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
Materials used for orthopedic implants should not only have physical properties close to those of bones, durability and biocompatibility, but should also exhibit a sufficient degree of antibacterial functionality. Due to its excellent properties, titanium is still a widely used material for production of orthopedic implants, but the unmodified material exhibits poor antibacterial activity. In this work, the physicochemical characteristics, such as chemical composition, crystallinity, wettability, roughness, and release of Ti ions of the titanium surface modified with nanotubular layers were analyzed and its antibacterial activity against two biofilm-forming bacterial strains responsible for prosthetic joint infection (Staphylococcus aureus and Pseudomonas aeruginosa) was investigated. Electrochemical anodization (anodic oxidation) was used to prepare two types of nanotubular arrays with nanotubes differing in dimensions (with diameters of 73 and 118 nm and lengths of 572 and 343 nm, respectively). These two surface types showed similar chemistry, crystallinity, and surface energy. The surface with smaller nanotube diameter (TNT-73) but larger values of roughness parameters was more effective against S. aureus. For P. aeruginosa the sample with a larger nanotube diameter (TNT-118) had better antibacterial effect with proven cell lysis. Antibacterial properties of titanium nanotubular surfaces with potential in implantology, which in our previous work demonstrated a positive effect on the behavior of human gingival fibroblasts, were investigated in terms of surface parameters. The interplay between nanotube diameter and roughness appeared critical for the bacterial fate on nanotubular surfaces. The relationship of nanotube diameter, values of roughness parameters, and other surface properties to bacterial behavior is discussed in detail. The study is believed to shed more light on how nanotubular surface parameters and their interplay affect antibacterial activity.
- MeSH
- antibakteriální látky * farmakologie chemie MeSH
- biofilmy účinky léků růst a vývoj MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- nanotrubičky * chemie MeSH
- povrchové vlastnosti * MeSH
- Pseudomonas aeruginosa * účinky léků MeSH
- Staphylococcus aureus * účinky léků MeSH
- titan * chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Nickel(Ni)-containing materials have been widely used in a wide range of medical applications, including orthopaedics. Despite their excellent properties, there is still a problem with the release of nickel ions into the patient's body, which can cause changes in the behaviour of surrounding cells and tissues. This study aims to evaluate the effects of Ni on bone cells with an emphasis on the determination of Ni localization in cellular compartments in time. For these purposes, one of the most suitable models for studying the effects induced by metal implants was used-the patient's osteoarthritic cells. Thanks to this it was possible to simulate the pathophysiological conditions in the patient's body, as well as to evaluate the response of the cells which come into direct contact with the material after the implantation of the joint replacement. The largest differences in cell viability, proliferation and cell cycle changes occurred between Ni 0.5 mM and 1 mM concentrations. Time-dependent localization of Ni in cells showed that there is a continuous transport of Ni ions between the nucleus and the cytoplasm, as well as between the cell and the environment. Moreover, osteoarthritic osteoblasts showed faster changes in concentration and ability to accumulate more Ni, especially in the nucleus, than physiological osteoblasts. The differences in Ni accumulation process explains the higher sensitivity of patient osteoblasts to Ni and may be crucial in further studies of implant-derived cytotoxic effects.
- MeSH
- buněčný cyklus účinky léků MeSH
- ionty metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- nikl * metabolismus MeSH
- osteoartróza * metabolismus patologie MeSH
- osteoblasty * metabolismus účinky léků MeSH
- proliferace buněk * účinky léků MeSH
- viabilita buněk * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
As the consumption of implants increases, so do the requirements for individual types of implants, for example, improved biocompatibility or longevity. Therefore, the nano-modification of the titanium surface is often chosen. The aim was to characterize the modified surface with a focus on medical applications. The titanium surface was modified by the anodic oxidation method to form nanotubes. Subsequently, the material was characterized and analyzed for medical applications-surface morphology, surface wettability, chemical composition, and release of ions into biological fluids. A human gingival fibroblasts (HGFb) cell line was used in the viability study. A homogeneous layer of nanotubes of defined dimensions was formed on the titanium surface, ensuring the material's biocompatibility-the preparation conditions influence the resulting properties of the nanostructured surface. Nanostructured titanium exhibited more suitable characteristics (e.g., wettability, roughness, ion release) for biological applications than compared to pure titanium. It was possible to understand the behavior of the modified layer on the titanium surface and its effect on cell behavior. Another contribution of this work is the combination of material characterization (ion release) with the study of cytocompatibility (direct contact of cells with metals).
- MeSH
- fibroblasty MeSH
- lidé MeSH
- nanostruktury * MeSH
- povrchové vlastnosti MeSH
- smáčivost MeSH
- titan * farmakologie chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE OF THE STUDY Nitinol (NiTi) is a biomaterial widely used in medicine based on super-elastic and shape memory properties. miR-124 has a key role in inflammatory process, osteoblasts differentiation, and mineralization. The aim of study was evaluating the differences in gene expression of miR-124 of human physiological osteoblasts (HOB) and human osteoarthritic osteoblasts (OSBA) as a response to NiTi alloy in different heat treatments. MATERIAL AND METHODS The cells were cultivated with NiTi discs with/without addition of bacterial lipopolysaccharide (LPS) for 72 hours. MicroRNAs were isolated, underwent reverse transcription and were analyzed by RT-PCR. RESULTS As a response to LPS, HOB overexpressed miR-124, while in OSBA expression change did not occur. Overexpression was also observed in both cell lines as a response to hydrogen and helium treated NiTi discs. HOB expressed significantly higher amount of miR-124 than OSBA as a response to hydrogen treatment of NiTi discs. In addition, hydrogen treatment caused significantly higher expression in HOB than LPS. The combination of NiTi disc and LPS treatment in HOB didn't cause any expression changes. Comparing to LPS-only treatment, the expression in HOB with combination of LPS and alloy was significantly lower. In OSBA, the expression was increased by the combination of LPS and hydrogen disc, in case of helium disc, the expression was decreased. CONCLUSIONS In conclusion, human physiological and osteoarthritic osteoblasts respond to NiTi alloy with both surface (hydrogen and helium atmosphere) treatment by overexpression of miR-124. The effect of LPS as inflammatory modulator suggests the presence of an "anti-inflammatory preconditioning" in osteoarthritic osteoblasts, as physiological osteoblasts overexpression was significantly higher. Key words: nitinol, osteoblast, miR-124, lipopolysaccharide.
- MeSH
- helium metabolismus farmakologie MeSH
- lidé MeSH
- lipopolysacharidy * farmakologie metabolismus MeSH
- mikro RNA * genetika metabolismus farmakologie MeSH
- osteoartróza genetika MeSH
- osteoblasty metabolismus MeSH
- slitiny metabolismus farmakologie MeSH
- titan MeSH
- vodík metabolismus farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2'-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker's ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin.
- Publikační typ
- časopisecké články MeSH
Recent medical applications have specific requirements on materials and Nitinol can fulfill them due to its exceptional characteristics, which can be further improved by modifications of the material surface. Various surface nanostructuring methods are utilized to enhance characteristics of oxide layer, which naturally develops on the Nitinol surface, leading to improved biocompatibility and corrosion resistance. This review is focused on studies investigating the behavior of various cell types on surface nanotubes and ordered nanopores prepared by anodic oxidation, a technique allowing fabrication of nanostructures with defined parameters. Results showed that certain dimensions of nanotubes positively affect adhesion and viability of osteoblasts and endothelial cells on the surface, contrary to negative effect on smooth muscle cells, both required by the medical applications. Furthermore, increased antibacterial effect correlated with the nanostructure topography and release rates of Ni ions.
Indirect evidences in reviews and case reports on Takotsubo syndrome (TTS) support the fact that the existence of oxidative stress (OS) might be its common feature in the pre-acute stage. The sources of OS are exogenous (environmental factors including pharmacological and toxic influences) and endogenous, the combination of both may be present, and they are being discussed in detail. OS is associated with several pathological conditions representing TTS comorbidities and triggers. The dominant source of OS electrones are mitochondria. Our analysis of drug therapy related to acute TTS shows many interactions, e.g., cytostatics and glucocorticoids with mitochondrial cytochrome P450 and other enzymes important for OS. One of the most frequently discussed mechanisms in TTS is the effect of catecholamines on myocardium. Yet, their metabolic influence is neglected. OS is associated with the oxidation of catecholamines leading to the synthesis of their oxidized forms - aminochromes. Under pathological conditions, this pathway may dominate. There are evidences of interference between OS, catecholamine/aminochrome effects, their metabolism and antioxidant protection. The OS offensive may cause fast depletion of antioxidant protection including the homocystein-methionine system, whose activity decreases with age. The alteration of effector subcellular structures (mitochondria, sarco/endoplasmic reticulum) and subsequent changes in cellular energetics and calcium turnover may also occur and lead to the disruption of cellular function, including neurons and cardiomyocytes. On the organ level (nervous system and heart), neurocardiogenic stunning may occur. The effects of OS correspond to the effect of high doses of catecholamines in the experiment. Intensive OS might represent "conditio sine qua non" for this acute clinical condition. TTS might be significantly more complex pathology than currently perceived so far.
- Publikační typ
- časopisecké články MeSH
