Electrophysiological effects of guanosine and MK-801 in a quinolinic acid-induced seizure model

TORRES, F ; FILHO, M.S. ; ANTUNES, C. ; KALININE, E. ; ANTONIOLLI, E. ; PORTELA, Luis Valmor ; SOUZA, Diogo Onofre ; TORT, A. B. L. . Electrophysiological effects of guanosine and MK-801 in a quinolinic acid-induced seizure model. Experimental Neurology , v. 221, p. 296-306, 2010

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

Imunoexpressão de galectinas em queilites actínias e sua relação com características clínicas e gradação histológica

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Análise comparativa da imunoexpressão do IMP-3 e Ki-67 em queilites actínicas e carcinoma epidermóide de lábio inferior

Epithelial changes observed in actinic cheilitis (AC) and squamous cell carcinoma of the lower lip (LLSCC) are mainly caused by chronic exposure to ultraviolet rays (UV) and are studied using different immunohistochemical markers trying to evaluate the process of carcinogenesis. The objective of this study was to comparatively evaluate the expression of Ki-67 proteins and IMP-3 in AC and LLSCC to contribute with additional information on carcinogenesis in lower lip. A total of 33 cases of AC and 33 cases of LLSCC were studied, analyzed the clinical and pathological features and immunostaining of Ki-67 and IMP-3. Immunohistochemical analysis of Ki-67 was made through the determination of the proliferation index (PI) and subsequent classification of the cases according to the scores: 0 (0% positive cells) +1 (≤30%) + 2 (> 30% and ≤60%) and +3 (> 60%). For statistical tests cases were classified as unmarked (score 0), low expression (score +1) and high expression (scores +2 and +3). For the expression of IMP-3, the percentage of immunostained epithelial cells was established, and assigned scores: 0 (corresponding to 0%), +1 (up to 30% of positive cells); +2 (From 30% to 60% of immunostained cells) and +3 (over 60% of positive cells). Statistical tests chi-square test, Mann-Whitney and Wilcoxon were used. The significance level was 5%. Most AC chaos was male (78.8%) with mean age of 50 years and cases of LLSCC also were male (69.89%) with an average of 62 years. The Ki-67 was expressed in all cases of AC and in cases of LLSCC, predominantly in the two injuries the score 2, corresponding to 81.8% of cases in ACs and 54.5% in the CELI. The expression of IMP-3 in ACs occurred in 72.7% of cases, predominantly in 36.3% of LLSCC cases score 1. Already in the IMP-3 was expressed in 60.6% of cases, especially in 27.3% of the score of the cases 3. These results allow us to conclude that the expression of IMP3 and proliferative activity are early events in carcinogenesis independently lower lip state of change.

Queilite actínica: expressão imuno-histoquímica da cox-2 e avaliação do diclofenaco sódico gel como uma terapia alternativa

Actinic cheilitis (AC) is a potentially malignant disorder which affects the lip vermilion and results from chronic exposure to sunlight. Currently, it is not possible to predict which cases of AC may progress to squamous cell carcinoma, and therefore, some biomolecular markers have been researched. Cyclooxygenase 2 (COX-2) is an enzyme associated with inflammatory response which is overexpressed in oral cancer; however, little is known about the role of this protein in actinic cheilitis. About the treatment of this lesion, currently available therapeutic modalities to AC may cause cytotoxic effects and deleterious results to patients. Therefore, the aim of this study was to evaluate the immunoexpression of COX-2 in AC of different risks of malignant transformation and analyse, through clinical follow-up, the efficacy of diclofenac sodium 3% gel in the treatment of this condition. Epithelial immunoexpression of COX-2 was analysed semi-quantitatively in 90 cases of AC classified as low risk (n = 55) and high risk (n = 35) of malignant transformation, in which the scores were assigned: (0) 0 to 5% of positive cells - Negative; (1) 6 to 30% of positive cells - Low expression; (2) 31 to 100% of positive cells - High expression. The chi-square test of Pearson was conducted to verify possible associations between immunoexpression of COX-2 and histologic grade of actinic cheilitis. The weighted kappa coefficient denoted a good interobserver agreement (0.677). Nineteen patients diagnosed with AC were instructed to perform topical application of the gel three times a day for a period of 90 days. In each biweekly visit, a follow-up record was accomplished through digital photographs and after treatment was completed, two researchers analysed all the images to assess clinical aspects of the lip. Furthermore, tolerability to the drug and patient satisfaction after treatment were evaluated. COX-2 was overexpressed in 74.4% of AC cases. Both low and high-risk groups revealed predominance of score 3, followed by scores 2 and 1. There was no significant association (p = 0.315) between COX-2 expression and histological grading. Among the total number of participants of this clinical study, ten showed total remission of all clinical features of the lesion and three had partial improvement of these characteristics. One participant presented worsening of the clinical condition. In five cases, the treatment was discontinued due to development of mild adverse effects at the site of gel application. Regarding analysis of satisfaction and tolerability to the drug, most patients were fully satisfied with the therapy (n = 11) and reported that the drug was not irritating to the lips (n = 9). Our study demonstrates that high expression of COX-2 is common in AC; however, this protein was not associated with malignant transformation risk of the analysed cases. Topical application of diclofenac sodium 3% gel provided a convenient and well tolerated approach in most cases, and may be a promising alternative for the treatment of actinic cheilitis.

A mediação do professor na constituição da autoria em textos de alunos de Letras

Textual composition in classroom has been object of research in language studies along this last three decades in Brazil. This thematic recurrence occurs is a demonstration of the gap between writing skill teaching and learner‟s performance. In this research, we argue that during writing process in classroom, teachers‟ mediated actions guide students to the exotopic exercise on their texts, facing it as a fundamental phase of their composition, with meaningful effect for the development of textual authorship. In this sense, we have chosen as investigation focus the textual composition of Letters Students at Universidade do Estado do Rio Grande do Norte – UERN - to study writing processual characteristics, based on teacher‟s mediation. The main aim of this research is to analyze students‟ (re)writing along Letters Course, to comprehend the process of authorship construction in their texts and the effects resulted through teacher mediation in this process. More specifically, a) to analyze teacher mediation as a mechanism for authorship development in texts composed by Letters Students; b) to deduce, based on different versions of textual composition, the effects of teacher mediation on students‟ writing; and c) to describe compositional textual process in classroom, identifying students‟ attitudes/behaviors before writing task. We have brought several voices into the dialogue, among them we highlight those based on bakhtinian studies. Some of those authors are related to Bakhtin circle, by themselves (BAKHTIN/VOLOCHINOV, [1929] 2006; BAKHTIN, [1979] 2003; [1963] 2008; [1975] 2010a; [1986] 2010b), their debaters (FARACO, 2008, 2009a, 2009b, 2010; PONZIO, 2010, 2012; GERALDI, 2010a; 2010b OLIVEIRA, 2006, 2008a, 2008b, 2010, among others), to guide us, mainly, on dialogism, author and authorship, and their conceptual implications: exotopy, finishing, esthetic activity, and ethical act. Data was constituted in teaching situation, involving teacher/researcher and 5th Term Letters/UERN students. Therefore, we have submitted an open questionnaire, textual discussion, and an article (re)writing. Data analysis has revealed subjects‟ little experience with writing composition in the Course, as a systematic practice, in their routine, dialogued, whose social function is explored. The texts are generally written in a single version and useful only to receive a score. Data analysis show insecure students in relation the writing, and with many difficulties to do it. On the other hand, writing movements, on the analyzed articles, have revealed that the subjects show a responsive attitude in relation to the mediated activities, to respond rewriting proposal. Despite some problems remain unsolved and many others emerge in each version of the article, in general, we consider that teacher mediation had a positive effect on student writing, considering that it boosted the author exotopic movement, something indispensable to compose a text. The three interventions carried out, in some way, provided opportunity for the subjects to modify their article.

A mediação do professor na constituição da autoria em textos de alunos de Letras

Textual composition in classroom has been object of research in language studies along this last three decades in Brazil. This thematic recurrence occurs is a demonstration of the gap between writing skill teaching and learner‟s performance. In this research, we argue that during writing process in classroom, teachers‟ mediated actions guide students to the exotopic exercise on their texts, facing it as a fundamental phase of their composition, with meaningful effect for the development of textual authorship. In this sense, we have chosen as investigation focus the textual composition of Letters Students at Universidade do Estado do Rio Grande do Norte – UERN - to study writing processual characteristics, based on teacher‟s mediation. The main aim of this research is to analyze students‟ (re)writing along Letters Course, to comprehend the process of authorship construction in their texts and the effects resulted through teacher mediation in this process. More specifically, a) to analyze teacher mediation as a mechanism for authorship development in texts composed by Letters Students; b) to deduce, based on different versions of textual composition, the effects of teacher mediation on students‟ writing; and c) to describe compositional textual process in classroom, identifying students‟ attitudes/behaviors before writing task. We have brought several voices into the dialogue, among them we highlight those based on bakhtinian studies. Some of those authors are related to Bakhtin circle, by themselves (BAKHTIN/VOLOCHINOV, [1929] 2006; BAKHTIN, [1979] 2003; [1963] 2008; [1975] 2010a; [1986] 2010b), their debaters (FARACO, 2008, 2009a, 2009b, 2010; PONZIO, 2010, 2012; GERALDI, 2010a; 2010b OLIVEIRA, 2006, 2008a, 2008b, 2010, among others), to guide us, mainly, on dialogism, author and authorship, and their conceptual implications: exotopy, finishing, esthetic activity, and ethical act. Data was constituted in teaching situation, involving teacher/researcher and 5th Term Letters/UERN students. Therefore, we have submitted an open questionnaire, textual discussion, and an article (re)writing. Data analysis has revealed subjects‟ little experience with writing composition in the Course, as a systematic practice, in their routine, dialogued, whose social function is explored. The texts are generally written in a single version and useful only to receive a score. Data analysis show insecure students in relation the writing, and with many difficulties to do it. On the other hand, writing movements, on the analyzed articles, have revealed that the subjects show a responsive attitude in relation to the mediated activities, to respond rewriting proposal. Despite some problems remain unsolved and many others emerge in each version of the article, in general, we consider that teacher mediation had a positive effect on student writing, considering that it boosted the author exotopic movement, something indispensable to compose a text. The three interventions carried out, in some way, provided opportunity for the subjects to modify their article.