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PubMed2004

Optimisation of selectivity in the separation of aromatic amino acid enantiomers using sulfated beta-cyclodextrin and dextran sulfate as pseudostationary phases.

Control of selectivity in the enantiomeric separation of three aromatic amino acids (phenylalanine, tyrosine and tryptophan) was demonstrated utilising two separate electrolyte additives. Sulfated-beta-cyclodextrin (s-beta-CD) was chosen as the chiral selector while the addition of dextran sulfate provided a means with which to predictably fine-tune separation selectivity. The two additives were found to interact independently with the amino acids, with the s-CD providing chiral interactions while the dextran sulfate provided ion-exchange (IE) interactions. The system was also very robust with reproducibility of migration times being < 2.0% RSD between runs and < 2.6% on using a new capillary. A physical model derived from first principles was also successfully used to describe the two additive system. The model accurately described the observed separations over the range of 0-20 mM s-beta-CD and 0-1% dextran sulfate with a correlation coefficient of 0.998 between predicted and observed mobilities. The physical model also provided useful information about the system including association constants between the analytes and the pseudostationary phases, together with the mobilities of the associated complexes (analyte-cyclodextrin and analyte-dextran sulfate). Selectivity optimisation was achieved using the normalised resolution product and minimum resolution criteria. The physical model also allowed a desired separation selectivity to be obtained, such that experimental conditions could be predicted to lead to a particular migration order.

Amino Acids, Aromatic↗
PubMed2005

Controlled release of EGF and bFGF from dextran hydrogels in vitro and in vivo.

In the present study, dextran-epichlorohydrin hydrogels were employed as carriers for the controlled release of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). The hydrogels were synthesized from 50% (by weight) monomeric cross-linker, epichlorohydrin, containing dextran mixtures by intermolecular side-chain reaction of dextran-hydroxyl groups with epichlorohydrin-epoxy groups. The hydrogel disks of 3-mm diameter and 1.5-mm thickness have a high swelling capacity (EWC = 650%) and enough mechanical stability for the studies in vivo. Impregnation of EGF and bFGF into the dried hydrogels was carried out by use of phosphate buffered saline solution (PBS, pH = 7.4) containing 0.5 microg mL(-1) EGF and 0.1 microg mL(-1) bFGF, respectively. The in vitro release of growth factors was detected by fluorescence spectroscopy. The prolonged release of EGF is continued up to the 14th day, in comparison with a 26-day release of bFGF. The in vivo studies were realized with subcutaneously implanted hydrogels in Wistar albino rats. The rate of neovascularization was analyzed statistically using one-way analysis of significance with EGF and bFGF incorporated hydrogels. In conclusion, dextran-epichlorohydrin hydrogels were shown to be an alternative delivery system for the release of growth factors.

Animals↗
PubMed2004

The molecular formula and proposed structure of the iron-dextran complex, imferon.

The first iron-dextran complex was discovered in 1953, when we attempted to synthesize an analog of ferritin, by substituting polysaccharide for its protein shell. This new complex soon became the most widely used parental therapy for hypochromic anemia in humans. No molecular formula has been proposed, but Cox has attributed an outline structure to it. The present article proposes a structure greatly different from the Cox model, by having a polynuclear beta-ferric oxyhydroxide core, closely similar or identical to Akaganeite, chelated firmly by an encircling framework of dextran gluconic acid chains and surrounded by a removable outer sheath of colloidal dextran gluconic acid. The molecular weight of the iron-dextran core molecule, including its chelated framework, has been determined by gel filtration and analysis and its molecular formula (1.3) calculated. Also, these new data and existing electron photomicrographic, X-ray diffraction and crystallographic studies, have enabled a molecular weight, formula, and model structure to be proposed for its complex (2), which includes the outer sheath. The 480 iron atoms in both the core molecule and its sheathed complex are close to the number calculated from the core's unit cell dimensions and volume.

Chemistry, Pharmaceutical↗
PubMed2005

Effect of polymer size and cosolutes on phase separation of poly(vinylpyrrolidone) (PVP) and dextran in frozen solutions.

The aim of this study was to elucidate the effect of the molecular weight of polymers on their miscibility in frozen solutions to model the physical properties of freeze-dried pharmaceutical formulations. Thermal analysis of frozen solutions containing poly(vinylpyrrolidone) (PVP) and dextran of various molecular weights was performed at polymer concentrations below the binodal curve at room temperature. Frozen solutions containing PVP 29,000 and dextran 10,200 showed two thermal transitions (glass transition temperature of maximally freeze-concentrated solution: Tg') representing two freeze-concentrated amorphous phases, each containing predominantly one of the polymers. A combination of smaller polymers (PVP 10,000 and dextran 1,060) was freeze-concentrated into an amorphous mixture phase across a wide range of concentration ratios. Combinations of intermediate size polymers separated into two freeze-concentrated phases only at certain concentration ratios. Addition of NaCl prevented the phase separation of PVP and dextran in the aqueous and frozen solutions. Higher concentrations of NaCl were required to retain the miscibility of larger polymer combinations in the freeze-concentrate. The molecular weights of the component polymers, polymer concentration ratio, and cosolute composition are the important factors that determine component miscibility in frozen solutions.

Calorimetry, Differential Scanning↗
PubMed1994

Molecular weight dependent tissue accumulation of dextrans: in vivo studies in rats.

The effects of molecular weight (M(r)) on the serum and urine pharmacokinetics and tissue distribution of dextrans, potential macromolecular carriers for drug delivery, were studied in rats. A single 5 mg/kg dose of fluorescein-labeled dextrans (FDs) with a M(r) of 4000 (FD-4), 20,000 (FD-20), 70,000 (FD-70), or 150,000 (FD-150) was administered into the tail vein of separate groups of rats. At different times after the administration of each FD, animals were sacrificed, and blood, urine, and various tissues were obtained. The concentrations of FDs in the samples were subsequently determined by using a sensitive and specific high performance size exclusions chromatographic method. Among the tissues studied, high accumulation of dextrans was found only in the liver (liver:serum AUC ratios < or = 29) and spleen (spleen:serum AUC ratios < or = 10), with high concentrations in these tissues persisting even at the last sampling time (96 h). In contrast, the serum concentrations of the studied FDs were not measurable beyond 12 h. The serum and urine kinetics and the liver, spleen, and kidney accumulation of FDs demonstrated a significant degree of M(r) dependency. The total and renal clearance of FDs consistently decreased with an increase in M(r). However, the effects of M(r) on the tissue accumulation of dextrans was tissue dependent. For the liver, the tissue:serum AUC ratios increased from 0.346 for FD-4 to 15.2 for FD-20 and 28.8 for FD-70, while a further increase in M(r) to 150 kDa (FD-150) resulted in lowering the ratio to 8.59 in this tissue. For the spleen, the ratios increased from 0.095 for FD-4 to 9.56 for FD-150.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

NMR studies on water and polymer diffusion in dextran gels. Influence of potassium ions on microstructure formation and gelation mechanism.

At room temperature aqueous solutions of dextrans with concentrations > 25% (w/w) exhibit a sol-gel transition in the presence of > 1.0 M potassium chloride. In dextrans the gelation was unexpected due to missing anionic groups that usually provide the binding sites for cations. The quantitative investigation of the gel formation is based on changes of the diffusibility of water and dextran chains. The apparent diffusion coefficients of bulk water (in the order of 10(-6) cm2/s) and of water trapped in the junction zones as well as of polymer chains (in the order of 10(-7) to 10(-8) cm2/s) are determined by employing pulsed field gradient stimulated echo (PFGSTE) NMR. The restricted diffusion of bulk water in viscous sols and in soft and rigid gels has been quantitatively analyzed providing data for interbarrier distances (pore size), permeabilities of the diffusion barriers (density of junction zones) and interbarrier diffusion coefficients of water. Based on already published x-ray structure data and in accordance with the diffusion data presented in this paper "potassium-bonding" is assumed to be the most important interaction for the formation of a microstructure and for the stabilization of cross-links. The ionic radius of the potassium ion perfectly fits to the cage established by six oxygen atoms of glucose units of three polymer chains. Other cations, such as Li+, Na+, Rb+ and Cs+, according to their nonfitting ionic radii, do not provoke dextran gelation under these conditions. The mechanism of the transitions from sol to soft gel and further to rigid gel is discussed on the basis of restricted diffusion and x-ray structure data.

Dextrans↗
PubMed1996

Dynamic electron spin resonance (ESR) imaging of the distribution of spin labeled dextran in a mouse.

The nitroxide group 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) was covalently bound to a dextran via an N-acetamido linkage to produce a novel spin probe, TEMPO-dextran (TEMPO-DX), which circulates for long time periods in an animal without metabolic degradation. TEMPO-DX was stable in mice, while small TEMPO analogs quickly disappeared after administration. Since dextran was reduced somewhat in size during synthesis, the resultant spin-labeled dextran could be excreted through the kidney. A strong L-band electron spin resonance signal was obtained shortly after intravenous administration of TEMPO-DX into the tail vein of a mouse, from which three-dimensional images of specific organs were calculated. The signal was found to persist for well over 1 h.

Animals↗
PubMed1997

Quantitation of the Escherichia coli methionine repressor-operator interaction by surface plasmon resonance is not affected by the presence of a dextran matrix.

The effect of a dextran matrix on the apparent rate constants measured for the interaction of the Escherichia coli methionine repressor, MetJ, with its immobilized consensus operator has been studied using surface plasmon resonance (SPR) in a commercial biosensor, BIACORE (Biacore AB). Based on the results of computer simulations, it has been proposed that such data can deviate from the expected simple kinetic behavior due to effects generated by the dextran matrix, used at the biosensor surface to anchor one of the interacting molecules. We have tested this possibility experimentally by measuring the apparent rate constants for the interaction of MetJ with its operator DNA on sensor chip surfaces with no dextran matrix or having matrices 30 or 100 nm thick. The data show that for the MetJ-operator interaction, the dextran matrix has no significant effect on the apparent rate constants measured and that comparative measurements using this technique are informative.

Bacterial Proteins↗
PubMed2000

Characterization of the surfaces generated by liposome binding to the modified dextran matrix of a surface plasmon resonance sensor chip.

The dextran matrix of a surface plasmon resonance (SPR) sensor chip modified with hydrophobic residues (BIAcore sensor chip L1) provides an ideal substrate for liposome adsorption. Liposomes of different lipid compositions are captured on the sensor chips by inserting these residues into the liposome membrane, thereby generating stable lipid surfaces. To gain a more detailed understanding of these surfaces, and to prove whether the liposomes stay on the matrix as single particles or form a continuous lipid layer by liposome fusion, we have investigated these materials, using atomic force microscopy (AFM) and fluorescence microscopy. Force measurements with AFM probes functionalized with bovine serum albumin (BSA) were employed to recognize liposome adsorption. Analysis of the maximal adhesive force and adhesion energy reveals a stronger interaction between BSA and the dextran matrix compared to the lipid-covered surfaces. Images generated using BSA-coated AFM tips indicated a complete and homogeneous coverage of the surface by phospholipid. Single liposomes could not be detected even at lower lipid concentrations, indicating that the liposomes fuse and form a lipid bilayer on the dextran matrix. Experiments with fluorescently labeled liposomes concurred with the AFM studies. Surfaces incubated with liposomes loaded with TRITC-labeled dextran showed no fluorescence, indicating a complete release of the encapsulated dye. In contrast, surfaces incubated with liposomes containing a fluorescently labeled lipid showed fluorescence.

Animals↗
PubMed1997

Vitrification properties of solutions of ethylene glycol in saline containing PVP, Ficoll, or dextran.

Vitrification solutions which are used for cells or embryos generally contain cryoprotectant, physiological saline, and one or more macromolecular solutes. The macromolecules modify the vitrification tendencies of these solutions, but there is little detailed information on the vitrification properties of ethylene glycol solutions containing the additives PVP, Ficoll, and dextran. This study therefore added ethylene glycol to 0.9% NaCl in water (saline) and used differential scanning calorimetry to determine the lowest concentration at which the solution would remain vitreous when a warming rate of 10 degrees C/min was used. In the absence of other additives 59 wt% ethylene glycol (EG) in saline formed a stable glass. When ethylene glycol was replaced by the polymers Ficoll and/or dextran on a weight for weight basis, the resulting solution vitrified less readily than an EG-saline solution even though the total solute concentration was kept constant. The total solute concentration required to form a stable vitreous solution increased as the Ficoll 70,000 and 400,000 MW or dextran 78,000 MW content increased (5, 10, and 20 wt%). Ficoll and dextran had little or no effect on the glass transition and melting points of the solutions. In the presence of PVP vitrification occurred at a total solute concentration of 59 wt% (PVP 360,000 MW) or 60 wt% (PVP 40,000 MW) for all three tested PVP concentrations (5, 10, and 20 wt%). Although this indicates that PVP and EG have comparable vitrification properties, the melting and the glass transition temperature of the solutions rose as the PVP content increased. When 1 m sucrose was added to saline and 0, 5, 10, or 20 wt% PVP 40,000 MW vitrification was achieved with 31, 26, 23, and 15% EG, respectively, indicating that the total solute concentration required for vitrification could be estimated with reasonable accuracy from the sum of the individual components. We conclude that the tested polymers differ in how they interact with ethylene glycol-based vitrification solutions.

Calorimetry, Differential Scanning↗
PubMed2001

Corneal cryopreservation with dextran.

Different methods of corneal cryopreservation have been introduced, those employing intracellular cryoprotectants such as Me2SO or glycerol being the most widely favored. We investigated the influence of several freeze-thaw trauma variables on the survival of porcine endothelial monolayers when employing the extracellular cryoprotective agent dextran. We first examined the effects of various dextran concentrations and then, having ascertained the optimal concentration, further investigated the influence of fetal calf serum (FCS) concentration in the cryopreservation medium, the cooling rate, the thawing temperature, and the length of the preincubation in the freezing medium prior to cryopreservation. The numerical densities of endothelial cells were determined at dissection in hypoosmotic balanced salt solution and after organ culture by staining with alizarin red S and trypan blue. Morphological evaluation was not performed directly after thawing but after a subsequent organ culture at 37 degrees C to detect latent cell damage after freeze-thaw trauma. Our data revealed that corneas cryopreserved in minimal essential medium containing 10% dextran but lacking FCS, preincubated for 3 h, frozen at a cooling rate of 1 degrees C/min, and thawed at 37 degrees C incurred the lowest cell losses (22.4%, SD +/- 3.8). We conclude that dextran is an effective cryoprotectant for freezing of porcine corneas. However, variations between species in the results of cryopreservation require further investigation of an in vivo animal model and studies with human corneas before its clinical use can be recommended.

Animals↗
PubMed1992

Effects of EGF-dextran-tyrosine-131I conjugates on the clonogenic survival of cultured glioma cells.

Epidermal growth factor, EGF, and 131I or 125I-labelled tyrosine were conjugated to the sugar polymer dextran. The conjugates bound to EGF-receptor rich human glioma cells in culture and the binding was mainly receptor specific because cells presaturated with nonradioactive EGF gave strongly reduced binding. The 131I labelled conjugates were used in tests on cellular retention and therapeutical effects. 131I activity delivered to the cells as EGF-dextran-tyrosine-131I remained cell-associated for much longer periods of time than 131I activity delivered by only EGF. The amount of cell-associated 131I activity was nearly constant for up to 25 hours. The 131I labelled conjugate gave, after a one hour incubation period for binding followed by a 25 hour incubation in nonradioactive medium, a good therapeutical effect. This effect, which corresponded to about 3.0 Gy of external 60Co radiation, was due to the specifically bound 131I. The comparatively small effects of nonbound 131I in the culture medium, present only during the first incubation hour, were measured in control experiments with presaturated receptors and were corrected for in the evaluation of the EGF-receptor mediated effects. Control experiments showed that neither nonradioactive EGF nor non-radioactive EGF-dextran conjugates gave measurable effects on clonogenic growth. The results obtained were promising and the possibilities to use EGF-dextran conjugates for therapy should be further examined.

Brain Neoplasms↗
PubMed1989

A controlled study of Dextran 40: effect on cerebral blood flow and metabolic rates in acute head trauma.

A controlled double-blind evaluation of the effects of Dextran 40 at different concentrations on cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2) and cerebral lactate production (CMRLact) was carried out. We studied 40 patients in coma due to recent head injury. Concentrations of Dextran solution were not significantly related to variations in CBF and metabolic rate over the period of infusion. The lack of effect of the Dextran infusion may be explained by the absence of global brain ischemia in these patients at the time of the study. The very low initial CBF values were a consequence of brain metabolic depression and not a sign of global ischaemia. The rheological benefits of treatment with Dextran 40 in head injured patients should preferably be investigated using techniques which permit detection of local changes in CBF and metabolism.

Adolescent↗
PubMed1996

A novel dextran 40-based preservation solution.

Although the University of Wisconsin (UW) solution has become the standard solution for the preservation of kidneys for transplantation, the importance of the colloid hydroxyethylstarch (HES), one of the key compounds of the UW solution, has been questioned repeatedly. It is now established that HES is not necessary for routine kidney preservation. However, colloids may still be advantageous in UW like solutions for the purpose of multiorgan procurements and the preservation of organs from marginal donors. It has been shown in various experimental models that dextran 40 may successfully substitute for HES. Dextran 40 is not only cheaper but also has a variety of biological effects that may be beneficial during the graft reperfusion phase. The aim of this clinical study was to examine the efficacy of a dextran 40-based preservation solution (Dex-PS) for its use in human kidney graft preservation and to compare the transplantation results with kidneys preserved with UW solution. A total of 87 kidneys were preserved with Dex-PS and matched with 87 kidneys preserved with UW solution. Both groups were comparable in terms of donor and recipient characteristics and both had a high proportion of kidneys from nonheart-beating donors. Patient survival and graft survival after 1 year were 95% and 86% for the Dex-PS group and 94% and 90% for the UW group, respectively (P = NS). Primary nonfunction, delayed graft function, postoperative need for dialysis, and follow-up of serum creatinine were statistically comparable between these two groups. We conclude that dextran 40 can safely replace HES in UW solution for the purpose of clinical kidney preservation. There were no statistically detectable differences in graft performance between the kidneys preserved with UW and those preserved with Dex-PS.

Adenosine↗
PubMed1993

Influence of dextrans on platelet distribution in arterioles and venules.

Dextrans bind to the surface of platelets, red blood cells and endothelium. We investigated whether a low doses (30 mg/kg IV) of 40-kDa (Dx40), neutral, 500-kDa (Dx500) or sulphated, 500-kDa (Dx500S) dextrans influence platelet distribution in rabbit mesenteric arterioles and venules (diameter 17-33 microns). Intravital fluorescence videomicroscopy was used to visualize platelets labelled in vivo with acridine red. Their concentration distribution determined within a thin optical section about the median vessel plane was expressed relative to the mean concentration in that vessel. In arterioles, Dx500 and Dx500S increased the relative platelet concentration in the centre [radial position (R): 0.0-0.4 R] from 0.60 to 1.07 (P < 0.001) and 1.20 (P < 0.003), and reduced it near the wall (0.8-0.9 R) from 1.59 to 0.93 (P < 0.02) and 0.95 (P < 0.03) respectively. In venules a similar, but non-significant, effect was observed. Dx40 did not change platelet distribution in arterioles, but decreased their concentration in venules in the centre from 1.08 to 0.71 (P < 0.03) and increased it at the wall from 0.89 to 1.27 (P < 0.04). The deformability of red blood cells was unchanged, but their aggregation tendency increased approximately two-fold after Dx500 and Dx500S injection, while Dx40 had no influence. Leucocyte margination in venules did not affect platelet distribution. Dextran injection did not change microvascular flow velocity or plasma viscosity, suggesting that the observed changes in arteriolar platelet distribution were caused by binding of dextran to the surface of platelets and/or red blood cells.

Animals↗
PubMed1981

FITC-dextran tracers in microcirculatory and permeability studies using combined fluorescence stereo microscopy, fluorescence light microscopy and electron microscopy.

Coupling fluorescein-isothiocyanate to dextrans (FITC-D) extends the usefulness of the dextrans as electron microscopic tracer particles by permitting preceding fluorescence stereo microscopy and high-power light microscopy of the tissue specimens. The fate of the tracer may thus be studied in vivo during the experiment, during fixation, and during the succeeding tissue processing. A study of some simple physicochemical characteristics of the tracer, and the influence, if any, of the fixing agent are also made possible. FITC-D was found to be uncharged in the pH range from 6.5 to 8.5, more rapidly precipitated by acetone than by alcohol, and to react with glutaraldehyde and osmium tetroxide in an unknown way during tissue fixation. FITC-D with molecular weights 70,000 and 150,000 showed no signs of diffusion during tissue preparation with the methods reported in the paper, whereas FITC-D 40,000 did so to a slight degree, when the tissue was kept for several days in the fixative vehicle. Securing the preservation of the lower molecular weight FITC-Ds during tissue fixation and preparation is more difficult and the described methods are not adequate. Dextrans provoke an anaphylactic reaction in most rat strains, but are well tolerated by Wistar Furth rats. The introduction of FITC into the dextran molecule might alter the biological reactions, but was also well tolerated by Wistar Furth rats. Combined fluorescence stereo microscopy, fluorescence microscopy of sections, light microscopy of strained sections and electron microscopy made it possible to follow a particular microcirculatory area, selected in vivo, to the final study in the electron microscope.

Animals↗
PubMed1979

Effect of metabolic regulation on renal leakiness to dextran molecules in short-term insulin-dependent diabetics.

Renal clearance of dextran of two ranges of molecular size and glomerular filtration rate (GFR, 51Cr-EDTA) were measured in seven short-term insulin-dependent diabetics (mean age 25 years). Measurements were carried out in the same patient during good and poor metabolic regulation (plasma glucose, mean +/- SEM, 6.5 +/- 0.9 and 14.8 +/- 1.5 mmol/l, respectively). GFR was elevated in all patients during poor metabolic regulation (119 +/- 6 ml/min/1.73 m2, versus 99 +/- 2 ml/min/1.73 m2 during good control, p less than 0.01). The average renal clearance of dextran with molecular weights ranging from 25,000 to 35,000 and 35,000 to 45,000 increased during poor metabolic regulation from 14.8 +/- 0.8 to 19.8 +/- 1.8 ml/min/1.73 m2, and 5.2 +/- 0.3 to 6.8 +/- 0.6 ml/min/1.73 m2, respectively (p less than 0.05). The elevated GFR and renal dextran clearance found during poor metabolic regulation were normalized within one to three weeks of effective insulin treatment. This rapid reversibility can hardly be explained by the previously demonstrated enlargement in glomerular size and filtration surface area, since these alterations remain unchanged after more than one month of insulin treatment. The metabolic regulation did not influence the size-selective properties of the glomerular wall. Therefore, we suggest that the dominating mechanism involved in the GFR and renal dextran clearance alterations is functional, viz. increased filtration pressure.

Adolescent↗
PubMed1992

Dextran administration avoids hemodynamic changes following paracentesis in cirrhotic patients. A safe and inexpensive option.

Paracentesis associated with albumin administration has been shown to be a safe and useful procedure in the treatment of patients with cirrhosis and ascites. Given the high cost of albumin, 20 patients with cirrhosis and ascites were treated in an open study, with daily paracentesis using dextran 70, an inexpensive volume expander, instead of albumin. In the first 10 patients, hemodynamic evaluation was performed in basal conditions, after each paracentesis (5 liter), and after dextran infusion. Twelve hours after each paracentesis without expansion, a significant drop in pulmonary capillary wedge pressure from 9.5 +/- 1.0 to 7.1 +/- 1.7 (P less than 0.01) and a reduction in cardiac output from 6.6 +/- 1.0 to 5.0 +/- 1.9 (NS) were observed. Moreover, the hematocrit rose significantly from 36.8 +/- 5.6 to 39.2 +/- 4.8 (P less than 0.01). These parameters returned to baseline values after the administration of 84 +/- 14 ml of dextran 70 for each 1000 ml of ascites removed. The other 10 patients received dextran 70 simultaneously with the paracentesis without hemodynamic control. No significant changes in renal and hepatic functions were observed at the end of the study. The mean volume of ascites removed was 12.3 +/- 4.6 liter. Two patients developed hyponatremia that required no treatment. No patient developed renal failure. One patient died because of gastrointestinal bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗