Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide

Glucose dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with therapeutic potential for type 2 diabetes due to its insulin-releasing and antihyperglycaemic actions. However, development of GIP-based therapies is limited by N-terminal degradation by DPP IV resulting in a very short circulating half-life. Numerous GIP analogues have now been generated exhibiting DPP IV resistance and extended bioactivity profiles. In this study, we report a direct comparison of the long-term antidiabetic actions of three such GIP molecules, N-AcGIP, GIP(LyS(37)PAL) and N-AcGIP(LyS(37)PAL) in obese diabetic (ob/ob) mice. An extended duration of action of each GIP analogue was demonstrated prior to examining the effects of once daily injections (25 nmol kg(-1) body weight) over a 14-day period. Administration of either N-AcGIP, GIP(LyS(37)PAL) or N-AcGIP(LyS37PAL) significantly decreased non-fasting plasma glucose and improved glucose tolerance compared to saline treated controls. All three analogues significantly enhanced glucose and nutrient-induced insulin release, and improved insulin sensitivity. The metabolic and insulin secretory responses to native GIP were also enhanced in 14-day analogue treated mice, revealing no evidence of GIP-receptor desensitization. These effects were accompanied by significantly enhanced pancreatic insulin following N-AcGIP(Lys(37)PAL) and increased islet number and islet size in all three groups. Body weight, food intake and circulating glucagon were unchanged. These data demonstrate the therapeutic potential of once daily injection of enzyme resistant GIP analogues and indicate that N-AcGIP is equally as effective as related palmitate derivatised analogues of GIP. (c) 2006 Elsevier Inc. All rights reserved.

The presence of the Aragonese language in the magazine "El Ebro" (1917-1936)

El Ebro (1917-1936) was a magazine published in Barcelona by Aragonese emigrants at the beginning of the 20th century. It was the first experience of coexistence of different dialectal varieties of the Aragonese language in the same media. El Ebro was an experience that has gone virtually unnoticed in the recent history of one of the most minority languages, and with minor media presence, of Western Europe. In its pages El Ebro mixed dialects spoken in different regions of linguistic Aragonese area together with transcripts of medieval documents. At the same time, this newspaper raised debates about the language issue that they were truncated due to disappearance of the publication and the lack of theoretical realization

Press, politic, and social order in Buenos Aires during the 1850s

The paper examines some reflections and discussions about the role and nature of the press that took place in Buenos Aires during the 1850s, referring to the difficulties involved in congenial freedom and order. This was caused by the fact that the press was considered a pillar of republican and civilized societies, but also an agent capable of corroding the social and political order.

Rubén Darío's new unpublished and unknown documents: on La "Isla de Oro", the "Poema del Otoño" and the years of "Mundial"

This article studies and reproduces a group of documents that includes some hand-written and typed texts most likely authored by Rubén Darío, along with others where Darío’s authorship can be easily contested. These documents seem to have originated during the years of Mundial Magazine (1912-1914), and besides the interest for their probably unpublished nature, they also show the cooperation between Darío and his collaborators in the preparation of his original manuscripts right before being sent to the publishers.

El pensamiento político de José Ortega y Gasset

Las siguientes páginas versan sobre el pensamiento político de José Ortega y Gasset, mostrando –entre otras cosas– su evolución desde lo que sería el neokantismo de mocedad de Ortega hasta su madurez. Para cumplir con nuestro objetivo se ha recurrido a los escritos de Ortega, así como a autores especializados en su pensamiento. La historia del pensamiento político contemporáneo tiene una deuda contraída con Ortega que desde sus primeros escritos manifestó un claro interés por la política concebida ésta como pedagogía social y cuyo fin debía ser, en primer lugar, solventar los problemas de la vida pública nacional. El pensamiento político de Ortega se define asimismo por la defensa de los valores liberales (liberalismo) compatibles con los principios socialistas (socialismo), que en una primera época de juventud idealista neokantiana adquieren un significado eminentemente cultural aunque también moral, que no se perderá completamente en su madurez o época de plenitud vital, aunque bien es verdad que aquellos dos conceptos (liberalismo y socialismo), así como también su idea de democracia, irán respondiendo a la evolución de su pensamiento.

The portrait of the first poster artists of Spanish cinema: From the genre scene to the realistic portrait

The article, which is part of a more detailed piece of work, aims to highlight the use of the portrait on the film posters of the first Spanish poster artists before the Star-System was introduced in Spain. For this it is posed the evolution that occurs in the representation of the characters in the film poster from the second decade to the beginning of the thirties in the twentieth century, a historical period of profound influences of the artistic and advertising vanguards in our poster artists´ work. However, in the late twenties moving from the simple inclusion of the scene based on the picture of a film, to the chromatic and realistic representation of the star´s face. These were the years when the influence of the major North American studios began to show in Spain. Nevertheless, it highlights their technical and compositional freedom and their influence on subsequent poster artists, as many of them will integrate the portraits and settings on their posters, following the guidelines of the major studios or the independent ones. But without forgetting their own personal way of painting the film stars’ faces on their posters.