Gastric Metaplasia in the Duodenal Bulb Shows Increased Mucosal Interleukin-8 Activity in Helicobacter pylori-Positive Duodenal Ulcer Patients

Background: Although increased levels of interleukin (IL)-8 are known to be associated with infiltration of neutrophils in the gastric mucosa with Helicobacter pylori infection, no study has investigated the relationship between local IL-8 levels and neutrophil infiltration in the duodenal mucosa of patients with duodenal ulcer (DU). Methods: Duodenal mucosal biopsy specimens with and without gastric metaplasia (GM) were obtained from patients with DU and controls with an endoscopic methylene blue (MB) staining method. Levels of IL-8 secreted in the organ cultures of biopsy specimens were measured with an enzyme-linked immunosorbent assay. The number of myeloperoxidase-positive neutrophils infiltrating the lamina propria was determined in immunohistochemically stained tissue sections. Results: Histologic assessment showed that there was a strong correlation between the absence of endoscopic MB staining and the extent of GM. The levels of IL-8 in both duodenal and antral mucosal tissues were significantly higher in patients with H. pylori infection than in those without infection. In patients with DU the duodenal mucosal tissues with GM (MB-unstained mucosa) showed significantly higher levels of IL-8 than those without GM (MB-stained mucosa) or the antral mucosa. The number of neutrophils showed similar variations among DU and control patients with a positive correlation with IL-8 activity. The levels of IL-8 and the number of neutrophils decreased after H. pylori eradication in both duodenal and antral mucosal tissues, and these changes were more remarkable in the duodenal mucosal tissues with GM. Conclusions: Increased IL-8 activity in the duodenal mucosa with GM may be important for ulcerogenesis in H. pylori-positive DU patients.     

Mucosal Expression of Interleukin-6 and Interleukin-8 Messenger RNA in Ulcerative Colitis and in Crohn's Disease

To elucidate the possible role ofproinflammatory cytokines in inflammatory bowel disease,the expression and localization of interleukin (IL)-6and IL-8 mRNAs were examined in colonic biopsy specimens obtained from 10 patients with activeulcerative colitis (UC), 5 with inactive UC, 6 withCrohn's disease (CD), and 5 normal controls. In situhybridization with digoxigenin-labeled probes andimmunohistochemistry for both cytokines were performed. The IL-6mRNA expression was enhanced in the inflamed mucosa in4 of 6 CD patients, while that of UC patients stayed atbaseline. In contrast, IL-8 mRNA expression was apparently augmented (P = 0.044) in 7 of 10active UC and 3 of 6 CD patients (NS). The cell countpositive for IL-8 mRNA per unit area was definitelyincreased in moderate/severe UC when compared to mild UC (53.1 ± 14.4/mm² vs 9.0± 5.1/mm², P = 0.028) according to thedegree of inflammation. IL-6 mRNA positive cells in CDwere preferentially located in deeper lamina propriathan IL-8 mRNA positive cells in UC. Interestingly, IL-8 mRNA wasexpressed in the mucosal epithelial cells in one UCpatient. The patients treated by corticosteroids tendedto show suppressed expression of each mRNA, except one patient with intractable UC. Our data suggestenhanced expression of mucosal IL-6 mRNA in CD and ofIL-8 mRNA in UC by infiltrating mononuclear cells,indicating the distinct participation of each cytokine in the pathogenesis of UC and CD. Moreover,intestinal epithelial cells in UC occasionally exhibitIL-8 mRNA.     

Helicobacter pylori-Positive Functional Dyspepsia in Elderly Patients Comparison of Two Treatments

The association of Helicobacter pylori andfunctional dyspepsia is not well defined. The role of H.pylori on dyspeptic symptoms is still controversial. Theaim of this study is to confirm the efficacy of H. pylori eradication by two differentcommonly used treatment regimens, as well as to examinethe improvement of the dyspeptic symptoms by eradicatingH. pylori. H. pylori functional dyspepsia is prevalent in people over 60 years old. In this age groupwe treated 126 patients with bismuth plus metronidazoleand amoxicillin (group A, 67 patients) versus omeprazoleplus amoxicillin (group B, 59 patients). Results were statistically analyzed utilizing theWilcoxon signed-rank test, McNemer test and chi-squaretest; P < 0.05 was considered significant. Two monthsafter the end of therapy we observed an eradication rate of 66.1% in group A vs 64.3% in group B.All treated patients showed improvement insymptomatology. Although there was no significantdifference between patients in whom H. pylori was or wasnot eradicated within the respective groups, when examiningall H. pylori-positive patients versus H.pylori-negative posttreatment patients, there was asignificant reduction (P < 0.05) in all four symptomsof functional dyspepsia measured. In conclusion, we suggestthat patients treated with H. pylori-eradicatingtherapeutic regimens have an improvement in functionaldyspepsia symptoms. We shall prefer the dual therapy as compared to the triple therapy. We believethat eradicating treatment to eradicate H. pylori in theelderly patients with H. pylori -related functionaldyspepsia will reduce health care costs by reducing the number of subsequent visits.     

Endoscopy in Dyspeptic Patients: Is Gastric Mucosal Biopsy Useful?

Should dyspeptic patients coming to endoscopy with "normal" findings also be biopsied? To assess this, we studied the sensitivity and specificity of endoscopic examination compared with histology, microscopic evidence of Helicobacter pylori, CP-TEST, culture, and serum IgG and IgA antibody titers to H. pylori to determine whether endoscopy and antral biopsies really are useful. One hundred seven consecutive dyspeptic patients (mean age 43 yr) were entered. Four antral biopsies were taken routinely for evaluation by histology, microscopy, CP-TEST, and culture. Serum IgG and IgA antibody levels were measured in all patients. Of symptoms, postprandial bloating was statistically more common in H. on-positive than in negative patients. Endoscopy had the poorest sensitivity (37.1 %) and specificity (53.3%). Patients with normal endoscopic appearances but histologically confirmed gastritis had significantly higher IgG and IgA titers than the patients normal by both endoscopy and histology and without evidence of H. pylori. This study has shown that endoscopy is unhelpful in dyspeptic patients if endoscopic biopsies are not routinely taken.     

Helicobacter pylori Infection in Rural and Urban Dyspeptic Patients from Venezuela

Health researchers have advocated for a cross-disciplinary approach to the study and prevention of infectious zoonotic diseases, such as Rift Valley Fever. It is believed that this approach can help bring out the social determinants and effects of the zoonotic diseases for the design of appropriate interventions and public health policy. A comprehensive literature review using a systematic search strategy was undertaken to explore the sociocultural and economic factors that influence the transmission and spread of Rift Valley Fever. Although the findings reveal a paucity of social research on Rift Valley Fever, they suggest that livestock sacrificial rituals, food preparation and consumption practices, gender roles, and inadequate resource base for public institutions are the key factors that influence the transmission. It is concluded that there is need for cross-disciplinary studies to increase the understanding of Rift Valley Fever and facilitate appropriate and timely response and mitigation measures.     

Proximal and Distal Gastric Distension in Normal Subjects and H. pylori-Positive and -Negative Dyspeptic Patients and Correlation with Symptoms

Aim of the study was to analyze gastricdistension with water in H. pylori-positive and-negative dyspeptic patients and normal subjects and thecorrelation with symptoms. Twenty dyspeptic patients and 19 normal subjects were studied. H. pylori wasdetermined in each dyspeptic patient with the rapid ureatest at endoscopy. Gastric distension was evaluated byreal-time ultrasonography with the ingestion of stepwise-increasing amounts of water up toa total of 600 ml. During distension, the symptom scorewas evaluated as well. The proximal stomach wassignificantly smaller in dyspeptic patients than in healthy controls, at 100-600 ml water (P <0.01). A larger distal stomach was observed at 500 and600 ml of water (P < 0.01). The score of bloating andfullness was greater in dyspeptics than in controls at 300 and 600 ml of water distension.The symptoms score was linearly correlated with proximaland distal gastric measurements in dyspeptic patientsand in controls. No significant difference was found in dyspeptic patients regarding theH. pylori status. In conclusion, dyspeptic patients showa defective adaptation of the whole stomach to waterdistension and an increased symptom perception score as compared to controls. H. pyloriinfection does not seem to be a determining factor inthese observed findings.     

慢性乙型病毒性肝炎患者血浆内毒素、白介素-6和白介素-8水平的研究

目的探讨血浆内毒素、IL-6、IL-8水平与慢性肝病炎症活动、肝细胞损害的关系,揭示内毒素、IL-6、IL-8在慢性乙型肝炎发病机制中的作用。方法采用鲎试剂与合成基质(鲎三肽)的偶氮显色法和ELISA法分别检测患者血浆内毒素、IL-6、IL-8。结果慢性肝病组血浆内毒素、IL-6、IL-8水平均高于正常对照组(P<0.001);相关性分析三者间呈正相关;慢性肝病组按血清丙氨酸氨基转移酶(ALT)、血清门冬氨酸氨基转移酶(AST)高低分组后,血浆内毒素、IL-6、IL-8含量由高到低依次为>200u/L、100～200u/L、<100u/L组。结论血浆内毒素、IL-6、IL-8可导致肝细胞的损害,参与慢性乙型肝炎的发病,且三者密切相关。内毒素、IL-6、IL-8的高低在一定程度上反映了肝细胞的损害程度,为临床估计病情,判断预后,制定治疗方案提供参考指标。     

Symptom Patterns and Pathophysiological Mechanisms in Dyspeptic Patients with and Without Helicobacter pylori

Helicobacter pylori (HP) has been proposed as a mechanism of functional dyspepsia, but its role is still unclear. Our aim was to investigate the association between HP infection and dyspeptic symptoms and to verify whether the infection affects the pathophysiological mechanism of functional dyspepsia. The presence of HP and its association with dyspeptic symptoms were studied in 326 patients. Also, the effect of HP infection on solid/liquid gastric emptying rates, gastric sensitivity, and accommodation to meal was studied. HP was present in 17% of the patients, who showed symptom prevalence similar to that of HP-negative patients. Presence of HP did not significantly affect gastric emptying rates for solids and liquids, discomfort sensitivity thresholds (8.7 +/- 0.3 vs 9.8 +/- 0.9 mm Hg), or meal-induced gastric relaxation (133 +/- 12 vs 125 +/- 29 ml; all P's NS). In conclusion, in patients with functional dyspepsia the presence of HP infection does not seem to affect significantly the overall prevalence of symptoms or the gastric sensory-motor functions.     

Cigarette Smoking Promotes Atrophic Gastritis in Helicobacter pylori-Positive Subjects

Aging and smoking are known to promote atrophic gastritis (AG) and intestinal metaplasia (IM). This study investigated the relationship between Helicobacter pylori (Hp) infection, aging, smoking, and AG/IM. Ninety-six Hp-negative and 231 Hp-positive subjects were divided according to age; (39 years, 40–59 years, and 60 years) and smoking history (never smoked, or currently smoking). Histologic grading was performed according to the updated Sydney system. Fasting pH, total bile acid (TBA) concentration, and ammonia (NH₃) concentration in gastric juice were measured. Comparisons were made based on Hp status, age, and smoking. Independent relative risks for severe AG and IM were calculated. Grades of atrophy and IM were significantly higher in Hp-positive subjects, and these increased with age. Within Hp-positive subjects, grades of atrophy and IM were higher in smokers and in the middle and upper age groups. Within Hp-positive subjects, gastric pH and TBA were similarly higher in smokers and older subjects. An increased risk of severe AG/IM was statistically associated with smoking (OR 9.31, 3.85–22.50/OR 4.91, 1.90–12.68) and high TBA concentrations (OR 2.92, 1.19–7.17/OR 3.28, 1.25–8.62). Both Hp infection and aging are closely related to the development of AG and IM. Cigarette use and high TBA concentrations may play a role in the progression of AG and IM in Hp-positive subjects.     

Salivary-Specific Immunoglobulin G in the Diagnosis of Helicobacter pylori Infection in Dyspeptic Patients

Objectives: Helicobacter pylori infection is arguably the most common chronic bacterial infection in humans. The high prevalence and the association with peptic ulceration and gastric cancer indicate that simple, non-invasive methods for diagnosis of the infection are needed. In this study, the accuracy of salivary diagnosis for H. pylori infection was assessed.
Methods: Saliva and serum samples of 152 dyspeptic patients were tested for H. pylori IgG and IgA by an in-house ELISA All patients underwent gastroscopy with biopsy.
Results: One hundred thirty-one patients (86%) were found to be H . pylori positive on histology. Duodenal ulcer was found in 67 patients; 85 had no macroscopic lesion. Salivary and serum H. pylori IgG as well as serum H . pylori IgA titers were significantly higher in H . positive- -positive than in H. pylori-negative patients. The sensitivity and specificity of salivary H. pylori IgG were 82% and 71 %, respectively; the positive and negative predictive values were 95% and 40%, respectively; and the accuracy 81%. The corresponding figures for serum H. pylori IgG were 97% and 91 %; 98% and 83%; and 96%. Those for serum H. pylori IgA were80% and52%;91% and30%;and76%. The sensitivity of salivary H. pylori IgG in detecting duodenal ulcer was 83% (56/67) that of serum H. pylori IgG was 97% (65/67) (odds ratio = 0.15; confidence interval = 0.02–0.8; p = 0.02).
Conclusions: Salivary H. pylori IgG was a fairly sensitive and accurate indicator of gastric H. pylori colonization, with a high positive predictive value in our population. Data, however, suggest that salivary H . pylori IgG measurements do not compare favorably with serology.     

Interleukin-1, -6, and -8 levels in juvenile chronic arthritis

Summary The immunoinflammatory pathogenesis of juvenile chronic arthritis (JCA) involves the activation of many pathways including various cytokines. We have evaluated the levels of interleukin (IL)-1, IL-6 and IL-8 in 29 JCA patients. The age range was 1–16 with a mean of 10.1. A disease activity score was developed on the basis of: 1.constitutional symptoms and/or morning stiffness, 2.presence of joint swelling, 3.warmth, 4.limited range of motion, and 5.joint pain. This score correlated very significantly with laboratory disease activity markers such as erythrocyte sedimentation rate (ESR) and CRP (both p=0.006) and also correlated with IL-1 and IL-6 levels. The levels of IL-1 decreased in four of the five patients with improved disease activity. IL-6 but not IL-1 correlated significantly with the number of inflamed joints (p=0.013); IL-6 also strongly correlated with rheumatoid factor supporting this cytokine's role in B cell induction (p=0). Haemoglobin values correlated negatively with the activity index, ESR, CRP, IL-1 and IL-6. IL-8 did not correlate with disease activity markers. In the systemic patients all cytokines tended to be higher. Our data suggest that interleukins 1 and 6 are effective in the pathogenesis of JCA. Whether cytokines may be used for monitoring therapy may be clarified with further studies.     

The Role of Interleukin-6 and Interleukin-8 Gene Polymorphisms in Non-Alcoholic Steatohepatitis

Background:

Genetic polymorphisms may play role in the pathophysiology of nonalcoholic steatohepatitis (NASH).

Objectives:

We purposed to assess the role of interleukin 6 (IL 6) and interleukin 8 (IL 8) gene polymorphisms in the pathogenesis of NASH.

Patients and Methods:

Consecutive patients with biopsy proven NASH and age- and gender-matched healthy individuals with normal liver function tests and normal ultrasonography were enrolled in the study. Histopathological findings were recorded according to nonalcoholic fatty liver disease activity score (NAS). Patients were classified according to fibrosis scores as fibrosis score < 2 (mild fibrosis group) and fibrosis score ≥ 2 (significant fibrosis group). Blood samples were collected and genomic DNA isolation kit was used to evaluate genetic polymorphisms.

Results:

Of thirty-eight patients, 27 (71%) were in mild fibrosis group and 11 (29%) in significant fibrosis group. Thirty-eight age- and gender-matched healthy controls were enrolled in the study. The frequencies of genotypes G/C and G/G of IL 6 among the NASH group and healthy controls were 39.5% and 60.5% vs. 53.6% and 46.4%, respectively (P = 0.32). The frequencies of the genotypes of IL 8 among the NASH group were 47.2%, 44.6%, and 8.2% for T/T, A/T, and A/A, and in healthy controls were 50%, 28.6% and 21.4%, respectively, (P = 0.568). The differences between IL 8 gene T/A and T/T genotypes were not significant statistically (P > 0.05). However, the frequency of A/A genotype in significant fibrosis group was higher than the mild fibrosis group (P = 0.0016). The differences of -251 A/T polymorphism in the IL 8 and -174 C/G polymorphism in the IL 6 were not statistically significant between fibrosis groups (P > 0.05).

Conclusions:

IL6 and IL8 gene polymorphisms have no role in NASH pathogenesis and liver fibrosis process, but presence of the A/A genotype in the IL8 gene is associated with disease progression.     

High Frequency of A2143G Mutation in Clarithromycin-Resistant Helicobacter pylori Isolates Recovered from Dyspeptic Patients in Iran

Background/Aim:

Resistance to clarithromycin in H. pylori isolates is accepted as a main cause of treatment failure in developing countries. We aimed to determine the prevalence of clarithromycin-resistant strains isolated from dyspeptic patients in northern Iran, furthermore we aimed to assess the relationship between clinical outcomes of infection with point mutations.

Materials and Methods:

A total of 147 consecutive patients infected with H. pylori were included for determining the status of resistant H. pylori strains. With upper gastroscopy, three antral biopsies were taken from each patient, first section for rapid urea test, second for pathology and third section was used for bacterial culture in microbiologic lab. The antimicrobial susceptibility tests in this examination were agar dilution, in accordance with clinical and laboratory standards institue guidelines. Restriction fragment length polymorphism-PCR (RFLP-PCR) method was applied to determine the frequency of point mutations in 23s rRNA gene. Statistical analysis was performed using SPSS software (15.0) (SPSS, Inc., Chicago, Ill). Chi-square and Fisher''s exact tests were applied to our analysis. A P value less than 5% was considered as statistically significant.

Results:

Our results showed that there was no point mutation in clarithromycin-susceptible strains of H. pylori.

Conclusion:

The important findings in our study indicate that A2143G is the most prevalent point mutation (30/32: 93.7%) attributed in clarithromycin resistance among the H. pylori strains. The current study concluded that clarithromycin could still be involved in the empirical treatment of H. pylori infection, although a high frequency of A2143G mutation may increase the concerns regarding treatment failure.     

Helicobacter pylori Prevalence in Diabetes Mellitus Patients with Dyspeptic Symptoms and its Relationship to Glycemic Control and Late Complications

Background There are contradictory reports on Helicobacter pylori prevalence and its relationship to late complications of diabetes mellitus (DM). The aim of this study was to determine the prevalence of H. pylori infection in type 2 DM patients and to evaluate the relationship between H. pylori infection and the glycemic control, late complications. Material and Method A total of 141 type 2 DM patients and 142 nondiabetic subjects with upper gastrointestinal symptoms were enrolled in the study. All patients underwent upper gastrointestinal endoscopy with biopsy specimens obtained from gastric antrum and corpus. H. pylori status was evaluated in each patient by both the rapid urease test and histopathological examination. Plasma glucose, HbA1c, microalbuminuria in 24 h collected urine, electroneuromyography, and fundoscopic examinations were performed in all subjects. Results The prevalence of H. pylori infection was 61.7% and 58.5%, respectively, among type 2 diabetic patients and nondiabetic controls and was not statistically significant (P = 0.577). The duration of diabetes, fasting blood glucose and haemoglobin A1c levels, nephropathy and retinopathy prevalence did not differ significantly between the two groups (diabetics versus nondiabetics). There was no late complication in 60.3% of the type 2 diabetic patients as compared to at least one late complication in the remainders. A statistically significant correlation was found between H. pylori infection and the presence of neuropathy (P = 0.021). Conclusions The prevalence of H. pylori infection did not differ significantly between the diabetic patients and nondiabetic controls. Interestingly, diabetics with H. pylori infection had a higher incidence of neuropathy, although there was no association between the duration and regulation of diabetes, retinopathy, nephropathy and H. pylori status.     

小儿幽门螺杆菌感染与白细胞介素-8含量的关系

目的:探讨小儿幽门螺杆菌(Hp)感染与胃黏膜及血清白细胞介素-8(IL-8)含量的关系。方法:对43例接受胃镜检查的患儿用双抗体夹心酶联免疫吸附法测定其胃黏膜培养上清及血清中IL-8的含量,并比较Hp感染与非Hp感染患儿胃黏膜及血清中IL-8含量的差异。结果:Hp感染患儿胃黏膜中IL-8含量显著高于非Hp感染患儿(P0.05)。Hp感染组根治Hp治疗前后血清IL-8含量亦无显著变化(P>0.05)。结论:Hp感染可以诱导胃黏膜炎症细胞合成IL-8,IL-8在Hp相关性胃十二指肠疾病的发病机制中起着重要作用。     

Effect of Vonoprazan,a Potassium-Competitive Acid Blocker,on the 13C-Urea Breath Test in Helicobacter pylori-Positive Patients

Digestive Diseases and Sciences - Vonoprazan (VPZ) is a new oral potassium-competitive acid blocker that has recently become available. The aim of this study was to investigate the effects of VPZ...     

Effects of Omeprazole and Lansoprazole on 24-Hour Intragastric pH in Helicobacter pylori-Positive Volunteers

Verdú EF, Fraser R, Armstrong D, Blum AL. Effects of omeprazole and lansoprazole on 24-hour intragastric pH in Helicobacter pylori-positive volunteers. Scand J Gastroenterol 1994;29:1065-1069.

Background: The comparative effects of omeprazole and lansoprazole on gastric acidity in Helicobacter pylori-positive subjects and the clearance of H. pylori are unknown.

Methods: Eighteen asymptomatic H. pylori-positive subjects were studied. Each volunteer received 7 days of omeprazole, lansoprazole, or placebo in a randomized, double-blind, crossover study, with a washout period of 4-6 weeks between treatments. At the end of each treatment period 24-h dual-point intragastric pH-metry was performed, and H. pylori clearance was assessed.

Results: Both omeprazole (corpus/antrum pH: 5.5/5.5) and lansoprazole (5.4/5.4) increased intragastric pH compared with placebo (1.5/1.3). Over the 24-h recording there was no difference between the two treatments with regard to control of intragastric pH or clearance of H. pylori.

Conclusion: Omeprazole, 20 mg once daily, and lansoprazole, 30 mg once daily, are comparably effective antisecretory agents in H. pylori-positive subjects. Both agents provide only transient clearance of H. pylori in a few subjects.