Elementary modes analysis of photosynthate metabolism in the chloroplast stroma.

We briefly review the metabolism of the chloroplast stroma, and describe the structural modelling technique of elementary modes analysis. The technique is applied to a model of chloroplast metabolism to investigate viable pathways in the light, in the dark, and in the dark with the addition of sedoheptulose-1,7-bisphosphatase (normally inactive in the dark). The results of the analysis show that it is possible for starch degradation to enhance photosynthetic triose phosphate export in the light, but the reactions of the Calvin cycle alone are not capable of providing a sustainable flux from starch to triose phosphate in the dark. When reactions of the oxidative pentose phosphate pathway are taken into consideration, triose phosphate export in the dark becomes possible by the operation of a cyclic pathway not previously described. The effect of introducing sedoheptulose-1,7-bisphosphatase to the system are relatively minor and, we predict, innocuous in vivo. We conclude that, in contrast with the traditional view of the Calvin cycle and oxidative pentose phosphate pathway as separate systems, they are in fact, in the context of the chloroplast, complementary and overlapping components of the same system.     

Potent, orally active inhibitors of lipoprotein-associated phospholipase A(2): 1-(biphenylmethylamidoalkyl)-pyrimidones.

A series of 1-(biphenylmethylamidoalkyl)-pyrimidones has been designed as nanomolar inhibitors of recombinant lipoprotein-associated phospholipase A(2) with high potency in whole human plasma. 5-(Pyrazolylmethyl) derivative 16 and 5-(methoxypyrimidinylmethyl) derivative 27 demonstrated excellent pharmacodynamic profiles which correlated well with their pharmacokinetic effects.     

A cartilage catabolic factor from synovium.

Porcine synovium in organ culture produces a factor that causes chondrocytes to degrade their matrix. A quantitative assay for the factor, for which the cartilage of bovine nasal septum is used, is described. Evidence is presented that the catabolic factor is a protein.     

Artificial induction of lactation in ewes: the role of prolactin.

The mammary glands of 30 non-pregnant, intact ewes were developed by subcutaneously injecting oestrogen plus progesterone at intervals of 3 days from day 0 to day 27. Two days later (day 29), 15 ewes were injected subcutaneously with 18 mg ergocryptine, to inhibit specifically secretion of prolactin. Then groups of ewes, each comprising five ergocryptiine-treated and five untreated ewes, were injected from days 30 to 34 with either four intravenous injections each day of 1 i.u. syntocinon, one subcutaneous injection each day of 10 mg dexamethasone trimethylacetate, or two subcutaneous injections each day of 2-5 mg oestradiol benzoate plus 6-25 mg progesterone. All ewes were milked by hand on days 30-50. Within 24 h of injecting ergocryptine, levels of prolactin in serum were reduced to negligible values (less than 2 ng/ml). Comparison of results for ewes not receiving ergocryptine showed that syntocinon, dexamethasone and oestradiol benzoate plus progesterone, at the doses used, were equally effective in initiating milk secretion. Peak yields of 0-23-0-27 kg/day were achieved. On the other hand, ewes treated with ergocryptine before syntocinon or dexamethasone produced peak yields of only 0-12-0-13 kg/day and ewes treated with ergocryptine before oestradiol benzoate plus progesterone produced negligible amounts of secretion. The results suggest that syntocinon and dexamethasone were either lactogenic per se or effected the release of hormones of the lactogenic complex other than prolactin. However, oestradiol benzoate plus progesterone appeared to be lactogenic by virtue of the influence of oestrogen on the secretion of prolactin.     

Electrocardiography during Manual Dilatation of the Anus

Manual dilatation of the anus was carried out on 50 unpremedicated outpatients under propanidid, nitrous oxide, and halothane anaesthesia with E.C.G.monitoring. About half of the patients received intravenous atropine with the propanidid. The operation induced a variety of changes in heart rate but in the whole experiment only two isolated cardiac arrhythmic complexes were seen—a single defect of conduction and a solitary ventricular extrasystole. Changes in rate were not modified by atropine. It is concluded that manual dilatation of the anus is a safe procedure when carried out under the anaesthetic described and that prior medication with atropine is not necessary. This work supports the view that propanidid protects patients from most abnormalities of heart action which result from intense visceral stimulation.