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Nora Mestorino

    Nora Mestorino

    REsuMEn: La resistencia a los antimicrobianos representa un severo problema a nivel mun-dial. Se han descripto variados mecanismos de resistencia, entre los cuales se encuentran las bombas de eflujo. Estas son proteinas transportadoras de... more
    REsuMEn: La resistencia a los antimicrobianos representa un severo problema a nivel mun-dial. Se han descripto variados mecanismos de resistencia, entre los cuales se encuentran las bombas de eflujo. Estas son proteinas transportadoras de membrana, organizadas en superfamilias y distribuidas ubicuamente entre organismos procariotas y eucariotas. Los genes que codifican para las bombas de eflujo pueden estar localizados en el cromosoma bacteriano o bien en elementos geneticos transmisibles como los plasmidos. Algunos sistemas tienen la capacidad de expulsar antimicrobianos estructuralmente disimiles (Multiple Drug Resistance: MDR). La presencia de los mismos en combinacion con otros mecanismos genera altos niveles de resistencia entre patogenos y comensales originando un consecuente fracaso terapeutico. Debido a la creciente importancia de este mecanismo de defensa microbiano se estan investigando diversas estrategias para modificar y revertir la resistencia bacteriana por eflujo. pa...
    Staphylococcus aureus frequently causes subclinical mastitis around the world with a high impact on the milk industry and public health. Essential oils (EO) are recognized antimicrobials that can be synergistic with antibiotics. The main... more
    Staphylococcus aureus frequently causes subclinical mastitis around the world with a high impact on the milk industry and public health. Essential oils (EO) are recognized antimicrobials that can be synergistic with antibiotics. The main objective of this study was to evaluate the essential oil (EO) of Melaleuca armillaris as an adjuvant of erythromycin (ERY) for the alternative treatment of bovine mastitis caused by S. aureus. The Minimum Inhibitory and Bactericidal Concentrations (MIC and MBC) of EO, ERY, and its combinations were established against S. aureus at different pHs (7.4, 6.5 and 5.0), emulating extra and intracellular conditions. Sensitive (N = 3) and resistant (N = 3) strains to ERY and S. aureus ATCC 29213 as control were used. Math models were applied to describe the antibacterial activity of EO and combinations EO-ERY. The EO was bactericidal against all the strains independently of the pH with a slight improvement in acid conditions. The synergism between EO and E...
    Control measures are being introduced globally to reduce the prevalence of antibiotic resistant (ABR) bacteria on farms. However, little is known about the current prevalence and molecular ecology of ABR in key opportunistic human... more
    Control measures are being introduced globally to reduce the prevalence of antibiotic resistant (ABR) bacteria on farms. However, little is known about the current prevalence and molecular ecology of ABR in key opportunistic human pathogens such asEscherichia colion South American farms. Working with 30 dairy cattle farms and 40 pig farms across two provinces in central-eastern Argentina, we report a comprehensive genomic analysis of third-generation cephalosporin resistance (3GC-R) inE. coli. 3GC-R isolates were recovered from 34.8% (cattle) and 47.8% (pigs) of samples from faecally contaminated sites. Phylogenetic analysis revealed substantial diversity suggestive of long-term horizontal transmission of 3GC-R mechanisms. Despite this, mechanisms such as CTX-M-15 and CTX-M-2 were detected more often in dairy farms, while CTX-M-8 and CMY-2, and co-carriage of amoxicillin/clavulanate resistance and florfenicol resistance were more commonly detected in pig farms. This suggests differe...
    Las garrapatas duras (ixodidae) se encuentran ampliamente distribuidas a nivel mundial, constituyendo un serio problema economico y de salud publica. La especie mas relevante para la ganaderia bovina es Boophilus microplus, debido a su... more
    Las garrapatas duras (ixodidae) se encuentran ampliamente distribuidas a nivel mundial, constituyendo un serio problema economico y de salud publica. La especie mas relevante para la ganaderia bovina es Boophilus microplus, debido a su amplia distribucion, a los danos que ocasiona y a la transmision de enfermedades. Diferentes metodos han sido propuestos para el control de garrapatas, siendo el quimico el mas difundido. El uso indiscriminado de estos compuestos dio lugar a contaminacion, afectando poblaciones no blanco, ocasionando peligros en la salud publica y promoviendo el desarrollo de resistencia a esas sustancias por parte de las poblaciones de garrapatas. Ante esta situacion se investigan en distintas partes del mundo diferentes opciones para el control de las garrapatas. El objetivo de este trabajo fue investigar la repelencia de larvas de B. microplus ocasionada por extractos de plantas medicinales para identificar posteriormente los compuestos quimicos presentes en ellos.
    Bioactive glasses have been proposed for bone tissue engineering due to their excellent biocompatibility and osteo-inductive behaviour. The generation of mesoporous bioactive glass (nano) particles adds a high surface area for the... more
    Bioactive glasses have been proposed for bone tissue engineering due to their excellent biocompatibility and osteo-inductive behaviour. The generation of mesoporous bioactive glass (nano) particles adds a high surface area for the dissolution and release of bioactive ions, and the possibility to load them with different drugs for antibacterial purposes. Essential oils (EO) are an interesting resource for alternative medical therapy, providing antimicrobial compounds that come from organic/natural resources like aromatic plants. Also, a biological polymer, such as chitosan, could be used to control the release of active agents from mesoporous bioactive glass (MBG) loaded particles. This work presents MBG particles with nominal composition (in mol) 60% SiO2, 30% CaO and 10% P2O5, loaded with essential oil of Melaleuca armillaris, which contains 1,8-cineol as the main active component, with an inhibitory in vitro activity against several bacterial species. Also, co-loading with a broad...
    Introduccion: distintos estudios han demostrado el papel preponderante que el peridomicilio cumple en la reinfestacion de las viviendas por Triatoma infestans (vinchucas). Con el objetivo de eliminar focos residuales de T. infestans que... more
    Introduccion: distintos estudios han demostrado el papel preponderante que el peridomicilio cumple en la reinfestacion de las viviendas por Triatoma infestans (vinchucas). Con el objetivo de eliminar focos residuales de T. infestans que habitan alrededor de los hogares se han desarrollado distintas estrategias. La administracion de diferentes compuestos que tengan actividad contra T. infestans a los animales que habitan zonas cercanas a los domicilios y sirvan como fuente de alimentacion a estos insectos, podria ser una buena manera de disminuir el riesgo de reinfestacion domiciliaria. Objetivo: evaluar la eficacia in vitro de tres agentes antiparasitarios, doramectina (DRM), ivermectina (IVM) y eprinomectina (EPR) frente a ninfas de quinto estadio de Triatoma infestans . Metodos: se disenaron alimentadores artificiales en donde se coloco sangre heparinizada y fortificada con distintas concentraciones de los tres endectocidas (100-0,4 ng/mL). Se utilizaron 600 ninfas de quinto estad...
    Essential oils (EO) are a great antimicrobial resource against bacterial resistance in public health. Math models are useful in describing the growth, survival, and inactivation of microorganisms against antimicrobials. We evaluated the... more
    Essential oils (EO) are a great antimicrobial resource against bacterial resistance in public health. Math models are useful in describing the growth, survival, and inactivation of microorganisms against antimicrobials. We evaluated the antimicrobial activity of Melaleuca armillaris EO obtained from plants placed in the province of Buenos Aires (Argentina) against Staphylococcus aureus. The minimum inhibitory and bactericidal concentrations were close and decreased, slightly acidifying the medium from pH 7.4 to 6.5 and 5.0. This result was also evidenced by applying a sigmoid model, where the time and EO concentration necessaries to achieve 50% of the maximum effect decreased when the medium was acidified. Moreover, at pH 7.4, applying the Gompertz model, we found that subinhibitory concentrations of EO decreased the growth rate and the maximum population density and increased the latency period concerning the control. Additionally, we established physicochemical parameters for qual...
    La problemática actual de la resistencia bacteriana, promovida básicamente por el abu­so en la utilización de antibióticos, lleva a la necesidad de encontrar alternativas terapéuticas más eficaces para enfrentar las infecciones... more
    La problemática actual de la resistencia bacteriana, promovida básicamente por el abu­so en la utilización de antibióticos, lleva a la necesidad de encontrar alternativas terapéuticas más eficaces para enfrentar las infecciones bacterianas. Los aceites esenciales representan una gran herramienta para enfrentar esta crisis. Nuestro objetivo fue evaluar la interacción farmacodinámica establecida al combinar aceite esencial de Melaleuca armillaris con cloxacilina en busca de un efecto sinérgico que maximice la actividad del antibiótico frente a Staphylococcus aureus. Cepas de referencia y salvajes de dicha especie fueron enfrentadas al extracto vegetal y al antimicrobiano en forma individual y combinada mediante microdilución en caldo, modificando las condiciones del pH para emular el ambiente subcelular. Se determinó la interacción mediante la técnica de tablero de damas o checkerboard, se calculó el índice de concentración fraccionaria inhibitoria y, finalmente, se estableció el índi...
    El objetivo principal de esta Tesis Doctoral fue evaluar la capacidad del aceite esencial (AE) de Melaleuca armillaris de actuar como coadyuvante de antimicrobianos utilizados en el tratamiento de la mastitis bovina por Staphylococcus... more
    El objetivo principal de esta Tesis Doctoral fue evaluar la capacidad del aceite esencial (AE) de Melaleuca armillaris de actuar como coadyuvante de antimicrobianos utilizados en el tratamiento de la mastitis bovina por Staphylococcus aureus, en busca de una alternativa más eficaz frente a infecciones de difícil resolución. El AE fue obtenido de plantas cultivadas en la provincia de Buenos Aires. Se caracterizó fisicoquímicamente para establecer parámetros de calidad, presentando 1.8 cineol (72.3%), limoneno (7.8%) y alfa-pineno (6%) como componentes principales. Se determinaron las Concentraciones Inhibitoria y Bactericida Mínimas (CIM y CBM) del AE y de cloxacilina, eritromicina y rifaximina, frente a S. aureus a diferentes pHs (7.4; 6.5 y 5.0), emulando condiciones extra e intracelulares. Utilizamos cepas sensibles a los 3 antimicrobianos, resistentes a eritromicina, una cepa meticilino resistente (SARM) y S. aureus ATCC 29213 como control. El sinergismo entre el AE y los antimic...
    Serum concentrations of ticarcillin were measured serially over a period of 12h in a cross over trial involving 6 healthy adult ewes after intravenous and intramuscular (IM) administration of 40 mg ticarcillin per kg body weight.... more
    Serum concentrations of ticarcillin were measured serially over a period of 12h in a cross over trial involving 6 healthy adult ewes after intravenous and intramuscular (IM) administration of 40 mg ticarcillin per kg body weight. Probenecid (40 mg/kg) was also administered IM immediately before the IM administration of 40 mg/kg ticarcillin. Pharmacokinetic values after intravenous administration were: half-life of elimination (T 1/2 beta) = 0.90 +/- 0.09 h; volume of distribution at steady state (Vdss) = 456.8 +/- 106.6 ml/kg, total body clearance (CIB) = 614.5 +/- 81.2 ml/h/kg. Ticarcillin persisted in serum at greater than or equal to 1.5 micrograms/ml for 4 hours. Pharmacokinetic and bioavailability values after intramuscular administration were: half-life of absorption (T 1/2 ab) = 8.08 +/- 1.98 min; T 1/2 beta = 0.96 +/- 0.07 h. Peak serum concentration (Cmax) was 31.11 +/- 6.02 micrograms/ml at 0.50 h (Tmax), bioavailability (F) was 0.82 +/- 0.09. After ticarcillin was administered IM together with probenecid the T 1/2 ab was 33.9 +/- 13.7 min, the T 1/2 beta 2.66 +/- 0.65 h, Cmax = 44.87 +/- 5.58 at 1.33 +/- 0.44 h, and F = 1.25 +/- 0.23.
    ABSTRACT
    Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated.... more
    Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mgkg(-1)). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 microghmL(-1) and its elimination half life (T(beta)(1/2)) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T(beta)(1/2) from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal.
    Staphylococcus aureus frequently causes subclinical mastitis around the world with high impact in milk industry and public health. Essential oils (EO) are recognized antimicrobials that can be synergistic with antibiotics. The main... more
    Staphylococcus aureus frequently causes subclinical mastitis around the world with high impact in milk industry and public health. Essential oils (EO) are recognized antimicrobials that can be synergistic with antibiotics. The main objective of this study was evaluating the essential oil (EO) of Melaleuca armillaris as an adjuvant of erythromycin (ERY) for the alternative treatment of bovine mastitis caused by S. aureus. The Minimum Inhibitory and Bactericidal Concentrations (MIC and MBC) of EO, ERY, and its combinations were established against S. aureus at different pHs (7.4, 6.5 and 5.0), emulating extra and intracellular conditions. Sensible (N=3) and resistant (N=3) strains to ERY and S. aureus ATCC 29213 as control were used. Math models were applied to described the antibacterial activity of EO and combinations EO-ERY. The EO was bactericidal against all the strains independently of the pH with a slightly improvement in acid conditions. The synergism between EO and ERY was es...
    Essential oils (EO) are a great antimicrobial resource against bacterial resistance in public health. Math models are useful describing the growth, survival, and inactivation of microorganisms against antimicrobials. We evaluated the... more
    Essential oils (EO) are a great antimicrobial resource against bacterial resistance in public health. Math models are useful describing the growth, survival, and inactivation of microorganisms against antimicrobials. We evaluated the antimicrobial activity of M. armillaris EO obtained from plants placed in the province of Buenos Aires (Argentina) against Staphylococcus aureus. Minimum Inhibitory and Bactericidal Concentrations were close and decreased slightly acidifying the medium from pH 7.4 to 6.5 and 5.0. This result was also evidenced by applying a sigmoid model, where the time and EO concentration necessaries to achieve 50% of the maximum effect decreased when medium was acidified. Moreover, at pH 7.4, applying the Gompertz model, we found that subinhibitory concentrations of EO decreased the growth rate and the maximum population density, and increased the latency period respect to the control. Additionally, we established physicochemical parameters for quality control and st...
    The close contact between dogs and humans creates the best bridge for interspecies transmission of antimicrobial-resistant bacteria. The surveillance of its resistance including the detection of extended-spectrum beta-lactamases (ESBLs)... more
    The close contact between dogs and humans creates the best bridge for interspecies transmission of antimicrobial-resistant bacteria. The surveillance of its resistance including the detection of extended-spectrum beta-lactamases (ESBLs) in Escherichia coli as indicator bacteria is an important tool to control the use of antimicrobials. The aim of this research was to evaluate the E. coli resistance in strains by phenotypic methods, isolated from pet and stray dogs of La Plata city, Argentina. Faecal samples were collected using rectal swabs from 50 dogs with owners (home dogs = HD) and 50 homeless dogs (stray dogs = SD). They were cultured in 3 MacConkey agar plates, with and without antibiotics (ciprofloxacin and cefotaxime). 197 strains were isolated, of which only 95 strains were biochemically identified as E. coli, 46 strains were from HD, and 49 were from SD. Antimicrobial susceptibility was evaluated by the Kirby–Bauer disk diffusion method. The most prevalent resistance was f...
    La otitis externa es una enfermedad de presentación frecuente en la práctica diaria. La comprensión de su fisiopatología es importante para su prevención, diagnóstico y tratamiento. El protocolo diagnóstico debe ser estricto, siendo... more
    La otitis externa es una enfermedad de presentación frecuente en la práctica diaria. La comprensión de su fisiopatología es importante para su prevención, diagnóstico y tratamiento. El protocolo diagnóstico debe ser estricto, siendo fundamental el rol que cumplen en estos casos el cultivo bacteriano y el antibiograma. Pseudomonas aeruginosaes un microorganismo oportunista e invasor, que constituye en sí mismo un factor perpetuante para las otitis crónicas. Además de sus factores de virulencia y la resistencia intrínseca a múltiples fármacos, forma biopelículas de protección sobre tejidos colonizados y posee gran capacidad para adquirir genes determinantes de resistencia cromosómica y extra cromosómica durante el tratamiento. Los casos crónicos o recurrentes con aislamientos de P. aeruginosa resultan un desafío constante para el veterinario. El oído externo tiene escasa irrigación, por lo cual los antimicrobianos sistémicos no alcanzan concentraciones adecuadas, siendo la terapia tóp...
    Helminth infections are widespread in the poultry industry. There is evidence of extra-label use of some drugs, such as ivermectin (IVM), in broiler poultry. Pharmacokinetic and residual studies of IVM in poultry, however, are rather... more
    Helminth infections are widespread in the poultry industry. There is evidence of extra-label use of some drugs, such as ivermectin (IVM), in broiler poultry. Pharmacokinetic and residual studies of IVM in poultry, however, are rather scarce. Our aim was to determine time restrictions for broiler chickens fed with balanced feed mixed with IVM for 21 days, and thus achieve acceptable residual levels for consumption as established by the European Union. Sixty 1-day-old chicks were fed with food supplemented with IVM at 5 mg kgfeed for 21 days. Groups of six treated animals were sacrificed at 0, 1, 2, 4, 8, 10, 15, 20 and 28 days after treatment. Liver, skin/fat, kidney and muscle samples were obtained. IVM were determined by liquid chromatography with fluorescence detection after automatic solid-phase extraction with SPE Ccartridges. The highest concentrations were measured in the liver, which is logical given that IVM is a drug that undergoes extensive hepatic metabolism. The optimal withdrawal time for edible tissues of these animals to stay within the permitted residual levels were: 12 days for liver, 8 days for skin/fat, 0 days for muscle and 10 days for kidney.

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