Establishment of Experimental Murine Peritonitis Model with Hog Gastric Mucin for Carbapenem-Resistant Gram-Negative Bacteria

Animal models are essential to studies of infectious diseases. The use of mice to test bacterial infection has been extensively reported. However, methods applied to clinical isolates, particularly for carbapenem-resistant bacteria, must be tailored according to the infection models and bacteria used. In this study, we infected 6-week-old female BALB/c mice intraperitoneally with different strains of resistant bacteria plus 3% hog gastric mucin. This method was found to be efficient and readily applicable for investigation of carbapenem-resisant Gram-negative pathogens (e.g., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) detected in Korea.

Gastroprotective Effects of Glutinous Rice Extract against Ethanol-, Indomethacin-, and Stress-induced Ulcers in Rats / 전남의대학술지

This study was designed to evaluate the efficacy of an orally administered aqueous extract of glutinous rice (GRE) to protect against acute gastric mucosal lesions induced by ethanol, indomethacin, and water immersion restraint stress in rats and to characterize the active substances responsible for the protection. GRE was shown to dose-dependently prevent the gastric lesions induced by the above ulcerogenic treatments at doses of 30 to 300 mg/kg. GRE treatment increased the gastric mucin content and partially blocked the ethanol-induced depletion of the gastric mucus layer. Also, it increased the nonprotein sulfhydryl concentration in the gastric mucosa. The gastroprotective action of GRE was markedly enhanced by co-treatment with 4-8 mg/kg tea extracts. The activity of GRE was completely lost by heat treatment at 80degrees C for 3 min or treatment with 0.01% pepsin at 37degrees C for 1 h. Protein extraction studies indicated that prolamins are involved in the gastroprotective activity of GRE. Our results suggest that glutinous rice proteins are useful for the prevention and treatment of gastritis and peptic ulcer.

Gastroprotective Effects of Glutinous Rice Extract against Ethanol-, Indomethacin-, and Stress-induced Ulcers in Rats / 전남의대학술지

This study was designed to evaluate the efficacy of an orally administered aqueous extract of glutinous rice (GRE) to protect against acute gastric mucosal lesions induced by ethanol, indomethacin, and water immersion restraint stress in rats and to characterize the active substances responsible for the protection. GRE was shown to dose-dependently prevent the gastric lesions induced by the above ulcerogenic treatments at doses of 30 to 300 mg/kg. GRE treatment increased the gastric mucin content and partially blocked the ethanol-induced depletion of the gastric mucus layer. Also, it increased the nonprotein sulfhydryl concentration in the gastric mucosa. The gastroprotective action of GRE was markedly enhanced by co-treatment with 4-8 mg/kg tea extracts. The activity of GRE was completely lost by heat treatment at 80degrees C for 3 min or treatment with 0.01% pepsin at 37degrees C for 1 h. Protein extraction studies indicated that prolamins are involved in the gastroprotective activity of GRE. Our results suggest that glutinous rice proteins are useful for the prevention and treatment of gastritis and peptic ulcer.

Two cases of mucinous adenocarcinoma of the stomach mistaken as submucosal tumor / 대한외과학회지

A gastric carcinoma with the endoscopic features resembling submucosal tumor (SMT) is rare, and reportedly account for only 0.1% to 0.63% of all resected gastric carcinomas. The preoperative diagnosis of SMT-like gastric carcinoma is challenging, and thus, diagnosis is usually made intraoperatively or postoperatively. Furthermore, mucinous adenocarcinoma is an uncommon histologic subtype of gastric carcinoma characterized as an elevated lesion resembling SMT due to abundant mucin pools in submucosa. Here, we report two cases in which a gastric mucinous adenocarcinoma was mistaken as a SMT.

Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes

BACKGROUND: Gastric cancers with microsatellite instabilities (MSI) have been reported to be associated with favorable prognosis. However, the significance of the effect of MSI on the clinicopathological features, as well as its association with mucin phenotype, remains unclear. METHODS: MSI status was assessed in 414 cases of gastric cancer using polymerase chain reaction analysis of five microsatellite loci, as recommended by National Cancer Institution criteria. The expression of mucins (MUC5AC, MUC6, MUC2, and CD10) was assessed. RESULTS: Out of 414 total cases of gastric cancer, 380 (91.7%), 11 (2.7%), and 23 (5.6%) were microsatellite stable (MSS), low-level MSI (MSI-L), and high-level MSI (MSI-H), respectively. Compared to MSS/MSI-L, MSI-H gastric cancers were associated with older age (p=0.010), tumor size (p=0.014), excavated gross (p=0.042), intestinal type (p=0.028), aggressive behaviors (increase of T stage [p=0.009]), perineural invasion [p=0.022], and lymphovascular emboli [p=0.027]). MSI-H gastric cancers were associated with tumor necrosis (p=0.041), tumor-infiltrating lymphocytes (> or =2/high power field, p or =10% of mass, p=0.031), tumor-infiltrating lymphocytes (p<0.001), intestinal type (p=0.014), and gastric mucin phenotypes (p=0.020) could represent independent features associated with MSI-H gastric cancers. MSI-H intestinal type gastric cancers had a tendency for poor prognosis in univariate analysis (p=0.054) but no association in Cox multivariate analysis (p=0.197). CONCLUSIONS: Our data suggest that MSI-H gastric cancers exhibit distinct aggressive biologic behaviors and a gastric mucin phenotype. This contradicts previous reports that describe MSI-H gastric cancer as being associated with favorable prognosis.

Formación de cálculos biliares de colesterol: nuevos avances científicos / Cholesterol gallstone formation: new scientific advances

La investigación científica sobre la formación de cálculos biliares de colesterol, ha comprobado la participación de numerosos genes, entre los cuales se encuentran receptores nucleares y transportadores biliares. El desequilibrio fisicoquímico entre los lípidos biliares más importantes produce hipersecreción de colesterol en la bilis, una etapa necesaria para sobresaturar la vesícula biliar. Las sales biliares son insuficientes para solubilizar al colesterol en micelas mixtas, por lo que esta molécula se solubiliza, en su mayoría, dentro de liposomas (fosfolípidos y escasas sales biliares), y en ellos existe en alta concentración, que tiende a precipitar y a formar cristales, evento considerado como limitante para la formación de cálculos biliares. El desarrollo del cálculo puede acelerarse si existe hipersecreción de proteínas mucinas y escasa motilidad vesicular. La presente revisión tiene el objetivo de informar los nuevos aportes científicos sobre la formación de cálculos biliares de colesterol, analizando y discutiendo sus resultados enfocados a la búsqueda de tratamientos farmacológicos, porque la litiasis no tiene terapia eficaz y la colecistectomía es el método quirúrgico invasivo, cuando la enfermedad produce síntomas

Scientific research about cholesterol gallstone formation has shown the involvement of many genes, such as nuclear receptors and biliary transporters. Physicochemical imbalance of three major biliary lipids produces hypersecretion of cholesterol in bile, a key process for supersaturation of gallbladder. Bile salts are insufficient for solubilization of cholesterol in mixed micelles; therefore this molecule is solubilized mostly into liposome (phospholipids and few bile salts); there is a high concentration of cholesterol into liposomes, which leads to its precipitation and crystallization, the key factor for cholesterol gallstone formation. Development of gallstones might accelerated when there is hypersecretion of mucins and gallbladder hypomotility. The aim of this review is to inform about new scientific contributions of cholesterol gallstone formation, analyzing them to the investigation of possible pharmacological treatments, since it is a disease that has no effective treatment and the only cholecystectomy is an invasive surgical treatment for symptomatic gallstone

Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression

BACKGROUND: It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer. METHODS: We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH). RESULTS: Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes. CONCLUSIONS: Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type.

A Case of Submucosal Tumor-like Gastric Mucinous Adenocarcinoma Showing Mucin Waterfall / 대한소화기내시경학회지

Muinous gastric carcinoma (MGC) is a rare histological type that accounts for approximately 3~7% of all gastric carcinomas. The results of clinicopathological studies suggest that the overall survival rate for patients with MGC is worse than that for patients with non-mucinous tumors as MGC is more frequently diagnosed in the advanced stage. In this report, we preoperatively predicted the type of a tumor from its endoscopic finding. An endoscopic ultrasonographic examination showed a submucosal tumor like mass showing mucin waterfall on the gastric cardia. A total gastrectomy with splenectomy was performed. The pathology of the tumor identified the lesion as a mucinous adenocarcinoma.

Preparation of suspension of gastric mucous membrane single cell and expression of cyclins in cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore a method which can remove the gastric mucus in order to prepare mucous membrane single cell suspension for the research of cytomics.</p><p><b>METHODS</b>Enzymology was used to remove the mucus gel and to separate mucous layer from the normal fresh gastric tissue. The mucous layer was broken to prepare single cell suspension with machine method. Expression of major cyclins in mucous layer cells was examined by cytoimmunochemistry, flow cytometry(FCM) and confocal microscopy.</p><p><b>RESULTS</b>The 0.1% pepsin could dissolve the mucus gel and 1.2-2.4 U/L dispase could separate the mucous layer completely. The single mucous cell suspension was prepared successfully. FCM results from mucous single cell suspension revealed that expression of cyclin D(3), B(1) was obvious, that of cyclin D(2) was weak and that of cyclin D(1), A, E was the least. Similar results were found with confocal microscopy.</p><p><b>CONCLUSIONS</b>Single cell suspension from mucous layer can be easily prepared by pepsin and dispase. Cyclins schedule expression in vivo is different from cyclins schedule expression in vitro.</p>

Preparation of lectin-conjugated PLGA nanoparticles and evaluation of their in vitro bioadhesive activity / 药学学报

In this study, wheat germ agglutinin (WGA), tomato lectin (TL) and asparagus pea lectin (AL) were covalently coupled to conventional poly lactic-co-glycolic acid (PLGA) nanoparticles using a carbodiimide method to take the bioadhesive properties. The influences of the amounts of activating agents and lectins, as well as the activating time and incubating time on the effect of lectin conjugating were investigated to optimize the preparation conditions. The mean diameters of the performed nanoparticles with or without lectin conjugation ranged from (140.7 +/- 5.7) nm to (245.6 +/- 18.3) nm. The yields of lectin conjugating and the lectin surface concentrations on nanoparticles were determined by Lowry's methods, and were calculated to be (18.97 +/- 2.9)% - (20.15 +/- 2.4)% and (9.46 +/- 1.45)--(10.05 +/- 1.19) microg x mg(-1), respectively. The in vitro bioadhesive activities of nanoparticles were evaluated by pig gastric mucin (PM) binding experiments. After incubation at room temperature for 60 min, the equilibria of binding between nanoparticles and PM reached. The percentages of the bulk PM which had interacted with different lectin-conjugated PLGA nanoparticles were 15.5%, 12.1% and 11.8%, respectively. The conjugation of lectin enhanced the interaction about 2.4 - 3.2 fold compared with that of the non-conjugated one. A mathematical model was used based on the Langmuir equation, and the rate constants of interaction (k) were calculated to be 2.373 x 10(-3), 1.536 x 10(-3) and 1.714 x 10(-3) (microg x min/mL)(-1), respectively. These interactions could be competitively inhibited by their corresponding sugars of lectins. The results suggested that lectin-conjugated PLGA nanoparticles greatly promoted the interaction with PM in vitro compared with the conventional PLGA nanoparticles, thus would improve the bioadhesion on gastrointestinal mucosa after oral administration resulting in a prolonged residence time in the gastrointestinal tract.

O papel das mucinas gástricas na infecção por Helicobacter pylori / The role of gastric mucins in Helicobacter pylori infection

Mucinas são glicoproteínas, agentes protetores de mucosas e potenciais moléculas de adesão para microrganismo. A bactéria H. Pylori coloniza o muco gástrico e adere-se ao epitélio por meio de adesinas que reconhecem receptores nas células superficiais. As interações de adesina-receptor contribuem para a cronicidade na infecção, que está associada à patogênese de gastrite, doença péptica e câncer gástrico. MUC5AC e MUC6 são mucinas secretadas respectivamente no epitélio superficial/foveolar e nas glândulas da mucosa gástrica. MUC5AC vem sendo apontada como molécula receptora de H. Pylori, enquanto para MUC6 é atribuído papel na defesa contra o microrganismo. O conhecimento da expressão dessas mucinas na mucosa gástrica infectada por H. Pylori pode contribuir para a compreensão de aspectos de adesão e patogênese da infecção H. Pylori.

Antiulcerogenic effect of Justicia prostrata Gamble.

Antiulcerogenic effect of the alcoholic (ALJP) and aqueous (AQJP) extracts of the whole plant of Justicia prostrata was studied in aspirin+pylorus ligated rat models and analysed for gastric volume, ulcer index, free and total acidity. Biochemical parameters like total proteins, total hexoses, hexosamine, fucose and sialic acid were also estimated. Both extracts (ALJP and AQJP) significantly reduced both the gastric volume and the acidity of gastric juice. It also significantly promoted gastric mucus secretion by increasing total carbohydrates and decreasing the protein concentration in aspirin+ pylorus ligated rats. The results suggest that both the extracts (ALJP and AQJP) possess antiulcer activity, whereas AQJP is more effective when compared with ALJP in aspirin+pylorus ligated rat models. The results were compared with the standard drug Rantidine, a H2 receptor antagonist.

A Case of Gastric Mucinous Adenocarcinoma Presenting as a Characteristic Mucin Pool / 대한소화기내시경학회지

Mucinous adenocarcinoma is a rare histologic type of gastric carcinoma. Most mucinous gastric carcinoma is diagnosed by histology after surgical resection. However, in this report, we preoperatively predicted the type of a tumor (mucinous type) from its characteristic endoscopic finding. An endoscopic examination showed a cauliflower-like mass on the upper body of the posterior wall. At first we could not find the mass because it was covered with a thick mucin-like substance. After gastric lavage and mucin aspiration we found a tumor mass which was surrounded with a characteristic mucin pool. Abdominal CT showed a 6 cm sized-mass connected with the gastric fundus. Total gastrectomy with esophagojejunostomy was performed. The pathology of the tumor proved to be a mucinous adenocarcinoma.

The change of gastric antral mucin expression after Helicobacter pylori eradication / 대한내과학회지

BACKGROUND: Helicobacter pylori colonizes the gastric surface epithelium and the mucus gel layer. It has been known that H. pylori infection decreased the gastric mucin expression. The aim of this study was to determine the effect of H. pylori eradication on mucin expression (MUC5AC, MUC6 and MUC1) in the gastric epithelium. METHODS: This study included 20 patients positive for H. pylori whom successful eradication was performed between March 1998 and December 1999. H. pylori status was determined by histology, rapid urase test and urea breath test. Gastric antral biopsy specimens were examined by immunohistochemistry for mucin (MUC5AC, MUC6 and MUC1) expression. The distribution of epithelial cells expressing MUC5AC was calculated at two sites (surface mucous cells, pyloric glands). Two scores system (weak-strong) was used to assess staining intensity. RESULTS: There was a gradient of MUC5AC expression, higher to lower from the surface to the glands. Increased MUC5AC expression in the surface mucous cell (p=0.013) and in the glands (p=0.008) was found after H. pylori eradication. MUC6 and MUC1 distribution was not changed after H. pylori eradication. CONCLUSION: MUC5AC expression was increased after H. pylori eradication. These results suggest that MUC5AC may relate in the pathogenesis of H. pylori.

Estudio cuantitativo e histoquimico de la mucina del epitelo gastrico superficial en gastritis asociada a Helicobacter Pylori / Annual reports 1995 / A quantitative and histochemical study of surface gastric epithelial mucus in Helicobacter Pylori-associated gastritis

Para analizar los cambios en la cantidad y tipo histoquímico de mucina del epitelio gástrico superficial según el grado de infección por el Helicobacter Pylori, se estudiaron materiales biópsicos de antro y cuerpo de 65 pacientes seleccionados aleatoriamente, que consultaron al Departamento de Endoscopía de la Facultad de Ciencias Médicas entre agosto de 1994 y mayo de 1995. Veinte casos fueron negativos para H. Pylori y en 45 casos se detectó infección leve (+), moderada (++) o severa (+++). Se utilizaron técnica de tinción con Giemsa para la identificación de H. Pylori y la de acido periódico-Schiff + azul de Alcian (PAS-AB) a pH 2.5 y 1.0 para el tipo de mucina. La disminución de moco se graduó en mínima, moderada y severa. La disminución del moco intracelular apical y de la cripta fue directamente proporcional al grado de infección por H.Pylori (p<0.01) con aumento del moco intraluminal y abundantes colonias bacterianas en infecciones de grado moderado y severo. La metaplasia intestinal fue focal y escasa y se observó preferentemente (12,5 por ciento) en las gastritis con infección (+++). La aparición de ribetes en cepillo se observó en 75 por ciento de H. Pylori (+++). Este estudio sugiere que la mucina neutra intraluminal es necesaria para la colonización de H. Pylori, con disminución de la mucina intracelular, y subsecuentemente podría producir lesiones epiteliales por efectos citotóxicos y cambios de la mucina neutra a mucina ácida

Differential Mucin Gene Expression Associated with Methotrexate Resistance of Human Colonic Adenocarcinoma Cell Line, HT29 / 대한암학회지

PURPOSE: In normal tissue, MUC2 mucin gene is expressed predominantly in goblet cells, while MUC3 is expressed in both goblet cells and columnar absorptive cells of small intestine and colon. MUC5 mucin genes are expressed predominantly in the surface epithelial cells, while MUC6 is expressed mainly in the mucus neck cells of gastric glands and pyloric glands of stomach. In this paper, we determined any changes of mucin in drug-resistant cell lines from those parental cells, and we evaluated the altered regulation of mucin production in drug-resistant cells. MATERIALS AND METHODS: In the study of 17 day postconfluent parental HT29 (HT29) and methotrexate-resistant HT29 (HT29-MTX) colon cancer cell lines were examined for the expression of MUC2, 3, 5 and 6 mucin polypeptide (apomucin) by Northern blot and slot blot analysis, and also by immunoblot analysis. RESULTS: The level of MUC2 expression was unchanged, while there was increase in MUC3 expression in HT29-MTX compared to HT29. Interestingly there was a marked increase in the expression of MUC5 mRNA in HT29-MTX. The densitometric readings expressed as HT29-MTX/HT29 at 17th day after the cells were confluent are MUC2 (1.1), MUC3 (1.3), MUC5 (>70), MUC6 (1.0) with RNA slot blot. Immunoblot analysis was consistent with these data. CONCLUSION: Marked induction in MUC5 but not MUC6 gastric mucin gene was found in MTX resistance in HT29 colon cancer cells. The possible biological consequences of altered regulation of mucin genes in drug resistant colon cancer cells require further investigation.

Effect of the tetracyclic antidepressant maprotiline ongastric secretion and ethanol induced ulcer in rats

The effect of maprotiline [a tetracyclic antidepressant] in a dose of 5 mg/kg, orally for 21 days on gastric secretions and ethanol induced gastric ulcer was tested in rats. Maprotiline decreased the volume, free and total HCI acid concentration and peptic activity. While it produced an increase in mucin content as compared with the control group. Moreover, Maprotiline pretreatment [5 mg/kg, daily for 21 days orally] decreased the ulcer index of ethanol induced ulcer by 59.2%. The data suggest that Maprotiline in the tested dose had acid-pepsin antisecretory effect and ulcer protective activity against ethanol induced ulcer. These effects may be mediated through anticholinergic, antihistaminergic and the possible antidopaminergic effects of Maprotiline

CT Findings of Mucinous Adenocarcinoma in Gastrointestinal Tract

PURPOSE: To evaluate CT findings of mucinous adenocarcinoma in the gastrointestinal tract. MATERIALS AND METHODS : CT scans of 24 gastric and five colorectal mucinous adenocarcinomas, proven by histology, were retrospectively analysed; the patients consisted of 18 men and 11 women (age range, 27-76; mean, 59). CT findings were analysed, with emphasis on : (a) tumor size and maximal wall thickness ; (b) the presence of a low attenuation area, suggestive of a mucin poll within the tumor ; (c) the presence, shape and location of calcification, and (d) correlation between primary tumor (T) staging and CT findings. RESULTS: The mean tumorsize of gastric mucinous adenocarcinoma was 8.2cm (range, 1.4 - 17cm) and the mean maximal wall thickness was2.3cm (range, 1-4.5cm). Low attenuation areas on enhanced CT were seen in 12 cases (50%). Mottled, punctate, diffuse calcifications were demonstrated in nine cases(38%), and were located in low attenuation areas in eight cases. The T staging could be determined in 22 cases. Of there, low attenuation areas were demonstrated in tencases and calcification in seven. Of those ten cases with low atteuation area T staging was T2 in two cases, T3 intwo, and T4 in six. Of the cases showing calcification, T staging was T3 in one case and T4 in six. The mean sizeof colorectal mucinous adenocarcinoma was 6cm(range, 3-13cm) and the mean maximal wall thickness was 3.6cm (range,1.5-7cm). Low attenuation area were seen in three cases. Mottled calcification within the low sttenuation was detected in one case. The T staging of three cases which showed a low attenuation area was T3 in tow cases and T4in one case. One case with calcification was T3 stage. CONCLUSION: The CT finding of mucinous adenocarcinoma inthe gastrointestinal tract was a relatively thick-walled mass containing an area of low attenuation or calcification. Although calcification is believed to be a pathognomonic finding for the specific diagnosis of mucinous adenocarcinoma, a low attenuation area may be an important CT finding because it can be detected at lower T staging and more frequently.

Mucin secretion by gastric carcinoma cells: PAS alcain blue stain study

Thirty cases of gastric cancer were studied. Slides were stained with PAS Alcian Blue. The staining characteristics of the mucin were correlated with gross characteristics of the tumours and histological types. Due to the few cases studied; there was no observed statistical significance between the various mucin staining characteristics with the histological type; sex site of tumour and ethnicity. In 84of cases the tumour cells secreted either neutral or mixed mucins. Acid mucins were demonstrated in 5 cases only. neutral mucin is normally secreted by gastric epithelium and neck cells of gastric glands. The observation in this study suggests that those tumours which secrete neutral and mixed mucin probably arise from gastric epithelium; neck cells of gastric glands or colonic metaplasia. In those cases where the tumour produces acid mucin it is possible the tumour arose from areas of intestinal metaplasia

La importancia clínica de Helicobacter pylori y el diagnóstico de laboratorio de las enfermedades que ocasiona al humano / The importance of clinic diagnostic of Helicobacter pylory and diseases cause

H. pylori es una bacteria curva o helicoidal que se establece y multiplica en la mucosa gástrica ÄÄbasándose en algunos de sus diversos factores de patogenicidadÄÄ y, aunque no invade los tejidos, provoca la progresiva degradación de la capa de moco que protege al epitelio estomacal, exponiéndolo a la acción lesiva del ácido clorhídrico, aún cuando éste no alcanza las concentraciones comunes, ya que el microorganismo también afecta a las células parietales (que son las responsables de la liberación del HCI). De esa manera, H. pylori promueve la ocurrencia de las gastritis y las úlceras gástricas, aunque también se acepta que desempeña un importante papel en las úlceras duodenales, e inclusive, se le relaciona con la aparición de adenocarcinoma gástrico. El diagnóstico de laboratorio de las gastritis y las úlcera gástricas contempla métodos invasivos y no invasivos, considerando que, en el caso de los primeros, las muestras apropiadas son las biopsias obtenidas mediante endoscopía, en tanto que, los segundos, se basan en la detección-cuantificativa de anticuerpos séricos anti-H. pylory