The efficacy of vitamin E in preventing arthrofibrosis after joint replacement.

BACKGROUND: Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues. Vitamin E is an antioxidant with potential anti-fibroblastic effect. The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis. METHODS: We simulated knee replacement in 16 male Sprague-Dawley rats. We immobilized the surgical leg with a suture in full flexion. The control groups were killed at 2 and 12 weeks (n = 5 per group), and the test group was supplemented daily with vitamin E (0.2 mg/mL) in their drinking water for 12 weeks (n = 6). We performed histological staining to investigate the presence and severity of arthrofibrosis. Immunofluorescent staining and α2-macroglobulin (α2M) enzyme-linked immunosorbent assay (ELISA) were used to assess local and systemic inflammation. Static weight bearing (total internal reflection) and range of motion (ROM) were collected for functional assessment. RESULTS: The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups. Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue. Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels. The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group. CONCLUSIONS: This model is viable for simulating arthrofibrosis after joint replacement. Vitamin E may benefit postsurgical arthrofibrosis, and further studies are needed for dosing requirements.

Mitomycin C induces fibroblast apoptosis and reduces intra-articular scar adhesion by regulating miR-21 and its target Programmed cell death 4.

Previous studies have shown that mitomycin C (MMC) can prevent scar adhesion after joint surgery, but the specific mechanism underlying this effect remains unclear. The purpose of this study was to explore the specific mechanism by which MMC promotes fibroblast apoptosis and prevents joint adhesion. The effect of MMC on fibroblasts was assessed using cell counting kit-8 (CCK-8) assays, western blotting, and TUNEL staining. We used qRT-PCR to measure the expression of miR-21 in fibroblasts treated with MMC. Luciferase activity assays were used to determine the relationships between miR-21 and Programmed cell death 4 (PDCD4). The effects of miR-21 and PDCD4 on fibroblast apoptosis were assessed using flow cytometry and western blotting. HE staining was used to determine the role of miR-21 in scar tissue formation in a model of joint adhesion. The results showed that MMC induced apoptosis of fibroblasts and decreased the expression of miR-21. Moreover, miR-21 down-regulation also induced apoptosis of fibroblasts. PDCD4 was confirmed to be a direct target of miR-21 by luciferase activity assay. The results from the animal model indicated that miR-21 attenuated the effect of MMC on reducing the number of fibroblasts. Our study shows that MMC can induce fibroblast apoptosis and prevent joint adhesion by regulating the expression of miR-21 and its target PDCD4.

Effect of a commercially available fish-based dog food enriched with nutraceuticals on hip and elbow dysplasia in growing Labrador retrievers.

The aim of this study was to evaluate the prevalence of hip and elbow dysplasia in a group of growing Labrador retrievers fed a fish-based diet enriched with nutraceuticals with chondroprotective properties. The puppies ranged from 3 to 12 mo of age and were divided into 2 groups, each fed a different diet. The control diet consisted of a high quality, chicken-based dog food, while the test diet was a fish-based dog food, enriched with nutraceuticals. Hip and elbow joints were radiographed and scored at 6 and 12 mo of age. Overall, 42 dogs completed the study. At 12 mo of age, no differences were found between the groups in the prevalence of hip and elbow dysplasia, although dogs fed the fish-based food enriched with nutraceuticals had a less severe grade of osteoarthritis at 12 mo. It was concluded that the fish-based diet with nutraceuticals did have beneficial effects on the development of severe osteoarthritis.

L'objectif de la présente étude était d'évaluer la prévalence de dysplasie de la hanche et du coude dans un groupe de chiens Labrador en croissance nourris avec une diète à base de poisson enrichie de neutraceutiques ayant des propriétés chondroprotectrices. L'âge des chiots variait de 3 à 12 mois et ils ont été divisés en deux groupes, chacun étant nourri avec une diète différente. La diète témoin consistait d'un aliment de haute qualité pour chien à base de poulet, alors que la diète test était un aliment pour chien à base de poisson et enrichi avec des neutraceutiques. Les articulations des hanches et des coudes ont été radiographiées à 6 et 12 mois d'âge. Un total de 42 chiens a complété l'étude. À 12 mois d'âge, aucune différence n'a été trouvée entre les groupes dans la prévalence de dysplasie de la hanche et du coude, bien que les chiens nourris avec la diète à base poisson enrichie de neutraceutiques avaient un score d'ostéoarthrite moins sévère à 12 mois. Il a été conclu que la diète à base de poisson enrichie de neutraceutiques avait des effets bénéfiques sur le développement d'ostéoarthrite sévère.(Traduit par Docteur Serge Messier).

Use of Neuromuscular Electrical Stimulation During Physical Therapy May Reduce the Incidence of Arthrofibrosis After Total Knee Arthroplasty.

INTRODUCTION: Arthrofibrosis remains a major complication following total knee arthroplasty (TKA) that negatively impacts patient outcomes and exhausts healthcare resources. The use of neuromuscular electrical stimulation (NMES) has demonstrated the ability to facilitate quadriceps muscle recovery and reduce pain. Therefore, the purpose of this study was to compare TKA patients who received physical therapy (PT) and adjuvant NMES therapy versus physical therapy alone in terms of: 1) rates of manipulation under anesthesia (MUA) to treat arthrofibrosis; and 2) post-therapy range of motion (ROM). MATERIALS AND METHODS: This was a retrospective review of TKA patients from multiple institutions who underwent physical therapy versus physical therapy and adjuvant NMES therapy following primary TKA. A total of 206 patients were reviewed in the two cohorts that either received PT alone (n=86) or PT and adjuvant NMES therapy (n=120). Data regarding the requirement of MUA postoperatively for treatment of arthrofibrosis were collected for every patient. Additionally, pre- and post-therapy knee ROM data was also collected. Outcomes in both cohorts were then compared and analyzed. RESULTS: Lower rates of arthrofibrosis requiring MUA were recorded in patients who used NMES therapy and PT when compared to PT alone (7.5% vs. 19.8%; p=0.009). Log regression analysis revealed lower odds of needing MUA in patients who utilized NMES therapy in adjunct with PT (odds ratio [OR]=0.36; 95% CI: 0.115 to 0.875; p=0.023). Patients who received the NMES therapy were shown to have a statistically greater mean improvement in ROM when compared to those patients who did not receive NMES (+2.63, p=0.04). Log regression analysis also demonstrated that post-PT ROM decreased the odds of receiving MUA with a larger ROM (OR=92; 95% CI: 0.824 to 0.9855; p<0.001). CONCLUSION: This study demonstrated that the use of NMES during PT may reduce the incidence of arthrofibrosis and improve patient ROM. Prospective, randomized controlled, and larger-scale studies are needed to validate these results. Nevertheless, this novel report demonstrated the positive outcomes for a new application of the NMES therapy.

Efficacy of an oral hyaluronate and collagen supplement as a preventive treatment of elbow dysplasia.

One hundred and five Labrador dogs were randomly divided into two groups to determine the number of animals that develop elbow dysplasia when treated with an oral supplement compared to untreated ones. Efficacy of the oral treatment was also evaluated once illness was diagnosed. The supplement (Hyaloral) contained hyaluronic acid, hydrolysed collagen, glucosamine, chondroitin sulphate, and gamma oryzanol. Clinical evaluation of the elbow joints was completed at months 3, 6, 12, and 20 by orthopaedic evaluations, radiography, serologic and blood analysis, and veterinarian evaluation of dysplasia symptoms. All side effects were recorded. In the control group, 33.3% of the dogs developed radiographic evidence of elbow dysplasia compared to 18.5% in the treated group. Symptoms of dysplasia at 12 months differed between the treated (12.5%) and control (61.5%) animals, and were significantly different at 20 months (p < 0.05). Differences in lameness along with movement and swelling of the elbows between groups were observed after 12 months. The treated group had improved significantly by the last visit (p < 0.05). No adverse side effects were reported. In conclusion, oral treatment with Hyaloral may have a potential cumulative action that provides protection against dysplasia and significantly improves symptoms of elbow dysplasia.

Efficacy of an oral hyaluronate and collagen supplement as a preventive treatment of elbow dysplasia

One hundred and five Labrador dogs were randomly divided into two groups to determine the number of animals that develop elbow dysplasia when treated with an oral supplement compared to untreated ones. Efficacy of the oral treatment was also evaluated once illness was diagnosed. The supplement (Hyaloral) contained hyaluronic acid, hydrolysed collagen, glucosamine, chondroitin sulphate, and gamma oryzanol. Clinical evaluation of the elbow joints was completed at months 3, 6, 12, and 20 by orthopaedic evaluations, radiography, serologic and blood analysis, and veterinarian evaluation of dysplasia symptoms. All side effects were recorded. In the control group, 33.3% of the dogs developed radiographic evidence of elbow dysplasia compared to 18.5% in the treated group. Symptoms of dysplasia at 12 months differed between the treated (12.5%) and control (61.5%) animals, and were significantly different at 20 months (p < 0.05). Differences in lameness along with movement and swelling of the elbows between groups were observed after 12 months. The treated group had improved significantly by the last visit (p < 0.05). No adverse side effects were reported. In conclusion, oral treatment with Hyaloral may have a potential cumulative action that provides protection against dysplasia and significantly improves symptoms of elbow dysplasia.

Activity study of a hydroxynaphthoquinone fraction from Arnebia euchroma in experimental arthritis.

Although various drugs for the treatment of rheumatoid arthritis (RA) have been used in clinics, RA is not completely curable to date. Thus, to seek new drugs for the treatment of RA has been a hotspot. Hydroxynaphthoquinones are the major anti-inflammatory active constituents in Arnebia euchroma (Royle) Johnst. The present study aims to evaluate the anti-arthritic activity of a hydroxynaphthoquinone mixture (HM) of A. euchroma (Royle) Johnst, including its anti-inflammatory and analgesic effects. The anti-arthritic efficacy of HM was examined using complete Freund's adjuvant- and bovine type II collagen-induced arthritic models. The paw edema, polyarthritis index and histopathological change were evaluated. The analgesic effect was assessed using the chemical and thermal models of nociception. Results found that HM administered prophylactically and curatively showed marked anti-arthritic activity by suppressing the paw swelling and development of inflammation, lowering the levels of TNF-α and IL-1ß and protecting cartilage and bone from damage. The protection of HM was superior to that of reference drugs such as prednisone acetate or etanercept, and showed no direct deleterious effect. Similarly, HM showed significant analgesic effects. In summary, HM possessed potent anti-arthritic activity. It could relieve inflammatory symptoms and protect against joint destruction. These findings indicate that HM would be a potential therapeutic agent for arthritic disease, which provide pharmacological evidence for its clinical application.

[Prevention of occupational diseases of lower limbs joints].

Study covered 84 personal computer users, 48 jewelry female polishers, 92 metallic ships body assemblers. Objective investigations revealed lower limbs joints stiffness. After prevention measures based on low-intensity laser rays, the joints functions recovered.

GATA-3 protects against severe joint inflammation and bone erosion and reduces differentiation of Th17 cells during experimental arthritis.

OBJECTIVE: Rheumatoid arthritis is associated with the infiltration of T helper cells into the joints. It is unclear whether interferon-gamma (IFNgamma)-producing Th1 cells or the novel T helper subset, interleukin-17 (IL-17)-producing Th17 cells, are the pathogenic mediators of joint inflammation in chronic nonautoimmune arthritis. Therefore, this study was aimed at examining whether the Th2-specific transcription factor GATA-3 can regulate arthritis, in an experimental murine model, by modulating Th1 and/or Th17 cell polarization. METHODS: Arthritis was induced with methylated bovine serum albumin (mBSA) in both wild-type and CD2 T cell-specific GATA-3 (CD2-GATA-3)-transgenic mice. At days 1 and 7 after the induction of arthritis, knee joints were scored macroscopically for arthritis severity and for histologic changes. Single-cell suspensions were generated from the spleens, lymph nodes, and inflamed knee joints. Cytokine expression by CD4+ T cells was determined using flow cytometry, and IL-17 expression in the inflamed knee joints was determined by enzyme-linked immunosorbent assay. Analyses of gene expression were performed for Th17-associated factors. RESULTS: Wild-type mice developed severe joint inflammation, including massive inflammatory cell infiltration and bone erosion that increased significantly over time, reaching maximal arthritis scores at day 7. In contrast, only mild joint inflammation was observed in CD2-GATA-3-transgenic mice. This mild effect was further accompanied by systemic and local reductions in the numbers of IL-17+IFNgamma- and IL-17+IFNgamma+, but not IL-17-IFNgamma+, CD4+ T cells, and by induction of Th2 cytokine expression. Moreover, GATA-3 overexpression resulted in reduced gene expression of the Th17-associated transcription factor retinoic acid-related orphan receptor gammat. CONCLUSION: These results indicate that enforced GATA-3 expression protects against severe joint inflammation and bone erosion in mice, accompanied by reduced differentiation of Th17 cells, but not Th1 cells, during mBSA-induced arthritis.

Selenium for preventing Kashin-Beck osteoarthropathy in children: a meta-analysis.

OBJECTIVE: To assess the efficacy of selenium supplementation for prevention of Kashin-Beck Osteoarthropathy in children. METHODS: We searched eight electronic databases and seven journals (upto July 2007) to identify randomized controlled trials (RCTs) and prospective non-RCTs comparing selenium supplementations with placebo or no intervention for preventing Kashin-Beck disease (KBD). The methodological qualities of included studies were assessed according to the guidelines of Cochrane Handbook for Systematic Reviews of Interventions for RCTs and the method described by Deeks et al. for non-RCTs. Outcomes were presented as Peto-odds ratios (Peto-ORs) with 95% confidence intervals (95% CIs) based on fixed effect model. The number needed to treat (NNT) was calculated. Meta-regression was also conducted to explore the possible impacts of potential confounding variables (place of study, age, selenium form, etc.) of included trials on the incidence of KBD. RESULTS: Five RCTs and 10 non-RCTs were included in this review. The methodological quality of included studies was low. The pooled Peto-OR and NNT favoring selenium supplement was 0.13 (95% CI: 0.04-0.47) and 21 in RCTs, and 0.16 (95% CI: 0.09-0.30) and 26 in non-RCTs. Meta-regression indicated that the effect of potential confounding variables on KBD incidence was not statistically significant. One trial reported the side effects of nausea and vomiting in the process of selenium supplementation. CONCLUSIONS: Current evidence supports the benefits of selenium supplementation for prevention of KBD in children. However, the evidence was limited by potential biases and confounders. Large, well-designed trials are still needed.

Multimodal pain management and arthrofibrosis.

Pain control after arthroplasty has been a key concern for orthopedic surgeons. After total knee arthroplasty (TKA), a small group of patients developed a painful joint with suboptimal range of motion. Manipulation under anesthesia increases flexion and extension while decreasing pain in most cases. The objective of the present investigation is to asses the effect of a multimodal pain management protocol on arthrofibrosis in primary TKAs. A cohort of 1136 patients who underwent primary TKA was selected. Patients were divided into 2 groups: group A had 778 procedures performed using a traditional approach to pain control; group B included 358 procedures that received multimodal pain management. Group A had an incidence of manipulation of 4.75% (37/778). Of 357 patients, 8 required manipulation in group B, which is an incidence of 2.24%. We recommend that orthopedic surgeons consider using a multimodal pain management protocol for TKA.

Multivariable analysis of factors influencing outcome of 2 treatment protocols in 128 cases of horses responding positively to intra-articular analgesia of the distal interphalangeal joint.

REASONS FOR PERFORMING STUDY: There is limited knowledge available of factors influencing response to treatments of the DIP-joint in horses with lameness responding to diagnostic analgesia of the DIP-joint. For this reason a multivariable statistical analysis was performed. HYPOTHESIS: Horses with lameness reduced by > or = 75% 10 min after intra-articular analgesia of the DIP-joint, can be treated successfully by intra-articular medication of the joint. Multiple factors influence the response to treatment. METHODS: The study was performed retrospectively based on clinical records of horses treated with either polysulphated glycosaminoglycan (PSGAG) or methylprednisolone acetate (MPA) in the DIP-joint between January 1996 and January 2003. Information was collected from clinical records and from the owners of the horses via a detailed questionnaire, in which they described their perception of the outcome a minimum of one year after treatment. Allocation of the horses to the 2 treatment groups was done mainly because of a change in treatment policy. In Regime A all horses received 3 intra-articular injections of PSGAG approximately 8 days apart, whereas in Regime B all horses received a single intra-articular injection of MPA as a first treatment. If the horse did not improve sufficiently to return to work by 4 weeks, a series of 3 intra-articular PSGAG injections was administered. RESULTS: Of the horses receiving Regime A, 67% had a successful outcome, compared with 46% of the group receiving Regime B. A significantly better result was obtained in dressage horses than in jumping horses (eventing and showjumping). Other variables such as age, duration of lameness, distribution of lameness, degree of lameness, response to DIP-joint analgesia and radiographic observations were also associated with success of treatment. CONCLUSIONS AND POTENTIAL RELEVANCE: There is a rationale for using either PSGAG or MPA intra-articularly in the treatment of lameness, reduced > or = 75% within 10 min of analgesia of the DIP-joint.

Nutritional considerations in joint health.

Osteoarthritis, a debilitating joint disorder, is the most common form of arthritis in the United States, where it affects an estimated 21 million people. In 2004, the direct and indirect health care costs associated with all forms of arthritis were approximately 86 billion dollars. Joint discomfort from osteoarthritis and other joint disorders may reduce physical activity in individuals experiencing this condition, resulting in energy imbalance and weight gain. Increased weight can exacerbate existing problems, as additional stress on joints stimulates risk of additional joint disorders. Dietitians play a role in preventing or reversing the problem of joint disorders by promoting nutrient-rich diets that support joint health through improvement in cartilage metabolism. In addition, counseling individuals on weight management and active lifestyles are key strategies for the management of joint health.

The effects of walking poles on shoulder function in breast cancer survivors.

Breast cancer treatment often results in impaired shoulder function, in particular, decrements in muscular endurance and range of motion, which may lead to decreased quality of life. The purpose of this investigation was to determine the effects of walking pole use on shoulder function in female breast cancer survivors. Participants had previously been treated with 1 or a combination of the following: mastectomy, breast conservation therapy, axillary lymph node dissection, chemotherapy, or radiation. Participants were randomly placed in experimental (n = 6) and control (n = 6) groups and met with a cancer exercise specialist 2 times each week for 8 weeks. The experimental group used walking poles during the 20-minute aerobic portion of their workout, whereas the control group did not use walking poles but performed 20 minutes of aerobic exercise per workout session. Both groups participated in similar resistance training programs. Testing was done pre- and postexercise intervention to determine upper body muscular endurance and active range of motion at the glenohumeral joint. Repeated-measures analysis of variance (ANOVA) revealed significant improvements in muscular endurance as measured by the bench press (P = .046) and lat pull down (P = .013) in the walking pole group. No within-group improvements were found in the group that did not use walking poles. The data suggest that using a walking pole exercise routine for 8 weeks significantly improved muscular endurance of the upper body, which would clearly be beneficial in helping breast cancer survivors perform activities of daily living and regain an independent lifestyle.

Arthrofibrosis following total knee replacement; does therapeutic warfarin make a difference?

Arthrofibrosis following total knee replacement (TKR) is a relatively common complication which results in a reduction in knee range of movement and patient dissatisfaction. A retrospective study examined the relationship between anticoagulation with therapeutic warfarin and rates of arthrofibrosis following TKR. Arthrofibrosis was defined as less than 80 degrees of knee flexion 6-8 weeks post-TKR. Patients were warfarinised if they had a history of thrombophilic tendencies or medical conditions necessitating anti-coagulation, rather than as routine thromboprophylaxis. All other patients received thromboprophylaxis using low molecular weight heparin. A total of 728 patients underwent 874 primary TKR between 1993 and 2002 in one centre, performed by four surgeons. Mean age was 68 years (range 48-89 years) and there were 483 female and 391 male knees. Eighty cases were warfarinised post-operatively (53 female, 27 male). Overall, 83 of 874 TKRs (9%) had arthrofibrosis (57 female, 26 male) requiring manipulation under anaesthetic (MUA). In the warfarinised group, 21 knees (26%) had an MUA (15 female, 6 male). This compared to 62 cases (8%) requiring MUA in the non-warfarinised group (42 female, 20 male). There was a statistically significant difference on Fisher's exact testing (P<0.0001) between groups. Following MUA, knee flexion improved in 95% cases to a minimum 95 degrees but 8 cases had a fixed flexion deformity of 5-10 degrees . In conclusion, therapeutic warfarinisation post-TKR leads to a statistically greater chance of the patient developing arthrofibrosis compared to prophylactic low molecular weight heparin and that patients should be counseled appropriately.

Prevention of progressive joint destruction in adjuvant induced arthritis in rats by a novel matrix metalloproteinase inhibitor, FR217840.

Matrix metalloproteinase (MMP) has been implicated in joint destruction of chronic arthritis diseases, such as rheumatoid arthritis. FR217840 (2R)-1-([5-(4-fluorophenyl)-2-thienyl]sulfonyl)-N-hydroxy-4-(methylsulfonyl)-2-piperazinecarboxamide is a potent, orally active synthetic MMP inhibitor that inhibits human collagenases (MMP-1, MMP-8 and MMP-13), gelatinases (MMP-2 and MMP-9) and membrane type MMP (MT-MMP) (MT1-MMP/MMP-14). FR217840 also inhibits rat collagenase and gelatinase. We studied the effect of FR217840 on a rat adjuvant induced arthritis model. Although oral administration (days 1-21) of FR217840 (3.2, 10, 32 mg/kg) to adjuvant injected Lewis rats did not affect inflammation, as indicated by both hind paw swelling and histological inflammatory infiltration, FR217840 suppressed both bone destruction and serum pyridinoline content in a dose-dependent manner. Also, FR217840 (32 mg/kg) reduced tartrate-resistant acid phosphatase (TRAP) cell number in the ankle joints of rats with arthritis. These results indicate that FR217840 successfully suppressed joint destruction and suggest that FR217840 may have potential as a novel anti-rheumatic drug.