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[Dextran-induced anaphylactoid reactions in two patients with gastrointestinal cancer].

We report dextran-induced anaphylactoid reactions (DIAR) subsequent to rapid infusion of Rheomacrodex (dextran 40) in two patients, a 67 year old man with gastric cancer undergoing distal gastrectomy and a 47 year old man with transverse colon cancer undergoing colectomy. Both showed sudden tachycardia, hypotension and skin flush, which were treated with epinephrine or etilephrine administration. Most cases of severe DIAR are immune complex anaphylaxis mediated by dextran-reactive antibodies (DRA) of the IgG class, which are considered to arise mainly in response to immunization with dextran-cross-reactive bacterial polysaccharides in the gastrointestinal tract. High titers of DRA have previously been reported in gastric ulcer patients with pyloric stenosis, suggesting bacterial polysaccharides permeation through the luminal wall which may easily occur in the presence of local inflammation or ulcer. Although serum DRA titers in our patients have not been examined, inflammation or ulcer around the tumor might have played a role in producing high titers of DRA. In patients suspected of gastrointestinal ulcer or inflammation, including cancer, dextran administration is not preferable or should be avoided, unless hapten-dextran preparation is used for the prophylaxis of severe DIAR.

Aged↗

IFN-gamma-induced MHC class II gene expression is suppressed in endothelial cells by dextran sulfate.

IFN-gamma-activated endothelial cells actively participate in initiating immune responses by interacting with immunocompetent cells via class II MHC proteins. In this study, dextran sulfate, a synthetic heparin analogue, was shown to selectively inhibit IFN-gamma-induced surface expression of HLA-DR molecules by human umbilical cord vascular endothelial cells, but not other cytokine-induced molecules such as ELAM-1 or ICAM-1. Inhibition occurred regardless of whether dextran sulfate was added 24 h before, at the same time as, or 24 h after IFN-gamma stimulation of cells. In addition, both high (500 kDa) and low (5 kDa) molecular mass dextran sulfate molecules were able to block class II expression, whereas treating cells with naturally occurring polysulfated glycosaminoglycans such as heparin, heparan, and chondroitin sulfate did not produce any suppressive effects. Radiolabeling of cells with [35S]methionine followed by radioimmunoprecipitation using anti-HLA-DR alpha mAb demonstrated that biosynthesis of class II proteins was specifically blocked. RT-PCR and Southern blotting were utilized to examine transcription of the HLA-DR alpha gene and demonstrated an absence of HLA-DR alpha mRNA from dextran sulfate-treated and IFN-gamma-induced cells. Dextran sulfate also prevented transcription of the gene encoding CIITA, a transactivator protein required for IFN-gamma-inducible expression of class II genes. Thus, dextran sulfate apparently inhibited this step or an earlier one in the intracellular signaling pathway for IFN-gamma in human endothelial cells, subsequent to IFN-gamma binding to its cell surface receptor.

Base Sequence↗

Cost effectiveness of use of a solution of 6% dextran 70 in young calves with severe diarrhea.

OBJECTIVE: To determine whether intravenous administration of 6% dextran 70 solution to young calves with severe diarrhea is cost effective. DESIGN: Randomized, prospective, clinical trial. ANIMALS: 22 calves < 2 months old that were hospitalized for diarrhea and that did not have pneumonia. PROCEDURE: All calves received antibiotics, were fed by use of an orogastic tube, were supplied with radiant heat, and were given crystalloids, i.v., as deemed appropriate by an attending veterinarian. A group of 12 calves also received 500 ml of 6% dextran 70 solution, i.v., over a 1-hour period as part of the initial treatment. Data were collected to determine whether early treatment with 6% dextran 70 solution resulted in a similar end cost for treatment because of a decrease in the volume of fluids administered i.v., a decrease in antibiotic usage, a decrease in the amount of time hospitalized, or a decrease in mortality. RESULTS: Capillary refill times, heart rates, respiratory rates, and rectal temperatures; and scores for dehydration, mucous membrane color, lung sounds, mental status, and suckling response were not different between the 2 groups of calves at admission. Differences were not detected in client charges or in hospitalized time (6% dextran 70 group, $89.68 +/- 11.05 and 36 +/- 3 hours; control group $88.02 +/- 4.93 and 36 +/- 4 hours), but those charges did not include costs for the 6% dextran 70 solution. CLINICAL IMPLICATIONS: Use of 6% dextran 70 solution as part of the resuscitation of most young calves with diarrhea requiring hospitalization is not likely to be cost effective.

Animals↗

Giving both enoxaparin and dextran increases the need for transfusion in revision hip arthroplasty.

OBJECTIVE: To find out if the need for transfusion was increased by volume substitution with dextran 70 in patients receiving prophylaxis against thrombosis with low molecular weight heparin. DESIGN: Open randomised controlled trial. SETTING: University hospital, Sweden. SUBJECTS: 40 patients undergoing revision hip arthroplasty. INTERVENTIONS: Enoxaparin 40 mg was given daily. Intraoperative normovolaemia was maintained with albumin (n = 20) or dextran 70 (n = 20). Intraoperative autotransfusion was used. Packed cell volume was kept above 0.29, if necessary with homologous blood. MAIN OUTCOME MEASURES: External blood loss, red cell balance. RESULTS: Dextran patients received 0.64 (0.2) g/kg of dextran (mean (SD)) and required more (p < 0.05) homologous blood (3.8 (2.4) units) than those receiving albumin (2.3 (1.6) units). The initial and final packed cell volumes were similar (0.40 and 0.32 compared with 0.41 and 0.32, respectively). The calculated loss of red cells was larger in the dextran group (1401 (511) compared with 1077 (374); p < 0.05). CONCLUSION: The combination of enoxaparin and dextran appreciably increased the need for transfusion compared with enoxaparin alone.

Aged↗

In vitro and in vivo evaluation of mucoadhesive microspheres consisting of dextran derivatives and cellulose acetate butyrate.

The objective of this study was to evaluate mucoadhesive properties and gastrointestinal transit of microspheres made of oppositely charged dextran derivatives and cellulose acetate butyrate (CAB). The microspheres were prepared by emulsion solvent evaporation method. A reference microsphere was made of lactose instead of dextran derivatives. Microspheres with a diameter of 425-710 microm were examined for in vitro mucoadhesion by the everted sac method. The results indicated that the percentage of adherence to the rat small intestine was affected by the amount of dextran derivatives in the microspheres. After 1.5h, the adhering percent of the reference microspheres and the microspheres containing 50% of dextran derivatives were 34 and 74%, respectively. Then gastrointestinal transit after oral administration to rats was evaluated by counting the microspheres remaining in the stomach and small intestine. The microspheres containing 40% of dextran derivatives adhered to the stomach rather than the small intestine. Mathematical analysis revealed that the time required for 50% of microspheres to leave the stomach was 1.42h, three times longer than the reference. These findings suggest that the microsphere is a promising device as a multiple-unit mucoadhesive system.

Adhesiveness↗

On thrombo-embolism after total hip replacement in epidural analgesia: a controlled study of dextran 70 and low-dose heparin combined with dihydroergotamine.

A prospective study of thrombo-embolism after total hip replacement in epidural analgesia was carried out in 116 patients, randomly allocated to dextran 70 or low-dose heparin combined with dihydroergotamine (HDHE). Amounts of blood loss and transfused bank blood did not differ significantly between dextran 70 and HDHE prophylaxis. There was a lower incidence of femoral deep vein thromboses in patients given dextran prophylaxis as compared with those on HDHE (P less than 0.05). However, the total frequency of DVT and the frequency of pulmonary embolism did not differ between the two groups. There was no case of fatal pulmonary embolism. The side effects were major bleeding complications in 7 per cent of the HDHE group as compared to none in the dextran group. No anaphylactic reaction was noted from dextran 70 using hapten-dextran prophylaxis.

Aged↗

Small-Angle X-Ray Scattering Studies on Nucleation Formation of Dextran Precipitation in the Presence of Boron.

In the present study, the nucleation formation process of dextran precipitation in the presence of boron was investigated by small-angle X-ray scattering (SAXS) techniques. The formation mechanism of aggregates or nuclei is very important in the initial step of crystallization. SAXS measurement is an excellent technique for observing these processes. The results of SAXS measurement suggest that boron, as a trace impurity, induces the aggregating of dextran molecules intermolecularly as a process in the nucleation formation of dextran precipitate nuclei and causes precipitation of dextran through an elongation process. These reactions occur readily at low boron concentrations. In fact, boron, which was detected at low levels in dextran solutions, was concentrated in the precipitates. Therefore, an aqueous solution of boron-free dextran should be resistant to precipitation. Copyright 2000 Academic Press.

Journal Article↗

Evidence of a lack of enteric side-effects induced by DEAE-dextran in man.

The breakdown of the carbohydrates by the colonic bacterial flora can cause intestinal symptoms, such as meteorism, abdominal pain and diarrhoea. The ability of human bacterial flora to break down the DEAE-dextran, a new lipid lowering resin, similar to cholestyramine, was investigated in man. Colonic bacterial flora did not appear to break down DEAE-dextran, as assessed by hydrogen respiratory excretion measured in healthy volunteers. Furthermore, the blood levels of vitamin A, E and D (as 25-OH and 1,25-OH derivatives) were measured in patients treated with the DEAE-dextran in order to study the interference of DEAE-dextran on the absorption of liposoluble vitamins. With the exception of slightly depressed vitamin A levels in 3 patients out of 16, the blood values of the vitamins A, E and D were within the normal ranges, indicating that DEAE-dextran does not interfere with liposoluble vitamin absorption by the gut.

Adult↗

Effect of dextran sulfate on the survival time and mitochondrial function of Adriamycin (doxorubicin)-treated mice.

The effect of dextran sulfate on the survival time and mitochondrial function of adriamycin (ADM)-treated mice was studied. ADM-induced toxicity in mice was reduced by treatment with dextran sulfate (60, 100, 300, and 600 mg/kg, sc). The optimum dextran sulfate dose for protection against ADM-induced toxicity in mice was about 200 mg/kg/day (sc) and 100 mg/kg/day (po). Groups treated with dextran sulfate (300 mg/kg) had significantly improved mitochondrial function as measured by oxygen uptake of state 3 (p less than 0.01), dinitrophenol-altered respiration (p less than 0.01), and respiratory control index level (p less than 0.01). From these observations, it was concluded that ADM-induced toxicity due to reduced mitochondrial function can be ameliorated by the membrane stabilizing effect of dextran sulfate.

Administration, Oral↗

Interaction of fibrinogen with dextran sulfate.

Interactions of fibrinogen with dextran sulfate, dextran, and carboxymethyl cellulose were investigated by turbidity measurement, chemical analysis, and electrophoresis. Dextran sulfate and fibrinogen combined even in the physiological pH region where both of them have negative net charges, and formed a precipitate and soluble complex. Since no complex formation was observed in the case of dextran, it seems that the electrostatic force plays a part in complex formation. However, sodium carboxymethyl cellulose which carries -COO(-) groups did not combine with fibrinogen. Therefore, it is considered that there is a specificity for the interaction among ionized groups. Further, temperature and molecular size of dextran sulfate influenced the interaction to a large extent. It is concluded from these facts that other intermolecular binding forces should be taken into consideration in addition to the electrostatic force.

Dextran Sulfate↗

Passage of ions and dextran molecules across the rete mirabile of the eel. The effects of charge.

The countercurrent-perfused rete mirabile of the eel is a preparation in which capillary permeability values can be determined accurately in broadscale fashion. To provide insight into charge effects on transendothelial passage, the permeability values of small inorganic cations (labeled sodium and rubidium, and stable potassium) and anions (labeled chloride, iodide, sulfate, and ferrocyanide) were compared to those expected for neutral solutes with approximately matched diffusion coefficients, and that of a neutral dextran fraction was compared to that of a negatively charged dextran sulfate with a similar diffusion coefficient. In the small ion experiments, the labeled iodide values were unexpectedly high, apparently due to the contamination of the labeled iodide solution with I-3. The permeabilities of the rest of the ions clustered at a level about 0.5 of the values which would have been expected for neutral solutes with similar diffusion coefficients. The decrement was interpreted to reflect the presence of both positive and negative charges along the transendothelial pathway, which effectively decrease the dimensions of the limiting part of the pathway for the charged microions relative to that accessible to comparable nonelectrolytes. The larger negatively charged dextran sulfate was also reduced in its passage, in comparison with its matching neutral dextran; this was taken to indicate the presence of a larger scale average net negative charge along its pathway. The data indicate the presence of a staggering of positive and negative charges along the transendothelial pathway accessible to the microions, and a net negative charge in the more restricted part of the pathway available to the dextrans.

Air Sacs↗

Acute hypotension due to platelet serotonin-induced chemoreflexes after intravenous injection of dextran sulfate in the rabbit.

The hypotension and bradycardia observed after intravenous injection of dextran sulfate in rabbits was prevented by prior depletion of circulating platelets, but was not prevented by depletion of the third component of complement or Hageman factor. Dextran sulfate injection caused immediate thrombocytopenia with temporary localization of platelets within lungs. Morphological analysis revealed platelet aggregates in lung capillaries. The platelets had changed shape and were in the process of degranulating. Serotonin and histamine levels in blood increased approximately 5-fold and 7-fold, respectively, after dextran sulfate injection. The cardiovascular events following dextran sulfate injection were mimicked by intravenous serotonin but not by intravenous histamine injection, although a combination of serotonin and histamine reproduced the pattern of blood pressure changes better than did either agent alone. Quantification of platelets trapped in lung revealed that the potential release of serotonin from trapped platelets could account for the rise in plasma serotonin concentration and the hemodynamic changes observed. Both the dextran sulfate-induced cardiovascular effects and serotonin-induced hypotension were markedly diminished by cutting vagus and depressor nerves, and were virtually abolished by carotid ligation in addition to nerve section. These results support the concept that platelet activation within rabbit lungs may cause hypotension via serotonin-induced chemoreflexes.

Angiotensin-Converting Enzyme Inhibitors↗

Dextran sulfate is poorly absorbed after oral administration.

STUDY OBJECTIVE: To determine whether dextran sulfate (molecular weight, 7000 to 8000 daltons; 17% to 20% sulfur), a synthetic heparin analogue with anti-human immunodeficiency virus (HIV) activity in vitro, is absorbed after oral administration. DESIGN: Open-label, single-center study in two parts. The first part was a bioavailability study in which six subjects received a single 1800-mg oral dose and a single 225- or 300-mg intravenous dose. The second part was a study of the dose-response relation between dextran sulfate and total plasma lipolytic activity in which twelve subjects were given a single infusion of either 0.05, 0.5, 5, or 50 mg of dextran sulfate. SUBJECTS: Eighteen healthy volunteers. MEASUREMENTS AND MAIN RESULTS: In the bioavailability study, plasma and urine dextran-sulfate concentrations were measured by a competitive binding assay after each dose. In addition, two bioassays were used to assess plasma concentrations: plasma lipolytic activity and activated partial thromboplastin time (APTT). After the oral dose, plasma concentrations were not measurable with the competitive binding assay (lower limit of sensitivity, 1 microgram/mL); less than 0.5% of the dose was recovered in the urine, the APTT did not increase, and the median increase in the plasma lipolytic activity was only twofold (maximum increase, 11-fold). In contrast, after the intravenous dose of 225 mg, peak plasma concentrations by competitive binding assay were 26 to 35 micrograms/mL (median, 28 micrograms/mL); 25% to 29% (median, 25%) of the dose was recovered in the urine; the APTT increased to 3.5 to 9.2 times the baseline value (median increase, 6.9 times), and the plasma lipolytic activity increased by 185 to 548 times the baseline value (median increase, 438 times). In the dose-response study, intravenous doses as low as 0.5 mg produced significant increases in the plasma lipolytic activity. There was a steep dose-response curve between 0.5 and 50 mg. CONCLUSION: Dextran sulfate is very poorly absorbed after oral administration.

Administration, Oral↗

Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV.

Dextran sulfate, heparin, and certain other sulfated polysaccharides potently inhibit the adsorption of HIV to CD4+ cells. The mechanism of this inhibition is unclear and, specifically, it is unknown if these agents act at the level of CD4-gp120 binding. For example, previous reports have demonstrated that dextran sulfate does not inhibit the cell surface binding of anti-CD4 mAb known to be directed at the gp120 binding site. In order to confirm and extend these observations, in the present study, it was shown that dextran sulfate does not inhibit the binding of OKT4A, OKT4C, Leu3a, or B66.6 to CD4+ cells as measured by cytofluorography. Next, recombinant forms of CD4 (rT4) and gp120 (rgp120) were utilized to directly study their molecular interaction in the absence of other viral or cellular structures. Reciprocal solid phase ELISA assays were developed to study directly the effects of sulfated polysaccharides on the binding of rT4 to immobilized rgp120 and vice versa. Dextran sulfate, heparin, and fucoidan, but not chondroitin sulfate, inhibited the binding of rgp120 to rT4. Importantly, dextran sulfate and heparin pre-treatment of immobilized rT4, but not immobilized rgp120, inhibited rT4-rgp120 binding. Taken together, these data suggest that while both sulfated polysaccharides and anti-CD4 mAb inhibit gp120 binding, the sulfated polysaccharides interact with sites on CD4 that are distinct from those with which the antibodies bind.

Adjuvants, Immunologic↗

The contact activation mechanism in human plasma: activation induced by dextran sulfate.

Incubation of normal human plasma with dextran sulfate for 7 min at 4 degrees C generates kallikrein amidolytic activity. No kallikrein activity is generated in factor XII or prekallikrein-deficient plasma and only small amounts (8%) in high molecular weight (HMW) kininogen-deficient plasma. Addition of specific antisera directed against prekallikrein or HMW kininogen to normal plasma blocked the generation of kallikrein activity by dextran sulfate. Thus, factor XII, prekallikrein, and HMW kininogen are essential components for optimal activation of prekallikrein. The role of limited proteolysis in the activation of prekallikrein induced by dextran sulfate was studied by adding 125I-prekallikrein to plasma. The generation of kallikrein activity paralleled the proteolytic cleavage of prekallikrein as judged on SDS gels in the presence of reducing agents. The same cleavage fragments were observed as obtained by activation of purified prekallikrein by beta-factor-XIIa. Addition of 131I-HMW kininogen and 125I-factor XII or 131I-HMW kininogen and 125I-prekallikrein to normal plasma followed by activation with dextran sulfate and analysis on SDS gels indicated that the observed cleavage of prekallikrein and HMW kininogen is fast compared to the observed cleavage of factor XII, which is much slower and less extensive. During the first minutes of incubation of normal plasma with dextran sulfate, mainly alpha-factor-XIIa is formed. During prolonged incubation, beta-factor-XIIa is also formed.

Dextran Sulfate↗

Effect of dextran sulfate on the interaction between very low density lipoprotein and lipoprotein lipase.

The effect of dextran sulfate on the interaction between very low density lipoprotein (VLDL) and purified bovine milk lipoprotein was studied. Dextran sulfate increased VLDL-triacylglycerol hydrolysis by lipoprotein lipase about 2-fold, but did not alter the Km value for triacylglycerol in VLDL. Strong association of dextran sulfate with the VLDL-lipoprotein lipase complex was demonstrated by gel filtration on BioGel A-5m, although dextran sulfate did not bind to VLDL and only very slightly to lipoprotein lipase. These findings suggest that dextran sulfate increases triacylglycerol hydrolysis in VLDL by binding to the VLDL-lipoprotein lipase complex.

Animals↗

Low-molecular-weight heparin (enoxaparin) vs dextran 70. The prevention of postoperative deep vein thrombosis after total hip replacement. The Danish Enoxaparin Study Group.

A prospective randomized study compared the thromboprophylactic efficacy and safety of a low-molecular-weight heparin (LMWH), enoxaparin (40.6 mg subcutaneously once daily), with a standard regimen of dextran 70 in patients undergoing elective total hip replacement. Deep vein thrombosis was diagnosed by bilateral ascending phlebography 7 to 11 days after operation. Two hundred forty-six patients were included and 219 were eligible for analysis. Deep vein thrombosis was diagnosed in seven of 108 patients in the LMWH group and in 24 of 111 patients in the dextran group. Clinical symptoms of pulmonary embolism did not develop in any patients during the study. In the postoperative period, patients receiving LMWH had a lower blood loss in drains and required fewer blood transfusions than patients receiving dextran, although no significant differences were noted between the groups with respect to the total number of blood transfusions required. Bleeding events and adverse events did not differ between the groups. None of the patients died in hospital during the study. One patient in the LMWH group died at home 15 days after the operation. Three patients receiving dextran had development of symptomatic deep vein thrombosis after hospital discharge. In conclusion, enoxaparin was a more effective thromboprophylactic than a standard regimen of dextran in patients undergoing total hip replacement. The two regimens were equally safe under the clinical conditions.

Adult↗

Dextran 40-containing infusion fluids and corneal swelling: a specular microscopic study.

We studied the effect of dextran 40 on corneal swelling with a specular microscope. The corneas were stressed by the addition of 10(-5)M ouabain to the infusion fluids for various time intervals. Dextran 40 inhibited swelling of functionally impaired corneas. However, when the dextran 40 was removed from the solution, the corneas swelled rapidly to reach the level of those incubated in ouabain without dextran 40. When the corneas were stressed in ouabain for a short period, dextran 40 had a protective effect that lasted even after its removal from the solution.

Animals↗