Effect of linoleic acid metabolites on Na(+)/K(+) pump current in N20.1 oligodendrocytes: role of membrane fluidity

Metabolic derivatives of linoleic acid, both monoepoxides and diols, have been reported to be toxic in humans and multiple animal tissue preparations. A previous electrophysiological study has shown these compounds produce multiple effects on the electrical activity of rat ventricular myocytes. The hydrophobic nature of these compounds suggests the possibility that these effects may be due to nonspecific lipid interactions, i.e., changes in membrane fluidity. This study investigates membrane fluidity as a possible mechanism by which linoleic acid metabolites inhibit Na(+)/K(+) pump current (I(p)). This study showed that positional isomers 9,10- and 12,13-epoxy-octadecenoic acid (EOA) and 9,10- and 12,13-dihydroxy-OA (DHOA) inhibit I(p) in a dose-dependent manner in N20.1 mouse oligodendrocytes, with greater inhibition produced by EOAs. These compounds, at 10 microM, inhibited I(p) by 4.7 +/- 1.6, 18.2 +/- 0.5, 11.7 +/- 0.5, and 25.1 +/- 0.9% for 12,13-DHOA, 9,10-DHOA, 12,13-EOA, and 9,10-EOA, respectively, in oligodendrocytes. Fluorescence recovery after photobleaching measurements showed that both DHOA isomers produced a 7-8% increase in diffusion coefficient of the probe at 10 microM, whereas the diffusion coefficient was decreased by 5 and 13% by 9,10-EOA and 12,13-EOA, respectively. There was no apparent correlation between membrane fluidity and inhibition of I(p) by these four linoleic acid metabolites. These results indicate that membrane fluidity alone cannot explain the effects of these compounds on I(p) and suggest that they have a specific interaction with the Na(+)/K(+) pump.     

Two generations of insulinotropic imidazoline compounds

The imidazoline RX871024 increased basal- and glucose-stimulated insulin release in vitro and in vivo. The compound inhibited activity of ATP-sensitive K(+) channels as well as voltage-gated K(+) channels, which led to membrane depolarization, an increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)), and insulin release. Importantly, RX871024 also enhanced the insulinotropic effect of glucose in cells with clamped [Ca(2+)](i) but in the presence of high ATP and Ca(2+)concentration inside the cell. We believe that the latter effect on insulin exocytosis was at least in part mediated by a rise in diacylglycerol, which then activated protein kinase C (PKC) and increased the generation of arachidonic acid (AA) metabolites. Activation of both the PKC and AA pathways resulted in potentiation of glucose effects on insulin secretion. Unlike RX871024, the novel imidazoline BL11282 did not block ATP-dependent K(+) channels, but similarly to RX871024, it stimulated insulin secretion in depolarized or permeabilized islets. Accordingly, BL11282 did not influence glucose and insulin levels under basal conditions either in vitro or in vivo, but it markedly enhanced the insulinotropic effects of glucose. BL11282 restored the impaired insulin response to glucose in islets from spontaneously diabetic GK rats. We conclude that BL11282 belongs to a new class of insulinotropic compounds that demonstrate a strong glucose-dependent effect on insulin exocytosis.     

Motor control and cerebral hemispheric specialization in highly qualified judo wrestlers

With the purpose of investigating motor and cognitive lateralization profiles associated with long-term motor training, we investigated differences in hemispheric specialization between proficient judo sportsmen and controls through the assessment of a number of handedness and footedness items including postural preferences as well as dichotic listening and lateralized visual field tests. Our data show that: (1) the different handedness and footedness items did differently relate to each other within the athlete and control groups as revealed by a principle component analysis (PCA); (2) stand side correlated differently to these motor profile factors in athletes and controls; (3) athletes preferred more frequently to perform certain movements with the left hand than controls, although overall right-handed; (4) this was especially true for athletes which proved to be most proficient/skilled; and (5) in a lateralized verbal listening task and a lateralized visual field task athletes revealed enhanced right-hemispheric involvement relative to controls. Our results suggest that during motor and postural skill acquisitions (long-term judo training) lateral preferences are modified, probably due to neuroplasticity. Moreover, the present findings support the multidimensional view of handedness by Steenhuis and Bryden [Cortex 25 (1989) 289] and the notion of a right-hemispheric "praxis system" involved in skilled action routines within peripersonal space [Brain and Cognition 23 (1993) 181].     

Parental and self-report of sleep in children with attention-deficit/hyperactivity disorder

OBJECTIVE: To determine the prevalence of parent-reported and self-reported sleep disturbances in a sample of school-aged children with attention-deficit/ hyperactivity disorder (ADHD). DESIGN: Cross-sectional survey questionnaire. SETTING: A multidisciplinary ADHD evaluation clinic in a children's teaching hospital (ADHD sample) and 3 elementary schools in southern New England (control sample). PARTICIPANTS: Forty-six unmedicated, school-aged children (mean age, 89.4 +/- 18.7 months; 74% male) diagnosed as having ADHD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria who had been screened for marked symptoms of sleep-disordered breathing, and 46 normal control children (mean age, 86.5 +/- 16.9 months; 70% male). INTERVENTION: None. MAIN OUTCOME MEASURE: Sleep habits and sleep disturbances reported by parents and children. RESULTS: Children with ADHD had significantly higher (more sleep-disturbed) scores on all sleep subscales of the Children's Sleep Habits Questionnaire (parent measure) than did controls; average sleep duration as reported by parents was also significantly shorter in the ADHD group. Children with ADHD also reported their own sleep to be more disturbed than controls did on the Sleep Self-report, particularly on items relating to bedtime struggles (P range, .05-.001). There was a much higher correlation between parent and child sleep report items for the children with ADHD (mean correlation, 0.55) than for the control children. CONCLUSIONS: Sleep disturbances, particularly at bedtime, are frequently reported by both parents and children with ADHD. Children undergoing evaluation for ADHD should be routinely screened for sleep disturbances, especially symptoms of sleep-disordered breathing. The causes of sleep-onset delay in children with ADHD should be considered in designing intervention strategies for children with difficulty falling and staying asleep.     

Effects of a holmium-166 incorporated covered stent placement in normal canine common bile ducts

PURPOSE: A specially designed self-expandable covered metallic stent incorporated with beta-emitting radioisotope, Holmium-166 (Ho-166), was developed for delivering intraluminal brachytherapy as well as for internal bile drainage in malignant biliary stricture. The purpose of the study was to demonstrate the safety and tissue response of the radioactive metallic stent on the normal canine common bile duct (CBD) prior to the clinical application. MATERIALS AND METHODS: Nitinol self-expandable stents (diameter; 4 mm, length; 20 mm) were covered with polyurethane membrane (50 microm thick) containing 21 to 135 muCi of Ho-166 (mean, 77.9 microCi). To prevent migration of stent, the membrane covered only the middle 1 cm of the stent and the ends of the stent were left uncovered. The stents were placed in the CBD of 20 healthy beagle dogs. For control, non-radioactive covered stents were placed in another three dogs. The dogs were killed 3 to 6 months after stent insertion and histopathologic examination of CBD was performed. RESULTS: There was no stent migration in all cases. Varying degrees of papillary mucosal hyperplasia leading to significant narrowing of the lumen was observed within the lumen of the bare portion and under the mucosal surface of the non-radioactive covered stents. However, fibrosis was noted in Ho-166 coated area, instead of mucosal hyperplasia. Severity of fibrosis was correlated with estimated radiation dose. Despite high dose, there was no perforation of CBD wall. The membrane of Ho-166 coat was disrupted in some cases of 6 months follow-up. CONCLUSIONS: Holmium-166 incorporated covered stents demonstrated fibrosis of CBD wall and inhibition of ingrowth of mucosal hyperplasia without serious complication such as perforation, while control group showed severe mucosal hyperplasia.