Impact Of Experimental Conditions Research Articles

Sometimes you see them, sometimes you don't: IPSCs in the rat superficial superior colliculus.

Superficial superior colliculus (SSC) neurones were voltage-clamped and the current-voltage relationship of synaptically evoked currents analyzed in vitro. A strong interplay between excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) was identified. Glutamate receptor antagonists not only fully blocked EPSCs but IPSCs were also frequently reduced by the specific d,l,-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist (by 66.9%), indicative of glutamate-driven inhibitory projections. The GABA(A )receptor antagonist bicuculline enhanced EPSCs and either abolished or reduced (by 79.3%) IPSCs. The GABA(C) receptor antagonist 1,2,5,6-tetrahydro-(pyridin-4-yl)methylphosphinic acid decreased IPSCs in 80% of cells tested (by 24.1%), but had no effect on EPSCs. Varying the recording conditions influenced postsynaptic currents. At a holding potential of -60 mV, IPSCs were generally produced with intracellular chloride concentrations of both 5 and 10 mM (total n=24/30). However, with perforated-patch recordings using gramicidin, IPSCs were less frequently encountered (n=5/21), suggesting a higher intracellular chloride concentration in a large proportion of SSC neurones. Further assessment of experimental conditions revealed that two frequently used sodium channel blockers, QX-314 (bromide salt, intracellular) or tetrodotoxin (extracellular), shifted the IPSC reversal potential towards more positive values. Hence, IPSCs were not encountered at -60 mV in their presence. The level of stimulation intensity (minimal or maximal) did not influence IPSC production in these conditions. Thus, the current study describes the pharmacological properties of PSCs in the SSC and highlights the impact of experimental conditions on synaptic transmission, which requires consideration for past and present data reported in this preparation.

Identification of IgE-Binding Egg White Proteins: Comparison of Results Obtained by Different Methods

The binding of IgE to egg white proteins was investigated for 34 sera from adults with a positive case history and/or positive RAST towards egg, and the impact of experimental conditions on IgE binding in commonly used methods was studied. Radioimmunoblotting after SDS-PAGE of both reduced and unreduced egg white extracts showed complex reaction patterns. The results were confirmed by crossed radioimmunoelectrophoresis (CRIE). Radio dot immunobinding was used to investigate the effect of treatment of allergens for SDS-PAGE and to evaluate the other methods. As a conclusion, the use of combinations of at least two methods is recommended for the identification of IgE-binding egg white proteins. Of the 34 sera, 18 reacted with ovotransferrin, 13 with ovomucoid, 11 with ovalbumin and 5 with lysozyme. The amounts of IgE bound to ovalbumin and lysozyme were generally lower than the amounts bound to ovotransferrin and ovomucoid.

The placebo effect in healthy volunteers: Influence of experimental conditions on the adverse events profile during phase I studies

In contrast to the plethora of publications on placebo effects in patients, very little is known about placebo effects in healthy volunteers during clinical pharmacology studies. We therefore reviewed the adverse events spontaneously reported during placebo administration in 109 double-blind, placebo-controlled studies involving 1228 volunteers. The overall incidence of adverse events in the healthy volunteers during placebo administration was 19%. As expected, complaints were more frequent after repeated dosing (28%) and in elderly subjects (26%). Overall, the most frequent adverse events were headache (7%), drowsiness (5%), and asthenia (4%), with some variation depending on study design and population. In conclusion, these data shed new light on the impact of experimental conditions on the results of safety evaluations in healthy volunteers participating in clinical pharmacology studies.