred to gastroenterology clinics with NUD and 35 people with no dyspeptic symptoms as a control group were included in this prospective study. Non-ulcer dyspepsia patients were classified as group 1 and control subjects classified as group 2. Upper gastrointestinal endoscopies were performed in both groups. Assessment of exocrine pancreatic function was performed by measuring fecal elastase-1 concentration with a commercial ELISA kit using polyclonal antibodies (BioServ Diagnostics) in NUD patients compared to control subjects. Mean fecal elastase-1 levels were significantly lower in group 1 patients compared with group 2 (367.47 ± 43.27; 502.48 ± 50.94 respectively; p = 0.04). The percentage of the patients with EPI was significantly higher in group 1 (p = 0.02). Patients with NUD should be re-evaluated if they do not show satisfactory improvement with treatment. Exocrine pancreatic insufficiency was significantly higher in patients with NUD in our study. Evaluation for the presence of EPI can be a cost effective approach in management of refractory patients during the process of ruling out organic reasons.

Changes of gastric mucosal mast cells in patients with functional dyspepsia after Hylicobacter pylori infection

Objective To investigate the changes of gastric mucosal mast cells in patients with functional dyspepsia (FD) after Helicobacter pylori (H.pylori) infection, and to explore the correlation between the changes and dyspeptic symptoms. Methods From November 2012 to March 2014, 32 patients with FD and 16 asymptomatic patients (control group) from Beijing Jishuitan Hospital were enrolled. H. pylori infection situation was examined. The mucosal biopsies from gastric antrum and gastric body were taken for histological examination. The mast cells of gastric mucosa were detected by immunohistochemical stain. T test was performed for statistical analysis. Results Among 32 FD patients, 17 had H. pylori infection (one with gastric body involved, two with gastric antrum involved, 14 with both gastric antrum and gastric body involved), and 15 had no H. pylori infection. Among 16 asymptomatic patients, 12 had H. pylori infection and four had no H. pylori infection. Among FD patients, the percentage of degranulated mast cells in gastric mucosa with H. pylori infection group was (61.45±24.86)%, which was higher than that without H. pylori infection group ((48.34±21.63)%), and the difference was statistically significant (t=-2.145, P=0.036). The percentage of degranulated mast cells in gastric mucosa with H. pylori infection group was (29.73±12.99)%, which was higher than that without H. pylori infection group ((20.77±10.86)%), and the difference was statistically significant (t=-2.856, P=0.006). In H. pylori infection group, the percentage of degranulated mast cells in gastric body mucosa of FD patients was (66.99±18.85)%, which was higher than that of asymptomatic patients in control group ((46.77±8.43)%), and the difference was statistically significant (t=3.642, P=0.002). The ratio of degranulated mast cells in gastric body mucosa and the density of mast cells in gastric antrum mucosa of prandial distress syndrome (PDS) patients, the density of mast cells in gastric body mucosa of epigastric pain syndrome (EPS) patients and the ratio of degranulated mast cells in gastric body mucosa and the degree of degranulation of mast cells of PDS and EPS patients were all higher than those of asymptomatic patients in control group, and the differences were statistically significant (t=2.750, 3.601, 2.799, 9.522 and 5.755, all P<0.05). Conclusions The dyspeptic symptoms of FD patients with H. pylori infection is correlated with the changes of mast cells. With the infection of H. pylori, dyspeptic symptoms of different subtypes of FD may be correlated with the changes of mast cells in different gastric region. H. pylori infection may cause the dyspeptic symptoms of FD patients by increase the number and activation of mast cells. Key words: Helicobacter pylori; Mast cells; Functional dyspepsia; Dyspeptic symptom

An Efficient and Improved Process for the Synthesis of Itopride Hydrochloride and Trimethobenzamide Hydrochloride

Aim and Objective: Itopride is a prokinetic agent used for treating conditions like non-ulcer dyspepsia. Itopride is administered as its hydrochloride salt. Trimethobenzamide is used for treating nausea and vomiting and administered as its hydrochloride salt. The aim is to develop a novel and environmental friendly method for large-scale production of itopride and trimethobenzamide. Materials and Methods: Itopride and trimethobenzamide can be prepared from a common intermediate 4- (dimethylaminoethoxy) benzyl amine. The intermediate is prepared from one pot synthesis using Phyrdroxybenzaldehye and zinc dust and further reaction of the intermediate with substituted methoxy benzoic acid along with boric acid and PEG gives itopride and trimethobenzamide. Results: The intermediate 4-(dimethylaminoethoxy) benzylamine is prepared by treating p-hydroxybenzaldehyde and 2-dimethylaminoethyl chloride. The aldehyde formed is treated with hydroxylamine hydrochloride. The intermediate is confirmed by NMR and the purity is analysed by HPLC. Conclusion: Both itopride and trimethobenzamide were successfully synthesized by this method. The developed method is environmental friendly, economical for large-scale production with good yield and purity.