Characterization of the Interactive Effects of Glycine and -Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence

Reduced responses to N-methyl-D-aspartate (NMDA) glutamate receptor antagonists in alcohol-dependent animals and humans provided evidence that chronic alcohol consumption increased NMDA receptor function. To further probe alterations in NMDA glutamate receptor function associated with human alcohol dependence, this study examined the interactive effects of agents acting at the glycine_B coagonist site of the NMDA receptor. In doing so, it tested the hypothesis that raising brain glycine concentrations would accentuate the antagonist-like effects of the glycine_B partial agonist, -cycloserine (DCS). Twenty-two alcohol-dependent men and 22 healthy individuals completed 4 test days, during which glycine 0.3 g/kg or saline were administered intravenously and DCS 1000 mg or placebo were administered orally. The study was conducted under double-blind conditions with randomized test day assignment. In this study, DCS produced alcohol-like effects in healthy subjects that were deemed similar to a single standard alcohol drink. The alcohol-like effects of DCS were blunted in alcohol-dependent patients, providing additional evidence of increased NMDA receptor function in this group. Although glycine administration reduced DCS plasma levels, glycine accentuated DCS effects previously associated with the NMDA receptor antagonists, ketamine and ethanol. Thus, this study provided evidence that raising glycine levels accentuated the NMDA receptor antagonist-like effects of DCS and that alcohol-dependent patients showed tolerance to these DCS effects.     

Aberrant expression of collapsin response mediator proteins-1, -2 and -5 in the brain of intrauterine growth restricted rats

Intrauterine growth restriction (IUGR) has been associated with increased perinatal morbidity, higher incidence of neurodevelopmental defects and increased risk for adult metabolic syndrome manifestations. Altered protein expression profiles associated with IUGR may be informative on the pathological mechanisms of this condition and might reveal potential markers for postnatal complications. We hypothesized that nutrient manipulation of the pregnant rat might influence the expression of important neurodevelopmental proteins in the resultant IUGR offspring. Therefore, we aimed to determine in newborn rat brain tissue the expression of collapsin response mediator proteins (CRMPs)-1, -2 and -5, commonly referred to as dihydropyrimidinase-related proteins (DPYLs) – playing a role in axon guidance, invasive growth and cell migration – and compare it to the corresponding expression in control rats. Two-dimensional electrophoresis and mass spectrometry, as well as Western blot analysis were employed in brain tissue from 24 IUGR newborn rats and 24 controls. With both methods, CRMP-1, CRMP-2 and CRMP-5 were decreased in the brains of the IUGR group as compared to the control group at the time of delivery. In conclusion, IUGR rat offspring are born with a decreased expression of CRMPs, suggesting that these proteins may be implicated in fetal stress-induced programming.     

Automatic metaphor processing in adults with Asperger syndrome: a metaphor interference effect task

This paper investigates automatic processing of novel metaphors in adults with Asperger Syndrome (AS) and typically developing controls. We present an experiment combining a semantic judgment task and a recognition task. Four types of sentences were compared: Literally true high-typical sentences, literally true low-typical sentences, apt metaphors, and scrambled metaphors (literally false sentences which are not readily interpretable as metaphors). Participants were asked to make rapid decisions about the literal truth of such sentences. The results revealed that AS and control participants showed significantly slower RTs for metaphors than for scrambled metaphors and made more mistakes in apt metaphoric sentences than in scrambled metaphors. At the same time, there was higher recognition of apt metaphors compared with scrambled metaphors. The findings indicate intact automatic metaphor processing in AS and replicate previous findings on automatic metaphor processing in typically developing individuals.

     

Controlled ten-day antimicrobial therapy in asymptomatic bacteriuria of old age: relations with localization,mobility and mortality

The effectiveness of a 10-day i.m. antimicrobial therapy in eradicating bacteriuria for six months, preventing decline of physical status and reducing mortality for five years was tested in 73 ambulant, self-caring bacteriuric residents of a retirement home (16 men) compared to 264 non-bacteriuric subjects (79 men), and in 29 bacteriuric controls under no treatment (4 men), all groups having a mean age of 82.5 years. Structural abnormalities by ultrasonography were detected in 29% of 69 treated bacteriuric subjects and 18.4% of 76 non-bacteriuric controls (N.S.). Seventy-five percent of bacteriuric men and 56% of women had positive antibody coated bacteria (ABC+) in the urine. One of three agents was used: netilmicine 150 mg/d (26 subjects), ceforanide 1.0 g/d (23 subjects), and cotrimoxazole 160/800 mg/d (24 subjects). At one week post therapy 61.6% of treated subjects had negative urines vs. 27.6% of untreated controls (p<0.005); at one and six months negative urines were present in 52.2% and 44.8% of subjects treated vs. 39.3% and 40% of controls (N.S.). Netilmicine and ceforanide were more effective at one week and one month, cotrimoxazole at six months. Elimination of bacteria ACB(+) or (?) was equal but relapses were more numerous in ACB(+) strains. At 18 months “good” mobility was more frequent among subjects originally non-bacteriuric than among the treated bacteriuric subjects (61.1% vs. 38.6%, p<0.01). There were no deaths among the treated bacteriuric subjects for six months, but thereafter mortality rose fast so that at 18 months their cumulative mortality was significantly higher than in the non-bacteriuric subjects (p<0.0001). Subsequently, however, mortality accelerated in both groups, so that at 5 years cumulative mortality was equally high among originally bacteriuric and non-bacteriuric subjects. The study shows that: (a) the treatment used was moderately effective in eradicating bacteriuria, urines remaining sterile in almost half of the subjects for up to six months; (b) successful therapy did not alter the evolution of physical disability; (c) therapy delayed the onset of mortality for six months but did not reduce subsequently the high death rate of bacteriuric subjects during 18 months; (d) over the 5-year follow-up the high mortality of subjects with mean age 87.5 years conceals earlier occurring mortality differences between groups which should be assessed in younger subjects.