Ateroskleróza je charakterizovaná perzistujúcim zápalom cievnej steny a je považovaná za hlavnú príčinu napomáhajúcu rozvoju kardiovaskulárnych ochorení, ktoré sú celosvetovo vedúcou príčinou úmrtí. Z dôvodu rozšírenia aterosklerózy a jej komplikácií sa zvyšuje potreba včasnej a pokiaľ je to možné neinvazívnej diagnostiky, aby sa predišlo vzniku fatálnych alebo invalidizujúcich komplikácií aterosklerózy. Na detekciu aterosklerotických plátov sa využívajú zobrazovacie metódy aj klinické vyšetrenia, ktoré zachytávajú až pláty hemodynamicky významné. Lepšia prevencia aterosklerózy si žiada vyhľadávanie vysokorizikových jedincov vo včasných štádiách. Zápal sa prejavuje počas celého priebehu aterogenézy, teda aj v štádiu subklinickej aterosklerózy, kedy je možné stanoviť koncentráciu zápalových biomarkerov v krvi. Biomarkery sú predmetom záujmu pre jednoduchosť stanovenia v plazme či sére a možnosť ich využitia na diagnostické, prognostické aj terapeutické účely. Pozitívne korelácie s aterosklerózou a jej komplikáciami boli dokázané u biomarkerov asociovaných s metabolizmom kostí ako fibro­blastový rastový faktor 23, osteokalcín, osteoglycín, osteopontín či osteoprotegerín.

Atherosclerosis is characterized by persistent inflammation of the vascular wall and is considered to be a major cause contributing to the development of cardiovascular disease, which is the leading cause of death worldwide. Due to the prevalence of atherosclerosis and its complications, the need for early and, if possible, non-invasive dia­gnosis is increasing in order to prevent the development of fatal or disabling complications of atherosclerosis. Ima­ging methods as well as clinical examina­tions are used for the detection of atherosclerotic plaques, which capture up to hemodynamically significant plaques. Better prevention of atherosclerosis requires the search for high-risk indivi­duals in early stages. Inflammation manifests itself throughout the course of atherogenesis, i.e. also in the stage of subclinical atherosclerosis, when it is possible to determine the concentration of inflammatory biomarkers in the blood. Biomarkers are of interest for the simplicity of determination in plasma or serum and the possibility of their use for diagnostic, prognostic and therapeutic purposes. Positive correlations with atherosclerosis and its complications have been demonstrated in biomarkers associated with bone meta­bolism such as fibroblast growth factor 23, osteocalcin, osteoglycin, osteopontin or osteoprotegerin.

• Klíčová slova
• osteoglycin,
• MeSH
• ateroskleróza * diagnóza   patofyziologie   MeSH
• biologické markery MeSH
• fibroblastový růstový faktor 2 analýza   MeSH
• lidé MeSH
• osteokalcin analýza   MeSH
• osteopontin analýza   MeSH
• osteoporóza * diagnóza   patofyziologie   MeSH
• osteoprotegerin analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Úvod: Primární myelofibróza je řazena mezi Ph (Philadelphia chromosome) negativní myeloproliferativní nemoci (Ph-MPN), spolu s pravou polycytemií a esenciální trombocytemií, které ve svém průběhu taktéž mohou přecházet do fibrózy kostní dřeně. V práci byly hodnoceny biochemické markery kostní remodelace a osteoprotegerin s cílem nalezení vhodného parametru pro neinvazivní monitorování pokročilosti fibrózy kostní dřeně, dále byl posuzován kostní metabolismus, zejména význam vitaminu D. Pacienti a metody: U 34 pacientů s myelofibrózou, 13 nemocných v prefibrotické fázi primární myelofibrózy a 28 nemocných s pravou polycytemií či esenciální trombocytemií byly analyzovány markery kostní remodelace (bALP, P1NP, ICTP), kostní metabolismus a osteoprotegerin. Výsledky: Nebylo prokázáno zvýšení bALP, P1NP byl zvýšen u 18 %, ICTP u 32 % nemocných s myelofibrózou. Hodnoty nekorelovaly s pokročilostí fibrózy, nevykazovaly významný rozdíl oproti prefibrotické fázi primární myelofibrózy ani ostatním Ph-MPN. Osteoprotegerin byl zvýšen u 53 % myelofibróz, hodnoty korelovaly s pokročilostí nemoci (p = 0,0043), ale nebyly signifikantně rozdílné ve srovnání s prefibrotickou fází primární myelofibrózy či ostatními Ph-MPN. Z hodnocených parametrů kostního metabolismu byly zaznamenány významné rozdíly v hladinách vitaminu D. Ve srovnání s ostatními Ph-MPN byl jeho deficit častěji zjištěn ve skupině myelofibróz (p = 0,0003), u kterých sérové koncentrace vitaminu D korelovaly s pokročilostí choroby (p = 0,05). Závěr: Testované plazmatické parametry nejsou dostatečně citlivé pro neinvazivní monitorování fibrózy kostní dřeně v rutinní klinické praxi. Zvýšená exprese OPG zřejmě hraje roli v patogenezi myelofibrózy. U MF jsou nižší sérové koncentrace vitaminu D ve srovnání s ostatními Ph-MPN, tíže jeho deficitu koreluje s pokročilostí choroby. S ohledem na skutečnost, že se vitamin D spolupodílí na inhibici JAK/STAT signální dráhy, vyvstává aktuální potřeba ověřit jeho prognostický význam v éře JAK inhibitorů.

Introduction: Primary myelofibrosis belongs to a group of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPN) together with essential thrombocythemia and polycythemia vera, which may also progress to bone marrow fibrosis. The study assessed biochemical markers of bone remodeling and osteoprotegerin to find a suitable marker for non-invasive monitoring of bone marrow fibrosis, as well as bone metabolism, in particular the role of vitamin D. Patients and methods: Bone remodeling markers (bALP, P1NP, ICTP), bone metabolism and osteoprotegerin were analyzed in 34 patients with myelofibrosis, 13 patients with prefibrotic primary myelofibrosis and a group of 28 patients with essential thrombocythemia and polycythemia vera. Results: There was no increase in bALP, P1NP and ICTP were elevated in 18% and 32% of MF, respectively. The values neither correlated with fibrosis stage nor showed significant differences compared to the other Ph-MPN. Osteoprotegerin was increased in 53% of myelofibrosis, values correlated with myelofibrosis risk status (p = 0.0043) but did not show a significant difference compared to the other Ph-MPN. Among bone metabolism parameters, significant differences were noted for vitamin D levels. Myelofibrosis had significantly lower vitamin D levels than the other Ph-MPN (p = 0.0003), the values correlated with MF risk status (p = 0.05). Conclusion: The tested parameters are not sensitive enough for non-invasive monitoring of bone marrow fibrosis in routine clinical practice. Increased expression of osteoprotegerin is likely to play a role in the pathogenesis of myelofibrosis. Serum concentrations of vitamin D are significantly lower in myelofibrosis; the severity of its deficiency correlates with disease stage. Given the fact that vitamin D participates in inhibition of the JAK/STAT signaling pathway, there is an urgent need to verify its prognostic value in the present-day era of JAK inhibitors.

• Klíčová slova
• Ph-myeloproliferace, kostní obrat,
• MeSH
• dospělí MeSH
• klinická studie jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• nedostatek vitaminu D * MeSH
• osteoprotegerin analýza   MeSH
• primární myelofibróza * genetika   patologie   MeSH
• senioři MeSH
• vitamin D analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

INTRODUCTION: Calcific aortic valve stenosis (CAVS) is a serious clinical problem. The strongest predictor of CAVS progression is the amount of calcium in the aortic valve. The pathogenesis of CAVS is largely consistent with the pathogenesis of atherosclerosis; however, about 50% of patients with CAVS do not exhibit significant atherosclerosis. Cardiovascular calcification is currently considered an actively regulated process, in which the important role is attributed to the RANKL/RANK/OPG (receptor activator of nuclear factor κB ligand/RANK/osteoprotegerin) axis. We measured OPG levels in the tissue of calcified, stenotic aortic valves in relation to the presence or absence of coronary artery disease (CAD). MATERIALS AND METHODS: Aortic valve samples were collected from 105 patients with calcified, mainly severe aortic stenosis, who were divided into two groups according to the presence of CAD. In Group A (n=44), there were normal coronary artery findings, while in Group B (n=61), there was angiographically demonstrated >50% stenosis of at least one coronary artery. The control Group C (n=21) consisted of patients without aortic stenosis and with normal angiographic findings on coronary arteries. RESULTS: The highest tissue concentrations of OPG [median (pmol/L), 25th-75th percentile] were found in Group A [6.95, 3.96-18.37], which was significantly different compared to the other two groups (P=.026 and .001, respectively). The levels of OPG in Group B [4.15, 2.47-9.16] and in Group C [2.25, 1.01-5.08] did not differ significantly (P=.078); however, the lowest concentrations of OPG were found in Group C. Neither age nor gender in our study had effect on tissue levels of OPG (P=.994 for gender; P=.848 for age). CONCLUSION: Calcified and narrowed aortic valves, compared to the normal valves, were accompanied by a change in tissue concentrations of OPG, which is, in addition, dependent on the presence or absence of CAD. The highest tissue concentrations of OPG in our work were found in patients with significant aortic stenosis without concomitant CAD.

• MeSH
• aortální chlopeň metabolismus   patologie   MeSH
• aortální stenóza komplikace   metabolismus   patologie   MeSH
• ELISA MeSH
• kalcinóza komplikace   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci koronárních tepen komplikace   metabolismus   patologie   MeSH
• osteoprotegerin analýza   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE OF THE STUDY A failure of total hip or knee artroplasty is associated with an increased production of joint fluid. This contains wear particles and host cells and proteins, and is assumed to be involved in the pathogenesis of aseptic loosening and periprosthetic osteolysis. This study investigated the effect of synovial fluid from patients with aseptically failed joint prostheses on osteoblast cultures. MATERIAL AND METHODS Synovial fluid samples were obtained from patients with failed total joint prostheses (TJP; n=36) and from control patient groups (n=16) involving cases without TJP and osteoarthritis, without TJP but with osteoarthritis, and with stable TJP. The samples were treated in the standard manner and then cultured with the SaOS-2 cell line which shows the characteristics and behaviour of osteoblasts. Each fluid sample was also examined for the content of proteins, cells and selected cytokines (IL-1?, TNF-&alfa;, IL-6, RANKL and OPG detected by ELISA). We tested the hypothesis assuming that the fluids from failed joints would show higher cytotoxicity to osteoblast culture and we also expected higher levels of IL-1?, TNF-&alfa;, IL-6, and RANKL in patients with TJP failure and/ or with more severe bone loss. The statistical methods used included the Kruskal-Wallis ANOVA and Mann-Whitney U test. RESULTS The fluids from failed TJPs showed the highest RANKL and the lowest OPG levels resulting in the highest RANKL/OPG ratio. However, there was no evidence suggesting that the joint fluids from failed TJPs would be more toxic to osteoblast culture than the fluids from control groups. In addition, no correlation was found between the fluid levels of molecules promoting inflammation and osteoclastic activity and the extent of bone loss in the hip (in terms of Saleh's classification) or the knee (AORI classification). In fact, the fluids from failed TJPs had higher protein levels in comparison with the controls, but the difference was not significant. DISCUSSION The finding of high RANKL levels and low OPG concentrations is in agreement with the theory of aseptic loosening and periprosthetic osteolysis. The other cytokines, particularly TNF-&alfa; and IL-1?, were found in low levels. This can be explained by the stage of particle disease at which the samples were taken for ELISA analysis. It is probable that the level of signal molecules reflects osteolytic process activity and is therefore not constant. The reason for no correlation found between cytokine levels and the extent of bone loss may also lie in the use of therapeutic classifications of bone defects that is apparently less sensitive to the biological activity of aseptic loosening and/or periprosthetic osteolysis. CONCLUSIONS Synovial fluids from failed total hip or knee joint prostheses are not toxic to osteoblast cultures. Cytotoxicity indicators and levels of pro-inflammatory and pro-osteoclastic cytokines (IL-1?, TNF-&alfa;, IL-6, RANKL and OPG) do not correlate well with the extent of periprosthetic bone loss.

• MeSH
• artróza kolenních kloubů chirurgie   metabolismus   MeSH
• artróza kyčelních kloubů chirurgie   metabolismus   MeSH
• interleukin-6 analýza   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• ligand RANK analýza   MeSH
• náhrada kyčelního kloubu MeSH
• osteoblasty cytologie   MeSH
• osteoprotegerin analýza   MeSH
• selhání protézy MeSH
• senioři MeSH
• synoviální tekutina fyziologie   chemie   MeSH
• TNF-alfa analýza   MeSH
• totální endoprotéza kolene MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH