Coopera��ão e conflito entre britânicos e portugueses na Ásia. Dos primeiros contactos em Bombaim (c.1600-1740)

A aquisição da ilha de Bombaim pela coroa inglesa e a consequente convivência fronteiriça com o Estado da Índia constituiu uma novidade relacional e diplomática entre os poderes português e britânico, não só no Índico como em todo o espa��o ultramarino. Esta nova situa��ão projectou a recentemente forjada e renovada aliança anglo-portuguesa para um diferente plano, até então não experienciado. De facto, o acordo de 1661 estipulou que o Estado da Índia entregasse parte do seu território a uma coroa europeia, o que significava uma mudança no seu paradigma de actua��ão e a partilha de fronteiras comuns com um vizinho europeu, “consentido” e aliado. A isto adicionava-se o facto da popula��ão residente em Bombaim, constituída por uma forte comunidade de grandes foreiros portugueses e jesuítas, passar a estar sujeita aos dictames da coroa inglesa. Todos estes pressupostos constituíram uma novidade para o Estado da Índia e para os seus súbditos e exigiram, necessariamente, uma adapta��ão no modo de interacção com tão próximo vizinho. O mesmo se terá passado com os oficiais britânicos, numa primeira fase da coroa (1665-1668) e doravante da East India Company, para quem o domínio territorial no espa��o asiático constituía uma experiência nova. Esta realidade tão próxima entre as duas potências europeias originou, necessariamente, a eclosão de problemas e tensões entre as duas estruturas de poder. Será a partir desta conjuntura sugestiva que procuraremos compreender como o entendimento anglo-português na Europa foi transposto e gerido na esfera ultramarina, através da análise do caso paradigmático de Bombaim. A gestão da aliança naquele espa��o assumiu contornos espec��ficos e de difícil administra��ão, pois a distância ditava uma maior autonomia decisória das autoridades de Goa e Bombaim, nem sempre em consonância com as directrizes europeias. A interacção na região de Bombaim e espa��os adjacentes foi pautada pela flexibilidade e, por isso, caracterizou-se por momentos de antagonismo, coopera��ão e conflito aberto. Nestes “encontros de (in)conveniência���, ambos os lados procuraram tirar partido das dinâmicas conjunturais da política indiana, o mesmo aplicando-se no sentido inverso, adaptando-se alinhamentos e rupturas consoante os interesses imediatos. Bombaim foi, assim, singular no relacionamento anglo-português na Ásia, o que não implica que não se procure compreender as ressonâncias da intera��ão entre portugueses e britânicos noutros espa��os do subcontinente indiano (como Madrasta) ou contrapor os modos de actua��ão da EIC noutros locais (como Cochim). Na disserta��ão em curso, propomos efectuar um estudo de longo tempo, que analise de forma sistemática a transversal as dinâmicas relacionais entre britânicos e portugueses desde a introdução britânica na Ásia até à perda portuguesa da Província

A percepção da ordem e a consciência do tempo em Mari no período Paleo-Babilónico (séc. XIX- XVIII a. C.)

O presente estudo tem como objectivo estudar as questões do tempo e da ordem no reino de Mari. A análise destas questões evidencia dois aspectos importantes: por um lado, a convergência de duas culturas distintas – uma cultura acádica, tipicamente mesopotâmica, e uma cultura amorrita, mais ocidental – num mesmo espa��o e, por outro lado, a importância do reino de Mari como um estudo de caso que retrata, por vezes com grande pormenor, a influência da penetra��ão dos povos nómadas nas terras da Mesopotâmia e as suas repercussões nos vários domínios da vida pública. Estudar a ordem implica compreender a organiza��ão do mundo e da sociedade, bem como a rela��ão entre as esferas humana e celeste. Estudar o tempo implica, por sua vez, entender como o homem se posiciona no espa��o, como entende a sua história e o seu destino. Uma análise focada nestes dois temas permitir-nos-á, pois, compreender qual era o verdadeiro sentido da vida e do mundo para o homem de Mari. Como veremos, para o mariota, a vida assentava numa intensa dinâmica na qual a família detinha o papel principal: era ela que o enquadrava na sociedade, que lhe permitia participar nos destinos da vida pública e receber as devidas honras após a morte. Nesta perspectiva, a família e os la��os de sangue adquiriam um papel preponderante em vários domínios da vida humana. Eram os la��os consanguíneos que imperavam aquando da escolha de aliados e partidários. Por outro lado, o culto do parentesco impunha uma visão da história segundo a qual o tempo passado se afirmava como o grande modelo teórico das acções desenvolvidas no quotidiano (no presente). Paralelamente à família, o homem de Mari acreditava que no mundo divino residia a sua verdadeira esperança de levar uma vida feliz. A imagem de uma teocracia, onde homem e deus partilhavam o mesmo destino, é transversal a todo o pensamento e acção do homem de Mari. Nesta tese, propomos desenvolver um estudo de conjunto, uma análise transversal que abranja todos os aspectos da vida social e humana: a religião, a política, a cultura e a sociedade

Vitamin C effects in mice experimentally infected with Trypanosoma cruzi QM2 strain

INTRODUCTION: To evaluate the efficacy of vitamin C in reducing the consequences generated by the production of free radicals in the acute and chronic phases of Chagas disease, two different doses of ascorbic acid were administered orally to 60 mice infected by Trypanosoma cruzi QM2 strain. METHODS: The animals were divided into six groups: G1, G2, and G3 for the acute phase study, and G'1, G'2, and G'3 for the chronic stage. The groups G1 and G'1 received 8.6x10-4mg/g of vitamin C daily, whereas G2 and G'2 received 7.14x10-3mg/g daily. The other groups, G3 and G'3, were considered placebos and received 10µL of mineral water. RESULTS: The study of the acute phase showed statistically significant differences between G1 and the other groups at various count days of the parasitemia evolution. The multiplying parasite was slower in G1 until the 11th day, but on the 22nd day it had greater parasitemia than in G2 and G3, and from the 36th day on, parasitemia stabilized at higher levels. However, when the histopathology of acute and chronic phases is considered, one does not note significant differences. CONCLUSIONS: The administration of two different doses of vitamin C was not able to protect mice and to contain the oxidative stress caused by free radicals formed by the metabolism of oxygen (reactive oxygen species) and nitrogen (reactive nitrogen species).

Avalia��ão da monitoriza��ão diária da proteína C-Reativa no doente crítico

RESUMO: O objectivo desta Tese de Doutoramento foi estudar o valor da Proteína CReactiva(PCR) como marcador de infec��ão e sepsis. Por definição, um marcador da infec��ão não está presente se o doente não está infectado, deve aparecer concomitantemente ou idealmente preceder a instala��ão da infec��ão, deve desaparecer com a instituição de terapêutica antimicrobiana adequada e permanecer elevado se a infec��ão for refractária ao tratamento. Do ponto de vista biológico, a PCR é o protótipo das proteínas de fase aguda, com uma marcada eleva��ão da sua concentra��ão sérica em resposta a diversos estímulos inflamatórios em particular infec��ões bacterianas. A sua concentra��ão sérica depende apenas da intensidade do estímulo e da velocidade de síntese hepática, não sendo influenciada por nenhum factor ou tratamento a não ser que este tenha influência directa sobre o estímulo desencadeante, o que a torna um marcador de infec��ão com grande potencial. Nesta Tese comparou-se a PCR com marcadores clássicos de infec��ão, temperatura e contagem leucocitária, em diversas situa��ões clínicas analisando doentes com infec��ões documentadas e doentes controlos, sem infec��ão. Globalmente os resultados dos trabalhos desta Tese mostram que a PCR é um bom marcador de infec��ão de acordo com a definição previamente apresentada. Em conjunto com a restante avalia��ão clínica e laboratorial, a monitoriza��ão diária da PCR nos doentes sem infec��ão mostrou ser útil como sentinela da infec��ão, isto é, apresenta valores baixos nos doentes sem infec��ão e sobe precocemente nos doentes que desenvolvem uma infec��ão. Nos doentes com infec��ão documentada revelou um ser bom marcador de resposta à terapêutica e evolução clínica, diminuindo naqueles que melhoravam e persistindo elevada nos que tinham mau prognóstico, bem assim como identificar diferentes perfis evolutivos. Em suma, a monitoriza��ão diária da PCR mostrou utilidade ao longo de todo o internamento na Unidade de Cuidados Intensivos, quer na presença quer na ausência de infec��ão. Deste todo, a monitoriza��ão diária da PCR pode a possibilitar uma utiliza��ão mais racional e judiciosa da terapêutica antimicrobiana, contribuindo dessa forma para uma diminuição da toxicidade e da pressão antibiótica, menor risco de emergência de resistências e finalmente diminuição dos custos. Uma vez que, os doentes internados nas Unidades de Cuidados Intensivos apresentam as mesmas doenças que os restantes doentes admitidos no hospital apenas se distinguindo pela sua maior gravidade, poder-se-á extrapolar que a PCR também é potencialmente um bom marcador de infec��ão nestes doentes. ----------------ABSTRACT: The aim of this PhD Thesis was to assess the value of C-Reactive Protein (CRP) as a marker of infection and sepsis. A marker of infection should be absent in a non-infected patient, should increase alongside or ideally precede the development of an infection, and finally should assess the therapeutic response, that is to say decrease or even disappear with adequate antimicrobial therapy or on the opposite remain elevated if the infection is refractory to the prescribed treatment. The biology of CRP makes it the prototype of acute phase proteins, with marked and sharp elevations of its serum concentration in response to several inflammatory stimulus in particular bacterial infections. Besides, CRP level depends only of the intensity of the stimulus and the rate of hepatic synthesis. Its concentration is not modified by any therapy or intervention. Only those interventions affecting the inflammatory process responsible for the acute phase reaction can change the CRP level. These properties make CRP a potentially good marker of infection. In this Thesis the value of CRP was studied in comparison to traditional markers of infection, like temperature and white cell count, in different clinical situations analysing patients with documented infections and a control group without infection. The aggregated results of the analysis presented in this Thesis illustrate that CRP could be used as a marker of infection. In conjunction with other clinical and laboratory manifestations of sepsis, daily CRP measurement in patients without infection was useful in prediction of infection as its concentration remains low in patients without infection whereas if an infection appears its levels raise markedly. In addition, in patients with documented infections CRP was useful as a marker of therapeutic response and follow-up, with marked decreases in patients with good outcome and remaining elevated in those with poor prognosis, as well as the recognition of different patterns of evolution. In summary, daily CRP measurement was helpful in critical ill patients along the entire Intensive Care Unit stay, both in the presence and in the absence of infection. As a result, daily CRP measurement can assure a better and more rational use of antibiotics and consequently contribute to a decrease in the antibiotic toxicity and demand, reducing the risks of emergence of resistant strains aas well as costs. Provided that patients admitted to an Intensive Care Unit presented the same clinical diagnosis as those admitted to the wards but with higher severity, one can speculate that CRP is also a potentially good marker of infection in these of patients.

Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

INTRODUCTION: Approximately 30% of hepatitis C virus (HCV) monoinfected patients present persistently normal alanine aminotransferase (ALT) levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV) coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive) with known time of HCV infection (intravenous drugs users) were selected. Patients with hepatitis B surface antigen (HBsAg) positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80%) were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26%) patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001) periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001) and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year) significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

Quality of life of patients with hepatitis C

INTRODUCTION: Self-report on the quality of life (QOL) is increasingly studied in the evaluation of various diseases, especially in chronic ones. However, there are few data in the literature focusing the QOL of patients living with chronic hepatitis C. The objective of this study was to evaluate the QOL in patients with hepatitis C assessed by the World Health Organization Quality of Life Assessment (WHOQOL)-bref scale. METHODS: One hundred and eight hepatitis C patients attending the Outpatient Healthcare Medical Specialties in Tubarão, State of Santa Catarina, Brazil, were contacted from May 2010 to February 2011. Patients answered the WHOQOL-bref scale and a questionnaire about their treatment and risk factors to hepatitis C virus (VHC) infection. RESULTS: Although most of patients with chronic hepatitis C considered their QoL good or very good (58.1%), 47 (44.8%) patients were poorly or very poorly satisfied with their health. About the WHOQOL answers, the environment domain had the highest score (25.15 + 5.77), while the lowest score was the social relationships domain (9.19 + 2.5). There was statistically significant association between household income and quality of life in all domains (p<0.001) and statistically significant association between education and the physical, psychological and social domains of quality of life (p<0.05). CONCLUSIONS: Based on the answers given in WHOQOL-bref, patients with chronic hepatitis C have a generally poor QOL, especially in social relationship domain. Household income and educational level were factors that interfered significantly with patients' QOL assessment.

Transplanta��ão hepática no C. H. Porto

RESUMO - Contexto: a actividade de transplanta��ão hepática envolve um número considerável de profissionais multidisciplinares e, possui uma alocação de verbas importante do ponto de vista do administrador hospitalar. Estudar e analisar a actividade de transplanta��ão hepática no Centro Hospitalar do Porto (CHP), é por isso, objecto do trabalho. Objectivos: Efectuar uma análise custo/proveito do processo de transplanta��ão hepática para o CHP nos anos de 2010, 2011 e 2012 e, caracterizar a popula��ão em estudo com o maior número de variáveis possível. Metodologia: Seleccionou-se para análise os pacientes com o Grupo de Diagnóstico Homogéneo (GDH) 480 que realizaram transplante hepático entre 1 de Janeiro de 2010 até 30 de Junho de 2012 de modo a quantificar os custos e proveitos dos 161 pacientes desde a fase pré-transplante, passando pelo internamento até aos 6 meses após a alta hospitalar da fase pós-transplante. Na análise de custos da fase pré-transplante consideraram-se os custos com recursos humanos (RH) médicos das consultas e o custo com meios complementares de diagnóstico e terapêutica (MCDT’s). Na fase de internamento considerou-se os custos relativos à cirurgia (RH e material de consumo clinico e farmacológico) e diárias de internamento. Para a fase pós-transplante contabilizou-se os custos relativos a RH médicos das consultas, o custo com MCDT’s e fármacos. O apuramento de proveitos decorreu do contrato programa da instituição, da Portaria 839-A/2009 de 31 de Julho para o c��lculo pelo peso relativo do transplante hepático, pelo Despacho nº 19964/2008 de 28 de Julho para a comparticipa��ão dos fármacos. Considerou-se ainda o incentivo à transplanta��ão pelos Despachos nº6155/2006, de 15 de Março e nº 10485/2011, de 19 de Agosto. Resultados: Da análise global dos 161 GDH’s o verificado foi um custo total para o CHP de 7.505.518,89euro (um custo médio de 46.618,13euro por paciente). Quanto aos proveitos utilizando o contrato programa do CHP bem como os Despachos relativos ao incentivo à transplanta��ão e à comparticipa��ão de fármacos, existiu proveitos de 7.089.462,77euro (proveito médio de 44.033,93euro). Se o c��lculo dos proveitos de internamento fosse pelo peso relativo do transplante hepático os proveitos seriam de 21.834.655,50euro (proveito médio de 135.618,98euro).

Secondary bronchiolitis obliterans organizing pneumonia during treatment of chronic hepatitis C: role of pegylated interferon alfa-2a

The treatment of chronic hepatitis C has frequent side effects such as cytopenias and neuropsychiatric symptoms. However, pulmonary toxicity associated with interferon is rarely described. This paper describes the clinical case of a 67-year-old female patient with chronic hepatitis C who presented an acute onset of dry cough, dyspnoea, and fever 36 weeks after the use of pegylated interferon alfa-2a and ribavirin. The lung biopsy confirmed the diagnosis of a bronchiolitis obliterans organizing pneumonia (BOOP). Corticotherapy was initiated, with clinical and radiological improvement. This paper aims to advise physicians to this occasional, though severe, adverse event related to hepatitis C virus (HCV) treatment.

Hepatitis C and cutaneous alterations

While most of those infected with hepatitis C virus (HCV) are asymptomatic or only develop liver manifestations, a significant percentage evolves with autoimmune and lymphoproliferative disorders, resulting in a clinical condition called HCV syndrome. This work involving case studies of six patients with hepatitis C and varied skin manifestation aimed to report skin lesions occurring with HCV infection and its treatment. Skin manifestations in hepatitis C have been based on epidemiological studies. This justifies the need for studies that correlate HCV infection and its treatment with skin manifestations.

Evaluation of the therapeutic response of hepatitis C in coinfected patients (HIV/HCV): a study of cases from a hospital for chronic liver diseases in the Eastern Brazilian Amazon

INTRODUCTION: The aim of this study was to evaluate the therapeutic response of hepatitis C in patients coinfected with human immunodeficiency virus (HIV-1). METHODS: A retrospective study of 20 patients coinfected with HIV-1/HCV who were treated in the outpatient liver clinic at the Sacred House of Mercy Foundation Hospital of Pará (Funda&#231;ão Santa Casa de Miseric&#243;rdia do Pará - FSCMPA) from April 2004 to June 2009. Patients were treated with 180µg PEG interferon-α2a in combination with ribavirin (1,000 to 1,250mg/day) for 48 weeks. The end point was the sustained virological response (SVR) rate (HCV RNA negative 24 weeks after completing treatment). RESULTS: The mean age of the patients was 40±9.5 years, of which 89% (n=17) were male, and the HCV genotypes were genotype 1 (55%, n=11/20), genotype 2 (10%, n=2/20) and genotype 3 (35%, n=7/20). The mean CD4+ lymphocyte count was 507.8, and the liver fibrosis stages were (METAVIR) F1 (25%), F2 (55%), F3 (10%) and F4 (10%). The early virological response (EVR) was 60%, the end-of-treatment virological response (EOTVR) was 45% and the SVR was 45%. CONCLUSIONS: The median HCV viral load was high, and in 85% of cases in which highly active antiretroviral therapy (HAART) was used, none of the patients with F3-F4 fibrosis responded to treatment. Of the twenty patients treated, 45% achieved SVR and 45% achieved EOTVR. Studies that include cases from a wider region are needed to better evaluate these findings.

Epidemiology of the viral hepatitis B and C in female prisoners of Metropolitan Regional Prison Complex in the State of Goiás, Central Brazil

INTRODUCTION: Little information regarding hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among Brazilian female prisoners exists. This study investigated the prevalence and risk factors associated with HBV and HCV infections and identified viral genotypes among female prisoners in Goiás, Central Brazil. METHODS: Women incarcerated in the largest prison in the State of Goiás were invited to participate in the study. All female prisoners were interviewed and tested for the detection of hepatitis B surface antigen (HBsAg), antibodies against HBsAg (anti-HBs), against hepatitis B core antigen (anti-HBc), and antibody against HCV (anti-HCV) by ELISA. HBsAg and anti-HCV positive samples were tested for HBV DNA and HCV RNA and genotyped, respectively. RESULTS: Participants (n=148; 98.6%) completed the study with an overall HBV prevalence of 18.9%. Age >30 years, a low education level, sex with a sexually transmitted diseases carrier, and a male sexual partner serving in the same penitentiary were associated with HBV infections. Only 24% of the women were anti-HBs positive suggesting previous HBV vaccination. Nine female prisoners (6.1%) were anti-HCV positive. Age >40 years, injecting drug use and length of incarceration were statistically associated with anti-HCV antibodies. Five samples were HCV RNA positive and classified as genotypes 1 (subtypes 1a; n=3 and 1b; n=1) and 3 (subtype 3a; n=1). The HBsAg-reactive sample was HBV DNA positive and genotype A. CONCLUSIONS: These findings highlight the necessity of public policies to control hepatitis B and C infections and emphasize the importance of hepatitis B vaccination in prison environments.

Autoantibody profile in individuals with chronic hepatitis C

IntroductionAutoantibodies are often produced during infection with chronic hepatitis C virus (HCV), but it remains controversial whether they influence the biochemical profile and histological features of this disease. Therefore, this current study sought to describe these autoantibodies and evaluate their impact on the clinical and histological presentation of hepatitis C.MethodsThis cross-sectional analytical study assessed patients with HCV (RNA+) from October 2011 to July 2012.ResultsThis study included 66 patients, with a mean age of 53.2±10.5 years. Of these patients, 60.6% were male, and 54.3% presented with genotype 1. Non-organ-specific autoantibodies (NOSA) were detected in 24% of the patients; of these, 7.6% were anti-mitochondrial antibodies (AMA+), 26.7% were anti-smooth muscle antibodies (SMA+) and 6.8% were liver kidney microsomal type 1 antibodies (LKM1+). With respect to the thyroid autoantibodies, 7.4% were anti-peroxidase (ATPO+) antibodies, and none were anti-thyroglobulin (ATG+) antibodies. Regarding celiac disease autoantibodies, 5.8% were endomysial antibodies (EMA+), and no transglutaminase (TTG+) antibodies were detected. Cryoglobulins were found in 2.1% of patients. When NOSA+ individuals were compared to patients without the presence of NOSAs, they exhibited higher median alkaline phosphatase (0.7 vs. 0.6 xULN; p=0.041), lower median platelet counts (141,500.0 vs. 180,500.0/mm3; p=0.036), lower mean prothrombin activity (72.6±11.5% vs. 82.2±16.0%; p=0.012) and an increased prevalence of significant fibrosis (E≥2) (45.5% vs. 18.2%; p=0.012). There was also a tendency for a greater proportion of NOSA+ cases to have marked periportal activity (APP≥3) (44.5% vs. 15.6%; p=0.087).ConclusionsIn addition to the high prevalence of autoantibodies associated with HCV infection, it was observed that NOSA positivity was associated with a more severe histological and biochemical profile of hepatitis C infection.

In vitro detection of hepatitis C virus in platelets from uninfected individuals exposed to the virus

IntroductionDespite hepatocytes being the target cells of hepatitis C virus (HCV), viral ribonucleic acid RNA has been detected in other cells, including platelets, which have been described as carriers of the virus in the circulation of infected patients. Platelets do not express cluster differentiation 81 CD81, the main receptor for the virus in hepatocytes, although this receptor protein has been found in megakaryocytes. Still, it is not clear if HCV interacts with platelets directly or if this interaction is a consequence of its association with megakaryocytes. The aim of this study was to evaluate the interaction of HCV with platelets from non-infected individuals, after in vitro exposure to the virus.MethodsPlatelets obtained from 50 blood donors not infected by HCV were incubated in vitro at 37°C for 48h with serum containing 100,000IU∕mL of genotype 1 HCV. After incubation, RNA extracted from the platelets was assayed for the presence of HCV by reverse transcription – polymerase chain reaction RT-PCR.ResultsAfter incubation in the presence of virus, all samples of platelets showed HCV RNA.ConclusionsThe results demonstrate that, in vitro, the virus interacts with platelets despite the absence of the receptor CD81, suggesting that other molecules could be involved in this association.

HIV, hepatitis B and C, and syphilis prevalence and coinfection among sex workers in Southern Brazil

Introduction Sex workers (SWs) are vulnerable to HIV, hepatitis, and syphilis coinfection. Methods A cross-sectional study was conducted in Tubarão, Laguna, and Imbituba, Southern Brazil. We surveyed 147 SWs using face-to-face interviews and blood sampling for serological evaluation. Results Prevalence of hepatitis B (HBV) was 23.1%, syphilis 19.7%, hepatitis C (HCV) 8.8%, and HIV 8.8%. Of 13 HIV-infected patients, 3 were co-infected with HCV, 4 with syphilis, and 5 with HBV. Conclusions SWs had high HIV infection rates, and coinfection with viral hepatitis and syphilis.