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Biomedical subjects

E Fink

Publications and source records attributed to E Fink.

At least 127 records · Page 7Linked to original sources
PubMed1979

Antimalarial activity of Floxacrine (HOE 991) I. Studies on blood schizontocidal action of Floxacrine against Plasmodium berghei, P. vinckei and P. cynomolgi.

Floxacrine (HOE 991), 7-chloro-10-hydroxy-3-(4-trifluoromethylphenyl)3,4-dihydroacridine-1,9-(2H, 10H) dion, shows a high level of antimalarial action against blood-induced infection of drug-sensitive and drug-resistant lines of Plasmodium berghei in mice, rats and Syrian hamsters. The drug is also a potent blood schizontocide against drug-sensitive P. vinckei strains in rodents and P. cynomolgi in rhesus monkeys. The CD50/CD90 values against the drug-sensitive P. berghei strain ascertained in the '28-day test' in mice were 4.3/6.7 mg/kg after the oral route and 1.7/3.6 mg/kg after the subcutaneous (sc) route. In the 'two- and four-day test' the ED50 against sensitive P. vinckei was 0.7 mg/kg in both mice and rats. A moderate prophylactic effect could be demonstrated after the sc route probably due to a 'depot effect' of the water-insoluble active principle. Floxacrine was also highly active against P. berghei-lines which were resistant to chloroquine, mepacrine, dihydrofolate reductase inhibitors, sulfadoxine and dapsone. Resistance to HOE 991 could be developed in P. berghei and P. cynomolgi when the compound was used alone and administered repeatedly in subcurative doses. The antimalarial activity of the compound was not influenced by p-aminobenzoic acid or folic acid supplements in diets. Structural changes induced by floxacrine on pigment cytoplasm and nucleus in erythrocytic stages of P. berghei differed in some aspects from those of mepacrine and chloroquine. It is therefore assumed that the mode of action of floxacrine differs from that of the known antimalarial drugs. The general tolerance of the compound in rodents and rhesus monkeys is good and there is a wide range between the effective and maximum tolerated doses. Floxacrine was also effective at 100 ppm against pathogen Eimeria species in chickens, at 1000 mg/kg orally against Fasciola hepatica in rats and at 300-800 mg/kg orally against Heterakis spumosa in rats.

4-Aminobenzoic Acid↗
PubMed1979

Kallikrein inhibitors.

So far the Cl inactivator, alpha 2-macroglobulin, antithrombin III (in the presence of heparin), and alpha 1-antitrypsin have been identified as inhibitors of plasma kallikrein; alpha 1-antitrypsin reacts slowly also with tissue kallikreins. Of the various naturally occurring kallikrein inhibitors the basic trypsin-kallikrein inhibitor of bovine organs, aprotinin (the active substance of Trasylol), has attained by far the most interest. This inhibitor, which is produced by mast cells, has unusual properties due to its compact tertiary structure. Additional topics of aprotinin and structurally related inhibitors discussed are the mechanism of enzyme-inhibitor complex formation, the production of chemical mutants of aprotinin, the structural basis of kallikrein inhibition, and selected aspects regarding aprotinin medication.

Amino Acid Sequence↗
PubMed1978

Glucagon metabolism in the rat.

The renal handling of the biologically active glucagon component (the 3,500-mol wt fraction of immunoreactive glucagon [IRG]) and the contribution of the kidney to its overall peripheral metabolism were studied in normal and uremic rats. The metabolic clearance rate of glucagon was 31.8 +/- 1.2 ml/min per kg in normal animals and was diminished by approximately one-third in each of three groups of rats with compromized renal function: 22.3+/-1.6 ml/min per kg in partially (70%) nephrectomized; 22.9+/-3.3 ml/min per kg in bilaterally ureteral ligated; and 23.2+/-1.2 ml/min per kg in bilaterally nephrectomized animals. In normal rats the kidney contributed 30% to the overall metabolic clearance of the hormone and the renal extraction of endogenous and exogenous glucagon was similar, averaging 22.9+/-1.6% and was independent of plasma IRG levels over a wide range of arterial concentrations. The remnant kidney of partially (70%) nephrectomized animals continued to extract substantial amounts (16.6+/-4.2%) of the hormone, but accounted for only 8% of the total peripheral catabolism of IRG. In the two groups of animals with filtering kidneys, renal glucagon uptake was linearly related to its filtered load and could be accounted for by glomerular filtration and tubular reabsorption. However, the kidneys of animals with both ureters ligated (renal extraction of inulin = 3.2+/-1.8%) and hence virtual absence of glomerular filtration, continued to extract 11.5+/-1.9% of the renal arterial glucagon, contributing by 9% to its overall metabolic clearance, indicating that IRG uptake occurs also from the post glomerular capillaries.

Animals↗
PubMed1978

Development of a radioimmunoassay for pig pancreatic kallikrein.

A radioimmunoassay for the determination of pig pancreatic kallikrein was developed. The chloramine-T method was employed for the labelling of the antigen with 125I. The assay allows the determination of kallikrein in concentrations as low as 0.4 microgram/l. Pig urinary and pig submandibular kallikreins are indistinguishable from pig pancreatic kallikrein by the assay. No cross reactivity was observed for bovine trypsin and chymotrypsin, porcine trypsin and kallikreins of guinea pig submandibular glands and guinea pig coagulation glands. Because of the high specificity of the assay, which is not attainable with conventional assays based on the enzymatic activity, the radioimmunoassay is highly suited for investigations into the physiological role and the pharmacological mechanism of action of pig glandular kallikreins.

Animals↗
PubMed1978

Demonstration of acrosin in mouse spermatozoa.

Gelatinolytic activity of whole mouse spermatozoa was demonstrated by the gelatin film test. The presence of a trypsin-like protease (acrosin) in acidic extracts of mouse spermatozoa was shown by an electrophoretic method to separate the enzyme from a putative inhibitor.

Acrosin↗
PubMed1978

[Antimalarial 6-aminoquinolines. VII. 2- and 4-Alkoxy derivatives of 6-(4-diethylamino-1-methylbutylamino)-5,8-dimethoxyquinoline (author's transl)].

19 derivatives, 10 a--t, of 6-(4-diethylamino-1-methylbutylamino)-5,8-dimethoxyquinoline (1a) with alkoxy-, hydroxy-, and methylmercapto substituents in 4- and/or 2-position were synthesized with the aim of studying the influence of these substituents on antimalarial activity and toxicity of 1a. The alkoxy derivatives of 1a are highly active against P. vinckei (mouse). The 2- and 4-hydroxy derivatives, 10 l and 10 m, are inactive.

Aminoquinolines↗
PubMed1978

[Antimalarial 6-aminoquinolines. VIII. 2- and 4-amino derivatives (author's transl)].

Ten 2- or 4-amino derivatives 10b-I of 6-(4-diethylamino-1-methylbutylamino)-5,8-dimethoxyquinoline were synthesised with the aim of studying the influence of these substituents on antimalarial activity and toxicity of the 6-aminoquinolines. The 4-dialkylamino derivatives 10c-h were less active against P. vinckei (mouse) than 4-alkoxy derivatives. The 4-amino derivative 10b was inactive.

Aminoquinolines↗
PubMed1978

[Antimalarial 6-aminoquinolines. XI. 2-, 3-, and 4-alkyl-, aryl-, and arylalkyl derivatives (author's transl)].

23 derivatives 17a--z of 6-(4-diethylamino-1-methylbutylamino)-5,8-dimethoxyquinoline (1a) were synthesized with the aim of studying the influence of an increased lipophilicity on the biological activity. 17a--z are active against P. vinckei (mouse), but none of these derivatives is superior to the 2,4-dimethyl derivative 1d. Flat molecules (e.g. 17k and 17e) and their bulky hydrogenated derivatives (17I and 17f) show a comparable activity. This indicates that a flat structure is not essential for the activity of the 6-aminoquinolines.

Aminoquinolines↗
PubMed1976

[Citrate values in the whole blood of patients with malignant tumors of various locations].

Based on reports on elevated concentrations of 2-oxoglutarate in the blood of human subjects with tumors of various locations, data are presented on the concentration of citrate and pyruvate in the whole blood of 41 patients with malignant tumors (mainly of the female breast and of the digestive tract), 30 patients with benign surgical diseases and 12 healthy subjects. Adopting a level of significance of 2P=0.10 differences of concentration were found between the following collectives: (1) The mean value of citrate for the patients in tumor stage T4 was decreased by 23%, compared with healthy persons, and by 19%, compared with patients with benign surgical diseases. (2) The mean value of pyruvate for the patients with malignant tumors was increased by 40%, compared with healthy subjects and by 17%, compared with patients with benign surgical diseases. (3) The maximum of the pyruvate concentration was reached in tumor stage T3, where an increase of 52% was noted, compared with healthy subjects. (4) The pyruvate value of the patients with tumors of the digestive tract was increased by 34%, compared with healthy subjects. With regard to the total group of patients with malignant tumors, even with a low level of significance, no differences in citrate values were found as compared with the control groups. Thus the results do not indicate a disturbance of the citric acid cycle in the organism of tumor bearing hosts in general.

Adult↗