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Platelet lysate (PL) is investigated as a potential replacement for fetal bovine serum (FBS) in cell culture. However, there is limited research on its impact on the immune profile of equine mesenchymal stromal cells (eMSCs). This study aimed to evaluate the effects of different PL formulations on the proliferative capacity, multipotentiality, and immune profile of equine adipose tissue-derived MSCs (eAD-MSCs). In vitro growth kinetics and trilineage differentiation of eAD-MSCs (n = 7) were assessed under three culture conditions: medium-concentration PL (MPL), high-concentration PL (HPL), and FBS as a control. The immune profile was evaluated by studying the expression of immunogenic receptors such as MHC I, MHC II, and immunomodulatory molecules IL-6, IL-10, and TNF-α, determined by gene expression, surface marker expression, and cytokine quantification. Both PL formulations, pooled from 5 donors, exhibited 3.3 and 6.5-fold higher platelet counts than baseline plasma for MPL and HPL, respectively. Higher concentrations of TGF-ß and PDGF were found in both PL formulations compared to baseline. Furthermore, MPL and HPL subcultures demonstrated proliferative, clonogenic, and multipotent capacities similar to FBS. The immune profile of PL-cultured cells exhibited gene expression levels related to immunogenicity and immunomodulation similar to the reference condition, and the surface antigen presence of MHC II was also similar. However, HPL media exhibited higher IL-6, IL-10, and TNF-α concentrations in the culture supernatant. In conclusion, both PL media contained higher concentrations of growth factors compared to FBS, supporting the in vitro culture of eAD-MSCs with proliferative, clonogenic, and multipotent capacity similar to the reference medium. Nonetheless, PL usage led to a variation in the immunomodulatory cytokine microenvironment, with higher concentrations of IL-6, IL-10, and TNF-α in HPL media compared to MPL and FBS.
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This article shows the direct and indirect impacts of COVID-19 on life expectancy in Chile in 2020, based on mortality statistics published in March 2023. To this end, a counterfactual mortality was estimated for 2020 without COVID-19; based on the pattern of mortality by cause of death from 1997 to 2019, mortality charts were created to calculate life expectancy from 2015 to 2020 and an estimation for 2020, and the difference between expected and observed life expectancy in 2020 was then separated by age group and cause of death. Life expectancy in 2020 interrupted the upward trend from 2015 to 2019, showing a decline of 1.32 years in men and 0.75 years in women compared to 2019. Compared to the estimated 2020, life expectancy was 1.51 years lower in men and 0.92 years lower in women, but the direct impact of COVID-19 on the decrease in life expectancy was greater (1.89 for men and 1.5 for women) in the 60-84 age group in men and the 60-89 age group in women. The direct negative impact of COVID-19 on life expectancy was partially mitigated by significant positive indirect impacts on two groups of causes of death: diseases of the respiratory system and infectious and parasitic diseases. This study shows the need to differentiate direct and indirect impacts of COVID-19, due to the implications for public health when the intensity of COVID-19 decreases and mobility restrictions are suspended.
El artículo muestra el impacto directo e indirecto del COVID-19 en la esperanza de vida de Chile durante el año 2020, utilizando las estadísticas de defunciones definitivas publicadas en marzo del año 2023. Para ello, se estimó una mortalidad contrafactual para año 2020 sin el COVID-19, siguiendo el patrón de mortalidad según causas de muerte desde 1997 a 2019, se elaboraron tablas de mortalidad para calcular la esperanza de vida para los años 2015 a 2020 y para el año 2020 estimado, y luego se descompuso la diferencia entre la esperanza de vida esperada y observada del año 2020 según grupos de edad y causas de muerte. La esperanza de vida del año 2020 quiebra la tendencia a su aumento entre 2015 y 2019, mostrando un retroceso, en hombres y en mujeres, con respecto al año 2019, de 1,32 y 0,75 años respectivamente. Con respecto al año 2020 estimado, la esperanza de vida del 2020 observado es 1,51 años menor en hombres y 0,92 en mujeres, pero el impacto directo del COVID-19 en pérdida de esperanza de vida fue mayor, 1,89 para los hombres y 1,5 para las mujeres, concentrándose en las edades entre los 60 y 84 años en hombres y entre 60 y 89 años en mujeres. El impacto directo negativo del COVID-19 a la esperanza de vida en parte fue contrarrestado por impactos indirectos positivos significativos en dos grupos de causas de muerte, las enfermedades del sistema respiratorio y las enfermedades infecciosas y parasitarias. El estudio muestra la necesidad de distinguir los impactos directos e indirectos del COVID-19, por la incidencia que pueden tener en la salud pública cuando el COVID-19 baje su intensidad y se eliminen las restricciones de movilidad.
Este artigo apresenta os impactos direto e indireto da COVID-19 na expectativa de vida no Chile em 2020 a partir de estatísticas de mortalidade publicadas em março de 2023. Para tanto, foi estimada uma mortalidade contrafactual para 2020 sem a COVID-19; a partir do padrão de mortalidade por causa de morte de 1997 a 2019, foram criadas tabelas de mortalidade para calcular a expectativa de vida para o período de 2015 a 2020 e para o ano estimado de 2020 e, em seguida, a diferença entre a expectativa de vida esperada e observada em 2020 foi separada por faixa etária e causa de morte. A expectativa de vida em 2020 interrompe a tendência de aumento entre 2015 e 2019, mostrando um declínio com relação a 2019 de 1,32 ano nos homens e 0,75 ano nas mulheres. Com relação ao ano estimado de 2020, a expectativa de vida observada é 1,51 ano menor nos homens e 0,92 nas mulheres, mas o impacto direto da COVID-19 na diminuição da expectativa de vida foi maior (1,89 para homens e 1,5 para mulheres), concentrando-se nas idades entre 60 e 84 anos nos homens e entre 60 e 89 anos nas mulheres. O impacto direto negativo da COVID-19 na expectativa de vida foi parcialmente atenuado por impactos indiretos positivos significativos em dois grupos de causas de morte: doenças do sistema respiratório e doenças infecciosas e parasitárias. Este estudo mostra a necessidade de diferenciar impactos diretos e indiretos da COVID-19, devido às implicações para a saúde pública quando a intensidade da COVID-19 diminuir e as restrições de mobilidade forem suspensas.
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COVID-19 , Causas de Muerte , Esperanza de Vida , Humanos , COVID-19/mortalidad , Esperanza de Vida/tendencias , Chile/epidemiología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Causas de Muerte/tendencias , Lactante , Adolescente , Adulto , Recién Nacido , Preescolar , Adulto Joven , Niño , SARS-CoV-2 , Pandemias , Factores SexualesRESUMEN
Resumen: El artículo muestra el impacto directo e indirecto del COVID-19 en la esperanza de vida de Chile durante el año 2020, utilizando las estadísticas de defunciones definitivas publicadas en marzo del año 2023. Para ello, se estimó una mortalidad contrafactual para año 2020 sin el COVID-19, siguiendo el patrón de mortalidad según causas de muerte desde 1997 a 2019, se elaboraron tablas de mortalidad para calcular la esperanza de vida para los años 2015 a 2020 y para el año 2020 estimado, y luego se descompuso la diferencia entre la esperanza de vida esperada y observada del año 2020 según grupos de edad y causas de muerte. La esperanza de vida del año 2020 quiebra la tendencia a su aumento entre 2015 y 2019, mostrando un retroceso, en hombres y en mujeres, con respecto al año 2019, de 1,32 y 0,75 años respectivamente. Con respecto al año 2020 estimado, la esperanza de vida del 2020 observado es 1,51 años menor en hombres y 0,92 en mujeres, pero el impacto directo del COVID-19 en pérdida de esperanza de vida fue mayor, 1,89 para los hombres y 1,5 para las mujeres, concentrándose en las edades entre los 60 y 84 años en hombres y entre 60 y 89 años en mujeres. El impacto directo negativo del COVID-19 a la esperanza de vida en parte fue contrarrestado por impactos indirectos positivos significativos en dos grupos de causas de muerte, las enfermedades del sistema respiratorio y las enfermedades infecciosas y parasitarias. El estudio muestra la necesidad de distinguir los impactos directos e indirectos del COVID-19, por la incidencia que pueden tener en la salud pública cuando el COVID-19 baje su intensidad y se eliminen las restricciones de movilidad.
Abstract: This article shows the direct and indirect impacts of COVID-19 on life expectancy in Chile in 2020, based on mortality statistics published in March 2023. To this end, a counterfactual mortality was estimated for 2020 without COVID-19; based on the pattern of mortality by cause of death from 1997 to 2019, mortality charts were created to calculate life expectancy from 2015 to 2020 and an estimation for 2020, and the difference between expected and observed life expectancy in 2020 was then separated by age group and cause of death. Life expectancy in 2020 interrupted the upward trend from 2015 to 2019, showing a decline of 1.32 years in men and 0.75 years in women compared to 2019. Compared to the estimated 2020, life expectancy was 1.51 years lower in men and 0.92 years lower in women, but the direct impact of COVID-19 on the decrease in life expectancy was greater (1.89 for men and 1.5 for women) in the 60-84 age group in men and the 60-89 age group in women. The direct negative impact of COVID-19 on life expectancy was partially mitigated by significant positive indirect impacts on two groups of causes of death: diseases of the respiratory system and infectious and parasitic diseases. This study shows the need to differentiate direct and indirect impacts of COVID-19, due to the implications for public health when the intensity of COVID-19 decreases and mobility restrictions are suspended.
Resumo: Este artigo apresenta os impactos direto e indireto da COVID-19 na expectativa de vida no Chile em 2020 a partir de estatísticas de mortalidade publicadas em março de 2023. Para tanto, foi estimada uma mortalidade contrafactual para 2020 sem a COVID-19; a partir do padrão de mortalidade por causa de morte de 1997 a 2019, foram criadas tabelas de mortalidade para calcular a expectativa de vida para o período de 2015 a 2020 e para o ano estimado de 2020 e, em seguida, a diferença entre a expectativa de vida esperada e observada em 2020 foi separada por faixa etária e causa de morte. A expectativa de vida em 2020 interrompe a tendência de aumento entre 2015 e 2019, mostrando um declínio com relação a 2019 de 1,32 ano nos homens e 0,75 ano nas mulheres. Com relação ao ano estimado de 2020, a expectativa de vida observada é 1,51 ano menor nos homens e 0,92 nas mulheres, mas o impacto direto da COVID-19 na diminuição da expectativa de vida foi maior (1,89 para homens e 1,5 para mulheres), concentrando-se nas idades entre 60 e 84 anos nos homens e entre 60 e 89 anos nas mulheres. O impacto direto negativo da COVID-19 na expectativa de vida foi parcialmente atenuado por impactos indiretos positivos significativos em dois grupos de causas de morte: doenças do sistema respiratório e doenças infecciosas e parasitárias. Este estudo mostra a necessidade de diferenciar impactos diretos e indiretos da COVID-19, devido às implicações para a saúde pública quando a intensidade da COVID-19 diminuir e as restrições de mobilidade forem suspensas.
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Background: For the diagnosis of tick sensitivity against different acaricides, there are in vitro and in vivo methods. The main in vivo method, the stable test, is considered a defining methodology. In Uruguay, the Rhipicephalus microplus (R. microplus) strain Mozo is used as the standard susceptible strain by the regulatory authorities. In vitro techniques applied both on adult and larvae stages are validated by FAO and can serve as an orientation diagnosis of the resistance profile developed in field conditions. An alternative was proposed as a modification of the larval immersion test (LIT), where syringes were used seeking to reduce the work necessary to perform the original technique, resulting in the syringe immersion test (SIT). Aim: The aim of this study was to expand the SIT for the characterization of sensitivity to Macrocyclic Lactones (MLs) in R. microplus and provide information on field strain sensitivity of R. microplus larvae. Methods: Log-logistic dose-response model for Ivermectin (IVM), Doramectin (DRM), and Moxidectin (MOX) were performed using concentrations ranging from 0.01 to 20.0 ppm (n = 6, 3 replicates per level on each drug). Larvae sensitivity results were determined after 24 hours of incubation at 27°C/90% RH, counting live/dead larvae. The final model will be decided as the best fit according to the model selection AIC criteria for each drug. Pharmacodynamic parameters [lower limit, slope, and effective dose at different levels (ED20, ED50, ED80, and ED95)] and its 95% confidence interval were considered for drug comparison. Results: Dose-response models were fitted for IVM, DRM, and MOX. MOX had the lowest ED50 of the three drugs, implying that MOX is of higher potency (two folds) when compared to IVM and DRM on R. microplus larvae using SIT. DRM had a different slope compared to IVM and MOX (p < 0.05), while IVM and MOX showed a similar slope (p > 0.05). Conclusion: This study allowed us to standardize the technique for larvae immersion for each ML, granting a new tool for in vitro test as a screening technique for tick sensitivity.
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Rhipicephalus , Jeringas , Animales , Lactonas/farmacología , Inmersión , Larva , Bioensayo/veterinariaRESUMEN
Background: Prostate disease represents about 0.7% of diseases in canines. The main diagnosed pathology is benign prostatic hyperplasia (BPH). However, the reports that study the association of a certain clinical sign with a specific prostate disease are scarce. Aim: The main objective of this study was to evaluate the clinical relevance of the most commonly observed clinical signs associated with the different prostatic disorders in canines admitted to the hospital of the Facultad de Veterinaria-Universidad de la República between 2011 and 2019. Methods: This retrospective study included 7,729 male canines treated at the hospital de la Facultad de Veterinaria-Universidad de la República (Montevideo, Uruguay) between 2011 and 2019. 289 canines with a presumptive/definitive diagnosis of prostate diseases were selected, recording the presence/absence of associated clinical signs. Results were reported in terms of odds ratios (ORs) using logistic regression (p < 0.05). Results: The five most frequently reported clinical signs were tenesmus (34%), anorexia (32%), lethargy (27%), prostatomegaly or pain during rectal examination (25%), and abdominal pain from palpation (22%). Diarrhea (3.39 vs. 0.33 OR), anorexia (2.07 vs. 0.39 OR), weight loss (2.27 vs. 0.27 OR), hematuria (3.25 vs. 0.44 OR), and urinary incontinence (2.96 vs. 0.33 OR) indicated a highest predictive value (p < 0.05) with prostatitis versus BPH, respectively. Being weight loss, the clinical sign is more frequently associated with neoplasia (20.2 OR, p = 0.002). Conclusion: This study shows that there are clinical signs with a higher degree of association for certain canine prostatic disorders than others.
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Enfermedades de los Perros , Hiperplasia Prostática , Masculino , Animales , Perros , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/veterinaria , Estudios Retrospectivos , Uruguay/epidemiología , Anorexia/complicaciones , Anorexia/veterinaria , Pérdida de Peso , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/epidemiologíaRESUMEN
The objective of this study was to characterize the domestic cat population of Uruguay in relation to breed, coat color, hair length, lifestyle (indoor vs. outdoor), age, sex, and spay/neuter status according to a survey completed by their owners or guardians. An online survey, distributed to residents of Uruguay, was completed in full by 2561 cat guardians. Descriptive statistics and Chi-squared tests were performed. The population of cats with guardians in Uruguay is characterized by the following data: higher frequency of female cats (53%), most of the cats were between two and six years old (49%), most of them were neutered (84%, mainly those older than one year of age), most of them have outdoor access (87%), a very low percentage (6%) are purebred (Siamese being the most frequent: 86%), and within the non-pure breeds, short hair cats were the most frequent (79%). This study, in addition to expanding the information on the characteristics of cats with guardians from other countries and continents, is the first study in Latin America to describe some key demographic aspects such as cat breeds, coat color, hair length, lifestyles, and frequency by age, sex, and spay/neuter status (spayed/neutered or not) at the country level.
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RHU is the oldest endurance sport in Uruguay. However, despite 80 years of racing, there are no studies to characterize this type of competition, explore rates and causes of death, and identify the associated risk factors. The aim was to characterize the Raid Hipico Uruguayo (RHU) competencies according to the distance (short (SR, 60 km) vs. long (LR, 80-115 km)), the causes of deaths, and the associated risk factors. The study population comprised horses (n = 16,856) that participated in RHU rides from 2007 to 2018. LR were more frequent than SR (p < 0.001). The average speed of winners was higher in SR (32.12 km/h) than in LR (28.14 km/h) (p < 0.001). There were 99 fatalities (5.9 per 1000 starts). SR had greater frequency of high comfort index (CI = Temp [°F] + Humidity [%]) than LR, and LR had greater frequency of low CI than SR (p < 0.001). The percentage of inexperienced horses and those who completed the ride was greater in SR than in LR (p < 0.001). In both types of rides, more horses died during than after the ride, and inexperienced horses were more likely to suffer fatalities than horses with prior experience in the sport (p < 0.05). SR were associated with increased risk of sudden death, while LR were associated with increased risk of death due to metabolic alterations. The high fatality index shown in this work warrants urgent investigation in this sport to minimize mortality associated with RHU-specific diseases.
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The Raid Uruguayo (RAID) is an equestrian endurance competition. This study characterized the hydroelectrolytic parameters (Na+, K+, Cl-, tCa++, and iCa++), hematocrit (Ht), total plasma protein (TPP), and blood pH from 900 equine athletes (finishers and non-finishers) competing over distances of 80 to 115 km under different climate conditions. Paired blood samples were taken prior to the start of the competition (sample 1) and at the end of the race or at the time of leaving the competition (sample 2). The association of the comfort index (CI: low, moderate, and high) with blood parameters was evaluated. Of the 900 horses included, 550 were not able to finish the trial. The comfort index was not associated with success in completing the race. In the horses that finished the race, the CI was not associated with Ht, pH, TPP, or Na+ concentrations in samples taken after finishing the RAID. In contrast, the decreases in chloride, K+, tCa++, and iCa++ concentrations found after the race were more pronounced at moderate and high CI values when compared with low CI values. In horses that did not finish the race, the CI was associated with all variables except for Ht. The data confirmed the relevance of considering the impact of the comfort index in hydroelectrolytic losses in the RAID, as it influence ssuccess or failure in the performance of endurance horses finishing the competition.
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Caenorhabditis elegans is a free-living nematode that has been validated for anthelmintic drug screening. However, this model has not been used to address anthelmintic dose-response-time and drug-drug interactions through matrix array methodology. Eprinomectin (EPM) and Ivermectin (IVM) are macrocyclic lactones widely used as anthelmintics. Despite being very similar, EPM and IVM are combined in commercial formulations or mixed by farmers, under the assumption that the combination would increase their efficacy. However, there is no data reported on the pharmacological evaluation of the combination of both drugs. In this study, we assessed the pharmacodynamics and drug-drug interactions of these two anthelmintic drugs. Since the action of these drugs causes worm paralysis, we used an infrared motility assay to measure EPM and IVM effects on worm movement over time. The results showed that EPM was slightly more potent than IVM, that drug potency increased with drug time exposure, and that once paralyzed, worms did not recover. Different EPM/IVM concentration ratios were used and synergy and combination sensitivity scores were determined at different exposure times, applying Highest Single Agent (HSA), Loewe additivity, Bliss and Zero Interaction Potency (ZIP) models. The results clearly indicate that there is neither synergy nor antagonism between both macrocyclic lactones. This study shows that it is more relevant to prioritize the exposure time of each individual drug than to combine them to improve their effects. The results highlight the utility of C. elegans to address pharmacodynamics studies, particularly for drug-drug interactions. Models in vitro can be integrated to facilitate preclinical and clinical translational studies and help researchers to understand drug-drug interactions and achieve rational therapeutic regimes.
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OBJECTIVE: Critical care air transport has played an important role during the coronavirus disease 2019 (COVID-19) pandemic. The goal of this article is to analyze results and lessons learned from the evacuation of the first 100 COVID-19 patients transported between medical facilities in Chile. METHODS: We reviewed prospective data of patients who were referred for air transport between March 27, 2020, and July 9, 2020. RESULTS: Of 115 referred patients, 100 were transported by air. All patients were intubated and mechanically ventilated. Hypertension, diabetes, and obesity were the most commonly observed comorbidities. Our service did not experience any major problems in patient care en route or among the crewmembers. We did not observe any severe acute respiratory syndrome coronavirus 2 infections among our flight team members during the study period. Twelve (12%) patients died at their destination intensive care unit, whereas the remaining 88 patients (88%) returned to their primary hospitals after recovery. CONCLUSIONS: Air transport of mechanically ventilated patients with COVID-19 infection has been shown to be a safe way of transport, with no in-flight deaths and an in-hospital mortality of 12%, which compares favorably with the in-hospital mortality of similar patients who did not undergo air transport.
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COVID-19 , Pandemias , COVID-19/epidemiología , COVID-19/terapia , Chile/epidemiología , Enfermedad Crítica , Humanos , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
ABSTRACT: Cereal grains are usually ensiled to improve their nutritional value and are one of the main sources of feed for dairy cattle. However, during storage, grains can be contaminated with toxicogenic fungi. Sorghum is one of the most economically important cereals in the world. Therefore, the aim of this work was to evaluate the influence of storage duration and tannin and moisture content (MC) on toxicogenic fungal populations in sorghum grain storage. Samples that were prepared with varieties high in tannins (genotypes Morgan 108 and ACA 558, >5 g/kg dry matter) and with varieties low in tannin content (genotypes Flash 10 and ACA 546, <1 g/kg dry matter) were collected and manually compacted in experimental laboratory silos where they received different MC treatments: low (15 to 25%), medium (26 to 32%), and high (33 to 42%). Freshly harvested grains were analyzed at time 0, and stored grains were analyzed at 30, 90, and 180 days. Fungal isolation and identification were performed following conventional mycological methods. Penicillium citrinum (34%), Aspergillus flavus (60%), and Fusarium nygamai (68%) were the most abundant species. Rapid detection of aflatoxins and fumonisins in each sample was performed using enzyme-linked immunosorbent assay according to the AOAC method, and the quantification of aflatoxin B1 was performed using high-performance liquid chromatography. In four samples of pre- and poststorage grains, aflatoxins were detected with levels of 6.7 to 28.8 µg/kg and aflatoxin B1 with a level of 2 to 14 µg/kg. Fumonisins were only detected in two freshly harvested samples, with levels of 500 to 900 µg/kg. In general, storage time favored the increase of Penicillium populations and reduced Aspergillus and Fusarium. Conversely the abundance of the three populations was not affected by the MC. The results of this study show that fungal populations must be analyzed at different times.
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Aflatoxinas , Fumonisinas , Sorghum , Aflatoxina B1/análisis , Animales , Bovinos , Grano Comestible/química , TaninosRESUMEN
BACKGROUND: Fluazuron is a chitin synthesis inhibitor administered as a pour-on formulation in cattle for tick control. This study analyzes under endemic tick infestation, the incidence of the pour-on application pattern on the plasma levels of fluazuron in calves and cows in the lactation period of the beef cow. Two hundred and ninety-two beef cows around parturition were treated with a commercial pour-on formulation of fluazuron at a rate of 2.5 mg/kg of body weight. A total of 4 treatments were carried out on days 0, 32, 77, and 117. At each administration time, the cows were grouped according to the pour-on administration pattern: long (~ 60 cm pour-on application surface) and short (~ 30 cm pour-on application surface). Fluazuron levels in cows and calves plasma were determined before the third and fourth application for each subgroup (n = 10) by HPLC-MS/MS. During the entire study, cow-calf pairs were maintained under field conditions and qualitatively examined for tick infestation on the day of each treatment. Both treatments (long and short) schemes were designed to prevent the annual persistence of ticks. RESULTS: No animals with presence of ticks were identified during the first 117 days of the study, except for three cows and one calf at the time of the third application (day 77). There were no differences after 40 days (day 77) post-treatment of the second application (30 ± 5 ppb vs. 28.5 ± 12 ppb, p > 0.05) and 45 days (day 117) after the third application (147 ± 55 ppb vs 140 ± 46 ppb, p > 0.05) between groups of cows treated with the long or short pour-on application, respectively. Plasma concentration of fluazuron at second and third application was increased (3.3 and 2.9 times, respectively) in calves under free suckling compared to cows. Nevertheless, both groups of cows and calves showed a significant increase in plasma concentration of fluazuron between times (4.9 times, p < 0.0001 and 2.8 times, p < 0.0001, respectively). In both groups, tick prevalence was 0% throughout the trial, except for day 77, which reached 1%. CONCLUSIONS: The main conclusions of this study were the following: 1) Different administration patterns (long vs. short) did not differ in plasma levels of fluazuron.; 2) Given that only the cows were treated and lactating calves presented higher plasma levels of fluazuron than cows, passage through milk appears to be relevant and possibly due to a cumulative effect and continuous drug intake.
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Enfermedades de los Bovinos , Compuestos de Fenilurea/administración & dosificación , Infestaciones por Garrapatas , Animales , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Enfermedades de los Bovinos/parasitología , Femenino , Lactancia , Leche , Embarazo , Espectrometría de Masas en Tándem/veterinaria , Infestaciones por Garrapatas/tratamiento farmacológico , Infestaciones por Garrapatas/veterinariaRESUMEN
Background: Novel combinations of ivermectin (IVM) and fluazuron (FLU) are presented as an alternative for the control of ticks in cattle. Applying a combination of drugs with the aim to affect different stages of the parasite's life cycle is established as a potential measure to achieve the control of ticks in cattle. Aim: To determine the therapeutic equivalence between two novel formulations of IVM 1% combined with FLU 12.5% tested on bovines naturally infested with Rhipicephalus (Boophilus) microplus. Methods: Forty adult beef cattle were randomized into four groups (n = 10): IVM [1% (0.2 mg/kg)], combinations groups A and B [IVM 1% (0.2 mg/kg) + FLU 12.5% (2.5 mg/kg), each], and control [untreated]). On days 14, 27, and 49 after administration, the presence of ticks was ranked as null, low, medium, and high; a cumulative link model was adjusted to evaluate treatment response. Results: Although all groups had some animals with the presence of ticks until day 27, on day 14 IVM [odds ratios (OR) 0.013, CI95%: 0.001-0.014, p < 0.01], A (OR 0.01, CI95%: 0.00-0.07, p < 0.01) and B (OR 0.01, CI95%: 0.00-0.148, p < 0.01) groups were different when compared to the control group, unlike on day 27 where only groups A (OR 0.02, CI95%: 0.00-0.17, p < 0.01) and B (OR 0.06, CI95%: 0.00-0.46, p < 0.01) remained different from the control group. On day 49 post-administration, IVM and B did not differ from the control group, with 0.95 probability (CI95% 0.92-1.02) of high parasite burden. At day 49 post-administration, group A was the only group free of ticks (OR 0.01, CI95%: 0.00-0.13, p < 0.01). Conclusions: Pharmacotechnical differences in combined formulations should be considered in therapeutic equivalence studies.
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Acaricidas/uso terapéutico , Enfermedades de los Bovinos/prevención & control , Ivermectina/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Rhipicephalus/efectos de los fármacos , Infestaciones por Garrapatas/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/parasitología , Composición de Medicamentos/veterinaria , Infestaciones por Garrapatas/parasitología , Infestaciones por Garrapatas/prevención & controlRESUMEN
The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (Cmax ) of amitriptyline was 30.7 ng/ml, time to maximum plasma concentration (Tmax ) 1-2 hr, elimination half-life (t1/2 ) 17.2 hr, area under plasma concentration-time curve (AUC) 487.4 ng ml-1 hr-1 , apparent clearance (Cl/F) 2.6 L hr-1 kg-1 , and apparent volume of distribution (Vd/F) 60.1 L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p < .05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations.
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Amitriptilina/farmacocinética , Antidepresivos Tricíclicos/farmacocinética , Caballos/metabolismo , Administración Oral , Amitriptilina/administración & dosificación , Amitriptilina/sangre , Animales , Antidepresivos Tricíclicos/administración & dosificación , Antidepresivos Tricíclicos/sangre , Área Bajo la Curva , Femenino , Semivida , Caballos/sangre , MasculinoRESUMEN
In the current study, the egg hatch test (EHT) has been evaluated as an in vitro technique to detect albendazole (ABZ) resistance in Fasciola hepatica. The intra- and inter-assay variations of the EHT were measured by means of the coefficient of variation in different fluke isolates and over time; then, the results of the EHT were compared with the "gold standard" controlled efficacy test, which assesses the in vivo anthelmintic efficacy. The EHT was used later to evaluate the intra-herd variability regarding the level of ABZ resistance in calves infected by the same fluke isolate. Finally, several factors of the initial protocol were modified to improve the simplicity of the assay, including the incubation time of eggs with the drug and the use of eggs collected from faeces. The greatest uniformity between results within the assay and over time until 8 weeks after gallbladder collection (the deadline proposed for egg analysis) was obtained with an ABZ concentration of 0.5 µM. The length of exposure to ABZ was shown to be critical, as prolonged incubation (15 days) led to a change of ovicidal activity. The ABZ concentration of 0.5 µM is suggested as a possible discriminating dose to predict ABZ resistance, due to the close agreement between the results of the EHT at an ABZ concentration of 0.5 µM and those of the in vivo assays.
Asunto(s)
Albendazol/farmacología , Enfermedades de los Bovinos/parasitología , Fasciola hepatica/efectos de los fármacos , Fascioliasis/veterinaria , Pruebas de Sensibilidad Parasitaria/métodos , Animales , Antihelmínticos/farmacología , Bovinos , Enfermedades de los Bovinos/diagnóstico , Resistencia a Medicamentos , Fascioliasis/diagnóstico , Fascioliasis/parasitología , Heces/parasitología , Óvulo/efectos de los fármacos , Factores de TiempoRESUMEN
Nematode parasites have a profound impact on humankind, infecting nearly one-quarter of the world's population, as well as livestock. There is a pressing need for discovering nematicides due to the spread of resistance to currently used drugs. The free-living nematode Caenorhabditis elegans is a formidable experimentally tractable model organism that offers key advantages in accelerating nematicide discovery. We report the screening of drug-like libraries using an overnight high-throughput C. elegans assay, based on an automated infrared motility reader. As a proof of concept, we screened the "Pathogen Box" library, and identical results to a previous screen using Haemonchus contortus were obtained. We then screened an in-house library containing a diversity of compound families. Most active compounds had a conjugation of an unsaturation with an electronegative atom (N, O, or S) and an aromatic ring. Importantly, we identified symmetric arylidene ketones and aryl hydrazine derivatives as novel nematicides. Furthermore, one of these compounds, (1E,2E)-1,2-bis(thiophen-3-ylmethylene)hydrazine, was active as a nematicide at 25 µm, but innocuous to the vertebrate model zebrafish at 50 µm. Our results identified novel nematicidal scaffolds and illustrate the value of C. elegans in accelerating nematicide discovery using a nonlabor-intensive automated assay that provides a simple overnight readout.
RESUMEN
The goals of the current trial were (a) to characterize the plasma disposition kinetics of levamisole (LEV), albendazole (ABZ) and ivermectin (IVM), each administered either alone (single active ingredient) or as a combined formulation to lambs; (b) to compare the clinical anthelmintic efficacy of the same drugs given either separately or co-administered to lambs infected with resistant nematodes. Fifty Corriedale lambs naturally infected with multiple resistant gastrointestinal nematodes were involved in the following experimental trials: (a) "Pharmacokinetic trial": the animals were allocated into five groups (n=10 each) and intraruminally treated with either LEV (8 mg/kg), ABZ (5mg/kg), IVM (0.2mg/kg), or with a LEV+ABZ+IVM combined formulation, where each active ingredient was administered at the same dose. Blood samples were collected over 15 days post-treatment and drug plasma concentrations measured by HPLC. (b) "Efficacy trial": the same treated groups plus an untreated control group were used to assess the comparative anthelmintic efficacy by the faecal egg count reduction test (FECRT). Although the overall LEV disposition kinetics was unaffected, significantly lower (61%) ABZ-sulphoxide and higher (71%) IVM systemic availabilities were obtained after administration of the combined formulation in comparison to those obtained after treatment with each drug alone. A multiple drug resistance situation was observed for Haemonchus spp. The observed efficacies were 52% (LEV), 72% (ABZ), 80% (IVM) and 87% (triple combined formulation). The results reported here contribute to the pharmaco-therapeutic knowledge on drug combinations. This type of research is crucial before further development of combined anthelmintic preparations reaches the market to deal with resistant nematode control. The co-administration of LEV+ABZ+IVM did not result in a significant advantageous anthelmintic effect compared to the treatment with IVM alone. The simultaneous/combined administration of LEV, ABZ and IVM may account for a drug-drug pharmacological interaction in infected lambs. The pharmacokinetic interaction accounted for a reduced ABZ-sulphoxide and enhanced IVM systemic exposure following the combined treatment.
Asunto(s)
Antihelmínticos/administración & dosificación , Antihelmínticos/farmacocinética , Infecciones por Nematodos/veterinaria , Enfermedades de las Ovejas/tratamiento farmacológico , Albendazol/administración & dosificación , Albendazol/análogos & derivados , Albendazol/sangre , Albendazol/farmacocinética , Animales , Antihelmínticos/sangre , Antihelmínticos/farmacología , Área Bajo la Curva , Interacciones Farmacológicas , Resistencia a Medicamentos/efectos de los fármacos , Heces/parasitología , Femenino , Ivermectina/administración & dosificación , Ivermectina/sangre , Ivermectina/farmacología , Levamisol/administración & dosificación , Levamisol/sangre , Levamisol/farmacocinética , Masculino , Nematodos/efectos de los fármacos , Infecciones por Nematodos/tratamiento farmacológico , Recuento de Huevos de Parásitos/veterinaria , Ovinos , TiempoRESUMEN
We studied the transport process of overdamped Brownian particles, in a chain of asymmetric cavities, interacting through a hard-core potential. When a force is applied in opposite directions a difference in the drift velocity of the particles inside the cavity can be observed. Previous works on similar systems deal with the low-concentration regime, in which the interaction is irrelevant. In this case it was found that large particles show a stronger asymmetry in the drift velocity when a small force is applied, allowing for the separation of different size particles [Reguera et al., Phys. Rev. Lett. 108, 020604 (2012)]. We found that when the interaction between particles is considered, the behavior of the system is substantially different. For example, as concentration is increased, the small particles are the ones that show a stronger asymmetry. For the case where all the particles in the system are of the same size we took advantage of the particle-vacancy analogy to predict that the left and right currents are almost equal in a region around the concentration 0.5 despite the asymmetry of the cavity.
RESUMEN
The main objectives of this study were (a) to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form.
Asunto(s)
Albendazol/administración & dosificación , Albendazol/sangre , Administración Oral , Albendazol/farmacocinética , Animales , Disponibilidad Biológica , Química Farmacéutica , Perros , Femenino , Dureza , ComprimidosRESUMEN
We derive and study a theoretical description for single-file diffusion, i.e., diffusion in a one-dimensional lattice of particles with hard core interaction. It is well known that for this system a tagged particle has anomalous diffusion for long times. The novelty of the present approach is that it allows for the derivation of correlations between a tagged particle and other particles of the system at a given distance with empty sites in between. The behavior of the correlation gives deeper insights into the processes involved. The numerical integration of differential equations are in good agreement with Monte Carlo simulations.