Correlation of serum C1q-tumour necrosis factor-related protein 5 levels with metabolic parameters and carotid intima-media thickness in newly diagnosed type 2 diabetes mellitus patients.

PURPOSE: Recent studies have shown that cytokines secreted from adipose tissues play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). CTRP5 (C1q-TNF-related protein 5) is a novel adipokine that has been shown to be associated with glucose and lipid metabolism. Varying levels of CTRP5 have been reported in individuals with diabetes, obesity and coronary artery disease. The aim of this study was to examine serum levels of CTRP5 and to show the relationship with cardiometabolic parameters in T2DM patients. METHOD: The study included 40 T2DM patients and 40 age- and sex-matched healthy control subjects. All the study participants were evaluated with respect to BMI, waist circumference, lipid profile, insulin resistance (HOMA-IR), serum CTRP5 levels, carotid intima-media thickness, and hs-CRP. RESULTS: No statistically significant differences were found between the control group and the diabetic group in terms of age, sex, or BMI. Serum CTRP5 levels (T2DM = 94.55 ± 28.70 ng/ml, control = 76.02 ± 27.22 ng/ml, P = 0.004*) were significantly higher in the group of newly diagnosed diabetic patients. A positive correlation was found between CTRP5 and the cardiometabolic parameters of carotid intima-media thickness (CIMT), hs-CRP, HOMA-IR and BMI. Regression analysis results showed that CTRP5 levels were independently correlated with insulin resistance estimated by HOMA-IR. CONCLUSION: Serum CTRP5 levels were correlated with cardiometabolic parameters and could therefore be a promising indicator of metabolic status and a possible biomarker of insulin resistance. However, the contradictory results reported in different studies indicate the need for further research to assess the significance of CTRP5 for diagnosis and monitoring of treatment efficacy.

Association of kallistatin with carotid intima-media thickness in women with polycystic ovary syndrome.

BACKGROUND: Kallistatin is a secreted protein that acts as a tissue kallikrein inhibitor. It has anti-inflammatory, antioxidant and vasoprotective properties. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with low-grade chronic inflammation and multiple risk factors for cardiovascular diseases. The aims of this study were to ascertain whether circulating kallistatin levels are altered in women with PCOS, and whether there is an association between kallistatin and carotid intima-media thickness (cIMT) as well as inflammatory markers high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α). METHODS: This cross-sectional study included 75 women with PCOS and 75 age- and BMI-matched controls without PCOS. Circulating kallistatin and TNF-α levels were measured using ELISA. Metabolic and hormonal parameters, hs-CRP levels and cIMT were also determined. All subjects underwent the 2-hour oral glucose tolerance test (2-h OGTT). RESULTS: Circulating kallistatin levels were significantly elevated in women with PCOS compared to controls (6.31±2.09 vs. 4.79±2.26 ng/mL, P<0.001). Inflammatory markers hs-CRP and TNF-α were found to be elevated in women with PCOS. Kallistatin levels positively correlated with insulin, insulin resistance index (HOMA-IR), free androgen index, hs-CRP, TNF-α and cIMT in both PCOS and control groups. Kallistatin levels did not show correlation with BMI, blood pressure, fasting blood glucose, 2-h OGTT or HbA1c. Multiple linear regression analysis revealed that kallistatin is an independent predictor for cIMT (ß=0.131, 95% CI: 0.114-0.150, P=0.019). CONCLUSIONS: Kallistatin levels may provide useful information regarding cardiovascular risk in women with PCOS.

Relationship between insulin resistance, hs-CRP, and body fat and serum osteoprotegerin/RANKL in prediabetic patients.

BACKGROUND: Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPN) are soluble members of the tumor necrosis factor superfamily. Growing evidence suggest that there is link between inflammation, insulin resistance and OPG, soluble RANKL (sRANKL). We aimed to ascertain whether OPG and sRANKL levels are altered in prediabetic subjects and there is association between OPG/sRANKL and metabolic parameters. METHODS: Forty prediabetic subjects and 40 age- and BMI-matched controls were recruited for this cross-sectional study. Circulating OPG, sRANKL were measured using ELISA. Anthropometric and metabolic parameters were also determined. RESULTS: Circulating sRANKL (97.74±17.67 vs. 55.00±11.19 pg/mL, P=0.010) and OPG (261.54±74.55 vs. 159.23±52.91 pg/mL, P=0.020) levels were found to be significantly higher in diabetic subjects compared with control subjects. There was a positive correlation between sRANKL and OPG. sRANKL also positively correlated with BMI, insulin resistance marker HOMA-IR, inflammatory marker hs-CRP. Logistic regression analyses revealed that the odds ratio was increased for prediabetes in subjects with having elevated sRANKL levels. CONCLUSIONS: Increased sRANKL and OPG levels were associated with prediabetic subjects. sRANKL and OPG may play a role in the pathogenesis of diabetes as well as metabolic disturbance.

Endocan is a predictor of increased cardiovascular risk in women with polycystic ovary syndrome.

PURPOSE: Endocan is a proteoglycan secreted mainly from endothelial cells. It has been implicated that there is a link between endocan and endothelial dysfunction. Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disease associated with increased risk of cardiovascular events. The aims of this study were to ascertain whether circulating endocan levels are altered in women with PCOS, and whether there is an association between endocan and carotid intima media thickness (cIMT). MATERIALS AND METHODS: This cross-sectional study included 80 women with PCOS and 80 age- and BMI-matched controls without PCOS. Circulating endocan levels were measured using ELISA. Metabolic, hormonal parameters and cIMT were determined. 2-h oral glucose tolerance test (2-h OGTT) was performed on all women. RESULTS: Circulating endocan levels were significantly elevated in women with PCOS compared with controls (5.99 ± 2.37 vs. 3.66 ± 1.79 ng/ml, P < 0.001). Endocan levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA-IR), free androgen index (FAI), high-sensitivity C-reactive protein (hs-CRP), and cIMT in both PCOS and control groups. Endocan levels did not correlate with fasting blood glucose, 2-h OGTT, A1C and lipid parameters. Multiple linear regression analysis revealed that endocan is an independent predictor for cIMT (ß = 0.128, 95% CI = 0.118-0.138, P = 0.011). CONCLUSIONS: Circulating endocan levels are significantly higher in women with PCOS and endocan is independently associated with cIMT. Elevated endocan levels can be a predictor of increased cardiovascular risk in PCOS subjects.

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. .

Prognostic significance of serum galectin-3 levels in patients with hepatocellular cancer and chronic viral hepatitis.

BACKGROUND/AIM: Galectins affect diverse physiological and pathophysiological processes such as development, inflammation, and tumor growth. We aimed to compare serum galectin-3 levels in three patient groups with chronic hepatitis B and C virus (HBV, HCV), cirrhosis secondary to HBV or HCV, and hepatocellular carcinoma (HCC) secondary to HBV or HCV and evaluate the role of galectin-3 during HCC progression. PATIENTS AND METHODS: Nineteen patients with hepatocellular cancer, 22 patients with cirrhosis, and 24 patients with chronic hepatitis B and C were included in this study. Serum galectin-3 levels in different liver diseases were assessed by enzyme-linked immunosorbent assay. RESULTS: The mean galectin-3 levels were 4.61 ng/mL (±2.32) in HCC patients, 5.68 ng/mL (±2,2) in cirrhotic patients, 1.98 ng/mL (±1.50) in chronic viral hepatitis group. There were no statistical differences between HCC and cirrhotic patients (P = 0.5), but lower in chronic hepatitis group statistically compared with cirrhosis and HCC (P < 0.001, P = 0.002, respectively). In case of cirrhotic patients, galectin-3 levels were significantly higher in patients with cirrhosis secondary to HCV compared with HBV (P = 0.03). When we evaluated galectin-3 levels in HCC patients, it was found to be 3.92 ng/mL in HCC secondary to hepatitis B and 5.37 ng/mL in HCC secondary to hepatitis C. CONCLUSION: Serum galectin-3 levels in patients with chronic HBV or HCV may guide us about progression to cirrhosis or HCC and prognosis of the disease. Especially, galectin-3 levels may be more pronounced in case of HCV.

Comparison of pre- and post-levothyroxine high-sensitivity c-reactive protein and fetuin-a levels in subclinical hypothyroidism

OBJECTIVE: The objective of this trial was to determine the levels of inflammatory markers, high-sensitivity C-reactive protein and fetuin-A pre- and post-levothyroxine treatment in cases of subclinical hypothyroidism. MATERIALS AND METHODS: A total of 32 patients with a diagnosis of subclinical hypothyroidism and a control group of 30 healthy individuals were tested for high-sensitivity C-reactive protein and fetuin-A, followed by the administration of 50 µg of levothyroxine in the patient group for 3 months. During the post-treatment stage, high-sensitivity C-reactive protein and fetuin-A levels in the patient group were re-assessed and compared with pre-treatment values. RESULTS: Pre-treatment levels of both high-sensitivity C-reactive protein and fetuin-A were observed to be higher in the patient group than in the control group. The decrease in high-sensitivity C-reactive protein levels during the post-treatment stage was not statistically significant. However, the decrease observed in post-treatment fetuin-A levels was found to be statistically significant. CONCLUSION: The decrease in fetuin-A levels in subclinical hypothyroidism cases indicates that levothyroxine treatment exerts anti-inflammatory and anti-apoptotic effects. Although the decrease in high-sensitivity C-reactive protein levels was statistically non-significant, it is predicted to reach significance with sustained treatment. .

The effect of regular colchicine treatment on biomarkers related with vascular injury in newly diagnosed patients with familial Mediterranean fever.

We aimed to evaluate some of the vascular biomarkers in newly diagnosed, colchicine naive familial Mediterranean fever (FMF) patients. Our primary aim was to investigate the effect of regular colchicine treatment on these variables. Twenty-four (12 males [M] and 12 females [F], 33.3 ± 13.4 years) newly diagnosed FMF patients were included in the study. These patients were started on colchicine treatment following the initial assessment and were studied again no earlier than 2 months. Five patients were lost to follow-up, and assessment of the on-treatment patients was performed on the remaining 19 patients (8 M and 11 F, 33.6 ± 11.8 years). There were 19 healthy subjects (11 M and 8 F, 32.2 ± 7.2 years) who served as a control group. Cellular adhesion molecules (CAMs; soluble intercellular adhesion molecule-1 [sICAM-1] and soluble CD146 [sCD146]), plasminogen activator inhibitor-1 (PAI-1), fetuin-A and hs-CRP were studied. Examinations were performed on attack-free periods. The levels of hs-CRP, fetuin-A, sICAM-1, and PAI-1 were significantly higher in newly diagnosed patients compared to those of controls (P < 0.05). All studied parameters were significantly downregulated after regular colchicine therapy (P < 0.05). Comparison of on-treatment data with controls showed that the levels of the vascular biomarkers, except sCD146, were similar between the groups (P > 0.05). On-treatment sCD146 was found significantly lower than the controls (P < 0.05). In regression analysis, none of the independent variables in the model significantly predicted the vascular biomarkers (P > 0.05). Administration of therapeutic doses of colchicine markedly reduces vascular injury parameters and normalizes the values in FMF.

Comparative levels of macrophage migration inhibitory factor, procalcitonin, osteoprotegerin, interleukin-8, hs-C reactive protein, D-dimer in febrile neutropenia, newly diagnosed cancer patients, and infectious fever.

BACKGROUND: The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and D-dimer during fever above 38.3°C due to various causes. MATERIAL AND METHODS: Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and D-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection. RESULTS: IL-8 and D-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs-CRP values. CONCLUSION: High serum IL-8 and D-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer.

Evaluation of the T helper 17 axis in ankylosing spondylitis.

To evaluate the T helper 17 (Th17) axis and its relation to tumor necrosis factor (TNF) alpha blockage and disease activity in ankylosing spondylitis (AS). The study included 127 AS patients (100M/27F) and 38 (27M/11F) controls. Spinal mobility was assessed by the bath ankylosing spondylitis metrology index (BASMI). Patients were also evaluated with the bath ankylosing spondylitis functional (BASFI) and bath ankylosing spondylitis disease activity index. Cytokines including IL-6, IL-12, TGF-ß, IL-17A, and IL-23 were measured in serum sample using commercially available ELISA kits. Cytokines including IL-6, IL-12, TGF-ß, IL-17, and IL-23 were significantly higher in the AS patients than the controls (P < 0.05). The Th-17-related cytokines were not different between patients treated with anti-TNF and conventional therapies (P > 0.05). Cytokines were also similar between patients with active and inactive disease (P > 0.05). On correlation analysis, IL-17 was correlated with IL-23 and IL-12 (P < 0.05) and IL-23 showed correlations with IL-12 and BASMI (P < 0.05). We found serum levels of Th-17-related cytokines to be significantly increased in the sera of AS patients. Disease activity and treatment type did not affect the level of these cytokines.

Treatment of a patient with adnexal lymphoma with Rituximab.

Orbital lymphoma is a very rare type of primary Non-Hodgkin lymphoma. The disorder is often small B-cell lymphoma, although large cell morphology may also be identified in rare cases. It may sometimes be confused with non-malignant, benign-course lymphoid hyperplasia. Although involvement is usually unilateral (80%), bilateral cases are also reported. Response to radiotherapy is achieved in the majority of cases, whereas the prognosis is poor in orbital involvement with large cell lymphoma and response to combined chemotherapy is inadequate. In this paper, we report a case with a diagnosis of unilateral adnexal involvement, who previously received CHOP treatment and developed a relapse 6 months later, then responded to treatment with Rituximab.

Subclinical hypercortisolism among polycythemia vera patients.

BACKGROUND: JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, occurs in nearly all patients with polycythemia vera (PV). JAK2 is also essential in hypothalamo-pituitary-adrenal (HPA) axis system which is known to play a role in subsequent steroid secretion. The purpose of this study was to determine whether or not PV induces subclinical hypercortisolism (SH). DESIGN: Cross-sectional study. In order to compare the prevalence of SH in PV and matched control individuals, we performed a case-controlled study, enrolling 31 PV and 20 age- and body mass index-matched patients. METHODS AND RESULTS: Adrenal endocrine function was assessed in a cohort of 31 patients with PV. Baseline serum cortisol levels and 2-day 2 mg DST (dexamethasone suppression test, 0.5 mg dexamethasone orally every 6 hours for two days) showed a trend for higher serum cortisol levels in PV patients than in control subjects. Among the 31 patients, 6 had biological abnormality of the hypothalamic-pituitary-adrenal axis and were diagnosed as subclinical hypercortisolism. None of the subjects in the control group exhibited cortisol responses to DST higher than 50 nmol/L. DISCUSSION: In conclusion, a relatively high prevalence of hypercortisolism was found in PV patients. As these observations were in a small cohort of PV, further studies are needed to evaluate HPA axis in PV patients.

Oral contraceptives alone and with spironolactone increase sCD40 ligand in PCOS patients.

BACKGROUND: The present study was designed to determine the effect of oral contraceptives (OCP) and OCP plus spironolactone (Sp) on plasma soluble CD40L levels in polycystic ovary syndrome (PCOS) patients. METHODS: Fifty-six women with PCOS were randomized into two treatment protocols: ethinylestradiol + cyproterone acetate (2 mg, EE/CA; n = 28), and EE/CA with spironolactone (Sp; n = 28). Plasma sCD40L levels were measured before and after a 3-month treatment. RESULTS: Before the initiation of treatment, the sCD40L levels were not significantly different between the groups [EE/CA (1.33 ng/mL) vs. EE/CA + Sp (1.23 ng/mL); P > 0.05]. In the post-treatment period, sCD40L concentrations were increased compared with pre-treatment values in the EE/CA and EE/CA + Sp groups (1.33 vs. 2.70 ng/mL, P = 0.011; and 1.23 vs. 2.41 ng/mL, P = 0.017; respectively). CONCLUSION: Increased plasma concentrations of sCD40L are associated with OCP and OCP + Sp treatment regimens in PCOS patients.

The effect of iron treatment on adhesion molecules in patients with iron deficiency anemia.

The present study was aimed to determine the effect of iron supplementation on levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with iron deficiency anemia (IDA). In this study, 26 female patients diagnosed with iron deficiency were treated approximately 3 months of oral iron supplementation (99 ± 10 days; ferrous glycine sulfate; 100 mg/day of elemental iron). Levels of sICAM-1 and sVCAM-1 were assessed prior to treatment and after approximately 3 months of treatment and compared with 26 healthy female subjects. A significant increase in sVCAM levels was found in the patients with iron deficiency at the end of the treatment relative to pretreatment levels compared to controls, whereas no significant differences were determined in sICAM levels. In the posttreatment period, no significant change was observed in sICAM levels compared to the pretreatment levels, whereas sVCAM levels decreased. However, after the treatment period, the sVCAM, hemoglobin, mean corpuscular volume (MCV), and serum ferritin levels did not return to the normal range compared to the controls. Pretreatment sVCAM-1 levels were inversely correlated with levels of hemoglobin, hemotocrit, MCV, serum iron, and ferritin. After treatment, the sVCAM-1 levels were negatively correlated with ferritin levels. Levels of sVCAM were significantly higher in patients with IDA than controls. After the treatment period, the sVCAM levels were not completely normalized in patients with IDA compared to controls, regardless of the presence of inadequate levels of hemoglobin, MCV, and serum ferritin. Thus, iron supplementation not only ameliorates anemia, but may also reduce the inflammation markers in cases with IDA.

The influence of Helicobacter pylori eradication on leptin, soluble CD40 ligand, oxidative stress and body composition in patients with peptic ulcer disease.

OBJECTIVE: To determine the effect of Helicobacter pylori (H. pylori) eradication on blood levels of soluble CD40 ligand, leptin, oxidative stress and body composition in patients with dyspepsia infected with H. pylori. METHODS: The infection of H. pylori was based on the presence of both (14)C urea breath test (UBT) and histology. Patients were given triple eradication therapy for 14 days and at 3 months after the treatment, (14)C UBT was reinstituted. Fasting glucose, leptin, body composition, soluble CD40 ligand, total oxidant status (TOS) were studied before and at 3 months after the treatment. RESULTS: In 33 subjects, H. pylori infection was successfully eradicated. sCD40L, and TOS levels were significantly decreased after H. pylori eradication. The percentage of body fat and body fat mass significantly decreased whereas the fat free mass (FFM) increased after eradication. However, eradication of the organism yielded no differences in leptin levels. CONCLUSION: These findings suggest that H. pylori eradication reduces the sCD40L and oxidative stress, fat mass with a significant increase in fat free mass. Thus, eradication of H. pylori infection not only improves ulcer healing, but may also reduce the presumed atherosclerosis risk.

The effect of ethinylestradiol (EE)/cyproterone acetate (CA) and EE/CA plus metformin treatment on adhesion molecules in cases with polycystic ovary syndrome (PCOS).

OBJECTIVE: To determine if EE/CA and EE/CA plus metformin treatment have any effect on adhesion molecules in cases with PCOS. METHODS: Among 40 patients diagnosed with PCOS, one study arm was administered EE/CA (n=20, cyproterone acetate 2 mg, ethinylestradiol 35 microg) and the other was administered metformin (1,700 mg) combined with EE/CA (n=20, cyproterone acetate 2 mg, ethinylestradiol 35 microg). Soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leukocyte adhesion molecule-1 (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte endothelial cell adhesion molecule-3 (sP-selectin), lipid profile, androgens, insulin, and HOMA-IR values were assessed prior to treatment and after 3 months of therapy. RESULTS: The comparison of the groups receiving EE/CA and EE/CA+metformin revealed a significant reduction in sVCAM (1,445+/-614 vs 1,167+/-482, p<0.05) and sICAM (442+/-141 vs 345+/-118, p<0.05) values relative to pre-treatment values while no significant changes were detected in sE-selectin and sP-selectin levels relative to pre-treatment levels in the EE/CA+metformin group (p>0.05). In the post-treatment period, sVCAM, sICAM, sE-selectin values did not significantly change compared to the pre-treatment values in EE/CA group (p>0.05). sP-selectin levels were also decreased but missed the significance in EE/CA group (229.4+/-68.0 vs 189.6+/-65.0, p=0.08). CONCLUSION: These results demonstrate that EE/CA+metformin treatment reduced inflammation markers in cases with PCOS compared to EE/CA treatment. The clinical relevance of this conclusion may be clarified by longer metformin treatment and clinical follow-up.