Effect of age on levels of diazepam in plasma and brain of rats

Summary The pharmacokinetics and distribution in brain and cerebellum of diazepam after a single dose were studied in middle aged (6 months) and old (18 months) rats. Following the single intravenous bolus of 5 mg/kg diazepam was eliminated more slowly in old rats (T _1/2()=3.1h) than in middle aged rats (1.4 h). This was due to an increase in the apparent volume of distribution Vd from 11.0 l/kg (control rats) to 29.5l/kg. Concentrations of diazepam in brain and cerebellum were in the same range (0.5–1.1 ng/mg) in both groups after this dose. We conclude that the distribution of diazepam is age-dependent which might be due to an altered body composition.     

Microcomputer voice-response telephone entry for balanced clinical trial randomization

Simple randomization of patients to treatment regimens in clinical trials can result in inbalance among stratum categories. Procedures that produce balance may lack randomness. Systems that are not deterministic yet produce balance are often extremely complex and are not easily performed by randomization clerks. A microcomputer-based voice-response system has been implemented that permits clinic staff to easily randomize patients in clinical trials despite the complexity of the algorithm. Data entry is accomplished by the use of Touch-Tone keys. Input prompts and regimen assignment are spoken by a commercially available voice synthesizer.     

Von der isolierten Optikusatrophie zur Multisystemerkrankung

Optic atrophy is an unspecific response to an injury of retinal ganglion cells or their axons. We report the case of a 13-year-old child with cone–rod retinal dystrophy due to a mitochondrial disorder. This rare differential diagnosis of progressive loss of visual acuity and papillary atrophy should be considered especially in the case of further systemic symptoms.     

Cell specific ultrasound effects are dose and frequency dependent

Ultrasound is widely used in clinical practice, mostly in diagnostic studies, but increasingly in therapeutic applications as well. This may be the case in acceleration of wound healing or treatment of cancer. Still, little is known about the direct effect of frequency or energy density of the ultrasound upon the cells themselves. We therefore investigated the impact of three different protocols using high, medium and low energy densities at three different frequencies on normal endothelial and epithelial as well as carcinoma cell lines (neuroblastoma and adenocarcinoma cell lines).Proliferation of endothelial and epithelial cell lines was significantly increased depending on the frequency and energy density applied. No influence on actin cytoskeleton formation was seen in these cells after treatment, while a significant decrease in the density of microvilli and the length of filopodia in the epithelial cell line could be noted. The proliferation rate of the carcinoma cell lines was reduced and cells destroyed. Apoptosis was induced in the adenocarcinoma cells after ultrasound exposure. Additionally, the expression of neurofilament was increased in neuroblastoma cells as evidence of beginning differentiation.So, different settings of frequency and energy density in an ultrasonic treatment protocol lead to different impacts on proliferation, morphology and differentiation and might be used to stimulate or inhibit the growth of individual cell types.