joint therapy what is new in horses?
TRANSCRIPT
Joint Theraphy
Joint Therapy
House officers rounds
2/11/15
OSTEOARTHRITIS
OPTIONS OF TREATMENT
Corticosteroids (TA-MP)
HA+GAG
Pentosan polysulfate
Standing Arthroscopy
Stem cells + PRP
Corticosteroids
Objectives: To describe the plasma pharmacokinetics of TA and time-related urine and synovial fluid concentrations following i.m. and intra-articular administration to exercised Thoroughbred horses.
12 TB horses
Exercise:
3 days/ week: Walker,
2 days/ week: treadmill
Triamcinolone acetonide
IM 0.1 mg/kg
IA: 9 mg antebrachiocarpal joint.
Samples:
Blood: every other day until 60 days post administration
Synovial fluid: once a week until 56 days
Urine: Various times until 60 days
IA: LOQ 0.75 ng/ml LOD approximately 0.5 ng/ml
The primary goal: knowledge of the disposition of MP in plasma, urine, and synovial fluid following intra-articular administration in the horse.
Relate MP plasma and synovial fluid concentrations following intra-articular administration of MPA to exercised horses
16 healthy TB
Exercise:
3 days/week horse walkers
2 days/week treadmill
Methylprednisolone acetate 100 mg
Samples:
Blood: until day 44.
Synovial: R-L antebrachiocarpal and middle carpal joints, once a week until 77 days
Urine: until day 49
LOQ 1.0 ng/mL LOD 0.15 ng/mL.
HA + GAG
Goal: Report findings of some potential clinical sign or disease modifying action of this compound administered IA at the tested dose and frequency.
16 horses ( 8 placebo/ 8 treatment)
Arthroscopic of the middle carpal joints. One OC fragment created
Day 15: exercised treadmill 5 days/week
Treatment: Days 0, 7, 14 and 28
PCB: 125 mg amikacin + 5 mL 0.9% saline.
IA PG: 5 mL IA PG plus +amikacin Days 0, 7, 14 and 28 OA affected joint and amikacin + 5 mL 0.9% saline sham operated joint
Carpal flexion: joint pain-Efussion
Lameness
Radiographic
Synovial fluid: 1/week, TP and WBC. 2 biomarker (GAG andPGE2)
Gross pathological examination
Histologic examination
Improve lameness (pain)
No xr difference
Increase full thickness erosion
Modest clinical sign and potential disease modifying effects of a hyaluronan, sodium chondroitin sulfate and N-acetyl-D-glucosamine combination when administered IA at the time of disease creation
Pentosan polysulfate
How they administer pentosan polysulfate (PPS) to horses and their perceptions of the efficacy of PPS for: the prevention and treatment of osteoarthritis (OA),
PPS is combined with other drugs, and the efficacy of PPS compared with other osteoarthritic drugs.
Survey 76 equine vets use PPS
The most common reason for using PPS was as prophylactic therapy prior to upcoming equestrian events (90%). Respondents also perceived that PPS was more effective as a prophylactic therapy than as treatment for horses with clinical signs of OA
Standing Surgery
Regenerative therapies
Evaluate the clinical response of horses treated with PRP, MSC or combination of treatment
1) 20 horses AO fetlock joint were divided in 4 groups
Injected: 1) PRP; 2) MSCs; 3) MSCs and PRP; or 4) chondrogenic induced MSCs and PRP.
Evaluated: Clinical scoring after 6 weeks (T1), 12 weeks (T2), 6 months (T3) and 12 months (T4) post
2) 30 horses randomly assigned combination therapies and evaluated at T1
ObjectiveTo evaluate intra-articular autologous protein solution (APS) for the treatment of osteoarthritis in horses.
40 horses, vary high motion joints AO
20 injected/ 20 placebo
Lameness exam
Force plate
Joint fluid analysis
Xr
Train 2/week treatmill
Increase of number sound gate
No significant changes
Evaluate the efficacy of bilayer gelatin/b-tricalcium phosphate (GT) sponges loaded with mesenchymal stem cells (MSCs), chondrocytes, bone morphogenetic protein-2 (BMP-2), and platelet rich plasma (PRP) for the repair of osteochondral defects of the talus in horses
6 horses
Sponges: Bone Narrow PRP, MS, chondrogenic differentiation
Lateral trochlear ridge of the talus by surgical drilling through the incision, the MSC/BMP2/GT was inserted into the lower part of the defect, and the Ch/MSC/PRP/GT was inserted into the upper part of the defect
Medial oblique xr 0, 1, 2, 3, and 4. osteochondral regeneration scored % area filled
CT : 4 months
Macroscopic evaluation
Histology
No remaining implant material and no inflammatory reactions in or near the defects
Investigate the blood and synovial immune and histologic response to intra-articular injection of autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses
6 Horses fetlock joints injected BMDMSC treatments 60days previously
BMDMSC treatments (1) auto, (2) auto-BMP2,(3) allo, or (4) xeno.
Synovial biopsies histologic and molecu-lar analyses.
Peripheral venous blood 60 day safter synovial biopsy
No abnormalities were observed in the synovium or the articular cartilage
increased cellularity with some small caliber vessels. Inflamatory cell severity
increase in number of CD4 positive cells days 3 and 6 upon re-exposure of PBMC to the xenoMSC
Cytokine analysis:
increases in IL-6 PBMCplus xeno group compared to all other groups
IL-2 concentrations not significantly different among the groups at any timepoints.
Interferon gamma concentrations were significantly greater in the PBMC
IL-10 significantly greater in PBMCplus auto, allo and xeno groups compared to the PBMC orMSC alone
A xenogeneic cell-mediated immune response was generated that may produce a more significant immune response if a second injection was performed in vivo. Allogeneic MSC may not induce a detectable immune response after intra-articular injection, but further work may be needed to identify a more subtle response.
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