New treatment strategies for Alzheimer's disease: is there a hope?

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, and corresponds to the most common cause of dementia worldwide. Although not fully understood, the pathophysiology of AD is largely represented by the neurotoxic events triggered by the beta-amyloid cascade and by cytoskeletal abnormalities subsequent to the hyperphosphorylation of microtubule-associated Tau protein in neurons. These processes lead respectively to the formation of neuritic plaques and neurofibrillary tangles, which are the pathological hallmarks of the disease. Clinical benefits of the available pharmacological treatment for AD with antidementia drugs (namely cholinesterase inhibitors and memantine) are unquestionable, although limited to a temporary, symptomatic support to cognitive and related functions. Over the past decade, substantial funding and research have been dedicated to the search and development of new pharmaceutical compounds with disease-modifying properties. The rationale of such approach is that by tackling key pathological processes in AD it may be possible to attenuate or even change its natural history. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and Tau pathology in AD, focusing on pharmaceutical compounds undergoing phase 2 and phase 3 randomized controlled trials.

Probióticos e prebióticos na atenção primária ao câncer de cólon

CONTEXTO: As neoplasias de cólon são a terceira forma mais comum de câncer atualmente. Seus tratamentos ainda estão associados a elevado risco de complicações, ressaltando, assim, a necessidade de elaborar novas estratégias de tratamento. A ingestão de probióticos, prebióticos ou a combinação de ambos (simbióticos), representa nova opção terapêutica. Diante da importância do equilíbrio quantitativo e qualitativo da microbiota intestinal para saúde humana e com objetivo de melhor elucidar o papel dos probióticos e prebióticos, o tema citado procura abordar a importância destes como coadjuvantes na prevenção e tratamento de câncer de cólon. METODOLOGIA: Foi realizada pesquisa em bancos de dados científicos (Medline, Lilacs, PubMed, Ovid, Scielo) através de levantamento de artigos científicos, além da busca direta aos periódicos, priorizando-se os mesmos do período de 2003 a 2008. Foram, também, coletadas informações através de sites da internet, como forma de melhor compreender a epidemiologia, conceitos e tratamentos dessa patologia. RESULTADOS: Estudos apontam relação inversa entre o consumo de probióticos e prebióticos e o diagnóstico de câncer de cólon, sendo que alguns dos possíveis mecanismos englobam: aumento da resposta imune, redução da resposta inflamatória, inibição de formação de células tumorais e da conversão de substâncias pré-carcinogênicas em carcinogênicas. CONCLUSÃO: Através da realização desta revisão literária foi possível obter respostas positivas quanto ao uso de probióticos e prebióticos na carcinogênese, colocando seu uso como recomendado de forma adequada.

Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease

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

Implication of RNA-Binding Protein La in Proliferation, Migration and Invasion of Lymph Node-Metastasized Hypopharyngeal SCC Cells

The 5-year survival rate for oral cavity cancer is poorer than for breast, colon or prostate cancer, and has improved only slightly in the last three decades. Hence, new therapeutic strategies are urgently needed. Here we demonstrate by tissue micro array analysis for the first time that RNA-binding protein La is significantly overexpressed in oral squamous cell carcinoma (SCC). Within this study we therefore addressed the question whether siRNA-mediated depletion of the La protein may interfere with known tumor-promoting characteristics of head and neck SCC cells. Our studies demonstrate that the La protein promotes cell proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells. We also reveal that La is required for the expression of beta-catenin as well as matrix metalloproteinase type 2 (MMP-2) within these cells. Taken together these data suggest a so far unknown function of the RNA-binding protein La in promoting tumor progression of head and neck SCC.

Seasonal variation in natural populations of Drosophila spp. (Diptera) in two woodlands in the State of São Paulo, Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The genetic diversity of Plasmodium vivax: a review

The genetic diversity of Plasmodium vivax has been investigated in several malaria-endemic areas, including the Brazilian Amazon region, where this is currently the most prevalent species causing malaria in humans. This review summarizes current views on the use of molecular markers to examine P. vivax populations, with a focus on studies performed in Brazilian research laboratories. We emphasize the importance of phylogenetic studies on this parasite and discuss the perspectives created by our increasing understanding of genetic diversity and population structure of this parasite for the development of new control strategies, including vaccines, and more effective drugs for the treatment of P. vivax malaria.

O transplante de células-tronco hematopoéticas como opção no tratamento de doenças não hematológicas

Nesta revisão são abordadas as doenças em que existem dados e perspectivas do uso de transplante de células-tronco hematopoéticas em suas diversas modalidades. São apresentados também os aspectos referentes aos regimes de condicionamento empregados, e sua relação com toxicidade e taxa de mortalidade ligadas ao transplante. São apresentadas as doenças autoimunes e particularizados dados específicos do lúpus eritematoso sistêmico, esclerose sistêmica e esclerose múltipla e diabetes mellitus tipo 1. A base do procedimento nas doenças autoimunes é a reprogramação imunológica. Aparentemente o procedimento tem sua indicação nas doenças em que os tratamentos convencionais de imunossupressão tenham falhado, e o dano orgânico não tenha sido definitivo, mas tenha chance de ocorrer caso não seja realizado o transplante. A modalidade aparentemente indicada no momento deve ser o transplante de células-tronco autogênico com regimes de condicionamento não mieloablativo para se obter sobrevivência estimada em mais de 50% em todas as doenças, com baixa toxicidade e com mortalidade nula ligada ao transplante. São apresentados também os resultados nos tumores sólidos, que são discutíveis, e particularidades no câncer de mama. A aparente indicação para os tumores sólidos é transplante de células-tronco alogênico e se baseia no tratamento intensivo com doses mieloablativas com a finalidade de se induzir o efeito enxerto contra o tumor. Os regimes não mieloablativos são preconizados com a finalidade de redução da toxicidade e indução de imunossupressão, sendo os dados insuficientes e discutíveis, o que obriga a introdução de novas estratégias terapêuticas baseadas na terapia imune e celular.

Inflammation-induced modulation of cellular galectin-1 and-3 expression in a model of rat peritonitis

Objective and design: To investigate the effect of galectin-1 (Gal-1) and -3 (Gal-3) on leukocyte migration and analyze the expression of both galectins in inflammatory cells using a model of rat peritonitis.Material or Subjects: Sprague-Dawley rats (n = 4 per group).Treatment: Peritonitis was induced in animals through intraperitoneal injection of carrageenin (1.5 mg/kg) and rat mesenteries were analyzed at different time points (0, 4, 24 and 48h). For pharmacological treatment, rats received intravenous injection of Gal-1 or -3 (3 mu g/kg) followed by carrageenin.Methods: Western blotting and immunoelectron microscopy analysis. Statistical analysis was performed using ANOVA followed by Bonferroni test.Results: Pharmacological treatment with Gal-1, but not Gal-3, inhibited (similar to 50%) leukocyte recruitment into the peritoneal cavity at 4h time-point. In this early phase, immunogold staining of mesenteries showed a diminished Gal-3 expression in degranulated mast cells and Gal-1 in transmigrated neutrophils (similar to 20% reduction compared to intravascular cells). In the later phases (24 and 48 h), leukocyte turnover was associated with augmented Gal-1 expression in neutrophils and macrophages and Gal-3 in mast cells and macrophages.Conclusions: These results point to a balanced expression of cell-associated-Gal-1/Gal-3 and might impact on the development of new therapeutic strategies for inflammatory diseases.

Gene discovery in Boophilus microplus, the cattle tick - the transcriptomes of ovaries, salivary glands, and hemocytes

The quest for new control strategies for ticks can profit from high throughput genomics. In order to identify genes that are involved in oogenesis and development, in defense, and in hematophagy, the transcriptomes of ovaries, hemocytes, and salivary glands from rapidly ingurgitating females, and of salivary glands from males of Boophilus microplus were PCR amplified, and the expressed sequence tags (EST) of random clones were mass sequenced. So far, more than 1,344 EST have been generated for these tissues, with approximately 30% novelty, depending on the the tissue studied. To date approximately 760 nucleotide sequences from B. microplus are deposited in the NCBI database. Mass sequencing of partial cDNAs of parasite genes can build up this scant database and rapidly generate a large quantity of useful information about potential targets for immunobiological or chemical control.

Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression

We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.

Shunt active compensation based on the Conservative Power Theory current's decomposition

Considering the operation of shunt active compensators, such as active power filters, this paper proposes possible compensation strategies by means of the recent formulation of the Conservative Power Theory (CPT). The CPT current's decomposition results in several current components, which are associated with specific load characteristics (power transfer, energy storage, unbalances and/or non linearities). These current components are used for the definition of different compensation strategies, which can be selective in terms of minimizing particular disturbing effects. In order to validate the applicability of these new compensation strategies, simulation and experimental results for three-phase four-wire systems are presented. © 2011 IEEE.

Methods for obtaining reliable and reproducible results in studies of Candida biofilms formed in vitro

Biofilm formation is one of the most important attributes for virulence in Candida species and contributes to increased resistance to antifungal drugs and host immune mechanisms. These features have led to the development of several methodologies to reproduce a sessile community in vitro that can be used to study the development of a biofilm, its interaction with other microorganisms and the environment, and its susceptibility to available antifungal agents and also to search for new therapy strategies. The purpose of this review is to describe the most commonly used methods to study Candida biofilms in vitro, to discuss the benefits and limitations of the different methods to induce biofilm formation, and to analyse the architecture, viability and growth kinetics of Candida biofilms. © 2013 Blackwell Verlag GmbH.

Recent mouse and rat methods for the study of experimental oral candidiasis

The Candida genus expresses virulence factors that, when combined with immunosuppression and other risk factors, can cause different manifestations of oral candidiasis. The treatment of mucosal infections caused by Candida and the elucidation of the disease process have proven challenging. Therefore, the study of experimentally induced oral candidiasis in rats and mice is useful to clarify the etiopathology of this condition, improve diagnosis, and search for new therapeutic options because the disease process in these animals is similar to that of human candidiasis lesions. Here, we describe and discuss new studies involving rat and mouse models of oral candidiasis with respect to methods for inducing experimental infection, methods for evaluating the development of experimental candidiasis, and new treatment strategies for oral candidiasis. © 2013 Landes Bioscience.

O papel da America do Sul na inserção internacional do Brasil: uma análise do governo de Luiz Inácio Lula da Silva (2003-2010)

Pós-graduação em Ciências Sociais - FCLAR

Líderes e motivadores profissionais: novos trabalhadores a serviço do capital (dimensões ideológicas, disciplinares e cooptativas)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)