Mustafa Gulsen

Metformin in the treatment of patients with non‐alcoholic steatohepatitis

Background : Increased insulin resistance is the major pathogenic mechanism in the development of non‐alcoholic steatohepatitis.

Serum leptin levels in patients with nonalcoholic steatohepatitis

OBJECTIVE:Leptin is a peptide hormone that mainly regulates food intake and energy expenditure of human body. A close correlation between serum leptin levels and the percentage of body fat stores is well known. Nonalcoholic steatohepatitis (NASH) is a common disorder which causes serum liver enzyme elevation. In this study, the serum leptin levels were investigated in patients with NASH to determine a possible role in the pathogenesis and in patients with chronic viral hepatitis to ascertain the effect of hepatic inflammation on serum leptin level.METHODS:Forty-nine patients (38 men, 11 women) with NASH diagnosed by biopsy, 32 patients with biopsy-proven chronic viral hepatitis (21 men and 11 women), and 30 healthy adults (17 men, 13 women) enrolled in the study. Fasting blood samples were obtained, and serum leptin levels were measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected.RESULTS:The mean serum leptin levels (±SEM) were 6.62 ± 0.71, 4.24 ± 1.0, and 4.02 ± 0.46 ng/ml in NASH, chronic hepatitis, and the control group, respectively. Mean serum leptin level in the NASH group was significantly higher than those in the other groups tested. BMI was also slightly higher in the NASH group when compared to the other groups (26.7 ± 0.3, 23.7 ± 0.6, and 24.6 ± 0.3, respectively). There was a significant correlation between BMI and serum leptin levels when all the subjects were evaluated together (NASH, hepatitis, and control groups, r= 0.337, p= 0.012) but not in the NASH group when evaluated alone (r= 0.238, p= 0.1). Of the predisposing factors for NASH, obesity was observed in 24% of patients and hyperlipidemia in 67%. Serum cholesterol and triglyceride levels were significantly higher in the NASH group than those in controls (p < 0.05). It has been detected that most of these patients consumed high amounts of fat in their dietary habits.CONCLUSIONS:The serum leptin levels were significantly higher in patients with NASH, while they were not affected by chronic hepatitis. This elevation is out of proportion to BMI of these patients and may be related to hyperlipidemia in most. Elevated serum leptin levels, therefore, may promote hepatic steatosis and steatohepatitis.

Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non‐alcoholic fatty liver disease

Background:  Although steatosis is common in patients with severe hyperhomocysteinemia due to deficiency of cystathionine β‐synthase, there are no satisfactory data on homocysteine concentrations in patients with non‐alcoholic fatty liver disease. The main aim of the present study was to evaluate the clinical significance of plasma homocysteine concentrations in patients with non‐alcoholic fatty liver disease.

Leptin levels in the acute stage of ulcerative colitis

Background and Aims:  Leptin, a recently discovered protein, acts as a hormonal feedback signal in regulating adipose tissue mass via hypothalamic mechanisms. Inflammatory bowel disease is often associated with anorexia and weight loss. The aim of the present study was to investigate serum leptin levels during the time course of the acute phase of ulcerative colitis (UC) and to evaluate whether leptin leads to anorexia and bodyweight loss in these patients.

Enteral nutrition via percutaneous endoscopic gastrostomy and nutritional status of patients: five-year prospective study.

Background:  Since it was described in 1980, percutaneous endoscopic gastrostomy (PEG) has been a widely used method for insertion of a gastrostomy tube in patients who are unable to swallow or maintain adequate nutrition. The aim of the present paper was to determine the complications of PEG insertion and to study pre‐ and post‐procedural nutritional status.

Do the Changes in the Serum Levels of IL-2, IL-4, TNFα, and IL-6 Reflect the Inflammatory Activity in the Patients with Post-ERCP Pancreatitis?

Background. Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. Goals. To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)α, and IL-6 levels and the development of post-ERCP pancreatitis. Study. Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFα, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. Results. Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFα levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFα/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. Conclusions. The enhancement of serum TNFα and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP.

Treatment of choledocholithiasis in pregnancy: a case report.

Abstract. Some difficulties have been encountered in treating pregnant patients with choledocholithiasis because of the probable harmful effect of scopic irradiation on fetus when endoscopic retrograde cholangiopancreatography (ERCP) is necessary. In this paper, we present such a patient, in whom endoscopic stone extraction without scopic examination was successfully carried out in the guidance of magnetic resonance cholangiopancreatography (MRCP) before the ERCP procedure.

Efficacy of omeprazole plus two antimicrobials for the eradication of Helicobacter pylori in a Turkish population.

Omeprazole combined with 2 antimicrobials has been suggested as a first-line option for Helicobacter pylori eradication in recent years. However, controversy exists regarding the efficacy of this protocol. This open-label, prospective clinical study investigated the efficacy of omeprazole-based triple therapy for H pylori eradication in 518 patients with H pylori-positive functional dyspepsia with or without duodenal ulcer. Amoxicillin, macrolides (clarithromycin or roxithromycin), and nitroimidazoles (metronidazole, ornidazole, or tinidazole) were the antibiotics used in the study. Nonulcer patients were randomly assigned to 1 of 8 different treatment protocols and duodenal ulcer patients were randomly assigned to 1 of 4 different treatment protocols consisting of omeprazole (20 mg once daily for nonulcer patients, 20 mg twice daily for ulcer patients for 14 days) with a combination of 2 of the above antimicrobials (for 10 days). H pylori infection was assessed by histologic findings and a rapid urease test before therapy and 4 weeks after therapy ended. Four hundred fifty-nine patients completed their regimens; 327 had functional dyspepsia (180 men, 147 women; median age, 39 years; range, 18 to 70 years) and 132 had ulcers (81 men, 51 women; median age, 40 years; range, 18 to 70 years). Eradication of H pylori was achieved in 58.8% (270 of 459) of all patients, 58.1% (190 of 327) of nonulcer dyspeptic patients, and 60.6% (80 of 132) of duodenal ulcer patients. The eradication rate varied from 47.2% to 69.4% in different treatment protocols. There were no statistically significant differences in eradication rates in any treatment group. All drugs were generally well tolerated in all groups, and no patient discontinued treatment because of side effects. Therapy with omeprazole and 2 antimicrobials for H pylori had limited efficacy in a Turkish population. The reason for these results, which conflict with those of other studies, is not clear. Further investigations of regimens for the eradication of H pylori in our population are necessary.

Pulse Wave Velocity, Intima Media Thickness, and Flow-mediated Dilatation in Patients with Normotensive Normoglycemic Inflammatory Bowel Disease.

Background:Patients with inflammatory bowel disease (IBD) have increased risk for atherosclerosis. The cause of increased cardiovascular risk is not fully understood. Chronic inflammatory process may predispose to atherosclerosis. We aimed primarily to investigate subclinical atherosclerosis in patients with IBD, by measuring carotid femoral pulse wave velocity (PWV), carotid intima media thickness, and flow-mediated dilatation compared with matched normal controls. Methods:Patients with IBD were recruited among individuals proven to have Crohns disease (CD) and ulcerative colitis (UC). To exclude any interference of confounding factors for endothelial dysfunction or atherosclerosis, we studied a specifically selected group with no additional cardiovascular risk. PWV, carotid intima media thickness, and flow-mediated dilatation levels were measured in all patients and controls. Results:The carotid femoral PWV levels were 8.13 ± 1.61 m/sec in the patients with UC, 8.16 ± 1.74 m/sec in the patients with CD, and 6.85 ± 0.95 m/sec in the healthy subjects. The levels of carotid femoral PWV were significantly higher in patients with CD and UC than control group (P < 0.001). Flow-mediated dilatation levels were significantly decreased in patients with UC and CD (9.6% ± 5.1% versus 108% ± 4.4%) when compared with control subjects (15.1% ± 9.7%) (P = 0.004). No significant difference in carotid intima media thickness was detected between UC, CD, and control groups (P = 0.152). Conclusions:This study suggests that patients with IBD without traditional cardiovascular risk factors have increased risk of endothelial dysfunction and atherosclerosis.

The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents

Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models.