Análise comparativa da imunoexpressão das proteínas hmlh1 e hmsh2 em carcinomas epidermóides de lábio inferior e queilites actínicas com graus variados de displasia

Lip squamous cell carcinoma (SCC) may develop from a premalignant condition, actinic cheilitis (AC) in 95% of the cases. Both premalignant and neoplastic lip diseases are caused mainly by chronic exposure to the ultraviolet component of solar radiation, especially UVB. This exposure causes disruption of the cell cycle and damage to DNA repair systems, like mismatch repair, altering proteins repair as hMLH1 and hMSH2. This research aimed to investigate the immunohistochemical expression of hMLH1 and hMSH2 proteins in lower lip SCCs and ACs, providing additional information about carcinogenesis of the lower lip. The sample consisted 40 cases of ACs and 40 cases of lower lip SCCs. Histological sections of 3 μm were submitted to immunoperoxidase method, for immunohistochemical analysis of lesions were counted in 1000 cells (positive and negative), data were evaluated both in absolute numbers and percentage of immunostained cells, the latter by assigning scores. Associations of the variables and comparative analysis of biomarker expression were performed by Fisher s exact and Pearson s chi-square, "t" student, one-way ANOVA, Mann- Whitney e Kruskal-Wallis tests. The level of significance was 5%. It was found that, in lower lip SCC, the mean of the proteins was higher in female patients (hMLH1= 369,80 + 223,98; hMHS2 = 534,80 + 343,62), less than 50 years old (hMLH1 = 285,50 + 190,65; hMHS2 = 540,00 + 274,79) and classified as low-grade malignancy (hMLH1 = 264,59 + 179,21; hMHS2 = 519,32 + 302,58), in these data only to sex, for hMLH1 protein, was statistically significant (p=0.034). Comparing the different lesions, we observed that for both hMLH1 and hMSH2 protein, the average of positive epithelial cells decreased as the lesion was graded at later stages. The ACs classified without dysplasia or mild dysplasia had the highest average of immunostained cells (hMLH1 = 721.23 + 88.116; hMHS2 = 781.50 + 156.93). The ACs classified as moderate or severe dysplasia had intermediate values (hMLH1 = 532,86 + 197,72; hMHS2 = 611,14 + 172,48) and SSCs of the lower lip had the lowest averages (hMLH1 = 255,03 + 199,47; hMHS2 = 518,38 + 265,68). There was a statistically significant difference between groups (p<0.001). In conclusion, our data support the hypothesis that changes in immunoexpression of these proteins is related to the process of carcinogenesis of the lower lip

Expressão Imuno-histoquímica das proteínas GLUT-1 e HIF-1α em lesões vasculares de mucosa oral

The correct histological diagnosis of vascular lesions in the oral mucosa is critical, especially in defining the treatment and prognosis, as some vascular lesions show spontaneous involution and others do not show such behavior. This study analyzed the expression immunohistochemistry of human glucose transporter protein (GLUT-1), in oral benign vascular tumors and to reclassify such lesions according to with his immunoexpression. In addition, we evaluated the immunohistochemical expression of hypoxia-inducible factor 1 alpha (HIF-1α), the main transcription factor involved in cellular adaptation to hypoxia. We analyzed 60 cases of benign oral vascular tumors: 30 cases with histological diagnosis of HEM and 30 cases of oral pyogenic granuloma (PG). The results of this research showed that of the 30 lesions initially classified as HEM, only 7 showed immuno-positivity for GLUT-1, remaining with the initial diagnosis. The remaining 23 were reclassified as vascular malformation (VM) (13 cases) and PG (10 cases). All cases in the sample with an initial diagnosis of PG were negative for GLUT-1, demonstrating the accuracy of histological diagnosis of these lesions. Concerning to the immunoexpression of HIF-1α, the Mann-Whitney test revealed a statistically significant difference between the cases of GP and MV (p = 0.002), where the median of GP (m=78) was higher than the MV (m=53). Based on these results, this study showed that a histological diagnosis alone is not always sufficient for the correct diagnosis of oral HEM and that HIF-1α participates in the pathogenesis of vascular lesions

Análise imuno-histoquímica das proteínas VEGF e HIF-1α na doença periodontal

Periodontal disease is a complex inflammatory and infectious condition that immune host, front of the microbial aggressions, can lead to disease progression, resulting in tissue destruction. The tissue damage induces the release of regulatory molecules, which protective roles and / or destructive, including proteins VEGF (vascular endothelial growth factor vascular) and HIF-1 α (hypoxia-induced factor α -1). Thus, this study investigated, quantitatively and comparatively, the immunohistochemical expression of VEGF (vascular endothelial growth factor) and HIF-1 α (hypoxia induced factor 1-α), proteins involved in inflammation, angiogenesis and hypoxia, in human gingival tissues. Therefore, 75 samples of gingival tissues were examined. Thirty samples were chronic periodontitis, 30 with chronic gingivitis and 15 healthy gingival. After sections analysis, positives and negatives inflammatory and endothelial cells in the connective tissue were counted and converted into percentage. Data were statistically analyzed using Kruskal-Wallis test and Spearman correlation. The results showed that both proteins marked. It was observed higher immunoreactivity for HIF-1 α at chronic gingivitis and periodontitis specimens compared to healthy sites, however, no statistically significant differences were observed among them (p>0.05). The VEGF immunostaining showed similarity among the cases of periodontitis, gingivitis and healthy gingiva. Moderate and positive correlation statistically significant differences were verified for the expressions of VEGF and HIF-1α in gingival health (r = 0,529, p = 0.04). Thus, it can be conclude that possibly the route of HIF-1 α, is activated in periodontal disease may have involvement of the protein in pathogenesis and progression of disease, and that activation of VEGF, can be in addition to being triggered transcription by HIF-1 α may be also influenced by other additional factors such as the action of periodontal microorganisms endotoxins

Expressão imuno-histoquímica das proteínas IFN-γ e TGF-β1 em cistos radiculares e cistos dentígeros

Odontogenic cysts are pathologic cavities covered by odontogenic epithelium and filled by liquid, desquamated cells or other materials. The intraosseous lesions, such as radicular cyst and dentigerous cyst, present a potential of expansion capable of promoting the destruction of the surrounding osseous tissue. The mechanisms related to this process of expansion are the proliferation of cystic epithelium, the increase of the osmolarity of the cystic fluid and the synthesis of reabsorption factors such as IFN-γ and TGF-β1. The aim of this study was to evaluate and compare the immunohistochemical expression of IFN-γ and TGF-β1 between radicular cysts and dentigerous cysts in order to understand the role and behavior of these proteins in the expansion of these cysts. We selected 20 cases of radicular cyst and 20 cases of dentigerous cyst chosen from the files of UFRN s Laboratory of Oral Pathology. After analyzing the clinical data, the cases underwent the routine staining technique (HE) and immunohistochemistry for the appearance of IFN-γ and TGF-β1 in the epithelium and capsule of these cysts. The statistical analysis using the Mann-Whitney test revealed no statistically significant difference in immunoexpression of IFN-γ between the epithelium (p = 0.565) and capsules (p = 0.414) of radicular cysts and dentigerous cysts. Moreover, there was no statistically significant difference of immunoexpression of TGF-β1 between the epithelium (p = 0.620) and capsules (p = 0.056) of radicular cysts and dentigerous cysts. The Wilcoxon test revealed no statistically significant difference between IFN-γ and TGF-β1 imunoexpressions in the epithelium (p = 0.225) and capsules (p = 0.370) of radicular cysts. There was no statistically significant difference between IFN-γ and TGF-β1 imunoexpressions in the epithelium (p = 0.361) of dentigerous cysts. However, there was a statistically significant difference between IFN-γ and TGF-β1 immunoexpressions in the capsule (p = 0.001) of dentigerous cysts, being TGF-β1 the factor which presented the most significant immunoexpression. Given these results, we conclude that there was no difference in immunohistochemical expression of IFN-γ and TGF-β1 between radicular and dentigerous cysts and that TGF-β1 was more significant than the IFN-γ in the capsule of dentigerous cysts

Estudo da expressão imuno-histoquímica das proteínas MMP-9, MMP-13 e TIMP-1 em ameloblastomas e tumores odontogênicos ceratocistos

Ameloblastomas and keratocystic odontogenic tumors (KOT) represent odontogenic lesions that, despite their benign nature, are distinguished by a distinct biological behavior, characterized by locally aggressive growth and recurrent episodes. The gnathic bone resorption caused by the growth of these lesions is a key to the expansion of the same, both being mediated by osteoclastic cells like enzymatic activity of various matrix metalloproteinases (MMPs) factor. The expression of stimulatory factors and inhibitors of bone resorption has been correlated with the development of these lesions, with emphasis to some MMPs such as collagenases and gelatinases and tissue inhibitors of metalloproteinases (TIMPs), among others. Based on the premise that stimulatory and inhibitory factors of osteolytic processes can be decisive for the growth rate of intraosseous odontogenic lesions, this experiment evaluated the immunoreactivity of MMP-9, -13 and TIMP-1 protein in the epithelium and mesenchyme of ameloblastoma and the KOT specimens, by a quantitative analysis of the immunoreactivity cells. Statistical analysis was performed using the Mann-Whitney and Wilcoxon tests with a significance level set at 5 %. Immunohistochemical expression of MMP-9, -13 and TIMP-1 was observed in 100% of cases both in the epithelium and in mesenchyme. The immunoreactivity in the epithelium of KOT and ameloblastomas revealed a predominance of score 3 for MMP-9 (p=0.382) and MMP-13 (p=0.069) and no statistically significance for TIMP-1, the latter being significantly higher immunoreactivity in ameloblastomas. In the mesenchyme, there was a higher score immunoreactivity of MMP-13 (p=0.031) in ameloblastomas in relation to KOT, whereas for MMP-9 and TIMP-1 no statistically significant difference (p=0.403 was observed, p=1.000). The calculation of the ratio of scores revealed expression of proteins in general, similarity of the lesions, a significant predominance of equal expression of TIMP-1 and MMP-9 was observed only in the epithelium of ameloblastoma. The marked immunostaining of MMP-9 , MMP-13 and TIMP-1 in epithelium and mesenchyme of the lesion indicate that these proteins involved in ECM remodeling required for tumor progression, however, specific differences in the expression of some of these proteins, are not sufficient to suggest differences in the biological behavior of ameloblastomas and KOTs

Expressão imuno-histoquimica da cicloxigenase-2 e p53 em cancinoma epidermóide oral

Squamous cell carcinoma is the most common malignant neoplasm in the oral cavity, accounting for more than 90% of all malignancies in this location. Cyclooxygenases (COX s) are key enzymes on arachidonic acid metabolism and prostaglandin synthesis, being expressed basically in two forms: the constitutive (COX-1) and the inducible (COX-2). Increased levels on the expression of COX-2 have been implicated in the pathogenesis tumor progression of various forms of human cancer, including oral squamous cell carcinoma, some of what suggesting a possible interaction between COX-2 and the protein expressed by the tumor suppressor gene p53, mutated in more than 50% of all human cancers. The mean of the present research consisted in analyze the correlation between the expression of COX-2 and p53, at the protein level, as well as evaluate the difference on the expression of these two proteins with the histological grading of malignancy. 34 cases of oral squamous cell carcinoma were selected and graded according to the histological grading system proposed by Bryne (1998) and the labeling indexes (LI s) for COX-2 and p53 evaluated using immunohistochemistry method. The results revealed that COX-2 was expressed in increased levels in most of the specimens, although there was no statistic significant correlation between LI s from COX-2 and p53 (p>0.05), and there were no statistical differences on the expression of these proteins between tumors of high and low grade of malignancy (p>0.05). Interestingly, the expression of COX-2 and p53 was detected in fragments of dysplastic oral epithelium adjacent to tumor areas, on basal and suprabasal layers. The absence of statistical correlation between the expression of COX-2 and p53 proteins do not rule ot the existence of a relation between them, were it may reflect the diversity of regulatory pathways between both, different direct and indirect inhibitory effects of COX-2 over p53, as well as the wide range of activation macheenisms for COX-2 and mutational status of the p53 gene Another conclusion point that the increased expression of COX-2 observed in oral squamous cell carcinomas suggest a role for this protein in the processes of pathogenesis and tumoral evolution of this malignant neoplasm

Estudo clínico-patológico do carcinoma epidermóide de língua e imunoistoquímico das proteínas BMP-2, BMPR-IA, BMPR-II e endoglina

Bone morphogenetic proteins (BMPs) are cytokines involved in proliferation and angiogenesis of many kind of human cancer. The present study analyzed the immunohistochemical expression of BMP-2, BMPR-II, BMPR-IA and endoglin (CD105) and their relationship with the biological behavior and local angiogenesis in tongue oral squamous cells carcinoma (SCC). The sample consisted of 25 cases of tongue SCC without metastasis, 25 tongue SCC with metastasis and 25 cases of Inflamatory Fibrous Hyperplasia (IFH).The histological grade of malignancy proposed by Bryne (1998), adapted by Miranda (2002) was used to classify all tongue SCC cases. Score 0 was attributed to absent-weak immunoexpression and score 1 for strong immunostaning and pattern of distribution was focal or diffuse. Microvessel counts (MVC) was established for CD105. Most of the patients with tongue SCC was male. The principal age in tongue SCC without metastasis was over 65 years and in tongue SCC with metastasis was between 45-65 years. There were predominance of stage II in TNM and in the specimens with high-grade, independent of studied group. For BMP-2, 56% of tongue SCC without metastasis and 72% tongue SCC with metastasis exhibited score 1 while the IFH showed secore 0 in 72% of the cases, with statistical association (p=0,007). Considering the BMPR-II, 52% of tongue SCC without metastasis exhibited score 0; 56% tongue SCC with metastasis and 60% IFH showed score 1. The majority cases of BMPR-IA demonstrated score 1 and 100% of CD105 exhibited strong immunoexpression in tongue SCC. Regarding the pattern distribution, it was noted a tendency to diffuse pattern for the proteins in all groups. The means of MVC were similar in tongue SCC without metastasis (32,91) and in tongue SCC with metastasis (32,05), however existed statistical difference with IFH (p<0,001). There was statistical association of BMP-2 expression with BMPR-II (p=0,008), BMPR-IA (p=0,006) and CD105 (p=0,046). An association between TNM and BMP-2 immunoexpression and their receptors was not detected, nevertheless this association was found with MVC (p=0,047) whose averages were higher for the stages II (35,97) e IV (35,69). No association between histological grading and these proteins was observed. This study suggests that the superexpression of BMP-2 signaling pathways acts on cell proliferation in tongue SCC and can be implicated with more invasive potential. Additionaly, the CD105 is a potent biological marker of neovascularization in this neoplasm and their association with BMP-2 and BMPR-IA receptor, showed that this type of cancer in BMP-2 is presented as pro-angiogenic in the metastatic process

Expressão imuno-histoquimica de proteínas relacionadas com a reabsorção óssea em carcinoma epidermoide de palato duro e língua

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Caracterização de subpopulações de interneurônios imunorreativos para proteínas ligantes de cálcio no córtex pré-frontal do Sagui (Callithrix jacchus): distribuição e morfologia

Cortical interneurons are characterized by their distinct morphological, physiological and biochemical properties, acting as modulators of the excitatory activity by pyramidal neurons, for example. Various studies have revealed differences in both distribution and density of this cell group throughout distinct cortical areas in several species. A particular class of interneuron closely related to cortical modulation is revealed by the immunohistochemistry for calcium binding proteins calbindin (CB), calretinina (CR) and parvalbumin (PV). Despite the growing amount of studies focusing on calcium binding proteins, the prefrontal cortex of primates remains relatively little explored, particularly in what concerns a better understanding of the organization of the inhibitory circuitry across its subdivisions. In the present study we characterized the morphology and distribution of neurons rich in calcium-binding proteins in the medial, orbital and dorsolateral areas of the prefrontal cortex of the marmoset (Callithrix jacchus). Using both morphometric and stereological techniques, we found that CR-reactive neurons (mainly double bouquet and bipolar cells) have a more complex dendritic arborization than CB-reactive (bitufted and basket cells) and PV-reactive neurons (chandelier cells). The neuronal densities of CR- and CB-reactive cells are higher in the supragranular layers (II/III) whilst PV-reactive neurons, conversely, are more concentrated in the infragranular layers (V/VI). CR-reactive neurons were the predominant group in the three regions evaluated, being most prevalent in dorsomedial region. Our findings point out to fundamental differences in the inhibitory circuitry of the different areas of the prefrontal cortex in marmoset

Detecção de predadores por dicromatas e tricromatas humanos e a sua implicação na evolução da visão de cores em primatas

Among placental mammals, primates are the only ones to present trichromatic color vision. However, the distribution of trichromacy among primates is not homogeneous: Old World primates shows an uniform trichromacy (with all individuals being trichromats) and New World primates exhibit a color vision polymorphism (with dichromatic males and dichromatic or trichromatic females). Visual ecology studies have investigated which selective pressures may have been responsible for the evolution of trichromacy in primates, diverging from the dichromat standard found in other mammals. Cues associated with foraging and the socio-reproductive status were analyzed, indicating a trichromatic advantage for the rapid detection of visually conspicuous objects against a green background. However, dichromats are characterized by an efficient capture of cryptic and camouflaged stimuli. These advantages regarding phenotype may be responsible for the maintenance of the visual polymorphism in New World primates and for the high incidence of color blindness in humans (standing around 8% in Caucasian men). An important factor that has not yet been experimentally taken into account is the predation risk and its effect on the evolution of trichromacy in primates. To answer this question, we prepared and edited pictures of animals with different coats: oncillas (Leopardus spp.), puma (Puma concolor) and ferret (Galictis cuja). The specimens were taxidermized and the photographs were taken in three different vegetation scenarios (dense forest, cerrado and grassland). The images of the predators were manipulated so that they fit into two categories of stimulus size (small or large). After color calibration and photo editing, these were presented to 40 humans (20 dichromats and 20 trichromats) by a computer program, which presented a set of four photos at a time (one picture containing the taxidermized animal amid the background vegetation and three depicting only the background vegetation) and recorded the response latency and success rate of the subjects. The results show a trichromatic advantage in detecting potential predators. The predator detection was influenced by the background, the predator species, the dimension of the stimulus and the observer s visual phenotype. As humans have a high rate of dyschromatopsias, when compared to wild Catarrhini or human tribal populations, it is possible that the increased rate of dichromats is a result of reduced pressure for rapid predator detection. Since our species came to live in more cohesive groups and resistant to attack by predators, with the advent of agriculture and the formation of villages, it is possible that the lower risk of predation has reduced the selection in favor of trichromats

Ferramentas quimiométricas aplicadas a classificação de amostras de leite em pó e quantificação de proteínas

In this work we used chemometric tools to classify and quantify the protein content in samples of milk powder. We applied the NIR diffuse reflectance spectroscopy combined with multivariate techniques. First, we carried out an exploratory method of samples by principal component analysis (PCA), then the classification of independent modeling of class analogy (SIMCA). Thus it became possible to classify the samples that were grouped by similarities in their composition. Finally, the techniques of partial least squares regression (PLS) and principal components regression (PCR) allowed the quantification of protein content in samples of milk powder, compared with the Kjeldahl reference method. A total of 53 samples of milk powder sold in the metropolitan areas of Natal, Salvador and Rio de Janeiro were acquired for analysis, in which after pre-treatment data, there were four models, which were employed for classification and quantification of samples. The methods employed after being assessed and validated showed good performance, good accuracy and reliability of the results, showing that the NIR technique can be a non invasive technique, since it produces no waste and saves time in analyzing the samples

CrossMDA2: Uma abordagem para minimizar o problema da fragilidade de pointcuts na evolução de sistemas orientados a aspectos

This work proposes a model based approach for pointcut management in the presence of evolution in aspect oriented systems. The proposed approach, called conceptual visions based pointcuts, is motivated by the observation of the shortcomings in traditional approaches pointcuts definition, which generally refer directly to software structure and/or behavior, thereby creating a strong coupling between pointcut definition and the base code. This coupling causes the problem known as pointcut fragility problem and hinders the evolution of aspect-oriented systems. This problem occurs when all the pointcuts of each aspect should be reviewed due to any software changes/evolution, to ensure that they remain valid even after the changes made in the software. Our approach is focused on the pointcuts definition based on a conceptual model, which has definitions of the system's structure in a more abstract level. The conceptual model consists of classifications (called conceptual views) on entities of the business model elements based on common characteristics, and relationships between these views. Thus the pointcuts definitions are created based on the conceptual model rather than directly referencing the base model. Moreover, the conceptual model contains a set of relationships that allows it to be automatically verified if the classifications in the conceptual model remain valid even after a software change. To this end, all the development using the conceptual views based pointcuts approach is supported by a conceptual framework called CrossMDA2 and a development process based on MDA, both also proposed in this work. As proof of concept, we present two versions of a case study, setting up a scenario of evolution that shows how the use of conceptual visions based pointcuts helps detecting and minimizing the pointcuts fragility. For the proposal evaluation the Goal/Question/Metric (GQM) technique is used together with metrics for efficiency analysis in the pointcuts definition

Um modelo conceitual baseado em MDD e padrões para evolução de sistemas OA

Aspect-Oriented Software Development (AOSD) is a technique that complements the Object- Oriented Software Development (OOSD) modularizing several concepts that OOSD approaches do not modularize appropriately. However, the current state-of-the art on AOSD suffers with software evolution, mainly because aspect definition can stop to work correctly when base elements evolve. A promising approach to deal with that problem is the definition of model-based pointcuts, where pointcuts are defined based on a conceptual model. That strategy makes pointcut less prone to software evolution than model-base elements. Based on that strategy, this work defines a conceptual model at high abstraction level where we can specify software patterns and architectures that through Model Driven Development techniques they can be instantiated and composed in architecture description language that allows aspect modeling at architecture level. Our MDD approach allows propagate concepts in architecture level to another abstraction levels (design level, for example) through MDA transformation rules. Also, this work shows a plug-in implemented to Eclipse platform called AOADLwithCM. That plug-in was created to support our development process. The AOADLwithCM plug-in was used to describe a case study based on MobileMedia System. MobileMedia case study shows step-by-step how the Conceptual Model approach could minimize Pointcut Fragile Problems, due to software evolution. MobileMedia case study was used as input to analyses evolutions on software according to software metrics proposed by KHATCHADOURIAN, GREENWOOD and RASHID. Also, we analyze how evolution in base model could affect maintenance on aspectual model with and without Conceptual Model approaches

Estudo comparativo da evolução e sobrevida de pacientes com claudicação intermitente, com ou sem limitação para exercícios, acompanhados em ambulatório específico

CONTEXTO: Os fatores de risco para doença aterosclerótica, que influenciam na evolução natural dessa doença, estão bem estabelecidos, assim como o benefício do programa de exercícios para pacientes claudicantes. Entretanto, faltam informações sobre a relação entres limitações clínicas e fatores de risco, com desempenho do programa de caminhadas e suas implicações na evolução e mortalidade destes pacientes. OBJETIVO: Comparar, ao longo do tempo, a distância de claudicação e sobrevida de pacientes claudicantes em ambulatório específico, com ou sem limitação para exercícios. MÉTODOS: Foi feito um estudo tipo coorte retrospectivo de 185 pacientes e 469 retornos correspondentes, no período de 1999 a 2005, avaliando-se dados demográficos, distância média de claudicação (CI) e óbito. Os dados foram analisados nos programas Epi Info, versão 3.2, e SAS, versão 8.2. RESULTADOS: A idade média foi de 60,9±11,1 anos, sendo 61,1% do sexo masculino e 38,9% do sexo feminino. Oitenta e sete por cento eram brancos, e 13%, não-brancos. Os fatores de risco associados foram: hipertensão (69,7%), tabagismo (44,3%), dislipidemia (32,4%) e diabetes (28,6%). Nos claudicantes para menos de 500 m, a CI inicial em esteira foi de 154,0±107,6 m, e a CI final, de 199,8±120,5 m. Cerca de 45% dos pacientes tinham alguma limitação clínica para realizar o programa de exercícios preconizado, como: angina (26,0%), acidente vascular cerebral (4,3%), artropatia (3,8%), amputação menor ou maior com prótese (2,1%) ou doença pulmonar obstrutiva crônica (1,6%). Cerca de 11,4% dos pacientes tinham infarto do miocárdio prévio, e 5,4% deles usavam cardiotônico. O tempo de seguimento médio foi de 16,0±14,4 meses. A distância média de CI referida pelos pacientes aumentou 100% (de 418,47 m para 817,74 m) ao longo de 2 anos, nos grupos não-limitante (p < 0,001) e não-tabagista (p < 0,001). A sobrevida dos claudicantes foi significativamente menor no grupo com limitação. A análise de regressão logística mostrou que a limitação para realização de exercícios, isoladamente, influenciou significativamente na mortalidade (p < 0,001). CONCLUSÃO: A realização correta e regular dos exercícios e o abandono do fumo melhoram a distância de claudicação, além de reduzir a mortalidade nesses casos, seja por meio de efeitos positivos próprios do exercício, seja por meio de controle dos fatores de risco e de seus efeitos adversos.

Caracterização genética e evolução dos vírus dengue no Estado do Rio Grande do Norte

Dengue is considered as the most important arthropod-borne viral disease throughout the world due to the high number of people at risk to be infected, mainly in tropical and subtropical regions of the planet. The etiologic agent is Dengue Virus (DENV), it is a single positive-stranded RNA virus of the family Flavivirus, genus Flaviviridae. Four serotypes are known, DENV-1, DENV-2, DENV-3 and DENV-4. One of the most important characteristic of these viruses is the genetic variability, which demands phylogenetic and evolutionary studies to understand key aspects like: epidemiology, virulence, migration patterns and antigenic characteristics. The objective of this study is the genetic characterization of dengue viruses circulating in the state of Rio Grande does Norte from January 2010 to December 2012. The complete E gene (1485 pb) of DENV1, 2 e 4 from Brazilian (Rio Grande do Norte) patients was sequenced. Phylogenetic analysis was performed using MEGA 5.2 software, Tamura-Nei model and Neighbor-Joining trees were inferred for the datasets. In Brazil, there is just one DENV-1 genotype (genotype V), one DENV-2 genotype (Asian/American) and two DENV-4 genotypes (genotypes I and II). Brazilian strains of DENV-1 are subdivided in two different lineages (BR-I and BR-II), the Brazilian strains of DENV-2 are subdivided in four lineages (BRI-IV) and genotype II of DENV-4 is subdivided in three Brazilian lineages (BRI-III). The viruses isolated in RN belong to lineage BR-II (DENV-1), BR-IV (DENV-2) and BR-III (DENV-4).The Caribbean and near Latin American countries are the main source of these viruses to Brazil. Amino acids substitutions were detected in three domains of E protein, this makes clear the necessity of studies that associate epidemiological and molecular data to better understand the effects of these mutations. This is the first study about genetic characterization and evolution of Dengue viruses in Rio Grande do Norte, Brazil