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Biomedical subjects

E Anggård

Publications and source records attributed to E Anggård.

At least 37 records · Page 2Linked to original sources
PubMed1985

Formation of phosphatidylethanol in frozen kidneys from ethanol-treated rats.

We recently identified phosphatidylethanol (Pet) in tissues from ethanol-treated rats. Since phosphatidyl esters are formed artefactually during freezing in plants we wanted to examine if PE was elevated during freezing in animal tissues. Rats were treated with 3 g/kg of ethanol, killed after 3 h and PE was isolated from kidneys at once or after storage at 0, -5, -10, -15, -20 and -80 degrees C for 7 days. Kidneys analyzed at once or after storage at -80 degrees C had Pet equivalent to 0.02 mumol Pet/g. Storage at -10 degrees C and -15 degrees C resulted in increases of Pet to 1.5 mumol Pet/g and 1.2 mumol Pet/g, respectively. Thus, Pet is artefactually elevated during storage of tissues from ethanol-treated rats at lower freezing temperatures, reflecting considerable changes in composition of acidic phospholipids.

Animals↗
PubMed1985

Platelet thromboxane formation and bleeding time is influenced by ethanol withdrawal but not by cigarette smoking.

Platelet count, mean volume, aggregation and associated thromboxane (TXB2) formation, circulating platelet aggregates and bleeding time were examined in 19 noncirrhotic male alcoholic cigarette smokers for four weeks following cessation of prolonged heavy drinking, and in 24 nonalcoholic healthy male volunteers (10 smokers and 14 nonsmokers). The alcoholics showed a 9-fold increase (p less than 0.001) in ADP-stimulated platelet thromboxane formation one to two weeks after ethanol withdrawal. The effect was transient and coincided with a significant (p less than 0.01) shortening of skin bleeding time and a slight increase in circulating platelet aggregates suggesting proneness to thrombosis. No differences were seen between the smoking and nonsmoking healthy volunteers. We conclude that the recovery phase after prolonged heavy drinking is characterized by a transient increase in platelet reactivity which may lead to increased spontaneous formation of circulating platelet aggregates and shortening of bleeding time.

Adult↗
PubMed1985

Analysis of buprenorphine and its N-dealkylated metabolite in plasma and urine by selected-ion monitoring.

A selected-ion monitoring method was developed for determination of buprenorphine and its N-dealkylated metabolite (norbuprenorphine) in human plasma and urine. N-Propylnorbuprenorphine was added as internal standard to 2-3 ml of sample and the alkaloids were extracted with toluene-2 butanol at pH 9.4. After back-extraction in dilute sulphuric acid, the compounds were heated at 110 degrees C. This procedure led to quantitative loss of methanol followed by ring formation between the 6-methoxy group and the branched side-chain of all compounds. The derivatives were extracted into dichloromethane-2-butanol and treated with pentafluoropropionic anhydride. The resulting derivatives were suitable for selected-ion monitoring analysis. The coefficient of variation was found to be 4.5% at 5 ng/ml and 8.9% at 50 ng/ml in urine. The corresponding values for plasma were 6.2% and 5.3%, respectively. The lower limit of detection in plasma was 150 pg/ml, permitting analysis of plasma levels of buprenorphine for 24 h and urine levels of buprenorphine and norbuprenorphine for more than seven days after a therapeutic dose of buprenorphine. This method is the first with sufficient specificity and sensitivity for characterization of the clinical pharmacokinetics of buprenorphine.

Buprenorphine↗
PubMed1984

Determination of morphine in biological samples by gas chromatography-mass spectrometry. Evidence for persistent tissue binding in rats twenty-two days post-withdrawal.

Combined gas chromatography-mass spectrometry with capillary and packed column gas chromatography and a deuterium-labelled internal standard was used to determine morphine in biological specimens from rats 22 days after abrupt withdrawal. Morphine was extracted from urine and body organs at pH 9 and the pentafluoropropionyl derivatives were made for analysis by gas chromatography-mass spectrometry. The stationary phase was OV-17 and the mass spectrometer was focused on m/z 414 for morphine and m/z 417 for the internal standard, [NC2H3]morphine. With fused-silica capillary columns, the sensitivity of the assay was increased about ten-fold over packed columns. Urinary excretion of total morphine (free + conjugated) was 22 ng/h (range 11-51 ng/h, n = 8) at 22 days post-withdrawal. Free morphine was mainly detected in the lung (1.8-6.5 ng/g, n = 7), kidney (1.5-4.0 ng/g, n = 7) and liver (1.8-4.6 ng/g, n = 4). Traces of morphine were also detected in brain of some rats. Treatment with the opiate antagonist naltrexone, 10 mg/kg on four consecutive days before death, failed to change the urinary excretion pattern or the concentration of free morphine in body organs. The biological significance of the residual morphine, if any, remains to be determined.

Animals↗
PubMed1984

Phosphatidylethanol formation in rat organs after ethanol treatment.

An abnormal acidic phospholipid was found in high concentration in kidney and brain, and also in other organs of rats exposed to ethanol by i.p. injection or by a liquid diet. The compound could be identified as phosphatidylethanol. Phosphatidylethanol is probably formed in cell membranes by a phospholipase D-catalyzed transphosphatidylation reaction.

Animals↗
PubMed1984

Time course of breath acetaldehyde concentrations during intravenous infusions of ethanol in healthy men.

A gas chromatographic method was developed for the quantitative determination of acetaldehyde in expired alveolar air of human subjects. A rapid and direct gas-sampling system allow serial determinations and avoid the need for correcting for sample losses or poor recoveries. This method was evaluated in experiments with healthy men during different modes of intravenous infusion of ethanol. The time course of breath-ethanol and breath-acetaldehyde concentrations were used to estimate the coexisting blood levels. Blood acetaldehyde concentration (y) was about 2000 times less than blood ethanol (x) and the values were highly correlated r = 0.90 +/- 0.05, P less than 0.001. The regression equation was y = 2.0 + 0.303x; the intercept was significantly different from zero. Breath acetaldehyde faithfully followed the changes in breath and blood ethanol concentrations for widely varying rates of ethanol infusion.

Acetaldehyde↗
PubMed1984

Norepinephrine metabolism in man using deuterium labelling: origin of 4-hydroxy-3-methoxymandelic acid.

A double isotope labelling technique was used to simultaneously determine the in vivo turnover rates of 4-hydroxy-3-methoxyphenylglycol (HMPG) and 4-hydroxy-3-methoxymandelic acid (HMMA, VMA) and the rate of HMPG oxidation to HMMA. Six healthy men were given intravenous injections of [2H3]HMPG and [2H6]HMMA and their plasma and urine samples analysed by gas chromatography--mass spectrometry (GC/MS) for the protium and deuterium species. HMPG and HMMA production rates were calculated by isotope dilution. The rate of HMPG oxidation to HMMA was obtained from the fraction of [2H3]HMPG recovered as [2H3]HMMA. The results showed that the entire production of HMMA, 1.11 +/- 0.21 mumol/h (mean +/- SE), could be accounted for by oxidation of HMPG, 1.49 +/- 0.31 mumol/h. In another experiment designed to avoid expansion of the HMPG body pool, a tracer dose of [14C]HMPG was given to the same subjects. The levels of [14C]HMPG and [14C]HMMA were measured in urine after extraction and separation by thin layer chromatography. Urinary excretion of endogenous HMPG and HMMA was determined by GC/MS. The results showed that the endogenous HMMA fraction of the total HMPG and HMMA urinary excretion rate, 0.57 +/- 0.04, was the same as the fraction of [14C]HMPG oxidized to [14C]HMMA, 0.62 +/- 0.01. Thus, HMPG is the main intermediate in the metabolic conversion of norepinephrine and epinephrine to HMMA in man.

Adult↗
PubMed1984

Dietary arachidonic acid protects mice against the fatty liver induced by a high fat diet and by ethanol.

Five groups of NMRI mice were fed ethanol or sucrose in a nutritionally adequate liquid diet for 9 days. The dietary fat consisted of olive oil with the fatty acid composition 18:1 77%, 18:2 10%, 18:0 and 16:0 12%. The ethanol treated groups received 5% w/v ethanol (E) or isocaloric sucrose (S). Two groups (S- and E-) received the diet without supplement. In two groups (S+ and E+) 7% of the fat was exchanged for arachidonic acid (20:4). In a fifth group (IE+) treated with ethanol and arachidonic acid the diet also contained indomethacin (10 mg/l). The mean intake of ethanol was about 20 g/kg/day. After 9 days animals were killed and liver lipids analyzed after Folch extraction. The post mortem accumulation of prostaglandin E2 in the kidney was measured by GC-MS. Dietary 20:4 was found to protect mice against fatty liver caused both by a high fat diet alone and in combination with ethanol. The liver triglycerides were 30.7 +/- 4.3 (S-), 46.1 +/- 6.9 (E-), 6.8 +/- 0.4 (S+) and 19.4 +/- 1.8 (E+). Prostaglandin levels in the kidney were depressed by ethanol treatment. Indomethacin gave variable degrees of PG synthesis inhibition. The degree of liver triglyceride accumulation in the IE+ group was inversely proportional to the degree of PG synthesis. The data suggest a role for liver 20:4 cyclooxygenase metabolites in fatty liver caused by high fat diets and ethanol.

Animals↗
PubMed1983

Pharmacokinetics of methadone in methadone maintenance treatment: characterization of therapeutic failures.

Deuterated methadone (M-d3) and GC-MS analysis were used to study the steady state pharmacokinetics of methadone (M) in eight patients reported as therapeutic failures in a methadone maintenance treatment programme. The patients were compared to an unselected group of 12 patients stabilized on M for 25 days. During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0). The pharmacokinetic parameters, half-life in the beta-phase (t1/2 beta), volume of distribution during the postdistributive phase (Vd beta) and during steady state (Vdss) were determined as well as the body (ClS) and renal (ClR) clearances of M. Pronounced differences in Vd beta and Vdss were found between the two groups. The therapeutic failures had a smaller Vd beta and Vdss 3.09 +/- 0.96 1/kg and 2.74 +/- 0.96 1/kg vs 4.56 +/- 1.00 1/kg and 4.20 +/- 0.78 1/kg in the control group. The differences were due to changes between the groups in the volume of the central compartment. Differences between the groups were also found in t1/2 beta - 24.5 +/- 2.6 h in the therapeutic failures and 34.0 +/- 7.0 h (p less than 0.001) in the comparison group. However, the change in t1/2 beta was probably a consequence of the change in Vd beta, as the body clearance of M was similar in the two groups - 104 +/- 36 ml/min vs 111 +/- 36 ml/min. The smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Determination of endogenous ethanol in blood and breath by gas chromatography-mass spectrometry.

We describe methods for the determination of endogenous ethanol in biological specimens from healthy abstaining subjects. The analytical methods were headspace gas chromatography (GC) for plasma samples and gas chromatography-mass spectometry (GC/MS) with deuterium labelled species 2H3-ethanol and 2H5-ethanol as internal standards for breath analysis. Ethanol in rebreathed air was about 10% higher than in directly analysed end-expired alveolar air. Known volumes of rebreathed air were passed through a liquid-N2 freeze trap and the volatile constituents of breath were concentrated prior to analysis by GC or GC/MS. Besides endogenous ethanol, peaks were seen on the chromatograms for methanol, acetone and acetaldehyde as well as several as yet unidentified substances. The endogenous alcohols ethanol and methanol were confirmed from their mass chromatograms and the GC/MS profile also indicated the presence of endogenous propan-1-ol. The concentration of endogenous ethanol in plasma showed wide inter-subject variations ranging from below detection limits to 1.6 micrograms/ml (34.8 mumol/l) and with mean +/- SD of 0.39 +/- 0.45 micrograms/ml (8.5 +/- 9.8 mumol/l). We aim to characterise further the role of endogenous ethanol with the main focus on dynamic aspects such as the rate of formation and turnover.

Adult↗
PubMed1983

Ethanol, essential fatty acids and prostaglandins.

In the body the essential fatty acid (EFA) linoleic acid (18:2, omega-6) is desaturated and chain elongated to form homo-gamma-linoleic acid (20:3, omega-6) and arachidonic acid (20:4, omega-6). Apart from their structural function in cell membranes, the EFAs serve as precursors to the prostaglandins and related substances. The prostaglandins can, in general terms, be described as a defensive regulatory system of importance for cardiovascular, gastrointestinal and urogenital function. Acute intake of ethanol gives facial flushing, inhibition of platelet aggregation and elevation of tissue c-AMP. These effects are consistent with release of vasodilatory and antiaggregating PGs. In epidemiological studies, moderate ethanol intake offers some protection against coronary heart disease. Chronic intake high doses of ethanol is associated with damage to, e.g., liver, heart, brain, immunoregulation and various hormonal systems. Decreased tissue levels of 18:2, 20:4 and PGs have been observed both in animals and man. The conversion of 18:2 to 20:4 is inhibited by chronic ethanol exposure. It is suggested that ethanol depletes the PG precursor pool by a dual mechanism of releasing precursor acids and by inhibiting their synthesis. This would lead to a functional EFA-deficiency, manifested by a hypoactive PG system.

Alcoholism↗
PubMed1983

Tolerance to ethanol in rats bred on essential fatty acid deficient diets.

We bred three generations of Sprague-Dawley rats on a diet deficient in essential fatty acids, low-EFA (0.3 energy %), whereas age matched controls received normal-EFA (3.0 energy %). Subgroups (N = 6) of female rats were given daily IP injections of ethanol (3.0 g/kg) or isocaloric glucose for 23 consecutive days. On days 1 and 22 blood-ethanol profiles, rates of ethanol metabolism and ethanol-induced impairment of motor coordination were measured after the challenge dose of 3.0 g/kg. Rats exposed to ethanol ate and drank more than controls and gained more body weight over the 23 days. Low-EFA rats were slightly more impaired than normal EFA rats after an acute dose of ethanol even though the peak blood ethanol concentrations reached were about the same at 2.9 mg/ml (63 mmol/l). After chronic ethanol treatment a functional tolerance developed in both dietary groups but the degree of tolerance was less clearcut in low EFA rats. Metabolic tolerance was confirmed after chronic treatment in both dietary groups as shown by steeper slopes (19-27%) of the ethanol elimination curves. But no significant differences in the development of metabolic tolerance were apparent in rats on low EFA and normal EFA diets.

Animals↗
PubMed1983

Norepinephrine metabolism in humans studied by deuterium labelling: turnover of 4-hydroxy-3-methoxyphenylglycol.

D,L(+/-)-4-Hydroxy-3-methoxyphenylglycol (HMPG) labelled with three deuterium atoms was used to study turnover of plasma free HMPG following an intravenous injection. Ten healthy men were given a pulse dose of either 4.3 mumol or 2.2 mumol of labelled HMPG ([2H3]HMPG piperazine salt). Plasma and urine levels of both endogenous and labelled HMPG were subsequently followed by gas chromatography-mass spectrometry with selected ion detection. Kinetic calculations based upon a single-compartment model were consistent with a monoexponential elimination of plasma free HMPG. The half-life of HMPG was 0.46 and 0.78 h (mean values in the two dose groups). The HMPG production rate was 2.01 and 2.35 mumol/hour, and the urinary excretion rate of HMPG (free and conjugated) was 0.48 and 0.47 mumol/h. The endogenous plasma level of free HMPG was 25 and 33 nmol/L. The results show that HMPG turns over rapidly and that HMPG is further metabolized extensively. About one-fourth of the HMPG produced is excreted in urine as free and conjugated HMPG.

Adult↗