La Prehistoria que nos rodea y la falsificación del pasado

Comunicació presentada a la Sessió 10 : "Los tópicos en arquología. Reflexiones en torno a la mitificaciónLa visión que la sociedad adquiere de la Prehistoria no siempre procede de canales divulgativos asesorados por especialistas. Esa imagen colectiva se adquiere poco a poco de la información que se extrae de aspectos cotidianos como el cine, la literatura, la publicidad y de otras muchas facetas que nos rodean en nuestro día a día y que nada tienen que ver con una idea pedagógica o divulgativa pero que acaban distorsionando este periodo de la historia. En este trabajo analizamos brevemente algunas de estas facetas cotidianas que generan una visión irreal de la Prehistoria.The vision that society have in general on Prehistory, most of the times do not come from exhibitions or publications developed by experts. The collective image of the Prehistory most of the times come from the Cinema, the Literature, the commercial spots and other aspects that surrounds us in our quatidianity and nothing has to do with a pedagogic or divulgative idea, but the end in the distortion of this History period. In the present paper we analyze some of this daily aspects that generate a false vision of Prehistory

Investigation of the hydrophobic sites of DREAM

DREAM (downstream regulatory element antagonist modulator) also known as calsenilin or KChIP-3 is a calcium binding protein that has been associated with memory retention, pain sensing, calcium homeostasis and Alzheimer’s disease. It has two EF hands that bind Ca2+ and change the conformation of the protein. DREAM has two hydrophobic cavities in both the N- and C- terminus. These hydrophobic sites act as important binding sites with Kv channels, presenilin and other small molecules. Previously our group has showed that hydrophobic molecules such as NS5806 and 1,8- ANS can bind to the hydrophobic cavities in the C-terminus. The aim of this investigation was to characterize interactions of other hydrophobic molecules with DREAM with a long-term goal of finding a potential inhibitor for DREAM interacting with presenilin. In silico and in vitro approaches were used to determine a mechanism of binding of DREAM with hydrophobic molecules NS5806, NS3623, bezafibrate, trifluoperazine, 5-biphenyl-2-yl-1H-tetrazole, N-[(4-phenylphenyl)methyl]- 2H-tetrazol-5-amine and cholesterol. Three binding sites were identified at the C-terminus and Nterminus. The most favored binding site was in the C-terminus in the hydrophobic pocket of the EF- 4. All the hydrophobic molecules tested showed strong binding in this region. The major contributing residues were HIS 214, TYR 174, MET 187 and PHE 218. Other binding sites found resided in the hydrophobic pocket in the N-terminus but binding was shown to be weaker with many unfavorable residue interactions. Additional binding site was identified in between EF-3 and EF-4 but had many unfavorable interactions. An inhibitor with a high affinity for DREAM binding to presenilin would be beneficial in the blocking of gamma secretase complex which may lead to a better understanding of the physiology and treatment of Alzheimer disease

Pharmacokinetic/pharmacodynamic modeling of the antinociceptive effects of (+)-tramadol in the rat: role of cytochrome P450 2D activity

In this study the role of cytochrome P450 2D (CYP2D) in the pharmacokinetic/pharmacodynamic relationship of (+)-tramadol [(+)-T] has been explored in rats. Male Wistar rats were infused with (+)-T in the absence of and during pretreatment with a reversible CYP2D inhibitor quinine (Q), determining plasma concentrations of Q, (+)-T, and (+)-O-demethyltramadol [(+)-M1], and measuring antinociception. Pharmacokinetics of (+)-M1, but not (+)-T, was affected by Q pretreatment: early after the start of (+)-T infusion, levels of (+)-M1 were significantly lower (P < 0.05). However, at later times during Q infusion those levels increased continuously, exceeding the values found in animals that did not receive the inhibitor. These results suggest that CYP2D is involved in the formation and elimination of (+)-M1. In fact, results from another experiment where (+)-M1 was given in the presence and in absence of Q showed that (+)-M1 elimination clearance (CL(ME0)) was significantly lower (P < 0.05) in animals receiving Q. Inhibition of both (+)-M1 formation clearance (CL(M10)) and CL(ME0) were modeled by an inhibitory E(MAX) model, and the estimates (relative standard error) of the maximum degree of inhibition (E(MAX)) and IC(50), plasma concentration of Q eliciting half of E(MAX) for CL(M10) and CL(ME0), were 0.94 (0.04), 97 (0.51) ng/ml, and 48 (0.42) ng/ml, respectively. The modeling of the time course of antinociception showed that the contribution of (+)-T was negligible and (+)-M1 was responsible for the observed effects, which depend linearly on (+)-M1 effect site concentrations. Therefore, the CYP2D activity is a major determinant of the antinociception elicited after (+)-T administration

Modeling of the Sedative and Airway Obstruction Effects of Propofol in Patients with Parkinson Disease undergoing Stereotactic Surgery

BACKGROUND: Functional stereotactic surgery requires careful titration of sedation since patients with Parkinson disease need to be rapidly awakened for testing. This study reports a population pharmacodynamic model of propofol sedation and airway obstruction in the Parkinson disease population. METHODS: Twenty-one patients with advanced Parkinson disease undergoing functional stereotactic surgery were included in the study and received propofol target-controlled infusion to achieve an initial steady state concentration of 1 microg/ml. Sedation was measured using the Ramsay Sedation Scale. Airway obstruction was measured using a four-category score. Blood samples were drawn for propofol measurement. Individual pharmacokinetic profiles were constructed nonparametrically using linear interpolation. Time course of sedation and respiratory effects were described with population pharmacodynamic models using NONMEM. The probability (P) of a given level of sedation or airway obstruction was related to the estimated effect-site concentration of propofol (Ce) using a logistic regression model. RESULTS: The concentrations predicted by the target-controlled infusion system generally exceeded the measured concentrations. The estimates of C(50) for Ramsay scores 3, 4, and 5 were 0.1, 1.02, and 2.28 microg/ml, respectively. For airway obstruction scores 2 and 3, the estimates of C(50) were 0.32 and 2.98 microg/ml, respectively. Estimates of k(e0) were 0.24 and 0.5 1/min for the sedation and respiratory effects, respectively. CONCLUSIONS: The pharmacokinetic behavior of propofol in patients with Parkinson disease differs with respect to the population from which the model used by the target-controlled infusion device was developed. Based on the results from the final models, a typical steady state plasma propofol concentration of 0.35 microg/ml eliciting a sedation score of 3 with only minimal, if any, airway obstruction has been defined as the therapeutic target

Numerical solution of the complex Ginzburg-Landau equation alternatives for its time integration

Treball de Fi de Màster Universitari en Matemàtica Computacional (Pla de 2013). Codi: SIQ527. Curs 2021/2022 (A distància)La ecuación Ginzburg-Landau compleja en su forma cúbica describe una amplia gama de fenómenos para muchos sistemas de la física y presenta muchas estructuras coherentes estables entre sus soluciones. De ahí que se haya estudiado intensamente a lo largo de los años y que sea un laboratorio ideal para aprender sobre los esquemas de integración temporal. Desde el punto de vista numérico se pueden utilizar métodos pseudoespectrales para resolver la discretización espacial, hay que resolverlo con variable compleja y se pueden utilizar métodos específicos para la integración temporal como la Exponential Time Differencing o Integrating Factor Methods gracias a la presencia de términos lineales y no lineales integrables. El objetivo de esta tesis es comparar algunos de estos métodos analizando su orden y eficiencia. Para ello, se han programado los diferentes esquemas en Fortran y se han validado sus resultados mediante una pila de casos de prueba. A continuación, utilizando uno de ellos como referencia y calculando la solución de una prueba con un paso de tiempo muy pequeño, se han comparado los demás. Entre otros resultados, se ha constatado la buena convergencia de los métodos de orden superior o la mejor velocidad de los métodos que integran analíticamente parte de la ecuación o que necesitan menos transformadas de Fourier

Contenciones mecánicas en geriatría: propuestas técnicas y recomendaciones de uso en el ámbito social

The bibliographical revision of national gerontological literature reveals some confusion in the use of terms that refer to mechanical contentions, lack of dialogue with regards to ethical conflicts that suggest their use, a significant generalization of the claims against and the absence of positive references despite its high prevalence as shown by some authors. This paper presents some technical proposals on the definition, the use of terms and the use of mechanical contentions in the social sphere such as putting the ethical dialogue before the argumentation based on the prevalence, define them in terms of their intent, agree on a classification of the different contention methods, identify the types and levels of risk and intervene specifically and in terms thereof. Finally, recommendations are added with regards to risks, the decision process, prescription and the withdrawal process.La revisión bibliográfica de la literatura gerontológica estatal desvela alguna confusión en la utilización de los términos que hacen referencia a las contenciones mecánicas, escasez de diálogo ante los conflictos éticos que sugieren su uso, una notable generalización de las afirmaciones en contra y la ausencia de referencias positivas a pesar de que como muestran algunos autores su prevalencia es de las más elevadas del mundo. En este trabajo se exponen algunas propuestas técnicas relativas a la definición, el empleo de los términos y el uso de las contenciones mecánicas en el ámbito social como anteponer el diálogo ético a las argumentaciones basadas en la prevalencia, definirlas en función de su intencionalidad, consensuar una clasificación de los diferentes métodos de contención, identificar los tipos y los niveles de riesgo e intervenir específicamente y en función de los mismos. Se añaden al final recomendaciones relativas al riesgo, al proceso de decisión, la prescripción y al proceso de retirada

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

Pharmacokinetic/Pharmacodynamic Modeling of Antipyretic and Anti-Inflammatory Effects of Naproxen in the Rat

Pharmacokinetic/pharmacodynamic modeling was used to characterize the antipyretic and anti-inflammatory effects of naproxen in rats. An indirect response model was used to describe the antipyretic effects of naproxen after short intravenous infusions. The model assumes that basal temperature (T(a)) is maintained by the balance of fever mediators given by a constant (zero order) rate of synthesis (K(syn)), and a first order rate of degradation (K(out)). After an intraperitoneal injection of lipopolysaccharide, the change in T(a) was modeled assuming an increase in fever mediators described as an input rate function [IR(t)] estimated nonparametrically. An inhibitory E(max) model adequately described the inhibition of IR(t) by naproxen. A more complex model was used to describe the anti-inflammatory response of oral naproxen in the carrageenin-induced edema model. Before carrageenin injection, physiological conditions are maintained by a balance of inflammation mediators given by K(syn) and K(out) (see above). After carrageenin injection, the additional synthesis of mediators is described by IR(t) (see above). Such mediators induced an inflammatory process, which is governed by a first order rate constant (K(IN)) that can be inhibited by the presence of naproxen in plasma. The sigmoidal E(max) model also well described the inhibition of K(IN) by naproxen. Estimates for IC(50) [concentration of naproxen in plasma eliciting half of maximum inhibition of IR(t) or K(IN)] were 4.24 and 4.13 microg/ml, for the antipyretic and anti-inflammatory effects, respectively

Role of the different catalytic sites in the h2o2-mediated aqueous-phase furfural partial oxidation

This study has been financial supported by the Ministry for Science and Innovation (PID2020–112587RB-I00). The authors acknowledge the Electronic Transmission Microscope Service of University of Cantabria. Paula Rapado acknowledges to the University of Oviedo the financial support of her PhD (PAPI-21-PF-19)