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Biomedical subjects

H Eriksson

Publications and source records attributed to H Eriksson.

At least 217 records · Page 12Linked to original sources
PubMed1977

Pharmacological studies on an iron-poly-(sorbitol-gluconic acid) complex for parenteral treatment of iron deficiency anaemia.

Intravenous injection of the iron-poly(sorbitol-gluconic acid) complex (IPSG) to cats anaesthetized with sodium pentobarbitone caused a transient decrease in mean arterial blood pressure and a temporary increase in central venous pressure, heart rate and femoral blood flow at large doses (cumulative doses up to 744 mg/kg). Tachyphylaxis developed upon repeated administration. A temporary reduction in the magnitude of the blood pressure responses to noradrenaline and isoprenaline was obtained after large doses of IPSG. The blood pressure effects of acetylcholine, histamine and bilateral carotid occlusion were not affected. No definite effects were seen on the electrocardiograms. The transient cardiovascular effects were interpreted as being due to the presence of small amounts of ferrous iron in the preparation. IPSG did not significantly affect blood coagulation or platelet aggregation as judged from results of in vitro and in vivo experiments. Immunogenicity studies in rabbits and antibody analyses of sera from patients treated with IPSG failed to demonstrate any effect of IPSG on the immune system.

Acetylcholine↗
PubMed1977

Effect of ethynylestradiol on biliary excretion of bile acids, phosphatidylcolines, and cholesterol in the bile fistula rat.

The effects of ethynylestradiol on endogenous bile acids, their capacity to conjugate and excrete intravenously infused cholic acid, the concentrations of biliary cholesterol and lecithin, and the individual molecular species of phosphatidylcholine have been determined in male and female Sprague-Dawley rats. Endogenous biliary bile acids were analyzed by gas-liquid chromatography-mass spectrometry. Eleven bile acids were identified and several minor bile acids, primarily muricholates, could not be completely characterized. After 5 days of treatment with ethynylestradiol (1 mg/kg per day), the percentage of cholic acid decreased and the percentage of 6beta-hydroxylated bile acids, including several monounsaturated species, increased. Ethynylestradiol caused a decrease in bile acid-independent bile flow. Intravenous infusion of cholic acid at a high concentration caused cholestasis in control animals but, after ethynylestradiol treatment, cholestasis developed during the infusion of a much lower concentration of cholate, indicating a lowered threshhold for bile acid-induced cholestasis. In the treated rats, there was a slight increase in excretion of unconjugated endogenous bile acids, and a striking impairment of conjugation of intravenously administered cholic acid. One of the few sex-related differences observed was an increased concentration of biliary phospholipids in untreated male rats. Both phospholipid and cholesterol concentrations in the bile were higher in the treated animals. The molar percentage of cholesterol was always 1-2%, but it was slightly higher in treated animals, especially males. Ethynylestradiol treatment also affected biliary phospholipid by causing a marked increase of phosphatidylcholine species containing palmitic and oleic acid residues and a decrease of species containing stearic and linoleic acid residues. There was no increase in biliary excretion of long chain polyunsaturated species, which might have indicated damage to membranes, in response to ethynylestradiol either alone or with cholic acid infusion. Some of these ethynylestradiol-induced changes in biliary bile acid and lipid excretion are probably peculiar to the rat, but others, such as the increase in molar percentage of cholesterol and cholestasis, may be relevant to disorders in man, especially cholesterol gallstones and idiopathic cholestasis of pregnancy.

Animals↗
PubMed1976

Hepatic 15-hydroxylation of corticosteroids in the rat. Substrate specificity studied in the isolated perfused liver.

The substrate specificity of a sex-specific hepatic 15-hydroxylase active on different C21O2 and C21O3 steroids was studied in the isolated perfused liver from female rats. Liquid-chromatographic separation methods in combination with computerized gas chromatography-mass spectrometry was employed to identify the metabolites formed. The majority (between 75-90%) of 15-hydroxylated compounds isolated were present as monosulphate conjugates while smaller amounts of disulphates were also detected. Hydroxylation was found to take place exclusively at position 15 beta. A certain number of 11-deoxy-21-hydroxy, 11-oxo-21-hydroxy and 11,21-dihydroxy steroids with a 3-keto-delta4-, 3-keto-5 alpha(5 beta)-, 3alpha, 5alpha- or 3 beta, 5 beta-structure were readily converted to 15 beta-hydroxylated metabolites. Depending on the structure of the substrate, between 20 and 87% of the total metabolites formed were 15 beta-hydroxylated. 5 alpha-Reduced steroids were better substrates for the hydroxylase than the corresponding 3-keto-delta4- or 5 beta-reduced compounds. The configuration of the hydroxylgroup at C-3 did not affect the degree of 15-hydroxylation. 11 beta-Hydroxylated steroids served as better substrates than the corresponding 11-dehydro-, 11-deoxy- or 11 alpha-hydroxy compounds. 5 alpha-Dihydrocorticosterone and 3 alpha, 5 alpha-tetrahydrocorticosterone were the best substrates for the 15 beta-hydroxylase.

Animals↗
PubMed1976

Role of the hypophysis in estrogen-mediated induction of enzymes in the regenerating liver from castrated male rats.

Perfusions with corticosterone, of isolated regenerated livers from adult male rats, subjected to castration, partial hepatectomy and hypophysectomy with or without estradiol treatment during parenchymal regeneration, yielded very similar patterns of biliary steroid metabolites. The degree of steroid conjugation was lower than that seen in livers from normal, untreated, adult male rats. In operated animals, with or without estradiol benzoate treatment, ring A-reduced 20-keto metabolites constituted about 20%, whereas metabolites with a 20-hydroxy group made up approximately 80% of the corticosterone metabolites formed. Furthermore, no 15-hydroxylated metabolites derived from corticosterone, quantitatively the most important compounds in bile from female rats, could be detected in bile from these treated male animals. However, livers from male rats which had been castrated, hepatectomized and treated with estradiol benzoate during liver regeneration, produced 15-hydroxy-tetrahydrocorticosterone to the same extent as female rat livers, when perfused with corticosterone. The results obtained indicate that the effects of estradiol on the induction and differentiation of steroid metabolizing enzymes in the regenerating liver are pronounced and manifested only in the presence of an intact hypophysis.

Animals↗
PubMed1975

Specific deuterium labelling and computerized gas chromatography -- mass spectrometry in studies on the metabolism in vivo of a steroid sulphate in the rat.

The metabolism of 3beta-hydroxy-5alpha-pregnan-20-one sulphate was studied in bile fistula rats and in isolated perfused livers. Computerized gas chromatography--mass spectrometry, in combination with specific deuterium-labelling, was employed to follow the metabolic transformations. Male animals excreted metabolites into bile more rapidly than females, a finding which could be correlated with the preferential formation of glucuronide conjugates in the male liver. The major metabolic pathway in male rats involved the steps: hydrolysis, 2alpha-hydroxylation, oxidoreduction at C-3 and glucuronide conjugation, yielding 2alpha, 3alpha-dihydroxy-5alpha-pregnan-20-one glucuronide as the major metabolite. Only traces of the injected steroid sulphate were detected in bile from male animals. In contrast, the administered compound was the major steroid excreted in bile of female rats, where the main metabolite was identified as 3beta,15beta-dihydroxy-5alpha-pregnan-20-one sulphate. A minor metabolite, 3beta,16alpha-dihydroxy-5alpha-pregnan-20-one, was found as a monosulphate in female rats and as both a disulphate and a glucuronide conjugate in male rats. The deuterium content of the sulphated 15beta-and 16alpha-hydroxylated metabolites was consistent with metabolic pathways involving direct hydroxylation of the injected steroid sulphate. The results obtained from the liver perfusions were essentially the same as those from the experiments with bile fistula animals. This indicates that all the observed metabolic reactions took place in the liver.

Animals↗
PubMed1975

Deuterium transfer from [1,1-2-H] ethanol during metabolism of bile acids and cyclohexanone in the isolated perfused rat liver.

Deuterium transfer from [1,1-2-H]ethanol (95 atoms % excess) to reducible substrates was studied in the isolated perfused rat liver. The dueterium excess in cyclohexanol formed from cyclohexanone was somewhat lower (49 atoms%) than found under conditions in vivo, and this was also true of the deuterium excess in lithocholic acid formed from 3-oxo-5beta-cholanoic acid. These results may reflect a slower rate of ethanol oxidation in the isolated organ than in vivo. Cycloserine decreased the dueterium transfer to both substrates, whereas addition of lactate and malate resulted in an increased deuterium excess in cyclohexanol and a decreased deuterium excess in lithocholic acid. Addition of heavy water to the perfusion fluid resulted in labelling at C-3 of lithocholic acid formed from 3-oxo-5beta-cholanoic acid, and at C-3, C-4 and C-5 of 3alpha-hydroxy-5alpha-cholanoic acid formed from 3-oxo-4-cholenoic acid. The deuterium excess of hydrogens derived from NADPH (at C-3 and C-5) was approximately the same as that of hydrogen derived directly from water (at C-4). Thus, the hydrogen of NADPH is extensively exchanged with protons of water, which explains the dilution of deuterium with protium during the transfer from [1,1-2-H]ethanol via NADPH to the bile acids. The labelling at C-5 in the reduction of the 4,5-double bond indicates that different pools of NADPH are used for reduction of this double bond and the 3-oxo group, since in a previous study it was shown that deuterium is transferred from [1,1-2-H]ethanol only in the latter reaction.

Animals↗
PubMed1975

A compact perfusion system for studies on the control of metabolic processes in isolated organs from small animals.

A compact apparatus for perfusion of isolated organs from small animals is described. The system is based on a module principle making it useable both in low and high pressure perfusions. 40-80 ml of heparinized, diluted rat blood used as liver-perfusion medium, is recirculated in the system, which is temperature controlled by means of a water jacket. A new type of capillary membrane oxygenator is used for oxygenation. The system permits rapid measurements of perfusate flow, vascular resistance, bile production (when the isolated liver is used), urinary production (when the isolated kidney is used), gas tensions, oxygen consumption, pH and perfusion pressure. Descriptions of the techniques used for operation and perfusion of isolated livers and kidneys from rats are given. By the generally accepted criteria of viability the isolated rat liver remains almost normal for the test period of 3 h. Liver functions were normal as judged by formation of glucose, respiratory rate, urea and bile production and gross morphology. There was very little leakage of liver enzymes into the perfusate. The transformation and elimination of labelled corticosterone were studied to test the steroid metabolizing activity of the isolated rat liver preparation.

Animals↗
PubMed1975

The biliary excretion of 3H-inulin and 3H-terbutaline in the unanesthetized rat.

An animal model which permits sampling of arterial blood and bile from unanesthetized rats with uninterrupted enterohepatic circulation is described. Pharmacokinetic data concerning inulin (0.2 mumol kg-1) and terbutaline (1.8 mumol kg-1) after intraarterial injection are presented. The following values for inulin were obtained Vdbeta equals 0.25 ml g-1, plasma clearance equals 2.3 ml min-1 kg-1 and bile clearance equals 0.03-0.04 ml min-1 kg-1, which mainly are in agreement with data from the literature. For terbutaline the corresponding values were 0.58 ml g-1, 5.2 ml min-1 kg-1 and 0.12-0.98 ml min-1 kg-1, respectively.

Animals↗
PubMed1974

The effects of two disulphides on cholinesterase activity in the spectrophotometric assay.

1. 5,5'-Dithiobis-(2-nitrobenzoate) did not influence serum cholinesterase activity, whereas 2,2'-dithiodipyridine had an inhibitory effect. 2. The lowering of the molar extinction coefficients observed in the presence of physostigmine may be a result of a reaction between thiolate ions with carbamate moieties. 3. The use of 5,5'-dithiobis-(2-nitrobenzoate) is still recommended in investigations, especially where the quantitative aspects are significant.

Acetylcholinesterase↗