RESUMO
The parasite Trichomonas vaginalis is the aetiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis uses drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Antimicrobial peptides could be an alternative or complementary treatment. In this sense, one attractive candidate is the human cathelicidin, being LL-37 its active form. LL-37 possesses microbicidal activity against many microorganisms such as bacteria, Candida albicans, and Entamoeba histolytica. Shorter sequences derived from this peptide, such as KR-20, FK-13 and KR-12, have been shown to possess a higher microbicidal effect than LL-37. In this study, we determined the activity of LL-37 and its derivatives against T. vaginalis, which was unknown. The results showed that the four peptides (LL-37, KR-20, FK-13-NH2 and KR-12) decreased the viability of T. vaginalis on a 5-nitroimidazole-sensitive and a 5-nitroimidazole-resistant strain; however, KR-20 was the most effective peptide, followed by FK-13-NH2. Low concentrations of all peptides showed a better effect when combined with metronidazole in the sensitive and resistant T. vaginalis strains. These results are promising for potential future therapeutic uses.
Assuntos
Antiprotozoários , Tricomoníase , Trichomonas vaginalis , Humanos , Metronidazol/farmacologia , Peptídeos Antimicrobianos , Resistência a Medicamentos , Antiprotozoários/farmacologiaRESUMO
Trichomoniasis-caused by the parasite Trichomonas vaginalis-is associated with a high inflammatory process that may contribute to the risk of suffering from other medical complications. Our study focused on the in vitro interaction of T. vaginalis with human neutrophils because these are the most abundant cells implicated in the characteristic inflammatory process of trichomoniasis. This study showed that T. vaginalis and its surface glycoconjugates (lipophosphoglycan and/or lipoglycan) induced the formation of human neutrophil extracellular traps (NETs). After the trichomonad-neutrophil interaction, parasite integrity was at 32.9%, and the subsequent parasite growth was at 35.2% compared to those of control trophozoites (100%) incubated under the same conditions without neutrophils. In the presence of an antibody against the TLR-4 receptor, DNase I or micrococcal nuclease (MNase), neutrophils reduced the DNA fibres of the NETs and the amount of extracellular DNA, allowing a higher subsequent growth of T. vaginalis, at 52% with the anti-TLR-4 antibody and 62.6% with the enzymes. These results indicated that T. vaginalis induced the formation of extracellular traps by human neutrophils and, because of the interaction with neutrophils and NETs, parasite integrity and growth decreased.
Assuntos
Armadilhas Extracelulares , Parasitos , Tricomoníase , Trichomonas vaginalis , Animais , Humanos , Neutrófilos , Tricomoníase/parasitologiaRESUMO
Antimicrobial peptides are widely distributed in nature; they play important roles in several aspects of innate immunity and may provide a basis for the design of novel therapeutic agents. In this study, C-amidated tritrpticin, a 13 amino acid tryptophan-rich antimicrobial peptide derived from a porcine cathelicidin, was tested against Trichomonas vaginalis, a protozoan that causes a serious non-viral sexually transmitted disease associated with preterm birth, low birth weight, and high risk of HIV-1 infection. Tritrpticin was selected due to its reasonably easy synthesis and because analogs with lower toxicity may be designed. Our results show that tritrpticin-NH(2) at either 100 or 200 µg/ml (52.5 or 105 µM) clearly reduces the viability and growth of Trichomonas vaginalis. Together with tritrpticin-NH(2), sodium bicarbonate further limited trichomonad growth. Additionally, a low concentration of metronidazole (5.8 µM), the most commonly used medication for Trichomonas vaginalis, was more effective against the growth of the parasite when it was combined with tritrpticin-NH(2).
Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Antiprotozoários/farmacologia , Oligopeptídeos/farmacologia , Trichomonas vaginalis/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Metronidazol/farmacologia , Viabilidade Microbiana/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Bicarbonato de Sódio/farmacologia , Trichomonas vaginalis/crescimento & desenvolvimento , Trichomonas vaginalis/fisiologiaRESUMO
Neutrophil defense mechanisms include phagocytosis, degranulation and the formation of extracellular traps (NET). These networks of DNA are triggered by several immune and microbial factors, representing a defense strategy to prevent microbial spread by trapping/killing pathogens. This may be important against Entamoeba histolytica, since its large size hinders its phagocytosis. The aim of this study was to determine whether E. histolytica and their lipopeptidophosphoglycan (EhLPPG) induce the formation of NETs and the outcome of their interaction with the parasite. Our data show that live amoebae and EhLPPG, but not fixed trophozoites, induced NET formation in a time and dose dependent manner, starting at 5 min of co-incubation. Although immunofluorescence studies showed that the NETs contain cathelicidin LL-37 in close proximity to amoebae, the trophozoite growth was only affected when ethylene glycol tetra-acetic acid (EGTA) was present during contact with NETs, suggesting that the activity of enzymes requiring calcium, such as DNases, may be important for amoeba survival. In conclusion, E. histolytica trophozoites and EhLPPG induce in vitro formation of human NETs, which did not affect the parasite growth unless a chelating agent was present. These results suggest that NETs may be an important factor of the innate immune response during infection with E. histolytica.
Assuntos
Entamoeba histolytica/fisiologia , Armadilhas Extracelulares/fisiologia , Neutrófilos/fisiologia , Peptidoglicano/farmacologia , Fosfolipídeos/farmacologia , Trofozoítos/fisiologia , Ácido Egtázico/farmacologia , Entamoeba histolytica/patogenicidade , Entamebíase/fisiopatologia , Armadilhas Extracelulares/efeitos dos fármacos , Imunofluorescência , Humanos , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Fagocitose/fisiologiaRESUMO
Se realiza un estudio observacional, descriptivo, longitudinal,ei universo estuvo integrado por 77 niños atendidos en el Servicio de Ortopedia del Hospital Comunitario de Augustinopolis, Estado de Tocantins,Brasil, en el periodo de Marzo 1998 a Marzo 2002, con el diagnostico de Fractura Supracondilea de Humero , De ellos 8 presentaron fracturas del Tipo I de Gartland, los cuales fueron excluidos por haber sido tratados conservadoramente La Reducción Cerrada con Enclavijamiento Percutáneo, fue la conducta tomada en los niños con Fractura Tipo II estables y de fácil reducción, cuando fueron inestables y de difícil reducción, se practicó Reducción Abierta con Fijación Interna, al igual que en las de Tipo III. Para el análisis estadístico se tuvo en cuenta el Método Porcentual, existió predominio en el grupo de 4- 9 años( 68.8 porciento) . Se presentaron con mayor frecuencia en el sexo masculino (71.4 porciento ); el lado izquierdo fue el más afectado (61 porciento); predominaron las fracturas del Tipo III (54.5 porciento) y fueron en extensión el 95.7 porciento . No se reportaron complicaciones vasculares , se reportaron cinco pacientes con Neuropraxia que regresaron espontáneamente , se presentaron tres casos con infecciones cutáneas superficiales por los alambres de Kirschner. Las Vías de Abordaje utilizadas fueron la Lateral y la Posterior
We conducted a descriptive observational longitudinal study which sample involved 77 children assisted at the Orthopedics Service of the community hospital of Agustinopolis, Tocantins state, Brazil in the time period from March 1998 to March 2002, diagnosed supracondylar fracture of humerus, of whom eight showed type I fracture of Gartland, so these were excluded for being discreetly treated. Close reduction and percutaneous bone peg were the most utilized in children with type II stable fractures of easy reduction; when unstable or difficult reduction, open reduction and Internal fixation were used as well as in type III fractures. Percentages was the statistical method used.The age group 4-9 years (68.8%) prevailed. Fractures were more frequently found in males(71.4); being the left side limb the most affected (61%). Prevailing fractures were those of type III (54.5%) and extension fractures (95.7%). No vascular complications were reported. Five pts were reported with Neuropraxia who expontaneously returned; three cases had superficial cutaneous infections due to the Kirsner wires. A postero-lateral approach was used.