Prediction of the corneal permeability of drug-like compounds.

Purpose: To develop a computational model for optimisation of low corneal permeability, which is a key feature in ocular drug development.

Methods: We have used multivariate analysis to build corneal permeability models based on a structurally diverse set of 58 drug-like compounds.

Results: According to the models, the most important parameters for permeability are logD at physiologically relevant pH and the number of hydrogen bonds that can be formed.

Defibrillation and the quality of layperson cardiopulmonary resuscitation-dispatcher assistance or training?

Aims Of The Study: To examine whether basic life support-defibrillation (BLS-D) training of laypersons enhances the speed of defibrillation and the quality of cardiopulmonary resuscitation (CPR) during a simulated ventricular fibrillation scenario compared with a situation where the care provider has no previous BLS-D training but receives dispatcher assistance with the use of an automated external defibrillator (AED) and the performance of CPR.

Methods: Fifty-two military conscripts of the Finnish Defence Forces who without previous medical education had been tested in a simulated cardiac arrest scenario with dispatcher assistance and thereafter received a 4-h BLS-D training. Six months later they were randomly divided to form teams of two and again tested in a similar scenario but without dispatcher assistance.

Can untrained laypersons use a defibrillator with dispatcher assistance?

Objectives: Automated external defibrillators (AEDs) provide an opportunity to improve survival in out-of-hospital cardiac arrest by enabling laypersons not trained in rhythm recognition to deliver lifesaving therapy. This study was performed to examine whether untrained laypersons could safely and effectively use these AEDs with telephone-guided instructions and if this action would compromise the performance of cardiopulmonary resuscitation (CPR) during a simulated ventricular fibrillation out-of-hospital cardiac arrest.

Methods: Fifty-four conscripts without previous medical education were recruited from the Western Command in Finland.

Reduction of dopamine synthesis inhibition by dopamine autoreceptor activation in striatal synaptosomes with in vivo reserpine administration.

In an attempt to clarify the mechanisms by which dopamine (DA) autoreceptor activation inhibits DA synthesis, the efficacy and potency of the D2 DA agonists bromocriptine, lisuride, and pergolide, and the D1-D2 DA agonist apomorphine were studied in rat striatal synaptosomes, in which the rate of DA synthesis (formation of 14CO2 from L-[1-14C]tyrosine) was increased 103% by treating the animals from which the synaptosomes were obtained with reserpine (5 mg/kg i.p. twice, 24 and 2 h before they were killed), using the striatal total homogenate as the standard synaptosomal preparation.

Synaptosomal dopamine autoreceptors: sensitivity changes after in vitro and in vivo treatments.

Dopamine (DA) synthesis in rat striatal synaptosomes was approximately doubled either by treating the animals from which the synaptosomes were obtained with reserpine, or by treating the preparations in vitro with d-amphetamine, ouabain or dibutyryl cyclic AMP. The concentration-response curve of DA synthesis inhibition by apomorphine was shifted to the right after treatment with all these compounds. The inhibitory effect of bromocriptine on DA synthesis was reduced completely after treatment with all the above compounds with the exception of dibutyryl cyclic AMP.