Orientador: Odair Correa Bueno / Resumo: Atualmente, a tribo Attini compreende 45 gêneros e entre eles estão as formigas-cortadeiras cultivadoras de fungo, pertencentes aos gêneros Atta e Acromyrmex, que causam grandes danos econômicos a agricultura devido ao intenso corte de materiais vegetais frescos para cultivo do seu fungo simbiôntico Leucogaricus gongylophorus. Essas formigas apresentam diferentes mecanismos de defesa para proteger seus ninhos contra organismos competidores. Dentre esses mecanismos está a defesa humoral e celular (inata e adquirida) do sistema imune interno e a defesa imune externa, que inclui qualquer característica atuando no ambiente capaz de melhorar sua proteção contra patógenos, sendo esta caracterizada em formigas pela remoção física de patógenos e pela secreção de compostos antimicrobianos advindos de glândulas exócrinas e simbiontes bacterianos. Poucos estudos buscam integrar os diferentes fatores envolvidos na capacidade defensiva das formigas a fim de compreender estratégias fisiológicas adquiridas para proteger a colônia. Diante disso, a presente pesquisa teve por objetivo investigar a defesa da formiga-cortadeira Atta sexdens contra patógenos. Para tanto, realizamos a revisão sistemática dos mecanismos de defesa das formigas discutidos na literatura, a qual nos direcionou para investigação da defesa química externa dessa espécie de formiga. Os ensaios conduzidos foram de atividade enzimática, análise cromatográfica e testes de inibição de fungos patógenos e antagonistas. Verificam... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Currently Attini tribe comprises 45 genera and among them are fungus-growing leaf-cutting ants belonging to the genera Atta and Acromyrmex. They cause great economic damage to agriculture due to the intense cutting of fresh plant material for cultivation of its symbiotic fungus Leucogaricus gongylophorus. These ants present different defense mechanisms to protect their nests against competing organisms. Among these mechanisms is the humoral and cellular defense (innate and acquired) of the internal immune system and the external immune defense. This last one includes any hereditary characteristic acting in the environment and being capable of improve its protection against pathogens. It is characterized in ants by the physical removal of pathogens and by secretion of antimicrobial compounds from exocrine glands and bacterial symbionts. Few studies have sought to integrate the different factors involved in ants' defensive capacity in order to understand physiological strategies acquired to protect the colony. In this way, the present research had the goal to investigate the defense of the ant-cutter Atta sexdens against pathogens. For this, we performed the systematic review of ant defense mechanisms discussed in the literature, which directed us to investigate the external chemical defense of this ant species. The tests carried out were of enzymatic activity, chromatographic analysis and tests of inhibition of pathogenic and antagonistic fungi. We have observed that secretion... (Complete abstract click electronic access below) / Mestre

Orientador: Cristiane Yume Koga Ito / Coorientadora: Marcia Hiromi Tanaka / Banca: Luana Marotta Reis de Vasconcellos / Banca: Bruno Mello de Matos / Banca: Soraya Carvalho da Costa / Banca: Daniel Freitas Alves Pereira / Resumo: A Fibrose Cística (FC) é uma doença genética de elevada prevalência global e que causa função anormal das glândulas exócrinas. As alterações nas funções das glândulas salivares podem impactar a saúde bucal que por sua vez podem influenciar a saúde geral. A boca pode representar um reservatório microbiano de potenciais patógenos e colonizadores das vias aéreas, causando infecções crônicas pulmonares. O objetivo deste estudo foi avaliar os impactos da FC na cavidade bucal, saliva e microbioma bucal. Foram incluídos no estudo 50 pacientes com diagnóstico de FC com idades de 3 a 20 anos, divididos em 2 grupos de acordo com o grau de severidade da doença determinado pelo escore de Shwachman-Kulczycki: G1 (baixa severidade) e G2 (alta severidade). Foi também incluído grupo controle pareado ao grupo de estudo quanto ao gênero e idade (G3, n=50). A presença de lesões de cárie foi avaliada. O impacto da FC sobre a saúde bucal foi avaliado por questionário preenchido pelos pais ou responsáveis. Amostra de saliva estimulada foi coletada de todos os pacientes. O microbioma bucal foi avaliado por Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) e metodologias de cultivo, para análise da microbiota potencialmente oportunista e cariogênica. Realizou-se ainda a análise proteômica da saliva e quantificação de imunoglobulinas salivares. Os resultados foram analisados e, de acordo com a distribuição dos dados e avaliação desejada, foram aplicados os testes estatístic... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract : Cystic Fibrosis (CF) is a genetic disease with high global prevalence that causes abnormal function of the exocrine glands. The functional alterations of salivary glands and saliva can impact the oral health and influence general health. Oral cavity may represent a microbial reservoir of potential pathogens that can colonize the airways and cause chronic pulmonary infections. The aim of this study is to evaluate the impact of cystic fibrosis on the oral cavity, saliva and oral microbiome. Fifty CF patients aged from 3 to 20 years were divided into two groups according to the disease severity determined by the Shwachman-Kulczycki score: G1 (low severity) and G2 (high severity). Also, age and gender paired control group was included in the study (G3, n = 50). The occurrence of caries was evaluated. The impact of CF on oral health was evaluated by a questionnaire filled by parents or responsible person. Stimulated whole saliva (WS) samples were collected from all patients. The oral microbiome was analyzed by Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) and by microbiological culture methodologies to evaluate the potential opportunistic and cariogenic microbiota. The proteomic analysis of saliva and quantification of salivary immunoglobulins were carried out. Statistical analysis was performed according to the normality of the data at a significance level of 5%. The applied questionnaire pointed out that oral health did not impact systemic health negatively, according to the parents in all groups. The groups of patients with CF had lower rates of dmft, DMFT, salivary flow rate and initial pH in comparison to the control group. The counts of staphylococcal and yeast from CF groups were significant higher than the controls. All fungal isolates were susceptible to the antifungal agents. Higher incidence of bacterial resistance was ... (Complete abstract click electronic access below) / Doutor

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Traditionally, the exocrine and endocrine cellular compartments of the pancreas have been considered distinct functional systems. However, recent studies suggest a more intricate relationship between the exocrine and endocrine, which may impact pancreatic growth and health. Additionally, translational control mechanisms have been linked to organ development. Our lab has shown that the mRNA translation factor eukaryotic initiation factor 5A (eIF5A), when in its post-translationally modified “hypusinated” form, plays a role in pancreas development. The hypusination of eIF5A requires the rate-limiting enzyme deoxyhypusine synthase (Dhps) to post- translationally modify a critical lysine residue which in turn produces the active form of eIF5A that functions in mRNA translation. When we generated animals with a deletion of Dhps in the pancreatic progenitor cells, there was no alteration in islet mass but significant exocrine insufficiency at embryonic (E) day 18.5 concomitant with downregulation of proteins required for exocrine pancreas development and function. Resultantly these animals died by 6 weeks-of-age. These observations prompted the question, is the phenotype caused by the absence of hypusinated eIF5A or the increase of unhypusinated eIF5A? To address this, we generated a mouse model wherein Eif5a is deleted in the pancreas (eIF5A∆PANC) and these mutant animals also display exocrine insufficiency. Interestingly, beta cell mass is increased at E18.5, and the mutant animals maintain euglycemia and survive up to 2 years. Ongoing analyses are interrogating the differences between these animal models with the goal to determine if mRNA translation facilitates cellular communication between the exocrine and endocrine pancreas.

Le diabète de type 1 (DT1) est une maladie auto-immune caractérisée par la destruction des cellules β pancréatiques par les cellules immunitaires, ce qui entraîne une insuffisance en insuline. L’étude des souris Non-Obese Diabetic (NOD), qui développent spontanément le diabète auto-immun, a permis l'identification de plusieurs loci de susceptibilité associés au diabète, appelés Idds. D’ailleurs, Idd1 est lié au locus du CMH. L’utilisation de souris congéniques NOD.B6-Idd1 et B6.NOD-Idd1 a démontré qu’Idd1 est nécessaire mais insuffisant pour la progression du diabète auto-immun. Précédemment, nous avons démontré que les allèles de résistance au locus Idd2 offrent une protection significative contre l’apparition du diabète auto-immun, semblable à Idd1. Pour identifier les facteurs génétiques minimaux requis pour l'apparition du DT1, nous avons introduit les loci NOD Idd1 et Idd2 chez des souris B6, générant des souris doubles congéniques B6.Idd1.Idd2. Bien que la combinaison de Idd1 et Idd2 n’est pas suffisante pour induire l’apparition du diabète, nous avons observé une infiltration immunitaire dans le pancréas exocrine des souches congéniques B6 Idd2. De plus, nous avons observé d'importantes différences phénotypiques dans les sous-populations de lymphocytes T chez les souris B6.Idd1.Idd2 par rapport aux souris simple congéniques, suggérant une interaction épistatique entre Idd1 et Idd2 dans la modulation des fonctions des lymphocytes T. De plus, des augmentations de neutrophiles et de la fibrose spécifiques à Idd2 ont été découvertes, suggérant qu’Idd2 est impliqué dans le processus cellulaire inflammatoire du diabète auto-immun. Dans l’ensemble, ces données montrent que la combinaison des allèles de susceptibilité Idd1 et Idd2 ne mène pas à la progression du diabète auto-immun. Des facteurs génétiques ou environnementaux supplémentaires sont donc nécessaires pour provoquer le diabète auto-immun chez la souris. Néanmoins, nous constatons que les allèles NOD au niveau des locus Idd2 coopèrent pour induire une inflammation et une infiltration immunitaire dans le pancréas. / Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of pancreatic β cells by immune cells, leading to an insulin deficiency. Non-Obese Diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, have enabled the identification of several loci associated with diabetes susceptibility, termed Idds. Notably, Idd1 is linked to the MHC locus and resistance alleles at this locus provide full protection from diabetes onset. Conversely, C57BL/6 (B6) mice bearing NOD Idd1 alleles exhibit immune infiltration in the pancreas without causing overt diabetes. These results show that NOD Idd1 alleles are necessary but not sufficient for autoimmune diabetes progression. In a previous study, we demonstrated that diabetes resistance alleles at the Idd2 locus provide significant protection from autoimmune diabetes onset, second to Idd1. To identify the minimal genetic factors required for T1D onset, we introduced the NOD Idd1 and Idd2 loci in B6 mice, generating B6.Idd1.Idd2 double congenic mice. Although the introduction of susceptibility alleles at both Idd1 and Idd2 was not sufficient to induce diabetes onset, we observed immune infiltration in the exocrine pancreas of B6 Idd2 congenic strains. In addition, we observed important phenotypic differences in T cell subsets in B6.Idd1.Idd2 mice relative to single congenic mice, suggesting epistatic interaction between Idd1 and Idd2 in modulating T cell functions. Moreover, Idd2-specific increases in neutrophils and fibrosis were discovered, suggesting that Idd2 is involved in the inflammatory cellular process of autoimmune diabetes. Altogether, these data show that susceptibility alleles at Idd1 and Idd2 together are not sufficient to autoimmune diabetes progression. Additional genetic factors or environmental triggers are therefore required to cause autoimmune diabetes in mice. Still, we find that NOD alleles at the Idd2 loci cooperate to induce inflammation and immune infiltration in the pancreas.

Introdução e objetivo: Elastase-1 fecal (EL-1) é um teste não invasivo que serve para avaliar a função pancreática exócrina. Neste estudo, buscou-se avaliar e quantificar a concentração da EL-1 fecal em pacientes com Fibrose Cística (FC), portadores da mutação ΔF508, e padronizar o teste Elastase monoclonal para a população estudada. Métodos: Estudo transversal prospectivo, com pacientes portadores de FC. Foram coletadas amostras de fezes para a quantificação da concentração da EL-1fecal pelo teste ELISA. A avaliação antropométrica baseou-se no percentil de IMC para crianças de 2 a 18 anos e percentil de P/E para crianças menores de 2 anos. Foi feita uma revisão nos prontuários dos pacientes para identificar a mutação da FC e coletar informações a respeito da dose da enzima administrada. Os desfechos analisados foram a insuficiência pancreática exócrina (IP) e sua intensidade, definida pela atividade da EL-1 fecal < 200μg/g. Resultados: Cinquenta e um pacientes com idade entre 4 meses e 17 anos participaram do estudo, divididos em 3 grupos: 17 homozigotos, 17 heterozigotos e 17 não ΔF508. A média de idade foi de 9,11 anos (± 4,74) e 62,8% eram do sexo masculino. As enzimas pancreáticas foram utilizadas em 46 pacientes (90,2%). Pacientes com o teste da EL-1 fecal com valores abaixo de 100μg/g representaram um total de 80,4% (n=41), sendo 17 homozigotos (41,5%), 14 heterozigotos (34,1%) e 10 com ausência de ΔF508 (24,4%). Houve associação estatisticamente significativa entre os homozigotos e a concentração da EL-1 fecal < 100μg/g. Todos os pacientes considerados IP pelo teste da EL-1 fecal faziam terapia de reposição enzimática (41 - 100%). Dez pacientes (19,6%) estavam com concentração da EL-1 fecal >200μg/g e, desses, 5 utilizavam enzimas pancreáticas. Onze pacientes (21,6%) apresentaram-se desnutridos, 10 (19,6%) em risco nutricional e 30 (58,8%) eutróficos. Não houve relação estatisticamente significativa entre estado nutricional, mutações e IP. Conclusões: A atividade de EL-1 fecal < 100 μg/g, indicativa de IP grave pelo teste, foi observada em 17/17 (100%) pacientes homozigotos para a mutação ΔF508 e em 14/17 (82,3%) heterozigotos para a mesma mutação. Não houve relação entre os valores de EL-1 fecal e o estado nutricional, avaliados pelo percentil do P/E para < 2 anos e percentil do IMC para >de 2 anos. O teste EL-1 fecal é de fácil execução e pode ser feito com uma pequena amostra de fezes; neste estudo, revelou-se útil na avaliação pancreática dos pacientes com FC. / Introduction and Objective: The fecal Elastase-1 (EL-1) is a noninvasive test used to assess exocrine pancreatic function. This study aims to assess and quantify the concentration of fecal Elastase -1 in patients with cystic fibrosis ΔF508 mutation carriers and to standardize the testing Elastase monoclonal test in our study group. Methods: Cross-sectional study with patients diagnosed with Cystic Fibrosis, being treated by the Hospital de Clínicas de Porto Alegre. Feces were collected for the quantification of Elastase concentration by ELISA. Nutritional assessment was calculated by percentile of BMI for children aged 2 to 18 years and percentile P / E for children under 2 years. Patient charts were reviewed to identify the cystic fibrosis mutation and to collect information about the dose of enzyme administered. The results analyzed were the exocrine pancreatic insufficiency and its intensity, defined by the activity of fecal EL-1 <200μg/g. Results: Fifty-one patients with ages ranging from 4 months to 17 years participated in the study and were divided into 3 groups: 17 homozygotes, 17 heterozygotes and 17 non ΔF508. The average age was 9.11 years (± 4.74) and 62.8% were male. The pancreatic enzymes were used in 46 (90.2%) patients. Patients with Elastase test with values below 100μg/g represented a total of 80.4% (n = 41) and 17 (41.5%) homozygous, 14 heterozygous (34.1%) and 10 with no ΔF508 (24.4%). There was a statistically significant association between the homozygous and the concentration of fecal EL-1 <100μg/g. All patients identified as PI by the EL-1 fecal test were in enzyme replacement therapy 41 (100%). Ten patients (19.6%) had a concentration of EL-1 fecal >200 μg / g, and 5 of pancreatic enzymes used. Eleven (21.6%) patients were malnourished, 10 (19.6%) were at nutritional risk and for 30 (58.8%) the nutritional status was normal. There was no significant relationship between nutritional status, mutations and pancreatic insufficiency. Conclusion: The activity of EL Fecal -1 <100 μg/g indicative of severe PI by the test, was observed in 17/17 (100%) patients homozygous for the mutation ΔF508 and 14/17 (82.3%) heterozygous for the same mutation. There was no association between the levels of fecal EL-1 and nutritional status assessed by the percentile of the P/E < 2 years and BMI percentile for >2 years. The fecal Elastase-1 test can be easily performed with a small stool sample and proved useful in the pancreatic evaluation of patients with cystic fibrosis.

Made available in DSpace on 2015-03-26T13:30:25Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1214817 bytes, checksum: 8b154dcb606a49177f6d7c486ae293d7 (MD5) Previous issue date: 2008-12-19 / Fundação de Amparo a Pesquisa do Estado de Minas Gerais / The study of intramandibular glands in ants may provide new insights for the comprehension of the mechanisms of exocrine glands linked with behavior and phylogeny in different Formicidae. In this work the occurrence of intramandibular glands in primitive ants Ponerini (Ponerinae) and derivate ants Attini (Myrmicinae) was investigated. In these ants glands found were of class I, III and secretory epithelial cells with reservoir. The intramandibular glands had different morphology varying according the species, changing its location, development level and intracellular structures. Our findings suggest that the glands of the different ant tribes, produce different substances, and this may indicate different functions, according the chemical nature of cellular products. A cladistic analysis using intramandibular gland characters resulted in the separation of the two tribes, suggesting that structural differences of intramandibulars glands may contribute to phylogenetic studies of Formicidae. / O conhecimento da morfologia interna da mandíbula de formigas é importante para a elucidação dos mecanismos que envolvem o sistema exócrino e suas relações com os aspectos comportamentais e filogenéticos nas diferentes subfamílias de Formicidae. Nesse trabalho foi investigada a ocorrência de glândulas intramandibulares em formigas primitivas Ponerini (Ponerinae) e derivadas Attini (Myrmicinae). Nessas formigas foram encontradas glândulas da classe I e III e, células epiteliais secretoras com reservatório. As glândulas intramandibulares apresentam histologia distinta nas espécies estudadas, variando a sua localização, grau de desenvolvimento. Com isso é possível conjecturar que as glândulas das diferentes tribos, produzem substâncias de naturezas distintas, e isso pode indicar funções diversas, dependendo da natureza química de constituintes celulares. A análise cladística utilizando caracteres das glândulas intramandibulares resultou na separação das duas tribos, sugerindo que as diferenças estruturais das glândulas intramandibulares possam contribuir para estudos filogenéticos de Formicidae.

Introdução e objetivo: Elastase-1 fecal (EL-1) é um teste não invasivo que serve para avaliar a função pancreática exócrina. Neste estudo, buscou-se avaliar e quantificar a concentração da EL-1 fecal em pacientes com Fibrose Cística (FC), portadores da mutação ΔF508, e padronizar o teste Elastase monoclonal para a população estudada. Métodos: Estudo transversal prospectivo, com pacientes portadores de FC. Foram coletadas amostras de fezes para a quantificação da concentração da EL-1fecal pelo teste ELISA. A avaliação antropométrica baseou-se no percentil de IMC para crianças de 2 a 18 anos e percentil de P/E para crianças menores de 2 anos. Foi feita uma revisão nos prontuários dos pacientes para identificar a mutação da FC e coletar informações a respeito da dose da enzima administrada. Os desfechos analisados foram a insuficiência pancreática exócrina (IP) e sua intensidade, definida pela atividade da EL-1 fecal < 200μg/g. Resultados: Cinquenta e um pacientes com idade entre 4 meses e 17 anos participaram do estudo, divididos em 3 grupos: 17 homozigotos, 17 heterozigotos e 17 não ΔF508. A média de idade foi de 9,11 anos (± 4,74) e 62,8% eram do sexo masculino. As enzimas pancreáticas foram utilizadas em 46 pacientes (90,2%). Pacientes com o teste da EL-1 fecal com valores abaixo de 100μg/g representaram um total de 80,4% (n=41), sendo 17 homozigotos (41,5%), 14 heterozigotos (34,1%) e 10 com ausência de ΔF508 (24,4%). Houve associação estatisticamente significativa entre os homozigotos e a concentração da EL-1 fecal < 100μg/g. Todos os pacientes considerados IP pelo teste da EL-1 fecal faziam terapia de reposição enzimática (41 - 100%). Dez pacientes (19,6%) estavam com concentração da EL-1 fecal >200μg/g e, desses, 5 utilizavam enzimas pancreáticas. Onze pacientes (21,6%) apresentaram-se desnutridos, 10 (19,6%) em risco nutricional e 30 (58,8%) eutróficos. Não houve relação estatisticamente significativa entre estado nutricional, mutações e IP. Conclusões: A atividade de EL-1 fecal < 100 μg/g, indicativa de IP grave pelo teste, foi observada em 17/17 (100%) pacientes homozigotos para a mutação ΔF508 e em 14/17 (82,3%) heterozigotos para a mesma mutação. Não houve relação entre os valores de EL-1 fecal e o estado nutricional, avaliados pelo percentil do P/E para < 2 anos e percentil do IMC para >de 2 anos. O teste EL-1 fecal é de fácil execução e pode ser feito com uma pequena amostra de fezes; neste estudo, revelou-se útil na avaliação pancreática dos pacientes com FC. / Introduction and Objective: The fecal Elastase-1 (EL-1) is a noninvasive test used to assess exocrine pancreatic function. This study aims to assess and quantify the concentration of fecal Elastase -1 in patients with cystic fibrosis ΔF508 mutation carriers and to standardize the testing Elastase monoclonal test in our study group. Methods: Cross-sectional study with patients diagnosed with Cystic Fibrosis, being treated by the Hospital de Clínicas de Porto Alegre. Feces were collected for the quantification of Elastase concentration by ELISA. Nutritional assessment was calculated by percentile of BMI for children aged 2 to 18 years and percentile P / E for children under 2 years. Patient charts were reviewed to identify the cystic fibrosis mutation and to collect information about the dose of enzyme administered. The results analyzed were the exocrine pancreatic insufficiency and its intensity, defined by the activity of fecal EL-1 <200μg/g. Results: Fifty-one patients with ages ranging from 4 months to 17 years participated in the study and were divided into 3 groups: 17 homozygotes, 17 heterozygotes and 17 non ΔF508. The average age was 9.11 years (± 4.74) and 62.8% were male. The pancreatic enzymes were used in 46 (90.2%) patients. Patients with Elastase test with values below 100μg/g represented a total of 80.4% (n = 41) and 17 (41.5%) homozygous, 14 heterozygous (34.1%) and 10 with no ΔF508 (24.4%). There was a statistically significant association between the homozygous and the concentration of fecal EL-1 <100μg/g. All patients identified as PI by the EL-1 fecal test were in enzyme replacement therapy 41 (100%). Ten patients (19.6%) had a concentration of EL-1 fecal >200 μg / g, and 5 of pancreatic enzymes used. Eleven (21.6%) patients were malnourished, 10 (19.6%) were at nutritional risk and for 30 (58.8%) the nutritional status was normal. There was no significant relationship between nutritional status, mutations and pancreatic insufficiency. Conclusion: The activity of EL Fecal -1 <100 μg/g indicative of severe PI by the test, was observed in 17/17 (100%) patients homozygous for the mutation ΔF508 and 14/17 (82.3%) heterozygous for the same mutation. There was no association between the levels of fecal EL-1 and nutritional status assessed by the percentile of the P/E < 2 years and BMI percentile for >2 years. The fecal Elastase-1 test can be easily performed with a small stool sample and proved useful in the pancreatic evaluation of patients with cystic fibrosis.

Introdução e objetivo: Elastase-1 fecal (EL-1) é um teste não invasivo que serve para avaliar a função pancreática exócrina. Neste estudo, buscou-se avaliar e quantificar a concentração da EL-1 fecal em pacientes com Fibrose Cística (FC), portadores da mutação ΔF508, e padronizar o teste Elastase monoclonal para a população estudada. Métodos: Estudo transversal prospectivo, com pacientes portadores de FC. Foram coletadas amostras de fezes para a quantificação da concentração da EL-1fecal pelo teste ELISA. A avaliação antropométrica baseou-se no percentil de IMC para crianças de 2 a 18 anos e percentil de P/E para crianças menores de 2 anos. Foi feita uma revisão nos prontuários dos pacientes para identificar a mutação da FC e coletar informações a respeito da dose da enzima administrada. Os desfechos analisados foram a insuficiência pancreática exócrina (IP) e sua intensidade, definida pela atividade da EL-1 fecal < 200μg/g. Resultados: Cinquenta e um pacientes com idade entre 4 meses e 17 anos participaram do estudo, divididos em 3 grupos: 17 homozigotos, 17 heterozigotos e 17 não ΔF508. A média de idade foi de 9,11 anos (± 4,74) e 62,8% eram do sexo masculino. As enzimas pancreáticas foram utilizadas em 46 pacientes (90,2%). Pacientes com o teste da EL-1 fecal com valores abaixo de 100μg/g representaram um total de 80,4% (n=41), sendo 17 homozigotos (41,5%), 14 heterozigotos (34,1%) e 10 com ausência de ΔF508 (24,4%). Houve associação estatisticamente significativa entre os homozigotos e a concentração da EL-1 fecal < 100μg/g. Todos os pacientes considerados IP pelo teste da EL-1 fecal faziam terapia de reposição enzimática (41 - 100%). Dez pacientes (19,6%) estavam com concentração da EL-1 fecal >200μg/g e, desses, 5 utilizavam enzimas pancreáticas. Onze pacientes (21,6%) apresentaram-se desnutridos, 10 (19,6%) em risco nutricional e 30 (58,8%) eutróficos. Não houve relação estatisticamente significativa entre estado nutricional, mutações e IP. Conclusões: A atividade de EL-1 fecal < 100 μg/g, indicativa de IP grave pelo teste, foi observada em 17/17 (100%) pacientes homozigotos para a mutação ΔF508 e em 14/17 (82,3%) heterozigotos para a mesma mutação. Não houve relação entre os valores de EL-1 fecal e o estado nutricional, avaliados pelo percentil do P/E para < 2 anos e percentil do IMC para >de 2 anos. O teste EL-1 fecal é de fácil execução e pode ser feito com uma pequena amostra de fezes; neste estudo, revelou-se útil na avaliação pancreática dos pacientes com FC. / Introduction and Objective: The fecal Elastase-1 (EL-1) is a noninvasive test used to assess exocrine pancreatic function. This study aims to assess and quantify the concentration of fecal Elastase -1 in patients with cystic fibrosis ΔF508 mutation carriers and to standardize the testing Elastase monoclonal test in our study group. Methods: Cross-sectional study with patients diagnosed with Cystic Fibrosis, being treated by the Hospital de Clínicas de Porto Alegre. Feces were collected for the quantification of Elastase concentration by ELISA. Nutritional assessment was calculated by percentile of BMI for children aged 2 to 18 years and percentile P / E for children under 2 years. Patient charts were reviewed to identify the cystic fibrosis mutation and to collect information about the dose of enzyme administered. The results analyzed were the exocrine pancreatic insufficiency and its intensity, defined by the activity of fecal EL-1 <200μg/g. Results: Fifty-one patients with ages ranging from 4 months to 17 years participated in the study and were divided into 3 groups: 17 homozygotes, 17 heterozygotes and 17 non ΔF508. The average age was 9.11 years (± 4.74) and 62.8% were male. The pancreatic enzymes were used in 46 (90.2%) patients. Patients with Elastase test with values below 100μg/g represented a total of 80.4% (n = 41) and 17 (41.5%) homozygous, 14 heterozygous (34.1%) and 10 with no ΔF508 (24.4%). There was a statistically significant association between the homozygous and the concentration of fecal EL-1 <100μg/g. All patients identified as PI by the EL-1 fecal test were in enzyme replacement therapy 41 (100%). Ten patients (19.6%) had a concentration of EL-1 fecal >200 μg / g, and 5 of pancreatic enzymes used. Eleven (21.6%) patients were malnourished, 10 (19.6%) were at nutritional risk and for 30 (58.8%) the nutritional status was normal. There was no significant relationship between nutritional status, mutations and pancreatic insufficiency. Conclusion: The activity of EL Fecal -1 <100 μg/g indicative of severe PI by the test, was observed in 17/17 (100%) patients homozygous for the mutation ΔF508 and 14/17 (82.3%) heterozygous for the same mutation. There was no association between the levels of fecal EL-1 and nutritional status assessed by the percentile of the P/E < 2 years and BMI percentile for >2 years. The fecal Elastase-1 test can be easily performed with a small stool sample and proved useful in the pancreatic evaluation of patients with cystic fibrosis.

The proposal of this work was to determine the contribution of functional MR imaging techniques, i.e. secretin-enhanced MRCP (S-MRCP) and dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging in the quantitative assessment of exocrine pancreatic function and perfusion.<p><p>The pancreas is both an exocrine and endocrine organ, though the exocrine tissue accounts for more than 90%. The exocrine pancreas is specialized in the synthesis and storage of digestive enzymes and in bicarbonate and water secretion in response respectively to various secretagogues (CCK, ach, GRP, VIP,…) and to secretin. <p>The arterial supply of the pancreas derives from branches of the celiac trunk and of the superior mesenteric artery. The microvascularity of the exocrine and the endocrine parts of the gland are anatomically and functionally separated, with differentially regulated blood perfusion. <p>Based on the knowledge of a close relationship between the activity of the gland and its blood supply, in normal conditions pancreatic perfusion responds to the functional state of the exocrine parenchyma: increased demands for exocrine secretions are associated with increased pancreatic blood flow. <p>The pancreatic gland can be involved at different degrees of severity in acute and chronic inflammatory processes due to various causes. In both processes microcirculatory changes occur and the pancreatic exocrine function can be impaired. Moreover, an exiguous microvascular component characterizes pancreatic ductal adenocarcinoma (PDA) related to a prominent stroma.<p><p><p>In the first section of this thesis, quantitative assessment of the pancreatic exocrine secretions was performed with S-MRCP in physiologic and non-physiologic conditions. The stimulating effect of secretin as well as the inhibitory effect of somatostatin on normal pancreas, both administered at different dose-regimens, were tested. The results of these investigations showed that quantitative S-MRCP is able to detect changes in pancreatic exocrine secretions correlated to the degree of stimulation or inhibition. <p>In pathologic settings, pancreatic exocrine secretions were assessed in chronic pancreatitis patients showing different degrees of severity, before and after endoscopic pancreatic duct drainage procedures (PDDP). In the group of patients presenting a reduced pancreatic exocrine reserve before treatment, quantitative S-MRCP showed a short-term improvement after PDDP. <p><p>In the second section, the feasibility and the reproducibility of DCE-MR imaging to quantify regional pancreatic perfusion was firstly investigated. DCE-MR imaging was performed in normal volunteers. Reference values for regional pancreatic perfusion were achieved with an intra-individual variability of 21%.<p>DCE-MR investigations were repeated during secretin stimulation and disclosed a significant increase of regional pancreatic perfusion in all individuals. <p>Secondly, DCE-MR imaging investigated benign and malignant focal pancreatic solid lesions and non tumoral tissue in patients undergoing pancreatic surgical resection. The purpose was to correlate DCE-MR quantitative parameters, (reflecting perfusion and/or permeability and the distribution volume fraction) with histologic features such as the degree of fibrosis and the microvascular density (MVD) in the corresponding tissues. A significant correlation was found between DCE-MR and histologic parameters: Ktrans was negatively correlated with the degree of fibrosis (high fibrosis was correlated with low perfusion), while the distribution volume fraction was positively correlated with the degree of fibrosis and with MVD (larger EES was correlated with high fibrosis and higher MVD). <p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished