Search results for "ODR"
showing 10 items of 434 documents
Small endogenous molecules as moiety to improve targeting of CNS drugs.
2016
A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purine…
Biological activity of PtIV prodrugs triggered by riboflavin-mediated bioorthogonal photocatalysis
2018
AbstractWe have recently demonstrated that riboflavin (Rf) functions as unconventional bioorthogonal photocatalyst for the activation of PtIV prodrugs. In this study, we show how the combination of light and Rf with two PtIV prodrugs is a feasible strategy for light-mediated pancreatic cancer cell death induction. In Capan-1 cells, which have high tolerance against photodynamic therapy, Rf-mediated activation of the cisplatin and carboplatin prodrugs cis,cis,trans-[Pt(NH3)2(Cl)2(O2CCH2CH2CO2H)2] (1) and cis,cis,trans-[Pt(NH3)2(CBDCA)(O2CCH2CH2CO2H)2] (2, where CBDCA = cyclobutane dicarboxylate) resulted in pronounced reduction of the cell viability, including under hypoxia conditions. Such …
Assessment of in vivo organ-uptake and in silico prediction of CYP mediated metabolism of DA-Phen, a new dopaminergic agent
2017
Abstract The drug development process strives to predict metabolic fate of a drug candidate, together with its uptake in major organs, whether they act as target, deposit or metabolism sites, to the aim of establish a relationship between the pharmacodynamics and the pharmacokinetics and highlight the potential toxicity of the drug candidate. The present study was aimed at evaluating the in vivo uptake of 2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) − a new dopaminergic neurotransmission modulator, in target and non-target organs of animal subjects and integrating these data with SMARTCyp results, an in silico method that predicts the sites of cytochrome P450-m…
New Symptomatic Treatments for the Management of Motor and Nonmotor Symptoms of Parkinson's Disease
2017
Motor symptoms are core features of Parkinson's disease, while nonmotor symptoms are present from the prodromal stage. Management strategies for the motor symptoms of Parkinson's disease have been widely researched and there have been many advances. Therapy has evolved from oral therapy to once a day to nonoral strategies, both for rescue and for infusion therapy. Treatment for nonmotor symptoms, however, has remained a key unmet need, although of late evidence base for management of some nonmotor symptoms such as pain, dementia, aspects of sleep dysfunction, and constipation has emerged. However, management of many nonmotor symptoms such as anxiety, apathy, fatigue, and insomnia remains un…
Diagnostic Criteria for Parkinson's Disease: From James Parkinson to the Concept of Prodromal Disease.
2018
The diagnosis of Parkinson’s disease (PD) is based on clinical features and differently to the common opinion that detecting this condition is easy, seminal clinico-pathological studies have shown that up one-fourth of patients diagnosed as PD during life has an alternative diagnosis at post-mortem. The misdiagnosis is even higher when only the initial diagnosis is considered, since the diagnostic accuracy improves by time, during follow-up visits. Given that the confirmation of the diagnosis of PD can be only obtained through neuropathology, to improve and facilitate the diagnostic-therapeutic workup in PD, a number of criteria and guidelines have been introduced in the last three decades.…
2021
Receptor tyrosine kinase inhibitors have become a central part of modern targeted cancer therapy. However, their curative potential is distinctly limited by both rapid resistance development and severe adverse effects. Consequently, tumor-specific drug activation based on prodrug designs, exploiting tumor-specific properties such as hypoxic oxygen conditions, is a feasible strategy to widen the therapeutic window. After proof-of-principal molecular docking studies, we have synthesized two cobalt(iii) complexes using a derivative of the clinically approved Abelson (ABL) kinase and fibroblast growth factor receptor (FGFR) inhibitor ponatinib. Acetylacetone (acac) or methylacetylacetone (Meaca…
Development of sense of coherence during two group interventions
2012
Burnout is a serious occupational hazard. This study investigated the possibility to develop an effective salutogenic group intervention among employees suffering from severe burnout symptoms. Participants consisted of employees aged 31 to 59 years working in different public service occupations, such as police officers, tax officers, (and other public service officers), and assigned to three different groups: analytic (N = 25), psychodramatic (N = 24) and controls (N = 28). The intervention comprised 16 separate days over a nine-month period. Changes in sense of coherence (SOC) were measured four times with the 13-item Orientation to Life Questionnaire during the intervention and at six-mo…
À la recherche du circuit idéal : le discours sur les autodromes et circuits automobiles dans L'Auto (1900-1939)
2022
Mujer y representación política institucional en la Comunidad Valenciana. 1977-1995. Diputadas, ministras y cargos institucionales
2014
“Mujer y representación política institucional en la Comunidad Valenciana. 1977-1995. Diputadas, ministras y cargos institucionales” es la primera parte de un trabajo de documentación para un capítulo de “La democracia en la Comunidad Valenciana. Partidos, elites políticas, elecciones y programas políticos”. “Mujer, poder político y democracia paritaria”. Se recoge el papel de la mujer en la vida política de la Comunidad Valenciana en la democracia actual, desde 1977. Es documentación sin elaborar, pero que aporta datos de la presencia de la mujer en las instituciones, partidos y sindicatos. Cuando este completa será una parte de la investigación referida, y de la que ya hay dos publicacion…
De la prohibición del terrorismo on-line : una reflexión constitucional
2021
The paper thinks out loud on the banning of the terrorist´s contents on the Internet, specifically within the international and national legal framework, with the interpretation given by the European Court´s of Human Right case-law and our Constitutional Court´s case-law.