The effects of paradoxical sleep deprivation and valine on spatial learning and brain 5-HT metabolism.

We have previously reported that rapid eye movement sleep deprivation (REMSD), induced by the flower pot technique, causes a deficit in reference spatial memory and increases rates of serotonin (5-HT) metabolism in the brain. In this study we used increased concentrations of dietary valine to inhibit tryptophan (TRP) transport across the blood-brain barrier in an attempt to modify the REMSD-induced increase of 5-HT metabolism. Rats were fed either a control diet or the same diet supplemented to 2% by weight valine, and were allocated to one of three experimental groups: cage control (CC), stress tank control (TC), or REMSD. Reference and working spatial memory of all rats was tested in a Morris water maze on Days 2, 3, and 4. REMSD produced a significant decrement in reference memory on Days 2 and 4, independent of dietary condition. The valine diet had a detrimental effect on the reference memory of TC rats on Day 2 but not Day 4. Measurements made on Day 4 indicated that the valine diet decreased brain TRP only in the CC rats. In contrast, the valine diet did not prevent increases in brain TRP or 5-HT metabolism in REMSD rats, and increased hypothalamic and brain stem TRP concentrations and the hippocampal 5-HIAA/5-HT ratio in TC rats. These results indicate that dietary valine does not prevent REMSD-induced changes in spatial memory or serotonin metabolism, although it does reduce brain TRP in nonstressed rats.

Apolipoprotein-E deficiency results in an altered stress responsiveness in addition to an impaired spatial memory in young mice.

It has been suggested that Alzheimer's disease (AD) is associated with an altered neurotrophic function of apolipoprotein-E (ApoE) and abnormal neuroendocrine activities. In the present study we investigated stress responsiveness of ApoE-deficient mice. Firstly, two sessions of restraint were introduced, 20 min per day for two (session 1) and three (session 2) consecutive days. In session 1, there was no difference between genotypes in open-field activity in response to restraint stress. In session 2, spatial memory was assessed in a Morris Water Maze 'Place Learning Set' task immediately following stress. Restraint stress caused a significant impairment of spatial memory in wild-type mice. The non-restraint ApoE-deficient mice showed a severe impairment of spatial memory similar to that of the restrained wild-type mice. Restraint stress had no obvious effect on spatial memory in ApoE-deficient mice until the third day of testing, when there was a decrease in reference memory compared with their non-restraint controls. In addition, the first session of restraint stress had an inhibitory effect on food intake in wild-type but not ApoE-deficient mice, and a longer-lasting effect on body weight in the wild-type than ApoE-deficient mice. ApoE-deficient mice showed a weaker corticosterone response to the initial restraint stress and a slower descending rate in serum corticosterone level during a 30-min post-stress period than their wild-type controls. However, higher baseline levels and stronger corticosterone responses were observed in ApoE-deficient mice than in wild-type mice when exposed to repeated restraint stress. The expression of ApoE mRNA was upregulated in the hypothalamus in wild-type mice exposed to repeated restraint stress. Taken together, these results demonstrate that ApoE deficiency causes a memory impairment and an altered stress responsiveness in mice.

Paired-ion liquid chromatographic method for the analysis of a phenanthrenemethanol antimalarial in whole blood.

A sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed for the determination of the candidate antimalarial (+/-)-(1,3-dichloro-6-trifluoromethyl-9-phenanthryl)-3-di-(n-butyl )aminopropanol hydrochloride in whole blood. A reversed-phase, paired-ion (lauryl sulfate) system achieved separation of the antimalarial and internal standard from interfering constituents with a sensitivity limit of 10 ng/mL by UV detection (254 nm). Chromatographic variables (counterion concentration, pH, and column temperature) were examined to determine their effect on assay characteristics (retention, efficiency, and relative response) in clinical analysis. The antimalarial was isolated from 2.0 mL of whole blood using overnight extraction with 30% ethyl acetate in hexane followed by an acid/base partition sequence to remove major interferences. Overall recovery for the antimalarial was 84% with a CV of 5.0%, and the recovery of the internal standard was 81% (CV = 3.6%). The assay was validated by analysis of both intra- and interlaboratory samples. The assay was applied to the analysis of whole blood samples taken from a 30-year-old healthy human male who had received a single 14.1-mg/kg oral dose. The stability of the antimalarial in whole blood for up to 4 months and in sample extracts for up to 34 d at -17 degrees C was also demonstrated.

A preliminary evaluation of hospital preparation for nonpatient children: primary prevention in a "let's pretend hospital".

This study evaluated the effectiveness of an innovative program about hospitalization presented to nonpatient children on a community-wide basis. The "Let's Pretend Hospital" (LPH) is an experiential and informational program wherein a mock hospital is set up for children to visit. The present study compared the self-reported medical fears and amount of medical knowledge for two groups of children--one that went through the LPH program and one that did not. The results provide preliminary evidence of LPH effectiveness in that children who participated in the program reported fewer medical fears and greater medical knowledge than children who did not participate. The potential benefits of this innovative program are demonstrated.