Análise fotocolorimétrica computadorizada dos efeitos da betametasona intra-articular sobre a concentração de proteoglicanos da matriz cartilaginosa de joelhos leporinos: influência do número de injeções intra-articulares

The major challenge in identifying dexamethasone, betamethasone, and paramethasone from a mixture of these corticosteroids is difficulty in achieving an efficient separation. In this study, we aimed to develop an efficient technique to identify these co-eluting isomers based on the mass spectral patterns of them and their corresponding phase II metabolites after electrospray ionization. Fragmentation pathways in tandem mass spectrometry revealed acceptable specificity within the groups of conjugates. The method was validated using individual isomers and mixtures at various compositions. The effects of concentration and collision energies on fragmentation patterns were also studied extensively. Matrix-fortified equine urine and plasma samples were also included so that matrix effects and interferences on fragmentation ratios could be elucidated. Preliminary results using biological samples demonstrated the suitability of this analytical strategy for direct measurement from their fragmentation patterns. Possible fragmentation pathways for each isomer were proposed.

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Mass spectrometric method for distinguishing isomers of dexamethasone via fragment mass ratio: An HRMS approach

Karatt

Nalakath

Perwad

et al. 2018

J Mass Spectrom

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Management of persistent inflammatory large joint monoarthritis

2012

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Persistent inflammatory monoarthritis is inflammation of one joint, with symptoms lasting beyond 3 months. Approximately 50 % of cases are self-limiting; others will transform into oligo- or polyarticular disease, but a significant minority remain as a persistent inflammatory monoarthritis, which are often resistant to standard therapies used for oligo- or polyarticular disease and constitute a difficult therapeutic problem. However, there are no clear guidelines for treatment of this category of patients or an evidence-based consensus view on best treatment. A literature search was done through PubMed using 'monoarthritis', 'chronic synovitis' and 'persistent inflammatory monoarthritis' as search terms. Reports were located using references to related articles; reports in humans and animals, published in English, were included. Persistent inflammatory monoarthritis has a variable disease course, generally with a better prognosis than polyarthritis. There is no clear evidence for the use of traditional DMARDS in monoarthritis, and treatment algorithms are extrapolated from oligo- or polyarticular disease. Intra-articular anti-tumour necrosis factor (TNF) has been used with similar efficacy to intra-articular corticosteroids, and as yet, there are no reported cases of systemic anti-TNF use in monoarthritis. Synovectomy may be of use, with lower risk of recurrent disease, in open synovectomy. There is paucity of evidence for best practice in the management of chronic monoarthritis. Questions remain concerning the indications for invasive procedures and the balance between toxicity of systemic therapies versus the intended benefits to prevent disability. There is a pressing need for further studies and randomised controlled trials to be performed in this subset of patients.

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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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Análise fotocolorimétrica computadorizada dos efeitos da betametasona intra-articular sobre a concentração de proteoglicanos da matriz cartilaginosa de joelhos leporinos: influência do número de injeções intra-articulares

Cited by 12 publications

References 12 publications

Mass spectrometric method for distinguishing isomers of dexamethasone via fragment mass ratio: An HRMS approach

Mass spectrometric method for distinguishing isomers of dexamethasone via fragment mass ratio: An HRMS approach

Management of persistent inflammatory large joint monoarthritis

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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