Relationship between the prevalence of antibodies to hepatitis B core antigen and arbovirus in fishermen from the Ribeira Valley, Brazil

Sera from 299 fishermen 16 to 80 years old, residents in Cananeia and Iguape counties, southern cost of São Paulo State, Brazil, were studied in order to identify a possible association between the prevalence of specific antibodies to the hepatitis B virus (HBV) and exposure to haematophagus mosquitoes evaluated by the prevalence of arbovirus antibodies. This professional group presented the highest prevalence of arbovirus antibodies (54.1%) in past investigations carried out in this heavily forested region. Detection of antibody to hepatitis B core antigen (anti-HBc) in the sera was done by enzyme immunoassay (Roche). Prevalence of anti-HBc antibodies in this group was 31.4% (94/299) which is very high compared with 7.2% to 15.0% for different groups of healthy adults in State of São Paulo. No significant difference is observed between the prevalences of HBV antibodies in Iguape and Cananeia. Prevalence of anti-HBc and anti-arbovirus antibodies increases with age. There is a concordance in the distribution according to age groups of the frequency of anti-HBc and anti-arbovirus positive sera. Ag HBs was detected in 4% of the studied sera. These results support the hypothesis that the transmission of the hepatitis B virus and the arboviruses may be due to the same factor, one of the possibilities would be by anthropophilic mosquitoes.

Immunogenicity of three recombinant hepatitis B vaccines administered to students in three doses containing half the antigen amount routinely used for adult vaccination

We evaluated the immunogenicity of three recombinant hepatitis B vaccines, one Brazilian (Butang, Instituto Butantan) and two Korean vaccines (Euvax-B, LG Chemical Ltd. and Hepavax-Gene, Greencross Vaccine Corp.), administered intramuscularly to students aged 17 to 19 years in three 10-µg doses (corresponding to half the amount of antigen routinely used for adult vaccination) at intervals of one month between the first and second dose, and of four months between the second and third dose. A total of 316 students non-reactive for any serological marker of hepatitis B virus infection were vaccinated: 77 (24.4%) with the Butang vaccine, 71 (22.5%) with Euvax-B, 85 (26.9%) with Hepavax-Gene and, for comparison, 83 (26.2%) with Engerix-B (GlaxoSmithKline), whose efficacy in young adults at the dose used here has been confirmed in previous studies. Similar seroconversion rates (anti-HBs > 10 mIU/mL about one month after application of the third dose) were obtained for the Butang, Euvax-B, Hepavax-Gene and Engerix-B vaccines (96.2%, 98.6%, 96.5% and 97.6%, respectively). The frequency of good responders (anti-HBs > 100 mIU/mL) was also similar among students receiving the four vaccines (85.8%, 91.6%, 89.4% and 89.2%, respectively). The geometric mean titers (GMT) of anti-HBs about one month after the third dose obtained with these vaccines were 727.78 ± 6.46 mIU/mL, 2009.09 ± 7.16 mIU/mL, 1729.82 ± 8.85 mIU/mL and 2070.14 ± 11.69 mIU/mL, respectively. The GMT of anti-HBs induced by the Euvax-B and Engerix-B vaccines were higher than those obtained with the Butang vaccine (p < 0.05); this difference was not significant when comparing the other vaccines two-by-two. No spontaneous adverse effects attributable to the application of any dose of the four vaccines were reported.

Influence of human t-cell lymphotropic virus type 1 (HTLV-1) Infection on laboratory parameters of patients with chronic hepatitis C virus

Hepatitis C virus (HCV) and human T-cell lymphotropic virus type 1 (HTLV-1) share routes of transmission and some individuals have dual infection. Although some studies point to a worse prognosis of hepatitis C virus in patients co-infected with HTLV-1, the interaction between these two infections is poorly understood. This study evaluated the influence of HTLV-1 infection on laboratory parameters in chronic HCV patients. Twelve HTLV-1/HCV-coinfected patients were compared to 23 patients infected only with HCV, in regard to demographic data, risk factors for viral acquisition, HCV genotype, presence of cirrhosis, T CD4+ and CD8+ cell counts and liver function tests. There was no difference in regard to age, gender, alcohol consumption, smoking habits, HCV genotype or presence of cirrhosis between the groups. Intravenous drug use was the most common risk factor among individuals co-infected with HTLV-1. These patients showed higher TCD8+ counts (p = 0.0159) and significantly lower median values of AST and ALT (p = 0.0437 and 0.0159, respectively). In conclusion, we have shown that HCV/HTLV-1 co-infected patients differs in laboratorial parameters involving both liver and immunological patterns. The meaning of these interactions in the natural history of these infections is a matter that deserves further studies.

Identification of mechanisms controlling the transcriptional activity of nuclear factor kappa B (NF-κB) p65/RelA

Dissertação para a obtenção do grau de doutor em Biologia pelo Instituto de Tecnologia Química e Biológica. Universidade Nova de Lisboa.

Nitric oxide levels are not changed in saliva of patients infected with hepatitis C virus

The aim of this investigation was to determine nitric oxide metabolite levels in saliva samples from hepatitis C virus-positive patients in an attempt to test the hypothesis if increased levels of nitric oxide metabolites correlates with the presence of HCV-RNA in saliva. Saliva of 39 HCV-positive patients and 13 HCV-negative patients, without clinical or laboratorial evidence of liver disease were tested for nitric oxide metabolites. HCV-RNA was detected in serum and saliva by a RT-PCR method and nitric oxide level was determined by evaluation of its stable degradation products, nitrate and nitrite. No differences were found between the concentration of nitrite in saliva from HCV patients and controls, in despite of the presence or not of HCV RNA in saliva. Patients with HCV and cirrhosis had higher concentrations of nitrite but not significantly different from the control group or the groups of anti-HCV patients without cirrhosis. Increased levels of nitrite were not detected in anti-HCV positive patients, an indirect indication that chronic sialoadenitis are infrequent in these patients or occurs with low intensity not sufficient to increase nitric oxide metabolite levels in saliva.

Role of Yap8 and Yap1 b-ZIP transcription factors in arsenic stress

Arsenic compounds are highly toxic substances; nevertheless they are used in the treatment of acute promyelocytic leukaemia. Therefore it is pressing to gain knowledge on its toxicity and detoxification mechanisms. The cellular entry pathways have been discovered and by transcriptome analysis it is known that arsenic activates the transcription of genes activated by, among others, Rpn4, Met4 and Yap1.(...)

Seroprevalence and risk factors for canine visceral leishmaniasis in the endemic area of Dias D'Ávila, State of Bahia, Brazil

INTRODUCTION: Visceral leishmaniasis (VL) is an important zoonosis in relation to public health systems. Dogs are the main domestic reservoir. This study aimed to investigate occurrences of canine VL in Dias D'Ávila, State of Bahia, Brazil. METHODS: The prevalence was evaluated by means of clinical and laboratory tests on a population of 312 domestic dogs from 23 localities in this municipality, using indirect immunofluorescence and immunoenzymatic assays. RESULTS: Among the animals examined, 3.2% and 6.7% showed signs of VL, confirmed by indirect immunofluorescence and immunoenzymatic assays, respectively, with a distribution of 29.9% (24 dogs) in the rural zone and 4.9% (288 dogs) in the urban zone (p = 0.001). The clinical evaluation on seropositive dogs showed both asymptomatic animals (2.4%) and symptomatic animals (47.6%), along with other abnormalities (e.g. normocytic and normochromic anemia, with leukocytosis and thrombocytopenia). Observations relating to phenotypic characteristics (e.g. sex, age, breed and hair) did not present statistical significance, although high seropositivity among male, short-haired and mixed-breed dogs was observed. CONCLUSIONS: The findings showed that VL was a predominantly rural zoonosis and that close contact between poultry and domestic dogs significantly increased the risk of canine infection in this region.

Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in southeastern Brazil: predominance of HBeAg negative cases

INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60% of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4% of the patients, among whom the risk of vertical/intrafamily transmission was 43.2% (p = 0.02). The consumption of alcohol in amounts exceeding 20g a day was observed in 21.3% of the subjects and was more frequent among men (33%) (p < 0.001). Among patients with cirrhosis, 54.1% were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4%) than in the HBeAg-negative group (10.2%) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.

Antibody levels in children after 10 years of vaccination against hepatitis B: a brazilian community-based study

INTRODUCTION: It is known that the hepatitis B (HB) vaccine is effective, but it is alarming that sudden drops of antibody levels may coincide with the onset of adolescence. METHODS: Antibody levels against HB vaccine surface antigen (anti-HBs) and HB vaccine core antigen (anti-HBc) were measured on the blood samples of children with a mean age of 11.4 years. RESULTS: About 54.8% had protective levels of anti-HBs. Of those who were anti-HBc-positive (4.4%), an average of 218.4 anti-HBs mIU/mL was found. CONCLUSIONS: Immunological protection was found in the majority of children. However, more studies are needed to elucidate the heritability of nonresponders and establish strategies against such events.

Prevalence of hypovitaminosis D and its association with oral lesions in HIV-infected Brazilian adults

Abstract: INTRODUCTION: This study assessed the prevalence of hypovitaminosis D and its association with oral candidiasis and clinical parameters of periodontitis (CPP) in HIV-infected patients. METHODS: Periodontal examinations for the 113 HIV-infected patients were recorded using the Community Periodontal Index. A cytological smear from the lateral borders of the tongue was performed to evaluate candidiasis. RESULTS: The frequency of hypovitaminosis D was 23.9%. In multivariate analysis, only the duration of exposure to HIV was associated with CPP [OR 4.72 (95% CI: 0.97-23.00)]. CONCLUSIONS: The prevalence of hypovitaminosis D was 23.9% and was not related with oral candidiasis or CPP.

A doença pulmonar obstrutiva crónica e o exercício: impacto da doença no declínio funcional e importância do treino de exercício nos benefícios para a saúde

RESUMO: A reabilitação respiratória (RR) é uma intervenção abrangente e interdisciplinar dirigida aos doentes respiratórios crónicos e inclui o treino de exercício, programas de educação e de modificação comportamental, entre outros, desenhados individualmente para melhorar o desempenho físico e psicossocial e promover a adesão a longo prazo a comportamentos promotores de saúde. A doença pulmonar obstrutiva crónica (DPOC) é uma doença comum, afetando cerca de 210 milhões de pessoas em todo o mundo, com elevada mortalidade e com custos económicos significativos decorrentes do agravamento progressivo da doença, das hospitalizações e de reinternamentos frequentes. Apesar do crescente conhecimento da DPOC e do papel da RR nos benefícios para a saúde, existem aspetos ainda não esclarecidos que têm impacto na prática clínica e de investigação e nas decisões das autoridades de saúde. A primeira parte desta tese focou a DPOC e o seu impacto negativo e incluiu: o estudo da prevalência da DPOC em Portugal; os fatores clínicos e funcionais que se associam à mortalidade em doentes com DPOC avançada; a morbilidade, impacto funcional e risco dos doentes se tornarem dependentes para as atividades diárias e a influência da inflamação sistémica. A prevalência estimada da DPOC de 14,2% indica que esta é uma doença comum em Portugal e alerta para a necessidade de uma maior sensibilização da população, dos profissionais de saúde e autoridades de saúde com vista a um diagnóstico precoce e à alocação dos recursos terapêuticos adequados. A elevada taxa de mortalidade em doentes com DPOC avançada - 36,6% em 3 anos - associou-se a insuficiência respiratória, a elevado número de exacerbações, ao cancro do pulmão e a reduzida capacidade funcional para a marcha, salientando a importância da referenciação precoce para RR, a identificação e o tratamento das comorbilidades e a prevenção das exacerbações. A aplicação de um questionário que avaliou as atividades da vida diária básicas e instrumentais, permitiu identificar um marcador clínico do risco de depend��ncia, complementando as avaliações funcionais e associando-se a outros marcadores de mau prognóstico, como as exacerbações. Em doentes com DPOC, com FEV1 médio de 46,76% (desvio padrão: 20,90%), 67% da categoria D do GOLD, verificou-se uma associação positiva entre a expressão de genes inflamatórios avaliada pela reação em cadeia da polimerase (ARN mensageiro de IFNg, IL1b, IL6, IL8, TNFa, TGFb1, iNOS) e o índice de massa corporal em repouso, acentuando-se após o exercício. Este estudo aponta a inflamação como o potencial elo de ligação entre a obesidade e a inflamação sistémica em doentes com DPOC. A segunda parte da tese focou a RR, nomeadamente os seus efeitos em doentes das categorias GOLD A, B, C e D; o impacto das comorbilidades nos resultados da RR e os resultados de diferentes intensidades de treino aeróbio. Após o programa de RR, verificaram-se melhorias significativas na capacidade de exercício funcional e de endurance e no estado geral de saúde dos doentes de todas as categorias GOLD. Esta classificação não distingue os doentes que melhor poderão beneficiar desta intervenção, indicando que devem ser referenciados para RR, os doentes sintomáticos ou com repercussão na qualidade de vida, independentemente da categoria da DPOC a que pertençam. A prevalência das comorbilidades no grupo de doentes com DPOC que é referenciado para RR, é elevada, sendo as mais frequentes, as cardiovasculares, as respiratórias e as psicológicas. Apesar de poderem diminuir o impacto da RR, os resultados desta foram semelhantes independentemente do número de comorbilidades. A identificação e o tratamento sistemáticos das comorbilidades conferem maior segurança clínica a esta intervenção terapêutica a qual, por apresentar bons resultados, não deve limitar a referenciação dos doentes. Com o programa de RR, verificou-se melhoria significativa em todos os resultados centrados no doente para ambas as intensidades de treino aeróbio, a 60% e a 80% da potência aeróbica máxima (Wmax), com melhoria do estado geral de saúde, nos sintomas e na capacidade para o exercício, o que questiona a indicação sistemática de elevadas intensidades de treino em doentes com DPOC para a obtenção de benefícios a curto prazo. Na terceira e última parte da tese foi estudado o papel da atividade física na DPOC, focando os fatores que influenciam a atividade física diária; a evolução da capacidade funcional e o estado de saúde 2 anos após um programa de RR e o papel da telemonitorização na quantificação e monitorização da atividade física. Confirmámos que os doentes com DPOC são marcadamente sedentários e os fatores que se associaram ao sedentarismo nestes doentes foram a dispneia e a distância percorrida na prova de marcha de seis minutos. Este estudo sublinha a importância do controlo sintomático, nomeadamente da dispneia, bem como, mais uma vez, o potencial papel da reabilitação respiratória no aumento da capacidade funcional para o exercício e na aquisição de hábitos de vida fisicamente ativa. Verificámos que, apesar de os doentes com DPOC apresentarem benefícios clinicamente significativos na capacidade funcional para o exercício e no estado geral de saúde com o programa de RR, apenas os que se mantêm ativos, podem, no final dos dois anos de seguimento, manter os efeitos benéficos desse programa. O sistema de telemonitorização que combina a oximetria e a quantificação da atividade física provou ser clinicamente útil na avaliação da necessidade de oxigenoterapia de longa duração (OLD) e na aferição do d��bito de oxigénio em repouso, no esforço e no sono, podendo contribuir para uma melhor adequação da prescrição da OLD. A monitorização dos níveis de atividade física regular é um importante instrumento de avaliação dos programas de RR e o seu uso potencial na telereabilitação permitirá prolongar a eficácia dos programas e reduzir os custos associados aos cuidados de saúde.---------------------------------------------------------------------------------------------------ABSTRACT: Pulmonary rehabilitation (PR) is a comprehensive interdisciplinary intervention that includes, but is not limited to, exercise training, education, and behavior change, individually designed to improve physical and psychological conditions of people with chronic respiratory disease and to promote long-term adherence to health-enhancing behaviors. Chronic obstructive pulmonary disease (COPD) is a common disease, affecting about 210 million people worldwide, with high mortality and significant health-related costs due to disease progression, hospitalizations and frequent hospital readmissions. Although the increasing knowledge about COPD and benefitial outcomes of PR, some aspects with impact in clinical practice, research and health authorities’ decisions, remain to be clarified. The first part of this thesis focused on COPD and its negative impact, including the study of COPD prevalence in Portugal; clinical and functional factors associated with mortality in advanced COPD patients; morbidity, functional impact and risk of others’ dependance to perform activities of daily living; and the role of systemic inflammation. The evidence of 14.2% estimated COPD prevalence as a common disease in Portugal raises the need of an increasing awareness of population, health care professionals and health authorities towards an earlier diagnosis and apropriate treatment resources allocation. High mortality in patients with advanced COPD – 36.6% in 3 years - was associated with respiratory failure, high frequency of exacerbations, lung cancer and a low functional capacity in walking. This highlightens the importance of an earlier referral to PR, comorbidity identification and treatment, and prevention of exacerbations. A questionnaire evaluated basic and instrumental activities of daily living, and identified a clinical marker of the risk of becoming dependent. This clinical marker complemented other functional evaluations and was associated with prognosis markers such as the number of exacerbations. In COPD patients with a mean FEV1 46.76% (SD 20.90%), 67% belonging to GOLD grade D, we found a positive association between inflammatory gene expression evaluated by polymerase chain reaction (IFNg, IL1b, IL6, IL8, TNFa, TGFb1, iNOS RNA messenger) and body mass index at rest, and a further increase with exercise. This study evidenced obesity as one potential link between COPD and systemic inflammation. The second part of this thesis focused PR, namely its outcomes in patients of GOLD categories A, B, C and D; comorbidities impact in PR outcomes, and the impact of different exercise training intensities in patient related outcomes. xviii With PR intervention, we found significant improvement in functional exercise capacity, endurance exercise capacity and health status in patients of all GOLD categories. This classification did not differentiate which patients would benefit more from PR, hence all symptomatic patients with a negative impact in health status should be referred to PR, regardless of the GOLD category they belong to. There is a high prevalence of comorbidities in COPD patients referred to PR, being cardiovascular, respiratory and psychological, the most prevalent. Although some comorbidities might reduce PR impact, the results were similar regardless of the number of comorbidities. Systematic comorbidities identification and treatment provides safety to PR intervention, and its good results should not preclude patients referral. With PR intervention we found a significant improvement in all patient reported outcomes for exercise training intensities at 60% and 80% maximum work rate (Wmax), namely in health status, symptoms and exercise capacity. These findings challenge the current systematic indication of high exercise training intensities to achieve PR short-term benefits. In the third and last part of the thesis, the role of physical activity in COPD was studied, focusing factors that may influence daily physical activity; the evolution of functional capacity and health status two years after a PR program, and the role of a telemonitoring system in physical activity quantification and monitoring. We confirmed that COPD patients are markedly inactive and factors associated with a sedentary lifestyle are dyspnea and 6 minute walking distance. This study emphasized the importance of symptom control, namely of dyspnea, as well as, once again, the potential role of PR in functional exercise improvement and in integrating physically active habits in daily life. We verified that, although COPD patients improve functional exercise capacity and health status after a PR program, only those who kept physical activity habits were able to maintain those effects after 2 years of follow-up. A telemonitoring system that combines oximetry and physical activity quantification proved to be clinically useful in the evaluation of long-term oxygen therapy (LTOT) indication, as well as in the titration of oxygen levels at rest, exertion, and sleeping, which might contribute to a more adequate LTOT prescription. Monitoring of daily physical activity levels is an important PR evaluation instrument and its potential use in telerehabilitation might allow lengthening programs efficacy, while reducing health-care costs.

Biomass production and essential oil yield from leaves, fine stems and resprouts using pruning the crown of Aniba canelilla (H.B.K.) (Lauraceae) in the Central Amazon

Aniba canelilla (H.B.K.) Mez. is a tree species from Amazon that produces essential oil. The oil extraction from its leaves and stems can be an alternative way to avoid the tree cutting for production of essential oil. The aim of this study was to analyse factors that may influence the essential oil production and the biomass of resprouts after pruning the leaves and stems of A. canelilla trees. The tree crowns were pruned in the wet season and after nine months the leaves and stems of the remaining crown and the resprouts were collected, in the dry season. The results showed that the essential oil yield and chemical composition differed among the stems, leaves and resprouts. The stems' essential oil production differed between the seasons and had a higher production in the resprouting stems than the old stems of the remaining crown. The production of essential oil and leaf biomass of resprouts were differently related to the canopy openness, indicating that light increases the production of the essential oil and decreases the biomass of resprouting leaves. This study revealed that plant organs differ in their essential oil production and that the canopy openness must be taken into account when pruning the A. canelilla tree crown in order to achieve higher oil productivity.

Endoparasite fauna of Brycon amazonicus and B. melanopterus(Characidae, Bryconinae) from Negro and Solimões rivers, Amazon, Brazil

ABSTRACTCongeneric host species present similar biological and behavioral aspects, what may favor the presence of a similar parasite fauna. The aim of the present study was to compare the composition and structure of the parasite community from congeneric species, Brycon amazonicus and B. melanopterus, collected on the Negro and Solimões Rivers. The fish internal organs were longitudinally opened and analyzed under stereomicroscope. The examination revealed that B. amazonicuswas parasitized by Procamallanus(Spirocamallanus) inopinatus(26.7% and 35.5%), Contracaecum type 2 (10% and 16.13%) and Rhabdochona acuminata(0% and 3.23%), prevalence values for Negro and Solimões River, respectively. The analysis of B. melanopterus, a fish species found only in the Solimões River, revealed P.(S.) inopinatus(33.3%), Contracaecum type 1 (60%) and R. acuminata(3.34%). These results indicate that the taxonomic proximity of the hosts was a stronger influence on the parasite species than external host environment.