Caffeine: its action on purine metabolizing enzymes.

The many pharmacological and biochemical effects of caffeine may be explained in part by its inhibitory action in vivo and in vitro upon enzymes which metabolize purines. We have demonstrated that in $\text{Crithidia}\text{fasciculata}$ this methylxanthine (as well as theophylline) is a rather weak competitive inhibitor of adenine aminohydrolase, ribonucleoside hydrolase, hypoxanthine and guanine phosphoribosyltransferases. Caffeine does not interfere with purine base transport in Crithidia, however in leucocytes purine uptake is reduced. While the methylxanthines are weak purine enzyme inhibitors, the large number of enzymes affected accounts for their physiological importance in these cells.     

Diazepam withdrawal syndrome: its prolonged and changing nature.

The diazepam withdrawal syndrome was studied in 10 patients who had abused the drug for 3 to 14 years. In the previous 6 months their consumption of diazepam had ranged from 60 to 120 mg daily; none had used other drugs during this period. The withdrawal period lasted about 6 weeks. The intensity of the symptoms and signs was high initially, fell during the first 2 weeks, then rose again in the third week, before finally declining. Three groups of symptoms and signs were identified. Group A symptoms occurred throughout withdrawal and included tremor, anorexia, insomnia and myoclonus. Group B symptoms and signs were largely confined to the first 10 days and were those of a toxic psychosis. Group C symptoms reached a peak in the third and fourth weeks of withdrawal and were characterized by sense perceptions that were either heightened or lowered. The symptom groups, the presence of tremor and myoclonus, and the relief of symptoms by a test dose permit diazepam withdrawal to be distinguished from anxiety. The biphasic course of the symptoms is probably related to the pharmacokinetics of diazepam.     

Procollagen peptidase: its mode of action on the native substrate.

Procollagen peptidase was recovered from the medium of human and mouse fibroblast cultures by precipitation with ammonium sulfate. The test substrate for the in vitro enzymatic reaction was radioactively-labeled, disulfide-linked procollagen prepared from the medium of human fibroblast cultures. The enzymatic digests were analyzed by electrophoresis in polyacrylamide gets containing sodium dodecyl sulfate and urea. The human and mouse enzymes reacted with the substrate to generate the same intermediates and final products. Procollagen peptidase acts as an endopeptidase which cleaves each of the three procollagen chains in turn. The final products of the reaction are collagen and a three-chain, disulfide-linked fragment derived from the nonhelical aminoterminal residues of procollagen.