The relations of circulating agouti-related peptide and leptin with altered sleep architecture in patients with active Cushing's disease: a pilot study.

AIM: To evaluate sleep architecture of patients with Cushing's disease (CD) and to explore whether agouti-related peptide (AgRP) and/or leptin play a permissive role in sleep alterations in patients with active CD. METHODS: We performed polysomnography on 26 patients with active CD and age 26 age- and sex-matched control subjects. Blood samples were obtained from all participants for the analyzes of AgRP and leptin. The laboratory and sleep-related parameters were compared. RESULTS: The groups were similar in age, gender, and body mass index. The CD group had reduced sleep efficiency (71.6 ± 12.1% vs. 78.8 ± 12.6%, p = 0.042) and increased wake after sleep onset (WASO%) (24.7 ± 13.1% vs. 17.4 ± 11.6%, p = 0.040) as compared to control group. Seventeen patients with CD (65.4%) and 18 control subjects (69.2%) had obstructive sleep apnea. Serum AgRP (13.2 ± 7.4 pg/ml vs. 9 ± 3.1, p = 0.029), leptin (59.5 mcg/l, [IQR] 32.6-94.6 vs. 25.3 mcg/l, [IQR] 12.9-57.5, p = 0.007) were higher in CD group. AgRP and leptin correlated negatively with total sleep time, sleep efficiency, stage N2 sleep (%), and positively with WASO%. In multiple regression analyses, serum cortisol (ß = - 0.359, p = 0.042) and AgRP (ß = - 0.481, p = 0.01) were significant predictor of sleep efficiency. AgRP was also significant predictor of WASO% (ß = 0.452 and p < 0.05). CONCLUSIONS: Active CD carries an increased risk of impaired sleep efficiency and continuity which may worsen health-related quality of life. Elevated circulating AgRP and, to a lesser extent, leptin may be associated with decreased sleep efficiency and continuity in patients with CD. Patients with CD who have subjective sleep symptoms should be screened with polysomnography.

The utility of TNF-α, IL-6 and IL-10 in the diagnosis and/or follow-up food allergy.

BACKGROUND: Several pro-inflammatory and anti-inflammatory mediators play a role in the immunopathogenesis of food allergy (FA). The aim of this study was to investigate the utility of serum biomarkers like interleukin (IL)-10, TNF-α, and IL-6 in the diagnosis and/or follow-up of FA. METHODS: Sixty (25 females, 41.6%) newly diagnosed FA patients [IgE mediated (group-1, n=37), non-IgE (group-2, n=23)] with a median age of nine (1-33) months were enrolled. Twenty-four healthy children with a median age of eight (1-36) months constituted the control group (CG). In all the subjects, serum TNF-α, IL-6 and IL-10 levels were evaluated at the time of diagnosis and reassessed four weeks after therapeutic elimination diet (TED). RESULTS: The mean white blood cell count and median absolute eosinophile count of the CG were significantly lower than group-1 (p values were 0.019 and 0.006, respectively). The mean absolute neutrophile count and the median IL-6 were significantly higher in group-1 when compared with group-2 (p values were 0.005 and 0.032, respectively. Median TNF-α and IL-6 levels were significantly higher in the pre-TED among all patients (p values were 0.005 and 0.018, respectively). In group-1, median TNF-α and IL-6 levels decreased significantly after TED (p values were 0.01 and 0.029, respectively). CONCLUSIONS: Our findings support the role of inflammation in the pathogenesis of FA. Serum TNF-α and IL-6 levels may be useful markers for follow-up in FA, especially among IgE-mediated FA patients. Evaluation of IL-10 results was not sufficient for an interpretation of clinical tolerance.

The relationship between carotid intima-media thickness and serum secreted frizzled-related protein-4 and dipeptidyl peptidase-4 in diabetic patients with cardiovascular diseases.

We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). This study consisted of four groups: control group (mean ages: 50.3±10.7 years; 20 females and 15 males), diabetic group (DM; mean ages: 53.9±11.1; 14 females and 23 males), CAD group (mean ages: 60.1±43.5; 17 females and 17 males) and CAD+DM group (mean ages: 62.6±11.8 years; 18 females and 18 males). CIMT levels in both CAD and CAD+DM groups are higher than those in controls. CIMT levels in CAD+DM group are also significantly higher than those in DM group. Left external carotid artery (ECA) was found different from controls only in DM group. The levels of SFRP-4 in control group were significantly lower than those in DM, CAD and CAD+DM groups. Serum GLP-1total levels were found to be significantly low in CAD+DM group when compared to control group. DPP-4 and SFRP-4 levels may be a predictive marker for atherosclerosis in diabetes while particularly in diabetes, they correlate well with HOMA-IR. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD (Tab. 3, Fig. 2, Ref. 39). Keywords: type 2 diabetes mellitus, carotid intima-media thickness, glucagon-like peptide-1, dipeptidyl peptidase-4, clusterin, amylin, secreted frizzled-related protein-4.

The relationship between IGF-2, IGFBP-2, and IGFBP-3 levels in patients suffering from pre-diabetes.

Many studies have shown that intervention in the early stages of diabetes may have a pivotal role in reducing the risk of cardiovascular diseases. This study was designed to assess possible relationships between insulin-like growth factor 2 (IGF-2), insulin-like growth factor binding proteins 2 and 3 (IGFBP-2, IGFBP-3) and pre-diabetes. A total of sixty clinically ascertained pre-diabetes cases and twenty-five healthy controls were included. Serum IGF-2 and binding proteins were estimated using commercially available ELISA kit. All groups had a positive correlation between all serum parameters. Multinomial logistic regression showed that all the study parameters directly affected each other. The results could not prove any correlation between IGF-2 and its binding proteins during pre-diabetes stage. Further assessments of these factors in larger groups of males and females in diabetic individuals could be useful to support our hypothesis that these factors change only in diabetes mellitus.

The relationship between preptin, Forkhead box protein O1 and mechanistic target of rapamycin levels in prediabetic patients.

Prediabetes is a state of high risk for developing some metabolic disorders. Previous studies have shown that components of some mediators involved in glucose metabolism regulation may have a profound effect during developing prediabetes state. This study investigates the effect of some novel prediabetic-related factors in prediabetes individuals for the first time. Sixty prediabetes (American Diabetes Association criteria) and 25 healthy control subjects were enrolled in the study. Systemic and chronic inflammatory diseases, coronary heart disease, and malignant disease patients were excluded. Anthropometric measurements and fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, preptin, and serum and leuckocyte levels of FOXO-1 and mTOR were determined. The findings showed an elevated level of leukocyte mTOR in the Impaired Glucose Tolerance (IGT) group and leukocyte FOXO-1 in the Impaired Fasting Glucose (IFG) and IGT groups compared to the control group. Moreover, higher levels of serum, and leukocyte FOXO-1 in the control group, and leukocyte mTOR level in the IFG group were detected in females compared to males. There was a positive correlation between all of the studied serum parameters, and a positive correlation between basal glucose concentration and leukocyte mTOR and FOXO-1. According to our results, elevated serum and cellular levels of mTOR in the IGT group and FOXO-1 in IFG and IGT groups may be triggered by increased glucose concentration. Indeed, mTOR-mediated variations in cellular level from female patients and FOXO-1-mediated variations of male patients indicated that these factors might play a critical role in glucose intolerance.

Effects of omega-3 polyunsaturated fatty acid supplementation on serum fetuin-A levels in type 2 diabetic patients.

Fetuin-A is an endogenous inhibitor of the insulin-stimulated insulin receptor tyrosine kinase recently shown that high levels of circulating fetuin-A are associated with insulin resistance in humans suggesting that fetuin-A may represent a novel mechanism involved in the pathophysiology of type 2 diabetes (T2DM). Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to reduce triglyceride levels, but their impact on glycemic control are not well known. The aim of this study to determine the effects of omega-3 PUFA supplementation on fetuin-A and glycemic control in patients with type 2 diabetes mellitus. 40 T2DM patients (17 males/23 females; aged 39-65 years) were included in the study. Serum fetuin-A levels and metabolic and biochemical profiles were measured before (baseline) and two months after n-3 PUFA supplementations (1.2 g/day). Serum fetuin-A levels were measured by enzyme-linked immunosorbent assay. Our results indicated that serum fetuin-A, fasting glucose, HbA1c and triglyceride levels were significantly decreased after supplementation (P<0.02, P<0.001, P<0.02 and P<0.01, respectively). At baseline, serum fetuin-A levels were correlated with HbA1c (r:-0.391, P<0.04). A significant positive correlation between fetuin-A and both triglycerides (r: 0.343, P<0.05) and total cholesterol (r: 0.330, P<0.05) and negative correlation between fetuin-A and fasting glucose (r: -0.405, P<0.01) were found after the supplementations. When performed multiply regression analysis, we found that serum fetuin-a levels were related with triglyceride levels (r: 0.351, P<0.01) at baseline and HbA1c levels (r: 0.344, P<0.04) after the supplementation. Based on the results, it thought that omega-3 PUFA intake decreases serum fetuin-A levels and serum fetuin-A is associated with plasma lipids and glycemic controls in type 2 diabetic patients. Further studies are required to resolve the question.

Effects of peritoneal-and hemodialysis on levels of plasma protein and lipid oxidation markers in diabetic patients.

AIM: The aim of this paper was to evaluate the effects of dialysis procedures on oxidative stress in diabetic patients. METHODS: The study was performed on 15 non-diabetic hemodialysis (HD) patients, 30 non-diabetic perinoteal dialysis (PD) patients, 18 diabetic HD patients (DHD), 15 diabetic PD patients (DPD), and 20 healthy controls. Plasma thiobarbituric acid reactive substances (TBARS), protein carbonyl (PCO), and oxidized LDL (oxLDL) were determined as oxidative stress markers. Plasma thiol (P-SH), erythrocyte glutathione (GSH) levels, and serum paraoxonase (PON1) activities were measured as antioxidants. RESULTS: HD patients have significantly higher oxLDL, TBARS and PCO levels and significantly lower P-SH levels than PD patients. DHD patients have significantly higher PCO levels and PON1 activities and significantly lower GSH levels than non-diabetic HD patients. There was no any difference in oxidative stress parameters between DPD and non-diabetic PD patients. CONCLUSION: Oxidative stress is exacerbated by HD in diabetic patients. Treatment strategy with antioxidants in dialysis patients may be associated with a worsened survival.

Serine protease inhibitor aprotinin ameliorates renal injury in a rat model of ischemia-perfusion injury.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. OBJECTIVE: To investigate the therapeutic effects of aprotinin on tissue protection against I/R injury in a rat model. N-acetylcysteine (NAC), a potent antioxidant, was also tested to assess the experimental model. MATERIALS AND METHODS: Twenty-four rats were categorized into 3 groups of 8 rats each: those receiving isotonic sodium chloride solution (control group); NAC, 150 mg/kg; and aprotinin, 40,000 KIU/kg. The animals underwent unilateral nephrectomy after 60 minutes of warm ischemia and 60 minutes of reperfusion of the kidney. Malondialdehyde, a lipid peroxidation marker, and antioxidant glutathione levels were measured in the kidney parenchyma. Tissue samples were obtained for histologic analysis. RESULTS: Compared with the control group, the NAC group demonstrated significantly low levels of malondialdehyde (P = .04) and high levels of glutathione (P = .01). At histopathologic analysis, less acute tubular necrosis (ATN) and cellular swelling was noted in the NAC group (P = .002 and P = .005, respectively). In the aprotinin group, histopathologic analysis revealed less tissue damage in terms of ATN (P < .001, cellular swelling (P < .001), and vacuolysis (P = .002). Compared with the NAC group, ATN (P = .01), vacuolysis (P = .04), and congestion (P = .05) were significantly less in the aprotinin group. CONCLUSIONS: Our results suggest that administration of aprotinin attenuates renal I/R injury. This observation has potential application for kidney preservation for transplantation, for aortic surgery, and for renal artery interventions by protecting cells from free radical damage.

The effects of sildenafil citrate on ischemic colonic anastomotic healing in rats: its relationship between nitric oxide and oxidative stress.

BACKGROUND: The purpose of this study was to examine the effects of sildenafil citrate on normal and ischemic colon anastomosis in the rat model by measuring the levels of blood and colonic tissues nitric oxide, thiobarbituric acid reactive substrates (as a marker of lipid peroxidation), and glutathione (as an antioxidant). METHODS: Normal (group 1 and 3) and ischemic anastomosis (group 2 and 4) were performed in four equal rat groups (n = 14). Orally 10 mg/kg per day of sildenafil citrate therapy were applied in group 3 and group 4 after operation. Seven rats of the each group were killed on postoperative days 3 and 7. RESULTS: Sildenafil citrate therapy was resulted in elevated nitric oxide levels in both normal and ischemic anastomotic tissues (p < 0.0001 and p < 0.03) at postoperative day 3. Tissue thiobarbituric acid reactive substrate levels were elevated in rats with normal anastomosis by sildenafil therapy (p < 0.001) at postoperative days 3 and 7 (p < 0.05). Sildenafil therapy given to the normal anastomosis group has significantly higher tissue nitric oxide levels than the normal anastomosis group without therapy at postoperative day 7 (p < 0.001). On postoperative day 7, plasma nitric oxide levels were decreased by sildenafil citrate in rats with normal (p < 0.01) and ischemic anastomosis (p < 0.05). The beneficial effect of sildenafil citrate also was seen for erythrocyte glutathione levels in rats with normal anastomosis at postoperative day 7 and in rats with ischemic anastomosis at postoperative day 3. CONCLUSIONS: Our results suggest that sildenafil citrate may affect ischemic anastomotic healing due to its possible effects on nitric oxide metabolism and lipid peroxidation. However, functional implication of this agent further needs to be elucidated.

Role of plasma viscosity and plasma homocysteine level on hyperinsulinemic obese female subjects.

Obesity is associated with atherosclerotic risk factors, including reduced blood flow, endothelial dysfunction, lipid disorders and hyperinsulinemia. In recent years, several studies have demonstrated that elevated homocysteine is a risk factor for atherosclerosis. This study was aimed at determining whether any relationship between plasma viscosity and homocysteine levels in patients with normo and hyperinsulinemic obese patients. Obese women (n=75) and healthy, age-matched non-obese women (n=70) was included in our study. Plasma viscosity, tHcy, insulin level, total-C, LDL-C, HDL-C, triglyceride and glucose level were significantly higher in obese subjects than in non-obese subjects. Obese subjects were also divided into two groups, according to the basal insulin levels as normo and hyper insulinemic. Hyperinsulinemic obese subjects had significantly higher PV level compared with normoinsulinemic subjects. When correlation analyses were performed normoinsulinemic obese subjects, significant correlations were found between PV and total-C (r: 0.776) and insulin level (r: 0.752), BMI (r: 0.580), HOMA-IR (r: 0.510). PV was positively correlated with total-C (r: 0.485), insulin level (r: 0.624), BMI (r: 0.624) and HOMA-IR ratio (r: 0.707), in hyperinsulinemic obese subjects. Hcy was positively correlated BMI in both groups. In conclusion that, it is point out that elevated homocysteine and increased PV are two factors that may act separately and probably do not affect each other.

Serum oxidized low density lipoprotein, paraoxonase 1 and lipid peroxidation levels during oral glucose tolerance test.

Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. To evaluate the effects of acute hyperglycemia on the oxidative stress, concentrations of serum-oxidized low density lipoprotein (oxLDL), paraoxonase 1 (PON1), and thiobarbituric acid reactive substances (TBARS) were measured in subjects with normal glucose tolerance (NGT) (n=35), impaired glucose tolerance (IGT) (n=25), and diabetic glucose tolerance (DGT) (n=20). In NGT group, the 2 hours' TBARS and oxLDL levels were not statistically different when compared to baseline, and 2 hours' PON1 activities were higher when compared to baseline (p<0.01). Subjects with IGT and DGT have higher 2 hours' serum TBARS and oxLDL levels than their baseline levels (p<0.01, for each). Baseline oxLDL levels of both IGT and DGT groups were higher than NGT group (p<0.01 and p<0.01, respectively). While there were not any significant differences in 2 hours' versus baseline PON1 activities in the IGT group, the 2 hours' versus baseline PON1 activities in the DGT group were significantly lower (p<0.01). The postchallenge 2 hours' PON1 activities of both IGT and DGT groups were lower than NGT group (p<0.01 and p<0.01, respectively). Baseline oxLDL was positively correlated with 2 hours' glucose (r=0.613, p<0.01) in IGT and DGT groups. PON1 activities were correlated with HDL-cholesterol, total cholesterol, and fasting glucose (r=0.680, r=0.698 and r=0.431, respectively, for each p<0.01) in NGT. In conclusion, oxidative stress occurs at an early stage in diabetes, and protective effects of HDL against atherosclerosis may be dependent on the PON1 activities.

Attenuation of acute lung injury following lower limb ischemia/reperfusion: the pharmacological approach.

AIM: The purpose of this study was to examine the effects of N-acetylcysteine (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage following ischemia/reperfusion injury in a rat hind limb model. A well known antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison. METHODS: Ischemia was induced in the lower limb for 4 h by vascular clamping and followed by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. P<0.005 was considered statistically significant. RESULTS: Plasma TBARS values were found to be significantly lower in the DMSO (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also in the aprotinin group lung TBARS values were found to be significantly lower compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological examination showed less prominent peribronchial leukostasis (P<0.005) and interstitial leukostasis (P<0.005) in all drug groups compared to the control group. CONCLUSION: These observations indicate that DOBE and NAC, which are known to have antioxidant properties and aprotinin, a serine proteinase inhibitor, acted effectively on the prevention of lung injury in a rat hind limb ischemia/reperfusion model. The reason why aprotinin exerts a more protective effect than the other drugs is not clear, however, its clinical use may have the dual advantage of hemostasis and lung protection in surgical practice.

Relationship between serum concentrations of interleukin-6 and tumor necrosis factor alpha in female Turkish subjects with normal and impaired glucose tolerance.

Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha) concentrations were measured in subjects during two-hour glucose loading in order to investigate the effects of glucose on serum IL-6 and TNFalpha concentrations. Twenty-six female subjects (mean age 60 +/- 10 years) had normal glucose tolerance (NGT) and nineteen female subjects (mean age: 63 +/- 9 years) had impaired glucose tolerance (IGT) according to WHO criteria. Serum IL-6 and TNFalpha concentrations were measured by chemiluminescent immunometric assay. Subjects with IGT have higher fasting serum TNFalpha levels than subjects with NGT (p < 0.01). Serum IL-6 and TNFalpha concentrations were elevated during glucose loading (for each comparison, p < 0.01). The increase in serum TNFalpha concentrations in IGT was greater than in NGT (p < 0.01). Serum IL-6 and TNFalpha concentration significantly correlated with insulin and glucose in IGT group (for each comparison, p < 0.01). The correlation between serum glucose and cytokines concentrations was significant in IGT (for each comparison, p < 0.01). There was also a positive correlation between serum IL-6 and TNFalpha in NGT and IGT (for each comparison, p < 0.01). In conclusion, hyperglycemia is associated with increased circulating cytokine concentrations and fasting TNFalpha concentrations seem to be more associated with IGT than IL-6.

The relationship between antioxidant enzymes and bladder cancer.

Carcinogenesis proceeds through at least three distinct stages - initiation, promotion and progression. Free radicals play an important role in the multistep complex course of carcinogenesis. Urinary bladder has been recognized as a target organ for many carcinogens, including benzidine, beta-napthylamine, 2 napthylamine, 4-aminobiphenyl. Antioxidants have been shown to inhibit both initiation and promotion in carcinogenesis. The aim of presented study was to determine and compare the oxidant and antioxidant status in different clinical stages of bladder cancer and of control groups. Study was conducted in fifty-two (n=52) patients with transitional cell epithelial cancer of bladder and in twenty-four (n=24) healthy adults as plasma and erythrocyte controls. Malondialdehyde levels (4.636+/-1.118, 2.853+/-0.576 / 262.112+/-61.772, 203.788+/-35.340) were significantly higher and erythrocyte glutathione levels (6.272+/-1.708, 7.523+/-1.346) were significantly lower in bladder cancer patients group than in control group. Erythrocyte glutathione reductase and glutathione peroxidase (3.935+/-1.155, 5.481+/-1.626 / 8.729+/-1.614, 12.362+/-1.707) activities were significantly lower in cancer patients. In the other hand, glutathione S-transferase activities (3.100+/-1.177, 1.071+/-0.471) were found significantly increases. We suggest that the values of glutathione S-transferase enzyme activity can be used for a tumor detection approach and even as an indicator of the biological behavior of the bladder carcinoma.

The role of antioxidant supplementation in cardiac transplantation: an experimental study in rats.

BACKGROUND: We investigated three antioxidants, inositol hexaphosphate (IP6), superoxide dismutase (SOD), and catalase (CAT), using a Langendorf model of heart transplantation. METHODS: Rat hearts were mounted on a Langendorf perfusion apparatus with addition of IP6, SOD+CAT, IP6+SOD+CAT to St. Thomas Hospital solution (n=6 for each) versus a control group (n=6), not containing supplementation. Global ischemia was achieved for 6 hours. RESULTS: The worst peak-to-peak (PP) and +dp/dt maximum values were observed in the IP6+SOD+CAT group, the values being significantly lower than those in the SOD+CAT group. The lowest plasma creatine kinase (CK), CK-muscle-band (CK-MB), and lactate dehydrogenase levels were measured from the SOD+CAT group. The highest values for CK were in the control group, and those for CK-MB were in the IP6 group. The lowest myocardial malondialdehyde and adenosine triphosphate values were observed in the SOD+CAT group. CONCLUSIONS: Supplementing St. Thomas Hospital solution with IP6 did not ameliorate myocardial damage following global ischemia. The contractility deteriorated further when IP6+SOD+CAT were used together; however, SOD+CAT improved cardiac mechanical functions, and significantly reduced myocardial damage.

Impaired glucose tolerance: its relevance to early endothelial dysfunction.

We studied the effects of acute glycemia on plasma nitric oxide (NO; nitrite plus nitrate) levels, Cu-Zn Superoxide dismutase (Cu-Zn SOD) activity and thiobarbituric acid-reactive substances (TBARS) levels in age-matched female subjects before and two hours after glucose loading. According to the results of glucose loading, subjects were divided in the three groups as normal (n = 13, NGT), impaired (n = 11, IGT) and diabetic glucose tolerance (n = 10, DGT). Plasma NO levels were significantly higher in subjects with DGT than in subjects with NGT (p< 0.001) and IGT (p< 0.05) at baseline. Two hours after glucose loading, plasma NO levels were significantly decreased in subjects with IGT and DGT (p< 0.001 and p< 0.001). Although plasma TBARS levels in subject with NGT did not change from the baseline levels after glucose loading, TBARS levels were significantly elevated in subjects with DGT and IGT (p< 0.001 and p< 0.001). Plasma Cu-Zn SOD activities were within a similar range in all subjects at baseline. Cu-Zn SOD activities were significantly increased in subjects with NGT, and were significantly decreased in subjects with IGT and DGT (p< 0.001 and p< 0.001) after glucose loading. There was a positive correlation between NO and glucose in subjects with NGT (r = 0.34, p< 0.01) and a negative correlation between NO and TBARS in IGT sum DGT during glucose tolerance (r= -0.38, p< 0.01). We suggest that NO availability was decreased when the blood glucose levels were only moderately elevated above normal levels. This might be related with the enhanced oxidative stress.

Plasma viscosity as a cardiovascular risk marker in patients with proteinuria.

Plasma viscosity is a major determinant of capillary blood flow. It has been suggested that alteration in plasma viscosity contributes to impaired blood flow and to increased cardiovascular risk. The aim of this study was to investigate the plasma viscosity levels and its possible role in the cardiovascular risk in patients with low grade nephrotic proteinuria. 20 patients with low-grade nephrotic proteinuria (mean age: 35+/-5 years) and 20 healthy controls (mean age: 33+/-4 years) were participated in the study. Plasma viscosity was measured by Harkness capillary viscometer. Biochemical analysis were measured by commercial enzymatic kits. Plasma viscosity, plasma levels of creatinine, fibrinogen and triglyceride were increased in patients with proteinuria than in the healthy controls (p<0.001, p<0.001, p<0.001, and p<0.001, respectively). The plasma levels of total protein and albumin were significantly lower in patients with low grade nephrotic proteinuria than in healthy controls (p<0.001 and p<0.001, respectively). Plasma viscosity was negatively correlated with plasma albumin (r= -0.835, p<0.001) and total protein (r= -0.862, p<0.001) in proteinuric patients. When the correlation analyses were performed a significant positive correlation was found between plasma viscosity and fibrinogen (r=0.636, p<0.001). In the stepwise multiple regression analysis plasma viscosity was found to be related with plasma total protein (t= -6.456, p<0.001) in the patients. When the stepwise multiple regression analysis were performed in healthy controls, the significant relationship was only found between plasma viscosity and fibrinogen (t= +2.202, p<0.01). These results suggested that altered plasma composition associated with low-grade nephrotic proteinuria may be involving the determination of plasma viscosity. Thus, the plasma viscosity in patients with low-grade nephrotic proteinuria may have a prognostic value in assessing cardiovascular risk in this group.

Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial disease [correction of disase].

The aim of this study was to investigate the relationship between plasma viscosity and lipoprotein and apolipoprotein pattern in normo- and hypercholesterolemic patients with peripheral occlusive arterial disease (POAD). 40 patients with POAD have been selected (8 females and 32 males, mean age: 54+/-3.2 years) with clinically evident superficial femoral occlusive artery disease. They were separated into two groups as normocholesterolemic (plasma total cholesterol <200 mg/dl) and hypercholesterolemic (plasma total cholesterol >200 mg/dl). Plasma total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides, total protein, and albumin levels were determined by enzymatic methods using commercial kits. Levels of apolipoprotein AI (apo AI), and apolipoprotein B (apo B) were measured using a immunoturbidometric method. Plasma viscosity (PV) was measured by capillary viscometer. Classifying the patients with PAOD according to the cholesterol levels; hypercholesterolemic (mean total-cholesterol: 227.90+/-26.97 mg/dl) patients had significantly higher LDL-C, PV and triglyceride levels compared with nornocholesterolemic patients (p<0.001, p<0.001, p<0.001, respectively). HDL-C and apo B were significantly lower in hypercholesterolemic patients than in normocholesterolemic patients (p<0.001, p<0.001, respectively). PV was positively correlated with total cholesterol (r=0.485, p<0.05), atherogenic index (r=0.624, p<0.01), total-C/HDL-C ratio (r=0.624, p<0.05), and LDL-C/HDL-C ratio (r=0.707, p<0.001) in hypercholesterolemic patients with POAD. PV was higher in hypercholesterolemic patients with POAD than in normocholesterolemic patients with POAD. We suggest that POAD patients should be regarded as a heterogenous group with lipid and lipoprotein parameters in order to assess the microcirculation in the affected limb. In case of dyslipidemia in POAD patients an elevated plasma viscosity should be considered as coexisting risk factor.

Levels of plasma vitamin E, vitamin C, TBARS, and cholesterol in male patients with colorectal tumors.

Vitamin E and vitamin C are involved in the defense of the body against free radical and reactive oxygen molecule induced damage. The best characterized biological damage caused by radicals is known as lipid peroxidation. Free radical formation is known to play a major role in the development of cancer. In this study, we measured plasma levels of thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, cholesterol, and vitamins E and C as antioxidants in male patients with colorectal tumors (n = 20, 54.5 +/- 8.3 years). The patients had significantly higher plasma TBARS levels than age-matched healthy subjects (p < 0.001). Plasma vitamin C levels were significantly lower in the patients compared to the healthy subjects (p < 0.001). On the other hand, plasma vitamin E levels in the patients were similar to those of healthy subjects. Plasma cholesterol levels were also found to be significantly elevated in patients with colorectal tumors (p < 0.001). Our results suggest that there is an imbalance between oxidant and antioxidant status in tumor genesis.

Plasma viscosity in female patients with hypothyroidism: effects of oxidative stress and cholesterol.

Hypothyroidism is associated with atherosclerotic events, however, the mechanism is unclear. We investigated the effects of oxidative stress and cholesterol on plasma viscosity in female patients with hypothyroidism (n = 20; mean age: 45.5 +/- 5.5 years) at baseline and after L-thyroxine replacement therapy (average daily dose being 0.1 to 0.15 mg). Two blood samples were taken after 2.3 +/- 1.2 months. In hypothyroid state plasma viscosity and thiobarbituric acid reactive substance (TBARS; marker of oxidative stress were significantly higher (p < 0.001 and p < 0.001), and plasma protein thiol (antioxidants) levels were significantly lower (p < 0.001) than in the healthy state (female; n = 15). After L-thyroxine replacement therapy, patients reached to euthyroid state. In this state, the levels of plasma viscosity and TBARS were decreased (p < 0.001 and p < 0.001), and protein thiol levels were significantly elevated (p < 0.001). There was a significant correlation between plasma cholesterol and viscosity (r = 0.64, p < 0.001), as well as plasma protein thiol (r = -0.59, p < 0.001) in the patients. The correlation between viscosity and TBARS was weak (r = 0.29, p < 0.01). Therefore hypothyroidism may be associated with atherosclerotic process by different mechanisms.