Long-Term Safety and Efficacy of Abatacept in Children With Juvenile Idiopathic Arthritis

Objective. We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study.Methods. This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6-17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect >= 21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008.Results. of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient.Conclusion. Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase.

Hormone profile in juvenile systemic lupus erythematosus with previous or current amenorrhea

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Macrophage Activation Syndrome in Juvenile Systemic Lupus Erythematosus A Multinational Multicenter Study of Thirty-Eight Patients

Objective. To describe the clinical and laboratory features of macrophage activation syndrome as a complication of juvenile systemic lupus erythematosus (SLE).Methods. Cases of juvenile SLE-associated macrophage activation syndrome were provided by investigators belonging to 3 pediatric rheumatology networks or were found in the literature. Patients who had evidence of macrophage hemophagocytosis on bone marrow aspiration were considered to have definite macrophage activation syndrome, and those who did not have such evidence were considered to have probable macrophage activation syndrome. Clinical and laboratory findings in patients with macrophage activation syndrome were contrasted with those of 2 control groups composed of patients with active juvenile SLE without macrophage activation syndrome. The ability of each feature to discriminate macrophage activation syndrome from active disease was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic curve.Results. The study included 38 patients (20 with definite macrophage activation syndrome and 18 with probable macrophage activation syndrome). Patients with definite and probable macrophage activation syndrome were comparable with regard to all clinical and laboratory features of the syndrome, except for a greater frequency of lymphadenopathy, leukopenia, and thrombocytopenia in patients with definite macrophage activation syndrome. Overall, clinical features had better specificity than sensitivity, except for fever, which was highly sensitive but had low specificity. Among laboratory features, the best sensitivity and specificity was achieved using hyperferritinemia, followed by increased levels of lactate dehydrogenase, hypertriglyceridemia, and hypofibrinogenemia. Based on the results of statistical analysis, preliminary diagnostic guidelines for macrophage activation syndrome in juvenile SLE were developed.Conclusion. Our findings indicate that the occurrence of unexplained fever and cytopenia, when associated with hyperferritinemia, in a patient with juvenile SLE should raise the suspicion of macrophage activation syndrome. We propose preliminary guidelines for this syndrome in juvenile SLE to facilitate timely diagnosis and correct classification of patients.

Hypertension favors the inflammatory process in rats with experimentally induced periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison between laser therapy and non-surgical therapy for periodontitis in rats treated with dexamethasone

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Radiographic assessment of photodynamic therapy as an adjunctive treatment on induced periodontitis in immunosuppressed rats

Objective: The aim of this study was to assess radiographically the effect of photodynamic therapy (PDT) as an adjunctive treatment to scaling and root planing (SRP) on induced periodontitis in dexamethasone-induced immunosuppressed rats. Material and Methods: The animals were divided into 2 groups: ND group (n=60): saline treatment; D group (n=60): dexamethasone treatment. In both ND and D groups, periodontal disease was induced by the placement of a ligature in the left first mandibular molar. After 7 days, ligature was removed and all animals received SRP, being divided according to the following treatments: SRP: saline and PDT: phenothiazinium dye (TBO) plus laser irradiation. Ten animals per treatment were killed at 7, 15 and 30 days. The distance between the cementoenamel junction and the height of the alveolar bone crest in the mesial surface of the mandibular left first molars was determined in millimeters in each radiograph. The radiographic values were analyzed statistically by ANOVA and Tukey's test at a p value <0.05. Results: Intragroup radiographic assessment (ND and D groups) showed that there was statistically significant less bone loss in the animals treated with PDT in all experimental periods compared to those submitted to SRP. Intergroup radiographic analysis (ND and D groups) demonstrated that there was greater bone loss in the ND group treated with SRP compared to the D group treated with PDT at 7 and 30 days. Conclusion: PDT was an effective adjunctive treatment to SRP on induced periodontitis in dexamethasone-induced immunosuppressed rats.

Histometric analysis of ligature-induced periodontitis in rats: a comparison of histological section planes

The purpose of this study was to analyze the histometry of ligature-induced periodontitis in rats at different histological section depths. Sixteen male adult Wistar rats were randomly assigned to two groups: ligature and control. In the ligature group, rats received a sterile 4/0 silk ligature around the maxillary right 2nd molar. Thirty serial sections containing the 1st and 2nd molars, in which the coronal and root pulp, cementoenamel junction (CEJ) in the mesial side of the 2nd molar, interproximal alveolar bone and connective fiber attachment were clearly visible, were selected for histometric analysis. The histological sections were clustered in groups of 10 sections corresponding the buccal (B), central (C) and lingual (L) regions of the of periodontal tissue samples. The distance between the CEJ in the mesial side of the 2nd molar and the attached periodontal ligament fibers (CEJ-PL) as well as the distance between the CEJ and the alveolar bone crest (CEJ-BC) were determined. From CEJ-PL and CEJ-BC distances measured for each specimen, the measurements obtained in the B, L and C regions were recorded individually and together. Data were submitted to statistical analysis. Significant differences (p<0.001) were observed between the control and ligature groups regarding CEJ-PL (0.05 mm and 0.26 mm, respectively) and CEJ-BC (0.47 mm and 0.77 mm, respectively) measurements. Regarding the depth of the buccal, central and lingual planes, the means of CEJ-PL and CEJ-BC of both groups showed no statistically significant differences (p>0.05). In conclusion, the selection of 10 serial sections of the central region of periodontal tissue samples at any depth can be considered as representative for the evaluation of periodontal ligament fiber attachment and bone loss in ligature-induced periodontitis in rats.

Effects of two chronic stress models on ligature-induced periodontitis in Wistar rats

Objectives: The present study aims at comparing the effects of physical and variable chronic stress on ligature-induced periodontitis in rats.Design: Forty-eight adult Wistar rats were randomly assigned to four groups (n = 12): physical stress, variable stress, positive control and negative control. The models of physical stress were immobilization and immobilization associated with exposure to cold. The models of variable stress were exposure to intermittent light, 24 h isolation, oral cavity examination, crowded environment, smell of blood and noise. After 10 days of physical or variable stress animals underwent experimental induction of periodontal disease in one oral side. Positive control also underwent experimental induction of periodontal disease on the 10th day. Negative control did not receive any type of intervention. At the end of the experimental period (60 days), all animals were euthanized. After routine laboratory processing, images of the histological sections were digitised and submitted to histometric measurement using two parameters: histologic attachment loss and bone loss.Results: Histological attachment loss and bone loss were greater (p < 0.05) in the physical stress group than in the other groups (variable stress, positive and negative control groups). on the non-periodontitis side, these same histological parameters did not significantly differ amongst groups.Conclusions: Physical stress negatively modulated the response pattern to experimentally induced periodontitis in rats. (C) 2011 Elsevier Ltd. All rights reserved.

A combination of clinical and microbiological management of generalized aggressive periodontitis in primary teeth. A case report

International Journal of Paediatric Dentistry 2012; 22: 310316 Background. Generalized aggressive periodontitis (GAP) in primary teeth is a rare periodontal disease that occurs during or soon after eruption of the primary teeth. An association with systemic diseases is a possibility. Case Report. A 4-year-old Brazilian girl presented with GAP involving the entire primary dentition. The patient and her parents and sister were subjected to microbiological testing to identify the microorganisms involved in the disease. The patient underwent tooth extraction to eradicate the disease and received a prosthesis for the restoration of masticatory function. After the permanent teeth erupted, fixed orthodontic appliances were place to restore dental arch form and occlusion. Conclusions. The results show the importance of an early diagnosis of GAP and of a multidisciplinary approach involving laboratory and clinical management to treat the disease and to restore masticatory function, providing a better quality of life for patients.

Antimicrobial potential of medicaments used in healing process in dogs' teeth with apical periodontitis

Estudou-se a influência de diferentes irrigantes no potencial antimicrobiano da pasta de hidróxido de cálcio em dentes de cães com periodontite apical. 48 pré-molares de cães adultos tiveram suas câmaras coronárias abertas e expostas à cavidade bucal por 6 meses. Os canais radiculares foram preparados, irrigados e medicados com diferentes substâncias, de acordo com os seguintes grupos: 1) 2,5% NaOCl + CHP; 2) 2% CHX + CHP; 3) vinagre + CHP; 4) vinagre + vinagre. No grupo 4, a solução irrigante e a medicação intracanal utilizada foi o vinagre. Neste grupo, a cada 7 dias, a solução era renovada. Cada amostra foi coletada, mantendo-se o cone de papel esterilizado em posição por 1 min, e a seguir transportado e imerso em 7 mL de Letheen broth, seguido de incubação a 37ºC por 48 h. O crescimento microbiano foi analisado por dois métodos, turbidade do meio de cultura e subcultura em meio nutritivo específico (brain heart infusion). Os resultados mostraram que em todos os grupos experimentais houve crescimento microbiano após 21 dias, em diferentes percentagens: grupo 1 - 30%; grupo 2 - 30%; grupo 3 - 40%; grupo 4 - 60%. Todos os materiais testados apresentaram potencial antimicrobiano. Entretanto, o processo de cura favorecido pela pasta de hidróxido de cálcio não pode ser esquecido, uma vez que muitos estudos já demonstraram sua ação antimicrobiana.

Occurrence of yeasts, enterococci and other enteric bacteria in subgingival biofilm of HIV-positive patients with chronic gingivitis and necrotizing periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Distribution of biotypes and leukotoxic activity of Aggregatibacter actinomycetemcomitans isolated from Brazilian patients with chronic periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of interferon-gamma, interferon-alpha and related genes in individuals with Down syndrome and periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of the Interleukin-10 Signaling Pathway Genes in Individuals With Down Syndrome and Periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of cyclosporin A on alveolar bone homeostasis in a rat periodontitis model

Objectives: the administration of cyclosporin A has been associated with significant bone loss and increased bone remodeling. The present investigation was designed to evaluate the effects of cyclosporin A on alveolar bone of rats subjected to experimental periodontitis, using serum, stereometric and radiographic analysis.Methods: Twenty-four rats were divided into one of the following groups with six animals each: group I, control rats; group II, in which the animals received a cotton ligature around the lower first molars; group III, in which the rats received a cotton ligature around the lower first molars and were treated with 10 mg/(kg body weight day) of cyclosporin A; group IV, in which the rats were treated with 10 mg/(kg body weight day) of cyclosporin A. At the end of experimental period, at 30 days, animals were killed and the serum calcium and alkaline phosphatase levels were measured in all groups. The distance from the alveolar bone crest to the cemento-enamel junction was measured radiographically for each mesial surface of the lower first molars of each rat. After histological processing, the stereological parameters: volume densities of multinucleated osteoclasts (V-o), alveolar bone (V-b), marrow (V-m), and relation of eroded surface/bone surface (Es/Bs) were assessed at the mesial region of the alveolar bone.Results: Significant decreases in serum calcium were observed in those groups that received cyclosporin A therapy. No significant changes in serum alkaline phosphatase were observed. The therapy with cyclosporin A combined with the ligature placement decreased the V-b and increased the V-o, V-m and Es/Bs at the mesial surface of lower first molars. on the other hand, the radiographic data showed that cyclosporin A therapy diminished the alveolar bone loss at the mesial surface of the lower first molars.Conclusions: Therefore, within the limits of this study, we suggest that cyclosporin A at immunosuppressive levels can bring about an imbalance in the alveolar bone homeostasis in rats. However, in the presence of inflammatory stimulation, the inhibition of the immune system by cyclosporin A may decrease the initial periodontal breakdown.