The fungal metabolite eugenitin as additive for Aspergillus niveus glucoamylase activation

Endophytic microorganisms live inside tissues of host plants apparently do not causing warning to them, and area promising source of bioactive molecules as antimicrobial and antitumoral drugs. In this work, we report the isolation of eugenitin from cultures of the endophyte Mycoleptodiscus indicus and its potential as additive for Aspergillus niveus glucoamylase activation. The glucoamylase hydrolytic activity increased twofold using 5 mM of eugenitin and this activation could be explained by the binding mode of eugenitin with the three-dimensional structure of glucoamylase. The in silica prediction of ligand binding sites revealed at least 9 possible interaction sites able to accommodate eugenitin on glucoamylase from Hypocrea jecorina. Besides, we evaluated the effect of pH and temperature on activity and stability, as well as in the hydrolysis of different substrates and kinetic parameters either in presence or absence of eugenitin. The results displayed by eugenitin as additive to glucoamylase activation are promising and provide novel perspectives for applications of fungal metabolites. (C) 2011 Elsevier B.V. All rights reserved.

Crotamine Pharmacology Revisited: Novel Insights Based on the Inhibition of K-V Channels

Crotamine, a 5-kDa peptide, possesses a unique biological versatility. Not only has its cell-penetrating activity become of clinical interest but, moreover, its potential selective antitumor activity is of great pharmacological importance. In the past, several studies have attempted to elucidate the exact molecular target responsible for the crotamine-induced skeletal muscle spasm. The aim of this study was to investigate whether crotamine affects voltage-gated potassium (K-V) channels in an effort to explain its in vivo effects. Crotamine was studied on ion channel function using the two-electrode voltage clamp technique on 16 cloned ion channels (12 K-V channels and 4 Na-V channels), expressed in Xenopus laevis oocytes. Crotamine selectively inhibits K-V 1.1, K-V 1.2, and K-V 1.3 channels with an IC50 of similar to 300 nM, and the key amino acids responsible for this molecular interaction are suggested. Our results demonstrate for the first time that the symptoms, which are observed in the typical crotamine syndrome, may result from the inhibition of K-V channels. The ability of crotamine to inhibit the potassium current through K-V channels unravels it as the first snake peptide with the unique multifunctionality of cell-penetrating and antitumoral activity combined with K-V channel-inhibiting properties. This new property of crotamine might explain some experimental observations and opens new perspectives on pharmacological uses.

In vitro cytotoxicity of Selol-loaded magnetic nanocapsules against neoplastic cell lines under AC magnetic field activation

The goals of this study are to evaluate in vitro compatibility of magnetic nanomaterials and their therapeutic potential against cancer cells. Highly stable ionic magnetic fluid sample (maghemite, gamma-Fe2O3) and Selol were incorporated into polymeric nanocapsules by nanoprecipitation method. The cytotoxic effect of Selol-loaded magnetic nanocapsules was assessed on murine melanoma (B16-F10) and oral squamous cell carcinoma (OSCC) cell lines following AC magnetic field application. The influence of different nanocapsules on cell viability was investigated by colorimetric MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the absence of AC magnetic field Selol-loaded magnetic nanocapsules, containing 100 mu g/mL Selol plus 5 x 10(12) particle/mL, showed antitumoral activity of about 50% on B16-F10 melanoma cells while OSCC carcinoma cells demonstrated drug resistance at all concentrations of Selol and magnetic fluid (range of 100-500 mu g/mL Selol and 5 x 10(12) -2.5 x 10(13) particle/mL). On the other hand, under AC applied fields (1 MHz and 40 Oe amplitude) B16-F10 cell viability was reduced down to 40.5% (+/- 3.33) at the highest concentration of nanoencapsulated Selol. The major effect, however, was observed on OSCC cells since the cell viability drops down to about 33.3% (+/- 0.38) under application of AC magnetic field. These findings clearly indicate that the Selol-loaded magnetic nanocapsules present different toxic effects on neoplastic cell lines. Further, the cytotoxic effect was maximized under AC magnetic field application on OSCC, which emphasizes the effectiveness of the magnetohyperthermia approach. (C) 2012 American Institute of Physics. [doi: 10.1063/1.3680541]

Mikania glomerata Sprengel (Asteraceae) influences the mutagenicity induced by doxorubicin without altering liver lipid peroxidation or antioxidant levels

As shown in numerous studies, natural compounds may exert adverse effects, mainly when associated with some drugs. The hydroalcoholic extract of Mikania glomerata is the pharmaceutical form present in commercially available syrup used for the treatment of respiratory diseases in popular Brazilian medicine. The objective of the present investigation was (1) to evaluate the preventive effects of standardized hydroalcoholic extract of M. glomerata (MEx) against antitumoral drug doxorubicin (DXR)-induced micronucleated polychromatic erythrocytes (MNPCE) in a subchronic assay in mice, and (2) to determine the liver content of malondialdehyde (MDA) and the antioxidants glutathione (GSH) and vitamin E (VE). Male Swiss mice were treated for 30 d with MEx added to drinking water, combined or not with DXR (90 mg/kg body weight) injected intraperitoneally (ip) 24 h before analysis. The results demonstrated that MEx produced no genotoxic damage, but significantly increased the frequency of MNPCE induced by DXR, indicating a drug-drug interaction. This rise was not accompanied by lipid peroxidation or antioxidants level reduction, as measured by MDA, GSH, and VE. Despite the presence of coumarin (a known antioxidant), MEx may exert adverse effects probably in association with mutagenic compounds, although this effect on DNA damage did not involve oxidative stress.

HEALTH PROBLEMS AWARENESS DURING TRAVEL AMONG FACULTY MEMBERS OF A LARGE UNIVERSITY IN LATIN AMERICA. PRELIMINARY REPORT

Health safety during trips is based on previous counseling, vaccination and prevention of infections, previous diseases or specific problems related to the destination. Our aim was to assess two aspects, incidence of health problems related to travel and the traveler’s awareness of health safety. To this end we phone-interviewed faculty members of a large public University, randomly selected from humanities, engineering and health schools. Out of 520 attempts, we were able to contact 67 (12.9%) and 46 (68.6%) agreed to participate in the study. There was a large male proportion (37/44, 84.1%), mature adults mostly in their forties and fifties (32/44, 72.7%), all of them with higher education, as you would expect of faculty members. Most described themselves as being sedentary or as taking occasional exercise, with only 15.9% (7/44) taking regular exercise. Preexisting diseases were reported by 15 travelers. Most trips lasted usually one week or less. Duration of the travel was related to the destination, with (12h) or longer trips being taken by 68.2% (30/44) of travelers, and the others taking shorter (3h) domestic trips. Most travelling was made by air (41/44) and only 31.8% (14/44) of the trips were motivated by leisure. Field research trips were not reported. Specific health counseling previous to travel was reported only by two (4.5%). Twenty seven of them (61.4%) reported updated immunization, but 11/30 reported unchecked immunizations. 30% (9/30) reported travel without any health insurance coverage. As a whole group, 6 (13.6%) travelers reported at least one health problem attributed to the trip. All of them were males travelling abroad. Five presented respiratory infections, such as influenza and common cold, one neurological, one orthopedic, one social and one hypertension. There were no gender differences regarding age groups, destination, type of transport, previous health counseling, leisure travel motivation or pre-existing diseases. Interestingly, the two cases of previous health counseling were made by domestic travelers. Our data clearly shows that despite a significant number of travel related health problems, these highly educated faculty members, had a low awareness of those risks, and a significant number of travels are made without prior counseling or health insurance. A counseling program conducted by a tourism and health professional must be implemented for faculty members in order to increase the awareness of travel related health problems.

Idosos com e sem plano de saúde e características socioepidemiológicas associadas

OBJETIVO: Analisar fatores epidemiológicos e sociodemográficos associados à saúde de idosos com ou sem plano de saúde. MÉTODOS: Foram realizadas entrevistas com 2.143 pessoas de 60 anos e mais, no município de São Paulo, em 2000 e 2006. A variável dependente, dicotômica, foi ter ou não plano de saúde. As variáveis independentes abrangeram características sociodemográficas e de condição de saúde. Foram descritas as proporções encontradas para as variáveis analisadas e desenvolvido modelo de regressão logística que considerou significantes as variáveis com p < 0,05. RESULTADOS: Houve diferenças, favoráveis aos titulares de planos, para renda e escolaridade. O grupo sem planos privados realizou menos prevenção contra neoplasias e mais contra doenças respiratórias; esperou mais para ter acesso a consultas de saúde; realizou menos exames pós-consulta; referiu menor número de doenças; teve maior proporção de avaliação negativa da própria saúde e relatou mais episódios de queda. Os titulares de planos relataram menor adesão à vacinação e, dentre os que foram internados, 11,1% em 2000 e 17,9% em 2006 tiveram esse procedimento custeado pelo Sistema Único de Saúde. A única doença associada à condição de titular de plano privado foi a osteoporose. CONCLUSÕES: Há diferenças representadas pela renda e pela escolaridade favoráveis aos titulares de planos e seguros privados, as quais estão relacionadas com o uso de serviços e com os determinantes sociais de saúde.

Designing a vaccination strategy against dengue

In this work we propose a mathematical approach to estimate the dengue force of infection, the average age of dengue first infection, the optimum age to vaccinate children against dengue in a routine fashion and the optimum age interval to introduce the dengue vaccine in a mass vaccination campaign. The model is based on previously published models for vaccination against other childhood infections, which resulted in actual vaccination programmes in Brazil. The model was applied for three areas of distinct levels of endemicity of the city of Recife in Northeastern State of Pernambuco, Brazil. Our results point to an optimal age to introduce the dengue vaccine in the routine immunization programme at two years of age and an age interval to introduce a mass vaccination between three and 14 years of age.

Hepatitis B revaccination for healthcare workers who are anti-HBs-negative after receiving a primary vaccination series

INTRODUCTION: This study aimed to evaluate the response to hepatitis B (HB) revaccination of healthcare workers (HCW) who are negative for antibodies to HB surface antigen (anti-HBs) after a complete vaccination series. METHODS: HCW whose anti-HBs test was performed > 90 days after a HB vaccination course were given a 4th dose. A post-vaccination test was done within 30 to 90 days. RESULTS: One hundred and seventy HCW were enrolled: 126 (74.1%) were anti-HBs-positive after the 4th dose. CONCLUSIONS: Rechecking anti-HBs after the 4th HB vaccine dose is a practical approach in case of post-vaccination tests performed >90 days after the full vaccination course.

Prevalência e determinantes do aleitamento materno exclusivo no município de Serrana, São Paulo, Brasil

Estudo transversal e quantitativo, com objetivos de identificar a prevalência e os determinantes do aleitamento materno exclusivo em crianças menores de 6 meses, no município de Serrana - SP, no ano de 2009. Aplicou-se um questionário semiestruturado validado junto aos responsáveis pelas crianças menores de 6 meses que compareceram à segunda etapa da Campanha Nacional de Vacinação contra a poliomielite. Foram realizadas análises uni e multivariadas apresentadas em Odds Ratio e intervalos de confiança. Do total das 275 crianças participantes, apenas 29,8% estavam em aleitamento materno exclusivo. Nas análises univariadas, verificou-se que mães que trabalham fora sem licença-maternidade, mães que não trabalham fora, adolescentes e o uso de chupeta apresentaram maior chance de interrupção do aleitamento materno exclusivo. Na análise multivariada, as mães que trabalham fora sem licença-maternidade têm 3 vezes mais chance de desmamarem precocemente seus filhos. Os resultados forneceram subsídios para o redirecionamento e planejamento de ações em aleitamento materno.

Contributions from the systematic review of economic evaluations: the case of childhood hepatitis A vaccination in Brazil

The aim of this study was to present the contributions of the systematic review of economic evaluations to the development of a national study on childhood hepatitis A vaccination. A literature review was performed in EMBASE, MEDLINE, WOPEC, HealthSTAR, SciELO and LILACS from 1995 to 2010. Most of the studies (8 of 10) showed favorable cost-effectiveness results. Sensitivity analysis indicated that the most important parameters for the results were cost of the vaccine, hepatitis A incidence, and medical costs of the disease. Variability was observed in methodological characteristics and estimates of key variables among the 10 studies reviewed. It is not possible to generalize results or transfer epidemiological estimates of resource utilization and costs associated with hepatitis A to the local context. Systematic review of economic evaluation studies of hepatitis A vaccine demonstrated the need for a national analysis and provided input for the development of a new decision-making model for Brazil.

Comparative analysis of the corps en cerise in several species of Laurencia (Ceramiales, Rhodophyta) from the Atlantic Ocean

Different species of Laurencia have proven to be a rich source of natural products yielding interesting bioactive halogenated secondary metabolites, such as terpenoids and acetogenins. It is shown that such compounds are accumulated in the spherical, reniform to claviform refractive inclusions called corps en cerise (CC), which are intensively osmiophilic and located mainly in the cortical cells of the thalli and also in trichoblast cells. Up to now, it was believed that CC were present only in these two kinds of cells. Recently, however, a species of Laurencia, L. marilzae, with CC in all cells of the thallus, i.e., cortical, medullary, including the pericentral and axial cells, as well as in the trichoblasts, was described from the Canary Islands, and subsequently also reported to Brazil and Mexico. Within the Laurencia complex, only Laurencia species produce CC. Since the species of Laurencia are targets of interest for the prospection of bioactive substances due to their potential antibacterial, antifungal, anticholinesterasic, antileishmanial, cytotoxic, and antioxidant activities, the present paper carries out a comparative analysis of the corps en cerise in several species of Laurencia from the Atlantic Ocean to obtain basic information that can support natural product bioprospection projects. Our results show that the number and size of the CC are constant within a species, independent of the geographical distribution, corroborating their use for taxonomical purposes to differentiate groups of species that present a lower number from those that have a higher number. In this regard, there was a tendency for the number of CC to be higher in some species of Laurencia from the Canary Islands. The presence of CC can also be used to distinguish species in which these organelles are present in all cells of the thallus from those in which CC are restricted to the cortical cells. Among the species analyzed, L. viridis displayed the most varied secondary metabolites composition, such as sesquiterpenes, diterpenes, triterpenes, all of which showed potent antiviral, cytotoxic, and antitumoral activities, including protein phosphatase type 2A (PP2A) inhibitory effects.

Fatores de risco associados ao desmame em crianças até seis meses de idade no município de São Paulo

OBJETIVO: Avaliar os fatores de risco associados à ausência de aleitamento materno exclusivo (AME) em crianças <6 meses de vida na cidade de São Paulo, em 2008. MÉTODOS: Aplicou-se o questionário do Projeto Amamentação e Municípios-1998 (AMAMUNIC) a pais/responsáveis de crianças <6 meses de idade durante a Campanha Nacional de Vacinação contra Poliomielite. Cálculo da amostra por conglomerados com sorteio em dois estágios. Os fatores analisados foram idade e educação materna, peso de nascimento, sexo, tipo de parto, nascer em Hospital Amigo da Criança, presença de aleitamento materno precoce, uso de chupeta nas últimas 24 horas e mãe trabalhando fora de casa. Análise estatística por regressão logística binária com SPSS, versão 15.0, sendo significante p<0,05. RESULTADOS: Foram realizadas 724 entrevistas, das quais 275 referiram (39,1%) aleitamento materno exclusivo (Grupo I - GI) e 429 (60,9%) sem aleitamento materno exclusivo (Grupo II - GII). Houve diferenças entre os grupos quanto ao uso da chupeta nas últimas 24 horas (GI 32,3 versus GII 59,8%; p<0.001), mães trabalhando fora (GI 12,4 versus GII 24,8%; p<0.001) e idade da criança (GI 74,1±45,3 versus GII 105,8±49,5 dias; p<0,0001).Na análise multivariada, houve associação entre ausência de aleitamento materno exclusivo e uso de chupeta (OR 3,02; IC95% 2,10-4,36), mãe trabalhando fora (OR 2,11; IC95% 1,24-3,57) e idade da criança (OR 1,01; IC95% 1,01-1,02). CONCLUSÕES: O uso da chupeta nas últimas 24 horas associou-se à ausência de AME em crianças menores do que seis meses, seguido pelo trabalho materno fora de casa e pela idade da criança, que são importantes fatores a serem controlados em programas de promoção do aleitamento materno.

Prevalência de aleitamento materno e fatores associados no município de Londrina-PR

OBJETIVO: Descrever a prevalência do aleitamento materno e fatores associados no município de Londrina-PR. MÉTODOS: Estudo quantitativo, descritivo, entrevistando 770 acompanhantes de crianças menores de 12 meses, durante a campanha de vacinação antipoliomielite, em agosto de 2008. RESULTADOS: Na primeira hora, foram amamentadas 72,5% das crianças; 33,8% estavam em aleitamento materno exclusivo de zero a seis meses, no quarto mês, 53,7% e no sexto mês 7,8%; 51,5% em aleitamento materno continuado entre 9 e 12 meses. As mulheres que mais amamentaram tinham idade igual ou superior a 35 anos, escolaridade de terceiro grau, mais de um filho e estavam em licença-maternidade. CONCLUSÃO: os índices de aleitamento materno do município apresentaram evolução, porém faz-se necessário analisar as ações nos serviços de saúde para melhora desses índices.

Epidemia midiática: produção de sentidos e configuração social da febre amarela na cobertura jornalística, 2007-2008

O objetivo deste artigo, situado no campo da comunicação em saúde, é analisar os sentidos atribuídos discursivamente à febre amarela silvestre durante a cobertura jornalística da epizootia da doença, ocorrida no Brasil no verão 2007-2008. Utilizando o referencial teórico das práticas discursivas e da produção de sentidos no cotidiano e as hipóteses de agendamento (agenda-setting) e enquadramento (framing) da notícia, foram analisadas todas as matérias sobre febre amarela veiculadas pelo jornal Folha de S. Paulo, no período de 21 de dezembro de 2007 a 29 de fevereiro de 2008, e todos os documentos oficiais sobre a epizootia emitidos pela autoridade brasileira de saúde pública entre 3 de janeiro e 28 de fevereiro de 2008. Os achados indicam que as estratégias discursivas da cobertura jornalística relativizaram o discurso da autoridade de saúde pública; priorizaram a divulgação do número de casos; enfatizaram a vacinação como o limite entre a vida e a morte, omitindo riscos do uso indiscriminado do imunobiológico; e propagaram a iminência de uma epidemia de febre amarela de grandes proporções. Essas estratégias deram novos sentidos à doença, deslocando o evento de sua forma silvestre, espacialmente restrita e de gravidade limitada, para a urbana, de caráter epidêmico e potencialmente mais grave. Secundariamente, o estudo permitiu identificar os impactos desse discurso midiático sobre o sistema nacional de imunização e os riscos a que a população foi exposta em função dos sentidos produzidos: em 2008, foram registrados 8 casos de reação grave à vacina, dos quais 6 foram a óbito.

Consenso 2012 da Sociedade Brasileira de Reumatologia para o tratamento da artrite reumatoide

OBJETIVO: Elaborar recomendações para o tratamento da artrite reumatoide no Brasil. MÉTODO: Revisão da literatura com seleção de artigos baseados em evidência e opinião de especialistas da Comissão de Artrite Reumatoide da Sociedade Brasileira de Reumatologia. RESULTADOS E CONCLUSÕES: 1) A decisão terapêutica deve ser compartilhada com o paciente; 2) imediatamente após o diagnóstico, uma droga modificadora do curso da doença (DMCD) deve ser prescrita e o tratamento ajustado para atingir remissão; 3) o tratamento deverá ser conduzido por reumatologista; 4) o tratamento inicial inclui DMCD sintéticas; 5) o metotrexato é a droga de escolha; 6) pacientes que não alcançaram resposta após a utilização de dois esquemas de DMCD sintéticas devem ser avaliados para DMCD biológicas; 7) excepcionalmente, DMCD biológicas poderão ser consideradas mais precocemente; 8) recomenda-se preferencialmente o uso de agentes anti-TNF como terapia biológica inicial; 9) após falha terapêutica a uma primeira DMCD biológica, outros biológicos poderão ser utilizados; 10) ciclofosfamida e azatioprina podem ser consideradas em manifestações extra-articulares graves; 11) recomenda-se a utilização de corticoide oral em baixas doses e por curtos períodos; 12) os anti-inflamatórios não hormonais devem sempre ser prescritos em associação à DMCD; 13) avaliações clínicas devem ser mensais no início do tratamento; 14) terapia física, reabilitação e terapia ocupacional são indicadas; 15) deve-se recomendar tratamento cirúrgico para correção de sequelas; 16) métodos de terapia alternativa não substituem a terapia tradicional; 17) deve-se orientar planejamento familiar; 18) orienta-se a busca ativa e o manejo de comorbidades; 19) atualizar e documentar a vacinação do paciente; 20) doenças transmissíveis endêmico-epidêmicas devem ser investigadas e tratadas.