Acute and Chronic Pretreatment With Atenolol Attenuates Intestinal Ischemia and Reperfusion Injury in Hypercholesterolemic Rats.

OBJECTIVE: To evaluate the protective effects of preinjury atenolol (acute v chronic) on apoptosis, contractility, oxidative stress, and inflammatory markers in hypercholesterolemic rats undergoing intestinal ischemia-reperfusion (I/R) injury. DESIGN: Prospective, experimental animal study. SETTING: University laboratory. PARTICIPANTS: Male Wistar rats (n = 32). INTERVENTIONS: Rats were divided into the following 4 groups: 1 group was fed a normal diet (ND) (group ND+NoAT [no atenolol]), and the other 3 groups were fed a high-cholesterol diet (HCD)-group HCD+NoAT, group HCD+ChAT (chronic atenolol, 3 mg/kg/day for 8 weeks), and group HCD+AcAT (acute atenolol, 1.5 mg/kg, given 5 minutes before intestinal clamping). All rats underwent I/R injury. The superior mesenteric artery was clamped for 60 minutes, then opened for 120 minutes (reperfusion). Apoptotic cells and stimulated contractions of ileal segments were examined. Tissue markers of intestinal I/R injury were examined. Intestinal malondialdehyde, superoxide dismutase, and nitrate/nitrite levels were measured. MEASUREMENTS AND MAIN RESULTS: The chronic atenolol group had fewer apoptotic cells and higher superoxide dismutase activity compared with the other groups. Intestinal contraction was higher in both atenolol pretreatment groups compared with the NoAT groups. Chronic and acute atenolol resulted in lower ileal levels of malondialdehyde and immunolabeling-positive cells (intestinal inducible nitric oxide synthase, endothelial nitric oxide synthase, interleukin-1, and interleukin-8) after I/R injury compared with the no atenolol groups. CONCLUSIONS: Both chronic and acute pre-I/R injury treatment with atenolol attenuated I/R injury in this hypercholesterolemic rat model. These findings should encourage future studies of atenolol in hypercholesterolemic patients undergoing procedures with a high risk of intestinal ischemia.

Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet.

Coronary heart disease because of atherosclerosis is still the most common cause of mortality. Elevated levels of low-density lipoprotein and total cholesterol are major risk factors for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the effects of the olive leaf extract on serum lipid profile, early changes of atherosclerosis and endothelium-dependent relaxations in cholesterol-fed rats. For this purpose, rats were fed by 2% cholesterol-enriched or standard chow for 8 weeks. Some rats in each group were also fed orally by olive leaf extract at doses of 50 or 100 mg/kg/day. Atorvastatin at dose of 20 mg/kg of body weight daily was also given as positive control. After 8 weeks, lipid profiles of rat serums were analyzed. Antioxidant enzyme activities (superoxide dismutase and glutathione peroxidase) and degree of lipid peroxidation (malondialdehyde levels) were also measured in the hearts isolated from rats. In addition, expression of adhesion molecules and endothelium-dependent relaxations of isolated thoracic aortas of rats were evaluated. Total cholesterol and LDL-cholesterol levels were found to be increased in cholesterol-fed rats, and both doses of olive leaf extract and atorvastatin significantly decreased those levels. In conclusion, because the olive leaf extract attenuates the increased cholesterol levels, it may have beneficial effects on atherosclerosis.

Elevated glucose level at 30 minutes during an oral glucose tolerance test in obese adolescents: a new disorder of glucose tolerance.

We observed glucose levels >140 mg/dL measured at 30 minutes (min) during an oral glucose tolerance test (OGTT) in some obese patients. We aimed to investigate the significance of this finding by comparing lipid profiles, insulin resistance indices, and systemic inflammatory mediators between obese adolescents with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and elevated glucose levels at 30 min. The study involved 80 obese (body mass index >95(th) percentile for age and sex) adolescents (48 female, 32 male) between 11 and 16 years of age. Depending on OGTT results, patients were divided into NGT and IGT groups. The third group was recruited from the NGT group as having glucose levels > 140 mg/dL at 30 minutes. Lipid profiles, [interleukin-6 (IL-6)], neopterin, and lipoprotein associated phospholipase A2 (Lp-PLA2)] were assessed. Neopterin and Lp-PLA2 levels were significantly higher in obese adolescents with elevated glucose levels at 30 min. compared with those in both NGT and IGT groups (p=0.013, and 0.004, respectively). In these adolescents, IL-6 levels were significantly higher only than the NGT group (p=0.01). In logistic regression analysis, IL-6, neopterin and Lp-PLA2 levels were detected to be related to high blood glucose levels at 30 min (OR 1.11, p=0.01; OR 9.03, p=0.013; OR 1.01, p=0.004 respectively). Obese adolescents with elevated glucose levels at 30 min. demonstrated higher inflammatory mediators levels, which were atherosclerotic indicators, than obese adolescents with NGT and IGT. These results suggest that glucose levels >140 mg/dL measured at 30 min during an OGTT may be a new disorder of glucose tolerance in obesity.

Effects of physical exercise on lung injury and oxidant stress in children with asthma.

BACKGROUND: The aim of this study was to investigate the influence of exercise training on oxidative stress and markers of lung inflammation in children with asthma. METHODS: Thirty children aged 8-13 years diagnosed with asthma were enrolled in the study as well as 13 healthy children. One group received only pharmacological treatment and the other group was also enrolled in an exercise programme. Venous blood and 24-hour urine samples were obtained from the children enrolled in the study at the beginning and end of the study. Leukotriene E4 and creatinine levels were measured in the urine and matrix metallopeptidase (MMP-9), endothelin-1(ET-1), malnodialdehyde (MDA), IgE and specific IgE levels were measured in blood samples. RESULTS: Leukotriene E4, MDA and MMP9 levels decreased significantly with treatment in both groups (p < 0.001). However, ET-1 levels decreased significant only in the exercise group (26.5 ± 3.6 vs 21.3 ± 2.4 pg/ml respectively, p = 0.001). Moreover, ET-1 levels were found to be significantly lower in the exercise group compared to the only pharmacotherapy group (24.2 ± 3.1 vs 21.3 ± 2.4 pg/ml, p=0.007). CONCLUSIONS: Positive influences of exercise training in children with asthma may be mediated by decrease in ET-1 levels.

Is genetic screening necessary for determining the possibility of venous thromboembolism in cancer patients?

OBJECTIVE: To determine the risk of an association with some genetic polymorphisms involved in venous thromboembolism (VTE) gene variations (FVL, FV H1299R, FII G20210A, MTHFR C677T, MTHFR A1298C, PAI-1 4G/5G, ß-fibrinogen -455 G → A, FXIII Val34Leu and GpIIIa HPA-1a) in cancer patients. SUBJECTS AND METHODS: Among 78 cancer patients, 28 who had proven first episode of VTE were selected as the patient group, with 50 control samples selected from age-, sex- and body mass index-matched healthy volunteers (healthy group). The differences in frequency of genetic polymorphisms were found to be statistically insignificant between these two groups. RESULTS: Logistic regression analysis after adjustment for age, sex, smoking and hypertension showed no difference. The screened mutations of these genes were not significantly associated with VTE risk. CONCLUSION: There is no possible benefit from genetic screening tests regarding VTE in cancer patients.

The beneficial effects of physical exercise on antioxidant status in asthmatic children.

BACKGROUND: The pathogenesis of asthma involves both airway inflammation and an oxidant/antioxidant imbalance. It is demonstrated in asthmatic adults that exercise programmes improve lung function, a mechanism yet to be elucidated. The purpose of this study was to investigate the possible beneficial effects of physical exercise on antioxidant status in asthmatic children which may lead to ameliorated lung function. METHODS: The study enrolled thirteen control and thirty asthmatic children. The asthmatic group was subdivided into two: the first group receiving only pharmacological treatment (n=15) and the second receiving pharmacological treatment with exercise programme (n=15) for 8 weeks. Blood samples were drawn from the subjects before and after treatment periods. As oxidant stress markers blood levels of malondialdehyde (MDA) and total nitric oxide (NO), and as antioxidant status, glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activities were assessed. RESULTS: Before any treatment was initiated, MDA and NO levels in the asthmatic group were significantly higher than the controls (3.40±0.96 nmol/ml vs 2.46±0.58 nmol/ml, and 12.53±2.10 vs 9.40±1.39 micromol/L, respectively). Both SOD (p=0.0001) and GSH-Px (p=0.023) activities were significantly lower in the asthmatic group. Pharmacological treatment and exercise programme together significantly improved lung performance and decreased the levels of oxidant stress markers, in concordance with a significantly increase in antioxidant enzyme activity measures when compared to the pharmacological treatment. CONCLUSION: Structured exercise programme in asthmatic children resulted in better lung function, which may be attributed to its effect on antioxidant status.

Oxidative stress impairs endothelial nitric oxide levels in Behçets' disease.

BACKGROUND: Behçet's disease (BD) is an inflammatory vasculitis. Endogenous nitric oxide (NO), produced by endothelial cells, has pleiotropic effects such as vasodilatator, antiplatelet, antiproliferative. Reactive oxygen species (ROS) are produced at sites of endothelial inflammation. ROS target polyunsaturated lipids, which results in malondialdehyde (MDA) production. OBJECTIVE: The aim was to investigate the oxidative stress in BD patients by measuring MDA and total antioxidant status (TAS) levels and to establish a possible relationship with respect to NO levels regarding disease activity. MATERIALS AND METHODS: 55 BD patients (30 active/25 inactive) and 20 healthy volunteers were included in the study. Blood samples were drawn following an overnight fasting. TAS and MDA levels were determined spectrophotometrically. Serum nitrite (NO(2-)) and nitrate (NO(3-)) levels were measured to estimate NO production. Data were expressed as mean ± SD. RESULTS: TAS levels were significantly lower in BD patients than the controls (1.19 ± 0.34 vs. 3.29 ± 0.89 mmol/L). In the active BD group, MDA levels (0.36 ± 0.19 nmol/mL) were significantly higher than both the inactive BD group (0.25 ± 0.18 nmol/mL) and controls (0.18 ± 0.41 nmol/mL). NO levels were significantly lower in the active group compared to the inactive group (18.0 ± 2.80 vs. 19.40 ± 2.70 µmol/L). MDA levels correlated negatively with NO levels in the active group. CONCLUSION: Decreased NO levels mediated by increased oxidative stress significantly contribute to endothelial dysfunction observed in BD.

The effect of tadalafil on anastomotic healing in ischemic small intestine in rats.

PURPOSE: To investigate the effect of tadalafil on anastomotic healing in an ischemic small intestine. METHODS: Standardized transection and anastomosis in the small intestine were performed in 48 male Sprague-Dawley rats divided into four equal groups (n = 12): group 1, normal anastomosis; group 2, ischemic anastomosis; group 3, normal anastomosis+tadalafil treatment; group 4, ischemic anastomosis+tadalafil treatment. Ischemia was established by ligating 2 cm of mesentery on either side of the anastomosis. Tadalafil was given to the rats once a day at dose of 5 mg/kg. The anastomotic bursting pressures and hydroxyproline concentrations were measured on postoperative day 4. A histopathological evaluation of the anastomoses was also performed. RESULTS: The bursting pressure and hydroxyproline concentration in group 2 were significantly lower than those in the other groups. There was no difference in the hydroxyproline concentration among groups 1, 3, and 4. While there was no difference between groups 3 and 4, the bursting pressures were significantly higher in groups 3 and 4 than in group 1. The histopathological evaluation revealed no significant differences in inflammatory cell infiltration, vascularization, or anastomotic collagen deposition among the groups. CONCLUSION: Tadalafil treatment improved the anastomotic bursting pressure and the hydroxyproline concentration in both normal and ischemic small intestine anastomosis.

Antibiotic treatment is superior to ursodeoxycholic acid on total parenteral nutrition associated hepatic dysfunction.

PURPOSE: This study aimed to investigate the apoptotic mechanisms, oxidative stress, and mechanisms of effect of antibiotics and ursodeoxycholic acid (UDCA) in total parenteral nutrition (TPN)-associated liver injury. METHODS: Four groups of young rabbits were used in the study as follows: Group 1 (n: 7): TPN + Metronidazole (30 mg/kg IV) + Gentamicin (6 mg/kg IV); Group 2 (n: 7): TPN + UDCA (15 mg/kg per oral); Group 3 (n: 6): TPN only; and Group 4 (n: 7): Control group. After 10 days, the animals were killed and livers were removed. Hepatic apoptosis, apoptotic proteins, malondialdehyde (MDA) and myeloperoxidase (MPO) levels were studied in liver, and direct bilirubin values were assessed in the blood samples. RESULTS: Direct bilirubin increased with TPN, and antibiotic combination, as the most effective group, significantly lowered its levels (p < 0.01). MDA values also showed significant differences in comparisons between G1 and G3 (p < 0.05) and G1-G4 (p < 0.01). An increased number of apoptotic cells was detected particularly in G2 and G3, whereas the lowest levels, other than in the control group, were found in G1. All TUNEL-positive cell number data were statistically significant except between G2 and G3(p < 0.05). Caspase-3 and Bax immunoreactivities were greatest in G2. Significant differences were shown in caspase-3 immunoreactivity between the groups (p < 0.01), except between G1 and G3 (p > 0.05). All comparisons between the groups were significant for Bax (p < 0.01). In contrast, Bcl-2 immunoreactivity was moderate and highest in G1: comparisons between G1 and the other groups demonstrated statistically significant differences (p < 0.01). Fas-L immunoreactivity was greatest in G2, and all comparisons between the groups were statistically significant (p < 0.01). CONCLUSIONS: Metronidazole and gentamicin combination is effective on TPN-induced liver injury by the Bcl-2 anti-apoptotic pathway, total anti-apoptotic effect and by decreasing bilirubin levels. Oxidative injury in the liver increased with therapy. UDCA seems less effective on TPN-associated liver injury.

Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease.

Single point mutations in the genes coding for hemostatic factors were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of non-diabetic coronary artery disease [nDCAD] remains controversial. Angiographically demonstrated nDCAD patients (n = 86) and healthy controls (n = 90) were included in the study. Genotype analysis of hemostatic gene polymorphisms were assessed by using CVD strip assay, based on allele specific oligonucleotide probes. The carrier frequency of factor V (FV) H1299R, prothrombin G20210A, glycoprotein (Gp) IIIa L33P, plasminogen activator inhibitor-I (PAI-1) 4G/5G, 4G/4G, 5G/5G, methylenetetrahydrofolate reductase (MTHFR) A1298C and beta-fibrinogen -455 G > A were similar between patients and controls. In contrast, frequency of FV Leiden was significantly higher among patients (12.5%) than controls (5%, OR: 7.94; 95%CI: 1.9-49.6) and FXIII V34L was significantly lower among patients (23.7%) than controls (40%, OR: 0.24; 95%CI: 0.1-0.89). In addition, the frequency of the MTHFR C677T polymorphism was 32.5% among patients compared with 42.5% in controls, of which the T/T genotype was significantly lower among patients (5%) than controls (17.5%, OR: 0.06; 95%CI: 0.01-0.58). No difference was observed in prevalence of prothrombin G20210A, FV H1299R, Gp IIIa L33P, PAI-1 4G5G, MTHFR A1298C, beta fibrinogen 455 G > A mutations between patients and controls. However, lower frequency of FXIII Val34Leu and MTHFR C677T polymorphisms may decrease, while FV Leiden polymorphism may increase development of nDCAD.

Oxidative stress but not endothelial dysfunction exists in non-obese, young group of patients with polycystic ovary syndrome.

OBJECTIVE: To determine if oxidative stress and endothelial dysfunction exist at the same time in a young, non-obese group of patients with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: Celal Bayar University, School of Medicine, Manisa, Turkey. SAMPLE: Thirty-one young, non-obese patients with PCOS and 23 age- and body mass index-matched controls. METHODS: Following clinical and biochemical diagnosis, malonyldialdehyde (MDA), superoxide dismutase (SOD), von Willebrand Factor (vWF), and nitric oxide (NO) levels of patients and controls were measured and compared. MAIN OUTCOME MEASURES: To find out oxidative stress and endothelial dysfunction parameters. RESULTS: MDA (0.12+/-0.03 vs 0.10+/-0.03, p=0.01) and SOD (8.0+/-0.7 vs 7.28+/-0.8, p=0.001) levels were significantly higher in PCOS group while there was no difference in vWF (527.2+/-280.1 vs 568.1+/-276.8, p>0.05) and NO levels (169.9+/-47.4 vs 168.9+/-80, p>0.05). When the results of the PCOS patients were divided into two subgroups in terms of insulin resistance (IR- and IR + ), the IR- subgroup had significantly higher MDA levels compared to the control (0.125+/-0.03 vs 0.101+/-0.03, p=0.03). Though IR+ group also had higher MDA than the control group, it did not reach to a significant level (0.117+/-0.05 vs 0.101+/-0.03, p>0.05). Both IR- and IR+ groups had significantly higher SOD levels compared with control group (7.99+/-0.7 vs 7.28+/-0.8, p=0.009 and 8.22+/-0.8 vs 7.28+/-0.8, p=0.03, respectively). vWF and NO levels were not different among these three groups (p>0.05). CONCLUSIONS: Oxidative stress is prominent while endothelial dysfunction does not exist in young, non-obese patients with PCOS.

Effects of silymarin and pentoxifylline on matrix metalloproteinase-1 and -2 expression and apoptosis in experimental hepatic fibrosis.

BACKGROUND: Many therapeutic strategies have been proposed to treat liver fibrosis, but no drugs have been proved effective. Matrix metalloproteinases (MMPs) have been reported to play a role in some cellular cascades of hepatic inflammation and fibrosis. OBJECTIVE: The purpose of this study was to investigate whether silymarin and pentoxifylline (PTX) have hepatoprotective and antifibrotic effects in experimental hepatic fibrosis. METHODS: Sprague-Dawley rats were divided into 4 groups: silymarin group (silymarin 4 mg/kg · d(-1) orally, common bile duct ligation [CBDL]); PTX group (PTX 2 mg/kg · d(-1) intraperitoneally, CBDL); sham group (common bile duct [CBD] exploration only); and control group (saline 1 mL/d orally, CBDL). The CBD was explored and dissected sufficiently to allow passage of a 3/0 silk suture via midline laparotomy. On day 10, all animals were euthanized via cervical dislocation. Then, 5-cm(3) liver samples from the right lobe were removed for histomorphologic evaluation and 3-mL blood samples were taken via cardiac puncture for biochemical analyses. Apoptosis was determined using the terminal deoxynucleotidyltransferase-biotin nick end-label (TUNEL) staining method. Plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase; total and indirect bilirubin concentration; hepatic MMP-1 and -2 and tissue inhibitor of MMP (TIMP)-l and -2 activity; and transforming-growth factor (TGF)-ß1 concentration were measured. Collagen content was determined by measuring hydroxyproline in liver samples. Malondialdehyde (MDA) was used to estimate lipid peroxidation. RESULTS: Thirty-two adult male Sprague-Dawley rats were divided into 4 groups: silymarin group (n = 7), PTX group (n = 7), sham group (n = 9), and control group (n = 9). Compared with the control group (14.6 [2.44]), mean (SD) hepatocyte apoptosis (as measured by the ratio of TUNEL-positive cells) was significantly suppressed in the silymarin group (1.2 [0.13]; P = 0.001) and the PTX group (3.8 [0.34]; P = 0.001). Mean (SD) MMP-2 activity in the silymarin group (57.35 [9.89] µg/mL; P = 0.04) and the PTX group (46.88 [9.56] µg/mL; P = 0.04) was significantly lower than that observed in the control group (232.32 [79.76] µg/mL). Compared with the control group (1.37 [0.38] µg/mL), TIMP-2 activity was significantly lower in the silymarin group (0.55 [0.13] µg/mL; P = 0.04) and the PTX group (0.42 [0.09] µg/mL; P = 0.01). Compared with the control group (909.17 [117.35] µg/mL), TGF-ß1 was significantly lower in the silymarin group (518.24 [30.34] µg/mL; P = 0.01) and the PTX group (519.57 [47.27] µg/mL; P = 0.01). Histomorphologic changes were significantly greater in the sham group than in the silymarin and PTX groups: hemorrhage (2.44 [0.29] vs 1.29 [0.18] and 1.57 [0.20], respectively; both, P = 0.04); sinusoidal dilatation (2.22 [0.22] vs 1.57 [0.20] and 1.71 [0.18]; both, P = 0.04); presinusoidal polymorphonuclear cell infiltration (3-44 [0.24] vs 2.57 [0.20] and 2.14 [0.26]; P = 0.03 and P = 0.008, respectively); and inflammation (3.44 [0.24] vs 2.57 [0.20] and 2.14 [0.26]; P = 0.03 and P = 0.008, respectively). In the control group, all biochemical markers were elevated, supporting the presence of liver injury. Compared with the control group (630.00 [46.80] U/L), plasma AST activity was significantly lower in the silymarin group (443.11 [78.73]; P = 0.04) and the PTX group (349.42 [34.00]; P = 0.03). Compared with the control group (191.12 [32.93] U/L), plasma ALT activity was significantly lower in the silymarin group (86.14 [4.97]; P = 0.04) and the PTX group (84.14 [11.21]; P = 0.04). MDA concentration was significantly lower in the silymarin group compared with the control group (0.08 [0.01] vs 0.22 [0.03] nmol/mL; P = 0.004); MDA was also significantly lower in the silymarin group than in the PTX group (0.11 [0.02]; P = 0.03). CONCLUSIONS: Silymarin and PTX were associated with lower histopathologic liver damage, hepatocyte apoptosis, and regulation of extracellular matrix proteins. Lipid peroxidation in hepatocytes was significantly lower in the silymarin group compared with the PTX group. Silymarin and PTX appeared to have hepatoprotective effects in this experimental liver fibrosis model, but further clinical and experimental studies are needed.

The effect of Misoprostol, a prostaglandin E1 analog, on apoptosis in ischemia-reperfusion-induced intestinal injury.

The aim of this study was to investigate whether Misoprostol, a synthetic prostaglandin (PG) E1 analog, has any effect on the prevention of apoptosis in ischemia-reperfusion (I/R)-induced intestinal injury. Thirty adult male Wistar albino rats were divided into three groups: group I=sham operated+saline; group II=I/R+saline; and group III=I/R+Misoprostol. Misoprostol (50microg/kg/d) was administered as an intragastric meal for 3 days. The terminal ileum was collected for histological and biochemical investigations. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelled (TUNEL) reaction. Immunohistochemical analysis was performed to determine the distribution of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS). Samples were also analyzed for malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). The number of TUNEL-positive cells was higher in group II when compared to the other two groups (p<0.05). In group III this value was higher when compared to group I, but lower than group II (p<0.05). iNOS immunoreactivity was not detected in ileum sections of group I animals, but moderate immunoreactivity was seen in group II and mild immunoreactivity in group III. The immunoreactivity of eNOS was moderate in ileum sections of all three groups. In ileum tissue, MDA was found to be higher in group II compared to group I (p<0.05), but there was no difference in group III. SOD was not different between groups I and III, but was significantly higher in group II (p<0.05). In our experimental model of I/R-induced intestinal injury, apoptosis is induced in enterocytes, whereas Misoprostol decreases enterocyte apoptosis in this experimental model. Our results indicate that Misoprostol may play a key role in the pathophysiologic events leading to failure of the intrinsic gut barrier defense mechanisms of intestinal epithelium.

Assessment of serum chemerin, vaspin and omentin-1 levels in patients with polycystic ovary syndrome.

OBJECTIVE: To determine serum chemerin, vaspin and omentin-1 in overweight and normal weight patients with polycystic ovary syndrome (PCOS) and investigate the possible relationship between these adipokines and metabolic syndrome. METHODS: This cross sectional study enrolled women with PCOS and healthy women. Serum chemerin, vaspin and omentin-1 were assessed by enzyme-linked immunosorbent assay methods. RESULTS: Forty patients with PCOS and 30 healthy controls were included in the study. In the PCOS group, 18 women were overweight (body mass index [BMI] = 25.0-29.9 kg/m(2)) and 22 had normal weight (BMI = 18.5-24.9 kg/m(2)). Chemerin, total cholesterol, dehydroepiandrosterone sulphate and free androgen index (FAI) were significantly higher; and high-density lipoprotein cholesterol and sex hormone binding globulin were significantly lower in overweight PCOS patients compared with normal weight PCOS patients. A positive correlation was found between chemerin and BMI, triglyceride, insulin, homeostatic model assessment of insulin resistance and FAI in the PCOS group. There was no difference in serum chemerin, vaspin and omentin-1 between PCOS patients and healthy controls. CONCLUSION: Circulating chemerin was increased in overweight compared with normal weight PCOS patients. The most predictive variables for circulating chemerin in PCOS patients were BMI, FAI and age.

Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats.

Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ-induced diabetic group (HFD+STZ) , HFD+STZ diabetic group received melatonin (10mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes.

The effect of trimetazidine on liver regeneration after partial hepatectomy under hepatic blood inflow occlusion.

BACKGROUND/AIMS: It has been shown that hepatic blood inflow occlusion impairs liver regeneration. Our aim in this study was to investigate the effect of trimetazidine, known as an anti-ischemic and anti-oxidant agent, on liver regeneration after hepatic blood inflow occlusion. METHODOLOGY: Sprague-Dawley rats were randomized into three groups. Rats in group 1 underwent 65% hepatectomy. Rats in group 2 and 3 were subjected to 15 minutes of hepatic blood inflow occlusion during 65% hepatectomy. Rats were treated with saline (in group 1 and 2) or trimetazidine (in group 3) 30 minutes before operation. Serum level of aspartate transaminase, wet to dry liver weight ratio, and liver injury score in light microscopy were studied for the evaluation of liver injury. Liver regeneration was evaluated by PCNA-labeling index (the percentage of hepatocytes staining for proliferating cell nuclear antigen), mitotic index (the percentage of mitotic hepatocytes), and liver regeneration rate (the percentage of initial liver weight). RESULTS: Rats in group 2 and 3 had significantly higher serum aspartate transaminase level, wet to dry liver weight ratio and injury score than those in group 1 on day 1 posthepatectomy. Except for serum aspartate transaminase level on day 4, these parameters were significantly higher in group 2 than in group 1 and 3 on day 1 and 4. PCNA-labeling index and mitotic index were significantly less in group 2 and 3 than in group 1 on day 1. In contrast to liver regeneration rate, both indices in group 2 were significantly less than those in group 3 on day 1. There were no differences in regeneration parameters between the groups on day 4. Survival rate was significantly higher in group 3 than in group 2. CONCLUSIONS: Fifteen minutes of hepatic blood inflow occlusion caused an injury in the remnant liver, impaired liver regeneration, and decreased survival rate after partial hepatectomy. However, pretreatment with trimetazidine reduced liver injury, and improved liver regeneration and survival rate. For situations where hepatic blood inflow occlusion is planned in major liver resection, trimetazidine pretreatment would be useful strategy to improve postoperative outcome.

Intestinal ischemia-reperfusion impairs liver regeneration after partial hepatectomy in rats.

BACKGROUND/AIMS: The deleterious effects of intestinal ischemia-reperfusion on liver are realized, but its effect on the regenerative capacity of the liver has not been studied. Our aim in this study was to determine the effect of intestinal ischemia-reperfusion on liver regeneration. METHODOLOGY: Sprague-Dawley rats were randomly divided into six groups; two sham-operated, two hepatectomy, and two hepatectomy with intestinal ischemia-reperfusion groups. To create intestinal ischemia-reperfusion, the superior mesenteric artery and collateral arteries supplying the small intestine were occluded for 20 minutes. Partial hepatectomy was performed during the period of ischemia. Ischemia-reperfusion injury in the mucosal layer of the small intestine was scored in light microscopy. Liver regeneration parameters (proliferating cell nuclear antigen labeling index for hepatocytes and liver regeneration rate), and serum levels of aspartate aminotransferase and alanine aminotransferase were studied on day 1 or 4 after operation. RESULTS: Mucosal injury score was high in the hepatectomy with intestinal ischemia-reperfusion groups. Liver regeneration rate and proliferating cell nuclear antigen labeling index were less in these groups than the hepatectomy groups on day 1 and 4. There were no differences in the serum levels of aspartate aminotransferase and alanine aminotransferase between hepatectomy and hepatectomy with intestinal ischemia-reperfusion groups. The mortality rate was higher in the hepatectomy with intestinal ischemia-reperfusion groups than the other groups. CONCLUSIONS: Ischemia and reperfusion of the small intestine impaired liver regeneration with high mortality after partial hepatectomy in the rats.

Effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial dysfunction, lipid peroxidation, and hepatocyte morphology in rats with sepsis-induced liver damage.

BACKGROUND: Sepsis remains a difficult problem for clinicians, with its systemic effects and high morbidity and mortality rates. The roles of oxidative stress, endothelial dysfunction, and lipid peroxidation in sepsis-induced organ damage are being investigated. OBJECTIVE: The aim of this study was to investigate the effects of selective cyclooxygenase (COX)-2 inhibition on tissue lipid peroxidation, endothelial dysfunction, and hepatic cell morphology in a rat model of sepsis. METHODS: Thirty rats with sepsis induced by cecal ligation and puncture were divided equally into 3 groups: treatment group (rofecoxib 1 mg/kg PO), control group (saline 1 mL PO), and sham group (sham surgery only). All the rats were sacrificed 1 day after sepsis induction. The livers were removed using a median laparotomy for histopathologic and biochemical analysis. RESULTS: Histomorphologic hepatic damage and lipid peroxidation were significantly reduced in the rofecoxib treatment group compared with the control group (P < 0.05 and P = 0.001, respectively). Endothelial nitric oxide synthase and inducible nitric oxide synthase staining of liver samples was statistically significantly reduced in the treatment group compared with the control group (both, P < 0.001). The hepatic nitric oxide level and malonyldialdehyde activity decreased significantly (P < 0.001 and P = 0.001, respectively) in the rofecoxib group compared with the control group. Hepatic myeloperoxidase activity was similar between the treatment and control groups. CONCLUSION: Further investigation of selective COX-2 inhibition as an alternate therapeutic choice for sepsis-induced hepatic damage should be considered.

Hyperbaric oxygen treatment in the experimental spinal cord injury model.

BACKGROUND CONTEXT: Spinal cord trauma is a major cause of mortality and morbidity. Although no known treatment for spinal cord injury exists, a limited number of effective treatment modalities and procedures are available that improve secondary injury. Hyperbaric oxygen (HBO) treatment has been used to assist in neurologic recovery after cranial injury or ischemic stroke. PURPOSE: To report the findings on the effectiveness of HBO treatment on rats with experimental traumatic spinal cord injury. Improvement was evaluated through motor strength assessment and nitrite level assay testing. STUDY DESIGN: We randomly distributed 40 rats among 5 groups of 8 rats each: sham incurable trauma, induced trauma, HBO treatment begun at the 1st hour, HBO treatment begun at the 6th hour, and HBO treatment begun at the 24th hour. METHOD: The HBO treatment was administered to rats in three of the groups and conducted in two 90-minute sessions, under an absolute atmospheric pressure of 2.4 at 100% oxygen for 5 days. In the motor strength evaluations, all the rats were observed during the inclined plane test and clinical motor examination on the first, third, and fifth days. In addition, the nitrite levels of spinal cord tissues on the sixth day were also studied. RESULTS: Results from the inclined plane levels and motor strength test from all the three groups undergoing HBO treatment were higher than those from Group 2. It was also determined that early HBO treatment resulted in higher recovery rates (groups 3 and 4). The highest levels were seen in the group in which the HBO treatments were started in the first hour (Group 3). It was noted that nitrite levels of rats in the group exposed to trauma increased, compared with the sham group, but increased levels also diminished after HBO treatments. Again, the greatest decrease in nitrite levels was evident in the group where the HBO treatment was started the earliest (Group 3). CONCLUSIONS: Prompt HBO treatment after trauma significantly contributed to the clinical, histopathologic, and biochemical recovery of the rats.

Are human adenovirus-5 and 36 associated with obesity in children?

OBJECTIVES: The aims of this study were to determine the association between adenovirus-5- and adenovirus-36-specific antibodies and obesity in children and to investigate their relationship with serum lipid and leptin levels. METHODS: A cross-sectional study was performed on a total of 120 children who were divided into subgroups according to body mass index percentile as obese (≥ 95th percentile) or nonobese (<95th percentile). The presence of adenovirus-36 and adenovirus-5-neutralizing antibodies was investigated by using the serum neutralization assay. Serum leptin levels were determined by microenzyme immonoassay; high-density lipoprotein, low-density lipoprotein, triglyceride, and cholesterol levels were measured by chemiluminescence method. RESULTS: The presence of adenovirus-5-specific antibodies was 28.3% and 6.6% in the obese children and in non-obese children, respectively (P = 0.02). The frequency of adenovirus-36-specific antibodies was significantly greater (P = 0.018) in the obese children (26.6%) than in the non-obese children (10.0%). Serum leptin level of the obese group were significantly higher than that of the non-obese group (P = 0.000). CONCLUSIONS: Our data support the association between obesity and the presence of specific antibodies to adenovirus-36 and adenovirus-5 in children. Our research has the feature of being the first national study to indicate the relationship between adenovirus-36 and human obesity as well as the first international study to indicate the relationship between adenovirus-5 and human obesity.