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Biomedical subjects

A Nørgaard

Publications and source records attributed to A Nørgaard.

At least 55 records · Page 3Linked to original sources
PubMed1987

Heart Na,K-ATPase activity in cardiomyopathic hamsters as estimated from K-dependent 3-O-MFPase activity in crude homogenates.

The hamster hereditary cardiomyopathy provides a unique model for the study of membrane abnormalities during chronic congestive heart failure. It is associated with intracellular calcium accumulation, mitochondrial calcification and cell necrosis. Previous studies have shown a decrease in Na,K-ATPase activity purified from ventricle sarcolemma. The present study demonstrates a decrease in K-dependent 3-O-methylfluorescein phosphatase (3-O-MFPase) activity from 1.93 to 1.30 mumol/g wet wt. or 33% in crude homogenates from the left ventricle of 7-months-old cardiomyopathic hamsters as compared to control animals. This represents an equivalent decrease in Na, K-ATPase activity. The values are several times higher than previously published for membrane fractions of myocardium from the hamster. Concomitantly, there was an increase in intracellular Na-concentration of the myocardium of 42% whereas the K-concentration was unchanged. The decrease in Na,K-pump concentration may be of importance for the increase in intracellular sodium and ensuing calcifying necrosis observed in the myocardium of cardiomyopathic hamsters. It is emphasized that quantification of the Na,K-ATPase or Na,K-pump should preferably be performed using crude homogenates.

Animals↗
PubMed1987

Single dose pharmacokinetics of etretin and etretinate in psoriatic patients.

Etretin, an aromatic retinoic acid derivative, has recently been introduced as a possible substitute for etretinate in the treatment of severe psoriasis and other dyskeratoses. A total of nine patients with psoriasis of either sex in the age range 23-76 years was investigated after single dose oral drug administration, six were given 40 mg of etretin and three 40 mg of etretinate. A newly developed reversed-phase HPLC method was applied for simultaneous determination of etretin and etretinate in plasma. In patients receiving etretinate, the lag-time i.e. the time elapsing until appearance of first-order drug absorption was 1.24 +/- 0.27 for the parent drug and 0.69 hrs +/- 0.16 (mean value +/- S.D.) for its metabolite, etretin. Absorption half-times were 0.86 +/- 0.04 and 0.55 hrs +/- 0.09, respectively. The patients receiving etretin showed a lag-time of 0.42 hrs +/- 0.23 and an absorption half-time of 0.33 hrs +/- 0.28. This suggests that a fraction of etretinate is rapidly hydrolysed to etretin during the absorption process. The mean half-times of the distributory phases of disposition for etretinate and etretin were about 1 and 1.3 hrs and the apparent terminal half-lives were 6.57 +/- 2.09 and 5.52 hrs +/- 1.76, respectively. Assuming 40% systemic availability for both drugs the mean apparent volumes of distributions were calculated to be 1.50 +/- 0.46 and 1.31 l X kg-1 +/- 0.53 and mean plasma clearances were 177.8 +/- 105.8 and 175.9 ml X kg-1 X hr-1 +/- 81.4 for etretinate and etretin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acitretin↗
PubMed1987

Electrical injury causing ventricular arrhythmias.

Dangerous or long lasting ventricular arrhythmias developed in three patients who had sustained an electrical injury in which current passed through the thorax. In all three cases there was a delay of 8-12 hours between the injury and the onset of symptoms. The ventricular arrhythmias were severe and long lasting. In two of the three patients, ventricular tachycardia or ventricular fibrillation or both occurred and in one patient ventricular parasystole developed. No enzymatic evidence of myocardial necrosis was found but the results of an endomyocardial biopsy carried out in two of the three patients showed focal myocardial fibrosis and increased numbers of Na, K-pumps. The two patients with ventricular tachycardia became symptom free after appropriate antiarrhythmic treatment and in the third patient ventricular parasystole disappeared spontaneously within two years. Patients sustaining electrical injury in which current passes through the thorax should be monitored electrocardiographically for at least 24 hours, and patients with unexpected arrhythmias should be questioned about previous electrical injury.

Adult↗
PubMed1987

Diabetes decreases Na+-K+ pump concentration in skeletal muscles, heart ventricular muscle, and peripheral nerves of rat.

Na+-K+-ATPase or the Na+-K+ pump is essential for some specific properties of muscle and nerve tissue such as contractility and excitability. Previous studies have shown conflicting variations in Na+-K+-ATPase activity or Na+-K+ pump concentration of muscle cells in experimental diabetes. Our study demonstrates that early untreated diabetes in rats induced by injection of streptozocin is associated with decreases in [3H]ouabain binding-site concentration of 24-48% in various skeletal muscles and 16% in peripheral nerves as well as a decrease in K+-dependent 3-O-methylfluorescein phosphatase activity of 21% in the heart ventricle. These effects could be prevented by insulin treatment. They probably represent a decrease in the concentration of Na+-K+ pumps. There was no evidence for more than one population of Na+-K+ pumps in intact samples of skeletal muscle and nerves from normal, diabetic, and insulin-treated animals. The decrease in Na+-K+ pump concentration in nerve cells may be due to atrophy of the axons. In skeletal muscles, myocardium, and peripheral nerves, the observed decrease in Na+-K+ pump concentration may be important for the pathophysiology of diabetes. We emphasize that quantification of Na+-K+-ATPase or the Na+-K+ pump in muscle and nerve tissue from diabetic animals should preferably be performed with either intact samples or crude homogenates of whole tissue.

Animals↗
PubMed1987

Effect of magnesium depletion on 3H-ouabain binding site concentration in rat skeletal muscle.

In young (4-week-old) rats, dietary Mg depletion for 1.5 weeks was followed by a significant decrease in 3H-ouabain binding site or Na,K-pump concentration of up to 21% and in total K content of up to 11% in various hind limb muscles. K depletion was associated with a decrease in 3H-ouabain binding site concentration of up to 64% and in total K content of up to 31%. Mg depletion was associated with a similar correlation between the decrease in 3H-ouabain binding site concentration and total K content, as was K depletion (r = 0.98, p less than 0.001). Taken together, the results indicate that the decrease in the concentration of 3H-ouabain binding sites following Mg depletion is not primarily caused by Mg deficiency per se, but is probably secondary to the associated K deficiency. The decrease in Na,K-pump concentration may be of importance for the retardation of K repletion as well as the increase in digitalis toxicity observed with Mg deficiency.

Age Factors↗
PubMed1986

Quantification of the 3H-ouabain binding site concentration in human myocardium: a postmortem study.

The 3H-ouabain binding site concentration in the human myocardium was determined by measuring vanadate facilitated binding of 3H-ouabain to necropsy specimens of the left ventricle. The 3H-ouabain binding to samples weighing 4-6 mg was specific and saturable and appeared to take place to only one population of high affinity binding sites. After death the 3H-ouabain binding capacity degraded relatively slowly. From 6 to 24 h after death a mean decrease of 11% was seen in five patients, being significant in only one. In 15 patients aged 64-86 years the concentration of 3H-ouabain binding sites measured 6 h after death varied from 223 to 577 pmol X g-1 wet weight with no obvious relation to age or sex. The mean (SEM) value (413(26) pmol X g-1 wet weight) was 1.7 times higher than that previously reported for human myocardium. The concentrations of 3H-ouabain and 3H-digoxin binding sites were identical, and an excess of unlabelled ouabain completely prevented the specific binding of 3H-digoxin. In necropsy specimens weighing 1-2 mg from the endomyocardium obtained using a biotome the 3H-ouabain binding site concentration was in the same range as that in the myocardium. These findings indicate that it is possible to determine the concentration of Na, K-pumps in the human myocardium by measuring the 3H-ouabain binding capacity of biopsy specimens obtained during heart catheterisation or of specimens obtained within the first 18 h after death. This finding may be of importance for studying conditions in which the Na, K-pump concentration is suspected of undergoing variation.

Aged↗
PubMed1986

Warfarin binding to plasma albumin, measured in patients and related to fatty acid concentrations.

A method for determination of reserve albumin equivalent for binding of warfarin as previously described [1] has been used for assessing the influence of non-esterified fatty acid concentration (NEFA) on binding of warfarin to human serum albumin (HSA). Reserve albumin concentration can be used for calculation of the expected fraction of bound warfarin in serum. It is shown in vitro that binding of warfarin increases with added oleate up to 4 mol of oleate per mol of albumin and then decreases. Twenty-four patients on permanent warfarin treatment showed no correlation of serum albumin and reserve albumin concentrations (r = 0.10, P greater than 0.50) indicating that warfarin binding is governed by other factors. However, in the same patients there was a significant correlation between reserve albumin concentration and NEFA/HSA (r = 0.54, P less than 0.01). In one human volunteer changes of NEFA were provoked by strenuous work and it was found that reserve albumin concentration increased with NEFA concentration as expected from the in vitro findings (r = 0.90, P less than 0.001). Five uraemic patients on permanent warfarin treatment showed increasing reserve albumin concentration with increasing NEFA concentration induced by heparin. These findings indicate that, both in vitro and in vivo, the reserve albumin concentration for binding of warfarin and hence the free warfarin concentration is markedly influenced by NEFA concentration. This may add to the understanding of warfarin dose requirement during anticoagulant therapy.

Adult↗
PubMed1985

K+-dependent 3-O-methylfluorescein phosphatase activity in crude homogenate of rodent heart ventricle: effect of K+ depletion and changes in thyroid status.

The total Na+-K+-ATPase activity in rodent heart ventricle was quantified by determination of K+-dependent, ouabain suppressible 3-O-methylfluorescein phosphatase activity. A K+-dependent phosphatase activity of 0.80 mumol/min per g wet wt was obtained from crude homogenate of heart ventricle from 4-week-old guinea pigs. The anticipated association between K+-dependent phosphatase activity and Na+-K+-activated ATP hydrolysis could be clearly demonstrated in the crude homogenate. Based upon a molecular activity of 550/min the corresponding cardiac glycoside receptor concentration in the crude homogenate was 1450 pmol/g wet wt. In crude homogenate of heart ventricle from 3-month-old rats the K+-dependent phosphatase activity was 1.16 mumol/min per g wet wt. Following 4 weeks of K+ depletion of the rats, a decrease of 13% in total K+ content of the heart ventricle was seen. This was associated with a 14% decrease in K+-dependent phosphatase activity. The induction of hypo- and hyperthyroidism for 3 weeks in rats was followed by a decrease of 27% and an increase of 13% in K+-dependent phosphatase activity, respectively.

Animals↗
PubMed1985

Effects of ouabain, age and K-depletion on K-uptake in rat soleus muscle.

The relationship between the number of 3H-ouabain binding sites and the Na, K-pump mediated K-uptake has been characterized in rat soleus muscle. By brief exposure to 3H-ouabain (1 X 10(-6)-1 X 10(-5) mol/l) in vitro, it could be measured that 19-94% of the ouabain binding sites had been occupied. This was associated with a proportionate decrease in the ouabain suppressible K-uptake indicating that under strictly standardized conditions, measurements of 3H-ouabain binding sites quantify functional Na,K-pumps. When 3 week old rats were K-depleted for a further week followed by K-repletion 2 h before measurements, the 3H-ouabain binding site concentration was 61% lower than in age-matched control soleus muscles. However, the ouabain suppressible K-uptake was only reduced by 35%, partly because intracellular Na remained higher in the muscles obtained from K-depleted rats. From the 1st to the 4th week of life, the 3H-ouabain binding site concentration increased 2.9-fold. In contrast, the ouabain suppressible K-uptake decreased by a factor 3.5. Accordingly, in muscles from 1 week old rats, the ouabain suppressible K-uptake per 3H-ouabain binding site was 10-fold higher than in muscles from 4 week old rats. This difference could not be accounted for by changes in intracellular Na, total or extracellular water. It may be related to differentiation and change in structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1985

Estimation of stability of [3H]-ouabain binding site concentration in rat and human skeletal muscle post mortem.

The post mortem stability of the [3H]-ouabain binding site concentration and 3-O-methylfluorescein phosphatase (MFPase) activity was evaluated in rat skeletal muscle. As compared with the values measured in fresh tissue, the [3H]-ouabain binding site concentration in rat soleus muscle only dropped by around 1% per hour post mortem and a significant decrease was only seen after 12 h (15%, p less than 0.02). The 3-O-MFPase activity in rat gastrocnemius muscle showed a similar decrease. After 4 days, both parameters had dropped by 65% (p less than 0.001). In contrast, when intact fresh rat soleus muscles were incubated in Krebs-Ringer bicarbonate buffer at 20 degrees C for 4 days no significant decrease was seen in the [3H]-ouabain binding site concentration. In 10 human subjects the concentration of [3H]-ouabain binding sites was measured in specimens of the vastus lateralis muscle obtained within half an hour and at 6 and 12 h post mortem. The relative decrease after 6 h was insignificant (8%, p less than 0.30), whereas it was significant after 12 h (29%, p less than 0.005). These results have shown that the [3H]-ouabain binding sites in human skeletal muscle are resistant to post mortem degradation during the first 6 h after death. This makes it possible to perform measurements post mortem of the [3H]-ouabain binding site concentration in human skeletal muscle.

Aged↗
PubMed1985

Significance of skeletal muscle digitalis receptors for [3H]ouabain distribution in the guinea pig.

The importance of specific digitalis glycoside binding sites in skeletal muscle for the digitalis glycoside distribution in the guinea pig was evaluated using [3H]ouabain and [3H]digoxin binding assays. Measurements of [3H]ouabain binding capacity (EOmax) in gastrocnemius and heart muscles in vitro gave values of 474 +/- 15 and 1,092 +/- 39 pmol/g wet wt., respectively, in 4-week-old guinea pigs. Hence the total amount of [3H]ouabain binding sites in skeletal muscle and the heart was around 42,700 and 1,200 pmol, respectively. The apparent dissociation constants (Kd) for ouabain receptor interaction was 0.7 X 10(-7) and 1.5 X 10(-7) M for skeletal muscle and heart, respectively. Comparison of [3H]ouabain and [3H]digoxin binding revealed that these drugs are competitive. From birth to maturity the concentration of [3H]ouabain binding sites in guinea pigs decreased from 803 +/- 58 to 304 +/- 28 pmol/g wet wt. in gastrocnemius muscle and from 1,458 +/- 31 to 1,079 +/- 19 pmol/g wet wt. in the heart. After i.p. injection, measurements of the distribution of [3H]ouabain in plasma, skeletal muscle and the heart showed an almost equal relative specific occupancy of digitalis glycoside receptors in skeletal muscle and the heart: When 10% of the digitalis receptors in the heart were occupied by [3H]ouabain, 13% of those in the skeletal muscles were occupied. It was calculated that 1 hr after the i.p. administration of [3H]ouabain the amount of [3H]ouabain specifically bound to the skeletal muscles and the heart corresponded to 5 times and 1/10 the amount available in the extracellular pool, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗