Les maladies ostéoarticulaires représentent environ 10% de l'ensemble des pathologiessurvenant en France chaque année. Les difficultés pour identifier les causes de ces maladiesproviennent pour une part d'un manque de compréhension du mécanisme de lubrificationd'une articulation synoviale saine. Dans ce contexte, un premier objectif de ce travail a été d'analyser la structurediscontinue du liquide synovial à partir de prélèvements animaux sains et de la reproduire àpartir de composants biomoléculaires commerciaux afin de comprendre le mécanisme delubrification dans le cas sain. Le deuxième objectif de cette thèse a été d'analyser l'évolution de la structure et despropriétés lubrifiantes du liquide synovial dans le stade précoce de pathologies noninflammatoiresou inflammatoires à partir de prélèvements pathologiques humains. Afind'étudier plus finement l'évolution de la lubrification pathologique cette thèse a visé àdévelopper aussi des modèles de lubrifiants obtenus à partir de cultures cellulaires desynoviocytes humains en combinant l'action de facteurs inflammatoire (cytokines).L'ensemble des résultats montre l'importance de la structure supramoléculaire duliquide synovial dans l'obtention de bonnes propriétés lubrifiantes ; cette relation devraitconstituer d'une part un paramètre clé dans le diagnostic précoce des pathologies articulaireset d'autre part une voie de développement de liquides thérapeutiques à base de lubrifiantsnanostructurés

Diss. (sammanfattning) Linköping : Linköpings universitet, 2007. / Härtill 4 uppsatser.

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Made available in DSpace on 2016-06-02T20:19:03Z (GMT). No. of bitstreams: 1 DissPFACN.pdf: 513373 bytes, checksum: e626d1bf009f8adbc96ccd8431d6b582 (MD5) Previous issue date: 2006-02-28 / Universidade Federal de Sao Carlos / Objective. To evaluate the influence of sulfated glycosaminoglycan (GAG) concentration in synovial fluid from individuals with chondral injuries, either isolated or associated with anterior cruciate ligament injury or meniscal injury, and check for an association between time since injury and the degree of chondral injury. Material and Method. Twenty-nine adult subjects (25 men and 4 women, mean age 38.3 ± 10.9 years) were selected. Samples obtained from all subjects were quantified to determine the GAG concentration using dimethylmethylene blue dye. The degree of chondral damage was macroscopically evaluated by arthroscopy and rated according to the International Cartilage Repair Society (ICRS) classification. Results. Significant differences were found concerning the GAG concentration in the control group compared with the other groups (p<0.05). No significant differences were found between the studied groups concerning time since injury and degree of chondral damage according to the ICRS. A strong correlation was found between GAG concentration and time since injury in the chondral injury group (r= -1). Conclusion. Damage to articular structures seems to be the determining factor in the change of synovial fluid GAG concentration, being higher in isolated chondral injury. When associated with anterior cruciate ligament rupture and/or meniscal injury, it will promote a tendency to fall, and is not related to sex, age, time since injury and degree of chondral injury in all groups studied. / Objetivo: Avaliar a influência da lesão condral na concentração de glicosaminoglicanas sulfatadas no líquido sinovial de indivíduos portadores de lesões condrais isoladas ou associadas com lesões do ligamento cruzado anterior e dos meniscos, bem como uma associação com o tempo da lesão e o grau de osteoartrite. Desenho do estudo: Foram avaliados 29 indivíduos adultos de ambos os sexos. Os sujeitos foram divididos em cinco grupos: grupo controle; grupo com lesão condral; grupo com lesão condral associada à lesão meniscal; grupo com lesão condral associada à lesão do ligamento cruzado anterior e grupo com lesão condral associado às lesões meniscal e do ligamento cruzado anterior. Métodos: As amostras foram quantificadas em relação à concentração de glicosaminoglicanas pelo método espectrofotométrico, utilizando o corante azul de dimetilmetileno. O grau de osteoartrite foi avaliado macroscopicamente, por artroscopia e graduado segundo classificação da Internacional Cartilage Repair Society, 2000, variando entre grau 0 e 4. Resultados: Encontramos diferenças significativas quando comparamos a concentração de glicosaminoglicanas do grupo controle em relação aos outros grupos (P<0,05), houve também correlação entre concentração de glicosaminoglicanas sulfatadas e o tempo pós lesão no grupo com lesão condral, (r= -1). Não houve diferenças significativas entre os grupos estudados quanto ao grau de osteoartrite e tempo após a lesão. Conclusão: A lesão condral isolada apresenta maior concentração de glicosaminoglicanas, entretanto a presença de lesão do ligamento cruzado anterior e meniscos influenciam uma tendência à queda desta concentração no líquido sinovial e sem apresentar relação com o tempo de lesão e o grau de osteoartrite entre os grupos estudados.

O presente trabalho visa desenvolver métodos analíticos que permitam determinar as concentrações de oxitetraciclina por Cromatografia Líquida de Alta Eficiência, no leite, plasma e líquido sinovial, além de analisar as concentrações correspondentes em gado leiteiro em lactação portadoras de doença do casco submetidos aos tratamentos intramuscular e tópico. Adicionalmente, são tecidos comentários sobre a eficácia clínica destes tratamentos. Desta forma, objetivando determinar a depuração de oxitetraciclina no organismo dos animais tratados, a concentração no sítio de ação e a quantidade residual em leite, as amostras biológicas foram colhidas e quantificadas em diferentes tempos pré e pós-administração do fármaco. Os métodos analíticos validados apresentaram linearidade, limite de detecção, quantificação, exatidão, precisão e recuperação adequadas à quantificação do antibiótico nas matrizes estudadas. Através da administração do medicamento por via intramuscular, observou-se resíduos acima dos limites máximos (100ppb) estabelecidos pela legislação brasileira para oxitetraciclina no leite até 120 horas após a última administração do medicamento pelo esquema seriado de doses. Já pela via tópica, não foram observados valores residuais na matriz biológica. Do ponto de vista clínico, o tratamento tópico foi eficiente nos animais tratados, levando a cura das lesões. Com relação ao tratamento intramuscular, não foram observados resultados satisfatórios, pois a maioria das lesões não regrediu após as administrações. / The purpose of the present work is to develop methods which allow the determination of oxytetracycline by High Pressure Liquid Chromatography in milk, serum and synovial fluid, as well as analyze the corresponding concentration in milk cattle with foot lameness subjected to intramuscular and topical administration of the antibiotic. It is also commented the clinical efficacy of these two treatments. Thus, to determine the clearance of oxytetracycline in the body of the treated animals, the concentration on the site of action, and the antibiotic residue in milk, biological samples have been collected and analyzed for the oxytetracycline content at different times before and after the drug administrations. The validated analytical methods showed suitable linearity, detection and quantification limits, accuracy, precision and recovery, allowing proper quantification of the antibiotic in the studied biological matrices. When administered intramuscular1y, oxytetracycline residues were observed in milk above the maximum limits (100ppb) established by the brazilian legislation up to 120 hour after the last administration of the medicine using multiple doses treatment, whereas on topical use, residues were not observed in this matrix. When analyzing the clinical aspects, topical treatment was very efficient, leading to the healing of the treated animals. In relation to intramuscular treatment, non satisfactory results were observed, as most of lesion did not disappear after the antibiotic administration.

O presente trabalho visa desenvolver métodos que permitam determinar as concentrações de tetraciclina, por Cromatografia Líquida de Alta Eficiência, no plasma e líquido sinovial, além de analisar as concentrações correspondentes em leite de gado leiteiro em lactação submetidos aos tratamentos intravenoso e intravenoso regional. Desta forma, objetivando determinar a depuração da tetracic1ina no organismo dos animais tratados, a concentração do fármaco no sítio de ação e a quantidade residual em leite, as amostras biológicas foram colhidas e quantificadas em diferentes tempos pré e pós-administração do fármaco. Os métodos analíticos validados apresentaram linearidade, limite de detecção, quantificação, exatidão, precisão e recuperação adequados à quantificação do antibiótico nas matrizes biológicas estudadas. As amostras de leite de animais tratados com o medicamento por via intravenosa regional, não apresentaram resíduos após 120h da administração do fármaco. O mesmo ocorreu plasma e líquido sinovial após 48 h. Através da administração via intravenosa do medicamento foram observados resíduos no leite em todos os tempos avaliados, ao passo que no plasma e líquido sinovial, a presença do princípio ativo não foi detectada após 72 horas pós-tratamento. / The purpose of the present work is to develop methods which allow the determination of tetracycline by High Pressure Liquid Chromatography in serum, synovial fluid, as well as analyze the corresponding milk concentrations in milk cows subjected to intravenous and regional intravenous treatment. Therefore, aiming to determine the clearance of tetracycline in the body of the treated animals, the concentration of the active principle in the action site and the residual quantity in milk, biological matrices were collected at different times. The validated analytical methods depicted suitable linearity, detection and quantification limits, accuracy, precision and recovery, allowing the quantification of the antibiotic in the studied biological matrices. In relation to the milk samples from animals treated with the drug by regional intravenous via, they did not present residues of tetracycline after 120 h post-administration. The values were also null for both serum and synovial fluid after 48 h. Through regional intravenous drug administration, milk residues were observed in all the evaluated times whereas for serum and synovial fluid, the presence of the active principle was not detected after 72h post-treatment.

Vasiliki Katrinaki Objektive Beurteilung diagnostischer Anästhesien von Hufgelenk, Bursa podotrochlearis und Palmarnerven bei Pferden mit Vorderhandlahmheiten und deren Ursprung in der Hufregion. Klinik für Pferde, Veterinärmedizinische Fakultät, Universität Leipzig Eingereicht Dezember 2023 Einleitung: Orthopädische Erkrankungen weisen eine hohe Prävalenz bei Pferden auf und können das Wohlbefinden sowie ihre sportliche Nutzung stark beeinträchtigen. Erkrankungen des Hufrollen-Apparates sind für etwa ein Drittel aller chronischen Lahmheiten der Vordergliedmaße beim Pferd verantwortlich. Perineurale Anästhesien (Leitungsanästhesien) werden genutzt, um den Ursprung der Lahmheit am Pferdebein zu lokalisieren. Um die Lahmheitsursache genauer eingrenzen zu können, werden intra-synoviale Strukturen innerhalb des Hufes (Hufgelenk und/oder Bursa Podotrochlearis) anästhesiert. Die subjektive Beurteilung von Bewegungsstörungen sowie die Interpretation von diagnostischen Anästhesien führt oft zu Unstimmigkeiten zwischen unterschiedlichen Beobachtern. In den letzten Jahren wurden verschiedene Systeme entwickelt, welche eine Quantifizierung der Bewegungsstörung ermöglichen. Hiermit kann die prozentuale Verbesserung der Lahmheit nach der Durchführung diagnostischer Anästhesien über die Zeit erfasst und dokumentiert werden. Eine Anwendung solcher Systeme zur objektiven Beurteilung von Hufgelenkanästhesie (HG-A) und Bursa Podotrochlearis Analgesia (BP-A) wurde bei Pferden mit Vorderhandlahmheit bis heute nicht beschrieben. Ziel: Ziel dieser Arbeit war es: I) Die zeitabhängige Verbesserung natürlich vorkommender Vorderhandlahmheiten mit Ursprung in der Hufregion, nach erfolgter HG-A und BP-A bei Pferden zu beschreiben und II) zu prüfen, ob Schmerzen, die vom Hufgelenk bzw. dem Strahlbeinapparat ausgehen, mittels Leitungsanästhesien (Tiefe Palmarnervenanästhesie (TPA) und Mittlere Palmarnervenanästhesie (MPA)) unterschieden werden können. Unter Anwendung eines auf nicht-invasiven Beschleunigungssensoren basierenden Systems (BMISS, body-mounted inertial sensor system), sollten die Veränderungen des Bewegungsmusters vor und nach Einfluss der oben genannten diagnostischen Anästhesien quantitativ und objektiv erfasst werden. Tiere, Material und Methoden: Es handelt sich um eine prospektive klinische Studie an Patienten, die aufgrund einer Vorderhandlahmeit an der Pferdeklinik, Freie Universität Berlin, zwischen 2012 und 2016 vorstellig wurden. Alle Patienten wurden an drei aufeinander folgenden Tagen subjektiv und objektiv (BMISS) anhand eines standardisierten Protokolls von derselben Person orthopädisch untersucht. Am ersten Tag wurde der Ursprung der Lahmheit mittels Leitungsanästhesie lokalisiert. Bei positiver TPA oder MPA erfolgte anschließend eine HG-A (Tag 2) sowie eine BP-A (Tag 3). Das Gangbild wurde jeweils 10 Minuten (perineurale Anästhesie) bzw. 2, 5 und 10 Minuten (intra-synoviale Anästhesie) nach Injektion des Lokalanästhetikums beurteilt. Entsprechend wurden ausschließlich Pferde in die Studie eingeschlossen, bei denen mindesten eine der perineuralen und eine der intra-synovialen Anästhesien als “deutlich positiv” gewertet wurde. Die diagnostischen Anästhesien wurden als „deutlich positiv“ gewertet, wenn mittels BMISS eine Reduzierung der Lahmheit um mindestens 70% vom Ausgangswert gemessen wurde. Ergebnisse: Das Patientenkollektiv bestand aus 23 Pferden im Alter zwischen 4 und 16 Jahren. Anhand der Ergebnisse der Leitungsanästhesien wurden die Pferde den Gruppen „TPA“ (TPA positiv, n = 16) und „MPA“ (MPA positiv, n = 7) zugeordnet. Es konnte kein signifikanter Zusammengang zwischen einer Verbesserung der Lahmheit nach perineuraler Anästhesie und HG-A bzw. BP-A festgestellt werden (p > 0,05). Innerhalb der Gruppe „TPA“ war 2 Minuten nach intra-synovialer Injektion die Anzahl der Pferde, bei denen sich eine BP-A im Vergleich zur HG-A verbesserte, signifikant höher (p = 0,02). Bei den restlichen Messzeitpunkten konnten keine signifikanten Unterschiede zwischen BP-A und HG-A innerhalb der Gruppe „TPA“ festgestellt werden (5 Minuten: p = 0,07; 10 Minuten: p = 0,1). Aufgrund der sehr kleinen Stichprobe wurden die Daten innerhalb der Gruppe „MPA“ ausschließlich deskriptiv analysiert. Bei Betrachtung der intra-synovialen Anästhesien (unabhängig von der Leitungsanästhesie), war 2 Minuten (p < 0,001) sowie 5 Minuten (p = 0,04) nach Injektion ein signifikanter Unterschied im durchschnittlichen Grad der Verbesserung der Lahmheit zwischen HG-A und BP-A deutlich. Zehn Minuten nach Injektion wurde für beide intra-synovialen Anästhesien kein bedeutender Unterschied im Bewegungsmuster gemessen (p = 0,06). Bezüglich der zeitabhängigen Verbesserung der Lahmheit unter Einfluss der verschiedenen intra-synovialen Anästhesien zeigten die Pferde nach BP-A eine signifikante Verbesserung der Lahmheit 2 Minuten nach Injektion, welche über die Zeit konstant blieb. Bei Pferden mit positiver HG-A wurde eher eine progressive Reduktion der Lahmheit beobachtet. Der Unterschied in der Verbesserung zwischen den Messzeitpunkten 2 und 10 Minuten (p = 0,04) war signifikant. Schlussfolgerungen: Perineurale Anästhesien der distalen Vordergliedmaße ermöglichen keine Differenzierung der genauen Schmerzlokalisation in der Hufregion. Intra-synoviale Anästhesien sollten in diesem Bereich sowohl 2 als auch 5 Minuten nach Injektion des Lokalanästhetikums evaluiert werden. Während nach PB-A eine schnelle und über den Zeitverlauf konstante Verbesserung der Lahmheit eintritt, ist bei der HG-A mit einer progressiven Verbesserung der Lahmheit über 10 min nach Injektion zu rechnen.:Table of contents I List of illustrations II Abbreviations III 1. Introduction..................................................................................................................1 2. Literature......................................................................................................................3 2.1. Anatomy...................................................................................................................3 2.2. Forelimb lameness...................................................................................................5 2.3. Necessity for objective gait analysis…………………………………………………....6 2.4. Objective lameness evaluation.................................................................................7 2.5. Body-mounted inertial sensor system, Lameness Locator……………………….….8 2.6. Diagnostic analgesia of the distal limb……………….…………………………….…..9 2.7. Diagnostic imaging.................................................................................................11 2.8. Therapy....................................................................................................................12 2.9. Hypotheses.............................................................................................................13 3. Publication.................................................................................................................14 4. Declaration of own portion of work in publication.....................................................23 5. Discussion..................................................................................................................24 6. Zusammenfassung.....................................................................................................34 7. Summary………………………………………………………......…………………..…....36 8. Literature....................................................................................................................38 9. Acknowledgements....................................................................................................46 / Vasiliki Katrinaki Title: Objective evaluation for analgesia of the distal interphalangeal joint, the navicular bursa and perineural analgesia in horses with naturally occurring forelimb lameness localised to the foot Department for Horses, Faculty of Veterinary Medicine, Leipzig University Submitted in December 2023 Introduction: Lameness is a very common problem in horses, and pathologies of the navicular apparatus constitute up to one-third of all chronic forelimb lameness. Despite its high occurrence, and the fact that it can severely impair the horse’s sporting career and affect their welfare, contradictory results of diagnostic analgesia are documented. The interpretation of perineural analgesia remains confusing regarding the ability of the palmar digital nerve block (PDNB) to differentiate pain coming from pathologies of the distal interphalangeal joint (DIPJ) or the navicular syndrome. Thus, the outcome and interpretation of intra-synovial diagnostic analgesia of the distal interphalangeal joint and the navicular bursa remain controversial, and no objective live over ground studies have been performed so far to establish the percentage of improvement over time from these two analgesia techniques. Aim of the study: The aim of the study was to objectively evaluate with the use of an inertial-sensor based system the qualitative and time-dependent outcome of distal interphalangeal joint analgesia (DIPJ-A) and navicular bursa analgesia (NB-A) in naturally occurring forelimb lameness and to assess if perineural analgesia of the distal limb can differentiate pain coming from the DIPJ or the navicular apparatus. Study design: Prospective clinical trial. Methods: Clinical cases with forelimb lameness were evaluated objectively using a body- mounted inertial sensor system (BMISS) at the Equine Hospital of Freie Universität Berlin, Germany between 2012 and 2016. The ages of the animals varied between four and 16 years. A three-day lameness examination was performed subjectively and objectively. The subjective evaluation was always performed by the same veterinarian during the 3 days and the objective examination was performed using the BMISS. The horses were hospitalised for the three-day lameness examination. Lameness was localised to the foot with a palmar digital nerve block and/or an abaxial sesamoidean nerve block (ASNB) at day 1, and analgesia of the DIPJ (DIPJ-A) and NB (NB-A) were performed at day 2 and 3. Improvement following perineural analgesia was measured after 10 min and intra-synovial blocks after 2, 5 and 10 min, respectively. Horses with at least 70% improvement measured objectively after diagnostic analgesia were included in the study. Results: A total of 23 cases of forelimb lameness were included in this study. The age of the horses varied between four and 16 years. The side and degree of baseline lameness remained stable during the 3 days of lameness examination. The PDNB group included horses with a positive PDNB (n=16) and the ASNB group included horses with a negative PDNB and a positive ASNB (n=7). The majority of the horses had a positive response to PDNB compared with ASNB but there was no significant association between improvement following perineural analgesia and the DIPJ-A and NB-A in the number of horses that improved after DIPJ and NB analgesia (p>0.05). Comparison between the PDNB group and intra-synovial analgesia showed that in 2 min assessments there was a statistically significant difference in the number of horses that improved with an NB-A compared to DIPJ-A (p=0.02). In 5 min and 10 min evaluations, such a result was no longer observed (p=0.07 in 5 min, p=0.1 in 10 min). Comparison of the ASNB group to intra-synovial analgesia was descriptive because the number of horses included in this group was small. The mean improvement in the lameness was different between DIPJ-A and NB-A at 2 min (p<0.001) and at 5 min (p=0.04); however, this difference was no longer observed after 10 min (p=0.06). Evaluation of intra-synovial analgesia over time showed that a positive NB-A revealed a high degree of improvement already after 2 min that remained stable, whereas the DIPJ-A improved over time showing a significant difference in mean improvement between 2 min and 10 min measurements (p=0.04). Conclusions: Our results suggest that perineural analgesia is not reliable enough to differentiate pain originating from DIPJ and NB. The DIPJ-A and the NB-A should be evaluated at 2 and 5 min, since a significant difference of lameness improvement was measured for these points of time, pointing out the necessity to perform both blocks to identify the painful region. An early evaluation of the DIPJ-A and NB-A can determine the origin of the pain. An improvement in NB-A was constant over time, whereas a progressive improvement in lameness over the 10 min after injection is to be excepted in DIPJ-A.:Table of contents I List of illustrations II Abbreviations III 1. Introduction..................................................................................................................1 2. Literature......................................................................................................................3 2.1. Anatomy...................................................................................................................3 2.2. Forelimb lameness...................................................................................................5 2.3. Necessity for objective gait analysis…………………………………………………....6 2.4. Objective lameness evaluation.................................................................................7 2.5. Body-mounted inertial sensor system, Lameness Locator……………………….….8 2.6. Diagnostic analgesia of the distal limb……………….…………………………….…..9 2.7. Diagnostic imaging.................................................................................................11 2.8. Therapy....................................................................................................................12 2.9. Hypotheses.............................................................................................................13 3. Publication.................................................................................................................14 4. Declaration of own portion of work in publication.....................................................23 5. Discussion..................................................................................................................24 6. Zusammenfassung.....................................................................................................34 7. Summary………………………………………………………......…………………..…....36 8. Literature....................................................................................................................38 9. Acknowledgements....................................................................................................46

The existence of hydrodynamically developed, laminar Viscoelastic Secondary Flows (VSFs) of non-Newtonian fluids in straight ducts of non-circular cross-section was proposed in the 1950's. VSFs have since been observed sporadically, and only once with a velocimetric technique. Using axial and transverse full flow-field velocity-position raster maps made with Rheological Nuclear Magnetic Resonance (Rheo-NMR), Newtonian and non-Newtonian fluid flows were quantified in Hagen-Poiseuille and Power Law contexts, over more than two orders of magnitude of flow rate, in ducts of circle, square, triangle, and pentagon cross-section. VSF was reliably and repeatedly observed to occur at between one part in 130 and one part in 600 of the primary axial flow velocity. Velocity measurements ranged from <10 µm/s to approximately 30 cm/s, suggesting a velocity dynamic range >3E4 without optimization. To obtain VSF flow direction information, a novel flow directional phantom was developed and characterized. Aqueous solutions of Polyethylene Oxide (PEO), Viscarin GP-109NF, Viscarin GP-209NF (V209), Hyaluronan (HA) in a Phosphate-Buffered Saline-like solvent, and an aqueous Polyethylene Glycol/PEO-based Boger fluid were investigated. Axial data was corroborated with related data gathered by an independent method. Basic simulations corroborated the VSF observations. Duct hydraulic diameters (>= 1.6 mm) approached the micro-channel regime. VSF detections in HA --- synovial fluid's principal component --- and V209 were novel, as were observations of some artifacts which were subsequently characterized and corrected. The detection of VSF in HA represents the first experimental evidence suggesting that its second normal stress (N_2) is comparable to that of better-characterized fluids. In the first application of a new VSF-based method, a particular Boger fluid's constant viscosity and, in the square duct, its lack of VSF were used with established criteria to suggest that the fluid's N_2 approached zero. The development of a rudimentary, but versatile and inexpensive home-built velocimetric spectrometer is detailed, as are several new components. An exhaustive VSF literature review is included. The remarkable transverse velocimetric ability of Rheo-NMR in both optically opaque and transparent system is highlighted, suggesting that perhaps the technique might represent, in both micro-channels and conventional ducts, the gold-standard in flow velocimetry.

vi Title: Biochemical and mechanical processes in synovial fluid - modeling, mathematical analysis and computational simulations Author: Petra Pustějovská (petra.pustejovska@karlin.mff.cuni.cz) Department: Matematický ústav UK, Univerzita Karlova v Praze Institut für Angewandte Mathematik, Universität Heidelberg Supervisors: prof. RNDr. Josef Málek CSc., DSc. (malek@karlin.mff.cuni.cz) Matematický ústav UK, Univerzita Karlova v Praze, Prof. Dr. Dr. h.c. mult. Willi Jäger (jaeger@iwr.uni-heidelberg.de) Institut für Angewandte Mathematik, Universität Heidelberg Abstract: Synovial fluid is a polymeric liquid which generally behaves as a viscoelastic fluid due to the presence of polysaccharide molecules called hyaluronan. In this thesis, we study the biological and biochemical properties of synovial fluid, its complex rheology and interaction with synovial membrane during filtration process. From the mathematical point of view, we model the synovial fluid as a viscous incompressible fluid for which we develop a novel generalized power-law fluid model wherein the power-law exponent depends on the concentration of the hyaluronan. Such a model is adequate to describe the flows of synovial fluid as long as it is not subjected to instantaneous stimuli. Moreover, we try to find a suitable linear viscoelastic model...

The biological half-life of several pro-inflammatory mediators involved in the pathogenesis of rheumatoid arthritis (RA) is controlled by molecules exhibiting dipeptidyl peptidase-IV (DPP-IV)-like enzymatic activity (Dipeptidyl peptidase-IV activity and/or structure homologues- DASH). The aim of this thesis was to identify the molecular source of the DPP-IV-like enzymatic activity in the peripheral blood and synovial fluid in patients with rheumatoid arthritis as compared to control patients with osteoarthritis (OA), and to evaluate the association of DPP-IV with the disease activity. We found that the main source of the DPP-IV-like enzyme activity in the plasma and in the synovial fluid in patients with RA is the canonical DPP-IV. DPP-IV-like enzymatic activity and canonical DPP-IV were also detected on the cell surface of blood and synovial fluid mononuclear cells. Significantly lower DPP-IV-like enzymatic activity and DPP-IV expression in the synovial fluid mononuclear cells was found in RA as opposed to OA patients. In the synovial fluid of RA patients there was also a negative correlation between the concentration of the pro-inflammatory DPP-IV substrate SDF (stromal cell-derived factor-1 and the proportion of the DPP-IV+ T cells. The blood plasma DPP-IV-like enzymatic activity and...