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Biomedical subjects

U Sprandel

Publications and source records attributed to U Sprandel.

At least 19 recordsLinked to original sources

Temperature-induced shape transformation of carrier erythrocytes.

Erythrocytes have been proposed as cellular carriers for enzymes and drugs for protected delivery, slow release, or targeting to specific organs. Several studies have established the heterogeneity of resealed carrier erythrocytes concerning various characteristics, including morphology. Carrier erythrocytes were prepared by hypo-osmotic dialysis and consecutive iso-osmotic resealing at different temperatures, and the morphology of these cells was studied by scanning electron microscopy. Different cell shapes could be prepared by temperature variations during resealing or incubation. All intermediate shapes of echinocytosis were observed at low temperatures or with depleted energy supply but could be reversed to biconcave discocytes. Resealing at 4 degrees C resulted in highest percentage of echinocytes III, spherocytes, and leaky cells. Spontaneous resealing of 20% of the cells was obtained at high lysis temperatures. Combining low temperatures for lysis and high temperatures for resealing and sufficient energy supply are advantageous for highest recovery of biconcave discocytes. Shape of the erythrocyte, is the result of divergent forces, and temperature during resealing was found to be an important factor.

Drug Carriers↗

Osmotic fragility of drug carrier erythrocytes.

Erythrocytes have been proposed as biogradable cellular carriers for drugs. Potentials of this therapeutic approach are organ-specific targeting, protection and prolonged in vivo function of the encapsulated drugs. Previous studies demonstrated the advantage of a hypo-osmotic dialysis procedure for macromolecule loading resulting in cells that are closely similar to normal erythrocytes. Osmotic fragility of unloaded and loaded "carrier" erythrocytes was studied both in respect of shelf-life and in vivo survival. Sudden haemolysis which is characteristic for normal erythrocytes was never obtained with carrier erythrocytes. Haemolysis appeared at all osmotic pressures and increased stepwise indicating the existence of various cell populations. However, the majority of cells were haemolysed at lower values of the osmotic fragility curve. Osmotic fragility was highly increased when cytotoxic chemotherapeutics were encapsulated, and these cells appeared as spherocytes using scanning electron microscopy. Osmotic fragility proved to be a simple but reliable method for the in vitro evaluation of carrier erythrocytes and the effect of the encapsulated substances.

Erythrocyte Aging↗

Organic-acid transport in resealed haemoglobin-containing human erythrocyte 'ghosts'.

The transport of organic acids across the membrane of resealed haemoglobin-containing erythrocyte 'ghosts' prepared by a dialysis technique has been studied. The present work forms part of studies directed towards the use of erythrocyte cellular carriers in enzyme-replacement therapy of inherited metabolic diseases. Oxalic acid, glycollic acid and glyoxylic acid were taken as representative of aliphatic acids of low molecular mass and benzoic and cinnamic acids as representative of unsubstituted aromatic acids. These selected acids are important in the diseases with which the present work is concerned. Comparison of influx and efflux transport characteristics showed that erythrocyte 'ghosts' retain transport properties closely similar to those of normal erythrocytes. Rapid transport was observed with all organic acids studied and there was a linear relationship between initial amount of influx and external concentration of aliphatic acid. Saturation of the transport system was not observed up to 1 mM external concentration, and the presence of plasma in the external medium had no effect on transport characteristics. Transport in intact erythrocytes and prepared erythrocyte 'ghosts' from patients with hyperoxaluria was also studied.

Biological Transport↗

In vivo life span of resealed rabbit erythrocyte 'ghosts'.

Resealed erythrocyte 'ghosts' have been proposed as biodegradable in vivo carriers for exogenous enzymes in the therapy of inherited metabolic diseases. Extended animal studies are essential prior to clinical application. The survival of rabbit erythrocyte 'ghosts' has been studied to find a suitable animal model. In vitro experiments have shown that incorporation of macromolecules into rabbit erythrocyte 'ghosts' is much lower than into human erythrocyte 'ghosts'. This could be related to the continuous cell destruction during 'ghost' preparation procedures. Rapid destruction of 'ghosts' in the circulation was obtained in all experiments particularly in the first minutes and hours. Cells surviving this initial period showed a longer life span and kinetics of further cell destruction followed a logarithmic function similar to that of normal erythrocytes. The experimental use of rabbits appears limited to studies where rapid uptake of the enzyme is required and other animal models must be studied when prolonged survival of the erythrocyte 'ghosts' is required, e.g., as the site of substrate degradation in the circulation.

Animals↗

Acceleration of ethanol elimination with fructose in man.

The elimination of ethanol is known to be accelerated by fructose. Studies of continuous infusions of both ethanol and fructose as the basis for quantitative calculations are not available. In healthy volunteers fructose infusions were given for several hours during and immediately after the end of ethanol infusions. Both increase and elimination of ethanol in blood were effected to the same extent by fructose when compared to control experiments. Average increases in the elimination rates of ethanol were up to 80%; however, each subject displayed individual variations.

Adult↗

In vitro studies on resealed erythrocyte ghosts as protein carriers.

Resealed erythrocyte ghosts have been proposed as in vivo carriers for enzyme replacement therapy of inherited metabolic diseases. In comparative studies of methods for reversible hypotonic haemolysis of erythrocytes, a five-fold increased entrapment of human serum albumin was obtained by use of a dialysis procedure instead of direct dilution. The percentage incorporation of protein was also affected by varying mixing procedure, haematocrit, lysis, and resealing times but not by varying buffer composition or added protein concentrations over a wide range. Higher protein entrapment was observed with time-expired blood compared to fresh blood and this may be ascribed to increased osmotic fragility of the erythrocyte membrane in stored cells. Haemolysed and resealed ghosts prepared by any method used were smaller than normal erythrocytes as measured with a Coulter Counter and with a fluorescence-activated cell sorter, and protein entrapment reduced the ghost size further.

Blood Preservation↗