Biomedical subjects

H Lösgen

Publications and source records attributed to H Lösgen.

5 recordsLinked to original sources

PubMed1985

[Artificial liver support 1985].

Many techniques have been developed to support liver function in patients with hepatic failure. Only two of these methods are suited to be used in adequately equipped hospitals under appropriate safety conditions. Exchange of toxin-rich patient plasma against fresh frozen plasma will decrease plasma toxin levels and substitute coagulation factors and proteins. This procedure however should be used in intervals of at least 3-4 days because more frequent application will lead to lung or cerebral complications. Dialysis and hemofiltration will remove water soluble toxins from patient blood as well as excess amino acids which are considered to be precursors of toxic lipophilic metabolites. Addition of certain amino acids to dialysis fluid in physiological concentrations will help to avoid loss of essential amino acids (with approx. normal plasma concentration). In a very few special centers treatment by liver perfusion of human or pavian livers, or by liver transplantation can be performed.

Blood↗

PubMed1985

Adsorption and desorption characteristics of nucleotide based coenzymes on agarose encapsulated resins for long term cofactor supply of enzymatic reactions.

In order to find optimal long term cofactor supply for continuous enzymatic detoxification processes, different resins of varying surface, dipole moment, pore size, and chemical structure were investigated for their adsorptive capacity as well as their desorption behaviour towards various nucleotide based coenzymes. UDPGA, NADPGH, NADH, and SAM were gently shaken with agarose coated resins XAD-12, XAD-8, XAD-7, XAD-4, XAD-2, Dowex 1 X 2 (50-100; 200-400), Dowex 1 X 4 (20-50; 200-400), Dowex 2 X 8, and charcoal until all nucleotide was adsorbed or a saturation of the resins was achieved. High adsorption capacity was not always found to correlate with a steady release of cofactor in desorption experiments. Under this premise the optimal resin-cofactor combinations for long term cofactor supply were found to be XAD-12 for UDPGA, Dowex 2 X 8 for NADPH, Dowex 1 X 4 (20-50) for NADH, and XAD-7 for SAM.

Adsorption↗

PubMed1979

The application of immobilized enzymes in an artificial liver support system.

A novel method of extracorporeal support for fulminant liver failure is reported whereby the most important detoxification processes of the liver are reproduced in an enzyme reactor. Most of the endogenous toxins involved in hepatic coma can be deactivated directly by conjugation with a hydrophilic residue such as glucuronic acid or glutathione, or by the neutralization of active groups through structural modification by methyl transfer. The enzymes responsible for these processes have been isolated and purified from rabbit liver, and covalently bound onto a hemocompatible form of agarose matrix. This system has been shown to be capable of catalyzing the desired reactions with endogenous toxins such as phenols and mercaptans in vitro, and phenols in rabbits in vivo.

Acetaminophen↗

PubMed1979

Large agarose beads for extracorporeal detoxification systems. Preparation and enzymatic properties of agarose-bound UDP-glucuronyltransferase.

UDP-glucuronlytransferase, E.C. 2.4.1.17, has been solubilised from the microsomal fraction of liver homogenate from phenobarbital pretreated rabbits by lipase or detergent treatments. A 110-fold purification of the enzyme with respect to the crude homogenate was achieved by precipitation and column separations. The cholate-detergent solubilised enzyme was far more stable than that prepared by the lipase method. The partially purified UDP-glucuronyltransferase has been covalently bound to cyanogen bromide-activated agarose in the form of large haemocompatible beads to the extent of 0.22 mg protein per mg agarose dryweight, equivalent to about 25 mg of swollen gel. The acceptors for glucuronidation employed were the non-physiological phenolic compounds p-nitrophenol and 1-naphthol, and an exogenous and endogenous substance of physiological importance, namely paracetamol and phenol respectively. The immobilised enzyme exhibited at least 80% of the original activity of the solubilised enzyme, and the catalytic function was preserved for a much longer period of time in the carrier-bound form. The system described in this publication could well be applied in an extracorporeal liver assist device for the replacement of glucuronidation function.

Animals↗

PubMed1978

Large agarose beads for extracorporeal detoxification systems.

A method is reported by which agarose beads of diameter 1000 to 10000 microns can be prepared from Sepharose (R) 4B (native bead diameter 40 to 190 microns). Haemoperfusion experiments indicate that the enlarged beads are relatively haemocompatible; platelet loss is considerably less than that reported for many other bio-materials employed in haemoperfusion, and haemolysis is slight even after perfusion for several hours at flow-rates in excess of 25 ml/min. The beads can be activated by cyanogen bromide for the immobilisation of proteins. The sites for protein fixation are not restricted to the outside surface of the beads; small water soluble molecules, and serum proteins diffuse quite rapidly through the enlarged beads. A possible medical application of the large beads is in extracorporeal detoxification by chromatographic extraction or enzymatic modification, particularly of lipophilic toxins, using the enlarged beads as a carrier-matrix. The results described in this publication prove the viability of this concept. Such methods should be especially useful as artificial supports in fulminant hepatic failure.

Acetaminophen↗