Meltdose Tacrolimus Pharmacokinetics

Background Nonadherence to immunosuppressive therapy contributes to the loss of grafts. One of the problem is the fractioning of immunosuppressive dose. In fact, it was demonstrated that a single daily dose (QD) is associated with an increased adherence to therapy compared with twice daily dosing (BID). Tacrolimus (TAC), calcineurin inhibitor, is one of immunosuppression pillar in organ transplantation and its action is strongly correlated with blood concentration and therefore the therapeutic drug monitoring is recommended in the guidelines. However, one of the critical points of TAC is the poor and variable bioavailability that influences immunosuppression, and is also responsible for adverse effects. Methods MeltDose\uae Technology is a new technology to improve efficacy and/or reduce side effects. This new technology applied to TAC (Envarsus\uae or LCP-TAC) has achieved 4 main objectives: (1) improved bioavailability, (2) reduced dose fractioning to one tablet per day, (3) limited variability concentrations of TAC, and (4) lower doses of TAC will be administered. Results We analyzed the pharmacokinetic profile, efficacy, and security of Envarsus\uae

Therapeutic Drug Monitoring of Micophenolate Mofetil in Cardiac Transplant Patients by Limited Sampling Strategy: An Update

In the last few years, much progress in avoiding acute and chronic rejection in transplanted patients has been made by introducing new and more effective drugs with different formulations and combinations, and fewer side effects. Standardized protocols have been proposed for different organs, but individualized therapy based on immunosuppressive therapy blood monitoring is necessary because of pharmacological interaction, new generic drug introductions, and different absorptions and biodistributions. In specific mycophenolate mofetil dosing through mycophenolic acid (MPA), therapeutic drug monitoring has demonstrated minimal risk of organ transplant rejection. Even if the MPA area under the 12 h concentration–time curve is more accurate than MPA levels, it appears to be resource consuming and clinically impractical because of the need for numerous blood samples. Limited sampling strategy (LLS) has been proposed to overcome this problem. In heart-transplanted patients, MPA LSS is useful in guiding clinical management and dosing. The purpose of this chapter is to describe the state of the art of MPA LSS employment in heart transplantation and to perform an update of the scientific literature

Steroid-free and steroid withdrawal protocols in heart transplantation: the review of literature.

Abstract Corticosteroids (CSs) are still the mainstay of induction, rescue, and maintenance in heart transplantation (HTx). However, their use is associated with significant and well-documented side effects usually related to the dose administered and the duration of therapy. Moreover, CSs interfere with the recipient's quality of life and with the active process of graft tolerance. Physicians have been exploring ways to avoid or reduce CSs in association with other immunosuppressive drugs, minimizing side effects and costs. The regimens are classified as steroid-free or steroid withdrawal protocols. The studies analyzed in this review come to similar conclusions as benefits and adverse consequences: steroid-free protocols should be advisable and mandatory in pediatric patients, insulin-dependent diabetes mellitus (IDDM), presence of infection, familial metabolic disorders/obesity, severe osteoporosis, and in the elderly. On the other hand, steroid withdrawal can be successfully achieved in 50-80%, with late better than early withdrawal, no increase in rejection-related mortality, no adverse impact on survival, and probably a better quality of live. Safety and efficacy can certainly be improved by an individualized approach to the transplant recipient

Perturbative Approach to the Gravitational Lensing by a Non-spherically Distorted Compact Object

We investigate the gravitational lens effect caused by a non-spherically distorted compact object. The non-spherical property of the gravitational potential is modeled by a quadrupole moment. Under the assumption that the quadrupole contribution is small, we solve perturbatively the lens equation and obtain the image positions and the amplification factors. We show that the separation angle of two major images is only slightly changed by the existence of the quadrupole contribution, whereas the difference of the amplification factors may be significantly modified. Our results indicate that even a tiny non-spherical distortion of the lens potential may cause significant amount of flux anomalies in the lensed images.Comment: 10 pages, version accepted for publication in PT

Mapping Ethiopia’s Ancient Spirituality and Amba Gishen: From Sacralisation to Desacralisation

Amba Gishen, a cross-shaped mountainous place in the Southern Wollo Zone of Ethiopia, has for centuries been the site of a royal medieval prison thanks to its geographical isolation on the top of an amba (flat-top mountain). The first African narrative source of the deposition of a relic at Amba Gishen is cited in one of the most sacred Christian manuscripts of Ethiopia, the Mäshafä Tefut (fifteenth century). The presence of a holy relic, the fragment of the True Cross brought here by emperor Zara Yacoq in 1446, changed the meaning of that space for the Ethiopian people. The shifting topographies, from Mountain of the Royal Family to Mount of Myrrh, metaphorically referring to the myrrh associated with the Passion of Christ, have given way to a devotional focus and function, making Amba Gishen one of the holiest places in the land. As a place and site of confinement, however, the space inspired distorted imagery of Abyssinia, as conveyed by Anglophone travel narratives. The scope of the present research is to illustrate the dynamics in determining the sacralisation of spaces by their topographical morphology. This is achieved through the (re-)appropriation of natural spaces from the Ethiopian Orthodox Tewahedo Church and through resisting the desacralisation featured in Western narratives

Diálogos sobre Educación Social.

La Educación Social viene teniendo un auge importante en Argentina, a partir de la creación de carreras en el nivel técnico superior. En la entrevista que sigue, realizada al Mgter. Eduardo Ribó, dialogamos sobre diversos tópicos, tales como: su encuentro con la Educación social, la creación de la primera tecnicatura universitaria en la Universidad Nacional de Cuyo de la Provincia de Mendoza, las tradiciones pedagógicas que nutren la formación, la especificidad del campo y sus diferencias con la Educación Popular, entre los más significativos.

Quasi-geometrical Optics Approximation in Gravitational Lensing

The gravitational lensing of gravitational waves should be treated in the wave optics instead of the geometrical optics when the wave length $\lambda$ of the gravitational waves is larger than the Schwarzschild radius of the lens mass $M$. The wave optics is based on the diffraction integral which represents the amplification of the wave amplitude by lensing. We study the asymptotic expansion of the diffraction integral in the powers of the wave length $\lambda$. The first term, arising from the short wavelength limit $\lambda \to 0$, corresponds to the geometrical optics limit. The second term, being of the order of $\lambda/M$, is the leading correction term arising from the diffraction effect. By analyzing this correction term, we find that (1) the lensing magnification $\mu$ is modified to $\mu ~(1+\delta)$, where $\delta$ is of the order of $(\lambda/M)^2$, and (2) if the lens has cuspy (or singular) density profile at the center $\rho(r) \propto r^{-\alpha}$ ($0 < \alpha \leq 2$), the diffracted image is formed at the lens center with the magnification $\mu \sim (\lambda/M)^{3-\alpha}$.Comment: 9 pages, 4 figures. Revised version accepted for publication in A&

Concepciones y tradiciones pedagógicas en la formación superior en Pedagogía/Educación Social en Argentina.

This article presents the work in progress of an exploratory research on the pedagogical traditions and conceptions found within the academic field of Social Pedagogy in Argentina, and the place the Latin American line of thought of Popular Education holds in it. For this purpose, we analyze two educational experiences in the cities of Mendoza and Buenos Aires. We look at and establish a dialogue with the educational practice of teachers regarding the contents and concepts they develop in the subjects they teach and we compare them with documentary sources. Using a qualitative approach, we adopted case study as the methodology for this research. We pose a series of hypotheses at the end aiming to further explore this discipline.Este artículo presenta un avance de investigación de carácter exploratorio sobre concepciones y tradiciones pedagógicas presentes en el campo académico de la Pedagogía Social en Argentina, así como el lugar de la Corriente Latinoamericana de Educación Popular en él. Para ello se analizan dos experiencias formativas con sede en las ciudades de Mendoza y de Buenos Aires. Miramos y dialogamos con la praxis educativa de docentes en relación con los contenidos y concepciones que desarrollan en sus asignaturas y las ponemos en juego con fuentes documentales. Desde una perspectiva cualitativa, se adoptó el estudio de casos como estrategia metodológica. Se finaliza planteando una serie de hipótesis para continuar indagando en esta disciplina. &nbsp