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Studies indicate that allergy sufferers remain dissatisfied with available antiallergic therapies. A new convenient formulation of solubilized steroid combined in the same nasal spray solution with antihistamine may provide added symptom relief. The objective was to evaluate effects of CDX-947 (solubilized budesonide) and CDX-313 (solubilized azelastine + budesonide) against their suspension-type comparators (budesonide [Rhinocort Aqua {RA}] or azelastine + budesonide [Astelin] {AS} + RA]) and placebo on nasal allergy symptoms of patients exposed to controlled levels of ragweed pollen in an environmental exposure chamber (EEC). Two separate EEC studies that enrolled 173 patients were analyzed. Total nasal symptom score (TNSS) and onset of action were captured. Mean change from baseline of TNSS was compared with analysis of covariance and the onset of action determined. Meta-analysis was performed to allow cross-comparisons between studies. All active treatments significantly reduced TNSS when compared with placebo and both CDX-947 and CDX-313 showed increased improvement over the suspension-type comparators. CDX-313 provided significantly faster onset of action for itchy nose and sneezing. No clinically significant adverse events were reported in this study. The novel combination product, CDX-313, provided fast, long-lasting relief for allergic rhinitis symptoms. Compared with products where corticosteroid remains suspended, the new solubilized nasal spray formulation provides added benefit including faster onset of action and superior, convenient dosing of two therapeutics in one convenient product.

Objective: To investigate whether any of 14 serum and urine molecular markers (MMs) used to monitor osteoarthritis (OA) would be associated with particular clinical end-points., Design: Thirty-nine OA patients were bled and urine collected at five time points: at baseline visit and at visits 1, 3, 6 and 12 months later. Twelve clinical measurements were made and the concentrations of each of 14 MMs were determined. Principal component analysis, stepwise linear regression with backward elimination, and logistic regression were used to determine the correlations between MMs and clinical measures., Results: Principal component analysis was used to reduce the 12 clinical measurements into three independent clinical clusters: baseline clinical assessments, changes in clinical assessments and signal joint measurements. The 14 MMs were similarly reduced to five MM clusters. Each of the three clinical clusters was correlated with a single but different MM cluster. Baseline clinical assessments were correlated with bone markers typified by hydroxylysyl pyridinoline (HP) crosslinks, swelling of the signal joint was correlated with inflammation markers, especially CRP, and the change in clinical assessments over the 1 year evaluation was correlated with TGFbeta1. There was no correlation between any of the skeletal markers and the clinical measures, a situation which draws attention to the need for a direct assessment of cartilage damage in OA to validate the use of cartilage markers., Conclusions: This study demonstrates statistical methodology for analysis of clinical trials using multiple MMs and clinical end-points. The patient numbers are sufficient to test hypotheses of relationships of single MMs such as CRP, TGFbeta1 and HP to clinical measures, but larger clinical trials are needed to validate hypotheses., (Copyright 2001 OsteoArthritis Research Society International.)

Objective: To investigate the relationships between serum and urinary molecular markers (MM) used to monitor osteoarthritis., Design: Forty osteoarthritis patients had blood and urine collected at baseline and 1, 3, 6 and 12 months later. Specimens from 20 controls were obtained twice at a one month interval. The concentration of 14 different markers was determined at each time point and the data were analyzed by statistical methodology., Results: The markers could be divided by the method of principal components analysis into five clusters of related markers: inflammation markers (C-reactive protein, tumor necrosis receptor type I and tumor necrosis receptor type II, interleukin 6, eosinophilic cationic protein), bone markers (bone sialoprotein, hydroxylysyl pyridinoline, lysyl pyridinoline), putative markers of cartilage anabolism (carboxypropeptide of type II procollagen, hyaluronan, epitope 846) and catabolism (keratan sulfate, cartilage oligomeric matrix protein), and transforming growth factor beta. Three markers (tumor necrosis factor receptor II, cartilage oligomeric matrix protein and epitope 846) from independent clusters discriminated osteoarthritis patients from controls. Inflammation was not a confounding factor in measurement, but a recognizable distinguishing factor in osteoarthritis., Conclusions: The markers separated into rational groups on the basis of their covariance, a finding with independent biochemical support. The covariance of markers from the same cluster suggests the use of a representative marker from the cluster to reflect changes in osteoarthritis. If multiple markers are being measured within a single cluster, then the use of a weighted cluster 'factor' may be preferable to the separate use of individual markers.

Objective: To compare the effects of tenidap and piroxicam on acute-phase protein and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to explore their associations with clinical disease activity., Methods: A double-blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam (20 mg/day)., Results: Median values for C-reactive protein (CRP), Westergren erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and interleukin-6 (IL-6) were significantly lower after tenidap treatment compared with piroxicam treatment, even in the presence of stable background treatment with prednisone, methotrexate, or prednisone plus methotrexate. The median within-patient treatment differences (after tenidap minus after piroxicam) in the CRP, ESR, SAA, and IL-6 values were -1.7 mg/dl, -10.0 mm/hour, -22.0 micrograms/ml, and -3.7 pg/ml, respectively, and represent -60.4%, -17.7%, -35.5%, and -26.1% of the respective baseline levels. IL-6 levels were positively correlated with CRP and SAA. Plasma IL-1 beta was generally below the level of detection. Tumor necrosis factor alpha levels were similar after tenidap and after piroxicam. Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not reach statistical significance. IL-6, CRP, and ESR were significantly correlated with clinical treatment differences. Tenidap and piroxicam toleration were similar, although tenidap-treated patients exhibited a reversible increase in urinary protein excretion., Conclusion: Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clinical parameters.

The enthalpies for the dissolution of lecithin by sodium salts of cholic, deoxycholic, and chenodeoxycholic acids and their glycine and taurine conjugates are reported. Exothermic enthalpies were found in each case. It is suggested that heat evolution is due to a bile salt-lecithin interaction other than hydrophobic interactions. These results provide strong support for the "mixed disk" model for the complex lecithin-bile salt micelle, which requires that a substantial fraction of the bile salt molecules be incorporated within a lecithin bilayer where hydrogenbonded pair formation can occur. Calorimetric studies of the interaction between sodium cholate and nonionic, cationic, and anionic detergents yielded exothermic heats. These results suggest that these bile salt molecules partition into the detergent micelle interior as hydrogenbonded pairs.

A worldwide increase in prevalence of allergic diseases has led to adaptations in national and international health care systems. ARIA (Allergic Rhinitis and Its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases. In collaboration with international initiatives, ARIA offers updates of real-life integrated care pathways (ICPs) for digitally assisted, integrated, and individualized treatment of allergic rhinitis (AR). This article presents certain aspects of the health care system in Kuwait with reference to the management of AR and the objective of introducing ICPs and adopting the latest ARIA recommendations. Guidelines for ICPs include aspects of patients and health care providers and cover key areas of management of AR. This model of guidelines supports real-life health care better than traditional models. ARIA recommendations will be locally integrated in the health care system with the aim of improving both pharmacotherapy and allergy immunotherapy. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a painful, chronic, and widespread disease. Early treatment for disease is very important to prevent the progression of the disease. Currently, X-ray and clinical history are still the most dependable ways to diagnose OA and estimate the severity of disease. However, the joint damage by OA disease begins before it is diagnosed by radiographic changes. Hence, further practices for early diagnosis are required. Biomarkers and particles that are released into fluids during the disease have received many research interests for early diagnosis of OA. Therefore, in order for the biomarker to be beneficial in diagnosing of OA preradiography, it must have a strong and direct association with the disease. Hence, a good approach to detect and follow-up this disease is cartilage oligomeric matrix protein (COMP). COMP is one of the important biomarkers, which is closely related to the breakdown of the articular cartilage and the loss of function. Many studies have suggested that the COMP level is an indicator of the diagnosis and severity of the disease. In this review article, we highlighted the importance's role of COMP in OA. [ABSTRACT FROM AUTHOR]

Purpose of Review: This paper explores how the Environmental Exposure Unit (EEU) experimental model can be used to further our understanding of pharmacotherapies and immunotherapies for the treatment of allergic rhinitis (AR). Recent Findings: EEUs are used increasingly for the study of combination therapies, immunotherapies, and novel AR treatments. A combined antihistamine/corticosteroid nasal spray formulation was seen to have a faster onset of action relative to the therapies individually in the Environmental Exposure Chamber. House dust mite sublingual immunotherapy tablets are both safe and efficacious as evaluated by the Vienna Challenge Chamber. The Kingston EEU found that a novel peptide-based immunotherapy approach to be effective in reducing grass pollen-induced AR. Lastly, nasal filters were determined to reduce seasonal AR symptoms, given out-of-season in the Denmark Environmental Exposure Unit. Summary: EEUs are controlled, replicable models that provide valuable insight into the efficacy, onset and duration of action, and dose-related impacts of AR therapeutics, with direct clinical relevance. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays a significant role in the pathogenesis of knee osteoarthritis (KOA). Although both electro-acupuncture (EA) and manual acupuncture (MA) are known to influence systemic inflammation, little is known about the potential changes in inflammation as a working mechanism of EA and MA in KOA. Methods: Data from the Acupuncture for Knee Osteoarthritis Trial (ATKOA) were used. Serum concentrations of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, IL-18, IL-4, IL-10, IL-13, IL-15, IL-17, monocyte chemotactic protein-1 (MCP-1), CC-chemokine ligand 5 (CCL5), and cartilage degradation biomarkers (matrix metalloproteinase-1 MMP-1, MMP-3, MMP-13 and cartilage oligomeric matrix protein COMP)) were measured at baseline and after 8 weeks of treatment. Clinical outcomes were valid and reliable self-reported pain and function measures for osteoarthritis using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analogue scale (VAS) at baseline and post-treatment. Results: Both 8-weeks EA and MA significantly reduced pro-inflammatory cytokines (TNFα, IL-1β), and cartilage degradation biomarkers (MMP-3, MMP-13) significantly increased the anti-inflammatory cytokine IL-13 compared with pre-treatment (p< 0.05). Further, the reduction of TNF-α was more significant in EA when compared to MA (p=0.046). While there was no significant difference between groups in cytokines IL-1β (p=0.102), MMP-3 (p=0.113), MMP-13 (p=0.623) or IL-13 (p=0.935). Moreover, in both EA and MA, the effect of acupuncture on the VAS and WOMAC function scale after 8 weeks is clinically important, although no significant differences were found between groups. Conclusion: Eight weeks of both EA and MA seem to provide improvement in pain relief and function among individuals with mild to moderate knee OA. This benefit is partly mediated by changes of major inflammatory factors TNF-α, IL-1β and IL-13. Trial Registration: Controlled-Trials.com Identifier: NCT03274713. [ABSTRACT FROM AUTHOR]

Copyright of Revista Alergia de Mexico is the property of Coleg. Mexicano de Inmunologia Clinica y Alergia A.C.; Soc. Lat. de Alergia, Asma e Inmunologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Steroids are abundant in living organisms and are responsible for various biological functions. They are good candidates for inclusion complexes formation with cyclodextrins; therefore, plenty of literature describes these complexes and their application in various fields. There are, however, hardly any reviews summarizing this tremendous amount of information. Here, we review steroid drugs in relation to their complexation with cyclodextrins, highlighting the effect of cyclodextrin-steroid interaction on the solubility, stability and bioavailability of the entrapped steroid drugs. We have collected data on the changes in the pharmacokinetics of cyclodextrin-formulated steroid drugs designed for various routes of administration. We show some cyclodextrin-enabled steroid formulations introduced to the market. Sugammadex, the first cyclodextrin derivative approved as active pharmaceutical ingredient, which revolutionized anesthesia, is also discussed. Several examples demonstrate the catalysis and inhibition of various biotransformation reactions of steroids by cyclodextrin complexation used in biotechnology. The laboratory- and pilot-scale experiments for environmental application of cyclodextrin-steroid interaction are based on cyclodextrin-containing sorbents for capturing residual steroid drugs, such as contraceptives from purified wastewater. [ABSTRACT FROM AUTHOR]

Copyright of Online Journal of Health & Allied Sciences is the property of Online Journal of Health & Allied Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Total knee arthroplasty (TKA) is a well-established modality for the treatment of advanced knee osteoarthritis (OA). However, the detrimental effects of intramedullary reaming used in conventional TKA for distal femur cutting are of concern. Avoiding intramedullary reaming with the use of computer-assisted navigation TKA can not only provide superior prosthetic alignment, but also mitigate perioperative blood loss and the dissipation of marrow emboli. We quantified local and systemic concentrations of inflammation markers for both techniques. Forty-four participants undergoing computer-assisted navigation and 53 receiving conventional TKA for advanced knee OA were recruited between 2013/02/08 and 2015/12/09. Blood samples were collected from all participants at baseline then again at 24 and 72 hours postoperatively and analyzed by ELISA for interleukin 6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-β1); these markers were also measured in Hemovac drain fluid collected at 24 and 72 hours. Serum levels of IL-6, IL-10, TNF-α and TGF-β1(unit for all markers: pg/mL) were increased from baseline by smaller increments in the navigation TKA cohort compared with the conventional TKA group at 24 hours (17.06 vs 29.39, p = 0.02; 0.51 vs 0.83, p = 0.16; –0.04 vs 0.36, p < 0.01 and –48.18 vs 63.24, p< 0.01, respectively) and at 72 hours (12.27 vs 16.87, p = 0.01; –0.40 vs 0.48, p < 0.01; 0.58 vs 0.98, p = 0.07 and –55.16 vs 63.71, p < 0.01, respectively). IL-10 levels in drainage fluids collected 24 hours after TKA were also significantly lower in the navigation group versus the conventional TKA group (8.55 vs 12.32, p < 0.01). According to our evidence, the merits of computer-assisted navigation TKA are augmented by low levels of inflammation markers. [ABSTRACT FROM AUTHOR]

Objectives: The existence of phenotypes has been hypothesized to explain the large heterogeneity characterizing the knee osteoarthritis. In a previous systematic review of the literature, six main phenotypes were identified: Minimal Joint Disease (MJD), Malaligned Biomechanical (MB), Chronic Pain (CP), Inflammatory (I), Metabolic Syndrome (MS) and Bone and Cartilage Metabolism (BCM). The purpose of this study was to classify a sample of individuals with knee osteoarthritis (KOA) into pre-defined groups characterized by specific variables that can be linked to different disease mechanisms, and compare these phenotypes for demographic and health outcomes. Methods: 599 patients were selected from the OAI database FNIH at 24 months’ time to conduct the study. For each phenotype, cut offs of key variables were identified matching the results from previous studies in the field and the data available for the sample. The selection process consisted of 3 steps. At the end of each step, the subjects classified were excluded from the further classification stages. Patients meeting the criteria for more than one phenotype were classified separately into a ‘complex KOA’ group. Results: Phenotype allocation (including complex KOA) was successful for 84% of cases with an overlap of 20%. Disease duration was shorter in the MJD while the CP phenotype included a larger number of Women (81%). A significant effect of phenotypes on WOMAC pain (F = 16.736 p <0.001) and WOMAC physical function (F = 14.676, p < 0.001) was identified after controlling for disease duration. Conclusion: This study signifies the feasibility of a classification of KOA subjects in distinct phenotypes based on subgroup-specific characteristics. [ABSTRACT FROM AUTHOR]

Background: This article summarizes a EUFOREA symposium, presented during the European Rhinology Research Forum in Brussels (9–10 November 2017; https://www.rhinologyresearch.eu/) which focused on novel pathways and therapeutic approaches in allergic rhinitis (AR). Main body: AR remains under‐diagnosed, under‐estimated and under‐treated. A key component in understanding the AR landscape has been the realization of a significant mismatch between how physicians instruct AR patients to manage their disease and what AR patients actually do in real life. Data from the Allergy Diary (developed by MACVIA ARIA) showed that AR patients take their medication prn, rapidly switch treatments, often experience poor control, use multiple therapies and stop treatment when symptoms are controlled. Better control of AR may be achievable by using an AR treatment which has a rapid onset of action and which effectively targets breakthrough symptoms. Indeed, AR patients report complete symptom relief, lack of breakthrough symptoms, rapid onset of action, safety and use on an 'as needed' basis as key targets for new nasal sprays. MP‐AzeFlu comprises intranasal azelastine and fluticasone propionate (FP) in a novel formulation delivered in a single device. It is the first AR treatment to break the 5 min onset of action threshold and provides clinically relevant symptom relief in 15 min, much faster than that noted for FP + oral loratadine. MP‐AzeFlu also significantly reduces nasal hyperresponsiveness (NHR) which may be responsible for the breakthrough symptoms frequently reported by AR patients. Mechanisms underlying MP‐AzeFlu's effect include inhibition of mast cell degranulation, stabilization of the mucosal barrier, synergistic inhibition of inflammatory cell recruitment and a unique desensitization of sensory neurons expressing the transient receptor potential A1 and V1 channels. Conclusion: With the most rapid onset of action and onset of clinically‐relevant effect of any AR medication currently available, and proven efficacy in the treatment of NHR, MP‐AzeFlu is an AR treatment which provides what patients want, and fits how patients manage their AR in real life. [ABSTRACT FROM AUTHOR]

Background Allergen exposure chambers ( AECs) are clinical facilities allowing for controlled exposure of subjects to allergens in an enclosed environment. AECs have contributed towards characterizing the pathophysiology of respiratory allergic diseases and the pharmacological properties of new therapies. In addition, they are complementary to and offer some advantages over traditional multicentre field trials for evaluation of novel therapeutics. To date, AEC studies conducted have been monocentric and have followed protocols unique to each centre. Because there are technical differences among AECs, it may be necessary to define parameters to standardize the AECs so that studies may be extrapolated for driving basic immunological research and for marketing authorization purposes by regulatory authorities. Methods For this task force initiative of the European Academy of Allergy and Clinical Immunology ( EAACI), experts from academia and regulatory agencies met with chamber operators to list technical, clinical and regulatory unmet needs as well as the prerequisites for clinical validation. Results The latter covered the validation process, standardization of challenges and outcomes, intra- and interchamber variability and reproducibility, in addition to comparability with field trials and specifics of paediatric trials and regulatory issues. Conclusion This EAACI Position Paper aims to harmonize current concepts in AECs and to project unmet needs with the intent to enhance progress towards use of these facilities in determining safety and efficacy of new therapeutics in the future. [ABSTRACT FROM AUTHOR]

Purpose:Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees.Materials and methods:Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels.Results:Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p< 0.05). Synovial fluid MMP activity and PGE2 concentrations were positively correlated in meniscus tear subjects (R = 0.83,p< 0.0001). In meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p< 0.05). Subjects with complex meniscus tears had higher synovial fluid MMP-10 (p< 0.05) and reduced serum TNFα and IL-8 (p< 0.05) compared to other tear types.Conclusions:Given the degradative and pro-inflammatory roles of MMP activity and PGE2, these molecules may alter the biochemical environment of the joint. Our findings suggest that modulation of PGE2 signaling, MMP activity, or both following a meniscus injury may be targets to promote meniscus repair and prevent OA development. [ABSTRACT FROM AUTHOR]

Background: Joint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disease on the biomarker concentrations were analysed, and their relationship with clinical and radiographic parameters were assessed. We hypothesized that the kinetics of pro-inflammatory cytokines and structural biomarkers of joint disease would demonstrate progression of degenerative joint status during post-traumatic osteoarthritis and clarify the effect of early joint trauma. Results: The concentrations of IL1-ß, IL-6, TNF-a in the SF of PTOA group peaked at T0, decreased at T1, and then progressively increased with time, reaching levels higher than those observed at baseline starting from T3. CTXII and COMP levels were similar in PTOA and control horses at baseline, and increased in serum and synovial fluid of PTOA horses starting from T2 (serum and synovial CTXII, and serum COMP) or T3 (synovial COMP). The percentual change of TNF-a in the SF of the affected joints independently contributed to explaining the radiological changes at T3 vs T2 and T4 vs T3. Conclusions: Temporal changes of selected biomarkers in STBRs with an acute episode of traumatic fetlock OA demonstrated that long-term increased concentrations of inflammatory cytokines, type II collagen fragments and COMP, in the SF and serum, are related to PTOA. Based on the observed decrease in inflammatory merkers at T1, we hypothesize that the progression of PTOA could be effectively modulated by proper treatment strategies. Annual variations of synovial concentration of TNF-a can reliably predict radiographic progression of PTOA. [ABSTRACT FROM AUTHOR]

Background: Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease. Methods: The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies. Results: A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time. Conclusions: This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population. [ABSTRACT FROM AUTHOR]

Aim This study was designed to examine the effect of Burdock root tea on inflammatory markers and oxidative stress indicators in patients with knee osteoarthritis ( OA). Methods Thirty-six patients (10 men and 26 women) aged 50-70 years old with knee osteoarthritis referred to the Physical Medicine and Rehabilitation Department of the Tabriz University of Medical Sciences Hospitals, were selected for the study and randomly divided into two groups. Anthropometric measurements, including height, weight and body mass index (BMI) were measured. For all individuals along the 42 days of study period, the same drug treatments, including two lots of 500 mg acetaminophen twice a day and one glucosamine 500 mg once a day,were considered. The intervention group received daily three cups of Burdock root tea (each cup containing 2 g/150 mL boiled water) half-hour after the meal. The control group received three cups containing 150 cc boiled water daily. We assessed inflammatory markers such as high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) and oxidative stress indicators such as total antioxidants capacity (TAC), glutathione peroxidase (GPX), superoxide dismutase (SOD) and thiobarbituric acid reactive substances before and after the intervention. Results The results showed that burdock root tea significantly decreased the levels of serum IL-6 ( P = 0.002), hs- CRP ( P = 0.003) and malondialdehyde ( P < 0.001), while the levels of serum TAC ( P < 0.001) and activities of SOD ( P = 0.009) were significantly increased. GPX activities increased but not significantly. Conclusions The results suggested that Arctium lappa L. root tea improves inflammatory status and oxidative stress in patients with knee osteoarthritis. [ABSTRACT FROM AUTHOR]

IMPORTANCE Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. DESIGN, SETTING, AND PARTICIPANTS Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. MAIN OUTCOMES AND MEASURES Mechanistic primary outcomes: kneejointcompressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS At 18 months, 399 participants (88%) completed the study. Compared with exercise participants, knee compressive forces were lower in diet participants and IL-6 levels were lower in diet and diet + exercise participants. 18-mo Outcomes, Mean (95% CI) Exercise Difference, Difference, E (E) Diet (D) D + E E vs D vs D+E Weight Loss, kg -1.8 -8.9 -10.6 (-5.7 to 1.8) (-12.4 to -5.3) (-14.1 to -7.1) Knee compressive 2687 2487 2543 200 144 forces, N (2590 to 2784) (2393 to 2581) (2448 to 2637) (55 to 345)a (1 to 287) IL-6, pg/ml_ 3.1 2.7 2.7 0.43 0.39 (2,9 to 3.4) (2.4 to 3.0) (2.5 to 3.0) (0.01 to 0.85)" (-0.03 to 0.81)a Pain 4.7 4.8 3.6 -0.11 1.02 (4.2 to 5.1) (4.3 to 5.2) (3.2 to 4.1) (-0.81 to 0.59) (0.33 to 1.71)a Function 18.4 17.4 14.1 0.98 4.29 (16.9 to 19.9) (15.9 to 18.9) (12.6 to 15,6) (-1,24 to 3,20) (2.07 to 6.50)a SF-36 physical 41.9 42.4 44.7 -0.55 -2.81 (40.5 to 43.2) (41.1 to 43.7) (43.4 to 46.0) (-2.53 to 1.43) (-4.76 to -0.86) a Differences were significant. CONCLUSIONS AND RELEVANCE Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCTOO381290 [ABSTRACT FROM AUTHOR]

Background: This study was designed to investigate the correlations of knee osteoarthritis (OA) with metabolic syndrome (MetS) and MetS parameters in Korean subjects. Methods: This study included data from 270 subjects with knee OA and 1964 control subjects with a mean age of 54.56 (SD 11.53) years taken from the Korean National Health and Nutritional Examination Survey (KNHANES) 2008. Multivariate logistic regression analysis was conducted to examine possible associations for knee OA with MetS and MetS parameters. Results: MetS was shown to be associated with an increased risk of knee OA in female subjects in unadjusted analysis (OR 1.798, 95% CI 1.392, 2.322), but this significance disappeared when adjusted for confounding factors (OR 1.117, 95% CI 0.805, 1.550). No significant association between MetS and knee OA was found in male subjects. Among parameters of MetS, only high waist circumference (WC) in female subjects was significantly associated with an increased prevalence of knee OA, even after adjusting for confounding factors, while no other significant associations were found in both male and female subjects. Conclusion: We found that WC was associated with knee OA in female subjects, but neither MetS nor any parameters thereof were shown to be associated with knee OA in the Korean subjects of this study. Although we found no relationship between a pre-inflammatory state of MetS and knee OA, we believe further investigation of this relationship in various aspects is warranted, as MetS may also be a risk factor for complications in knee OA related procedures. [ABSTRACT FROM AUTHOR]

Objective CTX-II (C-terminal telopeptide of type II collagen) has been put forward as a marker of collagen type II degradation being part of osteoarthritis. In this study, the authors describe similarities between CTX-II and bone markers arguing against CTX-II as a marker of (solely) cartilage degradation. Methods uCTX-II, the bone markers uCTX-I, uNTX-I, sPINP, and sOC (C-terminal and N-terminal telopeptides of collagen I, aminoterminal propeptide of type I procollagen, and osteocalcin, respectively), and other (candidate) cartilage markers sCOMP, sCS846, and sPIIANP (cartilage oligomeric matrix protein, chondroitin sulphate 846 and type IIA collagen N-propeptide, respectively) were assessed by ELISA in CHECK (Cohort Hip and Cohort Knee), a cohort of 1002 individuals with early pain and/or stiffness in knee and/or hip. Results uCTX-II was more strongly associated with the bone markers than with the other cartilage markers, while the other cartilage markers were not so strongly associated with the bone markers. Moreover, both uCTX-II and bone markers but not the other cartilage markers showed an abrupt menopausal shift in women aged 48-53 years, also when adjusted for age and BMI. Conclusion The similarities between uCTX-II and bone markers could be attributable to a link between cartilage and bone metabolism through metabolic and biomechanical mechanisms. However, other cartilage markers were hardly associated with uCTX-II and did not show such evident associations with bone markers. uCTX-II has unique relations with bone markers as compared to other cartilage markers and might refl ect bone rather than cartilage metabolism. More thorough molecular validation of uCTX-II is required. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate levels of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and soluble forms of the TNF-α receptor (sTNFR1 and sTNFR2) from plasma taken from the peripheral blood of elderly individuals presenting with osteoarthritis (OA) of the knee. These patients underwent aerobic treatment through the use of physical exercises. The study consisted of a longitudinal analysis of older individuals presenting clinical and radiographic diagnosis of knee OA that were submitted to 12 weeks of aerobic treatment. The individuals were evaluated during acute exercise or after chronic exercise. During acute exercise (walking slowly on the mat), blood samples of the patients were collected before, immediately after, and 30 min following the end of training. After chronic exercise (aerobic walking training, three times/week for 12 weeks), patient blood samples were obtained for comparison. Additionally, clinical and functional assessments (WOMAC test and 6-min walk) were performed at the end of all physical exercises. Plasma concentrations of cytokines and soluble receptors were measured by ELISA. Aerobic training increased the plasma concentration of sTNR1; however, it decreased the plasma concentration of sTNFR2, when compared with levels of resting patients. Acute exercise differentially affects the levels of sTNFR1 dependent on when the samples were taken, before and after aerobic training. However, the levels of sTNFR2 were not affected by training. For the population studied, we observed differences in the levels of sTNFR1 and sTNFR2 following acute and chronic exercise. Other additional factors, like the level of inactivity of the individual and the type of physical exercise that patients are exposed to, need to be considered as well. The variation in the levels of soluble receptors correlated with functional improvement; however, the inflammatory osteoarthritis markers (IL-6 and TNF-α) were unaffected by the walking exercises. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the effect of hyaluronic acid (HA) intra articular injections (IA) on osteoarthritis (OA) biomarkers in patients with knee OA. Prospective open label study. Fifty-one patients with unilateral symptomatic K-OA received IA injections of 2mL of HA on days (D) 1, 7, 14 and were followed 3 months. At D-15 patients were examined and X-rays performed, to exclude patients with bilateral K-OA, or those with more than three symptomatic OA joints. From 15 days (D-15) before the first injection to D90 concomitant therapies were unchanged. Walking pain (WP) on VAS was obtained at each visit. Urine (U) and serum (S) samples were obtained at D-15, D1, D30, and D90. S-C2C, S-Cartilage oligomeric matrix protein, S-HA, S-CS 846 epitope, S-type II collagen propeptide, and U-type II collagen C telopeptide (U-CTX II/creatinin) were assayed. Predictive factors of response were analyzed using logistic regression. Correlations between variables were obtained using Spearman test. Forty-five patients were analyzed. Between D-15 and D1 there was no difference for any biomarkers At D1, WP (SD) was correlated with U-CTX II/creat ( p = 0.006). Between D1 and D90: U-CTX II/creat decreased significantly. After adjustment for confounding variables there was a significant correlation between clinical response and U-CTX II/creat variation. U-CTX II and S-HA at baseline were independently predictive of clinical response. This study showed that 90 days after HA IA injections, U-CTX II levels significantly decrease compared to baseline, suggesting a slowdown of type II collagen degradation. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:679-685, 2012 [ABSTRACT FROM AUTHOR]

Objectives To explore the impact of disease-modifying osteoarthritis drug (DMOAD) treatment on biomarker levels and their correlation with cartilage volume loss and disease symptoms in a 2-year phase III clinical trial in patients with knee OA. Methods 161 patients with knee OA (according-to-protocol population) were selected from a 2-year DMOAD trial studying the effect of licofelone (200 mg twice daily) versus naproxen (500 mg twice daily). Clinical evaluation of patients was carried out using the Western Ontario and McMaster Universities (WOMAC) questionnaire. Biomarker measurements of matrix metalloproteinase (MMP)-1, MMP-3, interleukin (IL)-6, C reactive protein (CRP), cartilage oligomeric matrix protein (COMP) and type I collagen C-terminal telopeptide (CTX-I) in serum, type II collagen C-terminal telopeptide (CTX-II) in urine, and knee MRI were performed at baseline and 2 years. Results Over time an increase occurred in all biomarker levels with the exception of IL-6, CRP and CTX-II which decreased. The increase in MMP-1 and MMP-3 was significantly less (p=0.05; p<0.01, respectively) in the licofelone group. The baseline MMP-1 level was significantly but inversely predictive of cartilage volume loss for the medial compartment in both univariate (p=0.04) and multivariate (p≤0.04) regression analyses, and COMP, a predictor for the lateral compartment, in both univariate and multivariate models (p<0.01). Baseline levels of IL-6 and CRP also showed a significant relationship with volume loss for the medial compartment (univariate analysis, p=0.04 and p=0.01, respectively; multivariate analysis, p=0.03, p=0.01). A significant association (univariate) was observed between the change in the levels of MMP-1 (p=0.03) and MMP-3 (p=0.02) and cartilage volume loss (lateral compartment) over 2 years. Baseline levels of CTX-I correlated (p=0.02) with an increase in the size of the bone marrow lesion in the medial compartment. The baseline CRP levels correlated with worsening of symptoms: WOMAC total index (p<0.01), pain (p<0.01) and function (p<0.01). Conclusion Higher baseline values of IL-6, CRP and COMP are predictive of greater risk of cartilage loss in OA. However, over time a reduction in MMP-1 and MMP-3 levels correlated best with reduction in cartilage volume loss and the effect of drug treatment. Baseline CRP was found to be a good predictor of the symptomatic response to treatment. [ABSTRACT FROM PUBLISHER]

Objective To study the relationship between serum C reactive protein (CRP) levels, genetic variation in the gene and the prevalence, incidence and progression of radiographic osteoarthritis (ROA) in the Rotterdam Study-I (RS-I). A systematic review of studies assessing the relationship between osteoarthritis (OA) and CRP levels was also performed. Methods The association between CRP levels and genetic variation in the gene and ROA was examined in 861 patients with hand OA, 718 with knee OA, 349 with hip OA and 2806 controls in the RS-I using one-way analysis of covariance and logistic regression, respectively. PubMed was searched for articles published between January 1992 and August 2009 assessing the relationship between CRP levels and OA. Results In RS-I the prevalence of knee OA, but not hip OA or hand OA, was associated with 14% higher serum CRP levels compared with controls (p=0.001). This association disappeared after adjustment for age and especially body mass index (BMI) (p=0.33). Genetic variation of the gene was not consistently associated with the prevalence, incidence or progression of OA within RS-I. The systematic review included 18 studies (including RS-I) on serum CRP levels and the prevalence, incidence or progression of OA. Consistently higher crude CRP levels were found in cases of prevalent knee OA compared with controls. No association was observed between serum CRP levels and the prevalence of knee OA following adjustment for BMI (n=3 studies, meta-analysis p value=0.61). Conclusion There is no evidence of association between serum CRP levels or genetic variation in the gene with the prevalence, incidence or progression of OA independent of BMI. [ABSTRACT FROM PUBLISHER]

Extracts from the seed of the African shea tree Vitellaria paradoxa C.F. Gaertn have been used traditionally for the treatment of arthritic conditions. However, little is known about the mechanisms by which benefit is conferred. This single-site, 15-week randomized, double-blind, parallel, placebo-controlled study examined a range of biomarkers in 89 patients with osteoarthritis of the knees and/or hips to determine potential modes of action of SheaFlex70TM, a triterpene-rich extract of Vitellaria paradoxa. In the group of participants with levels of osteoarthritis biomarkers in the upper quartile at baseline, there were significant decreases in inflammation and cartilage breakdown and trend level decreases in bone remodeling in the SheaFlex70TM group versus placebo between commencement and completion of the study. Inflammation marker TNF-alpha fell 23.9% vs 6% (treatment vs placebo), p = 0.041. Cartilage degradation marker CTX-II fell 28.7% vs an increase of 17.6% (treatment vs placebo), p = 0.018. This marker also showed significant falls across the entire study group, 10.6% vs an increase of 11.6%, (treatment vs placebo), p = 0.016. Osteocalcin levels fell 9.2%, p = 0.014 (treatment) vs 1.2%, ns (placebo), p = 0.096 (treatment vs placebo). These findings indicate that in patients with the highest levels of osteoarthritis biomarkers, SheaFlex70TM demonstrated multiple beneficial activities consistent with slowing the disease process. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The goal of this study was to verify or reject the hypothesis that systematic differences exist in various profibrotic or antifibrotic factors between osteoarthritic patients and controls, as well as between different stages of osteoarthritis. The study group comprised 63 patients with knee osteoarthritis and 18 controls. Transforming growth factor-beta (TGF-)1, -2, -3; tissue inhibitor of metalloproteinase (TIMP)-1 protein levels; and gelatinolytic activity of matrix metalloproteinase (MMP)-1, -2, -3, -9 activitieswere measured by enzyme-linked immunosorbent assay and gelatin zymography,respectively. Visual analog scale scores, Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, Lequesne clinical osteoarthritis scales, and Kellgren-Lawrence radiographic grading were recorded for each patient. Transforming growth factor-2 and -3 (in contrast to TGF-1 and TIMP-1) serum protein levels were signifi cantly higher in osteoarthritic patients compared to controls (210%14% [P.001] and 232%7% [P10-7], respectively). Additionally, TGF-2 and -3 were strongly positively correlated to Kellgren-Lawrence radiographic grading of the disease (P10-5 and P10-7, respectively). Moreover, TGF-2 correlated positively with the WOMAC scale (P.007). However, TIMP-1 decreased as osteoarthritis progressed clinically, but remained irrelevant to radiographic staging. Furthermore, activities of MMP-2 and -9, but not MMP-13, were lower in patients with osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective: To examine serum markers of matrix turnover in an animal model of disk degeneration. Design: Randomized prospective in vivo study. Setting: Laboratory for Orthopaedic and Spine Research and Department of Large Animal Research. Participants: Twenty-one New Zealand White rabbits. Intervention: Rabbits were randomly grouped into control (n = 8), sham surgery (n = 5), or stab surgery (n = 8). The stab surgical group underwent annulotomy of L2-3, L3-4, and L4-5 to induce intervertebral disk degeneration. The sham surgical group underwent surgical exposure without annulotomy, and the control group received no intervention. Outcome Measurements: Lumbar spine magnetic resonance imaging (MRI) and serum samples were obtained before intervention and at 0, 3, 6, and 12 weeks thereafter. MRIs were analyzed for evidence of intervertebral disk degeneration via measurement of MRI index. The serum was assayed at 0, 3, 6, and 12 weeks for the aggrecan biosynthesis marker CS846 and the C-telopeptide of collagen II (CTX-II). Results: The stabbed disks demonstrate degeneration apparent by MRI criteria. CTX-II increased with time in the stabbed group compared to the control and sham surgery groups regardless of baseline levels. Aggrecan showed no statistically significant difference among groups. Conclusions: CTX-II shows promise as a useful serum biomarker for intervertebral disk degeneration. [Copyright &y& Elsevier]

The article focuses on the study that evaluates biomarkers in magnetic resonance imaging (MRI)-determined, pre-radiographicaly defined osteoarthritis (pre-ROA), and radiographically defined OA (ROA) in a population-based subjects. Different cartilage degradation markers are associated with pre-ROA that are associated with ROA. Moreover, biomarker ratios that contrast cartilage degradation with cartilage synthesis are able to distinguish OA stages compared to the levels of the individual markers.

This review article presents the current understanding of the molecular basis of articular cartilaginous homeostasis, and outlines potential areas to focus on within the developing field of therapeutics for cartilage disorders. Articular cartilage, an integral component of joints in extremities and the vertebral column, is essential for locomotion. Disturbance of joint development or cartilage homeostasis causes congenital osteocartilaginous dysplasia or osteoarthritic diseases, respectively. Symptomatic treatments and surgical replacement of joints are effective but can also be problematic in terms of quality of life over time. Recently, new insights into the molecular biological basis of chondrocyte differentiation and cartilage homeostasis have been reported. While joint formation is regulated by several growth factors such as Wnts (wingless-related MMTV integration site) and Gdfs (growth and differentiation factors), the pathology of osteoarthritis is now interpreted as the disruption of balance between anabolic and catabolic signals. Current findings in molecular biology on joint development are reviewed concisely to aid in the understanding of the molecular network that governs articular cartilage development and homeostasis. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 3, 464-481, 2008 [ABSTRACT FROM AUTHOR]

The article investigates whether the MRL/MpJ mouse is protected from posttraumatic arthritis following intraarticular fractures. According to the authors, the MRL/MpJ mouse has been found to have regenerative abilities when it comes to injuries. They report that results demonstrate that the MRL/MpJ mouse is relatively protected from posttraumatic arthritis that may occur following intraarticular fracture. They add that further studies are needed to understand the response mechanism.

The article presents a study which determined the association between individual biochemical markers and radiographic features. Serum and urinary biochemical markers were assessed in patients with predominantly tibiofemoral knee osteoarthritis (OA). Results of principal components analysis suggest that biochemical marker combinations may be more sensitive than individual marker for reflecting structural damage in patients with knee OA.

To examine the association between levers of cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1 (MMP-1), matrix metalloproteinases-3 (MMP-3), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in serum and synovial fluid, and MR imaging of cartilage degeneration in knee joint, and to understand the effects of movement training with different intensity on cartilage of knee joint. 20 adult canines were randomly divided into three groups (8 in the light training group; 8 in the intensive training group; 4 in the control group), and canines of the two training groups were trained daily at different intensity. The training lasted for 10 weeks in all. Magnetic resonance imaging (MRI) examinations were performed regularly (2, 4, 6, 8, 10 week) to investigate the changes of articular cartilage in the canine knee, while concentrations of COMP, MMP-1, MMP-3, TIMP-1 in serum and synovial fluid were measured by ELISA assays. We could find imaging changes of cartilage degeneration in both the training groups by MRI examination during training period, compared with the control group. However, there was no significant difference between these two training groups. Elevations of levels of COMP, MMP-1, MMP-3, TIMP-1, MMP-3/TIMP-1 were seen in serum and synovial fluid after training, and their levels had obvious association with knee MRI grades of cartilage lesion. Furthermore, there were statistically significant associations between biomarkers levels in serum and in synovial fluid. Long-time and high-intensity movement training induces cartilage degeneration in knee joint. Within the intensity extent applied in this study, knee cartilage degeneration caused by light training or intensive training has no difference in MR imaging, but has a comparatively obvious difference in biomarkers level. To detect articular cartilage degeneration in early stage and monitor pathological process, the associated application of several biomarkers has a very good practical value, and can be used as a helpful supplement to MRI. [ABSTRACT FROM AUTHOR]