DNA damage and repair in Helicobacter pylori-infected gastric mucosa cells

Helicobacter pylori is a common human pathogen and its infection is believed to contribute to gastric cancer. Impaired DNA repair may fuel up cancer transformation by the accumulation of mutation and increased susceptibility to exogenous carcinogens. To evaluate the role of infection of H. pylori in DNA damage and repair we determined: (1) the level of endogenous basal, oxidative and alkylative DNA damage, and (2) the efficacy of removal of DNA damage induced by hydrogen peroxide and the antibiotic amoxicillin in the H. pylori-infected and non-infected GMCs. DNA damage and the efficacy of DNA repair were evaluated by the alkaline single cell gel electrophoresis (comet assay). Specific damage to the DNA bases were assayed with the DNA repair enzymes formamidopyrimidine-DNA glycosylase (Fpg) recognizing oxidized DNA bases and 3-methyladenine-DNA glycosylase II (AlkA) recognizing alkylated bases. The level of basal and oxidative DNA in the infected GMCs was higher than non-infected cells. H. pylori-infected GMCs displayed enhanced susceptibility to hydrogen peroxide than control cells. There was no difference between the efficacy of DNA repair in the infected and non-infected cells after treatment with hydrogen peroxide and amoxicillin. Our results indicate that H. pylori infection may be correlated with oxidative DNA damage in GMCs. Therefore, these features can be considered as a risk marker for gastric cancer associated with H. pylori infection and the comet assay may be applied to evaluate this marker.     

Organ-specific autoantibodies in children with Helicobacter pylori infection

BACKGROUND: We compared the prevalence of organ-specific autoantibodies in a group of Helicobacter pylori infected children and a group of uninfected children and investigated the relationship between the presence of relevant autoantibodies and the status of the target organs. PATIENTS AND METHODS: One hundred and twenty-four children with dyspepsia (54 boys, 70 girls; mean age 10.5 years; range 4-19) underwent gastroscopy: 56 had H. pylori infection (31 girls, 25 boys), while 68 (37 girls and 31 boys), were H. pylori-negative. All sera were tested for the presence of: parietal cell autoantibodies (PCA), intrinsic factor autoantibodies (IFA), microsomial autoantibodies, thyroglobulin autoantibodies, islet cell autoantibodies, glutamic acid decarboxylase autoantibodies, adrenal cortex autoantibodies, steroid-producing cell autoantibodies; gastrin, pepsinogen A, pepsinogen C and anti-H. pylori antibodies. The histological features and the ureA and cagA genes were also considered. RESULTS: The frequency of organ-specific autoantibodies was higher in patients with H. pylori infection than in uninfected patients (chi2-test p < .0001). Specifically gastric autoantibodies were significantly higher: seven of the 56 H. pylori-positive children were PCA-positive and one was IFA-positive (chi2-test p = .0004). The presence of autoantibodies was not associated with any clinical or biohumoral signs of disease. CONCLUSIONS: Our study detected a relationship between H. pylori infection in childhood and the presence of organ-specific autoantibodies unassociated with any clinical or biohumoral signs of disease. Helicobacter pylori infection in childhood could trigger the onset of clinical autoimmune gastritis, and/or other clinical autoimmune diseases.     

Genetic susceptibility and risk of gastric cancer in a human population of Cauca, Colombia

Gastric cancer (GC) is the main cause of mortality by cancer in Colombia. Glutathione S-transferase (GST) enzymes are involved in the detoxification of many environmental carcinogens. The homozygous deletions of glutathione S-transferase M1 (GSTM1-0) and glutathione S-transferase T1 (GSTT1-0) have been associated with several types of cancer. The risk to develop GC has been associated with environmental factors and Helicobacter pylori infection. The tumor necrosis factor (TNF-alpha) and its levels are increased in patients infected with H. pylori. A G/ A transition in the position -308 of the promoter of the TNF-alpha has been related in several studies to an increased expression of the gene and is associated with susceptibility to GC. The association of these polymorphisms with GC and the interaction with other risk factors (life style) were investigated. Blood samples were obtained from 46 GC patients and 96 controls. The logistic regression model was used to obtain the odds ratio (OR) and their 95% confidence intervals. These statistics established the association between the enzymatic polymorphisms and GC and between other independent factors and GC. The frequency of the TNF-alpha polymorphism in people infected with H. pylori was 18% in the GC population and 7% in the control group. This transition was not significantly associated with H. pylori infection and GC. The frequencies of the deletion polymorphisms for patients and controls were as follows: GSTM1 65.2% and 37.5%; GSTT1 17.4% and 14.6%. These results suggested that the GSTM1 deletion polymorphism was associated with an increased risk of gastric cancer (OR of 5.5; 95%CI, 1.7-17.2). Furthermore, other risk factors such as H. pylori infection (OR 5.58, CI 1.8-17.2), smoking (OR 6.70, CI 2.2-20.3) and alcohol intake (OR 3.27, CI 1.1-9.4) were associated with GC.     

The micronucleus assay as a biological dosimeter in hospital workers exposed to low doses of ionizing radiation

The health risk associated with low levels of ionizing radiation is still a matter of debate. A number of factors, such as non-target effects, adaptive responses and low-dose hypersensitivity, affect the long-term outcome of low-dose exposures. Cytogenetic bio-dosimetry provides a measure of the absorbed dose, taking into account the individual radiation sensitivity. The aim of the present study is to evaluate the value of the micronucleus (MN) test as a bio-dosimeter in hospital workers exposed to low doses of ionizing radiation. Blood samples were obtained from 30 subjects selected among workers exposed to X- and gamma-radiation, and 30 controls matched for sex, age and smoking from the same hospital. Micronucleus frequencies were analyzed by use of the cytokinesis-block method. The MN frequency was compared among the groups considering the confounding factors and the length of employment. No increase in the number of bi-nucleated cells with MN (BNMN), but a significant increase in the number of mono-nucleated cells with micronuclei (MOMN) was observed in exposed subjects compared with the controls. The relationship between MN frequency and accumulated dose (mSv) was evaluated. The length of employment did not affect the extent of MN frequency, but an increase of BNMN and MOMN cells was observed based on the accumulated radiation dose. Our study shows the sensitivity of the MN test in the detection of cytogenetic effects of cumulative exposure levels, suggesting the potential usefulness of this assay in providing a biological index in medical surveillance programs.     

Elevated homocysteine levels in patients with slow coronary flow: relationship with Helicobacter pylori infection

BACKGROUND AND OBJECTIVE: Elevation of plasma homocysteine (Hcy) level has been implicated in the pathogenesis of slow coronary flow (SCF) as it can severely disturb vascular endothelial function. Helicobacter pylori chronically infect the human stomach and causes malabsorption of vitamin B(12) and folate in food, leading ultimately to an increase in circulating Hcy levels. METHODS: Forty-three patients with angiographically proven SCF (group I) were enrolled in this study; 43 cases with normal coronary flow pattern (group II) served as controls. Fasting plasma levels of Hcy, vitamin B(12), and folate were measured in all subjects. Presence of H. pylori infection was defined as positive 14 C urea breath test. Coronary flow patterns for each major epicardial coronary artery were determined with the Thrombolysis in Myocardial Infarction (TIMI) frame count method. RESULTS: Mean TIMI frame count was 46.3 +/- 8.7 in group I and 24.3 +/- 2.9 in Group II (p = .0001). Vitamin B(12) levels were similar, whereas folate levels were dramatically reduced in group I compared to group II (13.2 +/- 4.3 vs. 17.1 +/- 5.2, p = .0001). Plasma Hcy levels were significantly higher in group I compared to group II (13.4 +/- 5.6 vs. 7.9 +/- 2.5, p = .0001) as was the prevalence of H. pylori infection (90.7% in group I vs. 58.1% in group II, p = .001). Hcy levels were elevated (11.7 +/- 5.3 vs. 7.5 +/- 2.7, p = .0001) and folate levels were reduced (13.9 +/- 4.7 vs. 18.6 +/- 4.9, p = .0001) in patients with H. pylori infection, while vitamin B(12) levels were similar in patients with and without H. pylori infection. Correlation analysis revealed a significant negative correlation between plasma folate and Hcy levels and also between folate levels and mean TIMI frame counts (r = -.33, p = .002 vs. r = -.33, p = .003). Moreover, there was a significant positive correlation between plasma Hcy levels and mean TIMI frame counts (r = .66, p = .0001). In addition, the folate level was the only significant determinant of the variance of Hcy in multiple regression analysis (r = -.21, p = .03). CONCLUSION: Our data showed that plasma folate levels were decreased and plasma Hcy levels were increased in patients with SCF compared to controls. Also, the prevalence of H. pylori infection was increased in patients with SCF. These findings suggest that elevated levels of plasma Hcy, possibly caused by H. pylori infection, and/or a possible disturbance in its metabolism may play a role in the pathogenesis of SCF.     

Migraine, Helicobacter pylori, and oxidative stress

BACKGROUND: The aim of this study was to ascertain whether oxidative stress is a causative factor of migraine attacks for Helicobacter pylori-infected migraineurs. MATERIALS AND METHODS: A total of 35 consecutive migraine patients without aura who came to gastroenterology polyclinic with various complaints and diagnosed H. pylori infection were included in the study group and compared with a group of 29 patients (control group) without migraine and H. infection. H. pylori infection was diagnosed by histopathological biopsies, which were taken by endoscopy (Olympus-GIFXQ240 endoscope). Both the diagnosis and the classification of migraine were made according to the International Headache Society criteria. Blood samples for nitric oxide were taken from patients with migraine during headache-free period as well as the control group. The interaction of nitric oxide was measured by the determination of both nitrite and nitrate concentrations in the sample. RESULTS: The study group included 31 women and 4 men (mean age 49 +/- 8 years) and the control group included 25 women and 4 men (mean age 52.6 +/- 11 years). The mean frequency of migraine attacks was 2.94 +/- 1.58 days/month and the mean duration of attacks was 21.2 +/- 3 hours. It was found that the study group has lower nitrate levels than the control group. CONCLUSIONS: Our results do not support the role of oxidative stress in patients suffering from H. pylori infection and migraine.     

Proliferative activity of gastric epithelial cells in Helicobacter pylori infected children

Helicobacter pylori infection has been associated with gastric carcinogenesis. Gastric epithelial cells proliferative rate is accelerated in H. pylori infected adult patients. Our study was performed to evaluate proliferative cell activity in gastric epithelium in the course of H. pylori infection in the early stage of its natural history. Gastric antral biopsy specimens were obtained from thirteen H. pylori positive and seven negative children. To assess replication rates we used nucleolar organiser regions staining with colloidal silver nitrate technique (AgNOR). The number of AgNORs per nucleus, area of single AgNOR, and the quotient of these two parameters (AgNOR content) were analysed. The mean area of AgNOR was lower in H. pylori positive than in negative children. Conversely, both the mean number of AgNOR per nucleus and AgNOR content were higher in infected than non infected subjects. These results show accelerated proliferation of gastric antral epithelial cells in the course of H. pylori infection in children. Such alteration of cell replication occurring in an initial phase of natural history of long lasting infection provides an explanation for the association between acquisition of H. pylori infection in the first years of life and the development of gastric cancer.     

幽门螺杆菌在慢性阻塞性肺疾病发生及 发展过程中的作用

目的研究幽门螺杆菌(Helicobacter pylori,H.pylori)在慢性阻塞性肺疾病(COPD)发生及发展过程中的作用。方法对85例COPD患者(COPD组)和85例体检健康者(对照组)进行血清抗H.pylori抗体(抗Hp-IgG)检测,比较两组的抗Hp-IgG水平及H.pylori阳性率。全部COPD患者均行肺功能和免疫功能检查,分析抗Hp-IgG水平与COPD严重程度的相关性,比较合并H.pylori感染与无H.pylori感染COPD患者之间,以及合并H.pylori感染COPD患者根除H.pylori前后免疫功能的差异。结果 COPD组血清抗Hp-IgG水平和H.pylori阳性率均明显高于对照组(P0.05),FEV1%预计值与血清抗Hp-IgG水平呈负相关(P0.05)。与无H.pylori感染的COPD患者相比,合并H.pylori感染的COPD患者外周血CD_3~+和CD_4~+T细胞含量、CD_4~+/CD_8~+比值、血清免疫球蛋白(IgA、IgG、IgM)水平均明显较低(P0.05),经H.pylori根除治疗后各指标水平明显升高(P0.05)。结论 H.pylori感染可导致宿主免疫功能紊乱,可能因此促进了COPD的发生和发展。根除H.pylori可明显改善合并H.pylori感染COPD患者的免疫功能,有利于患者恢复。     

Role of gastrin in gastric cancerogenesis in Helicobacter pylori infected humans.

Numerous epidemiological studies demonstrated the association between Helicobacter pylori (H. pylori) infection and gastric cancer but the mechanism of the involvement of H. pylori in gastric cancerogenesis remains virtually unknown. This study was designed to determine the seropositivity of H. pylori and cytotoxin associated gene A (CagA), serum gastrin and gastric lumen gastrin levels under basal conditions and following stimulation with histamine in gastric cancer patients and controls. 100 gastric cancer patients aging from 21 to 60 years and 300 gender- and age-adjusted controls hospitalized with non-ulcer dyspepsia (NUD) entered this study. 13C-Urea Breath Test (UBT), serum immunoglobulin (IgG) antibodies to H. pylori and CagA were used to assess the H. pylori infection and serum levels of IL-1beta, IL-8 and TNFalpha were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the degree of gastric inflammation by H. pylori . Gastrin-17 mRNA and gastrin receptors (CCK(B)) mRNA expression in gastric mucosal samples taken by biopsy from the macroscopically intact fundic and antral mucosa as well as from the gastric tumor was determined using RT-PCR. The overall H. pylori seropositivity in gastric cancer patients at age 21-60 years was about 92%, compared, respectively, to 68%, in controls. A summary odds ratio (OR) for gastric cancer in H. pylori infected patients was about 5.0 . The H. pylori CagA seropositivity in gastric cancer patients was about 58.5% compared to 32.4% in controls, giving the summary OR for gastric cancer in CagA positive patients about 8.0. The prevalence of H. pylori- and H. pylori CagA-seropositivity was significantly higher in cancers than in controls, irrespective of the histology of gastric tumor (intestinal, diffuse or mixed type). Median IL-1beta and IL-8 reached significantly higher values in gastric cancer patients (9.31 and 30.8 pg/ml) than in controls (0.21 and 3.12, respectively). In contrast, median serum gastrin in cancers (as total group) was several folds higher (62.6 pM) than in controls (19.3 pM). Also median luminal gastrin concentration in gastric cancer patients was many folds higher (310 pM) than in controls (20 pM). This study shows for the first time that cancer patients are capable of releasing large amounts of gastrin into the gastric lumen to increase luminal hormone concentration to the level that was recently reported to stimulate the growth of H. pylori. There was no any correlation between plasma gastrin levels and gastric luminal concentration of gastrin suggesting that: 1) luminal gastrin originates from different source than plasma hormone, most probably from the cancer cells, 2) cancer cells are capable of expressing gastrin and releasing it mainly into the gastric juice and 3) the gastric cancer cells are equipped with gastrin-specific (CCK(B)) receptor so they exhibit the self-growth promoting activity in autocrine fashion. This notion is supported by direct detection of gastrin mRNA and gastrin receptor (CCK(B)-receptors) mRNA using RT-PCR in cancer tissue. To our knowledge this is the first study showing an important role of gastrin as self-stimulant of cancer cells in patients infected with H. pylori. Basal and histamine maximally stimulated acid outputs were significantly lower in gastric cancer patients than in controls despite of enhanced gastrin release, particularly in cancer patients and this might reflect the mucosal inflammatory changes (increased serum levels of proinflammtory interleukins - IL-1beta and IL-8), that are known to increase gastrin release. We conclude that: 1) H. pylori infected patients, particularly those showing CagA-seropositivity, are at greatly increased risk of development of gastric cancer, 2) H. pylori-infected cancer patients produce significantly more IL-1beta and IL-8 that might reflect an H. (ABSTRACT TRUNCATED)     

The infection by Helicobacter pylori strains expressing CagA is highly prevalent in women with autoimmune thyroid disorders.

H. pylori infection is putatively associated with extra-digestive disorders and may also play a role in the development of autoimmune thyroid diseases (ATD). It was recently found that monoclonal antibodies to an H. pylori strain with cagA-positivity reacted with follicular cells of the thyroid gland, and that an H. pylori organism possessing the cag pathogenicity island carried a gene encoding for an endogenous peroxidase. The aims of this study was (1); To ascertain whether the infection by strains endowed with an increased inflammatory potential (those expressing CagA) could further enhance the risk of developing ATD (2); To verify the possible existence of an immune cross-reactivity between autoantibodies to peroxidase and thyroglobulin and H. pylori antigens (3). To establish whether thyroid colloid antigens could cross-react with an anti-H. pylori serum. The study was partly designed retrospectively. We examined 41 consecutive women with ATD, and, as a control, 33 consecutive age- and socio-economic class-matched women without autoimmune thyroid disorders, living in the same area as patients, occurred at the same institution in the same period (six months). Both patients and controls were examined serologically for H. pylori infection and CagA status by Western blotting. Some serum samples were absorbed with H. pylori to determine whether the antibody levels decreased. Colloid proteins were resolved electrophoretically and matched with a hyperimmune serum raised in rabbits against a CagA-positive H. pylori. Thirty-two patients (78.0%) tested seropositive for H. pylori infection, vs. 16 controls (48.4%) (P = 0.008, OR = 3.78, RR = 1.61). The prevalence of anti-CagA antibodies was 71.8% in infected patients, and 50% in infected controls (P = 0.161, n.s.). The overall prevalence of infection by CagA-positive H. pylori was significantly higher in patients with ATD (23/41, or 56.0%) than that in controls (8/33, or 24.2%) (P = 0.006, OR = 3.99, RR = 2.31). The other tests gave negative or inexplicable results. In conclusion: CagA-positive H. pylori infection increases the risk of ATD development.     

Helicobacter pylori stimulates a mixed adaptive immune response with a strong T-regulatory component in human gastric mucosa

BACKGROUND: Host factors play an important role in the pathophysiology of Helicobacter pylori infection and development of gastritis and related disease. The established opinion is that the T-cell-mediated immune response to H. pylori infection is of Th1 type. Our earlier immune cell phenotype studies indicate a mixed Th1-Th2 profile of the effector cells. Therefore, an extensive adaptive and regulatory cytokine gene expression profile was conducted by quantitative real-time polymerase chain reaction (qPCR). MATERIALS AND METHODS: Biopsies from gastric mucosa of 91 patients diagnosed as H. pylori negative, H. pylori positive with gastritis, or H. pylori positive with peptic ulcer were obtained by endoscopy. Gene expressions of nine cytokines and CagA status were measured by qPCR. RESULTS: All cytokine genes showed higher expression levels in the presence of H. pylori when compared to H. pylori-negative samples (fold increase: IL8: x 11.2; IL12A: x 2.4; TNF-alpha: x 5.2; IFN-gamma: x 4.3; IL4: x 3.6; IL6: x 14.7; and IL10: x 6.7). Patients infected with CagA-positive strains had higher expression of IL1-beta and IL18 compared to patients infected with CagA-negative strains (x 1.6 for IL1-beta and x 2.0 for IL18). Patients with duodenal ulcer had a lower antral Th1/Th2 ratio than other H. pylori-positive patients. CONCLUSIONS: The cytokine profile of H. pylori-infected gastric mucosa shows a mixed Th1-Th2 profile. Furthermore, a high IL10 expression may indicate that also regulatory T cells play a role in the chronic phase of H. pylori infection.     

Evaluation of micronucleus induction in a Chilean population environmentally exposed to arsenic

In the present study we have evaluated whether or not environmental exposure to arsenic in ground drinking-water results in a significant increase in the frequency of micronuclei (MN) in peripheral blood lymphocytes. Thus, 106 individuals from the Antofagasta region (North Chile), together with 111 individuals from the area of Concepción, were used in this investigation. In the Antofagasta area, arsenic levels in drinking-water as high as 0.750 mg/L were measured. In Concepción, located about 2500 km towards the south and used as reference area, arsenic levels in tap water were as low as 0.002 mg/L. The total content of arsenic in fingernails was determined as a biomarker of individual exposure. The cytogenetic results obtained in this study indicate that in the exposed group the overall frequency of binucleated micronucleated cells (BNMN) is higher than in the reference group, the difference being statistically significant. In addition, no differences were found between the exposed and the reference groups, regarding the cytokinesis-block proliferation index (CBPI). No association was observed between BNMN and arsenic content in water or arsenic in fingernails. On the other hand, when the exposed group was divided according to their Atacameno or Caucasian ethnicity, no significant differences were observed between them. In addition, as usually found in other human biomonitoring studies, sex and age are factors that modulate the frequency of MN in both exposed and reference populations.     

CagA-positive Helicobacter pylori infection may increase the risk of food allergy development.

The aim of this study was to test whether patients with symptomatic food allergy and significant levels of immunoglobulin E (IgE) to alimentary antigens were more likely infected by H. pylori, especially by strains expressing the CagA protein, with respect to controls. A group of 38 patients with symptomatic food allergy and 53 age-matched controls were examined serologically for H. pylori infectious status, and for CagA seropositivity. IgE to alimentary allergens were measured by a commercial kit. The prevalence of H. pylori infection in patients with food allergy and controls was similar (42.1%, and 48.3%, respectively). However, anti-CagA antibodies in H. pylori-infected persons were detected in 62.5% of patients with food allergy, and 28% of controls (P = 0.030, odds ratio = 4.29). The mean level of IgE to the most common alimentary antigens in serum samples from infected patients with anti-CagA antibodies was significantly higher than in CagA-negative infected patients: 3.28 kU/L (SD 3.93), vs. 1.99 kU/L (SD 1.53), P = 0.002, 95% confidence interval = 0.61 to 2.53). Infection by CagA-positive H. pylori increases the risk of developing food allergy.     

Effects of selective cyclooxygenase-2 inhibitor and non-selective NSAIDs on Helicobacter pylori-induced gastritis in Mongolian gerbils

Background. It is still a point of controversy whether Helicobacter pylori‐infected patients are more likely to develop mucosal damage while taking NSADIs. Selective cyclooxygenase (COX‐2) inhibitors may be associated with less severe gastric mucosal damage than conventional NSAIDs, but this association is undefined in H. pylori‐induced gastritis. The aim of this study was to evaluate the effects of selective COX‐2 and nonselective NSAIDs on H. pylori‐induced gastritis. Methods. After intragastric administration of indomethacin, NS‐398 or vehicle alone, once daily for 5 days in H. pylori‐infected and uninfected Mongolian gerbils, we evaluated gastric mucosal damage, inflammatory cell infiltration and prostaglandin E₂ (PGE₂) concentration. We investigated whether H. pylori infection induced the COX‐2 expression. Results. In H. pylori‐uninfected groups, the indomethacin‐treated group showed the highest mucosal damage score and the lowest PGE₂ concentration. There was no difference in mucosal damage scores and PGE₂ concentration between NS‐398 and vehicle‐alone treated group. In H. pylori‐infected groups, there was no difference in mucosal damage scores, irrespective of the type of drugs administered. The indomethacin‐treated group showed the lowest PGE₂ concentration, similar to that of the NS‐398 and vehicle‐alone treated groups, both without H. pylori infection. Gastric neutrophil and monocyte infiltration scores were higher in H. pylori‐infected groups than in uninfected groups. However, there was no difference in these scores according to the type of drugs administered, within H. pylori‐infected or uninfected groups. COX‐2 protein expression was observed in H. pylori‐infected Mongolian gerbils but not in uninfected ones. Conclusions. Our animal study showed that H. pylori infection induced COX‐2 expression and increased prostaglandin concentration. Administration of NSAIDs decreased the prostaglandin concentration, but did not increase mucosal damage in H. pylori‐induced gastritis. Selective COX‐2 inhibitors, instead of conventional NSIADs, had no beneficial effect on preventing mucosal damage in H. pylori‐induced gastritis.     

Immunity markers in patients with Helicobacter pylori infection: effect of eradication

BACKGROUND: Helicobacter pylori is a microorganism able to stimulate a robust inflammatory and systemic immune response. AIM: The aim of our study was to evaluate autoimmune markers in dyspeptic patients positive for H. pylori infection compared to a control group of non-H. pylori-infected subjects. The kinetics of cryoglobulins and autoantibodies was evaluated after treatment of the infection. PATIENTS AND METHODS: Dyspeptic patients with active H. pylori infection and age- and sex-matched healthy H. pylori-negative controls were studied. Markers of immunity were compared, in H. pylori-infected patients before, 6 months and 1 year after the end of therapy. Results were also compared between those with and without successful eradication therapy. RESULTS: Eighty-six individual were entered (43 H. pylori-infected). H. pylori-infected patients had higher levels of IgG and/or IgA and/or IgM (22/43 versus 2/43). Circulating immune complexes and cryoglobulins were detected in patients more often than controls (p < .05 for both). Autoantibodies were observed in 13 patients (30% versus 5% in controls) and antithyroid antibodies in 12 (p < .04 versus controls). Lower levels of C3 and/or C4 complement fractions were observed in infected patients with respect to controls (7/43 versus 1/43; p = .014). After 1 year of follow-up, the markers of autoimmunity dramatically improved in patients eradicated for H. pylori infection compared to those in whom therapy failed. No patient developed a clinical autoimmune disorder. CONCLUSIONS: Additional studies are necessary to ascertain the clinical significance of the modifications of autoimmune markers in patients with H. pylori infection.     

Prevalence of cagA, vacA, babA2 and iceA genes in H. pylori strains isolated from Colombian patients with functional dyspepsia

The clinical outcome of Helicobacter pylori infection has been particularly associated with virulence genotypes. These genotypes are useful as molecular markers in the identification of patients that are infected and at high risk for developing more severe gastric pathologies. Our main objective was to determine the prevalence of virulence genotypes cagA, vacA, iceA and babA2 of H. pylori, in patients with functional dyspepsia who are infected with the bacteria. H. pylori genotypes babA2 and cagA as well as vacA and iceA allelic variants were identified by PCR in 122 isolates resulting from 79 patients with functional dyspepsia. A high prevalence of genes cagA+ (71%), vacAs1am1 (34%), babA2 (57%) and iceA1 (87%) was found. The most frequent combined genotype found were cagA+/vacAs1am1/babA2+/iceA1 and cagA-/vacAs1am1/babA2+/iceA1, regardless of any family history of gastric cancer or MALT lymphoma. The very virulent genotype cagA+/vacAs1am1/babA2+/iceA1 prevailed in the studied patients with functional dyspepsia. Our results provide information about the prevalence of four of the more important virulent factors and constitute new evidence on the prevalence of the most virulent H. pylori genotype in patients with functional dyspepsia.     

抗幽门螺杆菌治疗在儿童特发性血小板减少性紫癜中的作用

目的 探讨联合抗幽门螺杆菌（H.pylori）在特发性血小板减少性紫癜（ITP）患儿治疗中的作用.方法 将58例血清H.pylori抗体阳性的ITP患儿随机分为：A组：给予根治性抗H.pylori,大剂量丙种球蛋白和强的松治疗;B组：未予抗H.pylori,其他治疗相同.另设正常对照组（C组）：选血清H.pylori抗体阴性的健康入学儿童.观察A、B两组治疗前和3月后T细胞亚群分布,血小板相关免疫球蛋白G（PAIgG）水平变化,及两组临床疗效和复发率.结果 各组间总T细胞无变化,A、B两组治疗前T细胞亚群分布异常,CD4^＋细胞减少,CD8^＋细胞增加,CD4^＋/CD8^＋比值下降,PAIgG水平升高,两组间差异无显著性（P均＞0.05）.治疗后3月复查,A组CD4^＋细胞增加,CD8^＋细胞减少,CD4^＋/CD8^＋比值和PAIgG值恢复至正常对照组水平,而B组虽有所恢复,但未达正常,A组显效＋良效97%,复发率为3%,B组显效＋良效70%,复发率为30%,两组差异有显著性（P均＜0.05）.结论 对有H.pylori感染的ITP患儿,联合抗H.pylori治疗比单纯应用免疫抑制治疗,异常的T细胞亚群和PAIgG水平恢复较快,疗效较好,复发率低.     

Clinical and pathological importance of cagA-positive Helicobacter pylori strains in children with abdominal complaints

Background. The aim of this study was to assess the correlation between the prevalence of Helicobacter pylori strains possessing cytotoxin-associated gene A ( cag A) in children and the intensity of clinical complaints and morphological changes of the gastric mucosa.
Materials and Methods. A group of 80 children with gastrointestinal complaints was included in this study. Pathologists examined mucosal biopsy specimens from these patients. The urease test and multiplex polymerase chain reaction (MPCR) were used to identify H. pylori strains.
Results. In the group of children infected with cag A-positive H. pylori strains, fourth-degree gastritis was more frequent than in the group with cag A-negative H. pylori colonization. In histopathological assessment, infection with cag A-positive H. pylori was associated also with higher grades of inflammatory intensity and activity.
Conclusions. Marked inflammation of the antral mucosa was significantly more frequent in children infected with cag A-positive H. pylori than in those infected with cag A-negative H. pylori , as assessed endoscopically and histopathologically. No specific symptoms for cag A-positive and cag A-negative H. pylori infection were observed.     

The influence of cholecystokinin on gastric myoelectrical activity in duodenal ulcer following Helicobacter pylori eradication--an electrogastrographic study.

Cholecystokinin (CCK) plays an important role in the regulation of postprandial gastric motor activity which was found to be abnormal in duodenal ulcer patients. This study was designed to compare the influence of CCK on gastric myoelectrical function in duodenal ulcer patients and healthy controls. Fifteen patients with active duodenal ulcer and Helicobacterpylori (H. pylori) infection and 15 healthy controls were included into this study. Electrogastrography (EGG) was performed before and 4 weeks after the eradication of H. pylori in ulcer patients and in healthy controls. We compared EGG parameters in the fasting and postprandial period and during intravenous infusion of caerulein, an analog of CCK with or without addition of loxiglumide, a specific CCK-1 receptor antagonist. The amplitude of fasting EGG in duodenal ulcer patients was similar to that in control subjects and was not affected by H. pylori eradication. In contrast, the amplitude of postprandial EGG was markedly increased in duodenal ulcer patients when compared to that in healthy controls and it was significantly reduced following the eradication of H. pylori. The blockade of CCK-1 receptors with loxiglumide in healthy controls or H. pylori eradicated ulcer patients significantly enhanced postprandial EGG amplitude almost to the level observed in the infected duodenal ulcer patients, but failed to affect this amplitude in ulcer patients. Exogenous caerulein, an analog of CCK, failed to affect EGG amplitude in duodenal ulcer patients with H. pylori infection, but it reduced significantly EGG amplitude in these patients after H. pylori eradication and in control subjects. This inhibitory effect of caerulein in H. pylori negative ulcer patients and healthy controls was abolished by the addition of loxiglumide. Ulcer patients showed significant dysrhythmia with tachygastria up to 20% of the recording time both under basal conditions and postprandially and H. pylori eradication was followed by a significant decrease in tachygastria to about 5%, the value being similar to that in healthy controls. We conclude that the amplitude and frequency of gastric myoelectrical activity are enhanced in duodenal ulcer patients and impaired in response to CCK but these changes can be normalized by successful H. pylori eradication.     

Reactive Nitrogen Species Mediate DNA Damage in Helicobacter pylori-Infected Gastric Mucosa

Background:  Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected with Helicobacter pylori . 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated DNA oxidation, respectively. In this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify how H. pylori infection causes nitrative DNA damage to gastric epithelial cells.
Methods:  Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) with H. pylori -positive gastritis and 19 patients (11 men and 8 women) exhibiting successful H. pylori eradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system.
Results:  In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication in both corpus and antral mucosa ( p  = .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG ( p  = .004 and .007, respectively).
Conclusions:  Helicobacter pylori infection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG for H. pylori -induced DNA damage in gastric mucosa.