Therapeutic DNA Vaccine Encoding Peptide P10 against Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients

Representações sociais de Agentes Comunitários de Saúde acerca do consumo de drogas

Este artigo discute as representações sociais de Agentes Comunitários de Saúde (ACS) acerca do consumo de drogas, como recorte de um estudo qualitativo de cunho etnográfico, cuja produção dos dados ocorreu no período de janeiro/2006 a janeiro/2007. Um conjunto de técnicas foi aplicado para profissionais que atuam numa Unidade Básica de Saúde de Salvador-BA, dentre eles 22 ACS. A Teoria das Representações Sociais foi adotada como eixo teórico, e gênero como categoria de análise. Os ACS reconhecem a proximidade e o envolvimento das mulheres com o fenômeno das drogas na comunidade onde moram e atuam, porém não adotam em seu trabalho nenhuma ação direcionada para tal problemática. As representações sociais apreendidas reproduzem estereótipos e preconceitos em relação às drogas e às pessoas usuárias de drogas, vinculadas, sobretudo, ao sexo e classe social, assinalando a invisibilidade do consumo de drogas como um problema de saúde para o grupo estudado.Este artículo discute las representaciones sociales de Agentes Comunitarios de Salud (ACS) respecto del consumo de drogas, como elemento integrante de un estudio cualitativo, de cuño etnográfico, cuyos datos fueron recogidos en el período de enero 2006 - enero 2007. Se aplicó un conjunto de técnicas en profesionales con actuación en una Unidad Básica de Salud de Salvador, BA, Brasil, de los cuales 22 eran ACS. La Teoría de las Representaciones Sociales fue adoptada como eje teórico y el género como categoría de análisis. Los ACS reconocen la proximidad y el grado de compromiso de las mujeres con el fenómeno de las drogas en la comunidad en donde viven y actúan; no obstante no adopten en su trabajo ninguna acción direccionada hacia tal problemática. Las representaciones sociales aprehendidas reproducen estereotipos y preconceptos en relación a las drogas y a las personas usuarias vinculadas, sobre todo al sexo y clase social y señalan la invisibilidad del consumo de drogas como un problema de salud para el grupo estudiado.This paper discusses on the social representations of community health agents (CHAs) about drug use as part of a qualitative, ethnographic study with data collected by means of a set of research techniques among health professionals including 22 CHAs in a basic health unit in Salvador, Bahia (Brazil) from January, 2006 to January, 2007. The Theory of Social Representations was adopted as the theoretical framework whereas gender was the chosen analytical category. CHAs were found to recognize the women's proximity and participation in the drug phenomenon in the community where they live and act, although they take no professional measures towards such an issue. Their social representations were shown to reproduce stereotypes and prejudices towards drug users and drug use, especially gender- and social class-related, while highlighting the invisibility of drug use as a health problem for the population under study

Stimulation of potato tuber respiration by cold stress is associated with an increased capacity of both plant uncoupling mitochondrial protein (PUMP) and alternative oxidase

The CO2 evolution of intact potato tubers (Solanum tuberosum, L., var. 'Bintje') was analyzed during a 10-day period of their warm (25+/-2degreesC) or cold (5+/-1degreesC) storage, to evaluate cold-stress effects on expression and activities of plant uncoupling mitochondrial protein (PUMP) and alternative oxidase (AOX). CO2 evolution rates were analyzed at 20degreesC, to reflect their possible capacities. The 20degreesC CO2 production declined from 13 to 8 mg kg(-1) h(-1) after 2 days of warm storage and then (after 3 to 7 days) decreased from 8 to 6.5 mg kg(-1) h(-1). In contrast, 20degreesC CO2 evolution did not change after the first day of cold storage, increased up to 14.5 mg kg(-1) h(-1) after 2 days, and decreased to about 12 mg kg(-1) h(-1) after 3 to 7 days of cold storage. Cold storage increased PUMP expression as detected by Western blots and led to elevated capacities of both PUMP (44%) and CN-resistant AOX (10 times), but not the cytochrome pathway. Since we found that cold storage led to about the same mitochondrial respiration of 40 nmol O-2 min(-1) mg(-1) attributable to each of the respective proteins, we conclude that both AOX and PUMP equally contribute to adaptation of potato tubers to cold.35321122

Theoretical-Experimental Study of Formic Acid Photofragmentation in the Valence Region

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Photoionization and photofragmentation studies of formic acid (HCOOH) are performed for the valence shell electron ionization process. The total and partial ion yield of gaseous HCOOH were collected as a function of photon energy in the ultraviolet region, between 11.12 and 19.57 eV. Measurements of the total and partial ion yield of gaseous formic acid molecule are performed with a time-of-flight mass spectrometer at the Synchrotron Light Brazilian Laboratory. Density functional theory and time dependent density functional theory are employed to calculate the ground and excited electronic state energies of neutral and ionic formic acid as well as their fragments and normal vibration modes. The ionization potential energies, the stability of electronic excited states of HCOOH+, and the energies of opening fragmentation channels are estimated from theoretical-experimental analysis. Additionally, the main formic acid photofragmentation pathways by exposition of photons within that energy range are determined experimentally. These produced ions primarily have the following mass/charge ratios: 46 (HCOOH+), 45 (COOH+), 29 (HCO+), and 18 (H2O+).11625SI66936701Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao de Amparo a Pesquisa do Estado da Bahia (FAPESB, Brazil)Laboratorio Nacional de Luz Sincrotron (LNLS, Brazil)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

β-Actin-binding complementarity-determining region 2 of variable heavy chain from monoclonal antibody C7 induces apoptosis in several human tumor cells and is protective against metastatic melanoma

Complementarity-determining regions (CDRs) from monoclonal antibodies tested as synthetic peptides display anti-infective and antitumor activities, independent of the specificity of the native antibody. Previously, we have shown that the synthetic peptide C7H2, based on the heavy chain CDR 2 from monoclonal antibody C7, a mAb directed to a mannoprotein of Candida albicans, significantly reduced B16F10 melanoma growth and lung colony formation by triggering tumor apoptosis. The mechanism, however, by which C7H2 induced apoptosis in tumor cells remained unknown. Here, we demonstrate that C7H2 interacts with components of the tumor cells cytoskeleton, being rapidly internalized after binding to the tumor cell surface. Mass spectrometry analysis and in vitro validation revealed that β-actin is the receptor of C7H2 in the tumor cells. C7H2 induces β-actin polymerization and F-actin stabilization, linked with abundant generation of superoxide anions and apoptosis. Major phenotypes following peptide binding were chromatin condensation, DNA fragmentation, annexin V binding, lamin disruption, caspase 8 and 3 activation, and organelle alterations. Finally, we evaluated the cytotoxic efficacy of C7H2 in a panel of human tumor cell lines. All tumor cell lines studied were equally susceptible to C7H2 in vitro. The C7H2 amide without further derivatization significantly reduced lung metastasis of mice endovenously challenged with B16F10-Nex2 melanoma cells. No significant cytotoxicity was observed toward nontumorigenic cell lines on short incubation in vitro or in naïve mice injected with a high dose of the peptide. We believe that C7H2 is a promising peptide to be developed as an anticancer drug