Electroencephalographic sleep measures in prepubertal depression.

Two nights of electroencephalographic (EEG) sleep recording were performed in a group of prepubertal subjects with major depressive disorder (MDD) (n = 36, mean age = 10.4, SD = 1.5) and age-matched normal control children (n = 18, mean age = 10.1, SD = 1.6). All subjects were medically healthy and free of medications at the time of the study. There were no significant group differences for any major sleep variable after the initial adaptation night in this study. One subgroup of MDD subjects (n = 8) showed reduced REM latency on both recording nights, decreased stage 4 sleep, and increased REM time; this subgroup had significantly higher severity scores for depression but did not otherwise appear to be clinically distinct from the rest of the MDD subjects. Overall, the results indicate that the EEG sleep changes associated with depression in adults occurred less frequently in prepubertal MDD subjects.     

On the role of Ca2+ in the toxicity of alkylating and oxidizing quinone imines in isolated hepatocytes

The cytotoxicity of acetaminophen (paracetamol) has been shown to be associated with a disruption of intracellular Ca2+ homeostasis caused by the interaction of its metabolite N-acetyl-p-benzoquinone imine (NAPQI) with hepatocyte thiols [Moore, M., et al. (1985) J. Biol. Chem. 260, 13035-13040]. Inasmuch as NAPQI can both covalently bind to thiols and oxidize thiols, we investigated the effects of two dimethylated analogues of NAPQI, one of which (2,6-dimethyl-NAPQI) primarily binds to thiols and the other of which (3,5-dimethyl-NAPQI) primarily oxidizes thiols. Of the three compounds, 2,6-dimethyl-NAPQI decreased protein thiols to the greatest extent and also inhibited hepatocyte plasma membrane Ca(2+)-ATPase to the greatest extent. The 3,5-dimethylated analogue decreased protein thiols to the least extent and inhibited the plasma membrane Ca(2+)-ATPase to a lesser extent. The cytotoxicity of all three compounds was preceded by a sustained elevation in cytosolic Ca2+ as compared to the transient rise caused by the alpha-agonist phenylephrine. Again, the 2,6-dimethyl analogue was the most potent of the three compounds. The thiol reagent dithiothreitol (DTT), which reversed the inhibition of the Ca(2+)-ATPase and the rise in cytosolic Ca2+, also protected against cytotoxicity. Agents that are known to inhibit either Ca(2+)-dependent proteases or phospholipases significantly delayed the onset of cytotoxicity caused by NAPQI and its analogues. Our results suggest that both arylation and oxidation of protein thiols may result in the elevation of cytosolic Ca2+ and in cytotoxicity and that arylation of critical thiol groups appears to be the more lethal reaction.     

Impaired spatial working and reference memory in segmental trisomy (Ts65Dn) mice

To evaluate the cognitive phenotype of the segmental trisomy 16 (Ts65Dn) mouse, a model of Down Syndrome (DS, trisomy 21), we assessed spatial working and reference memory using a 12-arm radial maze (RAM). Ts65Dn mice made a greater number of reference memory errors across trials compared to control mice. Both genotypes showed improvement across trials, although improvement was slower in Ts65Dn mice. Ts65Dn mice also made a greater number of working memory errors on the RAM, and in contrast to control mice, did not improve across trials, always performing at near-chance levels. These results provide evidence for both spatial working and reference memory deficits in Ts65Dn mice, characteristics of cognitive dysfunction.     

The effects of photoperiod on olfactory c-fos expression in prairie voles,Microtus ochrogaster

Reproduction stops among the majority of prairie voles (Microtus ochrogaster) during the winter. Short day lengths suppress male reproductive function dramatically in the laboratory, but photoperiod exerts only subtle effects on female reproductive function. Thus, the regulation of seasonal breeding in this species remains partially unspecified. In contrast to commonly studied rodents, female prairie voles do not undergo spontaneous estrous cycles; rather, they are induced into estrus by exposure to chemosignals expressed in conspecific male urine. In the present study, the hypothesis was tested that seasonal breeding among female prairie voles in the field reflects photoperiod-mediated changes in the responsiveness of the chemosensory system to male urine. Responsiveness was assessed by localizing the product of the c-fos immediate early gene with an immunocytochemical procedure. Female prairie voles were maintained in either long (LD 16:8) or short (LD 8:16) photoperiods from birth until adulthood, and exposed to either male urine or skim milk. Immunocytochemistry forfos protein revealed an increased number of immunoreactive cells within the accessory olfactory system of female prairie voles, including the accessory olfactory bulbs, granule cell layer, as well as the medial and cortical divisions of the amygdala 1 h after exposure to a single drop of urine as compared to individuals exposed to skim milk. The number of immunoreactivefos cells induced in females by conspecific male urine was also affected by photoperiod; short day females displayed fewer immunoreactivefos neurons in the accessory olfactory system as compared to long-day animal. Taken together, these results indicate that similar mechanisms underlie the responses of different rodent species to the chemosignals of conspecifics and that the pattern offos expression observed in the present study has functional significance for the regulation of reproduction in prairie voles.     

Role of computed tomography in screening for hepatocellular carcinoma in patients with cirrhosis

One hundred patients with cirrhosis underwent abdominal computed tomography (CT) using a delayed contrast technique to determine liver and spleen volume. These scans were reviewed to screen this "at risk" population for hepatocellular carcinoma (HCC). Fifteen of the 100 screened patients had focal abnormalities suspicious for HCC. On biopsy, only 1 patient was shown to have HCC. The other 14 patients had either fatty infiltration or focal regeneration. In the same time interval, a total of 10 patients had histologically proven HCC. All presented with symptoms and died within 4 months of diagnosis. The results show that focal hepatic lesions can be detected by CT but in this population the lesions may not be due to HCC. The incidence of HCC was approximately 1%, probably reflecting a truly low incidence in this population.