Association between Biomarkers of Oxidative Stress and Inflammation with Cardiac Necrosis and Heart Failure in Non-ST Segment Elevation Myocardial Infarction Patients and Various Degrees of Kidney Function.

The aim of this study was to explore the possible association between markers of inflammation and oxidative stress (OS) and markers of cardiac function and necrosis in 100 NSTEMI (non-ST-elevation myocardial infarction) patients with various degrees of kidney dysfunction. At admission, ejection fraction (EF), brain natriuretic peptide (BNP), troponin (TnI), creatinine phosphokinase (CPK), alanine transaminase (ALT), aspartate transaminase (AST), high-sensitive C-reactive protein (hs-CRP), interleukins 6 and 10 (IL-6, IL10), myeloperoxidase (MPO), transforming growth factor beta (TGF-ß1), glomerular filtration rate (GFR), and albuminuria were assessed. Study participants were divided into 2 subgroups based on the median level of EF. Compared to the high, patients in the low EF group had higher GFR, BNP, CPK, hs-CRP, IL-10, IL-6, and MPO values and lower albuminuria levels. The levels of EF decreased in parallel with the progression of CKD, whereas the levels of BNP, IL-6, and TGF-ß were significantly higher in late stages of CKD. Spearman's rho correlation analysis showed that EF was inversely correlated with MPO (r = -0.20, p = 0.05) BNP (r = -0.30, p = 0.002), hs-CRP (r = -0.38, p < 0.0001), IL-10 (r = -0.30, p = 0.003), and IL-6 (r = -0.24, p = 0.02) and positively with GFR (r = 0.27, p = 0.008). TnI was correlated with CPK (r = 0.44, p < 0.0001), CPK-MB (r = 0.31, p = 0.002), ALT (r = 0.50, p < 0.0001), AST (r = 0.29, p = 0.004), IL-10 (r = 0.22, p = 0.03), and MPO (r = -0.28, p = 0.006). In multivariate regression analysis, only BNP (ß = -0.011, p = 0.004), hs-CRP (ß = -0.11, p = 0.001), and GFR (ß = 0.12, p = 0.0029) were independent determinants of EF. Similarly, MPO (ß = -1.69, p = 0.02), IL-10 (ß = 0.15, p = 0.006), and AST (ß = 0.04, p = 0.001) were the 3 major determinants of TnI. Based on these associations, we built a predictive model including markers of inflammation and OS (MPO, IL-10, and hs-CRP) to identify patients with the most severe cardiac injury (combined EF below median and troponin above median values). Receiver-operator characteristic (ROC) analysis showed that the area under the ROC curve of this model to detect patients with low EF and high TnI was 0.67 (p = 0.015, 95%confidence interval = 0.53-0.81).

Effects of Music Therapy on Endothelial Function in Patients With Coronary Artery Disease Participating in Aerobic Exercise Therapy.

Context • Pleasant music that evokes a positive emotional response may activate brain pathways of the insular cortex, central nucleus of the amygdala, and lateral hypothalamus, which are involved in the integration of emotional and ambient sensory input, with corresponding autonomic responses. Exercise training can improve endothelium-dependent vasodilatation, both in epicardial coronary vessels and in resistance vessels, for patients with coronary heart disease. Objective • The aim of the present study was to evaluate the effects on endothelial function when patients with stable coronary artery disease (CAD) listened to their favorite music. Design • The study was a randomized controlled trial. Setting • The study occurred at the Institute of Cardiology, Niska Banja, Faculty of Medicine, University of Nis (Nis, Serbia). Participants • Participants were 74 patients with stable CAD. Intervention • Participants were randomly assigned to 1 of 3 groups: (1) exercise training only (T) group (n = 33), (2) listening to music and exercise training (MT) group (n = 31), and listening to music only (M) group (n = 10). Participants in the T and MT groups received usual medical care and underwent 3 wk of supervised aerobic exercise training. In addition to the exercise training, participants in the MT group listened to their favorite music for 1.5 h every day. Participants in the M group received the usual medical care and listened to their favorite music for 1.5 h every day. Outcome Measures • At baseline and postintervention, outcomes were assessed through measurement of the changes in circulating blood markers of endothelial function-the stable end product of nitric oxide (NOx), asymmetric dimethylarginine, symmetric dimethylarginine, and xanthine oxidase-and through the results of submaximal or symptom-limited exercise test. Results • After 3 wk, the NOx significantly increased in both in MT and T groups, with P < .001 and P < .01, respectively. The level of NOx was associated with an improvement in exercise capacity, which increased in the T, MT, and M groups, with P < .001, P < .001, and P < .05, respectively. At the end of the study, the xanthine oxidase was significantly lower in the T, MT, and M groups, with P < .001 and P < .05, respectively. Conclusions • The patients with stable CAD significantly improved their endothelial function by listening to their favorite music in addition to participating in regular exercise training. Having a patient listen to his or her favorite music can be proposed as an additional nonpharmacologic intervention for improving a CAD patient's endothelial function. The music program should be adjusted individually to fit with a well-established training program for aerobic exercise, according to a patient's preferences.

Detrimental effects of a bout of physical exercise on circulating endogenous inhibitors of endothelial function in patients with coronary artery disease.

BACKGROUND: A bout of intense physical activity has been shown to transiently impair endothelial function; however, the underlying mechanisms are unclear. AIM: The purpose of the review was to assess the impact of a bout of physical exercise induced by exercise stress echocardiography, on blood concentration of the endogenous inhibitors of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), in patients with atherosclerosis. METHODS: Overall, 83 study participants were enrolled, 25 coronary artery disease (CAD) patients, 20 age and sex-matched asymptomatic study participants with at least one risk factor for CAD, and 38 healthy controls. RESULTS: Patients with CAD developed symptoms and/or left ventricular wall motion abnormalities during exercise; no changes were seen in study participants with risk factors, or in healthy controls. At baseline, in CAD patients and in study participants with risk factors, both ADMA and SDMA were higher than healthy controls (P < 0.001). However, a further large increase occurred during exercise stress echocardiography in both groups, regardless of development of symptoms (P < 0.001). CONCLUSION: Basal concentrations of ADMA and SDMA are high in CAD patients and in study participants with risk factors, consistent with impaired nitric oxide synthase activity in atherosclerosis. Large increase of these endogenous inhibitors of nitric oxide during intense exercise provide support to the hypothesis that in patients with atherosclerosis endothelial function may further deteriorate as a consequence of a bout of physical activity.

Osteoporosis--a risk factor for cardiovascular diseases: a follow-up study.

INTRODUCTION: Cardiovascular (CV) diseases and bone fractures due to osteoporosis are the leading causes of death in the elderly. OBJECTIVE: The aim of this study was to demonstrate a correlation between the overall risk for CV events, and low bone density in postmenopausal women, and its impact on the incidence of serious CV events. METHODS: Our prospective study involved 300 postmenopausal women. All the examinees were divided into three groups based on their measured bone density: Group I--84 examinees with osteoporosis; Group II--115 examinees with osteopenia; and Group III--101 examinees with normal bone density. In all examinees the overall ten-year risk for a fatal CV event was calculated using the SCORE system tables. RESULTS: After a 36-month follow-up, CV events occurred in 19 (6.3%) examinees. Significant differences in the incidence of CV events were demonstrated between the patients with osteoporosis, osteopenia, and normal bone density (χ2 = 28.7; p < 0.001), as well as between those with a high and low CV risk (χ2 = 22.6; p < 0.001). Multivariate logistic regression analysis showed that smoking (OR: 2.23; 95% CI: 1.02 to 6.19; p = 0.035), and increase of overall CV score (OR: 1.36; 95% CI: 1.17 to 1.58; p < 0.001) are associated with increased CV event risk, while the increase of T score value is associated with decreased risk of CV event (OR: 0.42; 95% CI: 0.25 to 0.73; p = 0.002). CONCLUSION: Measurement of bone density with a standard assessment of the total CV risk could be useful for selecting women who need intensive prevention and treatment of atherosclerosis.

Administration and effects of secondary prevention measures in coronary heart disease patients from Serbia according to gender and cardiometabolic risk.

BACKGROUND: The EUROASPIRE surveys showed high rates of modifiable cardiovascular risk factors in patients with coronary heart disease, identified after coronary artery bypass graft, percutaneous coronary intervention or myocardial infarction, with time trends in preventive cardiology over more than a decade. AIM: The aim of this study was to test the implementation of European recommendations for cardiac rehabilitation and secondary risk prevention programmes in the population of coronary heart disease patients from Serbia. SUBJECTS AND METHODS: A total of 665 consecutive coronary heart disease patients (432 men, 233 women, aged 59.43 +/- 11.62 years), admitted for specialized cardiovascular rehabilitation, interviewed and examined in relation to the presence of coronary risk factors and administration of secondary prevention measures, were enrolled in the study. RESULTS: High rates of smoking (27.67%), central obesity (58.05%), physical inactivity (61.50%) and adverse dietary habits (61.50%) were observed, as well as low frequency of patients who have reached recommended targets for waist circumference (41.95%), total cholesterol (40%), LDL-cholesterol (39.25%), HDL-cholesterol (59.69%) and triglycerides (59.25%), while systolic (82.26%) and diastolic blood pressures (95.49%) were well regulated. A significantly lower rate of achieved therapeutic targets, despite widely used cardioprotective drugs, was observed in diabetic patients and patients with the metabolic syndrome. CONCLUSION: The results have shown a low proportion of coronary heart disease patients, especially with diabetes mellitus and metabolic syndrome, who reached the recommended therapeutic targets for cardiometabolic risk profile parameters, in spite of widely used cardioprotective drugs, and therefore clearly demonstrated the compelling need for more effective lifestyle management in the secondary prevention of coronary heart disease.

Impact of reversible myocardial ischaemia on nitric oxide and asymmetric dimethylarginine production in patients with high risk for coronary heart disease.

BACKGROUND: The aim of the present study was to assess the impact of reversible myocardial ischemia, provoked by acute physical activity during an exercise stress echocardiography (ESE), on nitric oxide (NOx) and asymmetric dimethylarginine (ADMA) production in patients with high risk for coronary heart disease (CHD). MATERIAL/METHODS: An overall of 45 patients (27 men, 18 women; mean age, 55.87+/-6.39 years), was enrolled in the study and assigned into groups according to sex, CHD risk factors (RF), wall motion score (WMS), and diabetes mellitus (DM). An ESE was performed on an ergocycle, using a standardized protocol. The modified Saville-Griess method was used to determine NOx concentration. Production of ADMA was evaluated by high-performance liquid chromatography with fluorescent detection. RESULTS: A significant increase of NOx was observed in men (P<.05) and patients with stable WMS (P<.01), as well as its decrease in patients with increased WMS, whereas ADMA significantly increased in both sexes (P<.001 and P<.01 in men and women, respectively), independently of CHD risk (P<.05 and P <.001 in 1-2 RF and > or =3 RF groups, respectively), presence of DM (P<.001 and P<.01 in no-DM and DM groups, respectively), and WMS dynamic (P<.05 and P<.001 in WMS stable and WMS increased groups, respectively). The WMS was significantly higher in the > or =3 RF group (P<.01) after ESE and significantly increased in both sexes (P<.001 and P<.01 in men and women, respectively), with no regard to DM (P<.001 and P<.01 in no-DM and DM groups, respectively). CONCLUSIONS: The results of the present study clearly demonstrated a significant increase of NOx in patients with stable WMS and its decrease in patients with increased WMS after ESE, compared with the resting condition, as well as a significant increase of ADMA both in patients with stable WMS and those with increased WMS, irrespective of sex and CHD risk. A significant increase of WMS was observed in the > or =3 CHD RF group, in both sexes, with no regard to the presence of DM.

[Exercise as a therapeutic option in cardiometabolic risk reduction].

Regular physical activity is meant to be one of the most important nonpharmacological tools in reducing overall cardiometabolic risk since it significantly regulates body weight, blood pressure, blood glucose and lipid levels, and it also improves strength flexibility and quality of life and reduces stress. However, it should be individually prescribed, according to the patient's previous health status, individual desires and goals. Previous examinations (exercise stress testing, searching for vascular and neurological complications) are highly recommended in order to avoid potential risks (cardiovascular, microvascular, macrovascular, musculosceletal) ones. It should be strictly defined according to the type (aerobic vs. anaerobic activities), frequency (at least 3-5 times a week), duration (at least 20 to 60 minutes per session), intensity (55-90% of maximal heart rate) and energy expenditure (700-2000 kcal per week). It is highly recommended to be performed under supervision, at least at the beginning of the programme. Regular physical activity should become a part of everybody's lifestyle, especially in people at a high cardiovascular risk, in order to prevent the disease, as well as in those with already diagnosed cardiovascular disease, to prevent its complications.

Impact of interval versus steady state exercise on nitric oxide production in patients with left ventricular dysfunction.

AIM: The aim of the present study was to assess the impact of the interval exercise training (IET) vs. steady state exercise training (SSET) on nitric oxide production, through changes of circulating blood markers of endothelial function, including stable end-products of nitric oxide (NOx) and S-nitrosothiols (RSNOs) in patients with left ventricular dysfunction (LVD). PATIENTS AND METHODS: The impact of the IET vs. SSET on NOx and RSNOs production was assessed in a total of 31 (25 male, 6 female) patients with LVD (ejection fraction <40%), who were admitted to our residential rehabilitation centre. Patients were randomised into an IET group (n=18; 15 min interval exercise sessions, 2 times daily) and an SSET group (n=13; 5-10 min steady state exercise sessions, 2 times daily), and exercised every day over a period of 3 weeks. The modified Saville-Griess method was used to determine NOx and RSNOs concentrations. RESULTS: A significant increase was observed both for NOx (P < 0.05) and RSNOs (P < 0.001) in the IET group, as well as for RSNOs in the SSET group (P < 0.001). Both training methods were observed to significantly improve exercise capacity, as demonstrated for increased workload (P < 0.001 and P < 0.05 for the IET and SSET groups, respectively) and duration (P < 0.001 and P < 0.01 for the IET and SSET groups, respectively) of the exercise stress test at the end of the study. CONCLUSION: The results of the present study have demonstrated an increased nitric oxide production and improved exercise capacity in patients with left ventricular dysfunction, who were engaged in an interval exercise programme for three weeks, and clearly indicated an advantage of interval compared to steady state training method for cardiovascular rehabilitation.

Oxidative stress parameters as possible urine markers in patients with diabetic nephropathy.

OBJECTIVE: Reactive oxygen species play a crucial role in the pathogenesis of diabetic nephropathy (DN). The present study was performed to assess oxidative stress parameters-thiobarbituric acid reactive substances (TBARS), reactive carbonyl derivates (RCDs), and total sulfhydryl groups (TSHGs)-in serum and urine of patients with DN. METHODS: All parameters were determined in patients with type 2 and type 1 diabetes mellitus and microalbuminuria (DMT2-MIA, DMT1-MIA, respectively) and patients with type 2 diabetes mellitus and macroalbuminuria (DMT2-MAA) compared to healthy controls. RESULTS: Serum and urine TBARS levels were higher in all patients with DN and microalbiminuria compared to the control group. RCD levels significantly increased in serum of patients with DMT2 relative to the controls as well as in urine of patients with DMT2-MAA and DMT1-MIA. In all groups of patients, TSHGs decreased in serum but not in urine of patients with DMT2-MAA. CONCLUSION: Urine TBARS, RCDs, and TSHGs could be proposed as possible markers for oxidative damage of kidney in DN.

Diagnostic value of the aminopeptidase N, N-acetyl-beta-D-glucosaminidase and dipeptidylpeptidase IV in evaluating tubular dysfunction in patients with glomerulopathies.

AIM: The aim of the present study was to investigate the value of the urine cell glycoprotein 1 (PC-1), aminopeptidase N (APN), N-acetyl-beta-D-glucosaminidase (NAGA), and dipeptidylpeptidase IV (DPP IV) in the evaluation of tubular damage in patients with primary glomerulonephritis, diabetic nephropathy, and lupus nephritis. SUBJECTS AND METHODS: PC-1, APN, NAGA, and DPP IV activities were determined in serum, urine, and lymphocytes of 178 subjects, including 10 patients with membranous nephropathy, 38 with IgA nephropathy, 29 with lupus nephritis, 51 with diabetic nephropathy, and 50 control subjects. RESULTS: Urinary PC-1 excretion in IgA nephropathy group was significantly higher (p < 0.05) than in controls. Urinary NAGA excretion was markedly (p < 0.01) higher in membranous nephropathy group, and APN excretion in diabetic nephropathy group was significantly higher (p < 0.01) than in healthy controls. Urinary APN activity was significantly (p < 0.01) higher in both type 1 and type 2 diabetic patients with microalbuminuria, as well as urinary NAGA and DPP IV activities in type 2 diabetics with microalbuminuria (p < 0.01 and p < 0.05, respectively) compared to controls. Serum PC-1 and APN activities were significantly higher than the control level in membranous nephropathy group, as well as serum PC-1 and DPP IV activities in IgA nephropathy patients (p < 0.05). However, significantly lower serum DPP IV and APN activity was observed in type 2 diabetics with microalbuminuria compared to controls (p < 0.05). CONCLUSION: Damage of tubules in primary glomerulonephritis, lupus nephritis, and diabetic nephropathy is accompanied by a release of several tubular enzymes, with possible diagnostic and prognostic significance. Increased serum PC-1, APN, and DPP IV activities could be also of diagnostic significance.

Effects of regular exercise on cardiovascular risk factors profile and oxidative stress in obese type 2 diabetic patients in regard to SCORE risk.

AIM: The aim of the present study was to investigate not only the effects of aerobic exercise on overall cardiovascular risk factors profile and oxidative stress in obese, type 2 diabetic patients, but to elucidate if those effects depended on the previously estimated Systematic Coronary Risk Evaluation (SCORE) risk. SUBJECTS AND METHODS: Changes in several well-established cardiovascular risk factors and oxidative stress-defense parameters were measured in a total of 30 previously sedentary, obese type 2 diabetic patients, including 16 low-risk (SCORE < 5%, aged 48.8 +/- 6.0 years, with a mean BMI of 33.28 +/- 2.94 kg/m2) and 14 high-risk (SCORE > or = 5%, aged 56.3 +/- 6.9 years, with a mean BMI of 31.40 +/- 1.13 kg/m2) patients, in regard to the SCORE model, during six months of regular aerobic exercise, performed under supervision. RESULTS: Significant improvement was observed in the majority of cardiovascular risk factors, including body mass index, waist circumference, blood pressure, glycaemia, glycated haemoglobin, median blood glucose and lipid profile parameters in both diabetic subgroups during the exercise programme. However, the benefits of exercise on the majority of examined parameters became more evident in the low-risk subgroup, compared to the high-risk subgroup from baseline to 3 months. Regular exercise markedly reduced oxidative stress in both subgroups as well, as demonstrated for glutathione, plasma malondialdehyde, sulphydryl groups and catalase. CONCLUSION: Regular aerobic exercise, performed under supervision, has many beneficial effects in improving overall cardiovascular risk factors profile and reducing oxidative stress in both low-risk and high-risk (according to SCORE model), previously sedentary and obese type 2 diabetic patients.

PC-1 (ENPP1) K121Q polymorphism in overweight and obese type 2 diabetic coronary heart disease patients.

AIM: The aim of the present study was to investigate the prevalence of the PC-1 121Q allele and to test its association to cardiovascular risk factors in type 2 diabetes mellitus (DM) patients. METHODS: A total of 103 unrelated Caucasians from Serbia, including 71 DM patients without CHD (aged 59.4 +/- 8.9 years, with a mean body mass index (BMI) of 33.3 +/- 4.8 kg/m2) and 32 DM patients who suffered from coronary heart disease (DM+CHD) (aged 59.3 +/- 8.0 years, with a mean BMI of 30.37 +/- 3.71 kg/m2), were genotyped for PC-1 K121Q using a mutagenic separated PCR assay. RESULTS: The prevalence of the PC-1 121Q allele was significantly higher in DM+CHD, compared to DM (P < 0.001) and control (P < 0.001) groups, since it was found in 10 (14%) DM patients, 13 (41%) DM+CHD patients and 10 (17%) control subjects. When the association of PC-1 121Q allele and the risk of suffering from CHD were assessed within the DM group in a binary logistic regression model adjusting for age and sex, PC-1 121Q allele carriers had a 76% lower risk (OR 0.24; 95% CI: 0.08-0.67, P = 0.006) for developing CHD compared to subjects who exhibited PC-1 wild-type. CONCLUSION: The prevalence of the PC-1 121Q allele was significantly higher in type 2 diabetic patients who suffered from CHD, compared to type 2 diabetic patients without CHD. However, after a binary logistic regression model analysis, adjusting for age and sex., PC-1 121Q allele carriers had a 76% lower risk (OR 0.24; 95% CI: 0.08-0.67, P = 0.006) for developing CHD compared to subjects who exhibited PC-1 wild-type. Since these data were cross-sectional, the potential patient selection and survival bias, as well as community underdiagnosis of DM and CHD, could most likely substantially underestimate the genetic influence.

Effects of aerobic exercise on microalbuminuria and enzymuria in type 2 diabetic patients.

Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 +/- 7.3 years, with a mean BMI of 30.8 +/- 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p < 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.

The association of PC-1 (ENPP1) K121Q polymorphism with metabolic syndrome in patients with coronary heart disease.

BACKGROUND: Metabolic syndrome (MS) is a clinical feature, closely associated with insulin resistance, one of the prime underlying causes of overall cardiovascular morbidity, including coronary heart disease (CHD). Considering the association between PC-1 121Q genotype and insulin resistance phenotype, the aim of the present study was to investigate the contribution of PC-1 K121Q polymorphism to the development of MS and its concomitant disorders in CHD patients. METHODS: A total of 130 Caucasians from Serbia, including 80 CHD patients (aged 59.4+/-8.6 years, of a mean BMI 28.9+/-3.9 kg/m2) and 50 control subjects (aged 48.0+/-6.4 years, of a mean BMI 29.6+/-2.1 kg/m2), were genotyped for PC-1 K121Q using a mutagenic separated PCR assay, in order to determine the prevalence of the PC 121Q variant in individuals suffering from CHD and its association with MS. RESULTS: The frequency of PC-1 121Q allele found in CHD patients was 28.5%, with significantly (P<0.01) higher prevalence in those with MS (40% vs. 10%). Both MS (P<0.01) and its components [central obesity (P<0.01), low HDL-cholesterol (P<0.01) and high triglycerides (P<0.05)] were significantly more prevalent in CHD 121Q carriers compared to CHD patients who exhibited the wild-type genotype. A binary logistic regression model has revealed that PC-1 121Q allele carriers had a 5.5 fold increased odds (95%CI: 1.4-20.9, P=0.01) for the MS compared to wild-type carriers. The PC-1 121Q allele contributed to MS components as well, although these associations did not reach statistical significance. CONCLUSION: The findings of the present study support the hypothesis that the PC-1 (ENPP1) 121Q allele is associated with the genetic susceptibility for MS in patients with CHD. Further studies and more extensive research in this area are needed, not only to confirm this association, but to elucidate it in more details.

[Erythromycin-resistant Streptococcus pyogenes]. / Resistencija sojeva Streptococcus pyogenes na eritromicin.

Streptococcus pyogenes is the most prevalent cause of tonsillopharyngitis in children. The drug of choice for infections caused by this microorganism is penicillin. The problem of treating such infections arises when erythromycin-resistant strains occur. The aim of the study was to determine the prevalence of Streptococcus pyogenes resistant to erythromycin. The organism was recovered from the pharynx of children hospitalized or treated on outpatient basis at the University Children's Hospital in Belgrade. Streptococcus pyogenes was identified on blood agar, using bacitracin disc, and confirmed by latex agglutination test (Slidex bioMerieux). Disc diffusion test was carried out to estimate the penicillin resistance. Erythromycin disc was used as screening method to detect erythromycin-resistant Streptococcus pyogenes. MIC for erythromycin was performed by broth dilution method. In the study period from January 2001 to December 2003, all 1100 isolates of Streptococcus pyogenes had usual level of penicillin sensitivity. In 2001, only 0.45% of isolates were erythromycin-resistant. In 2002, erythromycin resistance was 0.63%, while in 2003, it was 1.09%. MIC for erythromycin was from 1 to 128 mg/l. Three strains had constitutive and one strain had inducible resistance to clindamycin. According to the results, our conclusion is that, despite sensitivity to penicillin, resistance to macrolides is the emerging phenomenon. Reasonable use of macrolide antibiotics is necessary to maintain the resistance at the lowest level.