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PubMed1995

Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal surgery. Multicentre trials 20 mg and 40 mg enoxaparin versus dextran.

OBJECTIVE: To compare enoxaparin and dextran 70 for the prophylaxis of venographically diagnosed deep vein thrombosis (DVT) after gastrointestinal operations. DESIGN: Part 1: randomised double blind trial; Part 2: single blind study with historical controls. SETTING: Eight Norwegian hospitals. SUBJECTS: 381 Patients undergoing elective gastrointestinal operations. INTERVENTIONS: Part 1 (n = 329): enoxaparin 20 mg subcutaneously starting two hours before operation and continuing until the patient was fully mobilised or had had 10 injections and a placebo infusion of 0.9% sodium chloride, or dextran 70,500 ml at the start of the operation, on the evening of operation, and on the first, third, and fifth postoperative days and placebo subcutaneous injections. Part 2 (n = 52): enoxaparin 40 mg in the same regimen as part 1 (compared with 39 historical controls). Venograms 4-6 days post-operatively. MAIN OUTCOME MEASURE: Venographically confirmed DVT. RESULTS: Part 1: Because of the high overall incidence of DVT an interim analysis was done which showed 33/101 DVT (33%) among high risk patients in the enoxaparin 20 mg group and 33/107 (31%) in the dextran 70 group. The corresponding figures for patients at medium risk were 2/27 (7%) for enoxaparin 20 mg and 5/27 (19%) for dextran 70 (95% confidence interval (CI) for the difference--11.9 to 9.8). Part 2: the dose of enoxaparin was therefore increased to 40 mg and prophylaxis restricted to patients with cancer. There were 6/49 DVT (12%), which was compared with a random sample from the dextran 70 group from part 1 (historical controls) in which the incidence was 15/39 (38%, 95% CI of the difference 4.0 to 8.4). There were no pulmonary emboli, only 4 thrombi were above the knee and there were 4, 1 and 3 clinical DVT in the 20 mg and 40 mg enoxaparin, and dextran 70 groups, respectively. CONCLUSIONS: Enoxaparin 20 mg and dextran 70 are effective prophylaxis for patients at medium risk, but enoxaparin 40 mg is required for those at high risk.

Adult↗

PubMed1996

The effect of dextran infusion on antithrombin III concentrations and on platelet function during minor surgery.

The effects of dextran on the antithrombin (AT) III activity and blood coagulation, evaluated with thromboelastography, were investigated in 26 patients (anaesthesia risk class I or II) scheduled for minor surgery under general anaesthesia. In the Dextran group the patients were infused first with dextran 7 ml/kg, then with Ringer's acetate. In the Ringer group, the patients received only Ringer's acetate. In the recovery room fluid therapy was continued with 5% dextrose in water until the first postoperative day. Blood loss and fluid replacement were comparable in the groups. Haematocrit (Hcr) decreased significantly in the Dextran group, and the platelet count decreased in both groups during surgery. The median baseline AT III values were similar in the study groups. In the recovery room, the median AT III value was lower in the Dextran than in the Ringer group, 78% and 92%, respectively (P < 0.05). By the following day, the AT III values had returned near the initial level. After surgery, the maximal amplitude of thromboelastogram was 48 mm in the Dextran group, and 58 mm in the Ringer group (P < 0.05). In conclusion, fluid replacement with dextran resulted in modest and short-lived alterations in blood coagulation.

Adult↗

PubMed1996

Perioperative volume effect of HES 120/0.7 compared with dextran 70 and Ringer acetate.

Hydroxyethyl starch 120 (HES 120/0.7, Plasmafusin) is the smallest medium molecular weight HES preparation used as a plasma substitute for all clinical purposes. We compared the volume and colloid osmotic effect of 6% HES 120 with 6% dextran 70 and Ringer's solution during and after surgery with minimal blood loss. Patients (n = 48) having general anaesthesia were randomly divided into six groups. A thirty-minute bolus infusion was started at the induction of anaesthesia, and thereafter the infusions were continued at two different rates for five hours. The volume of the bolus was 10% and 30% of the calculated volume (CPV) in colloid and Ringer groups, respectively. The constant infusion rates were 2% and 6% of the CPV for the colloids, and 10% and 20% for the two Ringer groups. Blood samples for the measurement of serum proteins and colloid osmotic pressure (COP) were obtained before induction, after the bolus, and thereafter hourly throughout the study. Albumin, prealbumin and total serum protein concentrations were used to calculate relative plasma volumes. After the bolus infusion, plasma volumes increased significantly in all six groups and the increments were sustained throughout the study. At the lower infusion rates of the volume changes of HES and Ringer groups were almost identical and comparable to dextran group up to the third floor. At the higher infusion rates, dextran 70 produced greater plasma volume expansions than HES 120, and the volume effect of Ringer's solution was clearly exceeded by both colloids. The hourly estimated half-lives of dextran were constantly longer compared with HES. With both infusions rates the COPs of dextran and HES groups were higher compared with Ringer groups. There were no differences in COP between the dextran and HES groups. It is concluded, that in this clinical setting the volume effect of 6% dextran 70 exceeds that of the HES 120/0.7, and that both colloids are superior to Ringer's solution.

Adult↗

PubMed1984

The polycation diethylaminoethyl dextran potentiates thermal cell killing.

The polycation diethylaminoethyl dextran (DEAE-dextran) causes marked potentiation of the effects of hyperthermia (45 degrees C) on HA-1 Chinese hamster ovary cells. The effects of the polycation appear to be mediated at the cell surface and are largely reversed by removal of DEAE-dextran with the polyanion dextran sulphate. Maximal potentiation is observed when polycation and heat are given simultaneously. The polycation also inhibits the capping of concanavalin-A acceptors when used singly and is additive with heat in inhibiting capping; reduction in con-A capping may indicate decreased mobility of cell surface glycoproteins. The mechanism of heat potentiation by DEAE-dextran is not fully understood. Effects on surface charge and cytoskeleton-membrane interactions may be involved. However, the polycation appears to have promise, both in probing mechanisms of heat killing and as an adjuvant to heat treatment; potentiation occurs at extremely low DEAE-dextran levels, with considerable potentiation at a concentration of 0.4 microM.

Animals↗

PubMed1999

Comparative Pore Structure Analysis of Dextran-Coated Polystyrene Particles.

Porous poly(styrene-divinylbenzene) (PS-DVB) particles were modified by adsorption of hydrophobically-modified dextrans, to provide chromatographic matrices for biomolecule chromatography. The dextran distribution and the pore characteristics of various coated PS-DVB beads were examined using nitrogen adsorption-desorption, mercury intrusion, and size exclusion chromatography. It was found that the adsorption of dextran does not result in homogeneous layers but rather in inhomogeneous ones. At high dextran loading and high content of hydrophobic groups in the adsorbed polymer, most of the pores of the macroporous rigid material are filled with a soft and porous dextran network being stabilized by hydrophobic interactions. According to chromatographic experiments, most of the surface was nevertheless expected to be covered at least by a thin and dense protecting layer since proteins-even those that are small enough to penetrate the dextran network-cannot interact nonspecifically with the internal pore surface. At low content of hydrophobic groups, dextran deposits preferentially as a thicker and more diffuse layer. However, the thickness of the coating is expected to be irregular and probably contributes to an increase in the roughness of the polystyrene surface. Copyright 1999 Academic Press.

Journal Article↗

PubMedDate not supplied

Preparation of sulfhydrylborane-dextran conjugates for boron neutron capture therapy.

This study presents a carrier system for boron, potentially useful in boron neutron capture therapy (BNCT). Na2B12H11SH (BSH) was covalently coupled to dextran derivatives. This was accomplished in two ways. The first method comprises activation of dextran with 1-cyano-4-(dimethylamino)pyridine (CDAP) with subsequent coupling of 2-aminoethyl pyridyl disulfide (method A). The thiolated dextran could then couple BSH in a disulfide exchange reaction. In the second procedure, dextran was derivatized to a multially derivative (method B) which reacted with BSH in a free-radical-initiated addition reaction. The assessment of boron content of the conjugates was done by elemental analysis of sulfur and atomic spectroscopy of boron (ICP-AES). With method A, only limited numbers of boron cages could be coupled (10-20 cages per dextran chain). With method B, 100-125 boron cages per dextran chain was obtained, corresponding to 1200-1500 boron atoms per dextran chain. This result makes this derivative a promising template for use in the development of BNCT agents.

Boranes↗

PubMed1981

Growth, water content, and solute accumulation of two tobacco cell lines cultured on sodium chloride, dextran, and polyethylene glycol.

Simulated drought tolerance was compared for an NaCl-adapted and a nonadapted cell line of tobacco (Nicotiana tabacum var. Samsum) to determine the relationship of salt and drought tolerances. The osmotic adjustment and growth of these two lines was followed when cultured on solid media which contained isosmotic concentrations of NaCl, KCl, polyethylene glycol (PEG) or dextran. One line was adapted to growth on 130 millimolar NaCl, but the other was not.The growth of NaCl-adapted and nonadapted cell lines was equally inhibited (61 per cent of control) by 130 millimolar NaCl. Growth inhibition was greater on PEG or dextran than on NaCl. Growth ceased on the second passage of dextran for the nonadapted cells, while the NaCl-adapted cells grew slowly for four passages on dextran. Water contents for both cell lines were 95 per cent on NaCl or KCl and 70 to 88 per cent on PEG 1540 or 4000 or dextran after the second passage on these media.On dextran or PEG 4000, 46 to 89 per cent of the cellular osmotic potential was produced by the solutes initially present in the medium. Similarly, on NaCl, almost 100 per cent was attributable to solutes in the medium. It was concluded that cells grown on the nonpenetrating solutes had a more negative osmotic potential than those grown in the absence of added solute due to partial dehydration, greater uptake of external ions, and possibly the production of unidentified osmotica. Adjustment to growth on penetrating solutes may have enabled the adapted line to overcome the osmotic stress produced by nonpenetrating dextran.

Journal Article↗

PubMed1995

Isolation of a dextranase constitutive mutant of Lipomyces starkeyi and its use for the production of clinical size dextran.

A derepressed and partially constitutive mutant for dextranase of Lipomyces starkeyi was selected after ethyl methane sulphonate mutagenesis by zone clearance on blue dextran agar plates. The mutant produced dextranase when grown on glucose, fructose and sucrose as well as on dextran, and more enzyme was produced by the mutant than by the parental strain when grown on 1% dextran. The pH and temperature optima for the mutant dextranase were 5.5 and 55 degrees C, respectively. Dextranase produced on sucrose produced more isomaltose and less glucose after dextran hydrolysis than the equivalent enzyme produced on dextran. The clinical size dextran (average mol. wt of 75,000 +/- 25,000) yield of mixed culture fermentation with the mutant and Leuconostoc mesenteroides was 94% of the total dextran produced.

Dextranase↗

PubMed1996

Hemoglobin-dialdehyde dextran conjugates: improvement of their oxygen-binding properties with anionic groups.

We studied the conjugates formed between hemoglobin and sulfated or unsulfated oxidized dextran. It appears that the presence of sulfated groups favors imino bond formation between the protein and the polymer, as the average molecular size of the conjugates is larger in this case. Under neutral conditions, the oxygen-binding properties of the conjugates depend on the presence or absence of oxygen during the coupling reaction. With unsulfated dextran, oxyhemoglobin leads to conjugates with increased oxygen affinity (P50/P50 native hemoglobin approximately 0.5) compared to that of free hemoglobin (P50 = 4 mm Hg), whereas deoxyhemoglobin leads to conjugates with decreased oxygen affinity (P50/P50 native hemoglobin approximately 3). The use of sulfated dextran reinforces this lowering in oxygen affinity, which indicates that sulfated dextran acts as a permanent macromolecular effector of hemoglobin (P50/P50 native hemoglobin approximately 4). Moreover, it can be assumed that some of the linkages involve the 2,3-diphosphoglycerate binding site, as the strong effector inositol hexaphosphate has only a slight effect on the oxygen-binding properties of the conjugate prepared in the deoxy state (P50/P50 native hemoglobin close to 4.4 and 6, respectively, for unsulfated and sulfated conjugates). Although dextran substituted with benzenehexacarboxylic acid (BHC) leads to a low-oxygen-affinity conjugate when linked to oxyhemoglobin through amide bonds (P50/P50 native hemoglobin approximately 5), oxidized dextran modified with BHC leads, with oxyhemoglobin, to a conjugate whose oxygen affinity is close to that of free hemoglobin (P50/P50 native hemoglobin approximately 1.2).

Aldehydes↗

PubMed1989

Dextran sulfate prevents LTB4-induced permeability increase, but not neutrophil emigration, in the hamster cheek pouch.

Leukotriene B4 (LTB4) is known to induce neutrophil-dependent macromolecular leakage in the hamster cheek pouch. LTB4 was superfused over cheek pouches dissected for intravital microscopy; and leukocyte rolling and firm adhesion in venules, neutrophil emigration, and macromolecular permeability as leakage of fluorescent dextran was quantified. Dextran sulfate (MW 500,000; 17.5 mg/kg iv bolus), but not uncharged dextran, reduced the LTB4-induced venular leakage of macromolecules by 85%. Histamine-induced leakage, which is neutrophil independent, was left unaffected. Dextran sulfate had no effect on leukocyte adhesion in postcapillary venules induced by LTB4, nor on their subsequent emigration to the surrounding tissue. Dextran sulfate significantly inhibited leukocyte rolling during nonstimulated conditions along the walls of collecting venules, but not postcapillary venules. Consequently, neutrophil-induced macromolecular leakage and neutrophil emigration appear to be independent, separable events. As an explanation of the present results it is proposed that the dextran sulfate complexes neutrophil granule cationic proteins, thus preventing neutrophil-mediated permeability increase.

Animals↗

PubMed1986

Binding of polycation DEAE-dextran to Chinese hamster ovary cells induces reversible Ca2+ influx and inhibits capping of concanavalin A acceptor proteins.

Binding of the polycation DEAE-dextran to the cell surface of HA-1 CHO cells caused a marked increase in 45Ca2+ exchange influx. The effect was fairly selective for Ca2+, undirectional (efflux was not increased) and was rapidly reversed by treatment with polyanion dextran sulfate. 45Ca2+ influx could not be stimulated by treatment with multivalent lectins or fibronectin. In addition to stimulating 45Ca2+ flux, DEAE-dextran inhibited the capping of concanavalin-A acceptor proteins. Inhibition of capping occurred over the same DEAE-dextran concentration range (20-200 micrograms/ml) which stimulated 45Ca2+ uptake, possibly implicating increased cellular [Ca2+] in the inhibition of concanavalin A acceptor protein capping in this cell type. The profound effect of DEAE-dextran on cellular Ca2+ uptake and the rapid reversal of the effect by dextran sulfate might make the polycation a useful agent for the induction of transient increases in cellular [Ca2+].

3-O-Methylglucose↗

PubMed2000

Correlation of transarterial transport of various dextrans with their physicochemical properties.

Local vascular drug delivery provides elevated concentrations of drug in the target tissue while minimizing systemic side effects. To better characterize local pharmacokinetics we examined the arterial transport of locally applied dextran and dextran derivatives in vivo. Using a two-compartment pharmacokinetic model to correct the measured transmural flux of these compounds for systemic redistribution and elimination as delivered from a photopolymerizable hydrogel surrounding rat carotid arteries, we found that the diffusivities and the transendothelial permeabilities were strongly dependent on molecular weight and charge. For neutral dextrans, the effective diffusive resistance in the media increased with molecular weight approximately 4.1-fold between the molecular weights of 10 and 282 kDa. Similarly, endothelial resistance increased 28-fold over the same molecular weight range. The effective medial diffusive resistance was unaffected by cationic charge as such molecules moved identically to neutral compounds, but increased approximately 40% when dextrans were negatively charged. Transendothelial resistance was 20-fold lower for the cationic dextrans, and 11-fold higher for the anionic dextrans, when both were compared to neutral counterparts. These results suggest that, while low molecular weight drugs will rapidly traverse the arterial wall with the endothelium posing a minimal barrier, the reverse is true for high molecular weight agents. With these data, the deposition and distribution of locally released vasotherapeutic compounds might be predicted based upon chemical properties, such as molecular weight and charge.

Animals↗

PubMed1988

Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.

The sulfated polysaccharides dextran sulfate and heparin have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Dextran sulfate (Mr 5000) and heparin (Mr 15,000) completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 25 micrograms/ml. Their 50% inhibitory concentrations were 9.1 micrograms/ml (dextran sulfate) and 7.0 micrograms/ml (heparin), respectively. No toxicity for the host cells was observed with these compounds at a concentration of 625 micrograms/ml. The anti-HIV-1 activity of heparins of various molecular weights correlated well with their anticoagulant activity. On the other hand, with dextran sulfates of low molecular weight (5000, 8000) a significant inhibitory effect on HIV-1 was achieved at a concentration that was not markedly inhibitory to the blood coagulation process. Dextran sulfate and heparin were not inhibitory to HIV-1 reverse transcriptase unless they were used at concentrations in excess of those that inhibited HIV-1 replication. They were highly effective against HIV-1 replication even when present only during the 2-hr virus adsorption period. Studies using radiolabeled HIV-1 virions indicated that dextran sulfate and heparin inhibit virus adsorption to the host cells.

Adsorption↗

PubMed1989

Oral dextran sulfate (UA001) in the treatment of the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.

STUDY OBJECTIVE: To evaluate the tolerance and safety of oral dextran sulfate (UA001), a potent in-vitro inhibitor of human immunodeficiency virus (HIV) in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. DESIGN: Unblinded, dose-escalation 8-week trial. SETTING: An AIDS outpatient clinic of a university-affiliated municipal hospital. PATIENTS: Thirty-four patients with stage III or IV HIV infection were enrolled. Five patients in six different dosage cohorts completed the study. The population was predominantly homosexual men with persistent generalized lymphadenopathy (stage III). INTERVENTIONS: Oral dextran sulfate was given three times daily in total daily doses of 900 to 5400 mg for 8 weeks. Patients were monitored for tolerance and toxicity. Immunologic and virologic values were also followed. MEASUREMENTS AND MAIN RESULTS: Oral dextran sulfate was given without significant side effects. The commonest minor subjective complications were mental hyperexcitability and gastrointestinal complaints. The most frequent laboratory abnormalities were leukopenia and hepatic transaminase elevations. Eleven patients required dose reductions, and therapy was stopped in 4 because of toxicities. The CD4 lymphocyte numbers did not change appreciably. No decline in beta-2 microglobulin levels occurred. The HIV antigen levels were unchanged from baseline. No assay for dextran sulfate plasma levels has yet proven successful. CONCLUSIONS: Oral dextran sulfate appears to be well tolerated. No evidence of systemic absorption of the parent compound is available. However, in view of the promising in vitro effects and acceptable toxicity, oral dextran sulfate as a potential antiretroviral agent continues to be studied.

AIDS-Related Complex↗

PubMed1990

Effect of oral dextran sulfate on the mouse intestinal tract.

Oral dextran sulfate is associated with adverse intestinal effects, including severe diarrhea, in some AIDS patients. We therefore investigated the intestinal flora and the intestinal histology of mice given drinking water supplemented with 8 mg/ml of dextran sulfate. There were no noticeable alterations in the major groups of intestinal bacteria in mice given oral dextran sulfate for 7 days. Likewise, there was no abnormal pathology in the ilea or colons of mice treated for 7 days with oral dextran sulfate. However, after 21 and 38 days, there was a noticeable overgrowth of facultative gram-negative bacilli in the colonic and cecal flora of dextran sulfate-treated mice. This overgrowth appeared to be due to bacterial species in the family Enterobacteriaceae, primarily Escherichia coli. Bacterial overgrowth was accompanied by mild histological alterations in the intestinal mucosa, i.e., blunting of ileal villi and colonic crypts, with mild epithelial cell dysplasia. Thus, oral dextran sulfate was associated with quantitative changes in the mouse intestinal flora, as well as histological changes in the intestinal mucosa.

Animals↗

PubMed1989

Shear-dependent inhibition of granulocyte adhesion to cultured endothelium by dextran sulfate.

Adhesion of polymorphonuclear granulocytes (PMNs) in microvessels occurs in the presence of shear forces exerted by the blood flow. To model this in vitro, phorbol myristate acetate (PMA)-activated PMN were exposed to shear stress on cultured human umbilical vein endothelial cells (HUVECs) and on plastic dishes coated with bovine serum albumin (BSA). PMN adhesion to HUVECs averaged 36% of the total PMNs added and was reduced to 21% by shear stress of approximately 1.5 dynes.cm-2. On BSA, adhesion was reduced from 59% to 35%. Dextran sulfate (molecular weight 500,000) inhibited PMN adhesion in a dose-dependent manner when shear stress was applied. At a concentration of 1 mg.ml-1, inhibition was 72% on HUVECs and 76% on BSA. Half-maximal inhibition was reached at approximately 1 microgram.mL-1 dextran sulfate, corresponding to 2 nmol/L. Without shear stress, dextran sulfate had no effect on HUVECs and only a moderate effect on BSA. The murine monoclonal antibody (MoAb) 60.3, recognizing an epitope on the leukocyte adhesion glycoprotein CD18, inhibited PMN adhesion equally well with and without shear. A low dose of MoAb 60.3 enhanced the effect of dextran sulfate without shear stress. Flow cytometry (FACS) did not show inhibition of MoAb 60.3 binding to PMNs by dextran sulfate. These results indicate that a dextran sulfate-inhibitable adhesion process is important for PMN adhesion in the presence of shear stress.

Antibodies, Monoclonal↗

PubMed1981

Induction of intestinal tumors in rats by dextran sulfate sodium.

The carcinogenicity of dextran sulfate sodium was studied in inbred ACI rats. In group 1, 10 male rats were fed a 10% dextran sulfate sodium diet; in group 2, 14 male and 12 female rats were fed a 5% dextran sulfate sodium diet; and in the control group, 9 male and 9 female rats were given the basal diet without dextran sulfate sodium. After the start of the feeding regimen, all rats given the 10% dextran sulfate sodium diet died of severe diarrhea and anemia within 14 days and 15 of 23 surviving rats fed a 5% dextran sulfate sodium diet developed intestinal tumors between 134 and 215 days. These tumors were induced in the colon and cecum and consisted of adenomas, adenocarcinomas, and papillomas.

Adenocarcinoma↗

PubMed1998

Anticoagulant activity of dextran derivatives.

Carboxymethyl dextran benzylamide sulfonate/sulfates (CMDBS) are synthetic polysaccharides with anticoagulant activity. We synthesized eight different highly substituted CMDBS and one CMDSu. We studied both their anticoagulant activity and the catalysis of thrombin (T) inhibition by heparin cofactor II (HCII) and antithrombin (AT) in the presence of these dextran derivatives relative to heparin and dextran sulfate (DXSu). The anticoagulant activity of CMDBS was due both to direct thrombin inhibition and to catalysis of thrombin inhibition by HCII. The anticoagulant and catalytic activities of CMDBS were related mainly to their molecular weight and sulfate content. The interaction of the dextran derivatives with thrombin does not involve the active site of the enzyme. A kinetic study showed that all the CMDBS exhibited higher affinity for thrombin than heparin did but lower affinity than DXSu did, suggesting that the benzylamide and sulfate groups potentiate the interaction between the dextran derivatives and thrombin. This study shows that the mechanism by which the dextran derivatives inhibit thrombin is original and is related to preferential interaction with thrombin; this both inhibits the clotting activity of the enzyme and increases the reaction rate of thrombin inhibition by HCII.

Anticoagulants↗