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Biomedical subjects

J Mørland

Publications and source records attributed to J Mørland.

17 recordsLinked to original sources

Co-variation between biological markers and self-reported alcohol consumption. A two-year study of the relationship between changes in consumption and changes in the biological markers gamma-glutamyl transpeptidase (GGT) and average volume per erythrocyte (MCV) among problem drinkers.

Co-variations between self-reported alcohol consumption and the biological markers MCV (average volume per erythrocyte) and GGT (gamma-glutamyl transpeptidase) over a 2-year period were studied in a group of 84 men and 53 women recruited to out-patient treatment by advertisements in the press. Upon admission, the drinking pattern of the participants during the preceding year was registered in detail. The participants were also medically examined, and blood samples taken. All the participants were followed up by new personal interviews, medical examinations and new blood sampling after 3, 9, 25 and 21 months. For the group as a whole, alcohol consumption was significantly lower at the end of the observation period than at admission. GGT was also decreased, but not MCV. Both self-reported consumption and the values for the biological markers showed large inter-individual and intra-individual variations during the observation period. The biological markers seemed to co-vary to a limited degree with changes in reported consumption. Both GGT and MCV seemed to have a low sensitivity but a high specificity to changes in consumption. Both markers also seemed to be somewhat more useful in identifying decreases than increases in consumption. The markers GGT and MCV should be used with caution in connection with therapeutic counselling to individuals.

Adult

Incorporation of labelled amino acids into proteins of isolated parenchymal and nonparenchymal rat liver cells in the absence and presence of ethanol.

Parenchymal and nonparenchymal cells were isolated from perfused rat livers and incubated at 37 degrees C in the absence and presence of ethanol (50 mM). 1. Nonparenchymal cells prepared by means of centrifugation showed a higher rate of incorporation of L-[U-14C]valine into protein than nonparenchymal cells prepared by means of pronase. Cells prepared by the former method were used for further studies. 2. Protein degradation was present in suspensions of both parenchymal and nonparenchymal cells evidenced by increasing levels of branched amino acids in the intracellular and extracellular compartment during cell incubation. 3. The rate of cellular protein synthesis (corrected for precursor pool specific radioactivity) was of the same order of magnitude in nonparenchymal and parenchymal cells when expressed as nmol valine incorporated per mg protein. This rate was also close to the value found in intact liver by other workers. 4. Approximately 25% of the total radioactivity incorporated during incubation for 2 h was found in proteins released to the medium from parenchymal cells, while the corresponding figure for nonparenchymal cells was 3.5%. 5. Ethanol inhibited incorporation of labelled valine into stationary and medium proteins of parenchymal cells. No such effects were found in nonparenchymal cells. 6. Nonparenchymal cells did not metabolize ethanol while parenchymal cells did, shown by changes in lactate/pyruvate ratio and medium pH. It was concluded that nonparenchymal cells are capable of synthesizing proteins at a rate comparable to that found in parenchymal cells. Protein synthesis in parenchymal cells was inhibited by ethanol, but nonparenchymal protein synthesis was unaffected. This difference may be linked to the ability of the former cell type to metabolize ethanol.

Animals

Inhibition of fracture healing by indomethacin in rats.

The effect of indomethacin (2 mg/kg/day) on the healing of closed unimmobilized femoral fractures was examined in rats. A standard femoral fracture was produced in 205 male adolescent rats, and three different experiments were done. In a long-term experiment, the rats were treated with either indomethacin or placebo for 29 days and fracture healing followed for a maximum of 91 days. In two short-term experiments, the rats were treated with either indomethacin or placebo for a week and followed for a maximum of 122 days. The effect of age was studied in one experiment. Indomethacin plasma levels were about 1 microgram/ml in the indomethacin-treated animals. In the long-term experiment, indomethacin inhibited fracture healing (P less than 0.006) and increased the angulation between the femur fragments. In the short-term experiments indomethacin inhibited fracture healding (P less than 0.033) and increased the interfragmentary angle as well as fracture instability. All untreated fractures healed within 10 weeks in younger rats (210 g), whereas only 44% healed in older rats (295 g).

Animals

Changes in protein, RNA and DNA content in various rat organs after long-term intake of ethanol.

Male Wistar rats were given ethanol (approximately 25% of total caloric intake), while two different control groups were pair-fed isocaloric amounts of lipids or sucrose. After 7--10 weeks the following organs were studied: liver, cerebrum, heart, diaphragm, kidneys and testes. In fasted, ethanol treated rats there was a reduction in the hepatic concentration of RNA and the cerebral RNA/DNA ratio, when compared to both control groups, while no effects were found with respect to organ weight and amounts of protein, RNA or DNA in heart, diaphragm, kidneys and testes. When fed, ethanol treated animals were compared to both control groups, no effects on organ weight and composition were found in any tissue studied. Several significant differences were registered in the ethanol group as compared to one control group only, as well as between the two control groups. The consumption of ethanol (25% of total calories) thus caused only minor alterations in gross organ composition. These results also indicate the importance of interpreting with care any apparent effect of ethanol ingestion, unless at least two different control groups have been employed.

Alcoholism

Ethanol-induced increase in drug acetylation in man and isolated rat liver cells.

Sixteen healthy volunteers took part in a cross-over study examining the effect of ethanol on the rate of sulphadimidine acetylation (blood ethanol concentration about 1 g/1). In both rapid and slow acetylators the apparent half life of the drug decreased by about 20% after ethanol (mean reduction 39 +/- SE 8 min) and the amount of drug acetylated, measured in blood and urine, increased. In three slow acetylators the rate of acetylation in blood increased so noticeably after ethanol that they would otherwise have been classified as rapid acetylators. Suspensions of isolated rat liver cells showed an increase of about 30% in the rate of sulphadimidine acetylation after the addition of ethanol (2 g/1). Patients' usual alcohol consumption should be taken into account in determining their acetylator status.

Acetates

Is moderate ethanol consumption teratogenic in the rat?

Female Wistar rats were given ethanol in their drinking fluid to cover 20-25% of the total calories consumed for 3-4 weeks prior to, during and also after pregnancy in some experiments. Soya oil was substituted for ethanol isocalorically in the control groups. Apart from a statistically significant reduction in litter size based on the number of apparent normal foetuses at intrauterine examination, no significant changes in reproductive performance could be recorded after ethanol treatment. In the offspring, examined up to 24 days of age, the body and some viscera weights were statistically significantly higher at some stages from 2 to 14 days. The general trend, however, showed that there were no significant differences in body, brain, liver, kidney, and heart muscle weights between control and ethanol offspring measured in rats between 0 and 24 days of age. Two gross malformations were recorded among 321 pups of ethanol treated mothers, whereas no malformations were found in 444 control pups. It was concluded that moderate ethanol consumption by rat mothers for 3-4 weeks before and during pregnancy as well as during the suckling period, had no serious effects on their reproductive performance and the development of their offspring measured by the parameters used in the present investigation.

Abnormalities, Drug-Induced

Activity of alcohol dehydrogenase and acetaldehyde dehydrogenases in the liver and placenta during the development of the rat.

The ontogenetic development of the enzymes alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenases (ALDH I and II) was followed in rats. ADH could be detected just before birth and increased gradually to reach 82% of adult values at 47 days. ALDH I and II were present from day 15 of gestation, increased rapidly at birth, and reached 80-90% adult values at 47 days. The ratio between ALDH and ADH activities decreased gradually during ontogenesis. The relative subcellular distribution of all enzymes was identical before birth, 7 days after birth and in adults. The placental activities of ADH and ALDH I and II were studied at 15 and 20 days of pregnancy. ADH could not be detected in placentas. Low activities of ALDH I and II were present in placentas studied at 15 days of gestation, and still lower activities were found in placenta at 20 days.

Acetaldehyde

Induction of tryptophan oxygenase by dexamethasone in isolated hepatocytes. Dependence on composition of medium and pH.

Hepatocytes were isolated from perfused rat livers. 4 x 10-6 cells/ml were incubated at at 37 degrees C in different media in the absence and presence of a steroid hormone, dexamethasone phosphate (2 x 10-5 M). 1. Hormonal enzyme induction occurred in cells suspended in a simple salt medium, devoid of amino acids and macromolecules. This induction was completely blocked by addition of either actinomycin D (2 mu-g/ml) or cycloheximide (50 mu-g/ml). 2. Incubation of cells in media containing defatted albumin did not enhance hormonal enzyme induction, although disintegration of cells during incubation was reduced. Addition of a crude albumin fraction reduced tryptophan oxygenase induction and dextran completely blocked enzyme induction by dexamethasone. 3. An increase of dexamethasone concentration in the presence of albumin to 9 x 10-5 M was unable to raise enzyme induction further, and a still higher concentration of hormone, 3 x 10-4 M, resulted in reduced enzyme induction. 4. The hormonal induction of tryptophan oxygenase was most pronounced when the pH of the medium was between 7.0 and 7.6, with an optium at 7.3. No induction was found when the pH of the medium was either 6.6 or 7.8. The basal tryptophan oxygenase activity was much less influenced by similar pH variations. It is concluded that hepatocytes in suspension are able to carry out hormone-stimulated enzyme synthesis and that factors influencing this process may be studied under controlled conditions in such systems.

Animals