Circulating vaspin and its relationship with insulin sensitivity, adiponectin, and liver histology in subjects with non-alcoholic steatohepatitis.

OBJECTIVE: Non-alcoholic steatohepatitis (NASH) is closely associated with components of metabolic syndrome. Vaspin is a novel adipocytokine that may link obesity, insulin resistance (IR), and type 2 diabetes mellitus. We aimed to investigate circulating vaspin levels in subjects with NASH and also to search for the association of vaspin with IR, adiponectin, and histological findings. MATERIAL AND METHODS: A total of 50 male patients with NASH and 30 healthy male controls were enrolled. Vaspin and adiponectin were measured with ELISA method. Insulin sensitivity determined by homeostasis model assessment (HOMA-IR) index. RESULTS: Plasma vaspin levels were higher and adiponectin levels were lower in NASH group compared with controls (p < 0.01 and p < 0.001, respectively). However, in multivariate analysis adjusted for glucose and lipid parameters, and HOMA-IR indexes, the difference in vaspin concentrations was disappeared. Nonetheless, the difference regarding the adiponectin levels remained significant between groups (p = 0.03). Vaspin was negatively correlated with low-density lipoprotein cholesterol (r = -0.32, p = 0.03) in subjects with NASH. CONCLUSIONS: This study indicates that circulating vaspin levels are not altered in male subjects with NASH. These results suggest that in the absence of metabolic risk factors, vaspin per se may not be involved in the pathogenesis of NASH.

Plasma apelin and ADMA Levels in patients with essential hypertension.

Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = -0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.

Relationship between hemoglobin and CD40 ligand in prediabetes.

PURPOSE: Hemoglobin (Hb) regulates the endothelial function by modulating the bio-availability of NO at the tissue level. A significant direct relationship is present between the Hb levels and endothelial functions in patients with Type 2 diabetes. Testing whether this association also exists in subjects with prediabetes is important because prediabetes is associated with an increased risk of cardiovascular disease and mortality. Therefore, we investigated the association of Hb both with the classical cardiac risk factors and the markers for endothelial dysfunction and inflammation, in subjects with impaired glucose tolerance (IGT). METHODS: We enrolled 69 normotensive, and cardiovascular events free subjects with IGT (M=40, age=45.50+/-6.8 yr). Plasma insulin, hsCRP, soluble CD40L, vonWillebrand factor, p-selectin levels were measured. The parameters given according to the higher and lower median Hb values of the subjects were compared. RESULTS: Subjects with the higher Hb levels exhibited lower HDL-C (46.68+/-10.8 mg/dl vs 51.5+/-8.9 mg/dl; P=0.04) and higher systolic (122.57+/-6.2 mmHg vs 116.17+/-7.4 mmHg; p < 0.001) and diastolic (79.14+/-3.73 mmHg vs 75.58+/-6.1 mmHg; P=0.005) blood pressures and sCD40L (7.9+/-3.8 ng/ml vs 6.07+/-2.1 ng/ml; P=0.02) levels. Hb levels were correlated to the HDL cholesterol, sCD40L, systolic and diastolic blood pressures and waist circumference (r=-0.28, P=0.02; r=0.29, P=0.02; r=0.53, P < 0.001; r=0.41, P=0.001; r=0.42, P < 0.001 respectively). According to the multiple logistic regression analysis, Hb was the determinant of sCD40L levels (beta=0.437, P < 0.001). CONCLUSION: These results indicate that there may be a link with higher Hb values and cardiovascular risk factors in patients with IGT. Further investigation is warranted to understand the clinical implications of these findings in subjects with prediabetes.

Pleural fluid and serum procalcitonin as diagnostic tools in tuberculous pleurisy.

BACKGROUND: Diagnosis of tuberculous pleuritis is difficult because of its nonspecific clinical presentation and decreased efficiency of traditional diagnostic methods. We investigated the use of procalcitonin (PCT) concentration in tuberculous pleuritis diagnosis. METHODS: A prospective clinical study was performed with two different patient groups. A total of 28 patients were included: 18 with tuberculosis and 10 with nontuberculous pleurisy. Serum and pleural fluid PCT concentrations were evaluated before treatment. RESULTS: Serum and pleural fluid PCT concentrations were statistically different between tuberculous and nontuberculous pleurisy groups (P = 0.012 and P = 0.004, respectively), even though they were not elevated in relation to the cut-off level of 0.5 ng/mL. A positive and significant correlation was detected between serum and pleural fluid PCT levels (r = 0.49, P = 0.008). Diagnostic specificity and sensitivity values for serum and pleural fluid PCT in discriminating tuberculous from nontuberculous pleurisy were 80% and 72.2%, and 90% and 66.7% at the 0.081 and 0.113 ng/mL cut-off values, respectively. CONCLUSION: Relative to the current cut-off level of 0.5 ng/mL, PCT concentration is not a useful parameter for the diagnosis of tuberculous pleurisy. Because there were PCT levels in patients with tuberculous pleurisy that were below the current cut-off level but were significantly different from those of the nontuberculous group, the use of PCT should be further investigated.

Elevated urine neopterin levels in nonalcoholic steatohepatitis.

OBJECTIVES: The aim of this study was to relate urine levels of neopterin, a marker of activation of the cellular immune system, with grading and staging of NASH. DESIGN AND METHODS: Urine concentrations of neopterin, routine tests, insulin and C-peptide levels were assessed in 50 patients with NASH, 25 patients with chronic viral hepatitis (CVH), and in 26 healthy controls. RESULTS: Urine neopterin levels were found elevated in the NASH and CVH groups compared with controls. There was no significant correlation between urine neopterin levels and inflammation grade in the liver. CONCLUSIONS: Urine neopterin levels are a marker of cellular immunity and are higher in patients with NASH. However, neopterin levels were not significantly associated with histopathological grade and stage of disease.

Serum fetuin-A levels in postmenopausal women with osteoporosis.

BACKGROUND/AIM: One of the functions of fetuin-A is the restriction of formation and expansion ofextraosseous hydroxyapatite crystals. TIhe exact correlation of fetuin-A with bone mineral density (BMD) has not been clearly elucidated yet. In this study, we aimed to assess the relationship between BMD and fetuin-A in postmenopausal women. MATERIALS AND METHODS: Fifty postmenopausal women (25 with osteoporosis, 25 healthy controls) were included in the study. All participants were comparable for age and body mass index. None of the osteoporotic patients had received any medical treatment for osteoporosis. Serum fetuin-A levels were measured by ELISA method. RESULTS: BMD scores of the groups were statistically significant (P < 0.001). Serum fetuin-A levels of the osteoporosis group were significantly lower compared to the control group (P = 0.009). Additionally, there was there was a mild to moderate positive correlation between fetuin-A and lumbar (r = 0.381, P = 0.06) and femoral (r = 0.143, P = 0.50) BMD in the osteoporotic group, though it did not reach statistical significance. CONCLUSION: Decreased fetuin-A levels in women with postmenopausal osteoporosis suggest that fetuin-A may have a role in the development of osteoporosis. Further studies are required to define the exact role of fetuin-A in bone metabolism.

Comparing the fatty acid levels of preterm and term breast milk in Turkish women.

AIM: Lipids are the main source of calories and considered very important in infant growth. We aimed to compare fatty acid composition of term and preterm breast milk. This is the first study that compares the fatty acid levels of preterm and term breast milk in Turkish women. MATERIALS AND METHODS: Breast milk samples were obtained from mothers of term (n = 15) and preterm (n = 15) infants on postnatal days 3, 7, and 28. Fatty acid composition of human breast milk was determined longitudinally by gas-chromatography/mass spectrometry. RESULTS: There Were 31 fatty acids measured in the milk samples. In the first month, 17 fatty acid levels had significant differences. In group comparison, some fatty acids (C14:0, C16:0, C18:1 and C20:5) had significantly increased in the preterm group (P = 0.041, P = 0.046, P = 0.027, P = 0.033, respectively), whereas myristoleic acid (C14:1) and eicosanoic acid (C20:0) had significantly increased in the term group (P = 0.015, P = 0.048, respectively). CONCLUSION: Term and preterm milk have different compositions of fatty acids. Breast milk composition changes over time. As a general conclusion, breast milk provides the lipid requirements of infants.

Plasma melatonin and urinary 6-hydroxymelatonin levels in patients with pulmonary tuberculosis.

Tuberculosis (TB) is the second most frequent cause of death in the world, after AIDS. Delay in diagnosing TB is an important worldwide problem. It seriously threatens public health. Cell-mediated immune responses play an important role in the pathogenesis of TB infection. The course of Mycobacterium tuberculosis (MTb) infection is regulated by two distinct T cell cytokine patterns. Melatonin is a biomolecule (mainly secreted by the pineal gland) with free radical scavenging, antioxidant and immunoregulatory properties. Melatonin has both its direct and indirect immunomodulatory effects on the immune system. In this study, we measured plasma melatonin and urine 6-hydroxy melatonin sulphate (6-HMS) concentrations in patients with newly diagnosed TB for the purpose of investigating whether there was a relationship between their levels and MTb infection. Thirty-one newly diagnosed patients presenting with active TB and 31 healthy subjects as the control group were included in this study. Blood and 24-h urine samples were collected from all individuals. Plasma melatonin levels and urine 6-HMS were measured. Our results show that in patients with TB, mean melatonin and 6-HMS concentrations were significantly lower than in the control subjects (p = 0.037, p < 0.001, respectively). We believe that the treatment of TB patients with melatonin might result in a wide range of health benefits including improved quality of life and reduced severity of infection in these patients. Supplementation with melatonin may be considered as an adjunctive therapy to classic treatment of pulmonary TB, especially during the acute phase of infection.

Decreased small dense LDL levels in Gilbert's syndrome.

OBJECTIVE: To investigate the role of small dense low density lipoprotein cholesterol (sd-LDL-C) in the mechanism of decreased incidence of cardiovascular disease in Gilbert's syndrome (GS). DESIGN AND METHODS: sd-LDL-C, ox-LDL, and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n=42) and compared to healthy controls (n=52). RESULTS: Age, gender and body mass index (BMI) distributions were similar between the two groups. sd-LDL-C, ox-LDL and hs-CRP levels were lower in GS than the healthy controls (p<0.001, p<0.001 and p=0.001, respectively). Unconjugated bilirubin was negatively correlated with sd-LDL-C, ox-LDL and hs-CRP (r=-0.594, p<0.001; r=-0.249, p=0.016 and r=-0.373, p<0.001 respectively). In addition, sd-LDL-C was positively correlated with ox-LDL (r=0.307, p=0.003). CONCLUSIONS: The findings of this preliminary study suggest that reduced sd-LDL-C, ox-LDL and hs-CRP levels may have a role in preventing atherosclerosis in subjects with GS.

Elevated serum neopterin levels in acetaminophen-induced liver injury.

Neopterin is synthesized in macrophage/Kupffer cells by interferon-gamma and other cytokines. This study aimed to evaluate the utility of using neopterin as a biomarker of acetaminophen (APAP)-induced liver injury. Wistar rats, randomly divided into two groups (APAP and normal), received APAP (1.0 g/kg) and distilled water, respectively, by gastric tube. The APAP group had a higher degree of liver necrosis than the control group. The APAP group also had significantly higher serum neopterin levels than the normal group. Serum neopterin levels correlated with serum AST, ALT activities, and degree of necrosis. This study demonstrates the preclinical utility of neopterin as a biomarker for the animal model of APAP-induced liver injury. Further research studies are required to determine the preclinical opportunities of using neopterin as a marker of APAP-induced liver injury.

Paraoxonase-1 activity determination via paraoxon substrate yields no significant difference in mild hyperhomocysteinemia.

Elevated plasma homocystein (Hcy) level has been recognized as an important risk factor for a number of cardiovascular diseases, peripheral arterial occlusive disease and venous thrombosis. A part of Hcy in the organism is turned to homocysteine thiolactone (HcyT) via a ring closure reaction, which gains rate in hyperhomocysteinemia, and in turn undergoes a hydrolytic reaction back to Hcy by paraoxonase enzyme (PON). Since this is a protective reflex action enzyme against hyperhomocysteinemia, we investigated how a mild hyperhomocysteinemic nutritional habit affected serum PON activity in a population-based study. The difference detected via enzymatic activity using the paraoxon substrate was statistically non-significant (p=0.19), suggesting a defective performance to reflect the expected significance. Determination of serum PON activity via substrate paraoxon yielded no significant difference in an acute mild hyperhomocysteinemic diet model in humans.

Soluble CD40 ligand and soluble P-selectin levels in Gilbert's syndrome: a link to protection against atherosclerosis?

OBJECTIVE: To investigate the role of CD40 ligand and P-selectin in the mechanism of decreased incidence of cardiovascular disease in Gilbert's syndrome (GS). DESIGN AND METHODS: The soluble forms of CD40 ligand (sCD40L) and P-selectin (sP-selectin), and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n=25) and compared to healthy controls (n=53). RESULTS: sCD40L and hs-CRP levels were significantly lower in GS compared to the controls (0.33+/-0.27 vs 0.71+/-0.37 ng/mL, p<0.001 and 0.51+/-0.45 vs 1.16+/-1.31 mg/L, p=0.046, respectively). Both sCD40L and hs-CRP were negatively correlated with total bilirubin (r=-0.5, p<0.001 and r=-0.34, p=0.002, respectively). sP-selectin levels were lower in GS when compared to the controls but the difference did not reach statistical significance (p=0.052). No correlation was found between the plasma levels of sCD40L, sP-selectin and hs-CRP. CONCLUSION: These novel findings suggest that reduced sCD40L and hs-CRP concentrations may have a role in the mechanism of protection against atherosclerosis in GS.

Nebivolol therapy improves endothelial function and increases exercise tolerance in patients with cardiac syndrome X.

OBJECTIVE: We sought to determine whether nebivolol affects coronary endothelial function and exercise induced ischemia in patients with cardiac syndrome X (CSX). METHODS: The study protocol undertaken was based on a single-blind randomized controlled prospective study. After a 2-week washout period, 38 patients with cardiac syndrome X were randomized to receive either nebivolol 5 mg daily (n=19) or metoprolol 50 mg daily (n=19) in a single- blind design for 12 weeks. The control group under study was consisted of 16 age- and gender-matched subjects with negative treadmill exercise tests. Plasma endothelial nitric oxide (NOx), L-arginine, and asymmetric dimethylarginine (ADMA) were measured in all patients at baseline and after 12 weeks of treatment. Statistical differences among groups were tested by one-way analysis of variance and unpaired samples t test for parametric; Kruskal-Wallis and Mann-Whitney U tests for non-parametric variables, respectively. A paired samples t test was used to compare continuous variables before and after drug therapy. RESULTS: At baseline, plasma level of NOx, L-arginine, and L-arginine/ADMA ratio were lower (p<0.001 for all) in patients with CSX than in the control patients. Whereas, the plasma ADMA levels were increased in the patient group (p<0.001). After 12 weeks of drug therapy, the patients taking nebivolol had increased levels of plasma NOx , plasma L-arginine, the L-arginine/ADMA ratio and decreased levels of plasma ADMA compared to those of the patients taking metoprolol (p<0.001). In addition, exercise duration to 1-mm ST depression and total exercise duration significantly increased after treatment in the nebivolol group compared to the metoprolol group (p<0.01). In the nebivolol group, Canadian Cardiovascular Society (CCS) angina classification improved by one or more categories in 12 (70%) patients, whereas it deteriorated or remained in the same category in 5 (30%) patients. Meanwhile, in the metoprolol group, the CCS angina classification improved by one or more categories in 7 (41%), whereas it deteriorated or remained in the same category in 10 (59%) patients. CONCLUSION: Circulating endothelial function parameters (plasma ADMA, L-arginine, NOx levels) were impaired in patients with CSX. Nebivolol treatment was associated with better improvements in both circulating endothelial function and exercise stress test parameters than metoprolol. We believe that further studies are needed to evaluate the effects of nebivolol treatment on long-term clinical outcomes in patients with CSX.

Pressure-related increase of asymmetric dimethylarginine caused by hyperbaric oxygen in the rat brain: a possible neuroprotective mechanism.

A decrease in nitric oxide availability in the brain tissue due to the inhibition of nitric oxide synthase (NOS) activity during the early phases of hyperbaric oxygen (HBO) exposure was found to be involved in hyperoxic vasoconstriction leading to reduced regional cerebral blood flow. We hypothesized that the concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), may be an important factor during this hyperoxic vasoconstriction state. Rats were exposed to 1, 2 and 3 atmospheres pure oxygen for two hours. A fourth group of animals served as control. Asymmetric dimethylarginine, L-Arginine and nitrite/nitrate (NOx) concentrations were measured from deproteinized rat brain cytosols. In rat brains exposed to 3 atmospheres O2, ADMA and L-Arginine levels were found to be significantly higher and NOx significantly lower than control levels. Additionally, statistically significant correlations between ADMA and L-Arginine, and ADMA and NOx concentrations were detected. In conclusion, this is the first study indicating increased ADMA levels in rat brains exposed to HBO. The simultaneously decreased NOx values suggest that ADMA elevation resulted in NOS inhibition and therefore may be responsible for the early phase hyperoxic vasoconstriction.

The effects of thyroxine replacement on the levels of serum asymmetric dimethylarginine (ADMA) and other biochemical cardiovascular risk markers in patients with subclinical hypothyroidism.

BACKGROUND: The relationship between subclinical hypothyroidism (SH) and cardiovascular disease (CVD) is still under debate. The purpose of the present study was to evaluate plasma total homocysteine (tHcy), high sensitive C-reactive protein (hsCRP), small dense low-density lipoprotein (sdLDL), L-arginine and asymmetric dimethylarginine (ADMA) concentrations and their relationship to nitric oxide (NO) production, measured as plasma nitrite-plus-nitrate (NO(x)) concentration, in patients with SH before and after thyroxine replacement therapy and compared with control group values. DESIGN: Eighty-four women with SH and 33 healthy women as controls matched to the patient group for sex, age and body mass index (BMI), were enrolled in this study. Lipoprotein profile, tHcy, hsCRP, sdLDL, ADMA, L-arginine and NO(x) were measured in pre- and post-treatment blood samples. RESULTS: The pretreatment total cholesterol (TC), LDL-C, hsCRP, ADMA and L-arginine levels were significantly higher and NO(x) levels were lower than in the control group. After treatment, hsCRP, ADMA and L-arginine levels were significantly reduced and sdLDL and NO(x) levels were significantly increased. CONCLUSION: The present study demonstrated an elevation of hsCRP and ADMA plasma levels of patients with SH associated with a reduction in NO production, which may contribute to some cardiovascular alterations. The elevated ADMA and hsCRP levels were reduced after thyroxine replacement. Also the sdLDL levels of SH patients were found to be lower than the control group values whereas TC and LDL were elevated. Even though we found an elevation in sdLDL levels after treatment, those values were still not higher than in the control group.