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PubMed2000

Pore structure analysis of swollen dextran-methacrylate hydrogels by SEM and mercury intrusion porosimetry.

The objectives of this study were to visually examine the surface and interior morphology of a new class of biodegradable hydrogels based on dextran-methacrylate and to quantify the porous structure of these hydrogels in swollen state. Two techniques (scanning electron microscopy and mercury intrusion porosimetry) were used to analyze pore structure of dextran-methacrylate hydrogels as a function of the degree of methacrylate substitution. SEM was used to observe 3-dimensional network structure of cryofixed and fractured swollen dextran-methacrylate hydrogels. Image analysis of the SEM data revealed different pore shapes and sizes, depending on the degree of substitution and the location within the hydrogel. A higher methacrylate-substituted dextran hydrogel showed a compact and rigid pore structure, while a lower substituted hydrogel showed a delicate and fragile pore structure. Mercury intrusion porosimetry analysis of the pore structure of dextran-methacrylate hydrogels provided useful and more reliable quantitative data of pore characteristics, such as total pore area, average pore diameter, their distribution, and bulk density. The total pore area and average pore diameter of swollen dextran-methacrylate hydrogels decreased with an increase in degree of methacrylate substitution, while bulk density increased with an increase in degree of substitution.

Biocompatible Materials↗
PubMed2000

Optimization of storage stability of lyophilized actin using combinations of disaccharides and dextran.

The storage stability of a dry protein depends on the structure of the dried protein, as well as on the storage temperature relative to the glass transition temperature of the dried preparation. Disaccharides are known to preserve the native conformation of a dried protein; however, the resulting T(g) of the sample may be too low ensure adequate storage stability. On the other hand, formulations dried with high molecular weight carbohydrates, such as dextran, have higher glass transition temperatures, but fail to preserve native protein conformation. We tested the hypothesis that optimizing both protein structure and T(g) by freeze-drying actin with mixtures of disaccharides and dextran would result in increased storage stability compared to actin dried with either disaccharide or dextran alone. Protein structure in the dried solid was analyzed immediately after lyophilization and after storage at elevated temperatures with infrared spectroscopy, and after rehydration by infrared and circular dichroism spectroscopy. Structural results were related to the polymerization activity recovered after rehydration. Degradation was noted with storage for formulations containing either sucrose, trehalose, or dextran alone. Slight increases in T(g) observed in trehalose formulations compared to sucrose formulations did not result in appreciable increases in storage stability. Addition of dextran to sucrose or trehalose increased formulation T(g) without affecting the capacity of the sugar to inhibit protein unfolding during lyophilization and resulted in improved storage stability. Also, dextran provides an excellent amorphous bulking agent, which can be lyophilized rapidly with formation of strong, elegant cake structure. These results suggest that the strategy of using a mixture of disaccharide and polymeric carbohydrates can optimize protein storage stability.

Actins↗
PubMed2001

Dextran reduces embolic signals after carotid endarterectomy.

One hundred fifty patients undergoing carotid endarterectomy were randomly assigned to receive intravenous 10% dextran 40 or placebo. Transcranial Doppler monitoring of the ipsilateral middle cerebral artery 0 to 1 hour postoperatively detected embolic signals in 57% of placebo and 42% of dextran patients, with overall embolic signal counts 46% less for dextran (p = 0.052). Two to 3 hours postoperatively, embolic signals were present in 45% of placebo and 27% of dextran patients, with embolic signal counts 64% less for dextran (p = 0.040). We conclude that dextran reduces embolic signals within 3 hours of CEA.

Aged↗
PubMed1984

Does dihydroergotamine potentiate the thromboprophylactic effect of dextran 70? A controlled prospective study in general and hip surgery.

In a prospective randomized controlled study on postoperative thromboembolism, 259 patients undergoing elective general surgery, emergency general surgery, total hip replacement or hip fracture surgery were given thromboembolic prophylaxis with either a combination of dextran 70 and dihydroergotamine (DHE) or with dextran 70 alone. 500 ml dextran 70 was infused twice on the day of operation, once on postoperative days 1 and 3, and also on day 5 if the patient was still confined to bed. 0.5 mg DHE was given s.c. twice daily starting before operation and continued for 3 or 5 postoperative days. In hip fracture patients prophylaxis was started as soon as the diagnosis was made. 500 ml dextran 70 was given every other day before operation. DHE was given twice daily if so indicated from randomization. The patients were screened for deep-vein thrombosis (DVT) with the 125I-labelled fibrinogen test for 8 days and followed for one month postoperatively. In hip fracture surgery the incidence of DVT was significantly reduced by the combination of dextran 70 and DHE compared to dextran 70 alone (1/32 vs. 11/36, P = 0.003). However, this synergistic effect of DHE could not be detected in the other patient groups. Fatal pulmonary embolism did not occur. No severe side effects attributable to prophylaxis were noted in either group.

Aged↗
PubMed2003

Capillary electrophoresis of proteins in dextran-coated columns.

A simple coating technique by using uncross-linked dextran has been developed for fused-silica capillaries to be used in capillary electrophoresis of basic proteins. The capillaries were first silanized with a heterobifunctional silane (gamma-aminopropyltriethoxylsilane), which served as a coupling agent between the capillary inner wall and the polysaccharide coating. Dextran of high molecular mass (about 70 kDa) was activated with 1,1'-carbonyldiimidazole. Then the activated dextran was coupled to the primary amino groups that were anchored onto the inner wall of the silanized capillaries. The residual reactive groups on the dextran were further substituted by neutral functions in a coupling reaction with excess ethanolamine. By using dimethyl sulfoxide (DMSO) rather than aqueous buffer as the reaction medium, the extent of substitution was improved by minimizing the residual reactive groups at the surface. Since they are ionogenic, the electrosmotic flow in the system is relatively low. The chemically bound dextran coating showed good reproducibility and stability. In electrophoretic experiments basic proteins were separated with high efficiency by use of the dextran-coated fused-silica capillary columns. The main advantage of the method described here is that both polysaccharide activation and amine-coupling reactions were carried out under mild conditions at room temperature without catalysts. For this reason, the method is recommended to coat the inner wall of microfluidic separation channels which would not tolerate a harsh treatment.

Dextrans↗
PubMed1989

Study of airway epithelial permeability with dextran.

We studied the penetration of fluorescein isothiocyanate (FITC) T-40 dextran into the paracellular spaces in the tracheal mucosa and its appearance in the blood plasma of guinea pigs exposed to cigarette smoke or (controls) breathing room air. Under general anesthesia, the dextran solution was instilled onto the tracheal surface via a tracheotomy tube, arterial blood was sampled serially for 40 min, and then the trachea was fixed by perfusion or immersion. Examination of the tracheal mucosa with light microscopy, with and without epifluorescence, and transmission electron microscopy, revealed dextran in the paracellular spaces in mucosa from experimental animals but not controls. In all control animals, the levels of the dextran in plasma was below the sensitivity of the assay. By contrast, dextran levels in the plasma from the experimental animals fell within the sensitivity range of the assay and increased in blood at a rate of 0.00125 +/- 0.00023 (SE) expressed as a percentage of the instilled dose/min. We conclude that FITC T-40 dextran provides a reliable, fairly simple, fast method for assessing major, but not subtle, changes in paracellular permeability of the tracheal mucosa.

Animals↗
PubMed1985

Macrophage activation by cross-linked dextran.

Cross-linked dextran (Sephadex) has been reported as an effective inducer of peritoneal exudates resulting in a large yield of macrophages after injection into mice, and macrophages obtained in this manner have been used for a variety of studies. We examined the possibility that cross-linked dextran not only induces peritoneal exudate but functions also as a macrophage activator. Following confirmation of a markedly increased yield of macrophages in Balb/c mice injected with preswollen Sephadex G-25 beads, glass adherence and migration in agarose of these macrophages were compared with the activities of cells isolated following the injection of saline, thioglycollate, or complete Freund's adjuvant (CFA). Dextran administration resulted in a significant increase in these activities in relation to saline and thioglycollate injections, and resembled CFA in the magnitude of its effect. Dextran-induced macrophages were then examined for activation as defined by nonspecific antitumor activity. Cells of a transplantable fibrosarcoma line and a urethane-induced primary lung adenoma served as targets. As compared with macrophages isolated from saline-injected mice, cells induced by Sephadex showed an approximately fivefold and twofold increase in activity against adenoma and fibrosarcoma targets, respectively. To examine the ability of Sephadex to induce macrophage antitumor activity in vitro, peritoneal macrophages were cultured in the presence of the dextran for 24 hours and tested against adenoma targets. The tumoricidal/static activity of such macrophages was significantly increased relative to controls and was nearly identical to the activity of macrophages induced by Sephadex in vivo. It is clear that cross-linked dextran in the form of Sephadex G-25 can function both as an inducer of peritoneal exudate and as an effective macrophage activator with regard to the activation criteria studied.

Adenoma↗
PubMed1979

Intravital and electron microscopic study of bradykinin-induced vascular permeability changes using FITC-dextran as a tracer.

Fluorescein-labelled dextran (FITC-dextran) of molecular weight 145,000 was used to study vascular permeability to macromolecules by intravital and electron microscopy. Anaesthetised hamsters prepared for intravital observation of the cheek pouch microvasculature were given an intravenous injection of FITC-dextran. Leakage of macromolecules was induced by topical application of bradykinin to the cheek pouch microvasculature and observed in fluorescent light. Leakages occurred only from postcapillary venules of a diameter well below 50 micrometer. The cheek pouch preparation was rapidly fixed by immersion and samples of tissue with intravitally identified leakages of FITC-dextran were studied by electron microscopy. FITC-dextran appeared as black precipitates in the vascular lumen and also outside the lumen in bradykinin-treated animals. In most animal; gaps were found between endothelial cells and these gaps contained dextran precipitates. The results support much other evidence that bradykinin induces macromolecular leakage by opening gaps between endothelial cells in postcapillary venules.

Animals↗
PubMed1997

In vitro study of the protective effect of trehalose and dextran during freezing of human red blood cells in liquid nitrogen.

Two nonpermeant cryoprotectants, the disaccharide trehalose and the polymeric carbohydrate (dextran, 40 kDa), were assessed as substitutes for glycerol in the cryopreservation of human red blood cells (RBC). The agents were evaluated by measuring the percentage of RBC recovery (total of free hemoglobin after freezing) and by evaluating the erythrocyte state after freezing. Ninety percent of the red cells were recovered after freezing in 30% (w/v) dextran in liquid nitrogen, which is very close to the recovery obtained in 35. 5% (w/v) glycerol (92%). The activities of pyruvate kinase and glucose-6-phosphate dehydrogenase of RBCs frozen and thawed with dextran were not modified, and the 2,3-diphosphoglycerate was reduced by 26%, but remained within normal values. ATP was reduced by 56%. The erythrocyte membrane integrity, evaluated by its osmotic fragility, was not altered, and the RBCs protected by dextran retained their normal discoid shape without the formation of microvesicles. The 24-h hemolysis of the washed red cells after storage at 4 degrees C was 7%. These results suggest that dextran protects red blood cells during freezing in liquid nitrogen, but that some effort is still needed to limit the drop of ATP concentration. One of the main advantages of dextran is that it does not penetrate the RBCs and requires less washing than glycerol.

Adenosine Triphosphate↗
PubMed1977

Studies on the kinetics and renal excretion of low and high molecular weight dextrans in preterm babies, newborns and young infants.

Administration of low and high molecular weight dextrans in the initial phase of shock is no longer controversial. The special conditions in newborns, however, have been insufficiently considered in planning therapy. This investigation aimed at determining the biological half-lives of dextran 40 (Rheomacrodex) and dextran 60 (Macrodex) in this age group. The half-life of dextran 40 was found to be 60 min and that of dextran 60 3 h. Preterm babies and newborns excrete up to 25% less dextran 40 and 60 in 24 h than infants and adults. Normal adult values for excretion are only reached towards the end of the first year of life.

Body Weight↗
PubMed1987

Haemodilution therapy in ischaemic stroke: plasma concentrations and plasma viscosity during long-term infusion of dextran 40 or hydroxyethyl starch 200/0.5.

In 21 patients with ischaemic strokes we have monitored plasma viscosity, total plasma concentration, numeric average molecular weight (Mn), and weight average molecular weight (Mw) of Dextran 40 (dextran) and hydroxyethylstarch 200/0.5 (HES) during 10 days of treatment (days 1-4, 2 X 500 ml; days 5-10, 1 X 500 ml). Plasma concentrations of dextran increased during the first 4 days (8.3 mg X ml-1 on the first day to 18.0 mg X ml-1 on the fifth day), reached an apparent steady state of 17.2 mg X ml-1 during the next 6 days, and declined subsequently with a half-time (t1/2) of 4.03 days. After ten days treatment Mn and Mw were shifted towards higher values. Plasma viscosity increased from 1.26 mPas to 1.69 mPas on Day 10 (p less than 0.01) and was linearly correlated with the total plasma concentration of dextran (p less than 0.001; r = 0.88). Total plasma concentrations of HES averaged 11.7 mg X ml-1 on Day 1 and 12.4 mg X ml-1 on Day 5. The molecular weight distribution did not change during the infusions but decreased in comparison with the administered solution. Plasma viscosity fell from 1.40 mPas to 1.30 mPas at Day 10 (p less than 0.05) and was not related to the concentration of HES. The haemodiluting effect, as indicated by a decrease of the haematocrit, was 22% and 16.8% for dextran and HES respectively. These data suggest several advantages of HES compared with dextran in haemodilution therapy of ischaemic stroke.

Aged↗
PubMed1975

Fluorescein labelled dextrans as tracers for vascular permeability studies in the nervous system.

Golden hamsters received i.v. injections of dextrans labelled with fluorescein isothiocyanate (FITC-Dextran). After 4 hrs samples from the cerebral hemispheres, Gasserian ganglia and sciatic nerves were fixed either by immersion in formalin or by cardiac perfusion with the same fixative. The distribution of the tracer was then studied by fluorescence microscopy of thin frozen sections. With this simple technique FITC-Dextrans could easily be detected in tissue sections. The tracers used (mol. w. 19000 and 154000) spread in the same way as fluorochrome-labelled albumin, remaining in the lumen of cerebral vessels but leaking extensively from vessels in the ganglia. FITC-Dextrans thus appear to be very useful tracers for vascular permeability studies of nervous tissue since dextrans can be obtained in a wide range of molecular weights. FITC-Dextrans can also be subjected to microscopic and quantitative studies.

Animals↗
PubMed1995

Fixation of various aldehydic dextrans onto human hemoglobin: study of conjugate stability.

Formation and stability of different aldehydic dextran-hemoglobin conjugates were studied. Two types of polymers were used: sulfated or unsulfated oxidized dextrans and 4-carboxamidobenzaldehyde dextran. Periodate-oxidized dextran forms imine and ketoamine linkages by reaction with hemoglobin and the obtained conjugates are not completely stable, as their molecular size increases with time or decreases after incubation with lysine. The sulfated conjugates are more sensitive to lysine action than the unsulfated ones, which is consistent with the decreased possibilities of Amadori rearrangement. Therefore, this proves the importance of ketoamines for ensuring the cohesion of oxidized dextran-based conjugates. Carboxamidobenzaldehyde dextran forms only imine linkages with hemoglobin and the corresponding conjugates possess a marked instability in the absence of reductive treatment. The different types of conjugates could be stabilized by a sodium borohydride treatment in a satisfying manner.

Benzaldehydes↗
PubMed1975

The response of the newborn rat to intraleural dextran: vascular and cellular aspects.

The development of hind paw oedema, in response to dextran injected in to the pleural cavity of rats, has been shown to differ with the age of rat studied. It was found that newborn rats were less responsive than adults, with respect to oedema formation induced by dextran. Attempts to suppress the dextran-indu.ced foot oedema using mepyramine and cyproheptadine, were successful only in rats from the adult age group. A semiquantitative analysis was made of the inflammatory cellular exudate produced by the intrapleural injection of dextran into rats of different ages. In contrast to the reaction of adult rats, it was found that accumulation of polymorphs in the pleura of newborn animals was delayed. The polymorph was the dominant cell type found in exudates induced either by intrapleural saline or dextran, in rats from the 6-hour age group. This contrasted strikingly with comparable exudates induced in adult rats, whose major cell type was the mononuclear cell (after saline), and the polymorph, followed by the mononuclear cell (after dextran). Fewer cells were observed in the reaction of 6-hour-old rats, compared with 7-day-old animals following intrapleural injection of the same volume of a 6-percent solution of dextran.

Aging↗
PubMed1994

Random-coil model for glomerular sieving of dextran.

Dextran has been the most commonly employed test molecule for probing the selectivity of glomerular filtration to macromolecules of varying size. The usual theories for hindered transport of solid spheres through pores have limited utility in interpreting clearance data for dextran or other linear polymers because such polymers in solution more closely resemble random, solvent-filled coils than solid spheres. To provide a model for glomerular filtration of random-coil macromolecules, the equilibrium partitioning of random coils between cylindrical pores and bulk solution was simulated using Monte Carlo calculations, and those results were combined with a hydrodynamic theory for restricted motion of solvent-filled polymer coils in pores. The rates of transport predicted for either neutral random coils or for solid spores of the same Stokes-Einstein radius were significantly lower than observed transport rates of dextran through the glomerular capillary wall or across synthetic porous membranes. This facilitation of dextran transport was modeled by postulating weak, attractive interactions between dextran monomers and the pore wall. The random-coil model with attractive interactions, modeled using a short-range, square-well potential, was found to adequately represent dextran sieving data in normal rats. Various limitations of this approach are discussed.

Animals↗
PubMed1999

The value of dextran 12,000 in ischemically damaged canine kidneys during machine perfusion.

The use of non-heartbeating (NHB) donor kidneys has led to the search for new methods of viability-testing. We investigated, in a canine model, the relationship between the filtration of dextran 12, 000 into urine and a certain period of warm ischemic time (WIT) during machine perfusion. Twenty-four canine kidneys were divided into three groups, sustaining 0 min, 30 min or 60 min of WIT. After cooling and flushing, the kidneys were perfused on a perfusion machine for 8 h. Three hundred milligrams of dextran 12,000 was added to the perfusate. In the perfusate, dextran and lactate dehydrogenase (LDH) concentrations were measured. Dextran concentrations were also analysed in urine. Intrarenal vascular resistance (IRR) was calculated from pressure and flow characteristics. The 30WIT group showed a higher dextran excretion rate than the other two groups. IRR and LDH measurements showed lower levels in the ischemic groups compared with the control group. Dextran 12,000 is not suitable as a viability test but does show interesting results regarding the low LDH and IRR levels in the ischemic groups.

Animals↗
PubMed1997

Stabilization of Escherichia coli penicillin G acylase against thermal inactivation by cross-linking with dextran dialdehyde polymers.

The thermostabilization of penicillin G acylase (PGA) obtained from a mutant of Escherichia coli ATCC 11,105 by cross-linking with dextran dialdehyde molecules, at a molecular mass of 11,500, 37,700 and 71,000 Da, was studied. The thermal inactivation mechanisms of the native and modified PGA were both considered to obey first-order inactivation kinetics during prolonged heat treatment, forming fully active but temperature-sensitive transient states. The highest enhancement to the thermostability of PGA was obtained using dextran-71000-dialdehyde modification, as a nearly ninefold increase at temperatures above 50 degrees C. The modification of PGA by dextran-11500-dialdehyde resulted in a considerable reduction of the Vm and Km parameters of the enzyme. However, other dextran dialdehyde derivatives used for modification did not cause a meaningful change in either Vm and Km. Modification by dextran dialdehyde derivatives did not result in significant change to either the optimal temperature or the activation energy of PGA. All modified PGA preparations showed lower inactivation rate constants but higher half-lives for inactivation than those of the native PGA at all temperatures studied. As indicated by the half-life times and Ki values, dextran 71000-dialdehyde was found to be more effective at cross-linking in the thermo-stabilization of PGA than any other agent studied in this work.

Dextrans↗
PubMed2005

The effect of maltose on dextran yield and molecular weight distribution.

Dextran synthesis has been studied since the Second World War, when it was used as blood plasma expander. This polysaccharide composed of glucose units is linked by an alpha-1,6-glucosidic bond. Dextransucrase is a bacterial extra cellular enzyme, which promotes the dextran synthesis from sucrose. When, besides sucrose, another substrate (acceptor) is also present in the reactor, oligosaccharides are produced and part of the glucosyl moieties from glucose is consumed to form these acceptor products, decreasing the dextran yield. Although dextran enzymatic synthesis has been extensively studied, there are few published studies regarding its molecular weight distribution. In this work, the effect of maltose on yield and dextran molecular weight synthesized using dextransucrase from Leuconostoc mesenteroides B512F, was investigated. According to the obtained results, maltose is not able to control and reduce dextran molecular weight distribution and synthesis carried out with or without maltose presented the same molecular weight distribution profile.

Dextrans↗