This thesis explores the development of Bertrand Russell‘s theory of definite descriptions. It aims at demonstrating the connection between Russell‘s views on the subject of denoting and his attempt, in the period 1903-05, to develop a solution to 'the Contradiction' (i.e. the Russell Paradox). The thesis argues that the discovery of the theory of descriptions, and the way in which it works, are best understood against the backdrop of Russell‘s work on the paradoxes. A new understanding of Russell‘s seminal paper 'On Denoting' is presented, including a novel interpretation of the notorious 'Gray‘s Elegy Argument', in which Russell argues against his earlier theory of denoting. That Russell‘s work on denoting is connected to his work on the paradoxes is reasonably well-known: the nature of the connection has not, however, been adequately brought out in the literature. This is addressed through demonstrating the relationship between Russell‘s work on denoting and his development of the 'substitutional theory' of classes and relations. This theory eliminates classes and propositional functions in favour of matrices and substitutions. The role of the theory of descriptions in the development of the substitutional theory is commonly supposed to be merely that the theory of descriptions facilitates the ontological elimination of classes. But this elimination was equally possible on Russell‘s earlier theory of denoting (which he had rejected in the Gray‘s Elegy Argument). In the thesis it is suggested that the theory of descriptions brings with it a new conception of analysis, and that it is through the introduction of this new form of analysis—rather than through the elimination of classes—that the theory of descriptions facilitates the substitutional approach.

This thesis presents an interpretation of David Williams' (1738-1816) Lessons to a young prince (1790) ostensibly from a publisher-centric viewpoint. Through close analysis of its English-language editions it argues that Lessons has been consistently misattributed, misread, and otherwise taken out of context. The agglomeration of both contextual and particular factors contributed to this general negligence, but the most important factors were anonymity and the transformation of the text by the addition of a tenth lesson on Edmund Burke's Reflections, which altered the way Lessons was read by contemporaries in light of the revolution controversy. The thesis suggests that the explicit ad-hominen attack on Burke in the tenth lesson overshadowed what amounted to an implicit attack on Burke-in-transition towards Reflections contained in the original nine lessons. Using a significant body of previously unknown material to identify Williams' intended audience and the effects of anonymity, genre, and advertising on reader-response to Lessons, the thesis adds to existing knowledge about Williams' intentions and to the way his texts were read and understood by contemporaries. More particularly it underscores the importance of his publishers and charts their impact upon his text. The influence that Lessons' publishers had on the impact of the text, both intentional and unintentional had received no scholarly attention, and they are themselves, as publishers, understudied. However, as this thesis shows, their direct textual interpolations increased the satirical vigour of Lessons, whilst a sophisticated marketing campaign attempted to influence reader reception as well as sales. Indirectly, anonymity caused readers to superimpose the political sympathies of the publishers onto Lessons, which further pre-ordained the terms on which they were read.

Whether Aristotle wrote the treatises of Metaphysics with different conceptions of the science of Being in mind has long puzzled scholars. The particular question that causes them unease is whether Aristotle's enterprise in establishing the science of Being through the several treatises of Metaphysics is marked by a general science of Being, studying all departments of Being whatsoever (metaphysica generalis), or whether his investigation of this science reflects an attitude towards a special metaphysics (metaphysica specialis) seeking knowledge of a special department of Being, in this case, God, and therefore should be regarded as a science that is eminently theological. In this thesis, I aim to show that Aristotle's enterprise in Metaphysics does not necessarily hinder reconciliation between the universal and the theological dimensions of the science of Being and that although Aristotle's conception of the science of Being is eminently theological it does not conflict with its also being universal. Furthermore, I aim to show that had the conception of the science of Being in Aristotle's mind not been theological, it would not be universal either.

INTRODUÇÃO: Os vírus das hepatites B (VHB) e C (VHC) são os principais causadores de hepatopatia crônica em todo mundo. Ambos compartilham vias semelhantes de transmissão. Em pacientes portadores crônicos de VHC com sorologia compatível com infecção pregressa pelo VHB (anti-HBcAg[+] e HBsAg [-]), o VHB DNA residual tem sido detectado por técnicas de biologia molecular altamente sensíveis no soro, em células linfomononucleares de sangue periférico e em hepatócitos (como cccDNA), de forma que o anti-HBcAg tem sido associado a pior prognóstico, tanto histológico quanto terapêutico. OBJETIVOS: Analisar a associação entre infecção pregressa pelo VHB nos portadores crônicos do VHC e o dano histológico hepático, além das características epidemiológicas, clínicas e laboratoriais destes pacientes em região de baixa prevalência para o VHB. MÉTODOS: A prevalência do anti-HBcAg foi avaliada em 574 pacientes portadores crônicos de VHC atendidos durante o ano de 2006 no ambulatório de Hepatites Virais do DMIP-HC FMUSP. Deste grupo, foram selecionados 215 pacientes (98 de 112 com anti-HBcAg[+] e 117 de 462 monoinfectados pelo VHC) para análise comparativa. Ainda, 145 indivíduos foram submetidos à análise estatística multivariada, por metodologia de Regressão Logística sequencial, para identificação de possíveis preditores de fibrose avançada. RESULTADOS: Foram avaliados 98 pacientes com marcadores sorológicos de infecção pregressa pelo VHB. Quarenta e seis indivíduos (47%) possuíam o anti-HBcAg de forma isolada. O principal fator de risco relacionado à infecção viral foi hemotransfusão (31,6%). Contudo, a freqüência de UDI foi maior no grupo com infecção pregressa pelo VHB, em relação aos 117 indivíduos monoinfectados pelo VHC (p<0,05). Não houve diferença estatisticamente significativa quanto ao estadiamento (p=0,40) ou à graduação necroinflamatória histológica (APP, p=0,70) entre esses dois grupos. O tempo de infecção e a taxa de progressão de fibrose também foram semelhantes (p=0,99 e p=0,61, respectivamente). A presença do anti-HBcAg não foi considerada preditora de fibrose hepática avançada (p=0,11), porém identificamos como variáveis independentes o tabagismo acentuado (OR 4,40; IC95%: 1,30-14,87), aumento da ALT (OR 1,01; IC95%: 1,00-1,03), de gamagt (OR 1,01; IC95%: 1,00-1,01) e leucopenia (OR 7,75; IC95%: 2,13-28,23). CONCLUSÃO: A prevalência de infecção pregressa pelo VHB em portadores de infecção crônica pelo VHC foi de 20%, sendo este valor compatível com outros estudos realizados em regiões de endemicidade semelhante. A freqüência do marcador anti-HBcAg isolado foi alta neste grupo, refletindo uma possível supressão da imunidade humoral contra o VHB frente a resposta dirigida ao VHC. A infecção pregressa pelo VHB não parece acentuar ou acelerar o dano histológico hepático no nosso meio. / INTRODUCTION: Hepatitis B (HBV) and C (HCV) virus are the main causers of chronic hepatic disease worldwide. Both viruses share similar transmission routes. In chronic HCV infected patients with serological markers of resolved HBV infection (anti-HBcAg [+] and HBsAg [-]), residual HBV-DNA has been detected through highly sensible techniques in serum, PBMC and hepatocytes (as cccDNA). In fact, anti-HBcAg has been associated with worse prognoses, severe histological liver damage and less sustained virological response to HCV treatment. OBJECTIVE: Assess the relationship between previous HBV infection (anti-HBcAg [+]; HBsAg [-]) in patients with chronic hepatitis C (HCV) and histological damage, considering epidemiological, clinical and laboratorial characteristics of this group in a region of low prevalence for HBV. METHODS: Anti-HBcAg prevalence was evaluated in 574 patients seen during a period of one year in a tertiary center (University of Sao Paulo General Hospital, Sao Paulo, Brazil). Of this group, 215 subjects addressed selection criteria and have been selected for evaluation (98 of 112 carriers of anti-HBcAg and 117 of 462 infected only by HCV). 145 individuals have undergone analysis for identification of predictors of advanced fibrosis through univariate and multivariate stepwise logistic regression. RESULTS: Nineteen-eight subjects with serological markers of previous HBV infection were evaluated. Forty-six (47%) patients had anti-HBcAg in isolated form. The main risk factor for infection was blood transfusion (31,6%). However, the IDU frequency was greater in this group (p<0.05). There was no difference regarding histological staging (fibrosis ranging from 0 to 4, p=0.40) or grading (portal inflammation, p=0.70) compared with subjects infected only by HCV with no markers of HBV infection. The rate of fibrosis progression (in units per year) and the infection length was similar in these two groups (p=0,61 and p=0,99, respectively). Anti-HBcAg was not considered a predictor for advanced fibrosis (p=0.11). However, we identified tobacco smoking (OR 4.40; CI 95%: 1.30-14.87), increased ALT (OR 1.01; CI 95%: 1.00-1.03), increased -gt (OR 1.01; CI 95%: 1.00-1.01) and leucopenia (OR 7.75; CI 95%: 2.13-28.23) as independent variables. CONCLUSION: The prevalence of resolved HBV infection in subjects with chronic hepatitis C was 20%. This result was equivalent to other studies carried out in regions of similar endemicity. The frequency of the isolated anti-HBcAg was higher in this group, reflecting a possible suppression of the humoral immunity against HBV caused by an active immune response directed to HCV. Former and resolved HBV infection does not seem to increase or accelerate histological damage in our geographical area.

Made available in DSpace on 2018-08-01T23:27:10Z (GMT). No. of bitstreams: 1 tese_10881_81 - Mylla Carla Cescon Freire.pdf: 1313608 bytes, checksum: 57fa1668897624f985a8b3440fe12072 (MD5) Previous issue date: 2017-04-07 / O Stenella coeruleoalba é um pequeno cetáceo pelágico da família Delphininae que apresenta uma ampla distribuição e pode ser encontrado em águas tropicais e temperadas dos oceanos Atlântico, Pacífico e Índico, bem como em mares adjacentes, como o Mar Mediterrâneo. O presente estudo teve por objetivo analisar a região do citocromo b (Cit-b) e a região controle (D-loop) do DNA mitocondrial de indivíduos do Nordeste e do Sul do Brasil (Oceano Atlântico Sul), além de compará-las com sequências de golfinhos-listrados provenientes do Oceano Atlântico Norte, e com isso avaliar os índices de diversidade e a presença ou a ausência de estruturação genética entre as diferentes localidades. Os S. coeruleoalba do Brasil apresentaram uma alta diversidade genética para ambos os marcadores mitocondriais analisados (D-loop: h= 0,984; &#960;= 0,294; Cit-b: h= 0,848; &#960;= 0,249) e considerando o marcador Cit-b constituem duas populações (FST= 0,180; P= 0,045). Uma diferenciação significativa entre as unidades amostrais de S. coeruleoalba do Atlântico Norte e do Atlântico Sul foi verificada a partir dos dois marcadores mitocondriais avaliados (D-loop: FST= 0,034/ P= 0,009; Cit-b: FST= 0,130/ P= 0,026). Ademais, com a região D-loop, foi possível evidenciar estruturação genética entre dois grupos de golfinhos-listrados do Mar Mediterrâneo (FST= 0,0913/ P= 0,000). Não foi possível identificar estruturação entre os indivíduos do oeste do Oceano Atlântico Norte com as unidades amostrais do Brasil, mesmo estes não apresentando compartilhamento de haplótipos. Tal fato sugere que estas unidades possam ter surgido de linhagens próximas geneticamente e ainda fazem parte de uma mesma população. Até então, nenhum estudo genético populacional com a espécie S. coeruleoalba havia sido realizado no Oceano Atlântico Sul. Entender como os golfinhos-listrados encontram-se estruturados é de suma importância para compreender a genética destes indivíduos e assim definir estratégias de conservação adequadas para cada população identificada.

Made available in DSpace on 2018-08-01T23:27:52Z (GMT). No. of bitstreams: 1 tese_8525_DISSERTAÇÃO VERSÃO FINAL - ANDRÉ MARTINS FONTES.pdf: 2962953 bytes, checksum: 69755d6ddef403f14185c70c81e35637 (MD5) Previous issue date: 2016-10-07 / A Organização Mundial de Saúde (OMS) estima que cerca de 2 bilhões de pessoas no mundo já tiveram contato com o vírus da Hepatite B (VHB), e que 325 milhões tornaram-se portadores crônicos. Uma parte considerável da população mundial e brasileira pode estar infectada por este vírus, visto que o mesmo na maioria das vezes faz com que a doença se apresente na forma assintomática. A hepatite B é uma das principais causas de hepatite crônica, cirrose hepática e carcinoma hepatocelular. Tanto os fatores virais, bem como a resposta imune do hospedeiro, têm sido implicados na patogenia e no resultado clínico da infecção por HBV. Diversas moléculas, que modulam a resposta imune, têm sido descritas, incluindo, HLA-G. Em algumas infecções virais humanas, agudas e crônicas, a expressão de HLA-G pode ser regulada, afetando desta forma a resposta imunológica do hospedeiro frente ao vírus, favorecendo o escape do mesmo do sistema imunológico. Considerando que o papel do HLA-G ainda não foi bem esclarecido, dentro dos mecanismos patogênicos da infecção pelo HBV. Este estudo se propõe a avaliar os polimorfismos gênicos do HLA-G e relaciona-los com os achados epidemiológicos, laboratoriais e clínicos. Palavra-chave: Hepatite B, Epidemiologia, Georreferenciamento, HLA-G, Polimorfismo de 14-pb, Polimorfismo de Nucleotideo Único.

Le lymphocyte B (LB) joue un rôle important dans la polyarthrite rhumatoïde (PR), en produisant des auto-anticorps qui ont un rôle pathogène, en activant les lymphocytes T, en sécrétant des cytokines pro-inflammatoires et en permettant la formation de centres germinatifs. Plus récemment, il a été montré que le LB pouvait également produire de l'interleukine (IL) 10, une cytokine anti-inflammatoire qui lui procure des fonctions régulatrices. Ces B régulateurs ont notamment la capacité de différencier les lymphocytes T en T régulateurs. De nombreux traitements sont actuellement disponibles dans la PR, notamment les anti-TNF alpha et les inhibiteurs du récepteur de l'IL-6 (tocilizumab). Dans la première partie de cette thèse, nous avons comparé les LB circulants de patients atteints de PR et de contrôles. Nous avons étudié l'influence de l'activité de la maladie et des traitements sur les LB. Nous avons montré qu'il existait une lymphopénie B globale chez les patients atteints de PR avec une répartition des différents sous-types de LB superposable à celle des contrôles. Les patients ayant une maladie active avaient significativement plus de LB mémoires totaux, pré- et post-switch, CD24hiCD27+ et double négatifs que les patients ayant une maladie peu active. Les traitements anti-TNF et le tocilizumab ne modifiaient pas la répartition des sous-types de LB. Nous avons également montré qu'un taux de plus de 26% de LB mémoires CD27+ avant l'instauration d'un traitement par anti-TNF était associé à la réponse clinique à 3 mois. Les LB mémoires semblent produire plus de TNF que les LB naïfs et par ce biais pourraient induire une réponse Th1. Dans la seconde partie de cette thèse, nous avons tout d'abord cherché à mieux définir les LB régulateurs. Nous avons ensuite étudié leur présence et leur rôle dans la PR. Chez les sujets sains, les LB CD24hiCD27+ et CD24hiCD38hi semblent produire plus d'IL-10 que les autres LB, qui peuvent néanmoins en sécréter. Il semble donc plus adapter de définir les B régulateurs comme B producteurs d'IL-10 ou B10. Les patients atteints de PR avaient significativement moins de B10 que les contrôles en pourcentage et en valeur absolue. Chez les patients ayant un facteur rhumatoïde (FR) positif, il y avait une corrélation inverse entre le pourcentage de B10 et le taux de FR. Il y avait une corrélation inverse entre l'activité de la maladie (DAS28) et le pourcentage de B10, qui était particulièrement marquée pour les PR évoluant depuis moins de 5 ans. Chez ces patients, il y avait également une corrélation inverse entre les B10 et l'inflammation biologique (protéine C réactive). L'instauration d'anti-TNF ou de tocilizumab ne modifiait pas le taux de B10. Les CD24hiCD27+ et CD24hiCD38hi induisaient plus de lymphocytes T régulateurs chez les contrôles que les autres LB (CD24lo/-) alors que ça n'était plus le cas chez les patients atteints de PR, montrant que ces sous-types ont perdu cette fonction régulatrice dans la PR. En conclusion, bien qu'il existe une lymphopénie B, la répartition des sous-types de LB ne semble pas différente entre les patients atteints de PR et les contrôles. Néanmoins, il existe des anomalies fonctionnelles avec notamment une perte de la capacité à produire de l'IL-10 et à induire des T régulateurs chez les patients atteints de PR. / B cells play an important role in rheumatoid arthritis (RA), producing autoantibodies which have a pathogenic role, activating T cells, secreting pro-inflammatory cytokines and allowing the formation of germinal centers. More recently, it was shown that the B cells could also produce interleukin (IL)-10, an anti-inflammatory cytokine which provides their regulatory functions. Those regulatory B cells have the ability to differentiate T cell into regulatory T cells. Many treatments are currently available in RA, including TNF-alpha inhibitors and IL-6 receptor inhibitor (tocilizumab). In the first part, we compared circulating B cells in RA patients and in controls, and we studied the influence of disease activity and treatment on B cells. We have shown that there is a global B cell lymphopenia in RA patients with a similar B cell subtype distribution as controls. Patients with active disease had significantly more pre- and post-switch, CD24hiCD27+ and double negative memory B cells than patients with low disease activity. Anti -TNF treatment and tocilizumab did not change the distribution of B cell subsets. We also showed than patient with more than 26% of CD27+ memory B cells prior TNF inhibitor initiation was associated with clinical response at 3 months. Memory B cells produced more TNF alpha than naive B cells and can potentially induce a Th1 response. B cell subtypes were not associated with response to tocilizumab. In the second part, we first sought to better define regulatory B cells. We then studied their presence and role in RA. In healthy subjects, CD24hiCD27+ and CD24hiCD38hi B cells seem to produce more IL-10 than the other B cells that can nevertheless rarely produce some. It seemed more acurate to define regulatory B cells as IL-10 producing B cells also called B10 cells. Patients with RA had significantly less B10 cells than controls in percentage and absolute values. In rheumatoid factor (RF) positive patients, there was an inverse correlation between the percentage of B10 and the rate of RF. There was an inverse correlation between disease activity (DAS28) and the percentage of B10, which was particularly significant for patients with a disease duration of less than 5 years. In these patients, there was also an inverse correlation between B10 and biological inflammation (C-Reactive Protein). TNF inhibitors or tocilizumab did not change B10 cell rate. The CD24hiCD27 + and CD24hiCD38hi induce more regulatory T cells in controls than other LB (CD24lo/-) while it was not the case in patients with RA, indicating that these subtypes have lost this regulatory function in RA. In conclusion, although there are B cell lymphopenia, the distribution of B cell subsets does not seem to differ between RA patients and controls. Nevertheless, there are functional abnormalities including a loss of the ability to produce IL -10 and induce regulatory T in patients with RA.

According to David Lewis’ influential thesis of Humean Supervenience, the world is a plurality of self-contained individuals standing in external relations of spatiotemporal distance. In the last decades, this thesis has been under attack by what I call ‘holistic ontologies’, the most salient of which are Dispositional Essentialism, Ontic Structural Realism, Priority Monism, and Existence Monism. These reactions obey different but closely related suspicions against the central features of Humean Supervenience. On one hand, there are suspicions against the idea of external relations; on the other hand, there are suspicions against the idea of self-contained plurals. Common to these holistic ontologies is to conceive the world not as an externally related heap but, in different degrees of strength, as an ‘internally related whole’. This work, following Bradley’s stance against relations, puts under critical scrutiny the merits of these holistic ontologies. The central aims are to make explicit the different senses of ‘wholeness’ and ‘internal relatedness’ that they happen to endorse; make explicit their internal flaws; and show the relative superiority of Existence Monism. As it happens, Existence Monism vindicates Bradley’s core ideas about relations, namely: that external relations are unable to relate; that internal relations are inherently unstable; and that all relations–external and internal–are better understood as imperfect abstractions from a more substantial, non-relational, kind of unity. I conclude with some skeptical remarks against my own metaphysical preferences and against ontology in general.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Os venenos de serpentes contem substÃncias biologicamente ativas, primariamente consistindo de proteÃnas (90-95%). Algumas delas apresentam atividade enzimÃtica como as fosfolipases A2 e L-aminoÃcido oxidase. O presente estudo verificou a aÃÃo dos venenos de Bothrops leucurus (BleuVT) e Bothrops marajoensis (BmarVT), e suas fraÃÃes PLA2 (BleuPLA2 e BmarPLA2) e LAAO (BleuLAAO e BmarLAAO) sobre cepas de bactÃria, C. albicans, Leishmania sp e T. cruzi, bem com sua toxicidade sobre macrÃfagos murinos. A susceptibilidade das cepas bacterianas e fÃngica foi analisada atravÃs do mÃtodo de difusÃo em Ãgar, para determinaÃÃo do potencial antimicrobiano; e microdiluiÃÃo em caldo, para determinaÃÃo da CIM e CLM, com modificaÃÃes. A atividade antiparasitÃria foi avaliada atravÃs do tratamento das culturas de parasitos com diferentes concentraÃÃes dos venenos ou de suas fraÃÃes. As formas promastigotas de Leishmania sp. foram cultivadas, durante 72h, em meio NNN/Schneider a 28ÂC; e as formas epimastigotas de T. cruzi foram cultivadas em meio LIT, durante 5 dias, a 28ÂC. Os macrÃfagos foram cultivados em meio RPMI 1640, em presenÃa de diferentes concentraÃÃes dos venenos e fraÃÃes, durante 24h, e submetidos ao ensaio com MTT. Os resultados foram estatisticamente analisados atravÃs do teste t ou ANOVA seguida do teste Bonferroni, quando apropriado, com p<0.05. A BmarLAAO foi capaz de inibir o crescimento bacteriano do Gram-negativo P. aeruginosa, da levedura C. albicans e do Gram-positivo S. aureus; e o BleuTV inibiu o crescimento de S. aureus, sendo a inibiÃÃo dose-dependente. A ordem de susceptibilidade dos microorganismos testados com BmarLAAO foi S. aureus > C. albicans > P. aeruginosa. Por outro lado o BmarTV, BmarPLA2, BleuPLA2 e BleuLAAO nÃo apresentaram nenhum grau de inibiÃÃo sobre as cepas em estudo. O potencial inibitÃrio foi mais significante sobre S. aureus apresentando CIM= 50Âg/mL e CLM=200Âg/mL para BmarLAAO, e CIM=CLM=25Âg/mL para BleuTV. Em concentraÃÃes maiores que 1.56Âg/mL a BmarLAAO foi capaz de inibir o crescimento de formas promastigotas de L. chagasi e L.amazonensis, sendo os valores de IC50, apÃs 72h de cultivo, para L. amazonenis, 2.55Âg/mL e 2.86 Âg/mL para L. chagasi. BmarTV e BleuTV tambÃm apresentaram significante inibiÃÃo sobre o crescimento parasitÃrio, sendo os valores de IC50 86.56 Âg/mL para L. amazonensis e 79.02Âg/mL para L. chagasi, quando tratado com BmarTV; e 5.49Âg/mL para L. amazonensis e 1.94Âg/mL para L. chagasi, quando tratado com BleuTV. Os venenos e BmarLAAO mostraram efeito inibitÃrio sobre formas epimastigotas de T. cruzi. Os valores de IC50 para BleuTV, BmarTV e BmarLAAO foram, respectivamente, 1.14Âg/mL, 24.19Âg/mL e 0.89Âg/mL. As fraÃÃes BmarPLA2, BleuPLA2 e BleuLAAO nÃo foram capazes de promover nenhum efeito inibitÃrio sobre os parasitos em estudo. O BmarLAAO , BmarTV e BleuTV apresentaram baixa toxicidade sobre macrÃfagos nas concentraÃÃes estudadas. Em conclusÃo, os veneno de B. leucurus e de B. marajoensis, bem como a L-aminoÃcido oxidase de Bothrops marajoensis mostraram ser capazes de interferir no crescimento de diferentes microorganismos como S.aureus, C. albicans, P. aeruginosa, Leishmania sp. e T. cruzi. / Snakes venoms contain biologically active substances primarily consisting of proteins (90-95%). Some of these present enzymatic activities, such as phospholipases A2 and the L-amino acid oxidases. In this study we verify the action of Bothrops leucurus (BleuTV) and Bothrops marajoensis (BmarTV) venoms, and fractions PLA2 (BleuPLA2 and BmarPLA2) and LAAO (BleuLAAO and BmarLAAO) on strains of bacteria, yeast, Leishmania sp and T. cruzi. The susceptibility of bacterial and yeast strains was analyzed through disc-diffusion assay, for determination of antimicrobial potential; and the microdilution method, for determination of MIC and MLC, with modifications. The antiparasitic activity was evaluated through of the culture treatment of parasites with different concentrations of venoms or their fractions. The forms promastigotes of Leishmania sp. had been cultived, during 72h, in NNN/Schneider media, 28ÂC; and the forms epimastigotes of T. cruzi had been cultived in LIT media, during 5d, 28ÂC. The macrophages were cultured in RPMI 1640 media, during 24h, 37ÂC and 5% of CO2, with different concentrations of venoms or fractions. After, they were analyzed by MTT method. The results was statistically analyzed with t test or ANOVA followed the Bonferroniâs test, when appropriated, with p<0.05. The BmarLAAO was able to inhibit the growth of gram negative P. aeruginosa, of yeast C. albicans and of gram positive S. aureus; and the BleuTV inhibited the growth of S. aureus, being the inhibitions dose-dependent. The order of susceptibility of microorganisms tested against BmarLAAO was S. aureus > C. albicans > P. aeruginosa. On the other hand the BmarTV, BmarPLA2, BleuPLA2 and BleuLAAO had not provided any degree of inhibition on strains in study. The inhibitory effect was more significant on S. aureus presenting CIM= 50Âg/mL and CLM=200Âg/mL for BmarLAAO, and CIM=CLM=25Âg/mL for the BleuTV. In concentrations greater than 1.56Âg/mL BmarLAAO was able to inhibit the growth of promastigotes forms of L. chagasi and L.amazonensis, after 72h of culture. The IC50 values were 2.55Âg/mL for L. amazonenis, and 2.86 Âg/mL for L. chagasi. BmarTV and BleuTV also provided significant inhibition of the parasitic growth, with an IC50 value of 86.56 Âg/mL for L. amazonensis and 79.02 Âg/mL for L. chagasi, when treated with BmarTV; and 5.49Âg/mL for L. amazonensis and 1.94Âg/mL for L. chagasi, when treated with BleuTV. The venoms and BmarLAAO showed inhibitory effect on epimastigotes forms of T. cruzi. The IC50 value for BleuTV, BmarTV and BmarLAAO where, respectively 1.14Âg/mL, 24.19Âg/mL and 0.89Âg/mL.This effects presented behavior dose-dependent. The fractions BmarPLA2, BleuPLA2 and BleuLAAO had not been capable to promote any inhibition on the growth of these parasites. The BmarLAAO, BmarTV and BleuTV presented low toxicity in studied concentrations. In conclusion, the whole venoms as well as the L-amino acid oxidase from Bothrops marajoensis showed to be capable to interfere in the growth of several microorganisms as S.aureus, Candida albicans, Pseudomonas aeruginosa, Leishmania sp. and T. cruzi.

INTRODUÇÃO: A infecção pelo vírus da hepatite B (VHB) é responsável por grande parte das doenças hepáticas crônicas em todo o mundo. Em pessoas vivendo com HIV/Aids (PVHA) a infecção pelo VHB tem maior risco de evolução para cirrose e carcinoma hepatocelular. A vacina da hepatite B é importante na prevenção de doença potencialmente grave, particularmente em PVHA, já que ambos os vírus têm as mesmas vias de transmissão e a coinfecção tem uma alta morbidade. Indivíduos imunocompetentes têm uma boa resposta humoral após uma primeira série de vacina da hepatite B e não há recomendações de rotina para doses de reforço. PVHA podem ter uma pior resposta à vacina da hepatite B, quando comparada à resposta em indivíduos imunocompetentes e a duração da imunidade nesses pacientes é desconhecida. OBJETIVOS: Geral: Avaliar os marcadores sorológicos de proteção e infecção pelo VHB em pacientes adultos vivendo com HIV/Aids, vacinados previamente para hepatite B. Específicos: Avaliar a persistência dos anticorpos anti-HBs em PVHA vacinadas previamente para hepatite B e que apresentaram resposta humoral protetora inicial; avaliar a resposta sorológica à revacinação para hepatite B nos pacientes vacinados previamente e que não apresentaram resposta humoral protetora inicial; investigar a presença de marcadores sorológicos de infecção pelo VHB em PVHA vacinadas previamente para hepatite B. MÉTODOS: Estudo observacional de coorte retrospectiva de PVHA vacinadas primariamente para hepatite B entre 2001 e 2002. Marcadores sorológicos de infecção e proteção para o vírus da hepatite B foram investigados nesses pacientes que ainda estavam em acompanhamento no Serviço de Extensão ao Atendimento de Pacientes HIV/Aids (SEAP), da divisão de Clínica de Moléstias Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre 2012 e 2014. RESULTADOS: Uma coorte de 121 PVHA foi analisada quanto à soroconversão e persistência do anti-HBs. A maioria era do sexo feminino (54,5%) com média de idade de 50,1 anos. Destes pacientes, 58 (grupo 1) eram inicialmente respondedores à primeira série da vacina (anti- HBs >=10 mUI/mL) e 63 (grupo 2) eram não respondedores. Após um período mediano de avaliação de 11 anos, nenhum dos pacientes teve evidência sorológica de infecção pelo VHB e 41/58 (70.7%) dos inicialmente respondedores mantinham anti-HBs >= 10 mUI/mL. Maior contagem de células T CD4+ e anti-HBs >= 100 mUI/mL, no momento da primeira série vacinal, estiveram associados à persistência de anti-HBs. Durante o período avaliado, 35/63 (55.6%) dos pacientes inicialmente não respondedores (grupo 2) soroconverteram com sucesso (anti-HBs >= 10 mUI/mL) em resposta a uma ou mais doses de reforço vacinal. Foi associado à soroconversão do anti-HBs o número de doses de reforço recebidas. A partir do momento da soroconversão (anti-HBs >=10 mUI/mL), 70 pacientes não receberam nenhuma dose adicional de vacina de hepatite B (grupo 3). Após um período mediano de 10 anos, 54/70 (77,1%) destes indivíduos mantinham anti- HBs >= 10 mUI/mL. CONCLUSÕES: A avaliação dos marcadores sorológicos para VHB em PVHA vacinadas previamente para hepatite B evidenciou: alta persistência de anti-HBs após um período de 10 a 11 anos; doses adicionais de vacina foram capazes de induzir resposta humoral em indivíduos inicialmente não respondedores; não foram detectados marcadores sorológicos de infecção (HbsAg ou Anti-HBc) após 11 anos da vacinação inicial / BACKGROUND: Hepatitis B Virus (HBV) infection is responsible for great part of chronic hepatic diseases worldwide. In people living with HIV (PLHIV), HBV infection has more risk of progressing to cirrhosis and hepatocarcinoma. Hepatitis B vaccine is important in the prevention of a potentially severe disease, particularly in PLHIV, since both viruses have the same routes of transmission and co-infection has greater morbidity. Immunocompetent individuals have a good humoral response after the first hepatitis B vaccine series and no recommendation is made regarding booster doses. PLHIV may have a poor hepatitis B vaccine response, when compared to immunocompetent and the duration of immunity in these patients is unknown. OBJECTIVES: General: Evaluate serological markers of infection and protection from HBV in PLHIV previously vaccinated for hepatitis B. Specific: Evaluate anti-HBs persistence in PLHIV previously vaccinated for HBV who responded to a primary vaccine series; evaluate response to revaccination for hepatitis B in patients who did not respond to first vaccine series; investigate serological markers of infection from HBV in PLHIV previously vaccinated for hepatitis B. METHODS: Observational retrospective study of a PLHIV cohort primarily vaccinated between 2001 and 2002 for hepatitis B. Serological markers of infection and protection from HBV were investigated in those patients who were still attending the HIV/AIDS Patient Care Extension Service at the Clinical Division of Infectious and Parasitic Diseases attached to Hospital das Clínicas at Faculdade de Medicina at Universidade de São Paulo between 2012 and 2014. RESULTS: A cohort of 121 PLHIV was analyzed for seroconversion and persistence of anti-HBs. The majority were female (54.5%) and mean age 50.1 years. From these patients, 58 (group 1) were initially responders to the first vaccine series (anti- HBs >=10 mIU/mL) and 63 (group 2) were non- responders. After a median period of 11 years, none of the patients had serologic evidence of HBV infection and 41/58 (70.7%) of the initially responders had maintained anti-HBs >=10 mIU/mL. Greater CD4+ cell counts and anti- HBs>= 100mIU/mL at the time of first vaccine series were associated with persistence of anti-HBs. During evaluation period, 35/63 (55.6%) of the initially non-responders (group 2) successfully seroconverted (anti-HBs >=10 mIU/mL) in response to one or more booster doses. Booster doses may be effective in PLHIV. Number of booster doses were associated to seroconversion. Seventy of the 121 patients did not receive any further booster doses of hepatitis B vaccine from the time of their seroconversion (anti-HBs >=10 mIU/mL) (group 3). After 10 years of the seroconversion, 54/70 (77,1%) of these individuals has maintained anti- HBs >= 10 mIU/mL. CONCLUSIONS: Evaluation of serological markers for HBV in PLHIV previously vaccinated for hepatitis B showed: strong persistence of anti-HBs after a period of 10 to 11 years; additional vaccine doses elicited humoral response in initially non-responders; there was no serologic evidence of HBV infection (HbsAg ou Anti-HBc) about 11 years after initial vaccination