S. Caner Karahan

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in systemic inflammatory response syndrome.

OBJECTIVES This study was intended to investigate the value of suPAR, C-reactive protein (CRP) and procalcitonin (PCT) in the determination and prognosis of systemic inflammatory response syndrome (SIRS) patients. METHODS The study was performed among patients with at least two SIRS criteria. PCT, CRP and suPAR were analyzed from the blood specimens taken. RESULTS Eighty-five patients were enrolled in the SIRS group (44 bacteremia, 20 urinary tract infection, 12 pneumonia and 9 non-infection), and 53 individuals in the control group. A significant correlation was determined between suPAR, PCT and CRP values in both groups (P<0.0001). A suPAR cutoff value of 2.8ng/mL was associated with an NPV of 87% and PPV of 91%, with 92% sensitivity and 85% specificity. A relatively high suPAR level that might predict fatality was also determined in fatal cases (P=0.001). CONCLUSION suPAR possesses high sensitivity and specificity levels in terms of differential diagnosis, and high suPAR levels can predict fatality.

Decreased nitric oxide end-products and its relationship with high density lipoprotein and oxidative stress in people with type 2 diabetes without complications

Diabetes mellitus is associated with hyperglycaemia, hyperlipoproteinaemia, increased oxidative stress and decreased nitric oxide production from endothelial cells. In the present study the aim was to determine the relationships between serum lipids, lipoproteins, erythrocyte malondialdehyde (eMDA), as a marker for oxidative stress, and serum nitrite and nitrate levels, as degradation products of nitric oxide in type 2 diabetic patients without complications. The study group included 30 patients and 30 sex- and age-matched healthy volunteers. Total cholesterol, triacylglycerol, LDL cholesterol, apo B, HbA(1c) and glucose levels in patients were significantly higher than in controls, and HDL cholesterol levels lower. Increased eMDA levels and decreased nitrate and nitrite+nitrate levels (+/-SD) were observed in patients compared to controls (87+/-22 vs 59+/-17 nmol/g-Hb (P<0.01); 11.8+/-8.6 vs 22.8+/-10.8 micromol/l (P<0.01); and 16.8+/-11.0 vs 28.8+/-11.3 micromol/l (P<0.01), respectively). When the patients were divided into two groups according to HDL cholesterol levels (< or =0.91 and >0.91 mmol/l), total plasma nitric oxide end-products were found to be decreased in patients with low HDL levels compared to those patients with high HDL levels [men, 11.7+/-6.4 vs 24.6+/-14.9 micromol/l (P<0.01); women, 12.5+/-6.6 vs 21.4+/-6.6 micromol/l (P<0.01]. Nitrite and nitrate levels were correlated with HDL cholesterol (r=0.50, P<0.05) and eMDA (r=-0.52, P<0.05). It was concluded that the patients with unregulated blood glucose levels have abnormal lipid and lipoprotein metabolism and decreased nitric oxide end-products, with relationships between nitric oxide products and dyslipidaemia, especially between low HDL cholesterol levels and increased oxidative stress.

Combined risk stratification with computerized tomography /echocardiography and biomarkers in patients with normotensive pulmonary embolism☆ , ☆☆

BACKGROUND Right ventricular dysfunction (RVD) detected by computerized tomography (CT)/echocardiography or elevated biomarkers is associated with a poor prognosis for pulmonary embolism (PE). However, these prognostic factors have not previously been concomitantly elucidated in the same patient group. METHODS This prospective study included 108 consecutive patients with normotensive PE confirmed by CT pulmonary angiography (CTPA). On admission, patient serum NT-proBNP and troponin T (Tn-T) levels were measured, and echocardiography was performed within 24 hours after diagnosis of PE. Receiver operating characteristic (ROC) analysis was performed to determine the optimal echocardiographic end-diastolic diameters of the right ventricle, the ratio of the right ventricle to left ventricle (RV/LV ratio) on CTPA, and NT-proBNP and Tn-T cut-off levels with regard to prognosis. RESULTS All-cause 30-day mortality was 13% and PE-related mortality was 5.6%. RVD was defined as a right/left ventricular dimension ratio≥1.1 on CTPA and RV>30 mm on echocardiography by ROC analysis. A cut-off level of NT-proBNP≤90 pmol/ml had a high positive predictive value of 98% for survival, whereas NT-proBNP>300 and Tn-T≥0.027 had a negative predictive value, for all-cause deaths, of 95% and 96%, respectively. PE mortality in patients with NT-proBNP>300 and Tn-T≥0.027 reached 64%. In univariable analysis, the combination of Tn-T≥0.027 ng/ml with a echocardiographic RVD were the most significant predictors of overall mortality and PE-related death [HR: 14 (95% CI: 4.6-42,) and HR: 37.6 (95% CI: 4.4-324)], respectively. In multivariable Coxs regression analysis, NT-proBNP>300 and Tn-T≥0.027 HR: 26.5 (95% CI: 4.1-169.9, p<0.001) were the best combination to predict all-cause of mortality. CONCLUSIONS The combination of NT-proBNP and Tn-T clearly appears to be a better risk stratification predictor than biomarkers plus RVD on CT/ echocardiography in patients with normotensive PE.

Decreased neutrophil antioxidative enzyme activities and increased lipid peroxidation in hyperlipoproteinemic human subjects.

Neutrophils have the capacity to produce free radicals. Free radicals are associated with hyperlipoproteinemia and atherosclerotic processes. For this reason, neutrophil superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), catalase (Cat) activities and thiobarbituric acid reactive substances (TBARS), as an index of lipid peroxidation, have been studied in hyperlipoproteinemic (HLP) and age-matched normolipidemic groups. Lipid parameters including triglycerides, total cholesterol, plasma TBARS, HDL-cholesterol, LDL-cholesterol, apo A-I, apo B have also been determined. Forty subjects (females 18, males 22) with HLP (mean age 43.8+/-8.7 (S.D.)) and 40 normolipoproteinemic subjects (females 17, males 23; mean age 46.4+/-11) were included in the study. Neutrophils were isolated by Percoll gradient centrifugation from venous blood samples. Methods used were as follows: INT method for SOD, UV method at 340 nm based on oxidation of NADPH for GSH-Px and GR, UV method at 240 nm based on degradation of hydrogen peroxide for catalase, and a method based on reaction with thiobarbituric acid for TBARS. Neutrophil SOD, GSH-Px, and catalase activities were found to be significantly low in the hyperlipoproteinemic group compared with the normolipoproteinemic group. GR activity did not differ between both groups. The mean TBARS level in the neutrophil fraction was found to be significantly higher in hyperlipoproteinemics than in that of the normolipoproteinemics. It was concluded that decreased neutrophil antioxidant enzyme activities in hyperlipoproteinemics may lead to insufficient detoxification of free radicals produced in these cells and contribute to increased lipid peroxidation.

The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever

BACKGROUND Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. It has recently been reported that soluble urokinase-type plasminogen activator receptor (suPAR), secreted from endothelial cells and the mononuclear phagocyte system, one of the main targets of the CCHF virus, is a potential biomarker for several bacterial and viral infection diseases. OBJECTIVES This study was intended to determine the diagnostic and prognostic significance of suPAR levels in CCHF. STUDY DESIGN This retrospective study was conducted between June 2006 and August 2009 using plasma from patients monitored with a diagnosis of CCHF and from healthy blood donors. Levels of plasma suPAR were determined using an enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturers instructions. RESULTS One hundred CCHF patients were enrolled in the study. The control group was made up of 53 healthy blood donors. suPAR values of 6.2 ± 4.2 were determined in the CCHF patients and of 2.3 ± 0.6 in the control group (p<0.0001). A suPAR level optimum diagnostic cut-off point of 3.06 ng/mL was determined, with an area underneath the ROC (AUROC) curve of 0.94 (95% CI: 0.89-0.97), sensitivity of 87% (95% CI: 79-93%), specificity of 92% (95% CI: 82-98%), PPV of 95% and NPV of 79%. Five of the patients died. suPAR was 18.4 ± 9.1 in the patients that died and 5.6 ± 2.6 in the survivors (p=0.034). In terms of mortality, suPAR level had an optimum diagnostic cut-off point of 10.6 ng/mL, AUROC of 0.97 (95% CI: 0.94-0.99), sensitivity of 100% (95% CI: 48-100%), specificity of 96% (95% CI: 90-99%), PPV of 50% and NPV of 100%. CONCLUSIONS Plasma suPAR level, a new biomarker, is a test that can be used in the differential diagnosis and monitoring of CCHF in patients admitted to hospital with suspected infection. The test is at the same time important in being a possible predictor of mortality.

Ovarian-Protective Effects of Clotrimazole on Ovarian Ischemia/Reperfusion Injury in a Rat Ovarian-Torsion Model

Background/Aims: To evaluate the ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury in a rat ovarian-torsion model. Methods: 32 Sprague-Dawley rats were randomly divided into four groups: (1) ischemia group (n = 8) in which only left adnexal torsion was performed for 2 h, but no treatment was given; (2) vehicle group (n = 8) in which left adnexal torsion was performed for 2 h and at the end of 2 h ischemia polyethylene glycol (3% PEG, 1 ml, i.p.) was administered and a 24-hour reperfusion was continued; (3) clotrimazole group (n = 8) in which left adnexal torsion was performed for 2 h and at the end of 2 h ischemia clotrimazole (30 mg/kg, i.p.) was administered and a 24-hour reperfusion was continued, and (4) control group (sham-operated, n = 6) in which no adnexal torsion and no treatment were given. The criteria for ovarian ischemia were follicular cell degeneration, vascular congestion, hemorrhage and infiltration by inflammatory cells. Each specimen was scored for each criterion (0, none; 1, mild; 2, moderate; 3, severe). Results: Clotrimazole significantly decreased plasma levels of serum malondialdehyde, ischemia-modified albumin, and total oxidant status. Conclusion: This study showed the ovarian-protective effects of clotrimazole on ovarian ischemia/reperfusion injury.

The Effects of Impaired Trace Element Status on Polymorphonuclear Leukocyte Activation in the Development of Vascular Complications in Type 2 Diabetes Mellitus

Abstract Impaired trace element metabolism may be involved in some of the metabolic dysfunctions, and contribute to the development of vascular complications in diabetic patients. In order to investigate the relationships among diabetes mellitus, trace element status, leukocyte activation and vascular complications, 55 type 2 diabetic patients (34 with vascular complications and 21 without vascular complications) and 50 non-diabetic control subjects were studied. The mean leukocyte count (p<0.001), polymorphonuclear elastase (p<0.001), erythrocyte malondialdehyde (p<0.001), and glycated haemoglobin (p<0.001) levels, and copper/zinc ratio (p<0.001) were found to be higher in diabetic patients than in the control group, but serum zinc levels (p<0.001) and erythrocyte superoxide dismutase activities (p<0.001) were lower, and serum copper levels showed no differences. In patients with vascular complications, the mean leukocyte count (p<0.05), zinc (p<0.05), polymorphonuclear elastase (p<0.05), erythrocyte malondialdehyde (p<0.001) and glycated haemoglobin (p<0.05) levels, and copper/zinc ratio (p<0.001) were significantly different from those patients without complications. Closer correlations between the copper/zinc ratio and polymorphonuclear elastase (r=0.82, p<0.01), erythrocyte malondialdehyde (r=0.46, p<0.05) or erythrocyte superoxide dismutase (r= −0.85, p<0.01) were found in patients with vascular complications compared to those without, and all of those showed significant relationships with poor glycaemic metabolic control. We conclude that zinc deficiency may provoke polymorphonuclear leukocyte activation, and contributes to the development of vascular complications in type 2 diabetic patients. Furthermore, copper/zinc ratio and polymorphonuclear elastase may be used as important markers to evaluate the presence of vascular complications.

Acute increase in plasma D-dimer level in ovarian torsion: an experimental study

BACKGROUND Torsion of the ovary is a rare but serious cause of gynecologic surgical emergency. Specific laboratory markers that support the preoperative diagnosis of ovarian torsion are not currently available in the clinical routine. The aim of this study was to investigate the diagnostic value of plasma D-dimer level as an early indicator of ovarian torsion in an experimental rat ovarian torsion model. METHODS Sixteen female adult Sprague-Dawley rats were used for this controlled experimental study. Eight rats in the sham operation group (Group I) underwent a surgical procedure similar to Group II but the ovary was not occluded. In Group II (eight rats), a torsion model was created by using atraumatic vascular clips just above and below the right ovary for a 2-h period of ischemia. Right ovaries were surgically removed at the end of the procedure in each group. Blood was sampled before and after operation to assess plasma D-dimer levels. The main outcome measure was ovarian histopathologic findings scores and plasma D-dimer levels. RESULTS There was no significant difference in pre-operative plasma D-dimer levels (0.5963 ± 0.2047 mg/l in Group I, 0.6344 ± 0.1348 mg/l in Group II, P = 0.815, Mann-Whitney U-test). However, mean plasma D-dimer value for Group II was significantly higher than that in the control group (1.2267 ± 0.3099 versus 0.6213 ± 0.2346 mg/l, respectively, Mann-Whitney U-test, P < 0.001), following 2 h of ovarian torsion. Ovarian tissue damage scores were also statistically significantly different among groups. CONCLUSIONS If the observations made in a rat model are extended to humans, plasma D-dimer measurement may be a valuable parameter in the early diagnosis of ovarian torsion.

New Marker of Platelet Activation, SCUBE1, Is Elevated in Hypertensive Patients

BACKGROUND Hypertension is associated with an increase in platelet activation and endothelial dysfunction and leads to a tendency to cardiovascular events (CVEs). Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) is a novel platelet activation marker. There are currently no studies showing the level of SCUBE1 in hypertensive patients. The purpose of this study was to determine the level of SCUBE1 in this patient group and to investigate the parameters affecting that level. METHODS Forty-five newly diagnosed, untreated, stage 1 hypertensive patients and 21 healthy individuals were included. Blood specimens were collected to determine SCUBE1, soluble CD40 ligand, prothrombin time, partial thromboplastin time, fibrinogen, D dimer, hemogram, lipid parameters, blood urea nitrogen, creatinine, and uric acid levels. The relation between SCUBE1 level and demographic data and biochemical parameters was then investigated. RESULTS SCUBE1 and sCD40L levels obtained from plasma specimens from the hypertensive group were significantly higher than those of the control group (P < 0.001; P < 0.05, respectively). Hypertensive group blood pressure (BP) values and uric acid, low-density lipoprotein, total cholesterol, and triglyceride levels were also statistically higher than those of the control group. Parameters affecting SCUBE1 levels were systolic and diastolic BP, sCD40L, lipid parameters, and uric acid levels. CONCLUSIONS We show elevated levels of SCUBE1, a novel platelet activation marker, in primary hypertensive patients. We think that, when supported by further clinical studies, this newly described marker may be useful in the monitoring of CVEs in this patient group, in which platelet activation is known to be associated with such events.

Treatment related changes in antifibrinolytic activity in patients with polycythemia vera

Abstract Polycythemia vera (PV) is a clonal myeloproliferative disorder characterized by predominantly excessive erythrocyte production. During the course of the disease, bleeding or thrombosis may be observed. In PV patients, the influence of antifibrinolytic activities on development of thrombohemorrhagic complications remains to be elucidated. In the present study, alterations in antifibrinolytic activity of PV patients and the effects of treatments on these alterations were investigated. Newly diagnosed and therapy-naive 22 PV patients were included. Thrombomodulin (TM), plasmin-alpha 2-antiplasmin complex (PAP), plasminogen activator inhibitor-1 (PAI-1) and thrombin activable fibrinolysis inhibitor antigen (TAFIa) levels were measured in all individuals and after phlebotomy and 5-hydroxyurea (5-HU) therapy in PV patients. TM, PAP, PAI-1 and TAFIa values of the patient group were higher than those of the controls. After phlebotomy, no changes were detected in TM, PAI-1 and TAFIa values, but PAP values decreased. On the contrary, 5-HU treatment resulted in a marked decrease in TM, PAI-1, PAP and TAFIa levels. These findings suggested that the changes in antifibrinolytic activity and endothelial dysfunction might be contributed to formation of intravascular thrombosis in PV patients, even though not clinically overt. 5-HU in addition to phlebotomy affects antifibrinolytic activity and may have an influence on diminishing predisposition of thrombosis.