Gastric mucosal superoxide dismutases in Helicobacter pylori infection

BACKGROUND: The mucosal pathology of Helicobacter pylori infection may in part be due to excessive production of reactive oxygen metabolites (ROMs) by phagocytes. The influence of H pylori infection on mucosal superoxide dismutases, some major scavenger enzymes of ROM was investigated. In humans superoxidase dismutase is present in at least two forms-that is, mitochondrial manganese (Mn)-superoxide dismutase and cytoplasmic copper-zinc (CuZn)-superoxide dismutase. METHODS: The amount and activity of both superoxide dismutases were measured, respectively by enzyme linked immunosorbent assay (ELISA) and spectrophotometrical enzyme activity assay, in gastric biopsy homogenates of patients with normal mucosa (n = 39) and in patients with H pylori related gastritis (n = 71). Infection and gastritis were confirmed by a combination of culture, serology, and histology. RESULTS: The amount (p < 0.001) and activity (p < or = 0.05) of Mn-superoxide dismutase were increased by about twofold to three-fold, whereas the amount and activity of CuZn-superoxide dismutase showed a slight decrease in gastric mucosa of patients with H pylori gastritis, in both antrum and corpus, compared with normal mucosa of patients without H pylori infection. Mn-superoxide dismutase concentrations in biopsy specimens of histologically normal corpus from patients with an inflamed antrum were significantly higher (p < 0.01) than that of patients with a histologically normal antrum. CONCLUSION: H pylori infection has a differential effect on mitochondrial and cytoplasmic superoxide dismutase in the gastric mucosa, reflected by a pronounced increase in the cytokine inducible Mn-superoxide dismutase and a marginal decrease in the constitutive CuZn-superoxide dismutase.     

Gastric mucosal hepatocyte growth factor in Helicobacter pylori gastritis and peptic ulcer disease

OBJECTIVES: Hepatocyte growth factor (HGF) is increasingly recognized for its role in a variety of hepatic and systemic diseases. Its relationship to gastritis has not been studied. We aimed at measuring gastric mucosal HGF levels in the presence or absence of Helicobacter pylori gastritis, in peptic ulcers, and in response to H. pylori eradication. METHODS: Fifty one patients were studied. Patients were not entered if they had liver disease, malignancy, or any systemic illness. HGF was measured in gastric antral incubates using an enzyme-linked immunosorbent assay. Assessments were repeated 6 wk after a 2-wk course of anti-H. pylori triple therapy in 12 patients. Code numbers were used for blinding. RESULTS: The median gastric mucosal HGF level was 36 ng/gm/tissue in patients with H. pylori gastritis (n = 33) compared with 19 ng/gm in 18 negative controls (p = 0.0024), 18 ng/gm after the eradication of H. pylori (p = 0.021), 23 ng/gm in all patients with ulcers (n = 10), and 26 ng/gm/tissue in H. pylori-positive ulcers (n = 7). CONCLUSIONS: Gastric mucosal HGF levels were elevated in H. pylori gastritis and reduced by its eradication. These results are relevant to our understanding of the increased gastric cell proliferation in patients with H. pylori-related gastritis.     

Experimental Helicobacter pylori infection induces antral gastritis and gastric mucosa-associated lymphoid tissue in guinea pigs

Humans infected with Helicobacter pylori have abnormally low levels of the antioxidant vitamin C, which protects against the formation of carcinogenic nitrosamines, in gastric juice. Guinea pigs, like humans and nonhuman primates, have a dietary requirement for vitamin C. As such, these species have gastrointestinal vitamin C transport systems not found in other animals. We have developed and characterized a guinea pig model of chronic gastric H. pylori infection with the rodent-adapted Sydney strain of H. pylori. At 4 weeks postinfection, five of six animals of the infected group and zero of two animals of the control group were positive for H. pylori as determined by culture or PCR. At 15 weeks, six of six animals of the infected group and zero of two animals of the control group were positive. H. pylori-specific seroconversion was observed among infected animals. There were no histologic abnormalities in the gastric antra or fundi of control guinea pigs. In contrast, there was multifocal, mild to moderate lymphohistiocytic antral gastritis and formation of antral lymphoid follicles in H. pylori-infected animals. The lesion distribution in the gastric antra paralleled that observed in H. pylori-infected humans. The H. pylori-infected guinea pig should prove useful in modeling the interaction of helicobacter and vitamin C in gastric carcinogenesis.     

Prevalence of Helicobacter pylori infection and gastric mucosal abnormalities in chronic pancreatitis

OBJECTIVE: Chronic pancreatitis is often associated with abnormal gastric acid secretion. However, previous studies have taken into consideration neither the potential role of Helicobacter pylori (H. pylori) infection nor histological features of the gastric mucosa in this context. The aim of this study was to analyze the prevalence of H. pylori infection as well as the pattern of gastritis in patients with chronic pancreatitis. METHODS: Forty patients with chronic alcoholic pancreatitis were included in the study: 40 patients with alcoholic liver cirrhosis and normal exocrine pancreatic function and 40 asymptomatic nonalcoholic subjects matched for age and sex used as control subjects. Endoscopy was performed in all patients, and five biopsy specimens from the antrum (three from the gastric body and two from the cardia) were taken for histological grading of gastritis and H. pylori assessment. RESULTS: Prevalence of H. pylori infection was similar in subjects with chronic pancreatitis (38%), asymptomatic subjects (28%) and liver cirrhosis (30%). Topography and expression of H. pylori-associated chronic gastritis was also not different among the three groups of subjects. In H. pylori-negative subjects, the presence of moderate to severe chronic antral gastritis was significantly more common in patients with chronic pancreatitis (40%) than in subjects with liver cirrhosis (18%) and in asymptomatic subjects (14%) (p < 0.05). No difference was found among the three groups of patients with regard to gastritis activity, atrophy, and intestinal metaplasia in the various gastric regions. The chronicity grade of gastritis did not correlate with the severity of pancreatic insufficiency. CONCLUSION: Prevalence of H. pylori infection is not different in patients with chronic pancreatitis as compared with subjects alcoholic liver cirrhosis and asymptomatic subjects. A severe H. pylori-negative chronic gastritis is more common in patients with chronic pancreatitis. This chronic inflammation of the gastric mucosa could contribute to determining the changes in gastric physiology described in patients with chronic pancreatitis.     

Helicobacter pylori infection, gastritis, and the temperature of choice for hot drinks

A 44-year-old male presented with a solitary cerebellopontine angle (CPA) metastasis from lung cancer. His initial symptoms were vertigo and hearing loss beginning 5 months after the diagnosis of the primary cancer. Two months later, right facial paresis developed. His neurological deterioration was rapid. Magnetic resonance (MR) imaging with enhancement disclosed the CPA tumor. The tumor was partially removed through the retroauricular retromastoid approach. Histological examination of the specimen revealed adenocarcinoma. The characteristic rapidly progressive symptoms and MR imaging with enhancement are the most sensitive and essential examinations for this lesion.     

HpSS: a new silver staining method for Helicobacter pylori

Fifty-seven patients with clinically localized prostate cancer were treated by radical prostatectomy or external radiation therapy following pelvic lymphadenectomy. Comparing the outcome of radiotherapy with that of prostatectomy in 42 T2 patients without lymph node metastasis, the 5-year cause-specific survival did not differ between the radical prostatectomy group (n = 31) and radiotherapy group (n = 11). The 5-year disease-free survival of the prostatectomy group, however, was superior to that of radiotherapy group (p = 0.01). To cure patients with T2 prostate cancer, therefore, it is supposed that radical prostatectomy should be performed. To improve the treatment outcome after radiotherapy, stereotactic radiosurgery for prostate cancer has been attempted in our institution. Phantom experiments using a linear accelerator demonstrated a round dose distribution, and high reproducibility of prostate positioning was confirmed by CT when a thermoplastic immobilization device was used to fix the pelvis. In one patient with localized prostate cancer treated by radiosurgery, acute complication has not been recognized during the 5 week follow-up. Radiosurgery may be available to treat clinically localized prostate cancer.     

Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication

BACKGROUND: Helicobacter pylori is an independent risk factor for gastric cancer, and this association may be due to the bacterium causing reactive oxygen species mediated damage to DNA in the gastric epithelium. High dietary ascorbic acid intake may protect against gastric cancer by scavenging reactive oxygen species. AIMS: To assess reactive oxygen species activity and damage in gastric mucosa in relation to gastric pathology and mucosal ascorbic acid level, and to determine the effect of H pylori eradication on these parameters. PATIENTS: Gastric biopsy specimens were obtained for analysis from 161 patients undergoing endoscopy for dyspepsia. METHODS: Reactive oxygen species activity and damage was assessed by luminol enhanced chemiluminescence and malondialdehyde equivalent estimation respectively. Ascorbic acid concentrations were measured using HPLC. RESULTS: Chemiluminescence and malondialdehyde levels in gastric mucosa were higher in patients with H pylori gastritis than in those with normal histology. Successful eradication of the bacterium led to decreases in both parameters four weeks after treatment was completed. Gastric mucosal ascorbic acid and total vitamin C concentrations were not related to mucosal histology, but correlated weakly with reactive oxygen species activity (chemiluminescence and malodialdehyde levels). CONCLUSIONS: Data suggest that reactive oxygen species play a pathological role in H pylori gastritis, but mucosal ascorbic acid is not depleted in this condition.     

The prevalence of Helicobacter pylori gastritis in patients with reflux oesophagitis: a case-control study

Head and neck cancers (HNCs) are malignancies that can be induced by tobacco use, although host-specific factors such as the DNA repair capacity (DRC) may modulate individual susceptibility to tobacco carcinogenesis. To test the hypothesis that genetically determined DRC modulates HNC susceptibility, we measured the DRC in the peripheral blood lymphocytes of 55 patients with newly diagnosed, previously untreated HNC and 61 healthy controls by the host-cell reactivation assay using a reporter gene damaged by benzo(a)pyrene diol epoxide, an ultimate tobacco-related carcinogen. The mean DRC was significantly lower in cases (8.6%) than it was in controls (12.4%; P < 0.001). The DRC was an independent risk factor for HNC (P < 0.01); those in the middle and lowest tertiles of DRC had increased odds ratios [2.17 (95% confidence interval, 0.74-6.39) and 4.27 (confidence interval, 1.45-12.5), respectively] for HNC. These findings suggest that individuals with reduced DRC may be at increased risk of developing HNC.     

Helicobacter pylori infection decreases gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol in man

Current world stockpiles of nuclear weapons and the status of treaties for nuclear disarmament and the ultimate elimination of nuclear weapons are summarised. The need for including stockpiles of civil plutonium in a programme for ending production and disposing of fissile materials is emphasized, and the ultimate difficulty of disposing of the last few nuclear weapons discussed.     

Touch cytology. A reliable and cost-effective method for diagnosis of Helicobacter pylori infection

A variety of reliable methods are available for detecting Helicobacter pylori (Hp) during upper gastrointestinal endoscopy. We evaluated the clinical utility and cost-effectiveness of rapid urease test (RUT), touch cytology (TC), and histology (H). Two hundred thirty-eight consecutive patients (178 without previous medical treatment and 60 formerly treated with anti-Hp therapy) were tested for Hp infection by RUT, TC, and H (H&E stain). The infection status for each patient was established by a concordance of two test results. The time to carry out the three tests and their cost were also calculated. Sensitivity of TC (100%) was significantly higher than that of RUT (86.8%; P < 0.001), but not than that of H (94.9%). RUT was significantly more specific than H (100% vs 95.6%; P < 0.05), but not than TC (96.4%). Hp infection was more frequent in the patients with chronic active gastritis than in those with chronic nonactive gastritis (P < 0.001). No Hp infection was detected in absence of chronic antral inflammation. RUT resulted the cheapest method and H the most expensive; TC is faster and cheaper than H. When additional information about the severity of mucosal damage or the presence of cell atypias is not necessary, histologic examination can be omitted, and a cost-effective strategy for assessing Hp status might consist in taking two antral biopsies, the former for performing RUT and the latter for preparing a slide by TC, which should be stained and examined only when the RUT result is negative.     

Value of serology as a noninvasive method for evaluating the efficacy of treatment of Helicobacter pylori infection

The systemic humoral response to Helicobacter pylori was studied in 86 infected adult patients before antimicrobial therapy and at intervals following therapy. Endoscopy with collection of biopsy specimens was performed immediately before treatment; a 13C-labeled urea breath test was performed, and blood specimens were collected before treatment and at 1, 3, 6, 9, and 12 months after treatment. Serum samples from three patient groups (eradication success [n = 50], eradication failure [n = 16], and no treatment [n = 20]) were assayed for IgA and IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Levels of antibody to H. pylori before treatment were similar in all three groups. As expected, the no treatment and eradication failure groups had no significant changes in antibody levels during the study period. In contrast, for the eradication success group, the specific IgA and IgG antibody levels decreased progressively and significantly. We conclude that serology is a potentially useful way to monitor the success of treatment of H. pylori infection without using invasive or more expensive methods.     

Evaluation of a serological test for diagnosis of Helicobacter pylori infection in children

A serological test for the diagnosis of Helicobacter pylori infection (Cobas Core Roche, IgG, 2nd Generation; Roche, France) was compared with the examination of biopsy samples (culture and histology) obtained after endoscopy in 115 children to assess its value. In 94 children (42 positive and 52 negative), results were concordant. In 10 children a positive serological test was associated with an absence of Helicobacter pylori, while in 11 others a negative serological test was associated with a positive culture. Sensitivity of the test was 79.2% and specificity 83.9%. A relationship between IgG titers and age (r = 0.31, p < 0.05) was found. Serological tests could be useful for the diagnosis of Helicobacter pylori infection, but a negative test result does not rule out infection, particularly in children under 10 years of age.     

Helicobacter pylori infection and genetic polymorphisms for cancer-related genes in gastric carcinogenesis

The development of gastric cancer is a multistep process that is multi-factorial. An association with the Helicobacter pylori infections, gastric atrophy and gastric cancer has received recent attention. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiological techniques for genetic susceptibility, gastric atrophy and serum markers including H pylori infection. We used an age- and gender-matched case-control study, where patients with benign gastric lesions were the controls. Low serum pepsinogen I levels (cut-off < 50 ng/mL) and low pepsinogen I/pepsinogen II ratios (cut-off < 3.0) were significantly associated with the risk of gastric cancer (odds ratio [OR] = 3.53: 95% confidence interval [CI] = 2.46-5.09 and OR = 4.73: 3.26-6.88, respectively). However, seropositivity of serum immunoglobulin G (IgG) antibody against H pylori (OR = 1.09: 0.74-1.61) was not associated with gastric cancer, even when analyzed by age greater than or less then 50 years. Specific genotypes of the cytochrome p450 2E1 (CYP2E1) RsaI polymorphism and glutathione-S-transferase (GST) M1 gene deletion were determined but were not associated with gastric cancer; however, a Lmyc genetic polymorphism was associated with gastric cancer (OR = 1.55: 1.03-2.34). Therefore, in this Japanese study, atrophic mucosal change, indicated by serum pepsinogen levels, is a possible risk factor for gastric cancer.     

Evaluation of a new urease reagent strip for detection of Helicobacter pylori in gastric biopsy specimens

OBJECTIVES: Determine sensitivity and specificity of a new urease reagent strip (URS) test for detection of Helicobacter pylori in gastric biopsy specimens. METHODS: Six paired biopsy specimens were obtained from the greater curvature of the distal antrum, the lesser curvature near the incisura, and the corpus along the greater curvature during 66 procedures on 59 patients with endoscopic findings of gastric antral mucosal erythema or erosions, or gastric or duodenal ulcers. One biopsy from each site was tested with the URS. The second was evaluated with histology. A final antral biopsy was evaluated with a urea/gel test. RESULTS: Twenty-eight of the 66 cases were histologically positive, with H. pylori observed in at least one of the three biopsy sites. The URS test correctly identified all 28. Of 193 individual biopsy specimens, 78 were positive for H. pylori. The URS correctly identified 77. Sensitivity was 0.99, specificity 0.95, positive predictive value 0.93, negative predictive value 0.99, and kappa 0.92. Average time to positive was 20 min. Twenty-seven antral biopsies were histologically positive for H. pylori. The URS test correctly identified all 27, whereas the urea/gel test correctly identified 21. For antral sites, URS sensitivity was 1.00 and specificity 0.95 versus urea/gel test sensitivity of 0.75 and specificity of 1.00. CONCLUSIONS: In this sample, the URS test is as accurate as histology in diagnosing H. pylori infections, and it provides results in less time and at a lower cost than histology.     

Two-day quadruple therapy for cure of Helicobacter pylori infection: a comparative, randomized trial

PURPOSE: Small intestinal transplantation remains a significant clinical problem. Allogeneic fetal intestinal (AFI) transplantation shows promise, particularly regarding procurement; however, no studiesto date have evaluated the potential success of true allogeneic loci implantation. The authors hypothesized that isolated segments of AFI could be heterotopically transplanted but would require immunosuppression to survive. METHODS: Donor tissue was obtained from late-gestation Brown Norway rat fetuses with a histo-locus RTN and Fischer fetuses with a histo-locus RT1L. The recipients were adolescent male Fischer rats with a histo-locus RT1L. A 1.2-cm segment of fetal small bowel was implanted in the omentum of the recipient rat and allowed to mature for 5 weeks. Animals were then separated into five groups. Group A served as controls with syngeneic fetal intestinal (SFI) transplant. Group B received AFI with no immunosuppression; group C, AFI transplant with five days of FK506; group D, AFI with 10 days of FK506; and Group E, AFI with daily FK506 for the entire 5-week maturation period. Animals were killed on day 35. RESULTS: All animals gained weight over the maturation period. Groups B, C, and D had no viable transplant segments at day 35. Groups A and E both had well-developed viable segments confirmed by gross and histological evaluation. CONCLUSIONS: FK506 allows for normal intestinal development for use in allogeneic fetal bowel transplantation. With this observation, the use of fetal intestine transplanted into the portal circulation emerges as a potentially viable alternative to present intestinal transplant models.     

Pantoprazole-based dual and triple therapy for the eradication of Helicobacter pylori infection: a randomized controlled trial

BACKGROUND/AIMS: The eradication of Helicobacter pylori (Hp) infection in duodenal ulcer and dyspepsia has been achieved using various therapy regimens. The efficacy of protein pump inhibitor pantoprazole as part of these regimens has not been widely studied. METHODOLOGY: During a prospective randomized trial, 250 Hp positive patients with either duodenal ulcer, erosive bulbitis, or gastritis and dyspepsia were treated using 14 days of therapy 1) pantoprazole 40 mg daily and clarithromycin 500 mg b.i.d. (PC), 2) pantoprazole 40 mg daily and clarithromycin 500 mg b.i.d. plus amoxicillin 1 g b.i.d. (PCA), or 3) bismuth subcitrate 120 mg t.i.d., roxithromycin 150 mg b.i.d., metronidazole 250 mg b.i.d. plus ranitidin 300 mg (BRMR). Hp status was assessed on 3 tests at the inclusion (2-specimen rapid urease test, 2-specimen histology, serology) and 2 tests (2-specimen rapid urease test, 2-specimen histology) 4 weeks after the end of the treatment. RESULTS: The entry criteria was fulfilled in 250 patients, of whom 13 missed the control endoscopy. The treatment had to be discontinued for adverse effects in 8 (10%) BRMR patients, and 1 (1%) PCA patients. Compliance was 100% in the PC group. All ulcers were healed at the end of the study with one exception in the BRMR group. The best eradication rate of Hp was shown by the PCA group with 94.8% (n = 73/77) followed by the PC group with 82.5% (n = 66/80) and finally the BRMR with 67.6% (n = 48/71)-PCA:BRMR - p < 0.001; PC:BRMR-p < 0.001; PCA:PC-p < 0.05. CONCLUSION: This study showed that triple therapy using PPI pantoprazole combined with antibiotics clarithromycin and amoxicillin was very effective in the eradication of Hp and treatment of duodenal ulcer with rare side effects. The dual pantoprazole and clarithromycin therapy had the highest rate of patient compliance, but is less effective than triple therapy. The combination of ranitidin with bismuth based triple therapy had the highest number of adverse events and the lowest rate of Hp eradication and therefore, should not be recommended.