Sternoclavicular Septic Arthritis Caused by Acupuncture over the Posterior Neck

Acupuncture has been used therapeutically for thousands of years and is considered a relatively safe procedure. Sternoclavicular joint (SCJ) arthritis is a rare joint infection and has never been reported as an adverse event of acupuncture. We report the case of a 50-year-old woman who presented with progressive left neck, shoulder and upper chest pain after acupuncture. A computerized tomography (CT) scan revealed septic arthritis over the left sternoclavicular joint (SCJ) and methicillin-sensitive Staphylococcus aureus bacteraemia was noted. The patient was discharged uneventfully after intravenous antibiotic treatment. SCJ septic arthritis should be considered if unilateral neck and upper chest pain occurs after acupuncture.

Comparison of the modes of action of Apremilast and Roflumilast

The phosphodiesterase 4 (PDE4) family are cAMP specific phosphodiesterases that play an important role in the inflammatory response and is the major PDE type found in inflammatory cells. A significant number of PDE4 specific inhibitors have been developed and are currently being investigated for use as therapeutic agents. Apremilast, a small molecule inhibitor of PDE 4 is in development for chronic inflammatory disorders and has shown promise for the treatment of psoriasis, psoriatic arthritis as well as other inflammatory diseases. It has been found to be safe and well tolerated in humans and in March 2014 it was approved by the US food and drug administration for the treatment of adult patients with active psoriatic arthritis. The only other PDE4 inhibitor on the market is Roflumilast and it is used for treatment of respiratory disease. Roflumilast is approved in the EU for the treatment of COPD and was recently approved in the US for treatment to reduce the risk of COPD exacerbations. Roflumilast is also a selective PDE4 inhibitor, administered as an oral tablet once daily, and is thought to act by increasing cAMP within lung cells. As both (Apremilast and Roflumilast) compounds selectively inhibit PDE4 but are targeted at different diseases, there is a need for a clear understanding of their mechanism of action (MOA). Differences and similarity of MOA should be defined for the purposes of labelling, for communication to the scientific community, physicians, and patients, and for an extension of utility to other diseases and therapeutic areas. In order to obtain a complete comparative picture of the MOA of both inhibitors, additional molecular and cellular biology studies are required to more fully elucidate the signalling mediators downstream of PDE4 inhibition which result in alterations in pro- and anti-inflammatory gene expression. My studies were conducted to directly compare Apremilast with Roflumilast, in order to substantiate the differences observed in the molecular and cellular effects of these compounds, and to search for other possible differentiating effects. Therefore the main aim of this thesis was to utilise cutting-edge biochemical techniques to discover whether Apremilast and Roflumilast work with different modes of action. In the first part of my thesis I used novel genetically encoded FRET based cAMP sensors targeted to different intracellular compartments, in order to monitor cAMP levels within specific microdomains of cells as a consequence of challenge with Apremilast and Roflumilast, which revealed that Apremilast and Roflumilast do regulate different pools of cAMP in cells. In the second part of my thesis I focussed on assessing whether Apremilast and Roflumilast cause differential effects on the PKA phosphorylation state of proteins in cells. I used various biochemical techniques (Western blotting, Substrate kinase arrays and Reverse Phase Protein array and found that Apremilast and Roflumilast do lead to differential PKA substrate phosphorylation. For example I found that Apremilast increases the phosphorylation of Ribosomal Protein S6 at Ser240/244 and Fyn Y530 in the S6 Ribosomal pathway of Rheumatoid Arthritis Synovial fibroblast and HEK293 cells, whereas Roflumilast does not. This data suggests that Apremilast has distinct biological effects from that of Roflumilast and could represent a new therapeutic role for Apremilast in other diseases. In the final part of my thesis, Phage display technology was employed in order to identify any novel binding motifs that associate with PDE4 and to identify sequences that were differentially regulated by the inhibitors in an attempt to find binding motifs that may exist in previously characterised signalling proteins. Petide array technology was then used to confirm binding of specific peptide sequences or motifs. Results showed that Apremilast and Roflumilast can either enhance or decrease the binding of PDE4A4 to specific peptide sequences or motifs that are found in a variety of proteins in the human proteome, most interestingly Ubiquitin-related proteins. The data from this chapter is preliminary but may be used in the discovery of novel binding partners for PDE4 or to provide a new role for PDE inhibition in disease. Therefore the work in this thesis provides a unique snapshot of the complexity of the cAMP signalling system and is the first to directly compare action of the two approved PDE4 inhibitors in a detailed way.

Periodontitis as a risk factor for systemic disease: Are microparticles the missing link?

International audience

Influência do estímulo por PAF no perfil de abundância proteica em neutrófilos : uma abordagem proteômica

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Biologia Celular, Pós-Graduação em Biologia Molecular, 2015.

A Qualidade de vida em doentes com Artrite Reumatóide

Dissertação de Mestrado realizada apresentada no Instituto Superior de Psicologia Aplicada para a obtenção do grau de Mestre na especialidade de Psicologia Clínica

Efeito do Fucoidam de Fucus vesiculosus em um modelo experimental de artrite reumatóide

Rheumatoid arthritis (RA) is systemic auto imune disorder. It is caracterized by chronic inflammation of joints leading to progressive erosion of cartilage and bone. We investigated the effect of the administration of fucoidan, sulfated polysaccharides, from algae Fucus vesiculosus in the acute (6h) in zymosan-induced arthritis (AZy). Wistar rats (180-230 g) were used for all groups experimental. Non-treated animals received just intraarticular injection of 1 mg the zymosan, control group received intraarticular injection of 50 µL the saline, groups received either fucoidan of Fucus vesiculosus (15, 30, 50 or 70 mg/Kg) or parecoxib (1 mg/Kg) 1 hour after injection of zymosan. After 6 h, the articular exudates were collected for evaluation of the cell influx and nitrite (Griess reaction) release. The sinovial membranes and articular cartilages were excised for histopathological analysis and by determination of the glycosaminoglycan (GAG), respectively. ZyA led to increased NO and cell influx into the joints. Therapeutic administration of the fucoidan or parecoxib did significantly inhibited the cell influx and the synovitis, as compared to non-treated rats (p<0,05), though being able to reduced NO release. Representative agarose gel electrophoresis of the GAGs, the content of condroitin-sulphate was observed during the process. These findings suggest that the fucoidan from Fucus vesiculosus has potential anti-inflammatory activity

The treatment of oral lesions in Behçet's Syndrome: case report

Behçet's disease (BD) is a multi-systemic vascular disorder characterized by oral and genital ulcers, cutaneous, ocular, arthritic, vascular, central nervous system and gastrointestinal involvement. It usually affects young adults and the etiopathogenesis is unknown. A 21-year-old girl, Caucasian, with diagnostic BD, presented with rheumatoid arthritis, genital lesions and multiple recurrent ulcers inside the mouth, with an erythematous halo, covered by yellowish exudates exacerbated during menstrual periods, and in situations of stress and anxiety. The application of low power laser in ulcers was considered in order to decrease the inflammatory symptoms and pain, beyond getting the healing process accelerated. The proposed therapy was able to promote pain relief, increase local microcirculation and repair ulcerated lesions, eliminating the need for administration of systemic or topical medications, leading to improved quality of life.

Avaliação demográfica, clinico-laboratorial e genética de indivíduos com lupus eritematoso sistêmico e artrite reumatóide residentes em região tropical

The aetiology of autoimmunes disease is multifactorial and involves interactions among environmental, hormonal and genetic factors. Many different genes may contribute to autoimmunes disease susceptibility. The major histocompatibility complex (MHC) genes have been extensively studied, however many non-polymorphic MHC genes have also been reported to contribute to autoimmune diseases susceptibility. The aim of the present study was to evaluate the influence of SLC11A1 gene in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Ninety-six patients with SLE, 37 with RA and 202 controls enrolled in this case-control study, were evaluated with regard to demographic, genetic, laboratorial and clinical data. SLE mainly affects females in the ratio of 18 women for each man, 88,3% of the patients aged from 15 to 45 years old and it occurs with similar frequency in whites and mulattos. The rate of RA between women and men was 11:1, with 77,1% of the cases occurring from 31 to 60 years. The genetic analysis of the point mutation -236 of the SLC11A1 gene by SSCP did not show significant differences between alleles/genotypes in patients with SLE or RA when compared to controls. The most frequent clinical manifestations in patients with SLE were cutaneous (87%) and joint (84.9%). In patients with RA, the most frequent out-joint clinical manifestation were rheumatoid nodules (13,5%). Antinuclear antibodies were present in 100% of the patients with SLE. There was no significant relation between activity of disease and presence of rheumatoid factor in patients with RA, however 55,6% of patients with active disease presented positive rheumatoid factor. Significant association between alleles/genotypes of point mutation -236 and clinical manifestations was not found

Efectividad de la deslaminación mecánica con bisturí en la eliminación de helomas e hiperqueratosis

Introducción El motivo principal por el que acuden los pacientes a las consultas de podología es el dolor producido por los callos y callosidades plantares. El dolor producido por las callosidades y callos plantares provocan en el paciente cambios de presiones y alteraciones en el apoyo, dificultando la deambulación correcta. Existen numerosos estudios sobre la eliminación de callosidades en pacientes diabéticos, con AR, pero pocos en personas sanas. La eliminación de estos callos y callosidades se puede realizar mediante deslaminación mecánica con bisturí o mediante queratolíticos. Objetivos Objetivo principal Analizar el efecto de la deslaminación mecánica con bisturí de las callosidades y callos plantares sobre el dolor y la calidad de vida en sujetos sanos Objetivos secundarios Determinar la existencia de modificaciones en los parámetros de la marcha con la eliminación de callosidades y callos plantares Observar las diferencias y efectividad de tratamientos de la eliminación de callosidades plantares mediante la técnica de deslaminación mecánica con bisturí versus parches de ácido salicílico Comprobar los cambios producidos en los parámetros psíquicos y fiscos del paciente antes y después de las diferentes técnicas de eliminación de las callosidades empleadas Método Se realizan dos estudios: un estudio cuasi experimental aleatorizado no controlado, en el que a un grupo de 34 pacientes con callosidades plantares dolorosas se les mide el dolor con una escala visual analógica y para analizar los parámetros de la marcha, la paltaformaWin-Track, antes del tratamiento de deslaminación mecánica con bisturí y a las 24 horas. El segundo estudio es un ensayo clínico aleatorizado inscrito en Australian New ZelandClinicalstrials y aprobado por el Comité ético de la Universidad de Málaga, en el que 62 participantes con callosidades plantares dolorosas se dividieron en dos grupos de tratamiento. El grupo A recibió tratamiento con parche de ácido salicílico y el grupo B recibió tratmiento de deslaminación con bisturí. Se utilizó la escala visual analógica para la medida de dolor antes, inmediatamente después de la intervención, a las 2 semanas y a las 6 semanas. Para el dolor y la discapacidad funcional del pie se utilizó el cuestionario Manchester FootPain and Disability antes del tratamiento, a las 2 semanas y a las 6 semanas. Para medir la calidad de vida general se utilizó el cuestionario SF-12 Conclusiones La deslaminación mecánica con bisturí de los callos y callosidades plantares es efectiva para su eliminación a nivel de la sensación de dolor, aunque no tanto en lo que se refiere a la mejora de calidad de vida. No hay resultados significativos de que la eliminación mecánica con bisturí de callos y callosidades plantares modifican los parámetros de la marcha medido con la plataforma Win-track. Se observa como la deslaminación mecánica con bisturí para la eliminación de callos y callosidades plantares pueden ser más efectiva a corto plazo que la eliminación mediante parche con ácido salicílico. Se observa cómo se modifica los paramentos psíquicos en el grupo de tratamiento con parche con ácido salicílico, aunque con una significación baja. Bibliografía Balanowski, K. R., & Flynn, L. M. (2005). Effect of painful keratoses debridement on foot pain, balance and function in older adults. Gait & Posture, 22(4), 302-307. http://doi.org/10.1016/j.gaitpost.2004.10.006 Collins, S. L., Moore, R. A., &McQuay, H. J. (1997). The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain, 72(1-2), 95-97. Coughlin, M. J. (2000).Common Causes of Pain in the Forefoot in Adults. Journal of Bone & Joint Surgery, British Volume, 82-B(6), 781-790. Farndon, L. J., Vernon, W., Walters, S. J., Dixon, S., Bradburn, M., Concannon, M., & Potter, J. (2013). The effectiveness of salicylic acid plasters compared with «usual» scalpel debridement of corns: a randomised controlled trial. Journal of Foot and Ankle Research, 6(1), 40. http://doi.org/10.1186/1757-1146-6-40 Freeman, D. B. (2002). Corns and calluses resulting from mechanical hyperkeratosis. American FamilyPhysician, 65(11), 2277-2280. Gijon-Nogueron, G., Ndosi, M., Luque-Suarez, A., Alcacer-Pitarch, B., Munuera, P. V., Garrow, A., & Redmond, A. C. (2014). Cross-cultural adaptation and validation of the Manchester Foot Pain and Disability Index into Spanish. Quality of Life Research: An International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation, 23(2), 571-579. http://doi.org/10.1007/s11136-013-0507-5 Grouios, G. (2005). Footedness as a potential factor that contributes to the causation of corn and callus formation in lower extremities of physically active individuals. The Foot, 15(3), 154-162. http://doi.org/10.1016/j.foot.2005.05.003 Landorf, K. B., Morrow, A., Spink, M. J., Nash, C. L., Novak, A., Potter, J., &Menz, H. B. (2013). Effectiveness of scalpel debridement for painful plantar calluses in older people: a randomized trial. Trials, 14, 243. http://doi.org/10.1186/1745-6215-14-243 Lang, L. M. G., Simmonite, N., West, S. G., & Day, S. (1994). Salicylic acid in the treatment of corns. The Foot, 4(3), 145-150. http://doi.org/10.1016/0958-2592(94)90019-1 Luo, X., Lynn George, M., Kakouras, I., Edwards, C. L., Pietrobon, R., Richardson, W., & Hey, L. (2003). Reliability, validity, and responsiveness of the short form 12-item survey (SF-12) in patients with back pain. Spine, 28(15), 1739-1745. http://doi.org/10.1097/01.BRS.0000083169.58671.96 Ramachandra, P., Maiya, A. G., & Kumar, P. (2012). Test-retest reliability of the Win-Track platform in analyzing the gait parameters and plantar pressures during barefoot walking in healthy adults. Foot & Ankle Specialist, 5(5), 306-312. http://doi.org/10.1177/1938640012457680 Siddle, H. J., Redmond, A. C., Waxman, R., Dagg, A. R., Alcacer-Pitarch, B., Wilkins, R. A., &Helliwell, P. S. (2013). Debridement of painful forefoot plantar callosities in rheumatoid arthritis: the CARROT randomised controlled trial. Clinical Rheumatology, 32(5), 567-574. http://doi.org/10.1007/s10067-012-2134-x

Inhibition of Neurotoxic Secretory Phospholipases A(2) Enzymatic, Edematogenic, and Myotoxic Activities by Harpalycin 2, an Isoflavone Isolated from Harpalyce brasiliana Benth

Secretory phospholipases A(2) (sPLA(2)) exert proinflammatory actions through lipid mediators. These enzymes have been found to be elevated in many inflammatory disorders such as rheumatoid arthritis, sepsis, and atherosclerosis. The aim of this study was to evaluate the effect of harpalycin 2 (Har2), an isoflavone isolated from Harpalyce brasiliana Benth., in the enzymatic, edematogenic, and myotoxic activities of sPLA2 from Bothrops pirajai, Crotalus durissus terrificus, Apis mellifera, and Naja naja venoms. Har2 inhibits all sPLA(2) tested. PrTX-III (B. pirajai venom) was inhibited at about 58.7%, Cdt F15 (C. d. terrificus venom) at 78.8%, Apis (from bee venom) at 87.7%, and Naja (N. naja venom) at 88.1%. Edema induced by exogenous sPLA(2) administration performed in mice paws showed significant inhibition by Har2 at the initial step. In addition, Har2 also inhibited the myotoxic activity of these sPLA(2)s. In order to understand how Har2 interacts with these enzymes, docking calculations were made, indicating that the residues His48 and Asp49 in the active site of these enzymes interacted powerfully with Har2 through hydrogen bonds. These data pointed to a possible anti-inflammatory activity of Har2 through sPLA(2) inhibition.

Small clonal B-cell population in the bone marrow as a possible tool in the diagnosis of occult primary parotid lymphoma

Case Description: An 82-years old Hispanic woman with a past medical history significant for pulmonary thromboembolism on oral anticoagulation, rheumatoid arthritis, and hypertension developed a new onset thrombocytopenia. Clinical Findings: Small clonal B-cells populations (SCBP) also known as monoclonal B-cell lymphocytosis was found as part of the workup for an idiopathic thrombocytopenia and lead ultimately to the diagnosis of parotid primary follicular lymphoma coexisting with Warthin tumor involving the bone marrow in a small extent and oncocytic papilloma located in the maxillary sinus. Treatment and Outcome: Patient was treated with Rituximab monotherapy with improvement on her platelet count. Clinical relevance: Although it is unclear the role of this clonal cells, they may work as a possible diagnostic tool for occult lymphomas. Further prospective studies are needed to confirm this possible association.

Fadiga em pacientes da Coorte Brasília de artrite reumatoide (AR) : estudo da prevalência e comparação entre diferentes instrumentos de avaliação

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, 2016.

Associação entre periodontite e artrite reumatoide

Introdução: A artrite reumatoide é uma doença inflamatória, crónica, de etiologia e patogénese ainda desconhecida, caraterizada pelo envolvimento preferencial da membrana sinovial das articulação, pelo desenvolvimento de erosões ósseas e progressiva destruição articular (Fonseca et al., 2002). A periodontite é uma doença infeciosa e crónica caraterizada por perda irreversível dos tecidos de suporte periodontais e de osso alveolar (Ziebolz et al., 2002). Liubomorova (1964) foi o primeiro autor a descrever os possíveis mecanismos inflamatórios comuns de ambas as doenças, assistindo-se, nos últimos anos, a um aumento de evidência científica relativa a uma possível associação entre a periodontite e a artrite reumatoide. Objetivo: A presente revisão de literatura teve como objetivo analisar a evidência científica disponível relativa a uma possível associação entre a periodontite e a artrite reumatoide, atentando-se em particular à prevalência e severidade da periodontite em pacientes com artrite reumatoide. Materiais e métodos: Foi realizada uma pesquisa bibliográfica na base de dados PubMed, priorizando-se revisões sistemáticas e meta-análises, estudos coorte e caso-controlo. Foram apenas incluídos estudos disponíveis em inglês e publicados entre 2010 a 2016. Resultados: Onze estudos compreenderam os critérios para integrar esta revisão. A grande maioria verificou que pacientes com artrite reumatoide são mais suscetíveis a manifestar periodontite e a apresentar piores parâmetros periodontais, quando comparados com indivíduos saudáveis.