Determination of systemic inflammatory biomarkers in multiple sclerosis.

Background: Multiple sclerosis (MS) is one of the most common demyelinating diseases of the central nervous system. We aimed to investigate serum and cerebrospinal fluid levels of different laboratory inflammatory biomarkers in patients with MS. Methods: A total of 120 subjects participated in the study, 60 of whom were diagnosed with MS, 30 with the final diagnosis of non-inflammatory diseases of the central nervous system (CNS), and 30 healthy subjects representing the control group. Regarding the progression of radiological findings after 2 years from the initial diagnosis, the MS group was divided into stationary radiological findings (n=30) and radiologically proven disease progression (n=30). In all patients, we analyzed levels of laboratory inflammatory biomarkers: C reactive protein (CRP), Neutrophil-to-lymphocyte ratio (NLR), Growth differentiation factor 15 (GDF15) in serum samples, and neurofilaments (NFs) in cerebrospinal fluid (CSF). NFs and GDF15 were analyzed initially, while CRP and NLR values were analyzed initially and after two years. Results: We found statistically lower GDF15 values and initial CRP values in the MS group regarding the group with non-inflammatory diseases of the CNS (p<0.0001). On the other side, we determined a significant elevation of laboratory markers CRP and NLR, initially and after a two-year period, in the MS subgroup with the progression of magnetic resonance imaging (MRI) findings (p<0.0001 and p=0.050, respectively). Also, we found a positive correlation between CRP and NFs (r=0.243, p=0.04), as well as a positive correlation between CRP and GDF15 in patients with MS (r=0.769, p<0.0001). Conclusions: We found a significant elevation of laboratory markers of systemic inflammation, CRP, and NLR in MS patients who developed disease progression based on MRI findings. There is a need for further studies to validate current parameters to be considered as useful markers of MS activity and disability.

Is There a Role for Growth and Differentiation Factor-15 in B-Cell Lymphoproliferative Neoplasms?

Growth and differentiation factor-15 (GDF-15) correlates with worse outcome of many tumours and any cause mortality. Data about its role in lymphoproliferative neoplasms (LPN) are scarce. Our research aimed to reveal the correlation between GDF-15 and standard laboratory parameters of LPN activity, and to get insight into the possible value of this cytokine assessment in lymphoma patients. Prospective research included 40 patients treated for aggressive or indolent LPN, and 31 with indolent LPN on "watch and wait" regimen. Analyses were performed before and after treatment in treated patients and on two separate occasions in the "watch and wait" group. ELISA technique with R&D assays according to the manufacturer manual, from stored sera at - 70 °C was used for GDF-15 level measurement. Statistical analyses were performed by IBM SPSS Statistics 22 using descriptive and inferential statistics. As appropriate, differences between groups were assessed by two tailed t-test, Mann-Whitney or x2 test. Spearman Rank Order Correlation was done to correlate GDF-15 with standard laboratory markers of disease activity. All tests are two-tailed with significance level p < 0. 05. GDF-15 (p = 0.028) and fibrinogen (p = 0.001) concentrations increased after treatment in indolent lymphoma patients while ß2 microglobulin decreased (p < 0.001). GDF-15 positively correlated with ß2microglobulin before (p < 0.001) and after (p = 0.031) therapy. There were no differences in any of the aforementioned parameters in the "watch and wait" group during observation. A positive correlation between GDF-15 and ß2 microglobulin in patients with indolent LPN who need treatment suggests potential value in risk assessment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01695-6.

PERCUTANEOUS DILATATIONAL TRACHEOSTOMY IN COVID-19 PATIENTS IN THE COVID HOSPITAL INTENSIVE CARE UNIT: THE UNIVERSITY CLINICAL CENTER OF VOJVODINA EXPERIENCE.

Patients with acute respiratory distress syndrome due to COVID-19 require intensive care unit (ICU) admission with consecutive endotracheal intubation and invasive mechanical ventilation. In patients with long-term mechanical ventilation, percutaneous dilatational tracheostomy (PDT) may be considered. This retrospective analysis includes clinical data on patients treated at the ICUs of the COVID Hospital of the Clinical Center of Vojvodina in the period from September 3, 2021 to May 1, 2022, and underwent PDT. Patients were predominantly male (n=48; 65.8%). Weaning from mechanical ventilation was achieved in 31 (42.5%) and decannulation in 25 (34.2%) patients. The mean time from polymerase chain reaction SARS CoV-2 positivity until PDT was 15.59±6.85 days. The mean time of endotracheal intubation before the PDT procedure was 7.37±4.89 days. The mean weaning time from mechanical ventilation was 10.45±7.92 days. Twenty-five (34.2%) patients were decannulated at the mean time of 19.60±11.81 days. The complications were tracheostomy related bleeding (2 patients), pneumothorax (4 patients), subcutaneous emphysema (1 patient) and cricoid cartilage injury (1 patient). PDT is a simple, safe, and effective procedure performed in COVID-19 patients in the ICU.

The Importance of Correlation between Aldosterone and Parathyroid Hormone in Patients with Primary Hyperparathyroidism.

In primary hyperparathyroidism, an increased risk of developing the cardiovascular disease may exist due to increased activity of the renin-angiotensin-aldosterone system. The aim of this study was to evaluate the relationship between parathyroid hormone and aldosterone in patients with primary hyperparathyroidism. The study included 48 patients with primary hyperparathyroidism and 30 healthy subjects who matched age and gender to the study group. This study was conducted at the Center for Laboratory medicine, Clinical center of Vojvodina, Novi Sad, Serbia. In addition to clinical data and laboratory determination of the concentration of total and ionized calcium, phosphorus, measurements of parathyroid hormone, vitamin D, direct renin, and aldosterone were performed by the method of chemiluminescent technology. Compared to the controls, the study group had statistically significantly higher values of aldosterone (p=0.028), total calcium (p=0.01), ionized calcium (p=0.003) and parathyroid hormone (P ≤ 0.001) Serum aldosterone and parathyroid hormone levels were correlated positively in patients with primary hyperparathyroidism (r=0.509, p < 0.05). A statistically significant positive correlation between renin and parathyroid hormone (r=0.688, p < 0.05) and renin and calcium (r=0.673, p < 0.05) was determined in hyperparathyroid patients. In multivariate regression analysis, the strongest predictive variable of aldosterone secretion was parathyroid hormone (p=0.011). An independent relationship between parathyroid hormone and aldosterone in patients with primary hyperparathyroidism and the correlation between renin and parathyroid hormone as well as with calcium indicate not only the direct but also the indirect associations between parathyroid hormone and aldosterone in primary hyperparathyroidism. These findings may represent another possible model of renin-angiotensin-aldosterone-induced organ damage.

Validation of the STANDARD Q COVID-19 antigen test in Vojvodina, Serbia.

BACKGROUND: Since COVID-19 pandemic is a global crisis, tests with high sensitivity and specificity are crucial for the identification and management of COVID-19 patients. There is an urgent need for low-cost rapid antigen COVID-19 test with a good diagnostic performance. Although various antigen rapid detection tests are widely available, strong evidence of their usefulness in clinical practice are still limited. Therefore, our aim was to evaluate clinical performance of STANDARD Q COVID-19 Ag Test (SD Biosensor, Gyeonggi-do, South Korea). METHODS: The performance of the STANDARD Q COVID-19 Ag Test for the detection of SARS-CoV-2 antigen was evaluated in comparison to RT-qPCR results in 120 symptomatic patients (median age 49, IQR 36-70) who presented to health care facility in Novi Sad, Vojvodina, Serbia. RESULTS: Twenty five out of 120 samples have been tested positive using STANDARD Q COVID-19 Ag Test, and all of them were also positive on RT-qPCR. Overall, the STANDARD Q COVID-19 Ag Test showed sensitivity of 58.1% (95% CI 42.1-73.0) but it was higher in the early days of disease, when the highest viral loads were detected. During the first five days after the symptom onset, the sensitivity ranged from 66.7% to 100% and the pooled accuracy and Kappa values were high (0.92 and 0.852). CONCLUSIONS: A strong agreement between performance of STANDARD Q COVID-19 Ag Test and RT-qPCR was observed during the first five days of illness, suggesting that this rapid antigenic test can be very useful for COVID-19 diagnosis in the early phase of disease.

Antinociceptive activity of Thyme (Thymus vulgaris L. ) and interactions with neurotropics and analgesics

The plant world represents an important source of potential therapeutic agents, but concomitant administration of herbal and conventional medications may result in interactions with subsequent beneficial or adverse effects. This study was designed to examine the analgesic effect of thyme tincture and thyme syrup, two commonly used thyme formulations, and their interactions with codeine, paracetamol, pentobarbital and diazepam in mice. The identification and quantification of thymol and carvacrol were carried out by GC/MS and GC/FID. The analgesic activity was studied using a hot plate method. Effects of thyme syrup on diazepam-induced motor coordination impairment in rotarod test and on pentobarbital-induced sleeping time were also determined. Thymol (175.3 µg/mL and 9.73 µg/mL) and carvacrol (10.54 µg/mL and 0.55 µg/mL) concentrations were measured in tincture and syrup, respectively. Thyme syrup and tincture exhibited effective analgesic activity in the hot plate pain model. Pretreatment with thyme formulations reduced analgesic activity of codeine, and potentiated the analgesic activity of paracetamol. Co-administration of thyme formulations has led to potentiation of diazepam and pentobarbital depressive central nervous system effects. Thyme formulations interacted with tested conventional drugs, probably through interference with their metabolic pathways and succeeding altered concentrations and pharmacological effects.

Hypomagnesemia in adults of northern Serbia: prevalence, nutritional risk factors, and associated comorbidities.

INTRODUCTION: Magnesium (Mg) deficiency is associated with numerous non-communicable diseases. The aim of the study was to estimate the prevalence of hypomagnesemia in the general adult population of Northern Serbia (NS), and to determine the level of Mg in drinking water. METHODS: This is a cross-sectional study with 5,122 adults from the general population. Serum level of Mg was determined by spectrophotometry, while the level of Mg in the drinking water was done by atomic absorption spectrophotometry. Standard laboratory methods were used to determine individual's blood lipid status and complete blood count. RESULTS: The prevalence of hypomagnesemia (Mg < 0.75 mmol/L) in the general population was 2.7%, while the prevalence of the subjects with high risk for the Mg deficiency (Mg 0.75-0.85 mmol/L) was 20.1%. The public water supply showed variable values between 17.3-35.3 mg/L. Age, systolic blood pressure, duration of diabetes mellitus, and glycemia increase with the decrease of Mg level. In addition, increased level of Mg was associated with higher red blood cell count and hemoglobin levels. CONCLUSIONS: The prevalence of hypomagnesemia in Northern Serbia is low (2.7%) and level of Mg in drinking water is not satisfactory. Serum level of Mg in the range 0.75-0.85 mmol/L is present in about 1/5 of the population. Glycemia, advanced age, gender, and smoking have a predictive role in hypomagnesemia occurrence. There is a significant correlation between serum level of Mg and lifestyle and dietary habits.

Hepatoprotective and antioxidant potential of Pycnogenol® in acetaminophen-induced hepatotoxicity in rats.

Pycnogenol® (PYC) has already being used as a food supplement and herbal medicine due to its potent antioxidant properties. The aim of the present study was to examine the protective effect of PYC on acetaminophen-induced acute liver injury in rats. The effect of PYC on acetaminophen-induced hepatotoxicity in rats was examined by determining biochemical parameters, in vitro antioxidant activity, histological assessment, and oxidative status in liver homogenates. The best antioxidant properties were demonstrated in methanolic extracts. Seven-day pretreatment with PYC suppressed elevation of CYP2E1 protein expression induced by administration of toxic dose of acetaminophen. PYC at 50 mg/kg showed the ability to significantly decrease malondialdehyde (MDA) level compared with the group received acetaminophen. Xanthine oxidase (XOD) enzyme activity was significantly elevated in acetaminophen-treated group compared with control, whereas concomitant administration of PYC in a dose of 50 mg/kg significantly reduced activity of this enzyme. Significant decrease of glutathione (GSH) hepatic content in acetaminophen-intoxicated rats compared with the control rats was improved by concomitant administration of PYC at 50 mg/kg. Protective effect of PYC on acetaminophen-induced acute liver injury in rats has showed the best in vitro antioxidant potential expressed in methanolic extract and consequent histological assessment and oxidative status in liver homogenates.

Serum Concentration of Hepcidin as an Indicator of Iron Reserves in Children.

BACKGROUND: Anemia represents a significant cause of maternal and perinatal mortality, as well as child mortality. The aim of the research was to determine the serum concentration of hepcidin in children aged 6 months to 2 years and adolescents aged 11 to 19 years which suffer from iron deficiency anemia and compare it with the serum concentration of hepcidin in the control groups, as well as to determine its connection with the parameters of the iron metabolism. METHODS: The research included 173 examinees, 89 of them suffered from iron deficiency anemia and 84 did not suffer from iron deficiency anemia (the latter represented the control group). Blood samples were collected from all study participants. The samples were analyzed for complete blood count and parameters of iron metabolism. ELISA method was used for establishing serum hepcidin levels. RESULTS: The research showed that the concentration of hepcidin is statistically lower in children (4.4 ng/mL) and adolescents (4.1 ng/mL) who suffer from iron deficiency anemia in comparison with the control group (14 ng/mL, 10 ng/mL, respectively). The positive correlation between serum hepcidin level and iron in the serum, ferritin, the mean corpuscular volume and transferrin saturation was confirmed, but the negative one occurred in serum hepcidin level, transferrin and reticulocytes. CONCLUSIONS: The age of the examinees does not influence the level of serum hepcidin which makes it a more sensitive indicator of the level of iron in the body. Besides this, serum hepcidin is a reliable biological marker for the assessment of iron deficiency anemia.

Fractional excretion of magnesium and kidney function parameters in nondiabetic chronic kidney disease.

AIM: Elevated fractional excretion of magnesium (FEMg) is a noninvasive biomarker of kidney damage, but its association with kidney functional parameters in nondiabetic chronic kidney disease (CKD) patients has not been sufficiently explored thus far. METHODS: We enrolled 111 adult patients with nondiabetic CKD and 30 controls. To precisely investigate kidney function, the following parameters were assessed measured glomerular filtration rate (mGFR), effective renal plasma flow (ERPF), Cystatin C, albuminuria, and fractional excretion of magnesium (FEMg). All the CKD patients were divided into two groups according to the values of mGFR (mL/min/1.73m2): the first group consisted of those with GFR≥ 60 mL/min/1.73m2, whereas the second group included those with GFR< 60 mL/min/1.73m2. RESULTS: FEMg (%) was significantly higher in the group of nondiabetic patients with CKD compared to the healthy subjects [6.3 vs. 5.3 %, P=0.013]. There was also significant difference in the value of FEMg between the first and second groups of CKD patients. Increased FEMg was significantly correlated with all the investigated kidney function parameters, mGFR, ERPF, Cystatin C and albuminuria (r=-0.62; r=-0.60; r=0.77; r=0.39; p<0.01 for all). In multiple regression analyses based on observed parameters of kidney function, only cystatin C was independently and significantly associated with FEMg (multiple correlation coefficients: 0.738, p < 0.001)). Nondiabetic CKD patients with GFR< 60 mL/min/1.73m2 have increased FEMg above 6.1% with 78.7 % specificity and 83.7% sensitivity. CONCLUSION: Highly significant association between kidney functional parameters and FEMg may indicate significance of this parameter in clinical practice.

Fecal pancreatic elastase-1 and erythrocyte magnesium levels in diabetes type 1 and type 2.

In both types of diabetes mellitus (DM), type 1 and type 2 (T1DM and T2DM), there are both endocrine and exocrine dysfunctions of the pancreas (PED), as well as disturbances in serum magnesium levels. The aim of this study was to examine the frequency of PED according to the level of fecal elastase-1 (FE-1) in patients with T1DM and T2DM, determining the correlation of the level of FE-1 with certain anthropometric parameters, certain indicators of metabolic regulation of diabetes, and certain nutritive markers of PED. MATERIALS AND METHODS: In the examinees, (56 with T1DM (F = 35 and M = 21), 62 with T2DM (F = 30 and M = 32), and 40 in the control group (F = 19 and M = 21)), we examined anthropometric parameters, and using standard biochemical methods, we measured the level of FE-1, magnesium concentration in blood and erythrocytes, and selected blood parameters. RESULTS: FE-1 concentration < 200 µg/g was present in 14.2% of the examinees with T1DM, 20.9% with T2DM, and 2.5% in the control group. In all examinees with DM, there was a statistically significant correlation (P < 0.05) between the level of FE-1 and Mg concentration in the erythrocytes (R = 0.40). CONCLUSIONS: Prevalence of pancreatic exocrine insufficiency (PEI), according to the level of FE-1, is significantly higher in patients with DM than in the control group, while it is a bit higher in patients with T2DM than the ones with T1DM. In both types of DM, Mg concentration in erythrocytes is in a significant correlation with the level of FE-1.

Serum magnesium level in the first trimester of pregnancy as a predictor of pre-eclampsia - a pilot study.

OBJECTIVES: The aim of this study was to evaluate the importance of serum concentration of magnesium (Mg) in the first trimester of pregnancy for predicting pre-eclampsia (PE). METHODS: This prospective study included 403 pregnant women over 18, with singleton pregnancy (from 11 to 14 weeks of pregnancy). The subjects were divided into a group who subsequently developed PE (PEKT) (n = 61), and a group of healthy pregnancies with no complications and with normal outcomes (TNT) (n = 342). In the first trimester, urea, creatinine, uric acid, Mg, free beta subunit of human chorionic gonadotrophin, plasma protein A related to pregnancy, and C-reactive protein were determined. We followed all subjects until the end of pregnancy. RESULTS: Serum Mg is significantly lower in PEKT than in TNT group (p < 0.001). The serum first trimester Mg level cutoff at ≤0.81 mmol/L had a sensitivity of 77.0% and specificity of 71.6% for the detection of women with PEKT. The level of serum Mg has the strongest significant positive correlation (p < 0.05) with the week of gestational outcomes (R = 0.442), weight (R = 0.416), and Apgar score (R = 0.343) of the newborns, and the strongest significant negative correlation with the number of miscarriages (R = -0.413), serum creatinine (R = -0.471), and the number of pregnancies (R = -0.326). The week of gestational outcome is predicted with the greatest reliability by the serum Mg. CONCLUSIONS: Serum Mg level during the first trimester of pregnancy is a significant prediction tool for PE and could also play an important role in predicting the week of gestational outcome and birth weight of newborns.

The relationship between the vitamin serum 25(OH)D and the B12 concentrations in obese women.

BACKGROUND: In obesity, low levels of vitamin D (VD) and vitamin B12 (VB12) may be the result of different pathophysiological mechanisms, but the possible association between them has not been defined yet. The aim of this cross-sectional analysis was to investigate the possible relationship between serum 25-hydroxyvitamin D (25(OH)D) and VB12 levels in middle aged women. METHODS: In 80 women, we indirectly evaluated body composition and body volumes [extracellular fluid volume (ECV) and total body water (TBW)] by anthropometric and bioelectrical impedance analysis. Vitamin D and VB12 status was assessed by laboratory measurement [serum 25(OH)D levels by electrochemiluminescent immunoassay; VB12 by chemiluminescent microparticle immunoassay]. RESULTS: Obese women were mostly VD deficient [25(OH)D below 50 nmol/L; 40/50, 80%]. Also, among obese we observed presence of VB12 deficiency [VB12 below 148 pmol/L; 13/50, 26%) and marginal depletion of VB12 level (marginal VB12 status 148-221 pmol/L; 20/50, 40%). All anthropometric indicators of obesity, ECV and TBW were significantly associated with both, 25(OH)D and VB12 (P<0.001) levels. In univariate regression analysis serum level of 25(OH)D was significantly associated with VB12 levels (R2=0.170, P<0.001). In regression models, 25(OH)D was significantly associated with VB12 level, independently of fat mass and extracellular fluid volume. CONCLUSIONS: Obesity may negatively affect VB12 level, indirectly, by reducing 25(OH)D level in middle aged women.

Screening for Chronic Kidney Disease in Adult Males in Vojvodina: A Cross-sectional Study.

BACKGROUND: Chronic kidney disease (CKD) is one of the most significant global health problems accompanied by numerous complicatons, with constant increase in the number of affected people. This number is much higher in early phases of disease and patients are mostly asymptomatic, so early detection of CKD is crucial. The aim was examination of the prevalence of CKD in the general population of males in Vojvodina, based on estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR), and exploring the determinants and awareness of CKD. METHODS: This cross-sectional study included 3060 male examinees from the general population, over 18 years of age, whose eGFR and ACR were calculated, first morning urine specimen examined, arterial blood pressure measured and body mass index calculated. Standard biochemistry methods determined creatinine, urea, uric acid and glucose serum concentrations as well as albumin and creatinine urine levels. RESULTS: Prevalence of CKD in the adult male population is 7.9%, highest in men over 65 years of age (46.7%), while in the other age groups it is 3.6-12.6%. The largest number of examinees with a positive CKD marker suffer from arterial hypertension (HTA) and diabetes mellitus (DM). Only 1.3% of examinees with eGFR<60 ml/min/1.73 m2 and/or ACR≥ 3 mg/mmol had been aware of positive CKD biomarkers. CONCLUSIONS: Obtained results show the prevalence of CKD in adult males is 7.9%, HTA and DM are the most important CKD risk factors and the level of CKD awareness is extremely low (1.3%) indicating the necessity for introduction of early stage disease recognition measures, including raising CKD awareness.

Antiphospholipid Antibodies and Renal Impairment Parameters in Diabetic Nephropathy: Preliminary Data.

OBJECTIVE: Antiphospholipid antibodies (aPL Abs) represented an independent factor that was associated with the occurrence and/or progression of nephropathy in patients with antiphospholipid syndrome, but their role in diabetic nephropathy is not elucidated. Therefore, we evaluated the association of aPL Abs with the renal impairment parameters in patients with diabetic nephropathy. METHODS: Concentrations of analyzed antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Cystatin C and anticardiolipin (aCL) antibodies of the immunoglobulin (Ig) G ( r = .349, P = .004) and the IgM isotype ( r = .316, P = .009) were in positive correlation. The IgG isotype of the aCL Abs was in positive correlation with creatinine ( r = .252, P = .038), urea ( r = .241, P = .048), and uric acid ( r = .271, P = .025). The concentrations of the IgG isotype of the aCL Abs were significantly different between subgroups of patients with diabetic polyneuropathy and patients without this clinical finding (Mann-Whitney, P = .033). CONCLUSION: This is the first report on positive correlation between aCL Abs and renal impairment parameters. Larger studies are necessary for elucidation whether this association is involved in further progression of the disease.

Cystatin C, vascular biomarkers and measured glomerular filtration rate in patients with unresponsive hypertensive phenotype: a pilot study.

BACKGROUND: Biomarkers are commonly used to estimate the presence of subclinical cardiovascular disease (CVD) in patients with essential arterial hypertension (HT). In addition to known association between cystatin C and glomerular filtration rate (GFR), elucidating the association between cystatin C and vascular biomarkers (intima-media thickness of common carotid arteries (CCIMT), carotid plaque and renal artery resistance index (RRI)) in patients with unresponsive hypertensive phenotype could be of significant clinical interest. METHODS: Participants (n = 200, median age 58 (52-64) years, 49% female) under treatment with antihypertensive drugs were stratified into two subgroups based on their blood pressure level as having responsive hypertension (RHT - compliant and responsive to treatment, n = 100), or nonresponsive (URHT - compliant but nonresponsive to treatment, n = 100). GFR was measured by isotopic (slope-intercept) method (99m Tc diethylene triamine penta-acetic acid - mGFR). RESULTS: The URHT group had significantly higher median cystatin C serum concentration (p = 0.02) and CCIMT (p = 0.00) compared to the RHT group, with no significant difference in RRI (p = 0.51) and mGFR among subgroups [69.9 ± 28.2 vs 76.74 ± 23.61 ml/min/1.73m2, p = 0.27]. In the URHT group, cystatin C was found to be associated with CCIMT (p = 0.02), hsCRP (p = 0.01) and duration of HT (p = 0.02), independently of mGFR and age. Independent predictors of URHT phenotype were CCIMT (p= 0.02) and hsCRP (p= 0.04). CONCLUSION: In addition to GFR, cystatin C serum concentration is positively and independently associated with CCIMT in patient with URHT phenotype and subclinical CVD. Prospective larger studies should further investigate the clinical importance of this relationship.

Ceruloplasmin and antioxidative enzymes in pre-eclampsia.

OBJECTIVE: To evaluate diagnostic value of ceruloplasmin together with other enzymatic and nonenzymatic antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and uric acid) and to evaluate the level of oxidative stress in patients with pre-eclampsia (PE) and compare it with normal pregnancy. METHODS: In this prospective study, antioxidative markers were investigated in two groups of pregnant women: patients with pre-eclampsia (n = 32) and the healthy pregnant women (n = 60). The following antioxidative markers and enzymes were evaluated: serum ceruloplasmin levels, uric acid, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). RESULTS: Serum levels of ceruloplasmin, uric acid and SOD were significantly higher in the PE group compared to the control group. Serum levels of GSH-Px were not significantly higher in the PE group compared to the control group. Serum ceruloplasmin and serum uric acid have the best diagnostic accuracy for oxidative stress in PE and are more accurate compared to antioxidative enzymes -SOD and specially more accurate than GSH-Px. CONCLUSIONS: Serum ceruloplasmin level may have significant role as the markers of oxidative stress in pre-eclampsia especially when used in combination with uric acid levels.

PLASMA ENDOTHELIN-1 LEVELS AND ALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

INTRODUCTION: Microalbuminuria is a very important independent risk factor for the progression of renal diseases as well as diseases of the cardiovascular system. Pathophysiological mechanisms that lead to the development ofmicroalbuminuria in patients with diabetes are complex and they are a result of numerous factors. In the past decade, endothelin-1, the most potent vasoconstrictor peptide, was identified as animportant factor that significantly contributes to the functional and structural renal changes. The objective of this study was to investigate the relationship between plasma concentration of endothelin-1 and urinary albumin excretion in patients with type 2 diabetes mnellitus. MATERIAL AND METHODS: There were 76 patients with type 2 diabetes who were divided into those having normoalbuminuria (n-33), microalbuminuria (n=29) and macroalbuinuria (n=14), and 30 healthy controls. Plasma levels of endothelin-1 were measured by enzyme-linked immunosorbent assay. RESULTS: There were significant differences in plasma concentration of endothelin-1 among groups (P<0.01). The correlation between endothelin-1. albuminuria. proteinuria and glomercular filtration rate was significant. In multiple regression analyses the plasma concentration of endothelin-l was independently and significantly associated with albuminuria (ß=0.01, p=0.009), proteinuria =.02, p<0.001) and glon.erular filtration rate (P3=0ßl. pO-.P=)6).0Conclu- sion. Higher plasma concentrations of endothelin-1 are independently associated with the levels of urinary, excretion of albumin Whicw May morroborate tlse hpothesis of apotenstial role of this peptide inl th de- vepment of microalbUminuriauin diabetic necphrpathy.

THE LABORATORY ASPECTS OF PROTEINURIA.

INTRODUCTION: The existence of proteinuria may be overlooked by applying the test strips. The aim of this study has been to determine the discrepancy between the findings ofproteinuria detected by test strips when compared to the results of its testing with the sulfosali- cylic acid. MATERIAL AND METHODS: The study sample consisted of 1106 subjects, who were divided into the proteinuria positive (test strips showed the presence of isolated proteinuria), and proteinuria negative group (microscopic examination revealed the presence of ≥10 fresh red blood cells4sL, and/or ≥1 dysmorphic erythrocyte/µL, and/or 10≥ leukocytes4uL, and or ≥1 cylinder, and/or ≥ 1 nonsquamous epithelial cells4µL, and/or ≥100 bacteria/µL). Both groups had the urine tested with sulfosalicylic acid. The chemical and microscopic examination of the urine was done by the analyzer LabUMat-UriSed. RESULTS: Proteinuria was confirmed with the sulfosalicylic acid test in 96.5% ofsublects from group I and in 85.3% ofsubiects from group 2. Among the patients with the negative finding of proteinuria on the test strip and with the positive sulfosalicylic acid test there was a significantly higher number of those with pathological findings of erythrocytes, leukocytes, bacteria and cylinders in the urine when compared to those of the same group with negative sulfosalicylic acid test. CONCLUSION: Sulfosalicylic acid test should be performed in cases of pathological microscopic findings in the urine in case of the presence of ≥10 fresh erythrocytes4iL and/or ≥ 1 dysmorphic eryth- rocyte/pL and/or 10≥ leukocytes/µL and/or 1≥ cylinder (except hyaline) and/or ≥1 nonsquamous epithelial cells/pL and/or≥ 100 bacterial pL even if the test strip examination is negative for proteinuria.

CYSTATIN C - MORE THAN THE MARKER OF THE GLOMERULAR FILTRATION RATE.

INTRODUCTION: Cystatin C is one of biomarkers that meet the conditions necessary for an endogenous substance to be a marker of the glomerular filtration rate. Cystatin c ­ properties. Cystatin C is produced in the nucleated cells in a constant amount, and its serum concentration does not depend on muscle mass and protein intake. The catabolism of cystatin C is mostly done in the kidneys. Determination of cystatin c level. Cystatin C may be determined in the serum, plasma, capillary blood and urine. The laboratory methods which are mainly used to determine its level are neplielometric and turbidimetric immunoassays. Cystatin c as a marker of glomerular filtration rate. Cystatin C is superior to creatinine as a marker of kidney function, especially in the early stages of chronic kidney disease. Several formulas are available for calculating the glomerular filtration rate from serum cystatin C. Cystatin c in various physiological/pathophysiological conditions. The level of cystatin C should be interpreted carefully because there are factors that can affect its level regardless of the renal function (thyroid dysfunction, glucocorticoids use, malignancies etc.). Higher cystatin C concentrations in general population are associated with an increased cardiovascular risk, as well as with preecampsia in pregnant women. CONCLUSION: The significant advantages of cystatin C as a kidney function marker are its use in the creatinine "blind" area, in pediatric and the elderly population. In addition, cystatin C could be used as a marker for cardiovascular risk assessment, in predicting and detecting preeclampsia, in patients with malignant diseases, etc.