868 resultados para Disfunção do trato urinário inferior


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Colon-specific drug delivery systems have attracted increasing attention from the pharmaceutical industry due to their ability of treating intestinal bowel diseases (IBD), which represent a public health problem in several countries. In spite of being considered a quite effective molecule for the treatment of IBD, mesalazine (5-ASA) is rapidly absorbed in the upper gastrointestinal tract and its systemic absorption leads to risks of adverse effects. The aim of this work was to develop a microparticulate system based on xylan and Eudragit® S- 100 (ES100) for colon-specific delivery of 5-ASA and evaluate the interaction between the polymers present in the systems. Additionaly, the physicochemical and rheological properties of xylan were also evaluated. Initially, xylan was extracted from corn cobs and characterized regarding the yield and rheological properties. Afterwards, 10 formulations were prepared in different xylan and ES100 weight ratios by spray-drying the polymer solutions in 0.6N NaOH and phosphate buffer pH 7.4. In addition, 3 formulations consisting of xylan microcapsules were produced by interfacial cross-linking polymerization and coated by ES100 by means of spray-drying in different polymer weight ratios of xylan and ES100. The microparticles were characterized regarding yield, morphology, homogeneity, visual aspect, crystallinity and thermal behavior. The polymer interaction was investigated by infrared spectroscopy. The extracted xylan was presented as a very fine and yellowish powder, with mean particle size smaller than 40μm. Regarding the rheological properties of xylan, they demonstrated that this polymer has a poor flow, low density and high cohesiveness. The microparticles obtained were shown to be spherical and aggregates could not be observed. They were found to present amorphous structure and have a very high thermal stability. The yield varied according to the polymer ratios. Moreover, it was confirmed that the interaction between xylan and ES100 occurs only by means of physical aggregation

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The subject of study of this work is the teacher spawning of the Instituto de Educação do Pará in the decades of 1970 and 1980. It aims the enablement offered by the institute concerning the racial issue. The thesis highlights the inferior condition to which the black student is relegated and the discrimination it suffers. Our argument is to affirm the omission of the curriculum and the reference resources as far as the racial issue is concerned. Before the singularity of the Brazilian case a country with a slavish background, with serious social unbalance problems, many of them resulting from the racial segregation implemented by that slavish system , this work claims that the preparation of the teachers for dealing with this issue is crucial, since the absence of this preparation leads to the reproduction of the prejudice inside the classroom. This thesis is based on the theory of Pierre Bourdieu on the notion of habitus and symbolic power

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O objetivo deste trabalho foi investigar o efeito da idade das matrizes pesadas sobre o desenvolvimento do trato gastrointestinal (TGI) dos embriões no terço final do período de incubação, bem como a utilização das reservas do saco vitelino nas 24 h pós-eclosão, em pintos alimentados ou em jejum. Foram utilizados ovos férteis da linhagem Cobb 500, oriundos de matrizes pesadas com 30 e 60 semanas de idade. O desenvolvimento do TGI (proventrículo+moela, segmentos do intestino delgado e saco vitelino) foi estudado entre o 17º e 21º dias de incubação (Experimento 1). Nas 24 h pós-eclosão foi pesquisado o efeito da presença ou não de alimento no lúmen intestinal sobre a utilização das reservas do saco vitelino (Experimento 2). Os achados deste trabalho mostraram que, ao contrário do embrião, o desenvolvimento do intestino delgado e o peso do saco vitelino não sofreram influência da idade das matrizes. Na fase pós-eclosão, na ausência de alimento, o desenvolvimento do intestino delgado foi maior nas matrizes com 60 semanas, sendo dependente do crescimento do jejuno. A presença do alimento no lúmen teve influência na utilização das reservas do saco vitelino apenas nas matrizes com 30 semanas de idade. Os resultados deste experimento mostraram que a idade da matriz é importante fator no desenvolvimento do trato gastrointestinal do embrião, sendo fator relevante no crescimento pós-ecloão dos pintos.

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O objetivo deste trabalho foi avaliar os efeitos da restrição alimentar qualitativa precoce sobre o desempenho, as características do trato gastrintestinal e a carcaça de frangos de corte. Um total de 975 pintos de corte de um dia da linhagem Ross, 15 parcelas com 30 machos cada e 15 parcelas com 35 fêmeas, foi distribuído em delineamento experimental inteiramente casualizado, em esquema fatorial 5 x 2 (forma de restrição x sexo), com três repetições por tratamento. As formas de restrição estudadas foram: 1 - testemunha, sem diluição; 2 -diluição com 15% de calcário; 3 - diluição com 30% de calcário; 4 - diluição com 15% de casca de arroz; e 5 - diluição com 30% de casca de arroz. Os frangos foram alimentados ad libitum com ração padrão, no período de 1 a 7 dias e de 15 a 45 dias de idade. A restrição alimentar por diluição das rações, conforme cada tratamento, foi aplicada do 8º ao 14º dia de idade. Para o período de restrição alimentar, foram formuladas rações com níveis normais de minerais e vitaminas, reduzindo-se os outros nutrientes, conforme a diluição. Os frangos submetidos à restrição alimentar qualitativa precoce, pela diluição com 15% de calcário e, 15 ou 30% de casca de arroz, apresentaram ganho compensatório, com bom desempenho final. Entretanto, a restrição com 30% de calcário foi muito severa, prejudicando o desempenho. Houve alteração nas características do trato gastrintestinal com a restrição alimentar, porém houve recuperação até o momento do abate. Os frangos submetidos à restrição alimentar qualitativa precoce apresentaram menor deposição de gordura e maior deposição de proteína na carcaça em comparação ao controle.

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O objetivo deste trabalho foi avaliar o efeito da adição do prebiótico mananoligossacarídeo (MOS) nas dietas de leitões sobre a digestibilidade dos nutrientes, o desempenho e as características morfofisiológicas do trato digestório. No primeiro experimento, foram utilizados 16 leitões com peso de 24,8±2,79 kg. Utilizou-se o método de coleta total de fezes para determinar a digestibilidade das rações controle e com 0,5% de prebiótico. No segundo experimento, avaliaram-se o desempenho e a incidência de diarreia em 30 leitoas com idade entre 22 e 63 dias e peso inicial de 6,28±1,40 kg. No terceiro experimento, foram avaliados a morfometria intestinal, os pesos relativos do fígado e do pâncreas e o pH dos conteúdos do estômago, intestino delgado e ceco em 15 leitoas com idade entre 22 e 63 dias e peso inicial de 5,74±0,93 kg. No segundo e terceiro experimentos, os tratamentos foram: controle positivo (dieta basal + sulfato de neomicina); controle negativo (dieta basal) e os tratamentos dieta basal acrescida de 0,25, 0,50 ou 0,75% de MOS. Utilizou-se o delineamento em blocos ao acaso. A utilização de diferentes níveis de mananoligassacarídeo nas dietas dos leitões não promove melhorias na digestibilidade dos nutrientes, no desempenho ou nas características morfofisiológicas do trato digestório.

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Este estudo foi realizado com o objetivo de avaliar o efeito da forma física da ração sobre o desempenho, a utilização dos nutrientes das rações e o desenvolvimento do trato disgestório de pintos de corte na primeira semana de vida. Foram utilizados 150 pintos machos Cobb distribuídos ao acaso em três tratamentos com cinco repetições de dez aves. Os tratamentos consistiram das formas físicas farelada, triturada e peletizada de uma ração pré-inicial comercial. Com exceção da moela, os órgãos do trato digestório e a estrutura morfométrica do intestino não foram influenciados pela forma física da ração. Maior digestibilidade do N foi obtida com a ração peletizada, enquanto a ração triturada possibilitou maior digestibilidade do EE. A energia metabolizável determinada para a ração farelada foi menor que a obtida nas demais formas físicas da ração. As aves alimentadas com ração farelada tiveram menor consumo de ração e ganho de peso e pior conversão alimentar. Ingeriram ainda menos energia, apresentaram menores retenções de proteína, gordura e energia corporal e utilizaram maior proporção da energia ingerida para produção de calor. As rações pré-iniciais na forma peletizada ou triturada possibilitam maior aproveitamento dos nutrientes da ração pelos pintos e melhor desempenho.

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Background: The myotonic dystrophy (MD) is a multisystem neuromuscular disease that can affect the respiratory muscles and heart function, and cause impairment in quality of life. Objectives: Investigate the changes in respiratory muscle strength, health-related quality of life (HRQoL) and autonomic modulation heart rate (HR) in patients with MD. Methods: Twenty-three patients performed assessment of pulmonary function, sniff nasal inspiratory pressure (SNIP), the maximal inspiratory (MIP) and expiratory (MEP) pressure, and of HRQoL (SF-36 questionnaire). Of these patients, 17 underwent assessment of heart rate variability (HRV) at rest, in the supine and seated positions. Results: The values of respiratory muscle strength were 64, 70 and 80% of predicted for MEP, MIP, and SNIP, respectively. Significant differences were found in the SF-36 domains of physical functioning (58.7 ± 31,4 vs. 84.5 ± 23, p<0.01) and physical problems (43.4 ± 35.2 vs. 81.2 ± 34, p<0.001) when patients were compared with the reference values. Single linear regression analysis demonstrated that MIP explains 29% of the variance in physical functioning, 18% of physical problems and 20% of vitality. The HRV showed that from supine position to seated, HF decreased (0.43 x 0.30), and LF (0.57 x 0.70) and the LF/HF ratio (1.28 x 2.22) increased (p< 0.05). Compared to healthy persons, LF was lower in both male patients (2.68 x 2.99) and women (2.31 x 2.79) (p< 0.05). LF / HF ratio and LF were higher in men (5.52 x 1.5 and 0.8 x 0.6, p <0.05) and AF in women (0.43 x 0.21) (p< 0.05). There was positive correlation between the time of diagnosis and LF / HF ratio (r = 0.7, p <0.01). Conclusions: The expiratory muscle strength was reduced. The HRQoL was more impaired on the physical aspects and partly influenced by changes in inspiratory muscle strength. The HRV showed that may be sympathetic dysfunction in autonomic modulation of HR, although with normal adjustment of autonomic modulation during the change of posture. The parasympathetic modulation is higher in female patients and sympathetic tends to increase in patients with longer diagnosis

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Objective:To analyze the immediate effects of the Kinesio Taping® application on the quadriceps neuromuscular performance, postural balance and lower limb function in healthy subjects. Materials andmethods:This is a randomized, controlled, blinded clinical trial. Sixtyfemale volunteers(age: 23.3±2.5 years old, BMI: 22.2±2.1kg/m2)wererandomly assigned intothreegroups with20memberseach,and performedone of these threeprotocols: control -10 minutesof rest,experimental 1- patch application ontherectusfemoris (RF), vastuslateralis(VL) and vastusmedialis(VM) and experimental 2-KT application on the same muscles. Allunderwent an evaluationfor singleand triple hop distance, postural balance (baropodometry), joint position sense(JPS), peak torque (concentric and eccentricevaluation at 60°/s)and electromyographic activityof VL,before andafter intervention.Results: There wasasignificant increasein the jump distanceof thethreestudied groups,with no differencebetween groups.There were nosignificant changesin postural balance,JPS, concentricpeak torqueand RMSof the VLin none of the groups. There was a reduction ineccentricpeak torquein all groups, without differencesbetween groups.Conclusion:The KT application on the RF, VL and VMmusclesis not able tosignificantly improvelower limbfunction and postural balance, as well as the kneeextensor peaktorque, JPSand the VL muscleactivation amplitudeof healthy women.

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O Acidente Vascular Cerebral (AVC) é uma síndrome clínica caracterizada por uma perturbação focal da função cerebral. Geralmente ocasiona quadro de disfunção motora acompanhada de prejuízo da função respiratória. Tendo em vista tal quadro e suas possíveis repercussões, a fisioterapia respiratória tem sido amplamente requisitada com o intuito reverter ou minimizar as complicações. Dentre os recursos utilizados para este fim, os espirômetros de incentivo são utilizados com o objetivo de restaurar os volumes pulmonares, modificando o padrão respiratório e de ventilação pulmonar, prevenindo a incidência das complicações pulmonares. O objetivo do presente estudo foi comparar o desempenho na realização da espirometria de incentivo volume-orientada (EI) e seus efeitos agudos sobre os volumes pulmonares em pacientes após AVC e sujeitos saudáveis. Foram selecionados 40 voluntários, de ambos os gêneros, divididos em grupo experimental (GE), composto por 20 pacientes após AVC e grupo controle (GC) composto por 20 sujeitos saudáveis, pareados quanto à idade, gênero e Índice de Massa Corpórea (IMC). A coleta dos dados foi realizada em duas etapas: (1) Avaliação cognitiva e neurofuncional (Mini Exame do Estado Mental, National Institute Stroke Scale, Medida de Independência Funcional, teste de desempenho da aprendizagem) (2) Avaliação Respiratória (espirometria, manovacuometria e cinemática tóraco-abdominal, através da Pletismografia Opto-eletrônica). A análise estatística foi realizada através do software Graphpad Prism 4.0, em que foram utilizados os testes t Student e ANOVA two-way para comparação intergrupos e adotado nível de significância de 5%. Os resultados mostraram que os pacientes apresentam desempenho inferior na aprendizagem da espirometria de incentivo, com uma média de erros maior 2,95 ± 1,39, quando comparados aos sujeitos saudáveis, 1,15 ± 0,98. Em relação à prática observacional utilizada não foi encontrada diferença entre a aprendizagem através do vídeo ou do terapeuta. Em relação aos efeitos agudos da espirometria de incentivo volume-orientada, os pacientes após AVC apresentaram valores de volume corrente 24,7%, 18% e 14,7% inferiores quando comparados aos sujeitos saudáveis nos momentos pré-EI, EI e pós-EI, porém a espirometria de incentivo induziu incrementos de volume similares em ambos os grupos estudados, com 75, 3% para os pacientes e 73,3% para os sujeitos saudáveis. A espirometria de incentivo promove ganhos significativos no volume corrente da parede torácica, tanto em pacientes acometidos por AVC como em sujeitos saudáveis, no entanto o desempenho da aprendizagem é inferior para os pacientes, para ambas as práticas com vídeo ou terapeuta

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Objective: To evaluate the acute effects of static stretching before and after isokinetic exercise, neuromuscular and biomechanical properties of muscles Biceps Femoris (BF) and semitendinosus (ST). Methods: Eighty-nine volunteers of both genders, healthy and physically active, with a mean age of 22.52 ± 2.6 years and mean BMI 23.86 ± 3.2 kg/m² were randomized into 4 groups: Control Group (CG) made only one Protocol Exercise (PE) without performing the stretching, the Experimental Group 1 (EG1) did stretching before PE; EG2 did the stretching after PE and EG3 did stretching before and after PE. The volunteers were evaluated on the following variables: Range of motion (ROM), soreness, dynamometric variables concentric and eccentric, Neuromuscular Latency Time (NLT) and electromyographic. In the data analysis was assigned a significance level of 5%. Results: ADM and TLNM reported significant reduction in CG, but remained unchanged in GE with p<0,05 and p<0,01, respectively. As for the soreness, no differences between the groups. The electromyographic activity of the BF and ST, in the concentric phase, showed a significant decrease in all groups (p<0,01). However, in the eccentric phase, ST revealed reduction in all groups (p <0.01), except for the CG, while the BF remained unchanged in all groups. The PT showed significant reduction in both conditions (concentric and eccentric) for all groups, with no difference between them (p<0,01). Conclusion: The results of this study do not favor the use of static stretching, even of short duration, before physical activity. However, after exercise or at times unrelated to the sport, he should be given with the aim of avoiding muscle shortening

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Some studies reported in the literature that emotional factors and quality of life may be involved both in aetiology, as in the progression of Temporomandibular disorders (TMD). Proposition: The purpose of this study is to observe a possible association between different forms of anxiety, quality of life and general health of patients diagnosed as carriers of various types and levels of Temporomandibular Dysfunction. Methodology: The sample consisted of 60 patients diagnosed as carriers of TMJD origin of muscle, joint, or both, with different levels of severity (mild TMD, moderate and severe). The patients were diagnosed with TMD-RDC (Research Diagnostic Criteria) to assess the type of dysfunction (muscle or joint) and by the Protocol of Fonseca to verify the degree of dysfunction (mild, moderate or severe). To evaluate the psychosocial aspects were used three self-applied, with the purpose of obtaining information about the general health (General Health Questionnaire - GHQ), the type of anxiety (Trait Anxiety Inventory-State - STAI) and quality of life (World Health Organization Quality Of Life Short WHOQOL-brief). Results: There was a correlation between all indicators studied in several forms of TMD with varying degrees of commitment. Quality of life appeared linked to the type and the level of TMD: Muscular and Articular TMD (p = 0,037), Disk Displacement With Reduction (p = 0.01) and Mild TMD (p = 0.042). The General Health showed association with the level of TMD, with the exception of the stress factor (p = 0.78). For the analysis of the types and levels to Severe Muscular TMD had a statistically significant indicator of the quality of life (p = 0049). The anxiety only showed association with the level of TMD (p = 0,047 for anxiety-trait). Conclusion: Besides the limitations of the study, it was concluded that anxiety, quality of life and general health are important psychosocial indicators, which are linked to several forms of TMD in different levels of severity

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Currently, bone morphogenetic proteins (BMPs) have effective participation in the growth of malignancies. Knowing that there are few studies involving BMPs and oral squamous cell carcinoma, this work constitutes an immunohistochemical study of BMP-2, BMPR IA and BMPR II in squamous cell carcinomas (SCC) of the lower lip relating to the clinical and pathological aspects of this lesion. The sample consisted of 40 cases of SCC of the lower lip, being 20 cases of SCC of the lower lip with regional metastasis and 20 cases without metastasis. We evaluated the intensity of expression (score 1 to mark absent / weak, score 2 for high ) and was found the percentage of labeled cells, where the score was 1 cases with 0 to 50% of positive cells, score 2 with 51 to 75% of positive cells, and score 3 more than 75% of positive cells. The sample comprised 72.5% of men with a mean age of 65.8 years, there was a predominance of stage II and 52.5% of the carcinomas were classified as low grade, being carcinoma with metastasis presenting most cases (70%) as carcinomas of high malignancy grade (p = 0.004). The largest number of cases of SCC of the lower lip that were in stages I / II (61, 9%) were classified as carcinomas of low grade malignancy and carcinomas in stages III / IV were classified as high-grade tumors (p = 0, 024). The BMP-2 showed strong intensity of immunostaining in 82.5%, BMPR-IA showed 55% of cases with an intensity of immunostaining absent / weak and BMPR-II showed 85% of cases with an intensity of immunostaining absent / weak. Only the protein BMPR-IA were significantly associated with all clinic-pathological parameters studied, metastasis (p <0.001), TNM (p <0.001) and histological grade of malignancy with (p = 0.028). The percentage of positive cells, all markers showed the highest number of cases with more than 75% of positive cells (score 3) and only BMPR-II showed statistical difference when related to the presence and absence of metastasis (p = 0.049 ). We conclude that there is disturbance in the BMP signaling pathway in EC-mediated lower lip and that high expression of BMP-2 associated with the expression of BMPR-IA and BMPR-II are associated with metastasis in carcinoma

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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

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The Epidermoid Carcinoma (EC) is the most common lesions located in the region of the head and neck and, despite advances in treatment modalities, the prognosis is still poor. The malignant cells show an increase in glucose uptake, process mediated by glucose transporters (GLUTs). Increased expression of GLUT 1 and GLUT 3 is related to the aggressive behavior of this lesion. The aim of this study was to evaluate, through immunohistochemistry, the expression of GLUTs 1 and 3 in EC of the lower lip. The sample consisted of 40 cases of EC of the lower lip, of which 20 had regional lymph node metastasis and the remaining 20 with absence of metastasis. The percentages of immunostained cells in front of tumor invasion and in the center of tumor were evaluated. These results were related to the presence and absence of lymph node metastasis, TNM classification and histological grading. The percentage of cytoplasmic/membranous expression of GLUT 1 ranged from 77.35% to 100%, while for GLUT 3 this value ranged from 0.79% to 100%. As for nuclear staining for GLUT 1, this percentage ranged from 0 to 0.42%, however. GLUT 3 showed only one case with nuclear staining. Despite the significant expression of tumor cells related to the proteins studied, we observed no statistically significant relationship between the variables and the antibodies analyzed, regardless of the region evaluated. However, there was a moderate positive correlation between cytoplasmic/membranous immunoexpressions of GLUT 1 in invasion front and in the tumor center (r = 0.679, p <0.001). Similarly, moderate positive correlation was found between the nuclear immunoexpressions of GLUT 1 in the invasion front and in the tumor center (r = 0.547, p <0.001). For GLUT 3, was also observed a moderate statistically significant positive correlation between cytoplasmic/membranous expression in tumor invasion front and in tumor center (r = 0.589, p <0.001). We also observed that the immunoreactivity for GLUT 1 was higher than GLUT 3 expression in invasion front (p <0.001) and tumor center (p <0.001). From these results, this study suggests that tumor hypoxia is a remarkable characteristic of the EC of the lower lip and GLUT 1 may be primarily responsible for glucose uptake into the interior of the malignant cells

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The presence of inflammatory cells within the tumor microenvironment plays a dual role that may contribute both to the progression and for inhibition of tumor growth. Recent studies suggest that the quality, not the quantity, of the inflammatory infiltrate is the most important determinant for prognosis. Therefore, TCD8 cells and natural killer cells are the main effector cells in combating cancer. The aim of this study was to assess, through the immunohistochemical study, the expression of TCD8 lymphocytes and NK cells in epidermoid carcinoma (EC) of the lower lip. The sample consisted of 32 specimens of EC of the lower lip, of which 16 had regional lymph node metastasis, and the 16 remaining, free of metastases. The total number of positive cells at the front of invasion were evaluated quantitatively and the results were related to clinical TNM staging, histological grade of malignancy and prognostic factors. It was observed for the group with metastasis, prevalence of stages III and IV (p<0.0001). Most patients with metastasis, had a high grade of malignancy (p=0.006). Most cases classified as high grade of malignancy had stages III and IV (p=0.032). Of the total sample, there were three cases of recurrence and five with death, however these variables were not statistically significant when associated with clinicopathological parameters. The immunostaining of CD8 and CD57, respectively, showed no statistically significant association with any of the clinicopathological parameters studied, metastasis (p=0.346, p=0.622), TNM classification (p=0.146, p=0.576), histological grade of malignancy (p=0.936, p=936), recurrence (p=0.075, p=0.075) and death (p=0.897, p=0.856). Believing in the function of the immunological system against malignant cells, it is concluded that the TD8 lymphocytes and NK cells, would be acting in the control of the progression of malignant neoplasms, but not in isolated manner