INTRODUCTION: In a previously published randomised, placebo-controlled trial, 800 mg/day of pharmaceutical-grade chondroitin sulfate (CS) was shown to be superior to placebo in reducing pain and improving function over 6 months in patients with symptomatic knee osteoarthritis (OA). The aim of the current post hoc analyses was to evaluate the cost-effectiveness of CS compared with placebo in a European perspective using individual patient data from this clinical trial. METHODS: Patients with knee OA randomised to CS or placebo were followed up at 1, 3 and 6 months. The algo-functional Lequesne index was used to derive the EuroQol Five-Dimension Five-Level (EQ-5D-5L) score based on a validated formula. The EQ-5D-5L scores at each time point were used to calculate the changes in quality-adjusted life years (QALYs) with the area under the curve method. Costs were assessed using the average price of CS in the countries where the original study took place and where CS is currently marketed. The costs of CS in three countries were then used (i.e. the Czech Republic, Italy and Switzerland). The incremental cost-effectiveness ratio (ICER) threshold for CS to be considered cost-effective was set at 91,870 EUR per QALY (equivalent to the usually recommended threshold of US $100,000). The study used an intention-to-treat population, i.e. patients who received one dose of the study drug, and imputed missing values using the basal observation carried forward method. RESULTS: No significant differences in baseline characteristics were observed between the CS group (N = 199) and the placebo group (N = 205). The mean cost of CS for 6 months of treatment was 194.74 EUR. After 6 months of treatment, CS showed a mean ICER of 33,462 (95% CI 5130-61,794) EUR per QALY gained, indicating cost-effectiveness compared with placebo. The acceptability curve for cost-effectiveness shows that the CS treatment is likely to be cost-effective compared with placebo, with a 93% probability when the ceiling ratio is set at 91,870 EUR per QALY gained. CONCLUSIONS: These results highlight the role of CS as a cost-effective therapeutic option in the management of OA. However, further studies taking into account the use of other healthcare resources are warranted for a more complete understanding.

• MeSH
• analýza nákladové efektivity MeSH
• analýza nákladů a výnosů * MeSH
• artróza kolenních kloubů * farmakoterapie   ekonomika   MeSH
• chondroitinsulfáty * terapeutické užití   ekonomika   MeSH
• kvalitativně upravené roky života * MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH
• Itálie MeSH
• Švýcarsko MeSH

Polysaccharides like hyaluronan (HA) and chondroitin sulfate (CS) are native of the brain's extracellular matrix crucial for myelination and brain maturation. Despite extensive research on HA and CS as drug delivery systems (DDS), their high water solubility limits their application as drug carriers. This study introduces an injectable DDS using aldehyde-modified hyaluronic acid (HAOX) hydrogel containing polyelectrolyte complexes (PEC) formed with calcium, gelatin, and either CS or aldehyde-modified CS (CSOX) to deliver minocycline for Multiple Sclerosis therapy. PECs with CSOX enable covalent crosslinking to HAOX, creating immobilized PECs (HAOX_PECOX), while those with CS remain unbound (HAOX_PECS). The in situ forming DDS can be administered via a 20 G needle, with rapid gelation preventing premature leakage. The system integrates into an implanted device for minocycline release through either Fickian or anomalous diffusion, depending on PEC immobilization. HAOX_PECOX reduced burst release by 88 %, with a duration of 127 h for 50 % release. The DDS exhibited an elastic modulus of 3800 Pa and a low swelling ratio (0-1 %), enabling precise control of minocycline release kinetics. Released minocycline reduced IL-6 secretion in the Whole Blood Monocytes Activation Test, suggesting that DDS formation may not alter the biological activity of the loaded drug.

• MeSH
• aldehydy chemie   MeSH
• chondroitinsulfáty * chemie   MeSH
• hydrogely * chemie   farmakologie   MeSH
• interleukin-6 metabolismus   MeSH
• kyselina hyaluronová * chemie   MeSH
• lékové transportní systémy metody   MeSH
• lidé MeSH
• minocyklin * chemie   farmakologie   aplikace a dávkování   MeSH
• nosiče léků * chemie   MeSH
• polyelektrolyty * chemie   MeSH
• uvolňování léčiv MeSH
• želatina * chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Human extracellular 6-O-endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6-O sulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented, and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). Despite its importance, limited information is available on direct protein-protein interactions of the Sulf-2 protein in the tumor microenvironment. In this study, we used monoclonal antibody (mAb) affinity purification and mass spectrometry to identify galectin-3-binding protein (LG3BP) as a highly specific binding partner of Sulf-2 in the conditioned media of HNSCC cell lines. We validated their direct interaction in vitro using recombinant proteins and have shown that the chondroitin sulfate (CS) covalently bound to the Sulf-2 influences the binding to LG3BP. We confirmed the importance of the CS chain for the interaction by generating a mutant Sulf-2 protein that lacks the CS. Importantly, we have shown that the LG3BP inhibits Sulf-2 activity in vitro in a concentration-dependent manner. As a consequence, the addition of LG3BP to a spheroid cell culture inhibited the invasion of the HNSCC cells into Matrigel. Thus, Sulf-2 interaction with LG3BP may regulate the physiological activity of the Sulf-2 enzyme as well as its activity in the tumor microenvironment.

• MeSH
• antigeny nádorové MeSH
• chondroitinsulfáty metabolismus   MeSH
• dlaždicobuněčné karcinomy hlavy a krku metabolismus   patologie   MeSH
• heparansulfát proteoglykany metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí MeSH
• nádory hlavy a krku metabolismus   patologie   MeSH
• pohyb buněk účinky léků   MeSH
• spinocelulární karcinom metabolismus   patologie   MeSH
• sulfatasy metabolismus   MeSH
• sulfotransferasy * metabolismus   MeSH
• vazba proteinů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• artróza kolenních kloubů * etiologie   farmakoterapie   MeSH
• chondroitin aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• injekce intraartikulární metody   MeSH
• kyselina hyaluronová aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• poranění kolena komplikace   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Osteoartritida (OA) je progresivně bolestivé onemocnění charakterizované degradací kloubní chrupavky se ztrátou proteoglykanu a kolagenu, sklerózou subchondrální kosti, periartikulární proliferací nové kosti a chronickým zánětem synoviálních membrán. Patogeneze osteoartritidy u psů zahrnuje genetické a environmentální faktory, které vyvolávají nebo urychlují poškození chrupavky a podporují degenerativní změny. Nadměrná tělesná hmotnost je rizikovým faktorem pro vznik osteoartritidy u psů. Obezita může vést k osteoartritidě v důsledku nadměrné zátěže působící na klouby a kloubní chrupavky. Osteoartritidu nelze vyléčit; cílem je zmírnění bolesti prostřednictvím omezení zánětlivých reakcí a dalšího odbourávání chrupavky. Regulace hmotnosti je při léčbě osteoartritidy prospěšná. Po dlouhou dobu byla souvislost osteoartritidy s výživou v medicíně malých zvířat středem pozornosti. Odhaduje se, že osteoartritida postihuje přibližně 20 % psů ve věku ≥ 1 rok a 90 % psů ve věku > 5 let. Kočky jsou osteoartritidou postiženy podobně, prevalence se pohybuje od 16,5 % do 91 % a s věkem se zvyšuje. Vzhledem k uváděné vysoké prevalenci je možné, že u společenských zvířat může být osteoartritida a s ní spojená bolest nediagnostikována a zůstává nepovšimnuta. Zejména kočky nemusí vykazovat klinické příznaky typické pro osteoartritidu; i nenápadné změny v chování kočky v domácnosti mohou být způsobeny bolestí spojenou s osteoartritidou.

Osteoarthritis (OA) is a progressively painful disease characterized by articular cartilage degradation with loss of proteoglycan and collagen, subchondral bone sclerosis, periarticular proliferation of new bone, and chronic inflammation of synovial membranes. The pathogenesis of osteoarthritis in dogs involves genetic factors and environmental factors that elicit or accelerate cartilage damage, promoting degenerative changes. Excessive body weight is a risk factor for development of osteoarthritis in canines. Obesity may result in osteoarthritis as a result of excess forces placed on joints and articular cartilage. Osteoarthritis cannot be cured and aims at the relief of pain through reduction of inflammatory reactions and further breakdown of cartilage. Weight management is beneficial in the management of osteoarthritis. Over a long period of time, the association of osteoarthritis with nutrition in small animal medicine has been a center of study. Osteoarthritis is estimated to affect approximately 20 % of dogs ≥ 1 year of age and 90 % of dogs > 5 years of age. Cats are similarly affected by osteoarthritis, with prevalences ranging from 16.5 % to 91 % and increasing with age. given the high prevalences reported, it is possible that companion animals may have undiagnosed osteoarthritis and the associated pain that goes unnoticed. Cats in particular may not show clinical signs typically associated with osteoarthritis, and even subtle changes in a cat’s behavior at home may be caused by osteoarthritis-associated pain.

• MeSH
• antiflogistika nesteroidní aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• chondroitinsulfáty terapeutické užití   MeSH
• glukosamin terapeutické užití   MeSH
• kočky MeSH
• kyselina hyaluronová terapeutické užití   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• omega-3 mastné kyseliny terapeutické užití   MeSH
• osteoartróza * diagnóza   terapie   veterinární   MeSH
• psi MeSH
• redukční dieta MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• psi MeSH
• zvířata MeSH

Výskyt močových infekcí v klinické praxi je velmi častý. Infekce močových cest představují spolu s respiračními infekcemi nejčastější zánětlivé onemocnění. S ohledem na současnou situaci antibiotické rezistence jsou u nekomplikovaných recidivujících infekcí močových cest doporučovány i neantibiotické strategie léčby. Jednou z možností je využití komplexního působení kyseliny hyaluronové, chondroitin sulfátu, kvercetinu a kurkuminu na obnovu funkce urotelu.

Incidence of urinary tract infections in clinical practice is hight. Urinary tract infections represent together with respirátory infections the most common inflammatory disease. In terms of currant situation og antibiotic resistence also antibiotic resistance also nonantibiotic strategyes of treatment are recommended. One option is to use complex effect of hyaluronic acid, chondroitinsulfate, quercetin and curcumin on support of bladder urothelium function restoration.

• MeSH
• chondroitinsulfáty terapeutické užití   MeSH
• infekce močového ústrojí * farmakoterapie   prevence a kontrola   MeSH
• kurkumin terapeutické užití   MeSH
• kyselina hyaluronová terapeutické užití   MeSH
• lidé MeSH
• quercetin farmakologie   terapeutické užití   MeSH
• recidiva MeSH
• urotel * imunologie   patologie   účinky léků   MeSH
• Check Tag
• lidé MeSH

Hyaluronan (HA) is a major component of peri- and extra-cellular matrices and plays important roles in many biological processes such as cell adhesion, proliferation and migration. The abundance, size distribution and presentation of HA dictate its biological effects and are also useful indicators of pathologies and disease progression. Methods to assess the molecular mass of free-floating HA and other glycosaminoglycans (GAGs) are well established. In many biological and technological settings, however, GAGs are displayed on surfaces, and methods to obtain the size of surface-attached GAGs are lacking. Here, we present a method to size HA that is end-attached to surfaces. The method is based on the quartz crystal microbalance with dissipation monitoring (QCM-D) and exploits that the softness and thickness of films of grafted HA increase with HA size. These two quantities are sensitively reflected by the ratio of the dissipation shift (ΔD) and the negative frequency shift (- Δf) measured by QCM-D upon the formation of HA films. Using a series of size-defined HA preparations, ranging in size from ~ 2 kDa tetrasaccharides to ~ 1 MDa polysaccharides, we establish a monotonic yet non-linear standard curve of the ΔD/ - Δf ratio as a function of HA size, which reflects the distinct conformations adopted by grafted HA chains depending on their size and surface coverage. We demonstrate that the standard curve can be used to determine the mean size of HA, as well as other GAGs, such as chondroitin sulfate and heparan sulfate, of preparations of previously unknown size in the range from 1 to 500 kDa, with a resolution of better than 10%. For polydisperse samples, our analysis shows that the process of surface-grafting preferentially selects smaller GAG chains, and thus reduces the average size of GAGs that are immobilised on surfaces comparative to the original solution sample. Our results establish a quantitative method to size HA and other GAGs grafted on surfaces, and also highlight the importance of sizing GAGs directly on surfaces. The method should be useful for the development and quality control of GAG-based surface coatings in a wide range of research areas, from molecular interaction analysis to biomaterials coatings.

• MeSH
• buněčná adheze MeSH
• chondroitinsulfáty MeSH
• glykosaminoglykany * chemie   MeSH
• kyselina hyaluronová * chemie   MeSH
• mikrorovnovážné techniky křemenného krystalu MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Osteoartróza je nejčastějšî kloubnî onemocněnî dané degeneracî chrupavek s následnou reakcî a transformacî okolnîch tkánî. U primárnî formy je osteoartróza dána stárnutîm a přibývá s věkem. V sekundárnî formě urychluje degeneraci hlavně vliv kongenitálnîch změn, úrazy a celkové systémové onemocněnî řîzené řadou zánětlivých mediátorů postiženého kloubu. Prvním příznakem je bolest různé intenzity, tzv. startovací, postupně otoky a omezenî pohyblivosti kloubu. Progrese je většinou dlouhodobá s různou intenzitou potîžî. Nejčastěji postihuje kyčelnî a kolennî kloub, ale může se vyskytnout na kterémkoliv kloubu včetně drobných kloubů rukou a nohou. Troufám si tvrdit, že mnohá osteoartróza je právě v lékárně "schovaná" za větu: "Dobrý den, jeden ibuprofen.".

Osteoarthritis is the most common joint disease caused by degeneration of cartilage with subsequent reaction and transformation of surrounding tissues. In the primary form, osteoarthritis is caused by aging and increases with age. In the secondary form, degeneration is accelerated mainly by the influence of congenital changes, injuries and general systemic disease controlled by a number of inflammatory mediators of the affected joint. The first symptom is severe pain, so-called starting pain, gradually swelling and limited joint mobility. Progression is usually long-term with varying degrees of difficulty. Most often affects the hip and knee joints, but can occur on any joint, including the small joints of the hands and feet. I dare say that many osteoarthritis are "hidden" in the pharmacy right after the sentence: "Hello, I would like one ibuprofen please....".

• MeSH
• antirevmatika terapeutické užití   MeSH
• chondroitinsulfáty terapeutické užití   MeSH
• glukosamin terapeutické užití   MeSH
• lidé MeSH
• osteoartróza * farmakoterapie   patologie   prevence a kontrola   MeSH
• paracetamol terapeutické užití   MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH

Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half-life. In this article we describe a novel device for viscosupplementation (NV) based on the cross-linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500-2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500-2000 kDa and cross-linked material without CS.

• MeSH
• artróza kolenních kloubů * MeSH
• chondroitinsulfáty farmakologie   MeSH
• hyaluronoglukosaminidasa terapeutické užití   MeSH
• injekce intraartikulární MeSH
• kyselina hyaluronová farmakologie   MeSH
• lidé MeSH
• osteoartróza * farmakoterapie   MeSH
• reaktivní formy kyslíku MeSH
• tyramin terapeutické užití   MeSH
• viskosuplementace * metody   MeSH
• viskosuplementy terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In this work the DBL3x domain of the erythrocyte membrane protein from Plasmodium Falciparum (PfEMP1), was revisited as a potential molecular target for the development of new drugs against malaria. This protein interacts with chondroitin sulfate A (CSA), a glycosaminoglycan present in the substance fundamental for connective tissues of vertebrates and is implicated in malaria complications in pregnant women. We performed molecular docking and molecular dynamic studies of DBL3x complexed with CSA and five analogues, where the sulfate group was replaced by phosphate, in order to evaluate if the better electrostatic interactions provided by phosphate groups could afford better binders capable of preventing the binding of CSA to DBL3x. Results suggest that all proposed compounds have high affinity towards DBL3x and could bind better to the DBL3x domain of PfEMP1 than CSA, qualifying as potential inhibitors of this protein and, therefore, new potential leads for the drug design against malaria.Communicated by Ramaswamy H. Sarma.

• MeSH
• antigeny protozoální chemie   MeSH
• chondroitinsulfáty chemie   metabolismus   farmakologie   MeSH
• erytrocyty metabolismus   MeSH
• fosfáty MeSH
• glykosaminoglykany metabolismus   MeSH
• lidé MeSH
• malárie * komplikace   metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• parazitární komplikace těhotenství * metabolismus   MeSH
• placenta metabolismus   MeSH
• Plasmodium falciparum chemie   MeSH
• protozoální proteiny chemie   MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• sírany metabolismus   MeSH
• těhotenství MeSH
• tropická malárie * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH