Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur

BACKGROUND The Bacille Calmette-Guérin (BCG) vaccine comprises a family of strains with variable protective efficacy against pulmonary tuberculosis (TB) and leprosy, partly due to genetic differences between strains. OBJECTIVES Previous data highlighting differences between the genomes and proteomic profiles of BCG strains Moreau and Pasteur led us to evaluate their behaviour in the macrophage microenvironment, capable of stimulating molecular responses that can impact the protective effect of the vaccine. METHODS Strain infectivity, viability, co-localisation with acidified vesicles, macrophage secretion of IL-1 and MCP-1 and lipid droplet biogenesis were evaluated after infection. FINDINGS We found that BCG Moreau is internalised more efficiently, with significantly better intracellular survival up to 96 h p.i., whereas more BCG Pasteur bacilli were found co-localised in acidified vesicles up to 6 h p.i. IL-1β and MCP-1 secretion and lipid droplet biogenesis by infected macrophages were more prominent in response to BCG Pasteur. MAIN CONCLUSION Overall, our results show that, compared to Pasteur, BCG Moreau has increased fitness and better endurance in the harsh intracellular environment, also regulating anti-microbial responses (lower IL-1b and MCP-1). These findings contribute to the understanding of the physiology of BCG Moreau and Pasteur in response to the intraphagosomal environment in a THP-1 macrophage model.

Aftershocks of the Samarco disaster: diminished growth and increased metal content of Raphanus sativuscultivated in soil with mining tailings

The collapse of the Fundão tailings dam of the Samarco mining complex in Mariana, Brazil, was the largest mining disaster in the world to date with many socio-economic and environmental impacts. Soil affected by mining tailings was severely altered with negative impacts for agriculture. We tested whether diluting mining tailings with organic soil would eliminate or at least attenuate the ecotoxic effects on plant development and performance. We cultivated radish, Raphanus sativus,in substrates containing different proportions of mining tailings and organic soil: pure tailings (T100%); 2) tailings75%+ soil25%(T75%); 3) tailings50%+ soil50%(T50%); 4) tailings25%+ soil75%(T25%), and 5) pure organic soil (Soil100%, control). There were large differences in soil quality parameters between the 100% tailings treatment (T100%) and the control (Soil100%), as well as for some parameters in the most diluted treatment -T25%(Ca2+, Fe, Mn) in relation to the controltreatment. Although dilution of the tailings soil improved radish development, there was lower radish productivity (leaf area, total biomass, and root/tuber biomass) than for pure soil (control). There were also significantly higher amounts of bioaccumulated metals in radish tubers grown with tailings, even when grown in T25%for Fe content and in T75%for Mn content. These results present a worrisome scenario for human communities in the region of the Doce river, as human consumption of crops produced in soil contaminated with tailingsis not recommended due to potential toxicological effects from high metal concentrations.(AU)

Gain of function in Mycobacterium bovis BCG Moreau due to loss of a transcriptional repressor

The Bacille Calmette-Guérin (BCG) vaccine comprises a family of genetically different strains derived by the loss of genomic regions (RDs) and other mutations. In BCG Moreau, loss of RD16 inactivates rv3405c * , encoding a transcriptional repressor that negatively regulates the expression of Rv3406, an alkyl sulfatase. To evaluate the impact of this loss on the BCG and host cell viability and the cytokine profile, THP-1 cells were infected with BCG Moreau (harbouring the empty vector) and a complemented strain carrying a functional copy of rv3405c. Viability of the host cells and bacteria as well as the pattern of cytokine secretion were evaluated. Our results show that the viability of BCG Moreau is higher than that of the complemented strain in an axenic medium, suggesting a possible functional gain associated with the constitutive expression of Rv3406. Viability of the host cells did not vary significantly between recombinant strains, but differences in the profiles of the cytokine secretion (IL-1β and IL-6) were observed. Our results suggest an example of a functional gain due to gene loss contributing to the elucidation of the impact of RD16 on the physiology of BCG Moreau.

Estimate of age through the analysis of x-ray of third molar and hand and wrist: case reports

The Forensic Anthropology and Forensic Dentistry, in one of its branches, aim to base skills making possible to estimate the age period for an individual, through factors such as tooth mineralization and bone development. This paper aims to report on two cases from Scientific Expertise Center - Renato Chaves, Belém- PA, where two individuals after committing crime, were referred to under 18s without supporting documents. Through data collected in the archives of the Scientific Expertise Center, an analysis of the mineralization of the teeth were made, highlighting the third molars by panoramic radiography; as well as the study of bone development of the hands and wrists of individuals through radiographs. After, the analysis was compared to surveys conducted by Nicodemos, Moraes and Médici-Filho, befitting the chronology of mineralization of permanent teeth among Brazilian citizens together with the work of Greulich-Pyle, Radiographic correlation concerning the chronology of the development of the hand and wrist. As a result of the analysis, it was obtained, for case 01, an estimated age of 17; and for case 02 the estimated age was between 18-19 years.

Oral bacillus Calmette-Guérin vaccine against tuberculosis: why not?

The bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine for human use against tuberculosis (TB). Although controversy exists about its efficacy, the BCG vaccine is able to protect newborns and children against disseminated forms of TB, but fails to protect adults against active forms of TB. In the last few years, interest in the mucosal delivery route for the vaccine has been increasing owing to its increased capacity to induce protective immune responses both in the mucosal and the systemic immune compartments. Here, we show the importance of this route of vaccination in newly developed vaccines, especially for vaccines against TB.

Saúde bucal em idosos / Bucal health in elderly

Objetivo: Determinar a prevalência e as condições bucais de idosos atendidos no Serviço de Estomatologia da UFPB. Material e Métodos: Foi realizado um estudo retrospectivo através da análise de 1.791 fichas clínicas dos pacientes atendidos no referido serviço, no período de janeiro de 2000 a janeiro de 2004. Foram coletados dados sobre idade, sexo, CPO-D, uso e necessidade de próteses dentárias e presença de lesão e/ou alterações na mucosa bucal. Resultados: Entre as 1.791 fichas, foram identificados 170 (9,4%) pacientes idosos, sendo 71,2% mulheres e 28,8% homens, com idade média de 65 ± 5,10 anos e índice CPO-D de 25±7,07. Observou-se que 25,3% dos pacientes eram edêntulos, 92,9% necessitavam de próteses dentárias, 67,1% necessitavam, mais não as usavam e 32,9% as usavam. Com relação às alterações bucais, 71,9% dos pacientes apresentavam uma ou mais alteração e/ou lesão na mucosa bucal. Foram identificadas 10 tipos de alterações e/ou lesões na mucosa bucal, sendo as mais frequentes aquelas sem significado patológico (56,2%), doença periodontal (13,0%), lesões brancas (10,05%) e lesões por próteses (8,9%). Conclusões: Houve importante demanda de pacientes idosos no serviço de estomatologia da UFPB, no período estudado. Os idosos apresentavam alto índice CPO-D, grande necessidade de próteses, péssimas condições bucais e alta prevalência de lesões e/ou alterações bucais.

Objective: To estimate the prevalence and buccal conditions of elderly assisted at the Stomatology Service of the UFPB (Federal University of Paraíba). Material and Methods: A retrospective study was performed by analysing 1791 clinical cards of patients in assistance at that health service, from January 2000 to January 2004. Data were collected on age, sex, DMF index (which quantifies the total of untreated decayed, missing and filled teeth in a person´s mouth) - or CLF-T - cavitated, lost and filled teeth - the wear and need of prosthesis and presence of lesions and/or alterations in the buccal mucosa. Results: Among the 1791 clinical cards analysed, 170 (9.4%) elderly patients were identified, of which 71.2% were women and 28.8% were men, whose average age was 65±5.10 years old, and the DMF index was 25±7.07. It was observed that 25.3% of the patients were edentulous, 92.9% needed dental prosthesis, of which 67,1% needed them but were not wearing them and 32.9% were wearing them. With respect to buccal alterations, 71.9% presented one or more alterations and/or lesions in the buccal mucosa. Of the ten types of alteration and/or lesion observed in the buccal mucosa, the most frequent ones were identified as: with no pathological significance, 56.2%; periodontal desease, 13.0%; white lesions, 10.05%; and lesions caused by prosthesis, 8.9%. Conclusions: There was a quite significant assistance of the UFPB's service of stomatology to elderly patients throughout the period of the present study. The elderly people presented high DMF index; and they were also in need of prosthesis, having very bad buccal conditions, and high prevalence of buccal lesions and/or alterations.

BCG Moreau Rio de Janeiro: an oral vaccine against tuberculosis - review

The vaccine Bacillus of Calmette Guérin (BCG) was originally developed in France as an oral vaccine against tuberculosis. The oral use of this vaccine was replaced by the parenteral route in almost all countries after the Lubeck disaster. In contrast, Brazil retained the oral delivery of the vaccine until the mid-seventies when it was replaced by the intradermal route. This change in route of delivery was mainly secondary to pressure by medical practitioners based on the poor responses of oral immunized subjects to purified protein derivative (PPD) skin tests. Even after the change of route of delivery, Ataulpho de Paiva Foundation continued making the oral vaccine. Currently, BCG Moreau has been described as one of the most immunogenic and with fewer side effects than other BCGs. The genomics, proteomics and vaccine trials for oral BCG Moreau Rio de Janeiro are currently under investigation. In this review, we intend to describe the history of BCG Moreau Rio de Janeiro in Brazil.

Fluxo salivar e consumo de medicamentos em diabéticos idosos / Salivary flow and consumer of drugs in elderly diabetic patients

O ojetivo deste estudo foi avaliar a função das glândulas salivares e consumo de medicamentos em diabéticos idosos. Foram selecionados 50 indivíduos diabéticos e 50 não diabéticos, com 60 anos ou mais de idade. Determinou-se a taxa de fluxo salivar total de repouso e estimulado, presença de xerosstomia e tipos de medicamentos consumidos. Utilizou-se teste T de Student e Coeficiente de Pearson, com nível de significância para p<0,05. A média de idade foi 68+ou- 6,6 anos nos diabéticos e 66+ou- 5,6 anos nos controles. 26 por cento dos pacientes eram homens e 74 por cento mulheres, em ambos grupos. Os diabéticos apresentaram média de fluxo salivar em repouso de 0,27+ou- 0,26 ml/min e os controles de 0,32+ou- 0,27ml/min. Nos diabéticos a média do fluxo salivar estimulado foi 1,58+ou- 0,84 ml/min e nos controles foi 1,91+ou- 0,98ml/min, não houve diferrenças estatisticamente significantes. 22 por cento dos diabéticos e 14 por cento dos controles apresentaram hipossalivação. 81,8 por cento dos diabéticos e 42,8 por cento dos controles apresentaram hipossalivação e xerostomia de forma concomitante. Nos diabéticos houve correlação estatisticamente significante do fluxo salivar em repouso com xerostomia e com o consumo de hipotensores/diuréticos. Os resultados sugerem que os pacientes diabéticos estudados não apresentaram disfunção das glândulas salivares; a hipossalivação estava correlacionada ao consumo de hipotensores/diuréticos; e o fluxo salivar em repouso estava relacionado com xerostomia e consumo de hipotensores/diuréticos

Análise retrospectiva dos pés de pacientes diabéticos do ambulatório de diabetes da Santa Casa de Belo Horizonte, MG / Retrsopective analysis of diabetic feet from patients followed in the diabetic clinic at Santa Casa of Belo Horizonte, MG

O pé diabético é uma das complicaçöes mais comuns do diabetes, causando uma queda significativa da qualidade de vida dos pacientes vulneráveis, além de seu elevado custo econômico. No presente trabalho, analisamos, retrospectivamente, 234 pacientes diabéticos no ambulatório de pé diabético, através de exames clínico-laboratoriais e avaliaçäo dos pés utilizando o monofilamento de l0g Semmes Weinstein, martelo neurológico básico, doppler vascular e pedígrafo. Os pacientes foram catalogados quanto à idade, sexo e duraçäo do diabetes sendo que a média foi de 10 anos de doença. Observamos que, inicialmente, mais de 30 por cento dos pacientes apresentavam perda da sensibilidade protetora, calosidades e lesöes dermatológicas, todas fatores de risco para o desenvolvimento de úlcera de pé. Notou-se ainda a desinformaçäo sobre a doença. Em resumo, os dados do trabalho mostram uma grande prevalência de alteraçöes e os autores alertam para a importância do atendimento enfocando os pés dos pacientes visando uma assistência global e preventiva para evitar complicaçöes futuras.

Estudo da resposta imunológica humoral e celular à vacinação oral com o BCG Moreau no Rio de Janeiro / ?

O BCG é a vacina mais usada no mundo e a única utilizada para prevenir a tuberculose e a hanseníase. Sabe-se que a resposta imunológica celular é fundamental durante a infecção causada por patógenos intracelulares, e em infecções micobacterianas é a resposta mais importante observada, apesar da presença dos anticorpos. A resposta DTH (Hipersensibilidade retardada) ao antígeno micobacteriano - reação de Mantoux, PPD ou tuberculina - é usada como método diagnóstico para tuberculose. Sua eficiência, no entanto, é questionável, uma vez que uma reação negativa não implica em ausência total de resposta imunológica. Esse trabalho teve como objetivo avaliar a resposta imunológica humoral e celular em voluntários que apresentaram o teste cutâneo negativo após imunização por via oral com o BCG Moreau. Para esse trabalho estudamos a reação ao teste cutâneo (PPD) em 100 voluntários saudáveis e observamos que 77 tinham PPD + (todos imunizados por via parenteral) e 23 tinham PPD negativo (19 imunizados por via oral, 3 imunizados por via parenteral na infância e 1 não imunizado). Destes 6 concordaram em ser imunizados por via oral (4 PPD- e 2 PPD+). Coletamos PBMC (células monucleares de sangue periférico) e plasma em dias específicos antes e após a imunização, que foram usados nos ensaios in vitro para avaliação da resposta imunológica ao BCG solúvel e ao PPD Rt 48. As técnicas usadas foram ELISpot, Western-blot, linfoproliferação e dosagem de citocinas. Não observamos nenhum efeito adverso à vacinação oral com o BCG Moreau. Notamos que a maioria dos voluntários imunizados por via oral, apresentam resposta negativa ao teste cutâneo, apesar de apresentarem resposta imunológica humoral, com presença IgA e IgG, e celular, com resposta linfoproliferativa a ambos os antígenos testados e produção expressiva de IFN-y, sugerindo resposta Th1. Demonstramos o tráfico de células T e anticorpos em resposta à vacinação, a presença de resposta de memória, que a revacinação com o BCG por via oral não torna positiva a resposta ao teste cutâneo, e ainda, que não houve diferença entre as respostas imunológicas humoral e celular apresentadas pelos voluntários reatores e não reatores ao teste cutâneo.