Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis.

OBJECTIVE: Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. METHODS: Mice received 0.1 mg/25µL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 µL or saline per os (systemic) or 500 µg/25 µL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. RESULTS: MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. CONCLUSION: MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis

Abstract Objective Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. Methods Mice received 0.1 mg/25μL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 μL or saline per os (systemic) or 500 μg/25 μL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. Results MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. Conclusion MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Antibody response 6 months after the booster dose of Pfizer in previous recipients of CoronaVac.

The most widely used vaccines were messenger RNA (mRNA), viral vector, and inactivated virus with two-dose schedules. In Brazil, the CoronaVac (Sinovac) was the first vaccine approved for emergency use, and the third dose was administered, preferably, with the BNT162b2 vaccine. We evaluated antibody levels after 6 months of the booster dose with BNT162B2 in previous recipients of CoronaVac and whether a subsequent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection enhances the antibody response. We analyze the humoral response (spike [S] IgM for the SARS-CoV-2 and IgG for the S and nucleocapsid [N] proteins) in samples collected before the third dose and 6 months after the third dose. The presence of antibodies was measured by using Abbott Architect i2000SR. The IgM and IgG antispikes were stimulated mainly 30 days after the third dose (30d/3D), with a decline over time. The IgG anti-N was stimulated predominantly in 90d/3D and 180d/3D. The N IgG levels were 50 and 35 times higher in the positive polymerase chain reaction (PCR) group in 90d/3D and 180d/3D, respectively. The S IgG titers were 1.5 times elevated in the positive PCR group, in 180d/3D. The BNT162b2 boosted the S IgG levels, decreasing after 60 days. The booster shot induced IgM and IgG antibodies against spike protein. Infection after vaccination increased antibodies against protein N.

Fatores associados a qualidade do sono ruim em universitários de enfermagem de uma universidade privada cearense / Factors associated with poor sleep quality in nursing students from a private university in Ceará

Sleep is essential for the physical, psychological, and social well-being of individuals. Its poor quality/quantity may lead to functional impairment in the performance of social activities and interpersonal relationships. In this context, studies have identified poor sleep quality in university students, especially those in healthcare. Despite the literature pointing out that nursing students do not sleep well, factors related to employment or daily commuting are not unanimous. Thus, the objective of the study is to evaluate the sleep quality of nursing students and its association with socioeconomic characteristics, life habits, academic, and extracurricular activities. This is a cross-sectional, descriptive study with quantitative analysis, carried out with 124 Nursing students from a private Higher Education Institution in Ceará. A questionnaire was used with socioeconomic variables, life-style habits, academic and extracurricular activities, and the Pittsburgh Sleep Quality Index. Descriptive and inferential statistical analyses were performed. The results of this study showed a predominance of poor sleep quality for 73 (59%) students and the presence of sleeping disorders for 38 (31%) of the participants. The variables associated with this result were the daily intercity commute (to-and-fro) to attend an undergraduate class or to have a concomitant job. Meanwhile, the other academic, extracurricular, and lifestyle variables did not have a statistically significant association with sleep quality. Therefore, it is necessary to adopt actions aimed at good sleep hygiene, for better use of the available time for sleep, better academic performance, and quality of life.

O sono é essencial para o bem-estar físico, psíquico e social dos indivíduos. Sua qualidade/quantidade ruim poderá levar a prejuízo funcional no desempenho dos papéis sociais e nas relações interpessoais. Nesse contexto, estudos comprovam uma qualidade do sono ruim em universitários, especialmente os da área da saúde. Apesar da literatura apontar que universitários de enfermagem são maus dormidores, fatores relacionados como vínculo empregatício ou deslocamento intermunicipal diário não são unânimes. Assim, o objetivo do estudo é avaliar a qualidade do sono de estudantes de enfermagem e sua associação com características socioeconômicas, hábitos de vida, atividades acadêmicas e extracurriculares. Trata-se de um estudo transversal, descritivo, com análise quantitativa, realizado com 124 estudantes de Enfermagem de uma Instituição de Ensino Superior privada cearense. Empregou-se questionário com variáveis socioeconômicas, hábitos de vida, atividades acadêmicas e extracurriculares, e o Índice da Qualidade do Sono de Pittsburgh. Foi realizada análise estatística descritiva e inferencial. Os resultados deste estudo demonstraram predominância de qualidade do sono ruim para 73 (59%) estudantes e presença de distúrbios do sono para 38 (31%) dos participantes. As variáveis associadas a esse resultado foram o deslocamento intermunicipal diário (movimento pendular) para cursar a graduação ou possuir vínculo empregatício concomitante. Enquanto, as demais variáveis acadêmicas, extracurriculares e de hábitos de vida não tiveram associação estatisticamente significante com a qualidade do sono. Logo, é necessária a adoção de ações visando a boa higiene do sono, para melhor aproveitamento do período disponível para o sono, melhor desempenho acadêmico e qualidade de vida

Potent anti-inflammatory activity of the lectin-like domain of TNF in joints.

In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N'N'-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.

Quantitative evaluation of very early cartilage damage in experimental osteoarthritis using scanning electron microscopy.

OBJECTIVE: To describe parametric changes observed using scanning electron microscopy (SEM) in very early stages in posttraumatic osteoarthritis (OA) models in mice. METHODS: Mice (5/group) had their knees subjected to anterior cruciate ligament transection (ACLT), ACLT plus meniscectomy (MNCT) or sham surgery, sacrificed after 3, 7 or 14 days, had the articular cartilage evaluated under optical microscopy using Osteoarthritis Research Society International (OARSI) parameters as well as cartilage thickness, roughness, and a damage index using SEM. RESULTS: Alterations of the cartilage under optical microscopy were not significantly relevant among groups. SEM analysis revealed reduction of femoral and tibial cartilage thickness in ACLT and MNCT groups at 7 and 14 days, with increased cartilage roughness in MNCT group as early as 3 days postsurgery, being sustained up to 14 days. Articular damage index was significantly higher at 14 days post surgery in ACLT and MNCT vs control groups. CONCLUSION: This is the first demonstration of very early quantitative changes in the cartilage of mice subjected to posttraumatic experimental OA using SEM, revealing increased roughness and thickness as early as 3 days post surgery. These changes may be used as early surrogates for later joint damage in experimental OA.

Dynamics of SARS-CoV-2 Antibody Response to CoronaVac followed by Booster Dose of BNT162b2 Vaccine.

We evaluated the longitudinal dynamics of antibody response to the SARS-CoV-2 vaccine CoronaVac and the effect of a booster dose of BNT162b2 vaccine. We found a robust antibody response after the second dose of CoronaVac that wanes over time. The response was recovered by BNT162b2, which boosted anti-spike antibody titers.

Associação entre fatores de risco cardiovascular e indicadores antropométricos em policiais militares / Association between cardiovascular risk factors and anthropometric indicators in military police officers / Asociación entre factores de riesgo cardiovascular e indicadores antropométricos en policías militares

Objetivo: Avaliar a associação entre fatores de risco cardiovascular e indicadores antropométricos em Policiais Militares. Métodos:Trata-se de um estudo transversal, com abordagem quantitativa,realizadoemdoismunicípios doEstado do Ceará, Brasil.A coleta dos dados foi realizada por meio de entrevista para obtenção de variáveis sociodemográficas, exercício policial, dados clínicos e aspectos comportamentais; e exame físico para obtenção dos indicadores antropométricos. Os dados foram analisados por estatística descritiva e inferencial. Resultados:Participaram do estudo107 policiais militares.Predominaram homens, com idade média de 37,17 anos, que exerciam atividades operacionais.Foi verificada associação esignificância estatísticaentre doisindicadores antropométricos equatro fatores de risco cardiovascular, a saber:índice de conicidadecom alcoolismo, hipertensão arterial, diabetes mellitus e função exercida na polícia; relação cintura-quadril com alcoolismo, hipertensão arterial, diabetes mellitus e antecedente familiar de doença cardiovascular. Cada um dosdemais índices antropométricosavaliados (peso,circunferência da cintura, circunferência do quadril, circunferência abdominal,índice de massa corporal,razão cintura-estatura) possuíam significância estatística com somente dois fatores de risco cardiovascular. A presença de hipertensãoarterialapresentou associação estatisticamente significante com todos os indicadores antropométricos avaliados, enquanto sedentarismo não teve associação significante com nenhum deles. O escore de Framingham simplificado descreveu baixo risco cardíacoentre os participantes e sóapresentou significância estatística com hipertensão arterial e diabetes mellitus.Conclusão:indicadores antropométricos, especialmente o índice de conicidade e a relação cintura-quadril, podem ser empregados para rastrear fatores derisco cardiovascular em policiais militares.

Objective: To evaluate the association between cardiovascular risk factors and anthropometric indicators in Military Police officers. Methods:This is a cross-sectional study, with a quantitative approach, carried out in two municipalities in the State of Ceará, Brazil. Data collection was performed by means of interviews to obtain sociodemographic variables, police practice, clinical data and behavioral aspects; and physical examination to obtain anthropometric indicators. Data were analyzed by descriptive and inferential statistics. Results:107 military police participated in the study. There was a predominance of men, with an average age of 37.17 years, who performed operational activities. An association and statistical significance were verified between two anthropometric indicators and four cardiovascular risk factors, namely: conicity index with alcoholism, arterial hypertension, diabetes mellitus and role in the police; waist-hip ratio with alcoholism, arterial hypertension, diabetes mellitus and family history of cardiovascular disease. Each of the other anthropometric indices evaluated(weight, waist circumference, hip circumference, abdominal circumference, body mass index, waist-to-height ratio) had statistical significance with only two cardiovascular risk factors. The presence of arterial hypertension showed a statistically significant association with all anthropometric indicators evaluated, while a sedentary lifestyle had no significant association with any of them. The simplified Framingham score described low cardiac risk among the participants and only showed statistical significance with arterial hypertension and diabetes mellitus. Conclusion: Anthropometricindicators, especially the conicity index and waist-hip ratio, can be used to track cardiovascular risk factors in military police officers.

Objetivo: Evaluarla asociación entre factores de riesgo cardiovascular e indicadores antropométricos en Policías Militares. Métodos:Se trata de un estudio transversal, con abordaje cuantitativa, realizado en dos municipios del Estado del Ceará, Brasil. La recolección de datos fue realizada a través de entrevista para obtención de variables sociodemográficas, ejercicio policial, datos clínicos y aspectos conductuales; y examen físico para obtención de los indicadores antropométricos. Los datos fueron analizados por estadística descriptiva e inferencial. Resultados:Participaron del estudio 107 policías militares. Predomininaron los hombres con edad media de 37,17 años, que realizaban actividades operacionales. Se verificó asociación y significancia estadística entre dos indicadores antropométricos y cuatro factores de riesgo cardiovascular, a saber: índice de conicidad con alcoholismo, hipertensión arterial, diabetes mellitus y función ejercida en la policía; relación cintura-cadera con alcoholismo, hipertensión arterial, diabetes mellitus y antecedente familiar de enfermedad cardiovascular. Cadauno de los demás índices antropométricos evaluados (peso, circunferencia de cintura, circunferencia de cadera, circunferencia abdominal, índice de masa corporal,razón cintura-estatura) tuvieron significación estadística con sólo dos factores de riesgo cardiovascular. La presencia de hipertensión arterial mostró asociación estadísticamente significativa con todos los indicadores antropométricos evaluados, mientrasque el sedentarismo no tuvo asociación significativa con ninguno de ellos. La puntuación de Framingham simplificado describió bajo riesgo cardíaco entrelos participantes y solo mostró significación estadística con hipertensión arterial y diabetes mellitus. Conclusión:indicadores antropométricos, especialmente el índice de conicidad y la relación cintura-cadera, pueden ser empleados para rastrear factores de riesgo cardiovascular en policías militares.

Restrição da ingestão de alimentos em pré-escolares com hipersensibilidade alimentar: impacto no crescimento e desenvolvimento / Restriction of food intake in preschoolers with food hypersensitivity: impact on growth and development / Restricción de la ingesta de alimentos en preescolares con hipersensibilidad alimentaria: impacto en el crecimiento y desarrollo

Objetivo: Analisar evidências científicas sobre os impactos da restrição alimentar no crescimento e desenvolvimento de crianças em fase pré-escolar com história de alergia a alimentos. Método: Trata-se de uma revisão integrativa da literatura que teve como intuito responder a seguinte pergunta norteadora "Quais os impactos da restrição alimentar no crescimento e desenvolvimento de crianças na fase pré-escolar com história de alergia a alimentos?". A busca na base de dados foi conduzida nas plataformas Scopus, PubMed, LILACS e CINAHL, em agosto de 2020. Resultados: Dos 9 artigos incluídos, 55,56% constavam na Scopus, todos estavam em inglês e 33,33% eram caso-controle. As publicações constataram um maior quantitativo de crianças que manifestavam alergia imunoglobulina E mediada, que costumavamevitar 1 ou mais alimentos, especialmente o leite de vaca. Foram observadas reduções nos escores Z (≤ -2) de altura/idade, peso/idade e peso/altura entre as crianças com alergia alimentar e restrição de alimentos. Conclusão: Os artigos se limitaram a determinadas áreas e a um nível de evidência mediano. Contudo, eles não se restringiram a avaliar o crescimento de crianças alérgicas a alimentos em dieta restritiva, investigando, dentre outros fatores, a qualidade de vida de cuidadores e as concentrações séricas de vitaminas.

Objetivo: Analizar la evidencia científica sobre los impactos de la restricción alimentaria en el crecimiento y desarrollo de preescolares con antecedentes de alergia alimentaria. Método:Se trata de una revisión integrativa de la literatura que tuvo como objetivo responder a la siguiente pregunta orientadora "¿Cuáles son los impactos de la restricción alimentaria en el crecimiento y desarrollo de niños en edad preescolar con antecedentes de alergia alimentaria?". La búsqueda en bases de datos se realizó en las plataformas Scopus, PubMed, LILACS y CINAHL en agosto de 2020. Resultados: De los 9 artículos incluidos, el 55,56% estaban en Scopus, todos estaban en inglés y el 33,33% eran sensibles a mayúsculas y minúsculas. Las publicaciones encontraron un mayor número de niños que manifestaban alergia mediada por inmunoglobulina E, que solían evitar 1 o más alimentos, especialmente la leche de vaca. Se observaron reducciones en las puntuaciones Z (≤ -2) para altura/edad, peso/edad y peso/talla entre niños con alergia alimentaria y restricción alimentaria. Conclusión:Los artículos se limitaron a ciertas áreas yun nivel de evidencia medio. Sin embargo, no se limitaron a evaluar el crecimiento de niños alérgicos a alimentos con dieta restrictiva, investigando, entre otros factores, la calidad de vida de los cuidadores y las concentraciones séricas de vitaminas.

Objective: To analyze scientific evidence on the impacts of food restriction on the growth and development of childrenin pre-school age with a history of food allergy. Method: This integrative literature review that aimed to answer the following guiding question "What are the impacts of food restriction on the growth and development of children in the preschool phase with a history of food allergy?". The database search was conducted on Scopus, PubMed, LILACS and CINAHL platforms, in August 2020. Results: Of the 9 articles included, 55.56% were in Scopus, all were in English and 33.33% were case-control. The publications found a greater number of children who manifested mediated immunoglobulin E allergy, who used to avoid 1 or more foods, especially cow's milk. Reductions in Z scores (≤ -2) in height / age, weight / age and weight / height were observed among children withfood allergy and food restriction. Conclusion: The articles were limited to certain areas and to a medium level of evidence. However, they were not restricted to assessing the growth of children allergic to foods on a restrictive diet, investigating, among other factors, the quality of life of caregivers and serum concentrations of vitamins.

Fatores associados a qualidade do sono ruim em universitários de enfermagem de uma universidade privada cearense / Factors associated with poor sleep quality in nursing students from a private university in Ceará

O sono é essencial para o bem-estar físico, psíquico e social dos indivíduos. Sua qualidade/quantidade ruim poderá levar a prejuízo funcional no desempenho dos papéis sociais e nas relações interpessoais. Nesse contexto, estudos comprovam uma qualidade do sono ruim em universitários, especialmente os da área da saúde. Apesar da literatura apontar que universitários de enfermagem são maus dormidores, fatores relacionados como vínculo empregatício ou deslocamento intermunicipal diário não são unânimes. Assim, o objetivo do estudo é avaliar a qualidade do sono de estudantes de enfermagem e sua associação com características socioeconômicas, hábitos de vida, atividades acadêmicas e extracurriculares. Trata-se de um estudo transversal, descritivo, com análise quantitativa, realizado com 124 estudantes de Enfermagem de uma Instituição de Ensino Superior privada cearense. Empregou-se questionário com variáveis socioeconômicas, hábitos de vida, atividades acadêmicas e extracurriculares, e o Índice da Qualidade do Sono de Pittsburgh. Foi realizada análise estatística descritiva e inferencial. Os resultados deste estudo demonstraram predominância de qualidade do sono ruim para 73 (59%) estudantes e presença de distúrbios do sono para 38 (31%) dos participantes. As variáveis associadas a esse resultado foram o deslocamento intermunicipal diário (movimento pendular) para cursar a graduação ou possuir vínculo empregatício concomitante. Enquanto, as demais variáveis acadêmicas, extracurriculares e de hábitos de vida não tiveram associação estatisticamente significante com a qualidade do sono. Logo, é necessária a adoção de ações visando a boa higiene do sono, para melhor aproveitamento do período disponível para o sono, melhor desempenho acadêmico e qualidade de vida.

Sleep is essential for the physical, psychological, and social well-being of individuals. Its poor quality/quantity may lead to functional impairment in the performance of social activities and interpersonal relationships. In this context, studies have identified poor sleep quality in university students, especially those in healthcare. Despite the literature pointing out that nursing students do not sleep well, factors related to employment or daily commuting are not unanimous. Thus, the objective of the study is to evaluate the sleep quality of nursing students and its association with socioeconomic characteristics, life habits, academic, and extracurricular activities. This is a cross-sectional, descriptive study with quantitative analysis, carried out with 124 Nursing students from a private Higher Education Institution in Ceará. A questionnaire was used with socioeconomic variables, life-style habits, academic and extracurricular activities, and the Pittsburgh Sleep Quality Index. Descriptive and inferential statistical analyses were performed. The results of this study showed a predominance of poor sleep quality for 73 (59%) students and the presence of sleeping disorders for 38 (31%) of the participants. The variables associated with this result were the daily intercity commute (to-and-fro) to attend an undergraduate class or to have a concomitant job. Meanwhile, the other academic, extracurricular, and lifestyle variables did not have a statistically significant association with sleep quality. Therefore, it is necessary to adopt actions aimed at good sleep hygiene, for better use of the available time for sleep, better academic performance, and quality of life.

Decreased Sulfate Content and Zeta Potential Distinguish Glycosaminoglycans of the Extracellular Matrix of Osteoarthritis Cartilage.

We aimed to determine the characteristics that distinguish glycosaminoglycans (GAGs) from osteoarthritis (OA) and normal cartilage and from men and women. Cartilage samples from 30 patients subjected to total joint arthroplasty secondary to OA or fracture (control) were evaluated, and the GAG content (µg/mg dry cartilage) after proteolysis was determined by densitometry, using agarose-gel electrophoresis. Relative percentages of carbon (C), nitrogen (N), and sulfur (S) in GAGs were determined by elemental microanalysis, as well as the zeta potential. Seventeen samples (56.6%) were from patients >70 years old, with 20 (66.6%) from women, and most [20 (66.6%)] were from the hip. The GAG content was similar regardless of patients being >/≤ 70 years old with 96.5 ± 63.5 and 78.5 ± 38.5 µg/mg (P = 0.1917), respectively. GAG content was higher in women as compared to men, with 89.5 ± 34.3 and 51.8 ± 13.3 µg/mg, respectively (P = 0.0022), as well as in OA than fracture samples, with 98.4 ± 63.5 and 63.6 ± 19.6 µg/mg, respectively (P = 0.0355). The GAG extracted from the cartilage of patients >70 years old had increase in N, and there were no gender differences regarding GAG elemental analysis. GAG from OA had a highly significant (P = 0.0005) decrease in S% (1.79% ± 0.25%), as compared to fracture samples (2.3% ± 0.19%), with an associated and significant (P = 0.0001) reduction of the zeta potential in the OA group. This is the first report of a reduced S content in GAG from OA patients, which is associated with a reduced zeta potential.

Increase in molar mass distinguishes chondroitin sulfate from osteoarthritis and normal extracellular cartilage matrix.

PURPOSE: To determine alterations of chondroitin sulfate (CS) that reflect cartilage damage in an experimental osteoarthritis (OA) model as well as in human OA samples. MATERIALS AND METHODS: Rats were subjected to anterior cruciate ligament transection (ACLT; OA) or a sham procedure and sacrificed 14, 28, or 70 days after ACLT for histopathology and analysis of extracted CS. Cartilage samples from 14 patients undergoing hip or shoulder arthroplasty secondary to OA or fracture (control) were subjected to the same protocol. The CS content (µg/mg dry cartilage) after proteolysis was determined by densitometry, using agarose-gel electrophoresis. Molar mass (MM) and peak MM of CS were determined using high-performance size-exclusion chromatography (HPSEC). RESULTS: OA and sham joints at 70 d had 24 [22-24] and 3 [1-6] median histopathology scores, respectively (p < 0.001). Relative CS content (77.7 ± 8.3 µg/mg) was significantly increased in OA samples 70 d after ACLT, as compared to sham (53.5 ± 10.0 µg/mg). Peak MM of CS was higher in OA than in sham samples (P < 0.05). Similarly, CS content and peak MM were higher in cartilage from human OA patients, as compared to fracture samples, reproducing experimental data. CONCLUSION: Cartilage matrix from experimental and human OA samples has increased in the relative CS content. Increase in the peak MM distinguishes CS of the extracellular matrix of OA from normal cartilage.

Tumor necrosis factor inhibitors prevent structural damage in hips in ankylosing spondylitis-time to reconsider treatment guidelines? A case series and review of literature.

Tumor necrosis factor inhibitors (TNFi) are indicated to treat ankylosing spondylitis (AS), also termed radiographic axial spondyloarthritis (axSpA). The main indication for TNFi is symptom relief, and whether they retard spinal structural damage as assessed by radiography is debated. Hips are the most common "non-spinal" joints involved in AS patients leading to major incapacitation. No major treatment guidelines mention measures to prevent peripheral joint damage, especially hips, in individuals with AS. We present our experience of prevention of structural damage in hips by TNFi in 4 AS patients from our practice. We conducted a literature review looking for articles describing prevention of structural damage progression in hips by TNFi. Over a 10-year period, three out of four patients were treated with TNFi and had no progression in hip damage as assessed by imaging. Only one patient that withdrew the TNFi due to infectious complications developed rapid worsening and required hip arthroplasty. Our literature review showed multiple case series with similar results suggesting that use of TNFi in patients with AS may prevent structural damage and at least postpone a hip replacement at a young age. Based on our experience, as well as from the literature review, we believe that treatment guidelines in axSpA should recommend prompt institution of TNFi following identification of hip involvement in patients to prevent a major source of disability. Whether interleukin (IL)-17 inhibitors or targeted synthetic anti-rheumatic drugs have hip sparing effects in patients with AS should also be investigated. Key Points • Hip involvement in ankylosing spondylitis is a major source of disability. • TNFi prevent hip damage in ankylosing spondylitis. • Prompt institution of TNFi should follow suspicion of hip involvement in ankylosing spondylitis.

Hylan G-F20 and galactomannan joint flares are associated to acute synovitis and release of inflammatory cytokines.

BACKGROUND: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. METHODS: Mice received 100 µg/25 µL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. RESULTS: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. CONCLUSION: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.

Hylan G-F20 and galactomannan joint flares are associated to acute synovitis and release of inflammatory cytokines

Abstract Background: Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. Methods: Mice received 100 μg/25 μL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology. Results: Neither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release. Conclusion: Intra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.(AU)

Cell sources of inflammatory mediators present in bone marrow areas inside the meniscus.

PURPOSE: To demonstrate the production of inflammatory mediators by cells located in bone marrow spaces inside rodent menisci. METHODS: Mice subjected to transection of the medial collateral and anterior cruciate ligaments and meniscotomy (osteoarthritis model) or to a sham procedure, as well as non-operated (naive) mice and rats, had knee joints excised. Tissues were stained with hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP). CD68+ cells, inducible nitric oxide synthase (iNOS), interleukin (IL)-1ß, and tumor necrosis factor (TNF) expression were detected using immunohistochemistry. RESULTS: Lamellar ossified areas, bone-entrapped osteocytes and bone marrow spaces were found inside menisci of one week up to 6 months-old naïve mice, regardless of gender. Menisci from naive rats also showed the same pattern with bone marrow areas. CD68+ cells were identified in bone marrow areas inside the meniscus of mice. TRAP+ osteoclasts, and hematogenous precursors expressing IL-1ß, TNF, and iNOS were identified inside bone marrow areas in meniscal samples from both naïve and sham operated mice. Quantitative immunoexpression of IL-1 ß, TNF and iNOS was more intense, P = 0.0194, 0.0293, 0.0124, respectively, in mouse knees from mice sacrificed 49 days after being subjected to an osteoarthritis (OA) model as compared to sham operated animals. CONCLUSION: We provide novel data showing that rodent menisci display bone marrow areas with cells able to produce inflammatory mediators. Immunoexpression of inflammatory mediators in those bone marrow areas is significantly more pronounced in mice subjected to experimental OA.

Tumor necrosis factor prevents Candida albicans biofilm formation.

Candida species are commensals but some develop biofilms in prosthetic materials and host surfaces that may represent up to 30% of deaths related to infections, particularly in immunosuppressed patients. Tumor necrosis factor (TNF) exhibits a plethora of functions in host defense mechanisms whereas excessive release of TNF in inflammation promotes tissue damage. Cytokines released in an inflammatory milieu may influence the development of microorganisms either by promoting their growth or displaying antimicrobial activity. In protozoa, TNF may affect growth by coupling through a lectin-like domain, distinct from TNF receptors. TNF was also shown to interact with bacteria via a mechanism that does not involve classical TNF receptors. Using an in vitro C. albicans biofilm model, we show that TNF dose-dependently prevents biofilm development that is blocked by incubating TNF with N,N'-diacetylchitobiose, a major carbohydrate component of C. albicans cell wall. This finding represents a relevant and hitherto unknown mechanism that adds to the understanding of why TNF blockade is associated with opportunistic C. albicans infections.

Strontium ranelate analgesia in arthritis models is associated to decreased cytokine release and opioid-dependent mechanisms.

OBJECTIVE: We investigated the anti-inflammatory activity of strontium ranelate (SR) in arthritis models. MATERIALS AND METHODS: Rats received 1 mg zymosan (Zy) or saline intra-articularly. Other groups were subjected to anterior cruciate ligament transection in the right knee, as an osteoarthritis (OA) model, or a sham procedure. Joint pain was assessed using the articular incapacitation and paw-pressure tests. Cell influx and cytokines were measured in joint exudates. TREATMENT: Groups received either SR (30-300 mg/kg per os) or saline. RESULTS: SR dose-dependently and significantly inhibited joint pain in both Zy and OA models, while not altering cell influx. Naloxone administration significantly reversed SR analgesia. SR significantly reduced levels of Interleukin-1ß and tumor necrosis factor-α in Zy arthritis, whereas those of cytokine-induced neutrophil chemoattractant (CINC)-1 were not altered. CONCLUSIONS: SR provides analgesia in arthritis that is associated to inhibition of the release of inflammatory cytokines into inflamed joints. This effect is abrogated by administration of the opioid antagonist naloxone.

Vitamin D levels in juvenile idiopathic arthritis from an equatorial region.

We aimed to describe the serum levels of 25-hydroxyvitamin D (25OHD) in juvenile idiopathic arthritis (JIA) patients living in a low-latitude (3°43'S) region. Fifty JIA patients, 31 (62 %) female, seen between May 2012 and April 2013 in the northeast of Brazil had clinical data and serum collected for determination of 25OHD and parathyroid hormone (PTH) using a chemiluminescent ELISA; 20 age- and sex-matched controls were used for comparison. Mean age was 13.4 ± 4 years. Twenty-five (50 %), 15 (30 %), 4 (8 %), 4 (8 %), and 2 (4 %) patients were of the polyarticular, oligoarticular, systemic, enthesitis-related, and undifferentiated categories, respectively. Mean 25OHD was 31.6 ± 10 and 30.4 ± 5.7 ng/mL in patients and controls (P > 0.05), respectively; PTH was normal in JIA and controls; 25OHD was similar regardless of JIA category, disease activity, or severity measured by JADAS-27, CHAQ, or presence of joint deformities. Twenty-six (52 %), 20 (40 %), and 4 (8 %) patients were considered to have optimal, sufficient, and deficient 25OHD levels, respectively, whereas 11 (52 %) and 10 (48 %) controls had optimal and sufficient 25OHD. Ethnicity, body mass index, seasonal variation, and use of steroids did not influence 25OHD levels. This is the first study on 25OHD levels in JIA patients living in a low-latitude region, showing the lowest prevalence of vitamin D deficiency ever reported. Serum 25OHD was similar in JIA and controls and did not vary regardless of JIA category or severity.

Anti-inflammatory and immunomodulatory effect of an extract of Coccidioides posadasii in experimental arthritis.

Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1ß, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.