Effects of ethanol and secretagogues on the composition of phosphatidylinositol in pancreas and submaxillary gland.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
T Curstedt
Publications and source records attributed to T Curstedt.
Release of corticosteroids from human adrenals in vitro.
Explore the source record for details and available documents.
Adolescent↗
Rabbit lung after inhalation of hexa- and trivalent chromium.
Rabbits were exposed to aerosols of hexavalent (Na2CrO4) and trivalent chromium (Cr(NO3)3) at concentrations of 0.9 and 0.6 mg/m3 of chromium respectively for 4-6 weeks (5 days/week and 6 hr/day). Three of eight rabbits exposed to Cr(VI) and three of eight rabbits exposed to Cr(III) showed nodular accumulations of alveolar macrophages, similar to the lesions observed in previous experiments after exposure to Ni2+, Cd2+, or metallic nickel. Macrophages from rabbits exposed to Cr(III) usually contained round dark inclusions, large lysosomes, and laminated inclusions similar to the lamellar bodies in the type II cells, and most macrophages from rabbits exposed to Cr(VI) showed enlarged lysosomes. However, the total amount of phospholipids and the volume density of type II cells did not differ significantly between exposed rabbits and controls. Our findings indicate that the macrophages are directly affected by chromium. The accumulation of laminated structures in the alveolar macrophages after Cr(III) exposure might be due to an impaired catabolism of surfactant.
Administration, Inhalation↗
Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage.
Severe respiratory insufficiency was induced in adult guinea pigs by repeated lung lavage. The animals were then ventilated for 75 min with 100% O2, insufflation pressure 28/6-8 cmH2O (2.7/0.6-0.8 kPa), frequency 30/min, and 33% inspiration time. One group of animals (I) was treated with protein-depleted porcine surfactant, prepared by a combination of sucrose-gradient centrifugation, heating to 90 degrees C, and chloroform/methanol extraction. Another group (II) received the phospholipid fraction of porcine surfactant, isolated from minced lungs by chloroform/methanol extraction and liquid-gel chromatography. Surfactant was administered in two 1-ml doses (lipid concentration 90 mg/ml) instilled via the tracheal cannula about 15 and 45 min after the lavage procedure. Non-treated, lavaged animals served as controls. After 75 min of ventilation, control values for PaO2 and PaCO2 were 13.3 +/- 6.8 and 6.8 +/- 2.3 kPa (mean +/- s.d.), respectively. The corresponding values in Group I of surfactant-treated animals were 52.9 +/- 7.7 and 4.4 +/- 1.1 kPa, in Group II 53.5 +/- 7.3 and 4.8 +/- 1.3 kPa (P less than 0.02-0.002). The two groups of surfactant-treated animals also had significantly improved alveolar air expansion in histological sections, as reflected by increased alveolar volume density (0.67 +/- 0.05 and 0.62 +/- 0.11 vs 0.45 +/- 0.08 in controls; P less than 0.002). The benefits of surfactant replacement in this experimental model were thus similar to those previously observed in animal models of neonatal surfactant deficiency as well as in babies with respiratory distress syndrome (RDS). Our data suggest that surfactant replacement might have a therapeutic effect also in clinical adult RDS.
Animals↗
Correlations between physical and physiological properties of various preparations of lung surfactant.
The physical and physiological properties of natural surfactant were investigated after the addition of various synthetic lipids. Three types of surfactant were studied: 1. Bovine surfactant with rapid spreading (1.6 s) and a relatively high minimal surface tension during surface compression (16 mN/m). 2. The same surfactant enriched with dipalmitoylphosphatidylcholine (DPPC), tripalmitin, and palmitic acid showing slow spreading (55 s) and low minimal surface tension (5 mN/m). 3. The same surfactant enriched with DPPC and dipalmitin, showing rapid spreading (1.8 s) and low minimal surface tension (6 mN/m). The physiological properties of these surfactants were evaluated in immature newborn rabbits. All three preparations effectively improved lung expansion and stability in pressure-volume recordings, increased tidal volumes during artificial ventilation, and enhanced alveolar volume density in histological sections. The magnitude of the therapeutic effects was similar for non-enriched and enriched materials. Thus, wide variations in in vitro surface properties do not seem to influence the in vivo activity of the surfactant preparations.
1,2-Dipalmitoylphosphatidylcholine↗
The role of the low-molecular weight (less than or equal to 15,000 daltons) apoproteins of pulmonary surfactant.
An artificial surfactant was prepared by combining synthetic dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylglycerol and the low-molecular weight (less than or equal to 15,000 daltons) surfactant apoproteins in the proportions 80:20:5. In the Wilhelmy balance, this surfactant formed a film with an equilibrium surface tension of 29 mN/m; surface tension was reduced to nearly zero during cyclic film compression, with effective respreadability during multiple compression-expansion cycles; similar surface properties were recorded with a pulsating bubble. When instilled into the airways of artificially ventilated immature newborn rabbits, the apoprotein-based artificial surfactant produced a five-fold increase in tidal volumes at insufflation pressure 25 cm H2O; this effect is similar to that obtained in previous experiments with natural surfactant phospholipids, administered in equal concentration (5 mg/ml). Higher concentration of the apoprotein-based surfactant could not be evaluated in vivo due to the high viscosity of the material. Systematic studies should be undertaken to find out whether an even more effective artificial surfactant could be prepared from the low-molecular weight apoproteins and other combinations of synthetic phospholipids.
1,2-Dipalmitoylphosphatidylcholine↗
Rabbit lung after inhalation of manganese chloride: a comparison with the effects of chlorides of nickel, cadmium, cobalt, and copper.
Rabbits were exposed to aerosols of MnCl2 (mass median aerodynamic diameter 1 micron) in metal concentrations of 1.1 and 3.9 mg/m3 for 4-6 weeks, 5 days/week, 6 h/day. The effects of alveolar type II cells, phospholipids, alveolar macrophages, and lung structure in general were compared with earlier reported effects of Ni2+, Cd2+, Cu2+, and Co2+. Except for a significant increase in the diameter of the alveolar macrophages after exposure to the higher Mn2+ concentration, no abnormalities were seen. The results of this and earlier studies indicate that these five metal ions have different, specific effects on the alveolar part of the lung.
Animals↗
Leakage of protein in the immature rabbit lung; effect of surfactant replacement.
Immature newborn rabbits, delivered on day 27 of gestation, were ventilated artificially for 60 min, with or without previous treatment with natural surfactant. Insufflation pressure was adjusted to maintain an average tidal volume of about 10 ml/kg. All animals received, before the onset of ventilation, 125I-labeled albumin via the airways and 131I-labeled albumin intravenously. At the end of the experiment 3.1 +/- 1.3% (means +/- SD) of the 131I-albumin had permeated into the alveolar compartment of control animals; the corresponding figures for surfactant-treated animals were 1.7 +/- 0.8% (P less than 0.002). In control animals only 18.2 +/- 4.4% of the 125I-albumin could be recovered from the airspaces after 60 min, whereas 69.9 +/- 14.6% of this label was recovered in surfactant-treated animals (P less than 0.002). Alveolar wash samples from control animals also contained significantly increased activity of surfactant inhibitor, as evaluated with pulsating bubble. The bidirectional flux of protein, including surfactant inhibitor, was thus significantly decreased in these immature lungs by surfactant replacement.
Albumins↗
Cushing's syndrome due to an ACTH-producing neuroendocrine tumour in the nasal roof.
A patient with ectopic adrenocorticotrophic hormone (ACTH) production from a neuroendocrine tumour of the nasal roof is presented. By indirect immunoperoxidase techniques the tumour cells were shown to be distinctly positive for ACTH and beta-endorphin but negative for other peptides derived from pro-opiomelanocortin. Neither corticotropin releasing hormone (CRF) found in some tumours associated with ectopic Cushing's syndrome, nor gastrin immunoreactivity, which coexists with ACTH in normal rat pituitary and in rat and human gastrointestinal cells, were demonstrable in the tumour. A review of other, previously recognized locations of CRF/ACTH producing tumours is given to increase the awareness of the ectopic Cushing's syndrome, which may lack the classical features and is characterized by fulminant clinical course, extreme fatigue, weakness, pale facial swelling, oedema and hypokalaemic alkalosis.
ACTH Syndrome, Ectopic↗
Surfactant treatment and ventilation by high frequency oscillation in premature newborn rabbits: effect on survival, lung aeration, and bronchiolar epithelial lesions.
Premature rabbit neonates delivered at gestational age 27 days were ventilated by high frequency oscillation for 60 min with 100% O2, using a frequency of 7-8 Hz, 50% inspiration time and mean airway pressures of 6-8 cm H2O. Twenty-five animals received bovine surfactant (2 ml/kg body weight; phospholipid concentration 85-100 mg/ml) in the tracheal cannula before onset of ventilation, and 22 littermates served as controls. In the surfactant-treated group, average tidal volume was about 10 times larger than in controls, yet only 15% of the estimated dead space. Judged from ECG recordings, the treated animals also had a much higher survival rate: 96 versus 5% (p less than 0.001). Morphometrically, mean alveolar volume density was increased in the surfactant-treated animals in comparison with controls: 0.65 +/- 0.08 versus 0.37 +/- 0.08 (means +/- SD; p less than 0.005). Bronchiolar epithelial lesions were found in all control animals and were severe in almost all cases. In the surfactant-treated group, epithelial lesions were absent in 12, mild in 11, and fairly prominent in two animals. We conclude that after treatment with surfactant, the premature newborn rabbit can be ventilated adequately with high frequency oscillation at comparatively low mean airway pressures and that surfactant replacement effectively reduces the development of epithelial lesions in conducting airways during high frequency oscillation.
Animals↗
Physiological activity of pulmonary surfactant with low protein content: effect of enrichment with synthetic phospholipids.
A natural surfactant with low protein content (1%) was prepared by a sequence of cold centrifugation, heating to 90 degrees C, sucrose-gradient centrifugation, and extraction with chloroform:methanol. Some of the material was enriched with dipalmitoylphosphatidylcholine (DPPC) and unsaturated phosphatidylglycerol (PG) to relative concentrations of 56% and 10%, respectively. The in vitro physical properties of these preparations were evaluated with pulsating bubble and Wilhelmy balance and their in vivo activity with experiments on artificially ventilated premature newborn rabbits, delivered on day 27 of gestation. The animals were kept in body plethysmographs at 37 degrees C and ventilated artificially with a standardized sequence of insufflation pressures: 25, 20, and 15 cm H2O. The lungs were fixed by vascular perfusion and the alveolar expansion evaluated morphometrically in histologic sections. Enrichment of surfactant with DPPC and PG resulted in lower minimal surface tension during surface compression but did not further improve lung compliance or the alveolar expansion pattern. Treatment with nonenriched surfactant at a phospholipid concentration of 100 mg/ml (individual dose = 200 mg/kg) caused a markedly increased lung compliance at all insufflation pressure levels (p vs. controls less than .01). Our data indicate that pulmonary surfactant remains physiologically active after removal of most of its protein components and that enrichment with DPPC and PG reduces the in vitro minimal surface tension without adding to the in vivo efficacy.
Animals↗
Heterogeneity of the sn-glycerol 3-phosphate pool in isolated hepatocytes, demonstrated by the use of deuterated glycerols and ethanol.
Hepatocytes were isolated from female rats and incubated with [1,1,3,3-2H4]glycerol or [2-2H]glycerol. The deuterium excess in phosphatidylcholines, sn-glycerol 3-phosphate and other organic acids was determined by g.l.c./mass spectrometry. The unlabelled fraction of the major phosphatidylcholines decreased exponentially, and the turnover was not changed by the presence of ethanol. The relative contribution of the two deuterated glycerols was about the same in the major phosphatidylcholine as in sn-glycerol 3-phosphate, indicating that formation by acylation of dihydroxyacetone phosphate is insignificant. [1,1,3,3-2H4]Glycerol had lost deuterium to a larger extent when it was incorporated in the phosphatidylcholine than when it was incorporated in sn-glycerol-3-phosphate, indicating that the phosphatidylcholines are formed from a separate pool of sn-glycerol 3-phosphate. Deuterium at C-2 was transferred between sn-glycerol 3-phosphate molecules to about 25%. Ethanol decreased the extent of deuterium transfer, the extent of glycerol uptake and the loss of deuterium at C-1 and C-3 in sn-glycerol 3-phosphate. The results indicate that the oxidation to dihydroxyacetone phosphate was inhibited by the NADH formed during ethanol oxidation. [2-2H]Glycerol also labelled an alcohol dehydrogenase substrate, malate and lactate, indicating oxidation of sn-glycerol 3-phosphate in the cytosol. The two acids appeared to be formed in reductions with different pools of NADH.
Animals↗
[Beneficial effect of surfactant treatment of IRDS].
Explore the source record for details and available documents.
Diseases in Twins↗
Decrease in arachidonoyl-containing phosphatidylinositols in pancreas of rats fed an ethanol-containing diet.
The composition of the glycerophosphatides in pancreas and liver was studied in rats fed an ethanol-containing diet and in pair-fed controls. The fraction of arachidonoyl-containing phosphatidylinositols in pancreas was much lower in the former rats, also when the rats were starved for a final 24 hr period. This fraction was also lower in fed than in starved control rats. The effect was not observed after acute administration of ethanol. It is suggested that the decrease in arachidonoyl-containing phosphatidylinositols was due to chronic pancreatic hyperfunction in the ethanol-fed rats.
Animals↗
Lung morphology and phospholipids after experimental inhalation of soluble cadmium, copper, and cobalt.
Rabbits were exposed to chlorides of cadmium, copper, or cobalt, for 4-6 weeks (5 days/week and 6 hr/day) at levels ranging from 0.4 to 0.6 mg metal/m3. After exposure to Cd2+ the lungs were enlarged and an interstitial infiltration of neutrophils and lymphocytes as well as intraalveolar accumulations of large, vacuolated macrophages were observed. Morphometrical measurement of volume density of type II cells showed a 2.5-fold increase due to enhancement of cell size as well as cell number. The phospholipid content of lung tissue, determined in the lower left lobe, increased by 40%, mainly due to elevated levels of disaturated phosphatidylcholines. The results indicate that Cd2+ induces a reaction pattern similar to that seen following exposure to Ni2+, in addition to which Cd2+ causes interstitial alveolitis. Exposure to Cu2+ and Co2+ only affected the type II cells. Exposure to Cu2+ resulted in a 1.5-fold increase in volume density, probably due to enhanced number of cells. Following exposure to Co2+ the type II cells formed nodules protruding into the alveolar lumen. However, no significant increase in volume density occurred. The possible association between this abnormal growth pattern and early tumor formation deserves further investigation.
Aerosols↗
Changes in glycerophosphatides and their ether analogs in lung lavage of rabbits exposed to nickel dust.
In rabbits exposed for 3 and 6 months to 1 mg/m3 of metallic nickel dust, the increase of pulmonary phospholipids was about 3 and 4 times, respectively. The corresponding increase of phospholipids in lung lavage was about 6 and 11 times, respectively. A detailed study of the phospholipid composition in lung lavage from the rabbits exposed for 3 months showed an increased amount of nonacidic phospholipids and a decreased amount of phosphatidylglycerols. Although most of the increase was due to the disaturated phosphatidylcholines, the relative increase was highest for the ether analogs of phosphatidylethanolamines. In the exposed rabbits the two ether analogs, 1-alk-1'-enyl-2-acyl- and 1-alkyl-2-acyl-sn-glycero-3-phosphoethanolamines, constituted 10.4 and 8.2%, respectively, of the phosphatidylethanolamine fraction. The corresponding values in the control rabbits were 5.2 and 0%, respectively. The occurrence of 1-alkyl-2-acyl-sn-glycero-3-phosphoethanolamines and the increase of 1-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoenthanolamines indicate that the biosynthetic synthetic pathway of ether lipids may be stimulated in the exposed rabbits. This is of interest since a high proportion of ether lipids is observed in many tumors and since some nickel compounds may give respiratory tumors.
Animals↗
Toxicology of nickel.
Rabbits were exposed to low levels of airborne metals for 1-8 months, 5 days/week, 6 hours/day. After exposure, lung tissue was examined by light and electron microscopy. Macrophages lavaged from the left lung were examined morphologically and functionally. Phospholipids were analysed in lung tissue or lavage fluid. Metallic nickel dust, 0.1-1 mg/m3, affected alveolar macrophages, alveolar epithelial type II cells and phospholipids. In the lung tissue, nodular accumulation of macrophages was seen, and the volume density of alveolar type II cells was elevated. The amount of phospholipids was markedly increased, mainly due to an increase in disaturated phosphatidylcholines. After 1 month of exposure the macrophages appeared active. After 3 months they appeared 'overfed' and inactive. Metallic iron, chromium and cobalt did not produce the same effects as nickel. Exposure to 0.2 mg/m3 soluble nickel as nickel chloride produced almost identical effects to those of metallic nickel, indicating that the effect of the metallic nickel particles was caused by nickel ions. Exposure to cadmium chloride produced nearly all the effects produced by nickel chloride. However, cadmium chloride increased the level of lysozyme in the macrophages whereas nickel chloride decreased it. Cadmium chloride also produced interstitial alveolitis and cytoplasmic blebs on the surface of the macrophages. Cobalt chloride affected the growth of the type II cells, which formed nodules, but did not seem to affect the production of surfactant material by those cells. Copper chloride produced no effect apart from a slight increase in volume density of the type II cells. Thus, of four divalent metal ions, three (Ni2+, Cd2+ and Co2+) in similar concentrations in the inhaled air produced clear but different pathological effects in the lungs.
Animals↗
Origin of biliary phosphatidylcholines studied by coenzyme labelling with [1,1-2H2]ethanol.
The labelling of individual molecular species of phosphatidylcholines in bile and liver was measured in bile fistula rats given [1,1-2H2]ethanol immediately after the cannulation of the bile duct. Corresponding species in liver and bile were labelled to the same extent, the deuterium excess in the glycerol moiety (at C-2) of biliary molecules with rapid turnover possibly being slightly higher in the bile than in liver. The labelling of different positions and the half-life times of different molecular species were about the same as previously found 48 h after the cannulation. The only exception was the 1-stearoyl-2-linoleoyl species, which had a half-life time 5-7 times longer immediately after operation than after 48 h of biliary drainage. The results support our previous conclusion that the molecular species of phosphatidylcholines in liver and bile represent the same, or very similar, pool(s) of molecules.
Animals↗