joint therapy what is new in horses?

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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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