Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma

Background: The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL). Patients and methods: Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle. Results: The median age of the patients was 53 years (range 37–77). Histological subtypes were low-grade follicular lymphoma (n=22) and B-cell small lymphocytic lymphoma (n=4). Twenty-one (81%) had stage III/IV disease. The median number of previous lines of chemotherapy was two (range one to six). A total of 87 cycles of ISIS 3521 were administered. Twenty-three patients were assessable for response. Three patients achieved a partial response. No complete responses were observed. Ten patients had stable disease. Grade 3–4 toxicity was as follows: neutropenia (3.8%) and thrombocytopenia (26.9%). Conclusions: ISIS 3521 has demonstrated anti-tumour activity in patients with relapsed low-grade NHL. There may be a potential role for this agent in combination with conventional chemotherapy for advanced low-grade lymphoma, and further trials are warranted.

Blogs as virtual environments for teaching and learning in Higher Education

The transformation of the Information and Communication Technologies (ICT) into knowledge and learning technologies is increasingly becoming a matter of concern. Teaching settings associated with the use of blogs in Higher Education are presented in this paper, proceeding from an innovative learning experience of projects carried out by a group of professors between 2009 and 2013. Both, teachers and students who took part in the subjects that implemented the blog, considered it as helpful resource to create a virtual and learning-teaching environment due to the multiple potentialities it offers. Among some of these potentialities, some stand out: it makes easier the access to knowledge, promotes a more active and reflective learning, expands the social experience of learning, provides evidence about the students’ progress which helps to reorient the teaching-learning process, and encourages the critical judgment. Nevertheless, several problems related with the students’ participation and the teacher’s blog management have been identified.

Indicadores de sostenibilidad ambiental en el periurbano de la ciudad de Mar del Plata, Argentina

Los indicadores de sostenibilidad conforman herramientas útiles para la toma de decisiones. Las ciudades latinoamericanas, y especialmente las áreas de expansión sin planificación adecuada, enfrentan desafíos cada vez mayores para revertir problemáticas que amenazan su sostenibilidad. El presente trabajo evalúa de manera preliminar, la sostenibilidad ambiental del periurbano de Mar del Plata (Argentina) tomando como referencia algunos de los indicadores propuestos por el modelo del Banco Interamericano de Desarrollo en la Iniciativa Ciudades Emergentes y Sostenibles. Se construyó un índice sintético (Índice de Sostenibilidad Ambiental, ISA) que integra trece indicadores agrupados en ocho temas. Las situaciones más críticas (ISA: 0,45-0,558) se identifican fundamentalmente en zonas en las que se desarrollan actividades rurales y en las que se localizan asentamientos de carácter precario. El estudio realizado profundiza en el conocimiento de la dimensión ambiental de la sostenibilidad, enfatizando en el análisis de los contrastes internos del periurbano marplatense.

Lys(9) for Glu(9) substitution in glucagon-like peptide-1(7-36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9-36)amide and exendin (9-39)

The incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) has been deemed of considerable importance in the regulation of blood glucose. Its effects, mediated through the regulation of insulin, glucagon, and somatostatin, are glucose-dependent and contribute to the tight control of glucose levels. Much enthusiasm has been assigned to a possible role of GLP-1 in the treatment of type 2 diabetes. GLIP-l's action unfortunately is limited through enzymatic inactivation caused by dipeptidylpeptidase IV (DPP IV). It is now well established that modifying GLP-1 at the N-terminal amino acids, His(7) and Ala(8), can greatly improve resistance to this enzyme. Little research has assessed what effect Glu(9)-substitution has on GLP-1 activity and its degradation by DPP IV. Here, we report that the replacement of Glu(9) of GLP-1 with Lys dramatically increased resistance to DPP IV. This analogue, (Lys(9))GLP-1, exhibited a preserved GLP-1 receptor affinity, but the usual stimulatory effects of GLP-1 were completely eliminated, a trait duplicated by the other established GLP-1-antagonists, exendin (9-39) and GLP-1 (9-36)amide. We investigated the in vivo antagonistic actions of (Lys(9))GLP-1 in comparison with GLP-1(9-36)amide and exendin (9-39) and revealed that this novel analogue may serve as a functional antagonist of the GLP-1 receptor. (C) 2004 Elsevier Inc. All rights reserved.

Roche tomography of cataclysmic variables - IV. Star-spots and slingshot prominences on BV Cen

We present Roche tomograms of the G5-G8 IV/V secondary star in the long-period cataclysmic variable BV Cen reconstructed from Magellan Inamori Kyocera Echelle spectrograph echelle data taken on the Magellan Clay 6.5-m telescope. The tomograms show the presence of a number of large, cool star-spots on BV Cen for the first time. In particular, we find a large high-latitude spot which is deflected from the rotational axis in the same direction as seen on the K3-K5 IV/V secondary star in the cataclysmic variable AE Aqr. BV Cen also shows a similar relative paucity of spots at latitudes between 40° and 50° when compared with AE Aqr. Furthermore, we find evidence for an increased spot coverage around longitudes facing the white dwarf which supports models invoking star-spots at the L1 point to explain the low states observed in some cataclysmic variables. In total, we estimate that some 25 per cent of the Northern hemisphere of BV Cen is spotted. We also find evidence for a faint, narrow, transient emission line with characteristics reminiscent of the peculiar low-velocity emission features observed in some outbursting dwarf novae. We interpret this feature as a slingshot prominence from the secondary star and derive a maximum source size of 75000 km and a minimum altitude of 160000 km above the orbital plane for the prominence. The entropy landscape technique was applied to determine the system parameters of BV Cen. We find M1 = 1.18 +/-0.280.16Msolar and M2 = 1.05 +/-0.230.14Msolar and an orbital inclination of i = 53° +/- 4° at an optimal systemic velocity of ? = -22.3 km s-1. Finally, we also report on the previously unknown binarity of the G5IV star HD 220492.

Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes

Dipeptidyl peptidase IV (DPP IV) is a widely distributed physiological enzyme that can be found solubilized in blood, or membrane-anchored in tissues. DPP IV and related dipeptidase enzymes cleave a wide range of physiological peptides and have been associated with several disease processes including Crohn's disease, chronic liver disease, osteoporosis, multiple sclerosis, eating disorders, rheumatoid arthritis, cancer, and of direct relevance to this review, type 2 diabetes. Here, we place particular emphasis on two peptide substrates of DPP IV with insulin-releasing and antidiabetic actions namely, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The rationale for inhibiting DPP IV activity in type 2 diabetes is that it decreases peptide cleavage and thereby enhances endogenous incretin hormone activity. A multitude of novel DPP IV inhibitor compounds have now been developed and tested. Here we examine the information available on DPP IV and related enzymes, review recent preclinical and clinical data for DPP IV inhibitors, and assess their clinical significance.

Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: Nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1

Dipeptidyl peptidase IV (DPP IV) is the primary inactivator of glucoregulatory incretin hormones. This has lead to development of DPP IV inhibitors as a new class of agents for the treatment of type 2 diabetes. Recent reports indicate that other antidiabetic drugs, such as metformin, may also have inhibitory effects on DPP IV activity. In this investigation we show that high concentrations of several antidiabetic drug classes, namely thiazolidinediones, sulphonylureas, meglitinides and morphilinoguanides can inhibit DPP IV The strongest inhibitor nateglinide, the insulin-releasing meglitinide was effective at low therapeutically relevant concentrations as low as 25 mu mol/l. Nateglinide also prevented the degradation of glucagon-like peptide-1 (GLP-1) by DPP IV in a time and concentration-dependent manner. In vitro nateglinide and GLP-1 effects on insulin release were additive. In vivo nateglinide improved the glucose-lowering and insulin-releasing activity of GLP-1 in obese-diabetic ob/ob mice. This was accompanied by significantly enhanced circulating concentrations of active GLP-1(7-36)amide and lower levels of DPP IV activity. Nateglinide similarly benefited the glucose and insulin responses to feeding in ob/ob mice and such actions were abolished by coadministration of exendin(9-39) and (Pro(3))GIP to block incretin hormone action. These data indicate that the use of nateglinide as a prandial insulin-releasing agent may partly rely on inhibition of GLP-1 degradation as well as beta-cell K-ATP channel inhibition. (C) 2007 Elsevier B.V. All rights reserved.

La música práctica en san Agustín: "vestigium" y "signum"

En distintos momentos de su producción intelectual, Agustín se refirió al asunto de la música. En este artículo mostraremos que Agustín uso dos esquemas conceptuales distintos para describir el fenómeno de la música práctica en su relación con el mundo espiritual, el esquema de las Artes Liberales y el de la teoría del signo, y que en virtud de ello la música sería concebida de dos modos diferentes: como vestigium y como signum del mundo espiritual, respectivamente. Al final del artículo analizaremos la diferencia entre las dos concepciones considerando tres elementos: la naturaleza de la relación entre mundo material y espiritual, el contenido espiritual al que remite y la noción de belleza que implica.

El Ser como mediación. Ontología, estética y analogía en la interpretación del ‘esse’ tomasiano de H. U. von Balthasar

El presente artículo expone los fundamentos de la interpretación que del esse tomasiano lleva a cabo Hans Urs von Balthasar. En ella ofrece von Balthasar, a partir de una interpretación en la línea de Siewerth, y como tal novedosa para la historia de la crítica, las directrices fundamentales de su propio pensamiento filosóficoteológico, cuyo eje lo constituye la diferencia entre esse y Dios como modelo para una hermenéutica no monista de la realidad. Con todo, la propuesta no está exenta de algunas dificultades y arbitrariedades que, desde una perspectiva crítica y aconfesional (por la que aquí se opta), conviene ineludiblemente subrayar.

El concepto de “posesión común originaria” en la doctrina kantiana de la propiedad

Los primeros parágrafos de la sección “El derecho privado” (§§ 1-17) de la Doctrina del derecho de Kant incluyen el conjunto de los elementos sistemáticos que conciernen a la justificación de los derechos relativos a la propiedad. El propósito central de este trabajo es analizar la función sistemática del concepto de “posesión común originaria” en la doctrina kantiana de la propiedad, con especial interés en el sentido novedoso que adquiere ese concepto —que pertenecía a la tradición del derecho natural— en su reformulación como un “concepto práctico de la razón, que contiene a priori, el principio según el cual tan solo los hombres pueden hacer uso del lugar sobre la tierra siguiendo leyes jurídicas” (RL, 262).