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PubMed1979

Dextran 40-containing incubation media: effect on lens electrolyte and water balance.

The effect of dextran 40 on lens swelling and electrolyte balance in lenses stressed by incubation in Ca++-free media was studied. Dextran 40 substantially inhibited lens swelling, Na+ gain, and K+ loss caused by six-hour incubation in Ca++-free media. After an additional 12-hour incubation in Ca++-enriched media, the water and electrolyte balance in the dextran 40-incubated group was essentially the same as that of lenses that were never exposed to a Ca++-free media. Those lenses that were not incubated in dextran 40 demonstrated significant residual lens swelling and electrolyte imbalance. It is concluded that dextran 40, by virtue of its oncotic effect, inhibits colloidal osmotic swelling and exerts a protective effect on lens function under a stress situation.

Animals↗

PubMed1975

Survivor's and nonsurvivors' responses to dextran 40. Hemodynamic and oxygen transport changes in critically ill patients.

Cardiorespiratory effects of dextran 40 administration were measured and compared retrospectively in 74 surviving and 73 nonsurviving critically ill patients. In the preinfusion control period, the survivors had higher mean arterial pressures and blood flow with lesser blood volume deficits. Dextran significantly improved pressure, blood flow, blood volume, oxygen transport, and derived calculations in both groups, but the average cardiorespiratory responses to dextran were somewhat greater in nonsurvivors than in survivors, About two thirds of the patients responded to dextran with significantly increased oxygen consumption (P smaller than .05), suggesting that this agent improved oxygen transport by its rheologic effects on the microcirculation. The cardiorespiratory effects of dextran were slightly greater in the patients who ultimately died; nevertheless, the salutary cardiorespiratory response did not reverse the clinical course in nonsurvivors, whose perfusion defect apparently had reached irreversible proportions prior to the administration of the drug.

Acid-Base Equilibrium↗

PubMed1993

A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride. The effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients.

OBJECTIVE: To evaluate the use of 250 mL of a 7.5% sodium chloride solution, both with and without added dextran 70, for the prehospital resuscitation of hypotensive trauma patients. DESIGN: Double-blind randomized trial. SETTING: Six trauma systems served by helicopter transport. PATIENTS: Injured patients with systolic blood pressures less than 90 mm Hg at any time in the field or during helicopter transport. INTERVENTIONS: Infusion of study solution, in the field or during transport, followed by conventional isotonic solutions as needed. Solutions studied in four cohorts were as follows: (1) lactated Ringer's; (2) 7.5% sodium chloride (hypertonic saline); (3) 7.5% sodium chloride combined with 6% dextran 70; and (4) 7.5% sodium chloride combined with 12% dextran 70. MAIN OUTCOME MEASURES: Blood pressure response; survival to time of hospital discharge among the treatment groups; and survival compared with that predicted by norms from the Major Trauma Outcome Study (MTOS). RESULTS: The mean (+/- SD) change in systolic blood pressure on arrival in the emergency department was significantly higher in the hypertonic saline solution group than that in the lactated Ringer's solution group (34 +/- 46 vs 11 +/- 49 mm Hg, P < .03). Overall survival in the four treatment groups was 49%, 60%, 56%, and 45% (not statistically significant). Survival in the hypertonic saline solution group, however, was significantly higher than that predicted by the MTOS norms (60% vs 48%, P < .001). Survival to hospital discharge in patients with baseline Glasgow Coma Scale scores of 8 or less was correlated with treatment group (P < .05 by logistic regression and P < .01 by Cox proportional-hazards analysis; with survival in the hypertonic saline solution group [34%] vs lactated Ringer's solution group [12%]). CONCLUSIONS: Prehospital infusion of 250 mL of 7.5% sodium chloride is associated with an increase in blood pressure and an increase in survival to hospital discharge compared with survival predicted by the MTOS norms. Patients with low baseline Glasgow Coma Scale scores seem to benefit the most from 7.5% sodium chloride resuscitation. Hypertonic saline solution without added dextran 70 is as effective as the more expensive solutions that contain dextran 70.

Adolescent↗

PubMed1996

Hapten resistant dextran induced ARDS reaction following intracoronary stent deployment.

A case of dextran induced adult respiratory distress syndrome is used to illustrate the most serious complication of dextran usage during intracoronary stent placement. This reaction occurred despite premedication with the hapten dextran 1. Mechanisms of dextran induced complications are discussed. A mechanism for hapten resistant dextran reactions is postulated. Suggestions to prevent such reactions are made.

Anticoagulants↗

PubMed1999

Carboxymethyl benzylamide sulfonate dextrans (CMDBS), a family of biospecific polymers endowed with numerous biological properties: a review.

The functionalized dextrans termed carboxymethyl benzylamide sulfonate dextran (CMDBS) represent a family encompassing a wide range of polymers. These soluble macromolecular compounds, which are substituted with specific chemical functional groups, are designed to interact with living systems. By analogy with glycosaminoglycan heparin, a natural highly charged anionic polysaccharide that exerts a variety of biological effects, we postulated that CMDBS compounds also possess binding sites capable of specific interactions with biological constituents, depending on the overall composition of the polymer. The synthesis and heparin-like properties of these CMDBS have been extensively investigated. Thus, it appears that dextran derivatives can mimic the action of heparin in regard to its interactions with antithrombin and serine proteases involved in blood coagulation. Other derivatives interact with various components of the immune system or with adhesive proteins such as fibronectin in modulating the proliferation of Staphylococcus aureus. Because they are able to stimulate wound healing in various in vivo models, these polysaccharides may also constitute a family of tissue repair agents because of their protecting and potentiating effects with heparin binding growth factors. Moreover, dextran derivatives in contact with cells such as endothelial cells, smooth muscle cells, or tumoral cells can affect both cell proliferation and metabolism. It appears that these bioactive polymers are also efficient tools to investigate the precise mechanism of action of individual biological activities by contrasting their mode of action to that of heparin. In addition to their numerous biological properties and biospecificity, functionalized dextrans are relatively simple to manufacture and exempt of donor contaminant, which make them attractive in a variety of clinical applications.

Animals↗

PubMed2000

Surface modification of poly(lactic acid) nanospheres using hydrophobically modified dextrans as stabilizers in an o/w emulsion/evaporation technique.

Sterically stabilized biocompatible poly(lactic acid) (PLA) nanospheres were prepared by an o/w emulsion/evaporation technique, using hydrophobically modified dextrans (DexP) as the emulsion stabilizer. Photon correlation spectroscopy, zetametry, and differential scanning calorimetry studies corroborated that interfacial adhesion between immiscible dextran and PLA chains was achieved by compatibilization of polymer segments via hydrophobic groups grafted onto dextran and thus leading to the formation of entanglements between the hydrophobic dextran parts and the PLA matrix. The presence of dextran exposed at the particle surface was confirmed by X-ray photoelectron spectroscopy and by the fact that the suspensions showed an increased stability in concentrated NaCl solutions and a reduction of bovine serum albumin adsorption compared to uncoated PLA nanoparticles. A comparison of the characteristics of PLA nanospheres DexP-coated via the emulsion procedure (NS(em)) with those of PLA particles coated by DexP adsorption (NS(ad)) suggests that the conformation of the polymer in the superficial layers may be different. However, both DexP layers behave similarly in terms of stability and protein adsorption.

Adsorption↗

PubMed2001

A comparative biocompatibility study of microspheres based on crosslinked dextran or poly(lactic-co-glycolic)acid after subcutaneous injection in rats.

Microspheres based on methacrylated dextran (dex-MA), dextran derivatized with lactate-hydroxyethyl methacrylate (dex-lactate-HEMA) or derivatized with HEMA (dex-HEMA) were prepared. The microspheres were injected subcutaneously in rats and the effect of the particle size and network characteristics [initial water content and degree of methacrylate substitution (DS)] on the tissue reaction was investigated for 6 weeks. As a control, poly(lactic-co-glycolic)acid (PLGA) microspheres with varying sizes (unsized, smaller than 10 microm, smaller and larger than 20 microm) were injected as well. A mild tissue reaction to the PLGA microspheres was observed, characterized by infiltration of macrophages (MØs) and some granulocytes. Six weeks postinjection, the PLGA microspheres were still present. However, their size was decreased indicating degradation and many spheres had been phagocytosed. The tissue reaction was hardly affected by size differences, except for particles smaller than 10 microm, which induced an extensive tissue reaction. The initial tissue reaction to nondegradable dex-MA microspheres was stronger than towards the PLGA microspheres, but at day 10 the tissue reactions were comparable for both groups. Six weeks postinjection, the dex-MA microspheres were completely phagocytosed, and no signs of degradation were observed. The size and initial water content of dex-MA microspheres hardly affected the tissue response, although less granulocytes were observed for microspheres with higher DS. Slowly degrading dextran microspheres composed of dex-(lactate(1)-)HEMA induced a tissue reaction comparable to the PLGA microspheres. However, degradation of the dex-(lactate(1,3)-)HEMA microspheres was associated with an increased number of MØ's and giant cells, both phagocytosing the microspheres and their degradation products. Similar to PLGA, no adverse reactions were observed for the nondegradable dex-MA and degradable dextran microspheres. This study shows that both nondegradable and degradable dextran-based microspheres are well tolerated after subcutaneous injection in rats, which make them interesting candidates as controlled drug delivery systems.

Animals↗

PubMed1982

Prevention of fatal postoperative pulmonary embolism by heparin dihydroergotamine or Dextran 70.

Eight thousand and one patients were admitted to a prospective, randomized multicentre trial comparing the prophylactic efficacy of heparin-dihydroergotamine (DHE) and Dextran 70 against fatal pulmonary embolism after emergency or elective orthopaedic surgery. Of the 7413 patients correctly admitted to the trial, 3698 were allocated to receive heparin-DHE and 3715 to receive Dextran 70. Twenty-eight patients in the heparin-DHE and 27 in the dextran group died within 40 days of operation. Necropsy was performed in 19 cases in each group. In 6 patients in the heparin-DHE and in 9 in the dextran group pulmonary embolism was the sole or a contributory cause of death (n.s.). In the dextran group there were more diffuse intraoperative bleeding complications (P less than 0.01), more massive postoperative haemorrhages (P less than 0.01), more small wound haematomas (P less than 0.05) and more allergic reactions (P less than 0.05). This is the first large multicentre trial dealing with elective and emergency procedures in orthopaedic patients.

Adolescent↗

PubMed1988

Dihydroergotamine and the thromboprophylactic effect of dextran 70 in emergency hip surgery.

In a prospective randomized controlled trial treatment with a combination of dextran 70 and dihydroergotamine (DHE) was compared with the administration of dextran 70 alone as prophylaxis against postoperative thrombo-embolic complications in emergency hip surgery. Forty-five consecutive patients with a fractured hip entered the study. Twenty-one were randomized to prophylactic treatment with dextran 70 (group 1) and twenty-four patients received dextran 70 and DHE (group 2). Both regimens were initiated pre-operatively and the surgical and postoperative procedures were the same in the two groups. On the first and fourth postoperative day, Tc-plasmin scintigraphy of the lower extremities and pulmonary ventilation/perfusion scintigraphy were performed to detect any deep vein thrombosis (DVT) and/or pulmonary emboli. A total of 19 per cent of group 1 patients developed DVT and so did 25 per cent in group 2; this difference was not statistically significant. Of the detected DVT, 60 per cent were subclinical, and 7 per cent of the patients had minor pulmonary emboli, all of which were symptomless. No therapeutic difference could be demonstrated between the two regimens. A recent report claiming that adding DHE to the prophylactic administration of dextran 70 considerably reduces the incidence of postoperative DVT in emergency hip surgery is questioned.

Aged↗

PubMed2003

Control of emboli in patients with recurrent or crescendo transient ischaemic attacks using preoperative transcranial Doppler-directed Dextran therapy.

BACKGROUND: Transcranial Doppler (TCD)-directed Dextran 40 treatment after carotid endarterectomy reduces the rate of early postoperative thrombosis. This study assessed the efficacy of intravenous Dextran 40 at controlling symptoms and emboli before elective carotid endarterectomy in patients with recurrent or crescendo transient ischaemic attacks (TIAs). METHODS: In a prospective study, patients with more than 70 per cent internal carotid artery stenosis who had two or more symptomatic episodes within 30 days and TCD-detected microemboli were studied. Dextran 40 was commenced at 20 ml/h and TCD was repeated to reassess the rate of embolization. The infusion was increased in 20-ml/h increments until symptoms and emboli were controlled. The patient then had carotid surgery on the next elective list. RESULTS: Nineteen patients with internal carotid stenosis greater than 70 per cent, recurrent symptoms and TCD-detected emboli were studied. All patients had symptoms and emboli controlled with Dextran 40. One patient with both unstable angina (awaiting urgent operation) and crescendo TIAs died from a myocardial infarct before undergoing operation. Of the 18 patients who had an operation, one suffered a non-disabling stroke on the third postoperative day. CONCLUSION: TCD-directed Dextran 40 offers a safe approach to high-risk patients before elective carotid endarterectomy, and warrants further study.

Adult↗

PubMed1985

Endocytosis in Saccharomyces cerevisiae: internalization of alpha-amylase and fluorescent dextran into cells.

In the preceding paper I reported that Saccharomyces cerevisiae spheroplasts were able to internalize particulate markers, enveloped viruses, into intracellular organelles. Here the internalization of soluble macromolecules into cells having an intact cell wall is described. alpha-Amylase was taken up into cells in a temperature- and concentration-dependent way. The kinetics of accumulation were linear for the first 20-40 min at 37 degrees C and then started to level off. Internalization of alpha-amylase into spheroplasts displayed similar characteristics, but the accumulation rate was about four times higher than into cells. Fluorescent dextran was used to mark morphologically the compartment into which internalization occurred. This marker was accumulated into the vacuole of the cells in a time-, temperature- and concentration-dependent way. A temperature-sensitive mutant deficient in exocytosis was found to be defective in intracellular accumulation of alpha-amylase and dextran. At the restrictive temperature, very little alpha-amylase accumulated into the cells and only faint staining of intracellular organelles with fluorescent dextran could be detected. At the permissive temperatures, accumulation of alpha-amylase and dextran into the mutant cells was comparable with accumulation into wild-type cells. I conclude that alpha-amylase and fluorescent dextran were internalized into S. cerevisiae cells and directed into the vacuoles.

Dextrans↗

PubMed1984

Effect of hydroxyethyl starch and dextran on plasma volume and blood hemostasis and coagulation.

Six healthy male subjects were given in a crossover fashion medium molecular weight (HES 125) and low molecular weight (HES 40) hydroxyethyl starch, dextran, and balanced salt solution by intravenous infusion. The plasma volumes were determined using labeled albumin and plasma protein measurements. Three properties of factor VIII protein complex and indices of blood coagulation and hemostasis were measured before and after the infusions. Both the salt solution and HES 40 increased plasma volume, but their effect wore off within 3 hours. Dextran and HES 125 increased plasma volume significantly (P less than 0.001) more than the salt solution did, and the expansion was maintained for 24 hours. Plasma volume increases (dextran and HES 125) were associated with high nonglucose carbohydrate levels in plasma and low levels in urine. No or slight increases in plasma volumes (HES 40), on the other hand, were associated with low and high carbohydrate levels in plasma and urine, respectively. Serum alpha-amylase activity increased significantly after both HES preparations as compared to salt solution. Dextran and HES 125 decreased all the three values of factor VIII, these decreases being maximal 3 to 6 hours after administration and highest (about 25 per cent) for F VIII R:Ag and F VIII R:cof. It is concluded that HES 125 and dextran are equally effective plasma expanders.

Adult↗

PubMed2004

Different behavior of dextrans in positive-ion and negative-ion mass spectrometry.

A mass spectrometric (MS) comparative study of dextran samples using two different ionization techniques (matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI)) in both positive- and negative-ion modes is reported. The experiments were carried out with two polydisperse dextrans (1000 and 8800 Da) and isomaltotriose. In the positive-ion mode, the expected alkali metal ion adducts of dextrans were observed in both techniques. In contrast, the expected preferential formation of deprotonated molecules [M - H](-) was not confirmed in negative mode MALDI time-of-flight (TOF) MS, where the series of ions [M(x)- H +42](-) or [M(x+1)- H - 120](-), coming either from some addition or fragmentation, were observed. In both ionization techniques, these ions formed the main distributions of dextrans in the negative-ion mode. It seems that the negative molecular ions formed from the alpha1 --> 6 linkage of polyglucose oligomers easily decompose, and the product ions [M - H - 120](-) markedly dominate. The fragmentation experiments and especially the investigation of the fundamental role of the nozzle-skimmer potential in ESI-MS supported our explanation of the observed behavior because its higher values caused higher fragmentation. The experiments with isomaltotriose excluded any addition of 42 Da during the MS procedures, which is not distinguishable from the loss of 120 Da in the case of polydisperse dextrans. MALDI-TOFMS was found to be more sensitive for the detection of higher oligosaccharides and ESI-MS more useful for structural studies.

Dextrans↗

PubMed2005

Low molecular weight dextrans stabilize nonviral vectors during lyophilization at low osmolalities: concentrating suspensions by rehydration to reduced volumes.

Stabilization of nonviral vectors during freezing and drying requires formulation with protective excipients such that transfection rates and physical characteristics are maintained upon reconstitution. While many studies have demonstrated the ability of disaccharides (e.g., sucrose) to effectively protect nonviral vectors during lyophilization, the sucrose/DNA weight ratios required to achieve stability result in formulations that are not osmotically compatible with the subcutaneous (SC) or intramuscular (IM) injection of a typical dose of plasmid DNA. In an effort to reduce the formulation osmolality, dextrans possessing a range of molecular weights were investigated for their ability to serve as protectants. Dextran 3000 proved to be the most effective of the dextrans tested, and offered similar protection to sucrose on a weight basis. However, the advantage of employing this excipient is that the resulting osmolality is reduced by approximately 40% as compared to an equivalent weight of sucrose. Moreover, the use of dextran allows lyophilized vector preparations to be rehydrated to reduced volumes, essentially concentrating vectors prior to administration. Utilizing a combination of dextran 3000 and sucrose, we demonstrate that complexes of polyethylenimine (PEI) and DNA lyophilized at 0.1 mg/mL can be concentrated tenfold upon rehydration, resulting in an isotonic formulation containing 1 mg/mL DNA that can provide more realistic injection volumes for animal studies, and is compatible with clinical trials involving SC and IM injection.

Animals↗

PubMed1989

Control of pharmaceutical properties of soybean trypsin inhibitor by conjugation with dextran. I: Synthesis and characterization.

The Kunitz-type soybean trypsin inhibitor (STI), a model protein, was conjugated with dextran (Mw, approximately 9900; STI-D), and its physicochemical and biochemical properties were studied to develop a novel delivery system for a protein drug. Conjugation was carried out using periodate oxidation, and cyanogen bromide, carbodiimide, cyanuric chloride, epichlorhydrin, and N-succiniimidyl-3-(2-pyridyldithio)propionate (SPDP) reagent methods. Dextran was conjugated to STI at a molar ratio of 1.5 to 4.6, but the degree of modification, as well as yield and contamination extent of unreacted STI and dextran, varied with the method of synthesis. Gel filtration and electrophoresis confirmed the covalent attachment of dextran to STI but also demonstrated the broad molecular weight distribution of the conjugates. The STI-D conjugate retained satisfactory activity, although the attachment partially reduced its inhibitory activity against trypsin. The periodate oxidation method seemed to be the best for the preparation of STI-D since it gave the conjugate with a high modification ratio (4.6 molecules per STI), high yield (95%), and satisfactory activity recovery (63%). Chemical modification of STI was also carried out with activated polyethylene glycol (PEG) for comparison. The STI-PEG conjugate was obtained in a satisfactory yield (96%) and modification degree (5.8 molecules per STI), but the remaining activity was considerably lower (34%). Thus, conjugation of protein with dextran by the periodate oxidation method is suggested to be preferable for preparing a protein-carrier system without significant diminution of its biological activity.

Carbodiimides↗

PubMed1991

A novel method for differentiating dextran sulfate from related sulfated polysaccharides.

A method is described for unequivocal identification of dextran sulfate, based on combined chemical desulfation and dextranase enzymolysis of dextran sulfate moieties to isomaltose, a specific indicator of dextran-type precursors. The method was developed using high-resolution (300 MHz) 1H NMR spectroscopy for assurance of the molecular transformations, identification, and estimation of the hydrolysis products. Overall conversion of approximately 80% of highly sulfated and moderately sulfated dextran sulfates was realized. Both 2-D 1H and 13C NMR spectra of a dextran sulfate (MW 500,000) clarified the extent of sulfation (75%) at C-4 and confirmed that sulfation at positions C-2 and C-3 was virtually complete. Estimation of the hydrolysis products (isomaltose, major; alpha-D-glucose, minor) is not restricted to 1H NMR now that the desulfation-enzymolysis methodology has been established; rather, it can be performed using HPLC or GLC (with derivatization).

Catalysis↗

PubMed1995

Effect of isovolemic hemodilution with dextran and albumin on thrombus formation in artificial vessel grafts inserted into the abdominal aorta of the rabbit.

The effects of isovolemic hemodilution with dextran-70 and albumin on thrombus formation in artificial arterial grafts were investigated. A polytetrafluoroethylene graft (PTFE, length 13 mm, inner diameter 3 mm) was inserted into the abdominal aorta of rabbits. Three groups of animals were studied; 1) animals receiving isovolemic hemodilution with dextran-70 (10 ml/kg body weight), 2) animals receiving isovolemic hemodilution with albumin (10 ml/kg body weight), and 3) nonhemodiluted controls. The blood flow increased by about 70% and 60% after the hemodilution with dextran and albumin, respectively, and remained high in the hemodiluted animals, after insertion of the graft. After 2 days, the vessel graft was removed and weighed. The thrombus mass was separately weighed. The results suggest that isovolemic hemodilution with both albumin and dextran is associated with a marked increase in blood flow in the rabbit. Hemodilution with dextran also reduced the amount of thrombus formation on the inner wall of the graft.

Albumins↗

PubMed1996

Characterization of keratinocyte growth factor binding to heparin and dextran sulfate.

Binding of keratinocyte growth factor (KGF) with heparin (molecular weight of 5000) and dextran sulfate (molecular weight of 8000) was studied using an online monitoring of size-exclusion chromatography with light scattering, refractive index, and uv absorbance detectors. This technique allows the determination of the molecular weight of KGF eluting as complexes with the above polymers. When mixtures of KGF with heparin were injected into the column, two peaks of heparin/KGF complexes were observed. The first peak corresponded to, on average, 3.4 KGF per complex and the second peak to an average of about 2 KGF per complex. These results suggest that the heparin/ KGF complex is heterogeneous, consisting of 1,2,3, and 4 KGF molecules per complex. To calculate the number of heparin molecules in these complexes, the rate of disappearance of free KGF was determined as heparin was added. The average number of KGF bound to 1 mol of heparin was calculated to be about 2 mol, suggesting that only one heparin molecule is present in these complexes. The heparin binding of two KGF mutants, i.e., (C1, 15S)KGF (with substitutions of serine for cysteines 1 and 15) and d28KGF (lacking 28 N-terminal amino acid residues), was essentially identical to that of the native sequence KGF. A similar experiment was carried out for KGF binding to dextran sulfate. The molecular weight of the complex corresponded to 2 to 2.6 KGF molecules per complex. The rate of disappearance of free KGF as the dextran sulfate added showed 2-3 mol of KGF bound to 1 mol of dextran sulfate, consistent with the idea that the complex contains only 1 dextran sulfate molecule.

Binding Sites↗