The effects of L-cysteine and N-acetyl-L-cysteine on homocysteine metabolism and haemostatic markers, and on cardiac and aortic histology in subchronically methionine-treated Wistar male rats.

Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways; methionine-rich diets were used to induce hyperhomocysteinemia, and cardiovascular pathology was often observed. Other sulfur amino acids interfere with this metabolism, i.e., L-cysteine (Cys) and N-aceyl-L-cysteine (NAC), and probably also affect cardiovascular system. Their effects are controversial due to their ability to act both as anti- or pro-oxidant. Thus, this study aimed to elucidate their influence on levels of homocysteine, folate and vitamin B12, levels of different haemostatic parameters (fibrinogen, D-dimer, vWF Ag, vWF Ac) in rat serum or plasma as well as their effects on cardiac and aortic tissue histology in subchronically methionine-treated rats. Wistar albino rats were divided into 4 experimental groups: (a) control group (0.9% sodium chloride 0.1-0.2 mL/day) (n = 10) (K); (b) DL-methionine (0.8 mmol/kg/bw/day) (n = 10) (M); (c) DL-methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (n = 8) (C); (d) DL-methionine (0.8 mmol/ kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (n = 8) (N). All substances were applied i.p., treatment duration 3 weeks. Lower levels of vitamin B12 in all the groups were found. Folate was reduced only in N group. Decreased fibrinogen was noted in C and N groups and increased D-dimer only in C. VWF activity was reduced in M and C groups. Deleterious effects in heart were observed, especially after Cys and NAC application. Aortic tissue remained unchanged. In conclusion, it could be said that sulfur amino acids have the significant impact on cardiovascular system in subchronically methionine-treated rats. This study points out the relevance of their complex interactions and deleterious effects mediated by either direct influence or procoagulant properties.

Vitamin D Is Inversely Related to Obesity: Cross-Sectional Study in a Small Cohort of Serbian Adults.

Objective: Vitamin D (vitD) mediates numerous health conditions other than bone health and mineralization. Its role in cardiometabolic condition is still inconclusive. Methods: We conducted a cross-sectional study in 87 apparently healthy Serbian adults. We assessed their dietary intake, anthropometric and biochemical parameters, blood pressure, and vitD status (as serum 25-hydroxyvitamin D, 25(OH)D). Unexpectedly, the status was significantly higher in January than in July. Therefore, we pooled the data from two time points, to enhance the statistical power for carrying out association analyses. We employed linear regression models to evaluate the associations between vitD status and the obesity biomarkers of serum lipids and blood pressure. Results: Mean vitD intake of 3.85 ± 4.71 µg in the cohort was below recommended. Of the subjects in the pooled cohort, 60.58% were vitD deficient (with serum 25(OH)D below 50 nmol/L), with the majority of them being women who were overweight. VitD status tended to be inversely related to percent body fat and waist/height ratio in the crude regression model. After age and gender adjustment, the status was significantly related to waist circumference, waist/height ratio, and waist/hip ratio (ß = -0.116, 95% confidence interval [CI]: -0.206, -0.025, ß = -0.001, 95% CI: -0.001, 0.000, and ß = -0.001, 95% CI: -0.001, 0.000, respectively). These associations remained only within women. Fully adjusted models supported the notion of vitD being independently associated with central adiposity, regardless of age, gender, and total obesity. Conclusions: In apparently healthy adults with low vitD intake, vitD status was inversely associated with obesity parameters, pronouncedly in women. Our data support the need for development and implementation of public health policies on increasing vitD intake also as part of obesity management strategies.

Vitamin B complex mitigates cardiac dysfunction in high-methionine diet-induced hyperhomocysteinemia.

This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.

The Clinical Importance of Cystatin C and Hepatic Artery Resistive Index in Liver Cirrhosis.

BACKGROUND: Data suggest cystatin C (CysC) levels and hepatic artery resistive index (HARI) correspond to the progression of chronic liver disease. We aimed to evaluate the clinical significance of these parameters in assessment of fibrosis in patients with liver cirrhosis. METHODS: The cross-sectional study included 63 patients with liver cirrhosis. A control group consisted of 30 age- and gender-matched healthy persons. RESULTS: We confirmed significantly higher values of CysC in patients with cirrhosis compared to control group (p = 0.036). Average value of HARI in the examined group was increased (0.72 ± 0.06) and there was the statistically significant difference compared to controls (0.66 ± 0.03) (p < 0.001). We found statistically significant correlation between HARI and CysC in the study group. Analyzing the possibility of distinguishing healthy subjects from patients with fibrosis, we have found that the area under the curve is far greater in the HARI index than CysC. Comparison of CysC among Child⁻Pugh stages and correlation with a model for end-stage liver disease (MELD) score showed statistically significant results. CONCLUSION: We confirmed HARI is a more accurate parameter than CysC in discriminating healthy subjects from patients with fibrosis, while CysC could be a better indicator of the stage of liver cirrhosis.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress.

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light-dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

Hyperhomocysteinemia induced by methionine dietary nutritional overload modulates acetylcholinesterase activity in the rat brain.

Methionine is the only endogenous precursor of homocysteine, sulfur-containing amino acid and well known as risk factor for various brain disorders. Acetylcholinesterase is a serine protease that rapidly hydrolyzes neurotransmitter acetylcholine. It is widely distributed in different brain regions. The aim of this study was to elucidate the effects of methionine nutritional overload on acetylcholinesterase activity in the rat brain. Males of Wistar rats were randomly divided into control and experimental group, fed from 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing to standard, 7.7 g/kg), respectively. On the 61st postnatal day, total homocysteine concentration was determined and showed that animals fed with methionine-enriched diet had significantly higher serum total homocysteine concentrations comparing to control rats (p < 0.01). Acetylcholinesterase activity has been determined spectrophotometrically in homogenates of the cerebral cortex, hippocampus, thalamus, and nc. caudatus. Acetylcholinesterase activity showed tendency to decrease in all examined brain structures in experimental comparing to control rats, while statistical significance of this reduction was achieved in the cerebral cortex (p < 0.05). Brain slices were stained with haematoxylin and eosin (H&E) and observed under light microscopy. Histological analysis of H&E-stained brain slices showed that there were no changes in the brain tissue of rats which were on methionine-enriched diet compared to control rats. Results of this study showed selective vulnerability of different brain regions on reduction of acetylcholinesterase activity induced by methionine-enriched diet and consecutive hyperhomocysteinemia.

Effect of Long-term Topiramate Therapy on Serum Bicarbonate and Potassium Levels in Adult Epileptic Patients.

BACKGROUND: Topiramate (TPM) is a sulfamate-substituted monosaccharide that is structurally different from other antiepileptic drugs. TPM inhibits carbonic anhydrase activity, which is associated with loss of bicarbonate from the kidney and consequently metabolic acidosis or electrolyte imbalance. OBJECTIVE: The objectives of the study were to investigate the influence of TPM therapy on bicarbonate and potassium levels in adult epileptic patients. METHODS: Data were collected from 59 adult patients on monotherapy or co-therapy of TPM and other antiepileptic drugs. Serum bicarbonate and potassium levels were available from all patients. Steady-state TPM trough concentrations were determined in blood samples by high-performance liquid chromatography. Data analysis was performed by SPSS software (version 17, Chicago, IL). RESULTS: Patients were divided into group A (duration of therapy shorter than or equal to 5 years) and group B (duration of therapy longer than 5 years). Significant difference (P < 0.05) in serum bicarbonate levels was observed between these 2 groups. Bicarbonate levels were linearly related to the TPM therapy duration. No correlation was found between the TPM dose or patient age and bicarbonate or potassium levels, as well as between therapy duration and potassium level. Linear regression analysis showed no significant association among 54 available TPM trough concentrations and bicarbonate or potassium levels. CONCLUSIONS: Results highlight the frequent occurrence of lower bicarbonate level associated with prolonged TPM therapy. Monitoring bicarbonate levels in patients on long-term TPM therapy might be useful.

Vascular endothelial growth factor in peritoneal dialysis patients.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a glycoprotein which exerts mitogenic effects on endo thelial cells, enhances neoangiogenesis and microvascular permeability, influences leukocyte kinetics when upreg ulated by hypoxia and high-glucose concentration in experimental conditions and in human pathology. Peritoneal synthesis of VEGF has been demonstrated in patients on peritoneal dialysis (PD) treated with glucose-based dialy sate solutions. METHODS: The aim of the study was to determine the serum and peritoneal effluent VEGF concentrations in patients on chronic PD and to assess the relationship between age, gender, comorbidities, dialysis modality and vintage, therapy with erythropoiesis stimulating agents (ESA), angiotensin-converting enzyme inhibitors (ACEi) and statins and VEGF concentrations. Data on the use of ACEi, ESA, and statins were collected from patients' medical histories. VEGF was measured in serum and peritoneal effluent using the quantitative sandwich enzyme immunoassay (ELISA) kits (Quantikine® Human VEGF, R&D Systems, USA & Canada). Complete blood count and standard biochemical analyses (serum glucose, urea, creatinine, total protein, albumin, cholesterol, triglycerides, sodium, potassium, chloride, iron, total iron-binding capacity, ferritin, fibrinogen, C-reactive protein, and intact parathyroid hormone) were performed in fasting venous blood samples. Dialysis and residual components of Kt/V and normalized weekly creatinine clearance were calculated based on 24-hour urine and effluent collections. Peritoneal transport type was determined using the peritoneal equilibration test. RESULTS: Samples from 63 PD patients (39 males and 24 females, average age 61.97 ± 11.01 years) were analyzed. The average serum and effluent VEGF concentrations (231.84 ± 173.91 pg/mL and 38.39 ± 49.38 pg/mL, respectively) correlated significantly (p = 0.002). No significant difference was found in serum and effluent VEGF concentrations in relation to demographic characteristics, comorbidities, dialysis modality, therapy with ESA, ACEi, and statins. Patients treated with PD longer than 5 years had significantly higher serum VEGF levels (p < 0.05). Correlation analysis showed a statistically significant relationship between statin therapy and lower effluent VEGF concentration (p = 0.030). Serum VEGF concentration significantly correlated with fibrinogen serum concentration (p = 0.034) and glycemia (p = 0.004). Effluent VEGF concentration significantly correlated with cholesterolemia (p = 0.004). CONCLUSIONS: Serum VEGF concentrations were significantly higher in long term PD patients, and peritoneal effluent VEGF concentrations were significantly lower in patients receiving statins, suggesting a protective effect of those drugs on peritoneal membrane.

The importance of the blood levels of homocysteine, folate and vitamin B12 in patients with primary malignant brain tumors.

PURPOSE: Glioblastoma multiforme and anaplastic astrocytoma represent one of the most frequently occurring primary brain tumors with dismal survival rates. The aim of our study was to investigate whether values of homocysteine, folates and vitamin B12 can be prognostic markers in relapse diagnosis, treatment and monitoring of adult patients with malignant brain tumors. METHODS: Twenty-seven patients from the Neurosurgical Clinic, Clinical Center of Serbia with diagnosed malignant brain tumors (anaplastic astrocytoma GR III and glioblastoma multiforme GR IV), were included in the study. The patients were divided in two groups according to the progression of disease, 15 with and 12 without progression. RESULTS: Mean values of homocysteine were significantly higher in the group with progression compared to the group without malignant tumor progression, at the baseline point and after six months. Mean values of folate were similar across groups in all measurements, except in the 3rd month after surgery. Results regarding vitamin B12 were similar to folate, without any significance in group comparisons in the examined time points, as well as in vitamin B12 values change. CONCLUSIONS: Our results pointed out that total homocysteine in blood circulation appears to be a tumor marker for monitoring primary malignant brain tumor patients before and after surgery. The association of hyperhomocysteinemia with folate deficiency, also provides strong support for viewing hyperhomocysteinemia as a predictive marker for carcinogenesis. It is hoped that future research will continue to explore the clinical relevance of homocysteine as a tumor marker and a risk factor for astrocytoma and glioblastoma.

Cerebrospinal fluid and serum uric acid levels in patients with multiple sclerosis.

BACKGROUND: Peroxynitrite was hypothesized to be involved in the pathogenesis of multiple sclerosis (MS) through its various neurotoxic effects. Uric acid (UA) was shown to be a strong peroxynitrite scavenger. METHODS: We analyzed cerebrospinal fluid (CSF) and serum UA concentrations in 30 MS patients and 20 controls with non-inflammatory neurological diseases (NIND) and correlated these findings with demographic and clinical characteristics of MS patients. Disease activity was assessed by brain magnetic resonance imaging (MRI) and the CSF/serum albumin quotient as an indicator of the state of blood-brain-barrier (BBB). RESULTS: Serum UA concentrations were found to be significantly lower in MS patients compared with controls (p=0.019). CSF UA concentrations were lower in MS patients as compared to controls, as well as in patients with active MS (clinical and/or MRI activity) in comparison to patients with inactive MS or controls, but these differences were not statistically significant. Significant correlation was found between CSF and serum UA concentrations (p=0.016) in MS patients, but not in controls; and between CSF UA concentrations and the CSF/serum albumin quotient in MS patients (p=0.043), but not in controls. CONCLUSIONS: Our results support the significance of UA in the pathogenesis of MS. Decreased serum UA concentrations in MS patients might be due to both intrinsically reduced antioxidant capacity and increased UA consumption in MS. CSF UA concentrations may not be a reliable marker of disease activity in MS since its concentration is dependent on leakage of UA molecules from serum through the damaged BBB and the balance between consumption/production within the central nervous system (CNS).

Calcitonin gene-related peptide levels in saliva of patients with burning mouth syndrome.

Burning mouth syndrome (BMS) is an intraoral burning sensation for which no medical or dental cause can be found. Recent studies suggest that primary neuropathic dysfunction might be involved in the pathogenesis of BMS. Calcitonin gene-related peptide (CGRP) plays an important role in the development of pain and serves as a biological marker of trigeminovascular activation. The aim of this study was to determine the levels of CGRP in the saliva of BMS patients and estimate the trigeminovascular activation in BMS. CGRP levels were measured, by RIA method in 78 BMS patients and 16 healthy subjects. The levels of CGRP were non-significantly decreased in BMS patients in comparison to healthy subjects. These results suggest that trigeminal nerve degeneration may be the underlying cause of BMS.

Risk factors for aortic valve calcification in patients on regular hemodialysis.

INTRODUCTION: Aortic valve calcification (AVC) accelerates development of aortic valve stenosis and cardiovascular complications. Hyperphosphatemia is one of the key risk factors for aortic valve calcification. AIM: The aim of this study was to evaluate the prevalence of AVC in patients on regular hemodialysis and to assess the impact of different factors on its appearance. METHOD: The study investigated a total of 115 patients treated in the Hemodialysis Department of the Urology and Nephrology Clinic at the Kragujevac Clinical Center in Serbia. The variables investigated were: serum albumin, C-reactive protein (CRP), homocysteine, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), Apolipoprotein A-I (Apo A-I), Apolipoprotein B (Apo B) and lipoprotein (a), calcium, phosphate and parathormone, and calcium-phosphorus product (Ca x P). Patients were evaluated by echocardiography for AVC. Statistical analysis included univariate and multivariate logistic regression analysis. RESULTS: Univariate regression analysis showed that serum phosphate levels and Ca x P are the most important risk factors for AVC (p<0.001). Multivariate logistic regression analysis revealed that hyperphosphatemia is an independent risk factor for AVC (p<0.001). CONCLUSION: Hyperphosphatemia is an independent risk factor for aortic valve calcification.

Cardiac troponins and left ventricular hypertrophy in hemodialysis patients.

BACKGROUND: Cardiovascular diseases are the leading cause of death in hemodialysis patients. Left ventricular (LV) hypertrophy is an important predictor of cardiovascular morbidity and mortality in these patients. Cardiac troponins (cTnT and cTnI) are indicators of myocardial cell damage. AIM: The aim of this study was to determine prevalence of LV hypertrophy, prevalence of elevated serum cTnT and cTnI in hemodialysis patients, and identify the correlation between cardiac troponins and LV hypertrophy. METHODS: The study included 115 hemodialysis patients (71 men and 44 women), mean age 53.30 +/- 12.17 years, mean time on dialysis 4.51 +/- 4.01 years and average Kt/Vsp 1.17 +/- 0.23. Mean serum cTnT was 0.14 +/- 0.23 ng/ml, mean serum troponin I 0.20 +/- 0.48 ng/ml. Mean LV posterior wall thickness in diastole (LVPWd) was 11.44 +/- 2.09 mm, mean LV interventricular septal wall thickness in diastole (IVSd) 11.21 +/- 2.12 mm, mean LV end diastolic volume index (iLVEDV) 100.80 +/- 34.62 mL/m2 and mean LV mass index (LVMi) 143.85 +/- 41.21 g/m2. RESULTS: We found statistically significant positive correlations (p <0.05) between serum troponin T concentration, IVSd, LVPWd and iLVEDV. A highly significant positive correlation (p < 0.01) was found between serum troponin T and LVMi. One-year follow-up showed that patients with cardiac troponin T > 0.10 ng/ml and cardiac troponin I > 0.15 ng/ml had significantly lower (p < 0.01) survival rate than patients with troponin T < or = 0.10 ng/ml and troponin I < or = 0.15 ng/ml. CONCLUSION: A significant positive correlation exists between serum troponin T concentration and echocardiographic indicators of LV hypertrophy in hemodialysis patients. Patients with higher serum levels of cardiac troponins have lower survival rates during one year follow up.

Troponin T levels in detection of perioperative myocardial infarction after coronary artery bypass surgery.

OBJECTIVES: The present study was designed to evaluate the clinical relevance of serum cardiac troponinT (cTnT) assay in detection of perioperative myocardial infarction (PMI) after coronary artery bypass grafting (CABG). MATERIALS AND METHODS: The clinical utility of cTnT was compared to that of total CK, CKMB mass, CKMB activity and myoglobin. Serial venous blood samples were obtained before surgery and 4, 8, 16, 24, 48 and 72 hours after aortic unclamping (AU) in 42 patients who underwent CABG. We had 6 PMI patients, 24 patients with minor myocardial damage (MMD) and 12 without ischemic myocardial changes (no IMC). RESULTS: In discriminating no IMC from PMI the diagnostic sensitivity, specificity and the predictive values of cTnT were superior to that of CKMB mass, CKMB activity, myoglobin and total CK during 72 hours after AU. In discriminating MMD from PMI the diagnostic performance for CKMB mass and CKMB activity was superior to that of cTnT during the first 24 hours. After 24 hours the diagnostic performance for cTnT was improved but began to decline for CKMB isoenzymes. The discriminatory power of myoglobin measurements was lower than that of cTnT and CKMB mass. CONCLUSION: Our results indicate that troponin T is an accurate marker for the detection and monitoring of perioperative myocardial damage, especially 24 hours after AU.

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis.

AIM: To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis. METHODS: We conducted a study of 63 patients with liver cirrhosis. A control group comprised of 30 age and gender-matched healthy persons. Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made. Estimated glomerular filtration rate from serum creatinine (GFRCr) and cystatin C (GFRCys) was calculated. RESULTS: We confirmed significant differences in values of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh (P = 0.01), and a significant correlation with model of end stage liver disease (MELD) score (r s = 0.527, P < 0.001). More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr (P < 0.001). Significantly higher renal resistive index was noted in Child-Pugh C than in A (P < 0.001) and B stage (P = 0.001). Also, a significant correlation between renal resistive index and MELD score was observed (r s = 0.607, P < 0.001). Renal resistive index correlated significantly with cystatin C (r s = 0.283, P = 0.028) and showed a negative correlation with GFRCys (r s = -0.31, P = 0.016). CONCLUSION: Cystatin C may be a more reliable marker for assessment of liver insufficiency. Additionally, cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.

Plasma homocysteine levels in patients with liver cirrhosis.

BACKGROUND/AIM: Homocysteine (2-amino-4-mercaptobutyric acid) is an amino acid that may be found in small quantities in all cells, and is quantitatively the major methionine metabolite. The most prevalent form is protein-bound homocysteine (about 80%), mostly to albumins. If catabolism of homocysteine is impaired either due to enzyme defect or deficiency of required intracellular cofactors, homocysteine accumulates in cells and reaches the circulation. The aim of our study was to determine homocysteine values and factors affecting homocysteine metabolism in patients with liver cirrhosis. METHODS: The prospective study included 35 patients with liver cirrhosis and 30 age and sex matched healthy controls. All the examinations were based on: medical history, physical examination, laboratory tests including serum homocysteine levels and liver biopsy. The degree of liver failure was assessed according to the Child-Pugh classification. RESULTS: The mean plasma homocysteine levels were much higher in the patients with liver cirrhosis than in the healthy controls (t-test, p < 0.001). There was no significant difference between the plasma homocysteine concentration and etiology of liver cirrhosis (ANOVA, p > 0.05). Correlation analysis showed a positive correlation between the homocysteine and creatinine concentrations and between the serum albumin and homocysteine values, (Pearson's correlation, p < 0.01, and p < 0.05 respectively). CONCLUSION: In liver cirrhosis, the genesis of homocysteinemia is multifactorial, influenced significantly by impaired catabolic liver function, renal failure and hypoalbuminemia.

Damage of tubule cells in diabetic nephropathy type 2: urinary N-acetyl-beta-D-glucosaminidasis and gamma-glutamil-transferasis.

BACKGROUND/AIM: A damage of tubular epithelial cells is followed by the release of cell enzymes and production of proinflammatory compounds, which lead to the tubulointerstitial damage. The aim of this study was to examine the function of renal tubules in the patients with diabetes mellitus type 2 (DM type 2) and the various proteinuria degrees, to establish the damage of the proximal tubule cells caused by DM type 2 by determining urinary N-acetyl-beta-D-glucosaminidasis (beta-NAG) and gamma-glutamil-transferasis (gamma-GT) activity in urine, as well as to compare the obtained results in the examined groups of patients with the values in the healthy examinees. METHODS: A complete examination of renal function and selective enzymuria was performed in 37 patients with DM type 2, and 14 healthy examinees as the controls. The patients were divided in three groups according to the degree of proteinuria. The first group consisted of the patients with diabetes without microalbuminuria; the second one consisted of the patients with proteinuria of < 300 mg/24 h, and microalbuminuria of > 20 mg/24 h, while the third one included the patients with proteinuria of > 300 mg/24 h. RESULTS: In the patients with DM type 2 and the preserved global renal function, fractional excretion of sodium, potassium and phosphates, as well as renal threshold of phosphates concentration, were not sensitive parameters for discovering the damage of the renal tubule function. The determination of beta-NAG activity proved to be the most sensitive parameter for early discovering of tubule cells damages. The difference among the examined groups was statistically highly significant. CONCLUSION: The increased presence of beta-NAG in the urine of DM type 2 patients, pointed out an early tubular disorder and damage of cells, while gamma-GT was a less sensitive indicator of this damage.

[Left ventricular hypertrophy in patients on hemodialysis: importance of anemia].

INTRODUCTION: Cardiovascular diseases are the most frequent cause of mortality in hemodialysis patients. Left ventricular hypertrophy is the main risk factor for development of cardiovascular morbidity and mortality in patients on hemodialysis. Anemia is the only main risk factor for the development of left ventricular hypertrophy in patients on hemodialysis. The aim of this study was to examine the impact of anemia in the development of left ventricular hypertrophy, and correlation between anemia and echocardiographic parameters for the assessment of left ventricular hypertrophy. MATERIAL AND METHODS: The research was conducted on 115 patients (M:F 71:44) regularly treated by hemodialysis, average age 53.30+/-1.2.17 years, average length of dialysis 4.51+/-4.01 years and average Kt/Vsp index 1.17+/-0.23. Depending on the level of hemoglobin, the patients were divided into three groups. The basic parameters investigated were the following: hemoglobin, hematocrite, serum concentrations of albumin, CRP, total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride serum concentrations, parathormon, diastolic thickness of interventricular septu-mIVSd, diastolic thickness of left ventricular posterior wall, relative wall thickness-RWT, left ventricular mass index-LVMi, index of left ventricular end-diastolic volume-iLVEDV. The results were statistically analyzed using ANOVA, Kruskal-Wallis test, Student t-test, Mann-Whitney U test, Univariate logistic regression analysis test, and Multivariate logistic regression analysis test. RESULTS: The patients with hemoglobin <80 g/l had a very significantly higher (p<0.01), while the patients with hemoglobin 80-100 g/l had a significantly higher (p<0.05) left ventricular mass index than patients with hemoglobin >100 g/l. The univariate logistic regression analysis has showed that lower HDL cholesterol, anemia, higher systolic arterial pressure and higher mean arterial pressure cumulatively lead to the development of left ventricular hypertrophy. Multivariate logistic regression analysis established anemia as an independent risk factor for the development of left ventricular hypertrophy. CONCLUSION: Anemia is an independent risk factor for the development left ventricular hypertrophy. Identification of patients with increased risk for development of left ventricular hypertrophy and application of appropriate therapy to attain target values of risk factors, result in the regression of left ventricular hypertrophy, reduced cardiovascular morbidity and mortality rates and improved quality of life in patients treated with regular hemodialyses.

[Tubular kidney function in patients with type 2 diabetes mellitus, microalbuminuria and proteinuria].

INTRODUCTION: Diabetes mellitus (DM) and hypertension are the most frequent causes of kidney function damage. Many different tests are developed to detect reversible functional kidney changes (detection of microalbuminuria and selective urinary enzymes). OBJECTIVE: The aim of our study was to examine tubular kidney function in type 2 DM patients with different proteinuria levels, and to compare these results with healthy people. METHOD: The patients with type 2 DM and creatinine clearance >80 ml/min were included in the study. According to the levels of proteinuria, the patients were classified in three groups: group I--patients with proteinuria <300 mg/24 h, and no microalbuminuria; group II--the patients with proteinuria <300 mg/24 h and microalbuminuria >20 mg/24 h; and group III--the patients with proteinuria >300 mg/24 h. The control group consisted of healthy subjects. RESULTS: The study revealed that in type 2 DM patients and normal global kidney function, fractional excretions of sodium, potassium, and phosphates as well as renal phosphate concentrations were not adequately sensitive markers to detect damage in tubular kidney function in DM. There were some changes of urate fractional excretion in these patients: this value was significantly lower in patients with microalbuminuria compared with those with proteinuria >300 mg/24 h, as well as in the control group (p < 0.05). Hormone dependent tubular kidney activity, urinary osmolarity, and urea fractional excretion in all patients were within normal ranges. CONCLUSION: It is evident that routine laboratory analyses are not sensitive markers to detect early changes of kidney function in type 2 DM.