Cardiac Remodeling Biomarkers as Potential Circulating Markers of Left Ventricular Hypertrophy in Heart Failure with Preserved Ejection Fraction.

Soluble suppressor of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor (GDF)-15 and syndecan-1 represent biomarkers of cardiac remodeling, involved in heart failure (HF) progression. We hypothesize that their plasma concentrations, together with brain natriuretic peptide (BNP), are different in HF stratified by ejection fraction (EF), demonstrating correlations with echocardiographic parameters that indicate left ventricular (LV) hypertrophy; LV mass index (LVMI) and posterior wall and septum diameters. HF patients (n = 77) were classified according to EF: reduced EF < 40% (HFrEF), mid-range EF = 40-49% (HFmrEF), preserved EF > 50% (HFpEF). We found that plasma concentrations of four cardiac remodeling biomarkers were highest in HFrEF and lowest in HFpEF, p < 0.001. In HFpEF, remodeling biomarkers independently correlated with LVMI: sST2 (p = 0. 002), galectin-3 (p < 0.001), GDF-15 (p = 0.011), and syndecan-1 (p = 0.006), whereas galectin-3 correlated after multivariable adjustments (p = 0.001). Independent correlates of septum and posterior wall diameters, in HFpEF, were sST2 (p = 0.019; p = 0.026), galectin-3 (p = 0.011; p = 0.009), GDF-15 (p = 0.007; p = 0.001), and syndecan-1 (p = 0.005; p = 0.002). In HFrEF, only sST2, adjusted, correlated with LVMI (p = 0.010), whereas BNP correlated with LVMI (p = 0.002) and EF (p = 0.001). GDF-15 correlated with diastolic dysfunction in HFpEF (p = 0.046) and HFrEF (p = 0.024). Cardiac remodeling biomarkers are potential circulating indicators of LV hypertrophy in HFpEF, which may ensure timely recognition of disease progression among high-risk patients.

Glutathione homeostasis disruption of erythrocytes, but not glutathione peroxidase activity change, is closely accompanied with neurological and radiological scoring of acute CNS inflammation.

OBJECTIVES AND METHODS: The levels of glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in the erythrocytes of 50 patients with clinically isolated syndrome of CNS (CIS) and 57 patients with relapsing remitting multiple sclerosis (RRMS). RESULTS: A decrease in GSH content and GPx activity showed significance in both study groups compared to the control values (p = 0.0025 and 0.007 for GSH and p = 0.005 and 0.003 for GPx, in CIS and RRMS patients, respectively). The depletions were more pronounced in RRMS than in CIS patients (p = 0.009 for GSH and p = 0.031 for GPx). The results significantly verify the negative correlations between GSH values and clinical severity (r = -0.513, p = 0.004), radiological findings (r = -0.351, p = 0.008) and disease duration (r = -0.412, p = 0.0025) in CIS patients. The same correlations were observed in RRMS patients between GSH values and clinical severity (r = -0.498, p = 0.004) and patients' radiological features (r = -0.454, p = 0.005). No correlations were observed between GSH values and other patient characteristics, or between GPx activity and all tested patient characteristics (p > 0.01). CONCLUSIONS: The results indicate that GSH content and GPx activity both decreased below the normal range and were accompanied with neuroinflammation, but although both might have great importance in neuroinflammation development, the data presented here confirm that only GSH might serve as a marker which is closely correlated with neurological and radiological scoring of acute CNS inflammation.

The Discriminatory Ability of Renalase and Biomarkers of Cardiac Remodeling for the Prediction of Ischemia in Chronic Heart Failure Patients With the Regard to the Ejection Fraction.

Background: Renalase has been implicated in chronic heart failure (CHF); however, nothing is known about renalase discriminatory ability and prognostic evaluation. The aims of the study were to assess whether plasma renalase may be validated as a predictor of ischemia in CHF patients stratified to the left ventricular ejection fraction (LVEF) and to determine its discriminatory ability coupled with biomarkers representing a range of heart failure (HF) pathophysiology: brain natriuretic peptide (BNP), soluble suppressor of tumorigenicity (sST2), galectin-3, growth differentiation factor 15 (GDF-15), syndecan-1, and cystatin C. Methods: A total of 77 CHF patients were stratified according to the LVEF and were subjected to exercise stress testing. Receiver operating characteristic curves were constructed, and the areas under curves (AUC) were determined, whereas the calibration was evaluated using the Hosmer-Lemeshow statistic. A DeLong test was performed to compare the AUCs of biomarkers. Results: Independent predictors for ischemia in the total HF cohort were increased plasma concentrations: BNP (p = 0.008), renalase (p = 0.012), sST2 (p = 0.020), galectin-3 (p = 0.018), GDF-15 (p = 0.034), and syndecan-1 (p = 0.024), whereas after adjustments, only BNP (p = 0.010) demonstrated predictive power. In patients with LVEF <45% (HFrEF), independent predictors of ischemia were BNP (p = 0.001), renalase (p < 0.001), sST2 (p = 0.004), galectin-3 (p = 0.003), GDF-15 (p = 0.001), and syndecan-1 (p < 0.001). The AUC of BNP (0.837) was statistically higher compared to those of sST2 (DeLong test: p = 0.042), syndecan-1 (DeLong: p = 0.022), and cystatin C (DeLong: p = 0.022). The AUCs of renalase (0.753), galectin-3 (0.726), and GDF-15 (0.735) were similar and were non-inferior compared to BNP, regarding ischemia prediction. In HFrEF patients, the AUC of BNP (0.980) was statistically higher compared to those of renalase (DeLong: p < 0.001), sST2 (DeLong: p < 0.004), galectin-3 (DeLong: p < 0.001), GDF-15 (DeLong: p = 0.001), syndecan-1 (DeLong: p = 0.009), and cystatin C (DeLong: p = 0.001). The AUC of renalase (0.814) was statistically higher compared to those of galectin-3 (DeLong: p = 0.014) and GDF-15 (DeLong: p = 0.046) and similar to that of sST2. No significant results were obtained in the patients with LVEF >45%. Conclusion: Plasma renalase concentration provided significant discrimination for the prediction of ischemia in patients with CHF and appeared to have similar discriminatory potential to that of BNP. Although further confirmatory studies are warranted, renalase seems to be a relevant biomarker for ischemia prediction, implying its potential contribution to ischemia-risk stratification.

The partnership between renalase and ejection fraction as a risk factor for increased cardiac remodeling biomarkers in chronic heart failure patients.

Objective: Heart failure (HF) represents a huge socio-economic burden. It has been demonstrated, experimentally, that renalase, a newly discovered protein, prevents cardiac hypertrophy and adverse remodeling, which is seen in HF. We postulated the following aims: to investigate associations of renalase with biomarkers of cardiac remodeling: galectin-3, soluble suppression of tumorigenicity, (sST2), growth differentiation factor 15 (GDF-15) and syndecan-1, myocardial stretch (BNP) and cardio-renal axis (cystatin C) in HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) to determine whether renalase, in combination with left ventricular ejection fraction (LVEF), represents a risk factor for plasma elevation in biomarkers.Methods: We classified HF patients (n = 76) according to LVEF (preserved/reduced), applied a median plasma renalase (113 ng/mL) as a cut-off value (low/high) and created four subgroups of HF patients: HFpEF/low renalase (n = 19), HFrEF/low renalase (n = 19), HFrEF/high renalase (n = 32) and HFpEF/high renalase (n = 6). A control group (n = 35) consisted of healthy volunteers.Results: Plasma concentrations of evaluated biomarkers were determined using an ELISA technique and were highest in HF patients with reduced EF (p < .001, respectively), and renalase's positive correlations were obtained relating to all biomarkers: galectin-3 (r = 0.913; p < .001), sST2 (r = 0.965; p < .001), GDF-15 (r = 0.887; p < .001), syndecan-1 (r = 0.922; p < .001), BNP (r = 0.527; p < .001) and cystatin C (r = 0.844; p < .001) and strong and negative correlation with LVEF (r = -0.456, p < .001). Increased renalase, regardless of the EF (preserved/reduced), was shown to be an independent risk factor for an increase in all evaluated cardiac remodeling biomarkers, p < .001, respectively. However, increased renalase and reduced EF was the only independent risk factor for BNP and cystatin C elevation, p < .001, respectively. Results after multivariable adjustments (age/gender) were identical.Conclusion: When elevated plasma renalase and HF are present, regardless of EF being reduced or preserved, that represents a significant risk factor for increase in cardiac remodeling biomarker plasma concentrations. However, only elevated renalase and reduced EF demonstrated significance as a risk factor for BNP and cystatin C plasma elevation. Renalase may be considered a promising molecule for the improved predictive abilities of conventional biomarkers and is worthy of further investigation.

Diltiazem prevention of toxic effects of monosodium glutamate on ovaries in rats.

The female reproductive system is very sensitive to different harmful environmental factors. A great danger is hidden in an increased use of food additives like monosodium glutamate (MSG). Numerous studies have shown that application of high doses of MSG to different kinds of animals during the neonatal period may cause lesions of neural structures and the retina. Later in adulthood animals exhibit a series of neuroendocrine disorders: a stunted growth, obesity and infertility. The mechanism of MSG action is not well explained yet. We hypothesized that high concentration of MSG could alter permeability of neural membrane for calcium. We studied whether pretreatment with diltiazem prevented the effects of MSG on ovaries in rats. Female rat pups were treated with: 0.9% NaCl, MSG, diltiazem or diltiazem with MSG. MSG treatment resulted in a cystic degeneration of ovaries and irregular and prolonged estrus phase of estrus cycle. The other treated groups of rats had normal ovarian histology and estrus cycle. The pretreatment with diltiazem prevented development of morphological and functional disorders of ovaries. Our results suggest that calcium overloading play an important role in mechanisms of MSG toxicity.

Neonatal influence of monosodium glutamate on the somatometric parameters of rats.

The glutamate receptors are expressed in various cell types including bone and adipose cells. The effects of neonatal administration of monosodium glutamate (MSG) on the "programming" of somatometric parameters in Wistar rats during the period up to 14th week of life were estimated. The rats were treated subcutaneously with five doses of 4 mg/g MSG (10 microl/g body mass) during the first 10 postnatal days (group M). The control (group C) was treated in the same manner with normal saline solution. During three months, body mass, naso-anal length and tail length were measured in 14 days intervals, while femoral and tibial masses and lengths, and testicular mass were measured following sacrificing. The body mass at the end of this period in the M group of males was higher than the body mass in the group C. Reduction in relative bone length, body and tail lengths and the relative as well as absolute testicular mass were registered in MSG-treated rats. A significant reduction in somatometric parameters was registered only in female MSG-treated rats during period of sexual maturation compared to controls.

Precancerous morphologic and functional aberrations in the rat mammary glands carcinogenesis.

The precancerous changes of mammary glands in 7,12-dimethylbenz(alpha)anthracene (DMBA) induced carcinogenesis in Wistar rats were examined. Carcinogen was inserted into the left fifth mammary gland of the anesthetised rats. After 35 days all the animals were sacrificed and mammary glands were extirpated. Macroscopic examination of mammary glands was performed and the tissue was processed for a pathohistological analysis. H&E, VanGieson's and Toluidine-blue methods were applied, as well as ABC immunohistochemical method with anti-cytokeratin antibodies.The identified precancerous changes resembled to aberrations of fibrocystic disease in women. The fibrosclerosis, lobular hyperplasia, cystic ductal dilatation and apocrine metaplasia of ductal epithelium were found. Micropapillomatoid hyperplasia was another frequent finding, but the presence of the real papilloma was not registered. The keratocysts with the squamous epithelial metaplasia were present in three of the animals. Dysplastic changes were found in the skin, above the treated glands. The difference in expression of cytokeratins, between normal and preneoplastic epithelium, makes cytokeratin useful for verification of early precancerous lesions. The epithelial ductus and ductulus cells of the mammary glands of animals belonging to the control group showed neither CK 19 nor CK 14 expression.

Association of Plasma Renalase and Left Ventricle Mass Index in Heart Failure Patients Stratified to the Category of the Ejection Fraction: A Pilot Study.

Heart failure represents a growing health problem, with increasing morbidity and mortality globally. According to the mechanisms involved in the pathogenesis of heart failure, many biomarkers have been proposed for the timely diagnosis and prognostication of patients with heart failure, but other than natriuretic peptides, none of them has gained enough clinical significance. Renalase, a new protein derived from kidneys was demonstrated to metabolize catecholamines and to have a cardioprotective role. The aim of the study was to determine whether renalase and brain natriuretic peptide (BNP) concentration could be used to differentiate heart failure patients stratified to the category of the ejection fraction and whether plasma renalase could be used as a biomarker for left ventricle hypertrophy in all subgroups of heart failure patients. We included patients diagnosed with heart failure and stratified them to the three subgroups according to the ejection fraction. Regarding echocardiographic parameters, HFmrEF had an intermediate profile in between HFrEF and HFpEF, with statistical significance in most evaluated parameters. BNP concentration was significantly different in all three subgroups (p < 0.001), and renalase was statistically higher in HFrEF (p = 0.007) compared to the HFmrEF and HFpEF, where its results were similar, without statistical significance. Renalase plasma concentration was demonstrated to be highly and positively associated with left ventricle mass index in HFrEF (p = 0.029), as well as increased plasma concentration of BNP (p = 0.006). In the HFmrEF group of patients, body mass index was positively associated with LVMI (p = 0.05), while in the patients with HFpEF, diabetes mellitus was demonstrated to have a positive association with LVMI (p = 0.043). These findings suggest that renalase concentration may be measured in order to differentiate patients with reduced ejection fraction. Plasma renalase concentrations positively correlated with left ventricle hypertrophy in patients with reduced ejection fraction, being strongly associated with increased left ventricular mass index.

Distribution of MEFV gene mutations and R202Q polymorphism in the Serbian population and their influence on oxidative stress and clinical manifestations of inflammation.

BACKGROUND: The Mediterranean fever (MEFV) gene codes for protein pyrin, one of the regulators of inflammasome activity in innate immune cells. Mutations in this gene are considered the primary cause of Familial Mediterranean fever, but are also found in other monogenic and multifactorial autoinflammatory diseases. The aim of the study was to determine if healthy carriers of MEFV gene mutations and R202Q polymorphism have clinical manifestations of inflammation and impaired oxidative stress parameters. METHODS: One hundred DNA samples from healthy volunteers (13.3 ± 8.87 years of age (mean ± SD); range 2-35) were sequenced by ABI PRISM 310 automated sequencer (PE Applied Biosystems, Norwalk, USA). The Eurofever questionnaire was used to collect retrospectively medical history data. Oxidative stress was determined by measuring spectrophotometrically thiobarbituric acid reactive substances (TBARS) in plasma and erythrocytes, as well as advanced oxidation protein products in plasma. Superoxide dismutase (SOD) activity was determined by McCord and Fridovich method in plasma and erythrocytes, while the catalase erythrocyte activity was assessed using a catalase ELISA kit. RESULTS: We found heterozygous carriers of K695R/N mutations in 5 %, E148Q/N mutations in 6 %, R202Q homozygous polymorphism in 10 % and heterozygous R202Q alterations in 45 % of healthy volunteers. The MEFV mutation carriers and R202Q polymorphism homozygotes reported significantly more often recurrent febrile episodes (p = 0.009), diffuse abdominal pain (p = 0.025), and malaise (p = 0.012) compared to non-carriers. Erythrocyte TBARS levels and plasma SOD activity were higher in persons with MEFV mutations and R202Q/R202Q (p = 0.03 and p = 0.049, respectively). CONCLUSIONS: Healthy individuals may bear E148Q and K695R MEFV gene mutations, as well as R202Q polymorphism in homozygous state. The determined gene alterations contribute to a subtle oxidative stress and may be associated with more frequent episodes of fever and unspecific inflammatory manifestations. An incomplete penetrance or variable expressivity of R202Q in populations of different ethnicity could influence the expression of autoinflammatory diseases phenotype.

Experimental closure of gunshot wounds by fibrin glue with antibiotics in pigs.

BACKGROUND/AIM: Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, after the primary surgical management, were closed with delayed primary suture during the next four to seven days. This period coincides with the fibroblastic phase of wound healing. Fibrin glue is used as a local hemostatic and as a matrix for the local dosed release of antibiotics. Antibiotics addition to fibrin glue resulted in continuous diffusion into the surrounding next 4 to 7 days. The aim of this study was to create the preconditions for gunshot wounds closing without complications by the application of fibrin glue with antibiotics 24 h after primary surgical treatment. METHODS: A total of 14 pigs were wounded in the gluteofemoral region by the bullet M67, initial velocity of 720 m/s. All wounded animals were surgically treated according to the principles of the war-surgery doctrine. Seven wounds were closed with primary delayed suture four days after the primary surgical treatment (traditional approach). Fibrin glue with antibiotics was introduced in seven wounds during the primary surgical treatment and primary delayed suture was done after 24 h. The macroscopic appearance and the clinical assessment of the wound were done during the primary surgical treatment and during its revision after 24 h, as well as histopathological findings at the days 4 and 7 after wounding. RESULTS: Gunshot wounds caused by the automatic rifle M70AB2 (AK-47) 7.62 mm, and treated with fibrin glue with antibiotics after primary surgical management, were closed with primary delayed suture after 24 h. In further wound evolution there were no complications. CONCLUSION: Uncomplicated soft-tissue wounds caused by an automatic M70AB2 rifle may be closed primarily with delayed suture without the risk of developing complications if on revision, 24 h after primary surgery, there were no present necrotic tissues, hematoma, and any signs of infection when fibrin glue with antibiotics (ceftriaxone and clindamycin) was applied. The use of this method should be limited to individual and strictly controlled cases in civil practice for now.

The assessment of renalase: searching for the best predictor of early renal dysfunction by multivariate modeling in stable renal transplant recipients.

BACKGROUND: Renal transplant dysfunction has been shown to be an independent risk factor for cardiac, non-cardiovascular, and all-cause mortality in post-transplantation follow-up. MATERIAL AND METHODS: We enrolled 73 renal transplant recipients who were more than 12 months post-renal transplant surgery, had stable graft function, and were on standard immunosuppression. The purpose of the study was to observe the relation between renal dysfunction and endothelial dysfunction parameters (nitrates, asymmetric and symmetric dimethylarginine, and endothelial nitric oxide synthase), and renalase, and to hypothesize the best predictor of early renal dysfunction by multivariate modeling. The other aim was to observe differences with regard to immunosuppression. RESULTS: Non-adjusted odds ratio showed a significant risk of reduced glomerular filtration rate in transplant recipients with increased renalase concentration (p=0.026); age-adjusted odds ratio showed a significant risk of reduced glomerular filtration rate with increased renalase concentration (p=0.042), also after multivariable adjustment (p=0.032). Increased plasma endothelial nitric oxide synthase concentration was a protective factor for glomerular filtration rate (p=0.011). After adjustment for age (p=0.045), and after multivariate modeling, endothelial nitric oxide synthase was shown to be a protective factor for glomerular filtration rate (p=0.014). Significant differences in immunosuppression were found in plasma renalase in patients maintained on cyclosporine (p=0.027). CONCLUSIONS: Renalase was shown to be strong predictor of decreased glomerular filtration rate and was significantly higher in the group of patients on cyclosporine. Endothelial nitric oxide synthase was identified as a strong protective factor for kidney function.

HPLC method development for determination of doxycycline in human seminal fluid.

The present paper reports the development and validation of an analytical method for doxycycline quantification in human seminal fluid by HPLC with UV detection. The separation of doxycycline was achieved at 40°C on a reversed-phase C18 column using isocratic elution. The mobile phase consisted of acetonitrile (A) and water buffered at pH 2.5 with a concentrated orthophosphoric acid (B) in the volume ratio of 20:80 (v/v), respectively. The detection was performed at 350nm. As an internal standard (IS), tetracycline was used. The proposed method involves the extraction of doxycycline from seminal fluid based on acidic precipitation of the proteins using perchloric acid. The method showed good intra- and inter-day precisions (RSD<7.0%), good accuracy (recovery for doxycycline>80%), and high correlation coefficient (r=0.998) for standards subjected to the entire procedure. The detection and quantification limits were 0.087µg/ml and 0.264µg/ml. The developed method was used to analyze doxycycline in the seminal fluids obtained from male subjects who were treated with doxycycline-hyclate. The mean doxycycline concentrations of 0.89±0.07µg/ml and 0.45±0.26µg/ml were detected in seminal fluid after 6h and 12h, respectively. This is the first study reporting extraction and HPLC determination of doxycycline in this complex sample and can be very useful in support of clinical and pharmacokinetic studies on this antibiotic.

Crosstalk of inflammatory mediators and lipid parameters as early markers of renal dysfunction in stable renal transplant recipients with regard to immunosuppression.

BACKGROUND: Kidney transplantation is still the treatment of choice for end-stage renal disease, therefore it is important to establish all modifiable risk factors for initiation of renal dysfunction. MATERIAL/METHODS: We enrolled 73 renal transplant recipients, who were more than 12 months post-renal transplant surgery, had a stable graft function, had no clinically present cardiovascular disease, and were on standard immunosuppressive therapy. The concentrations of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), CRP, lipids, and lipoproteins were measured. We used logistic regression to calculate non-adjusted, age, and multivariable-adjusted ORs and 95% confidence intervals for glomerular filtration rate, GFR <60 ml/min/1.73 m(2). RESULTS: Non-adjusted OR showed that there was a significant risk of reduced GFR in patients with total cholesterol higher than 5.19 mmol/L, LDL cholesterol ≥ 4.1 mmol/L, non- HDL ≥ 4.2 mmol/L, and higher VCAM-1 concentration. After adjustment for age and in multivariable model, OR showed a significant risk for reduced GFR in patients with total cholesterol ≥ 5.2 mmol/L, LDL ≥ 4.1 mmol/L, non-HDL ≥ 4.2 mmol/L, and higher VCAM-1 concentration. HDL, triglycerides, CRP, and lipoprotein ratios did not have any significance as predictors of renal dysfunction. There were no differences in all evaluated parameters between groups in regard to immunosuppressive therapy. CONCLUSIONS: Total cholesterol, LDL, non-HDL, and VCAM-1 are strong and independent predictors of renal dysfunction in stable renal transplant recipients. In contrast, HDL, CRP, triglycerides, and ICAM-1 did not seem to have any impact on renal dysfunction.

[Developmental conditions of medicine and spiritual culture at the time of grand Prince Stefan Nemanja].

Medieval medicine and pharmacy were the subjects of numerous researches. The enviable level of health culture and social care of the diseased and debilitated people of the Serbian medieval state was far advanced for the time. However, there are scarce written records of the conditions. The purpose of this paper is to point out the conditions which enabled the foundation of the first Serbian hospitals, development of scientific medicine and spiritual culture in medieval Serbian lands. Favourable conditions for the development of medieval medicine are linked with the arrival of the Nemanjic dynasty to the throne of the Serbian medieval state, i.e. Stefan Nemanja, and later with the life and work of his son Prince Rastko Nemanjic - Saint Sava. The wide field of activity of the Grand Prince Stefan Nemanja included the creation of stable and independent state ("the unifier of all Serbian lands") with a significant and shrewd political activity (vassal to Byzantine Emperor Manuel Comnenus, participation in great alliances against Byzantium), building of churches, defender of the Orthodox Christianity, foundation of the first Serbian hospital outside of borders of Serbian state in Hilandar monastery, social care about people and cultivating literary activity.

Identification and validation of six proteins as marker for endemic nephropathy.

Endemic nephropathy (EN) is defined as a slow progressive renal tubulointestitial disease that mainly occurs in the restricted areas of the Balkan Peninsula. The complexity of the pathogenesis of EN makes its earlier diagnosis very difficult. Urine samples from healthy volunteers from EN regions, EN patients with proteinuria less than 150 mg/L and EN patients with proteinuria more than 150 mg/L, patients with acute kidney injury, patients with diabetic nephropathy and healthy volunteers from Germany were collected. The urinary proteome analyses were performed using 2-D DIGE and mass spectrometry. The validation of biomarkers was investigated by two approaches (Western blot (WB) and dot blot) in successively increasing size - and partially overlapping - sample sets. Comparative and statistical analyses of the proteomics data from the different patient groups allowed the identification of six proteins (alpha-1-microglobulin, alpha-2-glycoprotein-1, beta-2-microglobulin, mannose-binding-lectin-2, protection-of-telomeres-protein-1, and superoxide-dismutase [Cu-Zn]), which were able to discriminate EN with low and high proteinuria from the other groups with high significance (p<0.05). The reliability of the identified proteins as EN marker was underlined with high statistical significance using WB analyses (sensitivity 66.7-98% and specificity 70-100%), whereas the dot blot analyses revealed a decrease in the sensitivity and specificity of these biomarkers.

[Drug interactions with grapefruit].

INTRODUCTION: The concentration of many orally given medications may be affected by grapefruit or grapefruit juice consumption. It may result in numerous harmful effects. INTERACTION OF GRAPEFRUIT WITH DRUGS: Taking only one cup of juice may induce interactions with different drugs even during the period of a few days. The effect is induced by suppression of cytochrome P450 isoenzyme CYP3A4 in the intestinal wall. The Latin name of grapefruit, Citrus paradisi, is quite opposite to the effects which could be induced by taking grapefruit and some medications at the same time. It is necessary to avoid taking grapefruit with the drugs whose pharmacokinetics could be altered by the active principles found in that fruit. DISCUSSION: The coloured grapefruit contains less furanocoumarins, but there is no difference in induction and intensity of pharmacokinetic interaction with drugs related to its colour. Other citrus fruits (orange, lemon) do not have such effects, but some other fruits (pomegranate, stella fruit, banpeiyu, hassaku, takaoka-buntan and kinkan) exert inhibitory effects on the activity of cytochrome P450 isoenzyme.

[Maternal smoking during pregnancy and socioeconomic factors as predictors of low birth weight in term pregnancies in Nis].

BACKGROUND/AIM: Low birth weight (LBW) is a result of preterm birth or intrauterine growth retardation, and in both cases is the strongest single factor associated with perinatal and neonatal mortality. It is considered that socioeconomic factors, as well as mothers bad habits, play the most significant role in the development of LBW, which explains notable number of researches focused on this particular problem. The aim of this study was to characterize socioeconomic factors, as well as smoking habits of the mothers, and their connection with LBW. METHODS: The questionnaire was carried out among mothers of 2 years old children (n = 956), born after 37 gestational weeks. The characteristics of mothers who had children with LBW, defined as < 2,500 g, (n = 50), were matched with the characteristices of mothers who had children > or = 2,500 g, (n = 906). For defining risk factors, and protective factors as well, we used univariant and multivariant logistic modeles. RESULTS: As significant risk factors for LBW in an univariant model we had education level of the mothers, smoking during pregnancy, smoking before pregnancy, the number of daily cigarettes, the number of cigarettes used during pregnancy, paternal earnings and socioeconomic factors. In a multivariant model the most significant factors were socioeconomic factors, education level of the mothers, paternal earnings and mothers smoking during pregnancy. CONCLUSION: Smoking during pregnancy and socioeconomic factors have great influence on LBW. Future studies should be carried out in different social groups, with the intention to define their influence on LBW and reproduction, as well. This should be the proper way of adequate health breeding planning for giving up smoking, the prevention of bad habits and melioration of mothers and children health, as the most vulnerable population.

[Overview of the scoring system for cardiovascular risk estimation: role and significance of lipids].

Practical recommendations for the regulation of hyperlipoproteinemia and the prevention of coronary disease and scoring systems for coronary disease risk estimation are based on the results of epidemiologic studies and international consensus guidelines. According to the Framingham point score the risk was defined as an absolute 10 year probability of myocardial infarction and coronary death, while the PROCAM function of risk was based on cardiovascular events: fatal and non-fatal myocardial infarction and sudden coronary death. The Third European Joint Task Force and other societies for the prevention of cardiovascular diseases revise the joint European guidelines and the recommendations for national population strategies. Global coronary disease risk is nowadays in Europe based on the SCORE system. The risk is defined as an absolute 10 year probability of afatal cardiovascular event, and high risk cut-off is at 5%.

[Acute myocardial infarction incidence and mortality rates in the population of the city of Nis in the period 1974-2000].

INTRODUCTION: The aim of this study was to investigate the annual incidence of hospital morbidity and mortality rates of acute myocardial infarction (AMI) in the population of Nis who were treated at the Cardiology Clinic in Nis during the period 1974-2000. MATERIAL AND METHODS: A retrospective clinical-epidemiological study was carried out in the population of the city of Nis aged 30 years and over. The number of citizens of Nis, aged 30 years and over, was 71,500 in 1974, and 100,000 in 2000, while the male to female ratio was 48%:52%. RESULTS: During the period from 1974 to 2000, 4319 patients of both sexes with AMI received hospital treatment. The average annual incidence rate was 159.92 per 100,000 inhabitants aged 30 years and over. The average annual incidence of AMI showed a trend of progressive increase, and in 2000 it was 274.87 (2.7 times higher than in 1974--102.19). The average annual mortality for both sexes was 1.57% (9.82% for males and 15.89% for females). The female mortality rate was significantly higher (p < 0.001). CONCLUSION: Trends in annual incidence rate of AMI in the population of the city of Nis aged 30 years and over are characterized by progressive increase during the period from 1974 to 2000. The trend line: yt = 159.92 + 6.2432x shows that without primary prevention further increase in the incidence of AMI can be expected.