Behind Recurrent Thromboembolic Events

We describe the case of a 68-year-old man, who presented with an ischemic stroke due to cardiac embolization related to mitral valve endocarditis. Blood cultures were always negative and post-operative valve histology did not show microorganisms. The patient also presented further recurrent peripheral embolic events. These clinical aspects were the first sign of a pancreas adenocarcinoma, which was only diagnosed in the clinical autopsy. In conclusion, these clinical findings of recurrent thromboembolic events with no microorganisms isolated suggests the diagnostic of a marantic endocarditis.

Diet, microbes and gut immune responses in the pathogenesis of experimental type 1 diabetes

Type 1diabetes (T1D) is an autoimmune disease, which is influenced by a variety of environmental factors including diet and microbes. These factors affect the homeostasis and the immune system of the gut. This thesis explored the altered regulation of the immune system and the development of diabetes in non-obese diabetic (NOD) mice. Inflammation in the entire intestine of diabetes-prone NOD mice was studied using a novel ex-vivo imaging system of reactive oxygen and nitrogen species (RONS), in relation to two feeding regimens. In parallel, gut barrier integrity and intestinal T-cell activation were assessed. Extra-intestinal manifestations of inflammation and decreased barrier integrity were sought for by studying peritoneal leukocytes. In addition, the role of pectin and xylan as dietary factors involved in diabetes development in NOD mice was explored. NOD mice showed expression of RONS especially in the distal small intestine, which coincided with T-cell activation and increased permeability to macromolecules. The introduction of a casein hydrolysate (hydrolysed milk protein) diet reduced these phenomena, altered the gut microbiota and reduced the incidence of T1D. Extra-intestinally, macrophages appeared in large numbers in the peritoneum of NOD mice after weaning. Peritoneal macrophages (PM) expressed high levels of interleukin-1 receptor associated kinase M (IRAK-M), which was indicative of exposure to ligands of toll-like receptor 4 (TLR-4) such as bacterial lipopolysaccharide (LPS). Intraperitoneal LPS injections activated T cells in the pancreatic lymph nodes (PaLN) and thus, therefore potentially could activate islet-specific T cells. Addition of pectin and xylan to an otherwise diabetes-retarding semisynthetic diet affected microbial colonization of newly-weaned NOD mice, disturbed gut homeostasis and promoted diabetes development. These results help us to understand how diet and microbiota impact the regulation of the gut immune system in a way that might promote T1D in NOD mice.

Efeito sacietogênico de um novo inibidor de tripsina da paçoca do amendoim com aumento plasmático de colecistocinina (cck)

Obesity is increasing, reaching epidemic levels in many regions of the world. Studies have shown that consumption of peanuts influences on weight control and this influence may be due to the action of trypsin inhibitors sacietogênica that condition increased plasma colescistocinina (CCK). Moreover, the peanut has other health benefits, and these assignments are guaranteed to increase their production and consumption of several of its products, including the paçoca peanut. The aim of this study was to identify the presence of a trypsin inhibitor in paçoca peanut and evaluate its effect on food intake, weight gain and histomorphological changes in swiss mice (n = 8) and Wistar rats (n = 6). Experimental diets were prepared based on the AIN-93G and supplemented with tack or peanut trypsin inhibitor partially purified paçoca peanut (AHTI). After each treatment, the animals were anesthetized and euthanized, their bloods were collected by cardiac puncture for the determination of CCK and other biochemical parameters (glucose, triglycerides, total cholesterol, high density lipoprotein, low density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase and albumin) and their pancreas removed for histologic and morphometric analysis. The supplementation with paçoca peanut and the AHTI showed a decrease of body weight gain and food intake in both mice and rats, due to the satiety, since the animals showed no evidence of impairment of nutritional status conditioned by consumption the AHTI. There were also observed biochemical or morphological important when compared with controls. However, AHTI led to increased secretion of CCK, a peptide sacietogênico. Thus, these results indicate that AHTI present in paçoca peanut, is able to enhance the secretion of plasma CCK and thereby reduce the weight gain associated with lower food intake of experimenta animals

Ação Sacietogênica de um inibidor de tripsina da semente de tamarindo (Tamarindus indica L.)

The seeds are excellent sources of proteinase inhibitors and have been highlighted owing to various applications. Among these applications are those in effect on food intake and weight gain that stand out because of the increasing number of obese individuals. This study evaluated the effects of trypsin inhibitor present in the seed of tamarind (Tamarindus indica L.) reduction in weight gain, biochemical and morphological alterations in Wistar rats. For this, we partially purified a trypsin inhibitor tamarind seed. This inhibitor, ITT2 at a concentration of 25 mg / kg body weight, over a period of 14 days was able to reduce food intake in rats (n = 6) by approximately 47%, causing a reduction in weight gain approximately 70% when compared with the control group. With the evaluation of the in vivo digestibility was demonstrated that the animals lost weight due to satiety, presented by the reduction of food intake, since there were significant differences between true digestibility for the control group (90.7%) and the group treated with inhibitor (89.88%). Additionally, we checked the deeds of ITT2 on biochemical parameters (glucose, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase, gamma glutamyl transferase albumin, globulin, total protein and C-reactive protein) and these, when assessed in the study groups showed no statistically significant variations. We also evaluate the histology of some organs, liver, stomach, intestine, and pancreas, and showed no changes. And to evaluate the effect of trypsin inhibitor on food intake due to the satiety is regulated by cholecystokinin (CCK) were measured plasma levels, and it was observed that the levels of CCK in animals receiving ITT2 were significantly higher ( 20 + 1.22) than in animals receiving only solution with casein (10.14 + 2.9) or water (5.92 + 1.15). Thus, the results indicate that the effect caused ITT2 satiety, reducing food intake, which in turn caused a reduction in weight gain in animals without causing morphological and biochemical changes, this effect caused by the elevation of plasma levels CCK

Rola fosfodiesterazy 3B w regulacji sekrecji insuliny u szczura (Rattus norvegicus Berkenhout)

Wydział Biologii

Imagiologia dos Tumores malignos do pâncreas

As neoplasias malignas do pâncreas englobam vários tipos histologicos com características ima giológicas e comportamentos que permitem distingui-los entre si numa boa percentagem de situações. Contudo, nem sempre a sua diferenciação se toma possível sem o recurso às técnicas anátomo-patoló gicas, constituindo um grande desafio à imagiologia o diagnóstico diferencial com lesões benignas, com referencia particular às massas inflamatórias. O adenocarcinoma constitui cerca de 95% das neo plasias pancreáticas e é uma das grandes causas de morte por cancro nos países desenvolvidos. As técnicas de imagem aplicadas no diagnóstico e no estadiamento dos principais tumores do pâncreas são muito diversificadas, englobando meios inócuos, como a ecografia, métodos invasivos utilizando técnicas angiográficas ou recurso aos meios endoscópicos para acesso endocavitário. A utilidade de cada uma destas variedades técnicas depende essencialmente do tipo de tumor a estudar, tomando-se fundamental o correcto e o completo conhecimento das possibilidades e limitações de cada uma, com vista à aplicação racional dos meios na imagiologia do pâncreas.

Adenocarcinoma pleomórfico de células giganates de vías biliares(osteoclastoma like)

Las células gigante tipo osteoclásticas (CGTO) del páncreas son una entidad poco frecuente descrito originalmente por Rosaien 1968, caracterizado por osteoclastos, que son células gigantes mononucleares idénticas a las células del estroma observadas en tumores óseos. Desde entonces, hay pocos informes de los tumores que contienen células gigantes en otras localizaciones anatómicas. Las CGTO se pueden distinguir de las células gigantes tipo pleomórficas (CGTP), debido a la falta de un marcado pleomorfismo nuclear asociado. A menudo, un carcinoma de páncreas histológicamente reconocibles acompaña CGTO, dando lugar a un mal resultado. Formas puras de CGTO presentan un mejor pronóstico porque se necesita mucho tiempo para desarrollar metástasis, pero esta forma es muy raros, con pocos casos reportados en la literatura Inglésa. La mayoría de veces se discute el diagnóstico de benignidad de estos tumores basados en la evaluación de inmunohistoquímica. El presente caso se trata de una paciente de sexo femenino de 56 años de edad con cuadro caracterizado por dolor tipo cólico que mejora con antiespasmódicos, de varios meses de evolución, con periodos de remisión y exacerbación. A examen físico presenta: en piel y mucosas ligero tinte subictérico, a nivel abdominal: abdomen doloroso de forma difusa sin viseromegalias o masas palpables

Síntese estereosseletiva da naftotectona

Tese (doutorado)—Universidade de Brasília, Instituto de Química, 2016.

Carcinoma colóide do pâncreas : a propósito de um caso não associado a neoplasia mucinosa papilar intraductal

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Insulinoma em furões

Dissertação de Mestrado Integrado em Medicina Veterinária

Reabilitação eco-sustentável do património dos faróis

Dissertação para obtenção do grau de Mestre em Arquitectura, apresentada na Universidade de Lisboa - Faculdade de Arquitectura.

Le traitement nutritionnel des épisodes d'hypoglycémie dans le diabète de type 1

Les patients atteints de diabète de type 1 (DbT1) semblent sur-traiter leurs hypoglycémies par rapport aux recommandations des Lignes directrices Canadiennes en diabète. Objectifs : 1) Décrire les habitudes des patients DbT1 pour le traitement des hypoglycémies et estimer les impacts sur le profil de risque cardio-métabolique et 2) explorer les excursions glycémiques suite à un traitement d’hypoglycémie qui respecte les recommandations. Méthodologie (analyses secondaires) : Objectif 1 : 121 patients DbT1 ont complété un journal alimentaire et de glycémies de 48 h. Des variables cardio-métaboliques ont été mesurées et un questionnaire sur la peur des hypoglycémies a été complété. Objectif 2 : 57 patients DbT1 ont complété les bras contrôles de notre programme sur le pancréas artificiel (traitement des hypoglycémies standardisé). Les valeurs de glycémie étaient disponibles aux 5 minutes. Résultats : Projet 1 : Les patients ont fait en moyenne 1,45 hypoglycémies/jour et 73% sur-traitaient avec une consommation moyenne de glucides de 32 ± 24 g. Ce sur-traitement est associé avec un plus jeune âge et une peur des hypoglycémies plus importante, mais pas avec un profil de risque cardio-métabolique plus défavorable. Projet 2 : Dans 20% des cas, traiter une hypoglycémie avec 15 g de glucides était efficace pour ramener la glycémie ≥ 4,0 mmol/L en 15 minutes, le temps moyen étant de 24 ± 12 minutes. La proportion d’insuline basale, le temps depuis le dernier repas et la pratique d’activité physique sont les éléments qui semblent avoir le plus d’impact sur l’efficacité du traitement. Conclusion : L’éducation entourant le traitement des hypoglycémies a besoin d’être renforcée et d’autres études sont nécessaires afin de valider les recommandations.

UTILIZING DIELECTROPHORESIS TO DETERMINE THE PHYSIOLOGICAL DIFFERENCES OF EUKARYOTIC CELLS

Type 1 diabetes affects over 108,000 children, and this number is steadily increasing. Current insulin therapies help manage the disease but are not a cure. Over a child’s lifetime they can develop kidney disease, blindness, cardiovascular disease and many other issues due to the complications of type 1 diabetes. This autoimmune disease destroys beta cells located in the pancreas, which are used to regulate glucose levels in the body. Because there is no cure and many children are affected by the disease there is a need for alternative therapeutic options that can lead to a cure. Human mesenchymal stem cells (hMSCs) are an important cell source for stem cell therapeutics due to their differentiation capacity, self-renewal, and trophic activity. hMSCs are readily available in the bone marrow, and act as an internal repair system within the body, and they have been shown to differentiate into insulin producing cells. However, after isolation hMSCs are a heterogeneous cell population, which requires secondary processing. To resolve the heterogeneity issue hMSCs are separated using fluorescent- and magnetic-activate cell sorting with antigen labeling. These techniques are efficient but reduce cell viability after separation due to the cell labeling. Therefore, to make hMSCs more readily available for type 1 diabetes therapeutics, they should be separated without diminishing there functional capabilities. Dielectrophoresis is an alternative separation technique that has the capability to separated hMSCs. This dissertation uses dielectrophoresis to characterize the dielectric properties of hMSCs. The goal is to use hMSCs dielectric signature as a separation criteria rather than the antigen labeling implemented with FACS and MACS. DEP has been used to characterize other cell systems, and is a viable separation technique for hMSCs.

Le traitement nutritionnel des épisodes d'hypoglycémie dans le diabète de type 1

Les patients atteints de diabète de type 1 (DbT1) semblent sur-traiter leurs hypoglycémies par rapport aux recommandations des Lignes directrices Canadiennes en diabète. Objectifs : 1) Décrire les habitudes des patients DbT1 pour le traitement des hypoglycémies et estimer les impacts sur le profil de risque cardio-métabolique et 2) explorer les excursions glycémiques suite à un traitement d’hypoglycémie qui respecte les recommandations. Méthodologie (analyses secondaires) : Objectif 1 : 121 patients DbT1 ont complété un journal alimentaire et de glycémies de 48 h. Des variables cardio-métaboliques ont été mesurées et un questionnaire sur la peur des hypoglycémies a été complété. Objectif 2 : 57 patients DbT1 ont complété les bras contrôles de notre programme sur le pancréas artificiel (traitement des hypoglycémies standardisé). Les valeurs de glycémie étaient disponibles aux 5 minutes. Résultats : Projet 1 : Les patients ont fait en moyenne 1,45 hypoglycémies/jour et 73% sur-traitaient avec une consommation moyenne de glucides de 32 ± 24 g. Ce sur-traitement est associé avec un plus jeune âge et une peur des hypoglycémies plus importante, mais pas avec un profil de risque cardio-métabolique plus défavorable. Projet 2 : Dans 20% des cas, traiter une hypoglycémie avec 15 g de glucides était efficace pour ramener la glycémie ≥ 4,0 mmol/L en 15 minutes, le temps moyen étant de 24 ± 12 minutes. La proportion d’insuline basale, le temps depuis le dernier repas et la pratique d’activité physique sont les éléments qui semblent avoir le plus d’impact sur l’efficacité du traitement. Conclusion : L’éducation entourant le traitement des hypoglycémies a besoin d’être renforcée et d’autres études sont nécessaires afin de valider les recommandations.

Privacy-enabled mobile-health (mhealth)-based diabetic solution

Diabetes is one of the leading chronic diseases affecting the lives of millions globally and early detection and treatment of this disease can serve to improve the quality of life for patients as well as suspend further health complications arising from diabetes. Continuous Glucose Monitors (CGM) and Insulin Pumps (IP) have been widely deployed to monitor the sugar levels in the blood stream and inject appropriate amounts of insulin to compensate for the underperforming pancreas functions of the patients’ bodies and thereby may provide appropriate treatment solutions for many diabetic sufferers. With the invention and deployment of Smartphones, the quality and performance associated with treating diabetes has reached new heights, however the privacy and security of mobilebased diabetic systems remain in ongoing challenges. This paper aims to focus on the privacy and security challenges of Mobile-Health (mHealth)-based Diabetic solutions.