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T Curstedt

Publications and source records attributed to T Curstedt.

At least 145 records · Page 8Linked to original sources
PubMed1983

Rabbit lung after inhalation of soluble nickel. II. Effects on lung tissue and phospholipids.

Rabbits were exposed to soluble nickel chloride, about 0.3 mg/m3 as nickel, for about 1 month (5 days/week, 6 hr/day). The upper lobe in the left lung was examined with light microscopy and samples from the left lower lobe with electron microscopy. Nodular accumulation of macrophages and laminated structures occurred in alveoli of all exposed rabbits, but otherwise no inflammatory reactions. Volume density of the alveolar epithelial type II cells was doubled due to increased cell number as well as cell volume. The tissue content of phospholipids, determined in the lower lobe of the left lung, had increased by about 40%, mainly due to elevated disaturated phosphatidylcholines. The effect pattern was almost identical to that seen earlier in inhalation experiments with metallic nickel dust, strongly indicating that nickel ions are responsible also for the changes seen after exposure to metallic nickel. This suggests that all nickel compounds may produce the pathological condition, which is similar to that seen in the disease pulmonary alveolar proteinosis.

Aerosols↗
PubMed1983

Rabbit lungs after long-term exposure to low nickel dust concentration. I. Effects on phospholipid concentration and surfactant activity.

Rabbits were exposed for 4 or 8 months (5 days/week, 6 hr/day) to 0.13 +/- 0.05 mg/m3 (mean +/- SD) of metallic nickel dust. After exposure the left lung was homogenized and its content of phospholipids as well as the concentration and composition of the phosphatidylcholines were estimated. The right lung was lavaged and the surface tension of the lavage fluid was studied with a pulsating bubble technique. Both exposed groups showed a similar increase in total phospholipids, about 20% in the upper lobe and 30% in the lower lobe. The increase was mainly, possibly totally, due to an elevated level of phosphatidylcholines, especially disaturated species. Surface tension was significantly lower in exposed rabbits after 4 months of exposure but it was similar to that of the controls after 8 months.

Animals↗
PubMed1983

Individual molecular species of phosphatidylcholines and phosphatidylinositols in liver of rats fed bis(2-ethylhexyl)phthalate.

Rats were given a diet containing 1% bis(2-ethylhexyl)phthalate (DEHP) for 3 weeks, and their hepatic lipids analyzed. Phosphatidylcholines increased by 20%, while other phospholipid classes and cholesterol remained unchanged and triglycerides fell. The composition of molecular species of phosphatidylcholines was changed. Thus, the hepatic content of the major species, 1-palmitoyl-2-oleoyl-, 1-palmitoyl-2-arachidonoyl- and 1-stearoyl-2-arachidonoylphosphatidylcholines, rose by about 150%, 90% and 70%, respectively. The content of the other major species, 1-palmitoyl-2-linoleoyl- and 1-stearoyl-2-linoleoylphosphatidylcholine fell by about 20% and 30%, respectively. The content of alkyl-acyl analogues of phosphatidylcholines increased by about 70%, but the composition of molecular species remained the same. The composition of molecular species of phosphatidylinositols was also unchanged. Thus, the analyses show that DEHP can induce selective changes in molecular species of certain phospholipids in the liver. This could be important for the functioning of membrane structures in the hepatocyte.

Animals↗
PubMed1982

Biosynthesis of molecular species of hepatic glycerophosphatides during metabolism of [1,1-2H2]ethanol in rats.

Rats were injected with [1,1-2H2]ethanol once every hour for 3-48 h and the fatty acid composition of and deuterium incorporation into different classes of hepatic phosphatidylcholines, phosphatidylethanolamines, phosphatidylserines and phosphatidylinositols were determined. Phosphatidylcholines and phosphatidylethanolamines with an oleoyl or a docosahexaenoyl residue at C-2 increased, while many of the species with a linoleoyl or an arachidonoyl residue at C-2 decreased throughout the experiment. No changes were seen in the phosphatidylinositols. The distribution of deuterium between the different positions of the glycerol moiety of the glycerophosphatides was similar for all species studied. The deuterium excess in molecules synthesized de novo was also similar for all species and remained relatively constant throughout the experiment. The mean excess was 8 atom% at C-1, 36 atom% at C-2 and 22 atom% at C-3 of the glycerol moiety. The apparent half-life times calculated for the glycerol moieties were different for the individual molecular species and varied between 1.1 and 36 h. However, the observed half-life times for the corresponding species of the different glycerophosphatides usually were similar. The deuterium excess in hepatic sn-glycerol 3-phosphate synthesized de novo was 8 atom% at C-1, 28 atom% at C-2 and 13 atom% at C-3. The excess at C-2 and C-3 was lower than that of the glycerol moiety of glycerophosphatides, indicating that a specific pool of sn-glycerol 3-phosphate with a gluconeogenetic origin was used for the biosynthesis of the different glycerophosphatides, and that the formation of this pool was closely coupled to ethanol oxidation. The deuterium excess in sn-glycerol moiety of the phosphatidylcholines indicated that these molecules had long half-life times or that the labelling of their precursor increased throughout the experiment.

Animals↗
PubMed1982

Transfer of 2H atoms to molecular species of ether analogues of hepatic phosphatidylcholines and phosphatidylethanolamines during metabolism of [l,l-2H2]ethanol in rats.

Rats were given [1,1-2H2]ethanol once every hour for 3-48 h and the concentrations of and deuterium incorporation into individual molecular species of either analogues of phosphatidylcholines and phosphatidylethanolamines were determined. The concentration of 1-alkyl-2-acyl-sn-glycero-3-phosphocholines increased 50-100%. The total amount of 1-alk-1'enyl-2-acyl-sn-glycero-3-phosphocholines was relatively constant but the percentage of 1-hexadec-1'-enyl-2-palmitoyl-sn-glycero-3-phosphocholine decreased throughout the experiment. A small increase of 1-alk-1'-enyl-2-sn-glycero-3-phosphoethanolamines was observed. The total deuterium content at C-2 and C-3 of the glycerol moiety of 1-alkyl-2-acyl- and 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphocholines was 2.7-4.4 atom% and 0.3-0.8 atom%, respectively, after 48 h of [1,1-2H2]ethanol administration. The corresponding values for 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamines were 1.2-2.9 atom%. The deuterium content at C-1 of the alkyl group of 1-alkyl-2-acyl-sn-glycero-3-phosphocholines was low. The results are compatible with formation of ether lipids from alkyl dihydroxyacetone phosphate followed by reduction with NADPH with low labelling, but argue strongly against participation of alcohol dehydrogenase in the formation of the fatty alcohol.

Animals↗
PubMed1982

Combined effects of surfactant substitution and prolongation of inspiration phase in artificially ventilated premature newborn rabbits.

Premature newborn rabbits, delivered by hysterotomy on day 27 of gestation, were tracheotomized at birth, kept in body plethysmographs, and subjected to pressure-generated ventilation at a working pressure of 25 cm H2O, 100% O2, and frequency 40/min. Thirty-seven animals received 50 microliters of heterologous surfactant (phospholipid content 40 mg/ml) via the tracheal cannula before onset of artificial ventilation, eight were ventilated with a positive end-expiratory pressure (PEEP) of 6 cm H2O, and 44 served as controls. All animals were ventilated in a randomized sequence of 2-min periods with 20, 40, 60, or 80% inspiration time. After the experiment the trachea was clamped at end-inspiration and the lungs fixed by immersion in formalin. Plethysmograph recordings of tidal volume revealed that lung-thorax compliance was low in control animals, even at inspiration time 80% (mean +/- S.E. = 0.17 +/- 0.03 ml/cm H2O X kg). In animals treated with surfactant or PEEP, compliance was significantly improved at all ventilator settings. The highest mean compliance values, obtained at 60% inspiration time were 0.91 +/- 0.07 and 0.73 +/- 0.14 ml/cm H2O X kg in surfactant- and PEEP-treated animals, respectively. Compliance of surfactant-treated animals was significantly higher than that of PEEP-treated animals at inspiration time 40% (0.85 +/- 0.07 versus 0.52 +/- 0.13 ml/cm H2O X kg; P less than 0.05). The relative volume of the alveolar compartment, determined morphometrically in histologic sections and expressed as the alveolar expansion index (Ia), was significantly higher in surfactant-treated animals than in controls (1.60 +/- 0.12 versus 0.74 +/- 0.06; P less than 0.005), but not improved in animals ventilated with PEEP. In animals receiving surfactant, Ia increased with the duration of the inspiration phase, from 0.99 +/- 0.10 at 20% to 1.95 +/- 0.22 at 80% inspiration time. There was also histologic evidence of enhanced recruitment of aerated alveoli in surfactant-treated animals ventilated with prolonged inspiration time.

Animals↗
PubMed1981

Molecular species of biliary phosphatidylcholines in gallstone patients: the influence of treatment with cholic acid and chenodeoxycholic acid.

Molecular species of phosphatidylcholines were analyzed in hepatic and gallbladder bile obtained from six subjects with adenomyoma of the gallbladder (gallstone-free controls) and 27 gallstone patients undergoing cholecystectomy. Seven of the gallstone patients had been treated with cholic acid and seven with chenodeoxycholic acid for at least 8 weeks before operation. The two predominant species were 1-palmitoyl-2-oleoyl- and 1-palmitoyl-2-linoleoyl-sn-glycerophosphocholines which together accounted for 75-80% of the total amount of phosphatidylcholines. Minor species were 1-palmitoyl-2-palmitoleoyl-, 1-stearoyl-2-linoleoyl-, 1-oleoyl-2-linoleoyl-, and 1-palmitoyl-2-arachidonoyl-sn-glycerophosphocholines. Gallstone patients had a higher portion of the 1-palmitoyl-2-oleoyl species and a concomitant lower proportion of the 1-palmitoyl-2-linoleoyl species than gallstone-free subjects. The ratio between the two species was about 0.7 and 0.4, respectively, in the hepatic bile of the two groups of patients. Treatment with bile acids was associated with a normalization of the pattern of phosphatidylcholines.

Bile↗
PubMed1981

Gallstone formation in guinea pigs under different dietary conditions. Effect of vitamin C on bile acid pattern.

Guinea pigs formed gallstones when fed chow supplemented with cholesterol and cholic acid. Although the stones contained little or no cholesterol the changes in biliary bile acid and lipid composition were similar to those observed in other rodents under conditions of cholesterol gallstone formation. Addition of cholestyramine to chow had a midly lithogenic effect. Hypovitaminosis C in animals given cholesterol and cholic acid resulted in an increase of the cholesterol content of the gallstones. The composition of biliary bile acids was markedly changed. Reductive formation of deoxycholic acid decreased and oxidative formation of ketonic bile acid increased. The results show that vitamin C may influence the redox state of the intestinal microorganisms microorganisms responsible for these conversions.

Animals↗
PubMed1980

Biosynthesis of 5 alpha- and 5 beta-cholanoic acid derivatives during metabolism of [1,1-2H]- and [2,2,2-2H]ethanol in the rat.

Female bile fistula rats were given [1,1-2H]ethanol in a single dose or [2,2,2-2H]ethanol repeatedly for 24 h and incorporation of deuterium into the following bile acids was determined: taurine conjugates of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5(alpha and beta)-cholanoic, 3 alpha, 7 alpha-dihydroxy-5(alpha and beta)-cholanoic and 3 alpha, 6 beta, 7 alpha-trihydroxy-5 beta-cholanoic acids; sulphates of 3(alpha and beta), 7 alpha, 12 alpha-trihydroxy-5 alpha-cholanoic, and 3(alpha and beta), 7 alpha-dihydroxy-5 alpha-cholanoic acids. The kinetics of deuterium incorporation from [2,2,2-2H]ethanol was the same for all bile acids indicating that they were formed from a single pool of cholesterol. The labelling pattern of bile acids formed during metabolism of [1,1-2H]-ethanol indicated that the hydrogen at C-5 was labelled in all bile acids. Taken together with previous results this indicates that 3-oxo-4-cholenoic acid is not an intermediate in the formation of allo bile acids. The results support the view that formation of allo bile acids via a mitochondrial pathway is of little importance in the bile fistula rat.

Animals↗
PubMed1977

Incorporation of the 1-pro-R and the 1-pro-S hydrogen atoms of ethanol into steroids and phosphatidylcholines in vivo.

The transfer of deuterium from chiral 1-monodeuteroethanols to various metabolites formed in the liver was studied in order to investigate the coupling of metabolic reductions to the alcohol dehydrogenase and the aldehyde dehydrogenase reactions. The ethanols were administered to female bile fistula rats for 10 h. The hydrogen at C-2 in the glycerol moiety of newly formed phosphatidylcholine molecules in bile, liver and plasma was derived to 22-25% from the 1-pro-R position and to 5-6% from the 1-pro-S position in the ethanol. sn-Glycerol 3-phosphate isolated from liver had a lower deuterium content at C-2. The ratio between the contributions from the two positions in ethanol to C-2 of free sn-glycerol 3-phosphate was the same as in the phosphatidylcholines. This indicates that the higher degree of labelling of this position in phosphatidylcholines is not due to a specific coupling between alcohol dehydrogenase and the formation of a phosphatidylcholine precursor. Cholesterol and chenodeoxycholic acid in bile became increasingly labelled, and the ratio between the incorporations from the 1-pro-S and the 1-pro-R positions of ethanol was about 0.37 in cholesterol and 0.46 in chenodeoxycholic acid. Thus, these NADPH-dependent reactions utilized hydrogen from the 1-pro-S position to a larger extent than NADH-dependent reactions.

Animals↗
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↗
PubMed1975

Biosynthesis of acyl groups on molecular species of biliary phosphatidylcholines during metabolism of [2,2,2-2H3]ethanol.

Incorporation of deuterium into different positions of individual molecular species of biliary phosphatidylcholines was determined in bile fistula rats given [2,2,2-2H3]ethanol under conditions ensuring maximal rate of oxidation for 24 h. The deuterium-labelling of the glycerol moiety of the major molecular species was about 6-8 atom% at the end of ethanol administration. The deuterium excess at each of the different positions of the glycerol moiety of 1-palmitoyl-2-linoleoyl phosphatidylcholine was less than 3 atom%. From the isotopic composition of the palmitoyl residues of the phosphatidylcholines, it was calculated that [2,2,2-2H3]ethanol supplied about 35-40% of the acetyl-CoA forming the terminal methyl group and about 25-30% of the other C2 units of the palmitic acid chain. This difference in deuterium incorporation was interpreted as being due to an isotope effect, probably in the rate-limiting carboxylation step of acetyl-CoA. Most or perhaps all of the acetyl groups derived from ethanol were introduced into the terminal methyl group without loss of deuterium. This indicates that citrate is not an important carrier of acetyl-CoA in the biosynthesis of fatty acids from ethanol.

Animals↗