Chitosan, a polycationic polymer and waste product from the sea food processing industry, is an abundant natural resource that has, as yet, not been fully utilized. Advantages of this polymer include availability, low cost, high biocompatibility, biodegradability and ease of chemical modification. In this paper, the physicochemical properties of chitosan, as well as its numerous applications, are reviewed with particular emphasis on its use in water treat ment, pharmaceutics, agriculture and membrane formation.
The thiadiazinone derivative [+]-EMD 60263 ((+)-5-(l-(alpha-ethylimino-3,4-dimethoxybenzyl)-1,2,3,4-tetrah ydroquinoline -6-yl)-6-methyl-3,6-dihydro-2H-1,3,4 -thiadiazine-2-on) is a Ca(2+)-sensitizing agent with only minor phosphodiesterase inhibitory activity. Our aim was to characterize the inotropic and electrophysiological effects of [+]-EMD 60263 and its enantiomer [-]-EMD 60264 in several cardiac muscle preparations. The Ca(2+)-sensitizing activity resided in the [+]-enantiomer only. [+]-EMD 60263 (3 microM) shifted the EC50 of Ca2+ for contractile activation of skinned fibers of pig heart from 2.41 microM to 0.73 microM, whereas [-]-EMD 60264 (30 microM) was ineffective. In Langendorff-perfused guinea pig hearts, [+]-EMD 60263 and [-]-EMD 60264 induced concentration-dependent positive and negative inotropic effects, respectively; both enantiomers reduced spontaneous heart rate but did not influence perfusion pressure. The maximum increase in force of human atrial trabeculae was 35% of pre-drug control with [+]-EMD 60263 in comparison to 113% with forskolin. In guinea-pig papillary muscles, [+]-EMD 60263 and [-]-EMD 60264 had opposite inotropic responses, however, both agents similarly prolonged action potential duration. Both enantiomers concentration-dependently blocked the rapidly activating component IKr of the delayed rectifier in guinea-pig myocytes. The block saturated at potentials positive to +30 mV, closely resembling the effects of the antiarrhythmic agent E-4031 which had been originally used to define IKr.
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