Development of an in-vivo active reversible butyrylcholinesterase inhibitor

Alzheimer’s disease (AD) is characterized by severe basal forebrain cholinergic deficit, which results in progressive and chronic deterioration of memory and cognitive functions. Similar to acetylcholinesterase, butyrylcholinesterase (BChE) contributes to the termination of cholinergic neurotransmission. Its enzymatic activity increases with the disease progression, thus classifying BChE as a viable therapeutic target in advanced AD. Potent, selective and reversible human BChE inhibitors were developed. The solved crystal structure of human BChE in complex with the most potent inhibitor reveals its binding mode and provides the molecular basis of its low nanomolar potency. Additionally, this compound is noncytotoxic and has neuroprotective properties. Furthermore, this inhibitor moderately crosses the blood-brain barrier and improves memory, cognitive functions and learning abilities of mice in a model of the cholinergic deficit that characterizes AD, without producing acute cholinergic adverse effects. Our study provides an advanced lead compound for developing drugs for alleviating symptoms caused by cholinergic hypofunction in advanced AD

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Il ruolo del medico competente nella valutazione del rischio

Occupational Physician has a marginal role in the Risk Assessment (RA). He is rarely involved and generally he only reads the documentation of RA made by other specialists in the prevention and safety. The law obliges him to work with the Employer, not only for the planning of health surveillance but also for the preparation of measures for the protection of the health and psycho-physical integrity of workers. But it is mainly for the content and methodology of the RA that it is necessary the contribution of the occupational physician. The RA is in fact a multi-stage and multi-disciplinary activity carried out in close collaboration with industrial hygienists, ergonomists, safety experts, psychologists. The occupational physician for his studies and education is the most appropriate professional to evaluate the quality of the data and to make an integration between indicators of environmental contamination and biological indicators of internal dose and effect or damage. We agree with the Italian Society of Occupational Health and Industrial Hygiene that is necessary to proceed to the recognition of the role of occupational physician as a "consultant" of the company about health and safety in the workplace and involved in RA even when it is not necessary the health surveillance

[Nervous system disease caused by acrylamide: 1st cases in Italy].

non disponibil

Fenotipizzazione in vivo del CYP 2E1: una nuova metodica per il monitoraggio biologico nell'esposizione occupazionale e sperimentale a benzene.

Abstrac