The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint

[Abstract] Background. Recent findings support a connection between mitochondrial dysfunction and activation of inflammatory pathways in articular cells. This study investigates in vivo in an acute model whether intra-articular administration of oligomycin, an inhibitor of mitochondrial function, induces an oxidative and inflammatory response in rat knee joints. Methods. Oligomycin was injected into the rat left knee joint on days 0, 2, and 5 before joint tissues were obtained on day 6. The right knee joint served as control. Results were evaluated by macroscopy and histopathology and by measuring cellular and mitochondrial reactive oxygen species (ROS), 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation), nuclear factor erythroid 2-related factor 2 (Nrf2), and CD68 (macrophages) and chemokine levels. The marker of mitochondrial mass COX-IV was also evaluated. Results. The macroscopic findings showed significantly greater swelling in oligomycin-injected knees than in control knees. Likewise, the histological score of synovial damage was also increased significantly. Immunohistochemical studies showed high expression of IL-8, coinciding with a marked infiltration of polymorphonuclears and CD68+ cells in the synovium. Mitochondrial mass was increased in the synovium of oligomycin-injected joints, as well as cellular and mitochondrial ROS production, and 4-HNE. Relatedly, expression of the oxidative stress-related transcription factor Nrf2 was also increased. As expected, no histological differences were observed in the cartilage; however, cytokine-induced neutrophil chemoattractant-1 mRNA and protein expression were up-regulated in this tissue. Conclusions. Mitochondrial failure in the joint is able to reproduce the oxidative and inflammatory status observed in arthritic joints.Instituto de Salud Carlos III; 09/02340Instituto de Salud Carlos III, RD12/0009/0018, RIERGalicia. Consellería de Innovación, Industria e Comercio; PXIB916357PRInstituto de Salud Carlos III; PI12/02771Xunta de Galicia; PS09/56Galicia. Consellería de Economía e Industria; INCITE 09E1R916139ESGalicia. Consellería de Economía e Industria; IN845B2010/176Galicia. Consellería de Economía e Industria; 10CSA916035P

Epidemiology of traumatic spinal cord injury in Galicia, Spain: trends over a 20-year period

[Abstract] Study design: Observational study with prospective and retrospective monitoring. Objective: To describe the epidemiological and demographic characteristics of traumatic spinal cord injury (TSCI), and to analyze its epidemiological changes. Setting: Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). Methods: The study included patients with TSCI who had been hospitalized between January 1995 and December 2014. Relevant data were extracted from the admissions registry and electronic health record. Results: A total of 1195 patients with TSCI were admitted over the specified period of time; 76.4% male and 23.6% female. Mean patient age at injury was 50.20 years. Causes of injury were falls (54.2%), traffic accidents (37%), sports/leisure-related accidents (3.5%) and other traumatic causes (5.3%). Mean patient age increased significantly over time (from 46.40 to 56.54 years), and the number of cases of TSCI related to traffic accidents decreased (from 44.5% to 23.7%), whereas those linked to falls increased (from 46.9% to 65.6%). The most commonly affected neurological level was the cervical level (54.9%), increasing in the case of levels C1–C4 over time, and the most frequent ASIA (American Spinal Injury Association) grade was A (44.3%). The crude annual incidence rate was 2.17/100 000 inhabitants, decreasing significantly over time at an annual percentage rate change of −1.4%. Conclusions: The incidence rate of TSCI tends to decline progressively. Mean patient age has increased over time and cervical levels C1–C4 are currently the most commonly affected ones. These epidemiological changes will eventually result in adjustments in the standard model of care for TSCI

Técnicas y tecnologías en hidrología médica e hidroterapia

El objetivo del presente informe es difundir entre los profesionales médicos la información que contribuya a orientarles en la materia, conocer las aplicaciones terapéuticas o rehabilitadoras que pueden ofrecer los distintos centros termales y explorar su interacción con los tratamientos médicos habituales a los que suelen estar sometidos los usuarios de estos programas de termalismo

AB0078 ANTI-FIBROTIC EFFECT OF DIFFERENT FUCOIDANS IN OSTEOATHRITIC FIBROBLAST-LIKE-SYNOVIOCYTES

Background:Synovial fibrosis is a pathological process observed in several musculoskeletal disorders that contributes to articular pain and stiffness. It is characterized by the excessive deposition of extracellular matrix, as well as cell migration and proliferation, being TGF-β main inductor of these processes. Fucoidans are sulfated polysaccharide obtained mainly from various species of brown algae and brown seaweed such as Fucus vesiculosus, Undaria pinnatifida, or Macrocystis pyrifera. Recent studies show that fucoidans are promising candidates to address the symptoms of OA. Although a wide spectrum of biological activities has been registered in these polysaccharides, their properties vary between fucoidans from different species.Objectives:Our aim was to evaluate and to compare the anti-fibrotic effects of different fucoidans on fibroblast-like synoviocytes (FLS).Methods:FLS were isolated from OA patients. Primary cultured cells were treated with fucoidans from Fucus vesiculosus (FF), Undaria pinnatifida (FU) and Macrocystis pyrifera (FM) at 5, 30. To activate pro-fibrotic pathways, cells were stimulated with TGF-β and cell viability and proliferation were analyzed by MTT and BrdU assay, respectively. Then gene expression of extracellular matrix proteins, collagen I and III and fibronectin, as well as plod2b, gene coding for alterative splice-variant of lysyl hydroxylases LDH2b, were evaluated by RT-qPCR. The presence of fibrotic maker, alpha smooth muscle actin (α-sma), was analyzed by immunocytochemistry and intracellular collagen levels were assessed by picrosirius red staining. Wound-clousure and transwell cell invasion assay were also performed to evaluate the capacity of cell motility and invasiveness.Figure 1.Measurement of expression of pro-fibrotic markersResults:TGF-β induced a clear pro-fibrotic response (Figure 1). Cell proliferation induced by TGF-β was attenuated in the presence of all tested fucoidans. These polysaccharides also reduced the gene expression of TGF-β-elicited collagen I and III (p&lt; 0.05), although FF failed to downregulate fibronectin levels and none of them showed modulation of plod2b expression. Results were confirmed at protein level. FF30 and FM5 reduced intracellular collagen accumulation induced by TGF-β (p&lt; 0.05). Likewise, the expression of a-sma in TGFb-activated FLS was significantly diminished in the presence of all fucoidans (p&lt; 0.05). By scratch wound assay, we observed that TGF-b induced cell mobility to close the scratch, which was inhibited by all fucoidans. Similarly, FU and FM were also able to attenuated cell invasion after TGF stimulation. Additionally, we also detected that fucoidans showed anti-inflammatory effects in FLS as they reduced the NO production and IL-6 expression induced by IL-1.Conclusion:Our results indicate a protective effect of fucoidans against activated pro-fibrotic pathways in fibroblast-like synoviocytes. However, we detected that these beneficial activities vary between fucoidans from different species and further studies are warranted.Disclosure of Interests:Carlos Vaamonde García: None declared, Herminia Domínguez: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research &amp; Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer, Rosa Meijide Failde: None declared</jats:sec