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Biomedical subjects

M Hallman

Publications and source records attributed to M Hallman.

At least 163 records · Page 9Linked to original sources
PubMed1985

Composition and surface activity of normal and phosphatidylglycerol-deficient lung surfactant.

The possibility that pulmonary surfactant, characterized by a phosphatidylglycerol deficiency, as in early fetal life, might have inferior surface properties was evaluated. We obtained this specific surfactant from adult rabbits by withholding glucose and giving them an excess of myoinositol by mouth and intravenously. Controls were given a similar quantity of glucose. The myoinositol resulted in a drastic reduction of surfactant phosphatidylglycerol, from 7.2 to 0.3% of phospholipids, and a corresponding increase in phosphatidylinositol from 4.8 to 11.3%. In addition, the myoinositol treatment increased the myoinositol that was disaturated from 18.5 to 27.3% (p less than 0.05). The corresponding figures for disaturated phosphatidyl-choline were 56.0 and 60.5%, respectively (NS). The myoinositol treatment for 4 days increased the pool size of alveolar surfactant by 32% (p less than 0.01). The surface activity was studied with modified Wilhelmy balance and the pulsating bubble surfactometer. Surfactant containing phosphatidylinositol rather than phosphatidylglycerol was not inferior, as compared to surfactant that contained phosphatidylglycerol (minimum surface tension: 2.0 versus 2.2 mN X m-1; collapse rate at 10 nM X m-1: 1.85 versus 1.95 min-1; rate of adsorption from subphase to surface: 32 versus 35 mN X m-1 X 30 s-1), nor was there a difference in the ability of the two surfactants to improve lung stability of 27-day-old rabbit fetuses (air retention at 35 cm H2O: 1.8 versus 1.8 ml/30 g; air retention at 0 cm H20: 0.8 versus 0.9 ml/30 g). We conclude that phosphatidylinositol surfactant does not have inferior surface properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of betamethasone and ritodrine on the fetal secretion of lung surfactant.

Beta-sympathomimetic drugs and glucocorticoid agents are given in preterm labor to prevent severe consequences of prematurity. It is unclear whether beta-sympathomimetics accelerate lung maturation, or whether they only tend to delay preterm delivery. We have evaluated the effects of betamethasone and ritodrine in rabbits on alveolar lavage phospholipids in premature rabbits, a mean of 28.7 days from conception. Betamethasone given to 26-day-old fetuses increased the surfactant phospholipids, phosphatidylinositol and disaturated phosphatidylcholine; increased disaturated phosphatidylcholine/sphingomyelin ratio, and phosphatidylinositol (percent of phospholipids), as compared to untreated littermates, or to saline treated controls. A low dose of ritodrine given to the pregnant doe, and a high dose given at premature birth had no detectable effects on alveolar lavage phospholipids. However, a high dose of ritodrine given one day before the delivery to the fetus and at premature birth decreased the disaturated phosphatidylcholine/sphingomyelin ratio and phosphatidylinositol in alveolar lavage. While glucocorticoid administration increases the synthesis and secretion of surfactant phospholipids, a high dose of a betasympathomimetic drug may decrease the surfactant. However, spontaneous premature labor is associated with accelerated lung maturation, and accordingly the present results do not contradict the use of a low dosage of betasympathomimetic drug to delay preterm delivery.

Animals↗
PubMed1985

Endobronchial surface active phospholipids in various pulmonary diseases.

In the present study we investigated the phospholipid composition of small-volume (up to 20 ml) in vivo bronchoalveolar lavage and that of quantitative ex vivo bronchoalveolar lavage. Furthermore, the accuracy of the small-volume lavage in predicting lung disease was evaluated. There was a positive linear correlation (r approximately equal to 0.87-0.91) between the amount of saturated phosphatidylcholine and the saturated phosphatidylcholine/sphingomyelin ratio in quantitative bronchoalveolar lavage. The phospholipid distributions in the small-volume lavage and the quantitative lavage were similar (r approximately equal to 0.78-0.94, n = 14). The overall accuracy of phosphatidylcholine/sphingomyelin ratio and phosphatidylglycerol/total phospholipid ratio in predicting the presence or absence of respiratory failure was 85-87% in newborns, children, and adults. In respiratory diseases without respiratory failure, the abnormalities in the phospholipids were frequent, although less distinct. According to animal experiments the surfactant system is inhibited at the onset of high permeability lung edema. Soon thereafter, the lavageable surfactant pool is decreased. Present findings support the view that surfactant defects are of importance in the pathogenesis of respiratory disease, and that surfactant-oriented therapy may be effective in the treatment and prevention of respiratory failure.

Animals↗
PubMed1985

Lung profile: sex differences in normal pregnancy.

The incidence of respiratory distress syndrome (RDS) is higher in male than in female infants. The lung profiles--lecithin/sphingomyelin (L/S) ratios, percent disaturated (acetone precipitated) lecithin, phosphatidylglycerol, and phosphatidylinositol--were obtained in amniotic fluid during 164 normal pregnancies of 30 or more weeks' gestation. The profiles were evaluated to determine any sex differences in fetal development of the surfactant components. According to regression analysis the L/S ratios for females reached 2:1 at 33.7 weeks, which is 1.4 weeks earlier than males. A similar trend was evident for disaturated lecithin. Phosphatidylglycerol first appeared at 34 weeks' gestation for females and 35 weeks for males. The rate of the increase in phosphatidylglycerol was higher in females than in males. Phosphatidylinositol began to decrease after 36 weeks for females and fell to levels below that of males after 37 weeks' gestation. All four indexes of the lung profile revealed a higher degree of lung maturity in female than in male fetuses during the last two months of normal pregnancy. This explains a higher incidence of RDS in male than in female infants.

Amniotic Fluid↗
PubMed1984

Effect of extracellular myo-inositol on surfactant phospholipid synthesis in the fetal rabbit lung.

In the present investigation, myo-inositol was elevated in fetal serum by dietary manipulation. The myo-inositol-containing diet doubled the already high fetal serum myo-inositol between fetal days 26 and 28 but had no detectable effects on the lung. However, myo-inositol decreased betamethasone-induced (0.2 mg/kg, days 26.3 and 27.3, to the doe) inhibition in lung growth and potentiated the hormone-induced increase in alveolar space saturated phosphatidylcholine. This effect could not be explained by alteration of glucocorticoid-stimulated enzyme activity (phosphatidate cytidylyltransferase, phosphatidic acid phosphohydrolase, choline phosphate cytidylyltransferase) in the lung. Lung explants from 26-day-old fetuses were grown in a serum-free medium for 4 days. myo-Inositol (1.5 mM) had only a small effect on the phospholipid incorporation. Dexamethasone and thyroxine increased the incorporation of the precursors into surfactant phosphatidylglycerol and saturated phosphatidylcholine. myo-Inositol, in the presence of the hormones, switched the acidic surfactant phospholipid from phosphatidylglycerol to phosphatidylinositol and further increased the incorporation of surfactant-associated saturated phosphatidylcholine. myo-Inositol-excess preferentially increased the incorporation of NADPH (derived from glucose) and acetate into the fatty acid moiety of surfactant phosphatidylcholine. It is proposed that the high extracellular myo-inositol in immature fetuses provides an environment that promotes both the hormone-stimulated differentiation and the growth.

Animals↗
PubMed1984

Hypoxanthine and oxygen induced lung injury: a possible basic mechanism of tissue damage?

Lung injury was induced in young rats by a continuous infusion of hypoxanthine intravenously and breathing 100% oxygen for 48 h (group 1). Control animals were rats infused glucose and breathing 100% oxygen (group 2), rats infused hypoxanthine in room air (group 3), and untreated rats (group 4). In group 1 rats interstitial and alveolar edema was found with a tendency toward marked margination of polymorphonuclear neutrophils in small vessels (P less than 0.025 compared with group 2). The main elastase inhibitor alpha 1-antitrypsin (alpha-1-PI) was significantly elevated in group 1; 2-, 3- and 5-fold, respectively, when compared with groups 2, 3, and 4. The surfactant phospholipids from alveolar lavage were normal in all groups. The protein-rich fraction of the lavage fluid from group 1 rats inactivated, however, the surface properties of lung surfactant. Minimum surface tension in group 1 rats was 14.5 dyn/cm compared with 7.0 dyn/cm in group 2, 2.9 dyn/cm in group 3 and 3.5 dyn/cm in group 4 (P less than 0.05, group 1 and 2 versus 4). We conclude that the combination of hypoxanthine and high levels of oxygen causes lung injury, possibly via free oxygen radicals. We discuss the possibility that these findings demonstrate a basic pathogenetic mechanism for the hypoxic-hyperoxic insult and can contribute to the understanding of pathogenesis of a variety of diseases both in pediatrics and adult medicine.

Animals↗
PubMed1984

Glycolipid accumulation in bronchoalveolar space in adult respiratory distress syndrome.

Surfactant lipids in the alveolar space are believed to play an important role in normal respiratory function. Although the surface-active phospholipids have been extensively studied, the possible role of glycolipids in the surfactant remains to be explored. We have studied the glycolipid composition of cell-free bronchoalveolar lavage from healthy subjects and from adult patients with respiratory distress syndrome. Glycolipids were barely detectable in bronchoalveolar lavage from healthy subjects. However, in adult respiratory distress syndrome, the amount of glycolipid relative to phospholipid was increased by more than twenty times. These lipids, identified as lactosylceramide (galactose-glucose-ceramide) and paragloboside (galactose-N-acetylglucosamine-galactose-glucose-ceramide), may prove to be sensitive markers of lung injury. Since the glycolipids decreased the surface activity of surfactant in vitro, their potential role in the pathogenesis of adult respiratory distress syndrome should be considered.

Carbohydrates↗
PubMed1983

The effect of betamethasone and fetal sex on the synthesis and maturation of lung surfactant phospholipids in rabbits.

In the present study we investigated the maturation of the surfactant phospholipids and the role of fetal sex on the effect of betamethasone in male and female rabbit fetuses. Betamethasone was administered to the doe (0.2 mg/kg intramuscularly) 42 and 18 h prior to killing. The fetuses were studied at 27 and 28 days from conception. Results from the alveolar lavage show that male fetuses tended to have a lower disaturated phosphatidylcholine/sphingomyelin ratio and lower levels of phosphatidylinositol. Phosphatidylglycerol was detected in trace amounts. This was apparently due to the high extracellular levels of myo-inositol inhibiting the synthesis of surfactant phosphatidylglycerol while increasing the synthesis of surfactant phosphatidylinositol. Betamethasone increased the recovery of disaturated phosphatidylcholine and phosphatidylinositol from the lung lavage in both sexes. As studied in lung slices in vitro, the betamethasone treatment decreased the incorporation of glucose into phospholipids, including into the fatty acid moiety of disaturated phosphatidylcholine, although it had no significant effect on the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. However, the addition of palmitate increased the incorporation of glucose into the glycerol moiety of disaturated phosphatidylcholine. The betamethasone treatment did not increase the incorporation of [1-14C]pyruvate into disaturated phosphatidylcholine. Following betamethasone administration, the availability of fatty acids may become rate-limiting for the synthesis of surfactant phospholipids. Betamethasone increased the activities of phosphatidic acid phosphohydrolase and phosphatidate cytidyltransferase in a fraction of microsomal membranes. The present evidence suggests that the glucocorticoid-induced lung maturation and the maturation of the normal lung are associated with an increase in the activity of the enzymes which are involved in metabolizing phosphatidic acid to neutral and acidic surfactant secretion of the male fetus was not explained by possible sex-related differences in the biosynthesis of the phospholipids.

Aging↗
PubMed1983

Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia.

Pulmonary effluent samples were obtained from 26 preterm or term infants throughout the period of endotracheal intubation. Infants with respiratory distress syndrome, infants with this disorder developing bronchopulmonary dysplasia, and intubated infants without lung disease were compared daily in terms of lung effluent cellularity, albumin, elastase activity, alpha 1-proteinase content and activity, and elastase inhibitory capacity. The elastase activity was determined to be neutrophilic in origin. Polyacrylamide gel electrophoresis of pulmonary effluents from two infants with respiratory distress syndrome and exposed to FiO2 greater than or equal to 0.6 up to 6 d revealed cleavage of alpha 1-proteinase inhibitor to a 47,000-mol weight fragment suggestive of oxidation. Pulmonary effluent neutrophils, macrophages, and elastase activity were increased by day 3 of life in infants with respiratory distress syndrome eventually developing bronchopulmonary dysplasia. Elastase inhibitory capacity and alpha 1-proteinase inhibitor activity were reduced in infants developing chronic lung disease. Bronchopulmonary dysplasia developed in infants with enhanced inflammatory response, but with less or inhibited antiprotease activity.

Albumins↗
PubMed1982

Myoinositol decreases N-nitroso-N-methylurethane induced lung surfactant deficiency.

Administration of 7.5 mg/kg body wt. of N-nitroso-N-methylurethane subcutaneously to rabbits decreased disaturated phosphatidylcholine, phosphatidylglycerol, and increased the minimum surface tension of alveolar lavage return. As compared to rabbits treated with N-nitroso-N-methylurethane alone, myoinositol supplementation (3-7 g/kg per day) of N-nitroso-N-methylurethane treated animals largely prevented both the decrease in disaturated phosphatidylcholine, and the increase in minimum surface tension. Myoinositol may be an important nutrient following damage of alveolar epithelium.

Animals↗
PubMed1982

Effects of maternal insulin or glucose infusion on the fetus: study on lung surfactant phospholipids, plasma myoinositol, and fetal growth in the rabbit.

Pregnant rabbits were given continuous intravenous insulin between days 26.7 and 28.7 after conception. The treatment decreased fetal serum glucose, insulin, and myoinositol. Furthermore, maternal insulin decreased fetal growth slightly, and improved the survival of the prematurely delivered fetuses. Analysis of phospholipids recovered by alveolar lavage revealed that the lung surfactant was quantitatively and qualitatively superior to the surfactant from the fetuses of the saline-glucose control animals. This effect on the lung was more striking than that of glucocorticoid. Another group of pregnant rabbits received continuous intravenous glucose between days 27.0 and 29.0 after conception. The hyperinsulinemic fetuses of the glucose-infused does weighed more and had higher serum glucose and myoinositol than did those of the control animals. There was no detectable difference in alveolar lavage phospholipids between hyperinsulinemic and normoinsulinemic fetuses of glucose-infused does. The possible importance of these findings in understanding the mechanism of acceleration of lung maturation is discussed.

Animals↗
PubMed1982

Changes of fatty acid composition of phospholipids in liver mitochondria and microsomes of the rat during growth.

The fatty acid patterns of rat liver mitochondrial and microsomal phospholipids were analyzed from term fetuses, 1 and 4 days old, and adult rats. The main fatty acids of phosphatidylethanolamine and -choline were stearic and palmitic acids, although the patterns differed slightly. The fatty acid composition of corresponding phospholipids in mitochondria and microsomes was similar. The fatty acid pattern of cardiolipin was dominated by linoleic acid. The most consistent feature of the developmental changes in the fatty acid patterns of all phospholipids studied was a decrease in the relative amount of monounsaturated fatty acids. The percentages of saturated fatty acids in phosphatidylethanolamine and -choline increased during neonatal development. It is suggested that the high levels of fetal monounsaturated fatty acids were due to low availability of polyunsaturated fatty acids.

Animals↗
PubMed1982

Effect of acute perinatal asphyxia on development of the lung and brain in the rat.

Fetal rats were exposed to asphyxia by compression of the umbilical vessels, and the animals were studied shortly after delivery, close to term (21st fetal day). Following asphyxia on the 20th fetal day, the lungs appeared immature. The surface active phospholipids, disaturated lecithin and phosphatidylglycerol, as well as the elastic tissue around the alveoli were lower than in the control littermates. However, lung maturity was little affected following asphyxia on the 17th-18th fetal day. As studied in the brain, hemorrhages in the periventricular area, sometimes intraventricular hemorrhages, were evident (asphyxia on the 17-18 and 20th fetal days). In addition, cells in cerebral cortex were altered following asphyxia of 17 - to 18-day-old fetuses. The present animal model clarifies the mechanism of increased incidence of respiratory distress syndrome following acute asphyxia and may prove to be useful in studies of pathogenesis of periventricular hemorrhages.

Animals↗