27 research outputs found
Benzodiazepines and derivatives. Overview, analysis and synthesis
Treballs Finals de Grau de Farmà cia, Facultat de Farmà cia, Universitat de Barcelona, 2018. Tutora: Maria Dolors Pujol Dilme[eng] Benzodiazepines are widely used drugs for several indications. This study provides, on the
one hand, a global vision of this family starting for their fortuitous discovery, the synthesis
of their derivatives, their mechanism of action which is well known nowadays, the actual
classification according to the chemical structure and the pharmacokinetic properties and
their uses and indications, including the traditional and the new ones.
On the other hand, the study is focused in the dependence and tolerance derived from their
use, many times lead by a misuse of the patient, wrong prescriptions or extended
treatments. A withdrawal program is proposed, including the important factors or criteria
to success, with a slow and gradual reduction of these drugs to avoid relapse or severe
adverse effects.
New lines of research related to benzodiazepines are taken into account, including the new
therapeutic uses but also the adverse effects in short and long-term. They are also
analyzed the new discoveries concerning the non-benzodiazepinic drugs due to the close
relation they have with benzodiazepines.[cat] Les benzodiazepines son medicaments à mpliament utilitzats per nombroses indicacions.
Aquest treball proporciona, per una part, una visió global de la famÃlia començant pel seu
descobriment fortuït, la sÃntesi dels seus derivats, el seu mecanisme d’acció à mpliament
conegut a l’actualitat, la classificació actual segons estructura quÃmica i propietats
farmacocinètiques i els seus pertinents usos i indicacions, tant els tradicionals com els mes
nous.
Per altre part, el estudi es centra en la dependència i tolerà ncia derivada del ús d’aquests
medicaments, molt cops per una mala utilització per part del pacient o per prescripcions
errònies i/o massa extenses. També es proposa un model de programa de retirada que té
en compte tots els factors necessaris per aconseguir reduir gradualment aquests
medicaments, sense patir cap recaiguda ni efectes secundaris severs, fins a aconseguir-ho
amb èxit.
Es tenen en compte les lÃnies de recerca actuals en relació a benzodiazepines, tant per nous
usos terapèutics com per efectes secundaris, ja sigui a curt o llarg termini. També
s’analitzen els nous descobriments pel que fa als derivats no benzodiazepÃnics ja que tenen
una estreta relació amb les benzodiazepines
Transcriptional variation in malaria parasites: why and how
Transcriptional differences enable the generation of
alternative phenotypes from the same genome. In malaria
parasites, transcriptional plasticity plays a major role in the
process of adaptation to fluctuations in the environment.
Multiple studies with culture-adapted parasites and field
isolates are starting to unravel the different transcriptional
alternatives available to Plasmodium falciparum and the
underlying molecular mechanisms. Here we discuss how epigenetic
variation, directed transcriptional responses and also genetic
changes that affect transcript levels can all contribute to
transcriptional variation and, ultimately, parasite survival.
Some transcriptional changes are driven by stochastic events.
These changes can occur spontaneously, resulting in
heterogeneity within parasite populations that provides the
grounds for adaptation by dynamic natural selection. However,
transcriptional changes can also occur in response to external
cues. A better understanding of the mechanisms that the parasite
has evolved to alter its transcriptome may ultimately contribute
to the design of strategies to combat malaria to which the
parasite cannot adapt
1,4-Benzodiazepines and New Derivatives: Description, Analysis, and Organic Synthesis
Benzodiazepines are widely used drugs for several indications. This study provides, on the other hand, a global vision of the family starting for their fortuitous discovery, the synthesis of their derivatives, their mechanism of action widely known nowadays, the actual classification according to the chemical structure and pharmacokinetic properties, and their uses and indications, the traditional and the new ones. On the other hand,the study is focused in the mainly problems of benzodiazepines, depedence, and tolerance, many times led by a misuse of the patient, wrong prescriptions, or extended treatments. A withdrawal program is proposed that includes the important factors or criteria to success, with a slow and gradual reduction of these drugs, avoiding relapse or severe adverse effects. New lines of research related to benzodiazepines are taken into account, which not only include the new therapeutic uses but also the adverse effects in short and long term. They are also analyzed the new discoveries concerning the nonbenzodiazepine drugs due to the close relation they have with benzodiazepines
Petrological characterization of flint from Montmaneu's Limestones Formation (Eastern sector of the Ebro Basin)
[EN] Flint from Montmaneu's Limestones Formation of Rupelian age (Oligocene) is being here characterized. The analysis of the compositional texture, mineralogy and geochemical features has revealed this flint is highly pure and of microcrystalline texture, with a significant content of moganite. This flint is product of an early diagenetic replacement of limestone from littoral lacustrine facies. This flint was exploited by human populations in a regional range, especially in the early stages of the Neolithic.[ES] Se caracteriza el sÃlex de la Formación calizas de Montmaneu, de edad Rupeliense (Oligoceno). El análisis textural, mineralógico y de sus rasgos geoquÃmicos indica que se trata de un sÃlex microcristalino, bastante puro, con una proporción significativa de moganita. Es producto del reemplazamiento diagenético temprano de calizas de facies lacustres litorales. Este sÃlex fue objeto de una explotación regional, especialmente en los primeros momentos del NeolÃtico.Este trabajo forma parte del proyecto de constitución de una litoteca de rocas silÃceas del NE peninsular (LITOcat). Los estudios sobre la explotación prehistórica del sÃlex de Montmaneu se llevan a cabo en el marco del proyecto "Aprofitament prehistòric i històric del sÃlex a Catalunya: contextos extractius i de primera transformació". Ambos proyectos son financiados por el CSIC-IMF y el Departamento de Cultura de la Generalitat de Catalunya.Peer reviewe
Design, synthesis, biological evaluation and in silico study of benzyloxybenzaldehyde derivatives as selective aldh1a3 inhibitors
Altres ajuts: This research was funded by Al-Zaytoonah University of Jordan, grant number 2019- 2018/18/03 and by UoB International Development Fund Scheme PhD, grant code studentship to E.B. R.J. is a recipient of a PIF predoctoral fellowship from Universitat Autònoma de Barcelona.Aldehyde dehydrogenase 1A3 (ALDH1A3) has recently gained attention from researchers in the cancer field. Several studies have reported ALDH1A3 overexpression in different cancer types, which has been found to correlate with poor treatment recovery. Therefore, finding selective inhibitors against ALDH1A3 could result in new treatment options for cancer treatment. In this study, ALDH1A3-selective candidates were designed based on the physiological substrate resemblance, synthesized and investigated for ALDH1A1, ALDH1A3 and ALDH3A1 selectivity and cytotoxicity using ALDH-positive A549 and ALDH-negative H1299 cells. Two compounds (ABMM- 15 and ABMM-16), with a benzyloxybenzaldehyde scaffold, were found to be the most potent and selective inhibitors for ALDH1A3, with IC50 values of 0.23 and 1.29 μM, respectively. The results also show no significant cytotoxicity for ABMM-15 and ABMM-16 on either cell line. However, a few other candidates (ABMM-6, ABMM-24, ABMM-32) showed considerable cytotoxicity on H1299 cells, when compared to A549 cells, with IC50 values of 14.0, 13.7 and 13.0μM, respectively. The computational study supported the experimental results and suggested a good binding for ABMM- 15 and ABMM-16 to the ALDH1A3 isoform. From the obtained results, it can be concluded that benzyloxybenzaldehyde might be considered a promising scaffold for further drug discovery aimed at exploiting ALDH1A3 for therapeutic intervention
TRPV4 Channels Promote Pathological, but Not Physiological, Cardiac Remodeling through the Activation of Calcineurin/NFAT and TRPC6
TRPV4 channels, which respond to mechanical activation by permeating Ca2+ into the cell, may play a pivotal role in cardiac remodeling during cardiac overload. Our study aimed to investigate TRPV4 involvement in pathological and physiological remodeling through Ca2+-dependent signaling. TRPV4 expression was assessed in heart failure (HF) models, induced by isoproterenol infusion or transverse aortic constriction, and in exercise-induced adaptive remodeling models. The impact of genetic TRPV4 inhibition on HF was studied by echocardiography, histology, gene and protein analysis, arrhythmia inducibility, Ca2+ dynamics, calcineurin (CN) activity, and NFAT nuclear translocation. TRPV4 expression exclusively increased in HF models, strongly correlating with fibrosis. Isoproterenol-administered transgenic TRPV4-/- mice did not exhibit HF features. Cardiac fibroblasts (CFb) from TRPV4+/+ animals, compared to TRPV4-/-, displayed significant TRPV4 overexpression, elevated Ca2+ influx, and enhanced CN/NFATc3 pathway activation. TRPC6 expression paralleled that of TRPV4 in all models, with no increase in TRPV4-/- mice. In cultured CFb, the activation of TRPV4 by GSK1016790A increased TRPC6 expression, which led to enhanced CN/NFATc3 activation through synergistic action of both channels. In conclusion, TRPV4 channels contribute to pathological remodeling by promoting fibrosis and inducing TRPC6 upregulation through the activation of Ca2+-dependent CN/NFATc3 signaling. These results pose TRPV4 as a primary mediator of the pathological response
Aprenentatge mòbil en el desenvolupament de la competència plurilingüe en comunitats d’aprenentatge
Projecte: 2018PID-UB/027L’objectiu general d’aquest projecte d'innovació és dissenyar i implementar diverses prà ctiques en què es fa ús de la tecnologia mòbil per al desenvolupament de les competències comunicatives en els estudiants dels Graus de Mestre i de Comunicació Audiovisual. Aquestes prà ctiques estan pensades per promoure la interacció entre els estudiants i afavorir la creació de comunitats d’aprenentatge més enllà del grup classe. En conseqüència, aquest projecte d’innovació ha pretès, a partir de l’aprenentatge mòbil, que els estudiants participin en accions didà ctiques amb companys d’altres grups i disciplines amb la intenció de desenvolupar la seva competència plurilingüe. Les actuacions didà ctiques s’han portat a terme en les assignatures de llengua de la Facultat d’Educació -català , castellà i anglès- i en altres assignatures relacionades amb el desenvolupament de les habilitats comunicatives dels estudiants i ha implicat un ús de les llengües amb objectius compartits entre els diferents participants.Projecte d'innovació docent RIMDA - 2018PID-UB/02
Alcohol intake and breast cancer in the European prospective investigation into cancer and nutrition
Alcohol intake has been associated to breast cancer in pre and postmenopausal women; however results are inconclusive regarding tumor hormonal receptor status, and potential modifying factors like age at start drinking. Therefore, we investigated the relation between alcohol intake and the risk of breast cancer using prospective observational data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Up to 334,850 women, aged 35-70 years at baseline, were recruited in ten European countries and followed up an average of 11 years. Alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. The study outcomes were the Hazard ratios (HR) of developing breast cancer according to hormonal receptor status. During 3,670,439 person-years, 11,576 incident breast cancer cases were diagnosed. Alcohol intake was significantly related to breast cancer risk, for each 10 g/day increase in alcohol intake the HR increased by 4.2% (95% CI: 2.7-5.8%). Taking 0 to 5 g/day as reference, alcohol intake of >5 to 15 g/day was related to a 5.9% increase in breast cancer risk (95% CI: 1-11%). Significant increasing trends were observed between alcohol intake and ER+/PR+, ER-/PR-, HER2- and ER-/PR-HER2- tumors. Breast cancer risk was stronger among women who started drinking prior to first full-time pregnancy. Overall, our results confirm the association between alcohol intake and both hormone receptor positive and hormone receptor negative breast tumors, suggesting that timing of exposure to alcohol drinking may affect the risk. Therefore, women should be advised to control their alcohol consumption. What's new? Although it is now established that alcohol consumption increases breast cancer risk, many questions remain. Using a prospective study design with 11,576 incident breast cancer cases across 10 European countries, the authors confirmed the increased risk of alcohol on breast cancer development. They further show that women who started drinking before their first full-term pregnancy have a higher risk than women who started afterwards. These effects were observed in hormone-receptor positive and -negative tumors pointing to non-hormonal pathways that need to be further investigated
Large-Scale Surface registration
The first part of this work presents an accurate analysis of the most relevant 3D registration techniques, including initial pose estimation, pairwise registration and multiview registration strategies. A new classification has been proposed, based on both the applications and the approach of the methods that have been discussed.The main contribution of this thesis is the proposal of a new 3D multiview registration strategy. The proposed approach detects revisited regions obtaining cycles of views that are used to reduce the inaccuracies that may exist in the final model due to error propagation. The method takes advantage of both global and local information of the registration process, using graph theory techniques in order correlate multiple views and minimize the propagated error by registering the views in an optimal way. The proposed method has been tested using both synthetic and real data, in order to show and study its behavior and demonstrate its reliability.La primera part d'aquest treball presenta una anà lisi acurada de les tècniques de registre 3D es rellevants, incloent tècniques d'estimació de la posició inicial, registre pairwise i registre entre múltiples vistes. S'ha proposat una nova classificació de les tècniques, depenent de les seves aplicacions i de l'estratègia utilitzada.La contribució mes important d'aquesta tesi és la proposta d'un nou mètode de registre 3D utilitzant múltiples vistes. El mètode proposat detecta regions ja visitades prèviament, obtenint cicles de vistes que s'utilitzen per tal de reduir els desalineaments en el model final deguts principalment a la propagació de l'error durant el procés de registre. Aquest mètode utilitza tant informació global com local, correlacionant les vistes mitjançant tècniques de grafs que permeten minimitzar l'error propagat i registrar les vistes de forma òptima. El mètode proposat ha estat provat utilitzant dades sintètiques i reals, per tal de mostrar i analitzar el seu comportament i demostrar la seva eficà cia