The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P ≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P ≤0.05). In addition, lactoferrin (P ≤0.002), transferrin receptor (P ≤0.05) and solute carrier family 11A1 (P ≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria.

Human gut microbiota and its relationship to health and disease

Probiotics are live microorganisms that confer a health benefit on the host when administered in appropriate amounts. Over 700 randomized, controlled, human studies have been conducted with probiotics thus far, with the results providing strong support for the use of probiotics in the clinical prevention or treatment of gastrointestinal tract disorders and metabolic syndrome. The present review is based on webinar presentations that were developed by the American Gastroenterological Association (AGA) in partnership with the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the North American branch of the International Life Sciences Institute (ILSI North America). The presentations provided gastroenterologists and researchers with fundamental and current scientific information on the influence of gut microbiota on human health and disease, as well as clinical intervention strategies and practical guidelines for the use of probiotics and prebiotics.

Piriformospora indica reduces Fusarium head blight disease severity and mycotoxin DON contamination in wheat under UK weather conditions

Piriformospora indica (Sebacinaceae) is a cultivable root endophytic fungus. It colonises the roots of a wide range of host plants. In many settings colonisation promotes host growth, increases yield and protects the host from fungal diseases. We evaluated the effect of P. indica on Fusarium head blight (FHB) disease of winter (cv. Battalion) and spring (cv. Paragon, Mulika, Zircon, Granary, KWS Willow and KWS Kilburn) wheat and consequent contamination by the mycotoxin deoxynivalenol (DON) under UK weather conditions. Interactions of P. indica with an arbuscular mycorrhizal fungus (Funneliformis mosseae), fungicide application (Aviator Xpro) and low and high fertiliser levels were considered. P. indica application reduced FHB disease severity and incidence by 70%. It decreased mycotoxin DON concentration of winter and spring wheat samples by 70% and 80% respectively. P. indica also increased above ground biomass, 1000 grain weight and total grain weight. P. indica reduced disease severity and increased yield in both high and low fertiliser levels. The effect of P. indica was compatible with F. mosseae and foliar fungicide application. P. indica did not have any effects on plant tissue nutrients. These results suggest that P. indica might be useful in biological control of Fusarium diseases of wheat.

Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson`s Disease

Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher`s disease, among patients with Parkinson`s disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson`s disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson`s disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. Conclusions Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson`s disease.

5-Lipoxygenase plays a role in the control of parasite burden and contributes to oxidative damage of erythrocytes in murine Chagas` disease

Chagas` disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO(-/-)) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T cruzi. impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T cruzi-infected mice but not in C57BL/6 iNOS-/- infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T cruzi in vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect. (C) 2009 Elsevier B.V. All rights reserved.

Functional interferences in host inflammatory immune response by airway allergic inflammation restrain experimental periodontitis development in mice

Aims Periodontal disease (PD) and airway allergic inflammation (AL) present opposing inflammatory immunological features and clinically present an inverse correlation. However, the putative mechanisms underlying such opposite association are unknown. Material and Methods Balb/C mice were submitted to the co-induction of experimental PD (induced by Actinobacillus actinomycetemcomitans oral inoculation) and AL [induced by sensitization with ovalbumin (OVA) and the subsequent OVA challenges], and evaluated regarding PD and AL severity, immune response [cytokine production at periodontal tissues, and T-helper transcription factors in submandibular lymph nodes (LNs)] and infection parameters. Results PD/AL co-induction decreased PD alveolar bone loss and periodontal inflammation while experimental AL parameters were unaltered. An active functional interference was verified, because independent OVA sensitization and challenge not modulate PD outcome. PD+AL group presented decreased tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, -gamma, IL-17A, receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells ligand and matrix metalloproteinase (MMP)-13 levels in periodontal tissues, while IL-4 and IL-10 levels were unaltered by AL co-induction. AL co-induction also resulted in upregulated T-bet and related orphan receptor gamma and downregulated GATA3 levels expression in submandibular LNs when compared with PD group. Conclusion Our results demonstrate that the interaction between experimental periodontitis and allergy involves functional immunological interferences, which restrains experimental periodontitis development by means of a skewed immune response.

Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil

The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, similar to 3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex 1) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T cruzi 11 (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T cruzi 11 cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

In vivo infection by Trypanosoma cruzi: The conserved FLY domain of the gp85/trans-sialidase family potentiates host infection

Trypanosoma cruzi is a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas` disease. The infection of host cells by T. cruzi involves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1 mu g/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection by T. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7.6-fold), heart (3-fold) and small intestine (3.6-fold). Moreover, an intense inflammatory response and increment of CD4(+) T cells (1.7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4(+)CD25(+)FoxP3(+) T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitates in vivo infection by T. cruzi and concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas` disease.

Atendimento ambulatorial versus programa de educação infantil : qual oferece mais mudança de hábito?

De acordo com um recente relatório da Organização Mundial de Saúde, a obesidade atingiu proporções epidêmicas em todo o mundo. Hoje a obesidade é muito comum e está começando a substituir a desnutrição e as doenças infecciosas. A obesidade está relacionada com doenças crônico-degenerativas e com sérias conseqüências psicológicas para o indivíduo. A obesidade é uma doença complexa e heterogênea, influenciada por diversos genes, no entanto, a combinação dos genes envolvidos no desenvolvimento de formas de obesidade ainda não foi definitivamente determinada (REILLY et al, 2002). A obesidade, ou o aumento da adiposidade, é geralmente atribuída a um desequilíbrio entre a energia ingerida (padrão alimentar) e a energia gasta (atividade física e metabolismo basal). Assim, o manejo da obesidade consiste em tornar esse balanço energético negativo, sendo o exercício considerado um dos aspectos principais, associado com mudanças alimentares e de estilo de vida saudáveis (ESCRIVÃO & LOPEZ, 1998). Dietas são, na maioria das vezes, transitórias. Então, a mudança de hábito alimentar e de atividade física são os aspectos principais, especialmente na criança, uma vez que a manutenção de peso irá proporcionar uma melhora dramática da composição corporal, já que o crescimento linear ainda existe. Mas, qualquer mudança de hábito necessita da colaboração da família (HILL et al, 1993). Assim, o presente estudo teve como objetivo principal comparar um programa de educação em obesidade infantil com o atendimento ambulatorial para manejo de obesidade infantil quanto a mudanças de hábitos alimentares e de atividade física e aquisição de conhecimentos em dieta saudável. Foi desenvolvido inicialmente um programa de educação em obesidade infantil e posteriormente comparado com o atendimento ambulatorial habitual. O presente estudo constou de um ensaio clínico randomizado entre crianças e adolescentes com idade entre 7 e 13 anos incompletos que tivessem IMC compatível para obesidade, de acordo com a idade e sexo, segundo classificação de COLE et al (2002). Os sujeitos foram aleatoriamente distribuídos em dois grupos. Cada grupo foi acompanhado por oito meses, sendo que o primeiro e o oitavo encontro serviram para responder questionários que avaliavam aspectos gerais, hábitos alimentares e de atividade física, conhecimentos gerais sobre dieta saudável e avaliação corporal. O grupo ambulatorial teve atendimento mensal com aferição de peso e orientações gerais quanto alimentação e atividade física. O grupo programa tinha encontro mensal, em grupo, seus participantes assistiam a uma aula expositiva e, posteriormente, eram divididos em grupos para atividades monitoradas, e os pais e/ou responsáveis ficavam discutindo suas dificuldades e como mudar hábitos. As 38 crianças inicialmente apresentavam algumas diferenças quanto a atividade física, mas após a intervenção elas se assemelharam, apresentando ambas tendência a desfechos favoráveis. O grupo programa passou a fazer mais atividade física e caminhar, e reduziu sedentarismo. O grupo programa foi mais efetivo em reduzir colesterol total. Houve também uma melhora do hábito alimentar do grupo programa, com menor consumo de massa + arroz, bebida láctea + leite, leite, salsicha + frios e sanduíche + bauru. Assim, conclui-se que as intervenções foram semelhantes e de sucesso, podendo-se aplicar mais o programa, que pode envolver menos profissionais, mais sujeitos e ser realizado em qualquer local, especialmente nas escolas, que são, na realidade, o local de mudança.

Host specificity of a Brazilian isolate of Alternaria cassiae (Cenargen CG593) under greenhouse conditions

Several Alternaria cassiae isolates were recovered from diseased sicklepod plants (Senna obtusifolia) in the southern regions of Brazil. A representative isolate (Cenargen CG593) was tested for its host range under greenhouse conditions. The fungus promoted symptoms in sicklepod, cassava (Manihot dulce), tomato (Lycopersicon esculentum) and eggplant (Solanum melongena) when tested at a spore concentration of 10(6) spores ml(-1). When the plants were inoculated with a suspension of 10(5) spores ml(-1) and held at a dew period of 12 h (cassava) or 18 h (tomato and eggplant), the plants showed symptoms of the disease, but they recovered and continued their normal vegetative growth. These results show that the fungus A. cassiae is safe to use for the control of S. obtusifolia under Brazilian conditions, because it did not cause excessive damage in the three plants tested.

Transmission of Citrus leprosis virus C by Brevipalpus phoenicis (Geijskes) to Alternative Host Plants Found in Citrus Orchards

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunity of an Alternative Host Can Be Overcome by Higher Densities of Its Parasitoids Palmistichus elaeisis and Trichospilus diatraeae

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Muscular Dystrophy in Dogs: Does the Crossing of Breeds Influence Disease Phenotype?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Behavior of Leishmania major metacyclic promastigotes during the course of infection and immune response development in resistant versus susceptible hosts

Pouco se conhece sobre os epítopos derivados de promastigotas metacíclicos de Leishmania que são importantes para a regulação ou destruição do parasita, como alvos de ação imunológica no hospedeiro vertebrado. Neste estudo, nós investigamos um método alternativo para obter promastigotas metacíclicos de Leishmania major, pela avaliação do curso da infecção e reação de hipersensibilidade do tipo retardado (HTR) em hospedeiros resistentes e susceptíveis. Promastigotas não-infectantes (procíclicos) de L. major, recentemente isolados de amastigotas, foram selecionados pela adesão a colunas de lã de vidro negativamente carregadas, enquanto que promastigotas metacíclicos não se aderem à coluna e podem ser recuperados com facilidade. Condições ótimas de cromatografia foram validadas por análise estatística. O rendimento médio de parasitas obtidos após separação em colunas de lã de vidro e a viabilidade dos promastigotas foram estimados por microscopia óptica. Os promastigotas metacíclicos tiveram um rendimento médio de 43,5% a 57,5%. Camundongos BALB/c (susceptíveis) e camundongos C57BL/6 (resistentes) apresentaram padrões distintos de lesões cutâneas, os primeiros com lesões mais agressivas, induzidas por promastigotas metacíclicos. As respostas à reação de HTR foram maiores nos grupos de camundongos C57BL/6, submetidos à infecção com promastigotas metacíclicos. Estes resultados indicam que o novo método poderia ser integrado aos protocolos existentes para estudar a metaciclogênese de parasitas do gênero Leishmania in vivo.

Is walking in daily life a moderate intensity activity in patients with chronic obstructive pulmonary disease?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)