Reference values for trace essential elements in the whole blood and serum samples of the adult Serbian population: significance of selenium deficiency.

This study was aimed to determine reference values (RVs) for the manganese (Mn), copper (Cu), zinc (Zn), and selenium (Se) in the whole blood (B) and serum (S) samples of the Serbian population. Blood specimens were collected from healthy persons (n = 295; women/men ratio = 149/146; mean age: 42 ± 2 years). The RVs were calculated as lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI) and were expressed as percentiles (P) in the range from P2.5 to P97.5. The influences of sex, age, and smoking habits on element profiles were considered. It was found that the contents of B-Cu and S-Cu were higher in women, while the contents of B-Zn and S-Zn were higher in men. Both trace elements were significantly increased in a group of persons above 40 when compared to a younger persons (≤ 40 years). According to smoking habits, increased content was found only for S-Mn in the nonsmoker's group (p < 0.05). Comparing our results to the results reported in other population groups worldwide, the Serbian population had significantly reduced content of Se in both types of samples. This finding could highlight the deficiency of Se in the investigated Serbian population and could contribute to the better understanding of the molecular basis for the increased incidence of thyroid and other diseases in which selenium plays a key role.

Determination of toxic and essential trace elements in serum of healthy and hypothyroid respondents by ICP-MS: A chemometric approach for discrimination of hypothyroidism.

Inductively coupled plasma-mass spectrometry ((ICP-MS)) was used to determine three toxic (Ni, As, Cd) and six essential trace elements (Cr, Mn, Co, Cu, Zn, Se) in blood serum of patients with hypothyroidism (Hy group) and healthy people (control group), in order to set the experimental conditions for accurate determination of a unique profile of these elements in hypothyroidism. Method validation was performed with standard reference material of the serum by varying the sample treatment with both standard and collision mode for analysis of elements isotopes. Quadratic curvilinear functions with good performances of models and the lowest detection limits were obtained for 52Cr, 66Zn, 75As, 112Cd in collision mode, and 55Mn, 59Co, 60Ni, 65Cu, 78Se in standard mode. Treatment of serum samples with aqueous solution containing nitric acid, Triton X-100 and n-butanol gave the best results. Chemometric tools were applied for discrimination of patients with hypothyroidism. All nine elements discriminated Hy group of samples with almost the same discriminating power as indicated by their higher values for this group of patients. Statistically significant correlation (p < 0.01) was observed for several elements. Results indicated clear differences in element profile between Hy and control group and it could be used as a unique profile of hypothyroid state.

Effects of dietary milled seed mixture on fatty acid status and inflammatory markers in patients on hemodialysis.

BACKGROUND: Plant seeds have gained interest for their health benefits due to their fatty acid content. The objective of this study was to determine the effects of dietary consumption of milled sesame/pumpkin/flax seed mixture on glycemic control, serum lipids, phospholipid fatty acid status, and inflammatory factors in patients on hemodialysis. METHODS: Thirty patients with well nutrition status (18 male, 12 female) were enrolled in the study. Participants consumed 30 g of milled sesame/pumpkin/flax (6 g/6 g/18 g, resp.) seeds mixture added to their habitual diet. RESULTS: Total n-6 and n-3 polyunsaturated fatty acids and levels of linoleic, dihomo-gamma-linolenic (DGLA), arachidonic, alpha-linolenic (ALA), eicosapentaenoic, docosapentaenoic, and docosahexaenoic (DHA) acid were increased after 12 weeks of supplementation. A significant decrease of the serum triglyceride level (P < 0.001), glucose, insulin, calculated IR HOMA (P < 0.05), and inflammatory markers (TNF-alpha, IL-6, and hs-CRP, P < 0.001) was observed after seed mixture treatment. The serum levels of CRP and TNF-alpha negative correlate with ALA, DHA, and DGLA. CONCLUSION: Results of this study indicated that dietary milled sesame/pumpkin/flax seed mixture added to a habitual diet lowered triglyceride and CRP, TNF-alpha, IL-6 levels, affect glycemic control and improved fatty acid profile and pruritus symptoms in hemodialysis patients.

Low levels of arsenic in drinking water and type 2 diabetes in Middle Banat region, Serbia.

Arsenic in drinking water presents a serious public health problem in Serbia, but its relationship with diabetes has not been studied previously. The aim of this study was to explore the association between exposure to arsenic in drinking water and the occurrence of type 2 diabetes in Middle Banat region, Serbia. This cross-sectional study comprised two populations. Exposed population in Middle Banat region consumes drinking water with arsenic (mean = 56 µg/L); unexposed population from six regions in Central Serbia consumes arsenic below detection limit (2 µg/L). Newly diagnosed cases of type 2 diabetes were obtained from the National Registry of Diabetes in 2008. The Registry included age, gender, family history of diabetes, presence of overweight, central obesity, cholesterol and triglyceride levels. In addition, the number of cases of diabetes reported in years 2006, 2007 and 2009 was used to calculate standardized incidence rates for both populations. Two populations were comparable by age, family history of diabetes and prevalence of overweight persons. Unexposed population was more likely to have central obesity, and high total cholesterol and triglycerides. Standardized incidence rates of type 2 diabetes were higher in exposed population. Odds ratios for type 2 diabetes were significantly higher for the exposed population, both men and women, in the period from 2006 to 2009, when compared with the unexposed population. The population from Middle Banat region, consuming drinking water with low levels of arsenic, was at higher risk for the occurrence of type 2 diabetes in comparison to the unexposed population in Central Serbia.

Relation of CuZnSOD activity with renal insufficiency in hypertensive diabetic patients.

Diabetes and renal insufficiency are interrelated metabolic disorders closely associated with redox homeostasis disturbances. The aim of this study was to compare the activity of copper zinc superoxide dismutase (CuZnSOD) in the erythrocytes of hypertensive diabetic patients with or without renal insufficiency with normal healthy control subjects. In both groups of diabetic patients, blood glucose level and the content of glycosylated hemoglobin (HbA1c) were higher than in the control group. However, CuZnSOD activity was significantly higher than control only in hypertensive diabetic patients with renal insufficiency. Our results suggest that disturbances in superoxide homeostasis do correlate with long-term complication in diabetes, i.e. diabetic renal insufficiency and hypertension.

Arsenic in drinking water and acute coronary syndrome in Zrenjanin municipality, Serbia.

BACKGROUND: Arsenic is constantly present in drinking water supply systems of Zrenjanin municipality across decades. It presents a great public health problem in Serbia, but its relationship with acute coronary syndrome (ACS) has not been studied previously. OBJECTIVES: The aims of this study were to assess the incidence of ACS in two areas from Zrenjanin municipality consuming different levels of arsenic in drinking water, and to explore the association between arsenic exposure and the probability of fatal outcome of ACS. METHODS: The research was a registry-based ecological study of two populations consuming water with different arsenic levels, based on current guidelines (10 µg/L). Median arsenic in the area above national standard was 80 µg/L; median arsenic in the other area was 1 µg/L. Newly diagnosed cases of ACS were obtained from the National Registry for Acute Coronary Syndrome from 2006 to 2010. RESULTS: The two populations were comparable by age, gender, and prevalence of risk factors for ACS. Standardized incidence rates (SIR) of ACS were higher for people consuming arsenic above standard (average five-year SIR was 237.00 per 100.000; 95% CI=214.93-260.74), in comparison to people consuming arsenic within limits (average SIR=124.40 per 100.000; 95% CI=96.00-158.56). Exposure to arsenic above limits was insignificantly associated with fatal outcome of ACS for the whole population, men and women. CONCLUSIONS: Consumption of arsenic above national standards was associated with higher risk for the occurrence of acute coronary syndrome and with insignificantly higher probability of fatal outcome of ACS in Zrenjanin municipality.

Association of blood pressure and metabolic syndrome components with magnesium levels in drinking water in some Serbian municipalities.

Chronic exposure to insufficient levels of magnesium (Mg) in drinking water increases the risk of magnesium deficiency and its association with hypertension, dyslipidemia and type 2 diabetes mellitus. The aim of the study was to assess the potential association of mineral contents in drinking water with blood pressure and other components of metabolic syndrome (MetS) (BMI as measure of obesity, triglycerides, glucose, and insulin resistance, index-HOMA IR), in a healthy population. This study was conducted in three randomly selected municipalities (Pozarevac, Grocka and Banovci), and recruited 90 healthy blood donors, aged 20-50 years. The Pozarevac area had a four times higher mean Mg level in drinking water (42 mg L(-1)) than Grocka (11 mg L(-1)). Diastolic blood pressure was lowest in subjects from Pozarevac. Serum Mg (sMg) was highest, and serum Ca(2+)/Mg (sCa/Mg) lowest in subjects from Pozarevac, and after adjustment for confounders (age, gender, BMI), only total cholesterol and sMg levels were independent predictors of diastolic blood pressure, sMg levels were independent predictors of triglycerides, and sCa/Mg predicted glucose levels. These results suggest that Mg supplementation in areas of lower magnesium levels in drinking water may be an important measure in the prevention of hypertension and MetS in general.

Lower serum paraoxonase-1 activity is related to linoleic and docosahexanoic fatty acids in type 2 diabetic patients.

BACKGROUND: Serum paraoxonase-1(PON-1) activity is decreased in clinical conditions associated with low high-density lipoprotein cholesterol (HDL-C), increased lipid peroxidation and low-grade chronic inflammation, as in type 2 diabetes mellitus (T2DM). Until now there are no data about the association of any fatty acid (FA) with PON-1 activity in T2DM. METHODS: Twenty patients with T2DM and 16 healthy controls were included in this cross-sectional study. Serum PON-1 activity, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity as well as plasma glucose, HbA1c, lipids, high-sensitivity C-reactive protein (hs-CRP) and insulin resistance, homeostasis model assessment (HOMA-IR) were measured. The preparation of FA methyl esters and their gas chromatography (GC) analysis were also performed. RESULTS: HbA1c, plasma insulin, HOMA-IR and triglycerides were higher in patients with T2DM, whereas HDL-C was lower in those subjects. Levels of pro-oxidative enzyme malondialdehyde (MDA) and hs-CRP were significantly higher, and anti-oxidative enzymes SOD and PON-1 activity were decreased in T2DM patients. N-6 PUFAs were higher in T2DM patients, particularly linoleic acid (LA, 18:2 n-6) and arachidonic acid (AA, 20:4 n-6), whereas n-3 PUFA, docosahexaenoic acid (DHA, 22:6 n-3) was lower in T2DM patients. Using regression analysis, we have shown that only LA and DHA independently predicted PON-1 activity of all participants, particularly in patients with T2DM. CONCLUSIONS: Decreased serum PON-1 activity may, in part, be influenced by higher levels of LA and lower levels of DHA in patients with T2DM. Prospective, randomized studies are necessary to confirm these preliminary findings.

Arsenic occurrence in drinking water supply systems in ten municipalities in Vojvodina Region, Serbia.

Vojvodina, a northern region of Serbia, belongs to the Pannonian Basin, whose aquifers contain high concentrations of arsenic. This study represents arsenic levels in drinking water in ten municipalities in Serbia. Around 63% of all water samples exceeded Serbian and European standards for arsenic in drinking water. Large variations in arsenic were observed among supply systems. Arsenic concentrations in public water supply systems in Vojvodina were much higher than in other countries in the Pannonian Basin.

Do components of metabolic syndrome contribute to cardiac autonomic neuropathy in non-diabetic patients?

OBJECTIVE: To evaluate whether autonomic dysfunction exist in patients with metabolic syndrome (MetS) to establish any association with components of MetS. METHODS: From July 2008 to January 2009, 32 outpatients attending the University Clinical Center, Zemun, Belgrade, Serbia, 15 with MetS, 17 with type 2 diabetes mellitus (T2DM), and 15 control subjects were recruited for cross-sectional study among adults. The study was completed at the University Clinical Center, Bezanijska Kosa, and University Clinical Center, Dragisa Misovic, Belgrade, Serbia. Inclusion criteria were the presence of MetS without T2DM, T2DM and healthy controls, matched for age and gender. Exclusion criteria were uncontrolled diabetes (glycosylated hemoglobin [HbA1c] higher than 9%), advanced complications of diabetes (retinopathy, nephropathy, coronary heart disease, or peripheral angiopathy). Besides anthropometric and metabolic parameters cardiovascular autonomic reflex tests, ambulatory ECG monitoring, and blood pressure monitoring for 24 hours was obtained. Power spectral analysis of heart rate variability (HRV) was carried out by Fourier transformation. RESULTS: Mean total power (TP) log-transformed (ln), very low frequency (VLF)ln power, and high frequency (HF)ln power were significantly lower in T2DM patients, when compared with controls, and only HFln power was significantly lower in the MetS group. The average value of low frequency (LF)/HFln ratio was significantly higher in T2DM and MetS, and significantly correlated with glucose level of the last one. CONCLUSION: Disturbed HRV indices were present in patients with MetS before the development of T2DM. With this in mind, improvement of glucose metabolism, as well as early detection of cardiac autonomic dysfunction should be important.

Insulin resistance and chronic inflammation are associated with muscle wasting in end-stage renal disease patients on hemodialysis.

Muscle wasting is independent predictor of mortality in end-stage renal disease (ESRD) patients on maintenance hemodialysis (MHD). We investigated the effect of insulin resistance on lean body mass (LBM), and association between insulin resistance, chronic inflammation, and body composition in these patients. We analyzed cross-sectionally body composition, nutritional status and biochemical parameters in 35 non-diabetic ESRD patients who were on MHD. Bioelectrical impedance analysis was performed to quantify body fat, lean body mass and total body water (FAT (%), FAT (kg), LBM (%), LBM (kg) and TBW(%)). The association between LBM (kg) and gender, FAT (kg), high sensitivity C-reactive protein (hs-CRP), and homeostatic model assessment score (HOMA-IR) was recorded. Multiple linear regression analysis using LBM (kg) as dependent variable showed that FAT (kg) (beta = 0.563, p = 0.05), HOMA-IR (beta = 0.619, p = 0.03), and hs-CRP (beta = 0.488, p = 0.04) were independently associated with LBM in males. In females, only FAT (kg) (beta = 0.648, p = 0.001) significantly predicted LBM. Those variables explained 37% of variance of LBM (kg) in males, and 44% in females. It seems that insulin resistance participates independently in the pathogenesis of muscle wasting in both sexes, particularly in males. The effect of chronic inflammation was not so strong in females, and this point out that regulation of muscle wasting in female patients probably differs from that in males.

Is the routine abdominal ultrasound a sufficiently sensitive method for the detection of colonic malignancy?

OBJECTIVE: This study examined the sensitivity of routine abdominal ultrasound scanning in the detection of colonic malignancy. PATIENTS AND METHODS: A case control prospective study included 101 patients hospitalized at the Department of Gastroenterology and Liver Diseases of Zemun Clinical Hospital over a four-year period. Since the complaints pointed to colonic malignancy, the patients underwent routine golden standard diagnostic procedures. These patients were referred to an experienced abdominal ultrasound operator who searched for some characteristic signs of colonic malignancy. All of the participants were surgically treated after the completion of relevant procedures for diagnosing colonic malignancy. SPSS for Windows 10.0 was used for data analysis. RESULTS: The sensitivity of an abdominal ultrasound scan in the detection and location of pathological changes pointed to colonic malignancy was different- 76% and 84% respectively. This method was very reliable in detecting right-sided colonic carcinoma (100%). Some specific ultrasonographic signs of colonic carcinoma were observed at the advanced stages of disease. CONCLUSIONS: The routine abdominal ultrasonography can be used for the screening of colonic malignancy owing to its high sensitivity, particularly in advanced disease, but solely in conjunction with other methods. Finally, abdominal ultrasonography cannot be a definitive diagnostic tool for colonic carcinoma.

Metabolic syndrome in HD patients: association with body composition, nutritional status, inflammation and serum iron.

OBJECTIVE: Insulin resistance and metabolic syndrome (MeS) are common in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Such metabolic and clinical abnormalities may lead to an increased risk for cardiovascular disease. METHODS: The study group included 22 well-nourished and 20 middle- to moderate-malnourished, stable ESRD patients, with median dialysis duration of 48 months (IQR 24.5-82.0). To determine nutritional status, body composition, inflammatory biomarkers and the presence of MeS subjective global assessment (SGA), anthropometrical measurements (BMI and waist circumference), bioelectrical impedance analysis (BIA), and biochemical parameters [the levels of serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, TIBC, transferrin saturation (TSAT), ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein (hs-CRP)] were used. All parameters were evaluated by comparisons between two groups, with MeS (Group 2) and without it (Group 1). Logistical regression analysis was used to evaluate the correlation between measured variables and the presence of MeS in HD patients. Independent variables for MeS were identified by backward multivariate regression analysis. To identify the independent predictors for insulin resistance index (HOMA-IR) multivariate regression analysis was conducted, after linear regression analysis. RESULTS: After adjustment for confounding variables, a model consisting of serum levels of iron, transferrin saturation (TSAT), and BMI which accounted for 62% of the variance in MeS, determined only BMI as an independent marker (according to ATP-III criteria). But, serum glucose level, iron, waist and total fat mass accounted for 68% of the variance in MeS, according to IDF criteria. Glucose level was an independent predictor. BMI and iron, as independent variables, contributed to 29% of the variance in IR HOMA, the sensitive marker of MeS. CONCLUSION: The present study demonstrated that serum iron participated together with independent predictors, glucose and BMI, in the pathogenesis of IR and MeS of ESRD patients on maintenance HD.

The effect of nutritional status, body composition, inflammation and serum iron on the developement of insulin resistance among patients on long-term hemodialysis.

We investigated the effect of body composition, nutrition, inflammation and iron status on insulin resistance in patients with long-term hemodialysis. We selected 43 stable end-stage chronic renal failure patients, on maintenance hemodialysis. We evaluated the nutritional status, body composition by subjective global assessment (SGA), anthropometric measurements (BMI and waist circumference), bioelectrical impedance analysis and biochemical parameters measurements [serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein]. All parameters were evaluated by comparisons between HOMA-IR tertiles, and after simple regression analysis, by backward multivariate regression analysis we identified independent variables for IR. As the tertile of HOMA-IR increased, serum level of glucose, insulin, and waist increascd, whereas HDL-cholesterol level decreased, or the prevalence of the metabolic syndrome increased across the tertiles of HOMA-IR. After adjustment for gender, age, hemodialysis duration, ferritin, phosphorus, waist and total fat percentages, multivariate regression analysis was performed and the association with HOMA-IR was still strong only for serum levels of iron and TNF-alpha. That explains 16% of the total variation in HOMA-IR. Our results suggest that the increase of IR in end-stage chronic renal failure patients on hemodialysis could be related to anemia and particularly to iron overload. Moreover, chronic inflammatory status with over-production of adipokine TNF-alpha participate in the pathogenesis of IR too. The present study demonstrated that adipokine TNF-alpha and serum iron participated as independent predictors in the pathogenesis of insulin resistance on long-term hemodialysis patients.

[Predictors of mortality in dialysis patients--association between malnutrition, inflammation and atherosclerosis (MIA syndrome)]. / Prediktori mortaliteta kod bolesnika na dijalizi--povezanost malnutricije, inflamacije i ateroskleroze (mia syndrome).

INTRODUCTION: Numerous recent studies have shown increased comorbidity and mortality in dialysis patients with malnutrition. Protein-energy malnutrition with muscle wasting occurs in a large proportion of patients with chronic renal failure and is, in addition to atherosclerosis, a strong risk factor for mortality in patients undergoing dialysis. Malnutrition is also associated with increased cardiovascular mortality in dialysis patients. PATHOGENIC FACTORS OF MALNUTRITION IN DIALYSIS PATIENTS: Malnutrition is associated with a number of metabolic and vascular abnormalities. These factors include hypoalbuminemia, dyslipidemia with raised triglyceride concentrations, low-density lipoprotein and very low-density lipoprotein concentrations, insulin resistance and high concentrations of acute-phase proteins. Low serum albumin concentration, usually used as an index of malnutrition, is highly associated with increased mortality risk in dialysis patients. However, serum albumin is affected by factors other than malnutrition and high concentrations of acute-phase proteins, such as C-reactive protein (CRP), which correlate with low serum albumin in malnourished patients on dialysis. Oxidative stress has emerged as an important cofactor for development of endothelial dysfunction as premature atherosclerosis. In this context, malnutrition, inflammation and markers of oxidative stress are associated with vascular diseases. ETIOLOGY OF MALNUTRITION IN DIALYSIS PATIENTS: In recent studies several reports have suggested that inflammation, alone or in combination with low protein intake, plays a significant role in etiology of malnutrition in uremic patients. Lipid abnormalities may not only be a consequence of renal disease, but also contribute to its progression. Lipoprotein (a) is also associated with various atherosclerotic diseases. THERAPY OPTIONS: New treatment strategies, such as high protein/energy vs. standard protein/energy nutritional regimens, are necessary as well as food intake and dietary supplements. Intensive supplementation of (1.5 g protein/kg/d and 45 kcal/kg/d) is necessary to improve nutritional status of dialysis patients. CONCLUSION: Cellular basis of pathogenetic factors in malnutrition is unclear. It is, however, now recognized that oxidative stress and inflammatory cytokine aggravates the nutritional status of these patients.