919 resultados para Intraperitoneal metastasis


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Several studies are carried out with aim to establish parameters to determine biologic behavior of oral squamous cell carcinoma, in order this neoplasm presents high rates of morbidity and mortality. The purpose of present research was to performe a clinic, morphologic and immunohistochemical analysis by the expression of galectins 1, 3, 4 and 7 in 65 cases of tongue squamous cell carcinoma, correlating this expression with clinics (outcome of the disease, metastasis and clinical staging) and morphologic parameters (malignancy histologic gradation system). The clinical and morphologic parameters analysed and expression of galectins 1, 3, 4 and 7 were submitted to statistical analysis (Qui2 test), observing that can be utilized as indicators of the biological behavior of the tongue squamous cell carcinoma. The galectin 1 was expressed in 87,7% of cases studied and it exhibit statistically significant correlation with metastasis (p=0,033) and clinical staging (p=0,016), it is located mostly in the citoplasm of the stomal cells. The immunoexpression of galectin 3 in 87,7% of cases was correlated with the presence of metastasis (p=0,033) and malignancy histological gradation system (p=0,031), observed, mostly of cases, in tongue squamous cell carcinoma of malignancy high grading. The galectin 4 showed no statistical significance to any of the parameters evaluated. The expression of galectin 7 in 73,8% of cases showed statistically significant correlation with the malignancy histologic grading (p=0,005), which is marking exclusively found in neoplastic epithelial cells, in the mostly of cases, it is found in cytoplasm and membrane (50%). The expressive immunopositivy of the galectins 1, 3 and 7, observed in this research, leads us to suggest a broad participation of these proteins in oral carcinogenesis, and its possible use as markers of biological behavior and tumor progression in cases of squamous cell carcinoma of the tongue

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Matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) modulate important functions strictly related to the development, invasion and metastasis of several human cancers among them the squamous cell carcinoma of the tongue (SCCT). However, individual genetic factors such as the functional single nucleotide polymorphisms (SNPs) influence the pattern of protein expression of these MMPs and thus may be related to the variability observed in the clinical behavior of patients with SCCT. In this context, the present cross-sectional study aimed to evaluate the association between the frequency of the functional SNPs MMP-7 -181 A/G and MMP-9 -1562 C/T and the clinical (age, gender and metastasis) and pathological (malignancy histological grading and immunohistochemistry expression) features of SCCT cases. Genotyping of these SNPs were performed by PCR-RFLP on DNA samples from 71 cases of SCCT and 60 individuals without cancer who constitute the control group. Among the results of this research, it was observed that the frequency of the polymorphic alleles MMP-7 -181 G and MMP-9 -1562 T in SCCT patients was 28% and 12%, respectively, and the frequency of the heterozygotes A/G (PR = 2.00; p < 0.001) and C/T (PR = 1.54; p = 0.014) were significantly higher in the patient group than in the controls. The prevalence of patients carrying the combination of SNPs studied was significantly associated with SCCT cases (PR = 2.00; p = 0.011) and metastasis (PR = 2.00; p < 0.001). Furthermore, with the frequency of SNPs analyzed, the age, gender, histological grading and immunoreactivity of MMP-7 and MMP-9 formed clinical and pathological parameters relevant to the identification of population subgroups more related to the development of SCCT and metastasis. Based on these results, it is suggested that the protein expression levels of MMP-7 and -9 substantially influence the balance between their pro- and anticancer biological functions and hence the clinicopathological profile of the squamous cell carcinoma of the tongue

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The balance between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) has been related to various physiological and pathological processes, including salivary gland morphogenesis and tumor invasion and metastasis processes. Pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) respectively represent benign and malignant neoplasias of salivary glands. Although they share the same cell origin, they present distinct biological behavior. The aim of this study was to compare the immunohistochemical expression of MMPs -2, -7, -9 and -26, and of TIMPs -1 and -2, in cases of PA and ACC of minor salivary glands. Twenty cases of PA and twenty cases of ACC were assessed according to the presence, intensity and location of MMPs and TIMPs in the tumor parenchyma. Most of the PAs and ACCs presented a high expression of MMP -2, -7, -9 and -26 and of TIMP -1 and -2, predominantly located in tumor cells. There was no significant difference in the expression of MMPs -2 (p=0.359), -7 (p=0.081) and -26 (p=0.553), as well as of TIMPs -1 (p=0.657) and -2 (p=0.248), between the parenchyma of PAs and ACCs. However, MMP-9 showed a significant difference of expression between the two tumors, with the ACC showing more intense marking for this gelatinase (p=0.041). The strong expression of MMP-9 observed in the parenchyma suggests that this gelatinase may play an important role in the biological behavior of these tumors. On the other hand, although there was no significant difference between the marking of MMP -2, 7 and 26 in the studied tumors, the data, when analyzed as a whole, suggest that these proteases may take part in the process of tissue remodeling in both tumors, but do not present a direct relation with the pattern of aggressiveness of ACC. Nonetheless, matrilisins may indirectly influence the behavior of this tumor due to their capacity of activating MMP-9, strongly expressed in the parenchyma of ACC

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The tumor hypoxia modulates a series of genetic changes related to adaptive development, invasion and metastasis of various human cancers, among which squamous cell carcinoma of the tongue (SCCT). The objective of this study was to analyze clinical, morphological and immunohistochemical expression by HIF-1α, GLUT-1 and CA-IX in 57 cases of CEL and correlated this expression to clinical parameters and morphological. After a descriptive analysis of data on gender, age, race, and habits of patients, it was found that the results were consistent with the literature. The clinical and morphological parameters analyzed and the expression of these markers of hypoxia were subjected to statistical analysis (Qui2 test), verifying that they can be used as indicators of the biological behavior of CEL. Among the results of this study, we observed that the intensity of expression for HIF-1α, in most cases located in the cytoplasm and nucleus, statistically correlated with clinical staging (p = 0.011) and histological grading (p = 0.002). As for the relationship between the distribution of labeling for HIF-1α and metastasis, the chi-square (Qui2) showed that there was statistically significant differences between the groups (p = 0.040). 75.8% of the sample who had metastases, there was the predominance of diffuse marking. The immunoexpression cytoplasmic/membrane GLUT-1 showed a statistically significant correlation with the clinical stage (p = 0.002) and histological grading (p = 0.000). Concerning the location of markings for GLUT-1 tumor on the island, there was a predominance of peripheral marking specimens in most low-grade (78.6%). In the sample of high-grade, prevailed the location center/periphery (55.8%). According to the chi-square (Qui2), the location on the island of the tumor (p = 0.025) showed statistically significant difference in histological grading. The immunoreactivity of CA-IX, in most cases located in the membrane and cytoplasm, exhibited a statistically significant correlation with histological grading (p = 0.005). Based on these results, we can conclude a broad participation of these markers of hypoxia in oral carcinogenesis and its possible use as markers of biological behavior and tumor progression in CEL

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Squamous cell carcinoma of the lower lip is among the most common malignant tumors of the oral and maxillofacial region, with good prognosis in more than 90% of patients with 5-year survival. In these carcinomas, the development of lymph node metastasis decreases the prognosis and it has been associated with the formation of new lymphatic vessels. It has been suggested the important role of vascular endothelial growth factor-C (VEGF-C), the receptor type 3 VEGF (VEGFR-3) and hypoxia-induced factor 1 (HIF-1) in this process. The aim of this study was to evaluate the immunoexpression of VEGF-C, VEGFR-3 and HIF-1α and correlate with intra and peritumoral lymphatic density in squamous cell carcinomas of the lower lip metastatic and non-metastatic. The sample consisted of 50 cases of squamous cell carcinoma of lower lip, of which 25 had regional lymph node metastasis and 25, absence of metastasis. The percentages of cells immunostained for VEGF-C, VEGFR-3 and HIF-1α in front of tumor invasion and in the center of tumor were evaluated. Microvessel density lymphatic (MDL) was determined by the counting of lymph microvessels immunostained by the anti-D2-40 in five fields (200×), in an area of evaluation with 0.7386 mm2. The invasion of the lymph vessels by malignant cells was also evaluated. Immunostaining was correlated with the presence and absence of metastasis, TNM clinical stage, local recurrence, disease outcome (remission of injury or patient death) and histological grading. The analysis of intra and peritumoral lymphatic density showed no significant association with clinicopathological parameters and immunoexpressions of VEGF-C, VEGFR-3 and HIF-1α (p > 0,05). There was a weak positive correlation, significant, between intra and peritumoral lymphatic density (r = 0,405; p = 0,004). VEGF-C showed no significant association with clinicopathological and prognosis parameters (p > 0,05). For VEGFR-3, there was scarce membrane staining and intense and homogenous cytoplasmic staining in neoplastic cells. Percentage of positive cytoplasmic VEGFR-3 in center of tumor, exhibited a statistically significant association with metastasis (p = 0,009), patient death (p = 0,008) and histological grades of malignancy proposed by Bryne et al. (1992) (p = 0,002) and World Health Organization (p = 0,003). A low positive correlation was statistically significant between the immunoreactivity of VEGFC and VEGFR-3 cytoplasmic (r = 0,358; p = 0,011) and between the percentage of positive cytoplasmic VEGFR-3 in front of tumor invasion and in the center of the tumor (r = 0,387; p = 0,005) was also demonstrated. There was no association between HIF-1α, clinicopathological and prognosis parameters, and VEGF-C and VEGFR-3. The percentage of nuclear positivity for HIF-1α was significantly higher in cases without invasion of peritumoral lymphatic (p = 0,040). Based on the results we can conclude that most cytoplasmic expression of VEGFR-3 in center of tumor in metastatic cases, high degree of malignancy and poorly differentiated, contributes to poor outcome of squamous cell carcinoma of the lower lip, including patient death. Intra and peritumoral lymphatic density seems to be not associated with lymph node metastasis in these carcinomas

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The objective of this study was perform, by the streptoavidin-biotin technique, an immunohistochemical analysis of the E-cadherin and CD44v6 in 15 lower lip squamous cell carcinomas and 15 of tongue, with varied histologic gradation of malignidade, in order to establish a possible relation between the expression these proteins and the anatomical localization of the lesions, metastasis, as well as with the Bryne`s histolologic grading of malignancy system. It was not observed significant statistical association between the localization of the lesions and the malignancy score, however, had a significant correlation between the histologic parameters of malignancy gradation and the total score of malignancy, being that the parameter degree of keratinization presented the highest correlation (r = 0,844). Taking in consideration the anatomical localization of the lesions, it was not significant difference between the profile of expression and the amount of immunopositive cells for Ecaderina and CD44v6. To the metastasis variable, also it was not observed significant difference between the profile of expression and the amount of immunopositive cells for evaluated proteins. However, it was observed a statistical significant difference in relation to the scores of malignancy, being that the low score presented the highest values for the profile of expression and the amount of immunopositive cells for the E-caderina and the CD44v6. It was observed a statistically significant and negative correlation between the expression profile, the amount of E-cadherin and CD44v6 immunopositive cells and the total score of malignancy. Therefore, based in the results of this study, it was concluded that the expression of the immunohistochemical markers E-caderina and CD44v6 did not constitute histological indicator of aggressiveness for the patients with lower lip and tongue squamous cell carcinomas

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The adhesion molecules E-cadherin and β-catenin have been studied as possible markers to distinguish carcinomas with and without metastatic potential. The objective of this research was to study the imunohistochemistry expression of the E-cadherin and β-catenin in oral squamous cell carcinoma (OSCC), aiming to contribute for the better understanding of the biological behavior of this lesion. The sample consisted of 30 cases of OSCC, being 15 of tongue and 15 of lower lip. The profile and intensity of labeling and semi quantitative analysis of the percentage of immunopositive tumoral cells in membrane for E-cadherin and β-catenin had been related with the anatomical localization of the lesion, the presence or not of nodal metastasis and the histological grade of malignancy in the invasive front area of the tumor. It was registered the presence or not of cytoplasmic and nuclear labeling of the β-catenin. The results had been submitted to the statistical analysis, being used the Mann-Whitney Test, the Fisher Test and the Spearman Correlation Coefficient (α=0, 05). The results showed that the expression in membrane for E-cadherin and β-catenin was, predominantly, the heterogeneous profile in the lower lip and tongue carcinomas, as well as in the cases with and without nodal metastasis. It was not observed significant statistical difference between expression profile and amount of immunopositive cells for E-cadherin, β-catenin and the anatomical localization of the lesion and for the presence or not of nodal metastasis. However, there was significant difference of the reduced expression of these proteins with the high score of malignancy. It was verified that the expression of the β-catenin in cytoplasm was present in 22 (73.33%) of the 30 analyzed cases, and 6 cases (20%) showed nuclear expression. The statistical analysis detected significant association between the expression of the β-catenin in the cytoplasm with the histological grade of malignancy, being this molecule more frequently present in the cytoplasm in the cases of high score of malignancy. It was concluded that the reduced immunoexpression of these proteins in membrane can be related with the lowest cellular differentiation, as well as with the pattern of invasion in nests and isolated cells, demonstrated in the cases of OSCC with high histological grade of malignancy

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Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the oral cavity and reach a large number of individuals, has become an important public health problem. Studies have demonstrated changes in pathway components BMP in various types of cancers as prostate, colon, breast, gastric and OSCCs. Is the current knowledge that these proteins may exert pro-tumor effect in more advanced stages of neoplastic development coming to favor progression and invasion tumor. The inhibition of the signaling pathway BMP-2 through its antagonists, have shown positive results of antitumor activity and use of Noggin may be a novel therapeutic target for cancer. Given this evidence and the few studies with BMP-2, Noggin and OSCC, the objective of this research was to evaluate the effect of BMP-2 and its antagonist Noggin on proliferation and migration cell in line of cell cultures of human tongue squamous cell carcinoma (SCC25). The study was divided in three groups, a control group, where SCC25 cells suffered no treatment, a BMP-2 group, in which cells were treated with 100ng/ml of BMP-2 and a group of cells that were treated with 100ng/ml of Noggin. For the proliferation assay and cell cycle were established three time intervals (24, 48 and 72 hours). Proliferative activity was investigated by trypan blue and cell cycle analysis by staining with propidium iodide flow cytometry. The potential for migration / invasion of SCC25 cells was performing by a cell invasion assay using Matrigel in a 48-hour interval. The proliferation curve showed a higher proliferation in cells treated with BMP-2 in 72 hours (p < 0.05), and lower overgrowth and cell viability in Noggin group. Recombinant proteins favored a greater percentage of cells in cell cycle phase Go/G1 with a statistically significant difference in the interval of 24 hours (p < 0.05). BMP- 2 produced a greater invasion of cells studied as well as its antagonist Noggin inhibits invasion of cells (p < 0.05). Thus, these results indicate that BMP-2 promotes malignant phenotype, dues stimulates proliferation and invasion of SCC25 cells and, its antagonist Noggin may be an alternative treatment, due to inhibit the tumor progression

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The progression of the oral squamous cells carcinomas (OSCCs) seems to suffer influence from related factors to the host, as local and systemic immunologic response, which are essential to the antineoplasic defenses. The purpose of this study was evaluate the local immunity in 30 tongue and 20 lower lip SCC by immunohistochemistry method, utilizing antibodies anti-CD3, CD4, -CD8, -CD25 e -ζ(zeta), which immunoexpressions were compared considering the anatomical localization, the intensity of the inflammatory infiltrate into the front of invasion and metastases. The CD4/CD8+ ratio was calculated for each case and associate with the mentioned variable, being the intensity of the inflammatory infiltrated also compared with the anatomical localization and metastase and for this the cases had been grouped in two categories: (n = 10) absent/scarce inflammatory infiltrate; and (n = 40) moderate/intense infiltrate. Fisher´s exact test was performed (α= 0.05) and it was not observed any significant correlation between these groups with anatomical sites and metastases. With regard to the immunoexpression, the CD3+, CD4+, CD8+ and CD25+ cells count was higher in the lower lip SCCs while the anti-ζimmunomarcation was more evident in the non metastatic cases. Through the statistical analyses, it was verified that the CD3 exhibited positive-significant correlation with the inflammatory infiltrate (p = 0.023). Furthermore, antibodies against CD8 and CD25 cells were also significantly correlated with the inflammatory infiltrate (p = 0.002 and 0.030, respectively) and with the anatomical site (p = 0.004 and p = 0.004) mainly in the lower lip SCCs. CD4/CD8 ratio did not show significant association with metastase nor with anatomical localization. We conclude that the inflammatory infiltrated of the Bryne s (1998) system did not constitute an indicator of aggressiveness in the tongue and lower lip SCCs analyzed and that clinical behavior of the SCCs studied was related in part to the immunohistochemical profile of infiltrated the inflammatory present in tumoral invasion front

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Toxoplasma gondii is a protozoan parasite that induces behavioral changes in rodents. The aim of this study was to evaluate the effect of infection by T. gondii during the chronic phase in working memory and impulsivity in rodents as well as the effect of antipsychotics to reverse any behavioral changes resulting from infection. Female Wistar rats (n = 40) were infected with 25 cysts of the strain ME-49 T. gondii after 4 months the animals were subjected to behavioral tests: tolerance to delay gratification, in which the animal must choose between two rewards, a smaller and more immediate, but delayed and the test of spontaneous alternation, in which the animal must use spatial cues to remember previously visited arms. Antipsychotic drugs were intraperitoneally administered during the testing of the behavioral experiments, the antipsychotic is haloperidol (1.5 mg / kg) administered 60 min before the start of the session and the antipsychotic clozapine (2.5 mg / kg) 30 min before. Animals infected with the parasite did not show operating deficits of memory, and motor impairment did not develop, however motor impairment was observed only in animals treated with haloperidol. It was found that administration of clozapine and haloperidol increased the percentage of alternation in infected and control groups in task switching espontânea.Não no distinction between control animals and infected the test of tolerance to delay gratification in relation to the percentage of choices greatest reward, during the pre-training and training, in which there is a delay of 15 s to access the great reward, however it was observed that infected animals prefer the greatest reward, when there is a delay of 30 s when compared to control group. The administration of clozapine possible that infected animals chose the greatest reward in the delay of 30 seconds during the test. These data suggest that infected mice do not exhibit deficits in working memory and that clozapine has therapeutic efficacy in improving cognitive performance of mice infected

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Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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JUSTIFICATIVA E OBJETIVOS: A dexmedetomidina, agonista alfa2-adrenérgico com especificidade alfa1:alfa2 1:1620, não determina depressão respiratória, sendo utilizada no intra-operatório como sedativo e analgésico. Esse fármaco tem sido empregado com os opióides em anestesia de procedimentos com elevado estímulo doloroso, como os abdominais intraperitoneais, não havendo referências sobre seu uso como analgésico único. Comparou-se a dexmedetomidina ao sufentanil em procedimentos intraperitoneais, de pacientes com mais de 60 anos de idade. MÉTODO: Foram estudados 41 pacientes divididos aleatoriamente em dois grupos: GS (n = 21), que recebeu sufentanil, e GD (n = 20), dexmedetomidina, ambos na indução e manutenção da anestesia. Os pacientes receberam etomidato (GS e GD) com midazolam (GD) na indução, isoflurano e óxido nitroso na manutenção da anestesia. Foram avaliados os atributos hemodinâmicos (pressão arterial média e freqüência cardíaca), tempos de despertar e de extubação ao final da anestesia, locais onde os pacientes foram extubados - sala de operação (SO) ou sala de recuperação pós-anestésica (SRPA), tempo de permanência na SRPA, necessidade de analgesia suplementar e antiemético na SRPA, complicações apresentadas na SO e SRPA, índice de Aldrete-Kroulik na alta da SRPA e a necessidade de máscara de oxigênio na alta da SRPA. RESULTADOS: Não houve diferença quanto à estabilidade hemodinâmica e GD apresentou menor tempo de permanência na SRPA e menor necessidade de máscara de oxigênio na alta da SRPA. CONCLUSÕES: A dexmedetomidina pode ser utilizada como analgésico isolado em operações intraperitoneais em pacientes com mais de 60 anos, determinando estabilidade hemodinâmica semelhante à do sufentanil, com melhores características de recuperação.