The impact of endogenous annexin A1 on glucocorticoid control of in ammatory arthritis

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

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb.

Heparin, heparin plus ASA and dipyridamole, and arteriovenous fistula as adjuvant methods to prevent rethrombosis after venous thrombectomy. Experimental study in rabbits

Venous rethrombosis following thrombectomy is a common event. The aim of the present study was to verify the action of heparin, heparin plus acetyl salicylic acid (ASA) and dipyridamole, and of an arteriovenous fistula (AVF) in the prevention of this complication. Thrombosis was induced in 48 male rabbits by the injection of thrombin in a segment of the left jugular vein, in which the blood flow was arrested for 10 minutes. After 48 hours, the animals were randomly allocated into one of 4 groups of treatment: (1) control, (2) subcutaneous heparin (600 S.I. Units/kg - 8/8 hours), (3) heparin, in the same dose, plus ASA (10 mg/kg/once a day), and dipyridamole (0.5 mg/kg thrice a day), (4) an AVF was surgically constructed between the left carotid after and the left maxillar vein. After 30 minutes, thrombectomy was performed. The venous blood flow, the hematocrit, activated partial thromboplastin time and thrombin time tests were performed before, right after the thrombectomy and 48 hours after thrombectomy. Venography was performed after thrombectomy and at the end of the experiment. The animals were killed 48 hours after thrombectomy and the veins were examined macroscopically. Venous rethrombosis was significantly prevented only in the AVF group (9/12), when compared to control group (0/12), heparin group (1/12) and heparin plus antiaggregating agents group (2/12). These results validate further clinical and experimental investigations with the use of AVF to prevent rethrombosis after venous thrombectomy, when a reduction of venous flow is present.

Deposition and leaching of tebuthiuron on sugar cane straw applied with and without alkyl polyglycoside adjuvant

A laboratory experiment was carried out aiming to study the effects of an alkyl polyglycoside adjuvant (APG) on deposition and leaching of the herbicide tebuthiuron applied on sugar cane straw. Tebuthiuron, at concentration of 1200 mg L-1, was applied separately and in tank mix with the APG adjuvant, at concentrations of 0.07 and 0.09% (wt v-1), using a spraying volume of 204 L ha-1. A precipitation equivalent to 20 mm of rain was simulated, 24 h after the applications, to evaluate the herbicide leaching. The quantification of tebuthiuron was carried out by the high performance liquid chromatography (HPLC). It was observed that the addition of APG adjuvant at 0.07% (wt v-1) provided an increase of 11.5% in the deposition of tebuthiuron on straw, reduction of 50.4% in the drift of the herbicide and it did not affect significantly the leached amount (68.5%), when compared with the treatment where tebuthiuron was applied alone (70.8%). At the concentration of 0.09% (wt v-1), the APG adjuvant caused an increase of 22.7% in the deposition; it reduced the drift of the herbicide by 99.9% and reduced the leached amount by 7.6% thereby increasing the retention of the herbicide by straw.

Periodontal condition in patients with rheumatoid arthritis

The purpose of this clinical study was to investigate if periodontal disease and rheumatoid arthritis (RA) are associated. The study included 39 RA patients (test group) and 22 age- and gender-matched healthy individuals (control group). Questionnaires on general and oral health were applied and a complete periodontal exam, including visible plaque, marginal bleeding, attachment loss (AL) and number of teeth present, was also performed by a single calibrated examiner. Diabetes mellitus patients and smokers were excluded. RA patients had fewer teeth, higher prevalence of sites presenting dental plaque and a higher frequency of sites with advanced attachment loss. Although the prevalence of dental plaque was higher in the test group (Chi-square test, p = 0.0006), the percentage of sites showing gingival bleeding was not different (Fisher's exact test, p > 0.05). Based on our results, we suggest that there is an association between periodontal disease and RA.

Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis

Objectives: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). Methods: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m2/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. Results: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. Conclusions: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer should be a good council for patients with hormone receptor-positive tumours and wish to preserve fertility

Infertility represents one of the main long-term consequences of combination chemotherapy used for the treatment of breast cancer. Approximately 60%-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ tumors with respect to recurrence-free survival and overall survival, Presentation of the hypothesis: It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. Testing the hypothesis: Assessment of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen. The recurrence-free survival and overall survival should be analysed. Implications of the hypothesis: The major implication will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

Uma análise clinimétrica dos índices articular extra-articular do Juvenile Arthritis Damage Index(JADI-A e JADI-E) na artrite isiopática juvenil

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

Equivalência métrica do Disease Activity Score (DAS 28) e Juvenile Arthritis Disease Activity Score (JADAS) na artrite idiopática juvenil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Freund's adjuvant-induced inflammation: clinical findings and its effect on hepcidin mRNA expression in horses

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

Validation of Relapse Risk Biomarkers for Routine Use in Patients With Juvenile Idiopathic Arthritis

Objective. The myeloid-related proteins 8 and 14 (MRP-8/MRP-14) and neutrophil-derived S100A12 are biomarkers of inflammation. They can be used to determine the relapse risk in patients with juvenile idiopathic arthritis (JIA) after stopping antiinflammatory treatment. In this study, we tested the performance of different enzyme-linked immunosorbent assays (ELISAs) in order to validate systems available for routine use.Methods. MRP-8/MRP-14 and S100A12 serum concentrations of 188 JIA patients in remission were analyzed. Commercially available test systems were compared to experimental ELISAs established in house. The ability of the assays to identify JIA patients at risk for relapse was analyzed.Results. For MRP-8/MRP-14, the PhiCal Calprotectin and Buhlmann MRP8/14 Calprotectin ELISAs revealed hazard ratios of 2.3 and 2.1, respectively. For S100A12, the CircuLex S100A12/EN-RAGE ELISA revealed a hazard ratio of 3.1. The commercial assays allowed a JIA relapse prediction that was at least comparable to the experimental ELISAs.Conclusion. For the prediction of JIA relapse after stopping medication, the biomarkers MRP-8/MRP-14 and S100A12 can be determined by using assays that are available for routine use. The tested commercial MRP-8/MRP-14 and S100A12 ELISAs showed a performance comparable to well-established experimental ELISA protocols when assay-specific cutoffs for the indication of relapse prediction are thoroughly applied.

Probability of remission of juvenile idiopathic arthritis following treatment with steroid joint injection

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)