Mass spectra of trimethylsilyl ethers of 2H-labelled mono- and diglycerides.
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Chromatography, Gas↗
Biomedical subjects
T Curstedt
Publications and source records attributed to T Curstedt.
Analysis of molecular species of 2H-labelled phosphatidylcholines by liquid-gel chromatography and gas chromatography-mass spectrometry.
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Animals↗
Stimulation of erythroblast maturation in vitro by sphingolipids.
A lipid factor previously isolated from leukocytes and found to stimulate basophilic erythroblast formation in an in vitro system of incubated rabbit bone marrow cells has been analyzed by thin-layer chromatography, gas-liquid chromatography, and gas-liquid chromatography-mass spectrometry. The biologically active components are sphingosine ceramides of tetracosanoic and dehydrotetracosanoic acids. Tests of a series of related ceramides show a high degree of structural specificity for the C(24)-V-acyl compounds with significant but markedly lower activity of the C(22) analog. Commercially available sphingomyelin shows activity comparable to that of the tetracosanoic acid ceramide. Sphingosine and tetracosanic acid supplied in equimolar amounts have negligible activity. The results, in the context of other findings, suggest a possible supportive role of plasma ceramides and sphingomyelins in red cell maturation.
Animals↗
Effect of amiloride and surfactant on lung liquid clearance in newborn rabbits.
Immature and nearly mature fetal rabbits (gestational age 27.5 and 29.5 days, respectively) were obtained by hysterotomy and tracheotomized at birth. Immature rabbits received, via the tracheal cannula, 2.5 ml/kg of either normal saline, porcine surfactant (60 mg/ml), 1 mM amiloride in normal saline, or a mixture of surfactant and amiloride; nearly mature rabbits received either normal saline, or 1 mM amiloride in saline. The neonates were ventilated with a tidal volume of approximately 10 ml/kg for 0-60 min (immature animals) or 0-120 min (nearly mature animals). The lungs were then excised for determination of wet lung weight/body weight ratio (LW/BW). The right lung was further processed for quantification of extravascular lung water (EVLW) per unit dry lung weight, and the left lung fixed for measuring the size of perivascular 'cuffs' (adventitial tissue including lymphatics) in histological sections, using vascular lumen as reference volume. Immature animals receiving surfactant had improved compliance and smaller perivascular cuffs in comparison with the other groups. In immature animals amiloride had no effect on compliance, LW/BW, and EVLW, but reduced perivascular cuff size at 15 min. Nearly mature animals receiving amiloride had higher values for LW/BW and EVLW at 120 min, and lower perivascular cuff size at 15, 60, and 120 min, in comparison with saline-treated litter-mates. We conclude that surfactant improves lung-thorax compliance and reduces perivascular fluid accumulation in immature newborn animals without influencing total lung water content, and that amiloride retards fetal lung liquid resorption in nearly mature newborn animals without affecting lung-thorax compliance during artificial ventilation.
Absorption↗
Phosphatidylinositol composition in pancreas and submaxillary gland of ethanol-fed rats.
The possibility that changes in the stimulus-secretion coupling are involved in the etiology of pancreatitis was investigated by analysis of the molecular composition of the phosphatidylinositols in pancreas of rats fed a liquid ethanol-containing diet and pair-fed controls. The arachidonoyl-containing phosphatidylinositols were about half as abundant in the ethanol-fed rats. Opposite differences were seen for the major species containing linoleoyl, oleoyl or stearoyl groups at C-2. Ethanol-induced lipid peroxidation did not seem to be involved, since carbon tetrachloride administration had no effect on the composition. In the submaxillary gland, that has a similar stimulus-secretion coupling, the arachidonoyl-containing phosphatidylinositols constituted about a 25% smaller fraction in the ethanol-fed rats. Dexamethasone administration did not change the effect. Possibly, decreased secretory response in these glands in ethanol-fed rats is caused by the change in phosphatidylinositol composition.
Animals↗
Steroid profiles in urine and plasma of alcoholics during withdrawal.
Metabolic profiles of steroids in urine and plasma were analyzed in 14 male and four female alcoholics during withdrawal. The daily excretion of 30 conjugated steroids in urine and the concentration of 13 steroid sulfates in plasma were measured on days 1, 7 and 29 of the period of observation, which started on day 5-7 of abstinence. While the total excretion of cortisol metabolites was normal in most cases, the profiles of metabolites were changed in the alcoholics during the period of observation. The ratio between tetrahydrocortisol and tetrahydrocortisone exceeded the mean normal value by more than one standard deviation in 97% of the samples analyzed. The same was true of the ratio between 20-hydroxy and 20-oxosteroids in 90% of the samples. The differences between alcoholic and healthy subjects were statistically significant (p less than 0.001). The major change in plasma was a significantly increased concentration of 5-androstene-3 beta, 17 beta-diol disulfate on the first day of the study. The concentration decreased to normal values during the first month of withdrawal. The rate of excretion of this steroid in urine was increased in half of the patients and also decreased with time. The rate of excretion and the degree of fatty infiltration in liver biopsies were positively correlated. It is suggested that the ratios between cortisol metabolites in urine might be of value as biochemical markers in alcoholism, and that the absolute or relative concentrations of steroid disulfates in plasma might serve as an indicator of recent alcohol intake.
Adult↗
Artificial surfactants based on analogues of SP-B and SP-C.
The hydrophobic proteins SP-B and SP-C are important components of natural surfactant preparations currently used in clinical practice, and physiologically active surfactants can be made from isolated SP-B and/or SP-C reconstituted with synthetic lipids. Efforts have been made to produce these polypeptides, or analogues with similarfunction, by organic synthesis or expression in heterologous systems. It is important to obtain proper folding of the synthetic peptides, as required for optimal interaction with the surfactant lipids. Another issue is to avoid loss of SP-C activity due to alpha-helix to beta-sheet transition. This latter problem can be circumvented by replacing the polyvaline stretch of SP-C with a polyleucine stretch containing a few lysines. Palmitoylation of cysteines or serines at positions 5 and 6 also seems important for the properties of SP-C. SP-B, which is too big a molecule to be easily produced by organic synthesis. apparently can be replaced in an artificial surfactant by a peptide capable of cross-linking phospholipid bilayers. The development of synthetic analogues of the surfacant proteins might make it possible to tailor artificial surfactants for specific therapeutic missions, for instance by enhancing resistance to inactivation by meconium, plasma proteins, or oxygen radicals or maximizing bacteriostatic effects.
Animals↗
Radiologic observations in severe neonatal respiratory distress syndrome treated with the isolated phospholipid fraction of natural surfactant.
Ten newborn babies with severe respiratory distress syndrome, all dependent on artificial ventilation, were treated via the airways with the isolated phospholipid fraction of bovine or porcine surfactant. After treatment with surfactant at a median age of 10.5 h, there was in all patients a striking improvement of lung aeration in chest films, with a decrease in parenchymal fluid retention and in distension of bronchioli. These radiologic findings were associated with a dramatic improvement of oxygenation and a significant reduction of the right-to-left shunt. In spite of the rapid therapeutic response, four patients died from cerebral hemorrhage. One of the surviving patients developed bronchopulmonary dysplasia. Our findings document efficacy of this new surfactant preparation in the neonatal respiratory distress syndrome, but the long-term effects need to be further tested in randomized clinical trials.
Blood Gas Analysis↗