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1.
Eur J Mass Spectrom (Chichester) ; 22(5): 275-287, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27882894

RESUMEN

Tetrahedral [Cu(P)4][BF4]-type complexes (P = tertiary phosphine) are a class of monopositively charged compounds that have shown notable antitumor activity in both in vitro and in vivo tests. This biological property appears to be related to the peculiar physicochemical characteristics of these compounds. Although thermodynamically stable, they are labile at micromolar concentrations. Such a behavior allows the Cu(I) ion in [Cu(P)n]+ assemblies (n < 4) to interact with surrounding molecules, including the rich peptide/protein environment that metal complexes have to face in the physiological milieu on the way to tumor cells. The scope of this investigation was to study the interaction products that originate from the treatment in water/methanol mixtures of representative phosphino Cu(I) compounds with an excess of individual amino acids (AAs) selected on the basis of the donor atom likely involved in metal coordination (i.e. O-glycine, S-methionine and N-histidine). These interactions have been investigated in electrospray ionization mass spectrometry (ESI-MS), mainly in the positive ion mode [ESI(+)MS], and the interaction products have been characterized by sequential collisional experiments, performed by an ion trap instrument. Histidine and methionine, but not glycine, were able to mine Cu(I) from [Cu(P)n]+ assemblies through the formation of mixed [CuI(P)(AA)]+ and eventually [CuI(AA)2]+ adducts. The ability to substitute phosphine(s) by AAs and the strongest affinity for Cu(I) was proved by the study of the energetics of collisional-induced decomposition (CID) reactions [CuI(P)(AA)]+ → CuI(AA) + P]+. Among the investigated AAs, histidine displayed the strongest affinity for Cu(I). Transchelation of Cu(I) was similarly observed when [Cu(P)n]+ species were treated with the model tripeptide GlyGlyHis (GGH), the most investigated member of the amino terminal Cu(II) and Ni(II) (ATCUN) peptide family. GGH was able to form robust metal adducts not only with Cu(II) and the related divalent Zn(II) and Ni(II) ions, but also with monovalent ions, including Cu(I) and Ag(I). CID pathways of [CuI(GGH)]+ and [AgI(GGH)]+ were qualitatively superimposable and proceeded through losses of neutral fragments. Similar losses of neutral fragments were observed from [ZnII(GGH)] and [NiII(GGH)]. CID pathways of [CuII(GGH)]-/+ adducts instead took place mainly through intramolecular electron-transfer reactions comprising the reduction of Cu(II) to Cu(I) and the formation of fragment radical cations.


Asunto(s)
Aminoácidos/química , Cobre/química , Citotoxinas/química , Péptidos/química , Fosfinas/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Aminoácidos/análisis , Sitios de Unión , Cobre/análisis , Citotoxinas/análisis , Péptidos/análisis , Fosfinas/análisis , Unión Proteica
2.
Ageing Res Rev ; 95: 102237, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38367812

RESUMEN

BACKGROUND: Deprescribing is an important intervention across different settings in medicine, but the literature supporting such a practice is still conflicting. Therefore, we aimed to capture the breadth of outcomes reported and assess the strength of evidence of the use of deprescribing for health outcomes. METHODS: Umbrella review of systematic reviews of the use of deprescribing searching in Medline, Scopus, and Web of Science until 01 November 2023. The grading of evidence was carried out using the GRADE for intervention studies, whilst data regarding systematic reviews were reported as narrative findings. RESULTS: Among 456 papers, 12 systematic reviews (six with meta-analysis) for a total of 231 RCTs and 44,193 patients were included. In any setting, deprescribing was able to significantly reduce the number of total and of potentially inappropriate medications (PIMs) in older patients (low certainty of evidence) and to reduce the proportion of participants potentially having several or PIMs (moderate certainty of evidence). In community, supported by a high certainty of evidence, deprescribing was not more effective than standard care in decreasing injurious falls, any falls or number of fallers. In nursing home, deprescribing was associated with a significantly lower PIMs than standard care (very low certainty of evidence). In end-of-life situations, deprescribing significantly reduced mortality rate of approximately 41% (high certainty of evidence). CONCLUSIONS: Deprescribing is a promising intervention across different settings and situations, but a notable gap in the literature concerning its effects on substantial outcomes still exists.


Asunto(s)
Deprescripciones , Anciano , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Revisiones Sistemáticas como Asunto , Metaanálisis como Asunto
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