Search results for "Agonist"

Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille’s heel to be exploited for the therapy of MYCN amplified neurob…

2012

The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mecha- nisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14ARF, significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treat- ment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Prote…

NMDA receptor antagonists and pain relief: A meta-analysis of experimental trials

2019

ObjectiveWe conducted a meta-analysis of controlled trials that used experimental models of acute pain and hyperalgesia to examine the analgesic effects of NMDA receptor (NMDAR) antagonists.MethodsSix major databases were systematically searched (to March 2018) for studies using human evoked pain models to compare NMDAR antagonists with no-intervention controls. Pain outcome data were analyzed with random-effects meta-analysis.ResultsSearches identified 70 eligible trials (n = 1,069). Meta-analysis found that low-dose ketamine (<1 mg/kg) produced a decrease in hyperalgesic area (standardized mean difference 0.54, 95% confidence interval [CI] 0.34, 0.74, p < 0.001) and a 1.2-point decr…

Pharmacogenomics: A Step forward Precision Medicine in Childhood Asthma.

2022

Personalized medicine, an approach to care in which individual characteristics are used for targeting interventions and maximizing health outcomes, is rapidly becoming a reality for many diseases. Childhood asthma is a heterogeneous disease and many children have uncontrolled symptoms. Therefore, an individualized approach is needed for improving asthma outcomes in children. The rapidly evolving fields of genomics and pharmacogenomics may provide a way to achieve asthma control and reduce future risks in children with asthma. In particular, pharmacogenomics can provide tools for identifying novel molecular mechanisms and biomarkers to guide treatment. Emergent high-throughput technologies, …

Humanization of Physical Education in Early School Educationen

2019

The article describes the possibilities offered by organising humanist-oriented physical education classes at the first stage of education. As part of physical education, which includes the process of physical upbringing and physical training, a teacher has the opportunity to influence pupils not only in terms of their physical fitness and health prevention, but also in terms of socially desirable values. In the research part of the paper, an assessment of the state of humanisation of physical education in early school education was undertaken, adopting the pupils' behaviour as a subject of research, which was in turn an indicator of the manifestation of values resulting from the assumption…

The martial art of judo as educational contents for children who living in an open society

2014

Los premios literarios y el canon literario. El caso Protagonista Jove

2021

El objetivo del estudio que presentamos en este capítulo1 es actualizar una de las líneas del trabajo realizado por la doctora Blanca Ana Roig Rechou (2013): los premios literarios en la literatura infantil y juvenil. Ahora, apor tamos los datos del Premi de Literatura «Protagonista Jove» que convoca el Consell Català del Llibre Infantil i Juvenil (ClijCAT) desde el curso 1996- 1997, dirigido a lectores de 12 a 16 años. Concretamente, presentamos los datos resultantes del análisis cuantitativo de las 23 ediciones del premio que tuvieron lugar entre 1996 y 2019. PID2019-10587RB-I00

Prenatal exposure to diazepam and alprazolam, but not to zolpidem, affects behavioural stress reactivity in handling-naïve and handling-habituated ad…

2002

A gentle long-lasting handling produces persistent neurochemical and behavioural changes and attenuates the impairment in the behavioural reactivity to novelty induced by the prenatal exposure to diazepam (DZ) in adult male rat progeny. This study investigated the consequences of a late prenatal treatment with three GABA/BDZ R agonists (DZ) alprazolam (ALP) and zolpidem (ZOLP)), on different stress-related behavioural patterns, in non-handled (NH), short-lasting handled (SLH) and long-lasting handled (LLH) adult male rats exposed to forced swim test (FST), acoustic startle reflex (ASR) and Vogel test (VT). The effects on motor activity were evaluated in the open field and in the Skinner box…

Medium-term effects of bisoprolol administration on renal hemodynamics and function in mild to moderate essential hypertension

2007

Arterial hypertension is a significant cause of end-stage renal failure; effective treatment of hypertensive patients reduces the rate of progression of this disorder. ss-Blockers, particularly nonselective agents, are associated with deterioration of renal function in patients with chronic renal failure. Previous studies on the interaction of the beta1-selective adrenergic antagonist bisoprolol with kidney function have been performed only acutely and over the short term. This study was designed to evaluate the antihypertensive efficacy and effects on renal hemodynamics and function of bisoprolol during medium-term (6 mo) treatment of patients with mild to moderate essential hypertension. …

A double-blind, placebo-controlled comparison of treatment with fluticasone propionate and levocabastine in patients with seasonal allergic rhinitis

1999

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double…

Synthesis and Structure-Affinity Relationships of Spirocyclic Benzopyrans with Exocyclic Amino Moiety

2019

σ1 and/or σ2 receptors play a crucial role in pathological conditions such as pain, neurodegenerative disorders, and cancer. A set of spirocyclic cyclohexanes with diverse O-heterocycles and amino moieties (general structure III) was prepared and pharmacologically evaluated. In structure-activity relationships studies, the σ1 receptor affinity and σ1:σ2 selectivity were correlated with the stereochemistry, the kind and substitution pattern of the O-heterocycle, and the substituents at the exocyclic amino moiety. cis-configured 2-benzopyran cis-11b bearing a methoxy group and a tertiary cyclohexylmethylamino moiety showed the highest σ1 affinity ( Ki = 1.9 nM) of this series of compounds. In…