Repetition errors in habitual prospective memory: elimination of age differences via complex actions or appropriate resource allocation.

A challenge in habitual prospective memory tasks (e.g., taking medication) is remembering whether or not one has already performed the action. Einstein, McDaniel, Smith, and Shaw (1998, Psychological Science, 9, 284) showed that older adults were more likely to incorrectly repeat an action on habitual prospective memory tasks. Extending this research, we (a) biased participants either toward repetition or omission errors, (b) investigated whether performing a more complicated motor action can reduce repetition errors for older adults, and (c) examined participants' resource allocation to the prospective memory task. Older adults committed more repetition errors than younger adults regardless of biasing instructions when ongoing task demands were challenging (Experiment 1). Performing the more complex motor action, however, reduced repetition errors for older adults. Further, when the ongoing task was less demanding, older adults' repetition errors declined to levels of younger adults (Experiment 2). Consistent with this finding, the resource allocation profiles suggested that older participants were monitoring their output (prospective memory execution) in each trial block.

Educational simulation of the electroencephalogram (EEG).

We describe a model for simulating a spontaneous electroencephalogram (EEG) and for simulating the effects of anesthesia on the EEG, to allow anesthesiologists and EEG technicians to learn and practice intraoperative EEG monitoring. For this purpose, we developed a linear model to manipulate the amplitude of the activity in each of the traditional EEG frequency bands. Burst suppression patterns are simulated by manipulating an overall gain. To demonstrate the model feasibility, model parameters for thiopental and isoflurane were estimated guided by published data on the EEG effects of these anesthetic drugs. Using these estimates, EEG time signals were simulated for isoflurane at various partial pressures, and for bolus intravenous doses of thiopental. Comparison with actual recorded EEG signals showed that the changes produced by isoflurane and thiopental in the simulated signals are very similar to the changes in the actual signals, which was confirmed by two clinicians with experience and routine practice in intraoperative EEG monitoring.

Dissolution kinetics of griseofulvin in mixed micellar solutions.

The dissolution kinetics of the poorly water soluble, lipophilic model drug substance griseofulvin were studied in solutions containing simple and mixed micelles of sodium cholate (BS) and phosphatidylcholine (PC). Variables under investigation were the concentration of BS and the ratio PC/BS. A rotating disk apparatus was used to monitor the dissolution process. With this method, (mixed) micellar diffusion coefficients could be calculated and some detailed information about the physicochemical behavior and composition of mixed PC/BS micelles could be derived.

Chemical stability of liposomes: implications for their physical stability.

In the first part of this article, chemical and physical stability of aqueous liposome dispersions have been addressed. Chemical stability of phospholipids has been considered in two parts: oxidation and hydrolysis. Major attention has been paid to hydrolysis kinetics of phospholipids as a function of pH, temperature, buffer concentration and ionic strength. Furthermore, the effect of chain length, head group, state of aggregation, addition of cholesterol and presence of charge on the hydrolysis kinetics of phospholipids has been dealt with. In the second part physical stability of chemically degraded liposome dispersions has been evaluated. In the final part quality control assays for liposome dispersions is presented and a HPLC method with a refractive index detector for the analysis of phospholipids from aqueous liposome dispersions is described.

Hydrolysis of partially saturated egg phosphatidylcholine in aqueous liposome dispersions and the effect of cholesterol incorporation on hydrolysis kinetics.

Hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine (PHEPC) were studied as a function of pH, temperature, buffer concentration, ionic strength, and the effect of cholesterol incorporation. Results showed that PHEPC has a maximum stability at around pH 6.5. General acid base catalysis was observed for acetate, HEPES and Tris buffers. Increasing the ionic strength of the buffer solutions did not influence the hydrolysis kinetics. The relationship between the observed hydrolysis rate constants and the temperature could adequately be described by the Arrhenius equation. Incorporation of cholesterol did not affect the hydrolysis kinetics. This result indicates that the hydrolysis kinetics of PHEPC do not depend on the changes in bilayer rigidity induced by cholesterol incorporation. Cholesterol is stable under the experimental conditions used in this study; no changes were observed in cholesterol concentration over the experimental time interval.

Hydrolysis of saturated soybean phosphatidylcholine in aqueous liposome dispersions.

Hydrolysis kinetics of saturated soybean phosphatidylcholine (PC) were investigated as a function of pH, temperature, buffer concentration, buffer species, and ionic strength in aqueous liposome dispersions. A high-performance liquid chromatography method was used to separate PC and the hydrolysis products. Hydrolysis of PC followed pseudo first-order kinetics. Hydrolysis of fatty acid esters at sn-1 and sn-2 positions initially resulted in the formation of 2-acyl lyso-phosphatidylcholine and 1-acyl lyso-phosphatidylcholine; because of acyl migration, the most stable isomer of lyso-phosphatidylcholine, 1-acyl lyso-phosphatidylcholine, was formed predominantly. General acid-base catalysis was observed for acetate and Tris ions. The pH profiles at 40 and 70 degrees C for a buffer concentration of 0.05 M showed a minimum hydrolysis rate at about pH 6.5. The relationship between the observed rate constant and temperature could be described adequately by the Arrhenius equation below and above the phase transition temperature of saturated soybean PC (52 degrees C).

The effect of surface charge on the hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine and egg phosphatidylglycerol in aqueous liposome dispersions.

The hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine (PHEPC) and egg phosphatidylglycerol (EPG) were investigated as a function of surface pH at 60 degrees C. The bulk pH of the liposome dispersions was varied from pH 3.0 to 8.0. Charge was introduced to the liposomal bilayers by addition of EPG. Different electrostatic profiles were obtained at the bilayer-water interface by varying the surface charge density and the ionic strength of the buffer solutions. With the Gouy-Chapman equation the surface potential and with the Boltzmann equation the resulting shift in the surface pH compared to the bulk pH was estimated. The hydrolysis rate of both phospholipids increased with surface charge density in acidic medium; in alkaline medium the opposite was true. The hydrolysis rate constants, however, plotted as a function of surface pH agreed reasonably well with the results found with neutral liposomes.

The effect of aging on the physical stability of liposome dispersions.

In this study, the effect of aging, in terms of hydrolytic decomposition of the bilayer forming (phospho)lipids, on the physical stability of aqueous liposome dispersion was investigated in partially hydrogenated egg phosphatidylcholine (PHEPC) and egg phosphatidylglycerol (EPG) containing liposomes with or without cholesterol. The physical stability of the liposome dispersions was assessed by measuring the leak-in rate of a non-bilayer interacting hydrophilic marker molecule, calcein and changes in the particle size and its distribution in time. Additionally, permeability of either partially hydrolysed phospholipids or exogenous lyso-phosphatidylcholine(LPC) containing bilayers was calculated. The experiments were performed at 40 degrees C. Liposome dispersions were aged artificially by storing at 60 degrees C. The size of the liposomes and polydispersity index of the dispersions, in general, did not change significantly. The leak-in rate of calcein in externally added LPC containing liposomes was increased relative to the incorporated LPC concentration. The higher the LPC content of the bilayers, the higher the leak-in rate of calcein into liposomes. The leak-in rate of calcein, however, decreased first in partially hydrolysed phospholipids containing liposomes up to around 10% of hydrolysis and, afterwards, it started to increase. The leak-in rate was always lower in partially hydrolysed phospholipids containing liposomes than externally added LPC containing ones. Furthermore, the permeability of cholesterol containing bilayers was also always lower than the bilayers without cholesterol. In conclusion, addition of LPC into liposomal bilayers increases the permeability of bilayer. However, bilayers containing the hydrolysis products of phospholipids, both lyso-phospholipids and free fatty acids, did not show any enhanced permeability up to around 15% hydrolysis. Bilayer permeability is enhanced above 15% hydrolysis.