Search results for "PAM"
showing 10 items of 1768 documents
Bases psicobiológicas de la adicción a cocaína
2006
El principal mecanismo de acción de la cocaína es la inhibición de la recaptación de dopamina y noradrenalina, produciendo un aumento de estos neurotransmisores en la sinapsis. El consumo agudo de cocaína produce una serie de cambios bastante conocidos en el sistema cerebral de recompensa. Sin embargo, el consumo crónico, produce, además, otra serie de cambios a nivel molecular que llevan al sujeto desde una situación de consumo puntual, a una situación de dependencia. Se han propuesto diferentes teorías explicativas de este fenómeno como la sensibilización del incentivo, o la homeostasis y alostasis neuroquímica, planteamientos basados en el condicionamiento clásico y operante. Por otra pa…
Quimiosensores y quimiodosímetros para la detección de neurotransmisores
2019
La presente Tesis Doctoral titulada “Quimiosensores y quimiodosímetros para la detección de neurotransmisores” está centrada en el desarrollo de nuevos sistemas para la detección cromogénica y fluorogénica de moléculas biógenas, haciendo especial hincapié en el uso del fenómeno conocido como Emisión Inducida por Agregación (AIE) como mecanismo de transducción. Para ello, se han sintetizado y estudiado una serie de derivados del tetrafenileteno (TPE), compuesto que presenta propiedades AIE que pueden ser modificadas fácilmente gracias a la adecuada funcionalización del mismo. En el capítulo 3 se describe cómo, en derivados del TPE funcionalizados con anillos de triazol sustituidos con cadena…
Metformin influences drug sensitivity in pancreatic cancer cells
2018
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, highly metastatic malignancy and accounts for 85% of pancreatic cancers. PDAC patients have poor prognosis with a five-year survival of only 5–10% after diagnosis and treatment. Pancreatic cancer has been associated with type II diabetes as the frequency of recently diagnosed diabetics that develop pancreatic cancer within a 10-year period of initial diagnosis of diabetes in increased in comparison to non-diabetic patients. Metformin is a very frequently prescribed drug used to treat type II diabetes. Metformin acts in part by stimulating AMP-kinase (AMPK) and results in the suppression of mTORC1 activity and the induction o…
Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1.
2014
The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibi…
Selective downregulation of the MDR1 gene product in Caco-2 cells by stable transfection to prove its relevance in secretory drug transport.
2005
Considerable interest is focused on overcoming multidrug resistance (MDR) in cancer chemotherapy. The in vitro experiments to characterize P-glycoprotein's (P-gp) function and to decrease its effects have led to a variety of strategies such as addition of competitors or supplementation of the medium with oligonucleotides complementary to the 5'-end of the MDR1-mRNA. For the Caco-2 cell line, an in vitro model for absorption screening, expressing multiple transporters including P-gp, which pumps substances back into the apical solution, P-gp activity might mask other relevant transport proteins' activity. The objective of the present study was to construct a Caco-2 subline with reduced P-gp …
Metabolic shift of polyphosphate-accumulating organisms with different levels of polyphosphate storage
2012
Previous studies have shown that polyphosphate-accumulating organisms (PAOs) are able to behave as glycogen-accumulating organisms (GAOs) under different conditions. In this study we investigated the behavior of a culture enriched with Accumulibacter at different levels of polyphosphate (poly-P) storage. The results of stoichiometric ratios Gly degraded/HAc uptake, PHB synthesized/HAc uptake, PHV synthesized/HAc uptake and P release/HAc uptake confirmed a metabolic shift from PAO metabolism to GAO metabolism: PAOs with high poly-P content used the poly-P to obtain adenosine tri-phosphate (ATP), and glycogen (Gly) to obtain nicotinamide adenine dinucleotide (NADH) and some ATP. In a test whe…
Phytosociology and ecology of deciduous forests in Tajikistan (Middle Asia)
2017
Aims: To present the first syntaxonomical classification for the mesophilous deciduous forests of the PamirAlai Mountains in Tajikistan with some remarks on its environmental gradients. Location: Tajikistan. Methods: Altogether 201 relevés were sampled between 2008‒2013 using the seven-degree cover-abundance scale of Braun-Blanquet. They were classified by the modified TWINSPAN method using the four-step interval scale with cutoff levels of 0%, 2%, 5% and 10% and total inertia as a measure of cluster heterogeneity. Diagnostic species were identified using the phi coefficient as a fidelity measure. Detrendended Correspondence Analysis was used to determine the relation between samples, veget…
Addictive-like behaviour for Acetaldehyde: involvement of D2 receptors
2013
Acetaldehyde (ACD), ethanol's first metabolite, is centrally active and shows rewarding and motivational properties. It is able to activate mesolimbic dopamine system, since it enhances neuronal firing of dopamine cells in ventral tegmental area and exerts dopamine release in the nucleus accumbens (Foddai et al., 2004; Melis et al., 2007; Deehan et al., 2013). ACD motivational properties are demonstrated by self-administration studies in rodents (Rodd et al., 2005), particularly behavioural evidence suggests that ACD could produce positive reinforcing effects in operant-conflict paradigms (Cacace et al., 2012). In order to shed light on neurobiological substrate underpinning ACD-related beh…
The impact of the EMA change in definition of "dose" on the BCS dose-solubility ratio: a review of the biowaiver monographs.
2013
The Biopharmaceutics Classification System (BCS) defines the solubility characteristics of an active pharmaceutical substance based on its dose-solubility ratio: for highly soluble drugs this ratio is less than 250 mL over a defined pH range. Prior to the revision of the European Medicines Agency (EMA, formerly EMEA) guideline in 2010, the "dose" in this ratio was consistently defined by the US FDA, the EMA, and the WHO biowaiver guidelines as the highest dosage strength. However, in the revised EMA guideline, the dose is defined as the highest single dose administered according to the Summary of Product Characteristics. The new EMA criterion for highly soluble may be closer to the actual c…
El actors socials davant del repte de l'actuació territorial al País Valencià. El cas dels sindicats
2012
En els anys viutanta té lloc l'inici d'un procés de descentralització política, amb la consegüent transferència de competències al nou govern autonòmic. Aquest procés s'acompanya d'un altre consistent en el creixent desplegament de polítiques de desenvolupament local. Ambdós suposen una oportunitat per a uns actors socials encara jovens en tant que s'obri un camp de possibilitats per a avançar en l'acció sociopolítica i la concentració social, tan a escala autonòmica com local. Amb tot, també suposa el repte per als actors socials de dotar-se d'unes estructures adequades per a desplegar una actuació territorial munícipal i comarcal satisfactòria. Sembla que els sindicats més representatius …