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Sixty-four patients aged 16-74 years with total body surface area burns (TBSA) ranging from 30 to 90 per cent, were given one bathing in 0.04 M cerium nitrate within 4 h of admission to hospital. Of 21 patients aged 16-30 years, one died (aged 28 with 90 per cent TBSA), and of those aged 31-74 years, two died, one (aged 50 years with 55 per cent TBSA) had multiple internal injuries, the other (aged 51 years with 55 per cent TBSA) had a pulmonary embolism at day 19. Two risk scores, developed from data on 11,200 burn patients treated by standard methods (Roi et al. 1983), were applied to the analysis of risk for 59 patients for whom both total burn surface (TB) and full thickness (FT) areas had been recorded. About 20 patients bore risk of 0.8 or greater on the FT scale and 1.0 on the TB scale, yet instead of 80 per cent deaths among these, only two died. No FT assessment had been made on the multiple injury death whose TB risk score was 0.66. Such survival results in high-risk patients should encourage the use of cerium nitrate for treating serious burn injury.

The lipid-protein complex (LPC) formed by thermal injury to skin, which has been shown to have a toxic effect on mice, and which suppresses the immune response, was tested for its specific influence on monocytes. Growth of bacterial endotoxin-stimulated peripheral blood mononuclear cells (PBMC) was inhibited in the presence of LPC, however, the inhibition was less at the time of the optimal rate of cell proliferation. Inhibition was proportional to LPC concentration. ConA-stimulated PBMC were also inhibited by LPC in a dose-related manner. PBMC, in the presence of LPC, secreted interleukin 1 (IL1) at an increasing rate as LPC concentration rose from 5 to 40 micrograms/ml, and the levels of IL1 which could be induced by endotoxin were increasingly amplified in the presence of LPC. In comparison to LPC, the native tissue proteins which were isolated from unburned skin by the same techniques which produced LPC from burned skin, were tested for their effect on PBMC. Native proteins had no effect on IL1 secretion, whether on background or endotoxin-stimulated levels. Thus, the thermally induced change in skin proteins has a specific effect on monocyte IL1 secretion which is not matched by the native proteins, indicating that burn injury to skin specifically affects the lymphokine cascade and consequent immune function.

Lipid peroxides, formed as a consequence of oxygen free radical formation, are responsible for tissue damage in a great variety of pathological conditions including thermal injury. 'Cutaneous burn toxin', formed by application of heat to skin, is thought to be specific to the burn injury. It causes dose-dependent damage to mitochondrial and red cell membranes, and dose-dependent inhibition of interleukin-2-dependent growth of lymphocytes. The possibility that the toxicity of 'cutaneous burn toxin', a lipid-protein, is exerted through lipid peroxides, was examined by measuring the levels of both agents in plasmas of eight burn patients during the first week after their injury. It was observed that plasma lipid peroxides did not appear in parallel with absorption into the circulation of 'cutaneous burn toxin'. Lipid peroxide levels equally common to very low and very high burn toxin levels, were recorded. The pair of agents correlated negatively (r = -0.26) at a significance of only 0.1. In addition, isolated purified 'cutaneous burn toxin' contained no measurable lipid peroxide. No relationship was therefore demonstrated between plasma levels of 'cutaneous burn toxin' and lipid peroxides.

Daily intravenous evening injections of 30 nmol/kg DSIP (Delta Sleep-Inducing Peptide) in rats adapted to a constant 24 hr light:dark cycle produced changes in the circadian locomotor behavior. After 3 days the normally high locomotor activity during the dark phase was reduced while during the light (sleeping) phase the animals became relatively more active. Similar, but more rapid and more marked changes were observed (with the same schedule of injections) after 0.1 nmol/kg DSIP-P (the analogue of DSIP phosphorylated at the serine in position 7). In fact the peptide and its analogue induced a relative reversal or shift of the circadian locomotor activity phases opposite to the persisting light:dark conditions (=Zeitgeber). This suggests that DSIP exerts rather complex "programming" effects on the circadian activities and has more than just a sleep-inducing activity.

Delta sleep-inducing peptide (DSIP) has been found to induce sleep as well as extra-sleep effects. Although the presence of endogenous DSIP-like material has been demonstrated, the metabolic fate of injected DSIP has not been clarified so far. A major obstacle in monitoring degradation of DSIP has been the lack of an easy method to separate DSIP from tryptophan (Trp). Cleavage of the N-terminal Trp apparently represents the first and most important step in the metabolism of the peptide. Adsorption to aluminum oxide has been found to separate the two compounds and optimal conditions for the separation are described. Quantitative determination of the degradation of DSIP in plasma or serum is now rapidly achieved. The method should help to advance metabolic studies of DSIP. Other applications such as extraction of DSIP from solutions are also possible.

Delta sleep-inducing peptide has been shown to exert extra-sleep effects as well as effects on sleep. In this study, the concentrations of DSIP-like immunoreactivity were measured by radioimmunoassay in the plasma of spontaneously hypertensive rats (SHR). They were found to be about 25% higher in SHR plasma than in the plasma of the normotensive Wistar-Kyoto (WK) controls. DSIP was then infused for 10 days by osmotic minipump (200 micrograms/kg/day) into SHR. This resulted in in maintenance of BP at a level of about 200 mm Hg as compared with the significant increase to about 220 mm Hg after 10 days in the SHR controls infused with 0.9% NaCl. After daily SC injection of a single dose of 200 micrograms/kg DSIP for each of 5 days in SHR, findings were similar. The results raise the possibility of an involvement of DSIP in the regulation of BP in SHR.

The influence of delta sleep-inducing peptide (DSIP) on the brain neurotransmitters 5-HT, dopamine and norepinephrine and plasma proteins/corticosterone concentrations for four time points within the 24 hr following IV injection of 30 nmol/kg was investigated in rats. DSIP administered in the morning or in the evening respectively induced changes in nearly all measured parameters. Different effects were observed for different times of administration. The most marked changes were found in the level of serotonin during daytime. In view of the multivariate results obtained by measuring several parameters at multiple time points, a method was developed to describe the time-dependent changes. By means of "circadian rhythm statistics" based on a statistical likelihood analysis we found that multiple and different changes within the factor's daily variation are induced by one injection of DSIP. A multidimensional scaling of the results provides further insights into the correlations of the DSIP-induced effects on plasma and brain factors which are therefore tentatively termed "programming functions." These apparently involve not just sleep induction but also act on multiple parameters within the 24 hr rest-activity period.

A pharmacological study was carried out of a case of severe insomnia following brain-stem lesions; several polygraphic controls were used. Initially total duration of sleep was brief (less than 4 h) with a high REM/NREM ratio and a short paradoxical sleep (PS) latency. In addition, periodic breathing and tremor were observed. Slow injection of delta-sleep-inducing peptide (DSIP) improved sleep both quantitatively and qualitatively, although PS latency remained short. These effects were reversible. The effects of 5-HTP + benzerazide, of L-DOPA + benzerazide (Modopar) and of clonazepam (Rivotril) were compared.