Drimanes from Drimys brasiliensis with leishmanicidal and antimalarial activity

This paper evaluates CHCl3 and CH3OH extracts of the stem bark, branches and leaves of Drimys brasiliensis and drimane sesquiterpenes isolated from the stem bark against strains of Leishmania amazonensis and Leishmania braziliensis promastigotes and Plasmodium falciparum trophozoites. All of the extracts and compounds were tested in cell lines in comparison with reference standards and cell viability was determined by the XTT method. The CHCl3 and CH3OH extracts from the stem bark and branches yielded promising results against two strains of Leishmania, with 50% inhibitory concentrations (IC50 ) values ranging from 39-100 µg/mL. The CHCl3 extract of the stem bark returned IC50 values of 39 and 40.6 µg/mL for L. amazonensis and L. braziliensis, respectively. The drimanes were relatively effective: 1-β-(p-coumaroyloxy)-polygodial produced IC50 values of 5.55 and 2.52 µM for L. amazonensis and L. braziliensis, respectively, compared with 1-β-(p-methoxycinnamoyl)-polygodial, which produced respective IC50 values of 15.85 and 17.80 µM. The CHCl3 extract demonstrated activity (IC50 of 3.0 µg/mL) against P. falciparum. The IC50 values of 1-β-(p-cumaroyloxyl)-polygodial and 1-β-(p-methoxycinnamoyl)-polygodial were 1.01 and 4.87 µM, respectively, for the trophozoite strain. Therefore, the results suggest that D. brasiliensis is a promising plant from which to obtain new and effective antiparasitic agents.

Tuberculosis patients co-infected with Mycobacterium bovis and Mycobacterium tuberculosis in an urban area of Brazil

In this cross-sectional study, mycobacteria specimens from 189 tuberculosis (TB) patients living in an urban area in Brazil were characterised from 2008-2010 using phenotypic and molecular speciation methods (pncA gene and oxyR pseudogene analysis). Of these samples, 174 isolates simultaneously grew on Löwenstein-Jensen (LJ) and Stonebrink (SB)-containing media and presented phenotypic and molecular profiles of Mycobacterium tuberculosis, whereas 12 had molecular profiles of M. tuberculosis based on the DNA analysis of formalin-fixed paraffin wax-embedded tissue samples (paraffin blocks). One patient produced two sputum isolates, the first of which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, and the second of which only grew on SB media and presented phenotypic profiles of Mycobacterium bovis. One patient provided a bronchial lavage isolate, which simultaneously grew on LJ and SB media and presented phenotypic and molecular profiles of M. tuberculosis, but had molecular profiles of M. bovis from paraffin block DNA analysis, and one sample had molecular profiles of M. tuberculosis and M. bovis identified from two distinct paraffin blocks. Moreover, we found a low prevalence (1.6%) of M. bovis among these isolates, which suggests that local health service procedures likely underestimate its real frequency and that it deserves more attention from public health officials.

Antagonistic activity expressed by Shigella sonnei: identification of a putative new bacteriocin

Bacteriocins are antibacterial, proteinaceous substances that mediate microbial dynamics. Bacteriocin production is a highly disseminated property among all major lineages of bacteria, including Shigella. In this paper, we addressed the purification and characterisation of a bacteriocin produced by a Shigella sonnei strain (SS9) isolated from a child with acute diarrhoea. The substance was purified through ammonium-sulphate precipitation and sequential steps of chromatography. The intracellular fraction obtained at 75% ammonium sulphate maintained activity following exposure to pH values from 1-11 and storage at -80ºC for more than two years and was inactivated by high temperatures and proteases. The molecular mass of the purified bacteriocin was determined by mass spectrometry to be 18.56 kDa. The N-terminal sequence of the bacteriocin did not match any other antibacterial proteins described. A putative new bacteriocin produced by S. sonnei has been detected. This bacteriocin may represent a newly described protein or a previously described protein with a newly detected function. Considering that SS9 expresses antagonism against other diarrhoeagenic bacteria, the bacteriocin may contribute to S. sonnei virulence and is potentially applicable to either preventing or controlling diarrhoeal disease.

Ecoepidemiology, short history and control of Chagas disease in the endemic countries and the new challenge for non-endemic countries

Chagas disease is maintained in nature through the interchange of three cycles: the wild, peridomestic and domestic cycles. The wild cycle, which is enzootic, has existed for millions of years maintained between triatomines and wild mammals. Human infection was only detected in mummies from 4,000-9,000 years ago, before the discovery of the disease by Carlos Chagas in 1909. With the beginning of deforestation in the Americas, two-three centuries ago for the expansion of agriculture and livestock rearing, wild mammals, which had been the food source for triatomines, were removed and new food sources started to appear in peridomestic areas: chicken coops, corrals and pigsties. Some accidental human cases could also have occurred prior to the triatomines in peridomestic areas. Thus, triatomines progressively penetrated households and formed the domestic cycle of Chagas disease. A new epidemiological, economic and social problem has been created through the globalisation of Chagas disease, due to legal and illegal migration of individuals infected by Trypanosoma cruzi or presenting Chagas disease in its varied clinical forms, from endemic countries in Latin America to non-endemic countries in North America, Europe, Asia and Oceania, particularly to the United States of America and Spain. The main objective of the present paper was to present a general view of the interchanges between the wild, peridomestic and domestic cycles of the disease, the development of T. cruzi among triatomine, their domiciliation and control initiatives, the characteristics of the disease in countries in the Americas and the problem of migration to non-endemic countries.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation.

Evaluation of Haemophilus influenzaetype b carrier status among children 10 years after the introduction of Hib vaccine in Brazil

The aim of the present study was to assess the prevalence of Haemophilus influenzaetype b (Hib) nasopharyngeal (NP) colonisation among healthy children where Hib vaccination using a 3p+0 dosing schedule has been routinely administered for 10 years with sustained coverage (> 90%). NP swabs were collected from 2,558 children who had received the Hib vaccine, of whom 1,379 were 12-< 24 months (m) old and 1,179 were 48-< 60 m old. Hi strains were identified by molecular methods. Hi carriage prevalence was 45.1% (1,153/2,558) and the prevalence in the 12-< 24 m and 48-< 60 m age groups were 37.5% (517/1,379) and 53.9% (636/1,179), respectively. Hib was identified in 0.6% (16/2,558) of all children in the study, being 0.8% (11/1,379) and 0.4% (5/1,179) among the 12-< 24 m and 48-< 60 m age groups, respectively. The nonencapsulate Hi colonisation was 43% (n = 1,099) and was significantly more frequent at 48-< 60 m of age (51.6%, n = 608) compared with that at 12-< 24 m of age (35.6%, n = 491). The overall resistance rates to ampicillin and chloramphenicol were 16.5% and 3.7%, respectively; the co-resistance was detected in 2.6%. Our findings showed that the Hib carrier rate in healthy children under five years was very low after 10 years of the introduction of the Hib vaccine.

Surveillance, health promotion and control of Chagas disease in the Amazon Region - Medical attention in the Brazilian Amazon Region: a proposal

We refer to Oswaldo Cruz’s reports dating from 1913 about the necessities of a healthcare system for the Brazilian Amazon Region and about the journey of Carlos Chagas to 27 locations in this region and the measures that would need to be adopted. We discuss the risks of endemicity of Chagas disease in the Amazon Region. We recommend that epidemiological surveillance of Chagas disease in the Brazilian Amazon Region and Pan-Amazon region should be implemented through continuous monitoring of the human population that lives in the area, their housing, the environment and the presence of triatomines. The monitoring should be performed with periodic seroepidemiological surveys, semi-annual visits to homes by health agents and the training of malaria microscopists and healthcare technicians to identify Trypanosoma cruzi from patients’ samples and T. cruzi infection rates among the triatomines caught. We recommend health promotion and control of Chagas disease through public health policies, especially through sanitary education regarding the risk factors for Chagas disease. Finally, we propose a healthcare system through base hospitals, intermediate-level units in the areas of the Brazilian Amazon Region and air transportation, considering the distances to be covered for medical care.

Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30%) or re-infection (20%). A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

Relationships and knowledge in the firm internationalization process

Based on the variables relationship and knowledge, this article aimed at analyzing how a multinational enterprise selects an entry mode to operate in a particular international market and how this initial choice evolves over time. We devised a rather new theoretical framework to address it by combining three theoretical approaches that have dealt with the firm internationalization: the Uppsala model, the relational approach, and the subsidiary development literature. We constructed a qualitative backward-looking longitudinal case study of the internationalization process of a North-American multinational enterprise in the Brazilian market. Results show that four types of relationships and three types of knowledge played the role in the events that characterized the internationalization of this firm. Based on these results, five new hypotheses concerning the interplay between relationships and knowledge in the internationalization process of the firm are suggested for future empirical tests.

A adesão ao tratamento na hipertensão arterial: análise da produção científica

O estudo teve como objetivo avaliar a produção científica publicada entre 1991 e 1995, para identificar como o assunto adesão ao tratamento anti-hipertensivo vem sendo abordado. Foram analisados 107 artigos científicos. Os resultados mostraram que a adesão foi abordada da seguinte maneira: 68% relacionaram ao paciente, 63% ao tratamento farmacológico, 62% a aspectos gerais, 39% ao tratamento não farmacológico, 34% a fatores institucionais, e 8% relativos à, doença. A adesão ao tratamento anti-hipertensivo tem sido um desafio no controle da hipertensão arterial e conhecer como este assunto está sendo enfocado na literatura pode contribuir para aumentar adesão ao tratamento na hipertensão arterial.

A pressão arterial está sendo medida?

A medida da pressão arterial faz parte do exame físico e deve ser realizada em toda consulta médica. Para avaliar se a pressão arterial é medida nas consultas médicas, foram consultados 500 prontuários de pacientes de primeira consulta ambulatorial, sendo 335 (67%) provenientes de clínicas médicas e cirúrgicas e 165 (33%) das clínicas ginecológica e obstétrica. A pressão arterial foi anotada em 39% das consultas realizadas (135±32/85±19 mm Hg), sendo que em 11% destas anotações a pressão diastólica estava acima de 90 mm Hg. Em relação ao diagnóstico prévio de hipertensão arterial verificou-se que: a) em 62% dos prontuários não havia esta informação; b) 20% referiram ter hipertensão, e em 79% destes a pressão arterial foi anotada; e c) 18% referiram não ter hipertensão e 46% destes tiveram registro da pressão arterial. Portanto, a maior parte dos pacientes não teve sua pressão arterial anotada.

O perfil de um grupo de pessoas hipertensas de acordo com conhecimento e gravidade da doença

Foram entrevistados 205 hipertensos em tratamento ambulatorial para avaliar o papel do perfil bio-social no conhecimento e grau de gravidade da doença. As características da população foram: 72% mulheres, 63% brancos, 78% com mais de 40 anos, 60% casados, 68% com baixa escolaridade, 41% com renda de 1 a 3 salários, 75% com peso elevado, 76% não fumantes, 89% sem atividade física regular, e das mulheres 48% já tinham usado hormônios anticoncepcionais. A análise evidenciou que a ausência de conhecimento se associou com sexo masculino, idade entre 20 e 40 anos, viúvo, não branco e peso normal. Pressão arterial mais elevada (diastólica> 110 mm Hg) se associou com mais de 60 anos, não casado, acima do peso, baixa escolaridade, baixa renda, com mais de 5 anos de hipertensão e já ter feito tratamento anterior.

Comparação dos perfis dos pacientes hipertensos atendidos em Pronto-Socorro e em tratamento ambulatorial

O estudo comparou 100 hipertensos atendidos no Pronto-socorro com 100 pacientes do Ambulatório. Os hipertensos do Pronto-Socorro foram diferentes (p < 0,05) em relação a: maior pressão arterial; menor renda salarial; maior consumo de bebida alcoólica; não pertenciam à comunidade do hospital; descobriram ser hipertensos por sentirem-se mal; mediram menos a pressão; e deixaram de tomar mais medicamentos. A análise multivariada revelou diferenças significativas entre os dois grupos quanto à renda, ao local onde é medida a pressão e não tomar os medicamentos. Concluiu-se que características desfavoráveis podem contribuir para não realizar o tratamento anti-hipertensivo, levando a atendimentos em unidades de emergência.

O conhecimento de profissionais da área da saúde sobre a medida da pressão arterial

Avaliou-se o conhecimento teórico e prático de 110 auxiliares de enfermagem, 44 médicos e 25 enfermeiros, por meio de 15 questões de múltipla escolha e pela observação do procedimento da medida da pressão arterial. O percentual de acerto quanto ao conhecimento teórico foi de 32%±12% para os auxiliares de enfermagem, 44%±14% para os enfermeiros e 56%±13% para os médicos, sendo que todos foram estatisticamente diferentes entre si (p<0,05). Quanto ao conhecimento prático, este foi de 41%±6% para os auxiliares de enfermagem, 44%±10% para os enfermeiros e 50%±12% para os médicos, sendo que os médicos apresentarem resultados significativamente superiores (p<0,05). Conclui-se que o conhecimento foi pouco satisfatório.

Instrumento de avaliação da qualidade de vida para hipertensos de Bulpitt e Fletcher

Este estudo realizou a tradução para o português e a validação do questionário específico para avaliação da qualidade de vida em hipertensos de Bulpitt e Fletcher. A tradução e o back-translation foram realizados por 4 professores de inglês e a versão final submetida a um corpo de juizes. Questões com Índice de Validade de Conteúdo menor que 80% foram modificadas e reavaliadas. O questionário foi aplicado em 110 hipertensos ambulatoriais (52 ± 8 anos, 65% mulheres, pressão arterial 128±17/ 75±13 mmHg), que também responderam ao SF-36, e em 20 normotensos, com características semelhantes às dos hipertensos. Os domínios do SF-36 e do instrumento de Bulpitt e Fletcher se correlacionaram (p<0,05), exceto em relação a aspectos sociais (r=0,07, p=0,44) e a estado geral de saúde (r=0,04, p=0,61). Os hipertensos apresentaram mais respostas positivas a sintomas (40%) do que os normotensos (15%). O instrumento foi validado e está apto para ser usado em nosso meio.