Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-02-02T14:33:26Z No. of bitstreams: 1 HelicarlosBatistaDeMorais_DISSERT.pdf: 1562953 bytes, checksum: 9d4f3c123ecc57b12aab4eed13855262 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-02-09T16:56:04Z (GMT) No. of bitstreams: 1 HelicarlosBatistaDeMorais_DISSERT.pdf: 1562953 bytes, checksum: 9d4f3c123ecc57b12aab4eed13855262 (MD5) / Made available in DSpace on 2017-02-09T16:56:04Z (GMT). No. of bitstreams: 1 HelicarlosBatistaDeMorais_DISSERT.pdf: 1562953 bytes, checksum: 9d4f3c123ecc57b12aab4eed13855262 (MD5) Previous issue date: 2016-08-31 / A doen?a periodontal representa um grupo de les?es imuno-inflamat?rias que afetam tanto os tecidos de prote??o como os de sustenta??o dos dentes. Seu principal agente etiol?gico ? o biofilme bacteriano, contudo a destrui??o do tecido periodontal ? provocada principalmente pela resposta exacerbada do sistema imunol?gico do hospedeiro. Estudos recentes evidenciam o efeito anti-inflamat?rio e antioxidante dos f?rmacos antidiab?ticos orais pertencentes ? classe das sulfonilur?ias sobre algumas doen?as inflamat?rias. O objetivo desse trabalho foi avaliar a a??o da gliclazida (GLI), um antidiab?tico oral que vem apresentando efeito anti-inflamat?rio e antioxidante, sobre a doen?a periodontal em ratos que foram induzidos atrav?s de ligadura. Utilizou-se 125 ratos da ra?a wistar que foram distribu?dos aleatoriamente em 5 grupos com 25 animais cada: (NL) n?o foi submetido a indu??o da doen?a periodontal, mas recebeu solu??o salina; (L) Foi submetido a indu??o da doen?a periodontal e recebeu solu??o salina; (GLI 1mg) Foi submetido a indu??o da doen?a periodontal e recebeu GLI 1 mg/kg; (GLI 5mg) Foi submetido a indu??o da doen?a periodontal e recebeu GLI 5 mg/kg; e (GLI 10mg) Foi submetido a indu??o da doen?a periodontal e recebeu GLI 10 mg/kg. Os grupos foram tratados com solu??o salina (NL e L) ou GLI (GLI 1, GLI 5 e GLI 10mg) por gavagem durante o per?odo de 10 dias. Ap?s a eutan?sia dos animais, que ocorreu no d?cimo primeiro dia, os tecidos periodontais foram removidos e passaram pelas seguintes an?lises: morfom?trica, histopatol?gica, imuno-histoqu?mica, glutationa (GSH), PCR em tempo real (RT-PCR), malonalde?do (MDA) e mieloperoxidase (MPO). Notou-se que o tratamento com GLI 1 mg/kg foi capaz de reduzir o MDA (p <0.05), IL-1? (p <0.05), TNF-? (p <0.05) e MPO (p <0.05). Reduziu ainda a express?o de MMP-2, RANK, RANKL, catepsina K, SOD e elevou a express?o de OPG. Tendo ainda a dose de GLI 1mg/kg de forma simult?nea diminu?do a express?o de NF-?B p65, de Pl3K e tamb?m do AKT em compara??o ao grupo L (p <0.01). Esses resultados denotam que a GLI na dosagem de 1mg/kg conseguiu apresentar a??o anti-inflamat?ria na doen?a periodontal induzida, pois diminuiu os efeitos da perda ?ssea alveolar, promoveu a redu??o dos n?veis de citocinas pr?-inflamat?rias e aumentou a express?o de agentes anti-inflamat?rios. / Periodontal disease is a group of immuno inflammatory diseases that have the potential to affect both the protective fabrics as support teeth, the principal etiologic agent is bacterial biofilm, but the destruction of periodontal tissue is primarily caused by excessive response the host immune system. Recent studies show anti-inflammatory and antioxidant effect of oral antidiabetic drugs belonging to the sulfonylurea class of some inflammatory diseases. The aim of this study was to evaluate the action of gliclazide (GLI), an oral antidiabetic which has shown anti-inflammatory and antioxidant effect on periodontal disease in rats that were induced by ligation. We used 125 Wistar rats were randomly divided into 5 groups of 25 animals each: (NL) inducing periodontal disease has not been submitted but received saline solution; (L) has undergone induction of periodontal disease and received saline; (GLI 1mg) inducing periodontal disease GLU has been made and received 1 mg / kg; (GLI 5mg) was subjected to induction of periodontal disease GLU and received 5 mg / kg; and (GLI 10mg) was subjected to induction of periodontal disease GLU and received 10 mg / kg. The groups were treated with saline (NL and L) or GLI (1 GLY, GLY GLY 5 and 10mg) over a period of 10 days. After sacrificing the animals, which occurred on the eleventh day, the periodontal tissues were removed and passed the following tests: morphometric histopathologic, immunohistochemical, glutathione (GSH), real-time PCR (RT-PCR), malondialdehyde (MDA) and myeloperoxidase (MPO). It is noted that treatment with GLI 1 mg / kg was able to reduce the MDA (p <0.05) IL-1? (p <0.05), TNF-? (p <0.05) and MPO (p <0.05). also decreased MMP-2 expression, RANK, RANKL, cathepsin K, SOD and increased OPG expression. Still in the dose GLI 1mg / kg simultaneously reduced NF-?B p65 expression of AKT Pl3K and also compared to the L group (p <0.01). These results show that the GLI dosage of 1mg / kg could provide the anti-inflammatory action induced periodontal disease because the effects of decreased alveolar bone loss, caused a reduction in the levels of pro-inflammatory cytokines and increase expression of anti-agents inflammatory.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-10-05T00:11:28Z No. of bitstreams: 1 LorenaDeSouzaAraujo_DISSERT.pdf: 7643028 bytes, checksum: 6b215a3176b087904cc8a05dd18daa3b (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-10-16T23:17:41Z (GMT) No. of bitstreams: 1 LorenaDeSouzaAraujo_DISSERT.pdf: 7643028 bytes, checksum: 6b215a3176b087904cc8a05dd18daa3b (MD5) / Made available in DSpace on 2017-10-16T23:17:41Z (GMT). No. of bitstreams: 1 LorenaDeSouzaAraujo_DISSERT.pdf: 7643028 bytes, checksum: 6b215a3176b087904cc8a05dd18daa3b (MD5) Previous issue date: 2017-07-21 / A Mucosite Oral (MO) ? uma das principais complica??es envolvidas no tratamento do c?ncer, em especial, da regi?o de cabe?a e pesco?o. Trata-se de uma inflama??o que afeta a mucosa da cavidade oral e se caracteriza clinicamente pelo surgimento de les?es eritematosas, ulceradas e dolorosas, o que pode ocasionar, em casos mais graves, interrup??o do tratamento quimioter?pico. O objetivo deste estudo foi avaliar o efeito da Olmesartana (Olme), um antagonista do receptor AT1 da angiotensina II (Ang II), na mucosite oral. Foi realizado um ensaio pr?-cl?nico, in vivo, randomizado, cego, com utiliza??o de grupos controles. 42 hamsters Golden Siriam foram divididos em 6 grupos: Controle, Trauma Mec?nico, 5-FU, Olme 1mg/kg, Olme 5mg/kg e Olme 10mg/kg. Nos grupos doentes a MO foi induzida nos dois primeiros dias do experimento com um quimioter?pico, o 5-fluorouracil (5-FU, 60 mg/kg dia 1 e 40 mg/kg dia 2). Os animais foram pr?-tratados com Olme oral (1, 5, ou 10 mg/kg) ou ve?culo (controles) 30 min antes da inje??o de 5-FU e diariamente at? o d?cimo dia. As amostras de mucosa da bochecha foram submetidas a an?lise macrosc?pica, histopatol?gica, an?lise de atividade enzim?tica bioqu?mica e imunohistoqu?mica. Rea??es em cadeia de polimerase de transcriptase reversa (RT-PCRs) foram utilizadas para quantificar a express?o de NF-?B, p65, PI3K e MKP1. Os n?veis de ?xido n?trico sintase induz?vel (iNOS) e quinase regulada extracelularmente (ERK) foram analisados com Western Blot. O tratamento com 10 mg/kg de Olme reduziu os n?veis de ulcera??o, mieloperoxidase (MPO) e malonalde?do (MDA), inflama??o celular, edema e hemorragia (todos p <0,05). O tratamento com Olme de 10 mg/kg tamb?m reduziu os n?veis do fator de necrose tumoral (TNF)-?, interleucina (IL)-1?, aumentando a express?o PI3K e diminuindo a express?o de NFKB, p65, MKP1 e diminuindo os n?veis de iNOS e ERK1/2. A utiliza??o da Olme na dose de 10 mg/kg reduziu o dano e a inflama??o da mucosa associados com a MO induzido por 5-FU. / Oral Mucositis (MO) is one of the main complications involved in the treatment of cancer, especially in the head and neck region. It is an inflammation that affects the mucosa of the oral cavity is clinically characterized by erythematous, ulcerated and painful lesions, Which can lead, in more severe cases, to an interruption of chemotherapy treatment. The aim of this study was to evaluate the effect of Olmesartan (Olme), an angiotensin II (Ang II) receptor antagonist, on oral mucositis. A pre-clinical trial was performed, in vivo, randomized, blind, with use of control groups. 42 Golden Siriam hamsters were divided into 6 groups: Control, Mechanical Trauma, 5-FU, Olme 1mg/kg, Olme 5mg/kg and Olme 10mg/kg. In the diseased groups MO was induced on the first two days of the experiment with a chemotherapeutic, 5- fluorouracil (5-FU, 60 mg / kg day 1 and 40 mg / kg day 2). Animals were pretreated with oral Olme (1, 5, or 10 mg/kg) or vehicle (control) 30 min before 5-FU injection and daily until day 10. Cheek pouch samples were subjected to histopathologic analysis, protein/immunology analysis, and immunoistochemistry. Reverse transcriptase polymerase chain reactions (RT-PCRs) were used to quantitate expression of NF- ?Bp65, PI3K, and MKP1. Inducible nitric oxide synthase (iNOS) and extracellular regulated kinase (ERK)1/2 levels were analysed with immunoblots. Treatment with 10 mg/kg Olme reduced ulceration, myeloperoxidase (MPO) and malonaldehyde (MDA) levels, cellular inflammation, edema, and hemorrhage (p<0.05). The 10 mg/kg Olme treatment also reduced tumour necrosis factor (TNF)-?, interleukin (IL)-1?, increasing expression PI3K, and decreasing expression of NFKBp65, MKP1, and decreasing iNOS and ERK1/2 levels. Olme at a dose of 10 mg/kg prevented the mucosal damage and inflammation associated with 5-FU? induced OM.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-11-01T21:08:44Z No. of bitstreams: 1 ViniciusBarretoGarcia_DISSERT.pdf: 3420241 bytes, checksum: 521464fbb3b5ad4dcf8800370812b249 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-11-07T00:13:01Z (GMT) No. of bitstreams: 1 ViniciusBarretoGarcia_DISSERT.pdf: 3420241 bytes, checksum: 521464fbb3b5ad4dcf8800370812b249 (MD5) / Made available in DSpace on 2017-11-07T00:13:01Z (GMT). No. of bitstreams: 1 ViniciusBarretoGarcia_DISSERT.pdf: 3420241 bytes, checksum: 521464fbb3b5ad4dcf8800370812b249 (MD5) Previous issue date: 2017-06-23 / A Doen?a Hep?tica Alco?lica (DHA) corresponde a diversas patologias hep?ticas revers?veis e irrevers?veis que ocorrem em resposta ? ingest?o do etanol, dentre elas a esteato-hepatite alco?lica que, embora revers?vel, ainda n?o possui terapia farmacol?gica espec?fica. O objetivo deste estudo foi avaliar os efeitos hepatoprotetores do carvedilol (CARV) em ratos com esteato-hepatite alco?lica. Para isso, ratos Wistar foram divididos em 5 grupos: controle negativo, controle positivo, CARV 1mg, CARV 3mg e CARV 5mg (5 animais por grupo ? sendo os grupos CARV duplicados). Durante 28 dias consecutivos os animais foram submetidos ? gavagem oral de solu??o salina (NaCl 0,9% - controle negativo) ou solu??o alco?lica a 30%, 7g/kg (grupo controle positivo e grupos CARV). Os grupos CARV recebiam a dose respectiva do f?rmaco por gavagem 1h antes da solu??o alco?lica. O sangue dos animais foi coletado via pun??o card?aca para dosagem de triglicer?deos (TG) e transaminases hep?ticas (AST e ALT) e as amostras hep?ticas foram submetidas ? an?lise colorim?trica do malonalde?do (MDA), mieloperoxidase (MPO) e glutationa reduzida (GSH), ? an?lise imuno-enzim?tica (ELISA) das citocinas Interleucina 1 beta (IL-1?), fator de necrose tumoral alfa (TNF-?) e interleucina 10 (IL-10), ? PCR quantitativa em tempo real (RT-qPCR) dos genes pr?-col?genos I e III, Fator Nuclear ?B (NF- ?B) e TNF-? e ? an?lise histopatol?gica por Hematoxilina e Eosina, Picro-Sirius, Imuno-histoqu?mica para COX-2, RANK, RANKL, IBA-1, ICAM-1, SOCS-1, SOD-1 e GPx-1 e imunofluoresc?ncia para IL-1? e NF- ?B. Todas as t?cnicas utilizadas demonstraram que o efeito hepatoprotetor do carvedilol se d? por meio da regula??o que ele desempenha sobre as C?lulas de Kupffer e C?lulas Estreladas, levando a respostas anti-inflamat?rias, antioxidantes e anti-fibr?ticas. / Alcoholic liver disease (DHA) corresponds to several reversible and irreversible liver diseases that occur in response to ethanol intake, among them alcoholic steatohepatitis which, although reversible, does not have specific pharmacological therapy yet. The aim of this study was to evaluate the hepatoprotective effects of carvedilol (CARV) in rats with alcoholic steatohepatitis. Therefore, Wistar rats were divided into 5 groups: negative control, positive control, CARV 1mg, CARV 3mg and CARV 5mg (5 animals per group - the CARV groups being duplicated). During 28 consecutive days the animals were submitted to oral gavage of saline solution (NaCl 0.9% - negative control) or alcohol solution at 30%, 7g / kg (positive control group and CARV groups). The CARV groups received a more adequate dose to the drug by gavage 1h before the alcoholic solution. The blood of the animals was collected via cardiac puncture for the determination of triglycerides (TG) and hepatic transaminases (AST and ALT), and as hepatic samples were submitted to colorimetric analysis of malonaldehyde (MDA), myeloperoxidase (MPO) and reduced glutathione (GSH), immunoenzymatic analysis (ELISA) of the cytokines Interleukin 1 beta (IL-1?), tumor necrosis factor alpha (TNF-?) and interleukin-10 (IL-10), real-time quantitative PCR (RT-qPCR) of Pro-collagen I and III genes, Nuclear Factor ?B (NF-?B) and TNF-? and hertopathological analysis by Hematoxylin and Eosin, Picro-Sirius, Immunohistochemistry for COX-2, RANK, RANKL, IBA-1, ICAM -1, SOCS-1, SOD-1 and GPx-1 and immunofluorescence for IL-1? and NF-?B. All techniques demonstrated that the hepatoprotective effect of carvedilol occurs through the regulation it plays on as Kupffer Cells and Star Cells, leading to anti-inflammatory, antioxidant and anti-fibrotic responses.

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-03-23T15:01:59Z No. of bitstreams: 1 TES_HELENA_FETTER_FILIPPINI_PARCIAL.pdf: 1312432 bytes, checksum: dda78ca2fa347004234d72add7b38398 (MD5) / Made available in DSpace on 2017-03-23T15:01:59Z (GMT). No. of bitstreams: 1 TES_HELENA_FETTER_FILIPPINI_PARCIAL.pdf: 1312432 bytes, checksum: dda78ca2fa347004234d72add7b38398 (MD5) Previous issue date: 2017-01-13 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / The central and peripheral mechanisms involved in pulpal pain are still unclear. This study compared, initially, the chronic pulpitis model evoked by the application of complete Freund's adjuvant (CFA) into the pulps of rats, with other models of pulpitis. For this purpose, the pulps of the left upper first molars of Wistar rats were accessed. There were four experimental groups according to the surgical procedure: open, closed, CFA and na?ve. Behavioral changes, as well as, body weight gain and food and water consumption, were evaluated at different experimental times (1, 2, 3 and 8 days). After euthanasia, blood, brain and trigeminal ganglion (TG) samples were collected for further analysis. All experimental groups with pulp acess had a decrease in body weight gain (for up to 3 days). A reduction in food consumption was observed in all the groups with pulp exposure, on the first day. The CFA group showed a significant reduction of locomotor activity (at 1 and 3 days), which was associated with increased satellite glial cells activation in the ipsilateral TG. Activation of astrocytes in the amygdala was not affected in the studied groups. The second part of this study investigated the relevance of Toll-like receptor 4 (TLR4) activation in the acute pulpitis caused by the application of the transient receptor potential ankyrin-1 (TRPA1) mustard oil (MO), into the rat pulps. Preliminary studies were performed to compare the sensorimotor activity of the masticatory muscles with the application of lipopolysaccharide (LPS) or MO in the dental pulp. The model using MO application into the pulp of rats was selected, because of the marked increase of the electromyographic activities evoked by this agent, when compared to LPS. The animals received a intrathecal (i.t.) pre-treatment with the TLR4 LPS-RS antagonist (25 ?g / 10 ?l) or saline solution (10 ?l) (vehicle group), 10 min before pulp application of MO. For this purpose, a stereotaxic surgery was performed to access the trigeminal subnucleus caudalis. Changes in electromyography activity (EMG) of masticatory muscles were recorded for 15 min after the MO application into the pulp. The trigeminal caudalis subnucleus was removed after euthanasia, for evaluation of TLR4 expression by western blotting analysis. Changes in EMG activity in anterior digastric muscles were significantly reduced by the intrathecal administration of LPS-RS in the trigeminal subnucleus caudalis (p ?0.05). The data obtained suggest the participation of satellite glial cells in the chronic pulpitis model induced by CFA, as well as, TLR4 receptors in the acute pulpitis model caused by MO application into the rat pulps. Altogether, the present results shed new light on the mechanisms underlying acute and chronic tooth pulp inflammatory pain. / Os mecanismos centrais e perif?ricos envolvidos na dor pulpar ainda n?o est?o totalmente claros. O presente estudo comparou, inicialmente, o modelo de inflama??o pulpar cr?nica induzido pela aplica??o de adjuvante completo de Freund (CFA), em polpas de ratos, com outros modelos de pulpite. Para tanto, as polpas dos primeiros molares superiores esquerdos de ratos Wistar foram acessadas. Foram criados 4 grupos experimentais conforme a abordagem pulpar: aberto, fechado, CFA e na?ve. As altera??es comportamentais, bem como, o ganho de peso corporal e o consumo de ?gua e ra??o, foram avaliados em diferentes tempos experimentais (1, 2, 3 e 8 dias). Ap?s a eutan?sia, amostras de sangue, c?rebro e g?nglio trigeminal (GT) foram coletadas para an?lises posteriores. Todos os grupos experimentais com exposi??o da polpa apresentaram diminui??o do ganho de peso corporal (at? o 3 ? dia). A redu??o do consumo de ra??o foi observada em todos os grupos no primeiro dia. O grupo CFA mostrou redu??o significativa na atividade locomotora (em 1 e 3 dias), que foi associada ao aumento da ativa??o das c?lulas sat?lites da glia no GT ipsilateral. A ativa??o de astr?citos na am?gdala n?o foi afetada nos grupos estudados. A segunda parte deste estudo investigou a participa??o do receptor Toll-like 4 (TLR4), na media??o da pulpite aguda causada pela aplica??o de ?leo de mostarda (OM), um agonista de receptores de potencial transit?rio anquirina-1 (TRPA1), em polpas de ratos. Estudos preliminares foram realizados comparando a atividade sensoriomotora dos m?sculos mastigat?rios diante da aplica??o de lipopolissacar?deo (LPS) ou OM na polpa dent?ria. O modelo utilizando OM na polpa de ratos foi escolhido, devido ao aumento marcante das atividades eletromiogr?ficas (EMG), quando comparado ao LPS. Os animais foram pr?-tratados por via intratecal (i.t.) com o antagonista seletivo dos receptores TLR4, o LPS-RS (25 ?g/10 ?l, 10 min antes da aplica??o pulpar de OM. O grupo controle recebeu solu??o salina (10 ?l) (grupo ve?culo), pela mesma via, no mesmo tempo de administra??o. Para tal, foi realizada uma cirurgia esterot?xica para permitir o acesso ao subn?cleo caudal trigeminal. As altera??es das atividades de EMG dos m?sculos mastigat?rios foram registradas durante 15 min ap?s a aplica??o de OM na polpa. O subn?cleo caudal trigeminal foi removido ap?s a eutan?sia, para avalia??o da express?o de TLR4, atrav?s da an?lise de western-blotting. As altera??es da atividade de EMG nos m?sculos dig?stricos anteriores foram significativamente reduzidas pela administra??o intratecal de LPS-RS no subn?cleo caudal do trig?meo (p?0,05), indicando um papel relevante para esses receptores nos mecanismos de sensibiliza??o central, ap?s a aplica??o de OM. O conjunto de dados obtidos sugerem a participa??o das c?lulas sat?lites da glia no modelo de pulpite cr?nica induzida por CFA, bem como, dos receptores TLR4 no modelo de pulpite aguda provocada pela aplica??o de OM em polpas de ratos. Essas evid?ncias contribuem para o melhor entendimento dos mecanismos relacionados com a transmiss?o da dor pulpar aguda e cr?nica.

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-05-23T17:25:42Z No. of bitstreams: 1 DIS_LENIO_TOGNI_PARCIAL.pdf: 1339619 bytes, checksum: f9a493b6c4f4be9a8d1569be186595f8 (MD5) / Made available in DSpace on 2017-05-23T17:25:42Z (GMT). No. of bitstreams: 1 DIS_LENIO_TOGNI_PARCIAL.pdf: 1339619 bytes, checksum: f9a493b6c4f4be9a8d1569be186595f8 (MD5) Previous issue date: 2017-01-17 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Objective: This study aimed to characterize the development of temporomandibular osteoarthritis (TMJ-OA) following the surgical anterior displacement of the articular disc (ADD) in rats, in comparison to the well-established model of OA induced by the intra-articular injection of the inflammatory agent CFA. Methods: Male Wistar rats (160-180 g) were randomly divided into two surgical groups, namely ADD (submitted to anterior disc displacement) and sham-operated (surgical access, without ADD). For purposes of comparison, two additional experimental groups received an intra-articular infiltration of complete Freund?s adjuvant (CFA; 50 ?l/site; 1:1 oil/saline emulsion), or the same volume of saline solution (0.9% NaCl). Different experimental subgroups (N=8 per group) were euthanized on 15, 30 or 60 days after procedures. The region corresponding to the left TMJ was collected for histological analysis of fibrocartilage thickness (hematoxylin-eosin staining), presence of proteoglycans (safranin-O and toluidine blue), subchondral bone metabolism (tartrate-resistant acid phosphatase; TRAP) and collagen levels (Masson's trichrome). The immunopositivity for the aggrecanase ADAMTS5 was examined in the fibrocartilage layers. Micro-CT images were acquired for morphological and microstructural evaluation (30 and 60 days; N=4 per group). The levels of inflammatory serum proteins (IL-1?, IL-6 and TNF) were assessed to evaluate the possible systemic outcomes of TMJ-OA induced by ADD or CFA. Results: The analysis of hematoxylin-eosin-stained sections revealed an increment of fibrocartilage thickness in the ADD group, on 15 and 30 days, mainly in the anterior third of the condyle. In the CFA group, a fibrocartilage thickening was seen in the posterior third, only at 15 days. Increased proteoglycan contents were present in the fibrocartilage of the ADD group, according to the qualitative analysis by safranin-O and toluidine blue staining. The ADD group also displayed an augmented immunopositivity for ADAMTS5 in the fibrocartilage cells, on 15 and 30 days, whereas the expression of this aggrecanase was subtly increased in the CFA group at 15 days. The histological evaluation of the subchondral bone did not reveal any evident difference in the collagen contents, or in the number of activated osteoclasts, in the ADD or CFA groups, as indicated by Masson?s trichrome and TRAP staining. However, the micro-CT analysis showed marked morphological and structural changes in condyles of the ADD group, with osteophyte formation on 30 days, and a flattening of condylar surface on 60 days. The anterior condyle third of the ADD group also presented an increment of trabecular separation and bone surface, associated to a reduction of trabecular thickness and bone volume. The serum levels of the pro-inflammatory cytokines, namely IL-1?, TNF or IL-6, were undetectable in all the experimental groups. Conclusion: The surgical model of ADD in rats led to long-term OA-like alterations, with the formation of osteophytes, followed by flattening of the condyle surface and trabecular derangements. This experimental model might represent a reliable strategy to investigate TMJ-OA-related mechanisms, allowing the identification of novel therapies for this condition. / Objetivo: Este trabalho teve por objetivo caracterizar o desenvolvimento de um modelo de osteoartrite, na articula??o temporomandibular (TMJ-OA), posteriormente ? cirurgia de anterioriza??o de disco articular em ratos, em compara??o a um modelo j? estabelecido de indu??o de osteoartrite (OA), pela infiltra??o intra-articular do agente inflamat?rio, CFA. M?todos: Ratos Wistar machos (160-180 g) foram randomicamente divididos em dois grupos, denominados ADD (submetidos ? anterioriza??o do disco articular) e falso-operados (acesso cir?rgico, sem a anterioriza??o do disco articular). Para fins de compara??o, dois grupos experimentais adicionais receberam a infiltra??o intra-articular do adjuvante completo de Freund (CFA; 50 ?l/s?tio; 1:1 ?leo/emuls?o salina) ou, o mesmo volume de solu??o salina (NaCl 0,9%). Diferentes subgrupos experimentais (n=8 por grupo) foram eutanasiados em 15, 30 ou 60 dias depois dos procedimentos. A regi?o correspondente ? articula??o temporomandibular (ATM) foi coletada para an?lises histol?gicas quanto ? espessura da fibrocartilagem (hematoxilina-eosina), ? presen?a de proteoglicanas (safranin-O e azul de toluidina), ao metabolismo ?sseo sub-condral (fosfatase ?cida tartarato-resistente; TRAP) e aos n?veis de col?geno (tricr?mico de Masson). A imunopositividade para a agrecanase, ADAMTS5, foi avaliada nas diferentes camadas de fibrocartilagem. Imagens de microtomografia foram adquiridas para avalia??o da morfologia e microestrutura (30 e 60 dias; N=4 por grupo). Os n?veis inflamat?rios das citocinas s?ricas, IL-1?, IL-6 e TNF, foram avaliados como indicativos dos poss?veis efeitos da indu??o de TMJ-AO, por ADD ou CFA. Resultados: A an?lise da colora??o por hematoxilina-eosina demostrou um aumento na espessura da fibrocartilagem no grupo ADD, em 15 e 30 dias, principalmente no ter?o anterior do c?ndilo. No grupo CFA, um espessamento da fibrocartilagem foi encontrado no ter?o posterior, somente em 15 dias. Um aumento da presen?a de proteoglicanas foi encontrado na fibrocartilagem do grupo ADD, de acordo com a an?lise qualitativa pelas colora??es de safranin-O e de azul de toluidina. O grupo ADD tamb?m apresentou um aumento da imunopositividade para ADAMTS5 nas c?lulas da fibrocartilagem, em 15 e 30 dias, enquanto que a express?o dessa agrecanase, no grupo CFA, apresentou-se discretamente aumentada em 15 dias. A avalia??o histol?gica do osso subcondral n?o revelou nenhuma diferen?a em rela??o ao conte?do de col?geno ou, ao n?mero de osteoclastos ativos, nos grupos ADD ou CFA, como indicado pelas colora??es de tricr?mico de Masson e TRAP. Contudo, a an?lise microtomogr?fica demostrou mudan?as marcantes na morfologia e na estrutura ?ssea dos c?ndilos do grupo ADD, com forma??o de oste?fitos em 30 dias e, achatamento da superf?cie articular em 60 dias. O ter?o anterior do c?ndilo do grupo ADD tamb?m apresentou um aumento na separa??o trabecular e na superf?cie ?ssea, associada com uma redu??o da espessura trabecular e do volume ?sseo. Os n?veis s?ricos de citocinas pr?-inflamat?rias (IL-1?, IL-6 e TNF) foram indetect?veis em todos os grupos experimentais. Conclus?o: O modelo cir?rgico ADD em ratos levou a altera??es cr?nicas compat?veis com OA, com forma??o de oste?fitos, seguida por achatamento da superf?cie condilar e altera??es trabeculares. Este modelo experimental pode representar uma nova estrat?gia para investigar os mecanismos relacionados ? TMJ-OA, permitindo a identifica??o de novas terapias para esta condi??o.

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:01:57Z No. of bitstreams: 1 DIS_KEILA_ABREU_DA_SILVEIRA_PARCIAL.pdf: 1040292 bytes, checksum: 89e950465b4a1448b10bb99039287e7a (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:02:03Z (GMT) No. of bitstreams: 1 DIS_KEILA_ABREU_DA_SILVEIRA_PARCIAL.pdf: 1040292 bytes, checksum: 89e950465b4a1448b10bb99039287e7a (MD5) / Made available in DSpace on 2017-06-30T18:02:11Z (GMT). No. of bitstreams: 1 DIS_KEILA_ABREU_DA_SILVEIRA_PARCIAL.pdf: 1040292 bytes, checksum: 89e950465b4a1448b10bb99039287e7a (MD5) Previous issue date: 2017-03-03 / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Background: asthma is a heterogeneous disease characterized by chronic inflammation of the lower airways. The inflammatory process is associated with bronchial hyperresponsiveness, resulting in recurrent episodes of wheezing, coughing, dyspnea and chest tightness. Asthma affects around 300 million people worldwide, with high prevalence, mainly in children. Chronic inflammation in the airways of patients with asthma is complex and involves a range of cells from the immune system, including T lymphocytes, granulocytes, epithelial cells, among others. Granulocytes are considered key cells to maintain inflammation. Neutrophils and eosinophils have different characteristics and functions for the immune response in asthma. Both type of cells release a variety of mediators that contribute to chronic inflammation and changes in the structure of the airways, secondary to external agents. In this context, it was demonstrated that after activation neutrophils and eosinophils are able to release extracellular DNA "traps" with specific proteins that kill extracellular pathogens. On the other hand, it is possible that these DNA "traps" contribute to immunopathology in chronic inflammatory diseases, such as asthma. Therefore, it has recently been shown that neutrophils and eosinophils generate extracellular DNA traps in the airways of asthmatics, possibly contributing to tissue damage. Objective: to verify whether there is extracellular DNA traps and the presence of inflammatory cells in sputum samples of children and adolescents with asthma. Methods: this cross-sectional study selected children and adolescents with asthma, between 6 and 18 years of age, in a regular follow-up at a reference center from southern Brazil. We have performed lung function (spirometry), allergen skin test, and induced sputum to identify the inflammatory cells profile, formation of extracellular DNA traps, and quantification of extracellular DNA. To visualize the extracellular DNA traps, the cells were stained with Hoechst 33342. The images were captured on a fluorescence confocal microscope. Results: 18 children and adolescents were included, 13 with severe asthma and 5 with non-severe asthma. Of these, 17 (94.4%) had a positive skin test for some type of allergens and all patients presented pulmonary function within the limits of normality. Patients with inflammatory cell profiles in sputum (7,12 [4,41,45,23]) showed a significant increase (p = 0.01) in extracellular DNA concentrations compared to patients with pauci-granulocytic profile (2.31 [1.47-3.56]). The extracellular DNA levels correlated positively (r = 0.73, p = 0.004) with the total granulocytic cells in the sputum of these patients. Likewise, there was a significant positive correlation between extracellular DNA and absolute sputum neutrophil counts (r = 0.71, p = 0.008) and absolute sputum eosinophils counts (r = 0.69; p = 0.0013) in the sputum samples. Conclusion: Our results show the presence of extracellular DNA traps in sputum with inflammatory pattern of children and adolescents with asthma suggesting that these traps are released by granulocytic cells, specifically neutrophils and eosinophils. / Base te?rica: a asma ? uma doen?a heterog?nea, caracterizada pela inflama??o cr?nica das vias a?reas inferiores. O processo inflamat?rio est? associado ? hiper-responsividade br?nquica, tendo como consequ?ncia, epis?dios recorrentes de sibil?ncia, tosse, dispneia e opress?o tor?cica. A doen?a atinge em torno de 300 milh?es de pessoas no mundo, sendo considerada uma doen?a com elevada preval?ncia, principalmente na popula??o infantil. A inflama??o cr?nica presente nas vias a?reas de indiv?duos com asma ? complexa e envolve um conjunto de c?lulas provenientes do sistema imunol?gico, incluindo linf?citos T, granul?citos, c?lulas epiteliais, entre outras. Os granul?citos s?o considerados c?lulas fundamentais para sustentar a inflama??o. Os neutr?filos e os eosin?filos apresentam caracter?sticas e fun??es diferentes para a resposta imune na asma. Ambos liberam uma variedade de mediadores que contribuem para inflama??o cr?nica e altera??es na estrutura das vias a?reas, com est?mulos externos. Neste contexto, foi demonstrado que os neutr?filos e eosin?filos, ap?s ativa??o, s?o capazes de liberar ?armadilhas? de DNA extracelular com prote?nas espec?ficas, que combatem agentes patog?nicos extracelularmente. Por outro lado, ? poss?vel que essas ?armadilhas? de DNA contribuam para a imunopatologia em doen?as inflamat?rias cr?nicas, como na asma. Portanto, recentemente, foi identificado que neutr?filos e eosin?filos geram redes extracelulares de DNA nas vias a?reas de asm?ticos adultos. Objetivo: verificar se existe forma??o de redes extracelulares de DNA com a presen?a de c?lulas inflamat?rias em amostra de escarro de crian?as e adolescentes com asma. M?todos: nosso estudo transversal selecionou crian?as e adolescentes com asma, entre 6 e 18 anos de idade, em acompanhamento regular em um centro de refer?ncia do sul do Brasil. Foram coletados dados relativos a fun??o pulmonar (espirometria), teste cut?neo para al?rgenos, e escarro induzido para identifica??o do perfil de c?lulas inflamat?rias, forma??o das redes extracelulares de DNA, e quantifica??o do DNA extracelular. Para a visualiza??o das redes extracelulares de DNA, as c?lulas foram coradas com Hoechst 33342. As imagens foram capturadas em microsc?pio confocal de fluoresc?ncia. Resultados: foram inclu?dos 18 crian?as e adolescentes, sendo 13 com asma grave e 5 n?o grave. Destes, 17 (94,4%) obtiveram o teste cut?neo positivo para algum tipo de al?rgenos e todos apresentaram fun??o pulmonar dentro dos limites da normalidade. Os pacientes com perfil de c?lulas inflamat?rias (7,12 [4,41-45,23]) obtiveram um aumento significativo (p=0,01) nas concentra??es extracelulares de DNA quando comparados com pacientes com perfil pauci-granuloc?tico (2,31[1,47-3,56]). Os n?veis de DNA extracelular correlacionaram-se positivamente (r=0,73; p=0, 0004) com as c?lulas granuloc?ticas totais no escarro destes pacientes. Do mesmo modo, houve uma correla??o positiva entre o DNA extracelular com a contagem absoluta de neutr?filos (r=0,71; p=0,008) e contagem absoluta de eosin?filos (r=0,69; p=0,0013) nas amostras de escarro. Conclus?o: nossos resultados mostram a presen?a de redes extracelulares de DNA no escarro com padr?o inflamat?rio em crian?as e adolescentes com asma sugerindo que estas redes s?o liberadas por c?lulas granuloc?ticas, especificamente neutr?filos e eosin?filos.

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:29:48Z No. of bitstreams: 1 TES_LEONARDO_PEDRAZZA_PARCIAL.pdf: 9312449 bytes, checksum: e82cef97eb17ae6eefdb30bc5fe133ed (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-06-30T18:29:54Z (GMT) No. of bitstreams: 1 TES_LEONARDO_PEDRAZZA_PARCIAL.pdf: 9312449 bytes, checksum: e82cef97eb17ae6eefdb30bc5fe133ed (MD5) / Made available in DSpace on 2017-06-30T18:30:01Z (GMT). No. of bitstreams: 1 TES_LEONARDO_PEDRAZZA_PARCIAL.pdf: 9312449 bytes, checksum: e82cef97eb17ae6eefdb30bc5fe133ed (MD5) Previous issue date: 2017-03-24 / Mesenchymal stem cells (MSC) were first identified by Friedenstein and Petrakova (1966), who isolated these progenitor cells from rat bone marrow and found that these cells are able to differentiate into connective tissue lineage including bone, adipose tissue, cartilage and muscle. MSCs have emerged in recent years as therapeutic tools based on four important features: differentiation potential, capacity to modulate immune responses, pro-angiogenic and repair promoting capacities, and low immunogenicity, the latter feature may allow allogeneic treatments. Based on their immunomodulatory properties and paracrine effects through trophic factors with anti-fibrotic, anti-apoptotic or pro-angiogenic properties, MSCs are considered a promising instrument for cell therapy, in particular for inflammatory diseases. MSCs regulate the function of a broad range of immune cells, and are activated by inflammatory mediators released from activated immune cells. The mechanisms involved in the immunoregulatory activity of MSCs are still under investigation. Therefore, MSCs become a potential treatment alternative for sepsis and for acute lung infection, which may lead to the interruption of the sequence in the pathogenesis and cause mortality reduction of both pathologies. The principal objective of this study was to evaluate the therapeutic and immunomodulatory effect of MSCs in the treatment of sepsis and acute lung injury and search for their possible mechanisms of action. Our results demonstrated for the first time that the reduction of inflammation in sepsis caused by treatment with MSCs is directly involved in the inhibition of the pathway of mitogen-activated proteins (MAPKs) and that MSCs were unable to modulate the expression of toll-like receptors. During acute lung injury (ALI), the immunomodulation caused by the treatment and the decrease of the oxidative stress that consequently led to a decrease in the formation of extracellular neutrophil network (NETs), leading to an increase in the survival of animals with LPA. The promising results obtained in these studies are encouraging and suggest that MSCs might be a therapeutic option to treat sepsis and acute lung infection in patients in the future. / As c?lulas-tronco mesenquimais (MSC) foram identificadas primeiramente por Friedenstein e Petrakova (1966), que isolaram estas c?lulas progenitoras a partir da medula ?ssea de rato e observaram serem capazes de se diferenciarem em linhagem de tecido conectivo, incluindo osso, tecido adiposo, cartilagem e m?sculo. As MSCs surgiram nos ?ltimos anos como ferramentas terap?uticas baseadas em quatro caracter?sticas importantes: potencial de diferencia??o, capacidade para modular a resposta imune, capacidades pr?-angiog?nicas promovendo regenera??o tecidual, e baixa imunogenicidade, sendo que esta ?ltima caracter?stica pode permitir tratamentos alog?nicos. Com base nas suas propriedades imunomoduladoras e efeitos par?crinos atrav?s de fatores tr?ficos com propriedades anti-fibr?ticas, anti-apopt?ticas ou pr?-angiog?nicas, as MSCs s?o consideradas um instrumento promissor para a terapia celular, em particular para doen?as inflamat?rias. As MSCs regulam as fun??es de uma ampla gama de c?lulas imunes, e s?o ativadas por mediadores inflamat?rios liberados de c?lulas imunes ativadas. Os mecanismos envolvidos na atividade imunorreguladora de MSCs est?o ainda sob investiga??o. Desta forma, as c?lulas-tronco mesequimais se tornam uma potencial alternativa de tratamento para a sepse e para infec??o pulmonar aguda, podendo levar a interrup??o do curso da patog?nese, e provocar a redu??o da mortalidade de ambas patologias. O principal objetivo deste trabalho foi avaliar o efeito terap?utico e imunomodulador de c?lulas-tronco mesenquimais no tratamento da sepse e da les?o pulmonar aguda e buscar os seus poss?veis mecanismos de a??o. Nossos resultados demonstraram pela primeira vez, que a redu??o da inflama??o na sepse provocada pelo tratamento com c?lulas-tronco mesenquimais est? diretamente envolvido a inibi??o da via das prote?nas ativadas por mit?genos (MAPKs) e que as MSCs foram incapazes de modular a express?o de receptores do tipo toll. Durante a les?o pulmonar aguda (LPA) ficou evidente a imunomodula??o provocada pelo tratamento e a diminui??o do estresse oxidativo que consequentemente ocasionou a uma diminui??o da forma??o das redes extracelulares de neutr?filos (NETs), levando a um aumento na sobrevida dos animais com LPA. Os resultados promissores obtidos neste estudo s?o encorajadores e sugerem que as MSCs podem ser uma op??o terap?utica para tratar a sepse e a les?o pulmonar aguda em pacientes no futuro.

Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2018-03-23T12:20:59Z No. of bitstreams: 1 CAUANA_OLIVA_TAVARES_TES.pdf: 7981094 bytes, checksum: f72aed348b44d9575861b810913cc7c3 (MD5) / Approved for entry into archive by Tatiana Lopes (tatiana.lopes@pucrs.br) on 2018-04-06T11:47:44Z (GMT) No. of bitstreams: 1 CAUANA_OLIVA_TAVARES_TES.pdf: 7981094 bytes, checksum: f72aed348b44d9575861b810913cc7c3 (MD5) / Made available in DSpace on 2018-04-06T11:50:47Z (GMT). No. of bitstreams: 1 CAUANA_OLIVA_TAVARES_TES.pdf: 7981094 bytes, checksum: f72aed348b44d9575861b810913cc7c3 (MD5) Previous issue date: 2017-12-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Infection and dysbiosis present a close relationship with metabolic diseases, although the influence of apical periodontitis (AP) in this context needs further investigation. This thesis includes a review and an experimental study that evaluated the influence of AP in a rat model of metabolic disorder induced by 10% fructose supplementation. 60 male Wistar rats were used. Animals that received high fructose diet (HFD; N=30) or filtered water (control; N=30) were subdivided into additional groups: (i) without induction of AP (N=20); (ii) with AP induction 2 weeks before euthanasia (14 days; N=20); (iii) with AP induction 4 weeks before euthanasia (28 days; N=20). HFD triggered obesity-related type2 diabetes, as indicated by induction of overweight and hyperglycemia, besides polydipsia, regardless of the AP induction. There was no variation in the serum or intestinal levels of TNF, IL-1? and IL-6 among the experimental groups. Serum leptin and adiponectin levels were significantly elevated in the HFD group, without AP induction. The intestinal levels of leptin were significantly increased in the groups with 28 days of AP induction, despite HFD. A significant elevation of liver glutathione levels was observed in animals submitted to HFD and AP for 14 days. AP induction (14 or 28 days) led to pulp and periapical tissue inflammation, without any influence of HFD. Either HFD or AP induction led to dysbiosis, as indicated by a significant reduction of fecal A. muciniphila expression. Conluding, we provide novel evidence that AP can have systemic impacts on metabolic disorders, likely by modulating intestinal metabolism and microbiota. / Infec??o e disbiose est?o correlacionadas com a s?ndrome metab?lica. Por?m, ainda ? necess?rio que haja investiga??es sobre a influ?ncia da periodontite apical neste contexto. Esta tese contempla uma revis?o de literatura acerca do tema e um trabalho experimental que avaliou a influ?ncia da periodontite apical em um modelo de desordem metab?lica induzido por suplementa??o com frutose 10% (HFD) durante 8 semanas. Foram utilizados 60 ratos wistar machos, os quais foram subdivididos em: G1- controle (ingest?o de ?gua filtrada e sem indu??o les?o periapical); G2- controle HFD (ingest?o de frutose e sem indu??o les?o periapical); G3- controle 14 dias PA (ingest?o de ?gua filtrada e com indu??o les?o periapical por 14 dias); G4- HFD 14 dias PA (ingest?o de frutose e com indu??o les?o periapical por 14 dias); G5- controle 28 dias PA (ingest?o de ?gua filtrada e com indu??o les?o periapical por 28 dias); G6- HFD 28 dias PA (ingest?o de frutose e com indu??o les?o periapical por 28 dias). Durante as 8 semanas de experimento, os animais foram pesados a cada 2 dias. Os consumos de ra??o e ?gua foram medidos diariamente. Ap?s as 8 semanas, foi realizada a medi??o da glicemia e coleta de fezes de cada animal para avalia??o da bact?ria Akkermansia muciniphila atrav?s de PCR. Em seguida, os animais foram eutanasiados. Foram removidas as mand?bulas, para an?lise histol?gica; o soro do sangue e o intestino para an?lise de citocinas (TNF, IL-1? e IL-6) e adipocinas (leptina e adiponectina) atrav?s de ELISA; o f?gado e o cora??o para an?lise de estresse oxidativo (catalase e glutationa) atrav?s de espectrofotometria. Os resultados demonstraram que houve aumento de peso, de ingesta de ?gua (polidipsia) e de glicemia nos grupos submetidos ao HFD, independente de indu??o de PA, confirmando que o modelo experimental foi capaz de induzir diabetes tipo2 relacionada ? obesidade. N?o houve varia??o nos n?veis de TNF, IL-1? e IL-6 entre os grupos experimentais. Os n?veis de leptina e de adiponectina estavam significantemente aumentados no G2. Os n?veis intestinais de leptina estavam aumentados nos grupos 5 e 6. Um aumento nos n?veis de glutationa foi observado nos animais do G4. Ocorreu indu??o de periodontite apical nos grupos 3, 4, 5 e 6, sem altera??es provocadas pela HFD. Tanto a PA quanto o HFD foram capazes de provocar disbiose, diminuindo significativamente os n?veis de express?o de A. muciniphila. Concluindo, o presente estudo demonstra, pela primeira vez, que a PA exerce influ?ncia sist?mica e impacta desordens metab?licas modulando o metabolismo intestinal e a microbiota.

Submitted by PPG Medicina e Ci?ncias da Sa?de (medicina-pg@pucrs.br) on 2018-06-12T14:01:32Z No. of bitstreams: 1 EVANDRA_DURAYSKI.pdf: 1831041 bytes, checksum: 14177d40991ac101fe309c07dd96d0a7 (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-06-22T18:42:06Z (GMT) No. of bitstreams: 1 EVANDRA_DURAYSKI.pdf: 1831041 bytes, checksum: 14177d40991ac101fe309c07dd96d0a7 (MD5) / Made available in DSpace on 2018-06-22T18:51:12Z (GMT). No. of bitstreams: 1 EVANDRA_DURAYSKI.pdf: 1831041 bytes, checksum: 14177d40991ac101fe309c07dd96d0a7 (MD5) Previous issue date: 2018-03-07 / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Introduction: Crohn's disease (CD) is an idiopathic inflammatory bowel disease, which mainly affects the terminal ileum A biopsy colonoscopy with regard to the gold standard in the assessment of disease and the area of education costly and with anesthetic risks. Noninvasive methods of evaluation such as magnetic resonance enterography (MRE) have been developed in the last decade. Evaluation systems such as the magnetic resonance index of activity (MaRIA) and Clermont score are used in clinical studies to quantify inflammation in patients with CD. A diffusion-weighted magnetic resonance imaging (DWI) evaluates a restitution of the water molecules in the tissues. Studies have shown a correlation between a restriction of diffusion on the wall of the intestine with inflammation. However, few studies with MRE of 3 Tesla support analysis a apparent diffusion coefficient (ADC) correlactionan in inflammatory proces in the terminal ileum. Purpose: To determine the applicability of the sequence DWI in 3 Tesla MRE in the identification of inflammatory signs in the distal ileum in patients with Crohn?s disease. Materials and Methods: We retrospectively studied 38 individuals with CD, who underwent MRE between March 2014 to september 2017 and had an anatomopathological and endoscopic evaluation in the distal ileum. The following variables were evaluated: diffusion (DWI), quantitative ADC, wall thickening, intramural edema, ulcerations, stricture, segmental mural hyperenhancement, relativo contrast enchancement (RCE), MaRIA and Clermont score. Results: The mean duration of the disease was 7 ? 5 years, 19 patients (50%) were male. Eighteen patients (47%) had active inflammatory disease and twenthy (53%) had disease in remission in the terminal ileum. Patients with active inflammatory disease in the distal ileum had a greater restriction on DWI, intramural edema, wall thickening, MaRIA and Clermont score, when compared to the group of patients without inflammation. The correlation between MaRIA and Clermont score (r = 0.975) was strong. The Kappa coefficient of interobserver agreement was excellent for the MaRIA, Clermont score and restriction DWI, moderate for ADC and weak for RCE. The best cut-off point in this study for the inflammation identified by the colonoscopy for the ADC was 2.1x103mm2/s, with sensitivity of 88.8% and specificity of 95.0%. The DWI presented accuracy of 89.4%, sensitivity of 88.9% and specificity of 90.0% in relation to inflammation identified by colonoscopy. Conclusion: The quantitative values of ADC have a good sensitivity in detecting inflammation at colonoscopy. Analysis of the diffusion sequence of good accuracy in the detection of ileum inflammmation in patients with Crohn's disease. However, when in association with intramural enhancement, edema and wall thickening it has a strong correlation with severe inflammation identified at colonoscopy. / Introdu??o: A Doen?a de Crohn (DC) ? uma doen?a inflamat?ria intestinal idiop?tica, que acomete principalmente o ?leo terminal. A colonoscopia seguida de bi?psia, apesar de ser considerada o padr?o-ouro na avalia??o de doen?a ativa, ? uma ferramenta de monitoramento onerosa e com riscos anest?sicos. M?todos de avalia??o n?o invasivos, como a enterorresson?ncia (Entero-RM), foram desenvolvidos na ?ltima d?cada. Os sistema de pontua??o como o ?ndice MaRIA e escore de Clermont s?o utilizados em estudos cl?nicos para quantificar a inflama??o em pacientes com DC. A difus?o ? uma sequ?ncia da resson?ncia que avalia a restri??o das m?leculas de ?gua nos tecidos. Estudos demonstraram correla??o entre a restri??o da difus?o na parede do intestino com a inflama??o. Entretanto, poucos estudos com a Entero-RM de 3 Tesla avaliaram se a an?lise quantitativa do ADC (coeficiente de difus?o aparente) teria sensibilidade na avalia??o de processo inflamat?rio no ?leo terminal. Objetivos: Determinar a aplicabilidade da sequ?ncia de Difus?o na Entero-RM de 3 Tesla na identifica??o de sinais inflamat?rios no ?leo distal em pacientes com DC. Materiais e M?todos: Foram estudados retrospectivamente 38 indiv?duos com DC, submetidos a entero-RM no per?odo mar?o de 2014 a setembro de 2017 e que tinham avalia??o anatomopatol?gica e endosc?pica no ?leo distal. Foram avaliadas a seguintes vari?veis: difus?o, ADC quantitativo, espessamento parietal, edema, ulcera??es, estreitamento, realce pelo contraste, realce relativo ao contraste (RCE), ?ndice MaRIA e escore de Clermont. Resultados: A m?dia da dura??o da doen?a foi de 7 ? 5 anos, 19 pacientes (50%) eram do sexo masculino. Dezoito pacientes (47%) tinham doen?a inflamat?ria ativa e 20 (53%) tinham doen?a em remiss?o no ?leo terminal. Os pacientes que apresentavam doen?a inflamat?ria ativa no ?leo distal tiveram maior restri??o a difus?o, edema na mucosa, espessamento parietal, ?ndice de MaRIA e maior valor no escore de Clermont, quando comparados com o grupo de pacientes sem inflama??o. Foi forte a correla??o entre o ?ndice MaRIA com o escore de Clermont (r=0,975). O Coeficiente Kappa de concord?ncia interobservador foi excelente para ?ndice MaRIA, escore de Clermont e restri??o a difus?o, moderada para ADC e fraca para o RCE. O melhor ponto de corte neste estudo para a inflama??o identificada pela colonoscopia para o ADC foi de 2,1x10-3mm2/s, com sensibilidade de 88,8% e especificidade de 95,0%. A sequ?ncia da difus?o apresentou acur?cia de 89,4%, sensibilidade de 88,9% e especificidade de 90,0% em rela??o a inflama??o identificada pela colonoscopia. Conclus?o: Os valores quantitativos do ADC t?m uma boa sensibilidade na detec??o de inflama??o na colonoscopia. A an?lise da sequ?ncia da difus?o tem boa acur?cia na detec??o de segmentos intestinais ileais inflamados em pacientes com doen?a de Crohn. Em suma, quando a restri??o a difus?o tem associa??o com realce, edema e espessura da parede, aumenta a correla??o com a inflama??o severa identificada na colonoscopia.

Made available in DSpace on 2015-04-14T14:51:02Z (GMT). No. of bitstreams: 1 425497.pdf: 1039069 bytes, checksum: f6309e74e675843d15c679f3c6d18090 (MD5) Previous issue date: 2010-07-05 / Neste estudo foram avaliados os efeitos antifibr?ticos e antiproliferativos do suco total da pimenta vermelha Dedo-de-Mo?a, Capsicum baccatum (CB) e de fra??es da semente e do fruto de CB extra?das com os solventes de diferentes polaridades: ?gua, metanol/?gua, butanol e diclorometano. O estudo foi realizado in vitro, em cultura de c?lulas GRX, uma linhagem murina de c?lulas hep?ticas estreladas, que est?o no est?gio de miofibroblastos, mimetizando um modelo de fibrose hep?tica humana. O suco de pimenta e suas fra??es inibiram a prolifera??o celular da linhagem GRX. Este efeito foi comparado com a indometacina, utilizado como controle positivo da revers?o fenot?pica e conhecido por exercer efeito antiproliferativo e anti-inflamat?rio. Para justificar se o suco total e fra??es de CB provocaram inibi??o do crescimento das c?lulas GRX atrav?s de um mecanismo celular ou por morte celular, foi dosada a libera??o da enzima Lactato Desidrogense (LDH) ap?s o tratamento. Os grupos foram comparados com o controle de morte celular total Tween 5%, que obteve valores significativamente maiores de LDH, demonstrando que o efeito antiproliferativo do suco e fra??es de CB n?o foi atrav?s de morte celular. Al?m disso, na tentativa de verificar se havia aumento do estresse oxidativo, foram dosadas as subst?ncias reativas ao ?cido tiobarbit?rico (TBARS). Nenhum dos grupos tratados diferiu significativamente do controle. Ap?s tratamento com suco total e fra??es de CB durante 5 dias, as culturas celulares foram coradas com Oil Red O, corante que evidencia a presen?a de gordura no citoplasma celular. Tanto as culturas tratadas com o suco total, quanto ?s culturas tratadas com as fra??es de CB, apresentaram forma??o de got?culas de gordura e mudan?a fenot?pica evidente maiores que o controle e que o controle positivo de revers?o do fen?tipo, a indometacina (aumento de 400x). Al?m disso, a quantifica??o do TGF-&#946;, que ? um mediador pr?-fibrog?nico, no sobrenadante das culturas tratadas com suco e fra??es de CB foi menor do quando comparada ao controle. Esses resultados demonstraram os efeitos antifibr?ticos da pimenta vermelha Capsicum baccatum e evidenciam seu importante potencial terap?utico como agente antifibr?tico.