Driving difficulties and adaptive strategies: the perception of individuals having sustained a mild traumatic brain injury.

Introduction. After a mild traumatic brain injury (mTBI), individuals quickly resume driving. However, relatively little is known about the impact of mTBI on driving ability and, notably, on the perceived influence of postconcussive symptoms on driving. Hence, the objective of this study was to document the perception of driving abilities in individuals with mTBI. Method. Twenty-seven drivers with mTBI were interviewed to document their perception regarding their driving abilities. Both driving-related difficulties and compensatory strategies used to increase driving safety were documented. A mixed quantitative and qualitative analysis of the data was completed. Results. 93% of participants reported at least one difficulty perceived as having an impact on everyday activities. Most frequently named problems affecting driving were fatigue and reduced concentration. In addition, 74% of participants had adapted their driving or developed strategies to compensate for driving difficulties. Discussion/Conclusion. Postconcussive symptoms have repercussions on driving ability. However, people with mTBI tend to be aware of their difficulties and develop, over time, adaptive strategies. Preventive measures are thus warranted to increase health care professionals' awareness of the potential consequences of mTBI on driving ability and to promote guidelines for the safe resumption of driving after injury.

Exploration of a new series of PAR1 antagonists.

Two series of new PAR1 antagonists have been identified. The first incorporates a cinnamoylpiperidine motif and the second a cinnamoylpyridine pattern. The synthesis, biological activity and structure-activity relationship of these compounds are presented. In each series, one analog showed potent in vivo antithrombotic activity in a rat AV shunt model, with up to 53% inhibition at 1.25mpk iv for compound 30.

Discovery of novel protease activated receptors 1 antagonists with potent antithrombotic activity in vivo.

Protease activated receptors (PARs) or thrombin receptors constitute a class of G-protein-coupled receptors (GPCRs) implicated in the activation of many physiological mechanisms. Thus, thrombin activates many cell types such as vascular smooth muscle cells, leukocytes, endothelial cells, and platelets via activation of these receptors. In humans, thrombin-induced platelet aggregation is mediated by one subtype of these receptors, termed PAR1. This article describes the discovery of new antagonists of these receptors and more specifically two compounds: 2-[5-oxo-5-(4-pyridin-2-ylpiperazin-1-yl)penta-1,3-dienyl]benzonitrile 36 (F 16618) and 3-(2-chlorophenyl)-1-[4-(4-fluorobenzyl)piperazin-1-yl]propenone 39 (F 16357), obtained after optimization. Both compounds are able to inhibit SFLLR-induced human platelet aggregation and display antithrombotic activity in an arteriovenous shunt model in the rat after iv or oral administration. Furthermore, these compounds are devoid of bleeding side effects often observed with other types of antiplatelet drugs, which constitutes a promising advantage for this new class of antithrombotic agents.

Synthesis and evaluation of a novel series of farnesyl protein transferase inhibitors as non-peptidic CAAX tetrapeptide analogues.

A novel series of compounds, derived from 4-amino-phenyl piperazine, has been designed to selectively inhibit farnesyl protein transferase (FPTase) as CAAX tetrapeptide analogues. Certain of these compounds were shown to possess low nanomolar inhibitory activity both against the isolated enzyme and in cultured cells.

From pure FPP to mixed FPP and CAAX competitive inhibitors of farnesyl protein transferase.

Starting from a FPP analogue with nanomolar inhibitory activity against isolated FPTase, yet lacking activity in cellular assays, structural modifications were performed to enhance cellular activity by removing all acidic functionalities. Overall, these changes resulted in the transformation of a pure FPP to a mixed FPP and CAAX competitive inhibitor with nanomolar activity on isolated FPTase and micromolar inhibitory activity in the farnesylation of H-Ras in cultured DLD-1 cells.

Solid-phase preparation of hydantoins through a new cyclization/cleavage step.

An efficient process for the solid-phase synthesis of hydantoins has been developed. The amino acid starting material is anchored to the resin from its carboxylic acid end through formation of a very stable amide bond. After introduction of different functional groups, the cleavage/cyclization step can be performed in acidic or basic conditions.