Nanostructured lipid carriers as a novel tool to deliver sclareol: physicochemical characterisation and evaluation in human cancer cell lines

Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties

The Genome of Anopheles darlingi, the main neotropical Malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vector–human and vector–parasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible a

The Genome of Anopheles darlingi, the main neotropical malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vectorhuman and vectorparasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles- darlingi. © 2013 The Author(s)

Microwave-assisted synthesis of borneol esters and their antimicrobial activity

<p>Seventeen borneol esters (<b>1</b>–<b>17</b>) were synthesised by conventional and microwave-assisted methodology using DIC/DMAP, and seven are described for the first time (<b>8</b>, <b>9</b>, <b>10</b>, <b>12</b>, <b>13</b>, <b>16</b> and <b>17</b>). The microwave-assisted methodology was carried out without use of solvents, displayed short reaction times, and showed equal or higher yields for all the long-chain esters and three aromatic compounds (<b>11</b>, <b>12</b> and <b>14)</b> when compared to the conventional approach. All the borneol esters were evaluated against the bacteria <i>Streptococcus sanguinis</i>, <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i> and the fungus <i>Candida albicans</i>. Compounds <b>12</b>, <b>13</b> and <b>14</b> displayed promising antibacterial activity with a MIC equal to ampicilin (62.5 mg mL⁻¹) for some microorganisms. In fact, bornyl 3′,4′-dimethoxybenzoate (<b>13</b>) was active against all tested bacteria and fungus.</p

Lupeol and its esters: NMR, powder XRD data and in vitro evaluation of cancer cell growth

<div><p>ABSTRACT The triterpene lupeol (1) and some of its esters are secondary metabolites produced by species of Celastraceae family, which have being associated with cytotoxic activity. We report herein the isolation of 1, the semi-synthesis of eight lupeol esters and the evaluation of their in vitro activity against nine strains of cancer cells. The reaction of carboxylic acids with 1 and DIC/DMAP was used to obtain lupeol stearate (2), lupeol palmitate (3) lupeol miristate (4), and the new esters lupeol laurate (5), lupeol caprate (6), lupeol caprilate (7), lupeol caproate (8) and lupeol 3’,4’-dimethoxybenzoate (9), with high yields. Compounds 1-9 were identified using FT-IR, 1H, 13C-NMR, CHN analysis and XRD data and were tested in vitro for proliferation of human cancer cell activity. In these assays, lupeol was inactive (GI50> 250µg/mL) while lupeol esters 2 -4 and 7 - 9 showed a cytostatic effect. The XRD method was a suitable tool to determine the structure of lupeol and its esters in solid state. Compound 3 showed a selective growth inhibition effect on erythromyeloblastoid leukemia (K-562) cells in a concentration-dependent way. Lupeol esters 4 and 9 showed a selective cytostatic effect with low GI50 values representing promising prototypes for the development of new anticancer drugs.</p></div

Angiotensin-(1-7) and Alamandine Promote Anti-inflammatory Response in Macrophages In Vitro and In Vivo

The renin-angiotensin system (RAS) peptides play an important role in inflammation. Resolution of inflammation contributes to restore tissue homeostasis, and it is characterized by neutrophil apoptosis and their subsequent removal by macrophages, which are remarkable plastic cells involved in the pathophysiology of diverse inflammatory diseases. However, the effects of RAS peptides on different macrophage phenotypes are still emerging. Here, we evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) and the most novel RAS peptide, alamandine, on resting (M0), proinflammatory M(LPS+IFN-γ), and anti-inflammatory M(IL-4) macrophage phenotypes in vitro, as well as on specific immune cell populations and macrophage subsets into the pleural cavity of LPS-induced pleurisy in mice. Our results showed that Ang-(1-7) and alamandine, through Mas and MrgD receptors, respectively, do not affect M0 macrophages but reduce the proinflammatory TNF-α, CCL2, and IL-1β transcript expression levels in LPS+IFN-γ-stimulated macrophages. Therapeutic administration of these peptides in LPS-induced inflammation in mice decreased the number of neutrophils and M1 (F4/80lowGr1+CD11bmed) macrophage frequency without affecting the other investigated macrophage subsets. Our data suggested that both Ang-(1-7) and alamandine, through their respective receptors Mas and MrgD, promote an anti-inflammatory reprogramming of M(LPS+IFN-γ)/M1 macrophages under inflammatory circumstances and potentiate the reprogramming induced by IL-4. In conclusion, our work sheds light on the emerging proresolving properties of Ang-(1-7) and alamandine, opening new avenues for the treatment of inflammatory diseases

Duration of post-vaccination immunity against yellow fever in adults

Submitted by Nuzia Santos ([email protected]) on 2015-06-22T17:37:43Z No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-06-22T17:37:52Z (GMT) No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-06-22T17:58:36Z (GMT) No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5)Made available in DSpace on 2015-06-22T17:58:36Z (GMT). No. of bitstreams: 1 2014_152.pdf: 756403 bytes, checksum: c18d98237e29e19e785cf895a2a68ddc (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Brasilia, DF, BrasilFundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Rio de Janeiro, RJ, BrazilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicosde Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos de Bio-Manguinhos. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Imunopatologia .Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Esquistossomose. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratório de Biomarcadores. Belo Horizonte, MG, BrasilFood and Drug Administration Center for Biologics Evaluation and Research. Bethesda, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de Fla-vivirus. Rio de JaneiroInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilInstituto de Biologia do Exército. Rio de Janeiro, RJ, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilMinas Gerais. Secretaria Estadual de Saude. Belo Horizonte, MG, BrasilUniversidade Federal de Alfenas. Alfenas, MG, BrasilUniversidade de Brasília. Faculdade de Medicina. Brasilia, DF, BrasilFundação Oswaldo Cruz. Instituto Evandro Chagas. Ananindeua, PA, BrasilINTRODUCTION: Available scientific evidence to recommend or to advise against booster doses of yellow fever vaccine (YFV) is inconclusive. A study to estimate the seropositivity rate and geometric mean titres (GMT) of adults with varied times of vaccination was aimed to provide elements to revise the need and the timing of revaccination. METHODS: Adults from the cities of Rio de Janeiro and Alfenas located in non-endemic areas in the Southeast of Brazil, who had one dose of YFV, were tested for YF neutralising antibodies and dengue IgG. Time (in years) since vaccination was based on immunisation cards and other reliable records. RESULTS: From 2011 to 2012 we recruited 691 subjects (73% males), aged 18-83 years. Time since vaccination ranged from 30 days to 18 years. Seropositivity rates (95%C.I.) and GMT (International Units/mL; 95%C.I.) decreased with time since vaccination: 93% (88-96%), 8.8 (7.0-10.9) IU/mL for newly vaccinated; 94% (88-97), 3.0 (2.5-3.6) IU/mL after 1-4 years; 83% (74-90), 2.2 (1.7-2.8) IU/mL after 5-9 years; 76% (68-83), 1.7 (1.4-2.0) IU/mL after 10-11 years; and 85% (80-90), 2.1 (1.7-2.5) IU/mL after 12 years or more. YF seropositivity rates were not affected by previous dengue infection. CONCLUSIONS:Eventhough serological correlates of protection for yellow fever are unknown, seronegativity in vaccinated subjects may indicate primary immunisation failure, or waning of immunity to levels below the protection threshold. Immunogenicity of YFV under routine conditions of immunisation services is likely to be lower than in controlled studies. Moreover, infants and toddlers, who comprise the main target group in YF endemic regions, and populations with high HIV infection rates, respond to YFV with lower antibody levels. In those settings one booster dose, preferably sooner than currently recommended, seems to be necessary to ensure longer protection for all vaccinee