The requirement for intensive care support for the pregnant population

Pregnancy-associated admissions to the Intensive Care Unit during the first 5 years of a newly established teaching hospital obstetric unit are reviewed. There were 23 such admissions; in the same period, 21,983 deliveries occurred. The most frequent cause for Intensive Care admission was hypertensive disease of pregnancy. Most patients required admission for less than 48 hours. Two patients died during the period of study.     

Synthesis and biological activity of locust AKH-I and its analogues with modifications at the threonine residues

A convenient method of synthesis, using a combination of solid and liquid phase methodology, for locust Adipokinetic Hormone-I (AKH-I) and its analogues with modifications at the threonine residues are reported. The N-terminal nonapeptide acid of AKH-I is synthesized in the solid phase using the 2-chlorotrityl chloride resin and the Fmoc/t-Bu strategy. Quantitative cleavage of the nonapeptide acid from the resin, with the tert-butyl type side-chain protection intact, is achieved with a mixture of acetic acid/trifluoroethanol/ dichloromethane. The nonapeptide acid is then coupled in solution to the threonine derivatives, H-Thr-NH₂ or H-Thr(Bz1)-NH₂, with the DCC/HOBt method. The efficiency of this approach in the synthesis of AKH-I is demonstrated by the high yields and purity of the synthesized peptides. All the synthesized peptides were tested in two ways: first, in a lipid mobilization assay in locusts in vivo; and second, in a novel assay in vitro concerned with the uptake of radiolabelled acetate into locust tissue. Replacement of the hydroxyl hydrogen in Thr⁵ of locust AKH-I by the bulky and highly lipophilic tert-butyl group reduced the potency markedly, whereas efficacy is unaffected, but when the hydroxyl hydrogen of Thr¹⁰ in AKH-I is replaced by a benzyl group, the activity of the resulting analogue is identical to that of the natural peptide. Structure-activity relationships are discussed. © Munksgaard 1994.     

THE RELATIONSHIP BETWEEN VENTRICULAR FLUID PRESSURE AND THE NEUROPATHOLOGY OF RAISED INTRACRANIAL PRESSURE

The relationship between ventricular fluid pressure and the neuropathology of raised intracranial pressure
The brains from 56 patients whose ventricular fluid pressure had been continuously monitored during life have been subjected to a neuropathological analysis. This has shown that the morphological criterion of a significantly high intracranial pressure during life is pressure necrosis in one or both parahippocampal gyri. In patients known to have had a high ventricular fluid pressure, there is also a high incidence of pressure necrosis in the cingulate gyrus and infarction in the medial occipital cortex ('calcarine infarction'), but these changes do not occur in the absence of pressure necrosis in the parahippocampal gyri. Conventional maeroscopic tentorial and supracallosal herniae may occur without the intracranial pressure having been high. There was no correlation between pressure necrosis in the parahippocampal gyri and hypoxic necrosis in the hippocampus: this suggests that a high intracranial pressure is not an important factor in the pathogenesis of such hypoxic necrosis. It is concluded that the neuropathologist can state with a high degree of accuracy post mortem if intracranial pressure has been significantly high, i. e. an increase associated with a pressure differential between the supratentorial and infratentorial compartments, even when it has not been monitored clinically.     

A possible role for mono(ADP-ribosyl)transferase in the signalling pathway mediating neutrophil chemotaxis

1 Mono(ADP-ribosyl)transferase activity has been identified on the external surface of human polymorphonuclear neutrophil leucocytes (PMNs). The enzyme is released from the plasma membrane by phosphoinositide-specific phospholipase C, suggesting a glycosylphosphatidylinositol (GPI) linkage of the enzyme to the plasma membrane. Partial sequence of cDNA encoding the enzyme suggests that it is identical to the GPI-linked mono(ADP-ribosyl)transferase identified previously on human skeletal muscle.
2 A panel of inhibitors of mono(ADP-ribosyl)transferase (including vitamins K₁ and K₃, novobiocin and nicotinamide) showed a rank order of inhibitory potency similar to that described for other mono(ADP-ribosyl)transferases. Furthermore, the mono(ADP-ribosyl)ation of agmatine was inhibited also by diethylamino(benzylidineamino)guanidine (DEA-BAG), another substrate of the enzyme related structurally to arginine.
3 There was a close linear correlation between the I C ₅₀ values for inhibition of mono(ADP-ribosyl)ation of agmatine by DEA-BAG or the enzyme inhibitors and their I C ₅₀ values for inhibition of receptor-dependent polymerization of cytoskeletal actin and chemotaxis.
4 These results suggest a role for mono(ADP-ribosyl)transferase in the transduction pathway involved in receptor-dependent re-alignment of the cytoskeleton during neutrophil chemotaxis.