Pulmonary surfactant: No mere paint on the alveolar wall

Abstract The gas-liquid interface within the alveolus is completely lined with a complex mixture of lipids and unique proteins termed pulmonary surfactant, which both reduces surface tension and permits it to vary directly with the radius of curvature. In this way it minimizes the work of breathing and permits alveoli of different sizes to exist in equilibrium. However, surfactant does far more in that it also controls fluid balance in the lung and appears to play a key role in host defence. Either a deficiency in surfactant or an aberrant surfactant results in atelectasis and oedema. The surfactant system is very dynamic: alveolar surfactant phosphatidylcholine, the principal component, having a half life of only a few hours, with as much as 85% being recycled. Although distortion of the alveolar type II cell is now accepted as the principal stimulus for release, much remains to be discovered of modulating factors and intracellular signalling in the control of surfactant homeostasis. Likewise, many questions remain concerning the control of synthesis of the surfactant phospholipids, neutral lipids and proteins and their assembly into the tubular myelin form of alveolar surfactant, the refining of the monolayer with breathing, the control of re-uptake of different components into the type II cells and the roles of the proteins.     

Fetal monitoring with pulse oximetry

Summary. Continuous fetal monitoring was achieved with a fetal scalp pulse oximetry sensor in 86 labours. The average recorded fetal oxygen saturation in early labour (cervical dilatation < 5 cm) was 68% (SD 13%). At the end of labour (cervical dilatation ≥ 9 cm) the recorded mean oxygen saturation was 58% (SD 17%). The largest range of readings during a single labour was 81%-11% but this drop was associated with cord compression. The average SD during 1 h of normal labour was 10%. A second group of 40 fetuses was monitored during induction of labour before and after elective amniotomy. Oxygen saturation did not appear to change after amniotomy (mean change −0.4%, SD 1.2%) and there was no difference between mean antenatal or early intrapartum readings. We excluded the amniochorionic membranes as a possible source of data corruption by measuring their in vitro absorption spectra and confirming that they do not preferentially absorb light of either 660 or 940 nm wavelength. Non-invasive pulse oximetry can be used to monitor the fetus before and during labour.     

Synthesis and conformation of constrained peptides with hypoglycaemic activity derived from human growth hormone

The α-aminosuccinimide (Asu¹¹) octapeptide analogue of human growth hormone hGH[6-13] (Leu⁶-Ser-Arg-Leu-Phe-Asu-Asn-Ala¹³) has been reported [Robson et al. (1990) Biol. Chem. Hoppe Seyler 371 , 423-431] to have hypoglycaemic activity whilst the corresponding peptide with Asp at position 11 is inactive. In order to determine whether this change in activity is caused by conformational and/or stereo-electronic effects, the incorporation of two different isomeric γ-lactam structures at position 11 has been investigated. One lactam structure (i) is of the type developed by Freidinger and coworkers [Freidinger et al. (1982) J. Org. Chem. 47 , 102-107], whilst the isomeric γ-lactam structure (ii) represents a new type of constrained synthon for use in peptide synthesis. The chiral type-ii γ-lactam was synthesized via a suitably protected desoxo-dipeptide prepared in several ways from L-aspartic acid. The solution conformations of the [Asu¹¹]- and the [γ-lactam¹¹]-containing hGH[6-13] peptide analogues were investigated with the aid of two-dimensional NMR (COSY and NOESY) spectroscopy. Conformational similarities were found for these hGH[6-13] peptide analogues. For example, for all peptide analogues studied, weak NOEs were evident between the Phelo ring protons and protons of the amino acid residues at the C-terminus. Overall, however, the NOESY NMR spectra of the [Asu¹¹]- and the [γ-lactam¹¹]-containing peptides related to hGH[6-13] suggest the presence of an extended structure in solution with a possible weak type II′β-turn at position 11. The extent of conformational constraint introduced into these hGH[6-13] peptide analogues by substitution of the Asu¹¹ residue with either isomeric γ-lactam structure was reflected as differences in their hypoglycaemic activity. In particular, the hGH[6-13] peptide analogue derived from the new chiral type-ii γ-lactam exhibits both lower activity in intravenous insulin tolerance tests in vivo and weaker NOEs than the isomeric hGH[6-13] peptide analogue derived from the type (i) γ-lactam structure. The relative change in blood glucose levels from 20 to 90 min for the racemic (R,S)-form of the type-ii γ-lactam compared to the control values was approximately half that of the (S)-stereoisomer. © Munksgaard 1994.     

False positive gel-acetylcholinesterase results in blood-stained amniotic fluids

Summary. The effect of blood contamination on the gel-acetylcholinesterase (AChE) test used in the diagnosis of fetal open neural-tube defects was studied with amniotic fluid samples artificially contaminated with fetal or maternal blood in concentrations covering a range exceeding that usually found in clinical practice. Amniotic fluid samples contaminated with maternal blood gave negative gel-AChE results at all concentrations. Contamination with fetal blood yielded positive results if the erythrocyte concentration was greater than about 60 × 10⁶ cells/ml. Thus contamination of amniotic fluid with blood is only likely to cause false positive gel-AChE results if this critical concentration is exceeded. Such samples will occur only rarely in clinical practice but when they do the diagnosis should be made with caution.