Gordana Perunicic-Pekovic

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.

Mycophenolate Mofetil in High-Risk Patients with Primary Glomerulonephritis: Results of a 1-Year Prospective Study

Background/Aims: Glucocorticoids and classic immunosuppressive drugs can improve disease activity in primary glomerulonephritis (GN). However, these drugs have serious toxicity and patients frequently experience inadequate response or relapse, so there is a need for alternative agents. This multicenter uncontrolled study analyzed the efficacy and safety of mycophenolate mofetil (MMF) in high-risk patients with primary GN. Methods: A total of 51 patients with biopsy-proven membranous (n = 12), membranoproliferative (n = 15), mesangioproliferative (n = 10), focal segmental glomerulosclerosis (n = 13) and minimal change disease (n = 1) received MMF with low-dose corticosteroids for 1 year. The primary outcome included the number of patients with complete/partial remission. Results: Proteinuria significantly decreased, from its median value of 4.9 g/day (IQR 2.9–8.4) to 1.28 g/day (IQR 0.5–2.9), p < 0.001. The urine protein/creatinine ratio significantly improved, from a median of 3.72 (IQR 2.13–6.48) to 0.84 (IQR 0.42–2.01), p < 0.001. The mean area under the curve for proteinuria significantly decreased, from 4.99 ± 3.46 to 2.16 ± 2.46, between the first (visits 1–2) and last (vists 4–5) treatment periods (p < 0.001). The change was similar for every type of GN, without difference between groups. eGFR slightly increased (62.1 ± 31.8 to 65.3 ± 31.8 ml/min, p = n.s.) and ESR, total proteins, albumins, total- and HDL-cholesterol parameters improved significantly. Systolic, diastolic and mean blood pressure decreased (p < 0.02 for systolic blood pressure). The age of patients was the only independent predictor of complete or partial remission. Conclusion: MMF proved to be efficient in 70% of high-risk patients with primary GN, who reached either complete or partial remission without safety concern after 12 months of treatment. Favorable effects of MMF therapy have to be confirmed in the long term and particularly after discontinuation of the drug.

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.

Treatment of Lupus Nephritis by Mycophenolate Mofetil

Background/Aims: Mycophenolate mofetil (MMF) has been increasingly used for the treatment of lupus nephritis (LN). The aim of this study was to examine the efficacy and safety of MMF used with low doses of corticosteroids as maintenance therapy in patients with LN. Methods: The study covered 35 patients, most of them with proliferative types of LN (5 WHO class III, 26 class IV), while 1 had class V and 3 class VI nephritis. MMF was administered in the dose of 1.5–2 g/24 h and prednisone at 10–20 mg/day. The treatment effects were followed over a 12-month period. Results: After 3 months of therapy significant reduction in proteinuria was achieved (2.1 ± 2.4 g/24 h vs. 1.0 ± 1.0 g/24 h, p < 0.01) and maintained to the end of the study. In parallel, a significant rise in serum albumin, a fall of cholesterol and a significant increase in mean glomerular filtration rate were noted. Complete remission was achieved in 16 patients (45.7%), including all patients in class III and V plus 10 patients in class IV. Not a single adverse effect was observed. Conclusion: MMF combined with low doses of steroids is an effective and safe treatment for the maintenance of stable remission of LN.

[Predictors of mortality in dialysis patients--association between malnutrition, inflammation and atherosclerosis (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.

Screening of Elderly for Chronic Kidney Disease

Background and Aims: The frequency of chronic kidney disease (CKD) markers was assessed in two groups of patients over 60 years – one without and the other with hypertension. Methods: The cross-sectional study involved 585 asymptomatic elderly patients (227 males), 93 without and 492 with hypertension. Data on patients were obtained by interview, analysis of medical records and physical examinations. Serum and urine creatinine, proteinuria, microalbuminuria (MAU, turbidimetry), and urinary sediment were analyzed. Results: Among the 585 patients, there were 54.5% with a positive family history for hypertension and 14% for kidney diseases. MAU was significantly more frequent (30 vs. 11%) and the mean estimated glomerular filtration rate (eGFR) higher (71 ± 14 vs. 64 ± 14 ml/min/1.73 m) in patients without hypertension than in those with hypertension. The majority of patients with stage 3 CKD had eGFR >45 ml/min/1.73 m2 with normal urinary findings. Multivariate logistic regression analysis found age and treatment with angiotensin-converting enzyme inhibitors to be associated with reduced eGFR, MAU and proteinuria. In addition, smoking was associated with eGFR, but a family history for kidney disease and belonging to the group without hypertension were associated with MAU. Conclusion: The high prevalence of markers for CKD in symptomless elderly without hypertension confirmed that the elderly, as a high-risk population, should be screened based on increased age alone.

Cholesterol: Factors Determining Blood Cholesterol Levels

Dominant factors that determine cholesterol balance are those responsible for cholesterol absorption, synthesis, and clearance. Age and sex differences in cholesterol metabolism exist. There are large evidences of strong connections between common variants in the genes involved in cholesterol metabolism through various enzyme activities. Influences of modern Western diet, low physical fitness, and relief from chronic stress to various blood cholesterol levels and their relationship and benefits of the intake of n −3 PUFA, soya, fruit, vegetables, and whole-grain products were evaluated. Exposure to environmental contaminants, even at low levels, may influence cholesterol metabolism.

Improvement of Heart Rate Variability with Benfothiamine and Alpha-Lipoic Acid in Type 2 Diabetic Patients - Pilot Study

According to hypothesis that the lower level of bioactive thiamine, vitamin B1, is partially responsible for microvascular complications in type 2 diabetes patients (T2DM), we investigated whether the supplementation with benfothiamine and alpha-lipoic acid (ALA) could improve cardiacautonomic neuropathy (CAN) in those patients. Heart rate variability (HRV) was used as a tool for the assessment of equilibrium in the activity of the autonomic nervous system (ANS) in the control of heart rate in T2DM patients, without serious co-morbidity. Blood samples for glucose, HbA1c, triglycerides, cholesterol, and HDL-C were obtained before and at the end of treatment. High-frequency ln (HFln) , was significantly lower (p< 0.01) and low- frequency/ high frequency ln (LF/HFln)was significantly higher (p<0.01) in T2DM. After 12 weeks of supplementation, very low-frequency ln (VLFln), HFln and LF/HFln indices were changed significantly (p=0.03; p=0.01; p=0.04, respectively), and we concluded that benfothiamine associated with ALA could participate in repairing cardiac autonomic dysfunction in T2DM.