The degree of mucosal damage to the small intestine and serum immunoglobulin G4 levels correlate with celiac disease.

BACKGROUND: Celiac disease (CD) is an immune-mediated and chronic inflammatory enteropathy, triggered by the ingestion of gluten in genetically susceptible individuals. Immunoglobulin G4 (IgG4)-related diseases are a recently defined emerging clinical condition, characterized by increased serum IgG4 concentrations. The aim of this study was to investigate whether IgG4 levels correlate with the titers of intestinal antibodies and the degree of mucosal damage in CD patients. MATERIALS AND METHODS: A total of 41 CD patients and 28 healthy controls were included in the study. All patients underwent a duodenal biopsy and were then diagnosed with the modified Marsh classification. Blood samples were obtained for IgG4 measurements. Serums were kept at -80 °C until the analysis was carried out and plasma IgG4 levels were determined using an enzyme-linked immune sorbent assay method with a diagnostic cutoff value of 135 mg/dl. RESULTS: The mean age of the CD and the control group was 26.8 ± 8.3 and 26.9 ± 6.2 years, respectively. The mean IgG4 levels were significantly higher in CD patients (283.21 ± 39.02 mg/dl) compared with the healthy control group (68.97 ± 15.89 mg/dl, P<0.0001). In the CD group, 27/41 patients and in the control group, 4/28 patients had high IgG4 levels (>135 mg/dl, P < 0.0001). A close correlation was found between the grade of mucosal damage, IgG4 levels, and antigliadin-IgA; the higher the grade Marsh score, the higher the measured IgG4 (P < 0.05). CONCLUSION: In our study, IgG4 levels of CD patients were higher than normal ranges whereas the results of the control group were within physiologic limits. We also showed for the first time that there was a correlation between IgG4 levels, autoantibody, and severity of mucosal damage. To the best of our knowledge, this is the first study to evaluate IgG4 levels and mucosal damage in CD patients.

The effect of fatty pancreas on serum glucose parameters in patients with nonalcoholic steatohepatitis.

OBJECTIVE: Fatty pancreas (FP) is related to obesity, and may have some clinical implications on glucose metabolism. The frequency and importance of FP in patients with nonalcoholic steatohepatitis (NASH) are not clear. This study aimed to investigate: the frequency of FP in patients with NASH, and its effects on serum glucose parameters. METHODS: FP was detected and graded by transabdominal ultrasonography (USG) in patients with biopsy-proven NASH and healthy controls. Body Mass Index and waist circumference were recorded, and serum lipids, fasting serum glucose, HbA1c, OGTT 2-h, insulin level, insulin resistance, type 2 diabetes mellitus (DM) and prediabetes rates were detected. RESULTS: Eighty-four subjects with NASH and 35 healthy controls were enrolled in the study. There was no FP in 41 (48.8%) of the NASH patients according to the study criteria. Forty-three of the NASH patients and 5 of the controls had different grades of fat in their pancreas (51.2% vs. 14%, p=0.001). The HbA1c and OGTT 2-h results were significantly higher in NASH patients with FP compared to those without FP (p=0.003 and p=0.018). The rates of both prediabetes and DM were also found to be significantly increased in NASH patients with FP (p=0.004). The mean waist circumference was higher in patients with FP (p=0.027). Grade of FP by USG showed no effect on study parameters in subgroup analysis. CONCLUSION: FP is common in patients with NASH and increases the rate of prediabetes and DM. The coexistence of both NASH and FP has a further impact on glucose metabolism and DM frequency.

Promoter hypermethylation of p16 and APC in gastrointestinal cancer patients.

BACKGROUND/AIMS: Cancer is a consequence of the disruption of cellular regulation. Epigenetic is one of the reasons of this disruption. Epigenetic factors play a role in the carcinogenesis by affecting proto-oncogenes and tumor suppressor genes and it is one of the most popular research areas in recent years. DNA methylation, which is an epigenetic mechanism, occurs in the early stages of tumorigenesis. Promoter methylation which causes the silence of tumor suppressor genes have been studied extensively in various tumor types. The aim of this study was to investigate promoter methylation of certain tumor suppressor genes, Cyclin-dependent kinase inhibitor 2A (p16) and Adenomatous polyposis coli (APC), which take part in gastrointestinal tumorigenesis. MATERIALS AND METHODS: To detect the promoter methylation of p16 and APC genes, tissue samples from 20 gastrointestinal cancer patients and peripheral blood samples from 15 healthy individuals were collected for Methylation-Specific Polymerase Chain Reaction (MSP) analysis. RESULTS: According to the statistical analysis, in tumor tissue, positive methylation ratio of p16 and APC genes was found respectively 30% (6/20) and 50% (10/20). The difference of promoter methylation of these genes between tumor tissues and control group was significantly observed (p=0.02 and 0.001, respectively). An alteration of promoter methylation of APC gene according to tumor localization was found (p=0.007), but there was no significant difference observed in p16. CONCLUSION: In our study, promoter methylation which was considered to be occurred as an early event in gastrointestinal carcinogenesis was observed in p16 and APC genes.

The efficacy of mesenchymal stem cell transplantation in caustic esophagus injury: an experimental study.

Introduction. Ingestion of corrosive substances may lead to stricture formation in esophagus as a late complication. Full thickness injury seems to exterminate tissue stem cells of esophagus. Mesenchymal stem cells (MSCs) can differentiate into specific cell lineages and have the capacity of homing in sites of injury. Aim and Methods. We aimed to investigate the efficacy of MSC transplantation, on prevention of esophageal damage and stricture formation after caustic esophagus injury in rats. 54 rats were allocated into four groups; 4 rats were sacrificed for MSC production. Group 1, untreated controls (n: 10). Group 2, membrane labeled MSCs-treated rats (n: 20). Group 3, biodistribution of fluorodeoxyglucose labeled MSCs via positron emission tomography (PET) imaging (n: 10). Group 4, sham operated (n: 10). Standard caustic esophageal burns were created and MSCs were transplanted 24 hours after. All rats were sacrificed at the 21st days. Results. PET scan images revealed the homing behavior of MSCs to the injury site. The histopathology damage score was not significantly different from controls. However, we demonstrated Dil labeled epithelial and muscle cells which were originating from transplanted MSCs. Conclusion. MSC transplantation after caustic esophageal injury may be a helpful treatment modality; however, probably repeated infusions are needed.

Long-term results of endoscopic resection for type I gastric neuroendocrine tumors.

BACKGROUND: A number of different therapies, including endoscopic resection, have been suggested for the treatment of Type 1 gastric neuroendocrine tumors (NETs). The current study aimed to determine the long-term efficacy of endoscopic resection for Type 1 gastric NETs. METHODS: Twenty-two patients (from 1999 to 2012) with Type 1 gastric NETs were included in the study. All patients were treated with endoscopic resection and received regular followed-up appointments at a tertiary referral center. RESULTS: All patients were initially diagnosed with hypergastrinemia, atrophic gastritis and intestinal metaplasia. Polyps' diameters were >1 cm in 4 patients, and between 0.5 and 1 cm in 18 patients. All detectable lesions were successfully resected. One patient required surgery due to gastric perforation during endoscopic mucosal resection. Recurrence was detected in four patients (18%) and endoscopic resection was performed again. Local or distant metastasis was not observed in any patient during follow-up. Median follow-up time was 7 years, with a maximum of 14 years. Seventeen patients (78%) completed a 5-year follow-up period, and overall disease-free survival rate was 100%. CONCLUSIONS: Long-term follow-ups with 22 patients suggest that endoscopic resection of Type 1 gastric NETs is a safe and effective treatment option with a relatively low recurrence rate.

Efficacy of a modified sequential therapy including bismuth subcitrate as first-line therapy to eradicate Helicobacter pylori in a Turkish population.

BACKGROUND: Eradication rates of Helicobacter pylori with standard triple therapy are not satisfactory. Sequential therapy is an alternative method to overcome this problem. OBJECTIVES: The aim of this study was to assess efficacy of a modified sequential therapy with the addition of a bismuth preparation, as first-line treatment in the eradication of H. pylori infection. MATERIALS AND METHODS: One hundred and forty-two H. pylori-positive patients were included in the study. Patients were given a 14-day sequential therapy program consisting of pantoprazole, 40 mg (b.i.d. for 14 days); colloidal bismuth subcitrate, 300 mg 4 (two tablets before breakfast and dinner, for 14 days); amoxicillin, 1 g (b.i.d.for the first 7 days); tetracycline, 500 mg (q.i.d. for the second 7 days); and metronidazole, 500 mg (t.i.d. for the second 7 days). Eradication was tested by urea breath test (UBT) 6 weeks after completion of treatment. RESULTS: Of the 142 patients included, 131 completed the study. "Per-protocol" and "intention-to-treat" analyses revealed high eradication rates in this group (92.0-95% CI, 87.2-96.8%, and 81.0-95% CI, 74.5-87.4%, respectively). There was no relation to sex and age with this modified sequential therapy. Compliance was satisfactory (11 patients - four women and seven men were unavailable for follow-up), and side effects were minimal (six patients had to stop treatment - metronidazole-related facial swelling and numbness on the face and hands in two patients; tetracycline-related fever and epigastric pain and nausea and vomiting in two patients; and amoxicillin-related diarrhea and vaginal discharge in two patients). These side effects were reversible and resolved after the cessation of the related medication. CONCLUSIONS: This 14-day modified sequential treatment, including bismuth, achieves a significantly high eradication rates in patients with H. pylori infection, with five satisfactory patient compliance and minor side effects.

Comparison of bismuth-containing quadruple and concomitant therapies as a first-line treatment option for Helicobacter pylori.

BACKGROUND/AIMS: Helicobacter pylori eradication rates with standard triple regimens are worsening, and alternative treatments are urgently needed in some populations. The present study aimed to compare the efficacy of bismuth-based quadruple and concomitant regimens. METHODS: Consecutive Helicobacter pylori-positive patients with non-ulcer dyspepsia were randomized to receive one of two regimens: (i) bismuth subsalicylate 300 mg q.i.d., esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., and amoxicillin 1 g b.i.d. (bismuth group) or (ii) esomeprazole 40 mg b.i.d., tetracycline 500 mg q.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg t.i.d. (concomitant group) for 14 days. Gastroscopy and 14C-urea breath test were performed before enrollment, and urea breath test was repeated six weeks after the treatment. RESULTS: A total of 200 patients were randomized, and 180 of them completed the protocols. The intention-to-treat and per-protocol eradication rates were 79% (95% confidence interval 71-87) and 89.7% (95% confidence interval 83-95) in the bismuth group and 74% (95% confidence interval 68-81) and 80.4% (95% confidence interval 72-87) in the concomitant group. The bismuth regimen achieved a slightly better eradication rate compared to the concomitant group in both per-protocol and intention-to-treat analysis, but results were not statistically significant (p>0.05). Ten patients (6 in bismuth, 4 in concomitant groups) dropped out of the study because of side effects. CONCLUSIONS: The quadruple regimens with or without bismuth achieved moderate eradication rates as a first-line eradication option of Helicobacter pylori in our population, in which a bismuth-based regimen seems more appropriate. The compliance and side effects are important issues affecting the success of these regimens.

Plasma ghrelin levels in patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an auto-inflammatory disorder characterized by febrile attacks. Increased acute-phase reactants are characteristic during febrile attacks. Ghrelin is a natural G-protein that decreases secretion of pro-inflammatory cytokines and acts as anti-inflammatory agent. The aim of this study was to investigate whether there is any change in ghrelin levels and whether increases in ghrelin levels can be used as a marker in these patients. SUBJECTS AND METHODS: Thirty-seven male patients and 30 healthy men as a control group were included in the study. Blood samples were obtained for ghrelin measurements both before the attacks (pre-attack period; ghrelin 1 group) and during the attacks (ghrelin 2 group). Samples were kept at -80°C until the analysis was conducted and plasma ghrelin levels were measured using an immune-sorbent assay method. RESULTS: Mean ghrelin levels measured during the attacks were significantly higher (11.01 ± 4.78 pg/ml) as compared to pre-attack levels (5.78 ± 2.17 pg/ml; p < 0.001). Similarly, mean ghrelin levels measured in FMF patients during an attack were significantly different from that of the control group (6.57 ± 4.13 pg/ml; p < 0.001). CONCLUSIONS: In this study, high ghrelin levels were measured during attacks in FMF patients. This finding is in line with previous results regarding the fact that inflammatory response arising during an FMF attack is an acute inflammatory event. Our findings suggest that ghrelin levels measured during FMF attacks could be used as a biochemical indicator for the FMF attack in FMF patients and that it could be used for support of the diagnosis of the disease.

Comparison of levofloxacin-containing sequential and standard triple therapies for the eradication of Helicobacter pylori.

BACKGROUND: There is an important concern about the success of standard triple treatment for Helicobacter pylori (H. pylori) in recent years. Better eradication rates have been reported with sequential treatment in current studies. This study aimed to compare the success of a novel levofloxacin-containing sequential regimen with standard triple therapy. METHODS: H. pylori-positive patients with non-ulcer dyspepsia were randomly allocated to one of the study groups. The patients on sequential arm were given esomeprazole 40 mg BID and amoxicillin 1g BID for the first week followed by esomeprazole 40 mg BID, levofloxacin 500 mg QD and metronidazole 500 mg TID for the second week. The patients on standard triple arm were given esomeprazole 40 mg BID, amoxicillin 1g BID and clarithromycin 500 mg BID for 2 weeks. Eradication was assessed by urea breath test on 6th weeks. RESULTS: Seventy-five patients were enrolled in each group; 72 in sequential arm and 67 in standard arm completed the protocols. H. pylori eradication rate of per protocol was 90% in sequential versus 57% in standard treatment groups with a statistical significance (p<0.000). Both regimens were similarly well tolerated and side effects were comparable. Only one patient in sequential arm stopped the treatment because of side effects. CONCLUSION: The levofloxacin-containing sequential therapy is a significantly better strategy than the standard triple treatment for H. pylori eradication. Standard triple treatment is no more effective for H. pylori in our population and levofloxacin-containing sequential regimen might be used as a first-line eradication option.

Serum progranulin as an independent marker of liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease.

BACKGROUND: Elevated progranulin levels are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. Progranulin has not been previously investigated as a biomarker of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether serum progranulin levels are altered in patients with biopsy-proven NAFLD and if they are associated with their clinical, biochemical, and histological characteristics. SUBJECTS AND METHODS: We measured serum progranulin levels in 95 patients with biopsy-proven NAFLD and 80 age- and sex-matched controls. The potential associations between progranulin and the characteristics of NAFLD patients were examined by multiple linear regression analysis. RESULTS: Serum progranulin levels were significantly higher in NAFLD patients (34 ± 13 ng/mL) than in controls (28 ± 7 ng/mL, P < 0.001). In NAFLD patients, serum progranulin levels were associated with lipid levels and the degree of hepatic fibrosis. After adjustment for potential confounders, serum progranulin remained an independent predictor of the degree of hepatic fibrosis in NAFLD patients (ß = 0.392; t = 2.226, P < 0.01). CONCLUSIONS: Compared with controls, NAFLD patients have higher serum progranulin concentrations, which are closely associated with lipid values and the extent of hepatic fibrosis.

Serum galectin-3 levels in patients with nonalcoholic fatty liver disease.

OBJECTIVES: Galectin-3 might serve as a biomarker of human metabolic alterations. We measured serum levels of galectin-3 in patients with nonalcoholic fatty liver disease (NAFLD) and examined their association with clinical and histological phenotypes. DESIGN AND METHODS: Serum levels of galectin-3 were assayed in 71 patients with biopsy-proven NAFLD and 39 controls. RESULTS: Serum galectin-3 levels did not differ in patients with NAFLD (median 4.1 ng/mL; interquartile range: 1.5-5.5 ng/mL) compared with healthy controls (median 3.1 ng/mL; interquartile range: 0.8-7.5 ng/mL, P=0.93). Among patients with NAFLD, however, serum galectin-3 levels correlated significantly with BMI (r=0.267, P<0.05). This association persisted after adjustment for potential confounders (ß=0.30; t=2.11, P<0.05). CONCLUSIONS: Although galectin-3 was modestly associated with BMI, our results do not support the hypothesis that levels of this molecule are altered in patients with NAFLD.

A new modified concomitant therapy for Helicobacter pylori eradication in Turkey.

BACKGROUND: Helicobacter pylori eradication rates have tended to decrease recently, mostly due to antibiotic resistance. In the present study, our aim was to determine Hp eradication rate with the LAC plus tid metronidazole regimen and the secondary objective of this study was to identify an effective regimen for our population. METHODS: Eighty-four Hp-positive patients with non-ulcer dyspepsia were assigned into the same group. Patients were administered the classical LAC protocole (lansoprazole 30 mg bid, amoxicillin 1 g bid and claritromycin 500 mg bid for 14 days) plus metronidazole 500 mg tid for 14 days. Gastroscopy and histopathological assessment were performed before enrollment and C(14) urea breath test and stool antigen test were performed 6 weeks after treatment. RESULTS: All 84 patients completed the study. No patient left the study because of drug side effect. Total eradication rate was 75% (63/84). CONCLUSION: Although LAC plus tid metronidazole regimen achieved a much better eradication rate compared with the standard LAC regimen; this is the first study that has a relatively low success with a concomitant therapy. So in areas of high resistance like Turkey, one cannot expect a high success with any clarithromycin containing regimen and those should be avoided.

Comparison of 7- and 14-day first-line therapies including levofloxacin in patients with Helicobacter pylori positive non-ulcer dyspepsia.

BACKGROUND/AIMS: Because of the increasing resistance to clarithromycin and metronidazole, the most frequently used antibiotics in the first-line therapy of Helicobacter pylori eradication, new therapeutic alternatives are needed. The aim of this study was to compare the efficacy of 7- and 14-day triple therapy including lansoprazole, levofloxacin and amoxicillin for Helicobacter pylori eradication as a first-line therapy. METHODS: Ninety-one non-ulcer dyspeptic patients infected with Helicobacter pylori as diagnosed by both histology and a rapid urease test were included in this study. Patients were randomized to receive either 7- (Group 1; 51 patients) or 14-day (Group 2; 40 patients) therapy with lansoprazole (30 mg b.i.d.), plus levofloxacin (500 mg o.i.d.) and amoxicillin (1000 mg b.i.d.) and they were followed for six weeks. Eradication was assessed by 14C-urea breath test four weeks after completing the treatment protocols. RESULTS: In Group 1, 41 patients completed the treatment and the eradication rate was 34.15%. In group 2, 36 patients completed the treatment and the eradication rate was 72.2% (p= 0.001 vs group 1). CONCLUSIONS: Triple therapy with lansoprazole, levofloxacin and amoxicillin for 14 days was effective for Helicobacter pylori eradication, but 7-day therapy with the same protocol had a lower and unacceptable cure rate and should not be used.

Evaluation for Helicobacter pylori in Meckel's diverticulum by using real-time PCR.

BACKGROUND: Although Helicobacter pylori (H. pylori) has been identified in heterotopic gastric mucosa of Meckel's diverticulum, controversial results are reported in the pertinent literature. AIMS: The aim of this study was to evaluate for the presence of H. pylori histologically using hematoxylin-eosin and Toluidine Blue in Meckel's diverticulum and by real-time TaqMan polymerase chain reaction (PCR) in those with heterotopic gastric mucosa. METHODS: The study included 21 consecutive patients who had undergone resection of Meckel's diverticulum at our hospital between 1995 and 2007. The paraffin-embedded tissues were retrieved and reviewed for the presence of histological abnormalities and H. pylori-like organisms and for the presence or absence of heterotopic mucosa. H. pylori was sought in those cases that contained heterotopic gastric mucosa using real-time TaqMan PCR to amplify a fragment of the 23S ribosomal RNA (rRNA) gene of H. pylori. RESULTS: Upon histological examination, heterotopic gastric mucosa was found to be present in 12 cases. H. pylori was not identified in any of the sections examined. A genomic PCR product was also not obtained in real-time PCR study. CONCLUSIONS: We have confirmed that colonization of H. pylori, if it occurs at all, is exceedingly rare in heterotopic gastric mucosa of Meckel's diverticulum.

The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan.

OBJECTIVES: Afghanistan is one of the endemic regions of chloroquine resistant P. falciparum. Mefloquine and doxycycline are among the recommended prophylactic regimes. The aim of the study was to compare the efficacy and tolerability of the two regimes on the Turkish soldiers settled in Kabul, Afghanistan. METHODS: A total number of 1400 soldiers were subjected to prophylactic regimes with either doxycycline 100 mg/day (n=986) or mefloquine 250 mg/week (n=414). Prophylaxis lasted about 12 weeks. The side effects and compliances were investigated by questionnaires. All soldiers were monitored up to 6 months after returning home. RESULTS: No malaria case was observed and there was no severe side effect in either group. The total side effects in doxycycline group were significantly higher (P<0.001). The compliance of mefloquine takers was better than the doxycycline takers (P<0.05). CONCLUSIONS: The tolerability of the mefloquine regime is better than the doxycycline regime in malaria prophylaxis.