Serum neopterin as a marker for reactional states in leprosy

Reactions, a relatively common phenomenon among leprosy patients in treatment, require early detection and proper management to prevent serious sequelae. It is generally accepted that reactional states are immunologically mediated and, as such, usually improve with immunomodulatory treatments such as corticosteroids or thalidomide. Neopterin, a product of gamma-interferon-activated macrophages, is a marker for cell-mediated immune activation and may be useful to detect reactional states in leprosy. Here, we compared neopterin levels in single serum samples from leprosy patients with and without reaction with untreated controls and, when available, serial samples among patients with and without reaction. Levels in the single sample measurements, conducted in 22 patients with a reversal reaction (mean 14.5 nmol l(-1), S.D. 8.7) and 13 with erythema nodosum leprosum (mean 16.9 nmol l(-1), S.D. 13.6), were significantly higher (P=0.02 and P=0.001, respectively) than levels in 26 untreated patients (mean 9.1 nmol l(-1), S.D. 7.3). Values above the upper limit of normal (10 nmol l(-1)) were found in seven of 26 untreated patients, 14 of the 22 reversal reaction patients (P=0.01) and 10 of the 13 ENL patients (P=0.003). Serial serum samples, obtained from six patients that developed reactions and 14 that remained free of reaction, indicated that reversal reaction or erythema nodosum leprosum paralleled a concomitant increase in the serum neopterin level. Neopterin levels generally declined upon corticosteroid therapy. Neopterin may be a useful marker for reactional states in leprosy by providing a laboratory parameter to assess the onset, progression, response to therapy and resolution.     

Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count

Background

While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression.

Methods

Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves.

Results

Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm³ (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP).

Conclusion

Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB.     

Neopterin in renal cell carcinoma: inhalational administration of interleukin-2 is not accompanied by a rise of urinary neopterin.

Inhalational administration of interleukin-2 (IL-2) is effective in controlling renal cell carcinoma (RCC) lung metastases with minimal toxicity. Neopterin is an indicator of systemic immune activation in metastatic cancer and is increased after systemic IL-2 administration. Urinary neopterin was investigated in 13 patients with metastatic RCC and 18 controls. In seven patients, urinary neopterin was followed before and after treatment with inhalational IL-2. Neopterin was measured by high-performance liquid chromatography and creatinine was determined by Jaffé reaction. Urinary neopterin was significantly increased in patients with metastatic RCC compared to controls (257 +/- 263 micromol/mol creatinine vs. 110 +/- 41 micromol/mol creatinine; Mann-Whitney U-test, p < 0.05). Median survival was significantly longer in patients with urinary neopterin <173 micromol/mol creatinine compared to patients with neopterin > or = 173 micromol/mol creatinine (698 vs. 245 days; log-rank test, p < 0.05). No significant increase was observed after inhalational IL-2 therapy (147 +/- 101 vs. 153 +/- 54 micromol/mol creatinine). We conclude that urinary neopterin is increased in patients with metastatic RCC, and higher neopterin concentrations are indicative of poor prognosis. The absence of an increase in urinary neopterin after inhalational IL-2 therapy is in accord with the lack of significant systemic toxicity.     

Markers of acute stress in pigs

This study explores the biological validation of markers of acute stress in pigs subjected to transportation for slaughter. The stress markers selected for monitoring were neopterin and cortisol. Their levels in pig serum were measured for two porcine stress syndrome genotypes, NN and Nn, after a 30-min transport to a slaughterhouse. Blood samples were withdrawn before transport (control group) and immediately after the animals' arrival (experimental group). The values of neopterin and cortisol measured before the transport were 5.60+/-1.65 nmol/l and 273.54+/-66.17 nmol/l respectively. After the transfer, the concentration of cortisol rose significantly compared to the control (355.69+/-85.13 nmol/l, p<0.01). Neopterin concentrations in the serum (8.25+/-1.60 nmol/l) were also significantly higher (p<0.01) after transportation. The elevated concentrations of both analytes were found to be independent of the genotype. These results document the stimulation of the endocrine system and the immune system that develops in animals undergoing transportation for slaughter.     

Mechanism of neopterin-induced myocardial dysfunction in the isolated perfused rat heart

Neopterin is a sensitive marker for diseases involving increased activity of the cellular immune system in humans. Many studies, however, provide evidence for neopterin not only as a marker, but also for its characteristic effects. Recently, we were able to demonstrate a considerable influence of exogenous neopterin at a concentration of 100 mumol/l on cardiac performance in the Langendorff model of isolated perfused rat hearts. The present study was designed to investigate its possible mechanism. During co-infusion of neopterin at a concentration of 100 mumol/l with the unspecific nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine monoacetate, the nitric oxide donor PAPA NONOate, the free radical scavenger N-acetylcysteine, or the pro-inflammatory cytokine tumor necrosis factor-alpha the effects on cardiac contractility parameters and coronary vascular resistance were studied in 67 male Sprague-Dawley rats. The temperature-controlled and pressure-constant Langendorff apparatus was used with retrograde perfusion of the aorta and a Krebs-Henseleit buffer. Neither the unspecific nitric oxide synthase inhibitor nor the nitric oxide donor excludes nitric oxide from playing a mechanistic role in our perfusion studies. Tumor necrosis factor-alpha was without any synergistic or antagonistic effects when co-treated with neopterin. N-acetylcysteine was most effective in abolishing neopterin-dependent effects on cardiac function. The negative effects of neopterin on cardiac performance might be due to an enhancement of oxidative stress by neopterin that can be attenuated by the antioxidant N-acetylcysteine. Neopterin has to be considered a pathogenic factor in the development of cardiac dysfunction in chronic disease states with high neopterin levels secondary to activation of the immune system.     

Monitoring of immune activation using biochemical changes in a porcine model of cardiac arrest

In animal models, immune activation is often difficult to assess because of the limited availability of specific assays to detect cytokine activities. In human monocytes/macrophages, interferon-gamma induces increased production of neopterin and an enhanced activity of indoleamine 2,3-dioxygenase, which degrades tryptophan via the kynurenine pathway. Therefore, monitoring of neopterin concentrations and of tryptophan degradation can serve to detect the extent of T helper cell 1-type immune activation during cellular immune response in humans. In a porcine model of cardiac arrest, we examined the potential use of neopterin measurements and determination of the tryptophan degradation rate as a means of estimating the extent of immune activation. Urinary neopterin concentrations were measured with high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA) (BRAHMS Diagnostica, Berlin, Germany). Serum and plasma tryptophan and kynurenine concentrations were also determined using HPLC. Serum and urine neopterin concentrations were not detectable with HPLC in these specimens, whereas RIA gave weakly (presumably false) positive results. The mean serum tryptophan concentration was 39.0 +/- 6.2 micromol/l, and the mean kynurenine concentration was 0.85 +/- 0.33 micromol/l. The average kynurenine-per-tryptophan quotient in serum was 21.7 +/- 8.4 nmol/micromol, and that in plasma was 20.7 +/- 9.5 nmol/micromol (n = 7), which corresponds well to normal values in humans. This study provides preliminary data to support the monitoring of tryptophan degradation but not neopterin concentrations as a potential means of detecting immune activation in a porcine model. The kynurenine-per-tryptophan quotient may serve as a short-term measurement of immune activation and hence permit an estimate of the extent of immune activation.     

Urinary neopterin in patients with advanced colorectal carcinoma

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 micromol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.     

Serum neopterin concentrations during treatment of leishmaniasis: useful as test of cure?

Neopterin, a product of gamma-interferon-activated macrophages, was measured in sera from 28 patients (12 patients with cutaneous leishmaniasis and 16 patients with visceral leishmaniasis) to determine the utility as a marker of disease activity and therapeutic efficacy. Patients originated from Kenya (n=5) and from the Academic Medical Center, Amsterdam, The Netherlands (n=23). In seven patients follow-up sera after treatment were available. Two patients at the time of diagnosis of visceral leishmaniasis were co-infected with HIV. The 12 patients with cutaneous leishmaniasis had serum neopterin levels below the upper limit of the normal range. All 16 patients with visceral leishmaniasis had elevated levels of serum neopterin before treatment. In six out of seven patients with visceral leishmaniasis followed during treatment neopterin levels decreased to values below the upper limit of the normal range (10 nmol l(-1)). Sequential measurements of serum neopterin levels may be useful for monitoring therapeutic efficacy in patients with visceral leishmaniasis.     

Salivary specific IgG is a sensitive indicator of the humoral immune response to Helicobacter pylori

Abstract In humans, salivary antibodies are secreted during humoral immune response. Helicobacter pylori infection is associated with systemic humoral immune response reflected by raised serum levels of specific IgG. The present study was aimed at exploring whether salivary concentrations of specific H. pylori IgG are a reliable indicator of H. pylori infection. Serum and salivary samples were obtained from 291 subjects attending the GI clinic and tested for H. pylori -specific IgG by a direct ELISA (94% sensitivity, 95% specificity for serum determinations) using a crude H. pylori sonicate as antigen. Data are given as optical density (mean±S.D.). Levels of salivary H. pylori IgG paralleled those of circulating specific IgG in the 291 subjects studied (0.981±0.431 vs. 0.777±0.682, respectively). A significant positive correlation was found between specific H. pylori IgG in sera and saliva samples (r = 0.981, P < 0.0001). An overall concordance between circulating and salivary H. pylori IgG was observed in 238 out of the 291 (81.7%) subjects. Salivary H. pylori IgG represent a sensitive marker of specific humoral immune response and they may substitute circulating H. pylori IgG measurement when sera samples are not available.     

Gastric Juice Polymerase Chain Reaction: An Alternative to Histology in the Diagnosis of Helicobacter pylori Infection

Background. Infection from Helicobacter pylori plays a role in several gastroduodenal diseases. The recent availability of molecular techniques, particularly the polymerase chain reaction (PCR), allows us to detect small amounts of this bacterium. The aims of this study were to compare PCR and histological findings and to ascertain the clinical usefulness of H. pylori PCR identification in different biological samples.
Materials and Methods. We studied 94 consecutive patients. Saliva, gastric juice, and four antral and four body biopsies were obtained from each patients. H. pylori was evaluated histologically in two antral and two body biopsies (Giemsa or Warthin-Starry stain). After extraction, DNA was submitted for PCR amplification using the two primers HPU1 and HPU2, which amplified a 411-bp product from the urease gene A.
Results. Forty-nine patients were H. pylori -positive at histological workup. The sensitivity of PCR was 92% for gastric juice, 73% for antral biopsies, 61% for body biopsies, and 13% for saliva. Of the 45 H. pylori -negative patients at histological assessment, 7 (16%) had positive findings on PCR, mainly when gastric juice was examined.
Conclusions. These results indicate that PCR is as sensitive as histological assessment. We suggest that PCR H. pylori detection in gastric juice is a sensitive method for diagnosing this infection.     

Helicobacter pylori Infection, Gastritis, and the Temperature of Choice for Hot Drinks

Background. The role of the temperature of the diet as a potential etiological factor for gastritis or peptic ulcer disease has been postulated since the beginning of the century. Animal studies have demonstrated damage to gastric mucosa caused by hot water at 60 to 80°C. In the pre- Helicobacter pylori era it was reported that the majority of ulcer patients preferred hot drinks. It also was reported that the temperature of choice for drinks increased with severity of histological grade of gastritis. We evaluated the association between the preferred temperature of hot drinks and the presence of H. pylori infection.
Methods. We tested the temperature of choice for hot drinking liquids among 12 H. pylori -negative and 43 H. pylori -positive volunteers. We also compared the effect of H. pylori therapy on hot drink temperature preference and, in 32 individuals, whether there was a relation between temperature and the degree of gastric atrophy.
Results. There was no difference in the preferred temperature for hot drinks between those volunteers with and without H. pylori infection (63.4°± 6°C compared to 61.3°± 7°C, respectively) (mean ± 1 SD, p =.3) There was no change in preferred temperature after successful therapy of the H. pylori infection compared to unsuccessful H. pylori therapy, nor was there a correlation between the preferred temperature and the presence, absence, or degree of gastric atrophy ( r ² < 0.001).
Conclusion. The temperature of preference for hot drinks was not influenced by H. pylori infection or by the presence of atrophic gastritis.     

Helicobacter pylori defines local immune response through interaction with dendritic cells

The bacterial pathogen Helicobacter pylori colonizes the human gastric and duodenal mucosa, evades clearance by the host response and is associated with peptic ulcer disease and an increased risk of gastric adenocarcinoma. Dendritic cells (DCs) are initiators of the immune response to H. pylori. The aim of the current study was to investigate the interaction between H. pylori with DCs. To determine the impact of H. pylori on the maturation and the activation of monocyte-derived DCs, the effect of 20 clinical H. pylori strains with different inflammatory backgrounds on adenocarcinoma gastric epithelial cells was investigated. The inflammatory background was defined according to the degree of lymphocyte and granulocyte infiltration and the bacterial density at the site of infection. DC maturation and activation varied after exposure to the different strains. While maturation appeared to be independent of any virulence factor tested, a significant increase in the average level of cytokine production was observed for the proinflammatory cytokines interleukin-12 (IL-12), tumour necrosis factor-α, IL-6 and IL-1β when comparing strains with low inflammatory backgrounds with those of the medium or high backgrounds. In conclusion, the DC response towards different strains in vitro was associated with the clinical outcome of the individual host, suggesting a major role of this cell type in modulating strain-specific H. pylori infection.     

High concentrations of D-amino acids in human gastric juice

Summary. The concentrations of free D- and L-amino acids were determined in the gastric juice from four groups: patients suffering from early gastric carcinoma with or without Helicobacter pylori infection, and patients without carcinoma but with peptic ulcers, duodenal ulcers or chronic gastritis with or without H. pylori infection. H. pylori is a bacterium associated with gastric inflammation and peptic ulcers and is a risk factor for stomach cancer. The highest D-amino acid ratios (free D-amino acid concentration to the total corresponding free D- and L-amino acid concentration) were 29%, 26%, 18%, 4% and 1% for proline, alanine, serine, aspartate and glutamate, respectively. The gastric juice levels of L-alanine, L-serine, L-proline, L-glutamate and D-alanine in the samples obtained from subjects bearing early gastric carcinoma and H. pylori were significantly higher than in the samples from the other three groups. Except for D-alanine, there was no correlation between the D-amino acid concentrations and presence of carcinoma or H. pylori.     

Isotypic analysis of specific antibody response in serum, saliva, gastric and rectal homogenates of Helicobacter pylori-infected patients

Abstract The relationship between systemic and local humoral immune response to Helicobacter pylori is poorly understood. To further address this issue we measured, using ELISA, H. pylori -specific IgG and IgA antibodies in serum, saliva, gastric and rectal homogenates of H. pylori -infected patients. A total of 107 patients who underwent upper GI endoscopy and/or sigmoidoscopy were studied. The isotypic pattern of H. pylori -specific antibodies appeared to differ at the serum, salivary, gastric and rectal mucosa level. Serum H. pylori IgG titers were higher than those of the serum-specific IgA. On the contrary, in saliva samples. H. pylori IgA titers were higher than specific IgG titers. In gastric homogenates, specific IgG and IgA titers were similar. H. pylori -specific IgG were detectable in rectal homogenates but no or very low H. pylori -specific IgA were found in the same material. Furthermore, no difference was found in H. pylori IgG and IgA in serum, saliva and gastric homogenates between duodenal ulcer and non-ulcer dyspepsia patients. Data of the present study indicate that, in H. pylori -infected patients, the specific immune response is as follows: (1) it involves the secretory immune system; (2) it is paralleled by the specific salivary IgA; (3) it does not differentiate duodenal ulcer from non-ulcer dyspepsia patients; and (4) it does not take place in the large bowel.     

Effect of Omeprazole Therapy on the Survival of Helicobacter pylori, Urease Activity, and Antral Gastric Histology in Patients with Duodenal Ulcer

Background. Helicobacter pylori is associated with chronic active gastritis and peptic ulceration (PU). Omeprazole is a proton pump inhibitor that is effective in healing PU and reducing gastritis. Previously it has been found that omeprazole has some bacteriostatic activity against H. pylori both in vitro and in vivo and in inhibiting urease activity in vitro. Our aim was to evaluate the effect of omeprazole on H. pylori colonization of the gastric mucosa, urease activity in vivo, and the presence of associated gastritis in patients with duodenal ulcer (DU).
Materials and Methods. We studied 12 patients (7 men and 5 women, ages 22–68 yr) with Du larger than 5 mm in diameter with a positive CLOtest (Delta West Ltd., Australia). Omeprazole, 20 mg bid, was given for 8 weeks to each patient, patients were endoscoped at the end of this period to check for healing of DU, and repeat biopsies were obtained from the gastric antrum for histologyical analysis, CLOtest, and culture.
Results. DU healed completely in all patients. Likewise in all patients there was significant reduction in the urease activity, from 22.1=4.17 to 1.58 ± 0.92 units/ml ( p <.001; 95% confidence interval of the difference between means, 32.7–14.1), and reduced H. pylori density, from 1,403.46 ± 128.23 to 422.5 ± 172.39 colony-forming units (CFU) per milligram of tissue biopsy ( p < .001; 95% confidence interval of the difference between means, 1,486.1–590.5). The numbers of H. pylori were reduced on the gastric mucosa after omeprazole therapy and disappeared in six patients, a result that correlated with a negative CLOtest reading after 24 hours.
Conclusion. Omeprazole, 20 mg bid, is capable of reducing H. pylori numbers and urease activity in vivo. There was no significant reduction in the severity of antral gastritis in DU patients studied.     

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)     

PCR detection of Helicobacter pylori in string-absorbed gastric juice

Molecular methods for detection of Helicobacter pylori infection have been shown to be highly sensitive in gastric biopsies and cultures. The objective of this work was to compare PCR detection of H. pylori DNA in string-absorbed gastric juice and in gastric biopsies. The study was performed in 47 dyspeptic adult patients undergoing endoscopy, and infection was detected by amplification of a segment of H. pylori ureA gene. Of the 29 patients positive in biopsy analysis, 23 (79%) were also positive in the gastric string. PCR analysis of gastric strings is a sensitive and safe procedure to detect H. pylori when endoscopy is not indicated, and may be of great clinical and epidemiological usefulness in determining effectiveness of eradication therapies, typing virulence genes and detecting antibiotic resistance mutations.     

Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation

BACKGROUND: Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. METHODS: Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. RESULTS: H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). CONCLUSIONS: The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.     

幽门螺杆菌通过激活磷脂酰肌醇3-激酶信号来调节细胞迁移

目的幽门螺杆菌被认为是诱发胃癌的最强的风险因素。幽门螺旋杆菌的毒性成分是可以增加癌症危险的cag分泌系统,它可以使cagA和肽聚糖易位进入宿主细胞,进而激活信号转导通路。AKT是磷脂酰肌醇3。激酶（PI3K）的目的蛋白,并在胃癌中被激活,但PI3K-AKT和具有潜在致癌性的幽门螺旋杆菌诱导的细胞反应之间的关系尚不清楚。方法我们揭示了介导幽门螺旋杆菌刺激的AKT活化和胃上皮细胞的这些生物学结果之间的分子通路。结果幽门螺旋杆菌以Scr和表皮生长因子受体依赖性方式增加PI3K-AKT的信号,是幽门螺旋杆菌诱导的细胞迁移不可或缺的。结论这些结果表明,PI3K-AKT信号调节幽门螺旋杆菌诱发的病理生理反应,从而降低癌变门槛。