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Role of granulocytes in the induction of an experimental endocarditis with a dextran-producing Streptococcus sanguis and its dextran-negative mutant.

The role of granulocytes in the induction of endocarditis with a dextran-producing Streptococcus sanguis and a dextran-negative mutant of this strain was studied. The number of colony-forming units of Streptococcus sanguis needed to colonize the vegetations in 50% of the rabbits (ID50) was significantly lower for the parent strain than for the dextran-negative mutant. However, in granulocytopenic rabbits the ID50s of both strains did not differ measurably. Dextran-negative streptococci were more readily cleared from the circulation than dextran-positive, but in this respect no difference was found between control and granulocytopenic rabbits, which indicates that clearance cannot account for the difference in ID50 between the two strains in the control group. At serum concentrations of 5% and lower, in-vitro granulocytes phagocytosed the dextran-negative streptococci more rapidly than the dextran-positive. The intracellular killing of the streptococci was no influenced by dextran production. This study suggests that an impaired phagocytic removal of attached bacteria from the vegetational surface can be a factor promoting the induction of endocarditis by dextran-producing streptococci.

Animals↗

Thromboembolism following total hip-replacement arthroplasty. The efficicy of dextran-aspirin and dextran-warfarin in prophylaxis.

The efficacy of two antithrombotic regimens, combined dextran and aspirin and combined dextran and warfarin, was analyzed by comparing the incidence of thromboembolism following total hip replacement in two groups of similar patients. Of the 427 who received dextran and aspirin, 7 per cent had thromboembolic complications, including one case of fatal pulmonary embolus and one case of recurrent emboli that required vena caval ligation, and 15 per cent had wound-healing complications. Of the 197 patients who received dextran and warfarin, 5 per cent had thromboembolism and 24 per cent had wound healing complications. Although both prophylactic regimens seemed effective, dextran and aspirin appeared less effective in reducing thromboembolic complications than dextran and warfarin, but there were fewer wound complications in that group. One-fourth of the patients on dextran-warfarin were not adequately anticoagulated despite close supervision. In forty-five patients with a history of thromboembolism who were excluded from the study and analyzed separately, warfarin alone and the two described regimens were equally ineffective in preventing thromboembolism, and the incidence of thromboembolic complications was high. Dextran-aspirin and dextran-warfarin appear to be satisfactory and relatively simple methods of thromboembolic prophylaxis.

Arthroplasty↗

Dextran-magnetite complex: conformation of dextran chains and stability of solution.

Three kinds of dextran-magnetite (DM) complexes were prepared using alkali-treated dextrans with molecular weights of 1900, 4200 and 9600, respectively. The number of dextrans binding to a magnetite core was determined. The number was proportional to the area of core surface and the area occupied by a dextran was 2.5 nm2 for molecular weight of 1900, 2.8 for 4200 and 3.8 for 9600. The binding of dextrans to core may be conditioned by the conformation of dextran chains in water (possibly by the steric hindrance between dextrans covering core). Stability of the DM solution was examined at 80 degrees C. Aggregation and/or precipitation of DM particles were observed within two weeks. The stability of DM solution was found to increase with increasing molecular weight of dextran. The dissociation of dextran from the core may cause the aggregation and subsequent precipitation of DM particles (the dissociation constant at 20 degrees C, 3.7 x 10(-6) for a molecular weight of 1900 and 5.4 x 10(-7) for 9600).

Journal Article↗

FITC-Dextrans as tracers for macromolecular movements in the nervous system. A freeze-drying method for dextrans of various molecular sizes injected into normal animals.

A freeze-drying method has been developed by which fluorescein thiocarbamoyl dextrans (FITC-dextrans) can be localized in thin sections from nervous tissue and muscles. Labelled dextrans with molecular weights of 3,000, 20,000, 70,000 and 150,000 were injected intravenously (i.v.) into golden hamsters and samples from brain, trigeminal ganglia and sciatic nerves were examined 30 min or 4 h later. For comparison experiments were also carried out in mice and some other tracers were tested as well. The dextrans did not pass out of blood vessels in cerebral cortex and white matter. The blood vessels in the trigeminus ganglion were permeable to all of the tested compounds, i.e. even the FITC-dextran with mol.wt. 150,000. Little, if any, i.v. injected dextran could be detected in the endoneurium of sciatic nerve fascicles. Even very high concentrations of dextrans (mol.wt. 3,000 and 150,000) injected around the sciatic nerves did not penetrate the perineurium of the sciatic nerve. As compared with other tracers dextrans have the advantage that they can be obtained in a wide range of molecular sizes. With the proposed technique presented at the end of this article they can be used for studies on vascular permeability in deep tissue like brain, ganglia and peripheral nerve. The use of these tracers will probably be particularly advantageous in investigations concerning the etiology of edematous conditions.

Animals↗

Effect of dextran and modified dextrans on the uptake and degradation of beta-galactosidase in isolated liver cells.

Conjugation of beta-galactosidase with either dextran, methylated dextran or acetylated dextran had only a small effect on uptake of the enzyme in isolated rat parenchymal and nonparenchymal liver cells. Conjugation of beta-galactosidase with dextran or the modified dextrans, reduced the intracellular degradation of the enzyme by up to about 45%. Methylated dextran had less effect than unmodified dextran or acetylated dextran on reducing the intracellular degradation of beta-galactosidase.

Animals↗

Silylation reaction of dextran: effect of experimental conditions on silylation yield, regioselectivity, and chemical stability of silylated dextrans.

The controlled synthesis of biodegradable copolymers of dextran grafted with aliphatic polyesters first requires the preparation of polysaccharide derivatives soluble in organic solvents. Silylation of dextran can thus lead to such organosoluble derivatives and allows the polymerization of cyclic esters initiated from the nonsilylated OH functions. Silylation of dextran was studied in DMSO by different reactants such as 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in the presence of various catalysts and N,O-bis(trimethylsilyl)acetamide (BSA). According to the silylating agent and the used experimental conditions, it was possible to obtain highly or totally silylated dextrans. In parallel, an investigation of the chemical stability of the dextran chain during silylation was performed. Thus, it was found that, when used at 50 degrees C, HMDS with or without catalysts gives a relatively high silylation yield and does not alter the dextran chain length, whereas at 80 degrees C, dextran degradation was observed. BSA is a very good silylating agent, which allows reaching 100% silylation even at 50 degrees C but provokes the degradation of the polysaccharide chains. The work was completed by a study of the reactivity order of the glucosidic OH functions toward silylation reaction. This order was found to be (OH(2) > OH(4) > OH(3)) as already reported for other reactions. 2D-NMR of highly silylated dextrans demonstrated that they are constituted of both quantitatively silylated glucose units and two types of disilylated ones.

Dextrans↗

Immunoglobulin class and subclass distribution of dextran-reactive antibodies in human reactors and non reactors to clinical dextran.

The red cell-linked antigen-antiglobulin reaction (RCLAAR) with stearoyldextran-coated erythrocytes was used to characterize the immunoglobulin (Ig) classes and IgG subclasses of dextran reactive antibodies (DRA) in 27 dextran reactors (DR) and 96 on reactors (DNR). High titres of dextran reactive IgG were regularly found in sera of patients with severe dextran-induced anaphylactoid/anaphylactic reactions (DIAR) prior to the infusion. In four lethal cases IgG antibodies were found to be in the highest titre range of 16,384 to 32,768. In addition, high IgA and IgM titres were also in severe DIAR. DNR had much lower titres of dextran reactive antibodies of IgG, IgM and IgA classes and IgD antibody was absent in both groups. Dextran reactive IgE antibodies were not demonstrable in DR. Dextran reactive IgG2, IgG3, IgG4 and IgG1 (indirect measurement) were demonstrated in both DR and FNR. Dextran infusion caused variable neutralization in all Ig classes and IgG subclasses, but the contribution of IgG2 was considered most important because of its high titres and most pronounced neutralization in severe DIAR. It is concluded that DRA mainly of the IgG class, play a critical pathogenic role in the induction of severe DIAR, which accordingly is classified as immune complex (Type III) anaphylaxis. The method of RCLAAR allows to delineate a risk group of about 2% of potential reactors.

Adolescent↗

Plasma volume after dextran infusion in rats sensitive and non-sensitive to dextran.

Plasma volume determinations were done with RIHSA under normal conditions and after intravenous infusion of dextran solutions. The plasma volume of normal rats in millilitre was found to be 0.026 X body weight + 0.92. Infusion of dextran into dextran-sensitive Sprague-Dawley rats was followed by a marked plasma volume reduction and haemoconcentration as consequence of an anaphylactoid reaction. This reaction could be partially inhibited by pretreatment with cyproheptadine chloride. Plasma volume determination with the method used in this study can be used to evaluate the dextran-anaphylactoid reaction. In dextran non-sensitive Wistar rats, infusion of dextran had a strong plasma volume-expanding effect comparable to the plasma volume-expanding effect of dextran in humans. No signs of abnormal leakage of fluid out into the extravascular space were evident, which indicated that the Wistar rats really were non-sensitive to dextran.

Animals↗

Effect of substitution on reactivity of B 512 dextran fractions with anti-B 512 dextran in heterologous passive cutaneous anaphylaxis.

The influence of type and degree of substitution of B 512 dextran fractions on reactivity with rabbit antibodies against unmodified B 512 dextran was studied on heterologous passive cutaneous anaphylaxis in guinea pigs. Low degrees of substitution, i.e. 1 substituent group per 7-30 glucose residues, affected reactivity with anti-dextran only slightly or not at all. This was shown for the following substituents: sulphate, carboxymethyl, phosphate, diethylaminoethyl, hydroxypropyl, butyryl, caprylyl, stearoyl, and fluoresceinoyl groups. With high degress of substitution, i.e. 1-3 substituents per 2 glucose residues, reactivity with anti-B-512-dextran is completely abolished for some substituents, and a new immunological identity conferred on the substituted dextran. Stongly charged groups like sulphate, carboxymethyl and diethylaminoethyl abolish reactivity with anti-B-512-dextran at relatively lower degrees of substitution than more neutral groups like methyl and acetyl. The anti-B-512-dextran represents a specific reagent for alpha-1,6-linked polyglucose, as evidenced by complete cross-reactivity with synthetic linear dextran; its specificity is emphasized by non-reactivity with alpha-1,6-linked synthetic manna, the monomeric residues of the two polymers differing only in position of the C-2 hydroxyl groups.

Animals↗

Dextran-induced anaphylactoid reactions in man: role of dextran reactive antibodies.

Dextran reactive antibodies (DRA) were studied in 123 patients having experienced dextran-induced anaphylactoid reactions (DIAR) during 1970-1975. No evidence for reaginic DRA was obtained by radioallergosorbent technique and passive cutaneous anaphylaxis in Cynomolgus monkeys; total IgE levels were within normal range. It is concluded that DIAR are not mediated by dextran-specific reagins. Further, no reaginic antibodies against potential contaminants from the dextran manufacturing process were demonstrable. In two population samples of normal human sera from Sweden and Germany hemagglutinating DRA (IgG, IgA, and IgM classes) were found in 63 and 74%, high titres (16-256) comprising 14 and 25%. In dextran reactors a direct positive correlation between titres of hemagglutinating DRA and increasing severity of DIAR was observed. The accumulation of high DRA titres in severe reactions may be taken as circumstantial evidence for the causal role of hemagglutinating DRA in these cases. However, if high titres of DRA alone were responsible for triggering DIAR, the expected frequency would be more than thousand times higher than the reported global incidence of DIAR. To explain this discrepancy, involvement of certain Ig classes or subgroups, possibly in combination with other predisposing factors is suggested. In mild reactions DRA appear to play a negligible role. Positive dextran wheal and flare reactions, often correlated with high titres of hemagglutinating DRA, were seen in 32% of dextran reactors, indicating that skin tests are of limited predictive value. No significant difference between sexes, age groups, or pre- and intraoperatively started dextran infusions was observed; association with certain diseases was not apparent.

Adolescent↗

Dextran antibodies, complement conversion and circulating immune complexes after intravenous iron dextran therapy in dialysed patients.

Serum immune complexes, plasma dextran antibodies and percentage conversion of complement have been measured in 20 dialysed patients before and after an intravenous infusion of iron dextran providing 600 mg elemental iron. Complement conversion was unmeasurable and there were no changes in circulating immune complexes. The presence of dextran antibodies in nine patients before the infusion was not related to prior exposure to iron dextran. They became undetectable in these patients within hours after the infusion, reappearing 1 month later in three. Two of three patients reporting mild aches and shivers on the day following the infusion had no detectable dextran antibodies. An adverse reaction involving inflamed joints occurred 1-2 days after a second infusion given to one of the patients studied above. The parameters under study were again measured and did not appear to relate to the reaction. The presence of dextran antibodies does not preclude the giving of iron dextran to patients on dialysis, and the immune complex and complement systems remain undisturbed by iron dextran infusions.

Adolescent↗