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Biomedical subjects

P Lund

Publications and source records attributed to P Lund.

At least 91 records · Page 5Linked to original sources

Inhibition of carbamoyl-phosphate synthase (ammonia) by Tris and Hepes. Effect on Ka for N-acetylglutamate.

The apparent Ka for N-acetylglutamate of rat liver carbamoyl-phosphate synthase is 11 microM in phosphate buffer, a value 10-fold lower than reported in other buffer systems. Tris and Hepes inhibit competitively with N-acetylglutamate. The proportion of carbamoyl-phosphate synthase in the active enzyme-acetylglutamate complex in vivo may be higher than previous calculations suggest, which re-opens the question of the involvement of N-acetylglutamate in the regulation of urea synthesis.

Animals↗

The matrix water space of mitochondria in situ in isolated hepatocytes.

The intracellular and mitochondrial matrix water-permeable spaces were measured in intact, respiring hepatocytes from normal fed, 48 h starved, and protein fed rats. The mitochondrial matrix constitutes 15-20% of the total intracellular water, a proportion greater than has generally been assumed.

Animals↗

Amino acid profiles during development of the fetal rat.

Umbilical blood venous-arterial differences for amino acids across the rat fetus show uptake of disproportionately large amounts of glutamine, alanine and lysine relative to their contribution to total body protein. Free amino acid concentrations in fetal liver tend to increase during development, but show a rapid adjustment to near-adult values within 24 h after birth.

Amino Acids↗

Symptoms and signs predictive of the voiding pattern after acute urinary retention in men.

Over a 9-month period 228 men were admitted for acute urinary retention to six different casualty wards in the Copenhagen area. The patients were followed in the corresponding urological departments for one year. Twenty-seven variables were registered for each patient. The cumulative rate of recurrent retention was 56% after one week and 68% after one year. Factors predictive of preserved voiding ability were a retained volume less than 500 ml, a known event provocative of acute retention, and a maximum flow rate of more than 5 ml/s after the retention. The maximum flow rate measured within the first week after the retention was reliable within the follow-up period if the voided volume was 150 ml or more. The etiology of the acute retention was infravesical obstruction in 90% of the patients, and 85% required subsequent surgical treatment. Predictive of surgical treatment for infravesical obstruction were recurrent urinary retention within one week, a volume of retention of more than 500 ml, the absence of a provocative situation prior to the retention episode and nocturia twice or more.

Acute Disease↗

Acute urinary retention in women: a prospective study of 18 consecutive cases.

Over a 9 month period 18 women were admitted for acute urinary retention to six different Copenhagen hospitals, serving a population of approximately 700,000 people. Urodynamically 9 patients had underactive detrusor function, 2 had infravesical obstruction and 3 had both underactive detrusor function and infravesical obstruction. In 4 patients bladder and urethral function were not classified. In 10 patients a provocative event preceded the retention episode. Eleven patients developed recurrent retention within 3 months and 7 patients had persistent severe obstructive voiding problems. Best prognosis was found for patients with correctable infravesical obstruction and for patients with minimal symptoms prior to the retention episode.

Acute Disease↗

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Anatomy↗

The ornithine requirement of urea synthesis. Formation of ornithine from glutamine in hepatocytes.

In hepatocytes, urea synthesis from glutamine is independent of added ornithine, even when rates are high after stimulation of glutamine metabolism by dibutyryl cyclic AMP, phenylephrine or vasopressin. Incubation with glutamine increases tissue [ornithine]. The increases parallel those of [N-acetylglutamate] under different conditions. The ornithine requirement of urea synthesis increases with increasing supply of ammonia. A function of the unique, highly regulated, glutaminase of liver may be to regulate ornithine synthesis.

Ammonium Chloride↗

The effect of l-thyroxine treatment on skin accumulation of acid glycosaminoglycans in primary myxoedema.

We assessed skin accumulation of acid glycosaminoglycans in ten patients with primary myxoedema (median age 70 years) before and during l-thyroxine treatment (median 7 months). Eight subjects matched for sex and age served as controls. Acid glycosaminoglycans were determined biochemically on small skin biopsies. Hyaluronic acid was elevated in untreated myxoedema, median 0.60, range 0.39-0.90 microgram hexosamine/mg dried defatted tissue compared to a median control value of 0.52, range 0.43-0.65 microgram hexosamine/mg dried defatted tissue, P less than 0.02. Chondroitin-4,6-sulphate and dermatan sulphate showed no elevation, while heparan sulphate was actually reduced in myxoedema, P less than 0.01. l-thyroxine treatment induced a significant reduction in hyaluronic acid, median 0.41, range 0.24-0.71 microgram hexosamine/mg dried defatted tissue, while no consistent changes occurred in the remaining three acid glycosamine glycans. The accumulation of hyaluronic acid might contribute to the peculiar non-pitting oedema of the skin in myxoedema, due to the strong water-binding capacity of the substance.

Adult↗

Free radicals appear to affect survival of hepatocytes at 4 degrees C.

1) Rat hepatocytes, stored in a simple salts medium for 24 h at 4 degrees C, retain more than 80% of their capacity to synthesize glucose from lactate. 2) The combination of NH4Cl with oleate is cytotoxic during storage and during subsequent incubation of hepatocytes from 48 h starved rats, but not to hepatocytes from fed rats. 3) Protection against cytotoxicity is afforded by albumin and by a number of other compounds, notably polyols and glycerol. 4) These compounds appear to exert their effects by scavenging free radicals and, in the case of polyols and glycerol, by supplying reducing equivalents to maintain the redox state of the cell in the face of increased flux through glutathione peroxidase.

Ammonium Chloride↗

N-Acetylglutamate in rat liver during foetal development.

N-Acetylglutamate is present in foetal rat liver at 17 days' gestation. The tissue content (approx. 50 nmol/g wet wt.) remains constant during later foetal life. The appearance of N-acetylglutamate does not parallel the developmental pattern of the urea cycle.

Animals↗

Allosteric properties of phosphate-activated glutaminase of human liver mitochondria.

The kinetics of human liver phosphate-activated glutaminase were studied in mitochondria isolated from surgical biopsies. The pH profile and activation by phosphate closely resembled rat liver glutaminase and differed clearly from human or rat kidney mitochondrial glutaminases. The activity responses to glutamine or phosphate were allosteric, showing positive cooperativity, as in the rat liver enzyme. Exogenous 1 mM NH4Cl shifted the glutamine concentration at half-maximal velocity, [Gln]0.5, to lower values without changing Vmax or sigmoidicity. Hill plots showed a parallel shift to the left with NH4Cl and the apparent number of binding sites, nH, was 2-3. 25 mM KHCO3 gave the same effects as NH4Cl on [Gln]0.5, Vmax, sigmoidicity and nH. The combination of the two activators was less than additive. Glutamate did not inhibit. We postulate that liver glutaminase is allosteric in its kinetics because it plays a key role in urea synthesis by regulating provision of glutamate for synthesis of N-acetylglutamate, the obligatory co-factor of carbamoylphosphate synthetase.

Adult↗

Is N-acetylglutamate a short-term regulator of urea synthesis?

A method is described for determining N-acetylglutamate as glutamate. N-Acetylglutamate content of hepatocytes from 48 h-starved rats is high. It shows no parallelism with rates of urea synthesis from glutamine. We question its accepted function as a short-term regulator of urea synthesis.

Animals↗

Lymphatic albumin clearance from psoriatic skin.

In nine patients with untreated psoriasis vulgaris, human serum albumin labelled with 125I or 131I was injected intradermally in symmetrically located involved and uninvolved skin. The activity of the depots was followed by external detection, and the arrival of labelled albumin in plasma was monitored. In involved psoriatic skin the local mean half-time (T1/2) for tracer disappearance was 20.8 +/- 8.2 (S.D.) hr and in clinically normal skin, 29.1 +/- 9.6 (S.D.) hr. The difference was significant (p less than 0.002). Accordingly, the tracer from involved skin reached higher plasma levels than the tracer from uninvolved skin. However, under slight lymphatic stasis the appearance rate of radiolabelled albumin in plasma from both tissues was minimal during 1 to 2 hours after the injection, indicating that a local direct transvascular drainage of plasma albumin from the interstitium of diseased and normal skin was negligible. We conclude that the previously demonstrated increased extravasation of plasma proteins in involved psoriatic skin is compensated by an increased lymphatic drainage of plasma proteins, and not by an increased local transvascular return.

Adult↗