Helicobacter pylori outer membrane protein Q genotypes and their susceptibility to anti-adhesive phytotherapeutic agents / 中西医结合学报

<p><b>OBJECTIVE</b>Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q (HopQ) mediates host-pathogen interactions; HopQ genotypes 1 and 2 are found associating with gastroduodenal pathologies. The authors measured the anti-adhesion effects of the extracts of Abelmoschus esculentus, Zingiber officinale, Trachyspermum ammi, Glycyrrhiza glabra, Curcuma longa and Capsicum annum against HopQ genotypes and H. pylori cytotoxin-associated gene A (CagA).</p><p><b>METHODS</b>DNA was extracted by polymerase chain reaction of the HopQ genotypes (i.e., type 1, type 2 and CagA) from 115 H. pylori strains. The effect of the extracts from selected dietary ingredients was determined using a gastric adenocarcinoma cell line and a quantitative DNA fragmentation assay. The anti-adhesive effect of these extracts on H. pylori was tested using an anti-adhesion analysis.</p><p><b>RESULTS</b>C. annum, C. longa and A. esculentus showed prominent anti-adhesion effects with resultant values of 17.3% ± 2.9%, 14.6% ± 3.7%, 13.8% ± 3.6%, respectively, against HopQ type 1 and 13.1% ± 1.7%, 12.1% ± 2%, 11.1% ± 1.6%, respectively, against HopQ type 2. C. longa (93%), C. annum (89%) and A. esculentus (75%) had better anti-adhesive activity against H. pylori with HopQ type 1 compared to HopQ type 2 with respective values of 70%, 64% and 51%. Extracts of C. annum (14.7% ± 4.1%), A. esculentus (12.3% ± 4.1%) and Z. officinale (8.4% ± 2.8%) had an anti-adhesion effect against CagA-positive H. pylori strains compared to CagA-negative strains.</p><p><b>CONCLUSION</b>The anti-adhesion properties of the tested phytotherapeutic dietary ingredients were varied with HopQ genotypes. HopQ type 1 was found to be more sensitive to extracts of C. annum, C. longa and A. esculentus compared to the HopQ type 2 genotype.</p>

Interferon lambda-3 rs12979860 variants and response to pegylated interferon in chronic hepatitis-c genotype-3

Objective: To assess the role of single nucleotide polymorphisms [SNPs] near the interferon lambda-3 [IFNX3] [formal IL-28B] gene rs12979860 in predicting sustained virologic response [SVR] in hepatitis-C virus genotype-3 [HCV-3]

Study Design: Descriptive, analytical study

Place and Duration of Study: Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014

Methodology: Patients with HCV-3 were classified as sustained virologic response [SVR], relapsers and non-responders. SNP rs12979860 was determined by PCR-RFLP protocol. Differences between categorical variables were assessed by chi-square or Fisher's exact test, while those between continuous variables were evaluated using the Mann-Whitney U-test. Binary logistic regression analysis by forward conditional method was performed by using significant variables with p-values less than 0.05 as the criteria for model inclusion

Results: Out of 115 patients, rs12979860 genotype-CC, CT, TT was found in 37 [32.2%], 70 [60.9%], and 8 [7%] patients. 72 patients were male with median age of 45 years. Cirrhosis was present in 32 patients. Patients with response failures [no response and relapse, n=36 and 29, respectively] had higher baseline gamma glutamyl transferase [GOT] level [p < 0.001], higher alanine aminotransferase [p=0.027] and cirrhosis [p=0.001] than patients with SVR. Genotype-CC was present in 16/65 in response failures compared to 21/50 who achieved SVR [p=0.048]. Rapid virologic response [RVR] [p < 0.001], low GGT [p=0.001] and absence of cirrhosis [p=0.039] were the independent predictive factors for SVR. In patients who could not achieve RVR and in patients with cirrhosis, SVR was seen more in with genotype-CC [p=0.007 and 0.038]

Conclusion: In patients infected with HCV-3, IFNA3 rs12979860, SNP has less impact on SVR

Varied presentation of celiac disease in Pakistani adults

The objective of this retrospective study was to evaluate presentation of celiac disease in adults. It included 77 patients, 41 [53.2%] males with median age 26 years and median body mass index of 18 [16 - 22] kg/m[2]. Typical presentation with gastrointestinal symptoms was seen in 76.6%. Atypical presentation with extra intestinal complaints in 7.8% and silent presentation in 15.6%. Major symptoms were diarrhea in 64.9%, weight loss 36.4%, abdominal pain 35.1%, vomiting 32.5%, pallor 24.7%, and weakness 13%. Iron deficiency was documented in 20.8%, B12 deficiency in 9.1%, folic acid deficiency in 6.5% and vitamin D deficiency in 10.4%. Half of the patients had haemoglobin less than 11 g/dl. Osteoporosis and osteomalacia, hypothyroidism, diabetes and atrophic gastritis were seen in 2.6% each. Raised alanine aminotransferase was documented in 23.4%. Duodenal biopsy, done in 39 patients, revealed increased intraepithelial lymphocytes in 11, along with crypt hyperplasia in 3, partial villous atrophy in 15 and sub-total villous atrophy in 10. In conclusion, celiac disease in adults should be looked for in patients with chronic diarrhea or irritable bowel syndrome like symptoms, underweight, anaemic, or having nutritional deficiencies

Comparison of the virulence markers of helicobacter pylori and their associated diseases in patients from Pakistan and Afghanistan

Helicobacter pylori is a Gram-negative bacteria, which is associated with development of gastroduodenal diseases. The prevalence of H. pylori and the virulence markers cytotoxin-associated gene A and E [cagA, cagE] and vacuolating-associated cytotoxin gene [vacA] alleles varies in different parts of the world. H. pylori virulence markers cagA, cagE, and vacA alleles in local and Afghan nationals with H. pylori-associated gastroduodenal diseases were studied. Two hundred and ten patients with upper gastrointestinal symptoms and positive for H. pylori by the urease test and histology were included. One hundred and nineteen were local nationals and 91 were Afghans. The cagA, cagE, and vacA allelic status was determined by polymerase chain reaction. The nonulcer dyspepsia [NUD] was common in the Afghan patients [P = 0.025]. In Afghan H. pylori strains, cagA was positive in 14 [82%] with gastric carcinoma [GC] compared with 29 [45%] with NUD [P = 0.006], whereas cagE was positive in 11 [65%] with GC and 4 [67%] with duodenal ulcer [DU] compared with 12 [18%] with NUD [P < 0.001 and 0.021, respectively]. The vacA s1a/b1was positive in 10 [59%] of GC compared with 20 [31%] in NUD [P = 0.033]. In Pakistani strains, cagE was positive in 12 [60%] with GC, 7 [58%] with GU, 12 [60%] with DU compared with 11 [16%] with NUD [P < 0.001, 0.004, and < 0.001, respectively]. In Pakistani strains, cagA/s1a/m1 was 39 [33%] compared with Afghans in 17 [19%] [P = 0.022]. Moderate to severe mucosal inflammation was present in 51 [43%] Pakistani patients compared with 26 [28%] [P = 0.033] in Afghans. It was also associated with grade 1 lymphoid aggregate development in Pakistani patients 67 [56%] compared with 36 [40%] [P = 0.016] in Afghans. Distribution of H. pylori virulence marker cagE with DU was similar in Afghan and Pakistan H. pylori strains. Chronic active inflammation was significantly associated with Pakistani H. pylori strains

Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan

The symptoms of irritable bowel syndrome resemble those of small intestinal bacterial overgrowth [SIBO]. The aim of this study was to determine the frequency of SIBO and lactose intolerance [LI] occurrence in patients with diarrhea-predominant irritable bowel syndrome [IBS-D] according to Rome III criteria. In this retrospective case-control study, patients over 18 years of age with altered bowel habit, bloating, and patients who had lactose Hydrogen breath test [H2 BT] done were included. The "cases" were defined as patients who fulfill Rome III criteria for IBS-D, while "controls" were those having chronic nonspecific diarrhea [CNSD] who did not fulfill Rome III criteria for IBS-D. Demographic data, predominant bowel habit pattern, concurrent use of medications, etc., were noted. Patients with IBS-D were 119 [51%] with a mean age of 35 +/- 13 years, while those with CNSD were 115 [49%] with mean age 36 +/- 15 years. Patients in both IBS-D and CNSD were comparable in gender, with male 87 [74%] and female 77 [64%]. SIBO was documented by lactose H2 BT in 32/234 [14%] cases. It was positive in 22/119 [19%] cases with IBS-D, while 10/115 [9%] cases had CNSD [P = 0.03]. LI was positive in 43/234 [18%] cases. Of these, 25/119 [21%] cases had IBS-D and 18/115 [16%] cases had CNSD [P = 0.29]. SIBO was seen in a significant number of our patients with IBS-D. There was no significant age or gender difference in patients with or without SIBO

Associations between the Plasticity Region Genes of Helicobacter pylori and Gastroduodenal Diseases in a High-Prevalence Area

BACKGROUND/AIMS: Genes associated with the Helicobacter pylori (H. pylori) plasticity region may play a role in the pathogenesis of H. pylori. We compared the genes jhp0940, jhp0947, and jhp0986 in H. pylori isolates from patients with different gastroduodenal diseases and in different age groups. METHODS: The H. pylori hyperplasticity region genes jhp0940, jhp0947, and jhp0986 were studied by PCR. We also evaluated whether these genes were related to the cytotoxin-associated gene (cagA) and histology findings. RESULTS: Of the patient cohort, 71 (62%) were positive for jhp0940, 67 (59%) for jhp0947, 12 (10%) for jhp0986, and 69 (60%) for cagA. jhp0940 (n=18, 67%) and jhp0947 (n=23, 85%) were found more frequently in duodenal ulcer (DU) patients than in gastritis patients (n=14, 39%; p=0.029 and p<0.001, respectively). Gastric ulcer (GU) was more frequently associated with jhp0940 (17 patients, 77%; p=0.003) than with gastritis (14 patients, 39%). Gastric carcinoma (GC) was more strongly associated with both jhp0940 (22 patients, 76%; p=0.003) and jhp0947 (22 patients, 76%; p=0.003) than was gastritis (14 patients, 39%). jhp0947 was more frequently associated with chronic active inflammation (58 patients, 87%; p=0.009) than with chronic inflammation (9 patients, 13%). Multivariate analysis demonstrated that jhp0947 was associated with DU (odds ratio, 6.1; 95% confidence interval, 1.87-20). CONCLUSIONS: The genes jhp0947 and jhp0940 were identified in H. pylori isolates from patients with GC and DU, while jhp0940 was also isolated from patients with GU. jhp0947 was independently associated with DU.

Gastric corpus polyps associated with proton pump inhibitors therapy

The prevalence of Gastroesophageal Reflux Disease [GERD] is rapidly rising in Asia. We describe here a case of 51 years old man who had surgery for esophageal leiomyoma and received long-term therapy with Proton Pump Inhibitors [PPIs] for persisting reflux symptoms. On Esophago-Gastroduodenoscopy [EGD] several sessile polyps were seen in the gastric corpus. Earlier EGD done 15 years back had not demonstrated those polyps. Sections revealed polypoid fragments of glandular epithelium with dilated glands and negative histology for H. pylori. Polymerase chain reaction for 16S ribosomal RNA gene [16S rRNA PCR] of H. pylori was also negative. This is the first report originating from an Asian country describing Fundal Gland Polyps [FGPs] in the corpus of stomach rather than fundus in a patient on long-term PPI therapy

Phloroglucinol in irritable bowel syndrome

To determine the efficacy and tolerability of phloroglucinol, an antispasmodic agent in the treatment of Irritable Bowel Syndrome [IBS]. It was an open label [quasi interventional] study. One hundred patients coming to the gastroenterology clinics of Aga Khan University Hospital with IBS as defined by the Rome II criteria were enrolled between February 2004 and September 2004 to participate in the trial and were treated as outpatients. Phloroglucinol [Himont] 50mg orally three times daily was given for two months. Symptoms were assessed before and during treatment using a questionnaire. One hundred patients were enrolled in the study. Of them 61% [61/100] were males and 39% [39/100] were females. Their mean age was 41'14 years. Sixty-eight patients completed the study and 28 dropped out. On Phloroglucinol treatment there was an overall statistically significant improvement in abdominal pain [p<0.001], frequency of stools per day [p<0.001], urgency [p<0.001], passage of mucus per rectum [p<0.001], sense of incomplete defecation [p=0.001] and bloating [p=0.001]. However, no response was seen in the feature of straining in both genders [p=0.676]. The difference in response to treatment according to gender separately showed statistically significant improvement in the sense of incomplete defecation in females alone [p=0.003]

Frequency of NSAID induced peptic ulcer disease

To determine the frequency of peptic ulcer disease in patients on nonsteroidal anti-inflammatory drugs [NSAID]. Record of eight hundred and twenty consecutive patients undergoing upper gastrointestinal [GI] endoscopy; from January 1998 to December 2000 were reviewed. The endoscopic diagnosis varied from gastritis, peptic ulcer to duodenitis. The use of NSAID was documented by reviewing medical records of patients with peptic ulcer. Peptic ulcers were found in 43% [353/820] patients. NSAID associated peptic ulcers were identified in 14.7% [52/353] patients. Diclofenac and aspirin were most common NSAIDs associated with peptic ulcers in 32.7% [17/52] and 30.7% [16/52] patients, respectively. Duodenal ulcer was more common than gastric ulcer 65.3% [34/52] and 42.3% [22/52], respectively. H. pylori infection was present in 46% [24/52] of the cases. NSAIDs treatment and / or H. pylori infection compared to non NSAIDs and non H. pylori infected peptic ulcer disease were significantly associated with gastric ulcer [p = 0.004] and duodenal ulcer [p = 0.009] respectively. NSAID-associated peptic ulcer disease is common in Pakistan and most frequently associated with gastric and duodenal ulcer. H. pylori infection is common in association with NSAID related peptic ulcers

Perception of gastroesophageal reflux disease in urban population in Pakistan

To determine the frequency and health care seeking behavior of patients with gastroesophageal reflux symptoms using American College of Gastroenterology [ACG] questionnaire for gastroesophageal reflux disease [GERD]. Cross-sectional study. Section of Gastroenterology, Department of Medicine, The Aga Khan University Hospital, Karachi, from April 2002 to November 2003. A total of 1267 persons above 15 years of age were interviewed using a modified questionnaire for GERD from the American College of Gastroenterology [ACG], which previously validated in our section as a screening tool in an urban population in Pakistan. Nine hundred and sixty-three individuals responded to the questionnaire. Mean age of the surveyed sample was 24 ' 9.3 years. Using the ACG criteria, the overall frequency of gastroesophageal reflux symptoms was 24% [228/963] with 58% [133/228] males and 42% [95/228] females. Symptoms experienced frequently were reflux from the stomach, 58% [133/228], with a bitter, acid taste in the mouth. Seventy-four percent [169/228] experienced this postprandially. Symptoms were associated with spicy fried food in 71% [161/228]. Sixty-seven percent [152/228] did not seek health care advice, 32% [74/228] practiced self-medications and 33% [76/228] consulted a physician. Gastroesophageal reflux is a common problem in the urban population of Pakistan

Polymerase chain reaction in the detection of helicobacter pylori infection

To determine the presence of Helicobacter pylori [H. pylori] infection, in patients suffering from gastritis and peptic ulcer disease by polymerase chain reaction [PCR] and correlate the results with the histological diagnosis. Design: Analytical, comparative study. Place and Duration of Study: Section of Gastroenterology, Department of Medicine and Pathology, Aga Khan University Hospital and School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore from November, 2001 to December, 2002. Patients and Gastric antral biopsies were obtained from 64 patients attending the Gastroenterology Section of Aga Khan University Hospital. Patients on nonsteroidal-anti-inflammatory drugs [NSAIDS] were excluded. Gastric biopsies were sent for histopathology and used for DNA extraction and PCR amplification of H. pylori 16S ribosomal RNA [rRNA] gene. Results were compared and statistically analyzed. H. pylori were not visible by histology in 57.6% [34/59] and could be seen in 42.4% [25/59]. PCR test was negative for H. pylori DNA in 44.1% [26/59] and positive in 55.9% [33/59] with p<0.001. PCR H. pylori DNA is a sensitive method for the diagnosis of H. pylori infection and its use as a diagnostic tool along with histology increases the detection rate of H. pylori infection. Two different staining methods for the organism should be used to avoid missing diagnosis of H. pylori infection