Síntesis y evaluación citotoxica de derivados halogenados y peracetylados de nucleósidos en celulas de cancer de mama

Objectives. To make the synthesis of halogenated derivatives on the nitrogenous base and their respective acyl ester and amide type derivatives for all hydroxyl and amine groups of the uridine and cytarabine nucleosides, and evaluate cytotoxicity against breast cancer cell line. Methods. First, it was accomplished the halogenation reaction on the 5-position of the nitrogenous base, subsequently, the ester and amide derivatives were performed for all hydroxyl and amine group present in the nucleosides. Besides, the uridine acetonide derivatives as prepared by acid catalysis. The products were characterized by nuclear magnetic resonance spectroscopy (1H RMN y 13C RMN) and mass spectrometry in positive mode by direct injection. Derivatives were evaluated in Chinese hamster ovary (CHO-K1) and human breast cancer (MCF-7) cell lines. Results. The four derivatives were obtained with chlorine and bromine for the uridine and cytarabine, respectively, their respective per-acetylated derivatives, the per-acetylated nucleoside and the uridine acetonide; the compounds were obtained with efficiency over 90%. The per-acetylated nucleosides and the halogenated and per-acetylated derivatives did not show inhibitory effects on cell viability in MCF-7 cell line. However, the per-acetylated and halogenated derivatives presented a higher cytotoxic activity than their respective per-acetylated nucleoside. The uridine 3’,4’-acetonide showed a significant cytotoxicity on both cell lines. Conclusions. The per-acetylated nucleoside, and the respective halogenated derivatives with chlorine and bromine were obtained with high yields, nevertheless, these compounds did not exhibit a significant anti-proliferative activity (p˂0.05), possibly due to a low intra-cellular activation.Objetivos: Sintetizar derivados halogenados sobre la base nitrogenada, sus respectivos derivados tipo éster o amida de todos los grupos hidroxilo y amina presentes en los nucleósidos uridina y citarabina, y evaluar su actividad citotóxica sobre una línea celular de cáncer de mama. Metodología: primero se realizó la reacción de halogenación en la posición 5 de la base nitrogenada, posteriormente se formaron los ésteres y amidas de todos los grupos hidroxilos y amino presentes en los nucleósidos. Además, se preparó el derivado acetónido con catálisis ácida. Los compuestos se caracterizaron por espectroscopía de resonancia magnética nuclear (RMN 1H y RMN 13C) y espectrometría de masas por inyección directa en modo positivo. Los derivados se evaluaron sobre líneas celulares de tumor de Ovario de Hámster Chino (CHO) y de cáncer de mamá (MCF-7). Resultados: Se obtuvieron 4 derivados mono-halogenados con cloro y bromo de la uridina y citarabina, respectivamente, sus respectivos derivados per-acetilados, los nucleósidos per-acetilados y el acetónido de la uridina; los compuestos se obtuvieron con rendimientos superiores a 90%. Los nucleósidos per-acetilados, y los derivados per-acetilados y halogenados no exhibieron una inhibición significativa de la viabilidad celular en ambas líneas celulares, sin embargo, de estos, los derivados per-acetilados y halogenados presentaron mayor actividad citotóxica que los respectivos nucleósidos per-acetilados. El derivado acetónido de la uridina mostró citotoxicidad significativa sobre ambas líneas celulares. Conclusiones: se obtuvieron los nucleósidos per-acetilados y los respectivos derivados clorados y bromados de estos, con rendimientos altos, sin embargo, estos compuestos no exhibieron una actividad anti-proliferativa significativa (p˂0,05), posiblemente debido a una baja activación intra-celular de los nucleósidos

Exploring pig trade patterns to inform the design of risk-based disease surveillance and control strategies

An understanding of the patterns of animal contact networks provides essential information for the design of risk-based animal disease surveillance and control strategies. This study characterises pig movements throughout England and Wales between 2009 and 2013 with a view to characterising spatial and temporal patterns, network topology and trade communities. Data were extracted from the Animal and Plant Health Agency (APHA)’s RADAR (Rapid Analysis and Detection of Animal-related Risks) database, and analysed using descriptive and network approaches. A total of 61,937,855 pigs were moved through 872,493 movements of batches in England and Wales during the 5-year study period. Results show that the network exhibited scale-free and small-world topologies, indicating the potential for diseases to quickly spread within the pig industry. The findings also provide suggestions for how risk-based surveillance strategies could be optimised in the country by taking account of highly connected holdings, geographical regions and time periods with the greatest number of movements and pigs moved, as these are likely to be at higher risk for disease introduction. This study is also the first attempt to identify trade communities in the country, information which could be used to facilitate the pig trade and maintain disease-free status across the country in the event of an outbreak

IMPORTANCIA DE LA NUTRICIÓN EN EL PLAN DE ESTUDIOS DE ENFERMERÍA DE LA FESI UNAM

Introduction: In Mexico there are some regions with starvation and undernourishment, therefore the medical research has to be increased. The Nursing Major program at Facultad de Estudios Superiores Iztacala of Universidad Nacional Autónoma de México (2006) includes the study of nutrition. This one is divided in different modules but not as an specific subject, however we have observed that students are not able to incorporate all the nutrition fundamental aspects. Currently the basic theory of nutrition takes 56 hours and 50 minutes, but this one is included such as a section in different courses. “Nutrition and Health care” is an elective subject and it takes 80 hours, nevertheless there are two disadvantages. The first one is that students are allowed to take it up to the fourth semester, and the second one is that there is a lack of time (23 hours), since nutrition is a wide topic. We need to get qualified people related to this topic in order to teach efficiently. We have noticed that students need to learn more about nutrition, for that reason it is necessary to assign the nutrition topic as a compulsory subject, otherwise not all the students will be able to take the course. Material and Method: Qualitative and quantitative methods were used for the current research. For the quantitative method was used a nominal scale that allowed to sort the 34 programs reviewed from mexican institutions which have the nursing major. Two researches (done by the students) were considerated to find out that only 70% of students enrolled in seventh semester had taken the nutrition subject. Regarding the qualitative method, 10 students proposed that nutrition must be included as a compulsory subject. Results: There was a study focused on the nursing major programs from mexican universities, in which 34 was the number of programs reviewed. 28 universities have already included nutrition topic in their programs and 6 universities have not considered this matter in their programs yet. According to the results from the qualitative research, nutrition must be considered as an essential subject on the programs. Discussion: As a result of a quantitative and qualitative research, it is important to take into account, in the next evaluation of the subject’s curriculum, the opportunity to reincorporate the nutrition topic in basic semesters, and emphasize this point on all the study programs. Conclusion: In an effort to improve the topics related to nutrition and health care, it is very important to reorganize and focus on study plans at Iztacala University.Introducción: México tiene algunas regiones con hambre y desnutrición. También la producción en investigación clínica en México se debe incrementar. El Plan de Estudios de la Licenciatura en Enfermería de la Facultad de Estudios Superiores Iztacala de la Universidad Nacional Autónoma de México (2006) sí contempla el estudio de la Nutrición pero de manera fraccionada en diferentes módulos. Hemos observado que las y los estudiantes no han integrado todos los aspectos fundamentales de Nutrición. El tiempo empleado para abordar la temática teórica básica sobre Nutrición es de 56 horas con 50 minutos. Como optativa de “Nutrición y Salud” se imparten 80 horas. El primer inconveniente es que la optativa la pueden llevar hasta el 4° semestre; el segundo, es que hay un déficit de 23 horas de trabajo en el aula, si restamos las horas asignadas al módulo optativo con respecto a las horas de trabajo en los módulos obligatorios. Si México tiene problemas de nutrición, necesitamos contar con personal preparado en el tema. Vemos que no estamos aportándoles suficientemente estas herramientas, por lo que es necesario que no se estudie en forma de materia optativa, porque no todos los estudiantes la van a cursar. Material y Método: Es una investigación evaluativa cuanti-cualitativa. La parte cuantitativa empleó el nivel de escala nominal que permitió clasificar los 34 programas revisados de Instituciones de Educación Superior que imparten la Licenciatura en Enfermería en México. Se tomaron en cuenta los resultados de 2 investigaciones realizadas por estudiantes que encontraron que sólo el 70% de la matrícula de séptimo semestre han llevado Nutrición. En la parte cualitativa, 10 estudiantes sugirieron que Nutrición fuera un módulo obligatorio. Resultados: 28 Programas de los 34 revisados de Universidades de México SÍ tienen especificado en su Plan de Estudios el abordaje de Nutrición. Mientras que 6 Programas de los 34 revisados NO tienen especificado en su Plan de Estudios el abordaje de Nutrición. Los resultados cualitativos fueron constantes en cuanto a que “la optativa de Nutrición debería pasar a módulo obligatorio”. Discusión: Hay un peso cuantitativo y cualitativo que se pronuncia hacia revisar en una próxima Evaluación Curricular, la pertinencia de reincorporar en los primeros semestres obligatorios la temática de Nutrición de un manera más explícita en nuestro Plan de Estudios. Conclusión: Hay que reorganizar los contenidos programáticos en materia de Nutrición y Salud dentro de nuestro Plan de Estudios

Modelling wave interaction with deformable structures based on a multi-region approach within OpenFOAM

© 2017 by the International Society of Offshore and Polar Engineers (ISOPE). This paper presents the development of a multi-region computational fluid-structure dynamics (CFSD) method which is integrated in our virtual wave structure interaction solver wsiFoam, based on the open-source OpenFOAM library, in order to account for the hydro-elastic effects produced by violent wave impacts against deformable bodies. This strategy relies entirely on the finite volume method (FVM) and does not require any third-party solvers, which renders it suitable for efficient parallel computing. We validate this novel approach against previous experimental and numerical results corresponding to a dam break of water impacting on a highly deformable plate as well as a flexible wedge entering water at a constant speed. In general, our preliminary results agree qualitatively well with previous data whilst the performance of parallel implementation evidences the potential of this method to be used in future high performing computing (HPC) applications

Olfactory Attraction of the Larval Parasitoid, Hyposoter horticola, to Plants Infested with Eggs of the Host Butterfly, Melitaea cinxia

Parasitoids locate inconspicuous hosts in a heterogeneous habitat using plant volatiles, some of which are induced by the hosts. Hyposoter horticola Gravenhost (Hymenoptera: Ichneumonidae) is a parasitoid of the Glanville fritillary butterfly Melitaea cinxia L. (Lepidoptera: Nymphalidae). Melitaea cinxia lays eggs in clusters on leaves of Plantago lanceolata L. (Lamiales: Plantaginaceae) and Veronica spicata L. (Lamiales: Plantaginaceae). The parasitoid oviposits into host larvae that have not yet hatched from the egg. Thus, though H. horticola is a parasitoid of Melitaea cinxia larvae, it must find host eggs on plants that have not been fed on by the larvae. Using a Y-tube olfactometer, the response of H. horticola to odors of Melitaea cinxia and extracts of the attacked plant species were tested. Three week-old eggs (near hatching) were attractive to young H. horticola, but one week-old eggs were attractive only to old or experienced H. horticola. Melitaea cinxia larvae were not attractive. A water extract of P. lanceolata was attractive, but ethanol or hexane extracts were not. None of the extracts of V. spicata were attractive. Leaves of V. spicata were attractive only if harboring eggs, but P. lanceolata leaves with eggs were not. Free flying H. horticola in a large outdoor enclosure were presented with host and plant cues. As in the olfactometer, V. spicata was attractive only when eggs were on it, and P. lanceolata was somewhat attractive with or without eggs. This study shows for the first time that a parasitoid of larvae uses egg volatiles or oviposition-induced plant volatiles, to find host larvae, and that Melitaea cinxia eggs or traces of oviposition induce the production of these volatiles by the plant. Based on the results, and given the natural distribution of the plants and M. cinxia eggs, parasitism of Melitaea cinxia eggs on P. lanceolata would be expected to be low. Instead, under natural conditions, a fraction of the eggs in virtually all egg clusters are parasitized on both plant species. The mismatch between the experimental results and the natural pattern of host-parasitoid interactions is discussed in terms of the expected coupling foraging cues with foraging success

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Fe d'errates disponible a: http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest