Effects of vitamin C supplementation on acute phase Chagas disease in experimentally infected mice with Trypanosoma cruzi QM1 strain

The tissue changes that occur in Chagas disease are related to the degree of oxidative stress and antioxidant capacity of affected tissue. Studies with vitamin C supplementation did not develop oxidative damage caused by Chagas disease in the host, but other studies cite the use of peroxiredoxins ascorbate - dependent on T. cruzi to offer protection against immune reaction. Based on these propositions, thirty "Swiss" mice were infected with T. cruzi QM1 strain and treated with two different vitamin C doses in order to study the parasitemia evolution, histopathological changes and lipid peroxidation biomarkers during the acute phase of Chagas disease. The results showed that the parasite clearance was greater in animals fed with vitamin C overdose. There were no significant differences regarding the biomarkers of lipid peroxidation and inflammatory process or the increase of myocardium in animals treated with the recommended dosage. The largest amount of parasite growth towards the end of the acute phase suggests the benefit of high doses of vitamin C for trypomastigotes. The supplementation doesn't influence the production of free radicals or the number of amastigote nests in the acute phase of Chagas disease.

Software development for estimation of optical clearing agent’s diffusion coefficients in biological tissues

The study of chemical diffusion in biological tissues is a research field of high importance and with application in many clinical, research and industrial areas. The evaluation of diffusion and viscosity properties of chemicals in tissues is necessary to characterize treatments or inclusion of preservatives in tissues or organs for low temperature conservation. Recently, we have demonstrated experimentally that the diffusion properties and dynamic viscosity of sugars and alcohols can be evaluated from optical measurements. Our studies were performed in skeletal muscle, but our results have revealed that the same methodology can be used with other tissues and different chemicals. Considering the significant number of studies that can be made with this method, it becomes necessary to turn data processing and calculation easier. With this objective, we have developed a software application that integrates all processing and calculations, turning the researcher work easier and faster. Using the same experimental data that previously was used to estimate the diffusion and viscosity of glucose in skeletal muscle, we have repeated the calculations with the new application. Comparing between the results obtained with the new application and with previous independent routines we have demonstrated great similarity and consequently validated the application. This new tool is now available to be used in similar research to obtain the diffusion properties of other chemicals in different tissues or organs.

EXPERIMENTAL INFECTION WITH Toxocara cati IN PIGS: MIGRATORY PATTERN AND PATHOLOGICAL RESPONSE IN EARLY PHASE

Experimental inoculations of approximately 100,000 infective Toxocara cati larval eggs were done in twelve pigs. The T. cati eggs used for inoculation were collected from cat's feces. Another group of three pigs served as an uninfected control. Groups of infected pigs were euthanized at seven, 14, 21, and 28 days post-inoculation (dpi). Tissue samples were taken for digestion and histopathology changes in early phase. The number of larvae recovered from the lungs peaked at seven and 14 dpi and were also present at 21, and 28 dpi. Larvae of T. cati were present in the lymph nodes of the small and large intestine at seven, 14, and 28 dpi and at seven, 14, 21, and 28 dpi respectively. In other studied tissues, no larvae or less than one larva per gram was detected. The pathological response observed in the liver and lungs at seven and 14 dpi, showed white spots on the liver surface and areas of consolidation were observed in the lungs. The lungs showed an inflammatory reaction with larvae in center at 28 dpi. In the liver we observed periportal and perilobular hepatitis. The lymph nodes of the intestines displayed eosinophil lymphadenitis with reactive centers containing parasitic forms in some of them. The granulomatous reaction was not observed in any tissues. The role of the other examined tissues had less significance. The relevance of this parasite as an etiological agent that leads to disease in paratenic hosts is evident.

Artroplastia Unicompartimental do Joelho Oxford Phase 3. Resultados a Médio Prazo

Introdução: A artroplastia unicompartimental evoluiu nos últimos 40 anos, sendo hoje em dia considerada uma estratégia cirúrgica apropriada para a osteoartrose do compartimento interno da articulação do joelho. Desenvolvimentos nos instrumentos cirúrgicos, desenho do implante, abordagem cirúrgica e selecção dos doentes levaram a uma grande melhoria dos resultados pós-operatórios e aumento da longevidade das próteses unicompartimentais do joelho. Comparada com a prótese total, tem como vantagens a preservação óssea, menos complicações pós‐operatórias (perdas sanguíneas, dor pós‐operatória, taxa de infecção, trombose venosa profunda (TVP) e tromboembolismo pulmonar (TEP)), manutenção da normal cinemática do joelho, alta precoce e reabilitação mais rápida. A prótese unicompartimental Oxford phase 3 foi introduzida em 1998 e é uma prótese cimentada com menisco móvel de polietileno. Material e Métodos: Foi realizado um estudo retrospectivo das artroplastias unicompartimentais do joelho Oxford phase 3 realizadas no nosso serviço. Desde 2006 realizaram-se 37 artroplastias unicompartimentais (num total de 34 doentes). Sete dos quais não compareceram à avaliação pós-operatória e por isso foram excluídos do estudo. Todos os doentes incluídos no estudo foram avaliados clínica e radiograficamente. Foram revistos os processos de consulta e do internamento. Registou-se a idade,sexo, classificação ASA (American Society of Anesthesiologists), grau de satisfação, flexão‐extensão actual, Oxford knee score pré e pós‐operatório e alterações radiográficas a salientar. Resultados: O follow‐up médio foi de 47 meses (10 ‐ 83 meses). A idade média dos doentes é de 64 anos, com predomínio do sexo feminino. O ASA médio foi de 2,4. Um dos doentes foi submetido a conversão para artroplastia total do joelho por falência do componente tibial. Há 2 doentes não satisfeitos com a cirurgia (que corresponde aos doentes em que o Oxford knee score piorou). Há 1 doente pouco satisfeito e 23 satisfeitos ou muito satisfeitos. Todos os doentes conseguem fazer extensão completa e a média de flexão é 111º. A média do Oxford knee score pré‐operatório é de 17,4 (5 ‐ 30) e pós‐operatório é 36,6 (11 ‐ 48). Radiologicamente, há uma média de desvio em varo de 1,68º (varo 8º ‐ valgo 5º). Ocorreu artrose femoro‐tibial externa em três casos (dois dos quais também com artrose femoro‐patelar),um caso com slope tibial exagerado (19º), um caso com componente femoral em varo (15º), um caso com componente tibial demasiado grande com protusão interna, um caso de extrusão do menisco de polietileno, um caso com o componente tibial em valgo e um caso com falência deste (descelamento?) com provável necessidade de conversão para artroplastia total. Dos doentes não avaliados não há registo de conversão para artroplastia total do joelho ou outras complicações. Discussão: A larga maioria dos doentes encontram‐se satisfeitos ou muito satisfeitos, havendo uma melhoria do Oxford knee score para mais do dobro. Não se registaram complicações pós‐operatórias imediatas. Das artropastias unicompartimentas realizadas só uma foi convertida para artroplastia total e outra provavelmente a necessitar de conversão, com uma longevidade de 94,6% aos 47 meses (em média). Conclusão: A artroplastia unicompartimental do joelho demonstrou‐se uma excelente opção para doentes com osteoartrose não-inflamatória do compartimento interno do joelho. Para se obterem bons resultados os doentes devem ser criteriosamente seleccionados. Considerando a curva de aprendizagem necessária para o sucesso da cirurgia, a pouca experiência da maioria dos cirurgiões que colocaram as próteses não teve influência nos resultados finais, estando de acordo com a literatura existente, provando que a artroplastia unicompartimental do joelho tem bons resultados clínicos e funcionais. Um maior tempo de follow-up será necessário para se avaliar a longevidade das próteses unicompartimentais.

EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE

Introduction:In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain.Methods:Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle.Results:Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever.Conclusion:Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory.

Locally Advanced and Metastatic Prostate Cancer Treated with Intermittent Androgen Monotherapy or Maximal Androgen Blockade: Results from a Randomised Phase 3 Study by the South European Uroncological Group

BACKGROUND: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). OBJECTIVE: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. INTERVENTION: During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. RESULTS AND LIMITATIONS: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. CONCLUSIONS: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Scanning electron microscopy and X-ray spectroscopy applied to mycelial phase of sporothrix schenckii

Scanning electron microscopy applied to the mycelial phase of Sporothrix schenckii shows a matted mycelium with conidia of a regular pattern. X-Ray microanalysis applied in energy dispersive spectroscopy and also in wavelength dispersive spectroscopy reveals the presence of several elements of Mendeleef's classification.

A technology diffusion perspective of Enterprise Resource Planning across European Small and Medium Enterprises: from determinants to Use to Value

Tese apresentada como requisito parcial para obtenção do grau de Doutor em Gestão de Informação

Joining copper to stainless steel by friction stir diffusion process

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do Grau de Mestre em Engenharia Mecânica

Coherence and phase locking disruption in electromyograms of patients with amyotrophic lateral sclerosis

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Dot enzyme-linked immunosorbent assay (dot-ELISA) for schistosomiasis diagnosis using dacron as solid-phase

Dacron and nitrocellulose were evaluated as matrices for the dot enzyme linked immunosorbent assay (dot-ELISA) for schistosomiasis and compared to indirect immunofluorescence (IMF). Titration of sera from 18 schistosomiasis patients against soluble worm antigen preparation (SWAP) was carried out and sera from healthy individuals from non-endemic areas were used as controls. The IMF was less sensitive than the dot-ELISAs, although the difference was not statistically significant (p > 0.05). The dot-ELISA based on nitrocellulose was as sensitive as that using dacron. Stability did not differ between nitrocellulose and dacron. Specificity was lower when dacron was used than when nitrocellulose was used, although the difference was not statistically significant (p > 0.05). In conclusion, this work showed that nitrocellulose and dacron performed similarly in dot-ELISA, suggesting that they may be used alternatively in population surveillance in endemic areas.

Héraldique des sceaux du clergé séculier portugais au Moyen Âge

Ce n’est que dans les dernières années que l’héraldique au Portugal a entamé le processus de rénovation qui, en France, a commencé il y a déjà quelques décennies. Dans ce processus, l’étude de l’héraldique médiévale a été peu contemplé, restant pratiquement à faire, en bonne partir dû à l’absence d’armoriaux antérieurs au XVe siècle qui permettent de connaître les armes utilisées par les familles et les diverses entités portugaises. Pour cette raison, les sceaux portant des représentations héraldiques ont une importance extrême, car ils constituent très fréquemment la seule source pour l’étude des armoiries, ayant en plus l’avantage d’être datés avec précision et liées à des personnages ou entités qui sont connues. Cependant, la sigillographie portugaise se trouve aussi dans une phase de son évolution qui, n’étant plus embryonnaire, est encore une phase de formation. Il nous manque des catalogues, des dépouillages systématiques, des études approfondies qui permettent aux héraldistes de faire leurs recherches. C’est dans ce contexte qui est née ce partenariat entre deux médiévalistes très intéressés à la sigillographie et un spécialiste d’héraldique, qui ensemble ont décidé d’entamer l’étude des origines des représentations héraldiques dans les sceaux portugais, en commençant par les sceaux du clergé séculier, qui constitue le sujet par excellence de la recherche des deux historiens. Dans ce vaste univers sigillaire, qui concerne des personnes d’une grande variété d’origines sociales, y compris la noblesse et la riche bourgeoisie urbaine, les éléments héraldiques semblent avoir émergé seulement à partir de la fin du XIIIe siècle, et d’une façon timide. Le XIVe siècle assiste à sa diffusion dans les sceaux d’évêques, dignités et chanoines, mais ce n’est qu’au XVe siècle que l’héraldique s’impose, gagnant même une place primordiale dans quelques représentations sigillographiques. Le but de cette communication sera donc l’analyse du processus d’héraldisation des sceaux du clergé séculier portugais, entre les dernières décennies du XIIIe et le XVe siècle, pour évaluer comme s’est procédé, dans le cas portugais, le phénomène d’«acculturation héraldique» de l’emblématique épiscopale et cléricale.

Application of NMR RDC’s, relaxation and self-diffusion for the study of dynamic processes of small molecules in solution

Spin-lattice Relaxation, self-Diffusion coefficients and Residual Dipolar Couplings (RDC’s) are the basis of well established Nuclear Magnetic Resonance techniques for the physicochemical study of small molecules (typically organic compounds and natural products with MW < 1000 Da), as they proved to be a powerful and complementary source of information about structural dynamic processes in solution. The work developed in this thesis consists in the application of the earlier-mentioned NMR techniques to explore, analyze and systematize patterns of the molecular dynamic behavior of selected small molecules in particular experimental conditions. Two systems were chosen to investigate molecular dynamic behavior by these techniques: the dynamics of ion-pair formation and ion interaction in ionic liquids (IL) and the dynamics of molecular reorientation when molecules are placed in oriented phases (alignment media). The application of NMR spin-lattice relaxation and self-diffusion measurements was applied to study the rotational and translational molecular dynamics of the IL: 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4]. The study of the cation-anion dynamics in neat and IL-water mixtures was systematically investigated by a combination of multinuclear NMR relaxation techniques with diffusion data (using by H1, C13 and F19 NMR spectroscopy). Spin-lattice relaxation time (T1), self-diffusion coefficients and nuclear Overhauser effect experiments were combined to determine the conditions that favor the formation of long lived [BMIM][BF4] ion-pairs in water. For this purpose and using the self-diffusion coefficients of cation and anion as a probe, different IL-water compositions were screened (from neat IL to infinite dilution) to find the conditions where both cation and anion present equal diffusion coefficients (8% water fraction at 25 ºC). This condition as well as the neat IL and the infinite dilution were then further studied by 13C NMR relaxation in order to determine correlation times (c) for the molecular reorientational motion using a mathematical iterative procedure and experimental data obtained in a temperature range between 273 and 353 K. The behavior of self-diffusion and relaxation data obtained in our experiments point at the combining parameters of molar fraction 8 % and temperature 298 K as the most favorable condition for the formation of long lived ion-pairs. When molecules are subjected to soft anisotropic motion by being placed in some special media, Residual Dipolar Couplings (RDCs), can be measured, because of the partial alignment induced by this media. RDCs are emerging as a powerful routine tool employed in conformational analysis, as it complements and even outperforms the approaches based on the classical NMR NOE or J3 couplings. In this work, three different alignment media have been characterized and evaluated in terms of integrity using 2H and 1H 1D-NMR spectroscopy, namely the stretched and compressed gel PMMA, and the lyotropic liquid crystals CpCl/n-hexanol/brine and cromolyn/water. The influence that different media and degrees of alignment have on the dynamic properties of several molecules was explored. Different sized sugars were used and their self-diffusion was determined as well as conformation features using RDCs. The results obtained indicate that no influence is felt by the small molecules diffusion and conformational features studied within the alignment degree range studied, which was the 3, 5 and 6 % CpCl/n-hexanol/brine for diffusion, and 5 and 7.5 % CpCl/n-hexanol/brine for conformation. It was also possible to determine that the small molecules diffusion verified in the alignment media presented close values to the ones observed in water, reinforcing the idea of no conditioning of molecular properties in such media.

Numerical prediction of diffusion and electric field-induced iron nanoparticle transport

Zero valent iron nanoparticles (nZVI) are considered very promising for the remediation of contaminated soils and groundwaters. However, an important issue related to their limited mobility remains unsolved. Direct current can be used to enhance the nanoparticles transport, based on the same principles of electrokinetic remediation. In this work, a generalized physicochemical model was developed and solved numerically to describe the nZVI transport through porous media under electric field, and with different electrolytes (with different ionic strengths). The model consists of the Nernst–Planck coupled system of equations, which accounts for the mass balance of ionic species in a fluid medium, when both the diffusion and electromigration of the ions are considered. The diffusion and electrophoretic transport of the negatively charged nZVI particles were also considered in the system. The contribution of electroosmotic flow to the overall mass transport was included in the model for all cases. The nZVI effective mobility values in the porous medium are very low (10−7–10−4 cm2 V−1 s−1), due to the counterbalance between the positive electroosmotic flow and the electrophoretic transport of the negatively charged nanoparticles. The higher the nZVI concentration is in the matrix, the higher the aggregation; therefore, low concentration of nZVI suspensions must be used for successful field application.