Is Serum Caveolin-1 a Useful Biomarker for Progression in Patients with Colorectal Cancer?.

BACKGROUND: Colorectal cancer (CRC) is the third most common cause of cancer diagnosed in males and the second in females. Survival is strongly related to stage at diagnosis. There is an urgent need to find a noninvasive biomarker that can be commonly applied for screening diagnosis, early detection of recurrence, and monitoring of metastatic CRC. Protein caveolin-1 (CAV-1) has been known to be expressed abnormally in colon cancer and appears to contribute to aberrant signaling and protein trafficking. There are controversial results regarding the role of CAV-1 in cancer. We hypothesized that levels of CAV-1 in serum of patients with CRC might be important to estimate the progression of the disease. Therefore, the purpose of this study is to investigate whether serum CAV-1 might be used as a factor determining progression of CRC. METHODS: A total of 61 patients with CRC (26 male, 35 female) and 46 controls (38 male, 8 female) were enrolled. Serum CAV-1 levels were measured by ELISA. The relationship between CAV-1 and progression-free survival (PFS) was analyzed with use of receiver operating characteristic (ROC) and Kaplan-Meier analysis. Results were given as median (95% CI). Mann-Whitney test was used for the comparison of groups. RESULTS: CAV-1 levels were found to be 11.5 ng/mL (10.4-12.9) in CRC and 11.9 ng/mL (10.7-14.4) in controls (p = 0.465). The serum CAV-1 levels in CRC patients with disease progression and without progression were respectively 10.0 ng/mL (8.5-11.3) and 12.2 ng/mL (11.1-14.8) (p = 0.023). In ROC analysis, if CAV-1 levels are equal or lesser than 10.73 ng/mL, it might show presence of progression with a sensitivity 73.3% and specificity 66.7% in patients with CRC (area under the ROC curve (AUC) = 0.697, p = 0.005). The mean PFS time was found to be 29.7 months (19.8-39.7, 95% CI for the mean) in patients who have CAV-1 level ≤ 10.73 ng/mL and 61.9 months (44.2-79.6) in patients who have CAV-1 level > 10.73 ng/mL [hazard ratios (HR) with 95% CI = 3.49 (1.26 - 9.68) (p = 0.017)]. CONCLUSIONS: Our results strongly suggest that CAV-1 levels might be used as a marker to determine progression of CRC. When considered in combination with other biomarkers of CRC, CAV-1 is clinically informative and instructive.

Paraoxanase as an indicator of myocardial ischemia and its utility in determining extension of ischemia.

BACKGROUND: The aim of this study was to investigate Paraoxanase 1 (PON-1) activity in patients with ST-elevated and non-ST-elevated acute myocardial infarction (AMI) and to determine its correlation with Gensini scores (GSs). METHODS: A total of 109 patients with AMI and 58 healthy subjects as control group were included in the study. Patients were divided into 2 subgroups as ST-elevated and non-ST-elevated AMI patients (Group I and II, respectively). Controls were named as Group III. PON-1 activity was determined on admission to emergency department for each group. In addition, GSs for patient groups were determined. Then, groups were compared according to their results. RESULTS: PON-1 levels in Group I and II were significantly lower when compared to Group III. Median GSs for Group I and II were 60 and 64, respectively. The cut-off value of PON-1 for diagnosis of AMI was ≤180 U/L, which was identified by receiver characteristics receiver curve analysis. However, we could not determine a significant relationship between serum PON-1 levels and GSs in patients with AMI. CONCLUSION: PON-1 levels measured on admission to emergency department may be used to rule out AMI. PON-1 levels in AMI patients are found to be inefficient in determining extension of ischemia measured by GS.

Low level of Nesfatin-1 is associated with gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) occurs in ∼10-25% of pregnancies. Nesfatin-1, plays a role in carbohydrate metabolism by inhibiting glucagon secretion, besides has a glucose-dependent insulinotropic effect. Explanation of the GDM pathogenesis is important due to preventing gestational complications. We aimed to investigate relationship between GDM and Nesfatin-1. MATERIAL AND METHODS: Seventy-nine pregnant subjects were randomly allocated to either GDM group (GDG, n = 38) or control group (CG, n = 41). For GDM diagnosis, 50 and 100 g oral glucose tolerance test (OGTT) were used. Nesfatin-1, insulin and other parameters were measured for all subjects. The homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. RESULTS: Nesfatin-1 was found lower and insulin was found higher in GDG than CG. Negative correlation has been founded between Nesfatin-1 with weight, BMI, fasting glucose, serum glucose level at first hour of the 50 g OGTT and HOMA-IR. CONCLUSION: In this study, patients with GDM had lower Nesfatin-1 levels than without GDM. Therefore, when the Nesfatin-1 effects on the GDM pathogenesis is clear, it may be contributed to diagnosis and treatment of the GDM.

Ischemia-Modified Albumin is not Elevated in Deep Venous Thrombosis.

BACKGROUND: In this article, we aimed to determine the diagnostic role of ischemia-modified albumin (IMA) in the evaluation of patients with deep venous thrombosis (DVT). METHODS: Fifty-five patients with a diagnosis of DVT and 47 healthy subjects as the control group were included in the study. Blood samples of the patients were obtained within the first 24 hours after DVT diagnosis for IMA analysis. Patient and control groups were compared with respect to IMA levels. RESULTS: We found that HDL and albumin levels were significantly higher in the control group. However, we could not determine a significant increase in IMA levels in patients with DVT when compared to the control group. CONCLUSIONS: Our study revealed that IMA is not a useful marker in the diagnosis of DVT.

Evaluation of ovarian reserve in women with overt or subclinical hypothyroidism.

INTRODUCTION: Thyroid dysfunction is among the most common autoimmune disorders in women of reproductive age. Previous studies have shown the association between autoimmune thyroid disease (AITD) and infertility. Anti-Müllerian hormone (AMH) is secreted by granulosa cells and is a useful marker for assessment of ovarian reserve. In the present study, we sought to evaluate the ovarian reserves of women with autoimmune thyroid disorder by measurement of AMH values. MATERIAL AND METHODS: This prospective study included women with newly diagnosed AITD aged between 20 and 40 years. Patients were divided into three groups: subclinical hypothyroidism (SCH, n = 21), overt hypothyroidism (OH, n = 21) and controls (CG, n = 32). Study parameters included serum free T4, free T3, thyroid-stimulating hormone, anti-thyroglobulin, anti-thyroid peroxidase antibodies, follicle-stimulating hormone, luteinizing hormone, estradiol and AMH concentrations measured in the early follicular phase. Antral follicle count (AFC) was assessed with ultrasound. Body mass index (BMI) and waist circumference of the patients were noted. RESULTS: No significant difference was found among SCH, OH and CG in regard to ovarian reserves measured by AMH values (p = 0.19) and AFC (p = 0.80). A significant negative correlation was found between AMH and BMI (r = -0.382, p = 0.001). Anti-Müllerian hormone and waist circumference (r = -0.330, p = 0.004) were also negatively correlated. CONCLUSIONS: Although AMH values were not significantly different among groups, AMH values were lower in OH and SCH patients, indicating a possible need for close monitoring of these patients.

The acute effects of interval exercise on oxidative stress and antioxidant status in volleyball players.

BACKGROUND: Volleyball is briefly described as an "interval" sport with both aerobic and anaerobic components. Exercise may influence antioxidant/prooxidant balance, which leads to differences in oxidative stress status between athletes in different sport disciplines, but the results of the previous studies are inconsistent. In this study, we aimed to determine the acute effects of exercise on oxidative stress parameters such as serum total oxidant status (TOS) and total antioxidant status (TAS) levels in volleyball players. METHODS: Thirteen male volleyball players from the same team participated in this study. The volleyball game lasted approximately 95 minutes including warm-up and cool-down periods. Blood samples were taken before the warm-up and after the cool down. Serum TOS and TAS levels were measured. Oxidative stress index (OSI), a predictor of antioxidant/prooxidant balance (TOS/TAS), was also calculated. RESULTS: The following data were revealed as median: TOS 6.84 µmol H2O2 Eq/L (95% CI: 5.80-8.13) and 5.15 (95% CI: 4.20-6.02); TAS 1.96 mmol Trolox Eq/L (95% CI: 1.91-2.08) and 1.95 (95% CI: 1.86-2.00); and OSI indexes, 3.31 (arbitrary unit) (95% CI: 2.84-4.00) and 2.64 (95% CI: 2.26-3.18) before and after the match with respectively. Serum TOS and OSI levels were significantly lower after volleyball match when compared to before (P<0.05). There was no significant difference in serum TAS levels (P>0.05). CONCLUSIONS: In individuals who exercise active sports, TOS level has been found to be decreased while TAS level has not been affected significantly after volleyball match. Our results suggested that volleyball training may not cause oxidative stress in these players. Regular physical exercise especially, volleyball training may provide adequate protection against exercise-induced oxidative stress.

Diagnostic value of CRP and Lp(a) in coronary heart disease.

OBJECTIVES: Increased lipoprotein (a) [Lp(a)] concentration was reported to be an independent risk factor for coronary heart disease (CHD). Recent epidemiological studies affirmed the value of C-reactive protein (CRP) as the strongest, univariate predictor of the cardiovascular events. We decided to establish cut-off levels providing maximum diagnostic efficiency for CHD. METHODS: In this study we measured CRP and Lp(a) concentrations in patients with angiographically demonstrated CHD (group A, n: 120), patients without any angiographically demonstrable lesion (group B, n: 62) and a group of healthy subjects (group C, n: 41). Data were evaluated correcting for lipid and lipoprotein concentrations, diabetes mellitus, hypertension, smoking, age, and body mass index in men and women. ROC curve based cut-off values (comparing group A versus groups B and C) and associated diagnostic performances of the assays were evaluated. RESULTS: Significant increases were noted in serum CRP concentrations in men and women, in groups A vs. B,A vs. C, B vs. C. Lp(a) concentrations were not different among groups in men but were higher in group A vs. B and C in women. Optimal cut-off levels for CRP in women and men were found as 2.1 and 3.0 mg/l with the diagnostic values of 0.792 and 0.770, respectively. For Lp(a) optimal cut-off levels were found as 22.6 and 9.8 mg/dl with the diagnostic values of 0.612 and 0.596 in women and men, respectively. CONCLUSION: The CRP level is quite efficient for separation of patients from controls. Therefore keeping in mind the lack of specificity, the CRP level may be a useful tool in the diagnosis of coronary heart disease. However, the Lp(a) level is not efficient enough to support the use of Lp(a) measurement for management of coronary heart disease.

Diagnostic value of C-reactive protein in patients with angiographically documented coronary heart disease.

AIM: The aim of this study was to evaluate the diagnostic value of serum C-reactive protein (CRP) level measurement in predicting coronary artery disease (CAD) that can be shown angiographically. METHODS: CRP levels were determined in the blood of 198 patients (patients group, PG) with angiographically documented coronary artery disease and compared with that of 85 patients (control group, CG) who had a clinical indication for coronary angiography but have no angiographically determined coronary artery stenosis, as well as with that of 41 healthy volunteers as a healthy control group (HG) who did not have any complaint and did not have coronary angiography. CRP levels were measured 24 hours prior to angiography in PG and CG patients, and in the morning after not having eaten for same time. Any coronary artery stenosis or plaque formation was defined as CAD. Severity of the disease was assessed by both the number of diseased vessels (0 to 3) and the degree of stenosis (<50% mild, 50-70% moderate and >70% severe). RESULTS: Receiver Operating Characteristics (ROC) curves of CRP in angiographically documented CAD group showed a diagnostic value of 0.659 in female patients, followed by 0.542 in male patients, in predicting CAD. CRP levels were found to be significantly different between groups, higher in PG (6.2 +/- 0.86 mg/L) than those of CG (3.7 +/- 0.92 mg/L) and HG (0.854 +/- 0.2 mg/L) (p<0.05). CRP levels were not associated with the number of diseased vessels, neither with the degree of the occlusion (p>0.05). Multiple logistic regression analysis after adjustment for the established coronary risk factors showed CRP as an independent discriminating risk factor for CAD. CONCLUSION: It is concluded that CRP measurement has a value in predicting the presence of angiographically documented CAD. However, CRP levels were not associated with the degree or severity of CAD.

Triglycerides predict plasma fibronectin in children with type I diabetes mellitus rather than diabetes.

Fibronectins are adhesive proteins considered as markers of endothelial activation. Plasma fibronectin levels in diabetes mellitus (DM) have been found to be associated with atherosclerotic risk factors. This study was carried out to investigate plasma fibronectin and its relation with serum lipids, apolipoproteins AI, B100 and lp(a) in diabetic children. 35 children (19F/16M) with type I DM and 30 non-diabetic age and gender-matched controls were enrolled. Apolipoprotein and fibronectin concentrations were determined with nephelometric methods. Plasma fibronectin levels of the children with type I DM and the control group are not statistically different. HbA1c and triglycerides concentration are found to be significant predictors of plasma fibronectin in diabetic children, while effect of plasma cholesterol, apolipoprotein AI, B100 and lp(a) are insignificant. Diabetic children with triglycerides 1.13 mmol/l have elevated plasma fibronectin (median, 25th-75th percentiles; 29.6, 8.3-40.8 mg/dL) compared to the diabetic > or = 19.9, 8.6-30.7 mg/dL, p < 0.05) and non-diabetic children (16.6, 12.7-32.4 mg/dL, p < 0.01) with triglycerides < 1.13 mmol/L. On the other hand plasma fibronectin concentrations of diabetic and non-diabetic children with high triglycerides are not significantly different. In conclusion our data does not support the concept that plasma fibronectin is elevated in type I diabetes mellitus at least in children, but high plasma triglycerides secondary to diabetes or not is associated with higher FNp concentrations which may have implications on atherogenesis. Plasma cholesterol, apolipoproteins AI, B100 and lp(a) are not significant determinants of FNp in type I diabetic children.

Increased serum heme oxygenase-1 levels as a diagnostic marker of oxidative stress in preeclampsia.

OBJECTIVE: To evaluate the utility of serum biomarkers in the diagnosis of preeclampsia (PE) and also investigate possible correlation with pathogenesis of PE. METHODS: Maternal serum concentrations of heme oxygenase-1 (HO1) and N-myc downstream-regulated gene 1 (NDRG1) were measured at 27-34 weeks of gestation in a case-control study of 33 pregnant women diagnosed with PE and in 43 normotensive pregnant women without proteinuria. The Mann-Whitney U test and Spearman's correlation were used for statistical analysis. RESULTS: The median serum HO1 level was found to be significantly higher in the PE group [76.7 ng/ml (23.4-445.7)] than control group [55.9 ng/ml (3.7-354.3)] (p = 0.006). Positive correlation was found between HO1 levels with presence of PE (r = 0.316, p = 0.005). There was no significant difference in NDRG1 values between the two groups (p = 0.226). CONCLUSIONS: Serum HO1 levels were found to be increased in patients with PE compared with normotensive pregnant women.

Acute effect of hemodialysis on serum levels of the proinflammatory cytokines.

Chronic inflammation is a common feature of end-stage renal disease, which carries a heightened risk of atherosclerosis and other co-morbid conditions. Dialysis treatment per se can bring additional risk factors for inflammation, such as increased risk of local graft and fistula infections, impure dialysate or bio-incompatible membranes. Our study was designed to determine whether a hemodialysis session leads to an acute substantial alteration in the plasma levels of the proinflammatory cytokines interleukin (IL)-6, IL-1beta and tumor necrosis factor (TNF)-alpha, the T-lymphocyte activation factor soluble IL-2 receptor (sIL-2R), and an inflammation mediator and chemotactic granulocyte factor, IL-8, in end-stage renal disease patients receiving chronic intermittent HD. In this study, 21 (12 male/nine female) patients undergoing chronic hemodialysis were enrolled. The acute effect of a hemodialysis session on serum cytokine concentrations was assessed by comparison of pre-hemodialysis and post-hemodialysis determinations. Serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha levels were determined with chemiluminescence enzyme immunometric assays. A significant difference was not observed for IL-1beta, IL-6, TNF-alpha, and sIL-2R concentrations in pre-hemodialysis and post-hemodialysis specimens (p>0.05). Serum median (25th-75th percentiles) IL-8 concentration was 69.4 (34.9-110.3) pg/ml before hemodialysis, and decreased to 31.5 (18.0-78.8) pg/ml following hemodialysis (p: 0.006). Clearance of IL-8 increased by 0.47+/-0.08 pg/ml for each unit increase in pre-dialysis IL-8 (p<0.001) and decreased by 5.63+/-2.59 pg/ml for each unit increase in pre-dialysis urea mmol/l (p<0.05). In conclusion, the results of our study demonstrate that a hemodialysis session markedly decreases IL-8 concentration, which is significantly affected by pre-dialysis concentrations, indicating that removal of IL-8 is a concentration gradient-dependent action, but does not change the serum levels of IL-1beta, sIL-2R, IL-6, and TNF-alpha, underlining importance of the structural characteristics of the molecules.

Leptin levels in obese women with and without type 2 diabetes mellitus.

INTRODUCTION: The role of leptin has been more clear in the endocrinology area after the discovery of its secretion from the adipose tissue. The aim of the study is to investigate the leptin levels in obese women in whom type 2 diabetes mellitus were present or absent. MATERIALS AND METHODS: Thirty-five obese women with type 2 diabetes mellitus (group 1) and 34 obese women without type 2 diabetes mellitus (group 2) were enrolled in the study. In both groups the body mass index (BMI), waist circumference, and waist-to-hip ratio were measured. Leptin, HbA1c, creatinine and the lipid profile were assessed. RESULTS: Leptin was found to be statistically significantly lower in group 1 than in group 2 (40.22 +/- 17.77 ng/ml versus 50.12 +/- 15.51 ng/ml, respectively; p = 0.019). It was well correlated with BMI in group 1 (r = 0.60, p = 0.0001). In group 1 also, correlation of leptin was moderate with creatinine and high-density lipoprotein-cholesterol (r = 0.36, p = 0.037 versus r = 0.37, p = 0.027, respectively), whereas triglyceride had a negative correlation (r = -0.34, p = 0.046). In group 2, the only significant correlation with leptin was BMI (r = 0.41, p = 0.02). Leptin was also significantly lower in 17 subjects with poorly controlled diabetes mellitus than in 18 well-controlled diabetics (33.54 +/- 15.82 ng/ml versus 44.61 +/- 17.54 ng/ml, respectively; p = 0.038). CONCLUSION: Since leptin is lower in obese women with diabetes than without diabetes and additionally it is even lower in the poorly controlled diabetes subgroup, we think that further studies a rerequired to make clear the issue for lower leptin levels, whether it is a reason or an outcome.

Comparative effect of intra-articular administration of hyaluronan and/or cortisone with evaluation of malondialdehyde on degenerative osteoarthritis of the rabbit's knee.

Hyaluronan and cortisone have controversial and an important role in the healing of degenerative osteoarthritis. The purpose of the research was to compare individual and combined effects of hyaluronan and cortisone on the healing of degenerative osteoarthritis and to determine the serum malondialdehyde level as a lipid peroxidation marker. A rabbit model was used in which a degenerative osteoarthritis was created in the articular cartilage by resection of anterior cruciate ligament. The rabbits divided into three groups namely were injected with hyaluronan (group A) and cortisone (group B) at days 31, 38 and 45. Cortisone at day 31 and hyaluronan at days 38 and 45 were injected to the third group (group C). We obtained blood samples from each rabbit to determine the malondialdehyde levels at days 1, 30, and 52. At day 52, 21 rabbits were sacrificed. In biopsies obtained from treated and untreated knees articular cartilage degeneration was examined by light microscopy. Histopathologically the healing rate was significantly higher in group C than the other groups. Degeneration decreased 72% in group A, 52% in group B and 88% in group C at day 22. Malondialdehyde levels were 2.056 +/- 0.37 in the control group, 1.94 +/- 0.54 in group A, 1.98 +/- 0.37 in group B and 1.55 +/- 0.41 in goup C. The malondialdehyde levels of group A and B were less than the control group (statistically insignificant, p > 0.05). But, there were statistically significant values between control group and group C (p < 0.05). The results showed that the combination of cortisone and hyaluronan is the most effective in the treatment of cartilage degeneration in the course of the ostearthritis and the malondialdehyde levels are correlated with the severity of degeneration.

Serum CA 125 levels in patients with chronic heart failure and accompanying pleural fluid.

Malignant and nonmalignant serosal fluids have been found to be associated with high serum levels of CA 125, suggesting that the presence of fluid in the serosal cavities may stimulate its release. In this study, we investigated the relationship between serum CA 125 levels and the presence of pleural fluid in patients with chronic heart failure (CHF). We performed a clinical study in 36 patients with CHF with and without pleural fluid. Patients with CHF were divided into two groups based on the presence of fluid in the pleural cavity. Group 1 included 18 CHF patients (6 females, 12 males) with pleural fluid. Group 2 consisted of 18 CHF patients (7 females, 11 males) without pleural fluid. The control group consisted of 30 healthy volunteers (12 females, 18 males). The serum CA 125 level was determined in all groups. Serum CA 125 levels were found to be 100.0 +/- 129.4 U/ml in CHF patients with pleural fluids, whereas they were 36.5 +/- 35.2 U/ml in CHF patients without pleural fluid and 8.9 +/- 6.1 U/ml in the control group. Significantly high serum CA 125 levels were found in CHF patients with pleural fluids (p < 0.05) when compared with both CHF patients without pleural fluid and the control group. There was also a statistically significant difference in CA 125 levels between patients without pleural fluid and the control group (p < 0.05). We concluded that serum CA 125 levels should be interpreted with caution in patients with CHF in the presence of pleural fluid. Invasive procedures to define the etiology of elevated serum CA 125 levels may be unnecessary in this patient group.