Erik Änggård

Arachidonic acid increases and indomethacin decreases plasma renin activity in the rabbit

Abstract Plasma renin activity (PRA) was measured in rabbits before and after infusion of the prostaglandin precursor, arachidonic acid (C20:4) and of the prostaglandin synthesis inhibitor, indomethacin. Non-hypotensive doses of C20:4 (10–15 μg/kg/min) increased PRA from 45 ± 7.3 to 91 ± 16 ng/ml/hr ( n = 6, p n = 4, p

Regional differences in the formation and metabolism of prostaglandins in the rabbit kidney

Abstract The biosynthesis and metabolism of prostaglandins was studied in three microscopically defined regions of rabbit kidney, the cortex, the outer and the inner medulla. PGE 2 formation was highest in the inner medulla, but significant biosynthesis occured also in the cortex. Metabolism of prostaglandins by 15-hydroxyprostaglandin dehydrogenase occured predominantly in the cortex with levels 10 times those seen in the inner medulla. The results thus demonstrate a clearcut dissociation between the sites of biosynthesis and metabolism in the kidney. The function of the cortical PGDH might be either to inactive prostaglandins formed in medulla or to protect medullary PG receptors from high levels of circulating prostaglandins.

Blockade of intravenous amphetamine euphoria in man.

In subjects who abuse amphetamine, the euphoric effect of 200 mg. of D,L‐amphetamine intravenously was reduced or abolished by oral pretreatment with α‐methyl‐p‐tyrosine (α‐MT) 2.0 to 4.0 Gm. The blockade of the amphetamine‐induced euphoria lasted for about 24 hours. After one week of daily administration of α‐MT, there was a reduction of the antiamphetamine effect. Three days after withdrawal, the renewed administration of α‐MT again caused a high degree of blockade of amphetamine‐induced euphoria.

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.

Prostaglandin profiles in nervous tissue and blood vessels of the brain of various animals

The endogenous formation of prostaglandin (PG) D2, E2, F2 alpha, and 6-keto-PGF1 alpha was determined in homogenates of mouse, rat, and rabbit brain, and of rat cerebral blood vessels, using gas chromatography mass spectrometry. In all species tested, 6-keto-PGF1 alpha could be identified in the brain homogenates, but was a minor component in relation to other PGs. In contrast 6-keto-PGF1 alpha was the most abundant PG in the blood vessels, being present in about 40-fold higher levels than in the brain tissue. PGD2 was the most abundant PG in rat and mouse brains, but was below detection limits in the analyzed blood vessels. These studies indicating differential metabolism of PG endoperoxides in nervous and vascular tissue, provide a biochemical basis for further studies on the role of the PGs in brain circulation and neuronal activity.

An abnormal phospholipid in rat organs after ethanol treatment

Interaction of ethanol with essential fatty acid (EFA) metabolism has been demonstrated in man [ 1,2] and in experimental animals [3,4]. Several laboratories have reported on the effects of ethanol on changed proportions of polyunsaturated fatty acids in cell membranes [5,6,7]. In a series of experiments with ethanol and EFA we found increased concentrations of phospholipids in the brain of rats after 3 weeks of ethanol administration (3 g/kg body weight, daily intraperitoneal injections). This phospholipid increase was due to an increase of the acidic fraction of the phospholipids [4]. Examination of the proportions of individual neutral and acidic lipids by thin-layer chromatography (TLC) revealed the occurrence of an abnormal lipid fraction in organs from rats exposed to ethanol. This article is a report on the appearance of this abnormal lipid in various organs and the relation to the amount and duration of ethanol administration. Our currently available information on the chemical structure of the lipid is also given.

Regional and species differences in endogenous prostaglandin biosynthesis by brain homogenates

Endogenously formed prostaglandins (PGs) D2, E2 and F2 alpha were determined in homogenates of brain regions from rat, guinea-pig, rabbit and cat, using gas-chromatography-mass spectrometry. The main PGs formed in the brain regions of the rat were PGD2, in the guinea-pig PGD2 and PGF2 alpha, in the rabbit PGF2 alpha and in the cat PGE2. Brain regions from the same animal species showed the same pattern of PG formation. They varied, however, in the amount of total PGs formed, the limbic system and the cerebral cortex being highest and cerebellum lowest.

Disposition of methadone in methadone maintenance

Six detoxified opiate addicts housed in a closed metabolic ward received methadone in stepwise increasing doses of 10, 20, 40, and 80 mg/day during 1 month. Four were given 14C‐methadone at the lowest dose and again at the highest dose. Of the subjects receiving radiomethadone, 2 excreted the major part of the radioactivity in urine and 2 about equally in urine and feces. In addition to methadone, 7 metabolites were isolated and identified in urine and 3 metabolites in feces. About 75% of the urinary and fecal radioactive metabolites were unconjugated. Urinary excretion of methadone and its major N‐monomethylated metabolite accounted for 17% to 57% of the given dose. The ratio of metabolite to parent drug increased in 5 of 6 subjects, and the urinary recovery of unchanged methadone decreased during the period. The results indicate that enhanced demethylation of methadone may occur during oral administration to man.

Methadone maintenance: Plasma levels and therapeutic outcome

Twenty‐one opiate‐dependent subjects were inducted into methadone maintenance treatment (MMT) in a closed metabolic ward. A daily dose of 30 mg of d,l‐methadone was given for 10 to 24 days followed by 60 mg Iday for another 10 to 24 days. Analysis of plasma levels at 4‐day intervals showed accumulation to a peak followed by a decrease to a lower level, indicative of development of dispositional tolerance. The outcome of treatment was assessed after 21 to 43 mo (median, 33 mo). The best record of rehabilitation was obtained in subjects discharged with steady‐state plasma concentrations above 200 ng/ml. Lower levels of plasma methadone were associated with higher frequency of urines containing illicit drugs and poorer psychosocial rehabilitation. This study indicates that a pharmacokinetically optimized dosage regimen would be useful in increasing the therapeutic effectiveness of MMT.

The sequence of the early steps in the metabolism of prostaglandin E1.

Abstract The pathway in the metabolism of prostaglandins E 1 in kidney, spleen and liver from swine is 1) oxidation of the 15-hydroxyl group to a ketone, 2) reduction of the Δ 13 -double bond and partly 3) stereospecific reduction of the 15-keto group to dihydro-prostaglandin E 1 (15 S).