Aplicación de elementos finitos en la predicción del factor de intensidad de esfuerzos para fisuras en modo abertura

Se expone la importancia del criterio KIC en Fractomecánica y su campo de aplicabilidad. Se indican Las Limitaciones de la formulación analítica. Se proponen dos criterios de evaluación de K1 en base al Método de Elementos Finitos: el Criterio del Promedio de Valores y el Criterio del Intercepto. Se entregan resultados para ambos criterios aplicados a tres especímenes finitos, incluyendo una evaluación de cada criterio

Encefalopatía hepática inducida en cerdos por semillas y vainas de Senna occidentalis

Senna occidentalis es una planta tóxica que afecta a diferentes especies de animales. La lesión hallada en la mayoría de los animales intoxicados es la degeneración muscular. Sin embargo, la encefalopatía hepática (EH) es observada en equinos y en humanos. El objetivo de este trabajo fue determinar si, además de la miodegeneración ya reportada, semillas y vainas de S. occidentalis inducen una EH tóxica en cerdos. Diez animales se dividieron en dos grupos (de cinco animales cada uno), un grupo se alimentó con una ración que contenía el 20% de vainas y semillas de S. occidentalis, y los animales controles recibieron ración comercial durante 14 días. Los animales intoxicados presentaron síntomas de aparición brusca, caracterizados por incoordinación, ataxia, desorientación, presión de la cabeza contra objetos duros, depresión y recumbencia lateral. La aspartato aminotransferasa y creatinquinasa incrementaron junto a la Bilirrubina Total en los animales intoxicados. La evaluación histopatológica de los cerdos alimentados con S. occidentalis evidenció tumefacción hepatocelular y necrosis centrolobulillar en el hígado; mientras que el encéfalo presentó vacuolización de la sustancia blanca y astrocitos Alzheimer tipo II en la corteza cerebral. La microscopía electrónica reveló lesiones mitocondriales en el hígado. Estos resultados muestran que en el presente estudio, la lesión muscular ya reportada no se observó, seguramente debido a que la EH tóxica reproducida en los animales evaluados se produjo antes de que ello ocurra. Por otro lado, los animales del presente estudio desarrollaron signos clínicos y lesiones histológicas que fueron similares a esas observadas en casos de envenenamiento accidental. Además futuros estudios son necesarios para identificar el tóxico responsable de la falla hepática aguda, observada en los animales de este estudio.Senna occidentalis is a toxic plant that affects different animal species. The predominant lesion found in most of the intoxicated animals is skeletal muscle degeneration. However, in horses and humans, this poisoning is primarily characterized by hepatic encephalopathy (HE). The aim of this paper was to determine whether, in addition to this myodegeneration, the seeds and pods of S. occidentalis induce toxic EH in pigs. Ten pigs were divided into two groups (of five animals each), one of which were fed with a ration containing 20 % of S. occidentalis pods and seeds, and the other with a commercial ration (control) for 14 days. Poisoned animals had a sudden onset of symptoms, characterized by incoordination, ataxia, disorientation and head pressing, depression and lateral recumbency. Aspartate aminotransferase and Creatine phosphokinase serum activities increased along with an increasement of serum bilirubin in intoxicated animals with S. occidentalis. Histopathological studies of the poisoned pigs showed hepatocellular swelling and centrilobular necrosis in the liver, vacuolization of the white matter and Alzheimer type II astrocytes in the cerebral cortex of the brain. Electron microscopy revealed mitochondrial lesions in liver. These results showed that in this study, the muscle injury previously reported was not observed, most probably because the toxic EH reproduced in the evaluated animals were produced before skeletal muscle degeneration occurred. On the other hand, the animals of the present study developed clinical signs and histological lesions that were similar to those observed in cases of accidental poisoning. Besides, further studies are needed to identify the specific toxin responsible for acute liver failure, observed in the animals of this study.Facultad de Ciencias VeterinariasConsejo Nacional de Investigaciones Científicas y Técnica

Encefalopatía hepática inducida en cerdos por semillas y vainas de Senna occidentalis

Senna occidentalis es una planta tóxica que afecta a diferentes especies de animales. La lesión hallada en la mayoría de los animales intoxicados es la degeneración muscular. Sin embargo, la encefalopatía hepática (EH) es observada en equinos y en humanos. El objetivo de este trabajo fue determinar si, además de la miodegeneración ya reportada, semillas y vainas de S. occidentalis inducen una EH tóxica en cerdos. Diez animales se dividieron en dos grupos (de cinco animales cada uno), un grupo se alimentó con una ración que contenía el 20% de vainas y semillas de S. occidentalis, y los animales controles recibieron ración comercial durante 14 días. Los animales intoxicados presentaron síntomas de aparición brusca, caracterizados por incoordinación, ataxia, desorientación, presión de la cabeza contra objetos duros, depresión y recumbencia lateral. La aspartato aminotransferasa y creatinquinasa incrementaron junto a la Bilirrubina Total en los animales intoxicados. La evaluación histopatológica de los cerdos alimentados con S. occidentalis evidenció tumefacción hepatocelular y necrosis centrolobulillar en el hígado; mientras que el encéfalo presentó vacuolización de la sustancia blanca y astrocitos Alzheimer tipo II en la corteza cerebral. La microscopía electrónica reveló lesiones mitocondriales en el hígado. Estos resultados muestran que en el presente estudio, la lesión muscular ya reportada no se observó, seguramente debido a que la EH tóxica reproducida en los animales evaluados se produjo antes de que ello ocurra. Por otro lado, los animales del presente estudio desarrollaron signos clínicos y lesiones histológicas que fueron similares a esas observadas en casos de envenenamiento accidental. Además futuros estudios son necesarios para identificar el tóxico responsable de la falla hepática aguda, observada en los animales de este estudio.Senna occidentalis is a toxic plant that affects different animal species. The predominant lesion found in most of the intoxicated animals is skeletal muscle degeneration. However, in horses and humans, this poisoning is primarily characterized by hepatic encephalopathy (HE). The aim of this paper was to determine whether, in addition to this myodegeneration, the seeds and pods of S. occidentalis induce toxic EH in pigs. Ten pigs were divided into two groups (of five animals each), one of which were fed with a ration containing 20 % of S. occidentalis pods and seeds, and the other with a commercial ration (control) for 14 days. Poisoned animals had a sudden onset of symptoms, characterized by incoordination, ataxia, disorientation and head pressing, depression and lateral recumbency. Aspartate aminotransferase and Creatine phosphokinase serum activities increased along with an increasement of serum bilirubin in intoxicated animals with S. occidentalis. Histopathological studies of the poisoned pigs showed hepatocellular swelling and centrilobular necrosis in the liver, vacuolization of the white matter and Alzheimer type II astrocytes in the cerebral cortex of the brain. Electron microscopy revealed mitochondrial lesions in liver. These results showed that in this study, the muscle injury previously reported was not observed, most probably because the toxic EH reproduced in the evaluated animals were produced before skeletal muscle degeneration occurred. On the other hand, the animals of the present study developed clinical signs and histological lesions that were similar to those observed in cases of accidental poisoning. Besides, further studies are needed to identify the specific toxin responsible for acute liver failure, observed in the animals of this study.Facultad de Ciencias VeterinariasConsejo Nacional de Investigaciones Científicas y Técnica

Haptoglobin improves shock, lung injury, and survival in canine pneumonia

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, mechanical ventilation, sedation, and continuous care are translatable to management in human intensive care units. We found, in this S. aureus pneumonia model inducing septic shock, that commercial human haptoglobin concentrate infusions over 48-hours bind canine CFH, increase CFH clearance, and lower circulating iron. Over the 96-hour study, this treatment was associated with an improved metabolic profile (pH, lactate), less lung injury, reversal of shock, and increased survival. Haptoglobin binding compartmentalized CFH to the intravascular space. This observation, in combination with increasing CFHs clearance, reduced available iron as a potential source of bacterial nutrition while decreasing the ability for CFH and iron to cause extravascular oxidative tissue injury. In contrast, haptoglobin therapy had no measurable antiinflammatory effect on elevations in proinflammatory C-reactive protein and cytokine levels. Haptoglobin therapy enhances normal host defense mechanisms in contrast to previously studied antiinflammatory sepsis therapies, making it a biologically plausible novel approach to treat septic shock

Phase I/II Trial of the Anti-HIV Activity of Mifepristone in HIV-Infected Subjects ACTG 5200

Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to have anti-HIV activity and anti-simian immunodeficiency virus activity in a macaque model. A phase I/II trial was performed to assess the drug’s safety and anti-HIV activity

Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21–45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics

Predicción numérica del factor de intensidad de esfuerzos en fisuras mediante el principio de liberación de energía

Se expone el Principio de Liberación de Energía y su uso en la obtención del Factor de Intensidad de Esfuerzos en fisuras para casos de extremos fijos y de carga constante.Se emplea el Método de Elementos Finitos en la discretización espacial y se simula el crecimiento de fisura mediante relajación de grados de libertad de borde, obteniéndose estimaciones para los valores de Energía de Deformación para cada longitud de fisura. Se evalúa la razón de liberación de energía mediante diferencias finitas centrales obteniéndose estimaciones para los valores de K1.Se presentan resultados numéricos para tres especimenes finitos comparándolos con valores analíticos