The general principles of in-vitro simulation of drug pharmacokinetic profiles for linear one-, two- and multi-compartment models are described. An in-vitro dynamic model constructed on the basis of these, incorporating a novel filtration unit to provide efficient filtration of drugs at constant inoculum size, was used to study the antimicrobial action of sisomicin on Escherichia coli A 20363, in conditions simulating the pharmacokinetic profile observed in humans after a single intramuscular dose of 1 mg/kg.
The intensification of nonspecific resistivity of macroorganisms caused by polysaccharides is a well established fact [3,9,15]. This protective action, due mainly to stimulation of the reticulo-endothelial system, occurs in different pathological conditions, especially in experimental infections and transplanted tumors in animals. There is however a lack of conclusive data on the relationship between the chemical structure and the biological action of the polysaccharides.A marked macromolecular heterogeneity of the microbial heteropolysaccharides has been found by a number of investigators [11,14]. R has been shown that molecules of relatively large dimensions are necessary for the appearance of biological activity of polysaccharides. Dissociation of polysaccharide macromolecules with the formation of smaller subunits is accompanied by considerable loss of biological activity. With reaggregation of the macromolecular complex the biological activity is restored [12].A study of the fine chemical structure of the heteropolysaccharides presents great difficulties, and therefore we have restricted ourselves to an investigation of the biological action of 2 homopolysaccharides, glucan and laminarin, the structure of which can be considered to have been interpreted. Both the polysaccharides are polyglucosides in which glucose residues are associated mainly with B-1,3-and to a smaller extent B-1,6-bonds.Glucan, a polysaccharide from the cellular membranes of the yeast fungi Saccharomyces cerevisiae, [5],is insoluble in cold and boiling water, diluted acids and alkalis,and organic solvents. Laminarin,* a polysaccharide from the alga Laminaria cloustoni, is readily soluble in boiling water [6]. It is assumed that the glucan moiecule is an unbranched chain in which groups of glucose residues joined by 8-1,3-bonds interchange with glucose residues joined by 13-1,6-bonds. The latter comprise 10-20% of the total number of bonds [13]. The laminarin als'o is an unbranched chain consisting of glucose residues joined by I3-1,3-bonds. On the ends of the chains are mannitol residues. The individual short chains are joined by B-1,6-bonds. The polymerization coefficient of laminarin is 20 and that of glucan 40 [10]. Apart from this, it is known [8] that the glucan molecules in the membrane of the yeast cells are connected by aeetylglucosamine residues. In our preparation there is about 3% hexosamine; it can therefore be assumed that the polysaccharide in question is a complex aggregate of molecules.
EXPERIMENTAL METHODSThe study was on crossbred white mice weighing 16-18 g. The polysaccharides (glucan and laminarin) were injected into the animals once at different periods before inoculation intravenously or ~ntraperitoneally at a rate of 5 to 30 mg/kg. The mice of the control group received intravenously or intraperitoneally 0.5 ml physiological solution. The ability of polysaccharides to increase the resistivity of the organism was tested on mice in conditions of experimental sepsis caused by intraperitoneal injection of 1 DLM of the...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.