Falla en la eficacia de dos formulaciones de ivermectina contra Psoroptes ovis (Hering, 1838) en ovinos / Failure of efficacy of two ivermectin formulations against Psoroptes ovis (Hering, 1838) in sheep

Resumen El presente trabajo evaluó la relación entre la eficacia y la farmacocinética de dos formulaciones comerciales inyectables de ivermectina (IVM) en ovinos merino adultos artificialmente infestados con Psoroptes ovis. Los animales fueron tratados por vía subcutánea con IVM 1 % en dos dosis con un intervalo de aplicación de 7 días, (0.2 mg/kg) o con una única dosis de IVM 3.15%, (1.05 mg/kg). Se realizaron conteos semanales de ácaros vivos mediante raspajes de piel entre el día 0 y 28 post-tratamiento para determinar la eficacia de los tratamientos, y se tomaron muestras de sangre para medir las concentraciones de IVM en plasma. Se observó una disminución significativa en los conteos de ácaros a partir del día 14 post-tratamiento, sin embargo, se encontraron ácaros vivos en todos los muestreos para ambos grupos. En el Grupo IVM 1%, la máxima eficacia se observó el día 28 post tratamiento (93.3%), mientras que en el Grupo IVM 3,15% este registro se obtuvo el día 21 (95.9%). Mayores concentraciones de IVM fueron observadas en los animales tratados con la formulación 3.15 %. La falla para obtener una cura parasitológica tras el tratamiento con ambas formulaciones de IVM puede ser indicativo de la presencia de ácaros resistentes a este principio activo.

Abstract The current work evaluated the relationship between efficacy and pharmacokinetics of two commercial injectable formulations of ivermectin (IVM) in adult merino sheep artificially infested with Psoroptes ovis. Animals were treated subcutaneously with IVM 1% formulation (two doses on days 0 and 7) at 0.2 mg / kg or with a single dose of IVM 3.15% preparation at 1.05 mg / kg. Live mites were counted weekly by performing skin scrapings between days 0 and 28 post-treatment to determine the efficacy of each IVM formulation. Blood samples were taken up to 35 days post-treatment to measure IVM plasma concentrations. A significant decrease in mite counts was observed from day 14 post-treatment. However, live mites were found in all samples for both groups throughout the entire trial. After IVM 1% administration, the highest effcacy was observed on day 28 (93.3% whereas in the IVM 3,15% group was obtained on day 21 post treatment (95.9%). Higher IVM plasma concentrations were observed in animals treated with the IVM 3.15% formulation. Failure to obtain a parasitological cure after treatment with both IVM formulations may reflect the presence of resistant mites to this drug.

Ivermectin-loaded lipid nanocapsules: toward the development of a new antiparasitic delivery system for veterinary applications.

Ivermectin (IVM) is probably one of the most widely used antiparasitic drugs worldwide, and its efficacy is well established. However, slight differences in formulation may change the plasma kinetics, the biodistribution, and in consequence, the efficacy of this compound. The present study focuses on the development of a novel nanocarrier for the delivery of lipophilic drugs such as IVM and its potential application in antiparasitic control. Lipid nanocapsules (LNC) were prepared by a new phase inversion procedure and characterized in terms of size, surface potential, encapsulation efficiency, and physical stability. A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess the stealth properties of this nanocarrier in vitro. Finally, a pharmacokinetics and biodistribution study was carried out as a proof of concept after subcutaneous (SC) injection in a rat model. The final IVM-LNC suspension displayed a narrow size distribution and an encapsulation rate higher than 90 % constant over the evaluated time (60 days). Through flow cytometry and blood permanence measurements, it was possible to confirm the ability of these particles to avoid the macrophage uptake. Moreover, the systemic disposition of IVM in the LNC administered by the SC route was higher (p < 0.05) (1367 ng h/ml) compared to treatment with a commercial formulation (CF) (1193 ng.h/ml), but no significant differences in the biodistribution pattern were found. In conclusion, this new carrier seems to be a promising therapeutic approach in antiparasitic control and to delay the appearance of resistance.

Prevalencia de patología cardíaca en la enfermedad de Chagas: años 2004-2012. Programa y Red de Chagas de CABA / Prevalence of cardiac pathology in Chagas disease: 2004 -2012. Program and Chagas CABA network

El Instituto Universitario de Ciencias de las Salud ha mostrado un particular compromiso con la formación de sus estudiantes en la estrategia de Atención Primaria de la Salud, con las prácticas asistenciales dedicadas al 1er nivel de atención ambulatoria y a las patologías prevalentes en ese ámbito. Del mismo modo se han desenvuelto las actividades de formación en investigación. Como exponente de esa orientación, la revista Ciencias de la Salud publicó en el Vol. 2, N°1, 2011:4-9, el artículo “Prevalencia de la Enfermedad de Chagas” de Érica G. Morais, que había obtenido el premio “Futuros Líderes”, otorgado por el Curso Anual Internacional de Investigación en Ciencias de la Salud (IUCS-AMA, Prof. Carlos Álvarez Bermúdez). Aquella investigación formaba parte de un proyecto más amplio realizado en el Hospital Teodoro Álvarez entre 2004 y 2012, en el que participaron un conjunto de investigadores, que compartieron la autoría de la actual publicación. El Dr. Jorge Mitelman, Prosecretario de Ciencia y Técnica del IUCS e integrante de ese equipo, preparó además una reseña sobre la jornada del INCOSUR, realizada en abril del presente año, describiendo asimismo el proceso de desarrollo de la Ciudad de Buenos Aires, como área no endémica, para encarar las consecuencias de la enfermedad de Chagas

Intestinal drug transport: ex vivo evaluation of the interactions between ABC transporters and anthelmintic molecules.

The family of ATP-binding cassette (ABC) transporters is composed of several transmembrane proteins that are involved in the efflux of a large number of drugs including ivermectin, a macrocyclic lactone (ML) endectocide, widely used in human and livestock antiparasitic therapy. The aim of the work reported here was to assess the interaction between three different anthelmintic drugs with substrates of the P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP). The ability of ivermectin (IVM), moxidectin (MOX) and closantel (CST) to modulate the intestinal transport of both rhodamine 123 (Rho 123), a P-gp substrate, and danofloxacin (DFX), a BCRP substrate, across rat ileum was studied by performing the Ussing chamber technique. Compared to the controls, Rho 123 efflux was significantly reduced by IVM (69%), CST (51%) and the positive control PSC833 (65%), whereas no significant differences were observed in the presence of MOX (30%). In addition, DFX efflux was reduced between 59% and 72% by all the assayed drug molecules, showing a higher potency than that observed in the presence of the specific BCRP inhibitor pantoprazole (PTZ) (52%). An ex vivo intestinal transport approach based on the diffusion chambers technique may offer a complementary tool to study potential drug interactions with efflux transporters such as P-gp and BCRP.

Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine.

Glyphosate (GLP), the active ingredient of many weed killing formulations, is a broad spectrum herbicide compound. Wistar rats were exposed during 30 or 90 days to the highest level (0.7 mg/L) of GLP allowed in water for human consumption (US EPA, 2011) and a 10-fold higher concentration (7 mg/L). The low levels of exposure to the herbicide did not produce histomorphological changes. The production of TBARS was similar or tended to be lower compared to control animals not exposed to the herbicide. In rats exposed to GLP, increased levels of reduced glutathione (GSH) and enhanced glutathione peroxidase (GPx) activity may act as a protective mechanism against possible detrimental effects of the herbicide. Overall, this work showed certain biochemical modifications, even at 3-20-fold lower doses of GLP than the oral reference dose of 2mg/kg/day (US EPA, 1993). The toxicological significance of these findings remains to be clarified.

Controlled injection and acceleration of electrons in plasma wakefields by colliding laser pulses.

In laser-plasma-based accelerators, an intense laser pulse drives a large electric field (the wakefield) which accelerates particles to high energies in distances much shorter than in conventional accelerators. These high acceleration gradients, of a few hundreds of gigavolts per metre, hold the promise of compact high-energy particle accelerators. Recently, several experiments have shown that laser-plasma accelerators can produce high-quality electron beams, with quasi-monoenergetic energy distributions at the 100 MeV level. However, these beams do not have the stability and reproducibility that are required for applications. This is because the mechanism responsible for injecting electrons into the wakefield is based on highly nonlinear phenomena, and is therefore hard to control. Here we demonstrate that the injection and subsequent acceleration of electrons can be controlled by using a second laser pulse. The collision of the two laser pulses provides a pre-acceleration stage which provokes the injection of electrons into the wakefield. The experimental results show that the electron beams obtained in this manner are collimated (5 mrad divergence), monoenergetic (with energy spread <10 per cent), tuneable (between 15 and 250 MeV) and, most importantly, stable. In addition, the experimental observations are compatible with electron bunch durations shorter than 10 fs. We anticipate that this stable and compact electron source will have a strong impact on applications requiring short bunches, such as the femtolysis of water, or high stability, such as radiotherapy with high-energy electrons or radiography for materials science.

Ivermectin disposition kinetics after subcutaneous and intramuscular administration of an oil-based formulation to cattle.

Slight differences in formulation may change the plasma kinetics and ecto-endoparasiticide activity of endectocide compounds. This work reports on the disposition kinetics and plasma availability of ivermectin (IVM) after subcutaneous (SC) and intramuscular (IM) administration as an oil-based formulation to cattle. Parasite-free Aberdeen Angus calves (n = 24; 240-280 kg) were divided into three groups (n = 8) and treated (200 microg/kg) with either an IVM oil-based pharmaceutical preparation (IVM-TEST formulation) (Bayer Argentina S.A.) given by subcutaneous (Group A) and intramuscular (Group B) injections or the IVM-CONTROL (non-aqueous formulation) (Ivomec, MSD Agvet) subcutaneously administered (Group C). Blood samples were taken over 35 days post-treatment and the recovered plasma was extracted and analyzed by HPLC using fluorescence detection. IVM was detected in plasma between 12 h and 35 days post-administration of IVM-TEST (SC and IM injections) and IVM-CONTROL formulations. Prolonged IVM absorption half-life (p < 0.05) and delayed peak plasma concentration (p < 0.001) were obtained following the SC administration of the IVM-TEST compared to the IVM-CONTROL formulation. No differences in total plasma availability were observed among treatments. However, the plasma residence time and elimination half-life of IVM were significantly longer after injection of the IVM-TEST formulation. IVM plasma concentrations were above 0.5 ng/ml for 20.6 (CONTROL) and 27.5 days (IVM-TEST SC), respectively (p < 0.05). The modified kinetic behaviour of IVM obtained after the administration of the novel oil-based formulation examined in this trial, compared to the standard preparation, may positively impact on its strategic use in cattle.

[Comparative evaluation of modern intraoperative diagnostic methods in malignant gliomas of the brain]. / Vergleichsbeurteilung moderner Methoden der intraoperativen Diagnostik maligner Gliome des Gehirns.

The following methods were employed: Intravital staining with bromphenol blue (70 patients), radiometry with P 32 (127 patients), echo encephalography (12 patients,) puncture biopsy (18 patients), rheometry (96 patients). Bromphenol blue is injected into the a. cerebri media or the supraclinoidal a. carotis interna and stains the periphery of malignant tumours and the entire tissue of benign tumours. Radiometry also serves for the intraoperative finding of tumour remainders which must be located at least 20 to 22 mm below the cortex of the brain. Tumour biopsy was carried out with a sharp cannula to avoid deformation of the tissue cylinder. Rheometry proved to be very useful when avoiding the mixing with blood, liquor, and cyst fluid at the measuring tip.