RESUMO
Photodynamic therapy has emerged as an alternative treatment for cutaneous leishmaniasis, and compounds with photocatalytic behavior are promising candidates to develop new therapeutic strategies for the treatment of this parasitic disease. Titanium dioxide TiO2 is a semiconductor ceramic material that shows excellent photocatalytic and antimicrobial activity under Ultraviolet irradiation. Due to the harmful effects of UV radiation, many efforts have been made in order to enhance both photocatalytic and antimicrobial properties of TiO2 in the visible region of the spectrum by doping or through modifications in the route of synthesis. Herein, Fe-, Zn-, or Pt- doped TiO2 nanostructures were synthesized by solution-combustion route. The obtained compounds presented aggregates of 100â¯nm, formed by particles smaller than 20â¯nm. Doping compounds shift the absorption spectrum towards the visible region, allowing production of reactive oxygen species in the presence of oxygen and molecular water when the system is irradiated in the visible spectrum. The Pt (EC50â¯=â¯18.2⯱â¯0.8⯵g/mL) and Zn (EC50â¯=â¯16.4⯱â¯0.3⯵g/mL) -doped TiO2 presented the higher antileishmanial activities under visible irradiation and their application as photosensitizers in photodynamic therapy (PDT) strategies for the treatment of cutaneous leishmaniasis should be considered.
Assuntos
Leishmania/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Fármacos Fotossensibilizantes/farmacologia , Titânio/química , Raios Ultravioleta , Animais , Antracenos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Ferro/química , Leishmania/metabolismo , Leishmania/efeitos da radiação , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/efeitos da radiação , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Microscopia Eletrônica de Transmissão , Perileno/análogos & derivados , Perileno/química , Perileno/farmacologia , Perileno/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Fluorescência , Difração de Raios X , Zinco/químicaRESUMO
Glycosomes are peroxisome-related organelles found in all kinetoplastid protists, including the human pathogenic species of the family Trypanosomatidae: Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. Glycosomes are unique in containing the majority of the glycolytic/gluconeogenic enzymes, but they also possess enzymes of several other important catabolic and anabolic pathways. The different metabolic processes are connected by shared cofactors and some metabolic intermediates, and their relative importance differs between the parasites or their distinct lifecycle stages, dependent on the environmental conditions encountered. By genetic or chemical means, a variety of glycosomal enzymes participating in different processes have been validated as drug targets. For several of these enzymes, as well as others that are likely crucial for proliferation, viability or virulence of the parasites, inhibitors have been obtained by different approaches such as compound libraries screening or design and synthesis. The efficacy and selectivity of some initially obtained inhibitors of parasite enzymes were further optimized by structure-activity relationship analysis, using available protein crystal structures. Several of the inhibitors cause growth inhibition of the clinically relevant stages of one or more parasitic trypanosomatid species and in some cases exert therapeutic effects in infected animals. The integrity of glycosomes and proper compartmentalization of at least several matrix enzymes is also crucial for the viability of the parasites. Therefore, proteins involved in the assembly of the organelles and transmembrane passage of substrates and products of glycosomal metabolism offer also promise as drug targets. Natural products with trypanocidal activity by affecting glycosomal integrity have been reported.
Assuntos
Microcorpos/metabolismo , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Animais , Transporte Biológico , Descoberta de Drogas , Humanos , Proteínas de Protozoários/metabolismo , Trypanosoma/metabolismoRESUMO
The kairomone octenol is known as attractive to hematophagous Diptera such as mosquitoes, tsetse flies, and midges. There is little evidence that traps baited with octenol are also effective in attracting phlebotomine sand flies. The present report evaluated octenol in modified Centers for Disease Control and Prevention (CDC) traps in two experiments: 1) modified CDC trap without light and 2) modified CDC trap with light. The traps were baited with octenol at concentrations of 0.5, 27, and 43 mg/h in Rincão locality, São Paulo, Brazil. Traps without octenol were used as controls. The sand fly Nyssomyia neivai (Pinto) (= Lutzomyia neivai) (Diptera: Psychodidae: Phlebotominae) was the prevalent species (99.9%) in both experiments. The results of the experiments showed that traps baited with octenol at 27 and 43 mg/h caught significantly more N. neivai than control and octenol at 0.5 mg/h with and without light. This is the first report that shows that octenol itself is attractive to N. neivai and associated with light traps significantly increases the catches.
Assuntos
Comportamento Apetitivo/efeitos dos fármacos , Octanóis/farmacologia , Psychodidae/efeitos dos fármacos , Animais , Feminino , Controle de Insetos , Luz , MasculinoRESUMO
The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made without the species identification of the Leishmania, even in areas without previous epidemiological surveys. Here we report the isolation of a Leishmania strain from a patient of Rincão, state of São Paulo, that was identified by isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections were made in the area where the patient live in order to investigate the likely vector species.
Assuntos
Animais , Humanos , Masculino , Feminino , Isoenzimas/análise , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Brasil , Leishmania braziliensis/enzimologia , Leishmaniose Cutânea/parasitologiaRESUMO
The diagnosis of human cutaneous leishmaniasis in small towns is sometimes made without the species identification of the Leishmania, even in areas without previous epidemiological surveys. Here we report the isolation of a Leishmania strain from a patient of Rincão, state of São Paulo, that was identified by isoenzyme characterization as L. (Viannia) braziliensis. Sand fly collections were made in the area where the patient live in order to investigate the likely vector species.
Assuntos
Ensaios Enzimáticos Clínicos/métodos , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/diagnóstico , Animais , Brasil , Feminino , Humanos , Isoenzimas/análise , Leishmania braziliensis/enzimologia , Leishmaniose Cutânea/parasitologia , MasculinoRESUMO
The mutants of Saccharomyces cerevisiae assigned to complementation group G199 are deficient in mitochondrial respiration and lack a functional cytochrome oxidase complex. Recombinant plasmids capable of restoring respiration were cloned by transformation of mutants of this group with a yeast genomic library. Sequencing indicated that a 2.1-kb subclone encompasses the very end (last 11 amino acids) of the PET111 gene, the COX7 gene and a new gene (YMR255W) of unknown function that potentially codes for a polypeptide of 188 amino acids (about 21.5 kDa) without significant homology to any known protein. We have shown that the respiratory defect corresponding to group G199 is complemented by plasmids carrying only the COX7 gene. The gene YMR255W was inactivated by one-step gene replacement and the disrupted strain was viable and unaffected in its ability to grow in a variety of different test media such as minimal or complete media using eight distinct carbon sources at three pH values and temperatures. Inactivation of this gene also did not affect mating or sporulation.