Cíl studie: Asymetrický dimethylarginin (ADMA) je endogenní inhibitor syntázy oxidu dusnatého a je považován za rizikový faktor aterosklerózy. Úloha ADMA v predikci přežití u hemodialyzovaných (HD) nemocných není objasněná. Rozhodli jsme se porovnat ADMA jako prognostický faktor s vybranými rizikovými faktory celkové mortality v této skupině pacientů. Typ studie: Observační, prospektivní studie. Název a sídlo pracoviště: Ústav klinické biochemie a hematologie a 1. interní klinika, Univerzita Karlova v Praze, Lékařská fakulta v Plzni; Dialyzační středisko B. Braun Avitum v Plzni, Česká republika. Materiál a metody: Analyzovali jsme sérové hladiny ADMA pomocí ELISA metody, C-reaktivní protein (CRP) ultrasenzitivní metodou, homocystein (hcy), albumin (alb), troponin I (cTnI) a natriuretický peptid B (BNP) u 202 chronicky hemodialyzovaných nemocných (77 žen, 125 mužů; medián věku [interkvartilové rozpětí] = 68 [60–74] let. V čase statistické analýzy bylo v naší studijní populaci zaznamenáno 44 úmrtí (medián času sledování byl 17,1 [10,4–17,3] měsíců. Testovali jsme každý měřený parametr jako prediktor přežití v Coxově modelu poměrného hazardu (s adjustací na věk, pohlaví a délku dialyzační léčby). Výsledky: Relativní rizika (RR) celkové mortality s 95% konfidenčními intervaly (CI) pro všechny měřené parametry byla následující [data jsou uvedena v následujícím pořadí: hodnota cut-off; RR (CI)]: ADMA 1,14–1,3 μmol/l; 2,44 (1,24– 4,79), hcy 34,1–41,8 μmol/l; 1,81 (0,89–3,68), CRP > 21,8 mg/l; 2,28 (1,17–4,43), alb < 35,4 g/l; 3,29 (1,63–6,63), cTnI > 0,04 μg/l; 2,18 (1,14-4,17) a BNP > 1485 ng/l; 1,23 (0,62–2,45). Závěr: Ze všech měřených parametrů pouze ADMA, alb, CRP a cTnI statisticky významně predikovaly celkovou mortalitu u hemodialyzovaných nemocných. Nicméně ADMA se neukázal jako hodnotný klinický marker v predikci přežití u hemodialyzovaných nemocných., Objective: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is considered as a risk factor for atherosclerosis. The role of ADMA in survival prediction of hemodialysis (HD) patients is not clear. We decided to compare ADMA as a prognostic factor with selected risk factors for overall mortality in this group of patients. Design: Observational, prospective study. Settings: Institute of Clinical Biochemistry and Hematology and 1st Department of Internal Medicine, Charles University in Prague, Faculty of Medicine and Faculty Hospital in Pilsen; Dialysis Centre B. Braun Avitum in Pilsen, Czech Republic. Material and Methods: We analyzed ADMA levels by ELISA method, C-reactive protein (CRP) measured by ultrasensitive method, homocysteine (hcy), albumin (alb), troponin I (cTnI) and brain natriuretic peptide (BNP) in serum of 202 chronically HD patients (77 females, 125 males; median age [interquartile range] = 68 [60–74] years). At the time of statistic analysis, there were 44 deaths in our study population (median [interquartile range] follow-time was 17.1 [10.4–17.3] months). We tested each measured parameter as a predictor of patients’ survival in a Cox proportional hazard model (adjusted for age, sex and duration of HD treatment). Results: Relative risks (RR) of overall mortality with their 95% confidence intervals (CI) for all measured parameters were [data are presented as follows: cut-off point; RR (CI)]: ADMA 1.14 to 1.3 μmol/l; 2.44 (1.24–4.79), hcy 34.1 to 41.8 μmol/l; 1.81 (0.89–3.68), CRP > 21.8 mg/l; 2.28 (1.17–4.43), alb < 35.4 g/l; 3.29 (1.63–6.63), cTnI > 0.04 μg/l; 2.18 (1.14–4.17) and BNP > 1485 ng/l; 1.23 (0.62–2.45). Conclusion: From all measured variables ADMA, alb, CRP and cTnI statistically significantly predicted overall mortality in HD patients. Nevertheless, ADMA doesn’t seem to have a clinical value in survival prediction of HD patients., Roman Cibulka, D. Rajdl, R. Široká, and Lit. 11
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
Fibrate therapy results in elevation of plasma total homocysteine (tHcy), which is known to induce oxidative stress and endothelial dysfunction. We aimed to establish whether fibrate-induced elevation of tHcy has also similar consequences and whether they may be prevented by folate co-administration. Eighteen subjects with hypercholesterolemia were included in an open, prospective, cross-over study. We compared intra-individually the effect of fenofibrate on tHcy, oxidative stress and endothelial dysfunction surrogates, in monotherapy and when combined with 10 mg of folate. These effects were also compared with fluvastatin monotherapy. Fenofibrate in monotherapy significantly decreased LDL cholesterol, increased the tHcy by 39.5 %, while oxidized LDL (oxLDL), malondialdehyde (MDA), von Willebrand factors (vWf) and thrombomodulin (TMD) remained unchanged. When fibrate was co-administered with folate, the tHcy remained on the initial post-diet level, while both the total and oxLDL as well as MDA, vWf and TMD decreased. In contrast to fenofibrate monotherapy, fluvastatin (80 mg) had a similar effect as combined therapy with fenofibrate and folate, while tHcy remained uninfluenced. In conclusion, fenofibrate decreases the LDL cholesterol, but in contrast to fluvastatin, has no significant antioxidative and endothelium-protective potential, probably due to a concomitant increase of tHcy. These effects may be improved by co-administration of folate.
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.
Pain increased the number of free radicals in the body.
Previously, we studied changes mainly in oxygen and nitroxide
free radicals and described these changes relative to the lipids
and saccharides. In this article we focus on changes relative to
proteins. Assessment of AGE products (advanced glycation
end-products) was carried out by measuring fluorescence.
Patients were divided into two groups: 15 patients with acute
pain and 17 patients with chronic pain. Acute pain was
associated with a variety of surgical procedures and patients
were examined before and after surgical procedures. The group
of patients with chronic pain suffered from various types of
chronic pain, but mainly back pain. In patients with acute pain,
total protein (TP) decreased after surgery, as did the level of AGE
and the AGE/TP ratio. Nonetheless, post-operative pain
increased. In patients with chronic pain, neither total protein,
AGE, or AGE/TP changed, despite significant pain relief being
reported after treatment. Changes in proteins, as biochemical
markers, before and after pain treatment did not show any
significant changes. In patients with acute pain, the recorded
changes only lasted for 3-5 days after the operation. While in
chronic pain, there were no significant changes at all. The
assumption that changes in proteins, as biomarkers, would have
the same importance as changes in lipids and saccharides was
not proven.
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.