Publikačná činnosť

„Nutritonal determinants of plasma homocysteine“

Šanca pre zdravie 1, 2007

„Závažný rizikový faktor srdcovo-cievnych ochorení Metabolický syndróm“

Abstrakty: 

Bratisl Lek Listy. 2010;111(10):527-34.

HSP60, oxidative stress parameters and cardiometabolic risk markers in hypertensive and normotensive Slovak females.

Kuka P, Bucova M, Penz P, Paulovicova E, Blazicek P, Atalay M, Lietava J.

2nd Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.

BACKGROUND:

The aim of our study was to analyse the relationships between hypertension, HSP60, oxidative stress, lipid profile and cardiometabolic risk in 126 females with arterial hypertension (AHW) and 39 normotensive females (AH-).

RESULTS:

Females with AH+ were significantly older and more frequently suffered from ischemic heart disease, angina pectoris, prior MI, abdominal obesity, obesity, metabolic syndrome and diabetes mellitus. On the other hand, normotensive females smoked significantly more often. Plasma levels of HSP60 were similar in both AH+ and AH- groups. However, hypertensive females exhibited almost two times lower values of oxidative glutation and lower levels of carbonyl protein, but significantly higher levels of homocysteine. In normotensive females, the total glutathione was the only parameter predicting females with the plasma level of HSP60 = 60 ng/ml. The independent predictors in hypertensive females were angina pectoris, triglycerides and the mean arterial pressure (MAP). MAP had also a borderline significance in normotensive females suggesting an association between HSP60 and blood pressure. MAP formed a J shaped curve with HSP60.

CONCLUSION:

Results suggest the association of blood pressure and heart shock protein 60 Kda in form of the J curve (Tab. 11, Fig. 3, Ref. 29).

Bratisl Lek Listy. 2010;111(8):420-5.

MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects.

Penz P, Bucova M, Lietava J, Blazicek P, Paulovicova E, Mrazek F, Bernadic M, Buckingham TA, Petrek M.

1st Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia. pnzptr@gmail.com

Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 -2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41).

J Hum Hypertens. 2010 Jul 15. [Epub ahead of print]

Insulin resistance in young, lean male subjects with essential hypertension.

Penesova A, Cizmarova E, Belan V, Blazicek P, Imrich R, Vlcek M, Vigas M, Selko D, Koska J, Radikova Z.

Laboratory of Human Endocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.

Impaired insulin action, frequently found in essential hypertension (HT), is modified by other factors, such as higher age, accumulation of body fat, dyslipidaemia, impaired glucose metabolism and endothelial dysfunction. In addition, antihypertensive and insulin-sensitizing medication itself may significantly affect cardiovascular and metabolic milieu. The aim of this study was to assess insulin sensitivity, acute insulin response, lipidaemic status and the adipokines' concentrations with regard to abdominal fat distribution in young, lean male subjects with treatment-naïve essential HT and in matched healthy normotensive (NT) subjects. We studied 27 HT patients (age: 19.9+/-0.6 years; body mass index (BMI): 22.9+/-0.5 kg m(-2)) and 15 NT controls (age: 22.3+/-1.0 years; BMI: 23.7+/-0.6 kg m(-2)). The subjects underwent an oral and an intravenous glucose tolerance test (OGTT, IVGTT) on separate days in random order. Higher fasting insulin (P<0.001), non-esterified fatty acids (P<0.05) and plasminogen activator inhibitor factor 1 concentrations (P<0.05) were found in HT patients when compared with NT patients. Despite comparable anthropometric parameters and body fat distribution assessed by magnetic resonance imaging in both groups, newly diagnosed untreated young hypertensive male subjects showed decreased insulin sensitivity, augmented insulin response to both oral and intravenous glucose load (P<0.01; P<0.05 respectively) and 'higher still normal' 2-h plasma glucose levels during OGTT. Untreated, young, lean hypertensive male subjects, with distribution of abdominal adipose tissue and lipid profile comparable with their healthy NT matched counterparts, showed considerable signs of insulin resistance and hyperinsulinaemia. We hypothesize that insulin resistance is the initial feature, which is influenced by several environmental factors, and HT is one of their common consequences.Journal of Human Hypertension advance online publication, 15 July 2010; doi:10.1038/jhh.2010.72.

Anthropol Anz. 2009 Sep;67(3):305-16.

Association of ACE (I/D) polymorphism with metabolic syndrome and hypertension in two ethnic groups in Slovakia.

Danková Z, Siváková D, Luptáková L, Blazícek P.

Department of Anthropology, Comenius University, Bratislava, Slovak Republic

The objective of this study was to examine the influence of ACE (I/D) genotypes on recognized risk variables for hypertension and Metabolic Syndrome in two ethnic population samples from Slovakia. A total of 150 Romany subjects (68 males and 82 females) and 167 Slovaks (45 males and 122 females) were examined. They were interviewed during a medical examination and they were investigated with respect to a variety of aspects such as medical, anthropometrical and life-style. The studied subjects were defined as hypertensive if the blood pressure was > or = 140/90 mm Hg and Metabolic Syndrome (MS) was defined according to criteria of the National Cholesterol Education Program Adult Treatment Panel III-(NCEP ATPIII). ACE (I/D) polymorphism was subsequently determined by PCR amplification of the ACE gene sequence. In the entire sample, the frequency of the mutant D allele was higher in the Slovak subjects (D = 0.527) than in the Romany subjects (D = 0.447), but the difference was not significant (p = 0.053). Neither the Slovak nor the Romany normotensive and hypertensive subjects differed significantly in the distribution of the three ACE genotypes (Slovak p = 0.169, Romany p = 0.116). In both ethnic samples hypertensive men prevailed (Slovak 51.1% vs. Romany 44.1%). The features of Metabolic Syndrome were identified in both samples; they occurred in 33.3% of Slovak men and 14.8% Slovak women vs. 42.9% of Romany men and 32.4% Romany women. Regression analysis showed no association between ACE genotypes and hypertension nor between ACE genotypes and MS in these Slovak population samples.

Neuro Endocrinol Lett. 2009;30(3):400-2.

Sweat: a potential marker of clinical activity in panic disorder.

Kukumberg P, Valkovic P, Blazicek P, Guth A, Martinkova J, Provaznik V, Jagla F.

2nd Department of Neurology, Faculty of Medicine, Comenius University in Bratislava, Slovak Republic.

OBJECTIVE:

Panic disorder (PD) is a paroxysmal neuropsychiatric disorder with unclear etiology and obscure pathophysiology. Despite the frequency of its occurrence, PD still has no reliable laboratory markers. The sweat is a neglected human secrete reacting immediately to various neurovegetative challenges including psychic imupulses. We hypothesized a possible dysfunction of sweat homeosthasis in PD.

SUBJECTS AND METHODS:

10 patients with active PD, 9 patients with PD in remission and 11 age-matched controls participated in this study. All subjects underwent a single 8-min session in the dry-heat sauna. Sweat and venous blood have been collected immediately after the end of this session. Concentrations of lactate, glucose, creatinine, natrium, potassium, chlorine, calcium and magnesium have been quantitatively estimated in both liquids and compared statistically among three groups.

RESULTS:

We did not find any significant difference in blood parameters of the three above groups. However, the patients with active PD had significantly higher sweat levels of lactate, glucose, creatinine and magnesium than both the other groups which did not differ. Moreover, sweat concentrations of natrium, potassium and chlorine were significantly higher in active PD comparing to the group of PD patients in remission.

CONCLUSIONS:

The sweat of patients with active PD in comparison to PD in its clinical remission exhibits surprisingly distinctive changes of selected parameters after dry-heat sauna exposure. Increased concentrations of lactate, glucose and magnesium in the sweat are not contradictory with presupposed neurotransmitter-metabolic firing mechanisms in PD. These findings appear to be perspective biochemical markers in PD and its course.

The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet.

Krivosíková Z, Krajcovicová-Kudlácková M, Spustová V, Stefíková K, Valachovicová M, Blazícek P, Nĕmcová T.

Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovakia. zorka.krivosikova@szu.sk

BACKGROUND:

A long-term vegetarian diet is generally poor in vitamin B group. The lack of vitamin B(12) together with vitamin B(6) and folate deficiency is closely related to homocysteine metabolism. Hyperhomocysteinemia was found to be associated with increased bone turnover markers and increased fracture risk. Thus, hyperhomocysteinemia, vitamin B(12) and folate deficiency may be regarded as novel risk factors for micronutrient deficiency-related osteoporosis.

AIM OF THE STUDY:

To assess the possible impact of a vegetarian diet on bone mineral density in cohort of Slovak vegetarian women.

METHODS:

Fasting serum glucose, albumin, calcium, phosphorous and creatinine as well as bone markers, serum vitamin B(12), folate and plasma levels of total homocysteine were assessed in two nutritional groups (vegetarians vs. nonvegetarians) of apparently healthy women (age range 20-70 years). Bone mineral density of the femoral neck, trochanter, total femur and lumbar spine was measured in all subjects.

RESULTS:

Vegetarians had a significantly lower weight (p < 0.05), higher PTH (p < 0.01) and homocysteine (p < 0.001). Vitamin B(12) was significantly higher in nonvegetarians (p < 0.001). No differences were observed in folate levels. Univariate analysis showed significant association between homocysteine and B(12) (p < 0.01), folate (p < 0.001), creatinine (p < 0.001), total proteins (p < 0.049), age (p < 0.001) and vegetarian food intake (p < 0.001). Vegetarians had a significantly lower TrFBMD (p < 0.05) and ToFBMD (p < 0.05). Age and CTx were significant predictors in all sites of measured BMD and PTH. A strong correlation between homocysteine and FNBMD (r = -0.2009, p < 0.002), TrFBMD (r = -0.1810, p < 0.004) and ToFBMD (r = -0.2225, p < 0.001) was found in all subjects.

CONCLUSION:

Homocysteine is one of the predictors of bone mineral density, and hyperhomocysteinemia is associated with lower bone mineral density. In healthy adults, homocysteine levels are dependent on age as well as on nutritional habits. Thus, elderly women on a vegetarian diet seem to be at higher risk of osteoporosis development than nonvegetarian women.

Anthropol Anz. 2009 Mar;67(1):1-11.

ACE insertion/deletion polymorphism and its relationships to the components of metabolic syndrome in elderly Slovaks.

Siváková D, Lajdová A, Basistová Z, Cvícelová M, Blazícek P.

Department of Anthropology, Faculty of Sciences, Comenius University, Bratislava, Slovak Republic sivakova@fns.uniba.sk

The purpose of this study was to assess clustering of Metabolic Syndrome components in aged Slovaks, and to investigate whether insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is associated with this syndrome. Data were available from 374 Slovak participants (200 females and 174 males) ranging in age between 60 and 90 years. ACE I/D polymorphism was determined by PCR amplification of the ACE gene sequence. Metabolic Syndrome was diagnosed according to criteria in the NCEP ATP-III. Elderly males and females differ significantly in the prevalence of Metabolic Syndrome (females 45.1%, males 24.8%). The males and females including subjects with and without metabolic syndrome, respectively, did not differ significantly in the three genotype distributions (p = 0.603 and p = 0.247). The allele frequencies (D = 0.5483, I = 0.4517) in the entire sample fell within the Hardy-Weinberg equilibrium. There was no confirmed association between ACE genotype and phenotypic variation in the recognized risk components for Metabolic Syndrome in elderly Slovaks. Among other factors which may induce a difference in Metabolic Syndrome, significant effect was detected for sex, BMI, HDL, TG, glucose and the ApoB/ApoA1 ratio.

Ann N Y Acad Sci. 2008 Dec;1148:556-61.

Sympathetic nervous system response to orthostatic stress in female patients with rheumatoid arthritis.

Vlcek M, Rovensky J, Blazicek P, Radikova Z, Penesova A, Kerlik J, Kvetnanský R, Imrich R.

Institute of Experimental Endocrinology, SAS, Bratislava, Slovakia. miroslav.vlcek@savba.sk

Sympathoneural and adrenomedullary impairments have been suggested in patients with rheumatoid arthritis (RA). In the present study, sympathoneural and adrenomedullary responses to orthostasis were evaluated in eight female RA patients and in eight matched healthy controls. The testing consisted of sequence of stabilization period in supine position, legs-up position, orthostasis, and supine position. In each body position, blood samples were drawn and ECG was recorded. Plasma levels of epinephrine (EPI), norepinephrine (NE) and neuropeptide Y (NPY) were measured and sympathoneural activity was evaluated by analysis of heart rate variability (HRV). Higher baseline NE levels were found in RA patients (P= 0.034), without any difference in response to orthostasis between the study groups. Levels of EPI tended to be lower in RA patients in base line (P= 0.053) and in response to orthostasis (P= 0.079). The RA and control groups did not differ in NPY levels or in HRV parameters considered to reflect sympathetic activity. A subtle tendency to decreased adrenomedullary reactivity but no evidence for abnormal sympathetic responses to orthostasis was found in RA females.

Ann N Y Acad Sci. 2008 Dec;1148:490-4.

The role of norepinephrine and insulin resistance in an early stage of hypertension.

Penesova A, Radikova Z, Cizmarova E, Kvetnanský R, Blazicek P, Vlcek M, Koska J, Vigas M.

Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia. adela.penesova@savba.sk

The interrelationship between activity of sympathetic nervous system and metabolic risk factors in youth with hypertension (HT) has been poorly studied. The aim of our present study was to assess the interrelationship between metabolic risk factors, such as insulin resistance, concentration of plasminogen activator inhibitor (PAI)-1, and catecholamines in an early stage of HT onset. An oral glucose tolerance test was performed in 17 young males with early-diagnosed nontreated HT grade 1 and 16 gender-, age-, and BMI-matched normotensive controls. Concentrations of glucose, insulin, epinephrine, norepinephrine, PAI-1, and plasma renin activity (PRA) were determined in venous plasma. Insulin sensitivity indices (ISIs) proposed by Cederholm, Matsuda, and Gutt were calculated. HT had higher baseline levels of norepinephrine, insulin (P= 0.02), and PAI-1 (P= 0.04). ISIs were lower in HT subjects (P < 0.001). Baseline concentrations of epinephrine were negatively associated with HDL cholesterol (r=-0.415, P= 0.02), ISI Matsuda (r=-0.361, P= 0.04), ISI Cederholm (r=-0.354, P= 0.04), and ISI Gutt (r=-0.429, P= 0.01), and positively with PRA (r= 0.609, P < 0.0001). Positive association was found between baseline concentrations of norepinephrine and PAI-1 (r= 0.418, P= 0.02). The sympathetic overactivity, which occurs in the early stage of HT may contribute to reduced insulin sensitivity even in young patients and intensify the undesirable development of metabolic cardiovascular risk factors and progress of the disease.

Vnitr Lek. 2008 Oct;54(10):961-4.

Evaluation of alternative calculation methods for determining LDL cholesterol.

Vohnout B, Vachulová A, Blazícek P, Dukát A, Fodor G, Lietava J.

2nd Dept. of Internal Medicine, School of Medicine, Comenius University, Bratislava, Slovakia. branislav.vohnout@rm.unicatt.it

BACKGROUND:

Due to limitations of the Friedewald formula, alternative methods for calculating low-density lipoprotein cholesterol (LDL-C) were suggested. We evaluated utility of these methods.

METHODS:

Ninety three subjects free of coronary heart disease were considered. LDL-C was measured by the homogeneous method, and calculated by the Friedewald formula LDL-C = TC-HDL-(TG/2.2) (LDL1) and alternative formulas LDL-C = 0.41 TC - 0.32 TG + 1.70 apoB - 0.27 (LDL2) and LDL-C = 0.94 TC - 0.94 HDL - 0.435 TG (LDL3).

RESULTS:

All three formulas underestimated the measured LDL-C, both in the whole group and in subgroups according to TG levels (TG < 1.7 and in a range of 1.7-4.5 mmol/l, p < 0.001 for all). We found significantly higher bias for all three formulas in subjects with 1.7 < or = TG < 4.5 mmol/l levels. The Friedewald formula showed the lowest assay bias in all the groups investigated. The mean absolute bias for LDL1 was 7.6%, 18.3% for LDL2 and 13.6% for LDL3, respectively. Linear regression analysis showed correlation of calculated LDL-C values with the direct method in the range of r = 0.82 - 0.90 (p < 0.0001 for all, except of LDL2 in 1.7 < or = TG < 4.5 mmol/l group where p = 0.0011).

CONCLUSIONS:

The Friedewald formula seems to be a better estimator of LDL-C in our study than the other two alternative formulas; however, it underestimated the LDL-C levels.

Anthropol Anz. 2008 Jun;66(2):199-209.

Relationships between blood pressure, polymorphism of angiotensin-converting enzyme (ACE), body composition and biochemical characteristics in elderly Slovaks.

Siváková D, Lajdová A, Basistová Z, Cvícelová M, Karabová P, Blazícek P.

Department of Anthropology, Comenius University, Bratislava, Slovak Republic. sivakova@fns.uniba.sk

Epidemiological studies have demonstrated that several specific environmental factors and candidate genes influence the human variation in blood pressure. The aim of this study was to investigate variables associated with blood pressure; with a particular emphasis on the differences in insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE), the body composition and the recognized risk factors for atherosclerosis among elderly males and females. A total of 374 participants (174 males and 200 females) aged from 60 to 90 years were recruited from different parts of Slovakia. The elderly were not bed-ridden, nor mentally impaired, they were able to manage their daily activities by themselves. The ACE I/D polymorphism was determined by PCR amplification of the ACE gene sequence. Body composition variables were obtained by bioelectrical impedance analysis, using the BIA 101 soft tissue-body impedance analyzer (Akern, S.r.l.). The subjects were determined to be hypertensive (blood pressure > or = 140/90 mm Hg) or normotensive (blood pressure < or = 140/90 mm Hg ). These two subgroups of males and females did not differ significantly in their mean ages. As expected, the hypertensive subjects of both sexes showed significantly higher mean values in systolic (SBP) and diastolic blood pressure (DBP), in body mass index (BMI), and in the mean values of their plasma glucose and extracellular water (ECW). The genotype distribution and allele frequencies in the whole sample (D = 0.5474, I = 0.4526) fell within the Hardy-Weinberg equilibrium. The frequency of the deleterious D allele in the normotensive (0.5532) and hypertensive (0.5516) subjects was not significantly different. The ACE I/D genotypes did not associate either with the systolic (p = 0.836) or diastolic BP (p = 0.629). From the other variables that may induce differences in blood pressure, a statistical effect was detected for glucose, Na/K, and Apo A1/ApoB ratios and physical activity on SBP, and for ApoA1, physical activity, BMI and total cholesterol on DBP.

Bratisl Lek Listy. 2007;108(12):510-5.

Nutritional determinants of plasma homocysteine.

Krajcovicova-Kudlackova M, Blazicek P, Mislanova C, Valachovicova M, Paukova V, Spustova V.

Slovak Medical University, Bratislava, Slovakia. marica.kudlackova@szu.sk

The total Hcy, methionine, vitamin B12, folic acid and vitamin B6 blood concentrations were measured in apparently healthy adult subjects aged 20-30 years with three types of nutrition - 52 normal weight subjects of general population on traditional mixed diet (non-vegetarians), 52 normal weight vegetarians and 24 overweight and obese non-vegetarians. In the groups with lower methionine intake (vegetarians, normal weight non-vegetarians; methionine intake 0.45-2.12 g/day), Hcy values are dependent on vitamin B12 and folic acid. Vegetarian Hcy concentration is significantly increased and hyperhomocysteinemia was found in 35% of vegetarians vs 10% of non-vegetarians. Elevated Hcy values in vegetarians are the consequence of vitamin B12 deficiency - 31% of vegetarians with deficient serum values vs 2% of non-vegetarians (vitamin is not contained in plant food). Non-vegetarians are more deficient in folic acid (8% vs 0% in vegetarians) due to of lower consumption of food rich in folic acid (vegetables, whole grain products, pulses, seeds). The results suggest that in healthy population, a correct nutritional regime with an optimal intake of nutritional Hcy determinants is crucial for the maintenance of Hcy concentration in normal range and for the prevention of hyperhomocysteinemia (Tab. 2, Fig. 2, Ref. 27). Full Text (Free, PDF) www.bmj.sk.

Nutr Neurosci. 2007 Jun-Aug;10(3-4):151-7.

Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (pycnogenol).

Dvoráková M, Jezová D, Blazícek P, Trebatická J, Skodácek I, Suba J, Iveta W, Rohdewald P, Duracková Z.

Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. monika.dvorakova@fmed.uniba.sk

Our study tested the hypothesis that treatment with a potent polyphenol complex not only reduces hyperactivity of children, but also catecholamine excretion and oxidative stress. Urine catecholamine concentrations were measured in attention deficit hyperactivity disorder (ADHD) children and healthy controls. ADHD children received either placebo (PL) or Pycnogenol (Pyc), a bioflavonoid extract from the pine bark, for one month. The study was performed in a randomized, double-blind, PL controlled design. Concentrations of catecholamines were higher in urine of ADHD patients compared to those of healthy children. Moreover, noradrenaline (NA) concentrations positively correlated with degree of hyperactivity of ADHD children. In ADHD patients, adrenaline (A) and NA concentrations positively correlated with plasma levels of oxidized glutathione. The treatment of ADHD children with Pyc caused decrease of dopamine (D) and trend of A and NA decrase and increased GSH/GSSG ratio. In conclusion, the data provide further evidence for the overactivity of the noradrenergic system in ADHD and demonstrate that A release may be increased, as well. Treatment of ADHD children with Pyc normalized catecholamine concentrations, leading to less hyperactivity, and, consequently, to reduced oxidative stress.

Bratisl Lek Listy. 2007;108(6):265-8.

Vitamin C protective plasma value.

Krajcovicova-Kudlackova M, Babinska K, Valachovicova M, Paukova V, Dusinska M, Blazicek P.

Slovak Medical University, Bratislava, Slovakia. marica.kudlackova@szu.sk

The relationship of plasma concentration and intake of vitamin C was measured in a randomly selected group of 368 apparently healthy adult subjects of two nutritional regimens: traditional mixed diet (general population, n=187) and vegetarians (n=181). The condition of protective plasma concentration over 50 micromol/l (50.3-89.4 micromol/l), the value of which reduces the risk of free radical disease, was found in 87 subjects from the general population group, in whom the average vitamin C intake was 124.2 mg per day in range of 92-181. The recommended dietary allowance for this group in amount of 77 mg of vitamin C daily was calculated from current Slovak recommendations being in amount of 80 mg per day for men and 75 mg for women. Previous epidemiological studies as well as the presented results show that approximately a half of Slovak general population have vitamin C deficient (below 23 micromol/l) or suboptimal (23-50 micromol/l) plasma concentrations with insufficient antioxidative protection. Significantly higher plasma vitamin C concentrations in comparison to non-vegetarians were observed in the vegetarian group. Protective concentrations were noted in 88% of vegetarians vs 46% of non-vegetarians. The significantly reduced values of products of oxidative damage of DNA (DNA breaks with oxidised purines and oxidised pyrimidines), lipids (conjugated dienes of fatty acids, malondialdehyde) and proteins (carbonyls) were found in subjects with plasma vitamin C concentrations being over 50 micromol/l vs. below 50 micromol/l. The data emphasize the role of vitamin C in free radical disease prevention under the condition of protective, antioxidative concentrations. The results of general population group document the need to revise the recommended dietary allowance for vitamin C as well as to change the nutritional habits including regular consumption of fruit and vegetables several times daily (Tab. 3, Ref. 28).

Bratisl Lek Listy. 2007;108(2):70-4.

The redox state of glutathione in erythrocytes of individuals with Down syndrome.

Muchova J, Garaiova I, Sustrova M, Liptakova A, Blazicek P, Kvasnicka P, Durackova Z.

Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovakia. jana.muchova@fmed.uniba.sk

BACKGROUND:

The redox state of glutathione has been used as indicator for the redox environment of the cell.

OBJECTIVES:

To investigate relationships between the redox environments, the SOD activity, total antioxidant status and the oxidation stress markers production (MDA and lipofuscin).

METHODS:

Individuals with Down syndrome and age-matched healthy controls were enrolled into a study. Some parameters of oxidative stress in serum were determined: reduced glutathione, oxidized glutathione, redox potential of this couple (Eh), activity of superoxide dismutase in the red blood cells as well as malondialdehyde and lipofuscin.

RESULTS:

In the group of persons with DS statistically significant decrease in the GSH concentration was found, however, no differences in the GSSG concentration versus controls was observed. The redox potential values for couple GSH/GSSG are a statistically significantly increased in DS individuals compared to controls.

CONCLUSION:

In this study we highlighted the different ways of view at the role of GSH in metabolism of persons with DS. It is useful to look at the GSH and GSSG concentrations separately as well as at redox potential value, which influence total redox state of organism (Tab. 2, Fig. 3, Ref. 30) Full Text (Free, PDF) www.bmj.sk.

Acta Biochim Pol. 2006;53(4):783-7. Epub 2006 Nov 14.

Activity of paraoxonase 1 (PON1) and its relationship to markers of lipoprotein oxidation in healthy Slovaks.

Sumegová K, Blazícek P, Waczulíková I, Zitnanová I, Duracková Z.

Department of Medical Chemistry, Biochemistry and Clinical Biochemistry, School of Medicine, Comenius University, Bratislava, Slovakia.

Low-density lipoproteins (LDLs), when modified by free radicals derived from artery wall cells, induce atherosclerosis. In contrast to oxidized LDL (ox-LDL), high-density lipoproteins (HDLs) are able to prevent atherosclerosis through a protein with antioxidant properties, paraoxonase 1 (PON1). The purpose of this study was to explore the association between the activity of HDL-associated PON1 and circulating ox-LDL as well as to investigate the relationship between ox-LDL and parameters of lipid profile in thirty Slovaks aged 21-73 years because recent studies have presented controversial results concerning PON1 and its role in LDL oxidation. For determination of circulating ox-LDL sandwich ELISA was used and other lipid parameters were determined by routine laboratory analyses. PON1 activities were assayed by two synthetic substrates - paraoxon and phenyl acetate. Lipid peroxides were determined spectrophotometrically. Of the lipid parameters examined, ox-LDL level correlated positively with total (P < 0.0001) and LDL-cholesterol (P < 0.001). Triacylglycerols (TAG) (P < 0.001), lipid peroxides (P < 0.01) and atherogenic index (AI = total cholesterol/HDL) (P < 0.0001) were also strongly correlated with ox-LDL. No inverse relationships were observed between ox-LDL and HDL-cholesterol or arylesterase/paraoxonase activities of PON1. Furthermore, it was found that ox-LDL (P < 0.01) and lipid peroxides (P < 0.05) were significantly higher in men than in women. PON1 arylesterase activity was marginally affected by sex. The results of this study suggest that the anti-atherogenic properties of HDLs are not directly related to their total concentration and that PON1 activity determined towards synthetic compounds (paraoxon and phenyl acetate) reflects no association with markers of oxidative stress. Furthermore, it follows from our results that men are more susceptible to developing atherosclerosis compared to women.

Mutat Res. 2006 Dec 10;611(1-2):64-70. Epub 2006 Sep 15.

The relationship between micronuclei in human lymphocytes and selected micronutrients in vegetarians and non-vegetarians.

Kazimírová A, Barancoková M, Krajcovicová-Kudlácková M, Volkovová K, Staruchová M, Valachovicová M, Pauková V, Blazícek P, Wsólová L, Dusinská M.

Research Base of Slovak Medical University, Institute of Preventive and Clinical Medicine, Limbová 14, 833 01 Bratislava, Slovak Republic. alena.Kazimirova@szu.sk

A vegetarian diet results in higher intake of vitamins and micronutrients, which - although providing antioxidant defence - may lead to deficiency in other micronutrients involved in DNA metabolism and stability (such as vitamins belonging to the B group). The principal difference among various vegetarian diets is the extent to which animal products are avoided. We have performed a pilot study to determine the relationship between the micronucleus frequency in lymphocytes and diet, and we compared the levels of Vitamins C and E, beta-carotene, B(12), folic acid, homocysteine and total antioxidant capacity in healthy vegetarians and non-vegetarians. The vegetarian group, consisting of 24 volunteers (13 women and 11 men), were matched for age and sex with 24 volunteers (12 women and 12 men) with a traditional dietary habit. Among the vegetarians were 13 lacto-ovo-vegetarians with average duration of vegetarian diet 10.8 years (ranging from 5 to 26 years) and 11 lacto-vegetarians with average duration of vegetarian diet 8.2 years (ranging from 3 to 15 years). Homocysteine, Vitamins C and E and beta-carotene levels in plasma were assayed by HPLC, and serum folate and Vitamin B(12) were determined with Elecsys Immunoassay tests. The total antioxidant capacity of plasma was estimated by measuring the ferric-reducing activity in a spectrophotometric assay. Micronuclei were measured in cytokinesis-blocked lymphocytes. Vegetarians had significantly higher levels of Vitamin C and beta-carotene (but not Vitamin E) in plasma compared with non-vegetarians (P<0.001). There were no significant differences in serum levels of folic acid and Vitamin B(12) between the monitored groups. Levels of folic acid in vegetarians correlated with length of vegetarianism (r=0.62, P=0.001, N=24). Vegetarians had elevated levels of homocysteine compared with non-vegetarians (P=0.007), as did vegetarian women compared with non-vegetarian women (P=0.031). We did not find any differences in total antioxidant capacity or in micronucleus frequency between the groups. Micronuclei correlated with age (r=0.62, P<0.001, N=48), women having higher frequencies than men. Multifactorial regression analysis showed significant effects of age, sex and total antioxidant capacity on micronucleus frequency (N=48, P<0.001).

Mol Nutr Food Res. 2006 Sep;50(9):858-68.

Association of metabolic syndrome risk factors with selected markers of oxidative status and microinflammation in healthy omnivores and vegetarians.

Sebeková K, Boor P, Valachovicová M, Blazícek P, Parrák V, Babinská K, Heidland A, Krajcovicová-Kudlácková M.

Research Base of Slovak Medical University, Bratislava, Slovakia. katarina.sebekova@szu.sk

Conditions predisposing to metabolic syndrome (MetS) are associated with increased oxidative stress and inflammation. We studied, in vegetarians (n = 90) and omnivores (n = 46), the impact of the dietary regimen on the occurrence of MetS risk factors (RFs: BMI, blood pressure, glucose metabolism and lipid profile) in relation to oxidative status (advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), malondialdehyde, ferric reducing ability of plasma, vitamins A, E, C, beta-carotene and superoxide dismutase activity) and microinflammation (C-reactive protein, leukocytes and neopterin). The proportion of subjects without/positive for one or two MetS RFs was comparable between the groups. From the components of MetS only immunoreactive insulin levels differed significantly (95% CI: omnivores: 5.0-7.1 microU/mL, vegetarians: 4.5-5.4, p = 0.03). Omnivores had lower AOPP (omnivores: 0.29-0.36 micromol/g albumin, vegetarians: 0.36-0.52, p = 0.01) and beta-carotene levels than vegetarians, they consumed more calories, proteins, fat and saturated fatty acids, and less fibres, beta-carotene and vitamin C. Multiple regression analysis revealed vitamin E and AOPP levels as the most important independent determinants of MetS RFs. The vegetarian diet seems to exert beneficial effects on MetS RFs associated microinflammation. Whether the vegetarian diet may counteract the deleterious effects of elevated AOPPs and AGEs, remains to be elucidated.

Coll Antropol. 2006 Jun;30(2):387-94.

Apolipoprotein E polymorphism in relation to plasma lipid levels and other risk factors of atherosclerosis in two ethnic groups from Slovakia.

Siváková D, Zacharová M, Gasparovic J, Raslová K, Wsólová L, Basistová Z, Blazícek P.

Department of Anthropology, Faculty of Sciences, Comenius University, Bratislava, Slovak Republic. sivakova@fns.uniba.sk

The influence of apolipoprotein E (ApoE) genotypes on plasma lipid levels and interaction with other environmental factors was determined in two Slovakian population samples; 146 Romany and 351 Slovak individuals. The two samples differ significantly in the distribution of E3/3 genotypes (p<0.014) and E3/2 (p<0.035). Analysis of variance did not reveal any significant effect of the ApoE genotypes on any of the plasma lipid levels in the Romany individuals. In the Slovak sample the variation in plasma low-density lipoprotein cholesterol (LDL-C) levels was significantly associated with the ApoE genotypes (p=0.012). We detected decreased LDL-C concentrations in males with E2 genotype when compared with E3 and E4 carriers (p=0.008). Further, the E2 genotype was found to be associated with high triglycerides levels (p=0.009). The ethnic samples differ significantly in the prevalence of metabolic syndrome and in the case of males of diabetes. Both the Romany and the Slovak males can be considered as having a more atherogenic profile compared with the females.

Bratisl Lek Listy. 2005;106(11):345-7.

C-reactive protein and nutrition.

Krajcovicova-Kudlackova M, Blazicek P.

Research Base of the Slovak Medical University, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia. marica.kudlackova@szu.sk

High sensitivity C-reactive protein (hsCRP) is a proven method to better predict the cardiovascular risk and target therapeutic interventions. Serum concentrations of hsCRP were measured in an adult apparently healthy population aged 19-75 years of different nutrition: a vegetarian group (lacto- and lacto-ovo-vegetarians who consumed plant food, dairy products and eggs) and a group of non-vegetarians (general population) on traditional mixed diet. The average hsCRP concentration was significantly reduced in the vegetarian group (0.72 +/- 0.07 vs 1.62 +/- 0.12 mg/l) with no risk values >3 mg/l vs 14 % in non-vegetarians. In non-vegetarians, a positive linear correlation of hsCRP values and age (r=0.35, p<0.001) was recorded vs horizontal trend line in vegetarians. Low and age independent concentration of hsCRP in vegetarians is the consequence of a long-term consumption of fruits and vegetables. These food commodities are important sources of dietary salicylates as well as other anti-inflammatory compounds (Tab. 1, Fig. 1, Ref. 15).

Eur J Nutr. 2006 Feb;45(1):52-4. Epub 2005 Jun 10.

No evidence of insulin resistance in normal weight vegetarians. A case control study.

Valachovicová M, Krajcovicová-Kudlácková M, Blazícek P, Babinská K.

Slovak Medical University, Institute of Preventive and Clinical Medicine, Limbová 12, 83301, Bratislava, Slovak Republic.

BACKGROUND:

Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet.

AIM OF THE STUDY:

Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age.

METHODS:

Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups.

RESULTS:

Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley.

CONCLUSION:

The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.

Physiol Res. 2006;55(2):227-31. Epub 2006 May 24.

Products of DNA, protein and lipid oxidative damage in relation to vitamin C plasma concentration.

Krajcovicová-Kudlácková M, Dusinská M, Valachovicová M, Blazícek P, Pauková V.

Research Base of the Slovak Medical University, Institute of Preventice and Clinical Medicine, Bratislava, Slovak Republic. marica.kudlackova@szu.sk

Oxidative stress plays an important role in the pathogenesis of numerous chronic age-related free radical-induced diseases. Improved antioxidant status minimizes oxidative damage to DNA, proteins, lipids and other biomolecules. Diet-derived antioxidants such as vitamin C, vitamin E, carotenoids and related plant pigments are important in antioxidative defense and maintaining health. The results of long-term epidemiological and clinical studies suggest that protective vitamin C plasma concentration for minimum risk of free radical disease is higher than 50 micromol/l. Products of oxidative damage to DNA (DNA strand breaks with oxidized purines and pyrimidines), proteins (carbonyls) and lipids (conjugated dienes of fatty acids, malondialdehyde) were estimated in a group of apparently healthy adult non-smoking population in dependence on different vitamin C plasma concentrations. Under conditions of protective plasma vitamin C concentrations (>50 micromol/l) significantly lower values of DNA, protein and lipid oxidative damage were found in comparison with the vitamin C-deficient group (<50 micromol/l). The inhibitory effect of higher fruit and vegetable consumption (leading to higher vitamin C intake and higher vitamin C plasma concentrations) on oxidation of DNA, proteins and lipids is also expressed by an inverse significant correlation between plasma vitamin C and products of oxidative damage. The results suggest an important role of higher and frequent consumption of protective food (fruit, vegetables, vegetable oils, nuts, seeds and cereal grains) in prevention of free radical disease.

nsonism Relat Disord. 2005 Jun;11(4):253-6. Epub 2005 Apr 20.

Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients.

Valkovic P, Benetin J, Blazícek P, Valkovicová L, Gmitterová K, Kukumberg P.

Department of Neurology, Derer's University Hospital, Limbová 5, Bratislava 83305, Slovak Republic. valkovicpeter@hotmail.com

Hyperhomocysteinemia is not only a major risk factor for atherothrombotic disease, but is also strongly associated with an increased risk of dementia and cognitive impairment, both of which are common in the course of Parkinson's disease (PD). Previous work has found that levodopa increases plasma homocysteine concentrations. Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. The objective of our study was to assess the impact of entacapone, a COMT inhibitor, on plasma levels of homocysteine, serum folate, and vitamin B12 in levodopa-treated PD patients. Nineteen PD patients receiving only levodopa and 21 PD patients on a combination of levodopa and entacapone participated in the cross-sectional study. The control group consisted of 17 subjects on dopamine agonists. The mean plasma homocysteine concentration in the subjects on only levodopa was higher than that in the subjects on a combination of levodopa and entacapone (P=0.001) or in the control group (P=0.0001). Concentrations of serum vitamin B12 and serum folate were on average normal in all groups, but levodopa-treated subjects (with or without entacapone therapy) were more prone to have hypovitaminosis B12 (45%) than controls on dopamine agonists (6%). We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. These preliminary findings and postulated hypotheses must now be confirmed in prospective studies.