Models animals per a l'estudi de la diabetis

La diabetis mellitus (DM) s'origina per mancança dels efectes de la insulina, bé perquè el pàncrees és incapaç de produir-ne, bé perquè els seus òrgans diana no responen adequadament, o per una combinació d'ambdues situacions, amb l'aparició d'hiperglucèmia, poliúria i polidípsia. En absència total de la insulina (DM tipus 1) hi ha metabolisme accelerat de proteïna muscular i greix, que pot acabar en cetoacidosi metabòlica i mort. Amb activitat insulínica residual (DM tipus 2), la malaltia es cronifica, amb obesitat, micro i macroangiopaties, i les seves manifestacions clíniques (insuficiència renal, alteracions retinals, neuropaties, infart de miocardi, etc.). La DM és un problema sanitari de primer ordre i, en ser una malaltia complexa, en la qual intervenen factors genètics i adquirits, no hi ha un model animal perfecte per estudiar-la que reprodueixi totes les característiques de la malaltia humana. La majoria de models utilitzen rosegadors, per una sèrie d'avantatges: petita grandària, facilitat d'obtenció, ràpid recanvi generacional i facilitat de manipulació genètica. En aquesta revisió parlarem de models induïts, en els quals reproduïm la malaltia mitjançant una manipulació determinada, models espontanis, consistents en soques d'animals que s'han seleccionat genèticament al llarg de successives generacions per tal que manifestin la malaltia, i models obtinguts per modificació genètica.Animal experimental models for the study of diabetes. Diabetes mellitus (DM) originates from a lack of insulin effects, due to a deficit of pancreatic production, or to an inadequate response of target organs, or a combination of both situations, ensuing hyperglycaemia, polyuria and polydipsia. When insulin is totally absent (Type 1 DM), there is an increased metabolism of muscular protein and fat, ending in metabolic ketoacidosis and death. With a residual insulin activity (Type 2 DM), diabetes becomes chronic, with obesity, micro- and macroangiopathies and their corresponding clinical manifestations (renal failure, retinal alterations, neuropathies, myocardial infarct, etc.). DM is a serious health problem and, as it is a complex illness, in which participate genetic and acquired factors, there is not a single perfect animal model for its study, able to reproduce all the characteristics of the human malady. The great majority of models use rodents, given their advantages: small size, easy access, fast reproduction rate, and a feasible genetic manipulation. We will discuss about induced models, in which the illness is reproduced by means of a specific manipulation, spontaneous models, comprised by animal breeds genetically selected along successive generations in order to them to develop the malady, and genetically engineered models

Toward an ICPMS-linked DNA assay based on gold nanoparticles immunoconnected through peptide sequences

Gold nanoparticles modified with anti-mouse IgG have been used to trace oligonucleotides carrying a c-myc peptide. Two strategies, a dot-blot format as well as inductively coupled plasma mass spectrometry (ICPMS) have been used to detect the nanoparticle tracer. For both cases, oligonucleotide-peptide conjugates were first applied to a nitrocellulose membrane using a manifold attached to a suction device. After immobilization of the oligonucleotide by UV radiation, the samples were incubated with an anti-c-myc monoclonal antibody. In the case of the dot-blot format strategy, it was followed by incubation with a secondary antibody conjugated to horseradish peroxidase and development with luminol as chemiluminescent substrate. In the case of ICPMS strategy, it was followed by incubation with the secondary antibody (anti-mouse IgG) conjugated to gold nanoparticles and their ICPMS detection after dissolving. The nonspecific adsorptions were found to be around zero. The limit of detection for peptide-modified DNA was 0,2 pmol. The method may have significant potential as an important ICPMS-based nonradioactive DNA detection method for the simultaneous determination of various sequences by labeling different kinds of inorganic nanoparticles. © 2005 American Chemical Society.This work was financially supported from MEC (Madrid) (Projects BIO2004- 02776, MAT2004-05164), by Spanish foundation “Ramón Areces” (project ‘Bionanosensores’). A.M. thanks the “Ramón y Cajal” program of Ministry of Science and Technology (Madrid).Peer reviewe

Simple sugar intake and hepatocellular carcinoma: epidemiological and mechanistic insight

Sugar intake has dramatically increased during the last few decades. Specifically, there has been a clear trend towards higher consumption of fructose and high fructose corn syrup, which are the most common added sugars in processed food, soft drinks and other sweetened beverages. Although still controversial, this rising trend in simple sugar consumption has been positively associated with weight gain and obesity, insulin resistance and type 2 diabetes mellitus and non-alcoholic fatty liver disease. Interestingly, all of these metabolic alterations have also been related to the development of hepatocellular carcinoma. The purpose of this review is to discuss the evidence coming from epidemiological studies and data from animal models relating the consumption of simple sugars, and specifically fructose, with an increased risk of hepatocellular carcinoma and to gain insight into the putative molecular mechanisms involved

Por qué el azúcar de la fruta es bueno para la salud y el de los procesados no

El consumo de fruta como tal en nuestra dieta es saludable. Procesada o disuelta en líquidos o en forma de zumo, menos

Simultaneous voltammetric determination of acetaminophen, ascorbic acid and uric acid by use of integrated array of screen-printed electrodes and chemometric tools

In the present work, ternary mixtures of Acetaminophen, Ascorbic acid and Uric acid were resolved using the Electronic tongue (ET) principle and Cyclic voltammetry (CV) technique. The screen-printed integrated electrode array having differentiated response for the three oxidizable compounds was formed by Graphite, Prussian blue (PB), Cobalt (II) phthalocyanine (CoPc) and Copper oxide (II) (CuO) ink-modified carbon electrodes. A set of samples, ranging from 0 to 500 µmol·L, was prepared, using a tilted (3) factorial design in order to build the quantitative response model. Subsequently, the model performance was evaluated with an external subset of samples defined randomly along the experimental domain. Partial Least Squares Regression (PLS) was employed to construct the quantitative model. Finally, the model successfully predicted the concentration of the three compounds with a normalized root mean square error (NRMSE) of 1.00 and 0.99 for the training and test subsets, respectively, and R ≥ 0.762 for the obtained vs. expected comparison graphs. In this way, a screen-printed integrated electrode platform can be successfully used for voltammetric ET applications

PAPEL DE LA SECUENCIACIÓN DE NUEVA GENERACIÓN EN EL DIAGNÓSTICO Y TRATAMIENTO EN LA ERA DE LA MEDICINA PERSONALIZADA

La Secuenciación de Nueva Generación es una técnica de diagnóstico molecular de reciente implantación en la práctica clínica, que permite detectar varias alteraciones moleculares al mismo tiempo en los tejidos analizados. Su aplicación en la Medicina y sobre todo en el campo de la Oncología ha supuesto una auténtica revolución ya que permite identificar dianas tumorales y con esto dirigir los tratamientos contra estas, sustituyendo a la terapia quimioterápica sistémica convencional y cambiando así el paradigma del tratamiento y el pronóstico de los pacientes, permitiendo entrar en la era de la Medicina Personalizada.En las últimas investigaciones vemos cómo va adquiriendo cada día mayor relevancia esta corriente, desarrollándose cada vez más fármacos dirigidos a mutaciones concretas, buscando individualizar el tratamiento para cada paciente en función de los hallazgos encontrados en las pruebas diagnósticas.El uso de NGS, pese a no estar aún extendido en el sistema sanitario debido a la complejidad y coste de la técnica, tiene un potencial enorme en esta nueva perspectiva y es previsible que esta técnica acabe implantándose en la cartera de servicios diagnósticos de la práctica clínica. Es por esto por lo que en este Trabajo de Fin de Grado nos vamos a centrar en estudiar bibliografía sobre este tema, recogiendo las nuevas indicaciones y tratamientos autorizados y buscando analizar la situación actual y futura de la Oncología de precisión en el panorama estatal e internacional.<br /

Models animals per a l'estudi de la diabetis

La diabetis mellitus (DM) s'origina per mancança dels efectes de la insulina, bé perquè el pàncrees és incapaç de produir-ne, bé perquè els seus òrgans diana no responen adequadament, o per una combinació d'ambdues situacions, amb l'aparició d'hiperglucèmia, poliúria i polidípsia. En absència total de la insulina (DM tipus 1) hi ha metabolisme accelerat de proteïna muscular i greix, que pot acabar en cetoacidosi metabòlica i mort. Amb activitat insulínica residual (DM tipus 2), la malaltia es cronifica, amb obesitat, micro i macroangiopaties, i les seves manifestacions clíniques (insuficiència renal, alteracions retinals, neuropaties, infart de miocardi, etc.). La DM és un problema sanitari de primer ordre i, en ser una malaltia complexa, en la qual intervenen factors genètics i adquirits, no hi ha un model animal perfecte per estudiar-la que reprodueixi totes les característiques de la malaltia humana. La majoria de models utilitzen rosegadors, per una sèrie d'avantatges: petita grandària, facilitat d'obtenció, ràpid recanvi generacional i facilitat de manipulació genètica. En aquesta revisió parlarem de models induïts, en els quals reproduïm la malaltia mitjançant una manipulació determinada, models espontanis, consistents en soques d'animals que s'han seleccionat genèticament al llarg de successives generacions per tal que manifestin la malaltia, i models obtinguts per modificació genètica

Farmacología y toxicología en I+D+i: adquisición de competencias a través de un ejemplo de desarrollo de un fármaco

The implementation of the subject Pharmacology and Toxicology in R+D+i in the Pharmacy Degree, has led to the launch of a new methodological approach and teaching performance with the aim of developing the generic skills of the University of Barcelona (e.g., self-learning, team-working). An additional objective was students' integration of knowledge from different subjects in the degree which form the basis of the preclinical and clinical development of a drug. For this purpose, the teaching strategy used in the development of the subject was based on: 1) re-developing the content that students had been taught previously or were being taught in the same semester as a part of other subjects, and framing them in the environment of the pharmaceutical industry, 2) introducing new and previously unseen contents to do with drug development and toxicology, 3) developing a battery of activities to be undertaken by teams of students relating to the R+D+i of a particular drug. During the development of these activities, students have to acquire generic skills in addition to the subject-specific skills. The results obtained from the student survey give us grounds for satisfaction and allow us to consider that we have reached the goal of improving students' learning in Pharmacology and Toxicology applied to drug development in the pharmaceutical world today

mTOR is a Key Protein Involved in the Metabolic Effects of Simple Sugars

One of the most important threats to global human health is the increasing incidences of metabolic pathologies (including obesity, type 2 diabetes and non-alcoholic fatty liver disease), which is paralleled by increasing consumptions of hypercaloric diets enriched in simple sugars. The challenge is to identify the metabolic pathways affected by the excessive consumption of these dietary components when they are consumed in excess, to unravel the molecular mechanisms leading to metabolic pathologies and identify novel therapeutic targets to manage them. Mechanistic (mammalian) target of rapamycin (mTOR) has emerged as one of the key molecular nodes that integrate extracellular signals, such as energy status and nutrient availability, to trigger cell responses that could lead to the above-mentioned diseases through the regulation of lipid and glucose metabolism. By activating mTOR signalling, excessive consumption of simple sugars (such as fructose and glucose), could modulate hepatic gluconeogenesis, lipogenesis and fatty acid uptake and catabolism and thus lipid deposition in the liver. In the present review we will discuss some of the most recent studies showing the central role of mTOR in the metabolic effects of excessive simple sugar consumption

Fructose effects on human health: Molecular insights from experimental models

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/63704Global changes in dietary habits in the last decades caused an increase of added sugar consumption all over the world, which has been linked to the increasing prevalence of obesity, dyslipidemia, insulin resistance and cardiovascular disease. Fructose is widely used as a sweetener in the food and beverage industry, either as an integrant of the sucrose molecule or as a component of high fructose corn syrups. The consumption of fructose in beverages is especially dangerous, as the process of energy compensation by reduction in the ingestion of other foods does not work equally well with liquid than solid foods. Besides, fructose is the carbohydrate with the highest ability to induce hypertriglyceridemia, due to a marked increase in lipogenesis compared with glucose. In this review we will discuss some of the most recent studies performed in animal models and in humans to investigate the effects of excessive fructose consumption