Page 924 - Adams and Stashak's Lameness in Horses, 7th Edition
P. 924

890   Chapter 8


            vascularity and subintimal fibrosis compared with     present in high amounts in  ACS.  Specifically, it has
                                                                                             45
              control horses when the drug was administered weekly   been reported that production of IL‐4, IL‐10, IRAP, and
  VetBooks.ir  beneficial effect on lameness. It was concluded that in   of whole blood with medical‐grade glass beads exposed
                                                               other growth factors is stimulated through incubation
            for 3 weeks.  However, neither PSGAGs nor HA had a
                       46
                                                               to chromium sulfate.
            the osteochondral fragment model, both drugs had ben-
                                                                                 82
            eficial disease‐modifying effects. Furthermore, in a study   A study in which ACS was injected into the middle
            that compared PSGAGs with IA CS (MPA 40 mg), a     carpal joints on day 14, 21, 28, and 35 following induc-
            regimen of weekly IA PSGAGs for three treatments gave   tion of OA through a chip fragment model revealed sig-
            significantly improved results (67%) compared with   nificant clinical improvement in lameness and reduced
            one treatment of CS (46%) in terms of returning horses   gross cartilage fibrillation and synovial membrane
            to performance.  It has also been suggested that, using   pathology.  This same study detected elevated levels of
                                                                        45
                          73
            the osteochondral fragment model, the IA combination   IRAP in the synovial fluid of the horses injected with
            of TA (5 mg) and PSGAG (250 mg) is less effective than   ACS at 70 days’ post‐OA induction.  Clinical trials in
                                                                                               45
            IA PSGAG used alone when administered at weekly    humans with OA have indicated that people injected
            intervals for five treatments. 48                  with ACS experienced greater reduction in clinical signs
                                                               and improved quality of life compared with people
                                                               whose joints were injected with HA. 11,116  Significant
            Clinical Considerations
                                                               pain reduction has also been seen following treatment of
              PSGAG is most likely more efficacious if adminis-  patients with varying degrees of hip OA with ACS alone,
            tered IA; however, due to the drug’s ability to potentiate   with no increase in beneficial effects seen when ACS was
            sub‐infective doses of contaminant bacteria, this route   combined with cortisone or cortisone + recombinant
            of administration should be accompanied with amika-  IRAP (rIRAP).  Use of this medication requires incuba-
                                                                            12
            cin in order to obviate this risk. 57,58  Currently, the   tion of equine serum with beads coated with chromium
            approved frequency of IA administration is three to five   sulfate to obtain the ACS solution. The ACS is usually
            injections (250 mg each) at weekly intervals. 1,93  It may   administered IA weekly for three to four treatments,
            be most efficacious in joints with known or suspected   depending on the quantity of ACS obtained. Treatment
            articular cartilage pathology. 1                   with ACS prior to injection of other biologic agents is
                                                               increasing in practice, although further clinical trials are
                                                               necessary to evaluate the benefits and effectiveness of
            POLYGLYCAN   ®                                     this technique.
              Polyglycan , which is not yet licensed for use as an IA
                        ®
            medication, is a patented formulation composed of HA,
            chondroitin sulfate, and  N‐acetyl‐d‐glucosamine and   PLATELET‐RICH PLASMA
            has been used clinically in horses IA for viscosupple-  Platelet‐rich plasma (PRP) is an increasingly popular
            mentation. This product is currently used extensively in   intralesional therapy used in equine practice to enhance
            equine practice; however, only one randomized blinded   the  regeneration  of  injured  tissues  with  poor  healing
            placebo‐controlled study has been performed to assess   capabilities (i.e. limited blood supply). However, IA use
            its efficacy. Using the OA osteochondral fragment model   of PRP has recently emerged as a potential treatment of
            of the middle carpal joints, horses that received   OA both in humans and horses. 19,33,34,39,71,83,94,101  PRP is
                     ®
            Polyglycan  IA (5 mL) at days 0, 7, 14, and 28 showed   a platelet‐concentrated, autologous blood product cre-
            significant improvements in lameness, bony prolifera-  ated through various centrifugation processes that deliv-
            tion, and degree of full thickness articular cartilage ero-  ers increased platelet‐derived growth factors (PDGF) to
            sions observed grossly.   Treatment with Polyglycan    the site of injury. 40,107  Various cytokines detected in PRP
                                                           ®
                                47
            resulted  in  a  mild  transient  reduction  in  lameness   that can potentially promote healing include transform-
            throughout the study, with the greatest improvement   ing growth factor‐β (TGF‐β), PDGF, insulin‐like growth
            (30% reduction) noted on day 42. When compared with   factor  (IGF‐I, IGF‐II), fibroblast growth  factor  (FGF),
            the use of HA alone in one in vitro study, cells treated   epidermal growth factor, vascular endothelial growth
            with HA had significantly better morphology scores;   factor (VEGF), and endothelial cell growth factor.  In
                                                                                                            40
            however, Polyglycan  resulted in superior suppression of   vitro, PRP has been shown to induce chondrogenesis by
                             ®
            lipopolysaccharides (LPS)‐induced production of proin-  stimulating proliferation of chondrocytes and extracel-
            flammatory cytokines, providing further support for its   lular matrix synthesis of proteoglycans and type II col-
            protective potential. 68                           lagen,  to induce chondroprotection by increasing the
                                                                     3
                                                               production and secretion of HA from synoviocytes,  and
                                                                                                           4
            AUTOLOGOUS CONDITIONED SERUM                       to inhibit inflammatory processes in chondrocytes. 19
                                                                  Due to the limited number of in vivo studies, IA PRP
              Autologous conditioned serum (ACS, also called   is not yet a standard treatment for OA but has shown
            interleukin receptor antagonist protein, IRAP) has been   potential as a therapeutic option in refractory cases. In
            used extensively in practice to treat intrasynovial inflam-  both horses and humans, IA PRP appears to incite an
            mation, especially in cases that are refractory to IA CS.   acute, short‐term inflammatory response within the
            Although clinical impressions have been favorable, this   injected joint; 83,94,104,107  however, studies evaluating its use
            method of treatment is not widely used due to cost.   in healthy equine joints have found IA PRP to be safe
            IRAP, a substance that inhibits IL‐1 activity, decreases   without long‐term detrimental effects. 83,101,107  One clini-
            the progression of joint disease and is believed to be   cal study evaluated PRP for the treatment of refractory
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