Maria Carmen Lopes Ferreira Silva Santos

Nandrolone decanoate determines cardiac remodelling and injury by an imbalance in cardiac inflammatory cytokines and ACE activity, blunting of the Bezold-Jarisch reflex, resulting in the development of hypertension.

The aims of this study were to evaluate the effects of nandrolone (ND) on cardiac inflammatory cytokines, ACE activity, troponin I, and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were administered either ND (20 mg/kg; DECA) or vehicle (control animals; CONT) for 4 weeks. BJR was analyzed by measuring the bradycardia and hypotension responses elicited by serotonin administration (2-32 μg/kg). Mean arterial pressure (MAP) was assessed and myocyte hypertrophy was determined by the heart weight/body weight ratio and by morphometric analysis. Matrix collagen deposition was assessed by histological analysis of the picrosirius red-stained samples. Mesenteric vascular reactivity was performed and central venous pressure (CVP) evaluated. Cardiac inflammatory cytokine levels and angiotensin-converting enzyme (ACE) activity were studied as well the biomarker of cardiac lesion, troponin I. DECA group showed enhancement of matrix type I collagen deposition (p < 0.01) and cardiac ACE activity (p < 0.01) compared with the CONT. Interleukin (IL)-10 was reduced (p < 0.01) and pro-inflammatory cytokines (TNF-α and IL-6; p < 0.01) were increased in the DECA group compared with CONT. Cardiac injury was observed in the DECA group shown by the reduction in cardiac troponin I (p < 0.01) compared with the CONT group. Animals in the DECA group also developed myocyte hypertrophy and reduction of BJR sensitivity. The MAP of animals treated with ND reached hypertensive levels (p < 0.01; compared with CONT). No changes in CVP and vascular reactivity were observed in both experimental groups. We conclude that high doses of ND elicit cardiotoxic effects with cardiac remodelling and injury. Cardiac changes reduce the BJR sensitivity. Together, these abnormalities contributed to the development of hypertension in animals in the DECA group.

Long-term treatment with supraphysiological doses of nandrolone decanoate reduces the sensitivity of Bezold-Jarisch reflex control of heart rate and blood pressure.

We investigated the influence of long-term treatment with supraphysiological doses of an anabolic-androgenic steroid on the Bezold-Jarisch reflex (BJR) control of heart rate (HR) and diastolic arterial pressure (DAP), and whether this treatment induced cardiac hypertrophy. Male rats were treated with nandrolone decanoate (ND) (10 mg kg(-1) body weight for 8 weeks; DECA) or vehicle (control animals; CON). After 8 weeks of treatment, the BJR was evaluated by bradycardia and hypotension responses that were elicited by serotonin administration (2-32 microg kg(-1)). Mean arterial pressure (MAP) was assessed and cardiac hypertrophy was determined by the ratio of the left and right ventricle weight/body weight (LVW/BW and RVW/BW, respectively) and by histological analysis. Total body protein (TBP) content was also evaluated. Nandrolone decanoate treatment increased MAP (CON=99+/- 1 mmHg; DECA=109+/-2 mmHg; p<0.01) but did not change the mean basal HR (CON=356+/-13 bpm; DECA=367+/-11 bpm). The treatment also induced LV and RV hypertrophy (LVW/BW: CON=1.86+/-0.04 mg g(-1), DECA=2.17+/-0.04 mg g(-1), p<0.01; RVW/BW: CON=0.42+/-0.02 mg g(-1), DECA=0.53+/-0.03 mg g(-1), p<0.05) and reduced the number of myocyte nuclei/high-power field (CON=23.0+/-2; DECA=9.4+/-1.0; p<0.01). ND treatment blunted the HR and DAP decreases induced by serotonin. ND determines an increase in the TBP content in DECA group (35+/-3%; p<0.01) compared with control animals (18+/-1%). We conclude that 8 weeks of ND treatment induces anabolic effect, cardiac hypertrophy and an elevation of MAP. This treatment also reduces the sensitivity of the BJR control of bradycardia and blood pressure, possibly due to cardiac hypertrophy. The blunted BJR response could contribute to the MAP elevation in DECA animals.

Antiproliferative and apoptotic potencies of glucocorticoids: nonconcordance with their antiinflammatory and immunossuppressive properties

Relative antiinflammatory and immunosuppressive potencies of glucocorticoids (GC) were previously well defined. Nonetheless, GC also regulate cell proliferation and programmed death (apoptosis). The aim of this study was to determine the relative potency of different GC on the modulation of cell survival. The GC-sensitive lymphoblast cell line CEM-c7/14 was submitted to 48 h-exposure to GC (dose-response curve from 10(-8) to 10(-5) M). Cell survival was analyzed employing the DimethylTiazol-Tetrazolium (MTT) test. For each GC at least 4 experiments were performed in quadruplicate. Responses to different GC at the same molarity were analyzed by ANOVA on Ranks. Cell responses to the same GC in different concentrations were tested by repeated measures ANOVA. The EC50 for each GC was calculated with the GraphPad Prism 3.0 software. The use of low concentrations (10(-8) and 10(-7) M) of hydrocortisone and methylprednisolone determined a similar effects on cell survival, which was less prominent than that observed with betamethasone, budesonide or momethasone. Momethasone was the most potent GC, inducing the most intense dexamethasone reduction on cell survival at the lowest concentration (10(-8) M). Momethasone and methylprednisolone were the two GC with the strongest impact on cell survival. Our findings suggest that antiproliferative and apoptotic potencies of GC are different from those previously reported antiinflammatory and immunosuppressive actions.

Disseminated cerebral thrombotic microangiopathy in a patient with adult's Still disease

OBJECTIVE The aim of this report is to describe a fatal disseminated thrombotic micoangiopathy with renal, pancreatic, and cerebral involvement in a patient with recently diagnosed adults Still disease (ASD). CASE REPORT A previously healthy 15 year old girl was admitted to our hospital. According to the clinical and laboratory data the diagnosis of adults still Disease was established. The treatment was begun and few days after an initial improvement a sudden neurologic deterioration with coma and seizures has occurred. Hours later the patient died. Clinical, laboratorial, and pathologic data will be presented. CONCLUSION To our knowledge this is the second description of a fatal disseminated cerebral thrombotic microangiopathy in a patient with adults Still disease, but with a much more fulminating evolution than previously reported. Some etiopathogenic mechanisms could be shared in these two disorders explaining this coexistence.

Recomendações para o tratamento da síndrome de Sjögren

The recommendations proposed by the Sjögrens Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjögrens syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 items classified according to Oxford & Grade were included. These recommendations were developed in order to guide the appropriate management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country.

Artigo originalValidação e propriedades psicométricas do Eular Sjögren's Syndrome Patient Reported Index (ESSPRI) para a língua portuguesaValidation and psychometric properties of the Eular Sjögren's Syndrome Patient Reported Index (ESSPRI) into Brazilian Portuguese☆

OBJECTIVE To carry out the cross-cultural adaptation of Eular Sjögrens Syndrome Patient Reported Index (ESSPRI) for Portuguese language and evaluate its psychometric properties. METHOD Cross-sectional study of patients with primary Sjögrens syndrome (SS). The psychometric properties (intraobserver reproducibility and construct validity) were studied. In construct validity, ESSPRI was compared with the Patients Global Assessment (PGA), Profile of Fatigue and Discomfort (Profad), Sicca Symptoms Inventory (SSI) and Functional Assessment of Chronic Illness Therapy (Facit-F). Statistical tests used were:Cronbachs alpha, intraclass correlation coefficient (ICC), Bland-Altman method and Spearman coefficient. A value of p ≤ 0.05 was considered significant. RESULTS There was no difference between versions in both languages; thus, a Brazilian consensual version was obtained. All subjects were women aged 49.4 ± 11.6 years, with onset of symptoms of 7.2 ± 5.4 years, and time of diagnosis of 3.0 ± 3.3 years. The mean ESSPRI was 6.87 ± 1.97. The intraobserver reproducibility was high and significant (0.911) and, with Bland-Altman method, there was no systematic bias in the agreement of measures among evaluations. A moderate correlation of ESSPRI with all tested instruments was observed. CONCLUSION The Brazilian Portuguese version of ESSPRI is a valid and reproducible version.

Validação e propriedades psicométricas do Eular Sjögren's Syndrome Patient Reported Index (ESSPRI) para a língua portuguesa

OBJECTIVE To carry out the cross-cultural adaptation of Eular Sjögrens Syndrome Patient Reported Index (ESSPRI) for Portuguese language and evaluate its psychometric properties. METHOD Cross-sectional study of patients with primary Sjögrens syndrome (SS). The psychometric properties (intraobserver reproducibility and construct validity) were studied. In construct validity, ESSPRI was compared with the Patients Global Assessment (PGA), Profile of Fatigue and Discomfort (Profad), Sicca Symptoms Inventory (SSI) and Functional Assessment of Chronic Illness Therapy (Facit-F). Statistical tests used were:Cronbachs alpha, intraclass correlation coefficient (ICC), Bland-Altman method and Spearman coefficient. A value of p ≤ 0.05 was considered significant. RESULTS There was no difference between versions in both languages; thus, a Brazilian consensual version was obtained. All subjects were women aged 49.4 ± 11.6 years, with onset of symptoms of 7.2 ± 5.4 years, and time of diagnosis of 3.0 ± 3.3 years. The mean ESSPRI was 6.87 ± 1.97. The intraobserver reproducibility was high and significant (0.911) and, with Bland-Altman method, there was no systematic bias in the agreement of measures among evaluations. A moderate correlation of ESSPRI with all tested instruments was observed. CONCLUSION The Brazilian Portuguese version of ESSPRI is a valid and reproducible version.

Correlação entre níveis de iodo na urina e alterações anatomopatológicas em tireoide

OBJECTIVES To determine iodine nutrition in the population and to correlate levels of iodine found in random samples of urine with pathological changes observed in thyroids collected in this population. MATERIALS AND METHODS Urinary iodine was determined in 30 random samples of urine and the pathological study was carried out in 55 thyroid glands from corpses received by the Department of Forensic Medicine of Vitória, Espírito Santo, Brazil from May to August 2011. RESULTS In 29 urine samples (96.7%) urinary iodine was above the maximum limit recommended by the World Health Organization (WHO), of 300 mg/L. Fourteen thyroids (25.5%) showed the presence of histological changes compatible with thyroiditis. Higher levels of iodine in urine were observed in females and in of thyroid that showed inflammation (thyroiditis). CONCLUSIONS We conclude that, in this population, there is excess iodine intake, and greater incidence of inflammatory thyroid disease.

Apudomas pancreáticos: um desafio para clínicos e cirurgiões

OBJETIVO: O proposito do presente estudo e analisar as dificuldades quanto ao diagnostico, avaliacao prognostica e conduta em sete pacientes portadores de tumores neuroendocrinos do pâncreas (apudomas), estudados na ultima decada, comparando os resultados com aqueles discutidos na literatura. METODO: A idade dos pacientes variou de 15 a 66 anos, com media de 38,4 anos. Todos foram submetidos a alguma forma de resseccao pancreatica por tumores neuroendocrinos. Os exames histologicos foram feitos pelas tecnicas tradicionais e por imuno-histoquimica. RESULTADOS: Tres pacientes tiveram um diagnostico inespecifico de tumor neuroendocrino; dois de vipoma e dois de gastrinoma. As sindromes nao se manifestaram claramente, ainda que cada caso tenha tido um rotulo diagnostico. Os exames por imuno-histoquimica demonstraram a presenca de multiplos hormonios, mas por falta de sintomas clinicos, as correlacoes ficaram prejudicadas na maioria dos casos, havendo correlacao somente em caso de gastrinoma. Um paciente faleceu no pos-operatorio; um sobreviveu sete anos e cinco estao vivos, com sobrevida variando entre tres e cinco anos. CONCLUSOES: Nao houve uma manifestacao sindromica evidente, porem a sobrevida dos pacientes tem sido compativel com os dados de literatura.

AB0533 Recommendations of Brazilian Society of Rheumatology for the Treatment of SjÖGren's Syndrome

Objectives Recommendations of Brazilian Society of Rheumatology for the treatment of Sjögrens syndrome (SS) were developed to guide management of SS considering the Brazilian social and economic context. Methods It was based on specialists opinion and systematic review on MEDLINE (PubMed) and Cochrane database until October 2014, including 127 articles classified according Oxford & Grade. Results Forty-four recommendations were organized in 3 main topics: Part 1. General recommendations and patient education: The management of SS should be conducted by multidisciplinary team. Systemic treatment should be according disease severity measured by EULAR Sjögrens Syndrome Disease Activity (ESSDAI). Patients should avoid caffeine, tobacco, alcohol, toothpaste with abrasive, and mouthrinses with alcohol. Patient should be educated about preventive measures for oral health and hydration. Aerobic exercise improves fatigue and quality of life. Immunization to influenza and pneumococo are indicated. Serum levels of vitamin D should be evaluated and supplemented if it is necessary. Part 2. Symptomatic treatment of dryness: Topical treatment for dry mouth includes saliva substitutes, sugar-free candies and gums. Topical treatments for dry eye are lubricants (glucanes or carboximethylcelulose), cyclosporine 0.05%, and punctual occlusion. Topical glucocorticoids may be used for severe dry eye for short time avoiding complications. Pilocarpine and cevimeline should be used for dry mouth and for severe dry eye. N-acetylcysteine may be used for dryness symptoms, including patients showing intolerance for muscarinic agonists. Omega-3 supplementation may be used to dry eye. Part 3. Systemic treatment: Immunosupressant and/or biological therapy are not indicated to dryness treatment. Hydroxichloroquine, glucocorticoid, and immunossupressants (azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine) should be indicated according severity of systemic involvement. Rituximab is indicated to treat systemic manifestations without improvement with immunosuppressive therapy. Abatacept and belimumab may be considered in patients not responding to rituximab and with high level of disease activity. Acknowledgements Sociedade Brasileira de Reumatologia (SBR) Disclosure of Interest None declared