Search results for "AGENT"
showing 10 items of 8904 documents
1,2,4-OSSADIAZOLI: UTILI SCAFFOLD NEL DESIGN DI NUOVI FARMACI
2021
Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…
2006
Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…
Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.
2012
To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia m…
Phenolic Profiles, Antioxidant and Anti-Inflammatory Activities of Hydrodistillation Wastewaters from Five Lamiaceae Species
2022
Distillation is the most widely used method to obtain an essential oil from plant material. The biomass used in the process is returned as a solid residue together with variable amounts of water rich in water-soluble compounds, which currently are not addressed to any further application. The scope of this work was to evaluate the phytochemical composition of wastewaters coming from hydrodistillation (DWWs) of five aromatic plants belonging to the Lamiaceae family, and to assess their in vitro antioxidant and anti-inflammatory activities. The phenolic profiles of the DWWs were determined by HPLC-DAD and HPLC-ESI/MS. Free radical scavenging ability, oxygen radical antioxidant capacity and su…
Rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes): A multicenter retrospective nationwide Italian study a…
2017
Background Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. Aims We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society. Data synthesis The primary objective of the study is to describe the baseline clinical characteristics (particularly HbA1c) of pa…
Global Real-World Evidence of Sofosbuvir/Velpatasvir as a Highly Effective Treatment and Elimination Tool in People with Hepatitis C Infection Experi…
2022
HCV elimination; Mental health disorders; Sofosbuvir/velpatasvir Eliminación del VHC; Trastornos de salud mental; Sofosbuvir/velpatasvir Eliminació del VHC; Trastorns de salut mental; Sofosbuvir/velpatasvir Hepatitis C virus (HCV) is prevalent in people with mental health disorders, a priority population to diagnose and cure in order to achieve HCV elimination. This integrated analysis pooled data from 20 cohorts in seven countries to evaluate the real-world effectiveness of the pangenotypic direct-acting antiviral (DAA) sofosbuvir/velpatasvir (SOF/VEL) in people with mental health disorders. HCV-infected patients diagnosed with mental health disorders who were treated with SOF/VEL for 12 w…
On the degree of binder activity of reclaimed asphalt and degree of blending with recycling agents
2020
It is common practice to assume full blending of the aged binder of reclaimed asphalt (RA) within the design of new asphalt mixtures. Although being practical, this assumption has often led designers to asphalt mixtures lacking binder. Hence, going towards recycled asphalt mixtures (RAM) there is a need to have a better understanding of the blending phenomena, to have a general agreement on terminology and finally adapting RA classification and mix design procedures accordingly. This manuscript aims at being both a reference and stimulus for the scientific community to work in this direction and on this basis provides a nomenclature and a theoretical framework of the blending phenomena. The…
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. …
Disciplinary Versus Institutional Approaches, Higher Education
2020
Institutional perspectives focus on HEIs as organisations and disciplinary perspectives focus on HEIs as cultural entities. This entry discusses the strengths and weaknesses of cultural and institutional approaches to higher education and higher education research. peerReviewed
Los problemas de agencia en las relaciones político-ciudadano dentro del régimen constitucional español contemporáneo
2018
Desde la transición política y con la firma de la constitución española de 1978 se han ido perpetrando ciertos problemas estructurales que han dificultado la representatividad de los ciudadanos así como la confianza en el agente que ha de representarles; de modo que la soberania popular se ha visto secuestrada por la burocracia de partidos que ha pasado a dictar la voluntad del pueblo. En esta investigación se lleva a cabo un repaso de los múltiples escollos que nuestra Carta Magna consagra, y se realiza un análisis de la coherencia interna respecto a la propia Constitución y los valores que en ella se promulgan.