Granulocyte superoxide production by different stimuli was studied in 14 patients suffering from rheumatoid arthritis, and in four cases defective O(2) generation was shown. The effect of two chemically related drugs, such as indomethacin and oxamethacin, was also evaluated, since we have previously investigated the action of antiinflammatory agents on cell locomotion. Indomethacin did not affect O(2) production, whereas oxamethacin reduced significantly superoxide generation in PMNs from all subjects tested. Moreover, the extent of the effect was dependent on the stimulant used, being larger when the activation of O(2) generating system was induced by opsonized zymosan.
Rationale Motivational deficits are a common symptom shared across multiple psychiatric and neurodegenerative disorders. Effort-based decision-making tasks are a translatable method for assessing motivational state. Much of the preclinical validation of the task derives from acute pharmacological manipulations in rats. However, mice currently offer a greater genetic toolkit to study risk genes and phenotypic models. Despite this, there is limited characterisation of their behaviour in this type of motivation task. Objectives Here, we investigate the effort for reward (EfR) task as a measure of motivational state in mice using drugs previously shown to modulate effort-based decision-making in rats and humans. Method Using male C57bl/6j mice, we test the effects of drugs which modulate DA transmission. We also test the effects of CP101-606 which does not act directly via DA modulation but has been shown to exert beneficial effects on motivational state. Finally, we test the sensitivity of the task to a chronic corticosterone (CORT) treatment. Results Amphetamine, methylphenidate, and CP101606 in mice increased high-effort responses for high-value reward, while administration of haloperidol decreased high-effort responses. Surprisingly, tetrabenazine had no effect at the doses tested. Chronic, low-dose CORT consumption did not alter task performance. Conclusion These data suggest that the EfR task is sensitive to acute dopaminergic modulation and NR2B selective antagonism in mice. However, it may lack sensitivity to non-acute phenotypic models. Further work is required to demonstrate the utility of the task in this context.
We have isolated peak II, which is the peak of the middle molecules containing polyamines, from dialysate of uremic patients in recirculating dialysis. We investigated the effect of total dialysate, chromatographic peaks, I, II, III, IV and commercial polyamines on polymorphonuclear leukocyte chemotaxis and superoxide production (i.e. phagocytic activity) in healthy and uremic patients. Polymorphonuclear chemotaxis was inhibited by total dialysate and peak II but not by polyamines; polyamines, total dialysate and peak II had no activity on polymorphonuclear phagocytosis.
Criteria used to predict the effect of neutral shampoos on fibroblast cultures were based on assays which were easy to perform, reproducible and adaptable to a large number of substances. The tests were based on the determination of the integrity of the plasma membrane, the rate of protein synthesis, and cell viability. Six different shampoos were tested: four were of the best quality commercially available, while the other two were new compounds. The substances were tested over a wide concentration range and were applied to human fibroblast cultures for various exposure times. Lactate dehydrogenase release into the medium was used as a marker of plasma membrane integrity, the amount of [3H]-labelled protein in the fibroblasts was measured to assess the function of the cell biosynthetic machinery, and the number of damaged cells which did not take up the neutral red dye showed the percentage of cytolysis. The results indicated significant differences between the six shampoos, and a relationship between the biochemical parameters was found. This suggests that these tests on cell functionality may represent reliable markers for monitoring the cellular target damaged by xenobiotic compounds.
We study how rank and file employees' financial wellness affects employers' myopic accounting decisions. By using staggered increases in consumer bankruptcy exemptions across US states to capture increments in employees' financial wellness, we find that firms reduce their real activities management, have fewer misstatements, and decrease their loss avoidance behaviors in response to higher consumer bankruptcy protection. We identify two channels that might explain these findings. First, we show that more consumer bankruptcy protection increases employees' productivity and reduces their absenteeism from the workplace, and second, we show that firm productivity and profitability improve when consumer bankruptcy protection increases. Thus, higher labor productivity and corporate profitability facilitate firms' achievement of their earnings-based targets, reducing the need for myopic performance-enhancing behaviors. Our evidence suggests that improving employees' financial wellness provides benefits to firms through higher profitability and fewer myopic decisions.
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