Anti-arthritis Effects of Zingiberaceae Extracts on Models of Inflammatory Joint Disease.

Due to this becoming an aging society, the number of arthritis cases has been increasing. Unfortunately, some currently available medications can cause adverse effects. Using herbal remedies as a form of alternative medicine is becoming increasingly popular. Zingiber officinale (ZO), Curcuma longa (CL), and Kaempferia parviflora (KP) are herbal plants in the Zingiberaceae family that have potent anti-inflammatory effects. This study investigates the anti-inflammatory and chondroprotective effects of ZO, CL, and KP extracts on in vitro and ex vivo inflammatory models. The combinatorial anti-arthritis effect of each extract is also evaluated in an in vivo model. ZO extract preserves cartilaginous proteoglycans in proinflammatory cytokines-induced porcine cartilage explant in a fashion similar to that of CL and KP extracts and suppresses the expression of major inflammatory mediators in SW982 cells, particularly the COX2 gene. CL extract downregulates some inflammatory mediators and genes-associated cartilage degradation. Only KP extract shows a significant reduction in S-GAGs release in a cartilage explant model compared to the positive control, diacerein. In SW982 cells, it strongly suppresses many inflammatory mediators. The active constituents of each extract selectively downregulate inflammatory genes. The combined extracts show a reduction in inflammatory mediators to a similar degree as the combined active constituents. Reductions in paw swelling, synovial vascularity, inflammatory cell infiltration, and synovial hyperplasia are found in the combined extracts-treated arthritic rats. This study demonstrates that a combination of ZO, CL, and KP extracts has an anti-arthritis effect and could potentially be developed into an anti-arthritis cocktail for arthritis treatment.

Effects of triangle grass decoction on bone metabolism in rats with chronic kidney disease complicated with mineral and bone abnormalities.

ETHNOPHARMACOLOGICAL RELEVANCE: Triangle grass is a liliaceous Chlorophytum perennial herb of ChlorophytumlaxumR.Br. It is distributed mainly in Guangdong and Guangxi Provinces of China. The initial use of triangle grass was mainly to treat bone pain and swelling caused by a fall injury. Triangle grass tablets (NO. Z20070544) are also used as a preparation in our hospital because of their analgesic, anti-inflammatory, anti-snake venom and microcirculation improvement properties and other pharmacological effects (Mei et al., 2006). Triangle grass tablets have been widely used in our hospital to treat patients with bone pain from chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the effects and mechanism of triangle grass on bone metabolism in chronic kidney disease complicated with mineral and bone abnormalities are unclear. AIM OF THE STUDY: The aim of the present study was to investigate the effects of a triangle grass decoction on bone metabolism in CKD-MBD rats. MATERIALS AND METHODS: CKD-MBD model rats were subjected to 5/6 nephrectomy combined with 0.5 g NaH2PO4/rat. Serum blood urea nitrogen (BUN), creatinine (Cr), phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels were measured with an automatic biochemical analyser. Bone mineral density was determined with a Viva CT 40 system. Bone morphogenetic protein 7(BMP-7),runt-related transcription factor 2 (Runx2) and Osterix protein levels were measured by Western blot analysis. Kidney, vertebra and thoracic aorta tissue samples were assessed by histopathology and immunohistochemistry (IHC). RESULTS: The degrees of membrane thickening, necrosis, swelling and cast deposition were significantly reduced in high-dose rats and Low-dose rats. Serum BUN levels were significantly reduced in the Pre-H group (P < 0.05). Hypocalcaemia and hyperphos phataemia were detected in triangle grass (P < 0.05, P < 0.05). In addition, iPTH levels were significantly increased in the Pre-H group (P < 0.05). Alkaline phosphatase (ALP)levels were significantly decreased in the Pre-H group (P < 0.05). The bone mineral density was improved in the Pre-H and Pre-L groups. BMP-7 protein levels were significantly increased in the Pre-H group (P < 0.05). The pathological changes in muscle fibres in the thoracic aorta middle membranes were significantly alleviated in rats in the Pre-H and Pre-L groups. Changes in SM22α and SMα-act in protein levels were significantly attenuated in the Pre-H group (P < 0.05, P < 0.05). Changes in Runx2 and Osterix protein levels were also significantly attenuated in the Pre-H and Pre-L groups (P < 0.05, P < 0.05). CONCLUSIONS: Triangle grass can simultaneously ameliorate vertebral bone loss and abnormal calcification in the thoracic aorta. Triangle grass has a definite effect on bone metabolism disorder in CKD-MBD rats.

Traditional therapies of Zhuang medicine improve pain and joint dysfunction of patients in rheumatoid arthritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease, which can lead to joint destruction, dysfunction, finally deformity. Currently, Western medicine treats it with disease-modifying antireheumatic drugs, NSAIDs, glucocorticoid, biological agents, etc, which can induce adverse drug reactions. And now, as an important mean of treating RA, Zhuang medicine has been widely used in clinics, and has achieved significant efficacy. METHODS AND ANALYSIS: The following databases will be searched for relevant information before July 2020: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. MAJOR RESULTS: levels of C-reactive protein, erythrocyte sedimentation rate, Rheumatoid factor. Secondary results: morning stiffness time, range of motion, arthralgia, joint tenderness index, joint swelling index, total effective rate, adverse event. Data will be collected independently by 2 researchers, and the risk of bias in meta analysis will be evaluated according to "Cochrane Handbook for Systematic Reviews of Interventions". All data analysis will be conducted using Review Manager V.5.3. and Stata V.12.0. RESULTS: The curative effect and safety of traditional therapies of Zhuang Medicine treatment for RA patients will be evaluated systematically. CONCLUSION: The systematic review of this study will summarize the currently published evidence of traditional therapies of Zhuang Medicine treatment for RA to further guide its promotion and application.Open Science Framework (OSF) registration number: https://osf.io/c4xv3/.

Manjarix attenuated pain and joint swelling in a rat model of monosodium iodoacetate-induced osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 µL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

Efficacy and Therapeutic Drug Monitoring of Continuous Beta-Lactam Infusion for Osteoarticular Infections Caused by Fluoroquinolone-Resistant Pseudomonas aeruginosa: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVES: Osteoarticular infections (OIs) caused by fluoroquinolone-resistant Pseudomonas aeruginosa, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, have poor outcomes. We evaluated the outcomes of an optimized strategy of continuous beta-lactam infusion (BL-CI) guided by therapeutic drug monitoring (TDM) for OIs caused by fluoroquinolone-resistant P. aeruginosa. METHODS: A prospective observational study of patients with P. aeruginosa OIs in a hospital-based BL-CI program (2016-2018) was carried out. TDM targeting free BL concentrations in plasma (fCss) of at least 3-4 × MIC was performed. We compared failure rates between patients with OIs caused by fluoroquinolone-resistant strains who were treated with BL-CI, with or without colistin, and patients with OIs caused by fluoroquinolone-susceptible strains who were treated with ciprofloxacin. RESULTS: Fifty-two patients were included in the study, 19 (36.5%) of whom had OIs caused by fluoroquinolone-resistant P. aeruginosa (13 (68.4%) MDR/XDR strains; 11 (57.9%) device-related infections). The median duration of BL-CI was 36 days; ten patients (52.6%) received BL-colistin combinations. Eighty-two samples were utilized in the TDM, and most patients were found to have a median fCss of 3-10 × MIC; 17 dose adjustments were performed and eight patients needed dose decreases, five of which were due to chronic kidney disease or acute kidney injury (AKI). BL-CI was well tolerated, with the most frequent adverse event being AKI. Failure occurred to 4 patients (21.1%), which was similar to the failure rate of patients with OIs caused by fluoroquinolone-susceptible P. aeruginosa treated with ciprofloxacin (5/30 [16.7%]) (p = 0.699). TDM was also used in the initial BL treatment of patients with OIs caused by susceptible strains before those patients were switched to treatment with ciprofloxacin alone (33 patients, 110 samples, 19 dose adjustments). CONCLUSIONS: BL-CI used with/without colistin and supported by TDM may be an alternative and effective treatment option for OIs caused by fluoroquinolone-resistant P. aeruginosa, where limited available therapeutic options exist, especially in the setting of multidrug resistance. Future research should elucidate whether this strategy can produce outcomes similar to those of patients treated for OIs caused by fluoroquinolone-susceptible strains.

Reduction of arthrofibrosis utilizing a collagen membrane drug-eluting scaffold with celecoxib and subcutaneous injections with ketotifen.

The dense formation of abnormal scar tissue after total knee arthroplasty results in arthrofibrosis, an unfortunate sequela of inflammation. The purpose of this study was to use a validated rabbit model to assess the effects on surgically-induced knee joint contractures of two combined pharmacological interventions: celecoxib (CXB) loaded on an implanted collagen membrane, and subcutaneously (SQ) injected ketotifen. Thirty rabbits were randomly divided into five groups. The first group received no intervention after the index surgery. The remaining four groups underwent intra-articular implantation of collagen membranes loaded with or without CXB at the time of the index surgery; two of which were also treated with SQ ketotifen. Biomechanical joint contracture data were collected at 8, 10, 16, and 24 weeks. At the time of necropsy (24 weeks), posterior capsule tissue was collected for messenger RNA and histopathologic analyses. At 24 weeks, there was a statistically significant increase in passive extension among rabbits in all groups treated with CXB and/or ketotifen compared to those in the contracture control group. There was a statistically significant decrease in COL3A1, COL6A1, and ACTA2 gene expression in the treatment groups compared to the contracture control group (P < .001). Histopathologic data also demonstrated a trend towards decreased fibrous tissue density in the CXB membrane group compared to the vehicle membrane group. The present data suggest that intra-articular placement of a treated collagen membrane blunts the severity of contracture development in a rabbit model of arthrofibrosis, and that ketotifen and CXB may independently contribute to the prevention of arthrofibrosis. Statement of clinical significance: Current literature has demonstrated that arthrofibrosis may affect up to 5% of primary total knee arthroplasty patients. For that reason, novel pharmacologic prophylaxis and treatment modalities are critical to mitigating reoperations and revisions while improving the quality of life for patients with this debilitating condition.

Curcumin: hopeful treatment of hemophilic arthropathy via inhibition of inflammation and angiogenesis.

Introduction: Hemophilic arthropathy (HA) is a serious complication among hemophilic patients causing a wide range of morbidity due to the inflammatory reactions followed by repeated episodes of bleeding. This condition has recently been shown to be accompanied by angiogenesis. The cascade starts with iron accumulation leading to an increase in CD68+ and CD11b+ cells responsible for initiating the inflammation.Areas covered: During inflammation, different factors and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor α (TNF-α) actively play parts in the pathogenesis of HA and also angiogenesis. It has been demonstrated that different pro-angiogenic and angiogenic factors such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), oxidative stress and matrix metalloproteinases (MMPs) are also important in the pathogenesis of HA. Curcumin is known for its strong anti-inflammatory and anti-angiogenic potentials. This agent is able to inhibit the mentioned inflammatory and angiogenic factors such as IL-1, IL-6, TNF-α, VEGF, MMPs, and HIF-1α. Also, as well as anti-angiogenic and anti-inflammatory activity, curcumin has a strong antioxidant potential and can decrease oxidative stress.Expert opinion: It seems that curcumin could be considered as a possible agent for the treatment of HA through inhibition of inflammation, oxidative stress, and angiogenesis.

Dissociation between the growing opioid demands and drug policy directions among the U.S. older adults with degenerative joint diseases.

We aim to examine temporal trends of orthopedic operations and opioid-related hospital stays among seniors in the nation and states of Oregon and Washington where marijuana legalization was accepted earlier than any others.As aging society advances in the United States (U.S.), orthopedic operations and opioid-related hospital stays among seniors increase in the nation.A serial cross-sectional cohort study using the healthcare cost and utilization project fast stats from 2006 through 2015 measured annual rate per 100,000 populations of orthopedic operations by age groups (45-64 vs 65 and older) as well as annual rate per 100,000 populations of opioid-related hospital stays among 65 and older in the nation, Oregon and Washington states from 2008 through 2017. Orthopedic operations (knee arthroplasty, total or partial hip replacement, spinal fusion or laminectomy) and opioid-related hospital stays were measured. The compound annual growth rate (CAGR) was used to quantify temporal trends of orthopedic operations by age groups as well as opioid-related hospital stays and was tested by Rao-Scott correction of χ for categorical variables.The CAGR (4.06%) of orthopedic operations among age 65 and older increased (P < .001) unlike the unchanged rate among age 45 to 64. The CAGRs of opioid-related hospital stays among age 65 and older were upward trends among seniors in general (6.79%) and in Oregon (10.32%) and Washington (15.48%) in particular (all P < .001).Orthopedic operations and opioid-related hospital stays among seniors increased over time in the U.S. Marijuana legalization might have played a role of gateway drug to opioid among seniors.

Effects of Oral Chondroitin Sulfate on Osteoarthritis-Related Pain and Joint Structural Changes: Systematic Review and Meta-Analysis.

Osteoarthritis (OA) is a disorder involving the deterioration of articular cartilage and underlying bone and is associated with symptoms of pain and disability. In military personnel, the incidence of OA has increased between 2000 and 2012 and was the first or second leading cause of medical separations in this period. It has been suggested that consumption of chondroitin sulfate (CS) may reduce the pain and joint deterioration associated with OA. This article reports on a systematic review and meta-analysis of the effectiveness of CS on reducing OA-related pain and joint deterioration. PubMed and Ovid Embase databases and other sources were searched to find randomized, double-blind, placebo-controlled trials on the effects of orally consumed CS on pain and/or joint structure. The outcome measure was the standardized mean difference (SMD) which was the improvement in the placebo groups minus the improvement in the CS groups divided by the pooled standard deviation. There were 18 trials meeting the review criteria for pain with SMD -0.41, 95% confidence interval (95% CI) -0.57 to -0.25 (negative SMD favors CS). Six studies met the review criteria for joint space narrowing with SMD -0.30, 95% CI -0.61 to +0.00. Two studies meet the review criteria for cartilage volume with SMD -0.11, 95% CI -0.48 to +0.26. Larger dosages (1200mg/d) had greater pain reduction efficacy than lower dosages (≤ 1000mg/d). These data suggest that CS has small to moderate effectiveness in reducing OA-related pain but minimal effects on joint space narrowing and no effect on cartilage volume. It is important that clinicians recommend pharmaceutical-grade CS to their patients due to the variability in the amount of CS in dietary supplements purporting to contain CS.

Clinical results of pulsed signal therapy on patellofemoral syndrome with patellar chondropathy.

This study was designed to evaluate the effect of pulsed signal therapy (PST) on patellofemoral pain syndrome associated with patellar chondropathy. A prospective randomized double-blind placebo controlled trial included 25 patients (41 knees) between 20 and 50 years with pain due to isolated patellofemoral syndrome with chondropathy. PST group received nine 60-min daily sessions of PST treatment. Control group received the same protocol of blinded placebo treatment. The main outcome was change from baseline Kujala score at 3 months. After 3 months, patients in the control group received effective treatment (placebo post-treatment). All patients were then followed, for up to 12 months. Seventeen knees (5 males and 12 females, mean age 36.7 ± 7.9) received placebo and 24 knees (8 males and 16 females, mean age 35.5 ± 8.9) received PST. By the third month, PST group exhibited a mean change from baseline of 9.63 ± 7.5 Kujala points, compared to 0.53 ± 1.8 in the placebo group (P < 0.001). A significant progressive improvement was seen in the PST group between the 3rd and 6th and between the 6th and 12th month (P < 0.016). Patients initially allocated in the control group also improved at 3 months (P < 0.001) and 6 months (P = 0.005) post-effective treatment. In conclusion, PST in patellofemoral pain syndrome with chondropathy was effective compared to placebo at 3 months, showing an important improvement of Kujala score. The improvement was progressive and maintained up to 12 months. PST is safe and should be considered as a non-invasive option for management of this condition. Bioelectromagnetics. 40:83-90, 2019. © 2019 Bioelectromagnetics Society.

Hyaluronic Acid.

In recent times, the field of tissue engineering and regenerative medicine (TERM) has considerably increased the extent of therapeutic strategies for clinical application in orthopedics. However, TERM approaches have its rules and requirements, in the respect of the biologic response of each tissue and bioactive agents which need to be considered, respected, and subject of ongoing studies. Different medical devices/products have been prematurely available on the market and used in clinics with limited success. However, other therapeutics, when used in a serious and evidence-based approach, have achieved considerable success, considering the respect for solid expectations from doctors and patients (when properly informed).Orthobiologics has appeared as a recent technological trend in orthopedics. This includes the improvement or regeneration of different musculoskeletal tissues by means of using biomaterials (e.g., hyaluronic acid), stem cells, and growth factors (e.g., platelet-rich plasma). The potential symbiotic relationship between biologic therapies and surgery makes these strategies suitable to be used in one single intervention.However, herein, the recent clinical studies using hyaluronic acid (HA) in the treatment of orthopedic conditions will mainly be overviewed (e.g., osteochondral lesions, tendinopathies). The possibilities to combine different orthobiologic agents as TERM clinical strategies for treatment of orthopedic problems will also be briefly discussed.

Telavancin for the treatment of methicillin-resistant Staphylococcus aureus bone and joint infections.

This retrospective, case series describes our experience with the use of telavancin in patients with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and prosthetic joint infection. The primary objectives were clinical outcomes and adverse events (AEs), and a secondary outcome described microbiological susceptibility. Fourteen patients were enrolled. Median duration of therapy was 58 days, and four patients had concurrent bacteremia. End-of-treatment outcomes were available in 78% of patients, with a clinical success rate of 91%. Thirty-day and 12-month outcomes were also obtained. Seven patients experienced AEs. Infusion-related reactions were most common, and three AEs required discontinuation of therapy. All MRSA isolates had a telavancin MIC ≤0.06µg/ml, which is susceptible. This study indicates that telavancin may have a role in treatment of MRSA osteomyelitis and prosthetic joint infection. Our study describes clinical success and adverse events for long duration of therapy, up to 8 weeks.

Phytomedicine in Joint Disorders.

Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even though many of them have been proven effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarize the available scientific information on the following joint-friendly medicinal plants, which have been tested in human studies: Arnica montana, Boswellia spp., Curcuma spp., Equisetum arvense, Harpagophytum procumbens, Salix spp., Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Whitania somnifera.

Mala correlación entre reactantes de fase aguda y afectación intestinal en paciente con comienzo de la enfermedad de Crohn bajo tratamiento con inhibidor de IL-6 por artropatía seronegativa / Poor correlation between acute phase reactants and intestinal involvement in patients with onset of Crohn's disease under treatment with an interleukin-6 inhibitor due to seronegative arthropathy

No disponible

Repercusiones clínicas de la introducción de las terapias biológicas: el paciente bien controlado / Clinical repercussions of introducing biological therapies: The well-controlled patient

No disponible

Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease.

UNLABELLED: Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution. Since its introduction in July 2014, CHIKV now circulates in the United States. The hallmark of alphavirus disease is crippling pain and inflammation of the joints, a similar immunopathology to rheumatoid arthritis. The use of glycans as novel therapeutics is an area of research that has increased in recent years. Here, we describe the promising therapeutic potential of the glycosaminoglycan (GAG)-like molecule pentosan polysulfate (PPS) to alleviate virus-induced arthritis. Mouse models of RRV and CHIKV disease were used to characterize the extent of cartilage damage in infection and investigate the potential of PPS to treat disease. This was assessed using histological analysis, real-time PCR, and fluorescence-activated cell sorting (FACS). Alphaviral infection resulted in cartilage destruction, the severity of which was alleviated by PPS therapy during RRV and CHIKV clinical disease. The reduction in cartilage damage corresponded with a significant reduction in immune infiltrates. Using multiplex bead arrays, PPS treatment was found to have significantly increased the anti-inflammatory cytokine interleukin-10 and reduced proinflammatory cytokines, typically correlated with disease severity. Furthermore, we reveal that the severe RRV-induced joint pathology, including thinning of articular cartilage and loss of proteoglycans in the cartilage matrix, was diminished with treatment. PPS is a promising new therapy for alphavirus-induced arthritis, acting to preserve the cartilage matrix, which is damaged during alphavirus infection. Overall, the data demonstrate the potential of glycotherapeutics as a new class of treatment for infectious arthritis. IMPORTANCE: The hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. In the past year, CHIKV has expanded into the Americas, with approximately 1 million cases reported to date, whereas RRV continues to circulate in the South Pacific. Currently, there is no licensed specific treatment for alphavirus disease, and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. Pentosan polysulfate (PPS) is a glycan derivative that is orally bioavailable, has few toxic side effects, and is currently licensed under the name Elmiron for the treatment of cystitis in the United States. Our findings show that RRV infection damages the articular cartilage, including a loss of proteoglycans within the joint. Furthermore, treatment with PPS reduced the severity of both RRV- and CHIKV-induced musculoskeletal disease, including a reduction in inflammation and joint swelling, suggesting that PPS is a promising candidate for drug repurposing for the treatment of alphavirus-induced arthritis.

Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) patients experience exaggerated pain during movements such as walking. Anti-nerve growth factor (NGF) antibodies have recently shown analgesic effects in OA patients. We examined the effect of a single dose of anti-NGF antibody on pain during motion, joint edema and lesion in a rat model of OA to determine whether the analgesic effect demonstrated in clinical studies can be translated to a preclinical model. METHODS: Sodium monoiodoacetate (MIA)-induced arthritic rats that develop a right-left gait imbalance when walking as an index of pain during motion. This imbalance was assessed using a gait analysis system called "CatWalk". Edema size and lesion score in the relevant knee joint were also measured. The effect of a single intravenous injection of an anti-NGF monoclonal antibody AS2886401-00 on these parameters was assessed. RESULTS: AS2886401-00 administered at 0.3 or 1 mg/kg on Day 3 post-MIA injection resulted in a statistically significant improvement in gait imbalance even on Day 35. When gait measurement was set on Week 3 post-MIA administration, administration of the antibody at a timing close to the gait measurement, i.e., 1 or 24 h prior to the measurement, was less effective. AS2886401-00 did not suppress either edema or lesion. CONCLUSIONS: A single dose of anti-NGF antibody exerts a long-lasting analgesic effect on pain during motion in a rat model of OA. This finding could be associated with the analgesic efficacies that anti-NGF antibodies have exhibited in clinical studies. It appears unlikely that analgesia is secondary to inhibition of joint edema and lesion.

A novel modified acrylic bone cement matrix. A step forward on antibiotic delivery against multiresistant bacteria responsible for prosthetic joint infections.

Currently the safe and responsible use of antibiotics is a world-wide concern as it promotes prevention of the increasing emergence of multiresistant bacterial strains. Considering that there is a noticeable decline of the available antibiotic pipeline able to combat emerging resistance in serious infection a major concern grows around the prosthetic joint infections once the available commercial antibiotic loaded polymethylmethacrylate bone cements (BC) are inadequate for local antibiotic treatment, especially against MRSA, the most commonly isolated and antibiotic-resistant pathogen in bone infections. In this paper a novel modified BC matrix loaded with minocycline is proposed. A renewed interest in this tetracycline arises due to its broad-spectrum of activity against the main organisms responsible for prosthetic joint infections, especially against MRSA. The modified BC matrices were evaluated concerning minocycline release profile, biomechanical properties, solid-state characterization, antimicrobial stability and biocompatibility under in vitro conditions. BC matrix loaded with 2.5% (w/wBC) of minocycline and 10.0% (w/wBC) of lactose presented the best properties since it completely released the loaded minocycline, maintained the mechanical properties and the antimicrobial activity against representative strains of orthopedic infections. In vitro biocompatibility was assessed for the elected matrix and neither minocycline nor lactose loading enhanced BC cytotoxicity.