The use of digoxin is limited by its narrow therapeutic index. American and European guidelines for the management of heart failure and atrial fibrillation recommend targeting a serum digoxin concentration (SDC) between 0.5 and 0.9ng/ml. The aim of the study was to retrospectively analyse SDCs and to assess compliance to the SDC target range recommended in the guidelines.

Tramadol is a centrally-acting analgesic that is widely used worldwide. It has been demonstrated to produce its antinociceptive effect in animals and its analgesic effect in humans by the combination of, and synergistic interaction between, its opioid and non-opioid mechanisms of action. Additional mechanisms have been proposed. Periodically, it is claimed that tramadol has an anti-inflammatory effect. We review this proposition.

Acetylcholine is recognised as a neurotransmitter substance, but it is also a ubiquitous messenger which acts in an autocrine and paracrine manner in a great variety of living organisms from bacteria to plants, from lower invertebrates to human beings. In vertebrates, the majority of cholinergic cells are non-neuronal. These cells give cholinergic signals to neighbour cells in tissues like skin, epithelia, endothelia, placenta, gut, lung, kidney, spermatozoids, lymphocytes, cancer cells, etc. These processes in the non-neuronal cholinergic system are becoming of prime pharmacological and toxicological importance. Cholinergic neuro-neuronal synapses are characterised by a moderately rapid initial nicotinic signal, followed by a complex trail of late responses. They are found in the autonomous nervous system, and also in several places of the central nervous system. Ultra-rapid cholinergic synapses such as neuromuscular junctions and nerve-electroplaque junctions of electric fish are able to transmit nerve impulses at a high frequency; the duration of individual impulses in these synapses has therefore to be very brief. Several mechanisms curtail the duration of individual impulses. One is present in the presynaptic membrane (the voltage-gated K+ current), the second is in the membrane of synaptic vesicles (the low affinity Ca2+/H+ vesicular antiport), and the third is highly active in the synaptic cleft (the asymmetric, collagen-tailed, molecular form acetylcholinesterase). Emphasis is also laid on mediatophore, a proteolipid complex localised in the active zones of the presynaptic membrane. Mediatophore is crucially involved in the mechanism of Ca2+-dependent and quantal release of transmitter. These observations force one to reconsider the classical “vesicle hypothesis”, as an explanation for acetylcholine release.

Studies conducted in the 1960s began to describe important changes in the behavior of women which were associated with the different phases of the menstrual cycle (for review, [1]).