¿CUÁLES SON LOS MEJORES INDICADORES PARA MEDIR EL DESARROLLO SUSTENTABLE? – ENFOQUE TOP DOWN VS BOTTOM UP

Presentación de avances del proyecto de investigación dirigido por la Dra. Roxana Piastrellini en Jornadas de Investigación UMaza 2019. Objetivo del proyecto: Encontrar el equilibrio entre los enfoques top-down y bottom-up, identificando sus fortalezas y debilidades mediante un análisis crítico de casos de estudio y reportes metodológicos disponibles en la bibliografí

Plasma pharmacokinetics tissue concentration and urine elimination after cephalotin intravenous administration to cats under surgical conditions

Pharmacokinetic profile, tissue concentrations and urine elimination of cephalothin in cats under surgical conditions after a single intravenous dose (30 mg/kg) were studied. Initial plasma concentrations were high (Cp(0), 353.79±118.92 μg/mL), with fast and moderately wide distribution (T1⁄2(d) 0.14±0.10 h) (V(d(ss)) 0.19±0.03 L/kg) and rapid elimination (ClB, 0.16±0.03 L/h.kg; T1⁄2, 1.07±0.23 h; MRT, 1.16±0.21 h). Thirty to 60 minutes after intravenous administration, cephalothin tissue concentrations were in the range of 3.73 μg/g (testicle tissue) to 25.63 μg/g (uterus). Tissue/plasma concentrations rate was in a range of 0.04 (testicle) to 0.21 (uterus). Cephalothin urine elimination was 66.49% in the first 6 hours after administration. Cephalothin plasma concentrations remained above a MIC≥1μg/mL up to 5.5 hours in all the studied cats. However, for MIC≥8μg/mL (MIC breakpoint) this time is reduced to 2.5 hours. This suggests that proper perioperative prophylactic use of cephalothin in cats requires a dose interval not longer than 2 hours.Fil: Albarellos, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Montoya, Laura. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lupi, Martin Pablo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Passini, Sabrina Mariela. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Lorenzini, Paula Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Área de Farmacología; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Trypanosoma rangeli Transcriptome Project: Generation and analysis of expressed sequence tags

Trypanosoma rangeli is an important hemoflagellate parasite of several mammalian species in Central and South America, sharing geographical areas, vectors and reservoirs with T. cruzi, the causative agent of Chagas disease. Thus, the occurrence of single and/or mixed infections, including in humans, must be expected and are of great importance for specific diagnosis and epidemiology. In comparison to several Trypanosomatidae species, the T. rangeli biology and genome are little known, reinforcing the needs of a gene discovery initiative. The T. rangeli transcriptome initiative aims to promote gene discovery through the generation of expressed sequence tags (ESTs) and Orestes (ORF ESTs) from both epimastigote and trypomastigote forms of the parasite, allowing further studies of the parasite biology, taxonomy and phylogeny

Cefuroxime plasma pharmacokinetics, tissue and urine concentrations after parenteral administration to cats

Cefuroxima es una cefalosporina de segunda generación que incluye en su espectro antibiótico a cocos gram-positivos, bacilos gram-negativos y anaerobios. El objetivo de este trabajo es caracterizar la farmacocinética plasmática de cefuroxima en gatos luego de su administración por vía intravenosa, intramuscular y subcutánea, y determinar la concentración de cefuroximaen algunos tejidos y en la orina de los animales. Luego de la administración del antibiótico (20 mg/kg), se tomaron muestras sanguíneas y de orina durante 8 horas y muestras de tejidos entre las 1-1,5 horas. Los principales parámetros farmacocinéticos (media±desvío estándar) para la administración intravenosa fueron: concentración inicial (μg/mL): 135,46±81,42; vidamedia de eliminación (h): 0,21±0,15. Para las administraciones intramuscular y subcutánea los principales parámetros farmacocinéticos fueron respectivamente: concentración máxima (μg/mL): 48,65±6,71 y 28,17±8,44, tiempo de la concentración máxima (h): 0,18±0,06 y 0,82±0,30, y vida media de eliminación (h): 1,04±0,10 y 1,59±0,18. Las concentraciones (μg/g) en tejidos estuvieron entre 3, 35±0,65 y 23.02±8.77. Al cabo de 8 horas se recuperó enla orina el 78,09±24,59% de la dosis administrada. Estos resultados indicarían que cefuroxima administrada a una dosis de 20 mg/kg por las vías estudiadas sería de utilidad para el tratamiento de infecciones producidas por microorganismos susceptibles en gatos.Cefuroxime is a second generation cephalosporin active against gram-positive cocci, gramnegative rods and anaerobes. The aim of the present study is to characterize cefuroxime plasma pharmacokinetics after intravenous, intramuscular and subcutaneous administration to cats; and, to determine cefuroxime concentrations in some tissues and in urine of the animals. After antibiotic administration (20 mg/kg), blood and urine samples were taken during 8 hours and, tissue samples at 1-1.5 hours. After intravenous administration, main pharmacokinetic parameters (mean±SD) were: initial plasma concentration (µg/mL): 135.46±81.42; half-life (h): 0.21±0.15. After intramuscular and subcutaneous administration, main pharmacokinetic parameters were, respectively: maximum plasma concentrations (µg/mL): 48.65±6.71 and 28.17±8.44; time of maximum plasma concentration were 0.18±0.06 h and 0.82±0.30 h; and, elimination half-life (h): 1.04±0.10 and 1.59±0.18. Tissue concentrations (µg/g) ranged between 3,35±0,65 and 23.02±8.77. After 8 hours, 78,09±24,59% of the administered cefuroxime was recovered from urine. The present results showed that cefuroxime, administered at a dosage of 20 mg/kg by intravenous, intramuscular or subcutaneous route, would be a useful tool for the infection treatment in cats when produced by susceptible microorganisms.Facultad de Ciencias Veterinaria

Cefuroxime plasma pharmacokinetics, tissue and urine concentrations after parenteral administration to cats

Cefuroxima es una cefalosporina de segunda generación que incluye en su espectro antibiótico a cocos gram-positivos, bacilos gram-negativos y anaerobios. El objetivo de este trabajo es caracterizar la farmacocinética plasmática de cefuroxima en gatos luego de su administración por vía intravenosa, intramuscular y subcutánea, y determinar la concentración de cefuroximaen algunos tejidos y en la orina de los animales. Luego de la administración del antibiótico (20 mg/kg), se tomaron muestras sanguíneas y de orina durante 8 horas y muestras de tejidos entre las 1-1,5 horas. Los principales parámetros farmacocinéticos (media±desvío estándar) para la administración intravenosa fueron: concentración inicial (μg/mL): 135,46±81,42; vidamedia de eliminación (h): 0,21±0,15. Para las administraciones intramuscular y subcutánea los principales parámetros farmacocinéticos fueron respectivamente: concentración máxima (μg/mL): 48,65±6,71 y 28,17±8,44, tiempo de la concentración máxima (h): 0,18±0,06 y 0,82±0,30, y vida media de eliminación (h): 1,04±0,10 y 1,59±0,18. Las concentraciones (μg/g) en tejidos estuvieron entre 3, 35±0,65 y 23.02±8.77. Al cabo de 8 horas se recuperó enla orina el 78,09±24,59% de la dosis administrada. Estos resultados indicarían que cefuroxima administrada a una dosis de 20 mg/kg por las vías estudiadas sería de utilidad para el tratamiento de infecciones producidas por microorganismos susceptibles en gatos.Cefuroxime is a second generation cephalosporin active against gram-positive cocci, gramnegative rods and anaerobes. The aim of the present study is to characterize cefuroxime plasma pharmacokinetics after intravenous, intramuscular and subcutaneous administration to cats; and, to determine cefuroxime concentrations in some tissues and in urine of the animals. After antibiotic administration (20 mg/kg), blood and urine samples were taken during 8 hours and, tissue samples at 1-1.5 hours. After intravenous administration, main pharmacokinetic parameters (mean±SD) were: initial plasma concentration (µg/mL): 135.46±81.42; half-life (h): 0.21±0.15. After intramuscular and subcutaneous administration, main pharmacokinetic parameters were, respectively: maximum plasma concentrations (µg/mL): 48.65±6.71 and 28.17±8.44; time of maximum plasma concentration were 0.18±0.06 h and 0.82±0.30 h; and, elimination half-life (h): 1.04±0.10 and 1.59±0.18. Tissue concentrations (µg/g) ranged between 3,35±0,65 and 23.02±8.77. After 8 hours, 78,09±24,59% of the administered cefuroxime was recovered from urine. The present results showed that cefuroxime, administered at a dosage of 20 mg/kg by intravenous, intramuscular or subcutaneous route, would be a useful tool for the infection treatment in cats when produced by susceptible microorganisms.Facultad de Ciencias Veterinaria

Plasma pharmacokinetics, tissue concentrations and urine elimination after cephalothin intravenous administration to cats under surgical conditions

Pharmacokinetic profile, tissue concentrations and urine elimination of cephalothin in cats under surgical conditions after a single intravenous dose (30 mg/kg) were studied. Initial plasma concentrations were high [Cp(0), 353.79±118.92 μg/mL], with fast and moderately wide distribution [T1⁄2(d) 0.14±0.10 h] [V(d(ss)) 0.19±0.03 L/kg] and rapid elimination (ClB, 0.16±0.03 L/h.kg; T1⁄2, 1.07±0.23 h; MRT, 1.16±0.21 h). Thirty to 60 minutes after intravenous administration, cephalothin tissue concentrations were in the range of 3.73 μg/g (testicle tissue) to 25.63 μg/g (uterus). Tissue/plasma concentrations rate was in a range of 0.04 (testicle) to 0.21 (uterus). Cephalothin urine elimination was 66.49% in the first 6 hours after administration. Cephalothin plasma concentrations remained above a MIC≥1 μg/mL up to 5.5 hours in all the studied cats. However, for MIC≥8 –μg/mL (MIC breakpoint) this time is reduced to 2.5 hours. This suggests that proper perioperative prophylactic use of cephalothin in cats requires a dose interval not longer than 2 hours.Facultad de Ciencias Veterinaria

Plasma and tissue clindamycin antimicrobial activity after parenteral administration to cats under surgical conditions

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats.Facultad de Ciencias Veterinaria

Pimobendan improves clinical signs in short term compared to digoxin or placebo in dogs with heart failure due to chronic degenerative mitral valve disease

Background: Chronic degenerative mitral valve disease (CDMVD) continues to be the most common cause of heart failure (HF) in small breed dogs. Pimobendan (PIMO) is a mixed action drug with inotropic and vasodilator properties and is widely used to treat heart disease in dogs. Therefore, PIMO increases cardiac output, reduces both preload and afterload and increases myocardial contractility without increasing energy consumption and myocardial oxygen. Digoxin (DIG) is a cardiac glycoside acting through inhibition of the sarcolemmal Na+/K+ ATPase pump, hence increasing intracellular calcium. It exerts benefi cial effects on left ventricular function, symptoms and exercise tolerance. The purpose of this prospective, randomized, double blind clinical trial was to evaluate the clinical response and QoLQ in heart failure (HF) dogs treated with digoxin or pimobendan in addition to conventional therapy (furosemide and benazepril). Materials, Methods & Results: Inclusion criteria: dogs in class III or stabilized class IV (NYHA). Exclusion criteria: use of positive inotrope and antiarrhythmic, presence of atrial fi brillation, renal or hepatic disease or neoplasia. Thirty three dogs were included and randomly assigned to DIG (n = 11), PIMO (n = 14) and placebo (PL) (n = 8) and followed up weekly. Data was evaluated for days zero, 7, 14 and 28. Increasing score was assigned to each variable depending on worsening of clinical evaluation (history and physical exam, QoLQ and echocardiogram (echo).Three dogs died during treatment due to worsening of HF, one of PL group and two of DIG group; furthermore, one of PIMO group was censored due to worsening of heart failure. There was no signifi cant difference between and within groups for echo and radiography. PL and DIG groups did not show any signifi cant difference throughout the 28 days of treatment. PIMO group showed lower physical exam score and increased early mitral infl ow velocity on day 28. Serum creatinine increased on days 14 and 28 compared to baseline, but within normal limits. The groups were similar within each evaluation day. Discussion: This is the fi rst short term prospective randomized double blind study comparing PIMO to DIG or PL additionally to conventional therapy (ACEi and furosemide) for dogs with HF due to CDMVD. It was observed an early signifi cant clinical improvement in dogs receiving PIMO compared to those receiving DIG or PL. The increase in early mitral infl ow velocity (E-wave) on day 28 for PIMO group is suggestive of diastolic dysfunction improvement, but this is only one variable related to diastolic function. Creatinine concentration increased in PIMO group, although it remained within normal range. In the present study, although all the three groups received furosemide, only PIMO group showed increase in blood creatinine between baseline and days 7 and 28. This result must be explored in later studies. Regarding the exercise intolerance assessment in a QoLQ, it must be aware that the owner evaluation is strongly infl uenced by the level of exercise that the dog is regularly submitted. Considering that most of the times, small breed dogs in a more advanced age is probably more sedentary and this fact surely precludes the owner to assess the exercise capacity. A more objective evaluation of the exercise tolerance should be considered in further clinical trials. Probably because of the small number of animals included in this study, differences in other studied variables were not found. The short-term follow-up of these patients may also have infl uenced the lack of differences among groups. Considering that stronger clinical evidence is needed to guide clinical decisions, longer prospective studies are also needed to compare the effects of DIG and PIMO, as well as to consider the benefi ts of the use or not of DIG associated with PIMO for dogs in HF due to CDMVD.Funding. This project was fi nancially supported by FAPESP - São Paulo Research Foundation, process number 08/57620-2

Microstructural and Microvascular Phenotype of Sarcomere Mutation Carriers and Overt Hypertrophic Cardiomyopathy

BACKGROUND: In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, and recent evidence suggests that these may occur early. As novel therapy provides promise for disease modification, detection of phenotype development is an emerging priority. To evaluate their utility as early and disease-specific biomarkers, we measured myocardial microstructure and MVD in 3 HCM groups-overt, either genotype-positive (G+LVH+) or genotype-negative (G-LVH+), and subclinical (G+LVH-) HCM-exploring relationships with electrical changes and genetic substrate. METHODS: This was a multicenter collaboration to study 206 subjects: 101 patients with overt HCM (51 G+LVH+ and 50 G-LVH+), 77 patients with G+LVH-, and 28 matched healthy volunteers. All underwent 12-lead ECG, quantitative perfusion cardiac magnetic resonance imaging (measuring myocardial blood flow, myocardial perfusion reserve, and perfusion defects), and cardiac diffusion tensor imaging measuring fractional anisotropy (lower values expected with more disarray), mean diffusivity (reflecting myocyte packing/interstitial expansion), and second eigenvector angle (measuring sheetlet orientation). RESULTS: Compared with healthy volunteers, patients with overt HCM had evidence of altered microstructure (lower fractional anisotropy, higher mean diffusivity, and higher second eigenvector angle; all P<0.001) and MVD (lower stress myocardial blood flow and myocardial perfusion reserve; both P<0.001). Patients with G-LVH+ were similar to those with G+LVH+ but had elevated second eigenvector angle (P<0.001 after adjustment for left ventricular hypertrophy and fibrosis). In overt disease, perfusion defects were found in all G+ but not all G- patients (100% [51/51] versus 82% [41/50]; P=0.001). Patients with G+LVH- compared with healthy volunteers similarly had altered microstructure, although to a lesser extent (all diffusion tensor imaging parameters; P<0.001), and MVD (reduced stress myocardial blood flow [P=0.015] with perfusion defects in 28% versus 0 healthy volunteers [P=0.002]). Disarray and MVD were independently associated with pathological electrocardiographic abnormalities in both overt and subclinical disease after adjustment for fibrosis and left ventricular hypertrophy (overt: fractional anisotropy: odds ratio for an abnormal ECG, 3.3, P=0.01; stress myocardial blood flow: odds ratio, 2.8, P=0.015; subclinical: fractional anisotropy odds ratio, 4.0, P=0.001; myocardial perfusion reserve odds ratio, 2.2, P=0.049). CONCLUSIONS: Microstructural alteration and MVD occur in overt HCM and are different in G+ and G- patients. Both also occur in the absence of hypertrophy in sarcomeric mutation carriers, in whom changes are associated with electrocardiographic abnormalities. Measurable changes in myocardial microstructure and microvascular function are early-phenotype biomarkers in the emerging era of disease-modifying therapy

Extreme precipitation occurrences in the Mendoza province and its relationship with El Niño phenomenon

Durante los últimos años se ha evidencia-do un incremento en la ocurrencia de eventos extremos de precipitación en Argentina, particularmente en regiones semi-áridas como es el caso de la provincia de Mendoza. Estos eventos han causado impactos negativos tanto a nivel económico como social, lo cual requiere una mejo-ra en el conocimiento de su variabilidad espacio-temporal. Si bien suele plantearse como hipótesis que el fenómeno de El Niño-Oscilación del Sur (ENOS) es responsable de la ocurrencia de estos eventos extremos en Mendoza, es necesaria una evaluación que considere registros recientes y una adecuada cobertura espacial de datos. Objetivos: cuantificar la contribución del fenómeno ENOS a la ocurrencia de eventos de precipitaciones extremas en la provincia de Mendoza en los últimos 30 años. Identificar la variabilidad espacio-temporal de estos fenómenos