Anders Bjørneboe

Effect of dietary supplementation with eicosapentaenoic acid in the treatment of atopic dermatitis

The effects of a dietary supplement of n‐3 fatty acids in patients with atopic dermatitis were investigated in a 12‐week, double‐blind study. The experimental group received 10 g of fish oil daily, of which about 1.8 g was eicosapentaenoic acid. This amount of eicosapentaenoic acid can be obtained from a daily intake of fat fish. The controls received an iso‐energetic placebo supplement containing olive oil. Compliance was monitored by gas‐chromatographic analysis of the fatty acid pattern in serum phospholipids. Results favoured the experimental group with regard to scale (P < 0.05), itch (P < 0.05) and overall subjective severity (P < 0.02) as compared to the controls.

Effect of dietary supplementation with n-3 fatty acids on clinical manifestations of psoriasis.

In a double‐blind, block randomized study we investigated the effect of dietary supplementation with eicosapentaenoic acid in patients with psoriasis. The experimental group received 10 g of fish oil daily containing approximately 1.8 g eicosapentaenoic acid, while the controls were given an isoenergetic amount of olive oil. We found no significant change in the clinical manifestations of psoriasis in either group after 8 weeks of treatment. In the experimental group, the amount of n‐3 fatty acids in serum phospholipids was significantly increased at the end of trial as compared to pre‐treatment values, whereas the level of n‐6 fatty acids was decreased.

Transport and distribution of α-tocopherol in lymph, serum and liver cells in rats

Rats were cannulated in the major mesenteric lymph duct and given an intraduodenal bolus of unlabeled and α-[3H]tocopherol, and [14C]oleic acid in soybean oil. The appearance of α-tocopherol in lymph was negligible during the first 2 h and peaked 4–15 h after feeding, whereas no detectable amount was recovered in the portal vein. Intestinal absorption via the lymphatic pathway was 15.4 ± 8.9% (n = 10) and 45.9 ± 10.8% (n = 4) for α-tocopherol and [14C]oleic acid, respectively. About 99% of α-tocopherol in lymph was associated with the chylomicron fraction (d < 1.006 g/ml). In non-fasting rats, 51% of serum α-tocopherol was associated with chylomicrons/VLDL (very-low-density lipoprotein, d < 1.006 g/ml) and 47% with HDL (high-density lipoprotein, 1.05 < d < 1.21 g/ml). Our study revealed that the liver, skeletal muscle and adipose tissue contain approx. 92% of the total mass of α-tocopherol measured in ten different organs. Parenchymal and nonparenchymal liver cells contributed to 75% and 25% of the total mass of α-tocopherol in the liver, respectively.

Reduced hepatic α-tocopherol content after long-term administration of ethanol to rats

We have studied the effects of long-term administration of ethanol on the distribution and pharmacokinetics of α-tocopherol. In rats fed ethanol (35% of total energy) for 5–6 weeks concentration of α-tocopherol in whole liver was reduced by 25% as compared to the pair-fed controls (P < 0.003). This reduction was significant in the parenchymal cells (28%, P < 0.004), whereas no significant difference was observed for the nonparenchymal cells. Mitochondrial α-tocopherol content was reduced by 55% in the ethanol-treated rats as compared to the controls (P < 0.002), whereas no significant difference was observed in microsomes, light mitochondria or cytosol. The serum levels of α-tocopherol showed no significant difference between the groups. When in vivo labeled chylomicron α-[3H]tocopherol was injected intravenously to anesthetized rats, we found a significant increase in serum half-life of α-tocopherol in the ethanol-treated group as compared to the controls (P < 0.025). Hepatic α-[3H]tocopherol content was similar in the two groups 24 h after injection.

The extent of postmortem drug redistribution in a rat model.

The aim of this study was to investigate the postmortem redistribution of several drugs in a rat model and to examine if any of the pharmacological properties was related to the extent of this phenomenon. One of the following drugs: phenobarbital (phenobarbitone), acetaminophen (paracetamol), carbamazepine, codeine, verapamil, amphetamine, mianserin, trimeprazine (alimemazine) or chloroquine was administered together with nortriptyline orally to rats 90 min prior to sacrifice. Heart blood was sampled immediately before sacrifice and after 2 h postmortem, as it has previously been shown that this is sufficient time for postmortem concentration changes to occur in heart blood. Blood was also sampled from the clamped abdominal inferior vena cava (representing peripheral blood) and tissue samples were taken from lungs, myocardium, liver, kidney, thigh muscle, forebrain, and vitreous humor together with a specimen from the minced carcass. Drugs were analyzed by high performance liquid or gas chromatography. For phenobarbital, acetaminophen and carbamazepine the postmortem to antemortem blood drug concentration ratios were close to 1.0 and tissue concentrations were low. The postmortem to antemortem heart blood drug concentration ratio for chloroquine (6.9 +/- 1.5) was higher than for nortriptyline (3.5 +/- 0.3), and the remaining drugs (codeine, verapamil, amphetamine, mianserin, and trimeprazine) showed ratios of the same magnitude as nortriptyline. The postmortem to antemortem blood drug concentration ratios for both heart blood and blood from the vena cava and also the lung to antemortem blood drug concentration ratio were closely related to the apparent volume of distribution for the drugs studied (p < 0.001). Accordingly, an apparent volume of distribution of more than 3-4 L/kg is a good predictor that a drug is liable to undergo postmortem redistribution with significant increments in blood levels. The postmortem drug concentration in blood from vena cava was closely related to the antemortem blood level, confirming that among the postmortem samples, the peripheral blood sample was the most representative for the antemortem blood concentration.

A comparison of serum carbohydrate-deficient transferrin with other biological markers of excessive drinking

In a study of suggested biological markers of excessive drinking, serum carbohydrate-deficient transferrin (CDT) was compared with serum activities of alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase and gamma glutamyltransferase; serum concentrations of high-density lipoprotein cholesterol; and erythrocyte mean cellular volume. Analytical data were studied in relation to self-reported alcohol consumption during the latest month for the 69 participating subjects. CDT was found to be the most sensitive and most specific marker of excessive drinking, and was also found to be the best marker for monitoring abstinence under treatment of alcoholics.

An animal model of postmortem amitriptyline redistribution.

An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood--PB) and the heart (HB). The rats were sacrificed by CO2 and left at room temperature for either 0.1, 0.5, 1, 2, 5, 10, 24, 48, or 96 hours, when samples of heart blood, blood from the inferior vena cava (PB) and tissue samples from different liver lobes, heart, lungs, kidney, thigh muscle, and brain were taken. Samples were analyzed by high performance liquid chromatography. The AMI concentration in HB increased fairly rapidly within the first 2 h postmortem and from then the average ratio was 6.4 +/- 0.8 (mean +/- sem) (n = 31). In PB, the post/antemortem AMI concentration ratio followed an approximately exponential rise; at 2 h postmortem the ratio was 1.6 +/- 0.3 (n = 5), and at 96 h 55.1 +/- 23.8 (n = 4). For the main metabolite nortriptyline (NOR), the concentration changes followed the same pattern, but to a lesser extent. Among the tissues, the liver lobes had high, but variable drug concentrations; lobes lying closest to the stomach had the highest drug concentrations. The drug concentration in the lungs declined significantly. This animal model demonstrates postmortem drug concentration changes similar to those described in humans. Probable mechanisms include drug diffusion from the stomach and GI tract to the surrounding tissues and blood; and postmortem drug release from the lungs and possibly other drug-rich tissues into the blood.

Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution

An experimental rat model was used to study postmortem redistribution of amitriptyline (AMI). Two hours after a subcutaneous injection with 20 mg of amitriptyline, the rats (n = 40) were anaesthetized and blood samples were drawn from the femoral vein and the heart. The rats were then sacrificed by CO2 and left at room temperature for either 0.1, 1, 2, 5, 24, 48, or 96 h. Postmortem blood samples from the heart and the inferior vena cava, and tissue samples from the lungs, heart, liver, right kidney, thigh muscle, the wall of the abdominal vena cava and brain were analyzed by high performance liquid chromatography. A significant increase was observed within 2 h postmortem in heart blood and later also in blood from the inferior vena cava. At 96 h postmortem the concentration increase was 4.4 +/- 0.5-fold (P < 0.01) and 3.0 +/- 1.1-fold (P < 0.05) as compared to the antemortem values observed in heart blood and blood from the inferior vena cava, respectively (mean +/- SEM). In the lungs there was a fall in the concentration of AMI from 148 +/- 16.7 mumol/kg at 0.1 h to 49.1 +/- 7.8 mumol/kg at 96 h postmortem (P < 0.01). In the vessel wall of the abdominal vena cava there was also a significant fall in drug concentration, while in heart muscle and liver an increase in drug concentration was observed. In animals where the lungs were removed agonally (n = 7), the drug concentration in heart blood had increased significantly less at 2 h postmortem.(ABSTRACT TRUNCATED AT 250 WORDS)

Diminished Serum Concentration of Vitamin E in Alcoholics

The effect of heavy alcohol consumption on serum concentrations of vitamin E (alpha-tocopherol) and selenium was studied in 13 alcoholics and 19 control subjects. Ethanol intake during the year previous to the study was in the range from 22 to 354 g/day and from 0 to 16 g/day among the alcoholics and controls, respectively. Of the 13 alcoholics, 6 had a serum concentration of alpha-tocopherol below the lower limit of reference (14 mumol/l) and mean serum concentration of alpha-tocopherol was reduced by 37% as compared to controls (p less than 0.002). Estimated dietary intake of alpha-tocopherol during the year previous to the study was approximately 40% lower for the alcoholics (p less than 0.05). During hard-drinking periods the alcoholics had a markedly reduced intake of alpha-tocopherol as compared to moderate-drinking and abstinent periods. Mean serum concentration of selenium was significantly reduced in the alcoholics (1.2 +/- 0.3 mumol/l) as compared to the controls (1.6 +/- 0.2 mumol/l) (p less than 0.002). The reduced serum levels of alpha-tocopherol and selenium may influence the maintenance of normal cell structure and function, and contribute to development of diseases frequently observed in alcoholics.

Serum half-life, distribution, hepatic uptake and biliary excretion of α-tocopherol in rats

Abstract The serum clearance of α-[3H)tocopherol has been studied after intravenous injection of intestinal lymph labeled in vivo with radioactive a-tocopherol. The half-life of the injected α-[3H]tocopherol was approx. 12 min. Fractionation of plasma by ultracentrifugation 10 min after injection of lymph showed that 91% of the radioactive α-tocopherol remaining in plasma was located in chylomicrons (d