Effect of gedunin on acute articular inflammation and hypernociception in mice.

Gedunin, a natural limonoid from Meliaceae species, has been previously described as an antiinflammatory compound in experimental models of allergic inflammation. Here, we report the antiinflammatory and antinociceptive effects of gedunin in an acute model of articular inflammation induced by zymosan (500 µg/cavity; intra-articular) in C57BL/6 mice. Intraperitoneal (i.p.) pretreatment with gedunin (0.005-5 mg/kg) impaired zymosan-induced edema formation, neutrophil accumulation and hypernociception in mouse knee joints, due to decreased expression of preproET-1 mRNA and production of LTB4, PGE2, TNF-α and IL-6. Mouse post-treatment with gedunin (0.05 mg/kg; i.p.) 1 and 6 h after stimulation also impaired articular inflammation, by reverting edema formation, neutrophil accumulation and the production of lipid mediators, cytokines and endothelin. In addition, gedunin directly modulated the functions of neutrophils and macrophages in vitro. The pre-incubation of neutrophil with gedunin (100 µM) impaired shape change, adhesion to endothelial cells, chemotaxis and lipid body formation triggered by different stimuli. Macrophage pretreatment with gedunin impaired intracellular calcium mobilization, nitric oxide production, inducible nitric oxide synthase expression and induced the expression of the antiinflammatory chaperone heat shock protein 70. Our results demonstrate that gedunin presents remarkable antiinflammatory and anti-nociceptive effects on zymosan-induced inflamed knee joints, modulating different cell populations.

[Effectiveness comparison between arthroscopic and nonsurgical treatments for ankle degenerative osteoarthropathy].

OBJECTIVE: To evaluate the effectiveness of arthroscopic treatment and nonsurgical treatment on ankle degenerative osteoarthropathy. METHODS: Between July 2009 and June 2011, 58 patients (58 ankles) suffering from ankle degenerative osteoarthropathy underwent arthroscopic treatment (arthroscopic group, n=28) and routine treatment (control group, n=30). There was no significant difference in gender, age, body mass index, disease duration, and degree of ankle degenerative osteoarthropathy between 2 groups (P > 0.05). Mazur score, visual analogue scale (VAS), and Tegner activity scale were used to evaluate the effectiveness. RESULTS: Incision healed primarily in arthroscopic group. The patients of 2 groups were followed up 1-2 years, averaged 1.5 years in arthroscopic group and 1.6 years in control group. At last follow-up, Mazur, VAS, and Tegner scores were significantly improved when compared with the preoperative scores in 2 groups (P < 0.05), but no significant difference was found at last follow-up between 2 groups (P > 0.05). According to Mazur scoring, the results were excellent in 8 cases, good in 14 cases, fair in 5 cases, and poor in 1 case, with an excellent and good rate of 79% in arthroscopic group; the results were excellent in 6 cases, good in 15 cases, fair in 6 cases, and poor in 3 cases, with an excellent and good rate of 70% in control group; and no significant difference was observed between 2 groups (u=0.98, P=0.77). Moreover, there was no correlation between Outerbridge classification and Mazur score in patients undergoing arthroscopic treatment (r=0.18, P= 0.34). CONCLUSION: Arthroscopic and nonsurgical treatments of ankle degenerative osteoarthropathy can both achieve good effectiveness.

Platelet-rich plasma or hyaluronate in the management of osteochondral lesions of the talus.

BACKGROUND: Nonoperative options for osteochondral lesions (OCLs) of the talar dome are limited, and currently, there is a lack of scientific evidence to guide management. PURPOSE: To evaluate the short-term efficacy and safety of platelet-rich plasma (PRP) compared with hyaluronic acid (HA) in reducing pain and disability caused by OCLs of the ankle. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: Thirty-two patients aged 18 to 60 years were allocated to a treatment by intra-articular injections of either HA (group 1) or PRP (plasma rich in growth factors [PRGF] technique, group 2) for OCLs of the talus. Thirty OCLs, 15 per arm, received 3 consecutive intra-articular therapeutic injections and were followed for 28 weeks. The efficacy of the injections in reducing pain and improving function was assessed at each visit using the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (AHFS); a visual analog scale (VAS) for pain, stiffness, and function; and the subjective global function score. RESULTS: The majority of patients were men (n = 23; 79%). The AHFS score improved from 66 and 68 to 78 and 92 in groups 1 and 2, respectively, from baseline to week 28 (P < .0001), favoring PRP (P < .05). Mean VAS scores (1 = asymptomatic, 10 = severe symptoms) decreased for pain (group 1: 5.6 to 3.1; group 2: 4.1 to 0.9), stiffness (group 1: 5.1 to 2.9; group 2: 5.0 to 0.8), and function (group 1: 5.8 to 3.5; group 2: 4.7 to 0.8) from baseline to week 28 (P < .0001), favoring PRP (P < .05 for stiffness, P < .01 for function, P > .05 for pain). Subjective global function scores, reported on a scale from 0 to 100 (with 100 representing healthy, preinjury function) improved from 56 and 58 at baseline to 73 and 91 by week 28 for groups 1 and 2, respectively (P < .01 in favor of PRP). CONCLUSION: Osteochondral lesions of the ankle treated with intra-articular injections of PRP and HA resulted in a decrease in pain scores and an increase in function for at least 6 months, with minimal adverse events. Platelet-rich plasma treatment led to a significantly better outcome than HA.

High throughput proteomic analysis of the secretome in an explant model of articular cartilage inflammation.

This study employed a targeted high-throughput proteomic approach to identify the major proteins present in the secretome of articular cartilage. Explants from equine metacarpophalangeal joints were incubated alone or with interleukin-1beta (IL-1ß, 10ng/ml), with or without carprofen, a non-steroidal anti-inflammatory drug, for six days. After tryptic digestion of culture medium supernatants, resulting peptides were separated by HPLC and detected in a Bruker amaZon ion trap instrument. The five most abundant peptides in each MS scan were fragmented and the fragmentation patterns compared to mammalian entries in the Swiss-Prot database, using the Mascot search engine. Tryptic peptides originating from aggrecan core protein, cartilage oligomeric matrix protein (COMP), fibronectin, fibromodulin, thrombospondin-1 (TSP-1), clusterin (CLU), cartilage intermediate layer protein-1 (CILP-1), chondroadherin (CHAD) and matrix metalloproteinases MMP-1 and MMP-3 were detected. Quantitative western blotting confirmed the presence of CILP-1, CLU, MMP-1, MMP-3 and TSP-1. Treatment with IL-1ß increased MMP-1, MMP-3 and TSP-1 and decreased the CLU precursor but did not affect CILP-1 and CLU levels. Many of the proteins identified have well-established extracellular matrix functions and are involved in early repair/stress responses in cartilage. This high throughput approach may be used to study the changes that occur in the early stages of osteoarthritis.

Assessment of biocompatibility and initial evaluation of genipin cross-linked elastin-like polypeptides in the treatment of an osteochondral knee defect in rabbits.

Polypeptides based on the alternating hydrophobic and cross-linking domain structure of human elastin are capable of undergoing self-assembly to produce polymeric matrices with unique biological and mechanical properties. Here, we test the initial feasibility of using a genipin cross-linked elastin-based material as an acellular plug in the treatment of an osteochondral defect in the rabbit knee. Full-thickness defects in the weight-bearing surface of the medial femoral condyle in 18 New Zealand White rabbits were surgically produced and press fitted with cylindrical pads composed of genipin cross-linked elastin-like polypeptides, with identical wounds in the opposite knee left untreated as controls. The biocompatibility of the material, overall wound healing and regeneration of subchondral tissue was assessed at 2, 4 and 6weeks by histological evaluation, synovial fluid analysis and microcomputerized tomography scanning. Histological analysis revealed the regeneration of subchondral bone at the periphery of the material, with evidence of hyaline-like overgrowth across the apical surface in 11/16 cases. Pads developed tight contacts with host tissue and appeared completely biocompatible, with no evidence of localized immune response or increased inflammation compared to controls. The material was stable to 6weeks, with an aggregate elastic modulus calculated at approximately 470kPa when tested under confined compression. Further studies are required to assess material degradation over time and long-term replacement with repair tissue.

Osteochondral lesion of the fifth metatarsal head in a triathlete.

Osteochondral lesions (OCLs) are rare joint disorders, typically found in the larger joints of the body and less so in smaller joints (J Bone Joint Surg Am 41-A:988-1020, 1959; Arthroscopy 6(3):190-197, 1990; Clin Orthop Relat Res 148:245-253, 1980). Although their specific cause is subject to frequent debate, they are often caused by trauma with subsequent compromise of the articular cartilage (Arthroscopy 6(3):190-197, 1990; J Bone Joint Surg Am 78(3):439-456, 1996). Symptoms are typically attributable to a mechanical defect, either of the bony defect or a flap of cartilage. The current case report describes an osteochondral lesion of the head of the fifth metatarsal which is a heretofore unreported location. Magnetic resonance imaging (MRI) of the lesion revealed a notable subchondral bone signal change, indicating a possible synovial fluid pressure phenomenon rather than a mechanical defect.

Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee.

BACKGROUND AND PURPOSE: Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees. MATERIAL AND METHODS: Osteochondral defects (5 mm in diameter) were created in the femoral patellar groove in rabbits. Soon after the procedure, a first subcutaneous injection of etanercept was performed. This single injection or, alternatively, 4 injections in total (twice a week for 2 weeks) were given. Each of these 2 groups was divided further into 3 subgroups: a low-dose group (0.05 microg/kg), an intermediate-dose group (0.4 microg/kg), and a high-dose group (1.6 microg /kg) with 19 rabbits in each. As a control, 19 rabbits were injected with water alone. The rabbits in each subgroup were killed 4 weeks (6 rabbits), 8 weeks (6 rabbits), or 24 weeks (7 rabbits) after surgery and repair was assessed histologically. RESULTS: Histological examination revealed that the natural process of repair of the osteochondral defects was promoted by 4 subcutaneous injections of intermediate-dose etanercept and by 1 or 4 injections of high-dose etanercept at the various time points examined postoperatively (4, 8, and 24 weeks). Western blot showed that rabbit TNFalpha had a high affinity for etanercept. INTERPRETATION: Blocking of TNF by etanercept enabled repair of osteochondral defects in rabbit knee. Anti-TNF therapy could be a strategy for the use of tissue engineering for bone and cartilage repair.

[Evaluation of the efficacy of therapeutic physical training in patients with osteochondrosis according to rheoencephalography data].

This paper reports results of clinical and rheoencephalographic examination of 40 middle-age women with cervical osteochondrosis and symptoms of insufficiency of vertebrobasiliar blood circulation. A system of methods for therapeutic physical training has beendeveloped to normalize hemodynamics in the basin of vertebral arteries. The system was tested on 20 patients during a year. It included special physical exercises, massage, and automobilization. The efficiency of therapeutic physical training was evaluated by rheoencephalography. The women involved in the testing reported a marked improvement of the health status. Their rheoencephalograms suggested diminishing of the asymmetry coefficient and beneficial effect of therapeutic physical training on the elastic properties of vertebral arteries. No such changes were documented in a control group of women with osteochondrosis.

[Efficiency of short courses of physiotherapy with the use of energy metabolism regulators in patients with dorsopathy].

The assessment of procedure tolerance, their efficiency at shortening of courses of dorsopathies physiotherapy to 12-14 days made possible to detect presence of unfavorable reactions to treatment in 32% of cases. Regulator of energy metabolism, included in the therapy, assists to good tolerance to shortened courses of dorsopathy rehabilitation (frequency of presence and expression degree of reaction to treatment reduced to 15%), stabilization of energy system in patients' organism, absence of hyper activation and stress of adaptive mechanisms, maintenance of compensatory abilities reserves.

Candida osteo-chondromyelitis complicating thoraco-abdominal esophageal surgery.

BACKGROUND: Candida albicans osteo-costochondromyelitis is a rare condition. Such pathology after esophagectomy has not been reported. METHODS: Report of four cases and review of pertinent English-language literature. RESULTS: Four patients underwent esophageal surgery via a left thoraco-abdominal approach between June, 1999 and March, 2000. After complicated post-operative courses, Candida osteomyelitis of the costochondral margin presented initially as a cutaneous sinus. CONCLUSIONS: All patients responded well to surgical debridement followed by a three-month course of oral fluconazole.

Osteochondral fragments involving the dorsomedial aspect of the proximal interphalangeal joint in young horses: 6 cases (1997-2006).

OBJECTIVE: To determine clinical and diagnostic imaging findings in young horses with osteochondral fragments involving the dorsomedial aspect of the proximal interphalangeal (PIP) joint. DESIGN: Retrospective case series. ANIMALS: 6 horses. PROCEDURES: Medical records were reviewed. Follow-up information was obtained through telephone conversations with owners or trainers or by examining race records. RESULTS: Horses were between 1 and 4 years old. Three had bilateral osteochondral fragments in the forelimbs (n = 2 horses) or hind limbs (1). Radiographically, all but 1 fragment seemed to originate from the dorsomedial aspect of the distal end of the first phalanx. Fragment size ranged from 6 x 9 mm to 11 x 21 mm. Three horses had lameness referable to the region of the affected joint; the other 3 horses did not have clinical signs referable to affected PIP joints. Two horses were euthanized shortly after diagnosis at the owners' request because of concerns that the horses would be unsuited for their intended athletic use. Two of the 3 horses in which fragments were incidental findings were able to race successfully, although 1 received intra-articular corticosteroid treatments; the third was retired because of unrelated orthopedic problems. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that osteochondral fragments involving the dorsomedial aspect of the PIP joint may be an incidental finding in young horses. Given the absence of clinical signs in 5 of 9 affected joints and the fact that 3 of 6 horses were affected bilaterally, a developmental origin of the fragments was suspected.

Positive effect of oral supplementation with glycosaminoglycans and antioxidants on the regeneration of osteochondral defects in the knee joint.

The effect of oral supplementation with glycosaminoglycans (GAG) and radical scavengers (vitamin E/selenium) on the regeneration of osteochondral defects was investigated in rabbits. After introduction of defined osteochondral defects in the knee joint, groups of ten animals were given a GAG/vitamin E/selenium mixture or a placebo (milk sugar) for 6 weeks. Following sacrifice, histological and histochemical analysis was performed. The amount of synovial fluid was increased in the placebo group, while the viscosity of the synovial fluid was significantly enhanced in the GAG group. The amount of sulfated GAG in the osteochondral regenerates (8.8 +/- 3.6 % vs. 6.0 +/- 5.6 %; p <0.03) was significantly higher in the GAG group. In both groups, the GAG amount in the cartilage of the operated knee was significantly higher than in the non-involved knee (p <0.05). Histological analysis of the regenerates in the GAG group was superior in comparison with the placebo group. For the first time, a biological effect following oral supplementation with GAG was demonstrated in healing of osteochondral defects in vivo. These findings support the known positive clinical results.

[The efficacy of paravertebral blockades in the complex treatment of patients with the combination of neurological symptoms of cervical-thoracic osteochondrosis and ischemic disease].

Sixty-seven patients with clinical symptoms of cervical-thoracic osteochondrosis and ischemic disease have been studied. In the main group included 43 patients, paravertebral blockades (PVB) were applied and in the control group (24 patients) - antianginal and metabolic therapy was used. Treatment efficacy was assessed by the dynamics of pain syndrome parameters as measured with the visual analogue scale and by changes of heart rhythm variability, ischemic disturbances and arrhythmia measured by Holter monitoring. The higher therapeutic efficacy of PVB in the complex treatment of these patients comparing to traditional treatment of ischemic disease was found.

[(Modic) signal alterations of vertebral endplates and their correlation to a minimally invasive treatment of lumbar disc herniation using epidural injections]. / (Modic-)Signalveränderungen vertebraler Endplatten und ihr Bezug zu einer minimalinvasiven Injektionstherapie lumbaler Bandscheibenvorfälle.

PURPOSE: To study the influence of (Modic) signal alterations (SA) of the cartilage endplate (CEP) of vertebrae L3-S1 on the outcome of an in-patient minimally invasive treatment (MIT) using epidural injections on patients with lumbar disc herniation (LDH). MATERIALS AND METHODS: The MR images of 59 consecutive patients with LDH within segments L3/L4 - L5/S1 undergoing in-patient minimally invasive treatment with epidural injections were evaluated in a clinical study. The (Modic) signal alterations of the CEP were recorded using T1- and T2-weighted sagittal images. On the basis of the T2-weighted sagittal images, the extension and distribution of the SA were measured by dividing each CEP into 9 areas. The outcome of the MIT was recorded using the Oswestry Disability Index (ODI) before and after therapy and in a 3-month follow-up. Within a subgroup of patients (n = 35), the distribution and extension of the signal alterations were correlated with the development of the ODI. RESULTS: Segments with LDH showed significantly more (p < 0.001) SA of the CEP than segments without LDH. Although the extension of the SA was not dependent on sex, it did increase significantly with age (p = 0.017). The outcome after MIT did not depend on the sex and age of the patients nor on the type of LDH. The SA extension tended to have a negative correlation with the outcome after MIT after 3 months (p = 0.071). A significant negative correlation could be established between the SA extension in the central section of the upper endplate and the outcome after 3 months (p = 0.019). CONCLUSION: 1. Lumbar disc herniation is clearly associated with the prevalence of (Modic) signal alterations. 2. Extensive signal alterations tend to correlate with a negative outcome of an MIT using epidural injections. 3. Such SA in the central portion of the upper CEP correlate significantly with a negative treatment result. 4. The central portion of the upper CEP being extensively affected by (Modic) SA is a negative predictor for the success of a minimally invasive pain therapy.

The in vitro effect of a lyophilized extract of wine obtained from Jacquez grapes on human chondrocytes.

The present work was aimed at evaluating the in vitro effects of a lyophilized extract of wine (JW-E) obtained from Jacquez grapes (Vitis aestivalis-cinereaxVitis vinifera grapes) on the production of key molecules released in inflammatory disease utilising interleukin-1beta (IL-1beta) activated chondrocytes. The extract contains large amounts of phenolic components, in particular some flavonoids (flavan-3-ols, also known as catechins) and proanthocyanidins, as hydroxycinnamic acids and anthocyanins, that possess several biological features such as antiinflammatory and antioxidant effects and a "radical scavenger" activity too. In this study, we assayed the effect of JW-E on the production of key molecules released during chronic inflammatory events as nitric oxide (NO), prostaglandins E(2) (PGE(2)) and reactive oxygen species (ROS) in human chondrocytes culture, stimulated with proinflammatory cytokine interleukin-1beta. The JW-E proved to possess good ability against the harmfull effects of IL-1beta. Our data showed the protective effects of JW-E in cartilage alteration, that appears greater than that elicited by indomethacin, a not steroidal antiinflammatory drug (NSAID), commonly employed in joint diseases.

Tissue engineering-based cartilage repair with allogenous chondrocytes and gelatin-chondroitin-hyaluronan tri-copolymer scaffold: a porcine model assessed at 18, 24, and 36 weeks.

We previously showed that cartilage tissue can be engineered in vitro with porcine chondrocytes and gelatin/chondoitin-6-sulfate/hyaluronan tri-copolymer which mimic natural cartilage matrix for use as a scaffold. In this animal study, 15 miniature pigs were used in a randomized control study to compare tissue engineering with allogenous chondrocytes, autogenous osteochondral (OC) transplantation, and spontaneous repair for OC articular defects. In another study, 6 pigs were used as external controls in which full thickness (FT) and OC defects were either allowed to heal spontaneously or were filled with scaffold alone. After exclusion of cases with infection and secondary arthritis, the best results were obtained with autogenous OC transplantation, except that integration into host cartilage was poor. The results for the tissue engineering-treated group were satisfactory, the repair tissue being hyaline cartilage and/or fibrocartilage. Spontaneous healing and filling with scaffold alone did not result in good repair. With OC defects, the subchondral bone plate was not restored by cartilage tissue engineering. These results show that tri-copolymer can be used in in vivo cartilage tissue engineering for the treatment of FT articular defects.

[Midocalm in complex therapy of chronic low back pain syndrome].

The aim of the study was to determine whether application of midocalm is appropriate in patients with chronic low back pain (LBP) from the point of view of quality of life (QL), efficacy and tolerance. The subjects were 50 patients with chronic LBP associated with spinal osteochondrosis, who underwent clinical examination and were questioned using four QL questionnaires: Health Assessment Questionnaire (HAQ), Womac osteoarthritis index Womac osteoarthritis index, Oswestry Low Back Pain Disability Questionnaire, and The 36-Item Short-Form Health Survey (SF-36). The subjects were divided into two groups. The 25 patients of Group I were administered nise in a dose of 100 mg twice a day during 10 days, the 25 patients of Group II--nise in a dose of 100 mg twice a day plus midocalm in a dose of 150 mg per day during the first two days and 450 mg per day from the third day through the tenth day. The study showed high efficacy of midocalm in complex therapy of patients with chronic LBP, as well as low rate of adverse reactions and high treatment tolerance. QL of the patients improved. Combining midocalm therapy with nise allows quicker positive effect in patients with chronic LBP and lowers need for long application of non-steroid antiinflammatory drugs.