Cardiovascular autonomic response to food ingestion in patients with gastritis: a comparison between Helicobacter pylori-positive and -negative patients

BACKGROUND: Feeding evokes a cardiovascular response associated to an increased sympathetic drive. The role of the parasympathetic component in this regard is less clear. Improvement of postprandial vasovagal complaints after Helicobacter pylori eradication in three cases led us to assess autonomic response to feeding in H. pylori-positive patients in search for an exacerbated parasympathetic response. MATERIAL AND METHODS: Patients with mild or moderate chronic histologic gastritis were studied. Subjects with the same diagnosis but testing negative for H. pylori were used as controls. Noninvasive cardiovascular tests were applied before and after feeding. RESULTS: On sympathetic tests, standing postprandial blood pressure was lower than preprandially in 5/12 H. pylori-positive patients and in 0/9 controls, p = .045. Resting postprandial BP on handgrip test was significantly lower than preprandially only in H. pylori-positive patients (71 +/- 8 versus 76 +/- 6 mmHg, p = .0068). Regarding parasympathetic tests, the 4-s unloaded exercise revealed greater initial heart rate response to unloaded cycling after feeding than preprandially again only in H. pylori-positive patients (1.40 +/- 0.20 versus 1.33 +/- 0.17, p = .0195). On tests influenced by both branches of the autonomic system, a difference was seen in the chronotropic response to handgrip. Postprandial heart rate on effort of H. pylori-positive patients was not higher than preprandially in contrast to controls [intervals between 2 consecutive R waves on electrocardiogram (R-R intervals) of 666 +/- 39 versus 685 +/- 62 ms, p = .0195], suggesting blunted sympathetic activation in the former. CONCLUSION: Supporting the observations that motivate the study, our findings indicate blunted sympathetic reactivity and exacerbated vagal response to feeding in H. pylori-positive patients.     

四联疗法治疗幽门螺杆菌阳性胃溃疡的疗效观察

目的：观察埃索美拉唑联合瑞巴派特、阿莫西林、克拉霉素治疗幽门螺杆菌阳性胃溃疡临床疗效。方法：60例确诊的Hp阳性胃溃疡患者随机分为对照组（30例）和治疗组（30例）,其中对照组患者给予奥美拉唑＋阿莫西林＋克拉霉素三联法治疗,实验组给予埃索美拉唑＋瑞巴派特＋阿莫西林＋克拉霉素四联法治疗。观察比较两组患者临床症状缓解情况,溃疡愈合率、Hp根除率及溃疡复发率。结果：①经过治疗,所有患者腹痛、腹胀、反酸、暧气等临床症状积分均显著降低（P〈0.01）,且治疗组下降程度大于对照组,两组间差异有统计学意义（P〈0.05）。②治疗组患者痊愈率为60.00%、总有效率为93.33%,明显高于对照组痊愈率（43.33%）和总有效率（80.00%）,两组间差异有统计学意义（P〈0.05）。③治疗组S2期获得率、溃疡愈合率和Hp根除率分别为93.33%、96.67%和93.33%,显著高于对照组60.00%的S2期获得率、70.00%的愈合率和83.33%的根除率（P〈0.01或0.05）。④随访1年后,治疗组患者溃疡复发率为11.54%,与对照组32.00%的复发率比较差异有显著性（P〈0.05）。结论：四联疗法治疗幽门螺杆菌阳性胃溃疡可有效缓解患者临床症状,提高溃疡愈合质量,根除Hp感染,减少复发,效果优于三联疗法。     

Serum leptin levels in patients with sideropenic and pernicious anemia: the influence of anemia treatment

Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure regulation and numerous other physiological processes. Recently, leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n = 18) and pernicious anemia (n=7) before and during anemia treatment. Blood samples for the blood count, leptin and erythropoietin determinations were obtained by venepunction at the time of the diagnosis of anemia and after partial and complete anemia recovery. The relationships of serum leptin levels to erythropoietin levels and blood count parameters were also studied. No significant differences in serum leptin levels between the groups studied were found. The serum leptin levels in none of groups were modified by treatment of anemia (basal levels, the levels during treatment and after anemia recovery were 13.1+/-14.5 vs 12.8+/-15.6 vs 12.0+/-14.8 ng/ml in patients with sideropenic anemia and 7.8+/-8.5 vs 9.5+/-10.0 vs 8.9+/-6.6 ng/ml in patients with pernicious anemia). The erythropoietin levels were higher at the time of anemia in both groups and decreased significantly after partial or complete recovery. Serum leptin levels in both groups correlated positively with the body mass index. No significant relationships were found between serum leptin levels and erythropoietin values or various parameters of the peripheral blood count. We conclude that serum leptin levels in patients with sideropenic and pernicious anemia positively correlate with the body mass index but are not influenced by the treatment of anemia.     

Local and peripheral cytokine response and CagA status of Helicobacter pylori-positive patients with duodenal ulcer

The mucosal production of TNF-alpha, IL-6, IL-8, IL-10 and nitrotyrosine was investigated in H. pylori-positive patients with duodenal ulcer (DU). The concentrations of these cytokines in gastric antrum mucosal specimens from patients infected with H. pylori (n = 40) were determined by ELISA and compared with data on mucosal specimens from H. pylori-negative patients (n = 12). Nitrotyrosine was determined by ECL Western blotting. It was additionally investigated whether the tissue levels of the cytokines correlated with the peripheral cytokine levels, and the CagA status of the patients. The local TNF-a, IL-6 and IL-8 concentrations in the antral biopsy samples were significantly higher (p < 0.001) in the patients infected with H. pylori than in the samples from the H. pylori-negative subjects. There was a negative correlation between the TNF-alpha and IL-10 concentrations. Further more, in 23 of the 40 biopsy specimens, considerable nitrotyrosine production was detected by ECL Western blotting. There was no significant difference in peripheral TNF-a and IL-6 production between the DU patients and healthy blood donors (n = 100; 58% of whom were also H. pylori-positive). Only the in vitro IL-8-producing capacity was higher in the peripheral blood of the DU group after ex vivo induction with H. pylori. CagA positivity was demonstrated in 39 (97.5%) of the 40 patients with DU, and in 41 (70.7%) of the 58 H. pylori-positive, healthy blood donors. This study suggests that besides the bacterial virulence factor, the host response, with an increased mucosal production of inflammatory cytokines and reactive oxygen and nitrogen species could be relevant to the gastric pathophysiology in H. pylori-induced DU. There is no generalized cytokine overproduction in these DU patients, but the moderate increase in in vitro IL-8 production might be of pathophysiological importance.     

Alkylhydroperoxide reductase of Helicobacter pylori as a biomarker for gastric patients with different pathological manifestations

The development of various gastrointestinal diseases was suggested to be associated with chronic inflammation as a consequence of Helicobacter pylori (H. pylori) infection. Our previous studies showed that an antioxidant protein alkylhydroperoxide reductase (AhpC) is an abundant and important antioxidant protein present in H. pylori. In this study we have explored the potential of utilizing antibodies to AhpC for detection of patients who are at high risks of evolving into severe outcomes of gastric malignancies after H. pylori infection. The correlation between AhpC and extents of inflammatory damage in tissues was demonstrated by immunoblotting assays and endoscopic examinations. Oxidative stress-induced high-molecular-weight (HMW) AhpC with chaperone activity in vivo was further investigated by co-immunoprecipitation, 2-dimensional gel electrophoresis (2-DE) followed by nano-liquid chromatography coupled tandem mass spectrometry (nanoLC-MS/MS). We found AhpC was consistently expressed in higher amounts in H. pylori strains isolated from patients with gastric cancer (GC) than gastritis (GA). Immunological analysis of seropositivity for AhpC indicated that positive diagnostic rates for H. pylori-infected patients with GA, gastric ulcer (GU) and GC were 68% (15/22), 100% (50/50) and 100% (50/50), respectively. In great contrast to low-molecular-weight (LMW) AhpC, HMW AhpC with chaperone function was found to distribute inside of H. pylori cells. We also found that LMW forms of AhpC were recognized by serum antibodies from GA patients whereas HMW forms of AhpC reacted mainly with those from GU and GC patients. Based on the significant difference between AhpC isolated from strains of GC and GA, it is conceivable that AhpC of H. pylori may prove to be useful as a prognostic or diagnostic protein marker to monitor varied clinical manifestations of gastrointestinal patients infected with H. pylori.     

Incidence and significance of micronuclei in pernicious anemia

The incidence of micronuclei in bone marrow erythroblasts of patients with pernicious anemia ranged between 0.5-5.6% as compared with the value of 0-0.5% noted in hematologically healthy patients. The mechanism of formation and the possible significance of micronuclei in megaloblastic anemia are briefly discussed.     

Colonization of Helicobacter pylori in the gastric mucosa of Mongolian gerbils

Helicobacter pylori was orally inoculated into Mongolian gerbils. The organisms were able to colonize in the gastro-mucosal layer of the gerbils, especially in those gerbils which had mucosal lesions caused by indomethacin treatment. The pathological changes developed by H. pylori infection were restricted to the stomachs, and only slightly inflammatory cells were observed.     

The role of endogenous and exogenous prostacyclin in the gastric mucosa under physiological and pathological circumstances

The intracellular effect of exogenously administered prostacyclin in the gastric mucosa seems to be a polyphasic effect, namely: 1. Effect on the cyclic nucleotide (cAMP, cGMP), turnover; 2. Effect on the calmodulin-content; 3. DNA and RNA changes; 4. Influence on protein synthesis; 5. New cell formation. While the endogenous prostacyclin exerts a natural protection against damaging noxae.     

Lectin histochemistry of the gastric mucosa in normal and Helicobacter pylori infected guinea-pigs

Helicobacter pylori attaches via lectins, carbohydrate binding proteins, to the carbohydrate residues of gastric mucins. Guinea-pigs are a suitable model for a H. pylori infection and thus the carbohydrate composition of normal and H. pylori infected gastric mucosa was investigated by lectin histochemistry. The stomach of all infected animals showed signs of an active chronic gastritis in their mucosa, whereas no inflammation was present in the control animals. The corpus–fundus regions of the controls showed heterogeneous WGA, SNA-I, UEA-I and HPA binding in almost all parts of the gastric glands. While these lectins labelled the superficial mucous cells and chief cells heterogeneously, the staining of the parietal cells was limited to WGA and PHA-L. Mucous neck cells reacted heterogeneously with UEA-I, HPA, WGA and PHA-L. In the antrum, the superficial mucous cells and glands were stained by WGA, UEA-I, HPA, SNA-I or PHA-L. WGA, UEA-I, SNA-I and HPA labelled the surface lining cells strongly. The mucoid glands reacted heterogeneously with WGA, UEA-I, HPA, SNA-I and PHA-L. In both regions, the H. pylori infected animals showed similar lectin binding pattern as the controls. No significant differences in the lectin binding pattern and thus in the carbohydrate composition between normal and H. pylori infected mucosa could be detected, hence H. pylori does not induce any changes in the glycosylation of the mucosa of the guinea-pig. This unaltered glycosylation is of particular relevance for the sialic acid binding lectin SNA-I as H. pylori uses sialic acid binding adhesin for its attachment to the mucosa. As sialic acid binding sites are already expressed in the normal mucosa H. pylori can immediately attach via its sialic acid binding adhesin to the mucosa making the guinea-pig particularly useful as a model organism.This work is dedicated to Professor B. Tillmann on the occasion of his 65th birthday     

Normalization of phospholipids concentration of the gastric mucosa was observed in patients with peptic ulcer after eradication of Helicobacter pylori

Background. Phospholipids concentration in the gastric mucosa decreased in patients with Helicobacter pylori infection. The aim of this study is to examine the effects of eradication of H. pylori on decreasing the phospholipids concentration in the gastric mucosa in patients with gastric or duodenal ulcer. Materials and Methods. Phospholipids (phosphatidylcholine, phosphatidylethanolamine, and sphingonomyeline) were measured in biopsy specimens from the antrum and corpus using thin‐layer chromatography. In H. pylori positive patients with gastric ulcer (n = 26) and duodenal ulcer (n = 13), and H. pylori negative controls (n = 20), the biopsy specimens were obtained before and 3 months after eradication. Eradication was performed using lansoprazole, amoxycillin, and clarithromycin. Results. Compared with the H. pylori negative control group, the concentrations of phosphatidylcholine and phosphatidylethanolamine decreased significantly in the gastric ulcer group in both antrum and corpus mucosa, and in the duodenal ulcer group in antrum mucosa. This decrease returned to the control level after eradication. Conclusions. This study demonstrates that the eradication of H. pylori in patients with peptic ulcer normalized the decrease of phosphatidylcholine and phosphatidylethanolamine in the gastric mucosa.     

Inflammatory gene profiles in gastric mucosa during Helicobacter pylori infection in humans

Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, ultimately leading to cellular hyperproliferation and malignant transformation. Hitherto, only expression of a single gene, or a limited number of genes, has been investigated in infected patients. cDNA arrays were therefore used to establish the global pattern of gene expression in gastric tissue of healthy subjects and of H. pylori-infected patients. Two main gene expression profiles were identified based on cluster analysis. The data obtained suggest a strong involvement of selected Toll-like receptors, adhesion molecules, chemokines, and ILs in the mucosal response. This pattern is clearly different from that observed using gastric epithelial cell lines infected in vitro with H. pylori. The presence of a "Helicobacter-infection signature," i.e., a set of genes that are up-regulated in biopsies from H. pylori-infected patients, could be derived from this analysis. The genotype of the bacteria (presence of genes encoding cytotoxin-associated Ag, vacuolating cytotoxin, and blood group Ag-binding adhesin) was analyzed by PCR and shown to be associated with differential expression of a subset of genes, but not the general gene expression pattern. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Future studies may help identify gene expression patterns predictive of complications of the infection.