Controlled release kinetics of p-aminosalicylic acid from biodegradable crosslinked polyesters for enhanced anti-mycobacterial activity

Unlike conventional polymeric drug delivery systems, where drugs are entrapped in polymers, this study focuses on the incorporation of the drug into the polymer backbone to achieve higher loading and sustained release. Crosslinked, biodegradable, xylitol based polyesters have been synthesized in this study. The bioactive drug moiety, p-aminosalicylic acid (PAS), was incorporated in xylitol based polyesters to impart its anti-mycobacterial activity. To understand the influence of the monomer chemistry on the incorporation of PAS and its subsequent release from the polymer, different diacids have been used. Controlled release profiles of the drug from these polyesters were studied under normal physiological conditions. The degradation of the polyesters varied from 48% to 76% and the release of PAS ranged from 54% to 65% of its initial loading in 7 days. A new model was developed to explain the release kinetics of PAS from the polymer that accounted for the polymer degradation and drug concentration. The thermal, mechanical, drug release and cytocompatibility properties of the polymers indicate their suitability in biomedical applications. The released products from these polymers were observed to be pharmacologically active against Mycobacteria. The high drug loading and sustained release also ensured enhanced efficacy. These polymers form biocompatible, biodegradable polyesters where the sustained release of PAS may be tailored for potential treatment of mycobacterial infections. Statement of significance In the present work, we report on novel polyesters with p-aminosalicylic acid (PAS) incorporated in the polymer backbone. The current work aims to achieve controlled release of PAS and ensures the delivered PAS is stable and pharmacologically active. The novelty of this work primarily involves the synthetic chemistry of polymerization and detailed analysis and efficacy of active PAS delivery. A new kinetic model has been developed to explain the PAS release profiles. These polymers are biodegradable, cytocompatible and anti-mycobacterial in nature. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Physical insights into salicylic acid release from poly(anhydrides)

Salicylic acid (SA) based biodegradable polyanhydrides (PAHs) are of great interest for drug delivery in a variety of diseases and disorders owing to the multi-utility of SA. There is a need for the design of SA-based PAHs for tunable drug release, optimized for the treatment of different diseases. In this study, we devised a simple strategy for tuning the release properties and erosion kinetics of a family of PAHs. PAHs incorporating SA were derived from related aliphatic diacids, varying only in the chain length, and prepared by simple melt condensation polymerization. Upon hydrolysis induced erosion, the polymer degrades into cytocompatible products, including the incorporated bioactive SA and diacid. The degradation follows first order kinetics with the rate constant varying by nearly 25 times between the PAH obtained with adipic acid and that with dodecanedioic acid. The release profiles have been tailored from 100% to 50% SA release in 7 days across the different PAHs. The release rate constants of these semi-crystalline, surface eroding PAHs decreased almost linearly with an increase in the diacid chain length, and varied by nearly 40 times between adipic acid and dodecanedioic acid PAH. The degradation products with SA concentration in the range of 30-350 ppm were used to assess cytocompatibility and showed no cytotoxicity to HeLa cells. This particular strategy is expected to (a) enable synthesis of application specific PAHs with tunable erosion and release profiles; (b) encompass a large number of drugs that may be incorporated into the PAH matrix. Such a strategy can potentially be extended to the controlled release of other drugs that may be incorporated into the PAH backbone and has important implications for the rational design of drug eluting bioactive polymers.

Stalking influenza by vaccination with pre-fusion headless HA mini-stem

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies indudced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.

A new model for the energy release rate of fibre/matrix interfacial fracture

On the basis of the well-known shear-lag analysis of fibre/matrix interface stresses and the assumption of identical axial strains in the fibre and matrix, a new model for predicting the energy release rate of interfacial fracture of the fibre pull-out test model is attempted. The expressions for stresses in the fibre, matrix and interface are derived. The formula for interfacial debonding energy release rate is given. Numerical calculations are conducted and the results obtained are compared with those of the existing models.

Effects of pre-treatment and plasma enhancement on chemical vapor deposition of carbon nanotubes from ultra-thin catalyst films

We report a detailed study of surface-bound chemical vapor deposition of carbon nanotubes and nanofibers from evaporated transition metal catalysts exposed to ammonia diluted acetylene. We show that a reduction of the Fe/Co catalyst film thickness below 3 nm results into a transition from large diameter (> 40 nm), bamboo-like nanofibers to small diameter (similar to 5 nm) multi-walled carbon nanotubes. The nanostructuring of ultrathin catalyst films critically depends on the gas atmosphere, with the resulting island distribution initiating the carbon nucleation. Compared to purely thermal chemical vapor deposition, we find that, for small diameter nanotube growth, DC plasma assistance is detrimental to graphitization and sample homogeneity and cannot prevent an early catalyst poisoning. (c) 2006 Elsevier B.V. All rights reserved.

Load-Unload Response Ratio and Accelerating Moment/Energy Release Critical Region Scaling and Earthquake Prediction

The main idea of the Load-Unload Response Ratio (LURR) is that when a system is stable, its response to loading corresponds to its response to unloading, whereas when the system is approaching an unstable state, the response to loading and unloading becomes quite different. High LURR values and observations of Accelerating Moment/Energy Release (AMR/AER) prior to large earthquakes have led different research groups to suggest intermediate-term earthquake prediction is possible and imply that the LURR and AMR/AER observations may have a similar physical origin. To study this possibility, we conducted a retrospective examination of several Australian and Chinese earthquakes with magnitudes ranging from 5.0 to 7.9, including Australia's deadly Newcastle earthquake and the devastating Tangshan earthquake. Both LURR values and best-fit power-law time-to-failure functions were computed using data within a range of distances from the epicenter. Like the best-fit power-law fits in AMR/AER, the LURR value was optimal using data within a certain epicentral distance implying a critical region for LURR. Furthermore, LURR critical region size scales with mainshock magnitude and is similar to the AMR/AER critical region size. These results suggest a common physical origin for both the AMR/AER and LURR observations. Further research may provide clues that yield an understanding of this mechanism and help lead to a solid foundation for intermediate-term earthquake prediction.

Estudio de pre-factibilidad de una propuesta de desarrollo ganadero para la finca "El Garabato" en Tola, Rivas

En el presente trabajo se evaluó EX-ante la factibilidad técnica y financiera de una propuesta de desarrollo ganadero para la finca "El Garabato" planteada por los socios de la Cooperativa Ezequiel N24 en el Municipio de Tola, Departamento de Rivas. Para ello se realizó un diagnóstico general de la finca, donde se determinó los recursos disponibles y las características propias del sistema productivo, basados en esto se estimaron los diferentes coeficientes técnicos así como las posibles fuentes de ingresos y egresos, permitiendo realizar las proyecciones del hato así como las proyecciones financieras, Dentro de los aspectos técnicos se determinó la composición de las pasturas donde el 69% de los pastos son naturalizados, el 23% son pastos mejorados y el 8% está conformado por pastos naturales. Los canales de comercialización en la zona del proyecto para la leche están representados por los manteros, el Proyecto Juan Agustín Guillén de la Tienda Campesina y el Centro de Acopio de La Selecta. En el caso de la carne por los intermediarios (matarifes) y productores dedicados a la crianza y engorde de novillos. Al considerar las inversiones en pastura que conlleva la propuesta, la distribución de pastos varia, ocupando los pastos mejorados el 41%, el 3% por pastos naturales y el 56% corresponden a pastos naturalizados. A la par de esto el área ganadera se incrementa en 64 mz. como consecuencia de la reducción del área agricola por la misma cantidad de mz. Las disponibilidades de pastos se ven mejoradas por las inversiones, disminuyendo el déficit de alimento a partir del segundo año. El uso de la Caña de Azúcar más urea, durante el verano permitirá mejorar la oferta de alimento para esta época, resultando menores pérdidas en la producción. Como efecto de la propuesta se producirá un incremento promedio anual de 7.18% del hato total, este incremento se da esperando que los índices de mortalidad de adultos y terneros disminuyan de un 4 al. 2% y de 14 al 7% respectivamente y que la tasa de descarte de vacas se mantenga en 12%1 considerando que la finca mantenga un 67% en tasa de natalidad. Al estructurar los gastos se encontró que en el año base los gastos de mano de obra representan el 71%, la suplementación el 8%, los gastos en manejo fueron de 8%, impuestos 7%, mantenimiento de equipo e infraestructura de 4% y gastos varios de 1%, con el proyecto esta estructura de gastos se ve un poco alterada al disminuir los gastos por mano de obra a un 63% e incrementarse los gastos por suplementacion y gastos varios a 12% y 6% respectivamente, el resto de los gastos presentan leves modificaciones. En los ingresos del año base la producción de leche representa el 46%, la producción de carne el 53% y el 1% corresponde a otros ingresos. Con el proyecto el aporte en los ingresos por producción de leche asciende a 62% y en producción de carne es de 34%, en otros ingresos representa el 4% al finalizar el sexto año. De las inversiones que se realizaran el 60% ésta destinado para pastos y el 40% corresponde a inversiones en infraestructura. El monto total de la inversión asciende a C$96,905.70 de los cuales el 71% será solicitado en préstamo y el restante 29% será asumido por la Cooperativa. Del análisis financiero resultó que la propuesta de los socios con uso de financiamiento para las inversiones a una tasa de interés del 12.5% presenta un VAN de C$41996.65 y una TIR de 15.16%. En cambió la realización de la propuesta con recursos propios presentó resultados superiores al anterior siendo el VAN de C$18,506.01 y una TIR de 18.01%•. Considerando estos resultados la propuesta es rentable, pero debido al déficit de efectivo que se presenta en los primeros años podría alterar la realización de las inversiones, ésta situación puede compensarse haciendo uso de otros recursos de la Cooperativa.

Caracterización de la curva de lactancia y el comportamiento reproductivo de vaquillas Holstein bajo implementación de medidas de manejo en el período pre-parto

Con el objetivo de caracterizar la curva de lactancia y evaluar el comportamiento reproductivo se analizaron los registros mensuales (N=10) de vaquillas Holstein bajo la implementación y falta de implementación de medidas de manejo pre-parto en la Empresa Agropecuaria “San Ignacio” Mateare, Nicaragua. Para caracterizar la curva de lactancia, se utilizó el modelo de Wood (1967) de forma linealizada Ln Yx = Lna + b Lnx - ex , donde Yx es la producción diaria en el período x, a representa la producción inicial, b el ascenso al pico, c el descenso de producción, a partir del mismo se generaron la Persistencia (S), Rendimiento al pico (RP), Tiempo al pico (TP), también se evaluó el Intervalo parto - concepción (IPC) y el Número de servicios por concepción (NSPC) . Al presentar problemas reproductivos la proporción de curvas atípicas encontradas en este Trabajo fue de 40%. Al analizar la curva de lactancia del grupo experimental se observa un a= 11.00212 kg, b = 0.083528 kg, e = 0.00407148 kg, RP = 12.790 kg, TP = 29.54 días, S = 6.126. El grupo testigo presenta un a = 6.4384 kg, b = 0.193048 kg, e = 0.00466974 kg, RP = 9.49 kg, TP = 34.32 días, S = 6.421. En el análisis de varianza se encontró que el RP tiene diferencia significativa entre los tratamientos a un nivel de significancia (P<0.05). Los parámetros reproductivos IPC y NSPC para el grupo experimental fueron de 243.6 días y 3 servicios respectivamente, el grupo testigo presentó un IPC = 221.8 días y NSPC = 3.6 servicios .

A comparison of winter pre-heating requirements for natural displacement and natural mixing ventilation

In winter, natural ventilation can be achieved either through mixing ventilation or upward displacement ventilation (P.F. Linden, The fluid mechanics of natural ventilation, Annual Review of Fluid Mechanics 31 (1999) pp. 201-238). We show there is a significant energy saving possible by using mixing ventilation, in the case that the internal heat gains are significant, and illustrate these savings using an idealized model, which predicts that with internal heat gains of order 0.1 kW per person, mixing ventilation uses of a fraction of order 0.2-0.4 of the heat load of displacement ventilation assuming a well-insulated building. We then describe a strategy for such mixing natural ventilation in an atrium style building in which the rooms surrounding the atrium are able to vent directly to the exterior and also through the atrium to the exterior. The results are motivated by the desire to reduce the energy burden in large public buildings such as hospitals, schools or office buildings centred on atria. We illustrate a strategy for the natural mixing ventilation in order that the rooms surrounding the atrium receive both pre-heated but also sufficiently fresh air, while the central atrium zone remains warm. We test the principles with some laboratory experiments in which a model air chamber is ventilated using both mixing and displacement ventilation, and compare the energy loads in each case. We conclude with a discussion of the potential applications of the approach within the context of open plan atria type office buildings.