Avaliação do efeito anti-inflamatório dos fármacos: atorvastatin, carvedilol, olmesartan e telmisartan, em modelo experimental da doença periodontal induzida em ratos

A periodontite é uma doença crônica inflamatória mediada por marcadores inflamatórios, tais como as citocinas: IL-1β, IL-10 e TNF-α, que provoca a destruição dos tecidos gengivais e osso alveolar, causando perda de inserção dentária e posterior perda dental. A perda óssea é causada pela ativação de prostaglandinas oriundas do ácido araquidônico, através da ação da enzima ciclooxigenase 2 (COX-2), promovendo a liberação de enzimas proteolíticas, as metaloproteinases de matriz, principalmente a MMP-2 e MMP-9, que promovem reabsorção óssea. Além disso, ocorre o desequilíbrio entre a ação de RANKL e OPG, havendo uma maior ativação de RANKL, e por consequência a maior ativação de osteoclastos e maior reabsorção óssea. Mediadores inflamatórios e espécies reativas de oxigênio (ROS) produzidos localmente possuem potencial para disseminar na corrente sanguínea e iniciar ou exacerbar doenças sistêmicas como as cardiovasculares. O tratamento atual da doença consiste em terapêutica local, mas a necessidade de estudos sobre fármacos de atuação sistêmica culminou nesta pesquisa, que realizou a avaliação dos fármacos: atorvastatin, carvedilol, olmesartan e telmisartan, quanto a sua ação anti-inflamatória sobre a doença periodontal induzida por ligadura em ratos Wistar. Os animais foram divididos em 5 grupos, para cada fármaco, separadamente: (NL) grupo não ligado, (L) grupo ligado sem tratamento, (1mg/Kg) grupo ligado que recebeu dose de 1mg/Kg de fármaco, (5 ou 6 mg/Kg) grupo ligado que recebeu dose de 5 ou 6 mg/Kg de fármaco, (10 mg/Kg) grupo ligado que recebeu dose de 10mg/Kg de fármaco. Foram realizadas avaliações: histopatológica, perda óssea alveolar, imuno-histoquímica (para COX-2, MMP-2, MMP-9, RANK-L, RANK e OPG), e ELISA (para mieloperoxidase, glutationa, malonaldeído e as citocinas: IL-1β, IL-10 e TNF-α). Os grupos tratados com olmesartana a 6 mg/Kg, e atorvastatin, carvedilol e telmisartan a 10mg/Kg, mostraram diminuição da perda óssea, redução de: MPO, MDA, IL-1β, TNF-α, MMP-2, MMP-9, COX-2, RANKL/RANK, e aumento na expressão da OPG e da IL-10.

Consanguinidade e efeito fundador da mutação G377S da doença de Gaucher em população de Tabuleiro do Norte – Ceará – Brasil

Gaucher’s disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n=5), carrier (n=20) and non-carrier (n=111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation

Indicadores e fatores preditivos de uso abusivo de álcool em adultos jovens

The abusive use of alcohol is closely related to dependence and to social and work damages. The main focus of this thesis is to create an instrument about alcohol abuse, in order to differentiate the degree of commitment of the symptomatology, considering its psychosocial factors of prediction. As specific goals: I) characterize the state of the art about assessment related to the abuse and dependence to alcohol; II) investigate and systematize aspects related to the predictive psychosocial factors for alcohol dependence; III) build an instrument for the assessment of alcohol abuse and protection and risk factors for the development of an alcohol dependence; and IV) verify validity evidence of the instrument built for the Brazilian population. In Study I, it was possible to observe the prevalence of articles related to the use of alcohol in a problematic way, without a classification dependence, it is lower than the one of articles that investigate the disease when it is already manifested, not to mention a few systematic studies about the theme of alcohol abuse in the scientific environment. In Study II, focus groups (FGs) were conducted, the analysis about the discourses of the focus groups were made through the ALCESTE software and it was possible to observe a response pattern that existed among the participants in different groups, with the generation of five classes. In Study III, we developed an instrument that contemplated aspects of the Alcohol Dependence Syndrome of the Millon Clinical Multiaxial Inventory-III, in addition to the characteristics defined in Study I and in Study II. The final version of the instrument had 59 items assessed through the likert scale of five points. In Study IV, the administration of the instrument was performed in an online format with university students ranging from 18 to 24 years old, residents in Brazilian metropolitan cities. The results evidenced that the internal consistency of the instrument is considered satisfactory (α = 0,882) and in what it refers to classes, the most significant data was the one related to financial loss and criteria for the diagnosis of alcohol abuse. It is important to consider the evaluative potential of risk and protective factors for the development of alcohol dependence of the instrument as a whole. Once the indicators of abuse and the profile of the abusers has been modified, the patient may have his/her treatment/intervention focused on the trouble and/or specific syndrome, thus having a clear and fast improvement.

Conhecimento da doença renal crônica entre médicos conforme as diretrizes práticas

INTRODUCTION: Chronic kidney disease (CKD) is a global health problem, with increasing prevalence in its terminal stage and one of the factors that can contribute is the failure to recognize the disease and its risk factors. OBJECTIVE: To evaluate the knowledge of medical residents (MR) and medical preceptors (MP) in hospitals in the Federal University of Rio Grande do Norte in Natal-RN - Brazil, on the DRC, based on the policy of the Kidney Disease Improving Global Outcomes (KDIGO ). METHODS: Cross-sectional study where 64 MR (R1 = 32; R2 = 15; R3 = 17) and 63 MP answered a questionnaire divided into seven sessions that addressed aspects of the DRC since the setting up referral to a nephrologist. RESULTS: Only 20 participants (15.7%) reported using any guidelines for the management of CKD. The scores obtained by session were: Definition and classification (46.1 ± 47.8); Risk factors (70.5 ± 27.9); Laboratory evaluation (58.2 ± 8.8); Clinical action plan (57.6 ± 19.9); Reduction in proteinuria (68.3 ± 15.0); Complications (64.8 ± 19.9); Referral to a nephrologist (73.0 ± 44.6). There was a statistically significant difference between the knowledge of MR and MP in the sessions: Laboratory evaluation (MR 61.5 ± 8.4 vs 54.8 ± 7.9 MP; p <0.001); Reduction in proteinuria (73.1 ± 11.4 vs MR MP 63.5 ± 16.7; p <0.001) and Referral to a nephrologist (MR 81.2 ± 39.3 vs 64.5 ± 48.2 MP; p = 0.035). Among the MR, the R2 obtained the best score (63.9 ± 22.6 vs R1 R2 R3 71.9 ± 17.2 vs 63.5 ± 22.5, p = 0.445). It identified a low percentage of success of the doctors on the definition of CKD (MP = 46%; R1 = 40.6%; R2 = 60%; R3 = 52.9%; p = 0.623) and classification (MP = 34.9%; R1 = 53.1%, R2 = 60%; R3 = 52.9%; p = 0.158). CONCLUSION: The study showed that most doctors do not use any guidelines for clinical management of CKD and that there are gaps in knowledge on the subject, even among physicians who work in the university environment. In this sense, we propose the realization of mini-workshops for participants and students from boarding UFRN, using Case-Based Learning Strategy (CBL), with small group discussion, to strengthen the incorporation of CKD guidelines in undergraduate teaching and in clinical medical practice in general.