Sobre caso de doença de Chagas aguda em região de vetores controlados no Estado de São Paulo, Brasil

No vector transmitted cases of Chagas disease had been notified in the state of São Paulo since the 1970s. However, in March, 2006, the death of a six-year-old boy from the municipality of Itaporanga was notified to the Center for Epidemiological Survey of the São Paulo State Health Secretariat: an autochthonous case of acute Chagas disease. The postmortem histopathological examination performed in the Hospital das Clínicas of the Botucatu School of Medicine confirmed the diagnosis. Reference to hospital records, consultation with the health professionals involved in the case and interviews with members of the patient's family supplied the basis for this study. We investigated parasite route of transmission, probable local reservoirs and vectors. No further human cases of acute Chagas disease were diagnosed. No locally captured vectors or reservoirs were found infected with Trypanosoma cruzi. Alternative transmission hypotheses - such as the possible ingestion of foods contaminated with vector excreta - are discussed, as well as the need to keep previously endemic regions and infested houses under close surveillance. Clinicians should give due attention to such signs as uni- or bilateral palpebral edema, cardiac failure, myocarditis, pericarditis, anasarca and atypical signs of nephrotic syndrome or nephritis and consider the diagnostic hypothesis of Chagas disease.Desde a década de 1970 não se notificavam casos autóctones de doença de Chagas aguda em São Paulo. Em março de 2006 a Vigilância Epidemiológica registrou óbito por doença de Chagas aguda, em Itaporanga, de paciente de seis anos de idade. Exame histopatológico post mortem realizado no Hospital das Clínicas da Faculdade de Medicina de Botucatu confirmou o diagnóstico. Consultamos prontuários de hospitais e entrevistamos profissionais de saúde envolvidos além de familiares do paciente. Descrevemos medidas adotadas in loco para identificar a via de transmissão, reservatórios e vetores. Discutimos as possíveis fontes de infecção. Na região não foram identificados outros casos humanos, vetores ou reservatórios vertebrados infectados por Trypanosoma cruzi. Salientamos a importância de manter a vigilância, mesmo em áreas onde a transmissão de doença de Chagas está interrompida e naquelas ainda infestadas por triatomíneos. Deve-se admitir a hipótese diagnóstica de doença de Chagas quando observados: edema palpebral (uni ou bilateral), insuficiência cardíaca, miocardite, pericardite, anasarca, quadros similares aos de síndrome nefrótica ou glomerulonefrite sem causas outras aparentes, em pacientes com dados epidemiológicos positivos. Encontro, mesmo em raras ocasiões, de triatomíneos na região ou ainda contato com alimento contaminável com formas infectantes de T. cruzi

Recombinant vaccines and the development of new vaccine strategies

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks

Microsomal Lipid Peroxidation Concomitant To Peroxidase-catalyzed Aerobic Oxidation Of Indole-3-acetate

[No abstract available]11428129

Different Lethal Effects By Enzyme-generated Triplet Indole-3-aldehyde In Different Escherichia Coli Strains

Strains of Escherichia coli which lack 4-thiouridine (S4U) exhibit a higher survival rate than their wild-type parents which contain S4U after treatment with enzyme-generated triplet indole-3-aldehyde. In a similar manner to results obtained with monochromatic 334 nm UV light, the survival is related to single-strand breakage of DNA in E. coli containing the pBR 322 plasmid. The effects of the excited states generated by an enzymatic system suggest that S4U is an important chromophore in the lethal effects observed. The results also suggest that the energy transferred from triplet indole-3-aldehyde to S4U may also be passed from S4U of T-RNA to DNA, possibly through a singlet oxygen intermediate generated by excited S4U, resulting in a decrease in the survival rate of E. coli containing S4U. These results emphasize the importance of excited states in biological systems. © 1990.44371378Peak, Peak, Nerad, The role of 4-thiouridine in lethal effects and in DNA backbone breakage caused by 334 nm ultraviolet light in Escherichia coli (1983) Photochem. Photobiol., 37, pp. 169-172De Mello, De Toledo, Durán, Photo- and biophotoenergized cycloaddition of indole-3-aldehyde to uridine (1981) Acta Sud Am. Quim., 1, pp. 135-141Durán, Brunet, Gallardo, An experiment in photochemistry α-Oxidation of indole-3-acetic acid catalyzed by peroxidase (1984) Biochemical Education, 12, pp. 173-178Durán, Cadenas, The role of singlet oxygen and triplet carbonyls in biological systems (1987) Reviews of Chemical Intermediates, 8, pp. 147-187De Mello, De Toledo, Haun, Cilento, Durán, Excited indole-3-aldehyde from peroxidase catalyzed aerobic oxidation of indole-3-acetic acid. Reaction with and energy transfer to transfer-ribonucleic acid (1980) Biochemistry, 19, pp. 5270-5275De Mello, de Toledo, Aoyama, Sarkar, Cilento, Durán, Peroxidase-generated triplet indole-3-aldehyde adds to uridine bases and excites the 4-thiouridine group in t-RNA(Phe) (1982) Photochem. Photobiol., 36, pp. 21-24Durán, Marcucci, De Mello, Faljoni-Alario, Enzymatically generated electronically excited molecules induce transformation of 4-thiouridine to uridine (1983) Biochem. Biophys. Res. Commun., 117, pp. 923-929Durán, De Mello, Photobiochemistry of 4-thiouridine in E coli t-RNA (1983) Photochemistry and Photobiology, 37, p. S11De Toledo, Zaha, Durán, DNA strand scission in E. coli by electronically excites state molecules generated by enzymatic systems (1982) Biochem. Biophys. Res. Commun., 104, pp. 990-995Menck, Cabral Neto, Faljoni-Alario, Alcantara-Gomes, Damage induced in λ-phase DNA by enzyme-generated triplet acetone (1985) Mutat. Res., 165, pp. 9-14Guillo, De Toledo, Durán, Attemptet detection by fluorescence probes of DNA modifications produced by bioenergized triplet acetone (1983) Photobiochem. Photobiophys., 6, pp. 177-186Nassi, Schiffmann, Fabre, Adam, Fuchs, Induction of the SOS function sfiA in E. coli by systems which generate triplet ketones (1988) Mutat. Res., 198, pp. 53-60Durán, Marcucci, De Mello, Leite, Faljoni-Alario, DNA modification through biophotoenergized processes on t-RNA (1984) Photochem. Photobiol., 39, p. 80SDurán, Marcucci, Gatti, Leite, Lethal effect and DNA breakage caused by biophotoenergized indole-3-aldehyde in E. coli (1986) Int. Symp. on Free Radicals and Excited State in Biological Systems, Buenos Aires, , Abstract 16Birnboim, Doty, A rapid alkaline extraction procedure for screening recombinant plasmid DNA (1979) Nucleic Acids Research, Z, pp. 1513-1520Durán, Faria-Furtado, Faljoni-Alario, Campa, Brunet, Freer, Singlet oxygen generation from the peroxidase-catalyzed aerobic oxidation of an activated —CH substrate (1984) Journal of Photochemistry, 25, pp. 285-295Hardwick, Von Sprecken, Yielding, Yielding, Ethidium binding sites in plasmid DNA determined by photoaffinity labeling (1984) J. Biol. Chem., 159, pp. 11090-11097Hass, Webb, Photodynamic effects of dyes on bacteria. I. V. Lethal effects of acridine orange and 460 or 500 nm monochromatic light in strains of Escherichiacoli that differ in repair capability (1981) Mutat. Res., 81, pp. 277-285Salet, Bazin, Moreno, Favre, 4-Thiouridine as photodynamic agent (1985) Photochemistry and Photobiology, 41, pp. 617-619Thomas, Favre, 4-Thiouridine triggers both growth delay induced by near-ultraviolet light photoprotection (1980) Eur. J. Biochem., 113, pp. 825-834Tsai, Jagger, The roles of the Rel(+) gene and of 4-thiouridine in killing photoprotection of Escherichia coli by near ultraviolet radiation (1981) Photochem. Photobiol., 33, pp. 825-834Caldeira de Araujo, Favre, Near ultraviolet DNA damage induces the SOS response in Escherichia coli (1986) EMBO J., 5, pp. 175-179Peak, Peak, MacCoss, DNA breakage caused by 334 nm ultraviolet light enhanced by naturally occurring nucleic acid components nucleotide coenzymes (1984) Photochem. Photobiol., 39, pp. 713-716Peak, Peak, Foote, Observation on the photosensitized breakage of DNA by 2-thiouracil and 334 nm ultraviolet radiation (1986) Photochem. Photobiol., 44, pp. 111-116Town, Smith, Kaplan, DNA polymerase required for rapid repair of X-rays-induced DNA strand breaks in vivo (1971) Science, 171, pp. 851-854Smith, Sargentini, Metabolically produced UV-like DNA damage and its role in spontaneous mutagenesis (1985) Photochem. Photobiol., 42, pp. 801-803Durán, Campa, Leite, Cilento, Cadenas, Microsomal lipid peroxidation concomitant to peroxidase-catalyzed aerobic oxidation of indole-3-acetate (1986) Photobiochem. Photobiophys., 11, pp. 281-29

Recombinant BCG-LTAK63 Vaccine Candidate for Tuberculosis Induces an Inflammatory Profile in Human Macrophages

Tuberculosis (TB) is one of the top 10 leading causes of death worldwide. The recombinant BCG strain expressing the genetically detoxified A subunit of the thermolabile toxin from Escherichia coli (LTAK63) adjuvant (rBCG-LTAK63) has previously been shown to confer superior protection and immunogenicity compared to BCG in a murine TB infection model. To further investigate the immunological mechanisms induced by rBCG-LTAK63, we evaluated the immune responses induced by rBCG-LTAK63, BCG, and Mycobacterium tuberculosis (Mtb) H37Rv strains in experimental infections of primary human M1 and M2 macrophages at the transcriptomic and cytokine secretion levels. The rBCG-LTAK63-infected M1 macrophages more profoundly upregulated interferon-inducible genes such as IFIT3, OAS3, and antimicrobial gene CXCL9 compared to BCG, and induced higher levels of inflammatory cytokines such as IL-12(p70), TNF-beta, and IL-15. The rBCG-LTAK63-infected M2 macrophages more extensively upregulated transcripts of inflammation-related genes, TAP1, GBP1, SLAMF7, TNIP1, and IL6, and induced higher levels of cytokines related to inflammation and tissue repair, MCP-3 and EGF, as compared to BCG. Thus, our data revealed an important signature of immune responses induced in human macrophages by rBCG-LTAK63 associated with increased inflammation, activation, and tissue repair, which may be correlated with a protective immune response against TB

Schistosoma mansoni venom allergen-like proteins: phylogenetic relationships, stage-specific transcription and tissue localization as predictors of immunological cross-reactivity

Host-parasite interactio

Recombinant BCG expressing LTAK63 adjuvant induces superior protection against Mycobacterium tuberculosis

International audienceIn order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0-3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosi