Grado de Satisfacción de los médicos, que son usuarios del Dpto. de Análisis Clínicos del Instituto de Investigaciones en Ciencias de la Salud (UNA) durante el año 2010 / Degree of satisfaction of physicians using the services of the Department of Clinical Analysis of the Health Sciences Research Institute (UNA) during 2010

El Instituto de Investigaciones en Ciencias de la Salud depende de la Universidad Nacional de Asunción, es un establecimiento público con laboratorios que brinda a la comunidad servicios de rutina y especializados que satisfacen requisitos de calidad; los cuales son accesibles, seguros, confiables y confidenciales. La satisfacción del usuario médico es un indicador reconocido de calidad asistencial, es por ello que el Instituto ha elaborado un estudio de opinión con el objetivo de conocer el grado de satisfacción de los profesionales médicos con respecto al Departamento de Análisis Clínicos (AC) mediante una encuesta dirigida a los mismos y mejorar si fuese necesario el servicio brindado por el laboratorio. Se realizó un estudio observacional descriptivo de corte transverso, la selección de los médicos fue a partir de los pedidos de análisis que llegaron al Dpto. de AC durante el año 2010. Se utilizó como instrumento de medición una encuesta con 11 ítems y sugerencias, relacionadas con la satisfacción de los usuarios médicos. Los pedidos médicos solicitados fueron 68.9 % del Hospital de Clínicas y el 31.1% correspondieron a Centros de Salud del Ministerio de Salud Pública, Hospital de Policía, Hospital de las Fuerzas Armadas, entre otros. Del estudio de opinión se concluye que el grado de satisfacción de los médicos con respecto al Departamento de AC es bueno pero que es necesario insistir en aspectos de comunicación y colaboración entre los servicios clínicos y los laboratorios para que la mejora en el trabajo participativo de estos estamentos sea más fructífera.

Correlación entre el aclaramiento de creatinina y la fórmula MDRD-4 en la estimación del filtrado glomerular / Correlation between creatinine clearance and MDRD-4 formula in the estimation of the glomerular filtrate

La creatinina sérica y el aclaramiento de creatinina (ClCr) son los métodos mayoritariamente empleados como medida del Filtrado Glomerular (FG), procedimientos no exentos de problemas tanto preanalíticos como analíticos. En los últimos años se viene proponiendo la utilización de fórmulas predictivas del FG. Buscamos comprobar la correlación entre el método analítico y el estimado por la ecuación de MDRD-4. Se estudiaron retrospectivamente 89 pacientes, con un promedio de 51 ± 14 años; 31 varones y 58 mujeres. Aunque la media del FG estimada por la fórmula MDRD-4 fue de 66 ± 28.83 ml/min y la obtenida con la depuración de creatinina fue de 62±30.22ml/min. (p<0.05); se encontró una correlación positiva entre ambos métodos (r=0,796; p=0,001). En nuestra población la ecuación MDRD-4 presenta una buena equivalencia con el ClCr y podría utilizarse para evaluar la función renal en pacientes con riesgo de desarrollar enfermedad renal crónica (ERC).

Serum creatinine and creatinine clearance (CrCl) methods are mostly used as measures of glomerular filtration (GF) and are procedures that are not exempt from both pre-analytical and analytical problems. In recent years, it has been proposed the use of predictive formulas of GF. In this study, we sought to verify the correlation between the analytical method and the estimated by the MDRD-4 formula. Eighty nine patients were studied retrospectively, they had a mean age of 51±14 years and there were 31 males and 58 females. Though the mean GF estimated by the MRDR-4 formula was 66 ± 28.83 ml/min and the obtained by creatinine depuration was 62 ± 30.22ml/min. (p<0.05), a positive correlation between both methods was found (r=0.796; p=0.001). In our population, the MRDR-4 formula has a good equivalence with the CrCl and could be used to assess the renal function of patients at risk of developing chronic kidney disease (CKD).

Three generations of automatically designed robots.

The difficulties associated with designing, building, and controlling robots have led their development to a stasis: Applications are limited mostly to repetitive tasks with predefined behavior. Over the last few years we have been trying to address this challenge through an alternative approach: Rather than trying to control an existing machine or create a general-purpose robot, we propose that both the morphology and the controller should evolve at the same time. This process can lead to the automatic design of special-purpose mechanisms and controllers for specific short-term objectives. Here we provide a brief review of three generations of our recent research, which underlies the robots shown on the cover of this issue: Automatically designed static structures, automatically designed and manufactured dynamic electromechanical systems, and modular robots automatically designed through a generative DNA-like encoding.

A new role for cryptochrome in a Drosophila circadian oscillator.

Cryptochromes are flavin/pterin-containing proteins that are involved in circadian clock function in Drosophila and mice. In mice, the cryptochromes Cry1 and Cry2 are integral components of the circadian oscillator within the brain and contribute to circadian photoreception in the retina. In Drosophila, cryptochrome (CRY) acts as a photoreceptor that mediates light input to circadian oscillators in both brain and peripheral tissue. A Drosophila cry mutant, cryb, leaves circadian oscillator function intact in central circadian pacemaker neurons but renders peripheral circadian oscillators largely arrhythmic. Although this arrhythmicity could be caused by a loss of light entrainment, it is also consistent with a role for CRY in the oscillator. A peripheral oscillator drives circadian olfactory responses in Drosophila antennae. Here we show that CRY contributes to oscillator function and physiological output rhythms in the antenna during and after entrainment to light-dark cycles and after photic input is eliminated by entraining flies to temperature cycles. These results demonstrate a photoreceptor-independent role for CRY in the periphery and imply fundamental differences between central and peripheral oscillator mechanisms in Drosophila.

Novel derivatives of 2-pyridinemethylamine as selective, potent, and orally active agonists at 5-HT1A receptors.

The aim of this work was to improve the oral bioavailability of a recently discovered, novel structural class of 5-HT1A receptor agonists: aryl-{[4-(6-R-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1 -yl-metha none. Incorporation of a fluorine atom in the beta-position to the amino function in the side chain led to analogues that exhibited, in general, enhanced and long-lasting 5-HT1A agonist activity in rats after oral administration. Location of the fluorine atom at the C-4 position of the piperidine ring was the most favorable, and among the various substituents tested, the ability of the fluorine was unique in improving the oral activity of this family of ligands. Thus, the derivatives 39, 46, and 61 bound with higher affinity and selectivity to 5-HT1A receptors (versus dopaminergic D2 and adrenergic alpha1 receptors) and displayed more potent 5-HT1A agonist activity in vitro and in vivo than their C-4 desfluoro analogues. To examine the relationship between the conformation of the pharmacophore and the level of agonistic activity of this type of ligand, we synthesized a series of 3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-(H or CH3)-6-R-pyridin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl-+ ++methanone derivatives and found that the combination of a 5-methyl and a 6-methylamino substituent on the pyridine ring synergistically affected their 5-HT1A agonist properties. Thus, the 3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-6-methylamino-pyridin- 2-ylmethyl)-amino]-methyl}-piperidin-1-yl-methanone 40 behaved as a more potent 5-HT1A receptor agonist in vitro and in vivo than its 5-unsubstituted analogue 38. The antidepressant potential of the lead compounds 40, 45, and 54 was examined by means of the forced swimming test (FST) in rats. The results indicated that, after a single oral administration, these compounds inhibited immobility in the FST more potently and more extensively than the clinically used antidepressant imipramine. Thus, 40, 45, and 54 are potent, orally active 5-HT1A receptor agonists with marked antidepressant potential.

Design and synthesis of a series of 6-substituted-2-pyridinylmethylamine derivatives as novel, high-affinity, selective agonists at 5-HT1A receptors.

A search for novel, selective agonists with high intrinsic activity at the 5-HT1A subtype of serotonin (5-HT) receptors was undertaken. Mechanistic and thermodynamic considerations led to the design of 6-substituted-2-pyridinylmethylamine as a potential 5-HT1A pharmacophore. Various adducts derived from the 6-substituted-2-pyridinylmethylamine moiety were tested for their affinity at 5-HT1A, alpha1-adrenergic, and D2-dopaminergic receptors. Compounds with high affinity for 5-HT1A receptors (pKi >/= 8) were examined for agonist properties by measuring their ability to inhibit forskolin-stimulated cAMP production in HA7 cells (i.e., HeLa cells permanently transfected with the h5-HT1A receptor gene and expressing the h5-HT1A receptor protein). Several compounds of the type aryl¿4-[(6-substituted-pyridin-2-ylmethylamino)methyl]piperidin -1-yl¿ methanone had nanomolar affinity for 5-HT1A binding sites and were more than 500-fold selective with respect to alpha1 and D2 sites. Importantly, their 5-HT1A agonist properties were demonstrated in HA7 cells where they behaved as potent inhibitors of cAMP accumulation. In particular, (3, 4-dichlorophenyl)¿4-[(6-oxazol-5-ylpyridin-2-ylmethylamin o)methyl]pip eridin-1-yl¿methanone (70) and (3, 4-dichlorophenyl)¿4-[(6-azetidinopyridin-2-ylmethylamino)met hyl]piper idin-1-yl¿methanone (36) appeared to be more potent than, and at least as efficacious as, the prototypical 5-HT1A agonist (+/-)-8-OH-DPAT. SAR studies revealed that the pyridine nitrogen atom and the nature and the position of the substituents on the pyridine ring were critically involved in the ability of the compounds to recognize and activate 5-HT1A receptors. Structural modifications of the nonpharmacophoric part of the molecule showed, however, that the entire structure was required for affinity at 5-HT1A binding sites.

Evolutionary body building: adaptive physical designs for robots.

Creating artificial life forms through evolutionary robotics faces a "chicken and egg" problem: Learning to control a complex body is dominated by problems specific to its sensors and effectors, while building a body that is controllable assumes the pre-existence of a brain. The idea of coevolution of bodies and brains is becoming popular, but little work has been done in evolution of physical structure because of the lack of a general framework for doing it. Evolution of creatures in simulation has usually resulted in virtual entities that are not buildable, while embodied evolution in actual robotics is constrained by the slow pace of real time. The work we present takes a step in addressing the problem of body evolution by applying evolutionary techniques to the design of structures assembled out of elementary components that stick together. Evolution takes place in a simulator that computes forces and stresses and predicts stability of three-dimensional brick structures. The final printout of our program is a schematic assembly, which is then built physically. We demonstrate the functionality of this approach to robot body building with many evolved artifacts.