A Camellia sinensis, vem sendo amplamente estudada, em função das suas propriedades medicinais, devido aos polifenóis com funções antioxidantes, tendo seu uso propostos como terapêutica para algumas doenças metabólicas como o Diabetes mellitus. A ingestão diária de antioxidantes, principalmente com compostos fenólicos pode retardar o aparecimento destas doenças. O atual trabalho o avaliou possível efeito terapêutico do chá verde (Camellia Sinensis) em ratos diabéticos induzido pela estreptozotocina, parâmetros clínicos (peso, ingestão hídrica) e laboratoriais (glicemia de jejum, colesterol total, triglicérides, proteínas totais, albumina e uréia) esse efeito na glândula submandibular pelo método morfométrico. Cento e sessenta ratos machos com 2 meses de idade foram distribuídos inicialmente em controle (n = 80) e diabéticos (n = 80). Os animais do grupo controle água (CA) e diabético água (DA) consumiram água como dieta líquida e os animais dos grupos controle chá (CC) e diabético chá (DC) receberam apenas dieta líquida de chá verde. Os parâmetros bioquímicos e morfométricos foram avaliados nos períodos experimentais de 15, 30, 60 e 90 dias (n = 5), após a indução. Os resultados mostraram que: a) a ingestão hídrica dos animais dos grupos DA e DC foram em média 6 vezes maior em relação aos controles; b) aos 15 dias, todos os animais dos grupos CA, CC e DA apresentaram aumento nos índices glicêmicos final de, respectivamente, 45 mg/dL, 65 mg/dL e 88mg/dL em relação ao período inicial, enquanto que todos os animais do grupo DC tiveram seus índices glicêmicos reduzidos em média de 119 mg/dL; c) nos ratos diabéticos o perfil bioquímico das proteínas totais e albumina foram menores em relação aos controles e o da uréia maior, enquanto que, o colesterol total, triglicérides não apresentaram diferenças; d) os ácinos das glândulas submandibulares dos animais dos grupos DA e DC exibiram aumento da eosinofilia citoplasmática e ausência da bosofilia basal, indicativos de alteração no conteúdo protéico e na síntese protéica, além de núcleos picnóticos, indicativos de morte celular por apoptose. Morfometricamente, o volume individual das células acinosas aumentou, enquanto que, o número total de células diminuiu, mantendo o volume total dos ácinos constante durante todo período experimental; e) os ductos granulosos, no grupo CA apresentaram aumento de 125% no seu volume total entre 15 e 90 dias, decorrente do desenvolvimento desta estrutura, aumentando o número e o volume celular. Já, nos DA e DC, o número e o volume individual das células mantiveram-se constante durante todo período experimental. Com base nos resultados obtidos, podemos inferir que a glândula submandibular é um órgão afetado pelo diabetes e a terapêutica utilizada neste experimento (Camellia sinensis) não foi efetiva para o tratamento do diabetes crônica. / The Camellia sinensis, has been widely studied because of their medicinal properties due to the polyphenols with antioxidant functions, and proposed its use as treatment for various metabolic disorders such as diabetes mellitus. The daily intake of antioxidants, mainly phenolic compounds may prevent or delay onset of these diseases. In this study, the possible therapeutic action of green tea (Camellia Sinensis) in diabetic rat induced chemically by streptozotocin was evaluated by clinical (weight, water intake) and laboratory parameters (fasting glucose, total cholesterol, triglycerides, total protein, albumin and urea) and its effect in the submandibular glands by morphometric methods. One hundred and sixty male rats with 2 months of age were distributed initially in control (n = 80) and diabetic (n = 80). The animals of the water control (WC) and water diabetic (WD) groups received only regular drinking water and green tea control (GTC) and green tea diabetic (GTD) groups received green tea solution ad libitum. Morphometric and biochemical parameters were evaluated after 15, 30, 60 and 90 days (n = 5) after induction. The results showed that: a) the water intake of animals from group WD and GTD were six times higher on average than control groups; b) at 15 days, all animals of the WC, WD and GTC groups showed an increase of the glycemic index of, respectively, 45 mg/dL, 65 mg/dL and 88 mg/dL compared to the initial period, while that all animals in CTD group, showed a decrease of 119mg/dL; c) in the diabetic rats of WD and GTD groups the total protein and albumin levels were lower than control groups and urea level higher, whereas, the total cholesterol and triglyceride did not show significant differences, d) the acini of submandibular glands of animals in groups WD and GTD showed increase of the cytoplasmic eosinophilia and absence of the basal basophilia, which may be indicative of changes in protein content and/or structure, and pyknotic nuclei indicative of cell death. Morphometrically, the volume of acinar cells increased, whereas the cell number decreased, maintaining the total volume of acini constant throughout the experimental period, e)the granular convoluted tubules in development showed an increase of 125% between 15 and 90 days in the WC group, due to increase in the number and volume of its cells. In DA and DC groups, the number and volume of cells remained constant throughout the experimental period. Based on the results, we infer that the submandibular gland is an organ affected by diabetes and that the green tea (Camellia sinensis) therapy used in this experiment is not effective for the treatment of chronic diabetes.

L’amertume fait partie intégrante de notre alimentation. Elle est par exemple fortement représentée dans certaines boissons (ex: café) ou dans certains légumes tels les crucifères. Néanmoins, la perception de l’amertume varie entre les individus et certains aliments considérés comme bénéfiques pour la santé peuvent être rejetés en raison de leur goût amer. Des facteurs génétiques (ex : polymorphisme génétique des récepteurs du goût amer) ou environnementaux (ex : âge, prise de médicaments) expliquent en partie les variations interindividuelles dans la perception de l’amertume. Cependant, d’autres facteurs péri-récepteurs pourraient intervenir, notamment la composition salivaire. Afin d’investiguer dans un premier temps le lien existant entre le protéome salivaire propre à un individu et sa sensibilité à l’amertume, le seuil de détection du goût amer de la caféine a été mesuré sur 29 hommes sains. Leur salive au repos a été étudiée par électrophorèse mono- et bidimensionnelle. L’analyse par électrophorèse bidimensionnelle de la salive au repos des 6 sujets les plus sensibles et 6 les sujets les moins sensibles à la caféine a permis la détection de 255 spots, dont 26 étaient significativement différents entre hyper- et hyposensibles. L’identification de ces 26 spots a révélé la surexpression de fragments d’alpha amylase, de fragments d’albumine sérique, et de sous-unités alpha de l’immunoglobuline A ainsi que la sous-expression de cystatine SN chez les hypersensibles. Ce dernier résultat a été confirmé par Western Blot. Ceci a permis de formuler une hypothèse sur le rôle de la protéolyse en bouche sur la sensibilité à l’amertume. Dans un deuxième temps et afin d’étudier l’effet des molécules amères sur la composition salivaire, une étude in vitro a été menée sur la lignée cellulaire de glandes salivaires humaines HSG différenciées en acini ou non. Après une mise au point des conditions de différenciation (culture dite en 3D), la cystatine SN a été détectée dans les cellules HSG par Western blot après traitement des cellules à la caféine, à la quinine, et à l’urée. Après traitement à la caféine à 5, 50 ou 100µM, une quantification par ELISA a mis en évidence que la cystatine SN était toujours plus abondante dans les cellules HSG différenciées que dans les cellules non-différenciées. Spécifiquement dans les cellules différenciées, l’exposition à la caféine induisait une sur-expression de cystatine SN, la teneur maximale en cystatine SN étant observée avec la caféine à 50 µM. La présence de cystatine SN a également été détectée dans les milieux de culture / Bitterness is present in every day beverages (e.g. coffee) and foods (e.g. vegetables such as cruciferous plants). However, bitterness is perceived differently among individuals and some foods considered as healthy may be rejected due to their bitter taste. Several genetic (eg. genetic polymorphism of bitter taste receptors) or environmental (eg. age, medications) factors partly explain the interindividual variability in bitterness perception. However, other peri-receptor factors may intervene, in particular salivary composition. First, in order to investigate the link between salivary proteome and sensitivity to bitterness, the detection threshold to the bitter taste of caffeine was measured in 29 male healthy subjects. Their resting saliva was studied by one- and two-dimensional electrophoresis. Two-dimensional electrophoresis revealed that 26 out of 255 spots were significantly different between the 6 hypersensitive and 6 hyposensitive subjects to the bitter taste of caffeine. Identification of the 26 spots revealed an overexpression of amylase-, serum albumin-, and immunoglobulin A fragments, and an underexpression of cystatin SN in hypersensitive subjects. The latter finding was confirmed by Western blotting. These results have led to formulate an hypothesis on the role of in-mouth proteolysis in bitterness perception. Second, in order to study the effect of bitter molecules on salivary composition, an in vitro study was performed on undifferentiated and differentiated human salivary cell line HSG. After setting the experimental conditions for HSG cell differentiation (culture in 3D conditions), cystatin SN was detected in HSG cells by Western blot after treatment with caffeine, quinine, and urea. After cell exposure with caffeine at 5, 50 and 100 µM, quantification by ELISA demonstrated that cystatin SN was always more abundant in differentiated vs undifferentiated HSG cells. Specifically in differentiated cells, caffeine exposure resulted in over-expression of cystatin SN, 50µM inducing the highest effect. Cystatin SN was also detected in culture media of the HSG cells

Dados da literatura mostram que a inervação simpática possui papel apenas na síntese e secreção das proteínas da saliva. Neste trabalho mostramos que após o tratamento crônico com reserpina, uma droga simpatolítica, houve alteração na síntese de diferentes proteínas em glândulas submandibulares e parótidas relacionadas com vários processos biológicos e a posterior administração de agonistas de adrenoceptores reverteu esses efeitos. Além disso, na glândula parótida, a estimulação da inervação simpática é importante para o processo de exocitose das proteínas secretadas. Esses resultados sugerem que a inervação simpática possui um importante papel para a funcionalidade das glândulas salivares de camundongos, isto é, mantendo estas glândulas em constante estado de ativação, regulando a síntese de diferentes proteínas dessas glândulas ou promovendo a exocitose de proteínas da saliva. Além disso, os resultados mostram que a inervação simpática atua de maneira diferente nas glândulas submandibulares e parótidas de camundongos. / Data in literature show that sympathetic outflow has a role only in stimulating synthesis and secretion of the saliva proteins in mammals. We show that after chronic treatment with reserpine, a sympatholytic drug, there were changes in the synthesis of different proteins in submandibular and parotid glands associated with various biological processes and subsequent administration of adrenoceptor agonists reversed these effects. Furthermore, in the parotid gland, stimulation of the sympathetic outflow is important to the process of exocytosis of secretory proteins. These results suggest that sympathetic outflow plays an important role for the functionality of the mouse salivary glands, namely, keeping these glands in a constant activated stage, regulating the synthesis of different proteins in these glands or promoting the exocytosis of saliva proteins. Furthermore, these results show that the sympathetic outflow acts differently in the mouse.

Orientador: Ana Lia Anbinder / Banca: Gilson César Nobre Franco / Banca: Adriana Aigotti Haberbeck Brandão / Resumo: A ação de beta-bloqueadores na melhoria da qualidade óssea e sua ação anti-inflamatória embasam a hipótese de que a modulação simpática pode influenciar a evolução da doença periodontal (DP). Estudos demonstram relação entre disfunção salivar e DP; no entanto, os efeitos da DP nas glândulas salivares, cuja secreção é controlada pelo sistema nervoso autônomo, são pouco estudados. Objetivou-se analisar os efeitos do bloqueio e da ativação de receptores beta-adrenérgicos na reabsorção alveolar na DP em ratos, assim como os efeitos da DP, associada ou não a tratamento adrenérgico, nas glândulas salivares. Foram utilizados 40 ratos divididos em quatro grupos: (1) Grupo Propranolol 0,1mg/Kg com indução de DP; (2) Grupo Isoproterenol 0,75mg/Kg e DP; (3) Grupo Controle sem DP, com administração solução fisiológica ; (4) Grupo Controle com DP, com administração solução fisiológica. Depois de 14 dias de tratamento, ocorreu a eutanásia. Removeram-se as hemimandíbulas e as glândulas submandibulares e sublinguais para análise. O suporte e a perda óssea alveolar foram determinados radiográfica e macroscopicamente. As glândulas foram pesadas, medidas e submetidas à preparação de rotina para coloração com hematoxilina e eosina e Alcian Blue. Avaliou-se histomorfometricamente a área de ácinos, ductos e a vacuolização celular. Após estatística (p<0,05), verificou-se menor suporte e maior perda alveolar na presença de ligadura e maior perda alveolar em animais com tratados com isoproterenol. O isoproterenol aumentou significantemente peso e dimensões glandulares, reduziu área ductal e vacuolização, e aumentou área acinar na submandibular. Propranolol apenas reduziu vacuolização em relação ao controle com DP, e as demais comparações não foram estatisticamente significantes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The action of beta-blockers in the improvement of bone quality and their anti-inflammatory actions base the hypothesis that sympathetic nervous system modulation can influence periodontal disease (PD). Studies demonstrate a relationship between salivary dysfunction and PD; however, there are few studies about the effects of PD in salivary glands, whose secretion is controlled by the autonomic nervous system. The aim of this study was to analyze the effects of the blockade and of the activation of beta-adrenergic receptors in alveolar resorption in PD in rats, as well as the effects of PD, associated or not to adrenergic treatment, in salivary glands. Forty rats were divided into four groups: (1) group Propranolol 0.1mg/Kg with PD induction; (2) group Isoproterenol 0.75mg/Kg and PD; (3) group Control without PD, which received saline; (4) group Control with PD, which also received saline. After 14 days of treatment, euthanasia occurred. Hemimandibles and submandibular and sublingual glands were removed for analysis. Alveolar bone support and alveolar bone loss were evaluated by radiographic and macroscopic analysis. Gland weight and dimensions were measured, and then the samples were submitted to routine preparation for hematoxilin and eosin and Alcian blue stainings. Acinar and ductal area and cellular vacuolization were histomorphometrically evaluated. After statistical analysis (p <0.05), less alveolar bone support and larger alveolar loss were verified in animals with ligatures for PD induction and larger alveolar loss were also verified in rats treated with isoproterenol. Isoproterenol also increased significantly glandular weight, size and acinar area, and reduced ductal area and cellular vacuolization in submandibular glands. Group Propranolol presented less vacuolization than group Control with DP... (Complete abstract click electronic access below) / Mestre

Diabetes mellitus is associated with several clinically significant abnormalities in the oral cavity and salivary glands, the most common being periodontitis, salivary gland enlargement and a sensation of dry mouth. The pre­valence of dental caries in diabetics is mostly reported to be decreased or unaffected. Since there is a shortage of information concerning the influence of metabolic control and duration of diabetes on these abnormalities, the present studies were performed. Three-month-old rats were made alloxan-diabetic and investigated after one and twelve months’ duration of dia­betes for oral lesions and feeding behavior. They had free access to a standard pellet diet and tap water. Strepto­coccus mutans and lactobacilli were naturally occurring. In diabetic rats the proportion of the oral flora which was lactobacilli was positively correlated to the blood glucose level. Untreated long-term alloxan-diabetic rats de­veloped advanced periodontal disease and root surface caries in the molars at sites of interdental impaction of foreign material. The degree of alveolar bone loss was positively correlated to the blood glucose level. Diabetic rats were hyperphagic and had a longer total eating time, including day-time eating, mainly by having longer meals but no significant increase of meal frequency, as compared with non-diabetic animals. The untreated al­loxan-diabetic rats developed reduced salivary gland weight which was of the same degree in short- and long­term diabetic animals. Short- and long-term untreated alloxan-diabetic rats showed a similar degree of morpho- metrically estimated lipid accumulation in the acinar cells of the submandibular glands, and the degree was posi­tively correlated to the blood glucose level. However, lipid inclusion occurred only in rats with a morning non­fasting blood glucose level exceeding 15 mmol/L. The capillaries in the submandibular glands of the untreated long-term alloxan-diabetic rats had a significantly increased thickness of the basement membranes as compared with the observations in short-term diabetic and non-diabetic rats. Untreated alloxan-diabetic rats were also shown to have a decreased salivary flow rate compared with non-diabetic rats, and the decreased flow was negatively correlated to the blood glucose concentration. Salivary flow rate increased with the duration of the disease. The diabetic rats had increased salivary glucose levels, which were positively correlated to blood glucose values when the latter were above 15 mmol/L, suggesting a threshold mechanism for salivary glucose excretion. Insulin therapy reversed salivary flow rate and salivary glucose concentrations toward normal. Salivary investigations were performed in eleven diabetic patients on two occasions with different metabolic con­trol. Salivary flow rate showed marked interindividual differences but was not significantly changed by improv­ed metabolic control although several of the patients initially had severely deranged glucose metabolism. A posi­tive correlation between the glucose concentration in blood and saliva was seen in the parotid saliva during secre­tory stimulation. No significant change in electrolytes, amylase or antimicrobial factors was found. / <p>S. 1-48: sammanfattning, s. 49-90: 5 uppsatser</p> / digitalisering@umu

Submitted by (lucia.rodrigues@ufrpe.br) on 2016-06-08T13:37:15Z No. of bitstreams: 1 Jaciel Benedito de Oliveira.pdf: 2001810 bytes, checksum: 849f2538ec8321a9c6a102564bb281e9 (MD5) / Made available in DSpace on 2016-06-08T13:37:15Z (GMT). No. of bitstreams: 1 Jaciel Benedito de Oliveira.pdf: 2001810 bytes, checksum: 849f2538ec8321a9c6a102564bb281e9 (MD5) Previous issue date: 2014-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The aim of this study was to observe the morphometric, histological and histométricos aspects of submandibular glands of rats treated with botulinum toxin type A (BTX-A) and with bovine gelatin. We used 80 submandibular glands of adult Wistar rats and divided into three groups: group I, control (n = 14); group II (n = 34) submitted the intraglandular injection of bovine gelatin (0.25 mg); and group III (n = 32) treated with intraglandular injection of botulinum toxin type A (2.5 U). The groups II and III were divided into 3 subgroups according to the day of analysis of glands (7, 15 and 28 days after treatment), when they were removed, heavy and measures immediately for morphometric analysis. Next, were fixed in paraformaldehyde 4 % and processed conventionally for light microscopy, stained in H.E., P.A.S., alcian blue, Gomori trichrome and picrosirius red. Morphometric differences were not observed between subgroups of group III, however in group II there was a significant difference between the three subgroups in the longitudinal length (p = 0.030) and transverse length (p = 0.025), having the gland has shown greater at day 28th after treatment. Histometrically, serous and mucous acini group III, were presented with a smaller diameter compared with the acinithe subgroups treated with bovine gelatina (group II). The wall thickness of the striated duct Group III was lower than in other. Histologically, there was a greater amount of cytoplasmic vacuolization in group III. addition to the greater spacing between the acini. Thus, we conclude that botulinum toxin type A interferes with the structural organization of the submandibular glands, promoting a reduction in the diameter of serous acini and in wall thickness striated ducts, macroscopically but this difference was not significant. / O objetivo deste trabalho foi observar os aspectos morfométricos, histométricos e histológicos das glândulas submandibulares de ratas tratadas com toxina botulínica tipo A (BTX-A) e com gelatina bovina. Foram utilizadas 80 glândulas submandibulares de ratas Wistar adultas e divididas em três grupos: grupo I controle (n = 14); grupo II (n = 34) submetidas a injeção intraglandular de gelatina bovina (0,25 mg); e grupo III (n = 32) tratadas com injeção intraglandular de toxina botulínica tipo A (2,5 U). Os grupos II e III foram divididos em 3 subgrupos de acordo com o dia de análise das glândulas (7, 15 e 28 dias após o tratamento), quando foram removidas, imediatamente pesadas e medidas para análise morfométrica. A seguir, foram fixadas em paraformaldeído 4% e processadas convencionalmente para microscopia de luz, coradas em H.E, P.A.S., alcian blue, tricrômico de Gomori e picrossirius red. Testes estatísticos dos resultados morfométricos e histométricos obtiveram o nível de significância de 0,05 (5%). Morfometricamente não foram observadas diferenças entre os subgrupos do grupo III, entretanto no grupo II houve diferença significativa entre os três subgrupos no comprimento longitudinal (p = 0,030) e comprimento transversal (p = 0,025), tendo a glândula se apresentado maior no 28º dia após o tratamento. Histometricamente, os ácinos serosos e mucosos do grupo III, apresentaram-se com diâmetro menor quando comparado com o ácinos dos subgrupos tratados com gelatina bovina (grupo II). A espessura da parede do ducto estriado do grupo III foi menor que nos demais. Histologicamente, observou-se a maior quantidade de vacuolizações citoplasmáticas no grupo III, além do maior espaçamento entre os ácinos. Dessa forma, concluímos que a toxina botulínica tipo A interfere na organização estrutural das glândulas submandibulares, promovendo uma diminuição no diâmetro dos ácinos serosos e na espessura da parede dos ductos estriados, mas que macroscopicamente tal diferença não se mostrou significante.

Dados da literatura mostram que a inervação simpática possui papel apenas na síntese e secreção das proteínas da saliva. Neste trabalho mostramos que após o tratamento crônico com reserpina, uma droga simpatolítica, houve alteração na síntese de diferentes proteínas em glândulas submandibulares e parótidas relacionadas com vários processos biológicos e a posterior administração de agonistas de adrenoceptores reverteu esses efeitos. Além disso, na glândula parótida, a estimulação da inervação simpática é importante para o processo de exocitose das proteínas secretadas. Esses resultados sugerem que a inervação simpática possui um importante papel para a funcionalidade das glândulas salivares de camundongos, isto é, mantendo estas glândulas em constante estado de ativação, regulando a síntese de diferentes proteínas dessas glândulas ou promovendo a exocitose de proteínas da saliva. Além disso, os resultados mostram que a inervação simpática atua de maneira diferente nas glândulas submandibulares e parótidas de camundongos. / Data in literature show that sympathetic outflow has a role only in stimulating synthesis and secretion of the saliva proteins in mammals. We show that after chronic treatment with reserpine, a sympatholytic drug, there were changes in the synthesis of different proteins in submandibular and parotid glands associated with various biological processes and subsequent administration of adrenoceptor agonists reversed these effects. Furthermore, in the parotid gland, stimulation of the sympathetic outflow is important to the process of exocytosis of secretory proteins. These results suggest that sympathetic outflow plays an important role for the functionality of the mouse salivary glands, namely, keeping these glands in a constant activated stage, regulating the synthesis of different proteins in these glands or promoting the exocytosis of saliva proteins. Furthermore, these results show that the sympathetic outflow acts differently in the mouse.

During marijuana and alcohol consumption as well as during inflammation the reproductive axis is inhibited, mainly through the inhibition of luteinizing hormone-releasing hormone release. In male rats, this inhibitory effect is mediated, at least in part, by the activation of hypothalamic cannabinoid type 1 receptors (CB1). During inflammation, this activation of the endocannabinoid system seems to be mediated by an increase in TNF-α production followed by anandamide augmentations, similarly the effect of intragastric administration of ethanol (3 g/kg) seems to be due to an increase in anandamide. On the other hand, a number of different actions mediated by the endocannabinoid system in various organs and tissues have been described. Both cannabinoid receptors, CB1 and CB2, are localized in the submandibular gland where they mediate the inhibitory effect of intrasubmandibular injections of the endocannabinoid anandamide (6 × 10–5M) on salivary secretion. Lipopolysaccharide (5 mg/kg/3 h) injected intraperitoneally and ethanol (3 g/kg/1 h) injected intragastrically inhibited the salivary secretion induced by the sialogogue metacholine; this inhibitory effect was blocked by CB1 and/or CB2 receptor antagonists. Similar to the hypothalamus, these effects seem to be mediated by increased anandamide. In summary, similar mechanisms mediate the inhibitory actions of endocannabinoids and cannabinoids in both hypothalamus and submandibular gland during drug consumption and inflammation. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

O tratamento anti-HIV conhecido como HAART (Highly Active Antiretroviral Therapy) se tornou comum por volta de 1996, e utiliza 3 ou 4 diferentes medicamentos em combinação - geralmente dois inibidores de transcriptase reversa + 1 ou 2 inibidores de protease. A introdução desse tipo de tratamento trouxe um grande impacto na morbidade e mortalidade de indivíduos infectados pelo HIV. Os inibidores de protease (PIs) são uma boa alternativa às falhas terapêuticas observadas com o uso dos inibidores de transcriptase reversa, no entanto também são associados a vários efeitos tóxicos, como desconforto abdominal, vômito, diarréia, dor de cabeça, tontura, lipodistrofia, hipercolesterolemia, hipertrigliceridemia e hiperglicemia. Em função da existência de efeitos adversos e da condição do ritonavir como protótipo desse tipo de medicação, nosso objetivo é avaliar o efeito desse medicamento sobre os epitélios de revestimento e glandular relacionados à cavidade bucal, de forma a identificar a possibilidade da existência de complicações bucais relacionadas ao uso de inibidores de protease. Ratos albinos (Wistar) foram tratados com Ritonavir (10mg/Kg) por períodos de 4 e 8 semanas. Foram avaliadas as taxas séricas de triglicérides e colesterol (total, HDL, LDL, VLDL). Ao final dos períodos de tratamentos propostos, os animais foram sacrificados, e as peças utilizadas no estudo foram colhidas, (sangue, pele, língua, palatos e glândulas salivares). O sangue coletado foi imediatamente centrifugado sendo o plasma foi utilizado para avaliação das lipoproteínas. Os tecidos colhidos foram fixados, descalcificados quando necessário, processados para inclusão em parafina, cortados com 6&micro;m de espessura, montados em slides e corados com hematoxilina e eosina, para avaliação histopatológica, morfométrica e estereológica. Os dados colhidos foram apresentados em valores médios, e as diferenças analisadas por testes estatísticos adequados para a comparação entre as amostras. Nossos resultados mostram pequenas variações nas características morfológicas de epitélios de revestimento e glandulares, variações essas que poderiam deixar esses tecidos mais propensos a sofrer alterações significativas com traumas ou injúrias, comuns nos tecidos bucais. Embora observadas com pequeno grau de expressão, essas variações, parecem ser progressivas, ou seja, mais expressivas com o uso continuado do medicamento. Mais estudos devem ser realizados, principalmente voltados para avaliações histoquímicas, bioquímicas e moleculares, no entanto nosso estudo é um alerta inicial para a avaliação dos tecidos bucais de pacientes que utilizam inibidores de protease. / HAART had a dramatic impact on the HIV infection, however, protease inhibitor exhibit significant drug-drug interactions, and side effects. There are only few data on effects of protease inhibitors on oral tissues. We propose to observe experimental effects of ritonavir on oral epithelial tissues, covering and glandular. Wistar rats received Ritonavir twice a week for 4-8 weeks. Controls received no treatment. At the time for sacrifice, plasma were collected for evaluation of triglycerides, total cholesterol, HDL, LDL and VLDL. Were also collected skin, tongue, palate and glandular tissues Lipoproteins were evaluated and histological examination of skin, mucosal epithelium on tongue, palate and salivar submandibular glandula were made under light microscope. Morphometric methods (cariometry and stereology) were used. Data were statistically analysed by Kruskal Wallis test for multiple samples, since our data were considered not-normal. P[U] 0.05 were considered statistically significant. Our results show that protease inhibitor may be associated with small alterations in epithelial tissues, significant mostly when on longer times using the medication. The complete significance of this data has to be better understood, and other studies has to be done to define these points.

INTRODUÇÃO: A doença de Chagas é a parasitose endêmica mais importante na América Latina. O acometimento das glândulas salivares nesta doença é ainda pouco estudado. Há estudo com portadores da doença através de sialografia convencional, o que motivou a realização deste estudo com a utilização da sialorressonância (sialo RM), por ter melhor sensibilidade e especificidade em relação a outros métodos e não ser invasiva, com o intuito de identificar alterações glandulares nos pacientes da forma indeterminada que possibilitem sua reclassificação para a forma digestiva. OBJETIVO: avaliar as alterações encontradas pela sialo RM e correlacionar com dados clínicos e laboratoriais. METODOLOGIA: Estudaram-se 180 glândulas salivares maiores em 45 pacientes pela sialo RM que foram divididos em três grupos: A portadores da doença de Chagas na forma clínica indeterminada; B portadores da doença de Chagas na forma digestiva; C controle. As idades médias encontradas foram: 48; 55 e 50 anos, respectivamente. Quanto ao sexo, 9; 11 e 10 pacientes dos grupos avaliados eram do feminino. Foram utilizadas seqüências anatômicas ponderadas em T1 e T2, e seqüências específicas para sialo RM T2 fast spin eco 2D e 3D. Realizou-se avaliação clínica específica, sialometria, nasofibroscopia, e dosagem sanguínea da amilase. RESULTADOS: Os volumes médios das glândulas parótidas nos grupos foram de: A (31,1cm3); B (27,4cm3); C (32,4cm3) e das submandibulares foram: A (6,1 cm3); B (5,2 cm3) e C (7,0 cm3). Observou-se um caso no grupo A e outro no grupo B, com afilamento e importante substituição gordurosa de uma das glândulas. O calibre médio dos ductos parotídeos principais foi de: A (1,5mm) tortuosidade e dilatação segmentar em um caso; B (1,3mm) um deles não visualizado e C (1,2mm). Os ductos submandibulares principais tiveram calibre médio de: A (1,5mm); B (1,7mm) - um deles não visualizado; C (1,3mm). Os ductos salivares secundários parotídeos não foram identificados em: A (13,3%); B (20,0%); C (6,7%) e submandibulares, apenas um caso no grupo B. Os ductos salivares terciários parotídeos não foram visualizados em: A (43,3%); B (43,3%); C (33,3%) e submandibulares: A (40,0%); B (23,3%); C (20,0%). Observou-se dilatação sacular/cisto em apenas um ducto parotídeo do grupo B. Das queixas clínicas a xerostomia foi a mais prevalente: A (40,0%); B (53,3%); C (13,3%), com p = 0,066. A sialometria após estímulo apresentou-se alterada nos grupos em: A (60%); B (86,67%) e C (53,33%). O diâmetro parotídeo principal dos indivíduos com amilase normal foi menor que nos indivíduos com amilase anormal (p=0,046). CONCLUSÕES: Os volumes médios das glândulas submandibulares foram menores e o calibre dos ductos salivares de Wharton foi maior nos pacientes infectados, com diferença estatística. Em 5 casos houve alteração na morfologia glandular e/ou ductal. Foram visualizados menos ramos ductais de segunda e terceira ordem das glândulas parótidas e submandibulares em relação ao controle. / INTRODUCTION: Chagas disease is the most important endemic parasitosis in Latin America. The salivary glands onsets for this disease have been poorly studied. For MR (magnetic resonance) sialography has a better sensibility and specificity when compared to different methods and for not being invasive, it is used to identify glandular alterations in patients in the undetermined form, which possibility its reclassification to the digestive form. OBJECTIVES: Present work intends to evaluate the alterations found by MR sialography in Chagas disease patient bearers and correlate them with clinical and laboratorial data. CASUISTIC and METHOD: 180 Major salivary glands were studied in 45 patients by MR sialography divided into 3 groups: A Chagas disease bearers in the uncertain clinical form; B Chagas disease bearers in the digestive form; C Control group. Average ages were: 48; 55 and 50 years, respectively. Concerning sex, nine; 11 and 10 of the evaluated groups were feminine. Anatomical sequences were pondered in T1 and T2, as well as specific sequences for MR sialography T2 fast spin eco 2D and 3D. Specific clinical evaluation, sialometry, nasofibroscopy and blood dosages of amilasis were also evaluated. RESULTS: The parotids glands volumes for groups and expressed, varied for as presented: A (31.1 cm3); B (27.4 cm3); C (32.4 cm3) and for submandibular glands were: A (6.1 cm3); B (5.2 cm3) and C (7,0 cm3). A case was observed in group A and another one in group B, presenting gauging and an important fatty substitution for one of the glands. Main parotid ducts caliber or firstrate order, varied from: A (1.5mm) tortuosity and segmental dilation in one case; B (1.3mm) one of them not visualized and C (1.2mm). Submandibular main ducts presented calibers of: A (1.5mm); B (1.7mm) - one of them not visualized; C (1.3mm). Secondary salivary ducts of the parotid were not identified in: A (13.3%); B (20.0%); C (6.7%) and concerning to submandibular glands, only one case in group B was not identified. Tertiary salivary ducts of the parotid gland were not visualized in: A (43.3%); B (43.3%); C (33.3%) and for submandibular glands: The (40.0%); B (23.3%); C (20.0%). Saccular dilatation was observed in only one parotid of the group B. Among the clinical complaints, xerostomy was the most prevailing A (40.0%); B (53.3%); C (13.3%) p = 0,066. The sialometry after stimulus showed to be altered in the groups as follows: A (60.0%); B (86.7%) and C (53.3%) - <0,001. The main parotid duct diameter of individuals with normal amilasis was smaller than those in the ones with abnormal amilasis (p=0,046). CONCLUSION: The salivary gland volumes were smaller and there was enlargement in Wharton ducts caliber in patients infected by the disease, with statistical difference. There was alteration in the glandular and/or ductal morphology in five cases. Ductal branches of second and third order salivary glands in Chagas disease chronic form bearers were not visualized more often than in healthy patients. Xerostomy was the most reported complaint by patients infected by Tripanosoma cruzi, and there was a bigger association with abnormal pharyngeal nasofibroscopy. Sialometry after stimulus showed to be altered in the groups, especially in patients with chronic digestive form.