Origins of the threshold for surgical intervention in intra-articular distal radius fractures.

AIMS: The aim of this study was to identify the origin and development of the threshold for surgical intervention, highlight the consequences of residual displacement, and justify the importance of accurate measurement. METHODS: A systematic review of three databases was performed to establish the origin and adaptations of the threshold, with papers screened and relevant citations reviewed. This search identified papers investigating functional outcome, including presence of arthritis, following injury. Orthopaedic textbooks were reviewed to ensure no earlier mention of the threshold was present. RESULTS: Knirk and Jupiter (1986) were the first to quantify a threshold, with all their patients developing arthritis with > 2 mm displacement. Some papers have discussed using 1 mm, although 2 mm is most widely reported. Current guidance from the British Society for Surgery of the Hand and a Delphi panel support 2 mm as an appropriate value. Although this paper is still widely cited, the authors published a re-examination of the data showing methodological flaws which is not as widely reported. They claim their conclusions are still relevant today; however, radiological arthritis does not correlate with the clinical presentation. Function following injury has been shown to be equivalent to an uninjured population, with arthritis progressing slowly or not at all. Joint space narrowing has also been shown to often be benign. CONCLUSION: Knirk and Jupiter originated the threshold value of 2 mm. The lack of correlation between the radiological and clinical presentations warrants further modern investigation. Measurement often varies between observers, calling a threshold concept into question and showing the need for further development in this area. The principle of treatment remains restoration of normal anatomical position. Cite this article: Bone Joint J 2021;103-B(9):1457-1461.

Molecular mechanism of down-regulating adipogenic transcription factors in 3T3-L1 adipocyte cells by bioactive anti-adipogenic compounds.

Obesity is growing at an alarming rate, which is characterized by increased adipose tissue. It increases the probability of many health complications, such as diabetes, arthritis, cardiac disease, and cancer. In modern society, with a growing population of obese patients, several individuals have increased insulin resistance. Herbal medicines are known as the oldest method of health care treatment for obesity-related secondary health issues. Several traditional medicinal plants and their effective phytoconstituents have shown anti-diabetic and anti-adipogenic activity. Adipose tissue is a major site for lipid accumulation as well as the whole-body insulin sensitivity region. 3T3-L1 cell line model can achieve adipogenesis. Adipocyte characteristics features such as expression of adipocyte markers and aggregation of lipids are chemically induced in the 3T3-L1 fibroblast cell line. Differentiation of 3T3-L1 is an efficient and convenient way to obtain adipocyte like cells in experimental studies. Peroxisome proliferation activated receptor γ (PPARγ) and Cytosine-Cytosine-Adenosine-Adenosine-Thymidine/Enhancer-binding protein α (CCAAT/Enhancer-binding protein α or C/EBPα) are considered to be regulating adipogenesis at the early stage, while adiponectin and fatty acid synthase (FAS) is responsible for the mature adipocyte formation. Excess accumulation of these adipose tissues and lipids leads to obesity. Thus, investigating adipose tissue development and the underlying molecular mechanism is important in the therapeutical approach. This review describes the cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds.

Ocular complications and prophylactic strategies in Stickler syndrome: a systematic literature review.

BACKGROUND: Stickler syndrome is a collagenopathy caused by mutations in the genes COL2A1 (STL1) or COL11A1 (STL2). Affected patients manifest ocular, auditory, articular, and craniofacial manifestations in varying degrees. Ocular symptoms include myopia, retinal detachment, cataract, and glaucoma. The aim of this systematic review was to evaluate the prevalence of ocular manifestations and the outcome of prophylactic treatment on reducing the risk of retinal detachment. METHOD: A systematic literature search was performed in the PubMed database. Information on the cross-study prevalence of myopia, retinal detachment, cataract, glaucoma, visual impairment, severity and age of onset of myopia and retinal detachments. Studies that reported on the outcome of prophylactic treatment against a control group were explored. RESULTS: 37 articles with 2324 individual patients were included. Myopia was found in 83% of patients, mostly of a moderate to severe degree. Retinal detachments occurred in 45% of patients. Generally, the first detachment occurred in the second decade of life in STL1 patients and later in STL2. Cataracts were more common in STL2 patients, 59% versus 36% in STL1. Glaucoma (10%) and visual impairment (blind: 6%; vision loss in one eye: 10%) were rare. Three studies reported on the effect of prophylactic treatment being protective. CONCLUSION: Ocular manifestations are common in Stickler patients, but the comparison between studies was difficult because of inconsistencies in diagnostic and inclusion criteria by different studies. Sight-threatening complications such as retinal detachments are common but although prophylactic therapy is reported to be effective in retrospective studies, evidence from randomized trials is missing.

Conditioned Medium of Mesenchymal Stromal Cells: A New Class of Therapeutics.

Mesenchymal stromal cell (MSCs) represent a class of biologics with the prospects for employment as immunomodulatory, tissue-protective, and regenerative therapeutics. In parallel with cellular therapy, cell-free therapy based on MSC-secreted bioactive factors is being actively developed. MSCs secrete a variety of protein, peptide, RNA, and lipid mediators which can be concentrated, frozen, or even lyophilized without loss of activity, which gives them a certain advantage over cellular products requiring liquid nitrogen storage and infrastructure to revive frozen cells. This review (i) describes currently conducted clinical trials of cell-free products containing MSC secretome; (ii) summarizes main approaches to the generation and characterization of conditioned media concentrates and extracellular vesicle isolates; (iii) analyzes a variety of preclinical studies where effectiveness of secretome products has been shown; and (iv) summarizes current knowledge about secretome bioactive components obtained by analysis of in vivo models testing the therapeutic potential of the MSC secretome.

Pain Coping Skills Training for Patients Who Catastrophize About Pain Prior to Knee Arthroplasty: A Multisite Randomized Clinical Trial.

BACKGROUND: Pain catastrophizing has been identified as a prognostic indicator of poor outcome following knee arthroplasty. Interventions to address pain catastrophizing, to our knowledge, have not been tested in patients undergoing knee arthroplasty. The purpose of this study was to determine whether pain coping skills training in persons with moderate to high pain catastrophizing undergoing knee arthroplasty improves outcomes 12 months postoperatively compared with usual care or arthritis education. METHODS: A multicenter, 3-arm, single-blinded, randomized comparative effectiveness trial was performed involving 5 university-based medical centers in the United States. There were 402 randomized participants. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Scale, measured at baseline, 2 months, 6 months, and 12 months following the surgical procedure. RESULTS: Participants were recruited from January 2013 to June 2016. In 402 participants, 66% were women and the mean age of the participants (and standard deviation) was 63.2 ± 8.0 years. Three hundred and forty-six participants (90% of those who underwent a surgical procedure) completed a 12-month follow-up. All 3 treatment groups had large improvements in 12-month WOMAC pain scores with no significant differences (p > 0.05) among the 3 treatment arms. No differences were found between WOMAC pain scores at 12 months for the pain coping skills and arthritis education groups (adjusted mean difference, 0.3 [95% confidence interval (CI), -0.9 to 1.5]) or between the pain coping and usual-care groups (adjusted mean difference, 0.4 [95% CI, -0.7 to 1.5]). Secondary outcomes also showed no significant differences (p > 0.05) among the 3 groups. CONCLUSIONS: Among adults with pain catastrophizing undergoing knee arthroplasty, cognitive behaviorally based pain coping skills training did not confer pain or functional benefit beyond the large improvements achieved with usual surgical and postoperative care. Future research should develop interventions for the approximately 20% of patients undergoing knee arthroplasty who experience persistent function-limiting pain. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Timing of Open Reduction and Internal Fixation of Ankle Fractures.

Background. Unstable ankle fractures are treated with open reduction internal fixation (ORIF) to prevent posttraumatic arthritis. Typically, ORIF is performed as an ambulatory surgery several days to a few weeks after injury. It is unclear what effect this delay may have on functional outcome. This study aimed to assess the effect of timing of ankle ORIF on wound complications and functional outcome. Methods. A retrospective review of 121 patients who underwent ankle ORIF was performed. A total of 58 patients had a follow-up of at least 24 months. Time between injury and surgery greater than 14 days was defined as "delayed." Demographic variables, injury characteristics, length of surgery, and postoperative stay were documented. Comparison of demographic variables, wound complications, and functional outcome determined by Foot and Ankle Outcome Score (FAOS) was performed. Results. 118 patients were included. The duration between injury and surgery was 6 days in the "early" group and 19 days in the "delayed" group. There were no significant differences in demographic variables, injury characteristics, and length of surgery between the groups. Wound complications in the early and delayed groups were 5% and 11.8%, although this difference was not statistically significant. Among 58 patients who had a follow-up of at least 24 months, the median follow-up time was 38 (range, 24-76) months. Each subscale of FAOS demonstrated no significant difference. Conclusion. Ankle ORIF more than 14 days after injury did not significantly increase the rate of wound complication, nor did it impair ultimate functional outcome in this group. Levels of Evidence: Level III.

Protección osteoarticular de Zea mays L. variedad morada (maíz morado) en artritis experimental en ratas / Osteoarticular protection of Zea mays L. purple variety (purple corn) in experimental arthritis in rats

RESUMEN Objetivos. Evaluar el efecto protector de Zea mays L. variedad morada (maíz morado) frente a la respuesta inflamatoria y daño osteoarticular en ratas con artritis experimental. Materiales y métodos. Se emplearon 65 ratas Holtzman, asignadas en siete grupos: G1 (n=5): control, G2 (n=10): pristane (PIA) + agua destilada, G3 (n=10): PIA + metotrexate 0,1 mg/kg, G4 (n=10): PIA + indometacina 0,6 mg/kg, G5 (n=10): PIA + Zea mays 100 mg/kg, G6 (n=10): PIA + Zea mays 1000 mg/kg y G7 (n=10): PIA + metotrexate 0,1 mg/kg + Zea mays 1000 mg/kg. Los tratamientos fueron administrados mediante cánula orogástrica diariamente durante 21 días; el pristane se administró vía subdérmica solo el día 1. Se registró el volumen de pata trasera con un pletismometro digital. El análisis radiológico de las patas se evaluó según los criterios de Clark modificado. Resultados. El porcentaje de inflamación al final del experimento fue: (G1) 1,50 ± 0,5, (G2) 13,73 ± 8,4; (G3) 14,76 ± 8,8; (G4) 14.22 ± 9,0; (G5) 10,81 ± 9.1; (G6) 5,31 ± 1.4; (G7) 6,38 ± 0,5. Los puntajes radiológicos de las áreas afectadas fueron: (G1) 0,6; (G2) 3,5; (G3) 0,6; (G4) 1,7; (G5) 1,9; (G6) 1,4; (G7) 1,0. Solo los grupos Zea mays L. 1000 mg/kg y metotrexate + Zea mays L. 1000 mg/kg mostraron una respuesta inflamatoria significativamente menor (p<0,05) y mostraron puntajes articulares significativamente bajos en relación a PIA. Conclusiones. El Zea mays L. (maíz morado) reduce el proceso inflamatorio y las modificaciones radiológicas de la artritis inducida por PIA en ratas de modo dosis dependiente.

ABSTRACT Objectives. To evaluate the protective effect of Zea mays L., purple variety (purple corn) against inflammatory response and osteoarticular damage in rats with experimental arthritis. Materials and Methods. Sixty-five Holtzman rats were used, assigned to seven groups: G1 (n=5): control; G2 (n=10): pristane (PIA) + distilled water; G3 (n=10): PIA + methotrexate 0.1 mg/kg; G4 (n=10): PIA + indomethacin 0.6 mg/kg; G5 (n=10): PIA + Zea mays 100 mg/kg; G6 (n=10): PIA + Zea mays 1000 mg/kg, and G7 (n=10): PIA + methotrexate 0.1 mg/kg + Zea mays 1000 mg/kg. Treatments were administered by orogastric cannula daily for 21 days; pristane was administered subdermal only on day 1. Volume of hind leg was recorded with a digital plethysmometer. The radiological analysis of the legs was evaluated according to the modified Clark criteria. Results. The percentage of inflammation at the end of the experiment was: (G1) 1.50 ± 0.5; (G2) 13.73 ± 8.4; (G3) 14.76 ± 8.8; (G4) 14.22 ± 9.0; (G5) 10.81 ± 9.1; (G6) 5.31 ± 1.4; (G7) 6.38 ± 0.5. The radiological scores of the affected areas were: (G1) 0.6; (G2) 3.5; (G3) 0.6; (G4) 1.7; (G5) 1.9; (G6) 1.4; (G7) 1.0. Only the groups Zea mays L. 1000 mg/kg and methotrexate + Zea mays L. 1000 mg/kg showed a significantly lower inflammatory response (p<0.05) and showed significantly lower joint scores in relation to PIA. Conclusions. Zea mays L. (purple corn) reduces the inflammatory process and radiological modifications of PIA-induced arthritis in rats in a dose-dependent manner.

Comparison of air exhausts for surgical body suits (space suits) and the potential for periprosthetic joint infection.

BACKGROUND: Periprosthetic joint infection is a major complication of total joint replacement surgery and is associated with significant morbidity, mortality and financial burden. Surgical body suits (space suits), originally designed to reduce the incidence of infection, have paradoxically been implicated in increased periprosthetic joint infection rates recently. Air exhausted from space suits may contribute to this increased rate of periprosthetic joint infection. AIM: To investigate the flow of air exhausted from space suits commonly used in modern operating theatres. METHODS: The exhaust airflow patterns of four commercially available space suit systems were compared using a fog machine and serial still photographs. FINDINGS: The space suit systems tested all air exhausted into the operating room. The single fan systems with a standard surgical gown exhausted air laterally from the posterior gown fold at approximately the level of the surgical field. The single fan system with a dedicated zippered suit exhausted air at a level below the surgical field. The dual fan system exhausted air out of the top of the helmet at a level above the surgical field. CONCLUSIONS: Space suit systems currently in use in joint replacement surgery differ significantly from traditional body exhaust systems; rather than removing contaminated air from the operating environment, modern systems exhaust this air into the operating room, in some cases potentially towards the sterile instrument tray and the surgical field.

Treating Early Undifferentiated Arthritis: A Systematic Review and Meta-Analysis of Direct and Indirect Trial Evidence.

OBJECTIVE: We undertook a systematic review and meta-analysis of direct and indirect trial evidence to evaluate the efficacy of treatments for patients with undifferentiated arthritis (UA). METHODS: We searched 4 electronic databases from inception to January 2016, clinicaltrials.gov, and bibliographies of relevant articles. Two reviewers independently screened and evaluated the studies. The primary outcome was development of rheumatoid arthritis (RA). RESULTS: Nine studies were included. Interventions included methotrexate, abatacept, infliximab, intraarticular or intramuscular glucocorticoids, and radiation synovectomy. Treating patients resulted in lower rates of RA at 12 months compared to placebo or no treatment (odds ratio [OR] 0.49 [95% confidence interval (95% CI) 0.26, 0.90]). From direct meta-analysis, patients treated with methotrexate were less likely to develop RA at 12 months compared to patients treated without methotrexate (OR 0.13 [95% CI 0.03, 0.48]). This difference was no longer significant at 30 or 60 months. From indirect comparisons, most interventions showed decreased risk of developing RA compared to placebo at 12 months, reaching statistical significance for methotrexate (OR 0.16 [95% CI 0.08, 0.33]) and intramuscular methylprednisolone (OR 0.72 [95% CI 0.53, 0.99]). Most individual interventions included a limited number of studies. CONCLUSION: Treating patients with UA resulted in a statistically significant delay in the development of RA, with the largest effect observed for methotrexate. These findings suggest that there is a window of opportunity to treat patients with UA early, to delay subsequent progression to RA.

Arthroscopic Transplantation of Osteochondral Autograft for Treatment of Cartilage Defects in the Wrist.

Focal chondral lesions are a common cause of chronic wrist pain, with no ideal treatment. The authors developed arthroscopic transplantation of osteochondral autograft from lateral femoral condyle to distal radius with satisfactory outcome in 4 consecutive patients between December 2006 and December 2010. In all cases, graft incorporation was completed by 3 months to 4 months postoperation. All patients showed improvement in wrist function with no pain at follow-up at an average of 70.5 months (range 24-116 months). Second-look arthroscopy in 3 patients confirmed the preservation of normal articular cartilage. Patient satisfaction was high with no complications.

[Dorsal ligamentoplasty for posttraumatic scapholunate dissociation]. / Die dorsale Bandplastik bei posttraumatischer skapholunärer Dissoziation.

Scapholunate dissociation in stages 2 and 3 may lead to posttraumatic damage if left untreated. Different types of treatment have been described, including capsulodesis, tenodesis, and others. The purpose of all procedures is to avoid palmar shift of the distal scaphoid resulting in secondary arthritis (SLAC wrist). This study aimed to evaluate a modified dorsal ligamentoplasty in second- and third-degree scapholunate dissociation in a prospective study design. Furthermore, the study aimed to find out if there is a correlation between radiological and clinical parameters at follow-up and whether or not a SLAC wrist can be avoided. From 2007 to 2011 we performed 29 dorsal ligamentoplasties in our hospital in patients with second- and third-degree scapholunate dissociation. In a prospective study design, 25 patients were followed up after an average period of 18 months. Parameters recorded preoperatively included ROM, the radiological parameters SL diastasis, SL diastasis in power grip and SL angle, the DASH score, and the VAS score. The postoperative evaluation additionally included power grip, the Mayo wrist score, and patients' subjective satisfaction. The average subjective satisfaction after surgery was good. The average postoperative ROM was 83.8 % of the ROM of the healthy wrist and decreased by 11 % compared with the preoperative level. The average postoperative grip strength was 85.7 % of the strength of the healthy hand. The VAS score was 2.7 with a significant reduction from 6.7 preoperatively. The average DASH score decreased significantly from 60 preoperatively to 22.5 postoperatively. The average Mayo wrist score after surgery was 73. All radiological parameters at follow-up were significantly better than preoperatively, although they remained in a pathological range. The Pearson correlation analysis showed no relevant correlation between clinical and radiological scores. Three cases (12 %) required revision surgery. The described modified dorsal ligamentoplasty at the carpus can be recommended in second- and third-degree scapholunate dissociation. Clinical results are comparable to other techniques, but there is only a single approach required and the complication rate is very low. The short average follow-up of 18 months must be viewed critically as the rate of SLAC wrists might be higher during longer follow-up periods.

Suppression of NFAT5-mediated Inflammation and Chronic Arthritis by Novel κB-binding Inhibitors.

Nuclear factor of activated T cells 5 (NFAT5) has been implicated in the pathogenesis of various human diseases, including cancer and arthritis. However, therapeutic agents inhibiting NFAT5 activity are currently unavailable. To discover NFAT5 inhibitors, a library of >40,000 chemicals was screened for the suppression of nitric oxide, a direct target regulated by NFAT5 activity, through high-throughput screening. We validated the anti-NFAT5 activity of 198 primary hit compounds using an NFAT5-dependent reporter assay and identified the novel NFAT5 suppressor KRN2, 13-(2-fluoro)-benzylberberine, and its derivative KRN5. KRN2 inhibited NFAT5 upregulation in macrophages stimulated with lipopolysaccharide and repressed the formation of NF-κB p65-DNA complexes in the NFAT5 promoter region. Interestingly, KRN2 selectively suppressed the expression of pro-inflammatory genes, including Nos2 and Il6, without hampering high-salt-induced NFAT5 and its target gene expressions. Moreover, KRN2 and KRN5, the latter of which exhibits high oral bioavailability and metabolic stability, ameliorated experimentally induced arthritis in mice without serious adverse effects, decreasing pro-inflammatory cytokine production. Particularly, orally administered KRN5 was stronger in suppressing arthritis than methotrexate, a commonly used anti-rheumatic drug, displaying better potency and safety than its original compound, berberine. Therefore, KRN2 and KRN5 can be potential therapeutic agents in the treatment of chronic arthritis.

Chronic physical conditions, multimorbidity and physical activity across 46 low- and middle-income countries.

BACKGROUND: There are no nationally representative population-based studies investigating the relationship between physical activity, chronic conditions and multimorbidity (i.e., two or more chronic conditions) in low- and middle-income countries (LMICs), and studies on a multi-national level are lacking. This is an important research gap, given the rapid increase in the prevalence of chronic diseases associated with lifestyle changes in these countries. This cross-sectional study aimed to assess the association between chronic conditions, multimorbidity and low physical activity (PA) among community-dwelling adults in 46 LMICs, and explore the mediators of these relationships. METHODS: World Health Survey data included 228,024 adults aged ≥18 years from 46 LMICs. PA was assessed by the International Physical Activity Questionnaire (IPAQ). Nine chronic physical conditions (chronic back pain, angina, arthritis, asthma, diabetes, hearing problems, tuberculosis, visual impairment and edentulism) were assessed. Multivariable logistic regression and mediation analyses were used to assess the association between chronic conditions or multimorbidity and low PA. RESULTS: Overall, in the multivariable analysis, arthritis (OR = 1.12), asthma (1.19), diabetes (OR = 1.33), edentulism (OR = 1.46), hearing problems (OR = 1.90), tuberculosis (OR = 1.24), visual impairment (OR = 2.29), multimorbidity (OR = 1.31; 95% CI = 1.21-1.42) were significantly associated with low PA. More significant associations were observed in individuals aged ≥50 years. In older adults, depression mediated between 5.1% (visual impairment) to 23.5% (angina) of the association between a chronic condition and low PA. Mobility difficulties explained more than 25% of the association for seven of the eight chronic conditions. Pain was a strong mediator for angina (65.9%) and arthritis (64.9%), while sleep problems mediated up to 43.7% (angina) of the association. CONCLUSIONS: In LMICs, those with chronic conditions and multimorbidity are significantly less physically active (especially older adults). Research on the efficacy and effectiveness of PA in the management of chronic diseases in LMICs is urgently needed. Targeted promotion of physical activity to populations in LMICs experiencing chronic conditions may ameliorate associated depression, mobility difficulties and pain that are themselves important barriers for initiating or adopting an active lifestyle.

Inhibition of c-Rel DNA binding is critical for the anti-inflammatory effects of novel PIKfyve inhibitor.

Aberrant production of proinflammatory cytokines is linked to many autoimmune diseases, and their inhibition by small molecule compounds is considered beneficial. Here, we performed phenotypic screening in IFNγ/LPS-activated RAW264.7, mouse macrophage cells, and discovered AS2677131 and AS2795440 as novel and potent inhibitors of IL-12p40, a subunit of IL-23. Interestingly, these compounds exhibited unique pharmacological activities in their inhibition of the production of IL-12p40, IL-6 and IL-1ß but not TNFα in activated macrophages or dendritic cells, and expression of IgM-induced MHC class II on B cells. To reveal these mechanisms, we synthesized two different activity probes which were structurally related to the AS compounds, and identified probe-specific binding proteins, including PIKfyve, a Class III PI kinase. The AS compounds inhibited PIKfyve activity and mimicked the properties of PIKfyve-deficient cells, eventually validating PIKfyve as target molecule. Regarding mechanism, AS2677131 regulated DNA binding activity of c-Rel on IL-12p40 and IL-1ß promoter. As expected, a PIKfyve inhibitor prevented the development of arthritis in rats. Taken together, our findings of the novel and potent PIKfyve inhibitors AS2677131 and AS2795440 reveal the critical role of PIKfyve in proinflammatory cytokine production and B cell activation, and may indicate a potential new therapeutic option for treatment of inflammatory diseases.

Secondary Reconstruction for Malunions and Nonunions of the Talar Body.

Malunions and nonunions after central or peripheral fractures of the talar body frequently lead to pain and disability. In properly selected, compliant patients without symptomatic arthritis or total avascular necrosis leading to collapse of the talar dome, and sufficient bone stock, secondary anatomic reconstruction with osteotomy along the former fracture plane and preservation of the essential peritalar joints may lead to considerable functional improvement. Bone grafting is needed after resection of a fibrous pseudarthrosis, sclerotic, or necrotic bone. Malunions and nonunions of the lateral or posterior process are treated with excision of the malunited or loose fragments.

Evaluation of the anti-inflammatory effects of two platelet-rich gel supernatants in an in vitro system of cartilage inflammation.

OBJECTIVES: To study, in normal cartilage explants (CEs) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the production and degradation of platelet-associated growth factors (GFs) (platelet-derived GF isoform BB [PDGF-BB] and transforming growth factor beta-1 [TGF-ß1]), pro-inflammatory (tumour necrosis factor alpha [TNF-α]) and anti-inflammatory cytokines (interleukin 4 [IL-4] and IL-1 receptor antagonist [IL-1ra]). METHODS: CEs from six horses were challenged with LPS and cultured for 96h with L-PRG and P-PRG supernatants at concentrations of 25% and 50%, respectively. The CE culture medium was changed every 48h and used for determination, by ELISA, of PDGF-BB, TGF-ß1, TNF-α, IL-4 and IL-1ra. RESULTS: Both the 25% and 50% PRG supernatants produced a different molecular profile in the culture media, unlike that of the CE challenged with LPS only. 50% L-PRG produced the most sustained release of growth factors and anti-inflammatory cytokines, although it produced the highest TNF-α release. PDGF-BB was significantly correlated with IL-1ra and TNF-α concentrations, whereas TNF-α was correlated with IL-4. CONCLUSIONS: 50% L-PRG supernatant produced a more sustained concentration of growth factors and anti-inflammatory cytokines than the other hemoderivatives evaluated. This substance could be evaluated in animal models of arthritis or in patients with arthropathies.

The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update.

The concept of using phytochemicals has ushered in a new revolution in pharmaceuticals. Naturally occurring polyphenols (like curcumin, morin, resveratrol, etc.) have gained importance because of their minimal side effects, low cost and abundance. Curcumin (diferuloylmethane) is a component of turmeric isolated from the rhizome of Curcuma longa. Research for more than two decades has revealed the pleiotropic nature of the biological effects of this molecule. More than 7000 published articles have shed light on the various aspects of curcumin including its antioxidant, hypoglycemic, anti-inflammatory and anti-cancer activities. Apart from these well-known activities, this natural polyphenolic compound also exerts its beneficial effects by modulating different signalling molecules including transcription factors, chemokines, cytokines, tumour suppressor genes, adhesion molecules, microRNAs, etc. Oxidative stress and inflammation play a pivotal role in various diseases like diabetes, cancer, arthritis, Alzheimer's disease and cardiovascular diseases. Curcumin, therefore, could be a therapeutic option for the treatment of these diseases, provided limitations in its oral bioavailability can be overcome. The current review provides an updated overview of the metabolism and mechanism of action of curcumin in various organ pathophysiologies. The review also discusses the potential for multifunctional therapeutic application of curcumin and its recent progress in clinical biology.

Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.

An estimated 12% of patients seeking surgical intervention for symptomatic arthritis have an etiology of post-traumatic arthritis (PTA). The onset of PTA is rapid in the setting of articular fracture (AF). The investigation began with development of a murine model of a closed AF that develops PTA. In the process of characterizing this model a technique was developed for assessing quantitative synovial fluid biomarker concentrations. The work began with observations of the natural history of PTA development in the C57BL/6 strain of mice. A species of mice (MRL/MpJ) was found that is protected from PTA after AF. Further work identified key differences between mouse strains that did and did not develop PTA. This knowledge led to an intervention based on anti-cytokine (interleukin 1 receptor antagonist, (IL-1Ra) delivery in the C57BL/6 strain of mice that successfully prevented PTA following AF. This success in preventing PTA in the murine model has elucidated several important clinical implications: 1) Pro-inflammatory cytokines play an important role in the development of PTA after joint injury, 2) Pharmacologic intervention can lessen the severity of PTA after an AF, and 3) The murine AF model of joint injury provides a novel means of studying mechanisms of PTA development.