Electrophoretic Studies of Synovial Fluid Proteins

Wilkinson, Matthew; Jones, Brian S.

doi:10.1136/ard.23.1.22

Cited by 8 publications

(7 citation statements)

References 9 publications

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“…If a similar relationship between joint size and hyaluronate concentration exists in humans, the greater affinity of rheumatoid arthritis for small joints might be explainable. T h e larger concentration of gamma globulin often present in rheumatoid synovial fluid (12,13) could contribute to increased aggregation of synovial fluid gamma globulin, thus perpetuating the rheumatoid process. The persistence of antigen in surface layers of intraarticular collagenous tissues may also influence localization of rheumatoid arthritis to joints (31).…”

Section: Discussionmentioning

confidence: 99%

“…Since rheumatoid arthritis is mainly a disease of diarthroidal synovial joints and since synovial fluid has the largest concentration of hyaluric acid in the human body (8)(9)(10)(11) as well as substantial amounts of gamma globulin (12,13), the present study was undertaken to determine the effect of hyaluronic acid on the thermal aggregation of human gamma globulin.…”

mentioning

confidence: 99%

“…that the reported beneficial effects of gold thiomalate, D-penicillamine, and L-histidine (4,5) in patients with rheumatoid arthritis are related to the ability of these compounds to inhibit the sulfhydryl-mediated thermal aggregation of human gamma globulin (6). Since rheumatoid arthritis is mainly a disease of diarthroidal synovial joints and since synovial fluid has the largest concentration of hyaluric acid in the human body (8)(9)(10)(11) as well as substantial amounts of gamma globulin (12,13), the present study was undertaken to determine the effect of hyaluronic acid on the thermal aggregation of human gamma globulin.…”

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confidence: 99%

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Sulfhydryl‐dependent thermal aggregation of human gamma globulin

Gerber

1975

Arthritis & Rheumatism

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Hyaluronic acid (4 mg/ml) augmented elevenfold the copper‐catalyzed (7 βxM) thermal (63°C, 2 hours) aggregation of human gamma globulin (2 mg/ ml) in 0.075 M phosphate buffer, pH 7.4. Almost no augmentation of aggregation occurred with hyaluron‐idase‐treated hyaluronate. Hyaluronate‐augmented copper‐catalyzed thermal aggregation was inhibited by L‐histidine, gold thiomalate, N‐ethylmaleimide, p‐chlo‐romercuribenzoic acid, and ethylenediaminetetraacetic acid. Together with previous reports of a decreased blood histidine concentration in rheumatoid arthritis, these studies provide a possible explanation for the affinity of this disease for joints.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Sulfhydryl‐dependent thermal aggregation of human gamma globulin

Gerber

1975

Arthritis & Rheumatism

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“…Comparable studies on synovial fluids have not been performed though Wilkinson and Jones (1964) demonstrated higher a2 and y globulins compared with rheumatoid disease.…”

Section: Discussionmentioning

confidence: 99%

Synovial fluid in ankylosing spondylitis.

Kendall¹,

Farr²,

Meynell³

et al. 1973

Annals of the Rheumatic Diseases

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“…The selected PK model was used to perform simulations and estimate plasma and SF TA concentrations after repeat doses of TA–ER and TAcs with Q1M and Q3M dosing. These simulations were also used to assess the duration for which the TA levels were maintained above a range of target effective concentrations (10, 30, and 100 ng/ml) in SF based on relative receptor potency, SF protein binding, and SF protein levels in OA patients [ 25 , 26 ]. See the Online Supplement for more information on PK model development and simulations.…”

Section: Methodsmentioning

confidence: 99%

Local Effects Following Single and Repeat Intra-Articular Injections of Triamcinolone Acetonide Extended-Release: Results from Three Nonclinical Toxicity Studies in Dogs

et al. 2018

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IntroductionSingle intra-articular (IA) injections of poly(lactic-co-glycolic acid) (PLGA) microsphere-based triamcinolone acetonide extended-release (TA–ER; formerly FX006) demonstrated sustained, clinically relevant benefits in patients with knee osteoarthritis. The local effects of TA–ER were assessed in normal canine knees in three nonclinical studies.MethodsKnees were evaluated for up to 6 weeks or 9 months after a single injection of TA–ER (2.1/6.25/18.75 mg TA), or TA crystalline suspension (TAcs, 18.75 mg TA), and for up to 6 months after three injections (every 1 or 3 months) of TA–ER (6.25/18.75 mg TA) or TAcs (18.75 mg). Vehicle-diluent, blank microspheres, and untreated knees were used as controls. Plasma and synovial fluid (SF) TA concentrations and standard histopathological assessment of the synovium were conducted. Articular cartilage morphology was assessed via modified Mankin scoring.ResultsPlasma and SF concentrations indicated prolonged dose-dependent TA joint residency with TA–ER compared with TAcs. Effects in articular cartilage were dose- and time-dependent and consistent with known effects of corticosteroids in the normal knee. Loss of Safranin O staining occurred, indicative of a reduction in cartilage matrix proteoglycan, and recovered in a similar manner for TA–ER and TAcs across all studies. Structural lesions were infrequent and generally comparable in severity between TA–ER and TAcs but slightly higher in incidence for TA–ER. Focal/multifocal foreign-body responses (FBR) to PLGA were observed in the superficial layer of the synovium, peaking after 4–6 weeks, with significant recovery or complete resolution by month 6.ConclusionsThese findings suggest that the effects of IA injections of TA–ER on cartilage are predominantly transient, and comparable to those observed with TAcs in the normal canine knee joint. These mild effects in the normal joint differ from the beneficial effects observed with TA–ER and other corticosteroids in disease models. The synovial FBR to PLGA microspheres was focal and transient.FundingFlexion Therapeutics, Inc.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s40744-018-0125-3) contains supplementary material, which is available to authorized users.

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Electrophoretic Studies of Synovial Fluid Proteins

Cited by 8 publications

References 9 publications

Sulfhydryl‐dependent thermal aggregation of human gamma globulin

Sulfhydryl‐dependent thermal aggregation of human gamma globulin

Synovial fluid in ankylosing spondylitis.

Local Effects Following Single and Repeat Intra-Articular Injections of Triamcinolone Acetonide Extended-Release: Results from Three Nonclinical Toxicity Studies in Dogs

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