Biomedical subjects

N Heinz

Publications and source records attributed to N Heinz.

At least 37 records · Page 2Linked to original sources

PubMed1978

[Lipophilicity-protein binding relationship in cardenolides (author's transl)].

By equilibrium dialysis the binding of 19 cardenolides and cardenolide conjugates to human plasma proteins has been measured. The binding constants were compared with octanol-water partition coefficients described previously. No correlation was found between the two properties. Glycosides and conjugates of a certain genine show the same extent of protein binding, even if some of the derivatives differ in their physicochemical properties more than by three log units. It is concluded that cardenolide protein binding depends solely on hydrophobic property of the genine involved.

Blood Proteins↗

PubMed1977

[Synthesis and characterization of some cardenolide glucuronides and sulphates (author's transl)].

Cardenolide glucuronides are synthesized in the following way: firstly cardenolide glucosides are prepared by the reaction with acetobromglucose; secondly the hydroxymethyl group of the glucose moiety is oxydized in presence of a platinum catalyst to the carboxyl group of the final glucuronic acid. Glucuronides of the following cardenolides are prepared and described: digoxin, digoxigenin, digitoxin, digitoxigenin-monodigitoxoside, digitoxigenin, and 3-epi-digitoxigenin. Sulphates of digoxigenin, digitoxigenin, and 3-epi-digitoxigenin are prepared by direct reaction of these cardenolides with chlorosulphonic acid in pyridine. The assumed structure of some conjugates has been confirmed by n.m.r. spectroscopy. A high water solubility (6.7-65.1 g/l), a minute chloroform solubility (0.0002-0.0005 g/l), and a low octanol/polar nature of these compounds. Inotropic or toxic cardiac activities of the conjugates are examined on isolated guinea pig papillary muscles and by the Hatcher method on cats. Conjugates with at least one digitoxose show cardioactivities comparable to digoxin or digitoxin. In contrast to that the conjugated genins indicate decreased activities which are at least one-tenth of the potency of the unconjugated glycosides.

Animals↗

PubMed1977

[Affinity of polar digoxin and digitoxin metabolites for digoxin and digitoxin antibodies].

The affinities of some polar and non-polar digoxin and digitoxin metabolites to the related antibodies are largely dependent on the structure of their genin parts. Metabolites with unchanged genins show high cross reactivities towards their related antibodies when compared to the original immunogenic cardenolides. Towards the digoxin antibody the following cross reactivities were found: digoxin-16'-glucuronide 50%, digoxigenin 89.5%, and digoxigenin-3-glucuronide 85%. Values of the same order of magnitude were found with the corresponding digitoxin metabolites and the digitoxin antibody. In contrast, there is a marked decrease in cross reactivity caused by only minor changes in the genin part. With the digitoxin antibody the following cross reactivities are found: digoxin (i.e. 12-OH-digitoxin) 9.1%, 3-epi-digitoxigenin 5.6% and 3-epi-digitoxigenin-3-sulphate 1%. Bcause 12-hydroxylation has been reported to be one of several possible ways of digitoxin metabolisation in man, from a theoretical point of view erroneous results in the clinical digitoxin estimation by radioimmuno-assay are possible. In the case of all of the other metabolites the alterations in positive inotropic activity and cross reactivity run largely parallel.

Antibody Specificity↗

PubMed1977

The influence of polar and non-polar digoxin and digitoxin metabolites on the 86Rb-uptake of human erythrocytes and the contractility of guinea pig papillary muscles.

The potency of various digoxigenin and digitoxigenin derivatives with different polarity was tested in two biological systems: First, in an 86-Rb-erythrocyte assay which allows to determine the influence on active cation transport (measured as the glycoside concentration exerting half maximal inhibition of 86-Rb-uptake of human erythrocytes = IC50). Second, with isolated guinea pig papillary muscle, which allows to determine glycoside effects on contractile force (measured as the glycoside concentration exerting 100% increase of contractile force = C+100%). The IC50 of the substances covered a range from 3.2 to 4800 X 10(-9) M, the C+100% from 0.7 to 978 X 10(-6) M. In both assay systems the glucuronides of glycosides and genins were between 1.4 and 11 times less potent than the original substances. A highly significant correlation (p less then 0.0001) was found between IC50 and C+100% (r = 0.9996) and between log IC50 and log C+100% (r = 0.9819), the slope for the latter correlation being nearly unite (= 0.9912). The results support the hypothesis that inhibition of active cation transport is and important step in glycoside incuced posite-inotropic effect.

Animals↗

PubMed1976

[Concentration of cardiac glycosides in the heart and brain (author's transl)].

In cats the concentration of cardio-active glycosides in the heart and brain were investigated with trititum-labelled substances. Steady-state conditions were achieved by repeated i.v. injections of ouabain, digoxin, beta-methyldigoxin, digitoxin, and oleandrin over 5 days. 5 h after the last application glycoside concentrations were measured in plasma, urine, heart, cerebrum and cerebellum. Furthermore the metabolic pattern in these compartments was determined. 1. The glycoside concentration in the heart per g wet weight ranges only from 0.93 (oleandrin) to 1.88% (ouabain) of the daily administered dose per kg. 2. The concentrations in the brain show much higher differences between the diverse glycosides: ouabain with a concentration of 0.02%/g wet weight in the cerebrum shows the lowest and oleandrin with 1.60% the highest value. 3. By calculating the mean relative weights for the hearts (3.9 g/kg) and the brains (11.1 g/kg) 3.7% of the daily administered ouabain activity were found in the whole heart and only 0.18% in the whole brain. In contrast to these data the content of heart and brain after giving the more lipophilic oleandrin was 3.6% and 17.7% (!), respectively. 4. Under steady-state conditions the glycosides ouabain, digoxin, beta-methyldigoxin and digitoxin in heart and brain are mainly unchanged whereas oleandrin is transformed at a higher rate to polar metabolites.

Animals↗

PubMed1973