Two important cytokines mediating inf lammation are tumor necrosis factor ␣ (TNF␣) and IL-1␤, both of which require conversion to soluble forms by converting enzymes. The importance of TNF␣-converting enzyme and IL-1␤-converting enzyme in the production of circulating TNF␣ and IL-1␤ in response to systemic challenges has been demonstrated by the use of specific converting enzyme inhibitors. Many inf lammatory responses, however, are not systemic but instead are localized. In these situations release and͞or activation of cytokines may be different from that seen in response to a systemic stimulus, particularly because associations of various cell populations in these foci allows for the exposure of procytokines to the proteolytic enzymes produced by activated neutrophils, neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (Cat G). To investigate the possibility of alternative processing of TNF␣ and͞or IL-1␤ by neutrophil-derived proteinases, immunoreactive TNF␣ and IL-1␤ release from lipopolysaccharide-stimulated THP-1 cells was measured in the presence of activated human neutrophils. Under these conditions, TNF␣ and IL-1␤ release was augmented 2-to 5-fold. In the presence of a specific inhibitor of NE and PR3, enhanced release of both cytokines was largely abolished; however, in the presence of a NE and Cat G selective inhibitor, secretory leucocyte proteinase inhibitor, reduction of the enhanced release was minimal. This finding suggested that the augmented release was attributable to PR3 but not NE nor Cat G. Use of purified enzymes confirmed this conclusion. These results indicate that there may be alternative pathways for the production of these two proinf lammatory cytokines, particularly in the context of local inf lammatory processes.

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Studies have shown that severe daytime restriction of dietary protein improves the efficacy of L-dopa and reduces response fluctuations in some Parkinson's disease (PD) patients. This study investigated the nutritional adequacy of the daytime restricted-protein diet. Eleven free-living PD patients suffering from unpredictable response fluctuations to L-dopa were counseled to limit protein intake to approximately 10 g before 1700. Three sets of 6-d food records obtained during the 8-wk study showed that while on the test diet, mean intakes of most nutrients remained above the recommended nutrient intakes, although significant decreases occurred in protein, calcium, iron, phosphorus, riboflavin, and niacin intakes. The impact of the test diet on nutritional status as evaluated by changes in body weight and serum prealbumin was small. We conclude that healthy and highly motivated patients can maintain adequate intakes of most nutrients while restricting daytime protein intake. However, nutrient intakes might be compromised in patients whose regular diets are marginally adequate.

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The experiment reports the effects of appropriate and inappropriate instructions and 2 drugs (.5 g chloral hydrate and 10 mg racemic amphetamine sulphate) on motor performance and mood measures. The Ss were 90 older men randomly assigned to 9 experimental groups. The design used was expansion of a model design involving Drug Disguised groups, Placebo groups (300 mg lactose), an Untreated group, and Amphetamine, Chloral Hydrate, and Neutral instructions. The drugs and placebos were given to the Ss in capsules, and all Ss received orange juice, which was also the vehicle for the disguise. The Untreated group received orange juice only. Instructions alone affected performance, but had little or no effect on mood. Instructions appropriate to the presumed drug effects produced performance deterioration on the simple motor tasks used. Instructions inappropriate to the presumed drug effects counteracted much of the drug produced decrement. A slight decrement in performance was found in the Placebo group which received Amphetamine instruction. Amphetamine treated Ss produced reports of greater comfort on the mood index than did chloral hydrate. On the other hand, the chloral hydrate instructions resulted in greater comfort than the Amphetamine instructions. There was no interaction between drug effects and instructional effects. The 2 Placebo groups did not differ significantly on the mood index. The effects of instructions on mood were found only when the drug was present. Several suggestions are offered for further research.