PubMed Health⌕ Search

Biomedical subjects

H G Weder

Publications and source records attributed to H G Weder.

At least 19 recordsLinked to original sources
PubMed1992

Activity of liposomal interleukin-2 in vitro.

Preclinical in vitro assessment of highly purified natural human interleukin-2 (IL-2) packed in egg lecithin liposomes was performed in short- and long-term T-cell cloning and propagation systems, and in experiments testing induction of lymphokine-activated killer (LAK) cells. Liposomal IL-2 (lip-IL-2) was essentially as active as free natural or recombinant IL-2 for cloning and culture of both helper and cytotoxic alloreactive T cells. However, lip-IL-2 was found to be markedly inferior to free natural or recombinant IL-2 for the induction of LAK cells from normal donors. Nevertheless, lip-IL-2 was able to maintain LAK cytotoxicity of populations preactivated with free IL-2. These results suggest that lip-IL-2 can interact with activated T cells and LAK cells in the same way as free IL-2, but that it is much less efficient at activating LAK-cell precursors.

Humans↗
PubMed1991

A lipophilic complex with 186Re/188Re incorporated in liposomes suitable for radiotherapy.

Liposomes with a 70 nm diameter were made by the detergent removal technique on a gel filtration column. The complex oxodichloroethoxy-bis-(triphenylphosphine)rhenium(V)=(Rephos) was irradiated by neutrons in the reactor at PSI. 45 +/ 5% of the radioactive complex was incorporated into the bilayer of the lipsomes during the liposome formation. The stablility of these radioactive liposomes was tested by dialysis: a loss of 40% of the radioactivity identified as perrhenate was observed after 8 days. Addition of the antioxidant ascorbic acid diminished the loss to 20%. Such liposomes carrying the lipophilic radioactive Re-complex can potentially be used in beta-radiotherapy. The gamma-lines of the two rhenium isotopes are helpful for localizing them in therapy controls by a gamma-camera, a big advantage compared to other nuclides proposed for therapy (e.g. 90Yttrium).

Isotope Labeling↗
PubMed1987

Studies of pharmacokinetics and therapeutic effects of glucocorticoids entrapped in liposomes after intraarticular application in healthy rabbits and in rabbits with antigen-induced arthritis.

Dexamethasone palmitate (DMP) entrapped in liposomes of defined sizes was administered intraarticularly in healthy rabbits and in rabbits with antigen-induced arthritis. The pharmacokinetics and therapeutic effect of liposomal DMP were measured and compared with corresponding experiments using microcrystalline triamcinolone acetonide (TAC). The small DMP liposomes (diameter 160 nm) showed a greater decrease in joint circumference than the 3-times-higher dose of microcrystalline TAC. Moreover, about 98% of administered TAC had already disappeared from the joint 6 h after injection, whereas about 36% of liposomal DMP was still measured in synovial fluid and synovium at the same time. Increasing the vesicle diameter from 160 to 750 nm (large liposomes) improved the retention of DMP by a factor of 2.6 within 48 h after injection in healthy rabbits. In addition, none of the liposomal glucocorticoid preparations ever suppressed the endogenous plasma cortisol level, which is in contrast to the suppression measured after administration of the microcrystalline preparation.

Animals↗
PubMed1986

(Na+ + K+)-ATPase in artificial lipid vesicles: influence of lipid structure on pumping rate.

(Na+ + K+)-ATPase from kidney outer medulla was incorporated into tightly-sealed, single-shelled lipid vesicles by a detergent-dialysis procedure. The rate of ATP-driven potassium extrusion from vesicles formed from different phosphatidylcholines (PC) was measured optically, using a voltage-sensitive dye in the presence of valinomycin. High transport rates were observed for di(18:1)PC, di(20:1)PC and di(22:1)PC, whereas vesicles formed from di(14:1)PC and di(16:1)PC were virtually inactive. The variation of pumping activity with lipid structure mainly results from differences in the amount of enzyme incorporated with the correct orientation into the vesicle membrane, and to a lesser extent from lipid-dependent variations of the intrinsic turnover rate of the enzyme. The activation energy of ion transport decreases in the order di(16:1)PC, di(18:1)PC, di(20:1)PC approximately equal to di(22:1)PC.

Adenosine Triphosphate↗
PubMed1986

Treatment of murine L1210 lymphoid leukemia and melanoma B16 with lipophilic cytosine arabinoside prodrugs incorporated into unilamellar liposomes.

Lipophilic prodrugs of I-beta-D-arabinofuranosyl cytosine (Ara-C), namely N4- and 5'-oleyl-I-beta-D-arabinofuranosyl cytosine (N4-oleyl-ara-C, 5'-oleyl-ara-C) and N4-palmitoyl-I-beta-D-arabinofuranosyl cytosine (N4-palm-ara-C) were incorporated into liposomes of various lipid compositions. The phospholipid vesicles were prepared by controlled dialysis of lipid/prodrug/detergent micelles yielding homogeneous and stable unilamellar liposomes. The liposome size ranged from 70 to 120 nm depending on the lipid composition and the amounts of prodrug incorporated. Depending on the total amount of micellized Ara-C prodrugs, a maximal incorporation rate of 250 micrograms prodrug per mg egg phosphatidylcholine was achieved. The incorporation efficiency was in the range of 85 to 97%. The in vivo antitumor activity of the liposome preparations against L1210 lymphoid leukemia was clearly superior by factors of 2-8 depending on the therapy schedule and route of drug application. The treatment of melanoma B16 with free Ara-C as well as with the prodrug-liposomes exhibit rather weak antitumor activity. Drug application by means of prodrug-liposomes yields equal or higher tumor-inhibitory effects at drug concentrations which were 2-4 times lower than those of free Ara-C. Although drug tolerance and myelosuppression studies with Swiss albino mice revealed that the prodrug-liposomes were 5-10 times more toxic than free Ara-C, a substantial improvement of efficiency could be observed. The incorporation of the ara-C prodrugs into liposomes provides protection against fast degradation and systemic elimination which might be an explanation for the improved antitumor effect of these preparations.

Animals↗
PubMed1985

5'-O-Palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine--novel lipophilic analogues of 5'-fluoro-2'-deoxyuridine: synthesis, incorporation into liposomes and preliminary biological results.

5'-O-palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine were prepared by the reaction of 5-fluoro-2'-deoxyuridine in dimethylacetamide with palmitic acid chloride. The incorporation of the synthesized prodrugs into liposomes composed of egg phosphatidylcholine/stearylamine/cholesterol/alpha-tocopherol at a molar ratio of 10:1:2:0.05 was nearly quantitative; homogeneous bilayer vesicles (75 nm diameter) were obtained. Preliminary tolerance studies revealed that the prodrug-liposome preparations are about 20-60 times more toxic than the parent drug. The prodrugs incorporated into liposomes were 10 to 30 times more active against murine colon 38 carcinoma compared to the free drug. In comparison to the administration of the prodrugs in peanut oil the liposomal preparations seem to exert improved effects and represent a valuable drug delivery system for parenteral applications.

Animals↗
PubMed1981

Liposomes of controllable size in the range of 40 to 180 nm by defined dialysis of lipid/detergent mixed micelles.

Liposomes, in the size range of 40--180 nm, are formed when lipid and additives are solubilized with detergent, yielding defined mixed micelles, and the detergent is subsequently removed by controlled dialysis. Their most important properties are that they are indeed unilamellar with usefully large encapsulated volumes and are homogeneous in size. Liposomes have been formed from both natural and synthetic phospholipids with cholesterol and charged molecules added. This relatively simple technique may be particularly useful for encapsulating drugs, enzymes and other macromolecules and in studies of reconstitution of membrane proteins.

Animals↗
PubMed1978

The preparation of large single bilayer liposomes by a fast and controlled dialysis.

A new method is described for the preparation of large, homogeneously sized, single bilayer phospholipid vesicles. This method, based on a fast and controlled dialysis of sodium cholate from phosphatidylcholine/cholate mixed micelles, has the advantage of high yield of homogeneous vesicles avoiding any dilution and mechanical stress during preparation. Physicochemical properties of these vesicles are examined by several techniques and compared with those prepared with other methods.

Cholic Acids↗
PubMed1978

The interaction of central acting drugs with glutamate dehydrogenase.

The neuroleptics chlorpromazine, fluphenazine, triflupromazine and thioridazine seem to effect the aggregation of glutamate dehydrogenase by binding to one single site of the polypeptide chain, possibly the GTP site. This interaction could biologically be of importance for the degree of activity at high enzyme concentrations found in vivo. Amitriptyline and fluorazepam also bind to a specific single site of the polypeptide chain without effecting the aggregation of the oligomers. Because of the rather low affinity of these sites the binding of these drugs in vivo does not seem to cause a concentrating effect in the mitochondria.

Adenosine Diphosphate↗
PubMed1977

[Androgen binding in human plasma and its physiological significance (author's transl)].

The literature on the determination and the meaning of androgen binding to plasma proteins is reviewed. Because of the high affinity for the active androgens the sex hormone binding globulin (SHBG) is of considerable importance. The blood level of this globulin varies according to sex, age, medicamentation and pathological conditions. The influence of protein binding on the metabolism and mechanism of action of androgens is discussed and the hypotheses of several authors are compared.

Age Factors↗
PubMed1976

Aminopeptidase II from Bacillus stearothermophilus.

1. The low molecular weight aminopeptidase (aminopeptidase II) from Bacillus stearothermophilus cells grown at 50 degrees C was purified to a homogeneous state. 2. Molecular weight determination by sodium dodecyl sulfate gel electrophoresis resulted in a value of 46 000 for the subunits. A molecular weight of 80 000-100 000 has been reported for the native enzyme. We therefore conclude that aminopeptidase II is a dimeric enzyme. 3. The amino-terminal sequence, the amino acid analysis and the subunit molecular weight of aminopeptidase II show no relationship to the corresponding data of aminopeptidase I. 4. Aminopeptidase II binds two Co2+ per subunit. The dissociation constants of these ions determined by binding studies and by kinetic analysis agree within experimental error.

Amino Acids↗
PubMed1976

Characterization of interactions of phenothiazines and related drugs with lipids by UV-spectrophotometry.

The UV-spectrum of chlorpromazine undergoes a red shift in the presence of vesicles of biological membranes or phospholipids, triglycerides, serum lipoproteins or fatty acids. The resulting difference spectrum has two positive peaks at about 260 and 320 nm and two negative peaks at 250 and 290 nm. This interaction signal, which was elicited in the presence of as little as 3 muM oleic acid, was dependent on the concentrations of both ligand and binder. It was abolished by 8 M urea, diminished by temperature increase up to 70 degrees C, but not changed by varying the ionic strength from 0 to 0.5. The chlorpromazine-triglyceride interaction signal was strongly enhanced with pH increasing from 6 to 10. The signal was only obtained with ligands fulfilling specific structural requirements, e.g., phenothiazines and most iminostilbenes, but not carbamazepine, imipramine, and amitriptyline.

Animals↗
PubMed1975

[Interactions of some parasympatholytics and structurally similar drugs with bovine serum albumin].

The interactions of the parasympatholytic drugs adiphenin, adiphenin H and propanthelin and the structurally related compounds, diphenhydramine, D-propoxyphene and methadone with bovine serum albumin (BSA) are studied by equilibrium dialysis and ultracentrifugation. The results show that BSA has a few binding sites (n less than 10) for the mentioned drugs. The association between the compounds under study and BSA are relatively weak. The binding constants are in the range of 10(3) l/Mol.

Binding Sites↗