Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Implantace totální kloubní náhrady je jednou z nejúspěšnějších a nejúčinnějších ortopedických operací v posledním století. V tomto projektu chceme monitorovat a porovnávat zátěž těžkými kovy v cirkulaci, zejména Ti, Co, Cr, Ni, u pacientů po implantaci kloubní náhrady ve srovnání s populací České republiky bez implantátů jakéhokoliv kovu. Korelace dynamiky hojení a tolerance kovového materiálu bude hodnocena s klinickou symptomatologií, funkčními parametry s ohledem na vývoj a průběh komplikací po implantaci endoprotéz, včetně reimplantace. Procesy spojené s aktivací imunitního systému, včetně reakcí přecitlivělosti, budou simulovány na modelu in vitro za použití imunitního systému individuálního pacienta. Pokus o nalezení prediktivních markerů spojených se špatnou prognózou po implantaci v periferní krvi by mohl vést k včasnému zjištění komplikací. Povrch explantovaných náhrad bude hodnocen z hlediska opotřebení, koroze, defektů kovu.; Total-joint arthroplasty is one of the most successful and effective orthopedic operations performed during the last century. In the present project, we intend to monitor and compare heavy metal load in circulation, especially Ti, Co, Cr, Ni, in patients after implantation of joint replacement compared to the Czech Republic without implants of any metal. The correlation of the healing process dynamics and the tolerance of the metal material will be evaluated with clinical symptomatology, functional parameters with respect to the development and course of complications after implantation of the endoprostheses, including reimplantation. Processes associated with the activation of the immune system, including hypersensitivity reactions, will be simulated on an in vitro model using individual patient immune systems. Attempting to find predictive markers associated with poor prognosis after implantation in peripheral blood could lead to early detection of complications. The metal surface of the explanted substitutes will be evaluated in terms of wear, corrosion, metal defects.
- Klíčová slova
- implantace, hypersenzitivita, implantation, hypersensitivity, kov, metal, imunitní systém, Osteoartróza, totální kloubní náhrada, osteoblasty, osteoarthrosis, total joint arthroplasty, immmune system, osteoblasts, reimplantace, reimplantation,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
The aim of study was to examine relation among miR-124 and serum levels of selected cytokines and chemokines, MMP-3, production of auto-antibodies, and factors describing clinical activity (DAS28) and radiographic progression in rheumatoid arthritis (RA). A total of 80 RA patients according to the ACR classification criteria, and 32 control subjects were recruited into study. The measurements of miR-124 and U-6 expression, CRP, anti-CCP, rheumatoid factors (RFs), radiographs of both hands with calculation of total sharp score (TSS), DAS28 and cytokines, chemokines and MMP levels in serum were obtained from all RA patients. miR-124 was down-regulated in RA patients compared to controls (7-fold decrease). The miR-124 expression correlated to MMP-3 levels (p < 0.001), which were in multivariate analysis associated to age of RA onset. Higher levels were detected in younger subjects. No relation of miR-124 expression to measures of RA activity (DAS28 score; TSS), auto-antibodies (anti-CCP, RF, RF IgG, RF IgA, RF IgM), acute inflammatory markers (CRP, IL-6), and other cytokine and chemokines (IL-13, IL-15, IL-8, TNF-α, MCP-1, RANTES) was observed. In conclusion, we present a down-regulation of miR-124 in RA patients and its correlation to MMP-3 levels, which associated to age of RA onset.
- MeSH
- akutní nemoc MeSH
- biologické markery krev MeSH
- cirkulující mikroRNA * krev MeSH
- infarkt myokardu s elevacemi ST úseků patofyziologie MeSH
- kardiogenní šok * patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard metabolismus MeSH
- prognóza MeSH
- senioři MeSH
- statistika jako téma MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
The influence of polymorphisms in the large group of MMP and TIMP genes on clinical outcomes in patients after ST elevation myocardial infarction (STEMI) treated with primary PCI was analysed. In total, 550 consecutive Caucasian patients with STEMI were included in the present study, with a median of 32 months. We analysed 19 polymorphisms in the genes coding MMP and TIMP genes. The MMP-1 -519A/G and -422A/T polymorphisms are associated with combined endpoint after myocardial infarction. The hazard ratio for AT variant of MMP-1 -422A/T was 1.75 (p < 0.001); the variants with at least one A allele of MMP-1 -519A/G have less risk of combined endpoint. The TT variants of -1562C/T MMP-9 and at least one T allele of +92C/T MMP-13 were considered in a trend to affect disease progression and long-term survival after myocardial infarction. According to reclassification analysis NRI and IDI, long-term risk stratification using MMP-1 -422A/T and -519A/G polymorphisms gives additional information to the commonly used GRACE risk score. Patient stratification after myocardial infraction (MI) according to risk genotypes of MMP-1 polymorphisms could have important clinical implications for identification of patients at risk and therapeutic strategies.
- MeSH
- alely MeSH
- dospělí MeSH
- infarkt myokardu s elevacemi ST úseků diagnóza genetika MeSH
- koronární angioplastika MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 1 genetika MeSH
- matrixová metaloproteinasa 13 genetika MeSH
- matrixová metaloproteinasa 9 genetika MeSH
- polymorfismus genetický MeSH
- prognóza MeSH
- rizikové faktory MeSH
- senioři MeSH
- tkáňové inhibitory metaloproteinas genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Vydání první 186 stran : ilustrace ; 25 cm
The aim of study was to examine relationship among levels of cytokines (IL-6, IL-13, IL-15, TNF-α) and chemokine (IL-8), production of autoantibodies, radiographic progression, and factors describing rheumatoid arthritis (RA). A total of 156 RA patients according to ACR criteria, and 55 control subjects were recruited into study. We observed higher levels of IL-15 within RA patients compared to healthy controls. Correlations among cytokine levels and the measures of rheumatoid factors, anti-CCP, measures of disease activity, and radiographic progression were observed. We conclude that IL-15 level in circulation could serve as one of the biomarkers for RA detection.
- MeSH
- autoprotilátky krev MeSH
- biologické markery krev MeSH
- cyklické peptidy imunologie MeSH
- cytokiny krev MeSH
- dospělí MeSH
- interleukin-15 krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- progrese nemoci MeSH
- revmatoidní artritida krev imunologie radiografie MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The MCP-1/CCL2 as well as RANTES/CCL5 chemokines are potent chemoattractants involved in immunoregulatory and inflammatory processes of rheumatoid arthritis. Recent studies demonstrated elevated levels of MCP-1 and RANTES in plasma, synovial fluid, and the synovial tissue of patients with RA. To examine the relationship among MCP-1 and RANTES single nucleotide polymorphisms and circulating levels and rheumatoid arthritis (RA), a total of 156 RA patients and 125 controls were recruited into the study. An association of -855 C/G MCP-1 polymorphism to IgM RF within the RA patients was observed. The lowest circulating levels of RANTES were observed in the AA variant of RANTES -403 G/A polymorphism. Furthermore, an association of -403 AA variant to circulating levels of IL-15 and IL-10 was found. No associations of factors describing rheumatoid arthritis (RFs, ANA, anti-CCP-positive/negative, DAS 28 score and number of swollen joints) with MCP-1 levels, genotype distribution, allelic frequencies and/or frequencies of haplotypes composed of all three studied polymorphisms in promoter region of MCP-1, and RANTES polymorphism were observed. We conclude that the RANTES promoter polymorphism is associated to circulating levels of RANTES, IL15 and IL10. However, our findings suggest that polymorphisms in the MCP-1 and RANTES gene promoters do not contribute significantly to the interindividual RA susceptibility and/or severity in Caucasians.
- MeSH
- chemokin CCL2 krev genetika imunologie MeSH
- chemokin CCL5 krev genetika imunologie MeSH
- dospělí MeSH
- imunoglobulin M genetika imunologie MeSH
- interleukin-10 krev MeSH
- interleukin-15 krev MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- promotorové oblasti (genetika) MeSH
- revmatoidní artritida genetika imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- synoviální membrána metabolismus MeSH
- synoviální tekutina metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Numerous association studies have been involved in studying the angiotensinogen (AGT) variants, AGT plasma levels and relations to cardiovascular diseases, such as hypertension, myocardial infarction, coronary heart disease. To investigate a role of AGT G(-6)A and M235T genetic variants for chronic heart failure (CHF) and advanced atherosclerosis (AA), a total of 240 patients with CHF and 200 patients with AA of the Czech origin were evaluated for the study. The study shows the role of polymorphism AGT G(-6)A in genetic background among advanced atherosclerosis patients and chronic heart failure patients (Pg=0.001). This difference was also observed in comparison of AA patients with subgroup of CHF with dilated cardiomyopathy (Pg=0.02; Pa=0.009), and ischemic heart disease (Pg=0.007). The greatest difference between triple-vessel disease and chronic heart failure groups was observed in frequency of GT haplotype (P<0.001) and GGMT associated genotype (P<0.001). Retrospectively, we found the same trend when the subgroups of CHF were compared to AA group (AA vs. IHD with CHF P<0.001; AA vs. DCM P<0.001). These results suggest AGT genetic variants as a risk factor for chronic heart failure compared to advanced atherosclerosis disease without heart failure, with a strong difference between IHD patients and chronic heart failure patients with ischemic heart disease, especially in haplotypes and associated genotypes. PMID:20945963[PubMed - in process] Free Article LinkOut - more resourcesFull Text SourcesInstitute of Physiology, Academy of Sciences of the Czech Republic, Prague - PDFEBSCO • Supplemental Content Related citations Association of two angiotensinogen gene polymorphisms, M235T and G(-6)A, with chronic heart failure. [Int J Cardiol. 2003] Association of two angiotensinogen gene polymorphisms, M235T and G(-6)A, with chronic heart failure. Goldbergova M, Spinarova L, Spinar J, Toman J, Vasku A, Vacha J. Int J Cardiol. 2003 Jun; 89(2-3):267-72. Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population. [Heart Vessels. 2009] Association between variants in the genes for leptin, leptin receptor, and proopiomelanocortin with chronic heart failure in the Czech population. Bienertová-Vasků JA, Spinarová L, Bienert P, Vasků A. Heart Vessels. 2009 Mar; 24(2):131-7. Epub 2009 Apr 1.Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease. [Am Heart J. 1999] Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease. Winkelmann BR, Russ AP, Nauck M, Klein B, Böhm BO, Maier V, Zotz R, Matheis G, Wolf A, Wieland H, et al. Am Heart J. 1999 Apr; 137(4 Pt 1):698-705. Renin-angiotensin system gene polymorphisms: assessment of the risk of coronary heart disease. [Kardiol Pol. 2003] Renin-angiotensin system gene polymorphisms: assessment of the risk of coronary heart disease. Buraczyńska M, Pijanowski Z, Spasiewicz D, Nowicka T, Sodolski T, Widomska - Czekajska T, Ksiazek A. Kardiol Pol. 2003 Jan; 58(1):1-9. Review A haplotype of the angiotensinogen gene is associated with hypertension in african americans. [Clin Exp Pharmacol Physiol. 2005] Review A haplotype of the angiotensinogen gene is associated with hypertension in african americans. Kumar A, Li Y, Patil S, Jain S. Clin Exp Pharmacol Physiol. 2005 May-Jun; 32(5-6):495-502. See reviews... See all... All links from this record Related Citations Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.Gene Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.Gene (GeneRIF) Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.HomoloGene HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.Nucleotide Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
- MeSH
- angiotensinogen genetika MeSH
- ateroskleróza genetika MeSH
- dospělí MeSH
- financování organizované MeSH
- frekvence genu genetika MeSH
- genotyp MeSH
- haplotypy MeSH
- hypertenze MeSH
- koronární nemoc genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční selhání genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il., tab. ; 31 cm
Zhodnocení genetické variability genů pro MMP, TIMP a ACE vzhledem k akutnímu infarktu myokardu a jeho intermediálnímu fenotypu, včetně analýzy sérovýchh hladin vybraných působků. Metod PCR a RFLP bude využito ke stanovení promotorových a intronových polymorfismů. Nové polymorfismy budou v regulačních oblastech genů detekovány pomocí heteroduplexní analýzy a SSCP. Proteinové hladiny vybraných působků budou hodnoceny pomocí ELISA metody. K vyjádření vtahu mezi genotypy a onemocněním bude využita tzv. "case-control" studie (asociační studie - "případ-kontroly"). Data budou sumarizována jednak běžnými statickým metodami (chi-kvadrát test, Fisher exakt test, odds ratio, ..) zaměřenými na hlavní cílové parametry projektu a dále je plánována vícerozměrná analýza rizikových faktorů.; Assesment of genetic variability of MMP, TIMP and ACE genes in respect to acute infarct myocardum and its intermediate phenotype, inclusive of the analysis of selected serum levels. For detection of pholymorphisms in promoter and intone regions, PCR andRFLP methods will be used. New polymorphisms in regulatory regions of MMP and TIMP genes will be detected by heteroduplex analysis and SSCP. The serum levels will be measured by ELISA method. The "case-control" (association) study will be used to assessthe relation between genotype and disease. The data will be summarised by common statistic methods (chi-square test, Fisher's exact test and odds ratio) and further the analysis of risk factors is planed.
- MeSH
- beta blokátory terapeutické užití MeSH
- infarkt myokardu MeSH
- inhibitory ACE terapeutické užití MeSH
- inhibitory matrixových metaloproteinas MeSH
- matrixová metaloproteinasa 12 MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- polymorfismus genetický MeSH
- polymorfismus konformace jednovláknové DNA MeSH
- prognóza MeSH
- remodelace komor MeSH
- tkáňové inhibitory metaloproteinas MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- kardiologie
- biologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
