Asymmetric and symmetric dimethylarginines are toxic non-coded amino acids. They are formed by post-translational modifications and play multifunctional roles in some human diseases. Their determination in human blood plasma is performed using capillary electrophoresis with contactless conductivity detection. The separations are performed in a capillary covered with covalently bonded PAMAPTAC polymer, which generates anionic electroosmotic flow and the separation takes place in the counter-current regime. The background electrolyte is a 750 mM aqueous solution of acetic acid with pH 2.45. The plasma samples for analysis are treated by the addition of acetonitrile and injected into the capillary in a large volume, reaching 94.5% of the total volume of the capillary, and subsequently subjected to electrophoretic stacking. The attained LODs are 16 nm for ADMA and 22 nM for SDMA. The electrophoretic resolution of both isomers has a value of 5.3. The developed method is sufficiently sensitive for the determination of plasmatic levels of ADMA and SDMA. The determination does not require derivatization and the individual steps in the electrophoretic stacking are fully automated. The determined plasmatic levels for healthy individuals vary in the range 0.36-0.62 µM for ADMA and 0.32-0.70 µM for SDMA.
Intradialytic hypotension is a major complication during hemodialysis session, associated with increased risk of cardiovascular events and mortality. Its pathophysiology is believed to be multifactorial and remains not well elucidated. The aim of this study is to put forward new mechanisms behind the development of intradialytic hypotension. The study included sixty-five subjects on chronic hemodialysis, divided into two groups: intradialytic hypotensive (n=12) and normotensive (n=53), according to the variation of systolic blood pressure between post-dialysis and pre-dialysis measurements. Renin and angiotensin converting enzyme I plasma concentrations increased in both groups but more likely in normotensive group. Aldosterone plasma concentration is increased in the normotensive group while it decreased in the intradialytic hypotension group. Plasma endothelin concentrations showed higher values in intradialytic hypotension group. Post-dialysis asymmetric dimethylarginine and angiotensin converting enzyme 2 plasma concentrations were significantly higher in intradialytic hypotension group as compared to normotensive one. Collectrin plasma concentrations were significantly lower in intradialytic hypotension group. Finally, post-dialysis vascular endothelial growth factor C plasma concentration significantly increased in intradialytic hypotension group. In conclusion, endothelial dysfunction characterized by a lower level of vasoactive molecule seems to play a critical role in intradialytic hypotension development.
- MeSH
- aldosteron krev MeSH
- arginin analogy a deriváty krev MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- cévní endotel metabolismus patofyziologie MeSH
- dialýza ledvin škodlivé účinky MeSH
- endotelin-1 krev MeSH
- hypotenze etiologie krev patofyziologie MeSH
- inhibitory ACE krev MeSH
- krevní tlak * MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny krev MeSH
- nemoci ledvin krev patofyziologie terapie MeSH
- renin krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor C krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.
- MeSH
- akutní lymfatická leukemie krev diagnóza patofyziologie MeSH
- arginin analogy a deriváty krev MeSH
- biologické markery krev MeSH
- C-reaktivní protein metabolismus MeSH
- cévní endotel metabolismus patofyziologie MeSH
- dítě MeSH
- E-selektin krev MeSH
- lidé MeSH
- mladiství MeSH
- nemoci cév krev diagnóza patofyziologie MeSH
- pletysmografie metody MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. OBJECTIVES: The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. METHODS: Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. RESULTS: Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients' age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p < 0.001) with both increased CHA2DS2-VASc and HAS-BLED scores, but decreased in the presence of diabetes. On multivariable analysis adjusting for established risk factors and treatment, tertile groups of ADMA concentrations were significantly associated with stroke/systemic embolism (p = 0.034), and death (p < 0.0001), whereas tertile groups of SDMA were associated with major bleeding and death (p < 0.001 for both). Incorporating ADMA and SDMA into CHA2DS2-VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither ADMA nor SDMA predicted differential responses to warfarin or apixaban. CONCLUSIONS: In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984).
- MeSH
- antikoagulancia terapeutické užití MeSH
- arginin analogy a deriváty krev MeSH
- biologické markery krev MeSH
- dvojitá slepá metoda MeSH
- fibrilace síní krev diagnóza farmakoterapie MeSH
- inhibitory faktoru Xa terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- pyrazoly terapeutické užití MeSH
- pyridony terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- warfarin terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- MeSH
- arginin analogy a deriváty analýza krev MeSH
- arterie patofyziologie MeSH
- aterosklerotický plát * diagnóza MeSH
- ateroskleróza * diagnóza MeSH
- ELISA metody MeSH
- klinická studie jako téma MeSH
- klinické laboratorní techniky * metody MeSH
- lidé MeSH
- matrixové metaloproteinasy analýza krev MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
BACKGROUND: Femoral neck fractures are a common occurrence in patients suffering from osteoporosis, while intracapsular hip fracture is rare in cases of osteoarthritis of the hip. Previous histomorphometric studies have emphasized the association between bone microarchitecture and the risk of low-impact fractures in osteoarthritis and osteoporosis patients. However, the strength of bone material is also a function of composition of organic bone matrix. In order to compare tissue material properties in these two clinical conditions, serum and bone pentosidine, a non-enzymatic collagen crosslinking element, was measured in patients who suffered a low-impact fracture, and in patients with advanced osteoarthritis. METHODS: The patient population consisted of 70 patients who underwent hemiarthroplasty surgery for a femoral neck fracture, and 41 patients with advanced hip joint osteoarthritis without a history of low- impact fracture, who were indicated for total hip joint replacement. Pentosidine content was analyzed in bone samples and in serum obtained from fracture and osteoarthritis patients using high performance liquid chromatography. RESULTS: Serum and bone concentrations of pentosidine were higher in subjects with hip fractures compared with osteoarthritis after adjustment for age, sex, weight, serum creatinine, and diabetes. A significant positive correlation was found between bone and serum pentosidine in fractured cases. A comparable relationship was also demonstrated for pentosidine levels in serum and bone relative to differentiation of fracture and osteoarthritis cases. CONCLUSIONS: Serum pentosidine can be considered a potential biomarker for identification of subjects with impaired bone quality and bone strength.
- MeSH
- arginin analogy a deriváty krev MeSH
- artróza kyčelních kloubů krev MeSH
- biologické markery krev MeSH
- biopsie MeSH
- femur chemie patologie MeSH
- fraktury krčku femuru krev chirurgie MeSH
- kostní denzita MeSH
- lidé středního věku MeSH
- lidé MeSH
- lysin analogy a deriváty krev MeSH
- náhrada kyčelního kloubu MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
The cornerstone of cardiovascular risk management is lifestyle intervention including exercise which could exert favorable impact also in renal transplant recipients. Nevertheless, reliable assessment of the effect of lifestyle interventions is complicated and the available data in this population are not consistent. The aim of the study was to evaluate the effect of physical activity on selected laboratory markers of vascular health including circulating stem cells, endothelial progenitor cells, microparticles, and plasma asymmetric dimethyl arginine in renal transplant recipients. Nineteen men and 7 women were recruited in 6-month program of standardized and supervised exercise. Control group consisted of 23 men and 13 women of similar age and body mass index not included into the program. One year after the transplantation, the main difference between intervention and control group was found in the change of endothelial progenitor cells (p=0.006). Surprisingly, more favorable change was seen in the control group in which endothelial progenitor cells significantly increased compared to the intervention group. The explanation of this finding might be a chronic activation of reparative mechanisms of vascular system in the population exposed to multiple risk factors which is expressed as relatively increased number of endothelial progenitor cells. Therefore, their decrease induced by exercise might reflect stabilization of these processes.
- MeSH
- arginin analogy a deriváty krev MeSH
- cévy fyziologie MeSH
- cvičení fyziologie MeSH
- dospělí MeSH
- endoteliální progenitorové buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikropartikule MeSH
- prospektivní studie MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
OBJECTIVE: The present study aimed to verify the reference intervals of plasma matrix metalloproteinases (MMPs) 2, 3, and 9 and serum asymmetric dimethylarginine (ADMA) in a healthy population with an average age corresponding to that of patients with cardiovascular diseases. METHODS: The study included 180 healthy volunteers. Plasma MMP-2, MMP-3, MMP-9, and serum ADMA levels were determined using an enzyme-linked immunosorbent assay. These levels were analyzed for association with age and gender. The Cbstat5, R software, and NCSS 2007 programs were used for statistical analysis. RESULTS: The average volunteer age was 47.4 years in the group in which MMP-3 and ADMA were analyzed, 40.3 years in the MMP-9 group, and 47.8 years for the MMP-2 group. Serum ADMA levels were determined to be independent of age and gender. Plasma MMP-2 levels were significantly correlated with age (p = 0.001), with lower levels detected in persons ≤ 49 years of age. Plasma MMP-3 was significantly associated with both age (p < 0.0001) and gender, with lower levels detected in persons of ≤ 47 years of age and among women. Plasma MMP-9 levels were not age dependent, but were associated with gender (p = 0.014), showing lower levels in women. CONCLUSIONS: Reference intervals of heparin-plasma MMP-2, MMP-3, and MMP-9 and serum ADMA levels were determined. MMP-2 and MMP-3 levels were found to be age dependent, and MMP-3 and MMP-9 levels were gender dependent.
- MeSH
- arginin analogy a deriváty krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 krev MeSH
- matrixová metaloproteinasa 3 krev MeSH
- matrixová metaloproteinasa 9 krev MeSH
- referenční hodnoty MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinická studie MeSH
- práce podpořená grantem MeSH
Levels of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) are elevated and endothelial progenitor cells (EPCs) decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. In this study, we tested the hypothesis that elevated ADMA and decreased EPC can be positively influenced with regular physical exercise early after Tx. Blood samples for analysis of ADMA and EPC were obtained from randomly selected 64 patients after Tx who agreed to participate in a supervised aerobic exercise program for 6 months (group I). Samples were collected before the training began, 1 month after surgery (with stabilized renal function), and at 6 months after initiation. Sixty-two age, sex, human leukocyte antigens (HLA) typing, duration of previous dialysis, history of cardiovascular disease, and immunosupression regimen-matched transplant patients who did not exercise regularly were examined as controls (group II). There were no differences in ADMA levels and EPC count between both groups before the training program began. After 6 months of exercise, ADMA concentration in the group I decreased (3.50 ± 0.45 vs. 2.11 ± 0.35 μmol/L; P < .01) and was also lower comparing with group II (2.11 ± 0.23 vs. 3.25 ± 0.35 μmol/L; P < .01). In the same period, EPC cells increased from 2.085 ± 650 cells/mL versus 3.991 ± 560 cells/mL, P < .01 in group I; but in group II, changes were nonsignificant (P = .11). Blood lipids, HbA1c, insulin, and systolic blood pressure were also affected by the training program. Elevated ADMA level and decreased EPC count were significantly influenced by early regular exercise in patients after Tx.
- MeSH
- arginin analogy a deriváty krev MeSH
- dospělí MeSH
- endoteliální progenitorové buňky * MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- pooperační komplikace prevence a kontrola MeSH
- prospektivní studie MeSH
- senioři MeSH
- terapie cvičením * MeSH
- transplantace ledvin * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND/AIMS: To assess, in a prospective cohort study of 238 renal transplant patients, our hypothesis that elevated ADMA levels may be influenced by physical exercise and obesity. METHODS: Blood samples before and after six months were obtained from 116 transplant patients participating in an aerobic exercise (Group I). A control group consisted of 122 matched transplant patients who did not exercise regularly (Group II). RESULTS: There were no significant differences in ADMA levels between both groups before the training program (Group IB vs. Group IIB). After six months of exercise, ADMA levels in Group I decreased (Group IB vs. Group IA : 3.50 ± 0.45 vs. 2.11 ± 0.35 μmol/L; p< 0.01) and were lower compared to those in Group II (Group IA vs. Group IIA : 2 11 ± 0 23 vs 3 25 ± 0 34 μmol/L; p< 0 01) Analysis of our results in obese renal transplant recipients (BMI B 30 kg/m(2)) confirmed a smaller effect of exercise training (Group IBO vs Group IAO : 3 75 ± 0 52 vs 3 45 ± 0 45; p< 0 05 and Group IAO vs. Group IIAO : 3.45 ± 0.45 vs. 3.74 ± 0.62; p<0.05). Blood lipids, HbA1C, insulin, and systolic BP were also affected by the training program. CONCLUSION: Elevated ADMA levels were significantly decreased by early exercise after renal transplantation. The effect of exercise was smaller in obese patients.
- MeSH
- antropometrie MeSH
- arginin analogy a deriváty krev MeSH
- dospělí MeSH
- glykovaný hemoglobin analýza MeSH
- inzulin krev MeSH
- kohortové studie MeSH
- krevní tlak fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy krev MeSH
- obezita krev MeSH
- prospektivní studie MeSH
- senioři MeSH
- tělesná výkonnost MeSH
- terapie cvičením metody MeSH
- transplantace ledvin metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
