Clearance, distribution volume, and dialyzer mass area transport coefficient of glucose in whole blood

The extracorporeal transport of glucose was studied to determine the dialyzer mass transfer coefficient K(0)A for glucose in whole blood under conditions of glucose delivery and glucose removal. Glucose was removed from blood or delivered to blood using glucose-free dialysate or dialysate with a glucose concentration of 200 mg/dl (11.1 mmol/L). FX8 dialyzers (Fresenius Medical Care, Bad Homburg, Germany) were studied at constant dialysate flow Q(d) (500 ml/min) and variable blood flows Q(b) (200, 300, and 400 ml/min) under countercurrent flow conditions in a series of laboratory bench studies. Glucose clearance K(d) and glucose distribution volume flow rate Q(e) were determined from glucose mass balance. In 32 studies done with bovine blood at different hematocrit levels glucose was calculated to distribute in plasma water and to be excluded from red cell water when passing the FX8 dialyzer. The dialyzer mass transfer area coefficient K(0)A for glucose computed from Q(e), Q(d), and K(d) was 301.6 ± 45.2 ml/min and not different between modes of glucose delivery or glucose removal but lower than expected from the diffusivity of glucose estimated for aqueous solutions.     

Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes

Objectives To investigate the influence of coffee consumption on CYP1A2 enzyme activity controlling for the effects of smoking and oral contraceptive (OC) use among Serbs and Swedes and to compare CYP1A2 activity between the two populations. Methods Data on oral contraceptive use, habitual coffee consumption and smoking habits were obtained from 100 Serbian and 149 Swedish healthy volunteers using a detailed questionnaire. CYP1A2 activity was estimated by plasma paraxanthine/caffeine (17X/137X) ratio analysed by reversed-phase HPLC after oral administration of 100 mg caffeine. Results Daily consumption of at least three cups of coffee significantly increased CYP1A2 enzyme activity in both Serbs (P = 0.0002) and Swedes (P < 0.0001). Among non-smokers and non-OC users, heavy coffee consumption significantly increased CYP1A2 activity in Serbs (mean difference 0.11; 95% CI of the mean difference 0.04, 0.18; P = 0.003) and Swedes (mean difference 0.07; 95% CI of the mean difference 0.01, 0.12; P = 0.02). Significantly higher 17X/137X ratio was detected in Serbian smokers compared to non-smokers. There was no significant gender difference in CYP1A2 activity in Serbs. Controlling for the effect of smoking, heavy coffee consumption habit and oral contraceptive use, significantly lower 17X/137X ratio was observed in Serbs than in Swedes (P = 0.0003). Conclusions Habitual heavy coffee consumption increases CYP1A2 activity. Polycyclic aromatic hydrocarbons formed during roasting of coffee beans might partly be responsible for this effect. The reason for the observed lower CYP1A2 activity in Serbs as compared to Swedes remains to be investigated.     

Characterization of mechanical withdrawal responses and effects of μ-, δ- and κ-opioid agonists in normal and μ-opioid receptor knockout mice

Clinical and experimental observations suggest that opiates can exert different influences on the perception of stimuli from distinct sensory modalities. Thermally-induced nociception is classically responsive to opiate agonists. μ-Opioid receptor-deficient transgenic mice are more sensitive to thermal nociceptive stimuli and morphine fails to attenuate the nociceptive responses to thermal stimuli in these animals. To enhance our understanding of opiate influences on mechanical sensitivity, we have examined withdrawal responses to a sequence of ascending forces of mechanical stimuli in mice with normal (wild type), half-normal (heterozygous) and absent (homozygous) μ-opioid receptor levels. We report data from mice examined without drug pretreatment or following pretreatment with morphine, the selective κ-opioid agonist, U50488H, and the selective δ-opioid agonist, DPDPE. Saline-pretreated mice of each genotype displayed similar, monotonically increasing frequency of withdrawal responses to the graded stimuli. Subcutaneously administered morphine produced a dose-dependent reduction in withdrawal responses in wild type and heterozygous mice, but had no significant effect in homozygous mice. Intraventricular administration of DPDPE also reduced the frequency of paw withdrawal (FPW) in wild type mice, but not in homozygous mice. In contrast, systemic U50488H produced a dose-dependent attenuation of paw withdrawal in both wild type and homozygous mice. These findings suggest that (1) interactions of endogenous peptides with μ-opioid receptors may not play a significant role in the response to mechanical stimuli in drug-free animals, and (2) deficiency of μ-opioid receptors has no functional consequence on the response to the prototypical κ-opioid receptor agonist, but decreases responses to the prototypical μ- and δ-opioid receptor agonists.     

Bright Light and LEET Effects on Circadian Rhythms,Sleep and Cognitive Performance

Shift work and jet lag can disrupt circadian rhythms, with detrimental effects on alertness, performance and sleep. This study examined the effects of two interventions to adapt circadian rhythms, sleep and performance to a 10-h phase delay of the work–rest cycle. Bright light was administered from 2200 to 0200 each night to promote phase delay of circadian rhythms. Low energy emission therapy (LEET) was administered for 20 min prior to daytime sleep periods to promote sleep. Twelve subjects received bright light, 12 subjects received LEET, 11 received both interventions and 10 control subjects received only placebo treatments. Bright light accelerated phase delay of the circadian melatonin rhythm after the work–rest schedule shift. Further, subjects who received bright light had greater total sleep time (TST) and improved sleep continuity. LEET treatment produced a trend (p=0.16) for increased TST, but LEET did not affect the melatonin circadian rhythm. After the schedule shift, cognitive performance measures showed few significant differences. Some minor improvements in cognitive performance were produced by light treatments but not by LEET. © 1997 John Wiley & Sons, Ltd.     

Practitioners' attitudes towards the use of standardized diagnostic assessment in routine practice: a qualitative study in two child and adolescent mental health services

There is tension within Child and Adolescent Mental Health Services (CAMHS) assessments between the richness of differing practitioner's perspectives and maintaining a basic level of assessment that is acceptable to all disciplines. Standardized assessments are mandatory in research, yet are rarely applied systematically across CAMHS.The use of standardized assessments in routine practice might aid the allocation of families to the practitioners best able to meet their needs and free up time for intervention. However, practitioners' attitudes towards standardized assessment will dictate the success of such an approach. Fifty practitioners working in two CAMHS completed semi-structured interviews that explored their attitudes towards the use of standardized assessments in clinical practice, which were analysed using thematic analysis. Practitioners could identify both advantages and disadvantages of the routine use of standardized assessment. While they valued standardization, opportunities for service organization and increased information, some expressed concerns related to the choice, accuracy and influence of measures, as well as labelling. Almost one-third complained about their lack of pre-registration training in working with children, let alone their assessment. Practitioners, clinicians and policy makers need to consider these issues if they wish to introduce standardized assessments into routine practice. Senior staff need to be aware how unskilled some junior practitioners feel when they start working in CAMHS and offer appropriate support and supervision.     

Evaluation of brain and kidney energy metabolism in an animal model of contrast-induced nephropathy

Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients, occurring from 24 to 48 h and up to 5 days after the administration of iodinated contrast media. Encephalopathy may accompany acute renal failure and presents with a complex of symptoms progressing from mild sensorial clouding to delirium and coma. The mechanisms responsible for neurological complications in patients with acute renal failure are still poorly known, but several studies suggest that mitochondrial dysfunction plays a crucial role in the pathogenesis of uremic encephalopathy. Thus, we measured mitochondrial respiratory chain complexes and creatine kinase activities in rat brain and kidney after administration of contrast media. Wistar rats were submitted to 6.0 ml/kg meglumine/sodium diatrizoate administration via the tail vein (acute renal failure induced by contrast media) and saline in an equal volume with the radiocontrast material (control group); 6 days after, the animals were killed and kidney and brain were obtained. The results showed that contrast media administration decreased complexes I and IV activities in cerebral cortex; in prefrontal cortex, complex I activity was inhibited. On the other hand, contrast media administration increased complexes I and II-III activities in hippocampus and striatum and complex IV activity in hippocampus. Moreover, that administration of contrast media also decreased creatine kinase activity in the cerebral cortex. The present findings suggest that the inhibition of mitochondrial respiratory chain complexes and creatine kinase caused by the acute renal failure induced by contrast media administration may be involved in the neurological complications reported in patients and might play a role in the pathogenesis of the encephalopathy caused by acute renal failure.