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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Fibrinogen-Coated Droplets of Olive Oil for the Targeted Delivery of Docetaxel to Fibrin(ogen)-Rich Tumors: Evaluation of Efficacy and Mechanism

Accurso, Charity Einhaus 31 March 2004 (has links)
No description available.
42

Hérnia de parede abdominal no paciente cirrótico: cirurgia ou tratamento conservador? / Abdominal hernia in cirrhotic patients: surgery or conservative treatment?

Pinheiro, Rafael Soares Nunes 04 July 2016 (has links)
INTRODUÇÃO: As hérnias de parede abdominal têm elevada incidência em pacientes cirróticos. Ascite e desnutrição contribuem para que essas hérnias adquiram grandes proporções, causando sintomas álgicos, decréscimo da qualidade de vida e maior risco de complicações locais que exijam tratamento cirúrgico de urgência. Contudo, o tratamento conservador é o mais empregado pela elevada morbimortalidade associada a procedimentos cirúrgicos nesses pacientes. OBJETIVO: O objetivo deste estudo é analisar os resultados do tratamento cirúrgico de hérnias de parede abdominal em pacientes cirróticos. MÉTODOS: Estudo prospectivo, baseado no seguimento de pacientes cirróticos com hérnia de parede abdominal no Ambulatório de Transplante Hepático do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, durante o período de 01/01/2009 à 01/11/2014. Foram analisadas as características demográficas, da hepatopatia, do tipo de hérnia, ocorrência de complicações e mortalidade dos pacientes que foram submetidos à cirurgia eletiva ou mantidos em acompanhamento clínico. Desse último grupo, os pacientes que apresentaram complicações com indicação de cirurgia, foram submetidos à cirurgia de urgência. Os pacientes submetidos à cirurgia eletiva foram selecionados de forma randômica. RESULTADOS: Foram avaliados 246 pacientes nesse período do estudo. A cirurgia eletiva foi realizada em 57 pacientes. Desses, 186 permaneceram em acompanhamento clínico. A incidência de complicações exigindo tratamento cirúrgico de urgência foi de 22,7% (43 pacientes). A sobrevida a longo prazo foi maior entre os pacientes submetidos à cirurgia eletiva em relação aos pacientes em acompanhamento clínico (p=0,012). A cirurgia de urgência apresentou maior incidência de complicações pós-operatórias e maior mortalidade em comparação à cirurgia eletiva (p=0,005). CONCLUSÕES: O paciente cirrótico, com hérnia de parede abdominal, apresenta elevada mortalidade em sua evolução, independente da realização da correção cirúrgica da hérnia. A cirurgia eletiva proporcionou maior sobrevida em comparação aos pacientes mantidos em acompanhamento clínico. A cirurgia de urgência foi um fator de risco para maior morbidade e mortalidade / INTRODUCTION: Cirrhotic patients have higher incidence of abdominal wall hernias. Ascistes and sarcopenia are risk factors to development of huge hernias, leading to pain, poor quality of life and need of urgent surgery due local complications. However, hernia surgery is usually delayed among cirrhotic patients due higher morbidity and mortality. OBJECTIVE: This study aimed to analyze the surgical treatment of abdominal wall hernias in cirrhotic patients. METHODS: A prospective, analytical study, based on follow-up of cirrhotic patients with abdominal wall hernia that were followed in Liver Transplant Clinic at the Hospital das Clinicas, Faculty of Medicine, University of São Paulo, during the period from January 2009 to November 2014. We analyzed demographics, characteristics of liver disease, type of hernia, complications and mortality of patients who underwent elective hernia surgery or were kept in exclusive clinical follow up. The exclusive clinical group underwent urgent hernia surgery when indicated. Elective surgery was performed in unselected patients. RESULTS: We enrolled 246 patients during the study period. Elective surgery was performed in 57 patients. 186 patients had clinical follow up, incidence of urgent surgery was 22,7% (43 patients). Elective surgery provided better long term survival then clinical follow up (p=0.012). Urgent surgery had higher morbidity and it was an independent risk factor for mortality (p=0.005). CONCLUSIONS: cirrhotic patients with abdominal wall hernia have higher mortality, regardless of performing the surgical correction. Hernia elective repair provided better survival than patients in conservative treatment. Urgent surgery imposes higher morbidity and mortality than elective surgery
43

Application de la technique CellSearch® Veridex pour la détection de cellules tumorales dans les liquides biologiques chez les patients atteints de cancers / Application of CellSearch® Veridex technology for the detection of tumor cells in biological fluids in cancer patients

Tu, Qian 02 July 2015 (has links)
L’apparition de la technique CellSearch® a permis d’obtenir la sensibilité et la spécificité suffisantes et de détecter les CTCs en ciblant les marqueurs spécifiques dans le sang périphérique. Elle permet la numération et l’étude morphologique des CTCs qui est largement utilisée et validée. Nous décrivons une adaptation de la méthode CellSearch® pour détecter les cellules tumorale chez les LM (métastases leptoméningées) patients atteints de cancers du sein, du poumon et mélanomes, qui semble atteindre une sensibilité améliorée en comparaison avec la cytologie conventionnelle. Nous présentons également un cas clinique pour la détection de cellules tumorales dans l’ascite et du sang chez un patient avec le cancer de l’oesophage métastatique. De plus, la détection des cellules tumorales dans le redon chez les patients subis une chirurgie de la tête et du cou a été également réalisée. En utilisant cette méthode, les résultats sont non seulement quatitatifs, mais aussi quantitatifs avec des images numériques de chaque cellule, et des résultats séquentiels ont été étudiés chez certains patients atteints de cancer du sein, de cancer du poumon et de mélanome. Les données ont montré des changements dynamiques des nombres de cellules tumorales détectées dans le LCR, mais leurs corrélations avec la réponse au traitement ou la progression de la maladie ont besoin des études supplémentaires plus contrôlées avec une grande cohorte de patients. La mise en évidence de cette application serait importante en clinique pour le diagnostic, le pronostic et le traitement des patients atteints de cancer avec des métastases aux niveaux du SNC, du péritoine / The introduction of CellSearch® technology allows to give sufficient sensitivity and specificity and to detect CTCs targeting specific markers in peripheral blood. The enumeration and morphological study of CTCs are widely used and validated. We described an adaptation of the CellSearch® method to detect tumor cells in LM (leptomeningeal metastases) patients with breast cancer, lung cancer and melanoma, which appeared to achieve an improved sensitivity in comparison with conventional cytology. We also presented a case report for the detection of tumor cells in the ascites and blood of a patient with metastatic oesophageal cancer. Furthermore, the detection of tumor cells in aspirative drains after neck dissectionin from the patients undergoing surgery for head and neck cancer was also performed. Using this method, the results were not only quatitative but also quantitative with digital images of each cell, and sequential results were studied in some patients with breast cancer, lung cancer and melanoma. The data showed dynamic changes of the numbers of tumor cells detected in CSF, but their correlation with the response to treatment or disease progression need additional more controlled studies with a large cohort of patients. The application would be important for the clinical diagnosis, prognosis and treatment of cancer patients with CNS metastases and peritoneal metastases
44

Influence de sécrétions ascitiques sur le comportement des cellules cancéreuses ovariennes : identification de cibles moléculaires adhésives.

Carduner, Ludovic 20 December 2013 (has links) (PDF)
Le cancer de l'ovaire représente la première cause de décès par cancer gynécologique. La survie globale des patientes à 5 ans est inférieure à 30%. Ce sombre pronostic s'explique à la fois par la découverte tardive de la maladie et par le développement d'une chimiorésistance. L'ascite est un fluide exsudatif qui est fréquemment accumulé dans la cavité péritonéale au cours de la progression des cancers de l'ovaire. Ce " microenvironnement tumoral " particulier contribue à la dissémination des cellules cancéreuses et à leurs implantations péritonéales.L'objectif global du travail de thèse a été, d'une part d'évaluer l'influence de l'ascite sur le comportement des cellules cancéreuses ovariennes et d'autre part, d'étudier les mécanismes de résistance à la perte d'ancrage des cellules cancéreuses ovariennes.Nous avons ainsi démontré que l'ascite induit une transition épithélio-mésenchymateuse partielle et que les modifications des comportements cellulaires observées sont dépendantes des intégrines alpha-v.Deux ligands de ces intégrines, la vitronectine et la fibronectine, ont été purifiés selon un protocole original permettant la caractérisation des deux protéines à partir d'une même ascite. Ces protéines ascitiques ont des propriétés différentes selon leur origine, donc selon les patientes dont elles sont issues, et influencent le comportement adhésif des cellules avec un degré variable. L'importance de la signalisation dépendante des intégrines alpha-v et des voies MAP Kinases a également été démontrée dans l'établissement d'une résistance des sphéroïdes tumoraux à l'anoïkis.En perspective, approfondir les connaissances des processus cellulaires et moléculaires conduisant à la dissémination intrapéritonéale et à l'émergence de chimiorésistance ainsi que déterminer le rôle potentiel de protéines ascitiques dans ces processus pourraient permettre la découverte de nouvelles cibles thérapeutiques.
45

Effects of arginine, vitamin E and vitamin C on cardiopulmonary function and ascites parameters in broilers exposed to cold temperature

Kawthekar, Sunil Bajirao. January 2007 (has links)
Two identical experiments were conducted to evaluate the combined effects of arginine (AR), vitamin E (VE) and vitamin C (VC) on cardiopulmonary performance and ascites parameters of broilers reared under cold environmental temperature. One d old male broilers were fed a basal corn-soybean meal diet (CTL, 1.2 % AR and 40 IU VE), the basal diet supplemented with 1% AR and either 200 IU VE (AE group), or 500 mg of VC (AC group), or a combination of VE and VC (AEC group) at the same level per kg of feed. Pulmonary arterial pressure (PAP) and mean arterial pressure (MAP) were recorded in clinically healthy anesthetized birds (28-42 d old) before and after an epinephrine challenge (EPI, 0.5 mg/kg BW i.v.), Amino-guanidine Hemisulphate (AG, 100 mg/kg BW i.v.) and N-Nitro L-Arginine Methyl Ester (L-NAME 50 mg/kg BW, i.v.) at 20 min intervals. The PAP increased 30 s after EPI in all birds, but the peak PAP was lower in the AEC group than in all the other birds. After 120 s of challenge the PAP was lower in AEC birds compared to the other birds. The PAP returned to pre-EPI levels within 300 s in all groups. The PAP was increased ( P< 0.05) within 60 s after the AG and L-NAME challenge in all groups, but no differences were found among groups. Plasma nitric oxide (NO) was higher in the AEC birds than in all the other groups before and after challenge. Our results showed that birds fed AEC maintained a lower PAP than the CTL birds after EPI elicited an increase in cardiac output and this can be explained by a higher production of NO. A combination of AR, VE, and VC may have complementary effects against oxidative stress, protecting the endothelium and preserving NO function.
46

Estudo da toxicidade e atividade antitumoral do derivado acridínico n’-(2-cloro-6-metoxi-acridin-9-yl)-2-ciano-3-(4-dimetilaminofenil)-acrilohidrazida em modelo experimental de tumor ascítico de ehrlich / STUDY OF TOXICITY AND ANTITUMOR ACTIVITY OF DERIVED ACRIDINE N’-(2-cloro-6-metoxi-acridin-9-yl)-2-ciano-3-(4-dimetilaminofenil)-acrilohidrazida AGAINST EHRLICH ASCITIC TUMOR.

Mangueira , Vivianne Mendes 27 February 2015 (has links)
Submitted by Cristhiane Guerra (cristhiane.guerra@gmail.com) on 2017-02-03T14:26:05Z No. of bitstreams: 1 arquivototal.pdf: 1920368 bytes, checksum: a0cab7d082218cd820a2d1c4f4b184f7 (MD5) / Made available in DSpace on 2017-02-03T14:26:05Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1920368 bytes, checksum: a0cab7d082218cd820a2d1c4f4b184f7 (MD5) Previous issue date: 2015-02-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Cancer is a major public health problem worldwide and is considered a group of diseases characterized by uncontrolled growth and multiplication of abnormal cells that can invade various tissues. Treatment has been benefited from research that seek to reduce toxicity and increase the effectiveness of different anticancer drugs. Acridine derivatives have a number of proven biological activities, and amsacrine, an antineoplastic used for the treatment of leukemias and lymphomas, is the main representative of the group. This study aimed to evaluate the toxicity and antitumor activity of acridine- derived N’-(2-chloro-6-methoxy-acridin-9-yl)-2-cyano-3-(4-dimethylaminophenyl)-acrilohydrazide (ACS-AZ10). In the assessment of cytotoxicity in mouse erythrocytes it was observed that ACS-AZ10 did not cause hemolysis at the concentrations tested (up to 1250 μg / ml), suggesting low toxicity in erythrocytes. After acute administration of ACS-AZ10 (2000 mg / kg) in mice intraperitoneally (ip), characteristic effects of changes in the central nervous system among them, writhing and abduction of the legs of the rear train, were observed. The estimated LD50 (dose that produces death in 50% of experimental animals) was around 2500 mg / kg. The ACS-AZ10 (15 or 30 mg / kg), after a nine days treatment (ip) showed significant antitumor activity in vivo in Ehrlich ascites carcinoma model (EAC), considering the volume parameters, mass, viability and total cell count. Treatment at the dose 7.5 mg/kg induced an increase in sub-G1 peak, with a consequent reduction in the percentage of cells in G0/G1 and S phases of cell cycle, suggesting death by apoptosis. However, treatment with 15 mg/kg induced cell cycle arrest in G2/M phase and a reduction of the fraction G0/G1 and S, suggesting a pre-mitotic blockade. The treatment with different doses of ACS-AZ10 significantly reduced the angiogenic capacity of the EAC, thus it can be inferred that the ACS-AZ10´s antitumor mechanism of action involves, at least in part, an anti-angiogenic effect. The toxicological analysis indicated that after nine days of treatment with ACS-AZ10, low haematological and biochemical toxicity were observed. Histopathological analysis indicated liver damage following treatment with ACS-AZ10, however, the damage was considered mild and reversible. ACS-AZ10 induced no increase in the quantity of micronucleated erythrocyte in micronucleus test, indicating the absence of genotoxic under the conditions evaluated. Therefore, it is possible to infer that the ACS-AZ10 has potent antitumor activity in vivo with low toxicity. / O câncer é um importante problema de saúde pública em nível mundial, sendo considerado um grupo de doenças caracterizadas pelo crescimento descontrolado e multiplicação de células modificadas que podem invadir diversos tecidos. Seu tratamento tem se beneficiado das pesquisas que buscam reduzir a toxicidade e aumentar a eficácia de diferentes fármacos antineoplásicos. Os derivados da acridina possuem diversas atividades biológicas comprovadas, sendo a amsacrina, um antineoplásico usado para o tratamento de leucemias e linfomas, o principal representante do grupo. Esse trabalho teve como objetivo avaliar a toxicidade e atividade antitumoral do derivado acridínico N’-(2-cloro-6-metoxi-acridin-9-yl)-2-ciano-3-(4-dimetilaminofenil)-acrilohidrazida (ACS-AZ10). Na avaliação da citotoxicidade em eritrócitos de camundongos foi possível observar que o ACS-AZ10 em concentração de até 1250 g/mL não causou dano direto a membrana de eritrócitos de camundongos, sugerindo atividade intracelular em hemácias. Após administração aguda do ACS-AZ10 (2000 mg/kg) em camundongos por via intraperitoneal (i.p.), foram observados efeitos característicos de alterações no Sistema Nervoso Central dentre estes, contorções abdominais e abdução das patas do trem posterior. O valor estimado da DL50 (dose que produz morte de 50% dos animais experimentais) foi em torno de 2500 mg/kg. O ACS-AZ10 (15 ou 30 mg/kg), após nove dias de tratamento (i.p.), mostrou significante atividade antitumoral in vivo em modelo de Carcinoma Ascítico de Ehrlich (CAE), considerando os parâmetros volume, massa, viabilidade e total celular. O tratamento na dose 7,5 mg/kg induziu um aumento do pico sub-G1, com consequente redução da percentagem de células nas fases G0/G1 e S do ciclo celular, o que sugere morte por apoptose. No entanto, o tratamento com a dose de 15 mg/kg induziu parada do ciclo celular na fase G2/M e diminuição da fração G0/G1 e S, o que sugere um bloqueio pré-mitótico. O tratamento com as diferentes doses de ACS-AZ10 diminuiu significativamente a capacidade angiogênica do CAE, desta forma, pode-se inferir que o mecanismo de ação antitumoral do ACS-AZ10 envolve, pelo menos parcialmente, um efeito antiangiogênico. As análises toxicológicas indicaram que, após nove dias de tratamento com ACS-AZ10 foi observada baixa toxicidade hematológica e bioquímica. A análise histopatológica indicou danos hepáticos após o tratamento com ACS-AZ10, entretanto, os danos foram considerados leves e reversíveis. O ACS-AZ10 não induziu aumento na quantidade de eritrócitos micronucleados no ensaio do micronúcleo, o que indica ausência de genotoxicidade, nas condições avaliadas. Portanto, é possível inferir que o ACS-AZ10 apresenta potente atividade antitumoral in vivo com baixa toxicidade.
47

Hérnia de parede abdominal no paciente cirrótico: cirurgia ou tratamento conservador? / Abdominal hernia in cirrhotic patients: surgery or conservative treatment?

Rafael Soares Nunes Pinheiro 04 July 2016 (has links)
INTRODUÇÃO: As hérnias de parede abdominal têm elevada incidência em pacientes cirróticos. Ascite e desnutrição contribuem para que essas hérnias adquiram grandes proporções, causando sintomas álgicos, decréscimo da qualidade de vida e maior risco de complicações locais que exijam tratamento cirúrgico de urgência. Contudo, o tratamento conservador é o mais empregado pela elevada morbimortalidade associada a procedimentos cirúrgicos nesses pacientes. OBJETIVO: O objetivo deste estudo é analisar os resultados do tratamento cirúrgico de hérnias de parede abdominal em pacientes cirróticos. MÉTODOS: Estudo prospectivo, baseado no seguimento de pacientes cirróticos com hérnia de parede abdominal no Ambulatório de Transplante Hepático do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, durante o período de 01/01/2009 à 01/11/2014. Foram analisadas as características demográficas, da hepatopatia, do tipo de hérnia, ocorrência de complicações e mortalidade dos pacientes que foram submetidos à cirurgia eletiva ou mantidos em acompanhamento clínico. Desse último grupo, os pacientes que apresentaram complicações com indicação de cirurgia, foram submetidos à cirurgia de urgência. Os pacientes submetidos à cirurgia eletiva foram selecionados de forma randômica. RESULTADOS: Foram avaliados 246 pacientes nesse período do estudo. A cirurgia eletiva foi realizada em 57 pacientes. Desses, 186 permaneceram em acompanhamento clínico. A incidência de complicações exigindo tratamento cirúrgico de urgência foi de 22,7% (43 pacientes). A sobrevida a longo prazo foi maior entre os pacientes submetidos à cirurgia eletiva em relação aos pacientes em acompanhamento clínico (p=0,012). A cirurgia de urgência apresentou maior incidência de complicações pós-operatórias e maior mortalidade em comparação à cirurgia eletiva (p=0,005). CONCLUSÕES: O paciente cirrótico, com hérnia de parede abdominal, apresenta elevada mortalidade em sua evolução, independente da realização da correção cirúrgica da hérnia. A cirurgia eletiva proporcionou maior sobrevida em comparação aos pacientes mantidos em acompanhamento clínico. A cirurgia de urgência foi um fator de risco para maior morbidade e mortalidade / INTRODUCTION: Cirrhotic patients have higher incidence of abdominal wall hernias. Ascistes and sarcopenia are risk factors to development of huge hernias, leading to pain, poor quality of life and need of urgent surgery due local complications. However, hernia surgery is usually delayed among cirrhotic patients due higher morbidity and mortality. OBJECTIVE: This study aimed to analyze the surgical treatment of abdominal wall hernias in cirrhotic patients. METHODS: A prospective, analytical study, based on follow-up of cirrhotic patients with abdominal wall hernia that were followed in Liver Transplant Clinic at the Hospital das Clinicas, Faculty of Medicine, University of São Paulo, during the period from January 2009 to November 2014. We analyzed demographics, characteristics of liver disease, type of hernia, complications and mortality of patients who underwent elective hernia surgery or were kept in exclusive clinical follow up. The exclusive clinical group underwent urgent hernia surgery when indicated. Elective surgery was performed in unselected patients. RESULTS: We enrolled 246 patients during the study period. Elective surgery was performed in 57 patients. 186 patients had clinical follow up, incidence of urgent surgery was 22,7% (43 patients). Elective surgery provided better long term survival then clinical follow up (p=0.012). Urgent surgery had higher morbidity and it was an independent risk factor for mortality (p=0.005). CONCLUSIONS: cirrhotic patients with abdominal wall hernia have higher mortality, regardless of performing the surgical correction. Hernia elective repair provided better survival than patients in conservative treatment. Urgent surgery imposes higher morbidity and mortality than elective surgery
48

Encéphalopathie hépatique chez les patiens atteints de cirrhose : le TIPS comme facteur de risque, apport de l'IRM multitmodale / Hepatic encephalopathy in aptients with cirrhosis : pathophysiology, TIPS as a risk factor, multimodal MRI for the prediction of neurological prognosis after TIPS placement

Rudler, Marika 11 December 2017 (has links)
Le TIPS (Transjugular Intrahepatic Portosystemic Shunts) est le traitement de référence au cours de l'hémorragie digestive par rupture de varices, ou dans le traitement de l'ascite réfractaire chez les patients atteitns de cirrhose. Il peut entraîner une encéphalopathie hépatique (EH), dans 35% des cas environ. L'imagerie par résonnance magnétique (IRM) cérébrale est l'examen de référence pour le diagnostic et le pronostic des maladies neurologiques. L'IRM multimodale combine la spectroscopie, l'imagerie par tenseur de diffusion, et l'IRM fonctionnelle de repos. La combinaison de ces différentes techniques a un intérêt pour le pronostic neurologique après traumatisme crânien ou arrêt cardio-respiratoire. Dans la première partie de ce travail, nous ferons une revue de la littérature sur l'EH en 2017. Nous décrirons les bénéfices du TIPS dans la prise en charge des complications de la cirrhose telles que l'hémorragie digestive et l'ascite, et aussi la probabilité de développer une EH après TIPS. La deuxième partie de ce travail sera consacrée à l'IRM cérébrale mutimodale. Nous en expliquerons les principes généraux, puis nous décrirons les données publiées dans la cirrhose. Enfin, nous présenterons les résultats obtenus en IRM cérébrale multimodale chez des patients candidats à la pose d'un TIPS. Nous décrirons en particulier qu'il existe des facteurs prédictifs de développement d'une EH après TIPS. En effet, la fraction d'anisotropie est plus basse dans notre série avant TIPS chez les aptients qui vont développer une EH après TIPS. Ainsi, le tenseur de diffusion pourrait aider à discrimier les patients qui sont les plus à risque de développer une EH. / TIPS placement is required for the management of variceal bleeding or ascites in cirrhosis. However, hepatic encephalopathy (HE) may occur in 35% of patients after TIPS placement. Magnetic resonance imaging (MRI) is the best exam for the diagnosis and the prognosis of several neurological diseases. Multimodal MRI combines spectroscopy, diffusion tensor imaging and resting state. It has been proven to help for neurological prognostic in comatose patients after traumatic brain injury or cardiac arrest. In this manuscript, we will explain HE pathophysiology and management of HE in 2017. We will also describe results obtained with TIPS placement in patients with variceal bleeding. The second part of the manuscript will be dedicated to multimodal MRI: we will clarify each technique and what has been published in the setting of cirrhosis. Last, we will explain our results obtained in patients who are candidate for non urgent TIPS placement and will suggest that a low fractional anisotropy before TIPS may help to identify patients that are at risk of developing HE after TIPS.
49

Effects of arginine, vitamin E and vitamin C on cardiopulmonary function and ascites parameters in broilers exposed to cold temperature

Kawthekar, Sunil Bajirao. January 2007 (has links)
No description available.
50

A influência da convivência com um parceiro doente sobre a resposta inflamatória alérgica pulmonar em camundongos / The influence of cohabitation with sick partner on pulmonary allergic inflammatory response in mice

Hamasato, Eduardo Kenji 26 April 2016 (has links)
As relações bidirecionais entre o Sistema Nervoso e o Sistema Imune são relevantes para a manutenção da homeostase do organismo. Estudos realizados em nosso laboratório mostraram que 14 dias de coabitação com um conspecífico doente (injetado com células do tumor de Ehrlich-TAE) produziu mudanças comportamentais, endócrinas e imunológicas. Este estudo analisa os efeitos da convivência com um animal portador de tumor de Ehrlich em camundongos OVA sensibilizados e desafiados sobre a resposta alérgica pulmonar. Pares de camundongos machos foram separados em três grupos: naïve, controle e experimental. Os animais do grupo naïve não foram manipulados sendo utilizados para a avaliação de parâmetros basais. Um animal de cada par dos grupos experimental e controle foi imunizado com OVA. No dia D(0), os animais imunizados receberam uma dose reforço de OVA. No dia D(0) os camundongos do grupo experimental que não foram manipulados foram inoculados com 5x106 células de tumor de Ehrlich; seus companheiros de gaiola moradia foram designados CAD (companheiro do animal doente). Os camundongos não perturbados de cada par do grupo controle foram tratados (i.p.) em D(0) com 0,9% de NaCl, sendo designados CAS (companheiro do animal saudável). O desafio intranasal com OVA foi realizado nos camundongos CAS e CAD nos dias D(12) e D(13); colheram-se o sangue e os tecidos no dia D(14). Em comparação com o grupo CAS, os camundongos do grupo CAD apresentaram 14 dias após a coabitação: (1) aumento do número de eosinófilos e neutrófilos no LBA, (2) diminuição na contagem de células da medula óssea, (3) aumento do níveis de IL-4 e IL-5 e diminuição de IL-10 e INF-ϒ no sobrenadante do LBA, (4) aumento dos níveis de IgG1-OVA, diminuição dos níveis de IgG2a-OVA e nenhuma alteração na IgE-OVA no sangue periférico, (5) aumento na expressão de ICAM-1, VCAM-1 e L-selectina em granulócitos do LBA, (6) diminuição da reatividade da traquéia à metacolina in vitro, (7) aumento da desgranulação de mastócitos, (8) nenhuma alteração nos níveis plasmáticos de corticosterona, (9) aumento dos níveis de adrenalina e noradrenalina plasmáticas, (10) diminuição no tempo de permanência e entradas nos braços abertos do labirinto em cruz elevado, (11) diminuição da expressão de IL-6 no PVN e (12) diminuição da expressão de C-fos no PFC. Estes resultados mostram que a convivência forçada com um animal portador de um tumor ascitico de Ehrlich exacerba a inflamação alérgica pulmonar de camundongos. Eles foram discutidos como decorrentes da estimulação do Sistema Nervoso Autônomo Simpático (SNS) pelo estresse psicológico gerado pela coabitação com o parceiro doente, via liberação de adrenalina e noradrenalina e consequente mudança no perfil de citocinas Th1/Th2 para uma resposta do tipo Th2. Esta alteração seria, provavelmente, um dos mecanismos responsáveis pelo aumento do recrutamento celular para as vias aéreas dos camundongos do grupo CAD. / The bidirectional relationship between the nervous system and the imune system is relevant for homeostatic organism maintenance. Studies from our laboratory showed that 14 days of cohabitation with a sick conspecific (injected with Ehrlich tumor cells-TAE) produced behavioral, endocrinological and immunological changes. This study analyzes the effects of cohabitation with an Ehrlich tumor-bearing animal on ovalbumin (OVA)-induced lung inflammatory response in mice. Pairs of male mice were separate into three groups: naïve, control and experimental. Animals of the naïve group were kept undisturbed being used for assessment of basal parameters. One animal of each experimental and control pair of mice was immunized with OVA. On D(0), these OVA-immunized animals received an OVA booster. At this day (D(0)) the experimental mice that were kept undisturbed were inoculated with 5x106 Ehrlich tumor cells; their immunized cage-mates were then referred as to CSP(companion of sick partner). The undisturbed mice of each control pair were i.p. treated on D(0) with 0.9% NaCl; their sensitized cage-mate were subsequently referred as CHP (companion of health partner). The intranasal OVA challenge was performed on CSP and CHP mice on D(12) and D(13); blood and tissue collection were performed on D (14). Fourteen days after cohabitation, in comparison to the CHP mice, the CSP mice displayed the following: (1) an increased number of eosinophils and neutrophils in the BAL, (2) a decreased bone marrow cell count, (3) increased levels of IL-4 and IL-5 and decreased levels of IL-10 and INF-ϒ in the BAL supernatant, (4) increased levels of IgG1-OVA, decreased levels of IgG2a-OVA and no changes in OVA-specific IgE in the peripheral blood, (5) increased expression of ICAM-1, VCAM-1 and L-selectin in the BAL granulocytes, (6) decreased tracheal reactivity to metacholine measured in vitro , (7) increased mast cell degranulation, (8) no changes in plasma corticosterone levels (9) increased levels of plasmatic adrenaline and noradrenaline, (10) decreased time and % of entries on open arms of elevated plus maze, (11) decreased expression of IL-6 on PVN and (12) decreased expression of C-fos on PFC. These results suggest that cohabitation with an Ehrlich tumor bearing mice exacerbates allergic lung inflammatory response in mice. Most probably, the changes observed in CSP mice are a consequence of the psychological stress induced by forced cohabitation with the sick partner. Strong involvement of the sympathetic nervous system through adrenaline and noradrenaline release and a shift of the Th1/Th2 cytokine profile toward a Th2 response were considered to be the mechanisms underlying the cell recruitment to the animal´s airways.

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