Differential class III and glibenclamide effects on action potential duration in guinea-pig papillary muscle during normoxia and hypoxia/ischaemia

1. Microelectrode recording techniques were used to study the effects of several potassium channel blockers which are considered to be Class III antiarrhythmic compounds. The effects of (+)-sotalol, UK-66,914, UK-68,798 and E-4031 on action potential duration (APD) were determined in guinea-pig isolated papillary muscles. The compounds were evaluated under normoxic or hypoxic/ischaemic conditions at 36.5 degrees C and compared to glibenclamide, which is considered to be a blocker of ATP-dependent potassium channels. Prolongation of action potential duration at 90% repolarization (APD90) was taken as an indirect measure of potassium channel blockade. 2. Under normoxic conditions, the Class III compounds prolonged APD in a concentration-dependent manner. According to EC15 values, the order of potency of the Class III compounds was found to be UK-68,798 > E-4031 > UK-66,914 > (+)-sotalol. Glibenclamide did not significantly prolong APD90 under normoxic conditions. 3. Perfusion with an experimental hypoxic or ischaemic bathing solution produced qualitatively similar effects on action potentials. Over a period of 20-25 min in either of the experimental solutions, there was a small decrease in action potential amplitude (APA) and a prominent shortening of APD. The ischaemic solution also depolarized the resting membrane potential by about 15 mV. 4. (+)-Sotalol and UK-66,914 did not reverse the shortening of APD induced by perfusion with hypoxic Krebs solution. High concentrations of glibenclamide (10 microM) and UK-68,798 (30 and 60 microM) partially reversed the hypoxia-shortened APD. Glibenclamide was more potent and exhibited a greater time-dependent action than UK-68,798. 5. During experimental ischaemia, the Class III compound E-4031 (10 microM, n = 7) produced small, but significant, increases in the APD90 (11 +/-3 ms after 20 min) which were not clearly time-dependent(14 +/- 4 ms after 30 min). UK-68,798 (10 microM) also produced a small, but insignificant, increase in APD90(12 =/-6 ms at 20 min, n = 4). Higher concentrations of UK-68,798 (30 and 60 microM, n = 4) did not produce a consistently significant increase in APD90 during ischaemia: significance was only attained after 20 min in the presence of 60 microM UK-68,798 (24 +/- 12 ms). However, in marked contrast to the effects of the Class III compounds, glibenclamide (10 microM) produced large time-dependent increases in ischaemic APD90 (34 +/- 11 ms at 7 min, n = 9) which were significant 15 min or more after drug addition(52 +/- 12 ms at 20 min, n = 7; 74 +/- 5 ms at 30 min, n = 6).6. The present microelectrode data suggest that blockers of ATP-dependent potassium channels, such as glibenclamide, might prove to be more effective than Class III compounds against ischaemia-induced shortening of cardiac action potentials.     

Individual differences in anterior brain asymmetry and fundamental dimensions of emotion.

Assessed whether individual differences in anterior brain asymmetry are linked to differences in basic dimensions of emotion. In each of 2 experimental sessions, separated by 3 wks, resting EEG activity was recorded from female adults during 8 60-sec baselines. Mean alpha power asymmetry across both sessions was extracted in mid-frontal and anterior temporal sites. Across both regions, groups demonstrating stable and extreme relative left anterior activation reported increased generalized positive affect (PAF) and decreased generalized negative affect (NAF) compared with groups demonstrating stable and extreme relative right anterior activation. Additional correlational analyses revealed robust relations between anterior asymmetry and PAF and NAF, particularly among Ss who demonstrated stable patterns of EEG activation over time. Anterior asymmetry was unrelated to individual differences in generalized reactivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The gene encoding human glutathione synthetase (GSS) maps to the long arm of chromosome 20 at band 11.2

Two forms of glutathione synthetase deficiency have been described. While one form is mild, causing hemolytic anemia, the other more severe form causes 5-oxo-prolinuria with secondary neurological involvement. Despite the existence of two deficiency phenotypes, Southern blots hybridized with a glutathione synthetase cDNA suggest that there is a single glutathione synthetase gene in the human genome. Analysis of somatic cell hybrids showed the human glutathione synthetase gene (GSS) to be located on chromosome 20, and this assignment has been refined to subband 20q11.2 using in situ hybridization.     

Electroencephalogram asymmetry in response to the approach of a stranger and maternal separation in 10-month-old infants.

We recently reported the presence of reliable asymmetries in frontal-brain electrical activity in infants that distinguished between certain positive- and negative-affect elicitors. In order to explore the degree to which these asymmetries in brain activity are associated with individual differences in affective response, 35 ten-month-old female infants were presented with a stranger-approach, mother-approach, and maternal-separation experience while an electroencephalogram (EEG) from the left- and right-frontal and left- and right-parietal scalp regions was recorded and facial and other behavioral responses were videotaped. Changes in frontal-EEG asymmetry reflected behavioral changes between conditions. In addition, individual differences in affective response to separation were related to differences in frontal-brain asymmetries. These findings indicate that lawful changes exist in asymmetries of frontal-brain activation during the expression of certain emotions in the first year of life and that individual differences in emotional responsivity are related to these measures of brain activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Frontal brain activation in repressors and nonrepressors.

Assessed whether resting anterior asymmetry would discriminate individual differences in repressive-defensive coping styles. In 2 sessions, resting electroencephalogram was recorded from female adults during 8 60-sec baselines. Ss were classified as repressors or nonrepressors on the basis of scores on the Marlowe-Crowne Social Desirability Scale (MC), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). In midfrontal and lateral frontal sites, repressors demonstrated relative left hemisphere activation when compared with other groups. The MC, but not the STAI or the BDI, contributed unique variance to frontal asymmetry. Relative left frontal activation may be linked to a self-enhancing regulatory style that promotes lowered risk for psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Models of high velocity impact phenomena

Models of craters formed by impacts at velocities of up to 24.5 km/sec have been computed using the Smooth Particle Hydrodynamics, MESA, EPIC and CALE codes. These modeling efforts are compared to data obtained from the Hypervelocity Microparticle Impact project at Los Alamos using the van de Graaff accelerator. A factor of 5 increase in yield strength was needed to account for high strain rate effects and to match the data. Structure in the data is addressed by using crater volume instead of crater diameter cubed. Detailed code comparisons were made between the four codes with good agreement found.     

A Multinational Survey of the Quality of Carbamazepine Tablets

The results of a multinational survey of the quality of carbamazepine tablets are reported. A total of 22 laboratories in nineteen countries worldwide participated in the study conducted under the auspices of the Official Laboratories and Medicines Control Services (OLMCS) Section of FIP. The results of tests conducted on 86 samples representing at least 34 different products, comprising the innovator's product Tegretol, 13 other branded products and 20 generic products, are presented. Most products fulfilled the requirements of pharmacopoeial quality standards. However, there were marked differences in dissolution behaviour which suggest that not all products are bioequivalent with each other. Most of the products tested would not comply with a requirement for the percentage of carbamazepine released at 15 minutes, that is proposed for inclusion in the USP monograph for Carbamazepine Tablets.