a1_Modification of low density lipoprotein (LDL) particles due to oxidation, glycation and binding of advanced glycation end-products (AGEs) or malondialdehyde (MDA, a final product of lipid peroxidation) is considered most important in the process of atherogenesis. Oxidatively modified LDL are distinguished by another receptor type, which was discovered on the surface of macrophages and was called the scavenger receptor. Uncontrolled intake of LDL converts macrophages to foam cells; their accumulation under the vascular endothelium is considered as the first stage of atherosclerosis. Oxidation of LDL is a complex process taking place in both the extra- and intracellular space. At the end of this oxidative process, modified LDL particles show chemotactic, cytotoxic and immunogenic properties. Oxidized LDL express a large number of epitopes and cause production of polyclonal autoantibodies against these products, especially against apoB100 modified by MDA and 4-hydroxynonenal. IgoxLDL (antibodies against oxidized LDL) can be demonstrated either directly in intimal lesions or as a component of circulating immune complexes. IgoxLDL do not form a homogeneous group but a varied mixture of antibodies-isoantibodies caused by HDL and LDL polymorphism, antibodies against the lipid phase of LDL and antibodies against modified apoB100 of the immunoglobulin class IgA or IgG. Antibodies against oxLDL were found in many diseases other than atherosclerosis such as diabetes mellitus, renovascular syndrome, uremia, rheumatic fever, morbus Bechtjerev or lupus erythematodes. Newborns have practically the same levels of IgoxLDL as their mothers; however, these values did not differ from those in the healthy population of non-pregnant women of the same age., a2_The decrease in IgoxLDL titer was very slow and lasted many months; that is why this parameter cannot be considered suitable for describing the rapid changes during oxidative stress of the organism. Positive correlation of IgoxLDL with antiphospholipids and other antibodies was repeatedly demonstrated; their determination can thus be used as a marker for the description of total production of autoantibodies in various diseases. The changes and correlations of IgoxLDL, anti-b-2-glycoprotein I IgG and antiphospholipid antibodies support the immunological link between thrombotic and atherosclerotic processes in the human body., A. Steinerová, J. Racek, F. Stožický, T. Zima, L. Fialová, A. Lapin., and Obsahuje bibliografii
Cíl studie: Asymetrický dimethylarginin (ADMA) působí jako endogenní inhibitor syntázy oxidu dusnatého a je považován za nový kardiovaskulární rizikový faktor. Plazmatická koncentrace ADMA je zvýšená u nemocných léčených hemodialýzou (HD) a může u nich přispívat k endotelové dysfunkci. V literatuře bylo publikováno, že metabolismus ADMA je úzce spojen s metabolismem homocysteinu. Cílem naší studie bylo otestovat vztah ADMA a dalších kardiovaskulárních rizikových faktorů u HD nemocných. Typ studie: Observační. Pracoviště: Ústav klinické biochemie a hematologie a 1. interní klinika LF UK a FN v Plzni, Česká republika. Materiál a metody: Stanovili jsme hladiny ADMA metodou ELISA, celkový cholesterol a HDL-cholesterol, apolipoproteiny AI (apoA) a B (apoB), triglyceridy (TG), oxidované LDL částice (oxLDL), C-reaktivní protein (CRP) měřením ultrasenzitivní metodou, lipoprotein (a), látky reagující s kyselinou thiobarbiturovou (TBARS) a homocystein (Hcy) v plazmě u 176 dlouhodobě HD nemocných (70 žen, 106 mužů; průměrný věk ± SD = 66,4 ± 10,63 roků). Plazmatické hladiny ADMA jsme stanovili navíc u 73 zdravých mužů (průměrný věk ± SD = 48,15 ± 5,78 roků), kteří tvořili kontrolní skupinu. Pro porovnání koncentrace ADMA mezi těmito dvěma skupinami byl použit Wilcoxonův nepárový test. Vztahy mezi proměnnými ve skupině HD nemocných byly vyhodnoceny použitím korelačního koeficientu podle Spearmana. Nezávislost ADMA byla hodnocena mnohočetnou regresní analýzou. Výsledky: Průměrná koncentrace ADMA u skupiny HD nemocných byla statisticky významně vyšší než u kontrolní skupiny (1,13 ± 0,22; medián = 1,14 μmol/l vs 0,75 ± 0,15; median = 0,72 μmol/l; CI = 0,33 – 0,44; p < 0,001). Významné korelace byly nalezeny mezi BMI a oxLDL (r = 0,33; p < 0,001), apoA a CRP (r = -0,28; p < 0,001); apoB a oxLDL (r = 0,75; p < 0,001) a mezi TG a oxLDL (r = 0,45; p < 0,001). Žádný vztah nebyl nalezen mezi ADMA a Hcy (r = -0,07; p = 0,39). Mnohočetná regrese prokázala, že hladina ADMA je nezávislá na BMI, věku, i na všech ostatních měřených parametrech. Závěr: Hladina ADMA je nezávislá na všech ostatních kardiovaskulárních rizikových faktorech včetně homocysteinu u HD nemocných., Objective: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is regarded as a novel risk factor for cardiovascular disease. ADMA concentrations are increased in blood of haemodialysis (HD) patients and may contribute to endothelial dysfunction in them. It was published that the metabolic pathways of ADMA are connected to the metabolic cycle of homocysteine. The aim of our study was to test a relation of ADMA to other cardiovascular risk factors in HD patients. Design: Observational study. Settings: Institute of Clinical Biochemistry and Haematology and 1st Department of Internal Medicine of Charles University Medical Faculty and Faculty Hospital, Pilsen, Czech Republic. Material and Methods: We analysed ADMA levels by ELISA method, total and HDL cholesterols, apolipoproteins AI (apoA) and B (apoB), triglycerides (TG), oxidized LDL (oxLDL), C-reactive protein measured by ultrasensitive method (CRP), lipoprotein (a), thiobarbituric acid reactive substances (TBARS) and homocysteine (Hcy) in plasma of 176 chronically HD patients (70 females, 106 males; mean age ± SD = 66.4 ± 10.63 years). ADMA levels were determined also in 73 healthy men (mean age ± SD = 48.15 ± 5.78). Comparison of ADMA concentration between the two studied groups was performed by the Wilcoxon unpaired test. Relations among variables in the group of HD patients were evaluated using the Spearman correlation. Independence of ADMA was assessed by multiple regression analysis. Results: Average ADMA concentration in HD patients was significantly higher than control values (1.13 ± 0.22, median = 1.14 μmol/l vs. 0.75 ± 0.15, median = 0.72 μmol/l; CI = 0.33 to 0.44, p < 0.001). Interesting correlations were found between BMI and oxLDL (r = 0.33, p < 0.001), apoA and CRP (r = -0.28, p < 0.001), apoB and oxLDL (r = 0.75, p < 0.001) and finally TG and oxLDL (r = 0.45, p < 0.001). No correlation was found between ADMA and Hcy (r = -0.07, p = 0.39). Multiple regression analysis revealed that ADMA is independent from BMI, age and all other measured parameters. Conclusion: ADMA is independent of all other measured cardiovascular risk factors including homocysteine in HD patients., Roman Cibulka, R. Široká, D. Rajdl, and Lit. 20
Level of asymmetric dimethylarginine (ADMA) is elevated and endothelial progenitor cells (EPC) and stem cells (SC) are decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. We tested the hypothesis that ADMA, EPC and SC can be influenced with regular physical exercise early after Tx. Blood samples of ADMA, EPC, SC, adipocytokines and metabolic parameters were randomly obtained from 50 transplant patients before and 6 months after exercise program (Group I). Fifty age, sex HLA typing, duration of dialysis and immunosupression regimen-matched non exercising transplant were examined as controls (Group II). After 6 months, in Group I ADMA decreased (3.50±0.45 vs 2.11±0.35 μmol/l, P<0.01) and was lower comparing to Grou II (P<0.01), SC and EPC also decreased (2816±600 vs 2071±480 cells/ml resp. 194±87 to 125±67 cells/ml, P<0.02). Next changes in Group I: adiponectin (P<0.01), leptin (P<0.01), resistin (P<0.02). Visfatin, blood lipids, HbA1c, insulin and blood pressure were also influenced by training program (P<0.05)., V. Teplan, I. Králová Lesná, J. Piťha, A. Mahrová, J. Racek, I. Valkovský, A. Sekerková, M. Štollová., and Obsahuje bibliografii
Oxidative stress is probably a pathophysiological process leading to disadvantageous outcomes in diabetic pregnancies. We aimed to map a complex of potential markers of oxidative stress in this condition. Diabetic mothers had significantly higher concentrations of thiobarbituric acid reactive substances in the plasma [TBARS] both before (p<0.0001) and after (p<0.001) delivery and also their newborns showed higher values of TBARS (p<0.0001) in comparison with the control group. Diabetic mothers also showed lower concentrations of reduced glutathione in erythrocytes [GSH] both before (p<0.05) and after (p<0.01) delivery and their infants also had lower levels of GSH (p<0.0001). We found a lower total antioxidative capacity of plasma [AOC] before delivery (p<0.05) in the diabetic group in comparison with the control group. Newborns of diabetic mothers had higher plasmatic concentrations of apolipoproteine B [apo B] (p<0.05), higher erythrocyte glutathione peroxidase [GPx] activity (p<0.05) and lower pH (p<0.001) in the umbilical cord blood, when compared with infants of control non-diabetic mothers. We conclude that pregestational and gestational diabetes mellitus represent increased oxidative stress for both mother and her infant. TBARS in plasma are a valuable marker of oxidative stress in this condition. Disruption of glutathione peroxidase/glutathione pattern can be involved in pathophysiology of enhanced oxidative stress in diabetic pregnancies.
The aim of this study was to observe the effect of folate and antioxidants alone on homocysteine levels and oxidative stress markers, and to evaluate whether their co-administration promotes their effects. One hundred patients with hyperhomocysteinemia were randomized into four equal groups, which were then treated with folate, antioxidants or
folate plus antioxidants for 2 months; group IV was a control group. Serum homocysteine, folate and oxidative stress markers were measured before the study, at the end of folate and/or antioxidants administration and 3 months later. Folate caused a significant decrease in homocysteine concentration. Antioxidants did not influence homocysteine concentration, but they improved the antioxidative defense (plasma antioxidant capacity and intraerythrocyte
glutathione were increased) and partially prevented lipid peroxidation (malondialdehyde level was slightly decreased). Supplementation with folate had a similar effect on intracellular glutathione and plasma malondialdehyde. Simultaneous administration of folate and antioxidants did not show any additive effect with the exception of a slower decrease of folate concentration after its supplementation had been discontinued. Folate may be considered as an effective antioxidant in patients with hyperhomocysteinemia; this can be a result of decreased production of free radicals due to a reduced level of homocysteine. Its antioxidative effect cannot be promoted by co-administration of antioxidants.
Cíl studie: Monitorování akutní a chronické kardiotoxicity antracyklinů pomocí biochemických markerů – N-terminálního pro brain natriuretického peptidu (NT-proBNP), kardiálního troponinu T (cTnT) a myokardiálního izoenzymu kreatinkinázy (CK-MB mass). Soubor a metodika: Do studie bylo zařazeno 26 pacientů s nově diagnostikovanou akutní leukémií (15 mužů a 11 žen, průměrný věk 46,2 ± 12,4 let). Pacienti byli léčeni 2–6 cykly chemoterapie (CHT) obsahující antracyklinový preparát v celkové kumulativní dávce 464,4 ± 117,5 mg/m2. Vyšetření biochemických markerů a echokardiografické vyšetření bylo provedeno vstupně, po první CHT s antracykliny, po poslední CHT s antracykliny a s odstupem přibližně 6 měsíců po ukončení léčby. Výsledky: Vstupní koncentrace NT-proBNP byla 117,7 ± 46,4 ng/l, hodnoty byly mírně zvýšené u 3 pacientů (nad 100 ng/l pro muže, nad 150 ng/l pro ženy). Po podání první CHT s antracykliny došlo k vzestupu na 299,7 ± 176,2 ng/l. Po poslední CHT s antracykliny byla koncentrace NT-proBNP 287,1 ± 147,4 ng/l. S odstupem 6 měsíců po ukončení léčby byla průměrná koncentarce NT-proBNP 362,5 ± 304,9 ng/l, zvýšené hodnoty byly u 16 pacientů. Rozdíly v NT-proBNP byly statisticky významné v porovnání se vstupní hodnotou (p < 0,001). Prokázali jsme korelaci mezi NT-proBNP a poruchou systolické a diastolické funkce levé komory (LK) na echokardiografii. Koncentrace cTnT byly negativní (pod 0,01 μg/l) během léčby u všech pacientů, s odstupem 6 měsíců po léčbě byly pozitivní u 3 pacientů. Koncentrace CK-MB mass byly během léčby i s odstupem po léčbě negativní (pod 4,94 μg/l) u všech pacientů. Závěr: Naše výsledky potvrzují, že onkologická léčba obsahující antracykliny má toxický účinek na srdce, který se projevuje jak během léčby (akutní kardiotoxicita), tak během sledování po léčbě (chronická kardiotoxicita). Dochází ke změnám biochemických markerů funkčního poškození myokardu (elevace NT-proBNP svědčící pro akutní a chronickou neurohumorální aktivaci) a ke zhoršování ukazatelů systolické i diastolické funkce LK na echokardiografii. U asymptomatických pacientů jsou tyto změny považovány za známku subklinické kardiotoxicity. Tyto nálezy představují riziko pro rozvoj manifestní kardiotoxicity v podobě srdečního selhání v budoucnosti a vyžadují další sledování v čase. Podle našich výsledků léčba antracykliny ani při vyšších kumulativních dávkách nevede k akutnímu poškození struktury kardiomyocytů., Objective: Monitoring of acute and chronic cardiotoxicity of anthracyclines with biochemical markers – N-terminal pro brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and myocardial izoenzyme of creatine kinase (CK-MB mass). Setting: University of Defence in Brno, Faculty of Military Health Sciences in Hradec Králové, Department of Field Internal Medicine, Charles University in Prague, Medical Faculty in Hradec Králové and Faculty Hospital Hradec Králové, Department of Internal Medicine II – Clinical Hematology, Department of Internal Medicine I, Institute of Clinical Biochemistry and Diagnostics, Department of Gerontology and Metabolic Care. Patients and Methods: Twenty six consecutive patients treated for newly diagnosed acute leukemia were studied. The patients consisted of 15 males and 11 females with the mean age of 46.2 ± 12.4 years. The patients were given 2–6 cycles of chemotherapy (CT) containing anthracyclines in the total cumulative dose of 464.3 ± 117.5 mg/m2. Evaluation of biochemical markers and echocardiography were performed at the baseline, after first CT with anthracyclines, after last CT with anthracyclines and circa 6 months after completion of the treatment. Results: Mean baseline NT-proBNP concentration was 117.7 ± 46.4 ng/l, values were slightly elevated in 3 patients (above 100 ng/l for male, above 150 ng/l for female). After the administration of the first CT with anthracyclines, NTproBNP elevation to 299.7 ± 176.2 ng/l was observed. After last CT with anthracyclines, NT-proBNP concentration was 287.1 ± 147.4 ng/l. Six months after completion of the treatment, NT-proBNP concentration was 362.5 ± 304.9 ng/l, values were elevated in 16 patients. Changes in NT-proBNP were statistically significant in comparison with the baseline value (p < 0.001). We found correlation between NT-proBNP and systolic and diastolic left ventricular (LV) dysfunction on echocardiography. CTnT concentrations were negative (bellow 0.01 μg/l) during the treatment in all patients. Six months after the treatment, cTnT became positive in 3 patients. CK-MB mass concentrations remained negative (bellow 4.94 μg/l) in all patients during the treatment and the follow-up.Conclusion: Our results show that oncology treatment containing anthracyclines has a toxic effect on the heart, which becomes manifest both during the treatment (acute cardiotoxicity) and during the follow-up (chronic cardiotoxicity). We found changes in biochemical markers of functional myocardial damage (NT-proBNP elevations showing acute and chronic neurohumoral activation) and deterioration of diastolic and systolic LV function on echocardiography. In asymptomatic patients, these changes are regarded as subclinical cardiotoxicity. These findings represent the risk for manifestation of cardiotoxicity in terms of heart failure in the future and require further follow-up. According to our results, anthracycline treatment – even in higher cumulative doses – does not lead to acute damage of cardiomyocyte structure., Jan M. Horáček, R. Široká, D. Rajdl, and Lit. 35