Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11+/-1.15 x 10(3) AU/g vs controls 4.08+/-0.71 x 10(3) AU/g, p<0.001, vs DM1 4.14+/-0.86 x 10(3) AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50+/-75.15 micromol/l vs healthy subjects 79.80+/-23.72 micromol/l, p<0.001, vs DM1 97.50+/-30.91 micromol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products.

• MeSH
• diabetes mellitus 1. typu krev   MeSH
• diabetes mellitus 2. typu krev   MeSH
• dospělí MeSH
• krevní proteiny analýza   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oxidace-redukce MeSH
• oxidační stres fyziologie   MeSH
• produkty pokročilé glykace krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• statistika jako téma MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• krevní proteiny MeSH
• produkty pokročilé glykace MeSH

OBJECTIVE: To determine umbilical cord blood total antioxidant capacity (TAC), ferric reducing antioxidant power (FRAP), thiobarbituric acid-reacting substances (TBARS), advanced glycation end products (AGEs) and markers of oxidative stress in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) and their associations with microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA), funisitis and selected aspects of short-term neonatal morbidity. MATERIALS AND METHODS: One hundred and sixty-five women with singleton pregnancies complicated by PPROM were included in this study. Blood samples were obtained by venipuncture from the umbilical cord vein after the delivery of the newborn. The umbilical cord blood concentrations of TAC, FRAP, TBARS and AGEs were measured. RESULTS: The presence of MIAC, HCA and funisitis did not show differences in the umbilical cord blood TAC, FRAP, TBARS and AGEs concentrations. Positive correlations were found between the gestational age at sampling and umbilical cord blood TAC and AGEs concentrations (TAC: rho = 0.26; p = 0.001; AGEs: rho = 0.35; p < 0.0001). There was no association between umbilical cord blood TAC, FRAP, TBARS and AGEs concentrations and selected aspects of short-term neonatal morbidity. CONCLUSIONS: Oxidative stress is associated with PPROM, as indicated by the presence of markers tested in the umbilical cord blood; however, the evaluated oxidative stress markers are not influenced by the presence of MIAC and/or HCA, and funisitis or subsequent development of selected aspects of short-term neonatal morbidity.

• Klíčová slova
• Advanced glycation end products, ferric reducing antioxidant power, histological chorioamnionitis, microbial invasion of the amniotic cavity, preterm delivery, rupture of membranes, thiobarbituric acid-reacting substances, total antioxidant capacity,
• MeSH
• antioxidancia metabolismus   MeSH
• biologické markery krev   MeSH
• chorioamnionitida krev   MeSH
• dospělí MeSH
• fetální krev chemie   MeSH
• gestační stáří MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• oxidační stres * MeSH
• předčasný odtok plodové vody krev   MeSH
• produkty pokročilé glykace krev   MeSH
• prospektivní studie MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antioxidancia MeSH
• biologické markery MeSH
• látky reagující s kyselinou thiobarbiturovou MeSH
• produkty pokročilé glykace MeSH

BACKGROUND: The aim of the study was to assess the contribution of carbonyl and oxidative stresses to the development of amyloidosis in patients suffering from chronic rheumatic diseases, and the potential influence of renal function to their concentrations was considered. METHODS: We investigated 17 patients with chronic rheumatological diseases and histologically proven diagnosis of AA amyloidosis (group AA-RA), 26 patients suffering from rheumatoid arthritis without any signs of AA amyloidosis (group nonAA-RA) and 20 healthy volunteers (Co). In all patients, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), pregnancy-associated plasma protein A (PAPP-A) and other selected proinflammatory markers were measured. RESULTS: An increase in serum levels of AOPP and AGEs was found in the AA-RA group in comparison with nonAA-RA patients and also with Co (p < 0.001 for all comparisons). AGEs positively correlated with serum creatinine (r = 0.67, p = 0.004) and negatively with glomerular filtration rate (r = -0.54, p = 0.027). We did not find a correlation between AOPP and any other assessed parameters including proteins and renal parameters. PAPP-A levels were not significantly increased in any group of patients (AA-RA, nonAA-RA) in comparison with Co. CONCLUSIONS: Increased plasma levels of AGEs and AOPP in the group of patients with AA-RA may have been partly explained by the diminished renal clearance. However, the increase in AOPP levels was higher than what is expected in this degree of renal failure (glomerular filtration rate in the AA-RA group corresponding to chronic kidney disease stage III).

• MeSH
• amyloidóza krev   etiologie   MeSH
• biologické markery krev   MeSH
• chronická nemoc MeSH
• cytokiny krev   MeSH
• glykosylace MeSH
• kohortové studie MeSH
• ledviny patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oxidace-redukce MeSH
• oxidační stres MeSH
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory imunologické krev   MeSH
• revmatické nemoci krev   komplikace   patofyziologie   MeSH
• senioři MeSH
• těhotenský plazmatický protein A metabolismus   MeSH
• vyšetření funkce ledvin MeSH
• zánět krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• receptor pro konečné produkty pokročilé glykace MeSH
• receptory imunologické MeSH
• těhotenský plazmatický protein A MeSH

While the pathogenic role of dicarbonyl stress and accelerated formation of advanced glycation end products (AGEs) to glucose intolerance and to the development of diabetic complications is well established, little is known about these processes in gestational diabetes mellitus (GDM), a condition pathogenically quite similar to type 2 diabetes. The aims of the present study were (i) to determine plasma thiamine and erythrocyte thiamine diphosphate (TDP) and transketolase (TKT) activity in pregnant women with and without GDM, (ii) to assess relationships between thiamine metabolism parameters and selected clinical, biochemical and anthropometric characteristics and, finally, (iii) to analyse relationship between variability in the genes involved in the regulation of transmembrane thiamine transport (i.e. SLC19A2 and SLC19A3) and relevant parameters of thiamine metabolism. We found significantly lower plasma BMI adjusted thiamine in women with GDM (P = 0.002, Mann-Whitney) while levels of erythrocyte TDP (an active TKT cofactor) in mid-trimester were significantly higher in GDM compared to controls (P = 0.04, Mann-Whitney). However, mid-gestational TKT activity - reflecting pentose phosphate pathway activity - did not differ between the two groups (P > 0.05, Mann-Whitney). Furthermore, we ascertained significant associations of postpartum TKT activity with SNPs SLC19A2 rs6656822 and SLC19A3 rs7567984 (P = 0.03 and P = 0.007, resp., Kruskal-Wallis). Our findings of increased thiamine delivery to the cells without concomitant increase of TKT activity in women with GDM therefore indicate possible pathogenic role of thiamine mishandling in GDM. Further studies are needed to determine its contribution to maternal and/or neonatal morbidity.

• Klíčová slova
• Advanced glycation end products, Gestational diabetes mellitus, Oral glucose tolerance test, Pregnancy, Thiamine,
• MeSH
• dospělí MeSH
• erytrocyty metabolismus   MeSH
• gestační diabetes krev   MeSH
• lidé MeSH
• membránové transportní proteiny krev   MeSH
• následné studie MeSH
• produkty pokročilé glykace krev   MeSH
• těhotenství MeSH
• thiaminpyrofosfát krev   MeSH
• transketolasa krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• membránové transportní proteiny MeSH
• produkty pokročilé glykace MeSH
• SLC19A2 protein, human MeSH Prohlížeč
• SLC19A3 protein, human MeSH Prohlížeč
• thiaminpyrofosfát MeSH
• transketolasa MeSH

The authors aimed to evaluate if the monitoring of serum advanced glycation end-products (s-AGEs) could help to predict a development of diabetic complications. Clinical and biochemical parameters including fructosamine (FAM), glycated hemoglobin (HbA1c) and serum AGEs were investigated in children and adolescents with 1 type diabetes with (+DC) and without (-DC) complications. FAM levels (in mmol/l) were significantly elevated in +DC diabetic group compared to -DC one (3.043+/-0.459 vs. 2.614+/-0.430; p<0.001) or to controls (3.043+/-0.459 vs. 1.620+/-0.340; p<0.001) as well as in -DC compared to controls (2.614+/-0.430 vs. 1.620+/-0.340; p<0.001). HbA1c (in %) were significantly elevated in +DC diabetic group compared to -DC one (10.48+/-1.83 vs. 8.41+/-1.19; p<<0.001) or to controls (10.48+/-1.83 vs. 5.0+/-0.38, p<<0.001) and also in -DC compared to controls (8.41+/-1.19 vs. 5.0+/-0.38; p<0.001). Serum AGEs levels (in A. U.) were significantly higher in +DC group than in -DC (73.0+/-14.09 vs. 65.8+/-9.05; p<0.05) and in group +DC than in controls (73.0+/-14.09 vs. 60.17+/-13.78; p<0.05), whereas there was no difference between -DC and controls. FAM correlated with HbA1c in both diabetic groups (+DC: r=0.374; p<0.05; -DC: r=0.719; p<0.001), but not in controls. Serum AGEs were correlated with HbA1c (r=0.478; p=0.003) in +DC, but not in -DC or controls. Enhanced serum AGEs levels show that they could be not only an attendant phenomenon of microangiopathies, but also a predictor of their development.

• MeSH
• diabetes mellitus 1. typu komplikace   MeSH
• diabetické angiopatie krev   MeSH
• dítě MeSH
• fruktosamin krev   MeSH
• glykosylace MeSH
• glykovaný hemoglobin metabolismus   MeSH
• kapilární permeabilita fyziologie   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• produkty pokročilé glykace krev   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• fruktosamin MeSH
• glykovaný hemoglobin MeSH
• krevní glukóza MeSH
• produkty pokročilé glykace MeSH

The receptor for the advanced glycation end products (RAGE) is a multiligand transmembrane receptor involved in chronic inflammation whose specific polymorphisms of the promoter gene were found to increase its transcriptional activity. We investigated the association of both allelic and genotypic -374T/A and -429T/C polymorphisms with inflammatory bowel disease. The STREGA guidelines were applied for planning and reporting. We enrolled 133 patients with Crohn's disease (CD), 149 with ulcerative colitis (UC), and 128 blood donors. Genomic DNA was extracted from peripheral blood leukocytes collected from each patient and control. RAGE polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. The Hardy-Weinberg equilibrium was first assessed, and then, the Kruskal-Wallis test and the Fisher exact test were used for etiologic group comparisons. Distribution of patients' characteristics across genotypes was evaluated by the Fisher exact test, while that across alleles was analyzed with a probit model. A 2-sided value of p < 0.05 was considered significant. Following the evidence of the Hardy-Weinberg equilibrium, we found a higher prevalence of the allele A of the -374T/A haplotype in UC (p = 0.043), and of the allele C of the -429T/C haplotype in CD (p < 0.001) with respect to the other groups. Moreover, the homozygous AA genotype of the -374T/A polymorphism resulted associated with late onset of CD, while its TT genotype with early onset (p = 0.049). The allele C of the 429T/C haplotype was associated with early onset of UC (p = 0.03), while a higher frequency of the heterozygous TC haplotype was found in those with pancolitis (p = 0.026). The differing distribution of these polymorphisms in healthy donors and CD/UC patients suggests a role in the development and outcome of these pathological conditions.

• Klíčová slova
• Gene polymorphisms, Inflammatory bowel disease, RAGE,
• MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• genotypizační techniky MeSH
• idiopatické střevní záněty genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• prevalence MeSH
• promotorové oblasti (genetika) * MeSH
• receptor pro konečné produkty pokročilé glykace genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AGER protein, human MeSH Prohlížeč
• receptor pro konečné produkty pokročilé glykace MeSH

Between the aggregated and in tissues properly deposited collagen molecules crosslinking elements, e.g. pyridinoline and deoxy-pyridinoline, are enzymatically formed. These triple-functional crosslinks are located at specific sites of the collagen chains, bind covalently its molecules, and contribute to the stability of collagen structure. Analogical quadruple-functional crosslinks are formed in the elastin, i.e. desmosine and isodesmosine, which have essential physiological functions in the body. When either collagen or elastin becomes resorbed, all the crossling elements are released into blood, and they concentrate in urine. Assessment of these elements in the body fluids can be used as an indicator of the disintegration kinetics of both tissues. Practically in all long-living tissues of the organism, a cascade of non-enzymatic chemical reactions between reducing sugars and free amino-groups generates the so-called AGE-derivatives. This family of substances, represented by pentosidine, acts in the body exclusively negatively. Their determination in tissues and in body fluids represents important markers in the clinical investigation of various diseases. The possible mechanisms of the enzymatically and non-enzymatically formed crosslinks are discussed, and the relation of AGE-derivatives to various diagnostical findings is mentioned.

• MeSH
• elastin chemie   metabolismus   MeSH
• glykosylace MeSH
• kolagen chemie   metabolismus   MeSH
• lidé MeSH
• molekulární struktura MeSH
• produkty pokročilé glykace metabolismus   MeSH
• reagencia zkříženě vázaná chemie   MeSH
• stárnutí metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• elastin MeSH
• kolagen MeSH
• produkty pokročilé glykace MeSH
• reagencia zkříženě vázaná MeSH

UNLABELLED: Two first-order mathematical models were developed to mimic the glycation of haemoglobin (H) and albumin (A). The total concentrations of A and H were assumed to be constant. The responses of the two models to varying blood glucose level were compared. The parameters of the haemoglobin model were not numerically estimated, only an informal fit was performed using clinical and published data. Nonlinear regression analysis was used to estimate the parameters of the albumin model. The level of glycated A (GA) was derived from the measured fructosamine level. Three diabetics were monitored daily for the level of fructosamine and blood glucose profile over a period of 10, 16 and 21 days, respectively. CONCLUSIONS: (1) The difference between GA and glycated H (GH) resulting from different elimination rates is decreased by the stratification of erythrocyte population. (2) Both GA and GH seem to have higher elimination rates than their nonglycated equivalents.

• MeSH
• biologické modely * MeSH
• diabetes mellitus 1. typu metabolismus   MeSH
• fruktosamin MeSH
• glykosylace MeSH
• glykovaný hemoglobin metabolismus   MeSH
• glykovaný sérový albumin MeSH
• hexosaminy metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• monitorování fyziologických funkcí MeSH
• obezita metabolismus   MeSH
• počítačová simulace * MeSH
• poločas MeSH
• produkty pokročilé glykace MeSH
• sérový albumin metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fruktosamin MeSH
• glykovaný hemoglobin MeSH
• glykovaný sérový albumin MeSH
• hexosaminy MeSH
• krevní glukóza MeSH
• produkty pokročilé glykace MeSH
• sérový albumin MeSH

Preventing factor VIII (FVIII) inhibitors following replacement therapies with FVIII products in patients with hemophilia A remains an unmet medical need. Better understanding of the early events of evolving FVIII inhibitors is essential for risk identification and the design of novel strategies to prevent inhibitor development. The Hemophilia Inhibitor Previously Untreated Patients (PUPs) Study (HIPS; www.clinicaltrials.gov #NCT01652027) is the first prospective cohort study to evaluate comprehensive changes in the immune system during the first 50 exposure days (EDs) to FVIII in patients with severe hemophilia A. HIPS participants were enrolled prior to their first exposure to FVIII or blood products ("true PUPs") and were evaluated for different immunological and clinical parameters at specified time points during their first 50 EDs to a single source of recombinant FVIII. Longitudinal antibody data resulting from this study indicate that there are 4 subgroups of patients expressing distinct signatures of FVIII-binding antibodies. Subgroup 1 did not develop any detectable FVIII-binding immunoglobulin G (IgG) antibodies. Subgroup 2 developed nonneutralizing, FVIII-binding IgG1 antibodies, but other FVIII-binding IgG subclasses were not observed. Subgroup 3 developed transient FVIII inhibitors associated with FVIII-binding IgG1 antibodies, similar to subgroup 2. Subgroup 4 developed persistent FVIII inhibitors associated with an initial development of high-affinity, FVIII-binding IgG1 antibodies, followed by IgG3 and IgG4 antibodies. Appearance of FVIII-binding IgG3 was always associated with persistent FVIII inhibitors and the subsequent development of FVIII-binding IgG4. Some of the antibody signatures identified in HIPS could serve as candidates for early biomarkers of FVIII inhibitor development.

• MeSH
• biologické markery MeSH
• faktor VIII MeSH
• hemofilie A * farmakoterapie   MeSH
• hemostatika * MeSH
• imunoglobulin G MeSH
• lidé MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• faktor VIII MeSH
• hemostatika * MeSH
• imunoglobulin G MeSH

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the endothelial surface markers CD31 and CD144 and the results of the functional analysis. Higher expression of endothelial progenitor markers CD34 and kinase insert domain receptor (KDR) was measured in hiPSC-derived ECs. An analysis of phosphorylated histone H2AX (γH2AX) foci revealed that an increased number of DNA double-strand breaks upon reprogramming into pluripotent cells. However, differentiation into ECs restored a normal number of γH2AX foci. Our hiPSCs retained a normal karyotype, with the exception of the HSVEC-derived hiPSC line, which displayed mosaicism due to a gain of chromosome 1. Peripheral blood from adult donors is a suitable source for the unlimited production of patient-specific ECs through the hiPSC interstage. hiPSC-derived ECs are fully functional and comparable to natural ECs. The protocol is eligible for clinical applications in regenerative medicine, if the genomic stability of the pluripotent cell stage is closely monitored.

• Klíčová slova
• endothelial differentiation, induced pluripotent stem cells, peripheral blood mononuclear cells,
• MeSH
• biologické markery metabolismus   MeSH
• buněčná diferenciace fyziologie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   metabolismus   MeSH
• endoteliální buňky cytologie   metabolismus   MeSH
• fibroblasty cytologie   metabolismus   MeSH
• fyziologická neovaskularizace fyziologie   MeSH
• indukované pluripotentní kmenové buňky cytologie   metabolismus   MeSH
• kultivované buňky MeSH
• leukocyty mononukleární cytologie   metabolismus   MeSH
• lidé MeSH
• regenerativní lékařství metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH