A esquistossomose mansoni é uma das principais doenças parasitárias no mundo e é conhecida por ser endêmica em aproximadamente 54 países nos continentes americano e africano. No Brasil o número de pessoas infectadas é estimado em 7 milhões. Em suas diversas formas clínicas, a esquistossomose mansoni assemelha-se a muitas outras doenças; portanto, essa inespecificidade e a variação nos sintomas dificultam o seu diagnóstico apenas pelo exame clínico do paciente. A doença é diagnosticada por métodos parasitológicos de fezes. A técnica de Kato/Katz é o procedimento internacionalmente recomendado pela Organização Mundial da Saúde (OMS) para o diagnóstico do Schistosoma mansoni, porque associa baixo custo à facilidade de execução. Atualmente, estão disponíveis Kits comerciais, a fim de minimizar as dificuldades de operacionalização e melhorar a sensibilidade do diagnóstico parasitológico, principalmente em áreas de baixa endemicidade. Este estudo avaliou comparativamente a efetividade de quatro técnicas parasitológicas de fezes em diagnosticar casos de esquistossomose mansoni. As amostras fecais foram examinadas pelas técnicas Kato/Katz, Sedimentação espontânea e pelos Kits Midi Parasep® e Paratest®. Foi coletada 1 amostra de cada indivíduo e para cada amostra foram preparadas 2 lâminas das quatro metodologias. Um total de 442 exames coproparasitológicos foram realizados em migrantes de áreas endêmicas para a esquistossomose, de três municípios sob jurisdição da Superintendência Regional de Saúde de Alfenas (SRS). A taxa de positividade da esquistossomose mansoni detectada pela técnica Kato/Katz foi de 1,8%. Pela técnica de Sedimentação espontânea e pelo Kit Paratest® foi detectada uma positividade de 0,45%. Pelo Kit Midi Parasep® a positividade foi de 0,23%. A menor efetividade da técnica de sedimentação espontânea e dos Kits Midi Parasep® e Paratest® pode ser comprovada pelo baixo grau de concordância diagnóstica com o exame referência (técnica Kato/Katz). As técnicas Kato/Katz e sedimentação espontânea apresentam os menores custos para realizar o exame de fezes, cerca de R$ 0,82/exame e R$ 0,48/exame, respectivamente. Entretanto, são as que apresentam o maior grau de exposição do analista à amostra biológica. Os Kits Midi Parasep® e Paratest® apresentam o menor grau de exposição à amostra fecal, mas são relativamente mais caros para realização do exame de fezes, cerca de R$ 3,10/exame e R$ 1,65/exame, respectivamente. Com relação as parasitoses intestinais, pelo “Padrão Ouro”, foram encontrados 97 (21,9%) indivíduos parasitados. As taxas de positividade das parasitoses intestinais detectadas pelas técnicas Kato/Katz, sedimentação espontânea, Midi Parasep® e Paratest®, foram respectivamente, 5,2%, 19,5%, 17,6% e 18,3%. Os resultados mostraram que a técnica de Kato/Katz apresentou melhor desempenho dos quatro testes no diagnóstico da esquistossomose mansoni. Assim, a vigilância epidemiológica através do exame censitário de todos os migrantes pela técnica Kato/Katz, deve ser implementada com o propósito de impedir o estabelecimento da transmissão da esquistossomose. / Schistosomiasis mansoni is a major parasitic disease in the world and is known to be endemic in about 54 countries in the American and African continents. In Brazil the number of infected is estimated at 7 million. In different clinical forms, schistosomiasis mansoni resembles many other diseases. So this lack of specificity and symptoms variety hinder its diagnosis only by clinical examination. The disease is diagnosed using stool examinations. The Kato/Katz technique is the procedure recommended by the World Health Organization (WHO) for the diagnosis of Schistosoma mansoni, because it associates low cost and easy execution. Currently, there are commercial Kits available, in order to minimize the operational difficulties and improve the sensitivity of parasitological diagnosis, especially in areas of low endemicity. This study comparatively evaluated the effectivity of four stool parasitological techniques in diagnosing cases of schistosomiasis. Stool samples were examined by the Kato/katz and spontaneous sedimentation techniques, Midi Parasep® and Paratest® kits. One sample was collected from each individual and for each sample were prepared two slides of the four methods. A total of 442 coproparasitological exams were accomplished with migrants from endemic areas for schistosomiasis, of three cities under Health Superintendence Office of Alfenas (HSO) jurisdiction. The positivity rate of Kato/Katz technique for schistosomiasis was 1,8%. The positivity rate schistosomiasis by the spontaneous sedimentation technique and Paratest® was of 0,45%. By Midi Parasep® Kit the positivity rate was of 0,23%. The lower effectivity of spontaneous sedimentation and Midi Parasep® and Paratest® can be demonstrated by low agreement diagnostic with the reference examination (Kato/Katz). Kato/Katz and spontaneous sedimentation techniques showed low cost for the exam stool, about R$ 0,82 per exam and R$ 0,48 per exam, respectively. However, are those with greatest degree of exposure of the expert to biological samples. Midi Parasep® and Paratest® Kits showed the lowest degree of exposure to fecal sample, but are relatively more expensive for perform the fecal exam, about R$ 3,10 per exam and R$ 1,65 per exam, respectively. Regarding intestinal parasites, by the "gold standard" were found 97 (21,9%) individuals parasitized. The positivity rates of intestinal parasitosis detected by the Kato/Katz, spontaneous sedimentation, Midi Parasep® and Paratest®, were respectively, 5,2%, 19,5%, 17,6% e 18,3%. The results showed that the Kato/Katz technique presented best of performance diagnosising of schistosomiasis mansoni. Thus, epidemiological surveillance should implement the Kato/Katz technique in order to prevent the establishment of transmission of schistosomiasis. / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq

Submitted by Setor de Tratamento da Informa??o - BC/PUCRS (tede2@pucrs.br) on 2016-04-13T16:30:14Z No. of bitstreams: 1 DIS_PRICILA_KURZ_DE_ASSUMPCAO_PARCIAL.pdf: 290160 bytes, checksum: d018575426ad9071019ec6e098c90a03 (MD5) / Made available in DSpace on 2016-04-13T16:30:14Z (GMT). No. of bitstreams: 1 DIS_PRICILA_KURZ_DE_ASSUMPCAO_PARCIAL.pdf: 290160 bytes, checksum: d018575426ad9071019ec6e098c90a03 (MD5) Previous issue date: 2016-01-12 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Objectives: To evaluate the functional capacity of obese children and adolescents compared with normal-weight individuals and investigate possible relationships with biochemical parameters in the blood. Methods: In this study were included children and adolescents, between 6 and 18 years, divided into control (eutrophic) and obese groups according to body mass index (BMI). Data were collected regarding demographic, anthropometric, waist circumference and functional capacity through the Shuttle Walk Test (SWT). In the obese group were evaluated biochemical parameters in the blood (total cholesterol, HDL, LDL, triglycerides and glucose), and the application of a physical activity questionnaire. For statistical analysis were used the chi-square test, Student's t test for independent samples and the Pearson correlation test. Results: 77 participants were included, 27 in the control group and 50 obese. There was no significant difference between the two groups regarding sample characteristics, except for body weight, BMI and waist circumference. Most obese presented results of biochemical tests within the desirable limit, though none were considered active. There was a significant reduction (p <0.001) functional capacity in obese group compared to control subjects. Positive correlations were identified SWT with age and height, and negative correlation with BMI. However, there were no correlations with the biochemical parameters analyzed. Conclusions: Obese children and adolescents have reduced physical capacity when compared to normal individuals. The SWT performance seems to have a negative association with BMI, but is not correlated with the blood biochemical parameters. / Objetivos: Avaliar a capacidade funcional de crian?as e adolescentes obesas em compara??o com indiv?duos eutr?ficos e verificar poss?veis correla??es com par?metros bioqu?micos no sangue. Materiais e m?todos: Foram inclu?das crian?as e adolescentes, entre 6 e 18 anos, divididos em grupos controle (eutr?fico) e obeso de acordo com o ?ndice de massa corporal (IMC). Coletaram-se dados referentes ?s caracter?sticas demogr?ficas, antropom?tricas, circunfer?ncia abdominal e capacidade funcional atrav?s do Shuttle Walk Test (SWT). No grupo de obesos, foram avaliados par?metros bioqu?micos no sangue (colesterol total, HDL, LDL, triglicer?deos e glicemia), al?m da aplica??o de um question?rio de atividade f?sica. Para an?lise estat?stica, utilizaram-se os testes de qui-quadrado, t de Student para amostras independentes e o teste de correla??o de Pearson. Resultados: Foram inclu?dos 77 participantes, sendo 27 no grupo controle e 50 obesos. N?o houve diferen?a significativa entre os dois grupos em rela??o ?s caracter?sticas da amostra, exceto quanto ao peso corporal, IMC e circunfer?ncia abdominal. A maioria dos obesos apresentaram resultados dos exames bioqu?micos dentro do limite desej?vel, por?m nenhum foi considerado ativo. Houve redu??o significativa (p<0,001) da capacidade funcional no grupo obeso quando comparado aos indiv?duos controles. Foram identificadas correla??es positivas do SWT com idade e altura, e correla??o negativa com o IMC. No entanto, n?o foram encontradas correla??es com os par?metros bioqu?micos analisados. Conclus?es: Crian?as e adolescentes obesos apresentam redu??o da capacidade f?sica quando comparados a indiv?duos eutr?ficos. O desempenho no SWT parece ter associa??o negativa com o IMC, por?m n?o se correlaciona com par?metros bioqu?micos no sangue.

Made available in DSpace on 2015-03-04T18:58:02Z (GMT). No. of bitstreams: 1 thesis (1).pdf: 2502829 bytes, checksum: 20035b341686418a94516986bc16b476 (MD5) Previous issue date: 2013-11-22 / In this dissertation, we present a detailed study of the model proposed by Hinow et al. 2009, in which, through a continuum model based on equations of reaction-diffusion type, the authors simulate the spatial dynamics of tumor growth. The dynamics of proliferating, hypoxic, necrotic and endothelial cells, extracellular matrix and nutrients are included in this model. An angiogenesis model is also included, allowing the evaluation of different treatment protocols for cancer through antiangiogenic and cytotoxic drugs. Numerical and computational models have been developed for this class of models. Further examination of the model from Hinow et al. 2009 indicated some inconsistencies in the model. By adding new hypotheses, a new model is developed, overcoming the observed non-biological behaviors. The new model aggregates new dynamics, including the interactions between healthy cells and other tissues. One of the major contribution of this model is the proposal of a haptotactic term responsible for the directional movement of healthy cells towards dead cells. The inclusion of such term provides a more realistic approach to the treatment of the disease. As an example, healthy cells are able to return to regions formerly occupied by the tumor after a successful cytotoxic treatment. Several numerical experiments are presented to justify the development of such model and to show its behavior when different treatment protocols for the disease are considered. / Nesta dissertacao de mestrado apresentamos um estudo detalhado do modelo proposto por Hinow et al. 2009, no qual os autores por meio de um modelo continuo baseado em equacoes do tipo reacao-difusao simulam a dinamica espacial do crescimento tumoral. Neste modelo sao incluidas as dinamicas das celulas proliferativas, hipoxicas, necroticas e endoteliais, alem da matriz extracelular e de nutrientes. Um modelo de angiogenese e tambem incluido, permitindo a avaliacao de diferentes protocolos de tratamento da doenca por meio de drogas antiangiogenicas e citotoxicas. Modelos numericos e computacionais foram desenvolvidos para esta classe de modelos tendo como base formulacoes consistentes de elementos finitos. O estudo aprofundado do modelo de Hinow et al. 2009 indicou algumas inconsist^encias. A partir da inclusao de novas hipoteses um novo modelo foi desenvolvido, eliminando as situacoes nao-biologicas observadas. O novo modelo agrega novas dinamicas, incluindo as interacoes das celulas saudaveis com as demais do tecido. Uma das maiores contribuicoes do novo modelo proposto e a consideracao de um termo haptotatico responsavel pelo movimento direcional das celulas saudaveis na direcao das celulas mortas. A inclusao de tal termo propiciou uma abordagem mais realista do tratamento da doenca, captando por exemplo, apos o tratamento citotoxico, a retomada pelas celulas saudaveis da regiao outrora ocupada pelo tumor. Diversos experimentos numericos sao apresentados para justificar o desenvolvimento de tal modelo, assim como a simulacao de diversos protocolos de tratamento da doenca.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2014-10-16T15:13:44Z No. of bitstreams: 2 Dissertacao Ely Rodrigues de Almeida - 2013.pdf: 1560361 bytes, checksum: 153a2514b81e70d5b31e01a1cc0d09b6 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-10-20T20:06:38Z (GMT) No. of bitstreams: 2 Dissertacao Ely Rodrigues de Almeida - 2013.pdf: 1560361 bytes, checksum: 153a2514b81e70d5b31e01a1cc0d09b6 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-10-20T20:06:38Z (GMT). No. of bitstreams: 2 Dissertacao Ely Rodrigues de Almeida - 2013.pdf: 1560361 bytes, checksum: 153a2514b81e70d5b31e01a1cc0d09b6 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-10-15 / INTRODUCTION: Anticoagulation with warfarin is used in the presence of hypercoagulability and as prophylaxis for thromboembolism. Prothrombin time and activity and the international normalized ratio (PTA/INR) are the standard tests for laboratory follow up of the anticoagulation rate. Hemorrhage is one complication of this therapy. Therefore, one speculates on the possibility of diagnosing cases in which there is excess anticoagulation, by means of the analysis of hematuria in urinalysis and the association with PTA/INR. OBJECTIVE: Analyze the existence of a correlation between hematuria in urinalysis and high PTA/INR, among users of warfarin. METHODOLOGY: This is a descriptive, analytical, primary, quantitative and cross-sectional investigation. The study included 128 patients, 63 of whom were being treated with warfarin, and formed the group of anticoagulated patients (ACG). The remaining 65 patients who were not using anticoagulants formed the non anticoagulated group (NACG). For this study, 152 blood and urine samples were collected; 24 patients of the ACG contributed twice for the PTA/INR and urinalysis, at two different times. All the participants of the NACG also had the PTA/INR and urinalysis tests done. Patients with a clinical suspicion of conditions that might cause hematuria were excluded. The social and demographic data of these individuals were analyzed and the numerical variables of hematuria and of other urinalysis and INR parameters were measured and analyzed. The prevalence and the correlation between hematuria and PTA/INR levels were calculated. Data from the tests, medical appointments and the records of patients recruited in the collection room of the Clinical Laboratory of the HC-UFG were evaluated statistically, and emphasis was placed on the Spearman's correlation for hematuria and PTA/INR (IC 95%; p< 0.05). The study was approved by the Committee on Ethics and Human Research of the HC-UFG, protocol No. 016/2012. RESULTS: The amount of warfarin given on a weekly basis ranged from 10 to 65 mg. If one considers the INR between 2 and 3.9 acceptable for adequate anticoagulation, 59.77% of the individuals were adequately anticoagulated, 35% were insufficiently anticoagulated and 5.75% were excessively anticoagulated. The prevalence of hematuria among the ACG members was 26.44 % (CI 95% 17.98 – 36.43) and among NACG members, 29.23 % (CI 95% 19.16 – 41.11). The correlation coefficient between hematuria and INR was 0.012 (p=0.887). CONCLUSIONS: The most of the patients (59.7%) were within the recommended therapeutic range for controlling patients. There was no correlation between hematuria as measured by urinalysis and anticoagulation levels measured by the INR. / INTRODUÇÃO: A anticoagulação com varfarina é usada na hipercoagubilidade e como profilaxia para o tromboembolismo. O tempo e atividade de protrombina e a relação normatizada internacional (TAP/RNI) são os exames padrões para acompanhamento laboratorial da taxa de anticoagulação. A hemorragia é uma complicação desta terapia. Dessa forma, especula-se a possibilidade de diagnosticar casos em que haja excesso de anticoagulação, por meio da análise da hematúria no exame dos elementos anormais e sedimentoscopia da urina (EAS) e a associação com TAP/RNI. OBJETIVO: Analisar a existência de correlação entre hematúria no EAS e TAP /RNI elevados, nos usuários do anticoagulante varfarina. METODOLOGIA: Estudo descritivo, analítico, primário, quantitativo e transversal. Incluíram-se 128 pacientes, sendo 63 tratados com varfarina, formando um grupo anticoagulado (GAC) e 65 que não faziam uso de anticoagulantes, grupo não anticoagulado (GNAC). Colheram-se 152 amostras de sangue e urina; das quais 24 pacientes do GAC contribuíram duas vezes para exames TAP/RNI e EAS, em dois momentos distintos. Todos os participantes do GNAC também se submeteram aos exames TAP/RNI e EAS. Excluíram-se pacientes com suspeita clínica de condições que causassem hematúria. Analisaram-se os dados sociodemográficos e fez-se a mensuração e a análise das variáveis numéricas hematúria e de outros parâmetros do EAS e RNI. Calculou-se a prevalência e a correlação entre hematúria e níveis de TAP/RNI. Os dados oriundos de exames, consultas médicas e dos prontuários dos pacientes recrutados na sala de coleta do Laboratório Clinico do HC-UFG, foram avaliados estatisticamente, com ênfase na correlação de Spearman para hematúria e TAP/RNI (IC 95%; p<0,05). O projeto foi aprovado pelo Comitê de Ética e Pesquisa Humana do HC-UFG sob o nº 016/2012. RESULTADOS: A quantidade de varfarina semanal variou de 10 a 65 mg. Considerando-se o valor de RNI entre 2 e 3,9, como valor aceitável para adequada anticoagulação, 59,77% estavam adequadamente anticoagulados, 35% insuficientemente e, com efeito anticoagulante excessivo, 5,75%. A prevalência de hematúria no GAC foi de 26,44 % (IC 95% 17,98 – 36,43) e no GNAC, foi de 29,23 % (IC 95% 19,16 – 41,11). O coeficiente de correlação entre hematúria e RNI foi de 0,012 (p=0,887). CONCLUSÕES: A maioria dos pacientes (59,7%) tinha a RNI na faixa terapêutica preconizada para anticoagulação. Não houve correlação entre hematúria ao exame EAS e os níveis de anticoagulação medidos pela RNI.

Submitted by Cristiane Chim (cristiane.chim@ucpel.edu.br) on 2018-10-08T12:04:48Z No. of bitstreams: 1 Felipe Simões Lopes Quintana.pdf: 77300691 bytes, checksum: ee08226cb6940ec6c50e71b9ec852ebe (MD5) / Made available in DSpace on 2018-10-08T12:04:48Z (GMT). No. of bitstreams: 1 Felipe Simões Lopes Quintana.pdf: 77300691 bytes, checksum: ee08226cb6940ec6c50e71b9ec852ebe (MD5) Previous issue date: 2017-10-10 / . / Descrever dois dermatofibromas, analisando seus aspectos clínicos, histológicos e ultraestruturais. 3.2 ESPECÍFICOS a) Descrever os achados da microscopia óptica com a coloração com hematoxicilina e eosina. b) Descrever os achados da microscopia óptica com a coloração Weigert. c) Descrever aspectos ultraestruturais tridimensionais com microscopia eletrônica de varredura. d) Descrever os aspectos clínicos do dermatofibroma.

Resumo: O objetivo deste estudo foi avaliar o papel do ácido retinóico na remodelação cardíaca induzida pela exposição à fumaça do cigarro. Os ratos foram divididos em três grupos: controle (C, n = 8); expostos animais expostos à fumaça do cigarro (EFC, n = 9); animais expostos à fumaça de cigarro e suplementados com ácido retinóico (EFC-AR, n = 9). Após dois meses, foram submetidos ao ecocardiograma e análise morfométrica. Os dados estão expressos em média ± desvio padrão ou medianas e intervalo interquartílico (Q1-Q3). Não houve diferença na pressão sistólica caudal entre os grupos (C = 116 ± 27 mmHg; EFC = 129 ± 17 mmHg; EFC-AR = 139 ± 19 mmHg; p = 0,102). O grupo EFC mostrou maior diâmetro diastólico do ventrículo esquerdo ajustado ao peso corporal (C = 18,42 ± 3,57 mm/kg; EFC = 23 ± 1,85 mm/kg; EFC-AR = 19,51 ± 0,99 mm/kg; p = 0,001) e sistólico ajustado ao peso corporal (C = 8,25 ± 2,16 mm/kg; EFC = 11,53 ± 1,31 mm/kg; EFC-AR = 8,25 ± 0,71 mm/kg; p = <0,001) quando comparado com C grupo e EFC-AR. Por outro lado, não houve diferença entre C e EFC-AR. A espessura da parede do ventrículo esquerdo ajustado ao diâmetro diastólico do ventrículo esquerdo foi maior no grupo C do que nos EFC (C = 0,20 (0,18-0,23); EFC = 0,15 (0,14-0,18); EFC-AR = 0,19 (0,17-0,22; p = 0,003). A fração de ejeção (C = 0,91 ± 0,02; EFC = 0,87 ± 0,03; EFC-AR = 0,92 ± 0,03; p = 0,003) e a fração de encurtamento (C = 55,77 ± 4,41%; EFC = 49,73 ± 4,43%; EFC-AR = 57,60 ± 5,15%; p = 0,005) foram mais elevados nos animais do grupo C e EFC-AR em relação aos animais do grupo EFC. Por outro lado, não houve diferenças entre C e EFC-AR. Além disso, o tabagismo está associado com um aumento significativo da área seccional do miócito (C = 294 ± 21 μm2; EFC = 347 ± 44 μm2; EFC-AR = 310 ± 37 μm2; p = 0,016). Por outro lado... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of this study was to evaluate the role of retinoic acid in the myocardial remodeling induced by tobacco smoke exposure. Rats were allocated into three groups: control (C, n=8); exposed to tobacco smoke (ETS, n=9); exposed to tobacco smoke and all-transretinoic acid (ETS-AR, n = 9). After two months, were submitted to echocardiogram, and morphometric analyses. Data are expressed as mean ± SD or medians (including the lower quartile and upper quartile). There were no differences in the tail systolic pressure among the groups (C = 116 ± 27 mmHg, ETS = 129 ± 17 mmHg, ETS-AR = 139 ± 19 mmHg; p = 0,102). ETS showed higher normalized left ventricular diastolic (C = 18,42 ± 3,57 mm/kg, ETS = 23 ± 1,85 mm/kg, ETS-AR = 19,51 ± 0,99 mm/kg; p = 0,001) and systolic (C = 8,25 ± 2,16 mm/kg, ETS = 11,53 ± 1,31 mm/kg, ETS-AR = 8,25 ± 0,71mm/kg; p = <0,001) diameters than C and ETS-AR. On the other hand, there were no differences between C and ETS-RA. LVWT/LVEDD was higher in C than ETS (C = 0,20 (0,18-0,23), ETS = 0,15 (0,14-0,18), ETS-RA = 0,19 (0,17-0,22; p = 0,030). The ejection fraction (C = 0,91 ± 0,02, ETS = 0,87 ± 0,03, ETS-AR = 0,92 ± 0,03; p = 0,003) and fractional shortening (C = 55,77 ± 4,41 %, ETS = 49,73 ± 4,43 %, ETS-AR = 57,60 ± 5,15 %; p = 0,005) were higher in C and ETS-RA animals than ETS animals. On the other hand, there were no differences between C and ETS-RA. Also, smoking was associated with significantly increased myocyte cross-sectional area (C = 294 ± 21 μm2, ETS = 347 ± 44 μm2, ETS-RA = 310 ± 37 μm2; p = 0,016). On the other hand, there were no differences between C and ETS-RA. Retinoic acid did not affect other functional or morphological variables. In conclusion, ...(Complete abstract click electronic access below) / Orientador: Leonardo A. M. Zornoff / Coorientador: Sergio A. R. de Paiva / Banca: Paula Schmidt Azevedo Gaiolla / Banca: Wilson Nadruz Junior / Mestre

“Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics”.(Paoloni and Khanna, 2008) In last years, the author has investigated some molecular features of cancer in dogs. The Thesis is articulated in two main sections. In section 1, the preliminary results of a research project aimed at investigating the role of somatic mutations of Ataxia-Telangiectasia mutated (ATM) gene in predisposing to cancer in boxer dogs, are presented. The canine boxer breed may be considered an unique opportunity to disclose the role of ATM somatic mutation since boxer dogs are known to be dramatically susceptible to cancer and since they may be considered a closed gene pool. Furthermore, dogs share with human the some environment. Overall, the abovementioned features could be considered extremely useful for our purposes. In the section 2, the results of our studies aimed at setting up accurate and sensitive molecular assays for diagnosing and assessing minimal residual disease in lymphoproliferative disorders of dogs, are presented. The results of those molecular assay may be directly translated in the field of Veterinary practice as well as the may be used to improve our objective evaluation of new investigational drugs effectiveness in canine cancer trials.

Aim: To evaluate the early response to treatment to an antiangiogenetic drug (sorafenib) in a heterotopic murine model of hepatocellular carcinoma (HCC) using ultrasonographic molecular imaging. Material and Methods: the xenographt model was established injecting a suspension of HuH7 cells subcutaneously in 19 nude mice. When tumors reached a mean diameter of 5-10 mm, they were divided in two groups (treatment and vehicle). The treatment group received sorafenib (62 mg/kg) by daily oral gavage for 14 days. Molecular imaging was performed using contrast enhanced ultrasound (CEUS), by injecting into the mouse venous circulation a suspension of VEGFR-2 targeted microbubbles (BR55, kind gift of Bracco Swiss, Geneve, Switzerland). Video clips were acquired for 6 minutes, then microbubbles (MBs) were destroyed by a high mechanical index (MI) impulse, and another minute was recorded to evaluate residual circulating MBs. The US protocol was repeated at day 0,+2,+4,+7, and +14 from the beginning of treatment administration. Video clips were analyzed using a dedicated software (Sonotumor, Bracco Swiss) to quantify the signal of the contrast agent. Time/intensity curves were obtained and the difference of the mean MBs signal before and after high MI impulse (Differential Targeted Enhancement-dTE) was calculated. dTE represents a numeric value in arbitrary units proportional to the amount of bound MBs. At day +14 mice were euthanized and the tumors analyzed for VEGFR-2, pERK, and CD31 tissue levels using western blot analysis. Results: dTE values decreased from day 0 to day +14 both in treatment and vehicle groups, and they were statistically higher in vehicle group than in treatment group at day +2, at day +7, and at day +14. With respect to the degree of tumor volume increase, measured as growth percentage delta (GPD), treatment group was divided in two sub-groups, non-responders (GPD>350%), and responders (GPD<200%). In the same way vehicle group was divided in slow growth group (GPD<400%), and fast growth group (GPD>900%). dTE values at day 0 (immediately before treatment start) were higher in non-responders than in responders group, with statistical difference at day 2. While dTE values were higher in the fast growth group than in the slow growth group only at day 0. A significant positive correlation was found between VEGFR-2 tissue levels and dTE values, confirming that level of BR55 tissue enhancement reflects the amount of tissue VEGF receptor. Conclusions: the present findings show that, at least in murine experimental models, CEUS with BR55 is feasable and appears to be a useful tool in the prediction of tumor growth and response to sorafenib treatment in xenograft HCC.

Dissertação (mestrado) - Universidade do Estado do Rio de Janeiro, Instituto de Medicina Social / Made available in DSpace on 2012-10-15T23:47:36Z (GMT). No. of bitstreams: 0

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia de Produção / Made available in DSpace on 2012-10-23T08:43:23Z (GMT). No. of bitstreams: 1 241054.pdf: 5221121 bytes, checksum: 47fc54981ae7596b9ac9d2be2f8b936d (MD5) / Esse estudo teve como objetivo identificar o processo de raciocínio clínico na elaboração de hipóteses diagnósticas, contextualizado a um tema protótipo em Clínica Médica (CM), tendo como pressuposto que a estratégia hipotético-dedutiva é a base do raciocínio clínico e a esquema-indutiva e o reconhecimento de um padrão são estratégias auxiliares ou combinadas. O delineamento foi transversal, com base epistemológica qualitativa, com amostra não-probabilística do tipo intencional. Foi realizado no Hospital Universitário, da UFSC, em Florianópolis - SC, com 30 médicos-professores de um Departamento de Ensino em CM, que exercem ou exerceram atividade clínica por mais de 5 anos. A construção de protótipos em CM pelos participantes permitiu selecionar um caso clínico real, que foi o estímulo para a aplicação da técnica "think aloud" ou "pensando em voz alta". O texto obtido do processo de raciocínio clínico com a verbalização dos participantes foi gravado, transcrito e analisado com a aplicação da técnica de análise temática, do método de análise de conteúdo; para o perfil profissional foi aplicado um questionário estruturado. A estratégia de raciocínio mais freqüente foi a hipotético-dedutiva (HD) (47% (72/153)), com a mesma freqüência para a esquema-indutiva (E-I) (15,6% (24/153)) e o reconhecimento de um padrão (RP) (15,6%(24/153)), seguida pela mista E-I (E-I + HD) e mista RP (RP + HD) (respectivamente, 11,7% (18/153) e 9,8% (15/153), ao estabelecerem 153 hipóteses dentro de 31 tipos distintos. Concomitantemente, foram criados 356 eixos semânticos inseridos em 135 tipos, e os dados processados com 515 interpretações e 290 combinações. O perfil geral da amostra mostrou expressivo tempo de exercício na atividade clínica (27,3 anos) e na docência (24,4 anos), com uma média de especialização latu sensu de 2,3/participante, e mais da metade (53% (16/30) com strictu sensu. Os médicos-professores têm conhecimento formal e tácito diferenciado, com organização e conteúdo, utilizando múltiplas e combinadas estratégias no processo de raciocínio clínico, no qual a estratégia HD é a base. The objective of this study is to identify the clinical reasoning process in the elaboration of the diagnoses hypothesis, inserted in a prototype subject in Medical Clinic (MC), having as presupposition that the hypothetic deductive strategy, is the base of the clinical reasoning, and the inductive-scheme and the pattern recognition are auxiliaries or combined strategies. The outline was cross-sectional, with epistemological qualitative basis, using non-probabilistic sample of intentional type. This research was done in the Hospital from Santa Catarina Federal University, in Florianopolis, Santa Catarina State, with thirty teachers from the Medical Clinic (MC) Teaching Department, which perform or performed the clinical activity for more than five years. The prototype definition in MC by the participants, allow selecting a real clinical case, which was stimulated to apply a think aloud technique. The text gathered from the clinical reasoning process with the participant's verbal stimulation was taped, transcribed and analysed with the application of the thematic analysis technique, this analysis used the content analysis method, for the professional profile was applied a structured questionnaire. The more frequent reasoning strategy was hypothetic-deductive (HD) (47% (72/153)), the inductive-scheme (IE) (15.6% (24/153)) and the recognition of a standard (RS) (15.6% (24/153)) have the same frequency, followed by the mixed IE (IE + HD) and the mixed RS (RS + HD), (respectively, 11.7% (18/153) and 9.8% (15/153)), which established 153 hypothesis into 31 different types. At the same time, was created 356 semantic axis into 135 types, and these dates were processed with 515 interpretations and 290 combinations. The sample general profile showed an expressive time of the clinical activity experience (27.3 years) and in the medical teaching (24.4 years), with a latu sensu specialization average of the 2.3 years/ participant, and more than a half (53%) with strictu sensu. The doctors-teachers as formal and tacit knowledge, with the organization and content, using multiple and combined strategies in the clinical reasoning process, in which the HD strategy is the basis.