Intronic in situ hybridization methodology provides a means of determining the rate of gene transcription under basal and stimulated conditions. In the present study, we have used intronic in situ hybridization to the corticotropin-releasing factor (CRF) gene to measure hypothalamic CRF gene transcription after stress as well as its modulation by glucocorticoids. Using this and conventional exonic in situ hybridization we examined the time course of changes in c-fos mRNA, and CRF heteronuclear RNA (hnRNA) and mRNA concentrations in the paraventricular nucleus (PVN) of male Wistar rats after restraint stress. In addition, we determined the effects of adrenalectomy and dexamethasone administration on c-fos and CRF gene expression in the PVN. Restraint stress induced a rapid induction (within 5 min) of c-fos mRNA and CRF hnRNA expression in the PVN. Both RNA concentrations peaked at 30 min then decreased and were undetectable 2 h after stress onset. In contrast, the concentration of CRF mRNA increased gradually and a significant elevation was first detected 60 min after the beginning of stress. Adrenalectomy augmented and dexamethasone pretreatment inhibited c-fos mRNA, CRF hnRNA, and mRNA induction after stress. The data suggest that stress-induced activation of neurons, CRF gene transcription, and CRF synthesis in the PVN are modulated by glucocorticoids. (J. CliH. Invest. 1995. 96:231-238.)
The literature investigating the relationship between objective and subjective sleep in depressed patients is limited and the results are inconsistent. Furthermore, many factors that influence the aforementioned relationship have not been investigated. The present study was carried out to clarify the characteristics of self-estimation of sleep in depressed patients. Sleep was estimated concurrently using a sleep log and polysomnography for 5 consecutive days to investigate the relationship between subjective sleep estimation and objective sleep estimation in 23 patients with major depression ( Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised; DSM-III-R). Factors related to a discrepancy between both types of estimation were identified. The subjective total sleep time showed a significant, but moderate, positive correlation (correlation coefficient: 0.63) with the objective total sleep time. The degree of discrepancy was significantly correlated with various objective sleep variables and severity of depression. In the underestimation group in which the subjective total sleep time was shorter than the objective total sleep time, the objective total sleep time and slow-wave sleep time were shorter, age was greater and the extroversion score (Maudsley Personality Inventory) was lower than in the overestimation group in which the subjective total sleep time was longer than the objective total sleep time. The data suggest that subjective sleep estimation in depressed patients is influenced by their objective sleep, severity of depression, age and personality.
Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected with methicillin-resistant Staphylococcus aureus (MRSA) who received vancomycin. The exact Cmin sampling time was used for Bayesian estimation. A significantly higher early treatment response was observed in patients with a day 2 AUC ≥ 400 µg·h/mL than those with <400 µg·h/mL, and a significantly higher early nephrotoxicity rate was observed in patients with a day 2 AUC ≥ 600 µg·h/mL than those with <600 µg·h/mL. These AUC cutoff values constituted independent factors for each outcome. In sub-analysis, the discrimination ability for early clinical outcomes using these AUC cutoffs was confirmed only in patients with q12 vancomycin administration. A significant difference in early treatment response using the 400 µg·h/mL cutoff was obtained only in patients with low-risk infections. The usefulness of the vancomycin AUC target to decrease nephrotoxicity while assuring clinical efficacy was even confirmed with a single Cmin measurement. However, assessment with two samples might be required in patients with q24 administration or high/moderate-risk MRSA infections.
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