Myeloid-related protein complex 8/14 increases in hypertensive patients with excessive renal damage
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AIM: Hypertension is a complex condition, and it is difficult to know whether inflammation is a cause or an effect. Information on the association between MRP-8/14 (myeloid-related protein) and hypertension is limited. In this study, we aimed to examine the relationship of MRP-8/14 with carotid intima-media thickness (CIMT) and albuminuria in hypertensive patients and to investigate whether early assay of MRP-8/14 levels could be helpful in assessment of renal damage and carotid atherosclerosis among hypertensive patients. MATERIALS AND METHODS: 61 hypertensive patients and 40 age-, gender-, and body mass index-matched controls were included into the study. Blood samples including fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total protein, albumin, urea creatinine, uric acid, sedimentation, C-reactive protein (CRP), and MRP-8/14 were collected. 24-hour urine albumin excretion and CIMT measurements were also obtained. RESULTS: All inflammatory variables including uric acid, CRP, sedimentation, MRP-8/14, and CIMT were statistically higher in patients with hypertension than in controls. MRP-8/14 was significantly higher in hypertensive patients with macroalbuminuria than in controls (339.3 (IQR (215.2 - 661.7)) ng/mL vs. 204.9 (IQR (140.1 - 339.3)) -ng/mL, p = 0.005, respectively). The levels of CIMT were the highest in macroalbuminuric hypertensive patients (controls vs. normoalbuminuria, microalbuminuria, macroalbuminuria groups, 0.57 (0.53 - 0.67) mm vs. 0.84 (0.76 - 0.89) mm, p = 0.000; 0.57 (0.53 - 0.67) mm vs. 0.87 (0.67 - 0.93) mm, p = 0.000; 0.57 (0.53 - 0.67) mm vs. 0.92 (0.85 - 0.97) mm, p = 0.000, respectively). CONCLUSION: Plasma MRP-8/14 levels were elevated in hypertensive patients with macroalbuminuria, however, it could not serve as an early marker to determine renal damage and carotid atherosclerosis in patients with hypertension.
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Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine.

Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic ß-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, ß-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and ß-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls ( p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or ß-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal ß-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.

The role of protein oxidation and DNA damage in elderly hypertension.

INTRODUCTION: This study aimed to evaluate the role of protein oxidation and DNA damage in the elderly hypertensive (HT) patients. MATERIALS AND METHODS: This study consisted of four groups: two elderly groups with 30 HT patients and 30 normotensive healthy volunteers, and two young groups with 30 HT patients and 30 normotensive healthy volunteers. Plasma total thiol (T-SH), advanced oxidation protein products (AOPPs), protein carbonyl (PCO), ischemia modified albumin (IMA), urine 8-hydroxy-2'-deoxyguanosine (8-OHdG), and prooxidant-antioxidant balance (PAB) levels were measured. RESULTS: In the elderly HT group AOPPs, PCO, 8-OHdG, and PAB were significantly higher than the elderly control group. In the young HT group T-SH levels were significantly lower and the other oxidative stress parameters were significantly higher than the young control group. In the elderly control group AOPPs, PCO, IMA, 8-OHdG and PAB were significantly higher than the young control group. T-SH was significantly lower in the elderly control than the young control group. In the elderly HT group, T-SH levels were significantly lower and AOPPs, PCO, IMA, 8-OHdG, and PAB levels were significantly higher than the young HT group. CONCLUSION: Protein and DNA cell damage occurs by oxidation of free radicals throughout life. Our study supports the view that these radicals may be responsible for the development of hypertension with aging process. Urine 8-OHdG levels can be used as a marker for oxidative DNA damage in the elderly hypertensive patients. Finally, our results suggest that oxidative stress may influence both the development and progression of hypertension and aging.

The Effect of Testicular Torsion Duration on Testicular Steroidogenesis in the Rat Model.

BACKGROUND: Testicular torsion is an emergency condition in which spermatogenesis may be irreversibly damaged. There have been controversial results about the effect of testicular torsion on steroidogenesis. We aimed at investigating the effect of testicular torsion on steroidogenesis. MATERIAL AND METHODS: A total of 40 adult male rats were divided into 4 groups. Left testicles were removed in all groups. Right testicles were torsioned and remained in the torsion position for 1, 3 and 5 h in study groups, whereas no torsion was performed in control. Serum luteinizing hormone (LH) and total testosterone (TT) levels were measured on the 3rd and 30th days of surgery and orchiectomy was performed on the 30th day of testicular torsion for histopathological evaluation. RESULTS: TT levels of study groups were significantly lower than that of the control group on the 3rd day of torsion. LH of study groups was higher than that of the control group, but the difference was significant only in the 5 h-torsion group. The total number of Leydig cells increased in 1- and 3-h groups, whereas it decreased in the 5-hour group. CONCLUSION: Testosterone production and Leydig cell functions significantly decreased after 5 h torsion in the rat model. The duration of torsion less than 5 h yielded partial dysfunction on steroidogenesis.

Effects of isoxsuprine hydrochloride on electrocardiographic and trace element status in sheeps.

OBJECTIVE: To study the effect of isoxsuprine hydrochloride on the ischaemic electrocardiographic change and trace element status in sheep. METHODS: This study was conducted from March 16 to 23, 2012, at Istanbul University, Turkey, and comprised sheep aged 6 months. The animals were divided into two equal groups. The control group was fed a standard diet and had free access to water. In the experimental group, isoxsuprine hydrochloride was injected at a dose of 0.6 mg/kg through the intramuscular route. Electrocardiographic changes, including creatine kinase and cardiac troponin-I, and serum levels of selenium, copper, calcium, magnesium, iron and zinc were investigated in healthy sheep. SPSS 15 was used for statistical analysis. RESULTS: The 14 sheep were divided into two groups of 7(50%) each. The overall mean weight of the study population was 35±10kg. Selenium, calcium, iron and zinc concentrations did not show any difference in serum samples (p>0.05). However, copper and magnesium concentrations decreased in serum after the administration of the drug (p<0.05). In the experimental group, ST segment depression and abnormal T-wave was found in 6(86%) animals within 60min. CONCLUSIONS: Isoxsuprine hydrochloride increased cardiotoxicity risk in sheep.

Effects of hormone replacement therapy on plasma and tissue fibrinolytic activity in a rat model of surgically induced menopause.

PURPOSE: The purpose of this study was to analyze the effects of estrogen deficiency and hormone replacement therapy (HRT) on fibrinolytic activity in a rat mode of surgically-induced menopause. METHODS: Twelve-week-old, sexually mature female Sprague-Dawley rats, each weighing 200-250 g, were randomly divided into four groups: (1) sham-operated group, (2) ovariectomy group, (3) ovariectomy group followed by oral administration of daily 17ß-estradiol (0.02 mg/kg/day) (E2) + norethisterone acetate (0.01 mg/kg/day), and (4) ovariectomy group followed by oral administration of daily 17ß-estradiol (0.01 mg/kg/day) + drospirenone (0.02 mg/kg/day). Tissue plasminogen activator (tPA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1/tPA levels were measured as markers of fibrinolysis in plasma and liver and brain tissue. RESULTS: Compared with sham-operated rats, ovariectomized rats showed higher levels of fibrinolytic activity; however, the increased fibrinolytic activity in plasma and liver tissue was significantly reduced by HRT regimens. No change was observed in the levels of fibrinolytic activity in brain tissue. CONCLUSIONS: HRT showed beneficial effects by decreasing fibrinolytic activity related to surgically-induced menopause. Short-term HRT treatment was associated with a shift in the procoagulant-anticoagulant balance toward a procoagulant state.

Validation of biochemical markers for the prediction of liver fibrosis and necroinflammatory activity in hemodialysis patients with chronic hepatitis C.

BACKGROUND: Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV). METHODS: The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system. RESULTS: The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy. CONCLUSION: The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.

The Effects of Nitric Oxide and Inhibitor, and Combination of Albendazole and Praziquantel On Liver in Mice Injected with Echinococcus granulosus Larvae.

In this study, the role of nitric oxide (NO) in the pathogenesis of hydatidosis and the interaction with effects of anthelmintic drugs, albendazole and praziquantel, were examined in larval infection caused by protoscolices obtained from hydatid cysts of sheep liver in Albino Balb/c mice. Animals were divided into ten groups including controls and infected groups. Larval infection was established with intraperitoneal injection of protoscolices. Eight months after infection with protoscolices, the infected animals were divided into 6 groups. The infected animals were given a selective inhibitor of inducible nitric oxide synthase (iNOS) L-N6-(1-Iminoethyl) lysine-hydrochloride (L-NIL), NO donor sodium nitroprusside (SNP), albendazole and praziquantel as anthelmintic drugs for 7 days. In addition, control groups were composed of intact group, control, anthelmintic drugs + L-NIL, and anthelmintic drugs + SNP. The liver and blood samples were taken for cytological, histological, immunohistochemical and biochemical analyses 7 days after treatments at the end of experiment. The animals injected with protoscolices showed histopathological changes including inflammation areas, infiltration and accumulation of leukocytes, dilation of sinusoids, and damage in endothelial cells and hepatocytes at light microscopy. Electron microscopy were revealed severe damage in sinusoidal endothelial cells, leukocytes especially eosinophils in sinusoid lumens and disorganization in endoplasmic reticulum and nuclear membrane. Endothelial nitric oxide synthase (eNOS) and iNOS reactions were increased in the tissue. Anthelmintic drugs decreased inflammation areas and damages; however, it did not change NOS reactions in the animals given protoscolices. L-NIL and SNP diminished both iNOS and eNOS reactions. Unlike the group administered the inhibitor, SNP treated group exhibited less inflammation areas. Combination of these substances and drugs resulted in decreased inflammation areas. eNOS and iNOS reactions decreased in the drugs and SNP administered group, while only iNOS reaction was decreased in L-NIL given infection group. In addition, the infected groups which received SNP displayed expanded sinusoids and hepatocytes with vacuoles, intriguingly. While levels of serum nitrite/nitrate elevated only in the infection group given drugs and SNP, it decreased in the L-NIL administered group. Tissue level of malondialdehyde increased in infection groups with drugs and SNP. In conclusion, the results indicated that NO plays an important role in the pathogenesis of hydatidosis.

Ezetimibe therapy and its influence on oxidative stress and fibrinolytic activity.

OBJECTIVE: The effect of ezetimibe on blood lipids, oxidative stress, and fibrinolytic activity in hyperlipidemic patients was investigated after three months of therapy. METHODS: Thirty hyperlipidemic patients were treated for twelve weeks with ezetimibe 10 mg/day. A healthy control group with matching age and gender was also included. Fasting blood glucose, lipid parameters, paraoxonase (PON1), protein carbonyl (PCO), oxidized LDL (oxLDL), 8-isoprostane (ISOPR), total antioxidant capacity (TAC) levels, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1), and PAI-1/t-PA levels were evaluated. RESULTS: Ezetimibe therapy for twelve weeks led to changes in lipid profile in accordance with the literature. Fibrinolytic activity parameters, PAI-1/tPA and tPA-1 decreased, whereas PAI-1 levels did not change significantly. Antioxidant parameters, serum PON1 activity, and TAC levels increased significantly compared with the basal values. Oxidant parameters, oxLDL, ISOPR, and PCO (which is an indicator of oxidative protein damage) decreased significantly after therapy. CONCLUSIONS: Ezetimibe therapy has beneficial effects on fibrinolytic activity and homeostasis between oxidant and antioxidant activity in hyperlipidemic patients This may be through lowering lipid levels or other mechanisms such as decreasing insulin resistance and the pleiotropic effects of the drug.

Assessment of low-density lipoprotein oxidation, paraoxonase activity, and arterial distensibility in epileptic children who were treated with anti-epileptic drugs.

OBJECTIVE: Studies show that anti-epileptic drugs increase oxidative stress. Thus, low-density lipoprotein oxidation increases and atherogenesis is induced. Paraoxonase-associated high-density lipoprotein protects low-density lipoprotein and high-density lipoprotein oxidation. The effects of anti-epileptic drugs on paraoxonase activity has not been investigated yet. The aim of this study is to investigate the effect of anti-epileptic drugs on paraoxonase activity, lipid profiles, folat, vitamin B12, homocysteine, thyroid hormones, apolipoprotein A-1, total anti-oxidant capacity, malondialdehyd, nitric oxide, and oxidised low-density lipoprotein. The association with carotid-femoral pulse wave velocity and current biochemical parameters had been searched for assessing the effects of anti-epileptic drugs on the vascular system. PATIENTS AND METHODS: We recruited 59 epileptic patients treated with anti-epileptic drugs and 23 controls (group IV) at least 6 months ago. The epileptic group was divided into three groups by receiving anti-epileptic drugs as follows: group I: carbamazepine, group II: valproic acid, and group III: carbamazepine and valproic acid. Arterial distensibility was assessed with the Complior device. RESULTS: There was no difference between the current biochemical parameters in epileptic children. Serum-free T4 was decreased, when compared with group IV. Thyroid-stimulating hormone was increased in group II, compared with group IV. The carotid-femoral pulse wave velocity was increased in group III, compared with group IV. The carotid-femoral pulse wave velocity was correlated with thyroid-stimulating hormone and valproic acid levels. CONCLUSIONS: Anti-epileptic drugs may induce atherogenesis by affecting the thyroid hormones. According to the current data, the effects of thyroid hormones on vascular system may be independent of other biochemical markers. Epileptic patients using anti-epileptic drugs must be followed closely for arterial stiffness, and also for the development and progression of atherosclerosis.

Serum paraoxonase activity and oxidative DNA damage in patients with laryngeal squamous cell carcinoma.

OBJECTIVES: To determine the possible role of oxidants and antioxidants in the pathogenesis of in laryngeal squamous cell carcinoma. DESIGN AND SETTING: Our study involved patients with newly diagnosed laryngeal cancer (n = 29) and same age- and sex-matched healthy individuals (n = 21). Serum malondialdehyde (MDA) and paraoxonase (PON1) levels were measured by colorimetric methods and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was measured using enzyme-linked immunosorbent assay in fasting blood samples of participants. RESULTS: The levels of 8-OH-dG (control, 4.61 ± 1.27 ng/mL; patient, 11.70 ± 2.44 ng/mL; P < 0.001) and MDA (control, 4.16 ± 1.02 nmol/mL; patient, 8.74 ± 1.65 nmol/mL; P < 0.001) were significantly higher, and those of PON1 (control, 170.86 ± 72.46 U/mL; patient, 80.44 ± 29.81 U/mL; P < 0.001) were significantly lower in patients. There were no statistically significant differences in the 8-OH-dG, MDA levels, and PON1 activity in relation to T (tumor) staging of differentiation and different smoking/drinking status. There was a statistically significant difference in MDA levels (10.24 ± 0.64 nmol/mL) only in stage II laryngeal cancer. There were a statistically significant positive correlation between serum MDA and 8-OH-dG (r = 0.887, P < 0.001), a statistically significant negative correlation between serum MDA and serum PON1 (r = -0.477, P < 0.01), and a statistically significant negative correlation between serum 8-OH-dG and serum PON1 in patients (r = -0.420, P < 0.05). CONCLUSIONS: We conclude that, in patients with laryngeal squamous cell carcinoma, the oxidant/antioxidant balance was impaired in favor of lipid peroxidation and DNA damage.

Intima-media thickening in patients with familial Mediterranean fever.

OBJECTIVE: The aim of this study was to assess the frequency of atherosclerotic plaques and intima-media thickness (IMT) in patients with FMF and suitable controls. METHODS: We studied 100 (46 males, 54 females; mean age: 40 +/- 6 years) patients with FMF. Also 94 (15 males, 79 females; mean age: 41 +/- 7 years) patients with SLE and 103 (44 males, 59 females; mean age: 40 +/- 5 years) apparently healthy volunteers were included as the control groups. Subclinical atherosclerosis was assessed by investigating atherosclerotic plaques and measuring IMT from carotid and common femoral arteries using B-mode ultrasonography (USG). Traditional atherosclerotic risk factors were also assessed. RESULTS: Both FMF and SLE patients had significantly higher carotid (C-IMT) and femoral artery IMT (F-IMT) compared with healthy controls. This was also true after adjustment for atherosclerotic risk factors. Only patients with SLE were found to have higher frequency of atherosclerotic plaques in the carotid and in the carotid and/or femoral artery. When all atherosclerotic risk factors were adjusted, again only patients with SLE were found to have risk for atherosclerotic plaques. In FMF, whereas the presence of atherosclerotic plaques was only associated significantly with diabetes mellitus; C-IMT was correlated with age, BMI and fasting glucose; and F-IMT with age and BMI. CONCLUSIONS: Increased atherosclerosis defined as the presence of plaques was not observed in patients with FMF. The significance of increased C- and F-IMT among patients with FMF must be further assessed.

The relationship between prolactin (PRL), leptin, nitric oxide (NO), and cytokines in patients with hyperprolactinemia.

Leptin is a key mediator in the maintenance of neuroendocrine homeostasis. The aim of this study was to determine the changes in serum leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nitric oxide (NO) levels in patients with hyperprolactinemia. The study consists of 16 consecutive patients with high prolactin (PRL) levels (group I) and a control group of 11 normoprolactinemic patients (group II). Pituitary tumor tissues of patients in groups I and II were analyzed for immunohistochemical (IHC) expression of prolactin and leptin. Group I has significantly higher levels of leptin than group II (P < 0.001). There is a strong correlation between PRL and leptin concentrations in group I. However, there were no statistically significant differences for NO, TNF-alpha, IL-6 between the two groups. IHC staining showed that there was strong immunoreactivity for leptin protein in PRL-secreting pituitary adenomas. Double immunostaining of adenoma tissues with PRL and leptin showed that the adenoma cells expressed both. These findings together are suggestive that leptin co-secretion from a prolactinoma may be the cause of increased serum leptin concentration, independently from the peripheral action of prolactin.

Is there any effect of tumor burden on hemostatic parameters in cancer patients? A case-control study of hemostatic abnormalities and anticardiolipin antibodies in solid tumors.

Hemostatic complications are one of the leading causes of mortality in cancer patients. In the present study, we assessed the hemostatic parameters and anticardiolipin antibodies in patients with solid tumors (n = 104) and healthy controls (n = 25) and also find out whether the abnormalities in these hemostatic parameters vary related to tumor burden. Prothrombin time, activated partial thromboplastine time, D-dimer, and fibrinogen as hemostatic parameters were determined by photo-optometric clot detection system, and serum anticardiolipin levels were measured by enzyme-linked immunosorbent assay. The plasma levels of fibrinogen, D-dimer, and serum anticardiolipin IgM levels in cancer patients were significantly higher compared with those in controls (P < .001, P = .001, and P = .01, respectively). Only fibrinogen levels were significantly higher in metastatic group than nonmetastatic group (P < .001 ). Hemostatic abnormalities that are detected in asymptomatic cancer patients may not give any clue about tumor burden or stage of the cancer patients.

Atherosclerosis in Behçet's Syndrome.

OBJECTIVES: We had the impression and preliminary evidence that atherosclerosis was not much increased in Behçet's syndrome (BS). Thus, we evaluated the presence of subclinical atherosclerosis in a sizeable group of patients with BS both with major organ involvement and mucocutaneous disease along with diseased and healthy controls. METHODS: We studied 239 (162 M/ 77 F; mean age: 40.7+/-7.0) patients with BS. Seventy-two (32 M/ 40 F) had only mucocutaneous and/or joint disease and 167 (130 M/ 37 F) had major organ involvement. Also 100 (24 M/ 76 F; mean age: 44.7+/-7.1) patients with rheumatoid arthritis (RA), 74 (58 M/ 16 F; mean age: 39.4+/-7.0) patients with ankylosing spondylitis (AS) and 156 (83 M/ 73 F; mean age: 39.2+/-6.6) healthy controls (HC) were studied as the control groups. We used B-mode USG to assess the frequency of plaques and intima-media thickness (IMT) in the carotid and femoral arteries. Traditional atherosclerotic risk factors were also evaluated. Men and women were analyzed separately. RESULTS: The frequency of plaques and the mean IMT in the carotid and femoral arteries were similar between patients with BS, AS and HC and also between the 2 subgroups of BS, among both men and women. Only men with RA were found to have significantly increased frequency of carotid artery plaques after adjustment for atherosclerotic risk factors. CONCLUSION: Increased atherosclerosis is not a prominent feature of BS, even among those patients with major organ involvement.

Donor heart preservation with iloprost supplemented St. Thomas Hospital cardioplegic solution in isolated rat hearts.

This study was designed to assess the influence of St. Thomas Hospital cardioplegic solution (St. Th.) on heart preservation in rat hearts subjected to 6h ischemia when supplemented with iloprost. In the control group (n=8), nothing was added to St. Th., whereas 10 or 1000 nmol L(-1) iloprost was added in the second (n=7) and third (n=8) groups, respectively. Mechanical contraction parameters, cardiac tissue damage and oxidative stress markers were evaluated. The 10 nmol/L iloprost group peak systolic pressure (71.0+/-30.9 versus 41.0+/-9.4 mm Hg) and -dp/dtmax (1103.8+/-94.3 versus 678.6+/-156.8 mm Hg s(-1)) were significantly higher than control group at 30 min of reperfusion (p<0.05). Iloprost supplemented groups had higher GSH and catalase levels of coronary perfusate at reperfusion, in comparison with initial values (p<0.05). AST, CK, CK-MB values increased at 0 min of reperfusion and cTnI values at 45 min of reperfusion (p<0.05) in all groups with no difference between groups. According to our results, iloprost supplementation had mild but significant improvement in postischemic values in mechanical and oxidative stress parameters, resulting in better heart preservation.

The relationship between nitric oxide and leptin in the lung of rat with streptozotocin-induced diabetes.

Lung structural changes and immunoreactivity of endothelial (eNOS)- and inducible nitric oxide synthase (iNOS) were investigated by light microscopy in lungs of treated and untreated diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of 65 mg kg(-1) streptozotocin (STZ) in Wistar albino male rats. Diabetic rats received daily i.p. doses of dexamethasone (2 mg kg(-1)), leptin (0.5 microg kg(-1)) and intramuscular insulin (20 U kg(-1)) or a combination of these drugs for 1 week starting 4 weeks after the STZ injections. After treatment, the blood levels of glucose, leptin, insulin and nitrate/nitrite (NO(3) (-)/NO(2) (-)) were measured. Dilatation of alveoli and alveolar ducts, partial alveolar wall thickening and increased eNOS- and iNOS characterized the diabetic rat lungs. High blood glucose and nitrate/nitrite levels as well as low insulin and leptin levels were also present. Treatment with insulin, dexamethasone and a combination of these drugs resulted in improvement of the structural and immunohistochemical abnormalities. The most effective treatment was insulin therapy. Leptin administration resulted in increased relative amounts of extracellular material, which led to noticeable respiratory efficiency in the diabetic rat lungs. All treatments except leptin lowered blood glucose levels. The combination of insulin and dexamethasone increased blood leptin and insulin, while the remaining diabetic rats had blood with low leptin and insulin concentrations. These results suggest that therapy with insulin plus dexamethasone but not therapy with leptin is beneficial for diabetics.

Leptin in nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. METHODS: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student's t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. RESULTS: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). CONCLUSION: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.

Serum gamma-glutamyltranspeptidase distinguishes non-alcoholic fatty liver disease at high risk.

BACKGROUND/AIMS: Hepatocyte apoptosis is an important and invasive predictor of liver injury and fibrosis in non-alcoholic fatty liver disease (NAFLD). Increased gamma-glutamyltranspeptidase (GGT) level is frequently observed in NAFLD. Hepatocyte growth factor (HGF) stimulates fibrogenesis and is correlated with GGT. The study aimed to determine whether GGT can distinguish NAFLD patients at high risk. METHODOLOGY: Fifty biopsy-proven NAFLD patients (M/F: 24/26) were divided as the normal GGT group (n = 25) and the high GGT group (n = 25) (each patients' GGT > two fold of upper-limit of normal). Liver histology was graded according to Brunt et al. TNF-sRp55, caspase-3 and 8, NFkappaB and Bcl-2 were measured by immunohistochemical methods. For statistical analysis, Student's t test, chi-square test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve were used. RESULTS: The high GGT group had significantly higher NFkappaB, caspase-3 and 8, and Bcl-2 levels (54.52 +/- 26.02, p = 0.002; 55.95 +/- 27.18, p = 0.002; 47.85 +/- 28.04, p = 0.001; 11.19 +/- 12.33, p = 0.016, respectively). Serum TNF-sRp55 levels of both groups were similar (2922.93 +/- 307.26, and 2885 +/- 194.47; p = 0.78). Differences in reference to histological steatosis grade and inflammation were not significant. However, fibrosis stage was higher in the high GGT group (p = 0.048). CONCLUSION: Multinominal logistic regression analysis showed that increased GGT level was a risk factor for advanced fibrosis in NAFLD (OR: 1.0, CI: 0.98-1.01; p =0.032). Using serum GGT levels the area under the ROC curve for the prediction of advanced fibrosis was 0.74 (95% CI: 0.54-0.94). The serum GGT cut-off value for the prediction of advanced fibrosis was 96.5 U/L; with 83% sensitivity and 69% specificity.

Inflammatory mediators in the diagnosis and treatment of acute pancreatitis: pentraxin-3, procalcitonin and myeloperoxidase.

INTRODUCTION: Acute pancreatitis (AP) is the third most common gastrointestinal disease at hospital admission. The etiology and pathogenesis of this disease are not completely clear. Our study was intended to determine the systemic levels of pentraxin-3 (PTX-3), myeloperoxidase (MPO), procalcitonin (PCT), and C-reactive protein (CRP) as prognostic parameters in early stages of AP. We also determined the effects of treatment on PTX-3, MPO, PCT and CRP levels in AP. MATERIAL AND METHODS: The study group comprised 44 AP patients (22 male, 22 female; age: 49.3 ±16.9 years) referred to our outpatient clinic. Additionally, our investigation included a control group of 30 healthy volunteers (18 male, 12 female; age: 50.8 ±12.6 years). RESULTS: Leukocytes, glucose, aspartate aminotransferase (AST (SGOT)), alanine aminotransferase (ALT (SGPT)), alkaline phosphatase (ALP), total and direct bilirubin levels were significantly higher in the AP group (p < 0.05, all). CRP, PTX-3, MPO and PCT were considerably higher in the AP group (p < 0.001, all), and after treatment, CRP, PTX-3, MPO and PCT levels were significantly lower (p < 0.001, all). CONCLUSIONS: Our findings indicated that the CRP, PTX-3, MPO and PCT levels increase in patients with AP and hence these indicators can be used as diagnostic factors to predict inflammation severity in AP. It was revealed that after treatment, there were significant reductions in biomarker levels. However, further research is needed in order to understand how these biomarkers can help to monitor inflammatory responses in AP.