Dissertations / Theses on the topic 'TNNs'

1. Marcel Kordoš and Sergej Vojtovic 2016 «Transnational Corporations in the Global World Economic Environment» 2. Porumbescu, Alexandra, and Livia Dana Pogan. "Transnational Corporations, as Subjects of International Law in the Globalization Context." Revista de Stiinte Politice, no. 64, 2019, p. 65+. Accessed 10 Mar. 2021. 3. Charter of Economic Rights and Duties of States General Assembly resolution 3281 (XXIX) [Electronic resource]. - Access mode: https://legal.un.org/avl/ha/cerds/cerds.html 4. Code of Conduct on Transnational Corporations. [Electronic resource]. - Access mode: https://digitallibrary.un.org/record/156251.
Intensive globalization of the world economy and international relations, the driving force of which are TNCs, gives special importance to the study of the current state of legal regulation of their activities within the system of private international law and national legal systems. The relevance of a topic in general is determined by two interrelated but separate factors.
Інтенсивна глобалізація світової економіки та міжнародних відносин, рушійною силою яких є ТНК, надає особливого значення вивченню сучасного стану правового регулювання їх діяльності в системі міжнародного приватного права та національних правових систем. Актуальність теми загалом визначається двома взаємопов’язаними, але окремими факторами.

1. Huntington, Samuel P. The Clash of Civilizations and the Remaking of World Order // Simon & Schuster, 2018. 368 pages 2. Perkins, John The New Confessions of an Economic Hit Man // Berrett-Koehler Publishers; 2nd edition, 2016. 384 pages 3. UNCTAD Transnational Corporations (Journal) (Volume 27, Number 1); United Nations, New York and Geneva, 2019. 99 pages 4. UNCTAD World Investment Report 2015 – Reforming International Investment Governance; United Nations, New York and Geneva, 2015. 252 pages
Currently, there is no single approach to the division of countries into underdeveloped countries, developing and developed ones. There are more common approaches of the UN, World Bank, WTO to ranking countries and territories. Although the current stages of development of TNCs are chaacterised by globalisation, and the flow of capital from one area to another, (which in theory should level the gap between countries) and the development of national economies is still uneven. For many reasons, because of the policy of protectionism, many because of the different levels of natural resources (as the main factor of economic growth).
В даний час не існує єдиного підходу до поділу країн на слаборозвинені країни, що розвиваються та розвинені. Існують більш загальні підходи ООН, Світового банку та СОТ до ранжирування країн та територій. Хоча нинішні етапи розвитку ТНК характеризуються глобалізацією, а потік капіталу з однієї області в іншу (що теоретично повинно нівелювати розрив між країнами) та розвиток національних економік все ще нерівномірний. З багатьох причин, через політику протекціонізму, багато через різний рівень природних ресурсів (як головний фактор економічного зростання).

Loxosceles laeta, conocida como “araña del rincón” o “araña casera”, es el principal artrópodo de importancia clínica en nuestro país debido a las graves alteraciones fisiológicas, con secuelas irreversibles que produce su mordedura en humanos pudiendo llevar a la muerte. El objetivo de este trabajo fue explorar y caracterizar parcialmente las enzimas proteolíticas presentes en este veneno; las enzimas evaluadas fueron proteolíticas sobre caseína y dimetilcaseína (DMC), así como la acción pro-coagulante sobre plasma humano citratado. El veneno fue fraccionado usando una columna cromatográfica de filtración molecular sobre Sephadex G-100, equilibrado con buffer acetato de amonio 0,05M pH 5,0. Mediante PAGE-SDS se determinó que la proteasa que hidroliza DMC es de naturaleza monomérica, con un peso aproximado de 35 kDa. En los ensayos de inhibición, con el agente quelante EDTA y el inhibidor de serinoproteasas (PMSF), se obtiene una inhibición de 60,4% de la actividad proteolítica usando 5 mM de EDTA y empleando 5 mM de PMSF la actividad pro-coagulante se redujo al 6,7%. Las pruebas de inmunodifusión doble, usando el antiveneno loxoscélico comercial (INS-Perú) mostraron la antigenicidad de las proteasas en estudio, así como del antiveneno total. Se concluye que el veneno de la araña L. laeta contiene por lo menos 2 tipos de proteasas, una del tipo metaloproteasa y la otra serinoproteasa, siendo ambas enzimas reconocidas por el antiveneno loxoscélico comercial.
Tesis

Context. Gravitationally bound multiple systems provide an opportunity to estimate the mean bulk density of the objects, whereas this characteristic is not available for single objects. Being a primitive population of the outer solar system, binary and multiple trans-Neptunian objects (TNOs) provide unique information about bulk density and internal structure, improving our understanding of their formation and evolution. Aims. The goal of this work is to analyse parameters of multiple trans-Neptunian systems, observed with Herschel and Spitzer space telescopes. Particularly, statistical analysis is done for radiometric size and geometric albedo, obtained from photometric observations, and for estimated bulk density. Methods. We use Monte Carlo simulation to estimate the real size distribution of TNOs. For this purpose, we expand the dataset of diameters by adopting the Minor Planet Center database list with available values of the absolute magnitude therein, and the albedo distribution derived from Herschel radiometric measurements. We use the 2-sample Anderson-Darling non-parametric statistical method for testing whether two samples of diameters, for binary and single TNOs, come from the same distribution. Additionally, we use the Spearman's coefficient as a measure of rank correlations between parameters. Uncertainties of estimated parameters together with lack of data are taken into account. Conclusions about correlations between parameters are based on statistical hypothesis testing. Results. We have found that the difference in size distributions of multiple and single TNOs is biased by small objects. The test on correlations between parameters shows that the effective diameter of binary TNOs strongly correlates with heliocentric orbital inclination and with magnitude difference between components of binary system. The correlation between diameter and magnitude difference implies that small and large binaries are formed by different mechanisms. Furthermore, the statistical test indicates, although not significant with the sample size, that a moderately strong correlation exists between diameter and bulk density.

Il cardiomiocita è un complesso sistema biologico in cui molti meccanismi interagiscono in maniera non lineare per regolare l'accoppiamento tra eccitazione elettrica e contrazione meccanica. Per questo motivo, lo sviluppo di modelli matematici è fondamentale nel campo dell'elettrofisiologia cardiaca, in cui l'uso di strumenti computazionali è diventato complementare alla sperimentazione classica. L'obiettivo di questo elaborato è stato quello di: 1) effettuare una revisione della letteratura sul tema delle alternans cardiache; 2) effettuare uno studio sperimentale in silico sulle alternans nei modelli di O'Hara-Rudy e di Ten Tusscher-Noble-Noble-Panfilov. Questo ha permesso di svelare le dinamiche molecolari e cellulari coinvolte nella genesi delle alternans, confermando come la modellazione matematica sia un ottimo strumento per lo studio dei meccanismi elettrofisiologici alla base delle aritmie cardiache.

This thesis is focused on examining the lack of balance of interests between transnational corporations (TNCs) and host developing states. It also examines the aspirational differences between the parties vis-à-vis the investment practice(s) over the past few decades and reviews the perception of foreign direct investments (FDIs). The contribution of TNCs has been a heated topic of debates in international circles and policy-makers were unable to find solutions, not for the lack of attempts such as the UN draft codes of conduct on TNCs, the Havana Charter, MAIs and others, but due to gaps in aspirations between the parties, the negotiations were unsuccessful. There were also some successful attempts from the developing states, namely the UN Declaration on Permanent Sovereignty over Natural Resources and the UN Charter on Economic Rights and Duties of States. This revealed the limits of law in regulating the conduct of TNCs in host developing states during the course of foreign investments. Emphasis is given to the capacity building and the system of protection of investments, namely by means of bi-lateral investment treaties (BITs), as well as protecting the interests of both of the parties. International efforts to regulate foreign investments are gaining momentum. Research showed that changes are underway and the re-negotiations clause might be a way forward. It also makes an attempt in understanding the international investment law and increasing frustration with the existing mechanism for settlement of investment disputes, which arises from violations of BITs. It revealed that the role of law is of fundamental importance to offer protection to the investments and to ensure that both parties benefit from such investments, by balancing their interests.

Orientador: Luiz Claudio Di Stasi
Resumo: A Doença Inflamatória Intestinal engloba duas principais doenças sendo elas a Doença de Crohn e a Retocolite Ulcerativa onde ambas se caracterizam por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prologados com remissão dos sintomas. Sua etiologia é considerada multifatorial e ainda pouco elucidada. Considerando-se que não existe cura, que os fármacos utilizados são de alto custo, além de apresentarem sérios efeitos colaterais e ainda muitos pacientes não responderem a esses tratamentos disponíveis, a busca por estratégias complementares de prevenção e tratamento dessa doença que combinem eficácia e segurança, como o uso de alimentos funcionais, compostos antioxidantes e compostos bioativos se apresentam como uma perspectiva promissora. Com base nisso, a espécie vegetal Hibiscus esculentus L. conhecida popularmente como quiabo, foi selecionada para o presente estudo com o objetivo de avaliar a atividade anti-inflamatória intestinal das dietas enriquecidas com o fruto no modelo experimental da inflamação intestinal induzida por ácido trinitrobenzenosulfônico em ratos. Para tanto, a farinha dos frutos foi incorporada na dieta de ratos Wistar machos nas concentrações de 5% e de 10% por 28 dias antes e 7 dias após a indução do processo inflamatório intestinal. Os animais foram mortos no 35º dia e seus cólons foram extraídos. Para a caracterização da atividade anti-inflamatória intestinal foram analisados parâmetros macroscópicos (escore,... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Inflammatory Bowel Disease comprises two major diseases, Crohn´s disease and ulcerative colitis where both are characterized by chronic inflammation of the intestine, with periods of exacerbation followed by prolonged intervals with remission of symptoms. This disease is multifactorial with complex and not fully elucidated etiology. Considering that there is no cure and the drugs may cause serious side effects, and many patients do not respond to the available treatments, researches focused on the development of new treatment strategies are important. The pursuit of complementary strategy of prevention and treatment of disease that combine effectiveness and safety, such as the use of functional foods, antioxidant compounds and bioactive compounds if known as a promising perspective. Based on this, a vegetable species Hibiscus esculentus L., populary known as okra, was selected for this study with the objective to evaluate the activity of enriched diet in the experimental model of intestinal inflammation induced by trinitrobenzenesulfonic acid in rats. For this, a fruit flour was incorporated in the diet of male Wistar rats in concentrations of 5% and 10% for 28 days before and 7 days after of induction of intestinal inflammation by TNBS. The animals were killed on the 35th day and their colons were removed. For the characterization of the intestinal antiinflammatory activity, were performed macroscopic studies (score, lesion length, weight ratio length of the colon, occurrenc... (Complete abstract click electronic access below)
Mestre

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A Doença Inflamatória Intestinal (DII) engloba, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (CU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados de remissão dos sintomas. Apesar da DII ser objeto de pesquisa há várias décadas, a sua etiologia ainda é desconhecida e a principal limitação no entendimento dos mecanismos fisiopatológicos desta doença é a disponibilidade de modelos experimentais adequados que mimetizem o caráter crônico e de recidiva da DII em humanos e que possam ser de baixo custo, reprodutível, fácil de induzir e que apresente características clínicas e histopatológicas, respostas terapêuticas e mediadores inflamatórios similares ao que ocorre com a doença em humanos. Dentre os vários modelos experimentais disponíveis, o modelo de colite induzida por ácido trinitrobenzenosulfônico (TNBS) em ratos tem sido considerado o mais adequado para a avaliação de novos fármacos, assim como aquele que melhor mimetiza esta doença em humanos. Assim sendo, a caracterização do papel de diferentes mediadores do processo inflamatório intestinal neste modelo permitiria a determinação de novos alvos terapêuticos, assim como geraria informações importantes da fisiopatologia desta doença. Neste sentido, o presente projeto teve como objetivo determinar a participação da HSP70, Heparanase e HPRT, mediadores do processo inflamatório intestinal em humanos, na fase aguda do processo inflamatório intestinal induzido TNBS em ratos, assim como estudar os efeitos de fármacos das três principais classes farmacológicas usadas no tratamento da DII em humanos, os aminossalicilatos (sulfassalazina), os glicocorticóides (prednisolona) e os imunomoduladores (azatioprina) sobre esses mediadores. Este estudo demonstrou que HSP70, Heparanase...
The idiopatic inflammatory bowel diseases comprise two types of chronic intestinal disorders: Crohn’s disease and ulcerative colitis that are characterized by a chronic inflammation of the intestine, with periods of remission and reactivation of the inflammatory process. Although IBD is the subject of research for several decades, its etiology remains unknown, and the major limitation to understanding the IBD pathophysiology is the availability of experimental models that mimic the chronic and relapse of human IBD. Is still important that experimental models can be inexpensive, reproducible, easy to induce and present clinical and histopathological features, therapeutic responses and inflammatory mediators similar to what occurs in humans. Among experimental models available, the model of colitis induced by trinitrobenzenesulphonic acid (TNBS) in rats has been considered the most suitable for the evaluation of new drugs, as well as the one that best mimics the disease in humans. Therefore, the involvement of different IBD mediators in this experimental model would allow the determination of new therapeutic targets, as well as generate important information on the pathophysiology of this disease. In light of this, the aim of present study was to determine the participation of HSP70, Heparanase and HPRT, mediators of intestinal inflammatory process in humans, in acute phase of inflammatory process induced by TNBS in rats, as well as, to study the effects of drugs of the three main classes used in the treatment of human IBD, i.e., aminosalicylates (sulphasalazine), glucocorticoids (prednisolone) and immunomodulators (azathioprine) on these mediators. This study showed that HSP70, Heparanase and HPRT participate as mediators of intestinal inflammation induced by TNBS since these mediators are increased in colitic animals when compared to healthy animals... (Complete abstract click electronic access below)

Orientador: Luiz Claudio Di Stasi
Banca: Marcelo Fabio Gouveia Nogueira
Banca: Alessandra Gambero
Resumo: A Doença Inflamatória Intestinal (DII) engloba, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (CU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados de remissão dos sintomas. Apesar da DII ser objeto de pesquisa há várias décadas, a sua etiologia ainda é desconhecida e a principal limitação no entendimento dos mecanismos fisiopatológicos desta doença é a disponibilidade de modelos experimentais adequados que mimetizem o caráter crônico e de recidiva da DII em humanos e que possam ser de baixo custo, reprodutível, fácil de induzir e que apresente características clínicas e histopatológicas, respostas terapêuticas e mediadores inflamatórios similares ao que ocorre com a doença em humanos. Dentre os vários modelos experimentais disponíveis, o modelo de colite induzida por ácido trinitrobenzenosulfônico (TNBS) em ratos tem sido considerado o mais adequado para a avaliação de novos fármacos, assim como aquele que melhor mimetiza esta doença em humanos. Assim sendo, a caracterização do papel de diferentes mediadores do processo inflamatório intestinal neste modelo permitiria a determinação de novos alvos terapêuticos, assim como geraria informações importantes da fisiopatologia desta doença. Neste sentido, o presente projeto teve como objetivo determinar a participação da HSP70, Heparanase e HPRT, mediadores do processo inflamatório intestinal em humanos, na fase aguda do processo inflamatório intestinal induzido TNBS em ratos, assim como estudar os efeitos de fármacos das três principais classes farmacológicas usadas no tratamento da DII em humanos, os aminossalicilatos (sulfassalazina), os glicocorticóides (prednisolona) e os imunomoduladores (azatioprina) sobre esses mediadores. Este estudo demonstrou que HSP70, Heparanase... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The idiopatic inflammatory bowel diseases comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis that are characterized by a chronic inflammation of the intestine, with periods of remission and reactivation of the inflammatory process. Although IBD is the subject of research for several decades, its etiology remains unknown, and the major limitation to understanding the IBD pathophysiology is the availability of experimental models that mimic the chronic and relapse of human IBD. Is still important that experimental models can be inexpensive, reproducible, easy to induce and present clinical and histopathological features, therapeutic responses and inflammatory mediators similar to what occurs in humans. Among experimental models available, the model of colitis induced by trinitrobenzenesulphonic acid (TNBS) in rats has been considered the most suitable for the evaluation of new drugs, as well as the one that best mimics the disease in humans. Therefore, the involvement of different IBD mediators in this experimental model would allow the determination of new therapeutic targets, as well as generate important information on the pathophysiology of this disease. In light of this, the aim of present study was to determine the participation of HSP70, Heparanase and HPRT, mediators of intestinal inflammatory process in humans, in acute phase of inflammatory process induced by TNBS in rats, as well as, to study the effects of drugs of the three main classes used in the treatment of human IBD, i.e., aminosalicylates (sulphasalazine), glucocorticoids (prednisolone) and immunomodulators (azathioprine) on these mediators. This study showed that HSP70, Heparanase and HPRT participate as mediators of intestinal inflammation induced by TNBS since these mediators are increased in colitic animals when compared to healthy animals... (Complete abstract click electronic access below)
Mestre

This research investigates whether Transportation Network Companies (TNCs), such as Uber and Lyft, live up to their stated vision of reducing congestion by complementing transit and reducing car ownership in major cities. The objective of this research study is to answer the question: are TNCs are correlated to traffic congestion in the city of San Francisco? If found to be so, do they increase or decrease traffic congestion for the case of San Francisco? If and how TNC pickups and drop-offs impact traffic congestion within San Francisco? And finally, how does the magnitude of this measured command of TNCs on congestion compare to that caused by pre-existing conventional drivers of traffic and congestion change? Apart from answering these questions, it is also sought to establish a framework to be able to include TNCs, a seemingly fledgling mode of transportation but one that is demonstrably shaping and modifying extant transportation and mode choice trends, as part of the travel demand models estimated by any geographic jurisdiction. Traffic congestion has worsened noticeably in San Francisco and other major cities over the past few years. Part of this change could reasonably be explained by strong economic growth or other standard factors such as road and transit network changes. The sharp increase in travel times and congestion also corresponds to the emergence of TNCs, raising the question of whether the two trends may be related. Existing research has produced conflicting results and been hampered by a lack of data. Using data scraped from the Application Programming Interfaces (APIs) of two TNCs, combined with observed travel time data, this research finds that contrary to their vision, TNCs are the biggest contributor to growing traffic congestion in San Francisco. Between 2010 and 2016, weekday vehicle hours of delay increased by 62%, compared to 22% in a counterfactual 2016 scenario without TNCs. The findings provide insight into expected changes in major cities as TNCs continue to grow, informing decisions about how to integrate TNCs into the existing transportation system. This research also decomposes the contributors to increased congestion in San Francisco between 2010 and 2016, considering contributions from five incremental effects: road and transit network changes, population growth, employment growth, TNC volumes, and the effect of TNC pick-ups and Drop-offs. It is so done through a series of controlled travel demand model runs, supplemented with observed TNC data. The results show that road and transit network changes over this period have only a small effect on congestion, population and employment growth are important contributors, and that TNCs are the biggest contributor to growing congestion over this period, contributing about half of the increase in vehicle hours of delay, and adding to worsening travel time reliability. This research contradicts several studies that suggest TNCs may reduce congestion and adds evidence in support of a recent empirical analysis showing that their net effect is to increase congestion. This research gives transportation planners a better understanding of the causes of growing congestion, allowing them to more effectively craft strategies to mitigate or adapt to it.

Opioids are powerful analgesics. Despite their high efficacy for the management of moderate to severe pain, their clinical utility is limited due to the occurrence of adverse effects. The main problem associated with opioid use is the differential rate of tolerance development to the various pharmacological effects of opioids, with tolerance to respiratory depression occurring at a slower rate than analgesic and euphoric effects. The development of analgesic tolerance, where the efficacy of the drug progressively diminishes with repeated administration, requires higher doses of the drug to achieve a maximum effect. Reports have implicated inflammation as a major driver of analgesic tolerance development. With surmounting evidence that the prototypical opioid, morphine induces pro-inflammatory cytokine release in the brain, spinal cord, and gastrointestinal tract, a question arises of whether pro-inflammatory cytokine release in the gut as a result of chronic morphine treatment is paralleled with the development of morphine antinociceptive tolerance. This dissertation investigated the rate at which antinociceptive tolerance to various doses of morphine developed to a different degree in the presence of colonic inflammation. Using a mouse model, colonic inflammation was induced with 2,4,6-Trinitrobenzenesulfonic acid (TNBS) and then the mice were pelleted with 25 mg, 50 mg (2x25), or 75 mg morphine pellet. Antinociceptive tolerance to morphine was determined in a warm-water tail-immersion assay upon an administration of a morphine challenge dose (10 mg/kg). Inflammatory cytokine expressions and protein levels were measured from whole colon using qPCR and ELISA, respectively. Morphine antinociceptive tolerance was significantly enhanced in the presence of colonic inflammation in a dose and time dependent manner. With a daily injection of 0.5 mg/kg peripheral opioid receptor antagonist 6β-N-heterocyclic substituted naltrexamine derivative (NAP), mice pelleted with 25 mg, 50 mg (2x25), or 75 mg morphine pellets were tested on day 5, 4, or 3, respectively. Tolerance to morphine as well as the enhanced tolerance observed in the presence of colonic inflammation was prevented with daily NAP treatment. However, NAP did not block morphine-induced or TNBS-induced inflammation. Collectively, our findings indicate that inflammation is a major modulator of morphine antinociceptive tolerance and peripheral opioid receptors may be responsible for mediating antinociceptive tolerance.

The overall aim of this thesis is to analyse the social consequences of a transnational corporation(TNC) from the global North investing capital in the global South, and the communal processes that evolve in response. The study highlights the TNC’s construction of leadership and domination in the areas in which it settles, as well as the forces of popular resistance to the TNC’s exploitation of the region’s natural resources and the resulting socio-environmental conditions. The study is based on empirical fieldwork (including 22 interviews) carried out in Uruguay and Argentina related to the establishment of a pulp mill by Botnia/UPM. The analyses focus on discursive processes whereby the TNC establishes itself in the community. The found patterns are discussed in the thesis based on the following themes: “Making the TNC indispensible” ; “Dominating the spaces of communication” ; “Controlling the narratives” ; “Contradictions of external and internal colonialism” and “Establishing and maintaining hegemony”. All of these have to do with socio-political and discursive strategies and circumstances whereby the TNC—symbolically and materially— becomes a powerful force in the country and community where it establishes itself. This creates certain social positions, and gives rise to tensions within a number of areas. In relation to these processes, the thesis also highlights the formation and mobilization of resistance against the changing social, cultural and economic conditions created through the arrival of the TNC. What appears to be crucial for the deployment of a successful counter-force is the creation of spaces for organisation, for practices of resistance and to sustain democratic values and practices. This makes the social movement an autonomous voice that incarnates disobedience against thestate, the juridical international apparatus and the hegemonic practices of TNCs.

As doenças inflamatórias intestinais são caracterizadas por uma desregulação na resposta imune contra a microbiota. O zebrafish, tem emergido como um novo modelo para o estudo de doenças inflamatórias. Os ácidos graxos de cadeia curta (AGCCs) são produtos da microbiota intestinal, que possuem papéis antiinflamatórios e aparecem como uma das possíveis terapias contra doenças inflamatórias. A implementação do modelo de inflamação intestinal induzido pelo ácido trinitrobenzenesulfônico (TNBS) em larvas de zebrafish aumentou a mortalidade de forma dose-dependente. Se observou dilatação do lúmen com alisamento das vilosidades intestinais. Não se detectaram mudanças na produção de muco nem no número de células caliciformes mas teve um leve aumento da apoptóse e diminuição da proliferação, nos expostos ao TNBS. Teve aumento de células mielóides infiltrantes e de citocinas inflamatórias, assim como disbiose da microbiota. O tratamento com AGCCs gero alta mortalidade a concentrações acima de 10 mM, mas existe ação anti-inflamatória a esta mesma concentração.
Inflammatory bowel diseases are characterized by a dysregulation in immune response against microbiota. The zebrafish has emerged as a new model for the study of inflammatory diseases. Short chain fatty acids (SCFAs) are products of the intestinal microflora, which have anti-inflammatory roles and appear as a possible therapy against inflammatory diseases. The implementation of intestinal inflammation model induced by trinitrobencenesulfonic acid (TNBS) in zebrafish larvae, increased mortality in a dose-dependent manner. Was observe dilatation lumen and straightening of the intestinal villi. No changes were detected in the production of mucus or in the number of goblet cells but had a slight increase in apoptosis and decreased proliferation in exposed to TNBS. Also has, increased cytokines and infiltrating myeloid cells, and dysbiosis of the microbiota. Treatment with SCFAs generate high mortality above 10 mM concentrations, but there anti-inflammatory action to this same concentration.

Over the last several years, new transportation service business platforms like Uber and Lyft have appeared in cities across the U.S. Since these new business models do not fit into existing regulatory and policy frameworks, and their entrance into markets is typically abrupt and sometimes illegal, these companies, which have come to be known as transportation network companies (TNCs), provoke city governance actors and the public to react in many different ways. Some cities take a free market approach, while others opt toward heavy handed regulation. In addition to policy action, there is a great deal of policy narrative swirling around these services and their place in existing mobility systems. There is wide variation in the dominant stories or narratives that emerge about TNCs when they suddenly enter a metropolitan market. Said narratives about these mobility providers also evolve as the companies continually operate in different cities. Some stories are thematically tied to specific interest groups and others seem to originate as a result of specific contextual nuances or incidents that occur. Sometimes stories originate in the context of local, state or national political backdrops and discourse. This dissertation argues that stories emerge in the context of urban regime characteristics. Using urban regime theory along with Mark Bevir and R.A.W. Rhodes decentered theory of governance, I will look at TNC operation in four U.S. cities: Indianapolis, IN, Austin, TX, Portland, OR, and Washington, DC. This dissertation explores the ways in which narratives emerge and change around TNCs, how those narratives are influenced by existing urban regime dynamics, and how they influence policy making.
PHD

An abnormally large plasmid has been discovered to naturally exist in two strains of Pseudomonas syringae, appropriately called the "Megaplasmid" due to the genetic content of over one million base pairs of DNA. Costs have been observed with the presence of the Megaplasmid, including growth at elevated temperatures. A technique called Tn5 mutagenesis has been utilized to ameliorate the cost to the host. Results show the initial phenotype of Tn5 mutants overcame elevated temperature growth inhibition, but presence of another mutation is likely in order for the strain to grow at elevated temperatures while harboring the Megaplasmid. Further research must be done to identify genes responsible for increased fitness.

Orientador: Luiz Claudio Di Stasi
Resumo: A Doença Inflamatória Intestinal (DII) é uma doença com etiologia desconhecida e sem terapêutica curativa disponível, englobando, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (RCU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados com remissão dos sintomas, cujo tratamento com os fármacos disponíveis apresentam sérios efeitos colaterais. Portanto, o desenvolvimento de novas estratégias de tratamento que combinem eficácia e segurança é uma importante meta na terapia da DII. Produtos de origem natural, especialmente oriundos de fontes vegetais com propriedades de modificar a microbiota intestinal têm sido amplamente estudados como agentes preventivos e/ou curativo destas doenças, visto que a manipulação da microbiota intestinal tem se mostrado como uma estratégia importante na manutenção da homeostase colônica. Neste contexto, muitos frutos de origem tropical, com ampla utilização pela população e ricos em fibras e/ou componentes que ativos como antioxidantes e/ou anti-inflamatórios podem representar uma nova estratégia complementar para a prevenção ou cura da DII. Dentre eles se destacam os frutos das espécies Theobroma grandiflorum (cupuaçu) e Musa spp AAA (banana nanica), ricos em fibras alimentares e compostos fenólicos, os quais são potencialmente benéficos no tratamento e prevenção da DII. O objetivo do presente trabalho foi avaliar os efeitos de uma d... (Resumo completo, clicar acesso eletrônico abaixo)
Doutor

Orientador: Alba Regina Monteiro Souza Brito
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-18T00:28:36Z (GMT). No. of bitstreams: 1 Socca_EduardoAugustoRabelo_M.pdf: 1268769 bytes, checksum: eee2c6686e3a3fb123101e6954836a0f (MD5) Previous issue date: 2010
Resumo: Retocolite ulcerativa idiopática e doença de Crohn são doenças inflamatórias intestinais caracterizadas por inflamação crônica da mucosa, resultando em diarréia, fezes sanguinolentas, dores abdominais, anemia, febre, fadiga e perda de peso, tanto em homens quanto em mulheres. Acredita-se que essas manifestações sejam resultado de uma interação multifatorial envolvendo indivíduos geneticamente susceptíveis, condições ambientais específicas, desbalanço na microflora intestinal e desajuste da resposta imune. Drogas derivadas do acido 5-aminossalicilico (sulfassalazina, mesalamina), corticosteroides e agentes imunomoduladores são utilizadas, em conjunto no tratamento dessas patologias. No entanto tais drogas apresentam efeitos adversos importantes, o que acaba por motivar pesquisas envolvendo produtos naturais como alternativas de tratamento. Neste contexto, este trabalho avaliou os efeitos de antocianinas presentes nos frutos de Sambucus nigra L. (sabugueiro), espécie arbustiva pertencente a família Adoxaceae, em modelo de colite ulcerativa induzida pelo acido 2,4,6-trinitrobenzeno sulfônico (TNBS). Os frutos do sabugueiro apresentam grandes concentrações de metabolitos secundários como antocianinas, alem de outros compostos fenólicos, que acabam por conferir aos frutos propriedades antioxidantes, anti-inflamatorias, imunomoduladoras e laxativas. Neste trabalho, foram avaliadas as propriedades antioxidantes e anti-inflamatorias da fração de antocianinas monoméricas presentes nos frutos de S. nigra. Os resultados comprovaram o efeito antioxidante in vitro das antocianinas, sendo elas eficazes em reduzir tanto o radical 2,2-difenil-1-picrilhidrazil (DPPH), teste que avalia a redução do radical via transferência de elétrons, quanto a taxa de oxidação do radical 2,2 azobis amidinopropano (AAPH), teste que verifica a oxidação do radical via transferência de átomos de hidrogênio. Nos ensaios in vivo concluiu-se que a dose de 5mg.Kg-1 de antocianinas apresentou a melhor resposta em reduzir a lesão causada pelo TNBS, sendo efetiva em manter os níveis de GSH (5,709 ± 0,931) comparado ao grupo TNBS (0,8525 ± 0,298) e ao grupo salina (6,610 ± 3,926). Essas antocianinas foram efetivas ainda em aumentar a atividade da SOD (8,487 ± 2,505), quando comparada com o grupo TNBS (3,884 ± 0,925) e ao grupo salina (12,240 ± 4,199), e reduzir a atividade da MPO (4,519 ± 2,016), quando comparada ao grupo TNBS (7,572 ± 2,572) e ao grupo salina (1,314 ± 0,319). Os resultados obtidos na avaliação da atividade das enzimas GPx (17,03 ± 3,951 no grupo tratado e 22,13 ± 11,510 no grupo TNBS) e GR (0,6524 ± 0,1180 no grupo tratado e 0,7249 ± 0,3968 no grupo TNBS), comparados ao grupo salina (84,22 ± 41,88) e (2,131 ± 0,9858) respectivamente, indicam que houve queda na ativação destas enzimas apos 24h de indução da colite, sendo que esta situação não foi revertida apos administração das antocianinas. Do mesmo modo não foram encontradas alterações nos níveis de LPO (5,756 ± 1,884 no grupo tratado e 5,113 ± 0,8254 no grupo TNBS) comparados ao grupo salina (4,688 ± 1,126) . Já os ensaios anti-inflamatórios revelaram atividade antiinflamatória promissora, visto que as antocianinas foram capazes de manter os níveis de IL-10 (466,7 ± 56,32) próximos aqueles obtidos no grupo não-colitico (492,4 ± 154,5), quando comparados ao grupo TNBS (264,8 ± 66,35), e de reduzir a produção de IL-12 (202,3 ± 53,33) quando comparados com os animais não tratados (319,3 ± 111,5) e ao grupo salina (149,8 ± 51,76). Neste estudo concluiu-se que as antocianinas presentes nos frutos de sabugueiro apresentam atividade antioxidante, alem de aumentar os níveis de IL-10, citocina essa que, provavelmente, participa na redução dos níveis de citocinas pro - inflamatórias como IL-12 e, consequentemente, a expressão de mediadores inflamatórios
Abstract: Ulcerative colitis and Crohn's disease are inflammatory bowel disease characterized by chronic inflammation of the mucosa, resulting in diarrhea, bloody stools, abdominal pain, anemia, fever, fatigue and weight loss in both men and women. It is believed that these manifestations are the result of a multifactorial interaction involving genetically susceptible individuals, environmental conditions, imbalance in intestinal microflora and immune response imbalance. Drugs derived from 5-aminosalicylic acid (sulfasalazine, mesalamine), corticosteroids and immunomodulatory agents are used together to treat these diseases. However, such drugs have significant adverse effects, which ultimately motivate research involving natural products as alternative treatments. In this context, this study evaluated the effects of anthocyanins in the fruits of Sambucus nigra L. (Elderberry), shrub species belonging to the family Adoxaceae, in a model of ulcerative colitis induced by 2,4,6-trinitrobenzenes sulfonic acid (TNBS). The fruits of elderberry have large concentrations of secondary metabolites such as anthocyanins and other phenolic compounds, which ultimately give the fruit antioxidant, anti-inflammatory, immunomodulatory and laxative properties. In this study we investigated the antioxidant and anti-inflammatory properties of the monomeric anthocyanins fraction in the fruits of S. nigra. The results confirmed the in vitro antioxidant effect of anthocyanins, which were effective in reducing both the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test to evaluate the reduction of the radical via electron transfer and the rate of oxidation 2,2 azobis amidinopropane (AAPH), a test that checks radical oxidation via the transfer of hydrogen atoms. In vivo tests concluded that the dose of anthocyanins 5mg.Kg-1 had the best response to reduce the damage caused by TNBS, being effective in maintaining the levels of GSH (5.709 ± 0.931) compared to TNBS group (0, 8525 ± 0.298) and the saline group (6.610 ± 3.926). These anthocyanins were also effective in increasing the activity of SOD (8.487 ± 2.505) compared with the TNBS group (3.884 ± 0.925) and the saline group (12.240 ± 4.199), and reduce the activity of MPO (4.519 ± 2.016) when compared to TNBS group (7.572 ± 2.572) and the saline group (1.314 ± 0.319). The results obtained in the enzymatic activities of GPx (17.03 ± 3.951 in the treated group and 22.13 ± 11.510 in group TNBS) and GR (0.6524 ± 0.1180 in the treated group and 0.7249 ± 0.3968 TNBS group) compared to saline group (84.22 ± 41.88) and (2.131 ± 0.9858) respectively, indicate that there was a decrease in the activation of these enzymes after 24h of colitis induction. Likewise there were no changes in the levels of LPO (5.756 ± 1.884 in the treated group and 5.113 ± 0.8254 in group TNBS) compared to saline group (4.688 ± 1.126). The anti-inflammatory assays have shown promising antiinflammatory activity, whereas anthocyanins were able to maintain levels of IL-10 (466.7 ± 56.32) than those obtained in non-colitis group (492.4 ± 154 , 5), when compared to TNBS group (264.8 ± 66.35), and reduce the production of IL-12 (202.3 ± 53.33) compared with untreated animals (319.3 ± 111 , 5) and the saline group (149.8 ± 51.76). In this study it was concluded that anthocyanins present in elderberry fruits have antioxidant activity, and increased levels of IL-10, this cytokine, which probably participates in reducing levels of proinflammatory cytokines such as IL-12 and consequently the expression of inflammatory mediators
Mestrado
Fisiologia
Mestre em Biologia Funcional e Molecular

Orientador: Aline Witaicenis Fantinati
Resumo: A Doença Inflamatória Intestinal (DII) engloba duas principais doenças: a Doença de Crohn e a Retocolite Ulcerativa. Esta doença é multifatorial com etiologia complexa e não totalmente elucidada. Considerando-se que não existe cura e que os fármacos utilizados podem apresentar sérios efeitos colaterais, além de muitos pacientes não responderem aos tratamentos disponíveis; estudos voltados para o desenvolvimento de novas estratégias de tratamento são importantes. Estudos têm evidenciado que a associação entre fármacos e alimentos funcionais, pode resultar em uma relação de muito sucesso no tratamento de pacientes com doenças crônicas, sobretudo nas doenças que afetam o trato gastrointestinal. Assim, o uso de alimentos funcionais, especialmente, os ricos em fibras, compostos antioxidantes e lipídeos bioativos podem ser potenciais na prevenção ou tratamento da DII. Com base nisto, a espécie Persea americana Mill., conhecida popularmente como abacate ou avocado, foi selecionada para o presente estudo, pois além de possuir estes compostos, apresenta descrita atividade antioxidante, anti-cancerígena, anti-bacteriana, anti-inflamatória e cicatrizantes. Diante disso, o presente estudo teve como objetivo avaliar a atividade da dieta enriquecida com a polpa de Persea americana Mill. var. Hass no modelo experimental de inflamação intestinal induzida por TNBS em ratos. Para tanto, a polpa da espécie foi incorporada na dieta de ratos Wistar machos, nas concentrações de 5%, 10% ou 20%, por... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Inflammatory Bowel Disease (IBD) comprises two major diseases: Crohn Disease and Ulcerative Colitis. This disease is multifactorial with complex and not fully elucidated etiology. Considering that there is no cure and the drugs may cause serious side effects, and many patients do not respond to the available treatments; therefore researches focused on the development of new treatment strategies are important. Studies have evidenced that the association between drugs and functional foods can result in a very successful relationship forward treating patients with chronic diseases, mainly diseases that affect the gastrointestinal tract. Thus, the use of functional foods, especially ones rich in fibers, antioxidants and bioactive lipids could be potential candidates to the prevention or treatment of IBD. Based on this, Persea americana Mill., popularly known as avocado, was selected for this study, due to the presence of mentioned compounds and also for the antioxidant, anti-cancer, anti-bacterial, anti-inflammatory and cicatrizing activities. Therefore the present study aimed to evaluate the activity of enriched diet with Persea americana Mill. var. Hass pulp in the experimental model of intestinal inflammation induced by TNBS in rats. For this, the fruit pulp was incorporated in the diet of male Wistar rats, in concentrations of 5%, 10% or 20% for 21 days before and 7 days after of induction of intestinal inflammation by TNBS and the animals were killed on the 29º day. Addition... (Complete abstract click electronic access below)
Mestre

Influence of stress factors on tunneling nanotubes in cultivated human retinal pigment epithelial cells (ARPE-19). The eye as one of the most important sense organs of the human body is exposed to visible light radiation and other stress factors every day. Especially the retina (of the eye) is a sensible tissue for oxidative damage (Wu et al., 2006). The retinal pigment epithelium (RPE) is an important layer of the retina, which forms the outer layer and phagocytises the shed disc membranes of the photoreceptor outer segments. Furthermore, the RPE is involved in the maintenance of the visual cycle and regulates the retinal balance (Bok, 1993). To maintain those functions, a steady communication between the RPE-cells and the adjacent neighbour cells is necessary. Tunneling nanotubes (TNTs) build a newly discovered variety of cell communication and thus establish intercellular signal transduction and transport different cell components including pathogens (Rustom et al., 2004; Onfelt et al., 2006; Sherer und Mothes, 2008; Veranic et al., 2008). The formation of TNTs in the neuron-like pheochromocytoma cell line PC12 was first reported by Rustom et al in 2004. In the following years a growing number of cell types containing TNTs were described. For example a lot of TNT-reports were found between immune cells (Onfelt et al., 2004; Sowinski et al., 2008). Chinnery et al. first described TNTs in vivo in 2008. Here they found TNTs between dendritic cells in the cornea of the mouse. An important characteristic of TNTs is that they do not attach to the substratum. They contain F-actin as a characteristic feature of there structure (Rustom et al., 2004). Our study group detected the formation of TNTs between ARPE-19-cells, a human retinal pigment epithelial cell line. They contain F-actin, but no microtubules. Further it was observed an exchange of electrical signals, small molecules and even the transfer of organelles between cells via TNTs (see publication Wittig et al., 2012). It is often described in the literature, that TNTs are very sensitive against stress factors, like prolonged light excitation, mechanical and chemical stress, which then can result in rupture of the TNTs (Rustom et al., 2004; Koyanagi et al., 2005; Gurke et al., 2008a; Pontes et al., 2008; Sowinski et al., 2008; Domhan et al., 2011; Wang und Gerdes, 2012). Up to now it is widely unclear how pathological conditions influences TNTs. There are several studies, which report an induction but also an inhibition of TNT-formation by different factors. The reaction of cell-cell-interactions between RPE cells on stress factors is not jet analysed. So our motivation was, to analyse the influence of different stress factors on the number, the morphology and formation of TNTs. ARPE-19-cells were treated with blue light, with a wavelength of 470 and 405 nm, with 3000 μM glyoxal, with 200 μM H2O2, with medium without serum as well as with cytochalasin-D and latrunculin-B. With the help of differential interference contrast (DIC) microscopy the formed TNTs were counted and the morphology was evaluated. A 24 hours cultivation of untreated ARPE-19 cells resulted in 15 TNTs per 100 cells on average. After excitation of the ARPE-19-cells with blue light 470 and 405 nm the number of TNTs decreased 50 % and 28,5 % accordingly in comparison to untreated cells (100 %). Furthermore, the cell culture, which was treated with glyoxal and H2O2 resulted in a reduction of 17,5 % and 53 % TNTs in comparison to the untreated cell culture. Cells which were cultured with serum free medium had an decreased TNT-number of 56.8 % in comparison with serum containing medium. TNTs of untreated ARPE-19-cells have a diameter from 50 to 300 nm (Wittig et al., 2012). Every TNTs, which were formed under named stress factors had the same diameter like untreated cells. In this study an average TNT length of 23 +/- 16 μm was measured between cells without treatment. This correlated with the TNT-lengths of cells which excitated with blue light 405 and 470 nm with 26 +/- 13 μm and 24 +/- 14 μm. In contrast the TNT-lenghts of cells treated with glyoxal and H2O2 with 16 +/- 11 μm and 15 +/- 13 μm were less and from cells cultured without serum with 34 +/- 20 μm were above the average length of TNTs of untreated cells. TNTs of ARPE-19-cells without treatment and TNTs which were treated with stress factors contained F-actin but no microtubules. Depolymerisation of F-actin, induced by addition of cytochalasin-D or latrunculin-B, led to disappearance of TNTs. This is an evidence for the importance of F-actin as an essential component of TNTs between ARPE-19-cells. Under the influence of blue light excitation the TNTs formed as good as untreated cells after contact of migrating cells. Reason for the reduced TNT-formation under stress factors could be explained by the generation of oxidative stress due to reactive oxygen species (ROS). ROS induced under blue light- or glyoxal-treatment as well as H2O2 could influence cell function by inactivation of cell-mediated proteins or induction of F-actin oxidation with subsequent destruction of the actin-network and inhibition of the actin-polymerisation (Chen, 1993; Ballinger et al., 1999; Thornalley et al., 1999; Valen et al., 1999; Dalle-Donne et al., 2002; Nilsson et al., 2003; Shangari und O'Brien, 2004; Zhu et al., 2005; Knels et al. 2008; Roehlecke et al., 2009). The reduced actin-polymerisation as well as the disruption of the TNTs due to changes at the actin-cytoskeleton and at the membranes could explain the reduced TNT-formation (Valen et al., 1999; Dalle-Donne et al., 2002; Reber et al., 2002; Zhu et al., 2005; Knels et al., 2008). The inhibition of the cell growth under oxidative stress conditions and under nutritional deficiency by serum free medium could lead to a reduced TNT-formation too. In this study we found a reduction of TNT-number between ARPE-19-cells under different stress conditions. It is possible, that TNTs are formed between RPE- and photoreceptor-cells in vivo, where they can exchange useful or recyclable materials between cells (Wang et al., 2011; Wittig et al., 2012). Disruption of TNTs by reactive oxygen species could cause a decreased exchange of informations. It is possible, that the cells, RPE- as well as photoreceptor-cells, die due to a deficiency of nutrients. This could be another reason in the formation of age related macular degeneration, which shows a destruction of RPE-cells and secondary of the photoreceptorcells
Das Auge ist als eines der wichtigsten Sinnesorgane des Menschen täglich sichtbarer Lichtstrahlung und weiteren Stressfaktoren ausgesetzt. Die Netzhaut des Auges ist besonders empfindlich für oxidative Schäden (Wu et al., 2006). Eine bedeutende Schicht der Netzhaut im Auge stellt das retinale Pigmentepithel (RPE) dar, welches die äußere Schicht der Retina bildet und täglich die abgeworfenen Photorezeptoraußensegmentscheiben phagozytiert. Zudem ist das RPE wesentlich am visuellen Prozess sowie der Aufrechterhaltung des retinalen Gleichgewichts beteiligt (Bok, 1993). Um diese Funktionen zu gewährleisten, ist eine ständige Kommunikation zwischen den RPEZellen sowie zu angrenzenden Nachbarzellen innerhalb der Netzhaut notwendig. So ist über Tunneling Nanotubes (TNTs), als neu entdeckte Kommunikationsform, ein interzellulärer Transport von Signalen und verschiedensten Zellkomponenten, aber auch von Pathogenen, möglich (Rustom et al., 2004; Onfelt et al., 2006; Sherer und Mothes, 2008; Veranic et al., 2008). Erstmals 2004 beschrieben Rustom et al. die Bildung von TNTs zwischen Rattennierenzellen in vitro. In den folgenden Jahren kam es zu einer Vielzahl weiterer TNT-Entdeckungen zwischen verschiedensten Zellen in vitro. So findet man zum Beispiel vermehrt TNTBeschreibungen zwischen Immunzellen (Onfelt et al., 2004; Sowinski et al., 2008). Ein erster Nachweis an TNTs in vivo erfolgte 2008 durch die Arbeitsgruppe Chinnery et al.. Hierbei fand man TNTs zwischen dendritischen Zellen in der Mauscornea. Ein wichtiges Merkmal von TNTs ist, dass sie sich als frei im Medium schwebende interzelluläre Verbindungen darstellen, ohne Kontakt zum Substrat zu haben. TNTs sind im Wesentlichen als stabilisierendes Hauptstrukturmerkmal aus Aktin aufgebaut (Rustom et al., 2004). In unserer Arbeitsgruppe wurde die Bildung von TNTs zwischen ARPE-19-Zellen, einer humanen Pigmentepithelzelllinie, entdeckt. Neben dem strukturellen Aufbau aus Aktin, konnte ein Austausch von elektrischen Signalen sowie molekularen Stoffen und der Transport von Organellen (Mitochondrien) durch TNTs zwischen ARPE-19-Zellen nachgewiesen werden (siehe Publikation Wittig et al., 2012). Wie schon mehrfach in der Literatur beschrieben, reagieren TNTs sehr sensibel auf Stressfaktoren, so zum Beispiel auf längere Lichtreizung, mechanischen und chemischen Stress, was jeweils zur Ruptur der Strukturen führen kann (Rustom et al., 2004; Koyanagi et al., 2005; Gurke et al., 2008; Pontes et al., 2008; Sowinski et al., 2008; Domhan et al., 2011; Wang und Gerdes, 2012). Weitgehend unklar ist bisher der Einfluss von pathologischen Bedingungen auf die TNTs. Es gibt mehrere Studien, in denen durch verschiedenste Faktoren über eine Induktion, aber auch über eine Hemmung der TNT-Bildung berichtet wurde. Die Reaktion von Zell-Zell-Interaktionen zwischen RPE-Zellen auf Stressfaktoren wurde bisher in wissenschaftlichen Arbeiten nicht untersucht. Dies nahmen wir zum Anlass, den Einfluss von unterschiedlichen Stressfaktoren auf die Anzahl von TNTs, ihre Morphologie und Bildung zu untersuchen. Es erfolgte eine Behandlung der ARPE-19-Zellen mit Blaulicht in den Wellenlängen 405 und 470 nm, mit 3000 μM Glyoxal, mit 200 μM H2O2, mit serumfreiem Medium sowie mit Cytochalasin D und Latrunculin B. Die gebildeten TNTs wurden anschließend mit Hilfe der Lichtmikroskopie ausgezählt sowie deren Morphologie beurteilt. So bildeten unbehandelte ARPE-19-Zellen nach 24 Stunden Kultivierung im Durchschnitt 15 TNTs pro 100 Zellen aus. Nach 24stündiger Bestrahlung der ARPE-19-Zellen mit Blaulicht 470 nm und 405 nm fiel die TNT-Anzahl auf 50 % und 28,5 % im Vergleich zu unbehandelten Zellen (100 %). Weiterhin fanden sich in den Glyoxal- und H2O2-behandelten Kulturschalen 17,5 % und 53 % TNTs verglichen mit der unbehandelten Zellkultur. In der serumfreien Kulturschale verringerten sich die TNTs 24 Stunden nach Ausplattierung der Zellen auf 56,8 % im Vergleich zu in Medium mit Serum kultivierten Zellen. TNTs unbehandelter ARPE-19-Zellen besitzen einen Durchmesser von 50 bis 300 nm (Wittig et al., 2012). Alle unter oben genannten Stressfaktoren gebildeten TNTs befanden sich in Hinblick auf ihren Durchmesser im Bereich der TNTs unbehandelter Zellen. Bei TNTs unbehandelter Zellen wurde in dieser Arbeit eine durchschnittliche Länge von 23 +/- 16 μm gemessen. Dies entsprach dem TNT-Längendurchschnitt von mit Blaulicht 405 nm und 470 nm bestrahlter ARPE-19-Zellen mit 26 +/- 13 μm und mit 24 +/- 14 μm. Unter Glyoxal und H2O2 gebildete TNTs lagen im Gegensatz dazu mit 16 +/- 11 μm und 15 +/- 13 μm unterhalb und unter serumfreier Kultivierung mit 34 +/- 20 μm über dem TNTLängendurchschnitt unbehandelter Zellen. Alle TNTs, sowohl unbehandelter als auch mit Stressfaktoren behandelter ARPE-19-Zellen, sind aus Aktin aufgebaut. Jedoch ließ sich kein Tubulin nachweisen. Nach Zugabe von Aktinpolymerisationshemmern waren keine TNTs nachweisbar, was beweist, dass F-Aktin essentieller Bestandteil von TNTs zwischen ARPE-19-Zellen ist. Unter dem Einfluss von Blaulicht 470 und 405 nm bildeten sich die TNTs, wie auch bei unbehandelten Zellen, durch ein Zusammentreffen der Zellen mit anschließendem Auseinandergleiten. Die Ursache für die verminderte Bildung an TNTs unter verschiedenen Stressfaktoren könnte in der Entstehung von oxidativem Stress durch die Ausbildung von reaktiven Sauerstoffspezies (ROS) begründet sein. So können zum Beispiel die unter Blaulicht- und Glyoxalexposition entstehenden ROS sowie H2O2, als eine Hauptform der ROS, die Zellfunktion durch Inaktivierung zellulärer Proteine beeinflussen sowie eine direkte Oxidation an Aktin hervorrufen mit folglicher Aktinnetzwerkzerstörung und Hemmung der Aktinpolymerisation (Chen, 1993; Ballinger et al., 1999; Thornalley et al., 1999; Valen et al., 1999; Dalle-Donne et al., 2002; Nilsson et al., 2003; Shangari und O'Brien, 2004; Zhu et al., 2005; Knels, Worm et al. 2008; Roehlecke et al., 2009). Die verminderte Aktinpolymerisation, aber auch die Zerreißungen der TNTs durch Veränderungen am Aktinzytoskelett sowie an den Membranen könnten zu einer verringerten TNT-Bildung führen (Valen et al., 1999; Dalle-Donne et al., 2002; Reber et al., 2002; Zhu et al., 2005; Knels et al., 2008). Auch eine Hemmung des Zellwachstums unter oxidativen Stressbedingungen sowie unter Nährstoffmangel durch Serumentzug könnte mit einer verminderten TNT-Bildung einhergehen. Wir haben in unserer Untersuchung gezeigt, dass es durch verschiedene Stresseinflüsse zu einer Reduktion der TNTs zwischen ARPE-19-Zellen kommt. Es ist denkbar, dass solche TNTs in vivo zwischen RPE- und Photorezeptorzellen ausgebildet werden, wo sie nützliches oder recycelbares Material zwischen Zellen austauschen (Wang et al., 2011; Wittig et al., 2012). Bei Zerstörung der TNTs durch zum Beispiel oxidative Faktoren könnte es zu einer Verringerung des Informationsaustausches kommen. Es ist möglich, dass durch die Minderversorgung die Zellen absterben, sowohl RPE- als auch Photorezeptorzellen. Dies könnte ein weiterer möglicher Ursachenansatz in der Entstehung der altersabhängigen Makuladegeneration sein, welche als Erkrankungserscheinung den Untergang der RPEZellen und damit sekundär der Photorezeptorzellen aufweist

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A Doença Inflamatória Intestinal (DII) é uma doença com etiologia desconhecida e sem terapêutica curativa disponível, englobando, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (RCU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados com remissão dos sintomas, cujo tratamento com os fármacos disponíveis apresentam sérios efeitos colaterais. Portanto, o desenvolvimento de novas estratégias de tratamento que combinem eficácia e segurança é uma importante meta na terapia da DII. A espécie Baccharis dracunculifolia DC (família Asteraceae) é uma planta medicinal brasileira usada popularmente contra úlceras, inflamação e problemas hepáticos e tem sido amplamente reconhecida como a principal fonte botânica da resina e dos constituintes químicos da própolis brasileira (própolis verde), a qual tem sido incorporada em alimentos e bebidas para a melhora da saúde. Estudos mostram que as inúmeras atividades biológicas da própolis verde decorrem exclusivamente dos constituintes presentes em Baccharis dracunculifolia, a qual possui várias atividades biológicas, especialmente agindo como imunomoduladora, anti-inflamatória e anti-inflamatória intestinal, sequestradora de radicais livres, antiúlcera e analgésica. A atividade anti-inflamatória intestinal está associada à presença de diferentes ácidos fenólicos presentes na espécie, tais como ácidos cafeico, p-cumárico, 3-prenil-p-cumárico (drupanina), 3,5-diprenil-p-cumárico (artepilina C), bacarina e metil-éster de aromadendrina. Estes compostos possuem íntima associação biossintética com os derivados cumarínicos também ativos na doença inflamatória intestinal, justamente por fazerem parte de sua rota biossintética. Com base nestas...
The Inflammatory Bowel Disease (IBD) is a disease with unknown etiology and no curative treatment available, encompassing essentially two distinct diseases: Crohn's disease (CD) and ulcerative colitis (UC), both characterized by chronic inflammation of the intestine, with periods of exacerbation followed by long intervals with symptom remission whose treatment with available drugs have serious side effects. Therefore, the development of new treatment strategies that combine effectiveness and safety is an important goal in the treatment of IBD. The species Baccharis dracunculifolia DC (Asteraceae) is a Brazilian medicinal plant popularly used against ulcers, inflammation and liver problems and has been widely recognized as the main botanical source of the resin and the chemical constituents of Brazilian propolis (green-propolis), which has been incorporated in foods and beverages to improve health. Studies show that the numerous biological activities of green propolis derived exclusively from the constituents present in Baccharis dracunculifolia, which has several biological activities, especially acting as immunomodulatory, anti-inflammatory and anti-inflammatory intestinal free radical scavenging, antiulcer and analgesic. The intestinal anti-inflammatory activity is associated with the presence of different phenolic acids in this specie, such as caffeic acid, p-coumaric acid, 3-prenyl-p-coumaric (drupanina), 3,5-diprenyl-p-coumaric acid (C artepilina ) bacarina and methyl ester aromadendrin. These compounds have a close association with the biosynthetic coumarin derivatives also active in inflammatory bowel disease, just by being part of their biosynthetic pathway. Based on this information, the aim of this study was to identify potential pharmacological targets of anti-inflammatory action of the extract... (Complete abstract click electronic access below)

Orientador: Mário Roberto Maróstica Junior
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Resumo: A doença inflamatória intestinal (DII) édoença crônica recidivante que atinge milhões de pessoas no mundo, englobando a Doença de Crohn (DC) e a Retocolite Ulcerativa (RCU). A diferença entre as duas éa sua localização, sendo a RCU específica da região do cólon e reto. O tratamento atual para estas patologias é realizado a base de corticosteróides, imunomoduladores ou anti -TNF-a, conhecido como terapia biol ógica, os quais apresentam diversos efeitos colaterais ao paciente. A patogênese desta doença está relacionada com fatores gen éticos, imunol ógicos e ambientais. Acredita-se que o desequilíbrio da microbiota, assim como a ruptura na barreira natural exercida pela mucosa intestinal seja o primeiro passo para o desencadeamento da resposta inflamatória. As fibras alimentares apresentam função sobre a modulação da microbiota, sendo utilizada como substrato para a formação de ácidos graxos de cadeia curta (AGCC), gerados por meio do processo de fermentação. Em adição, os compostos fenólicos presentes nos alimentos apresentam atividade antioxidante e anti -inflamatória que podem atuar na modulação do processo inflamatório. Sendo assim, o objetivo deste trabalho foi avaliar a utilização de um subproduto da indústria de alimentos, a casca do maracujá, como fonte de fibras e compostos fenólicos, na alimentação de ratos com colite induzida por TNBS e sua influência no processo inflamatório. Ratos Wistar foram alimentados com dieta AIN-93, sendo substituídos 50% da celulose da dieta padrão (AIN) por fibras da casca do maracujá (PFF), em dois ensaios biológicos: prevenção e tratamento. O dano causado àmucosa foi avaliado macro e microscopicamente, assim como a expressão de marcadores inflamatórios. Avaliação da microbiota e formação de AGCC foram realizadas no conteúdo cecal. Embora a avaliação macroscópica da mucosa tenha apresentado um escore maior para o grupo PFF no ensaio prevenção, a avaliação microscópica em ambos os ensaios não mostrou diferença no dano àmucosa entre os grupos. O ensaio tratamento mostrou diminuição da peroxidação lipídica do cólon, diminuição na contagem de enterobactérias e aeróbios totais, assim como aumento de ácido acético e butírico nas fezes do grupo PFF. Jáno ensaio prevenção foi observada modulação dos lactobacilos e bifidobactérias. Com relação aos marcadores inflamatórios, foram observadas modulações significativas da expressão de IKK?, COX-2 e iNOS nos animais alimentados com a dieta PFF. Estes resultados sugerem que a casca do maracujá Passiflora edulis pode modular a microbiota aumentando a produção de AGCC, assim como a expressão de marcadores inflamatórios observados na colite induzida por TNBS. Desta forma, a casca do maracujá poderia ser utilizada como coadjuvante na terapêutica da DII como fonte de fibras e polifenóis
Abstract: Inflammatory bowel disease (IBD) is a chronic relapsing disease that affects millions of people worldwide, encompassing Crohn's disease (CD) and ulcerative colitis (UC). UC is an inflammation specific to the region of the colon and rectum. Current treatments for these diseases are based on the use of corticosteroids, immunomodulators or biological therapy, which have various side effects to the patient. The pathogenesis of IBD is related to genetic, immunological and environmental factors. It is believed that the microbial imbalance as well as natural break in the barrier exerted by the intestinal mucosa is the first step in triggering the inflammatory response. Food dietary fiber presents capacity to modulate the microbiota and improve short chain fatty acids (SCFA) formation, by fermentation process. In addition, the phenolic compounds present in the food have antioxidant and anti-inflammatory activities that can modulate the inflammatory process. Thus, this study aimed to evaluate the use of a byproduct of the food industry, the passion fruit peel, as a source of fiber and phenolic compounds in the diet of rats with TNBS-induced colitis and its influence on the inflammatory process. Wistar rats were fed a modified AIN-93 (50% of cellulose was replaced by passion fruit peel PFF) to evaluate prevention and treatment of colitis induced by TNBS. The damage to the mucosa was evaluated macroscopically and microscopically, as well as the expression of inflammatory markers. Evaluation of the microbiota and formation of SCFA in cecal contents were performed. The macroscopic appearance of the mucosa damage in the group PFF was higher than AIN in prevention trial. However, the microscopic evaluation in both trials showed no difference in mucosal damage amongst the groups. Treatment trial showed that PFF could promote a decrease in lipid peroxidation of the colon, decrease in enterobacteria and total aerobics counts, as well as increase in acetic and butyric acid in the stool. On the other hand, the prevention trial showed that the ingredient could exert modulation on lactobacilli and bifidobacteria. The inflammatory markers showed significant modulation, mainly IKK?, COX-2 and iNOS in animals fed with PFF diet. These results suggest that the passion fruit peel, Passiflora edulis, can modulate the microbiota, increase the production of SCFA, and modulate the expression of inflammatory markers observed in TNBS-induced colitis. Passion fruit peel could be used in the treatment of IBD as a source of fiber and polyphenols
Doutorado
Nutrição Experimental e de Alimentos
Doutora em Alimentos e Nutrição

Orientador: Luiz Claudio Di Stasi
Coorientador: Aline Witaicens
Banca: Jose Mauricio Sforcin
Banca: Carlos Augusto Real Martinez
Resumo: A Doença Inflamatória Intestinal (DII) é uma doença com etiologia desconhecida e sem terapêutica curativa disponível, englobando, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (RCU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados com remissão dos sintomas, cujo tratamento com os fármacos disponíveis apresentam sérios efeitos colaterais. Portanto, o desenvolvimento de novas estratégias de tratamento que combinem eficácia e segurança é uma importante meta na terapia da DII. A espécie Baccharis dracunculifolia DC (família Asteraceae) é uma planta medicinal brasileira usada popularmente contra úlceras, inflamação e problemas hepáticos e tem sido amplamente reconhecida como a principal fonte botânica da resina e dos constituintes químicos da própolis brasileira (própolis verde), a qual tem sido incorporada em alimentos e bebidas para a melhora da saúde. Estudos mostram que as inúmeras atividades biológicas da própolis verde decorrem exclusivamente dos constituintes presentes em Baccharis dracunculifolia, a qual possui várias atividades biológicas, especialmente agindo como imunomoduladora, anti-inflamatória e anti-inflamatória intestinal, sequestradora de radicais livres, antiúlcera e analgésica. A atividade anti-inflamatória intestinal está associada à presença de diferentes ácidos fenólicos presentes na espécie, tais como ácidos cafeico, p-cumárico, 3-prenil-p-cumárico (drupanina), 3,5-diprenil-p-cumárico (artepilina C), bacarina e metil-éster de aromadendrina. Estes compostos possuem íntima associação biossintética com os derivados cumarínicos também ativos na doença inflamatória intestinal, justamente por fazerem parte de sua rota biossintética. Com base nestas... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract:The Inflammatory Bowel Disease (IBD) is a disease with unknown etiology and no curative treatment available, encompassing essentially two distinct diseases: Crohn's disease (CD) and ulcerative colitis (UC), both characterized by chronic inflammation of the intestine, with periods of exacerbation followed by long intervals with symptom remission whose treatment with available drugs have serious side effects. Therefore, the development of new treatment strategies that combine effectiveness and safety is an important goal in the treatment of IBD. The species Baccharis dracunculifolia DC (Asteraceae) is a Brazilian medicinal plant popularly used against ulcers, inflammation and liver problems and has been widely recognized as the main botanical source of the resin and the chemical constituents of Brazilian propolis (green-propolis), which has been incorporated in foods and beverages to improve health. Studies show that the numerous biological activities of green propolis derived exclusively from the constituents present in Baccharis dracunculifolia, which has several biological activities, especially acting as immunomodulatory, anti-inflammatory and anti-inflammatory intestinal free radical scavenging, antiulcer and analgesic. The intestinal anti-inflammatory activity is associated with the presence of different phenolic acids in this specie, such as caffeic acid, p-coumaric acid, 3-prenyl-p-coumaric (drupanina), 3,5-diprenyl-p-coumaric acid (C artepilina ) bacarina and methyl ester aromadendrin. These compounds have a close association with the biosynthetic coumarin derivatives also active in inflammatory bowel disease, just by being part of their biosynthetic pathway. Based on this information, the aim of this study was to identify potential pharmacological targets of anti-inflammatory action of the extract... (Complete abstract click electronic access below)
Mestre

La pathogénèse de la plupart des maladies neurodégénératives incluant les maladies transmissibles comme les encéphalopathies à prion, les maladies génétiques de type maladie de Huntington et les maladies sporadiques comme les maladies d’Alzheimer et de Parkinson est directement liée à la formation d’agrégats protéiques fibrillaires. Pendant de nombreuses années, le concept de dissémination et d’infectivité de ces agrégats a été réservé aux maladies à prion. Cependant, de récents résultats montrent que ces protéines amyloidiques extracellulaires (β-amyloïde) comme intracellulaires (α-synucléine, tau, huntingtin) sont capables de bouger (et possiblement de se répliquer) d’une zone à l’autre du cerveau à la façon des prions (Brundin et al., 2010; Jucker and Walker, 2011; Aguzzi and Rajendran, 2009). Récemment une nouveau lien a été établie entre prions et différentes protéinopathies à agrégats. Il a été suggéré que le prion cellulaire, PrPC, dont la forme pathologique (PrPSc) est responsable des maladies à prion, pourrait servir de médiateur dans la toxicité de la protéine β-amyloïde impliquée dans la maladie d’Alzheimer comme dans d’autres conformations-β, indépendamment de la propagation des prions infectieux (revue de Biasini et al., 2012). Malgré une intense recherche sur les maladies neurodégénératives à prion ou non, de nombreuses questions restent ouvertes à la fois au niveau du mécanisme de dissémination des agrégats protéiques que du mécanisme de toxicité. Dans la première partie de ma thèse, j’ai contribué à étudier le rôle de cellules dendritiques (DCs) dans la dissémination de l’infection à prion aux neurones. J’ai démontré que le transfert de PrPSc des cellules dendritiques infectées par un homogénat de cerveau infecté par du prion vers les neurones était dû à contact direct entre ces cellules et a pour résultat la transmission de l’infectivité aux neurones en co-culture. Ces résultats confirment le possible rôle des cellules dendritiques dans la propagation du prion de la périphérie vers le système nerveux central. J’ai aussi trouvé un potentiel mécanisme de transfert de PrPSc des cellules dendritiques aux neurones via des nanotubes (TNTs) et exclu l’implication de la sécrétion de PrPSc dans notre système. Dans la seconde partie de ma thèse, j’ai étudié les mécanismes de dissémination et de toxicité des agrégats protéiques huntingtin et le possible rôle de PrPC dans ces évènements. J’ai démontré que les agrégats Htt sont transférés entre les lignées de cellules neuronales et les neurones primaires et qu’un contact direct cellule à cellule est requis. De même, j’ai montré l’implication des TNTs dans ce transfert et l’agrégation des Htt sauvages endogènes dans les neurones primaires, probablement en suivant le transfert des agrégats Htt. La dernière partie de mes résultats montre que PrPC est impliqué dans la propagation de la toxicité induite par les Htt mutants dans des neurones primaires en culture
The pathogenesis of most neurodegenerative diseases, including transmissible diseases like prion encephalopathies, inherited disorders like Huntington’s disease, and sporadic diseases like Alzheimer’s and Parkinson’s diseases, appear to be directly linked to the formation of fibrillar protein aggregates. For many years, the concept of aggregate spreading and infectivity has been confined to prion diseases. However, recent evidence indicate that both extracellular (e.g. amyloid-β) and intracellular (α- synuclein, tau, huntingtin) amyloidogenic protein are able to move (and possibly replicate) within the brains of affected individuals, thereby contributing to the spread of pathology in a prion-like manner (Brundin et al., 2010; Jucker and Walker, 2011; Aguzzi and Rajendran, 2009). Recently another intriguing connection has been made between prions and other aggregation proteinopathies, as it was suggested that the cellular prion protein, PrPC, whose pathological counterpart is responsible for prion diseases, possibly mediates the toxicity of Aβ, the pathogenic protein in Alzheimer’s disease, and of other β- conformers independently of the propagation of infectious prions (reviewed in Biasini et al., 2012). However, despite the intense research, many questions in prion and non-prion neurodegenerative diseases are still open regarding both the mechanism of protein aggregate spreading and the mechanism of toxicity. In the first part of my thesis, I contributed to investigate the role of DCs (dendritic cells) in the spreading of prion infection to neuronal cells. I demonstrated that the transfer of PrPSc from DCs (loaded with prion infected brain homogenate) to primary neurons was triggered by direct cell–cell contact and resulted in transmission of infectivity to the co-cultured neurons. These data confirm the possible role of DCs in prion spreading from the periphery to the nervous system. I also provided a plausible transfer mechanism of PrPSc through tunneling nanotubes (TNTs) shown to connect DCs to primary neurons and excluded the involvement of PrPSc secretion in our system. In the second part of my thesis, I investigated the mechanisms of the spreading and toxicity of Htt aggregates and the possible role of PrPC in these events. I demonstrated that Htt aggregates transfer between neuronal cells and primary neurons and that cell-cell contact is required. I also showed the involvement of TNTs in the transfer and reported the aggregation of endogenous wild-type Htt in primary neurons, possibly following the transfer of Htt aggregates. Finally, the last part of my results provides evidences that PrPC is involved in the spreading of the toxicity mediated by mutant Htt in primary neuronal cultures

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Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Compounds derived from fungi has been the subject of many studies in order to broaden the knowledge of their bioactive potential. Polysaccharides from Caripia montagnei have been described to possess anti-inflammatory and antioxidant properties. In this study, glucans extracted from Caripia montagnei mushroom were chemically characterized and their effects evaluated at different doses and intervals of treatment. It was also described their action on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and its action on cells of the human colon carcinoma (HT-29). Compounds extracted of C. montagnei contain high level of carbohydrates (96%), low content of phenolic compounds (1.5%) and low contamination with proteins (2.5%). The (FT-IR) and (NMR) analysis showed that polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed a reduction of colonic lesions in all groups treated with the glucans of Caripia montagnei (GCM). GCM significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that such glucans acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01), nitric oxide (p < 0.001), and myeloperoxidase (p < 0.001). These results were confirmed microscopically by the reduction of cellular infiltration. The increase of catalase activity suggest a protective effect of GCM on colonic tissue, confirming their anti-inflammatory potential. GCM displayed cytostatic activity against HT-29 cells, causing accumulation of cells in G1 phase, blocking the cycle cell progression. Those glucans also showed ability to modulate the adhesion of HT-29 cells to Matrigel? and reduced the oxidative stress. The antiproliferative activity against HT-29 cells displayed by GCM (p <0.001) can be attributed to its cytostatic activity and induction of apoptosis by GCM
Compostos derivados de fungos tem sido alvo de muitos estudos a fim de desenvolver o conhecimento acerca de seu potencial bioativo. Polissacar?deos de Caripia montagnei j? foram descritos por possu?rem propriedades anti-inflamat?ria e antioxidante. Neste estudo, os polissacar?deos extra?dos do fungo Caripia montagnei foram caracterizados quimicamente e seus efeitos sobre as les?es intestinais foram avaliados em diferentes intervalos de tratamento no modelo de colite induzida por ?cido 2,4,6 - trinitrobenzenossulf?nico (TNBS), verificou-se ainda sua a??o sobre c?lulas do carcinoma de c?lon humano, HT-29. Na an?lise realizada no extrato obtido de C. montagnei foi verificado que este ? formado principalmente, por carboidratos (96%) apresentando um baixo teor de compostos fen?licos (1,5%) e baixa contamina??o prot?ica (2,5%). As an?lises por espectroscopia de infra vermelho (FT-IR) e resson?ncia magn?tica nuclear (RMN) mostraram que os polissacar?deos desta esp?cie de fungo s?o α e β -glucanas. O dano col?nico foi avaliado por an?lises macrosc?picas, histol?gicas, bioqu?micas e imunol?gicas. Os resultados mostraram a redu??o das les?es no c?lon em todos os grupos tratados com as glucanas (GCM). GCM reduziram significativamente os n?veis de IL-6 (50 e 75 mg/Kg, p < 0,05), uma importante citocina inflamat?ria. As an?lises bioqu?micas mostraram que essas glucanas atuaram na redu??o dos n?veis de fosfatase alcalina (75 mg/Kg, p < 0,01), ?xido n?trico (p < 0,001) e mieloperoxidase (p < 0,001). Estes resultados foram confirmados pela redu??o da infiltra??o celular observado microscopicamente. O aumento da atividade da catalase, sugere um efeito protetor de GCM no tecido do c?lon, o que confirma o seu potencial anti-inflamat?rio. GCM mostraram atividade citost?tica sobre as c?lulas HT-29, causando ac?mulo de c?lulas na fase G1 e impedindo, assim, a progress?o do ciclo celular. As glucanas deste estudo tamb?m mostraram habilidade em modular a ades?o de c?lulas HT-29 ao Matrigel? e reduzir o estresse oxidativo nessas c?lulas. A atividade antiproliferativa contra c?lulas HT-29 exibida por GCM pode ser atribu?da ? sua a??o citost?tica ou indu??o da apoptose por essas glucanas

Orientadores: Alba Regina Monteiro Souza Brito, Anderson Luiz Ferreira
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A retocolite Ulcerativa Inespecífica e a Doença de Chron são as principais doenças inflamatórias intestinais. Apesar dos crescentes esforços, não se sabe ainda suas causas. Os tratamentos ainda não são eficazes, as drogas atuais são eficazes na indução da remissão mas não determinam sua cura. Os efeitos colaterais são severos, o que acarreta em baixa adesão ao tratamento. Os produtos naturais tem sido fonte de compostos usados por todo o mundo em diferentes áreas da medicina e ciência. O tratamento oral com geléia real na dose de 100 mg/Kg mostrou-se capaz de aumentar os níveis de grupamentos sulfídrica (GSH) e também a atividade da enzima glutationa peroxidase (GSH-Px) em camundongos com colite induzida por TNBS. A expressão de COX-2 e NF-kB também foram diminuídos, tais resultados demonstram efeitos antioxidantes e antiinflamatórios da geléia real nesta dose neste modelo de colite experimental. O Tratamento intrarretal com a proteína MRJP3 (50 ?g/animal) foi capaz de diminuir os níveis de IL-1? no cólon dos camundongos Balb/c submetidos a colite induzida por DSS. Uma vez que os níveis de IL-6 e IL-10 não foram alterados pelo tratamento intrarretal com MRJP3 50 ?g/animal, podemos afirmar que a proteína não atua pela via da IL-10. Estes efeitos antioxidantes e anti-inflamatórios observados durante o desenvolvimento da colite induzida por TNBS e por DSS em camundongos, podem ser de significativa importância pois abrem portas e encorajam novas pesquisas com a geléia real e sua respectiva proteína MRJP3, motivando novos estudos acerca de outos agentes antioxidantes e outros mediadores anti-inflamatórios envolvidos nestes modelos de colite experimental
Abstract: Ulcerative Colitis and Chron's Disease are the two major forms of IBD. Despite all efforts, these complications of the GTI are still lacking an effective therapy for their cure. Side effects, high cost and low adhesion to treatment are among the negative aspects. Natural products have been a source of widely used compounds in distinct areas of medicine and research. Royal Jelly (RJ) 100 mg/Kg was capable of augmenting the levels of glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px) in mice undergoing TNBS-induced colitis. Furthermore, COX-2 and NF-kB had their expression decreased by the oral administration of RJ 100 mg/Kg. Intra-rectal MRJP3 treatment (50 ?g/animal) was capable of decreasing the levels of IL-1? in mice undergoing DSS-induced colitis, whereas the levels of IL-10 and IL-6 were not altered by MRJP3 50 ?g instillation, what indicates that this decrease is not IL-10-induced. The antioxidant and anti-inflammatory effects observed during the development of DSS and TNBS-induced colitis in mice, may be of crucial importance, since they open and encourage new studies focused on this nourishing substance, especially in experimental models of colitis
Mestrado
Farmacologia
Mestre em Farmacologia

FundaÃÃo de Amparo à Pesquisa do Estado do CearÃ
A etiopatogenia das doenÃas inflamatÃrias intestinais idiopÃticas (DII) envolve fatores genÃticos, ambientais e imunolÃgicos. Hà relatos do uso da acupuntura no tratamento da DII, porÃm seus mecanismos ainda sÃo incertos. A proposta deste trabalho à estudar a aÃÃo antiinflamatÃria e analgÃsica da eletroacupuntura em modelo de colite experimental. Utilizaram-se camundongos machos Swiss, distribuÃdos em seis grupos (n=6-9), submetidos a induÃÃo de colite por TNBS em etanol a 50%. Os controles do modelo foram salina (SAL) e etanol (ETNL). Os animais com colite foram tratados com eletroacupuntura (EAC) no acuponto ST-36, 100Hz, falsa-eletroacupuntura (FEAC) 100Hz e dexametasona (DEXA) 1mg/Kg/dia. A hiperalgesia visceral foi avaliada pelo teste de Von Frey. ApÃs trÃs dias, foi coletado segmento de cÃlon para anÃlises macroscÃpicas, histopatolÃgicas (H-E), dosagem da atividade de mieloperoxidase, imunoistoquÃmicas para iNOS e dosagem de malonaldeÃdo, e citocinas (TNF-α, IL-1β, IL-10). Os dados paramÃtricos foram analisados por ANOVA/teste de Tukey ou teste T e os dados nÃo paramÃtricos por Kruskal-Wallis/teste de Dunn. Houve aumento do peso Ãmido dos cÃlons no grupo TNBS e prevenÃÃo desse evento no grupo EAC. Os grupos TNBS e EAC apresentaram aumento na infiltraÃÃo de neutrÃfilos no cÃlon em relaÃÃo aos demais grupos. O grupo TNBS apresentou aumento na pontuaÃÃo dos escores microscÃpicos em relaÃÃo aos grupos tratados. Os grupos TNBS e EAC apresentaram aumento na concentraÃÃo de IL-1β no cÃlon. O grupo TNBS apresentou supressÃo na concentraÃÃo de IL-10 no cÃlon, prevenido pelo tratamento com EAC. O grupo EAC apresentou diminuiÃÃo na concentraÃÃo de MDA no cÃlon em relaÃÃo ao grupo TNBS. O grupo EAC apresentou diminuiÃÃo na expressÃo de iNOS no conjuntivo em relaÃÃo ao grupo TNBS. O grupo TNBS nÃo apresentou alteraÃÃo da hipernocicepÃÃo, avaliada pelo Von Frey, nos tempos 24 e 72 horas. Conclui-se que eletroacupuntura, a 100Hz no acuponto ST-36, apresentou aÃÃo antiinflamatÃria na colite por TNBS em etanol a 50% atravÃs do aumento na concentraÃÃo de IL-10 e reduÃÃo na expressÃo de iNOS.
The etiology of inflammatory bowel disease (IBD) involves genetic, environmental and immunological factors. There are clinical reports of the use of acupuncture on IBD, however its therapeutic mechanisms are still uncertain. The purpose of this work is to study the anti-inflammatory and analgesic actions of electroacupuncture on a experimental colitis model. Male Swiss rats, divided in six groups (n=6-9), were subjected to induction of colitis by TNBS in 50% ethanol. The controls were saline (SAL) and ethanol (ETNL). The animals with colitis were treated with electroacupuncture (EAC) at the ST-36 acupoint, 100Hz, false electroacupuncture (FEAC), 100Hz, and dexamethasone (DEXA), 1 mg/Kg/day. Visceral hyperalgesia was evaluated by means of the Von Frey test. After three days, a colon segment was obtained for macroscopic and histopathological analysis, quantification of the activity of myeloperoxidase, Immunohistochemistry for iNOS, and quantification of malondialdehyde and cytokines (TNF-α, IL-1β, IL-10). The parametric data were analyzed with ANOVA/Tukey test or test T, and the non-parametric data with Kruskal-Wallis/Dunn test. There was an increase on the wet weight of the colons on group TNBS, and prevention of this event on group EAC. The groups TNBS and EAC showed an increase on neutrophil infiltration, as compared to the other groups. The group TNBS showed increased values for the microscopic scores, as compared to the treated groups. The groups TNBS and EAC showed an increase on the concentration of IL-1β in the colon. The group TNBS showed suppression of the concentration of IL-10 in the colon, prevented by treatment with EAC. The group EAC showed decrease on the concentration of MDA in the colon, as compared to the other groups. The group EAC showed decrease on the expression of iNOS in the connective, as compared to the treated groups. The group TNBS did not show any alterations of hypernociception, as evaluated with Von Frey, at 24 and 72 hours. It can be therefore concluded that electroacupuncture, at the acupoint ST-36, 100Hz, showed anti-inflammatory action on the colitis induced by TNBS in 50% ethanol, by means of increase of IL-10 concentration and decrease on the expression of iNOS.

Neste trabalho foi estudado o potencial imunorregulador da crotoxina (CTX) obtida do veneno de C. d. terrificus, em modelo experimental de colite induzida pelo TNBS em camundongos. A CTX foi capaz de diminuir a perda de peso, o score clínico e histológico, síntese de MPO e citocinas pró-inflamatórias. Menor número de neutrófilos e macrófagos com fenótipos M1 e M2 na lâmina própria foi observado nos grupos TNBS/CTX em relação ao TNBS. A CTX induziu TGF-b e IL-10, PGE2 e LXA4. A neutralização in vivo dessas citocinas ou o bloqueio da síntese desses eicosanoides indica que estas moléculas exercem papel relevante na ação moduladora da CTX no quadro inflamatório. As análises das diferentes populações celulares da lâmina própria, linfonodos e Placas de Peyer mostraram que não houve diferença nos linfócitos CD4+Tbet+ entre os grupos TNBS e TNBS/CTX. No entanto, a CTX promoveu aumento de CD4+FoxP3+ e diminuição de CD4+RORg+. Estes resultados indicam que a CTX é capaz de modular a resposta inflamatória aguda intestinal melhorando o quadro clinico observado nos animais.
In this work it was analyzed the immunomodulatory effect of crotoxin (CTX) isolated from C.d. terrificus snake venom, on the experimental model of colitis induced by TNBS in mice. The CTX was able to inhibit the weight loss, clinical and histological score, MPO synthesis and pro-inflammatory cytokines. Lower number of neutrophils and macrophage (M1 and M2) in lamina propria was observed in TNBS/CTX mice compared with the TNBS group. In contrast, the CTX induced increased TGF-b, IL-10, PGE2 and LXA4. The in vivo neutralization of these cytokines or eicosanoids synthesis indicates that these molecules exert significant role in the modulatory effect of CTX. The analyzes of distinct cell populations from lamina propria, lymph nodes and Peyers pathes showed no difference in CD4+Tbet+ between TNBS or TNBS/CTX mice. However, CTX induced an increase of CD4+FoxP3+ and decreased CD4+RORgt+. Together, these results indicate that CTX is able to modulate intestinal acute inflammatory response induced by TNBS improving the clinical status of the mice.

O perfil metabólico é usado na clínica médica com a finalidade de ajudar o diagnóstico e permite o diagnóstico precoce de alterações metabólicas e também a funcionalidade dos principais órgãos. A transferência nuclear de células somáticas (TNCS - clonagem), apesar de apresentar resultados positivos, ainda possui baixa eficiência, com alta mortalidade embrionária, fetal e pós-natal. Observa-se na primeira semana de vida principalmente nas primeiras 24-48 horas um grande número de bezerros que morrem, devido a distúrbios de adaptação neonatal. Essas alterações placentárias e más formações determinam alterações bioquímicas que são as causas de muitos óbitos verificados nos clones. Este trabalho teve como objetivo estudar o perfil bioquímico de bezerros Nelore clonados durante os 30 primeiros dias de vida, procurando verificar as possíveis modificações no metabolismo de animais obtidos por transferência nuclear de células somáticas (TNCS - clonagem). Foram utilizados 20 bezerros Nelores e realizou-se de cada animal 13 coletas de sangue nos seguintes momentos: ao nascimento, 6, 12, 24, 48, 72, 96, 120, 168, 240, 360, 480 e 720 horas de vida. Determinou-se de cada amostra os valores séricos para função renal, função hepática, proteinograma, lipidograma e minerais. As amostras foram analisadas em analisador bioquímico automático, da marca Randox, modelo RX Daytona. Observou-se, ureia 22,78 ± 0,84 mg/dL e 29,03 ± 0,92 mg/dL, creatinina 1,61 ± 0,05 mg/dL e 1,39 ± 0,03 mg/dL, relação ureia/creatinina 16,07 ± 0,76 e 21,16 ± 0,75 mg/dL; aspartato alanina quinase (AST), 57,84 ± 3,06 U/L e 22,91 ± 0,99 U/L; gama-glutamil transferase (GGT) 1294,05 ± 152,37 U/L e 287,26 ± 28,05 U/L; fosfatase alcalina (FA) 2311,63 ± 146,22 e 836,05 ± 41,07 U/L e creatina quinase (CK) 223,47 ± 30,73 mg/dL e 64,82 ± 9,18 mg/dL; proteína total 6,43 ± 0,09 g/dL e 5,68 ± 0,05 g/dL; albumina 2,82 ± 0,02 g/dL e 2,63 ± 0,01 g/dL; globulina 3,61 ± 0,09 g/dL e 3,06 ± 0,05 g/dL e relação albumina/globulina 0,90 ± 0,04 e 0,90 ± 0,02; colesterol 74,00 ± 3,63 mg/dL e 56,31 ± 2,84 mg/dL; triglicérides 35,18 ± 1,98 mg/dL e 38,71 ± 2,79 mg/dL; glicose 126,72 ± 3,30 mg/dL e 106,70 ± 2,88 mg/dL e lactato 26,27 ± 0,98 mg/dL e 30,71 ± 1,61 mg/dL ; cálcio 10,74 ± 0,07 mg/dL e 10,63 ± 0,08 mg/dL; fósforo 8,96 ± 0,13 mg/dL e 9,87 ± 0,20 mg/dL, para o grupo de bezerros de parto normal e bezerros clonados, respectivamente. Apesar de bezerros clonados da raça Nelore apresentaram perfil bioquímico dentro dos valores fisiológicos descritos na literatura observou-se importantes e significativas diferenças no seu metabolismo, principalmente, na primeira semana de vida.
The metabolic profile is used in clinical medicine with the purpose of assisting in the study of metabolic diseases origin, allowing early diagnosis of metabolic abnormalities and also aids the evaluation of major organs functionality. The somatic cell nuclear transfer (SCNT - cloning), despite showing positive results, still has low efficiency and it is associated with high embryonic, fetal and postnatal mortality. It has been observed in the first week of life, especially in the first 24-48 hours, that a large number of calves die due to neonatal adaptation disorders. Among these, placental disorders and malformations have been related to biochemical changes, possibly being the major cause of deaths in clones. This study aimed to evaluate the influence of age on the concentrations of serum biochemical parameters of Nellore calves born through normal delivery, compared with cloned ones, from birth to 30 days of life. Twenty Nellore calves were used in this study and 13 blood samples of each animal were collected at the following periods: at birth, 6, 12, 24, 48, 72, 96, 120, 168, 240, 360, 480 and 720 hours of life. Serum values for kidney and liver function, proteins, lipid and minerals were determined. The samples were analyzed with a biochemical automatic analyzer, Randox brand, model RX Daytona. It was observed: urea 22.78 ± 0.84 mg/dL and 29.03 ± 0.92 mg/dL, creatinine 1.61 ± 0.05 mg/dL and 1.39 ± 0.03 mg/dL urea / creatinine 16.07 ± 0.76 and 21.16 ± 0.75 mg/dL; alanine aspartate kinase (AST) 57.84 ± 3.06 U/L and 22.91 ± 0.99 U/L; gamma-glutamyl transferase (GGT) 1294.05 ± 152.37 U/L and 287.26 ± 28.05 U/L; alkaline phosphatase (ALP) 2311.63 ± 146.22 and 836.05 ± 41.07 U/L and creatine kinase (CK) 223.47 ± 30.73 mg/dL and 64.82 ± 9.18 mg/dL ; total protein 6.43 ± 0.09 g/dL and 5.68 ± 0.05 g/dL; albumin 2.82 ± 0.02 g/dL and 2.63 ± 0.01 g/dL; globulin 3.61 ± 0.09 g/dL and 3.06 ± 0.05 g/dL and the albumin/globulin 0.90 ± 0.04 and 0.90 ± 0.02; cholesterol 74.00 ± 3.63 mg/dL and 56.31 ± 2.84 mg/dL; triglycerides 35.18 ± 1.98 mg/dL and 38.71 ± 2.79 mg/dL; glucose 126.72 ± 3.30 mg/dL and 106.70 ± 2.88 mg/dL; lactate 26.27 ± 0.98 mg/dL and 30.71 ± 1.61 mg/dL; Calcium 10.74 ± 0.07 mg/dL and 10.63 ± 0.08 mg/dL; phosphorus 8.96 ± 0.13 mg/dL and 9.87 ± 0.20 mg/dL for the group of normal delivery and cloned calves, respectively. Although cloned calves Nellore showed biochemical profile within the physiological range described in the literature and observed important differences in their metabolism, especially in the first week of life.

Orientador: Luiz Claudio Di Stasi
Resumo: A Doença Inflamatória Intestinal (DII) inclui duas principais doenças: a Doença de Crohn e a Retocolite Ulcerativa, ambas caracterizadas por períodos de exacerbação dos sintomas acompanhados por intervalos prolongados de remissão. Apesar da etiologia ser pouco elucidada, sabe-se da influência de fatores genéticos, imunológicos e ambientais. A terapia farmacológica atual não é eficaz para todos os pacientes, apresenta alto custo e desencadeia diversos efeitos colaterais, portanto é necessário o desenvolvimento de novas terapias sendo que as plantas medicinais e componentes presentes na dieta, devido as suas propriedades antioxidantes e/ou imunomoduladora, apresentam uma opção atrativa como terapia complementar. A espécie Cnidoscolus aconitifolius (Mill.) I.M. Johnst, popularmente conhecida como chaya, foi selecionada dada sua composição química, rica em fibra e compostos antioxidantes e suas atividades antioxidante e anti-inflamatória testadas em outras afecções. O objetivo deste trabalho foi avaliar a atividade anti-inflamatória intestinal das folhas escaldadas e desidratadas de chaya em duas formas: como extrato metanólico 70% (100, 200 e 300 mg/kg, via oral por gavage) e como farinha incorporada na dieta nas concentrações 5, 10 e 20%, no modelo de indução de inflamação intestinal pelo ácido trinitrobenzenosulfonico (TNBS) em ratos. Para tanto, foram avaliados os parâmetros clínicos gerais (ingestão diária de alimentos, peso corporal, diarréia), parâmetros macroscópicos da l... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Inflammatory Bowel Disease (IBD) comprise two major diseases, Crohn's disease and Ulcerative Colitis, both characterized by periods of exacerbation of symptoms accompanied by prolonged remission intervals. Although the etiology is not certain elucidated, the influence of genetic, immunological and environmental factors is well known. The current pharmacological therapy is not effective for all patients, due to a high cost and triggers several side effects. Therefore, it is necessary to develop new therapies and medicinal plants with their antioxidant and/or immunomodulatory properties are an attractive option as complementary therapy. Cnidoscolus aconitifolius (Mill.) I.M. Johnst, popularly known as chaya, was selected because of its chemical composition, rich in fiber and antioxidant compounds and its antioxidant and anti-inflammatory activity tested in other diseases. The aim of this study was to evaluate the intestinal anti-inflammatory activity of the blanched and dehydrated Chaya leaves in two preparations: as a 70% methanol extract (100, 200 and 300 mg/kg, oral route by gavage) and as flour incorporated in the diet at 5%, 10% and 20% concentrations in the experimental model of intestinal inflammation induced by trinitrobenzenesulfonic acid (TNBS) in rats. For that, clinical parameters (daily food intake, body weight, diarrhea), macroscopic damage (score, lesion extension, weight/length ratio and adherence), biochemical parameters (quantification of total glutathione con... (Complete abstract click electronic access below)
Doutor

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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil
A leishmaniose tegumentar (LT) é um problema de saúde pública, não somente por sua alta incidência e ampla distribuição geográfica, mas também, pela possibilidade de produzir lesões destrutivas. São considerados grupos de alto risco para aquisição da doença: agricultores, obreiros de fazendas, madeireiro, caçadores, excursionistas e naturalistas. Para definir estratégias e ações de controle e prevenção para LT, devemos considerar tanto os aspectos epidemiológicos quanto aspectos genéticos. Desta forma este trabalho teve como objetivo estabelecer o perfil epidemiológico da área de estudo, correlacionando os fatores de risco já bem estabelecidos na literatura com os diferentes grupos de indivíduos infectados e não infectados a partir de inquérito epidemiológico na população e caracterizar marcadores moleculares (SNP-Single Nucleotide Polymorphism) da região promotora do TNF-α, que poderão estar envolvidos na susceptibilidade ou resistência da doença LT na comunidade de Florestal-BA.Das 129 famílias que participaram do inquérito, 80,6% dos chefes de famílias pertence ao sexo masculino e possui como atividade principal o trabalho no campo, 69,8% recebe menos que um salário mínimo por mês. A análise das variáveis que se refere às condições de moradia mostra que 66,7% das residências eram construídas de alvenaria, quase todas as casas eram cobertas por telhas, com piso de cimento ou cerâmica Pouco mais que a metade das moradias tinha como fonte de água a rede pública. A maioria das casas 81,4%, possuía energia elétrica, um alto percentual 36,4% lançam lixo no terreno próximo a sua casa. 70,5% das famílias, cria em sua residência algum tipo de animal doméstico, a maior parte dos indivíduos não usam proteção individual contra mosquitos, 70,5% dos domicílios se situavam próximo às matas, rios, e criação de galinha, 77,5% domicílios, havia descrição de diversos tipos de animais nos seus arredores. A prevalência na comunidade de Florestal foi dada com a utilização do teste de Montenegro (IDRM), e do exame sorológico ELISA, sendo que os valores dessa prevalência foram praticamente similares para ambos os testes. A IDRM acusou uma prevalência de 28,9%, enquanto que, o ELISA identificou uma prevalência de 27,4%. Apesar de alguns dados não terem sido estatisticamente significativo, alguns fatores de risco analisados demonstraram maiores prevalências a infecção (IDRM+), dentre eles estão: Indivíduos do sexo masculino, adultos, trabalhadores rurais, presença de mais que uma espécie de animal na residência ou próximo a ela, residência próxima a matas e rios, construções domiciliar mais aberta, lixo no terreno, ausência de água encanada. Assim os fatores responsáveis pelo aumento de casos da doença na área, foram falta de saneamento básico, situação econômica precária, construções inadequadas, convívio com animais silvestres ou mesmo domesticados. Com relação ao estudo dos marcadores genéticos da região promotora do TNF, O loco TNF-308 mostrou estar em equilíbrio de Hardy- Weinberg, p-valor 0,464 ao contrário do loco TNF-238, que demonstrou uma deficiência na freqüência de heterozigotos para esta região. Não foi encontrada associação dos polimorfismos da região promotora do TNF com a susceptibilidade ou resistência à infecção ou com o desenvolvimento da doença LT, vale ressaltar que o alelo*A mesmo não mostrando resultado estatisticamente significativo mostrou ser um fator de risco para o desenvolvimento da doença, OR= 8,77 e 1,14 para o TNF – 238 e -308 respectivamente, sugerindo a realização de novos estudos com amostragem ampliada para esclarecimento desta questão.
The cutaneous leishmaniasis (CL) is a public health problem, not only for its high incidence and wide distribution, but also by the possibility of producing destructive lesions. Groups are considered at high risk for acquiring the disease: farmers, farm workers, loggers, hunters, hikers and naturalists. To define strategies and actions to control and prevention for LT, we must consider both the epidemiological aspects regarding genetic aspects. Thus this study aimed to establish the epidemiological profile of the study area by correlating the risk factors already well established in the literature with different groups of infected and uninfected individuals from an epidemiological survey in the population and characterize molecular markers (SNP- Single Nucleotide Polymorphism) in the promoter region of TNF-á, may be involved in susceptibility or resistance of disease in the community of Forest LT-BA. Das 129 families who participated in the survey, 80.6% of heads of households are male and has as main activity work in the field, 69.8% earn less than minimum wage per month. Analysis of variables with regard to housing conditions shows that 66.7% of the homes were built of masonry, almost all the houses were covered with tiles, with cement floors or ceramic Slightly more than half of households had a source of water to the public. Most houses 81.4% owned electric power, a high percentage 36.4% throw trash on the ground near his home. 70.5% of families, establishing his residence in some kind of domestic animal, the largest share of respondents did not use personal protection against mosquitoes, 70.5% of households were located near the forests, rivers, and creation of chicken, 77, 5% of households, there were descriptions of various types of animals in their surroundings. The prevalence in the community of Forest was given using the Montenegro skin test (IDRM), and ELISA serology, and the values of prevalence were almost similar for both tests. The MST has accused a prevalence of 28.9%, whereas the ELISA identified a prevalence of 27.4%. Although some data were not statistically significant, some risk factors analyzed showed higher prevalence infection (IDRM+), among them are: Males, adults, rural workers, the presence of more than one species of animal in the residence or nearby to her residence near forests and rivers, home building more open, trash on the ground, no running water. Thus factors responsible for increasing cases of the disease in the area were poor sanitation, poor economic status, inadequate buildings, living with wild animals or domesticated. Regarding the study of genetic markers in the promoter region of TNF, the TNF-308 locus was shown to be in Hardy-Weinberg p-value 0.464 in contrast to TNF-238 locus, which showed a deficit in heterozygote frequency for this region . There was no association of polymorphisms in the promoter region of TNF with the susceptibility or resistance to infection or disease development with LT, but it is noteworthy that the allele *A The same is not showing a statistically significant result was found to be a risk factor for the development of disease, OR = 2.00 and 1.13 respectively, suggesting the new studies with larger samples to clarify this issue.

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior
A etiopatogenia das doenÃas inflamatÃrias intestinais idiopÃticas (DII) envolve fatores genÃticos, ambientais e imunolÃgicos. Hà relatos do uso da acupuntura no tratamento da DII, porÃm seus mecanismos ainda sÃo incertos. A proposta deste trabalho à estudar a aÃÃo antiinflamatÃria e analgÃsica da eletroacupuntura em modelo de colite experimental. Utilizaram-se camundongos machos Swiss, distribuÃdos em seis grupos (n=6-9), submetidos a induÃÃo de colite por TNBS em etanol a 50%. Os controles do modelo foram salina (SAL) e etanol (ETNL). Os animais com colite foram tratados com eletroacupuntura (EAC) no acuponto ST-36, 100Hz, falsa-eletroacupuntura (FEAC) 100Hz e dexametasona (DEXA) 1mg/Kg/dia. A hiperalgesia visceral foi avaliada pelo teste de Von Frey. ApÃs trÃs dias, foi coletado segmento de cÃlon para anÃlises macroscÃpicas, histopatolÃgicas (H-E), dosagem da atividade de mieloperoxidase, imunoistoquÃmicas para iNOS e dosagem de malonaldeÃdo, e citocinas (TNF-α, IL-1β, IL-10). Os dados paramÃtricos foram analisados por ANOVA/teste de Tukey ou teste T e os dados nÃo paramÃtricos por Kruskal-Wallis/teste de Dunn. Houve aumento do peso Ãmido dos cÃlons no grupo TNBS e prevenÃÃo desse evento no grupo EAC. Os grupos TNBS e EAC apresentaram aumento na infiltraÃÃo de neutrÃfilos no cÃlon em relaÃÃo aos demais grupos. O grupo TNBS apresentou aumento na pontuaÃÃo dos escores microscÃpicos em relaÃÃo aos grupos tratados. Os grupos TNBS e EAC apresentaram aumento na concentraÃÃo de IL-1β no cÃlon. O grupo TNBS apresentou supressÃo na concentraÃÃo de IL-10 no cÃlon, prevenido pelo tratamento com EAC. O grupo EAC apresentou diminuiÃÃo na concentraÃÃo de MDA no cÃlon em relaÃÃo ao grupo TNBS. O grupo EAC apresentou diminuiÃÃo na expressÃo de iNOS no conjuntivo em relaÃÃo ao grupo TNBS. O grupo TNBS nÃo apresentou alteraÃÃo da hipernocicepÃÃo, avaliada pelo Von Frey, nos tempos 24 e 72 horas. Conclui-se que eletroacupuntura, a 100Hz no acuponto ST-36, apresentou aÃÃo antiinflamatÃria na colite por TNBS em etanol a 50% atravÃs do aumento na concentraÃÃo de IL-10 e reduÃÃo na expressÃo de iNOS
The etiology of inflammatory bowel disease (IBD) involves genetic, environmental and immunological factors. There are clinical reports of the use of acupuncture on IBD, however its therapeutic mechanisms are still uncertain. The purpose of this work is to study the anti-inflammatory and analgesic actions of electroacupuncture on a experimental colitis model. Male Swiss rats, divided in six groups (n=6-9), were subjected to induction of colitis by TNBS in 50% ethanol. The controls were saline (SAL) and ethanol (ETNL). The animals with colitis were treated with electroacupuncture (EAC) at the ST-36 acupoint, 100Hz, false electroacupuncture (FEAC), 100Hz, and dexamethasone (DEXA), 1 mg/Kg/day. Visceral hyperalgesia was evaluated by means of the Von Frey test. After three days, a colon segment was obtained for macroscopic and histopathological analysis, quantification of the activity of myeloperoxidase, Immunohistochemistry for iNOS, and quantification of malondialdehyde and cytokines (TNF-α, IL-1β, IL-10). The parametric data were analyzed with ANOVA/Tukey test or test T, and the non-parametric data with Kruskal-Wallis/Dunn test. There was an increase on the wet weight of the colons on group TNBS, and prevention of this event on group EAC. The groups TNBS and EAC showed an increase on neutrophil infiltration, as compared to the other groups. The group TNBS showed increased values for the microscopic scores, as compared to the treated groups. The groups TNBS and EAC showed an increase on the concentration of IL-1β in the colon. The group TNBS showed suppression of the concentration of IL-10 in the colon, prevented by treatment with EAC. The group EAC showed decrease on the concentration of MDA in the colon, as compared to the other groups. The group EAC showed decrease on the expression of iNOS in the connective, as compared to the treated groups. The group TNBS did not show any alterations of hypernociception, as evaluated with Von Frey, at 24 and 72 hours. It can be therefore concluded that electroacupuncture, at the acupoint ST-36, 100Hz, showed anti-inflammatory action on the colitis induced by TNBS in 50% ethanol, by means of increase of IL-10 concentration and decrease on the expression of iNOS.

GOES, Annya Costa Araújo de Macêdo. A eletroacupuntura atenua a colite experimental induzida por TNBS via ativação de interleucina 10 e inibição de óxido nítrico sintase induzida. 2014. 113 f. Tese (Doutorado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2014.
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The etiology of inflammatory bowel disease (IBD) involves genetic, environmental and immunological factors. There are clinical reports of the use of acupuncture on IBD, however its therapeutic mechanisms are still uncertain. The purpose of this work is to study the anti-inflammatory and analgesic actions of electroacupuncture on a experimental colitis model. Male Swiss rats, divided in six groups (n=6-9), were subjected to induction of colitis by TNBS in 50% ethanol. The controls were saline (SAL) and ethanol (ETNL). The animals with colitis were treated with electroacupuncture (EAC) at the ST-36 acupoint, 100Hz, false electroacupuncture (FEAC), 100Hz, and dexamethasone (DEXA), 1 mg/Kg/day. Visceral hyperalgesia was evaluated by means of the Von Frey test. After three days, a colon segment was obtained for macroscopic and histopathological analysis, quantification of the activity of myeloperoxidase, Immunohistochemistry for iNOS, and quantification of malondialdehyde and cytokines (TNF-α, IL-1β, IL-10). The parametric data were analyzed with ANOVA/Tukey test or test T, and the non-parametric data with Kruskal-Wallis/Dunn test. There was an increase on the wet weight of the colons on group TNBS, and prevention of this event on group EAC. The groups TNBS and EAC showed an increase on neutrophil infiltration, as compared to the other groups. The group TNBS showed increased values for the microscopic scores, as compared to the treated groups. The groups TNBS and EAC showed an increase on the concentration of IL-1β in the colon. The group TNBS showed suppression of the concentration of IL-10 in the colon, prevented by treatment with EAC. The group EAC showed decrease on the concentration of MDA in the colon, as compared to the other groups. The group EAC showed decrease on the expression of iNOS in the connective, as compared to the treated groups. The group TNBS did not show any alterations of hypernociception, as evaluated with Von Frey, at 24 and 72 hours. It can be therefore concluded that electroacupuncture, at the acupoint ST-36, 100Hz, showed anti-inflammatory action on the colitis induced by TNBS in 50% ethanol, by means of increase of IL-10 concentration and decrease on the expression of iNOS.
A etiopatogenia das doenças inflamatórias intestinais idiopáticas (DII) envolve fatores genéticos, ambientais e imunológicos. Há relatos do uso da acupuntura no tratamento da DII, porém seus mecanismos ainda são incertos. A proposta deste trabalho é estudar a ação antiinflamatória e analgésica da eletroacupuntura em modelo de colite experimental. Utilizaram-se camundongos machos Swiss, distribuídos em seis grupos (n=6-9), submetidos a indução de colite por TNBS em etanol a 50%. Os controles do modelo foram salina (SAL) e etanol (ETNL). Os animais com colite foram tratados com eletroacupuntura (EAC) no acuponto ST-36, 100Hz, falsa-eletroacupuntura (FEAC) 100Hz e dexametasona (DEXA) 1mg/Kg/dia. A hiperalgesia visceral foi avaliada pelo teste de Von Frey. Após três dias, foi coletado segmento de cólon para análises macroscópicas, histopatológicas (H-E), dosagem da atividade de mieloperoxidase, imunoistoquímicas para iNOS e dosagem de malonaldeído, e citocinas (TNF-α, IL-1β, IL-10). Os dados paramétricos foram analisados por ANOVA/teste de Tukey ou teste T e os dados não paramétricos por Kruskal-Wallis/teste de Dunn. Houve aumento do peso úmido dos cólons no grupo TNBS e prevenção desse evento no grupo EAC. Os grupos TNBS e EAC apresentaram aumento na infiltração de neutrófilos no cólon em relação aos demais grupos. O grupo TNBS apresentou aumento na pontuação dos escores microscópicos em relação aos grupos tratados. Os grupos TNBS e EAC apresentaram aumento na concentração de IL-1β no cólon. O grupo TNBS apresentou supressão na concentração de IL-10 no cólon, prevenido pelo tratamento com EAC. O grupo EAC apresentou diminuição na concentração de MDA no cólon em relação ao grupo TNBS. O grupo EAC apresentou diminuição na expressão de iNOS no conjuntivo em relação ao grupo TNBS. O grupo TNBS não apresentou alteração da hipernocicepção, avaliada pelo Von Frey, nos tempos 24 e 72 horas. Conclui-se que eletroacupuntura, a 100Hz no acuponto ST-36, apresentou ação antiinflamatória na colite por TNBS em etanol a 50% através do aumento na concentração de IL-10 e redução na expressão de iNOS.

Saab Bofors Dynamics har som huvudsaklig verksamhet att utveckla missiler. Ofta krävs det att någon form av navigationsfunktion byggs in, och eftersom det inte är lätt att testa nya lösningar och algoritmer direkt på missilerna har man tagit fram två autonoma testplattformar, Freke och Gorm, i form av självgående bilar som kan ta sig fram inomhus i t.ex. en korridor.

För navigation utomhus lämpar sig GPS väl i många situationer, men i autonoma sammanhang är det inte tillräckligt. GPS är inte alltid tillgänglig på grund av att man inte alltid har fri sikt till minst fyra satelliter och i militära sammanhang är den också lätt att störa ut. Därför förlitar man sig hellre på noggranna tröghetsnavigeringssystem (TNS) som kan ge data i 100-tals Hz, och kompletterar med GPS för att korrigera för avvikelser. Oftast integrerar man sensorerna med någon form av Kalmanfilter för att kunna skatta felparametrar. Om GPS:en faller ifrån kan man med hjälp av felparametrarna navigera noggrannare med ett TNS än man skulle ha gjort annars

Noggranna TNS är dock både relativt stora och dyra. Referenssystem kan kosta uppåt en miljon kronor, och lämpar sig alltså varken för engångsbruk (i missiler) eller små billiga autonoma bilar. Nu finns det små och relativt billiga tröghetssensorer (IMU, Inertial Measurement Unit) som storleksmässigt lämpar sig väldigt väl, men som dock har ganska låg noggrannhet.

I detta examensarbete görs en studie av två olika navigationsmodeller där en billig IMU och en GPS integreras med hjälp av ett Extended Kalmanfilter (EKF).

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Not available

Orientador: Luiz Claudio Di Stasi
Banca: Clélia Akiko Hiruma Lima
Banca: Ramon Kaneno
Banca: Adair Roberto Soares dos Santos
Banca: Elfriede Marianne Bacchi
Resumo: Não disponível
Abstract: Not available
Doutor

Parallèlement aux progrès réalisés en immunologie, la notion d'immunosurveillance a été développée. Il a été montré une implication et une collaboration de l'immunité innée et de l'immunité adaptative dans la surveillance immune anti-tumorale. Le système immunitaire semble potentiellement compétent pour la détection et l'élimination des cellules tumorales mais différents mécanismes permettent aux cellules tumorales d'échapper à la réponse immune. Au cours de ce travail, nous nous sommes intéressés à l'absence de signal de costimulation délivré par les cellules tumorales. Le but de ce travail a été d'induire une réponse immune anti-tumorale par des modifications géniques de cellules tumorales qui permettent l'expression de molécules de costimulation appartenant à la famille des TNFs (Tumor Necrosis Factors): CD40L et CD70. Dans un premier temps, nous avons montré que l'expression de CD40L membranaire par les cellules tumorales elles-mêmes ou à distance des cellules tumorales induit des réponses immunes protectrices anti-tumorales. Les lymphocytes T sont impliqués dans ces réponses immunes, ainsi que les cellules NK selon le statut CMH-I des tumeurs. Dans un deuxième temps, nous avons réalisé la construction d'un ADNc codant la molécule CD70 soluble (sCD70). L'apport de cellules sécrétant sCD70 en périphérie des tumeurs CMH-I positives entraîne le rejet tumoral par les lymphocytes T CD8+ et la mise en place d'une mémoire immune protectrice. Ce travail a permis de démontrer que l'apport de deux molécules de costimulation CD40L et CD70 sur des cellules tumorales génétiquement modifiées permet d'induire des réponses immunes protectrices. La nature et l'amplitude de ces réponses immunes varient en fonction de la molécule apportée et en fonction du statut CMH-I des tumeurs. D'autre part, nos travaux montrent qu'il est intéressant de développer des molécules de costimulation sous forme soluble permettant la régulation de leur délivrance et une administration facilitée
In parallel to the progresses made in immunology, the immunosurveillance concept was developed. It was shown an implication and a collaboration of innate and adaptative immunity in the antitumor immune response. The immune system seems potentially qualified for detection and elimination of tumor cells. But various mechanisms developed by tumor cells allow tumor escape. During this work, we were interested in the absence of costimulatory signal delivered by tumor cells. The goal of this work was to induce antitumor immune response by genetically modification of tumor cells. These modifications allow costimulatory molecules expression belonging to the TNF (Tumor Necrosis Factor) family: CD40L and CD70. Initially, we showed that membrane CD40L expression by tumor cells themselves or in periphery of tumor cells induced antitumor protective immune responses. The T lymphocytes are implicated in these immune responses, as well as NK cells according to tumor MHC-I status. In a second time, we carried out construction of a cDNA encoding soluble molecule CD70 (sCD70). Injection of secreting sCD70 cells in periphery of positive MHC-I tumors induces tumor rejection by CD8+ T lymphocytes and a protective immune memory. .

The study addresses the outward cross-border linking of the Swedish economy and its most important transnational corporations during the 20th century. It explores the aggregate level of Swedish industry, and most importantly, the firm level of a group of eight long-standing transnational corporations, which during the post-1945 period represented roughly half of Sweden’s foreign industrial activity in terms of employment, e.g., Alfa Laval, ASEA, Ericsson, Sandvik, SKF, AGA, Electrolux and Atlas Copco. Since most of these corporations existed already a century ago it was possible to explore their historical trajectories within the general process of globalization. Hence, the study contributes to the testing of the globalization thesis with a small, open, developed economy as the point of reference. Based on aggregate national data and data on levels of foreign activity of Swedish transnational corporations the study presents a phase model of globalization, identifying first an ‘initial phase’ of globalization from ca 1871 to 1929, second a ‘stagnation phase’ (1930-1949), then a third ‘expansion phase’ (1950-1979) and finally, a ‘highlight of globalization’ phase, beginning in 1980 and continuing into the 21st century. In order to gain deeper insights into the historical process of Sweden’s outward economic linking it then looked in more detail at the eight firms mentioned above. Employing a quantitative formal model of foreign corporate activity, the study focusses on changes in the relative magnitude of foreign employment and sales (‘intensity’) and on the geographical distribution of foreign subsidiaries (‘extensity’). The two former categories are combined into an ‘index of transnationality’, which serves as a principal analytical tool for uncovering long-term change. The study concludes that for Swedish industry and its largest transnational corporations the term globalization represents more of a historical, continuous long-term trend than an exclusively contemporary development. In fact, the only period in time when we see a general stagnation in the positive trends was 1930-1945. Moreover, the study found at least two periods of rapid outward linking on the part of some of the most important Swedish corporations, apart from the current one, that is, the decade and a half preceding World War I and the 1960s. Nevertheless, levels of relative magnitude of activity abroad and of geographical spread attained by Swedish industry and its transnational corporations during the last two decades, were in many respects unprecedented. Findings on the variations in the actual pace of globalization during the whole 20th century demonstrated firstly, that positive change in geographical spread of the group of long-standing transnational corporations proceeded at an increasing pace when calculated in absolute terms. For the 1960-1999 period, the existence of positive long-term trends in the magnitude of both foreign sales and foreign employment were discovered. Also, there was an acceleration of the pace at which foreign sales increased over time, when calculated in absolute terms.

Orientador: Luiz Claudio Di Stasi
Resumo: A Doença Inflamatória Intestinal é uma doença considerada multifatorial com etiologia ainda pouco elucidada que compreende duas principais formas clinicas, denominadas como Retocolite Ulcerativa e a Doença de Crohn que induzem quadros crônicos de inflamação em diferentes regiões do trato gastrointestinal, com períodos de exacerbação e remissão dos sintomas. Os tratamentos farmacológicos disponíveis para a doença apresentam sérios efeitos colaterais e alto custo, o que faz com que o desenvolvimento de estratégias complementares de prevenção e tratamento seja uma importante meta na terapia da DII. A busca por estratégias complementares de prevenção e tratamento, como o uso de alimentos funcionais ricos em fibras e compostos bioativos, é uma perspectiva promissora, visto que as fibras têm sido associadas à promoção de efeitos prebióticos com consequente proteção ao processo inflamatório intestinal. Coix lacryma-jobi L., é uma planta cuja semente é rica em fibras e são amplamente utilizadas tanto na culinária quanto na medicina tradicional chinesa onde são indicadas para o tratamento de diversas doenças. Este trabalho tem como objetivo avaliar os efeitos da dieta enriquecida com farinha das sementes inteiras C. lachryma-jobi. no modelo de inflamação intestinal induzida por ácido trinitrobenzenosulfônico em ratos. Para tanto foram testadas três dietas com ração enriquecida de farinha de C. lachryma-jobi nas proporções de 5%, 10% e 20%, onde foram avaliados parâmetros clínicos (con... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Inflammatory Bowel Disease is a multifactorial disease with a not fully elucidated etiology that comprises two main clinical forms designate as Ulcerative Colitis and Crohn's Disease, which present chronic inflammation in different regions of the gastrointestinal tract, with periods of exacerbation and remission of the symptoms. The pharmacological treatments available for the disease have serious side effects and high cost, which makes the development of complementary prevention and treatment strategies an important goal in IBD therapy. The search for complementary treatment and prevention strategies, such as the use of functional foods rich in fiber and bioactive compounds, are a promising prospect, since the fibers have been associated with the promotion of prebiotic effects with consequent protection of the inflammatory bowel process. Coix lacryma-jobi L., is a plant containing seed rich in fiber and are widely used both in cooking and traditional Chinese medicine for the treatment of several diseases. This work aims to evaluate the effects of the diet enriched with flour of the whole seeds of C. lachryma-jobi in the experimental model of intestinal inflammation induced by trinitrobenzenesulfonic acid in rats. Three diets enriched with C. lachryma-jobi flour were tested in the proportions of 5%, 10% and 20% and were evaluated in the clinical parameters (daily food intake, body weight, diarrhea), macroscopic damage (score, lesion extension, weight/length ratio, adherence),... (Complete abstract click electronic access below)
Mestre

A presente pesquisa teve a finalidade de estudar a hematologia de bezerros clonados da raça Nelore, originados por meio da técnica de transferência nuclear de células somáticas (TNCS) por meio da avaliação do quadro eritrocitário, da dinâmica dos tipos de hemoglobina e do metabolismo do ferro destes animais durante o primeiro mês de vida. O delineamento experimental envolveu a colheita de 260 amostras de sangue e soro sanguíneo de 20 bezerros distribuídas nos seguintes momentos: imediatamente após o nascimento, 12 horas após o nascimento, 1 dia de vida, 2 , 3 , 4, 5, 7, 10, 15, 20 e 30 dias de vida. Os animais foram divididos em quatro grupos experimentais: 12 bezerros obtidos por meio da técnica de TNCS pelos laboratórios A e 8, 4 por meio de fertilização in vitro (FIV) e 4 por monta natural (MN). A ocorrência de anemia de grau moderado a grave, do tipo normocítico e normocrômico, foi observada em 100 % (5/5) dos 5 bezerros clonados pelo Laboratório A, enquanto a incidência nos bezerros clonados pelo Laboratório B foi igual a 14,2 % (1/7), nos bezerros obtidos por fertilização in vitro foi igual 50,0 % (2/4) e em bezerros obtidos por monta natural foi igual a 50,0 % (2/4). A avaliação do eritrograma dos bezerros cio nados pelo Laboratório A evidenciou que a anemia instalou-se gradualmente a partir das 12 horas de vida atingindo ao final da primeira semana, a, sua intensidade máxima, sendo observada a recuperação gradativa dos valores eritrograma a partir do 15°dia de vida. Os valores médios obtidos para o eritrograma dos bezerros clonados do Laboratório A no 7º dia de vida foram os seguintes: Hemácias - 4,33X106/mm3-; Volume Globular - 23 %, Taxa de Hemoglobina - 7,25 g/dL; VCM - 52,89 µ3-; HCM - 16,65 pg; CHCM - 31,47%. A anemia observada nos bezerros clonados pelo Laboratório A era de origem ferropriva, pois se evidenciou nesses animais uma significativa diminuição dos teores séricos de ferro associada à diminuição do índice de saturação da transferrina (1ST), enquanto os valores da capacidade total de ligação do ferro (CTLF) não sofreram influência durante o período. Os valores médios obtidos para o metabolismo de ferro dos bezerros clonados pelo Laboratório A no 7º dia de vida foram os seguintes: teores séricos de ferro - 47,35 mg/dL; capacidade total de ligação de ferro - 455,90 mg/dL, índice de saturação da transferrina - 9,64%. Durante o estudo dos tipos de hemoglobinas, utilizando-se técnica de eletroforese foram identificados três fenótipos de hemoblogina adulta (Hb-A; Hb-B e Hb-AB) e a presença de hemoglobina fetal (Hb-F), não sendo observadas anomalias que pudessem sugerir a ocorrência de hemoglobinopatias hereditárias e/ ou congênitas. Verificou-se que as taxas de Hb-A, nos clones com fenótipo Hb-AB e Hb-A, permaneceram estáveis durante todo o período experimental, enquanto nos bezerros obtidos por fertilização in vitro ou monta natural com os mesmos fenótipos (Hb-A e Hb-AB) observou-se a partir de 120 horas de vida um gradativo aumento das taxas de Hb-A. Durante a avaliação da dinâmica da hemoglobina do tipo fetal (Hb-F) no primeiro mês de vida observou-se, que todos os grupos animais apresentaram comportamento similar, caracterizado por sua diminuição com o desenvolvimento etário.
The present work aimed to study the hematology of cloned Nelore calves produced using the technique of somatic cell nuclear transfer (SCNT), by evaluating erythrocyte parameters, hemoglobin dynamics, and iron metabolism in the animals during the first month after birth. The experimental design included the collection of 260 blood and blood serum samples from 20 calves in the following times: immediately after birth, 12 hours after birth, 1st of life, 2nd, 3rd, 4th, 5th, 7th, 20th and 30th day of life. The animals were classified in four experimental groups: 12 calves produced, using SCNT for two commercial laboratories (laboratory A=5 calves and laboratory B= 7 calves), four calves produced by in vitro fertilization (IVF) and four calves produced by natural mating (NM). Mild to severe normocytic and normochromic anemia was observed in 100% (5/5) cloned calves from laboratory A, and 14.2% (117) cloned calves from laboratory B. In both IVF and NM calves, anemia was observed in 50% (214) of the calves. Erytrogram evaluation of cloned calves from laboratory A showed that anemia developed gradually from 12 hours after birth, was most intense at the end of the first week, and then erytrogram normal values were recovered after the 15th day of life. Mean values for the laboratory A cloned calves erytrogram in the 7th day of life were the following: Red cells 4033X106/mm3, hematocrit 23%, hemoglobin 7.25g/dL, MCV 52.89µ3-; MCH 16.65, MCHC 31.47%. Anemia observed in cloned calves from laboratory A was caused by iron deficiency, since a significant decrease in iron se rum levels together with a decrease in transferrin saturation index (TSI) was confirmed. At the same time, Total iron-binding capacity (TIBC) was not changed in this period of time. Mean iron metabolism values for cloned calves from laboratory A were the following: serum iron amount: 47,35mg/dL, TIBC 455,90 mg/dL and TSI 9,64%. Hemoglobin identification by eletrophoresis identified three adult hemolglobin phenotypes (A-Hb; B-Hb e AB-Hb) and the fetal hemoglobin (F-HB), and there was no sign of hereditary hemoglobin disorders were observed. The rate of A-Hb in cloned calves with A-Hb and AB-Hb phenotypes was maintained during the experimental period. Nonetheless, for the IVF calves with the same phenotypes (A-Hb and AB-Hb) a constant increase in the A-Hb was noticed. For the evaluation of F-Hb dynamics in the first month of life, results showed similar pattern, characterized by its decrease with age.

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pos-Graduação em Farmacologia, Florianópolis, 2008.
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Os neutrófilos são células importantes para a eliminação de patógenos, no entanto, o recrutamento excessivo dessas células pode levar a lesão tecidual. Essa migração é mediada pelas quimiocinas CXC, e seus receptores, CXCR1 e CXCR2 presentes nos neutrófilos. Dessa forma, a redução do influxo de células durante o processo inflamatório, através da inibição desses receptores, pode ser uma alternativa terapêutica apropriada para o tratamento de inúmeras doenças inflamatórias, como as doenças inflamatórias intestinais (IBD). O presente estudo buscou avaliar se o tratamento sistêmico curativo com antagonista seletivo para o receptor CXCR2, SB225002, era capaz de reduzir a inflamação intestinal, no modelo de colite induzida pelo TNBS em camundongos. O SB225002 (SB) ou dexametasona (DEX) (controle positivo) foram administrados 24 h após a indução da colite, de 12 em 12 horas por três dias. No terceiro dia após a indução da colite, os animais foram sacrificados e diferentes parâmetros inflamatórios foram avaliados. A administração do TNBS induziu danos macro e microscópicos no cólon dos animais, encurtamento e edema desse tecido, além de aumento do peso do baço, causando, em muitos casos, a morte dos animais. Os tratamentos com SB ou DEX reduziram de forma significativa todos os parâmetros analisados, demonstrando uma melhoria no quadro inflamatório. Alguns dos mecanismos envolvidos nos efeitos do SB também foram analisados. O tratamento sistêmico reduziu o influxo de neutrófilos, a atividade da enzima MPO, os níveis de IL-1ß e KC além da expressão das proteínas VEGF, iNOS e COX-2, no cólon dos animais. Adicionalmente, os níveis das citocinas antiinflamatórias IL-4 e IL-10 estavam aumentados no cólon de animais que receberam SB. Dessa forma, nossos resultados demonstraram que o bloqueio seletivo do receptor CXCR2, através da ação do antagonista SB, se mostrou eficaz em reduzir a inflamação colonica no modelo de colite induzida por TNBS, sugerindo que o SB é um potencial agente terapêutico para o tratamento das doenças inflamatórias intestinais.