Class III antiarrhythmic activity of novel substituted 4-[(methylsulfonyl)amino]benzamides and sulfonamides.

The synthesis and Class III antiarrhythmic activity of a series of 4-[(methylsulfonyl)amino]benzamides and sulfonamides are described. Selected compounds show a potent Class III activity and are devoid of effects on conduction both in vitro (dog Purkinje fibers) and in vivo (anesthetized dogs). Compounds having a 2-aminobenzimidazole group were found to be the most potent, and one compound having this heterocycle (5, WAY-123,398) was selected for further characterization. Compound 5 was shown to have good oral bioavailability and a favorable hemodynamic profile to produce a 3-fold increase of the ventricular fibrillation threshold and to terminate ventricular fibrillation, restoring sinus rhythm in anesthetized dogs. Voltage-clamp studies in isolated myocytes show that 5 is a potent and specific blocker of the delayed rectifier potassium current (IK) at concentrations that cause significant prolongation of action potential duration.     

Maintenance of long-term adaptation of synaptic transmission requires axonal transport following induction in an identified crayfish motoneuron

Motoneurons can adapt to altered levels of electrical activity by effecting semi-permanent changes in their neuromuscular synaptic physiology. In the present study, we tested the hypothesis that maintenance of activity-dependent long-term adaptation of synaptic transmission in a crayfish abdominal extensor motoneuron (phasic axon 3) required axonal transport following induction. Intact crayfish were chronically wired for periodic in vivo stimulation of axon 3. Periodic unilateral stimulation for 3-5 consecutive days (2 h/day) induced long-term adaptation (LTA) of neuromuscular synaptic transmission in axon 3. Initial EPSP amplitudes (measured at 0.1 Hz) were significantly reduced to approximately 40% of contralateral control amplitudes over a 7-day poststimulation period. Additionally, synaptic depression during 5 Hz test stimulation of axon 3 was significantly less in chronically stimulated neurons: excitatory postsynaptic potential (EPSP) amplitudes measured after 20 min of 5 Hz test stimulation (final EPSPs) were significantly larger in conditioned neurons than in unstimulated controls. The depression of initial EPSP amplitudes persisted for 7 days postinduction, while the increased synaptic stamina persisted for 4 days but was absent at 7 days postinduction. Axotomy of axon 3 following induction of LTA had no effect on long-term maintenance of the activity-induced reduction in initial EPSP amplitudes. Initial EPSP amplitudes in conditioned, axotomized neurons were still reduced to 42% of control amplitudes over the 7-day postinduction period. In contrast, postinduction axotomy of axon 3 elicited an accelerated decay of the enhanced synaptic stamina. Following axotomy, final EPSP amplitudes were significantly larger in conditioned neurons for only 1 day poststimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

View ordering for magnetization prepared steady state free precession acquisition: application in contrast-enhanced MR angiography.

Magnetization prepared segmented acquisition requires a view order that maximizes signal contrast during the acquisition of the central portion of k-space. Steady state free precession (SSFP) acquisition further requires a view order that minimizes changes in phase-encoding gradients from one repetition to the next in order to minimize eddy current artifacts. In this article, optimal view ordering schemes satisfying these two requirements are formulated and applied to inversion prepared 3D SSFP contrast-enhanced MR angiography (MRA). Experiments on phantoms and pigs demonstrated improved background suppression and reduced image artifacts.     

Estimation of the bronchodilatory effect of deep inhalation after a free run in children.

The bronchomotor effects of a deep inhalation (DI) may provide relevant information about the mechanisms of exercise-induced airway obstruction in children and may be assessed by respiratory conductance (Grs) measured using the forced oscillation technique. The aims of the present study were to assess the effect of DI on Grs after exercise in relationship to the lung function response to exercise. Grs at 12 Hz using a head generator and spirometric data were measured in 62 children suspected of asthma before and 5 min after a 6-min free run. After exercise, Grs was significantly increased by DI in 38 subjects, who also showed larger Grs and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise regression indicated significant correlation between the response of Grs to DI and both Grs and FEV1/FVC responses to exercise. The data are consistent with exercise-induced bronchoconstriction being reversed by deep inhalation.     

Azide function and polyaddition: reaction of 2-azido-2,4,4-trimethylpentane and monoazidopoly(2-methylpropene) with some dienophiles

The 1,3-dipolar addition of 2-azido-2,4,4-trimethylpentane ( 1 ) to acetylene and ethylene derivatives such as phenylacetylene (2), acrylonitrile, diphenyl fumarate ( 4 ) and N,N′-methylenebis(1,4-phenylene)dimaleimide ( 8 ) leads to the corresponding triazole and triazoline derivatives. This study demonstrates that tertiary azides are able to react with dienophiles, and the application of this reaction for the synthesis of block copolymers was investigated with monoazido-telechelic poly(2-methylpropene) (PMP). It was shown that the azido group is stable under the severe conditions of the polycondensation reaction without decomposition (170°C, 24 h), and the monoadduct PMP- 8 is produced with acceptable yield.     

Analyses and perspectives in cancer immunotherapy.

Since the last two decades, rapid progress has been made in the field of cancer immunotherapy relevant to manipulation of adaptative cytotoxic T lymphocytes (CTLs) and innate immunity natural killer (NK) cells as well as antibodies. Many possibilities are now offered for therapeutic purposes contributing to better approaches in treatment of cancer.     

Validating the use of two-item measures of pain beliefs and coping strategies for a veteran population.

Previous research has demonstrated that 2-item versions of subscales from the Chronic Pain Coping Inventory, Coping Strategy Questionnaire, and the Survey of Pain Attitudes appear adequately reliable and valid for use in studies with large sample sizes. It was suggested that use of the abbreviated scales might help to expand the testing and application of cognitive-behavioral models of pain to new settings and with new populations where assessment burden might be a key issue. This study explored the utility of these brief scales among veterans in a Veterans Affairs setting. Strong associations were found between the 2-item versions and their respective parent scales. In addition, the 2-item scales were found to be associated with other pain-related measures, supporting their predictive validity. The results of this study replicate previous findings and offer support for the use of the 2-item versions for both screening and research purposes in Veterans Affairs settings with a veteran population. PERSPECTIVE: This article presents the psychometric properties of brief versions of 3 commonly used pain coping and belief questionnaires in a unique population. These measures could be used clinically for initial screening purposes, as well as for treatment monitoring.