Homogeneous alignment of liquid crystalline dendrimers confined in a slit-pore. A simulation study.

In this work we present results from isobaric-isothermal (NPT) Monte Carlo simulation studies of model liquid crystalline dendrimer (LCDr) systems confined in a slit-pore made of two parallel flat walls. The dendrimers are modelled as a collection of spherical and ellipsoidal particles corresponding to the junction points of the dendritic core and to the mesogenic units respectively. Assuming planar uniform (unidirectional) soft anchoring of the mesogenic units on the substrates we investigate the conformational and alignment properties of the LCDr system at different thermodynamic state points. Tractable coarse grained force fields have been used from our previous work. At low pressures the interior of the pore is almost empty, since almost all LCDrs are anchored to the substrates forming two-dimensional smectic-like structures with the mesogens aligned along the aligning direction of the substrates. As the pressure grows the LCDrs occupy the whole pore. However, even at low temperatures, the smectic organization does not transmit in the interior of the pore and is preserved for distances of 2-3 mesogenic diameters from the walls. For this reason, the global orientational order decreases with increasing pressure (density). In the vicinity (2-3 mesogenic diameters) of the pore walls, mesogenic units preserve the smectic structure whose layers are separated by layers of spherical beads. In this region individual LCDrs possess a rod like shape.

Malnutrition and pharmacokinetics of penicillin in Ethiopian children.

Penicillin was given to 104 children with different nutritional status, normal, underweight, marasmus and kwashiorkor. Penicillin was given either intravenously, intramuscularly or orally and the plasma concentration was followed at regular times after administration. There was a significantly decreased plasma clearance of penicillin in all malnourished groups compared to the normal weight-for-age group. The half-lives of penicillin were, however, not significantly different between the nutritional groups. This was explained by the fact that also the volume of distribution was decreased in the malnourished group with a net result that the half-life was unchanged. The bioavailability was decreased if penicillin was given to non-fasting individuals. The greatest difference between fasting and non-fasting was seen in the severely malnourished children with marasmus and kwashiorkor. Therefore, it is advised that, if penicillin is given orally to very sick and undernourished children, the dose should be increased and preferably be given in the fasting state.

Disposition of salicylic acid in malnourished Ethiopian children after single oral dose.

The disposition of salicylic acid and salicyluric acid was studied in 57 Ethiopian children of varying nutritional status after oral administration of sodium salicylate in single doses of either 12.5 or 25 mg/kg. There was no apparent influence of nutritional status on oral salicylate disposition when related to total plasma concentrations. Unbound concentrations were predicted from total plasma concentrations on the basis of a single time point determination of protein binding in each individual, according to a Scatchard model. Areas under the unbound plasma concentration-time curve were larger and the fractional excretion of salicyluric acid was lower in children with kwashiorkor compared with control individuals. This was interpreted as lower hepatocellular metabolic activity in patients with kwashiorkor. Children with marasmus retained an unimpaired capacity for salicylate metabolism. The influence of saturable distribution and elimination are discussed.

Protein binding of salicylic and salicyluric acid in serum from malnourished children: the influence of albumin, competitive binding and non-esterified fatty acids.

The serum protein binding of salicylic and salicyluric acid has been determined by ultrafiltration in 60 children after administration of oral salicylate. The children were classified according to nutritional status: well-nourished (n = 12), underweight (n = 12), marasmic (n = 17) marasmic-kwashiorkor (n = 7) and kwashiorkor (n = 12). Salicylic acid free fractions were 0.106 +/- 0.026, 0.114 +/- 0.069, 0.141 +/- 0.037, 0.285 +/- 0.279 and 0.438 +/- 0.190 in the five groups, respectively. Salicyluric acid free fractions were 0.184 +/- 0.057, 0.280 +/- 0.282, 0.236 +/- 0.114, 0.484 +/- 0.497 and 0.646 +/- 0.261, respectively. The degree of binding was dependent on serum albumin levels, ligand concentrations and non-esterified fatty acids (NEFA). The NEFA/albumin ratio ranged from 0.05 to 6.6. The fitting of a one-site Scatchard binding model to the collective data was improved when a decrease was allowed for in the number of binding sites in proportion to NEFA concentrations. Salicyluric acid binding could be fitted only when inhibition of the parent compound was included. Binding was not affected by age or sex. The major determinants of salicylate binding in sera from malnourished children have thus been identified.