1. The 2',3'-dialdehyde derivative of ADP (oADP) at concentrations approaching the millimolar range induces human blood platelets to undergo the transition from discoid to globular morphology (the 'shape change') but is incapable of inducing aggregation.2. When incubated with platelets for 1 min before addition of the agonist, oADP acts as a competitive inhibitor of shape change and aggregation induced by ADP. Under these conditions secretion and hence aggregation induced by low concentrations of collagen ; and secretion and hence secondary aggregation induced by adrenaline, thrombin and vasopressin are also inhibited by this analogue. In addition, oADP stimulates the rate of primary aggregation induced by adrenaline and causes partial inhibition of primary aggregation induced by thrombin or vasopressin. When longer preincubation times are employed the extent of inhibition with respect to all agonists, except for high concentrations of collagen, is increased and the competitive character of the inhibition with respect to ADP is no longer apparent.3. Incubation of human platelets with the 2',3'-dialdehyde derivative of ATP (oATP) causes effects similar to those described for oADP except that the analogue neither induces platelet shape change, nor stimulates the rate of primary aggregation induced by adrenaline. In addition oATP fails to cause significant inhibition of platelet shape change induced by serotonin. The extent and character of inhibition caused by addition of oATP is not a function of the time of incubation.4. The 2',3'-dialcohol derivatives of ADP and ATP (orADP and orATP) effect the aggregation properties of human blood platelets in a manner generally resembling those observed for the 2',3'-dialdehyde analogues. However, orADP is only weakly effective in causing platelet shape change and stimulating the rate of primary aggregation induced by adrenaline and does not inhibit secretion induced by adrenaline, collagen, thrombin and vasopressin. The extent of inhibition by OI-ADP increases only slightly with increased time of incubation. 5.The data suggest that oADP acts as a partial agonist, and oATP as an antagonist, at the platelet ADP receptor, but that platelet membrane stabilisation also results from interaction with these dialdehyde analogues. Such membrane stabilisation does not complicate the interaction of platelets with orADP, which appears to act as a classical antagonist for the ADP receptor.Many agonists are capable of inducing platelet aggregation including adrenaline, thrombin, vasopressin and serotonin. In citrated plasma and under suitable conditions these agonists induce a biphasic response in which only the first, or reversible, phase is the direct result of platelet-agonist interaction. This initial interaction causes secretion of platelet constituents some of which are themselves inducers of aggregation and hence cause a further response associated ~~ -~ Ahhwviu/iorw. oATP and oADP. the 2',3'-dialdehyde derivatibe of ATP and ADP; orATP and orADP, the 2',3'-dialcohol derivative of AT...

The relationship between post-natal changes in blood glucose and hepatic enzyme induction was examined in the newborn rat after delivery in the last 3 days of gestation (22 days). A period of transient hypoglycaemia followed normal birth, delivery under ether anaesthesia on day 21 and delivery without anaesthesia on day 22. When fetuses were delivered without anaesthesia on days 20 and 21 the blood glucose concentration was low at birth, was constant for 3 h then increased at a rate similar to that observed for older animals. Phosphopyruvate carboxylase and tyrosine aminotransferase developed in utero after day 21 and at term the activities were high and increased immediately after birth. The time lag for the increase in enzyme activity shortened as gestation progressed. It is concluded that postnatal changes in blood glucose concentration do not have any specific effect on hepatic enzyme induction.

Summary The lipids of muscle and adipose tissue from normal males and of muscle from males with Duchenne muscular dystrophy were investigated. Triglyceride, the major neutral lipid, showed similar fatty acid compositions in all tissues examined. When the phospholipids of dystrophic muscle and of normal adipose tissue were compared with those of normal muscle, it was found that there was an increase in the proportion of sphingomyelin in dystrophic muscle, while adipose tissue had higher proportions of sphingomyelin and lysophosphatidylcholine but lower choline phosphoglyceride. In dystrophic muscle only small alterations from normal were observed in the fatty acid compositions of the individual phospholipids, whereas the phospholipids of adipose tissue had quite distinctive fatty acid compositions. An atrophic muscle sample resulting from poliomyelitis consisted almost entirely of connective tissue and fat and had a phospholipid composition similar to that of adipose tissue. From a comparison of the results for all the types of tissue studied, it is evident that the increase in sphingomyelin in dystrophic muscle biopsies and the changes in the fatty acid compositions of individual phospholipids may be accounted for by the increased amounts of fat and connective tissue which are present in dystrophic muscle samples. In a case each of polymyositis, limb girdle muscular dystrophy and an autosomal recessive form of muscular dystrophy, the results obtained for the phospholipid composition of the muscle sample were also normal or consistent with some contamination from fat and connective tissue.