Design, synthesis, ADME properties, and pharmacological activities of β-alanyl-D-histidine (D-carnosine) prodrugs with improved bioavailability.

β-Alanyl-D-histidine (D-CAR, the enantiomer of the natural dipeptide carnosine) is a selective and potent sequestering agent of reactive carbonyl species (RCS) that is stable against carnosinase, but is poorly absorbed in the gastrointestinal tract. Herein we report a drug discovery approach aimed at increasing the oral bioavailability of D-CAR. In our study we designed, synthesized, and evaluated a series of novel lipophilic D-CAR prodrugs.

[Application of the balanced scorecard for evaluating the training process].

A training project in which nurses acted as tutors to novice nurses was introduced in the Ferrara University Hospital, with the aim of helping them to achieve the skills and professional expertise required in an operating theatre environment. Owing to the involvement of all the surgical divisions of the hospital and the continual addition of new staff, the Balanced Scorecard method (BSC) was used to assess the impact of training on the entire organization. The BSC method, a multidimensional method born in the USA in the 1990's, made it possible to assess the utility of training in the light of achieving institutional goals.

Albumin is the main nucleophilic target of human plasma: a protective role against pro-atherogenic electrophilic reactive carbonyl species?

The aim of this work was to study the metabolic fate of 4-hydroxy- trans-2-nonenal (HNE) in human plasma, which represents the main vascular site of reactive carbonyl species (RCS) formation and where the main pro-atherogenic target proteins are formed. When HNE was spiked in human plasma, it rapidly disappeared (within 40 s) and no phase I metabolites were detected, suggesting that the main fate of HNE is due to an adduction mechanism. HNE consumption was then monitored in two plasma fractions: low molecular weight plasma protein fractions (<10 kDa; LMWF) and high molecular weight plasma protein fractions (>10 kDa; HMWF).

Identification of actin as a 15-deoxy-Delta12,14-prostaglandin J2 target in neuroblastoma cells: mass spectrometric, computational, and functional approaches to investigate the effect on cytoskeletal derangement.

A proteomic approach was used to identify 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) protein targets in human neuroblastoma SH-SY5Y cells. By using biotinylated 15d-PGJ2, beta-actin was found as the major adducted protein; at least 12 proteins were also identified as minor biotin-positive spots, falling in different functional classes, including glycolytic enzymes (enolase and lactate dehydrogenase), redox enzymes (biliverdin reductase), and a eukaryotic regulatory protein (14-3-3gamma). 15d-PGJ2 induced marked morphological changes in the actin filament network and in particular promoted F-actin depolymerization as confirmed by Western blot analysis.

Actin Cys374 as a nucleophilic target of alpha,beta-unsaturated aldehydes.

We have recently shown that actin can be modified by the Michael addition of 4-hydroxynonenal to Cys374. Here, we have exposed purified actin at increasing acrolein concentrations and have identified the sites of acrolein addition using LC-ESI-MS/MS. Acrolein reacted with Cys374, His87, His173, and, minimally, His40.