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Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits.

ABSTRACT: INTRODUCTION: Adrenomedullin is a potent vasodilatory and hypotensive peptide as well as an endogenous immunomodulatory factor with predominantly anti-inflammatory effects. The purpose of the present study was to evaluate the therapeutic effects of adrenomedullin in rabbits with antigen-induced arthritis, an experimental model of rheumatoid arthritis. METHODS: Following the induction of arthritis in both knee joints by ovalbumin injection into the joint spaces of pre-immunized rabbits, increasing daily doses of adrenomedullin were injected into the knee joint spaces or saline was injected into the contralateral knee joint spaces as the control. For time-course experiments, adrenomedullin and saline were injected into the knee joint spaces daily for 7 days and 20 days. The degree of joint swelling and the histological change in the knee joints injected with adrenomedullin were compared with the control knee joints. Histological evaluation of the infrapatellar fat pads and synovial tissue was performed. TNFalpha, IL-6, vascular endothelial growth factor and transforming growth factor-beta mRNA levels in the synovial tissue were measured using real-time quantitative PCR. RESULTS: Daily injections of adrenomedullin into the knee joint spaces of rabbits with antigen-induced arthritis decreased joint swelling. Histological examination revealed that adrenomedullin reduced edematous changes and the infiltration of inflammatory cells in the synovial tissues. Analysis of mRNA levels showed that adrenomedullin significantly reduced TNFalpha mRNA expression by 21% to 49% in a dose-dependent manner, and dose-dependently increased IL-6 mRNA expression by 45% to 121%. CONCLUSIONS: These results suggest that daily injections of adrenomedullin into the knee joint spaces of rabbits with antigen-induced arthritis ameliorated the inflammatory response in arthritic joints. Adrenomedullin may thus be useful as a treatment for rheumatoid arthritis; however, the effect of adrenomedullin on IL-6 production in the synovial tissue may be an undesirable adverse effect in rheumatoid arthritis therapy.

SUBMITTER: Okura T

PROVIDER: S-EPMC2656235 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits.

Okura Toshiyuki T Marutsuka Kousuke K Hamada Hiroaki H Sekimoto Tomohisa T Fukushima Tsuyoshi T Asada Yujiro Y Kitamura Kazuo K Chosa Etsuo E

Arthritis research & therapy 20081113 6

<h4>Introduction</h4>Adrenomedullin is a potent vasodilatory and hypotensive peptide as well as an endogenous immunomodulatory factor with predominantly anti-inflammatory effects. The purpose of the present study was to evaluate the therapeutic effects of adrenomedullin in rabbits with antigen-induced arthritis, an experimental model of rheumatoid arthritis.<h4>Methods</h4>Following the induction of arthritis in both knee joints by ovalbumin injection into the joint spaces of pre-immunized rabbi ...[more]

PMID: 19014513

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Project description:Repairing damaged articular cartilage is particularly challenging because of the limited ability of cartilage to perform self-repair. Intra-articular injections of N-acetylglucosamine (GlcNAc) comprise a method of repairing full-thickness articular cartilage defects in the rabbit knee joint model. To date, the effects of administration of GlcNAc and hyaluronic acid (HA) have been investigated only in the context of osteoarthritis treatment. Therefore, we evaluated the therapeutic effects of using cell-free porous poly lactic-co-glycolic acid (PLGA) graft implants and intra-articular injections of GlcNAc or HA in a rabbit model of osteochondral regeneration to investigate whether they have the potential for inducing osteochondral regeneration when used alone or simultaneously. Twenty-four rabbits were randomized into one of four groups: the scaffold-only group (PLGA), the scaffold with intra-articular injections of GlcNAc (PLGA+G) group, twice per week for four weeks; the scaffold with intra-articular injections of HA group (PLGA+HA) group, once per week for three weeks; and the scaffold with intra-articular injections of GlcNAc and HA (PLGA+G+HA) group, once per week for three weeks. Knees were evaluated at 4 and 12 weeks after surgery. At the end of testing, only the PLGA+G+HA group exhibited significant bone reconstruction, chondrocyte clustering, and good interactions with adjacent surfaces at 4 weeks. Additionally, the PLGA+G+HA group demonstrated essentially original hyaline cartilage structures that appeared to have sound chondrocyte orientation, considerable glycosaminoglycan levels, and reconstruction of the bone structure at 12 weeks. Moreover, the PLGA+G+HA group showed organized osteochondral integration and significantly higher bone volume per tissue volume and trabecular thickness. However, there were no significant differences between the PLGA+G and PLGA+HA groups except for gap formation on subchondral bone in the PLGA+G group. This study demonstrated that PLGA implantation combined with intra-articular injections of GlcNAc and HA allowed for cartilage and bone regeneration and significantly promoted osteochondral regeneration in rabbits without supplementation of exogenous growth factors. And the combination of this two supplements with PLGA scaffold could also prolong injection interval and better performance than either of them alone for the reconstruction of osteochondral tissue in the knee joints of rabbits.

Project description:BackgroundAs an essential component of multimodal analgesia approaches after total knee arthroplasty (TKA), local infiltration analgesia (LIA) can be classified into peri-articular injection (PAI) and intra-articular injection (IAI) according to administration techniques. Currently, there is no definite answer to the optimal choice between the two techniques. Our study aims to investigate analgesic efficacy and safety of PAI versus IAI in patients receiving simultaneous bilateral TKA.MethodsThis randomized controlled trial was conducted from February 2017 and finished in July 2018. Sixty patients eligible for simultaneous bilateral total knee arthroplasty were randomly assigned to receive PAI on one side and IAI on another. Primary outcomes included numerical rating scale (NRS) pain score at rest or during activity at 3?h, 6?h, 12?h, 24?h, 48?h, and 72?h following surgery. Secondary outcomes contained active or passive range of motion (ROM) at 1, 2, and 3?days after surgery, time to perform straight leg raise, wound drainage, operation time, and wound complications.ResultsPatients experienced lower NRS pain scores of the knee receiving PAI compared with that with PAI during the first 48?h after surgery. The largest difference of NRS pain score at rest occurred at 48?h (PAI: 0.68, 95%CI[0.37, 0.98]; IAI: 2.63, 95%CI [2.16, 3.09]; P <?0.001); and the largest difference of NRS pain score during activity also took place at 48?h (PAI: 2.46, 95%CI [2.07, 2.85]; IAI: 3.90, 95%CI [3.27, 4.52]; P =?0.001). PAI group had better results of range of motion and time to perform straight leg raise when compared with IAI group. There were no differences in operation time, wound drainage, and wound complication.ConclusionPAI had the superior performance of pain relief and improvement of range of motion to IAI. Therefore, the administration technique of peri-articular injection is recommended when performing local infiltration analgesia after total knee arthroplasty.Trial registrationThe trial was retrospectively registered in the Chinese Clinical Trial Registry as ChiCTR1800020420 on 29th December, 2018.Level of evidenceTherapeutic Level I.

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Dataset Information

Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits.

Publications

Therapeutic efficacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits.

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