In Vitro

Nothing is known about the possible effect of thymol or other compounds of essential oils against the adult worms of cestodes. The aim of the present work was to determine in vitro cestodicidal activity of thymol against Mesocestoides corti adult worms. Moreover, the in vitro effect on tetrathyridia was also demonstrated. Tetrathyridia exposed to different concentrations of thymol showed a concentration and time-dependent effect. At lower concentrations, the main change observed was mainly in morphology, with larvae exhibiting an elongation of the body. When tetrathyridia were exposed to higher concentrations, increased surface alterations and damage were detected. The body appeared elongated and flattened, and a complete loss of morphology and microtriches was observed. Thymol was able to kill M. corti tetrathyridia, since following inoculation of treated parasites in mice no parasites could be recovered. The effect on M. corti adult worms was dose and time-dependent. Changes in motility coincide with the tissue damage were observed at the structural and ultrastructural level. Thymol caused severe damages to both developmental stages analyzed. Damages were more significant in fully segmented worms. The data reported in this paper demonstrate a clear in vitro effect of thymol against M. corti tetrathyridia and adult worms

¿Es posible optimizar el tratamiento de la hidatidosis utilizando formulaciones de benzimidazoles de liberación modificada?

La hidatidosis es considerada por la Organización Mundial de la Salud como una de las principales enfermedades desatendidas a nivel mundial. La quimioterapia en humanos se limita al uso de fármacos benzimidazoles, dentro de los cuales el más utilizado es albendazole. Esta droga puede detener el crecimiento del parásito, pero hasta el momento no se cuenta con ningún fármaco realmente eficaz. El Grupo de Investigación Zoonosis Parasitarias de la Facultad de Ciencias Exactas y Naturales, Universidad de Mar del Plata, trabaja desde hace 12 años en la quimioterapia experimental de la hidatidosis. Desde el año 2011 y en un trabajo conjunto con el Laboratorio de Farmacotecnia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, se están estudiando diferentes formulaciones de albendazole de liberación modificada con el propósito de optimizar el tratamiento de la enfermedad en el modelo murino, como paso previo a una potencial aplicación clínica en humanos.Asociación Parasitológica Argentin

The potential for histone deacetylase (HDAC) inhibitors as cestocidal drugs

Background: Echinococcosis and cysticercosis are neglected tropical diseases caused by cestode parasites (family Taeniidae). Not only there is a small number of approved anthelmintics for the treatment of these cestodiases, but also some of them are not highly effective against larval stages, such that identifying novel drug targets and their associated compounds is critical. Histone deacetylase (HDAC) enzymes are validated drug targets in cancers and other diseases, and have been gaining relevance for developing new potential anti-parasitic treatments in the last years. Here, we present the anthelmintic profile for a panel of recently developed HDAC inhibitors against the model cestode Mesocestoides vogae (syn. M. corti).Methodology/principal findings: Phenotypic screening was performed on M. vogae by motility measurements and optical microscopic observations. Some HDAC inhibitors showed potent anthelmintic activities; three of them-entinostat, TH65, and TH92 -had pronounced anthelmintic effects, reducing parasite viability by ~100% at concentrations of ≤ 20 μM. These compounds were selected for further characterization and showed anthelmintic effects in the micromolar range and in a time- and dose-dependent manner. Moreover, these compounds induced major alterations on the morphology and ultrastructural features of M. vogae. The potencies of these compounds were higher than albendazole and the anthelmintic effects were irreversible. Additionally, we evaluated pairwise drug combinations of these HDAC inhibitors and albendazole. The results suggested a positive interaction in the anthelmintic effect for individual pairs of compounds. Due to the maximum dose approved for entinostat, adjustments in the dose regime and/or combinations with currently-used anthelmintic drugs are needed, and the selectivity of TH65 and TH92 towards parasite targets should be assessed.Conclusion, significance: The results presented here suggest that HDAC inhibitors represent novel and potent drug candidates against cestodes and pave the way to understanding the roles of HDACs in these parasites.Fil: Vaca, Hugo Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Celentano, Ana M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Toscanini, María Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Heimburg, Tino. No especifíca;Fil: Ghazy, Ehab. No especifíca;Fil: Zeyen, Patrik. No especifíca;Fil: Hauser, Alexander Thomas. Albert Ludwigs University of Freiburg; AlemaniaFil: Oliveira, Guilherme. Instituto Tecnológico Vale.; BrasilFil: Elissondo, María Celina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Jung, Manfred. Albert Ludwigs University of Freiburg; AlemaniaFil: Sippl, Wolfgang. No especifíca;Fil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Settling-driven gravitational instabilities associated with volcanic clouds: new insights from experimental investigations

Downward propagating instabilities are often observed at the bottom of volcanic plumes and clouds. These instabilities generate fingers that enhance the sedimentation of fine ash. Despite their potential influence on tephra dispersal and deposition, their dynamics is not entirely understood, undermining the accuracy of volcanic ash transport and dispersal models. Here, we present new laboratory experiments that investigate the effects of particle size, composition and concentration on finger generation and dynamics. The experimental set-up consists of a Plexiglas tank equipped with a removable plastic sheet that separates two different layers. The lower layer is a solution of water and sugar, initially denser than the upper layer, which consists of water and particles. Particles in the experiments include glass beads as well as andesitic, rhyolitic and basaltic volcanic ash. During the experiments, we removed the horizontal plastic sheet separating the two fluids. Particles were illuminated with a laser and filmed with a HD camera; particle image velocimetry (PIV) is used to analyse finger dynamics. Results show that both the number and the downward advance speed of fingers increase with particle concentration in the upper layer, while finger speed increases with particle size but is independent of particle composition. An increase in particle concentration and turbulence is estimated to take place inside the fingers, which could promote aggregation in subaerial fallout events. Finally, finger number, finger speed and particle concentration were observed to decrease with time after the formation of fingers. A similar pattern could occur in volcanic clouds when the mass supply from the eruptive vent is reduced. Observed evolution of the experiments through time also indicates that there must be a threshold of fine ash concentration and mass eruption rate below which fingers do not form; this is also confirmed by field observations.Published395V. Dinamica dei processi eruttivi e post-eruttiviJCR Journa

Echinococcus granulosus: first report of microcysts formation from protoscoleces of cattle origin using the in vitro vesicular culture technique

The aim of this work was the achievement of microcysts formation from protoscoieces of E. granulosus of cattle origin using the in vitro vesicular culture technique. Vesiculated protoscoieces and protoscoieces with posterior bladders appeared during the first week of incubation. After 14 days of culture, a laminated layer appeared like a fine membrane in one of the extremes of the protoscoieces. On day 20, some microcysts with a complete laminated layer were observed. By day 48, microcysts completely developed could be observed. This is the first study where microcysts formation was obtained using protoscoieces of E. granulosus of cattle origin

Strain characterization of Echinococcus granulosus protoscoleces of cattle origin using the in vitro vesicular development

The aim of this work was to characterize the strain of protoscoleces of E. granulosus of cattle origin using the in vitro vesicular development. The in vitro development of these samples was compared to samples of sheep origin determined previously by genetic analyses as common sheep strain (G1). There were similarities between sheep and cattle samples not only in the time of microcysts formation, but also in the development process. Vesiculated protoscoleces and protoscoleces with posterior bladders appeared during the first week of incubation. After 14 days of culture, a laminated layer appeared like a fine membrane in one of the extremes of the protoscoleces. In the sheep samples, microcysts were observed between 19 and 20 days. In the cattle samples, microcysts appeared between 20 and 23 days. The coincidence between the development times and physiological characteristics found in the present study may indicate that the parasites from cattle and sheep were of the same strain

Efficacy of Essential Oils of Thymus vulgaris and Origanum vulgare on Echinococcus granulosus

The aim of the present work was to determine the in vitro effect of T. vulgaris and O. vulgare essential oils against E. granulosus protoscoleces and cysts. Essential oils were added to the medium resulting in thymol final concentrations of 10 μg/mL. The essential oils had a time-dependent effect provoking the complete loss of protoscolex viability after 72 days of postincubation. The results were confirmed at the ultrastructure level. Loss of infectivity in protoscoleces incubated with O. vulgare after 60 days was observed. On the other hand, the weight of cysts recorded in mice inoculated with T. vulgaris treated protoscoleces was significantly lower than that obtained in control group. Gamma-glutamyl-transpeptidase activity was readily detected in the culture supernatant of protoscoleces treated either with the essential oils or thymol. T. vulgaris and O. vulgare essential oils and thymol can induce cell apoptosis of protoscoleces after short incubation times. The efficacy of T. vulgaris and O. vulgare essential oils was also demonstrated in vitro on E. granulosus murine cysts. Our data suggest that essential oils of T. vulgaris and O. vulgare have anthelmintic effect against protoscoleces and cysts of E. granulosus