Plasma visfatin concentrations in subjects with type 1 diabetes mellitus.

BACKGROUND/AIMS: Visfatin is a recently discovered adipokine, and its circulating concentrations have not been adequately studied in type 1 diabetes mellitus (DM). Therefore, this study was designed to examine plasma visfatin levels in type 1 diabetic patients and to determine the relationships between visfatin and duration of diabetes, body mass index, glycemic control, insulin dosage and lipid profile. METHODS: Forty-eight patients with type 1 DM and 26 healthy controls were investigated. RESULTS: Type 1 diabetic patients had significantly low visfatin levels compared with controls (18.8 +/- 1.7 vs. 20.2 +/- 0.3 ng/ml; p < 0.0001). Visfatin levels were comparable between patients with a short duration of diabetes (<10 years) and patients with a long duration of diabetes (>or=10 years) (18.9 +/- 1.7 vs. 18.2 +/- 2.0 ng/ml; p > 0.05). There was a significant correlation between visfatin and hemoglobin A1c (HbA1c) even after the adjustment for age, sex, body mass index and duration of diabetes (r = -0.48, p = 0.005) in the patient group. Multivariate analysis showed that significant determinants of visfatin concentrations were HbA1c and duration of diabetes (r(2) = 0.27). CONCLUSION: These data emphasize that plasma visfatin concentrations are lower in patients with type 1 DM and related to glycemic control reflected by HbA1c.

Effect of melatonin on healing of colonic anastomosis in a rat model of peritonitis.

BACKGROUND: The aim of this study is to determine the effect of melatonin on intestinal anastomosis in the presence of peritonitis. MATERIAL AND METHODS: 32 Wistar albino rats were randomized into four groups (n = 8): A (sham), B (control), C (melatonin 5 mg/kg), and D (melatonin 10 mg/kg). In group A, only cecal dissection was carried out. In the other groups, cecal ligation and puncture (CLP) followed cecal dissection in order to induce bacterial peritonitis. 24 h after the previous operation, cecal resection and ileocolic anastomosis were performed in the rats of all groups. In group C (5 mg/kg) and group D (10 mg/kg), melatonin was injected for 5 consecutive days starting after CLP. At the 48th hour of the CLP procedure, blood was drawn via the tail vein for tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) analysis, and on the 4th day of the experiment relaparotomy was carried out for bursting pressure (BP) measurements. The intestinal tissue containing the anastomotic line was then snap-frozen in liquid nitrogen and stored at -80 degrees C for determination of tissue levels of malondialdehyde (MDA) and glutathione (GSH). RESULTS: The tissue MDA level, blood TNF-alpha and IL-6 levels of group B were significantly higher than in the other groups, whereas the BP results and GSH levels of group B were found to be significantly lower than in the other groups. The results of groups C and D are statistically different from those of group B. When we compared the results of groups C and D, we found significantly higher results in terms of BP and GSH levels in group D and also significantly lower results in terms of MDA, blood TNF-alpha and IL-6 levels in group D. CONCLUSION: The findings of this experiment suggest that melatonin has a dose-independent positive effect on wound healing of colonic anastomosis.

The effect of the sulfonylurea glyburide on glutathione-S-transferase and glucose-6-phosphate dehydrogenase in streptozotocin-induced diabetic rat liver.

Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. Glutathione-S-transferase (GST) catalyses the conjugation of glutathione with a variety of organic peroxides to form more water-soluble compounds. Glucose-6-phosphate dehydrogenase (G6PDH) is essential to control intracellular reductive potential by increasing glutathione intracellular levels, which in turn decrease the amount of reactive oxygen species. Glyburide decreases glucose production and enhances insulin action in liver. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the liver tissue of diabetic rat. We investigated the activities of GST and G6PDH in the liver of both control and streptozotocin-induced diabetic rats. Forty male albino rats were included in this study. Liver GST and G6PDH activities decreased significantly in five-week diabetic rats (p<0.001 and p<0.001 respectively) compared to controls and glyburide therapy restored these activities (p<0.001 for GST and p<0.001 for G6PDH). Elevations of hepatic antioxidant enzymes with glyburide administration suggest that glyburide may directly alter hepatic enzyme activities.

Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) attacks are characterized by serosal inflammation rich in PMNL leukocytes and activation of a definite cytokine network. Moreover, there is sustained inflammation in attack-free FMF patients. Interleukin (IL)-17 and IL-18 are recently described proinflammatory cytokines, which can modulate certain neutrophil functions. In this study we measured serum levels of IL-17 and IL-18 in FMF patients. METHODS: The study groups comprised of 18 FMF patients in attack-free period (mean age: 30.2 +/- 9.5 years; male/female: 10/8), and 18 patients with an acute FMF attack (mean age: 25.4 +/- 4.9 years; male/female: 10/8). Twenty age-matched healthy subjects were included as a control group (male/female: 10/10). Levels of IL-17 and IL-18 were determined by commercial ELISA kits (Biosource International, USA). RESULTS: Serum IL-17 levels were 42.8 +/- 3.7, 42.7 +/- 3.2, and 39.9 +/- 2.3 pg/mL for FMF patients in attack-free period, FMF patients with acute attack, and healthy controls, respectively. Serum IL-18 levels were 878.8 +/- 315.0, 854.2 +/- 261.4, and 314.6 +/- 80.8 pg/mL for FMF patients in an attack-free period, FMF patients with acute attack, and healthy controls, respectively. Levels of both IL-17 and IL-18 were significantly higher in FMF patients with and without acute attack compared to control group (p < 0.05). Concentrations of those cytokines were comparable in FMF patients with acute attack and in attack-free period (p > 0.05). CONCLUSION: Our data suggest that IL-17 and IL-18 contribute to the cytokine network in the inflammatory cascade of FMF. However, their roles for the initiation of FMF attacks remain to be established.

Serum interleukin 18 and tumour necrosis factor-alpha levels are increased in Behcet's disease.

Inflammation in Behcet's disease is thought to be mediated by cytokines derived from T-helper type 1 (Th1) lymphocytes. In this study, we tried to determine serum interleukin (IL)-18 and tumour necrosis factor (TNF)-alpha levels of patients with Behcet's disease. Twenty-seven patients with active Behcet's disease, and 20 healthy control subjects were included in this study. Differences between mean serum IL-18 and TNF-alpha level of patients with Behcet's disease were significantly increased when compared with the control group. A significant correlation was found between serum IL-18 and TNF-alpha levels of Behcet patients (rs = 0.627, P < 0.0001). IL-18 and TNF-alpha levels may be related to disease pathogenesis. Increased levels of IL-18 also support Th1 predominance in Behcet's disease.

The effects of the sulfonylurea glyburide on glutathione peroxidase, superoxide dismutase and catalase activities in the heart tissue of streptozotocin-induced diabetic rat.

Oxygen free radicals have been suggested to be a contributory factor in diabetes complications. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the heart tissue of diabetic rats. We investigated the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in the hearts of both control and streptozotocin-induced diabetic rats. In the heart of diabetic rats, the activity of total superoxide dismutase decreased significantly (p < 0.005), whereas the activity of catalase and glutathione peroxidase increased to a large extent (p < 0.0001 and p = 0.05, respectively) at the end of the fourth week compared with the control group. Glyburide treatment of diabetic rats for 4 weeks corrected the changes observed in diabetic heart. In addition, blood glucose levels of untreated diabetic rats decreased following the glyburide treatment. These results demonstrate that the sulfonylurea glyburide is capable of exerting direct insulin-like effect on heart superoxide dismutase, catalase and glutathione peroxidase activities of diabetic rats in vivo.

Serum hepatocyte growth factor and interleukin-6 levels can distinguish patients with primary or metastatic liver tumors from those with benign liver lesions.

Hepatocyte growth factor (HGF) is a potent stimulator of angiogenesis and cancer metastasis. Interleukin-6 (IL-6) is a pleiotropic cytokine that can act as an autocrine or paracrine growth factor in various tumor cells. In this study, we investigated the role of serum HGF and IL-6 levels to distinguish primary or metastatic liver tumors from benign liver lesions. Serum HGF and IL-6 levels were measured in 64 cancer patients and 12 healthy controls. Patients were divided into 5 groups: Group-1 (n=24): Breast cancer patients in complete remission without any liver lesion, Group-2 (n=8): Breast cancer patients in complete remission with benign liver lesion, Group-3 (n=10): Breast cancer patients with liver metastasis, Group-4 (n=11): Metastatic breast cancer patients without liver metastasis, Group-5 (n=11): Patients with hepatocellular carcinoma. Group-6 (n=12): Healthy controls. Serum HGF levels were found to be higher in group-5 (606.4+/-255.8 pg/ml) than those in group-1 (*305.6+/-42.3 pg/ml), group-2 (*293.9+/-44.8 pg/ml), group-4 (**358.4+/-81.9 pg/ml) and group-6 (*305.8+/-24.9 pg/ml) (*p<0.001, **p<0.05). Patients in group-3 (448.9+/-157.3 pg/ml) had higher serum HGF levels than those in group-1, group-2 and group-6 (p<0.05). Serum IL-6 levels were found to be higher in group-5 (54.9+/-37.4 pg/ml) than those in group-1 (9.7+/-6.4 pg/ml), group-2 (9.5+/-4.8 pg/ml), group-4 (17.6+/-19.6 pg/ml) and group-6 (12.6+/-5.2 pg/ml, p<0.05). Patients in group-3 (32.5+/-36.9 pg/ml) had higher serum IL-6 levels than those in group-1, 2 and group-6, but these were not statistically significant (p>0.05). This study showed that primer and metastatic liver tumors had higher serum HGF and IL-6 levels than other patients and controls. Measurements of these markers in serum may be used to distinguish patients with primer liver tumors or breast cancer patients with liver metastasis from those with benign liver lesions or non-metastatic patients.

Serum levels of interleukin-18 and nitrite+nitrate in renal cell carcinoma patients with different tumor stage and grade.

Interleukin (IL-18) and nitric oxide (NO) are immunoregulatory cytokines that have been suggested to participitate in the multistep process of carcinogenesis. In this study, serum IL-18 and nitrite+nitrate levels (as an index of NO generation) were measured in 26 patients with histologically confirmed renal cell carcinoma (RCC) before surgical procedure and in 8 healthy controls. RCC patients showed significantly higher serum IL-18 levels when compared to the control subjects (p<0.001). Serum IL-18 levels were found to be similar in patients with T1 and T2, T3, T4 tumors (p>0.05). Patients with grade 3 and 4 tumors showed significantly higher serum IL-18 levels when compared to the patients with grade 1 and 2 tumors (p<0.05). No significant difference was found in serum nitrite+nitrate levels between RCC patients and control subjects (p>0.05). Serum nitrite+nitrate levels were lower in patients with grade 3 and 4 tumors than those with grade 1 and 2 tumors, but this was not statistically significant (p=0.063). In conclusion, elevated serum level of IL-18 in RCC patients than in controls and extra-increase of this level in those with high grade tumors may reflect the degree of human defence mechanisms against tumor cells in RCC.

Nitric oxide levels in Behçet's disease.

Behçet's disease (BD) is a chronic multisystemic disorder which is characterized by a relapsing systemic inflammatory process. In certain inflammatory conditions such as rheumatoid arthritis, over production of nitric oxide (NO) could damage host cells and tissues, either directly and/or following reaction with other free radicals, such as superoxide anion to form species including peroxynitrite or hydroxyl radicals. Excessive superoxide radical production and impaired antioxidant mechanism in both the neutrophils and plasma of patients with BD have been reported. Our study was designed to investigate the role of NO in BD. NO is an extremely unstable molecule and rapidly converted in vivo and in vitro to nitrate (NO3-) and nitrite (NO2-). For this reason serum NO2- and NO3- have been used as an index of NO generation. We measured serum nitrate + nitrite levels, by using an enzymatic one-step methodology based on the reduction of nitrate to nitrite by nitrate reductase from Aspergillus species, in the presence of beta-NADPH. When compared to healthy controls, serum nitrate + nitrite levels were found to be higher in active periods of BD patients (P < 0.01). It was concluded that increased NO production in patients with BD might have critical biological activities relevant to vasculitic events in the active period of disease.

Serum and ascitic fluid nitrate levels in patients with cirrhosis.

BACKGROUND: Increased nitric oxide level may play a critical role in the hemodynamic disturbances in patients with cirrhosis. There are few reports investigating the factors related to this increase and their results are controversial. The purpose of this study was to reveal the clinical importance of nitric oxide levels and the possible factors related to this increase in patients with cirrhosis. METHODS: Serum and ascites nitrate levels were studied in 50 patients with cirrhosis and 10 control subjects. RESULTS: All cirrhotic patients (groups 2, 3, 4, 5, 6) showed significant increase in serum nitrate levels in comparison with that in control subjects (group 1) (p<0.001). Serum nitrate levels were significantly higher (282.4+/-111.3 micromol/l; p<0.05) in patients with spontaneous bacterial peritonitis (group 2) when compared with those in cirrhotic patients without spontaneous bacterial peritonitis (group 3) (186.4+/-87.6 micromol/l). Ascitic fluid nitrate levels were significantly higher (302.4+/-66 micromol/l; p<0.001) in patients with spontaneous bacterial peritonitis (group 2) when compared with those in cirrhotic patients without spontaneous bacterial peritonitis (group 3) (135.4+/-65.8 micromol/l). Serum nitrate levels were significantly lower in cirrhotic patients without ascites (group 5) when compared with those in cirrhotic patients with ascites (group 3) (98.8+/-52.6 vs. 186.4+/-87.6 micromol/l; p<0.05). No significant differences were found among patients with severe anemia (groups 4, 6) and other cirrhotic patients (group 3) (174.5+/-54.5, 168.8+/-63.8 vs. 186.4+/-87.6 micromol/l; p>0.05). Cirrhotic patients with Child--Pugh B and C scores showed higher serum nitrate levels (179.4+/-81.1, 222.5+/-101.7 micromol/l; p<0.001) than did cirrhotic patients with Child--Pugh A score (85.8+/-59.7 micromol/l). CONCLUSION: Our findings suggest that overproduction of nitric oxide in cirrhotic patients may be related to the severity of liver damage and spontaneous bacterial peritonitis but not related to their anemia.