Background-Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities. We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis.

Lithium is a unique drug with therapeutic as well as prophylactic value for both manic and depressive phases of manic-depressive illness. The precise mechanisms of its clinical efficacy remain unknown, but there are two main theories of its biochemical action. One proposes that lithium inhibits adrenergically activated adenylate cyclase function whereas the other suggests that it inhibits phosphatidyl inositol turnover, which is known to be activated by cholinergic agonists. Neither mechanism alone, however, can explain both the antimanic and antidepressant effects of lithium. Because of the pivotal role of G proteins in post-receptor information transduction, we have investigated the interaction of lithium with G protein function. Lithium at therapeutically efficacious concentrations completely blocked both adrenergic and cholinergic agonist-induced increases in [3H]GTP binding to membranes from rat cerebral cortex, in both in vitro and ex vivo experiments. The same lithium treatments also abolished guanine nucleotide modulation of agonist binding. Our findings suggest G proteins (Gs and Gi or Go) as the molecular site of action for both the antimanic and antidepressant effects of lithium.

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Ethyl arachidonate was administered orally to 4 healthy male volunteers in a dose of 6 gm daily for a 2 to 3 wk period after a JO-day control period. The increased intake of this precursor of the dienoic prostaglandins resulted in significant increases in the relative and absolute amount of arachidonate in plasma triglycerides, phospholipids, and cholesteryl esters. Similar changes in lipid composition were noted in platelets. The excretion of 7 a-hydroxy-5, ll-diketotetranorprostane-1 ,16-dioic acid, the major urinary metabolite of E prostaglandins in man, was increased by an average of 47% in 3 of the 4 volunteers. Platelet reactivity was assessed by determining the threshold concentration of adenosine diphosphate (ADP) necessary to induce secondary, irreversible aggregation of platelet-rich plasma. This threshold concentration dropped significantly in all volunteers (10% to 60% of control values). It is concluded that the biosynthesis and function of prostaglandins can be augmented in man by oral administration of an esterified precursor fatty acid.Free arachidonic acid is the precursor of the dienoic prostaglandins, including prostaglandins E2 and F 2a . In tissue and plasma, arachidonic acid is found in the ester linkage of phospholipids, cholesteryl esters, and triglycerides. Before arachidonic acid becomes available to prostaglandin synthetase, it must be released by either phospholipases or tri-

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