Age-related deficits in generation and manipulation of mental images: I. The role of sensorimotor speed and working memory.

The authors investigated age-related slowing of information processing in mental imagery tasks. Eighty-five healthy adults (ages 18 to 77) performed a visual, sensorimotor, reaction-time task; a visual-perceptual choice reaction task; and 3 mental imagery tasks that varied in apparent difficulty and involved stimuli at 2 levels of graphic complexity. Age was associated with prolongation of response time across all tasks and both levels of stimulus complexity. Accuracy of response was adversely affected by increase in stimulus complexity in all tasks, whereas it was negatively related to age only on the tasks with substantial mental imagery requirements. Slowing of information processing and reduction in accuracy were mediated by declines in working memory but not by decrease of sensorimotor speed.

Prenatal nicotine effects on memory in rats: pharmacological and behavioral challenges.

Cigarette smoking during pregnancy has been shown in a variety of studies to be associated with cognitive deficits in the children. Nicotine administration to rats during gestation has been found to cause subtle cognitive effects in the offspring. Some individual differences in cognitive impairment may be related to prenatal nicotine effects on noradrenergic (NE) systems. In the current study, 10 Sprague-Dawley rat dams were infused with approximately 2 mg/kg/day of nicotine ditartrate via osmotic minipumps and 10 control dams were exposed to vehicle-containing minipumps from gestational day (GD) 4-20. Starting on postnatal day (PND) 50, the offspring were tested for T-maze rewarded spatial alternation with intertrial intervals of 0, 10, 20, or 40 s. There was a sex- and delay-dependent effect of prenatal nicotine exposure on T-maze alternation. Nicotine-exposed males showed a significant deficit at the 0 s delay. In radial-arm maze (RAM) acquisition training there were no significant nicotine effects. However, significant nicotine-related effects were seen with subsequent behavioral and pharmacological challenges in the RAM. Changing the RAM testing location to an identical maze in a different room elicited a significant choice accuracy deficit in the prenatal nicotine-exposed rats compared with controls. Acute nicotine challenge did not cause any differential effects in the prenatal nicotine and control groups. During the isoproterenol (beta-NE agonist) challenge phase there appeared a significant facilitation of choice accuracy and speeding of response in the prenatal nicotine exposure group which was not seen in the control group. The alpha-NE agonist phenylpropanolamine caused a significant deficit in control females but not in the females prenatally exposed to nicotine. No differential effects of the alpha-NE antagonist phenoxybenzamine were seen in the prenatal nicotine and control groups. Throughout RAM testing there was a significant sex effect with males having better choice accuracy than females. These results demonstrate that the persisting cognitive effects of prenatal exposure to 2 mg/kg/day cause subtle effects in cognitive performance which can be elicited with behavioral and pharmacological challenge. These results also support previous studies suggesting the involvement of NE systems in persisting effects of prenatal nicotine exposure.

The efficacy of conjugated linoleic acid in mammary cancer prevention is independent of the level or type of fat in the diet.

The objective of the present study was to investigate whether the anticarcinogenic activity of conjugated linoleic acid (CLA) is affected by the amount and composition of dietary fat consumed by the host. Because the anticancer agent of interest is a fatty acid, this approach may provide some insight into its mechanism of action, depending on the outcome of these fat feeding experiments. For the fat level experiment, a custom formulated fat blend was used that simulates the fatty acid composition of the US diet. This fat blend was present at 10, 13.3, 16.7 or 20% by weight in the diet. For the fat type experiment, a 20% (w/w) fat diet containing either corn oil (exclusively) or lard (predominantly) was used. Mammary cancer prevention by CLA was evaluated using the rat dimethylbenz[a]anthracene model. The results indicated that the magnitude of tumor inhibition by 1% CLA was not influenced by the level or type of fat in the diet. It should be noted that these fat diets varied markedly in their content of linoleate. Fatty acid analysis showed that CLA was incorporated predominantly in mammary tissue neutral lipids, while the increase in CLA in mammary tissue phospholipids was minimal. Furthermore, there was no evidence that CLA supplementation perturbed the distribution of linoleate or other fatty acids in the phospholipid fraction. Collectively these carcinogenesis and biochemical data suggest that the cancer preventive activity of CLA is unlikely to be mediated by interference with the metabolic cascade involved in converting linoleic acid to eicosanoids. The hypothesis that CLA might act as an antioxidant was also examined. Treatment with CLA resulted in lower levels of mammary tissue malondialdehyde (an end product of lipid peroxidation), but failed to change the levels of 8-hydroxydeoxyguanosine (a marker of oxidatively damaged DNA). Thus while CLA may have some antioxidant function in vivo in suppressing lipid peroxidation, its anticarcinogenic activity cannot be accounted for by protecting the target cell DNA against oxidative damage. The finding that the inhibitory effect of CLA maximized at 1% (regardless of the availability. of linoleate in the diet) could conceivably point to a limiting step in the capacity to metabolize CLA to some active product(s) which is essential for cancer prevention.

Alkaline elution analysis of DNA fragmentation induced during apoptosis.

We report that alkaline elution analysis fails to provide a complete profile of DNA fragmentation induced by some genotoxic agents, particularly if these agents induce apoptotic cell death resulting in fragmentation of DNA into oligonucleosomal length multimers. It was questioned whether these oligonucleosome fragments are responsible for the more rapidly eluting component of DNA that is observed as a biphasic elution profile when cells treated with certain genotoxic agents are subjected to alkaline elution. The results of this study indicate that DNA fragmented during apoptotic cell death is eluted in fractions before alkaline denaturation that are normally discarded. Collection of fractions prior to alkaline denaturation is recommended for complete evaluation of the total spectrum of damage induced by genotoxic agents, especially when the compound is suspected of inducing cell death by apoptosis.

Sertraline attenuates hyperphagia in rats following nicotine withdrawal.

Chronic nicotine administration can decrease food consumption and body weight. Abrupt withdrawal from nicotine can cause the reverse effect, hyperphagia and rapid weight gain. In the current study, the efficacy of sertraline, a serotonin reuptake inhibitor, on nicotine withdrawal-induced hyperphagia and rapid weight gain was assessed in rats. Sertraline was found to be effective in reversing the increase in feeding that occurred after withdrawal from chronic nicotine administration. Sertraline caused a dose-related decrease in food consumption in control rats not given nicotine. Doses of 5 and 10 mg/kg/day caused significant decreases while 2.5 mg/kg/day caused a slight though nonsignificant decrease in food consumption. Rats in which nicotine was abruptly withdrawn after 3 weeks of administration showed a significant increase in food consumption relative to controls. This increase was eliminated by the high dose of sertraline (10 mg/kg/day), but not by the lower two doses (2.5 and 5 mg/kg/day). Water consumption was affected in a similar fashion. Body weight gain was also affected by sertraline. During the first week after nicotine withdrawal, rats rapidly gained weight, but sertraline attenuated this. The 10-mg/kg dose of sertraline significantly attenuated the nicotine withdrawal-induced weight gain. These results suggest that sertraline can counteract the hyperphagia and rapid weight gain associated with nicotine withdrawal, and might therefore be a useful adjunct to smoking cessation.

Zinc and copper status of severely burned children during TPN.

Alterations in zinc (Zn) and copper (Cu) homeostasis have been reported during the acute recovery period following thermal injury in both children and adults. Increased urinary losses of Zn and Cu and decreased plasma concentrations of Zn, Cu, and ceruloplasmin (CP), the major copper transport protein, occur despite adequate provision of these elements in enteral feedings. We now report data for moderately to severely burned children receiving total parenteral nutrition (TPN) supplemented to provide Zn and Cu. Hyperzincuria occurred consistently when 50 micrograms/kg Zn was delivered daily to older children. Similarly, when younger children received 100 micrograms/kg Zn daily, profound hyperzincuria ensued despite a reduction in total plasma Zn. Hypozincemia was accompanied by low levels of Zn in the plasma subfraction normally associated with albumin-bound Zn. The delivery of Cu via TPN was 4-12 micrograms/kg daily, and urinary Cu losses were not elevated. Plasma total Cu and plasma CP were invariably reduced. These findings are discussed in relation to guidelines published for pediatric trace element supplementation during TPN.