Zeki Yesilova

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.

Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy.

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-α, TGF-β1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-α) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-β1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-β1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.

Systemic Markers of Lipid Peroxidation and Antioxidants in Patients with Nonalcoholic Fatty Liver Disease

OBJECTIVES:The aim of the present study was to examine the systemic parameters of oxidative stress and antioxidants in patients with nonalcoholic fatty liver disease and investigate the relationship between these parameters and clinical and biochemical outcomes.METHODS:Fifty-one male patients with nonalcoholic fatty liver disease (group I), 30 age-matched and body mass index (BMI)-matched healthy male subjects, and 30 age-matched male patients with chronic viral hepatitis (group II) were enrolled in the study.RESULTS:Increased systemic levels of malondialdehyde and depletion of antioxidants such as coenzyme Q10, CuZn-superoxide dismutase, and catalase activity were observed in group I. Coenzyme Q10 and CuZn-superoxide dismutase correlated negatively with increasing necroinflammatory activity and fibrosis. Body fat was negatively associated with plasma coenzyme Q10 levels, while an inverse association was found between plasma catalase levels and TG. However, LDL was positively associated with plasma malondialdehyde levels. CuZn-superoxide dismutase levels were negatively associated with glucose, insulin, and HOMA-IR. In addition, the levels of CuZn-superoxide dismutase correlated significantly in a negative manner with BMI.CONCLUSIONS:Our results concerning correlations suggest that disturbances in BMI, body fat, and lipid metabolism may contribute to altered oxidative status in NAFLD, and insulin resistance may be related to decreased antioxidants in NAFLD as well as products of lipid peroxidation. However, although our results suggest interesting correlations, this different mostly “weak” relationships must be taken with caution.

Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease

OBJECTIVES In this study we aimed to determine the levels of Glutathione peroxidase (GSH-Px) and Malondialdehyde (MDA) in patients with inflammatory bowel disease (IBD) to investigate their contribution to tissue injury in inflammatory bowel disease. DESIGN AND METHODS Forty-seven GSH-Px patients (35 with ulcerative colitis and 12 with Crohns disease) and 30 healthy controls were included in the study. Their plasma and MDA levels were compared using nonparametric statistical methods. RESULTS Plasma GSH-Px levels of the patients group were significantly higher than the control group (p < 0.001). There was no significant difference between patients and controls in view of plasma levels of MDA. CONCLUSIONS High levels of GSH-Px, which is response against oxidative stress, indicates the increase of free radicals in IBD, while normal plasma MDA levels suggest the clearance of free radicals without leading to lipid peroxidation. Our result reveals that there is an existing antioxidant capacity despite oxidative stress in patients with IBD.

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.

Comparison of sequential and standard triple-drug regimen for Helicobacter pylori eradication: a 14-day, open-label, randomized, prospective, parallel-arm study in adult patients with nonulcer dyspepsia.

BACKGROUND The eradication rates of Helicobacter pylori with standard treatments are decreasing worldwide. OBJECTIVES The primary aim of this study was to compare the eradication success of a 14-day sequential regimen with proton pump inhibitor (PPI)-based triple treatment. The secondary objectives of the study were to evaluate the effect of gastritis score and smoking on eradication rates as well as evaluation of compliance and tolerability of both regimens. METHODS Consecutive H pylori-positive patients with nonulcer dyspepsia were randomized into 1 of 2 groups in this 14-day, open-label, randomized, prospective, parallel-arm study. An upper endoscopy with biopsy and (14)C-urea breath test ((14)C-UBT) were performed before enrollment. The first group was administered a sequential regimen consisting of pantoprazole 40 mg and amoxicillin 1 g for 7 days, followed by pantoprazole 40 mg, tetracycline 500 mg, and metronidazole 500 mg for the next 7 days. The second group was administered pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg (PAC group) for 14 days. All drugs were administered BID, with the exception of tetracycline, which was administered QID. Eradication was confirmed by (14)C-UBT 6 weeks after the end of the treatment. Histologic examination and (14)C-UBT were conducted by investigators blinded to the protocols. Patients were asked to report any adverse events (AEs) during the treatment period. RESULTS Three hundred white patients were enrolled in the study and evenly randomized into the sequential treatment group (98 males and 52 females; mean age, 40.2 years) and the PAC group (86 males and 64 females; mean age, 41.2 years). A total of 274 patients completed the study per protocol (PP). Twenty-six patients discontinued: lost to follow-up (16), withdrawn due to AEs (9); and noncompliance (1). The intent-to-treat (ITT) and PP H pylori eradication rates were 72.6% and 80.1% in the sequential group, and 58% and 63% in the PAC group, respectively. The eradication rate was significantly higher in the sequential group compared with the PAC group in both the ITT and PP populations (P=0.01 and P=0.002, respectively). The eradication rates were higher in nonsmoking patients compared with smoking patients both in the sequential group (85.8% vs 70.5%) and the PAC group (67.7% vs 53.3%), but the results were not statistically significant when the groups were analyzed separately. Overall, 32 patients (10.7%) reported an AE. Treatment was discontinued in 9 patients because of serious AEs (sequential group--abdominal pain [2 patients], diarrhea [1], chest pain [1], and vaginal pruritus [1]; PAC group--nausea/vomiting [2], chest pain [1], and numbness [1]). There were no significant between-group differences in regard to compliance or AEs. Univariate analyses found no significant effect of sex, age, alcohol consumption, antacid usage, or gastritis score on the eradication rates. CONCLUSIONS A 14-day sequential treatment regimen achieved a significantly higher eradication rate of H pylori compared with standard PPI-based triple regimen in this small selected population. Large, double-blind, controlled studies are needed to confirm these results.

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.

Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert's syndrome

Background and Aim:  The association of hyperbilirubinemia in Gilberts syndrome (GS) with a decrease in prevalence of coronary artery disease is a well‐known phenomenon. In this study, the state of low‐density lipoprotein (LDL) oxidation which has been postulated to be a significant determinant at the etiopathogenesis of atherosclerotic disorders was investigated among individuals with GS.