The Na,K-ATPase is of major importance for active ion transport across the sarcolemma and thus for electrical as well as contractile function of the myocardium. Furthermore, it is receptor for digitalis glycosides. In human studies of the regulatory aspects of myocardial Na,K-ATPase concentration a major problem has been to obtain tissue samples. Methodological accomplishments in quantification of myocardial Na,K-ATPase using vanadate facilitated 3H-ouabain binding to intact samples have, however, made it possible to obtain reliable measurements on human myocardial necropsies obtained at autopsy as well as on biopsies of a wet weight of only 1-2 mg obtained during heart catheterisation. However, access to the ultimately, normal, vital myocardial tissue has come from the heart transplantation programs, through which myocardial samples from cardiovascular healthy organ donors have become available. In the present paper we evaluate the various values reported for normal human myocardial Na,K-ATPase concentration, its regulation in heart disease and the association with digitalization. Normal myocardial Na,K-ATPase concentration level is found to be 700 pmol/g wet weight. No major variations were found between or within the walls of the heart ventricles. During the first few years of life a marked decrease in myocardial Na,K-ATPase concentration is followed by a stable level obtained in early adulthood and normally maintained throughout life. In patients with enlarged cardiac x-ray silhouette a significant positive, linear correlation between left ventricular ejection fraction (EF) and Na,K-ATPase concentration was established. A maximum reduction in Na,K-ATPase concentration of 89% was obtained when EF was reduced to 20%. Generally, heart failure associated with heart dilatation, myocardial hypertrophy as well as ischaemic heart disease is associated with reductions in myocardial Na,K-ATPase concentration of around 25%. During digoxin treatment of heart failure patients a further reduction in functional myocardial Na,K-ATPase concentration of 15% has been found. Thus, the total reduction in functional myocardial Na,K-ATPase concentration in digitalised heart failure patients may well be of the magnitude 40%. In conclusion, it has become possible to quantify human myocardial Na,K-ATPase in health and disease. Revealed reductions are in heart failure of importance for contractile function, generation of arrhythmia and for digoxin treatment.

Binding Sites↗

PubMedDate not supplied

Chemical stability and plasma-catalyzed dealkylation of peptidyl-alpha-hydroxyglycine derivatives--intermediates in peptide alpha-amidation.

The production of alpha-amidated peptides has recently been shown to occur via a two-step process with peptidyl-alpha-hydroxyglycine being an intermediate. In this study the chemical stability and plasma-catalyzed conversion of various peptidyl-alpha-hydroxyglycine derivatives to their parent amide product have been examined. This conversion was shown to be independent of pH in the range pH 1-5 and to be apparently specific base-catalyzed at pH 6-10. At pH 7.4 and 37 degrees C the half-lives of decomposition of the derivatives ranged from 5.8 to 13.3 h. In 80% human plasma solutions (pH 7.4) the half-lives decreased to 1.3-3.9 h, indicating the occurrence of an enzyme activity in plasma catalyzing the dealkylation of peptidyl-alpha-hydroxyglycine derivatives. The best substrate for the plasma catalytic activity was found to be N-benzyloxycarbonyl-L-alanyl-alpha-hydroxyglycine.

Alkylation↗

PubMedDate not supplied

Hyperaldosteronemia in rabbits inhibits the cardiac sarcolemmal Na(+)-K(+) pump.

Aldosterone upregulates the Na(+)-K(+) pump in kidney and colon, classical target organs for the hormone. An effect on pump function in the heart is not firmly established. Because the myocardium contains mineralocorticoid receptors, we examined whether aldosterone has an effect on Na(+)-K(+) pump function in cardiac myocytes. Myocytes were isolated from rabbits given aldosterone via osmotic minipumps and from controls. Electrogenic Na(+)-K(+) pump current, arising from the 3:2 Na(+):K(+) exchange ratio, was measured in single myocytes using the whole-cell patch clamp technique. Treatment with aldosterone induced a decrease in pump current measured when myocytes were dialyzed with patch pipette solution containing Na(+) in a concentration of 10 mmol/L, whereas there was no effect measured when the solution contained 80 mmol/L Na(+). Aldosterone had no effect on myocardial Na(+)-K(+) pump concentration evaluated by vanadate-facilitated [(3)H]ouabain binding or by K(+)-dependent paranitrophenylphosphatase activity in crude homogenates. Aldosterone induced an increase in intracellular Na(+) activity. The aldosterone-induced decrease in pump current and increased intracellular Na(+) were prevented by cotreatment with the mineralocorticoid receptor antagonist spironolactone. Our results indicate that hyperaldosteronemia decreases the apparent Na(+) affinity of the Na(+)-K(+) pump, whereas it has no effect on maximal pump capacity.

4-Nitrophenylphosphatase↗

PubMedDate not supplied

The ongoing assessment of the supply of medical doctors in Denmark.

Explore the source record for details and available documents.

Adult↗

PubMedDate not supplied

Methods for assessment of future demand of medical doctors in Denmark.

BACKGROUND: Whereas supply prognoses is mainly a matter of establishing mathematical scenarios with ongoing adjustments of variables, reliable demand prognoses are more difficult and complex to establish. However, optimum use of human and educational resources and--on the other hand--sufficient supply of medical doctors calls for reliable supply as well as demand prognoses. METHODS: Based on a number of technical and political considerations the first demand prognosis was based on three different methods; 1. Changes in demand due to demographic changes. 2. An evaluation made by the owners of the hospitals. 3. An evaluation made by the scientific medical societies. RESULTS: The demand prognosis was found to be hampered by a number of limitations. Demographic changes beyond the next 10 years was found to be unreliable. Moreover, the demand observed during the last 20 years was only to a very limited extent explained by demographic changes. The owners of the hospitals could only prognosticate for an election period, i.e. for about 5 years,--and only in very general terms that were difficult to interpretate. From some counties the answers did only seem to be based on rather superficial analysis and gave very little information. Each of the Scientific Medical Societies claimed increasing demands for the next 25 years, despite marked expectations for diagnostic and therapeutic advantageous technological developments. The overall conclusion from the combined weighed analysis was an expected increase in the demand of medical doctors of about 1% per year in the short as well as in the long term (25 years). This should be compared to the observed development during the last 10 years, i.e. an annual increase of 1.7-1.8%.

Demography↗