No relationship between lipoprotein-associated phospholipase A2, proinflammatory cytokines, and neopterin in Alzheimer's disease.

OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a reported risk factor for dementia. However, the relationship between Alzheimer's disease (AD) and Lp-PLA2 is still debatable and, to the best of our knowledge, no study has evaluated the associations between levels of Lp-PLA2, proinflammatory cytokines, and neopterin in AD. METHODS: In total, 59 patients with AD and 38 non-demented individuals were included in the case-control study. Fasting serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), neopterin, and Lp-PLA2 were determined using ELISA. The associations between AD and each of the variables were analyzed by logistic regression. RESULTS: The median Lp-PLA2 levels in AD and controls were similar (P=0.29, not significant). Median serum neopterin and IL-6 levels were significantly higher in patients with AD than in controls (P=0.0001 and P=0.03, respectively). In regression analyses, median neopterin levels, a lower level of education, and female gender were significantly associated with AD when compared with controls (OR, 31.44, 95% CI 3.59-275.28, P=0.002; OR, 4.35, 95% CI 1.13-16.61, P=0.032; OR, 7.25, 95% CI 1.88-28.00, P=0.004, respectively). CONCLUSION: In contrast to previous evidence suggesting its role in dementia and AD, Lp-PLA2 enzyme levels were higher in the controls, and no relationship between Lp-PLA2 and either proinflammatory cytokines or neopterin was identified in AD. Elevated neopterin levels may be considered inflammatory markers of AD.

Diagnosing metabolic syndrome in type 2 diabetic Turkish patients: comparison of AHA/NHLBI and IDF definitions.

OBJECTIVES: The objective of this study was to determine the percentage of metabolic syndrome (MetS) in a Turkish population with type 2 diabetes mellitus (T2DM) according to the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and International Diabetes Federation (IDF) definitions and to assess the agreement among these definitions. BACKGROUND: It is essential to identify the prevalence of MetS in diabetic patients, as MetS is a stronger risk factor for cardiovascular disease in patients with T2DM than in non-diabetic subjects. METHODS: 235 consecutive patients with T2DM were included in the study. The MetS was defined according to AHA/NHLBI and IDF definitions. Cohen's kappa was used as a measure of agreement between the two definitions. Logistic regression analysis was performed to calculate the odds ratios. RESULTS: The percentage of MetS was 85.1% by AHA/NHLBI and 87.2% by IDF criteria. The agreement between AHA/NHLBI and IDF was fairly good (kappa = 0.55). Females were more affected than males. When the frequencies of each individual feature of the MetS according the definitions were assessed, hypertension was the most common feature in males, whilst abdominal obesity was in females. Serum triglyceride and waist circumference had the highest predictive ability for MetS according to AHA/NHLBI and IDF definitions, respectively. CONCLUSION: The MetS is a common condition among diabetic patients. Since diabetic patients carry a cluster of cardiovascular risk factors, correct identification of the MetS among this population is of great importance, for an integrated approach to reduce the high costs and the associated disabilities (Tab. 5, Fig. 2, Ref. 54).

Serum N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) and homocysteine levels in type 2 diabetic patients with asymptomatic left ventricular diastolic dysfunction.

AIMS: : The aim of this study was to determine serum NT-proBNP and plasma Hcy levels and to explore the relationship between serum NT-proBNP and plasma Hcy levels in type 2 diabetic patients with and without asymptomatic LVDD. METHODS: : NT-proBNP and Hcy levels were measured 31 patients with type 2 diabetes mellitus. According to echocardiographic data, diabetic patients were divided into two groups: normal LV function or LV diastolic dysfunction. RESULTS: : Serum NT-proBNP levels in diabetic patients with LVDD were significantly higher than in diabetic patients with normal LV function and controls. The area under the receiver-operating characteristic (ROC) curve for NT-proBNP to separate normal vs. diastolic dysfunction was 0.96 in type 2 diabetic patients. Plasma Hcy levels were significantly higher in both diabetic groups than in controls. Positive correlation was noted between NT-proBNP and Hcy levels in diabetic patients with LVDD (r=0.881, p=0.0001). CONCLUSIONS: : The correlation between elevated NT-proBNP and Hcy levels in diabetic patients with LVDD suggest an association between homocysteinemia and increased NT-proBNP secretion. Our data indicate that NT-proBNP may be a simple screening tool to select diabetic patients with LVDD requiring further examination with echocardiography.

Effect of different levels of cigarette smoking on lipid peroxidation, glutathione enzymes and paraoxonase 1 activity in healthy people.

The purpose of this study was to examine the effect of different levels of cigarette smoking on lipid peroxidation, glutathione enzymes and paraoxonase 1 (PON1) activity in a healthy population. The study included 130 subjects who were classified as mild (20 cigarettes daily, Group III, n=33) and never smokers (controls, Group IV, n=32). Malondialdehyde (MDA) levels, PON1 and erythrocyte glutathione enzyme activities were measured. MDA levels were significantly higher in smokers than never smokers (P<0.05 for Group I, P<0.001 for Group II and III). PON1 activity was significantly lower in heavy smokers (P<0.001). Glutathione peroxidase (GSH-Px) activity was significantly lower in the smokers (P<0.0001). Glutathione reductase (GR) activity was significantly higher in smokers (P<0.0001). MDA levels negatively correlated with PON1 and GSH-PX activities (P<0.01), whereas they positively correlated with GR activities (P<0.001). At every level, cigarette smoking is associated with increased lipid peroxidation and causes an impairment in antioxidant systems.

Beta2-microglobulin and cystatin C in type 2 diabetes: assessment of diabetic nephropathy.

BACKGROUND: Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy (DN). This study was designed to demonstrate the clinical values of serum cystatin C (Cys C) and beta2-microglobulin in the assessment of renal function in type 2 diabetics by comparing them with the GFR, estimated from the uptake phase of 99 m technetium dimetiltriamino pentaacetic acid renogram (GFR-DTPA) and creatinine clearances. MATERIALS AND METHODS: 68 type 2 diabetic patients with (urinary albumin excretions (UAE) 30 - 300 mg/24 h) (n = 39) and without (UAE < 30 mg/24 h) (n = 29) microalbuminuria and 32 controls were enrolled in the study. Serum Cys C, beta2-microglobulin, creatinine, urinary microalbumin levels, creatinine clearances and GFR-DTPA values were determined in all groups. Non-parametric ROC curves, using a cut-off GFR-DTPA of 60 mL/min/1.73 m (2), were obtained for these markers. RESULTS: Serum Cys C, beta2-microglobulin, glucose and HbA1c concentrations were significantly higher in the group with diabetes compared to controls. In the patients with microalbuminuria, serum Cys C and glucose concentrations increased significantly in comparison to patients with normoalbuminuria, while no differences were observed for beta2-microglobulin levels. Serum creatinine concentrations, GFR-DTPA values and creatinine clearances were not different between both diabetic groups and controls. Cys C was positively correlated with beta2-microglobulin and creatinine and negatively with GFR values; beta2-microglobulin was also positively correlated with serum creatinine in microalbuminurics. A significant inverse correlation was found between beta2-microglobulin and GFR values in both microalbuminurics and normoalbuminurics. CONCLUSIONS: Increased Cys C and beta2-microglobulin in diabetics may be early indicators of incipient DN. The diagnostic accuracies of Cys C and beta2-microglobulin are superior to that of serum creatinine in distinguishing between mild and moderately reduced GFR.

Spuriously elevated inorganic phosphate level in a multiple myeloma patient.

We report the case of a patient with IgG multiple myeloma and pseudohyperphosphatemia. The patient had no clinical features of hyperphosphatemia. Subsequent investigations demonstrated that this hyperphosphatemia was spurious and was caused by a high concentration of the paraprotein. Deproteinization of the serum samples by sulfosalicylic acid resulted in normalization of the elevated phosphate values. This pseudohyperphosphatemia resulted from an increase in optic density because of interference between monoclonal immunoglobulin and the molybdic reagent used to determine phosphate in serum. These data indicate that the finding of marked hyperphosphatemia in multiple myeloma patients should always prompt an assay carried out on a deproteinized sample. In addition, knowledge of this phenomenon may avoid confusion, unnecessary testing and obviate confusion in the clinical evaluation of patients with multiple myeloma.

The urinary excretion of glycosaminoglycans and heparan sulphate in lupus nephritis.

Renal involvement in systemic lupus erythematosus (SLE) affects the disease outcome. In order to advance the diagnosis and the initiation of therapy, non-invasive diagnostic techniques are required. In this study, urinary glycosaminoglycans (GAG) and heparan sulphate (HS) were measured in 26 patients with biopsy-proven lupus nephritis and compared to 16 healthy controls. Uronic acid as a representative of GAGs in urine was determined spectrophotometrically with the meta-hydroxydiphenyl, following acid treatment. HS was determined as hexosamine by the method of Smith and Gilkerson. The median values of GAG (3.99 mg/g crea./day) and HS (2.41 mg/g crea./day) in patients were significantly ( P = 0.001) higher than in the control group (1.98 and 0.87, respectively). There was a positive correlation between GAG and HS values ( P = 0.000, r = 0.924) in SLE patients. There were no differences in HS excretion, microalbuminuria and SLE-DAI scores between different classes of lupus nephritis. However, GAG values in class 3 nephritis were significantly ( P = 0.033) higher than from both class 2 and class 4 lupus nephritis. There were no differences in all the measured parameters between normoalbuminuric, microalbuminuric and macroproteinuric patients. Furthermore, there were no correlations between GAG, HS excretions and SLE-DAI scores or microalbuminuria. These results suggest that urinary GAG and HS may serve as useful, independent and non-invasive markers of lupus nephritis.

Association between homocysteine and neopterin in healthy subjects measured by a simple HPLC-fluorometric method.

OBJECTIVES: Neopterin and homocysteine promote vascular smooth muscle cell proliferation through the activation of nuclear factor(kappa) B. The aim of this study was to investigate the relation between these two compounds in healthy subjects by a rapid HPLC-fluorometric method which simplifies sample pretreatment for the measurement of neopterin in serum. DESIGN AND METHODS: In 40 healthy subjects (45.9 +/- 2.1 yr, mean +/- SEM, 10 males, 30 females) serum neopterin concentrations were measured by HPLC-fluorometry and enzyme-linked immunusorbant assay-ELISA and the results were compared. Urinary neopterin and plasma total homocysteine concentrations were assayed by HPLC-fluorometry. RESULTS: Serum neopterin concentrations measured by HPLC and ELISA were 7.5 +/- 0.4 and 7.4 +/- 0.3 nmol/L, respectively, r = 0.92, p < 0.01. Urinary neopterin level was 163.9 +/- 11.0 nmol/mmol creatinine and plasma total homocysteine 7.6 +/- 0.4 micromol/L. A significant positive correlation was observed between serum neopterin and plasma total homocysteine (r = 0.59, p < 0.01). CONCLUSIONS: A simple and rapid sample pretreatment for the measurement of neopterin in serum has been introduced. The significant positive correlation between neopterin and homocysteine implies that, interference with leukocyte function might be a new possible mechanism for the deleterious effects of homocysteine on vascular function.

Age-associated changes in nitric oxide metabolites nitrite and nitrate.

Aging is an important determinant of vascular disease. Endothelial dysfunction accompanying vascular disease may be related to cardiovascular risk factors such as aging, hypertension, and atherosclerosis. Experimental models suggest that endothelium-derived nitric oxide is reduced with aging, and this reduction is implicated in atherogenesis. The aim of this study was to determine whether increased age resulted in altered serum nitrite and nitrate levels, end-products of nitric oxide, in healthy subjects. Sixty-nine healthy individuals were divided into five different age groups: group I (6-15 years), group II (16-30 years), group III (31-45 years), group IV (46-60 years), and group V (>61 years). In these subjects, serum nitrite was measured by the Griess reaction and nitrate by the nitrate reductase method. Statistical analysis showed that serum nitrite levels were not significantly different in any of the groups, while serum nitrate concentrations exhibited significant differences (P<0.001). These findings suggest that nitric oxide synthesis and/or secretion is reduced with age and consequently endothelium-dependent vasodilation is impaired.