Characterization of flgK gene and FlgK protein required for H pylori Colonization-from cloning to clinical relevance

AIM： To characterize the role of flgK and its protein product in Hpylori colonization. METHODS： The PCR cloning method identified the flgK gene. An isogenic flgK mutant was constructed by gene replacement and confirmed by Southern blot analysis and PCR analysis. The recombinant FlgK protein （r-FlgK） was purified. Electron microscopy （EM） was applied to demonstrate the flagella of H pylori. An in vitro motility test was assessed in semisolid medium. The densities of H pylori colonization with either the wild-type strain or its flgK mutant were compared among BALB/c mice with or without pre-immunization with r-FlgK. The serological responses to r-FlgK were analyzed for 70 clinical patients with different densities of H pylori colonization. RESULTS： From a duodenal ulcer strain, the flgK gene was cloned and it contained 1821 bp, with a 95.7% identity to the published sequences. No flagella were observed under EM for the mutant strain, which had a loss of motility. Hpylori density was lower in the BALB/c mice inoculated by the mutant or with pre-immunization with r-FlgK compared to unimmunized mice or mice inoculated by the wild-type strain （P 〈 0.05）. In the H pylori-infected patients, the serological responses to r-FlgK were uniformly low in titer.CONCLUSION： FlgK encoded by flgK is important for flagella formation and H pylori motility. Deficiency in FlgK or an enhanced serological response to r-FlgK can interfere with Hpylori colonization. FlgK of Hpylori could be a novel target for vaccination.

Intravenous proton pump inhibitors for peptic ulcer bleeding:Clinical benefits and limits

Peptic ulcer bleeding is a common disease and recurrent bleeding is an independent risk factor of mortality.Infusion with proton pump inhibitors(PPIs) prevents recurrent bleeding after successful endoscopic therapy.A gastric acidic environment of less than pH 5.4 alters coagulation function and activates pepsin to disaggregate platelet plugs.Gastric acid is secreted by H+,K+-ATPase,naming the proton pump.This update review focuses on the mechanism and the role of PPIs in the clinical management of patients with peptic ulcer bleeding.An intravenous omeprazole bolus followed by high-dose continuous infusion for 72 h after successful endoscopic therapy can prevent the recurrent bleeding.In the Asian,however,the infusion dosage can possibly be diminished whilst preserving favorable control of the intragastric pH and thereby still decreasing rates of recurrent bleeding.Irrespective of the infusion dosage of PPIs,rates of recurrent bleeding remain high in patients with co-morbidities.Because recurrent peptic ulcer bleeding may be prolonged in those with co-morbidities,a lowdose infusion of IV PPIs for up to 7-day may result in better control of recurrent bleeding of peptic ulcers.Due to the inter-patient variability in CYP2C19 genotypes,the infusion form of new generation PPIs,such as esomeprazole,should be promising for the prevention of recurrent bleeding.This article offers a comprehensive review of clinical practice,highlighting the indication,the optimal dosage,the duration,and the potential limitation of PPIs infusion for peptic ulcer bleeding.

Eradication of Helicobacter pylori increases childhood growth and serum acylated ghrelin levels

AIM: To determine whether Helicobacter pylori (H. pylori)infected children have reduced body weight (BW) and height (BH) growth, and if H. pylori eradication may restore growth while improving serum acylated ghrelin. METHODS: This longitudinal cohort study with oneyear follow-up enrolled 1222 children aged 4 to 12 years old into an observation cohort (18 with and 318 without H. pylori ) and intervention cohort (75 with and 811 without). The 7-d triple therapy was used for eradication in the intervention cohort. The net increases of BW and BH as well serum acylated ghrelin after oneyear follow-up were compared between successful eradicated H. pylori-infected children and controls. RESULTS: In the observation cohort, the H. pylori - infected children had lower z score of BW (-1.11 ± 0.47 vs 0.35 ± 0.69, P = 0.01) and body mass index (BMI) (0.06 ± 0.45 vs 0.44 ± 0.73, P = 0.02) at enrollment and lower net BW gain after one-year follow-up (3.3 ± 2.1 kg vs 4.5 ± 2.4 kg, P = 0.04) than the non-infected controls. In the intervention cohort, the H. pylori - infected children had lower z score of BMI (0.25 ± 1.09 vs 0.68 ± 0.87, P = 0.009) and serum acylated ghrelin levels (41.8 ± 35.6 pg/mL vs 83.6 ± 24.2 pg/mL, P < 0.001) than the non-infected controls. In addition to restoring decreased serum ghrelin levels (87.7 ± 38.0 pg/mL vs 44.2 ± 39.0 pg/mL, P < 0.001), the H. pylori - infected children with successful eradication had higher net gains (P < 0.05) and increase of z scores (P < 0.05) of both BW and BH as compared with non-infected controls after one-year follow-up. CONCLUSION:H. pylori-infected children are associated with low serum acylated ghrelin and growth retardation. Successful eradication of H. pylori restores ghrelin levels and increases growth in children.