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PubMed1985

Crossbridge kinetics in chemically skinned rabbit psoas fibres when the actin-myosin lattice spacing is altered by dextran T-500.

The actin-myosin lattice spacing of chemically skinned rabbit psoas fibres was osmotically altered by dextran T500, and the transient kinetic response of tension arising from maximally cycling cross-bridges was measured by sinusoidal length perturbations. The lattice spacing was estimated from the width of the fibres measured under a light microscope. As the dextran concentration was increased, the widths during both relaxation and Ca-activation decreased monotonically. The tension increased to a maximum at 7% dextran, and decreased again at further increases in dextran. Dynamic modulus (stiffness) increased monotonically with compression by dextran; this increase is primarily due to the elastic modulus. The rate constants slightly decreased between 0% and 4% dextran, then decreased rapidly at higher concentrations. The rate of oscillatory work output stayed approximately constant between 0% and 4% dextran, and sharply decreased at higher concentrations. Apparently, two independent effects occur as the lattice is compressed by dextran: (1) a compensation for the spacing change through an increase in tension and a decrease in the rate constants (this takes place at low dextran concentrations); and (2) an alteration of the crossbridge kinetics by grossly decreasing both the tension and the rate constants (at high dextran concentrations). The first effect is interpreted as a decrease in the detachment rate, while the second effect is interpreted as a decrease in the rate of the 'power stroke' reaction.

Actins↗

PubMed1996

Benefits of various dextrans after delayed therapy in necrotizing pancreatitis of the rat.

OBJECTIVE: Ultrahigh-molecular dextran (500,000 Da) has been shown to prevent pancreatic necrosis when given 30 min after induction of pancreatitis. This study should clarify the following: (a) are dextrans still effective after prolongation of the therapy-free interval? (b) what is the impact of the molecular weight of the dextrans? and (c) is their effect influenced by the dextran concentration or by the addition of hypertonic saline? ANIMALS AND INTERVENTIONS: Acute pancreatitis was induced in 70 male dextran-tolerant Wistar rats using intraductal bile-salt infusion and intravenous hyperstimulation. After 3 h, animals were assigned to one of seven groups (n = 10 per group) receiving either Ringer solution or different dextrans (10%) including 70,000 Da (DEX-70), 160,000 Da (DEX-160), 300,000 Da (DEX-300) or 500,000 Da (DEX-500). Additional groups included DEX-70 (6%) and DEX-70 (10%) in combination with hypertonic NaCl (7.5%) (HHS-70). Ringer solution was given at 24 ml/kg and all dextrans at 8 ml/kg. MEASUREMENTS AND RESULTS: Trypsinogen activation peptides (TAP) were quantified in ascites and acinar necrosis after death or sacrifice at 9 h. As an index of less pathological trypsinogen activation, the mean TAP levels in ascites were significantly lower in DEX-70 and DEX-160 compared to Ringer controls (p < 0.05, t-test). Furthermore, the amount of acinar necrosis was significantly lower in all dextran groups except the HHS-70 in comparison with Ringer controls (p < 0.01, t-test). Finally, mortality was significantly reduced from 60% in Ringer controls to 10 and 0%, respectively, in the groups treated with DEX-70 and DEX-160 (p < 0.03, Fisher's Exact test). There was a similar trend in all other groups except the HHS-70. CONCLUSIONS: Despite a therapy-free interval of 3 h, dextrans reduce trypsinogen activation, prevent acinar necrosis, and improve survival in necrotizing rodent pancreatitis. The molecular weight and concentration of dextran are of secondary importance for these beneficial effects.

Animals↗

PubMed1987

Covalent linkage of carboxypeptidase G2 to soluble dextrans--II. In vivo distribution and fate of conjugates.

The in vivo fate of the therapeutic enzyme, carboxypeptidase G2 (CPG2) in native form and covalently-linked to soluble dextrans was studied in the mouse using radiolabelled compounds. Clearance, from the blood, of all compounds tested was found to be as intact, active material, whilst excreted radiolabel was associated in all cases with low molecular weight substances. The clearance and excretion rates of native CPG2 were found to balance, but this was not so for dextran-CPG2 conjugate or CNBr-activated dextran. Tissue distribution studies demonstrated that there was little or no tissue uptake of native CPG2, whereas dextran-CPG2 conjugate, and CNBr-activated dextran were retained in the liver. Within the liver, the CPG2 component of dextran-CPG2 conjugate was degraded more rapidly than the dextran moiety. Blockade of reticulo-endothelial system (RES) led to increased half-lives of dextran CPG2 conjugate and CNBr-activated dextran, demonstrating the involvement of the RES in the clearance of these compounds. Impairment of RES activity did not affect the clearance rate of native CPG2. These results are discussed in relation to the potential use of dextran-CPG2 conjugates in cancer chemotherapy.

Animals↗

PubMed1993

Fast axonal diffusion of 3000 molecular weight dextran amines.

The distances of anterograde and retrograde axonal movement per hour were examined for dextran amines of 3000, 10,000 and 40,000 molecular weights (MW) conjugated to different fluorochromes (Cascade blue, fluorescein, tetramethylrhodamine, Texas red) or to biotin. Lateral line nerves of Xenopus laevis tadpoles were used as an easily accessible test system. Only 10,000 and 3000 MW dextran amines underwent significant anterograde and retrograde movement. Dextrans of 3000 MW progressed about twice as far (2 mm/h at 22 degrees C) than 10,000 MW dextrans. Dextrans conjugated to different fluorochromes or to biotin did not show differences in their distance covered. Tracers traveled over the same distance in amphibians pre-treated with either 1 microM colchicine for 2-6 h or 10 micrograms/ml nocodazole for 5 h prior to the application to depolymerize microtubules needed for active transport. This suggests that diffusion is the major mechanism of movement for dextran amines over short distances. In the developing Xenopus retina, 3000 MW dextrans traveled from the optic disc as far away as the ora serrata within 1 h. In mouse embryos, chicken embryos and larval lampreys dextran amines progress within 1 h from cut peripheral nerves through efferent and afferent tracts. These data show that 3000 MW dextrans can be used in much the same way as 10,000 MW dextrans, but label neuronal profiles in a shorter time in a wide variety of species.

Ambystoma↗

PubMed1983

Free energy potential for aggregation of erythrocytes and phosphatidylcholine/phosphatidylserine vesicles in Dextran (36,500 MW) solutions and in plasma.

The free energy potential (affinity) for aggregation of human red blood cells and lipid vesicles in Dextran solutions and blood plasma has been quantitated by measuring to what extent a vesicle is encapsulated by the red cell surface. The free energy reduction per unit area of contact formation (affinity) was computed from the observation of the fractional extent of encapsulation at equilibrium with the use of a relation based on the elastic compliance of the red cell membrane as it is deformed to adhere to the vesicle surface. Micromanipulation methods were used to select and transfer single lipid vesicles (2-3 X 10(-4) cm diameter) from a chamber that contained the vesicle suspension to a separate chamber on the microscope stage that contained red cells in an EDTA buffer with Dextran or whole plasma. The vesicle and a red cell were maneuvered into close proximity and contact allowed to take place without forcing the cells together. To evaluate the effects of surface charge density and steric interactions on aggregation, vesicles were made from mixtures of egg phosphatidylcholine (PC) and bovine phosphatidylserine (PS) over a range of mole ratios (PC/PS)from (1:0) to (1:1); the vesicles were formed by rehydration in buffer. The Dextran solutions were made with a sharp-cut fraction of 36,500 MW in a concentration range of 0-10% by weight in grams (wt/wt). It was found that the Dextran 36,500 MW fraction produced aggregation behavior for red cells and vesicles similar to red cell-red cell aggregation in Dextran 70,000-150,000 MW fractions, when the vesicle surface charge density was comparable with that of normal red cells (i.e., PC/PS ratio of -3:1). This result indicated that Dextran molecules penetrate between the carbohydrate groups on the red cell surface and that either steric interactions between cell surface carbohydrates are important or many of the charge groups on red cells are superficial. Electrostatic repulsion effects were apparent, as no aggregation in Dextran 36,500 MW occurred for PC/PS ratios <2.6:1; the level of affinity increased with the PC content at a specific Dextran concentration. Affinities were measured in the range of 0-2 x 10-2 ergs/cm2. When adherent red cell-vesicle pairs were transferred into a Dextran-free buffer, the pair did not spontaneously separate.They maintained adhesive contact until forcibly parted, after which they would not read here. This demonstrates that Dextran forms a "cross-bridge" between the membrane surfaces. Red cell-vesicle aggregation was also tested in whole plasma, which normally yields affinity values in the range of 2-4 x 10-3 ergs/cm2 for red cell-red cell aggregation.However, no red cell-vesicle aggregation occurred in plasma, even for pure PC vesicles. This result indicates that either the aggregating plasma proteins (primarily fibrinogen) do not bind sufficiently to the lecithin surface, or they are shielded from binding to the surface by the presence of other nonaggregating components (perhaps albumin).

Dextrans↗

PubMed1978

The dextran acceptor reaction of dextransucrase from Streptococcus mutans K1-R.

Soluble dextransucrase activity(ies) was eluted with a solution of clinical dextran from the insoluble dextran--cell complex produced by Streptococcus mutans K1-R grown in the presence of sucrose. Studies of the dextran acceptor-reaction of the soluble enzyme-preparation indicate that it is highly specific for dextran of high molecular weight. Increased dextran synthesis in the presence of dextran acceptor and the apparent inhibition of this stimulation by higher concentrations of dextran result from product modification rather than a direct effect on the level of enzyme activity. The results demonstrate that the potentially water-insoluble structure synthesized by dextransucrase on exogenous, soluble dextran acts as a more-efficient acceptor than the soluble dextran. The role of the acceptor reaction in the biosynthesis of complex dextrans is discussed.

Dextrans↗

PubMed1997

Synthesis of mono- and bifunctional peptide-dextran conjugates for the immobilization of peptide antigens on ELISA plates: properties and application.

Dextran has been used as a carrier molecule for the synthesis of monofunctional peptide-dextran conjugates. The immunodetection of such carrier immobilized peptides on ELISA plates was compared to that of peptides adsorbed directly to immunoplates. The main features observed with peptide-dextran conjugates were as follows: only small amounts of peptide (1-2 mg) were necessary for coupling via alpha- or epsilon-amino groups to NaIO4-activated dextran (4 mg); the coupling yield was up to 68%; an amino acid analysis of the conjugate enabled the amount of carrier immobilized peptide to be calculated; an estimated 15-17 peptides were bound per dextran molecule (MW 73,500); using a carbohydrate as carrier reduces the possibility of non-specific interactions because no hydrophobic or ionic sites and no protein-like epitopes exist on the carrier apart from the peptide ligand. It can be assumed that some peptide ligands provide the forces for an interaction with the plate surface whereas other remain free for the interaction with the antibody. Thus, the detection with monoclonal anti-peptide antibodies allowed peptide-dextran conjugates to be used at coating concentrations of 1-3 nM peptide, corresponding to 0.6-2.6 ng peptide-dextran per well. In contrast, concentrations of 150-500 nM were required for coating with peptides. The applicability of monofunctional peptide-dextran conjugates was demonstrated by investigating the titer and specificity of a polyclonal anti-peptide serum developed against human gastrointestinal glutathione peroxidase. The introduction of biotin as a second ligand of the dextran conjugate permitted its capture on streptavidin coated plates. This synthesis of bifunctional peptide-biotin-dextran conjugates opens up additional possibilities for applications.

Adsorption↗

PubMed1999

Effect of Ca2+-alginate gel dissolution on release of dextran with different molecular weights.

Release of macromolecular drug from calcium-alginate gel beads was investigated. Fluorescein isothiocyanate-labeled dextrans with molecular weight ranging from 9400 to 145000 were used as a model macromolecular drug. Dextran release was observed to be molecular weight-dependent, with the release pattern changing from pseudo first-order for dextran with 9400 molecular weight to sigmoidal for dextran with molecular weight of 145000. Release of a lower molecular weight dextran is mainly governed by the drug diffusion through the calcium-alginate gel matrix. With increasing dextran molecular weights, dextran release was strongly influenced by the dissolution of alginate matrix through the exchange of Ca2+ ions which act as a cross-linker. Rapid and complete release was achieved for dextran with 145000 molecular weight in a "burst" fashion showing a initial lag time. Minimal dextran release was observed in pseudo-gastric fluid at pH 1.2, while rapid dextran release within a narrow time range was achieved in simulated intestinal fluid at pH 6. 8. These results strongly suggest that calcium-alginate gel is a useful vehicle for pulsatile release of macromolecular drugs in oral drug delivery.

Alginates↗

PubMed2003

Lyoprotection of aviscumine with low molecular weight dextrans.

The aim of this research was to ascertain whether dextrans with low molecular weight will stabilize aviscumine. During freeze-drying increasing concentrations of dextran T1 (MW 1000) stabilized aviscumine. Eight percent of dextran resulted in a nearly 100% recovery of the activity and in addition a complete amorphous structure of the solid phase was obtained. By decreasing the molecular weight of the dextran from 75 to 1 kDa, the protein activity was increased by 20% in the lyophilisate. Combinations of dextran with either trehalose or mannitol showed no additional effects on stability. The improved stabilization of aviscumine using low molecular weight dextrans is explained by an increased interaction between the protein and the dextran molecules (like hydrogen bonds), whereas they are sterically hindered if larger dextran molecules are used. When the protein concentration was increased from 10 to 100 microg/ml (in formulas with 8% dextran T1), no influence on the protein activity could be found. With regard to the carbohydrate-binding activity of the protein, it was shown that the optimal content of residual water in the lyophilisate should be about 2%. Above and below this percentage a destabilization of the protein was observed. The often discussed failure of dextran as a stabilizing excipient in the freeze-drying of proteins seems to be a question of the selection of the correct molecular weight.

Antineoplastic Agents↗

PubMedDate not supplied

Dextran retention in the rat brain following release from a polymer implant.

Intracranial controlled release polymers may improve drug administration to the brain, where therapy is frequently limited due to the low permeability of brain capillaries to therapeutic agents. On the basis of drug transport and elimination rates, we proposed that high molecular weight, water-soluble molecules would be retained in the brain space following release from an intracranial implant. To test this hypothesis, solid particles of different molecular weight fractions of fluorescein isothiocyanate labeled dextran (FITC-dextran; 4 x 10(3) Da (4 kDa) < weight-averaged molecular weight (Mw) < 150 kDa) or fluorescein were uniformly dispersed in matrices of a polyanhydride copolymer synthesized from a fatty acid dimer and sebacic acid in a 50:50 ratio, P(FAD:SA). When incubated in buffered saline, FITC-dextran fractions of 70 kDa Mw were released from the polymer within 48 h; 4 kDa Mw FITC-dextran and fluorescein were released more slowly. Following implantation of P(FAD:SA) matrices containing either 70 kDa Mw FITC-dextran, 4 kDa Mw FITC-dextran, or fluorescein into the brains of normal rats, fluorescent tracers were continuously released into the brain tissue for 30 days. Tracer concentrations within the brain were significantly higher for large molecular weight tracers (70 kDa Mw FITC-dextran >> 4 kDa Mw FITC-dextran > fluorescein). The rate of elimination, kapp, of each tracer from the brain was determined by comparing experimental data with a model describing tracer diffusion/elimination in the brain extracellular space; kapp decreased with increasing molecular weight (fluorescein > 4 kDa Mw FITC-dextran > 70 kDa Mw FITC-dextran).

Animals↗

PubMed2006

Interaction forces measured using AFM between colloids and surfaces coated with both dextran and protein.

Both proteins and polysaccharides are biopolymers present on a bacterial surface that can simultaneously affect bacterial adhesion. To better understand how the combined presence of proteins and polysaccharides might influence bacterial attachment, adhesion forces were examined using atomic force microscopy (AFM) between colloids (COOH- or protein-coated) and polymer-coated surfaces (BSA, lysozyme, dextran, BSA+dextran and lysozyme+dextran) as a function of residence time and ionic strength. Protein and dextran were competitively covalently bonded onto glass surfaces, forming a coating that was 22-33% protein and 68-77% dextran. Topographic and phase images of polymer-coated surfaces obtained with tapping mode AFM indicated that proteins at short residence times (<1 s) were shielded by dextran. Adhesion forces measured between colloid and polymer-coated surfaces at short residence times increased in the order protein+dextran < or = protein < dextran. However, the adhesion forces for protein+dextran-coated surface substantially increased with longer residence times, producing the largest adhesion forces between polymer coated surfaces and the colloid over the longest residence times (50-100 s). It was speculated that with longer interaction times the proteins extended out from beneath the dextran and interacted with the colloid, leading to a molecular rearrangement that increased the overall adhesion force. These results show the importance of examining the effect of the combined adhesion force with two different types of biopolymers present and how the time of interaction affects the magnitude of the force obtained with two-polymer-coated surfaces.

Colloids↗

PubMed1997

Dependence of the molecular mobility and protein stability of freeze-dried gamma-globulin formulations on the molecular weight of dextran.

PURPOSE: The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum gamma-globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. METHODS: The molecular mobility of freeze-dried BGG formulations containing dextrans of various molecular weights was determined based on the free induction decay of dextran and water protons measured by proton NMR. The protein stability of the formulations was determined at temperatures ranging from 20 to 70 degrees C by size exclusion chromatography. RESULTS: Changes in the molecular mobility of freeze-dried formulations that occurred at temperatures below the glass transition temperature could be detected as the molecular mobility-changing temperature (Tmc), at which dextran protons started to exhibit a Lorentzian relaxation decay due to higher mobility in addition to a Gaussian relaxation decay. Tmc increased as the molecular weight of dextran increased. The proportion of dextran protons which exhibited the higher mobility relaxation process (Phm) at temperatures above Tmc decreased as the molecular weight of dextran increased. Protein stability was closely related to molecular mobility. The temperature dependence of the denaturation rate changed at around Tmc, and denaturation in the microscopically liquidized state decreased as Phm decreased with increasing molecular weight of dextran. CONCLUSIONS: The effect of the molecular weight of dextran on the protein stability of freeze-dried BGG formulations could be explained in terms of the parameters obtained by 1H-NMR such as Tmc and Phm. These parameters appear to be useful in preformulation and stability prediction of freeze-dried formulations.

Calorimetry, Differential Scanning↗

PubMed1998

Covalent fixation of soluble derivatized dextrans to model proteins in low-concentration medium: application to factor IX and protein C.

Factor IX and protein C are zymogens implicated in blood clotting, and an increase in their plasmatic residence time would be of interest for the treatment of the disorders caused by their deficiency. In this context, the conjugation of these proteins to polymers such as modified dextrans could be used to approach the problem. Conjugate formation in concentrated medium ([protein] >50 g/L) is well documented, whereas drastic dilution ([protein] <1 g/L) is quite unfavorable. Before studying the binding of factor IX and protein C to polymers, the coupling of model proteins (human hemoglobin, Hb; human serum albumin, HSA) in low-concentration medium to benzenetetracarboxylate dextran (BTC-dextran) and dialdehyde dextran was investigated. To obtain soluble benzenetetracarboxylate dextran-based conjugates, the conditions of coupling were optimized; the use of sulfo-NHS was necessary to form a conjugate with benzenetetracarboxylate dextran. In fact, the O-acylurea intermediate formed between coupling agent [1-ethyl-3(3-dimethylaminopropyl) carbodiimide, EDC] and BTC-dextran must be stabilized. Concerning dialdehyde dextran, a more oxidized polymer and a higher pH of the buffer of coupling than for highly concentrated solution must be used to obtain a conjugate. Whatever polymer is used, HSA appeared clearly less reactive than Hb, which can be attributed to the better reactivity of N-terminal amino groups in this latter protein and to the marked affinity of benzenetetracarboxylate dextran for it. No soluble conjugate was formed between the same dextran derivatives and factor IX or protein C. Moreover, the activity of both coagulation factors was dramatically decreased by contact with EDC and glutaraldehyde, a small molecule. Thus, bad accessibility of protein amino groups is probably responsible for this lack of reactivity. Nevertheless, it could be shown that carboxylate and amino groups were essential to the activity of factor IX and protein C.

Blood Coagulation Factors↗

PubMed1980

Characterization of collagenous meshworks by volume exclusion of dextrans.

The volumes from which 3H-labelled dextrans are excluded by dermal collagenous fibres were calculated by dilution of dextran probes. Five dextrans, of average Stokes' radii 1.72, 2.53, 3.92, 4.54 and 14.24nm, were investigated at concentrations between 0.1 and 3% (w/w). The excluded volume was dependent on dextran concentration only for the two smaller probes. The largest dextran was shown not to bind to the fibres. A plot of the square root of excluded volume against Stokes' radius was linear for the four smallest dextrans, corresponding to the predictions of Ogston's [(1958) Trans. Faraday Soc. 54, 1754--1757] rod-and-sphere model of fibrous exclusion, and suggesting that dextrans of Stokes' radius between 1.72 and 4.54 nm were excluded by a cylindrical solid fibre of radius 2.90 +/- 0.72 nm. Larger molecules were excluded by a structure of much greater size, since the volume exclusion for the largest dextran was only slightly greater than that of the dextran less than one-third its radius. The excluded volume of 3H2O fell slightly below the line describing the dextran data, indicating that water had access to most of the volume not occupied by the collagenous fibres.

Chemical Phenomena↗

PubMed1998

Acute and chronic exposure of rat intestinal mucosa to dextran promotes SGLTI-mediated glucose transport.

BACKGROUND: The intestinal handling of dextran, an alpha-1,6-linked glucose polymer, is poor compared with starch, and some ingested dextran might therefore reach the lower small intestine. As luminal sugar up-regulates SGLT1 (sodium-dependent glucose transporter) locally, we report the effects of a dextran-enriched diet on jejunal and ileal brush border membrane (BBM) glucose uptake. METHODS: Rats were maintained on a diet containing 65% maltodextrin or 32.5% maltodextrin + 32.5% dextran (10 kD or 40 kD) for 8-10 days, and the kinetics of phlorizin-sensitive [3H]-glucose uptake by purified BBM vesicles was determined. RESULTS: Ingestion of 40-kD but not 10-kD dextran increased Vmax for jejunal and ileal glucose uptake (+64.3% and +61.8% respectively, both P < 0.02). The transport response to 40-kD dextran was in keeping with lower levels of expired H2 at the end of the feeding period. High-performance liquid chromatography (HPLC) analysis of luminal contents indicated extensive hydrolysis of ingested dextran. Finally, 3-h jejunal exposure to 40-kD dextran in vivo increased the Vmax for glucose uptake by jejunal BBM. CONCLUSION: It is likely that increased SGLT1-mediated glucose uptake after short or longer term mucosal exposure to dextran results from luminal dextran per se or a hydrolysis product. The clinical implications of this up-regulation are discussed.

Acute Disease↗

PubMed2000

Dextran reduces surfactant inhibition by meconium.

We have previously shown that an addition of dextran to surfactant increases resistance to inactivation by albumin. The present study was designed to investigate whether dextran has a protective effect against inactivation of surfactant by meconium. The dynamic surface properties of various mixtures of modified natural surfactant (Curosurf), meconium and dextran were evaluated with the pulsating bubble technique. In the absence of meconium, an addition of dextran at 10 mg ml(-1) significantly shortened the surface adsorption time of Curosurf suspended in normal saline at a concentration of 5 mg ml(-1) from 1.6+/-1.3 (mean +/- SD) sec to 0.4+/-0.4 sec (p < 0.05). Meconium at 5 mg ml(-1) increased the mean minimum surface tension (gammamin) after 3 min of pulsation from 2.1 mN m(-1) to 24 mN m(-1) (p < 0.05). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture significantly reduced the gammamin to 6.4+/-4.5 mN m(-1) and 2.6+/-5.6 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). Meconium also increased the maximum surface tension (gammamax) of Curosurf from about 33 mN m(-1) to 53 mN m(-1). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture reduced the gammamax to 41 and 39 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). There were significant negative correlations between dextran concentration and both gammamin and gammamax. We conclude that dextran reduces surfactant inhibition by meconium in a dose-dependent manner.

Adsorption↗

PubMed1993

Penetration and binding of epidermal growth factor-dextran conjugates in spheroids of human glioma origin.

Targeting with toxic EGF-based conjugates against tumour cells with amplified EGF-receptors might be a possible approach towards improved therapy of certain malignancies such as gliomas and squamous carcinomas. In this study, the penetration and binding of 125I delivered by EGF-dextran conjugates were analysed in cultured spheroids applied as a tumour nodule model. The spheroids consisted of human glioma cells, U-343MGaCl2:6, with large amounts of EGF-receptors. The penetration and binding patterns of 125I delivered by 125I-EGF and 125I-dextran were analysed for comparison. The EGF-dextran associated 125I-activity showed a rather slow penetration but after some hours significant amounts of radioactivity had reached the deeper regions and good penetration was obtained within 5 hours. The penetration seemed somewhat faster when the 125I-activity was delivered with EGF possibly dependent on the lower molecular weight allowing for faster diffusion. Furthermore, EGF-dextran associated 125I seemed to penetrate somewhat faster after the EGF-receptors were blocked with non-radioactive EGF, probably due to the lack of binding preventing free diffusion. After administration of 125I-EGF-dextran or 125I-EGF, the binding patterns were superimposed on the penetration patterns. In the penetration studies, the superimposed accumulations due to binding were removed by presaturation of the receptors with non-radioactive EGF. After a 1 hour incubation, binding of EGF-dextran associated 125I-activity could be seen only in an outer region, with an approximative thickness of 50 microns, of the viable cell layer. Extensive receptor specific binding in the deeper regions, at a depth of 100-200 microns, was seen after several hours incubation. In addition, low levels of non-specific binding in the central regions were seen when the 125I-activity was delivered with dextran without EGF. A similar low background binding was seen also in the centre of spheroids incubated with 125I-EGF-dextran or 125I-EGF after saturation of the receptors with non-radioactive EGF. However, the major amount of radioactivity delivered as 125I-EGF-dextran or 125I-EGF had a receptor specific binding and, also in inner regions, it could be displaced by non-radioactive EGF. Thus, EGF-dextran, which is a candidate compound for targeted therapy, allowed penetration of the applied radioactivity and binding could be observed, after some hours, also in the inner regions of the spheroids.

Dextrans↗

PubMed1986

Effectiveness of dextran 70 versus Ringer's acetate in traumatic shock and adult respiratory distress syndrome.

During a 3-yr period, 31 adult victims of severe traumatic shock were enrolled in a prospective randomized investigation of the relative effectiveness of dextran 70 vs. Ringer's acetate to treat shock and protect against trauma-induced adult respiratory distress syndrome (ARDS). Fourteen patients were given dextran 70 and Ringer's acetate to compensate for interstitial fluid loss, and whole blood as required; the remaining 17 patients received three to four times the total fluid volume of Ringer's acetate given in the former group, and whole blood as required. Hemodynamics improved significantly more rapidly in the dextran group. In the 7 to 8-day post-trauma period, no patient in the dextran group developed ARDS, compared to five cases of ARDS in the Ringer's acetate group. Also, the cardiac index of dextran patients was significantly higher, and patients challenged with 0.5 L of dextran 70 showed a significantly higher increase in cardiac index than those challenged with 2 L of Ringer's acetate. It is concluded that in the severely traumatized patient, a fluid program based on dextran 70 is superior to Ringer's acetate alone. Furthermore, patients should continue on a fluid program containing dextran 70 to counteract unrecognized hypovolemia. Our results support the assumption that early aggressive shock treatment with dextran 70, followed by continued dextran administration in the post-trauma period might prevent complications such as ARDS.

Accidents, Traffic↗