[Antigenic activity of oral whole-culture meningococcal serogroup B vaccine]. / Antigennaia aktivnost' peroral'nogo tsel'nokul'tural'nogo preparata meningokokkov serogruppy B.

The whole-culture vaccine preparation of Neisseria meningitidis, serogroup B, obtained by cultivation in a computer-controlled bioreactor, was studied. The preparation was shown to contain antigenically active polysaccharide, outer membrane proteins, as well as lipooligosaccharide, faintly pyrogenic and with low toxicity. After oral immunization of rabbits a multiple increase in the levels of IgG antibodies to these antigens in their blood serum was noted during the period of observation (303 days).

Toxicity and immunogenicity of Neisseria meningitidis lipopolysaccharide incorporated into liposomes.

To obtain nontoxic and highly immunogenic lipopolysaccharide (LPS) for immunization, we incorporated Neisseria meningitidis LPS into liposomes. Native LPS and its salts were incorporated by the method of dehydration-rehydration of vesicles or prolonged cosonication. The most complete incorporation of LPS into liposomes and a decrease in toxicity were achieved by the method of dehydration-rehydration of vesicles. Three forms of LPS (H+ form, Mg2+ salt, and triethanolamine salt) showed different solubilities in water, the acidic form of LPS, with the most pronounced hydrophobic properties, being capable of practically complete association with liposomal membranes. An evaluation of the activity of liposomal LPS in vitro (by the Limulus amoebocyte test) and in vivo (by monitoring the pyrogenic reaction in rabbits) revealed a decrease in endotoxin activity of up to 1,000-fold. In addition, the pyrogenic activity of liposomal LPS was comparable to that of a meningococcal polysaccharide vaccine. Liposomes had a pronounced adjuvant effect on the immune response to LPS. Thus, the level of anti-LPS plaque-forming cells in the spleens of mice immunized with liposomal LPS was 1 order of magnitude higher and could be observed for a longer time (until day 21, i.e., the term of observation) than in mice immunized with free LPS. The same regularity was revealed in a study done with an enzyme-linked immunosorbent assay. This study also established that antibodies induced by immunization belonged to the immunoglobulin M and G classes, which are capable of prolonged circulation. Moreover, liposomal LPS induced a pronounced immune response in CBA/N mice (defective in B lymphocytes of the LyB-5+ subpopulation). The latter results indicate that the immunogenic action of liposomal LPS occurs at an early age.

Structure of the sugar-phosphate moiety of lipid A from lipooligosaccharide of Neisseria meningitidis group B, strain BC5S No. 125. Hydrolytic stability of phosphate and pyrophosphate substituents.

On the basis of chemical and NMR data the partial structure of lipid A from lipooligosaccharide (LOS) of Neisseria meningitidis group B, strain BC5S No 125 was established. Lipid A consisted of disaccharide 2-deoxy-6-O-[2-deoxy-2-(3-hydroxytetradecanoylamino)- beta-gluco-pyranosyl]-2-(3-hydroxytetradecanoylamino)- alpha-glucopyranose carrying the beta-(2-aminoethyl)pyrophosphate residue at 0-4' and the pyrophosphate or phosphate residue at 0-1. On hydrolysis of the acidic form of LOS with 1% acetic acid the substituent at 0-1 was practically completely removed whereas that at 0-4' was stable. The analogous hydrolysis of the Mg-salt of LOS was accompanied by splitting off the pyrophosphate linkage in the substituent at 0-4'. Hydrolysis of LOS at pH 4.5 in the presence of SDS led mainly to a lipid A preparation retaining both pyrophosphate residues.

Intraoperative management of phaeochromocytoma with sodium nitroprusside.

Sodium nitroprusside (SNP) is a powerful, peripherally acting hypotensive agent with a rapid onset but short duration of action. It is highly effective for hypertensive episodes in patients with a phaeochromocytoma and may be used safely with adrenoceptor-blocking agents. Two cases are described that illustrate its effectiveness in this condition, even in the presence of exceptionally high circulating concentrations of catecholamines. A simple and reliable regimen for preparing these patients for surgery may be based on oral adrenoceptor-blocking medication (phenoxybenzamine and propranolol) to provide "background" hypotensive and antiarrhythmic cover. SNP by infusion is then used as the principal intraoperative hypotensive agent, dysrhytmias being controlled with additional intravenous propranolol if required.