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PubMed1977

Exclusion of dextrans by meshworks of collagenous fibres.

Insoluble collagen from human dermis was equilibrated in a physiological medium with mixtures of 3H2O and fluorescein-conjugated dextrans of different molecular weights. Dextrans of mol.wts. greater than 10(5) were excluded from a volume of 3.82+/-0.87 ml(S.D.) per g of collagen; dextrans of lower molecular weight occupied a larger volume. The apparent excluded volume was proportional to the weight of the collagen. Dansylated albumin behaved similarly to dextran; the polymeric collagen from rat skin exhibited a much larger excluded volume than the insoluble collagen. These results indicated that the volume available to the plasma proteins in human dermis was limited by insoluble collagen as well as by the glycosaminoglycans of the tissue.

Aged↗
PubMed1977

Enhanced plasma persistence of therapeutic enzymes by coupling to soluble dextran.

Conjugation of carboxypeptidase G and arginase, two enzymes of therapeutic interest, to a soluble dextran significantly enhanced plasma persistence in normal and tumour-bearing mice. A prolonged decrease in arginine concentrations in plasma of tumour-bearing mice was demonstrated by using the dextran-linked arginase. Gel filtration of dextran-enzyme conjugate showed that enzyme activity co-chromatographed as a single peak with carbohydrate, and enzyme was shown to be covalently linked to the dextran.

Animals↗
PubMed1979

The molecular compression of dextran.

The suggestion is made that, in solution, the flexible-chain molecules of dextran can undergo an osmotic compression as concentration is increased. Approaches are developed described the molecular shrinkage (i) as arising from intra- and inter-molecular forces, (ii) based on the molecular characteristics of the dextran, and (iii) as estimated by viscosity measurements. Comparison with the macroscopic shrinkage of cross-linked dextran (Sephadex) beads [Edmond, Farquhar, Dunstone & Ogston (1968) Biochem. J. 108, 755-763] is made. In all systems studied, the experimental estimates of compression, both from gel-shrinkage and viscosity measurements were in reasonable agreement with theoretical predictions. The interpretation of the viscosity concentration-dependence was applied to compact structures (albumin and Percoll). Their behaviour was in marked contrast with that of dextran. It is noted that molecular compression may be important in considering transport processes in and thermodynamic properties of concentrated systems.

Biopolymers↗
PubMed1996

Regulation of vesicular pH in liver macrophages and parenchymal cells by ammonia and anisotonicity as assessed by fluorescein isothiocyanate-dextran fluorescence.

Short-term-cultivated rat hepatocytes and Kupffer cells were allowed to endocytose fluorescein isothiocyanate (FITC)-coupled dextran, in order to study the effects of aniso-osmotic exposure and NH4Cl on apparent vesicular pH (pHves) by single-cell fluorescence. Following a 2 h loading period with FITC-dextran in normo-osmotic (305 mosmol/l) medium, the apparent pHves was 6.01 +/- 0.05 (n = 39) in parenchymal cells and 4.94 +/- 0.04 (n = 76) in Kupffer cells. Under these conditions pHves in parenchymal cells, but not in Kupffer cells, was sensitive to changes in ambient osmolarity. Inhibition of vacuolar H(+)-ATPase by concanamycin A did not affect the osmosensitivity of pHves in parenchymal cells. However, the effects of anisotonicity on pHves were largely abolished in the presence of 4.4'-di-isothiocyanato-stibene-2,2'-disulphonic acid (DIDS) or when extracellular chloride was substituted for gluconate. In neither Kupffer cells, nor liver parenchymal cells did hypo-osmotic cell swelling cause an increase in intracellular Ca2+. With regard to vesicular acidification, the following differences were noted between parenchymal and Kupffer cells. (1) In Kupffer cells endocytosed FITC-dextran reached a strongly acidic compartment with a pH value of approx. 5 within 5 min, whereas it took 4-5 h in parenchymal cells. Modification of pHves by hypo-osmolarity in Kupffer cells was only observed in a short-lived "early' compartment with a pH value of approx. 6. (2) In contrast to pHves in parenchymal cells, pHves in Kupffer cells was very sensitive towards alkalinization by NH4Cl: addition of NH4Cl at 1 or 10 mM increased apparent pHves by 0.80 or 1.46 in Kupffer cells, but only by 0.18 or 0.56 in parenchymal cells. The low ammonia sensitivity of pHves in parenchymal cells was observed not only a the less acidic (pH approx. 6) endocytotic compartment which is reached by FITC-dextran within 2 h, but also in the stronger acidic compartment (pH approx. 5) which is reached after 4-5 h. (3) NH4Cl had no effect on the osmosensitivity of pHves in parenchymal cells, whereas in Kupffer cells pHves became sensitive to anisotonicity when NH4Cl was present. Osmosensitivity of pHves in Kupffer cells under these conditions, however, was not affected by genistein, DIDS or colchicine, whereas these compounds abolished the osmosensitivity of pHves in parenchymal cells. It is suggested that regulation of pHves by cell volume in liver parenchymal cells involves changes of vesicular chloride conductance. In addition, there are marked differences between Kupffer and parenchymal cells with respect to vesicular ammonia permeability and the kinetics of endocytotic membrane flow and acidification.

Ammonia↗
PubMedDate not supplied

Stimulation of wound healing by positively charged dextran beads depends upon clustering of beads and cells in close proximity to the wound.

We have previously shown that positively charged dextran (DEAE A25) increases wound breaking strength in linear incisions in rats and nonhuman primates at days 10-14 postwounding. In this article, we examined the cellular responses to different types of charged dextran beads (DEAE A50 and Cytodex-1) in culture studies and in rat incisional wounds. We show that Cytodex 1 and DEAE A50 beads also increased wound breaking strength in a rat linear incisional model. However, the increase was approximately 30-40% less than that observed in wounds treated with DEAE A25 beads. The main distinction between the three types of beads was the presence of bead clusters observed in tissue sections. Wounds treated with DEAE A25 beads formed distinct clusters while both Cytodex 1 and DEAE A50 beads clustered to a lesser extent or failed to cluster at all. We propose that the different types of charged dextran beads improve healing by promoting cell adhesion and encouraging proliferation in close proximity to the wound. We also hypothesize that the 30-40% improvement in wound breaking strength seen with DEAE A25 beads compared to other types of charged dextran beads (DEAE A50 and Cytodex-1) originates from the unique characteristic of DEAE A25 beads in forming cell-bead aggregates adjacent to the wounded area. This clustering, in turn, affects the distribution of cells infiltrating the wounded area (such as macrophages) during the healing process and, as a consequence, alters the distribution of matrix molecules and growth factors secreted by these cells.

Animals↗
PubMedDate not supplied

Plasma exchange using dextran 40-electrolyte solution as the sole replacement fluid in malignant paraproteinemia.

The relative safety of 3 percent Dextran 40-electrolyte solution alone as replacement fluid during plasma exchange is described. Using an automated blood cell separator, the authors exchanged 3.21 of plasma 64 times in 11 patients with paraproteinemia secondary either to Waldenström's macroglobulinemia or multiple myeloma (malignant paraproteinemia). Then they replaced the plasma with an equal volume of 3 percent Dextran 40-electrolyte solution. They administered no protein-containing solutions during or after the plasma exchanges. Despite marked hypoalbuminemia immediately after plasma exchange, the plasma colloid osmotic pressure level fell only slightly because of the high concentration of plasma low-molecular dextran. The hemostatic abnormalities were similar to those seen in patients whose plasma was replaced with albumin solution. The exchanges were tolerated well clinically and no serious complications occurred during or after exchange. The authors believe that the 3 percent Dextran 40-electrolyte solution can be used safely as the sole replacement fluid in intensive plasma exchange programs for patients with malignant paraproteinemia.

Complement C3↗
PubMed2000

Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial.

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

Anemia, Iron-Deficiency↗
PubMed1999

Transcranial Doppler directed dextran therapy in the prevention of carotid thrombosis: three hour monitoring is as effective as six hours.

BACKGROUND: Six hours' monitoring by transcranial Doppler (TCD) has been successful in directing Dextran therapy in patients at high risk of thrombotic stroke after carotid endarterectomy (CEA). OBJECTIVES: Is 3 h of routine monitoring as effective as 6 h in the prevention of early postoperative thrombotic stroke? DESIGN: Prospective, consecutive study in all patients with an accessible cranial window. METHODS: One hundred and sixty-six patients undergoing CEA underwent 3 h of postoperative monitoring by TCD. Any patient with > 25 emboli detected in any 10 min period or those with emboli that distorted the arterial waveform were commenced on an incremental infusion of dextran 40. RESULTS: The majority of patients destined to embolise will do so within the first 2 postoperative hours. Dextran therapy was instituted in nine patients (5%) and rapidly controlled this phase of embolisation although the dose had to be increased in three (33%). No patient suffered a postoperative carotid thrombosis but one suffered a minor stroke on day 5 and was found to have profuse embolisation on TCD; high dose dextran therapy was again instituted, the embolus count rate fell rapidly and he made a good recovery thereafter. Overall, the death and disabling stroke rate was 1.2% and the death/any stroke rate was 2.4%. CONCLUSION: Three hours of postoperative TCD monitoring is as effective as 6 h in the prevention of postoperative carotid thrombosis.

Adult↗
PubMed1976

[Dextran 40 in the prophylaxis of deep vein thrombosis in surgery (author's transl)].

The effectiveness of 4 X 500 ml dextran-40 infusions (Rheomacrodex) for the prevention of postoperative deep vein thrombosis was evaluated in a prospective, controlled, randomized study in urological and general surgical patients. The 125I-fibrinogen test was performed daily in all patients. 36 of 100 control patients developed deep vein thrombosis, but only 20 out of 92 (21.7%) did so in the dextran group (P less than 0.05). The number of patients showing bilateral deep vein thrombosis was significantly reduced under dextran prophylaxis (P less than 0.01). No side effects of dextran prophylaxis were seen.

Adult↗
PubMed1986

[Dextran 40 or HES 200/0.5? Hemorheology of the long-term treatment of ischemic cerebral attacks].

Haemorheological parameters on long-term treatment of ischaemic stroke were measured in two groups of 12 patients receiving dextran 40 or hydroxyethyl starch (HES 200). Both substances similarly lowered haematocrit and whole-blood viscosity. Dextran produced a clear-cut increase in plasma viscosity and red-cell aggregation. The effects were due to a marked increase in the plasma concentration of dextran caused by an accumulation of large molecules. HES 200 improved plasma viscosity and red-cell aggregation. Since these haemorheological parameters are of special importance for improving a disordered microcirculation as would occur at the margins of the ischaemic lesion, HES 200 would seem to be the appropriate plasma expander in long-term treatment with haemodilution. The differences between dextran 40 and HES 200 become the more marked the higher the volume infused.

Blood Viscosity↗
PubMed2000

Low-potassium dextran solution ameliorates reperfusion injury of the lung and protects surfactant function.

OBJECTIVE: This study was designed to compare the effect of lung preservation with low-potassium dextran solution and Euro-Collins solution on reperfusion injury and surfactant function by using an in situ model of warm ischemia. METHODS: The left lungs of 6 minipigs were selectively perfused with Euro-Collins solution. In an additional 6 animals low-potassium dextran solution was used for flush perfusion. After 90 minutes of warm ischemia, the lungs were reperfused, and the contralateral pulmonary artery and bronchus were clamped. Hemodynamic and respiratory measurements were obtained for 7 hours of reperfusion. Surface tension of bronchoalveolar lavage and surfactant small and large aggregates were determined before perfusion (right lung) and after 2 hours of reperfusion (left lung). RESULTS: In the group receiving Euro-Collins solution, right heart failure developed within 215 +/- 39 minutes of reperfusion. An increase in minimal surface tension (P =.03), surfactant small aggregates/large aggregates ratio (P =.003), and bronchoalveolar lavage protein content (P =.012) were found after 2 hours of reperfusion. In the group receiving low-potassium dextran solution, all minipigs survived (P =.0001). Dynamic lung compliance (P =.034) and oxygen tension/inspired oxygen fraction ratios were higher (P =. 0001). Lung water content was lower (P =.049). The increase of minimal surface tension (P =.02) and bronchoalveolar lavage protein concentration (P =.015) were significantly less. CONCLUSION: Preservation of the lung with Euro-Collins solution leads to a reduction of physical surfactant function during reperfusion. Low-potassium dextran solution protects surfactant function and metabolism, thereby reducing reperfusion injury of the lung.

Animals↗
PubMed1976

Soluble dextran-hemoglobin complex as a potential blood substitute.

A complex between soluble dextran and human hemoglobin has been synthesized by two different methods. In the alkylation method, hemoglobin was allowed to react with bromoacetyl groups incorporated into the dextran; the yield of the complex was about 80% in terms of the hemoglobin used. In the dialdehyde method, hemoglobin was allowed to react with dialdehyde groups on the dextran generated by periodate oxidation; the yield of the complex was about 60%. Both soluble dextran-hemoglobin complexes could bind and release oxygen reversibly, but the oxygen-binding curves were shifted to the left relative to that of free hemoglobin. In the rabbit, the complex obtained by the alkylation method was excreted by the kidneys and cleared from the circulation much more slowly than free hemoglobin.

Chemical Phenomena↗
PubMed2000

Human plasmin enzymatic activity is inhibited by chemically modified dextrans.

Some synthetic dextran derivatives that mimic the action of heparin/heparan sulfate were shown to promote in vivo tissue repair when added alone to wounds. These biofunctional mimetics were therefore designated as "regenerating agents" in regard to their in vivo properties. In vitro, these biopolymers were able to protect various heparin-binding growth factors against proteolytic degradation as well as to inhibit the enzymatic activity of neutrophil elastase. In the present work, different dextran derivatives were tested for their capacity to inhibit the enzymatic activity of human plasmin. We show that dextran containing carboxymethyl, sulfate as well as benzylamide groups (RG1192 compound), was the most efficient inhibitor of plasmin amidolytic activity. The inhibition of plasmin by RG1192 can be classified as tight binding hyperbolic noncompetitive. One molecule of RG1192 bound 20 molecules of plasmin with a K(i) of 2.8 x 10(-8) m. Analysis with an optical biosensor confirmed the high affinity of RG1192 for plasmin and revealed that this polymer equally binds plasminogen with a similar affinity (K(d) = 3 x 10(-8) m). Competitive experiments carried out with 6-aminohexanoic acid and kringle proteolytic fragments identified the lysine-binding site domains of plasmin as the RG1192 binding sites. In addition, RG1192 blocked the generation of plasmin from Glu-plasminogen and inhibited the plasmin-mediated proteolysis of fibronectin and laminin. Data from the present in vitro investigation thus indicated that specific dextran derivatives can contribute to the regulation of plasmin activity by impeding the plasmin generation, as a result of their binding to plasminogen and also by directly affecting the catalytic activity of the enzyme.

Dextrans↗
PubMed2006

Oral immunoadjuvant activity of Lactobacillus casei subsp. casei in dextran-fed layer chickens.

We recently reported that synbiotic Lactobacillus casei subsp. casei together with specific substrate dextran elicited an enhancement in humoral immune response against bovine serum albumin (BSA) as a model antigen in BALB/c mice. The present study was designed to evaluate the oral immunoadjuvant effects of the synbiotic in layer chickens. Using a PCR assay, L. casei subsp. casei was detected specifically in the intestinal chyme of chickens (10 d of age, Julia strain) fed ad libitum on a diet supplemented with 75 mg dextran/kg (dextran-supplemented diet, DSD) and administered orally with 10(7) colony-forming units (CFU) L. casei subsp. casei in 0.1 ml PBS with the aid of an intubation needle at 1, 2 and 3 d of age. Furthermore, oral administration of 10(7) CFU L. casei subsp. casei at 1-3 d of age significantly enhanced the production of anti-BSA antibody in DSD-fed chickens (60 d of age) administered orally with 1 mg BSA at 32 and 33 d of age and subcutaneously with 5 microg BSA at 33 d of age. In addition, among bacterial numbers tested, 10(6) CFU L. casei subsp. casei together with dextran induced an effective increase in humoral immune response to mixed inactivated vaccines against Newcastle disease and avian infectious bronchitis, and the treatment may be advantageous in protecting against these infectious diseases in chickens in actual application. These results suggest that dietary supplementation of L. casei subsp. casei with dextran leads to immunomodulation of humoral immune responses.

Adjuvants, Immunologic↗
PubMedDate not supplied

Effects of cell damage and glycosaminoglycan degradation on available extravascular space of different dextrans in a rat fibrosarcoma.

Drug delivery to solid tumors may be enhanced through increasing the available volume fraction (K(AV)) of drugs. Therefore, two approaches were investigated that may increase K(AV) of dextrans in a rat fibrosarcoma: (a) damaging cells in tumours via ex vivo incubation of tumour tissues, and (b) degrading tumour glycosaminoglycans (GAGs) with exogenous hyaluronidase. The molecular weights of dextrans used in this study were approximately 10,000 (D10), 70,000 (D70) and 2,000,000 (D2000), respectively. It was found that GAG degradation had minimal effects on K(AV) of dextrans. Ex vivo incubation at 37 degrees C for up to 3 h caused only minor cell damage and had minimal effects on K(AV) of D10 and D70. However, the ex vivo incubation reduced K(AV) of D2000 (p < 0.05). When the incubation at 37 degrees C was maintained for 20 h, the amount of viable cells in tumours was reduced by 56% and K(AV) of all dextrans were significantly increased (p < 0.05). Ex vivo incubation at 41 degrees C for 3 h caused similar cell damage to that at 37 degrees C for 20 h, but only K(AV) of D10 and D70 were increased significantly (p < 0.05). There was no significant change in K(AV) of D2000, although it was higher than that in tumours incubated at 37 degrees C for 3 h (p < 0.05). These data suggest that cell damage is a more effective approach than GAG degradation for increasing K(AV) of macromolecules and that the amount of increase depends on the degree of cell damage and the size of molecules.

Animals↗
PubMed2002

Platelet activation during carotid endarterectomy and the antiplatelet effect of Dextran 40.

OBJECTIVE: To determine changes in platelet activation during carotid endarterectomy (CEA) and the antiplatelet effect of Dextran 40. METHODS: Prospective study in 40 patients undergoing CEA. Platelet activity was measured by whole blood flow cytometry and platelet aggregometry during CEA. The expression of P-selectin and the PAC-1 antigen were used as markers of platelet activation and aggregation. Patients received aspirin (75-300 mg) preoperatively and 5,000 units unfractionated heparin during surgery. High intensity transient signals (HITS) in the ipsilateral middle cerebral artery were monitored using transcranial Doppler (TCD) perioperatively. RESULTS: P-selectin expression increased after carotid clamping (P < 0.01) and clamp release (P < 0.05). There was higher expression of PAC-1 after carotid clamping (p < 0.05). Spontaneous and ADP-induced platelet aggregation increased after carotid clamping (P< 0.01) and release (P < 0.01). TCD monitoring showed an increased HITS count from preoperative levels, after clamp release (P < 0.01) and during recovery (P < 0.01). After the operation, patients with more than 50 HITS per 30 min were started on an infusion of dextran 40 (n = 6). P-selectin expression decreased 24 h after dextran 40 (P < 0.01). CONCLUSION: Significant platelet activation and aggregation occurs during CEA despite the current use of antiplatelet treatment. Dextran 40 had an antiplatelet effect after CEA providing further evidence that it may contribute to reducing thromboembolic complications.

Aged↗
PubMed2003

Release profiles of theophylline from microspheres consisting of dextran derivatives and cellulose acetate butyrate: effect of polyion complex formation.

The objective of this study was to evaluate the utility of mixtures among oppositely charged dextran derivatives as constituents of a controlled release microsphere. Carboxymethyldextran (CMD) and dextran sulfate (DS) were used as polyanions, and [2-(diethylamino) ethyl] dextran (EA) and [2-hydroxypropyltrimethylammonium] dextran (CDC) as polycations. The microspheres consisting of hydrophilic and hydrophobic polymers were prepared by emulsion-solvent evaporation method. The mixtures, CMD/EA, CMD/CDC, DS/EA, and DS/CDC, were used as hydrophilic polymers, because they can interact with each other to form polyion complexes for the improvement of sustained-release performances. Cellulose acetate butyrate and theophylline were used as a model hydrophobic polymer and a model drug, respectively. The yield of microspheres was excellent (more than 95%). According to observation, by scanning election microscopy (SEM) microspheres were spherical with a rough surface. The in vitro drug release from microspheres was examined in the JP XIV first fluid, pH 1.2, and second fluid, p H 6.8, at 37 degrees C, and 100 rpm. In the DS/CDC system, drug release was depressed by formation of a polyion complex and not affected by pH of dissolution medium. The release rate was modulated by the ratio of hydrophilic and hydrophobic matrix. This particulate system, in which the polyion complex matrix is strengthened by a hydrophobic polymer, is a promising formulation for drug delivery.

Cellulose↗
PubMed2004

Studies on acyclovir-dextran conjugate: synthesis and pharmacokinetics.

Acyclovir is an antivirus drug which has a good in vitro activity against hepatitis B virus. But because of the low solubility and low distribution in liver, the clinical application of acyclovir in hepatitis B was limited. To increase the solubility and the distribution in liver, acyclovir-dextran conjugate was synthesized by formation of Schiff's base. The solubility of obtained conjugate was 12 times greater than free acyclovir. Acyclovir will be slowly released from the obtained conjugate in pH 7.4 phosphate buffer solution (PBS) at 37 degrees C with a rate constant of 0.0035 hr(-1). Pharmacokinetic studies of acyclovir and acyclovir-dextran conjugate were conducted in mice by i.v. administration. Acyclovir concentrations in plasma, liver and kidney were determined by HPLC method. Relatively higher distribution of acyclovir in liver was observed when i.v. acyclovir-dextran conjugate as compared with i.v. free acyclovir. The results of pharmacokinetic studies indicated that acyclovir-dextran conjugate will be a good candidate to treat hepatitis B.

Acyclovir↗