Molecular charge effects on the protein permeability of the guinea-pig placenta.

The effect of molecular charge on protein permeability of the dually perfused guinea-pig placenta has been investigated by measurement of the permeability surface area products (PS) and observation of the ultrastructural localization of cationic horseradish peroxidase (cHRP) and anionic horseradish peroxidase (aHRP) molecules. Steady-state PS calculated from the experimental data was 0.032 +/- 0.0045 and 0.0045 +/- 0.0008 ml min-1 (mean +/- s.e.m.) for cHRP and aHRP respectively (P less than 0.01). The PS for a diffusional marker, 51Cr-ethylenediaminetetraacetic acid, showed no significant difference between the two groups. Ultrastructurally, placentae perfused with cHRP showed fewer microvilli and a dilated interstitial space compared with placentae perfused with aHRP; large vacuoles were also found in the syncytiotrophoblast in the former but not in the latter tissue. Reaction product in placentae perfused with cHRP was localized to the maternal-facing plasma membrane of the syncytiotrophoblast, in vacuoles and vesicles of the syncytiotrophoblast, and also in the basement membrane of the interstitial space, whereas placentae perfused with aHRP only had reaction product in vesicles in the syncytiotrophoblast. These results suggest that anionic sites in the guinea-pig placenta affect its permeability to charged proteins, cationic molecules inducing structural changes associated with increased permeability.

Hypoplastic lungs and abnormal phospholipids in asphyxiating thoracic dystrophy.

The respiratory impairment of asphyxiating thoracic dystrophy previously has been attributed to slower growth of the ribs which reduces chest size and limits chest expansion during breathing. Two siblings with this condition are described. One was found to have an abnormally low crying vital capacity; in the other the peak flow rate was reduced markedly. Chest X-rays and ventilation-perfusion nuclear scans were suggestive of hypoplastic lungs. Nasopharyngeal aspirates of airway secretions were found to contain significantly less total phospholipids and differences in phospholipid composition in comparison with a normal control group. These findings raise the possibility that the lungs are hypoplastic and have an abnormal phospholipid content in asphyxiating thoracic dystrophy.

Effect of labour on the lecithin/sphingomyelin ratio in serial samples of amniotic fluid.

Serial samples of amniotic fluid were taken from 48 patients during labour. The lecithin/sphingomyelin (L/S) ratio was estimated and found to rise in 52 per cent, remain almost unchanged in 33 per cent and fall in 15 per cent. The rate of rise in the L/S ratio seemed inversely related to the length of labour.

Effects of histamine on vascular resistance and protein permeability in the isolated dually perfused guinea-pig placenta.

The possibility that histamine can affect both the vascular resistance and permeability of the isolated dually perfused guinea-pig placenta has been investigated. Change from control to histamine (2.7 x 10(-4)M) perfusion of the fetal circulation elicited a significant (P less than 0.01, paired 't' test) maximum increase of 1.17 +/- 0.14 (SEM) kPa in fetal perfusion pressure 3 min later, representing a 33% rise. This vasoconstriction was completely blocked by the H1 antagonist diphenhydramine (10(-4)M) but not by the H2 receptor antagonist cimetidine (10(-4)M). In the same experiments the clearance (calculated as the ratio of fetal to maternal perfusate concentration times fetal flow-rate) of a macromolecular tracer, anionic horseradish peroxidase from the maternal to fetal circulation was significantly increased (P less than 0.05, paired 't' test) when steady state (15-20 min of perfusion) values were compared, from 5.9 +/- 1.7 (SEM) microliter min-1 placenta-1 to 12.9 +/- 3.5 (SEM) microliter min-1 placenta-1 (n = 20) for control and histamine respectively. By contrast the steady state clearance (calculated as before) of a smaller hydrophilic tracer, 51Cr-EDTA, was not significantly affected, being 587 +/- 59 (SEM) microliter min-1 placenta-1 in control and 587 +/- 55 (SEM) microliter min-1 placenta-1 (n = 20) with histamine perfusion. When histamine was perfused simultaneously with an H1 or H2 antagonist there was no change in anionic horseradish peroxidase clearance. Electron microscopy of placentas perfused with histamine failed to reveal any obvious alteration in morphology or anionic horseradish peroxidase localisation as compared to placenta perfused without histamine. This study thus demonstrates that histamine may cause changes in the macromolecular permeability of the placenta as well as vasoconstriction of the placental vasculature.

Maternal diabetes and neonatal respiratory distress. I. Maturation of fetal surfactant.

The phospholipid composition of amniotic fluid samples from 30 normal patients and 44 diabetic patients over the last 10 weeks of pregnancy was studied. Higher levels of phosphatidylcholine (PC) and phosphatidylinositol (PI) were found in diabetic pregnancies where there was excellent glucose control. These differences were statistically significant at 34-36 weeks. Phosphatidylglycerol (PG) appeared significantly earlier in the well controlled diabetic pregnancies, but even in the poorly controlled diabetics the levels of PC, PI and PG were comparable to those in normal pregnancies. There was no evidence of delayed appearance of fetal surfactant phospholipids in either the well or poorly controlled diabetic pregnancies. The absolute lecithin (PC)/sphingomyelin (SM) ratio in diabetic pregnancies was generally greater for any given gestational age than those in normal pregnancies. Whilst in most cases this was due to a higher PC concentration, in a few poorly controlled diabetics it was the result of a lower concentration of SM.

Maternal diabetes and neonatal respiratory distress. II. Prediction of fetal lung maturity.

Fifty babies were born at less than or equal to 37 weeks to mothers with diabetes. Delivery was undertaken in all patients with the reassurance that the L/S ratio was greater than or equal to 2.0 within the preceding 72 h. Five babies (10%) developed respiratory distress syndrome (RDS). Prediction of fetal lung maturity was improved dramatically by measuring amniotic fluid concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidylglycerol (PG). Fourteen babies were predicted as having 'no surfactant' (PC less than 20 mg/l, PI less than 2 mg/l and PG less than 2 mg/l), five developed RDS. None of the remaining 36 babies developed the illness: they were predicted as having either 'early surfactant' (PC greater than or equal to 20 mg/l, PI greater than or equal to 2 mg/l but PG less than 2 mg/l) or 'late surfactant' (PC greater than or equal to 20 mg/l, PI greater than or equal to 2 mg/l and PG greater than or equal to 2 mg/l). Measurement of PC levels alone was the most was the most accurate method of predicting RDS. There was a significant association between low surfactant phospholipid concentrations and the development of transient tachypnoea of the newborn.

Non-specificity of surfactant deficiency in neonatal respiratory disorders.

The phospholipid content of lung fluid taken from 77 babies during the first day of life was studied. Babies with hyaline membrane disease had low concentrations of the surfactant phospholipids phosphatidylcholine, phosphatidylinositol, and phosphatidylglycerol. The palmitic acid content in phosphatidylcholine was also lower than normal. Surfactant deficiency was not, however, specific for hyaline membrane disease, as similar phospholipid abnormalities were observed in babies with congenital pneumonia and transient tachypnoea of the newborn. These findings have important clinical implications. They are relevant to research into surfactant substitution and cast doubts on the value of the antenatal phospholipid lung profile of amniotic fluid in predicting the risk of hyaline membrane disease.

Surfactant maturation and preterm premature membrane rupture: a case study.

Preterm premature membrane rupture (PPROM) is known to accelerate fetal lung surfactant maturation. The mechanism for this is unclear. We report a case of prolonged PPROM, where the maturation of fetal surfactant was studied in detail by the serial analysis of surfactant phospholipids in the drained liquor.

Amniotic fluid optical density determination as a rapid test for assessment of fetal lung maturity.

The lecithin/sphingomyelin (L/S) ratios and optical densities at 650 nm were determined for 158 samples of amniotic fluid obtained by amniocentesis. A further 24 samples collected by vaginal aspiration from patients with spontaneous rupture of the membranes were also analysed. The relation between the L/S ratio and the optical density suggests that the more rapidly obtainable optical density measurement could be used as a screening procedure for fetal pulmonary maturity. A valid estimate of maturity by optical density is not possible in amniotic fluid aspirated from the vagina.