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PubMed1975

Permselectivity of the glomerular capillary wall to macromolecules. II. Experimental studies in rats using neutral dextran.

To determine the permselectivity characteristics of the glomerular capillary wall, known molecular size fractions of [3H]dextran, prepared by gel chromatography, were infused into normally hydrated Wistar rats, thus permitting simultaneous measurement of Bowman's space/plasma water (BS/P) and urine/plasma water (U/P) concentration ratios, along with glomerular pressures and flows. Since (BS/P)inulin = 1.01 +/- 0.01 SE(n = 34, radius = approximately 14 A) and since (BS/P)dextran/(BS/P)inulin equaled (U/P)dextran/(U/P)inulin for dextrans ranging in molecular radius from 21 to 35 A, these findings validate that dextrans are neither secreted nor reabsorbed. For dextran radii of 20, 24, 28, 32, 36, 40, and 44 A, (U/P)dextran/(U/P)inulin averaged 0.99, 0.92, 0.69, 0.42, 0.19, 0.06, and 0.01, respectively. In accord with theoretical predictions that these fractional dextran clearances should vary appreciably with changes in glomerular transcapillary pressures and flows, an increase in glomerular plasma flow rate, induced in these same rats by plasma volume expansion, resulted in a highly significant lowering of fractional clearance of all but the smallest and largest dextrans studied. These findings emphasize that fractional solute clearances alone are inadequate to describe the permselective properties of the glomerular capillary wall unless glomerular pressures and flows are also known. This sensitivity of fractional dextran clearance to changes in plasma flow indicates that dextrans are transported across the capillary not only by bulk flow but also to an important extent by diffusion.

Animals↗

PubMed2000

Dextrans for targeted and sustained delivery of therapeutic and imaging agents.

Dextrans are glucose polymers which have been used for more than 50 years as plasma volume expanders. Recently, however, dextrans have been investigated for delivery of drugs, proteins/enzymes, and imaging agents. These highly water soluble polymers are available commercially as different molecular weights (M(W)) with a relatively narrow M(W) distribution. Additionally, dextrans contain a large number of hydroxyl groups which can be easily conjugated to drugs and proteins by either direct attachment or through a linker. In terms of pharmacokinetics, the intact polymer is not absorbed to a significant degree after oral administration. Therefore, most of the applications of dextrans as macromolecular carriers are through injectable routes. However, a few studies have reported the potential of dextrans for site (colon)-specific delivery of drugs via the oral route. After the systemic administration, the pharmacokinetics of the conjugates of dextran with therapeutic/imaging agents are significantly affected by the kinetics of the dextran carrier. Animal and human studies have shown that both the distribution and elimination of dextrans are dependent on the M(W) and charge of these polymers. Pharmacodynamically, conjugation with dextrans has resulted in prolongation of the effect, alteration of toxicity profile, and a reduction in the immunogenicity of drugs and/or proteins. A substantial number of studies on dextran conjugates of therapeutic/imaging agents have reported favorable alteration of pharmacokinetics and pharmacodynamics of these agents. However, most of these studies have been carried out in animals, with only a few being extended to humans. Future studies should concentrate on barriers for the clinical use of dextrans as macromolecular carriers for delivery of drugs, proteins, and imaging agents.

Animals↗

PubMed2001

Synthesis and properties of dextran-nalidixic acid ester as a colon-specific prodrug of nalidixic acid.

Dextran-nalidixic acid ester (dextran-NA) with a varied degree of substitution (DS) was synthesized as a colon-specific prodrug of nalidixic acid (NA). Solubility in water (mg/ml) of dextran-NA with DS (mg NA/100 mg dextran-NA) of 7, 19, or 32 was 57.57 (equivalent to 4.00 mg NA/ml), 0.53 (equivalent to 0.10 mg NA/ml), or 0.03 (equivalent to 0.01 mg NA/ml), respectively, and that for NA was 0.03 at 25 degrees C. To ensure the chemical stability of dextran-NA at conditions similar to those of the stomach and small intestine, dextran-NA was placed in a solution of pH 1.2 hydrochloric acid buffer or pH 6.8 phosphate buffer and incubated at 37 degrees C; no NA was detected during the 6 h of the incubation period, which indicated that dextran-NA might be chemically stable during the transit through the gastrointestinal tract. Degree of depolymerization (%) by dextranase determined by the 2,4-dinitrosalicylic acid (DNS) method at 37 degrees C for dextran-NA with DS of 7, 19, or 32 was 81, 68, or 8, respectively, in 8 h, and that for dextran was 91. When dextran-NA (equivalent to 50 microg of NA) with a DS of 7 or 17 was incubated with cecal contents (100 mg) of rats at 37 degrees C, the extent of NA released in 24 h was 41% or 32% of the dose, respectively. NA was not liberated from the incubation of dextran-NA with the homogenate of tissue and contents of the small intestine.

Animals↗

PubMed1960

The interaction of dextran with serum albumin, gamma globulin, and fibrinogen.

The interaction between dextran and serum albumin, gamma globulin, and fibrinogen can be studied by an electrophoretic method, which depends on obtaining electrophoretic patterns, first of each protein, then of dextran, and finally of mixtures of each protein with dextran. The areas under the electrophoretic spikes for each protein, for dextran, and for the mixtures are measured. At pH's between 9.6 and 6.6, there is a transference of albumin to dextran when the two components are mixed, the amount of albumin lost being nearly equal to the gain in the new component, albumin plus dextran. This new species has a specific refractive index of about 0.00205 and seems to be composed of about one albumin molecule for every four dextran molecules. The method is unsuitable for studying interaction between dextran and gamma globulin because these substances are almost immobile and do not separate into two spikes. The method shows that a mixture of dextran and fibrinogen gives only one slowly moving spike (pH 6.6 to 8.6), the area under which is the sum of the areas under the dextran and the fibrinogen spikes taken separately. Either there is no interaction, or the new species has virtually the same refractive index increment as fibrinogen and dextran taken separately (0.0014 to 0.0015).

Dextrans↗

PubMed1985

Maintenance of peritoneal catheter function by the intraperitoneal administration of 32% dextran 70.

Thirty-two percent dextran 70 was administered to 53 patients receiving intraperitoneal (i.p.) chemotherapy in an attempt to better maintain catheter function. One hundred milliliters of 32% dextran 70 was administered i.p. at the time of catheter placement and at the completion of each course of chemotherapy (every 3 to 4 weeks). Analysis of the functional survival of the dextran treated catheters and 20 historical controls was performed. The cumulative probabilities of catheters maintaining bi-directional function in the dextran treated and control groups were 0.75 and 0.50 respectively. This difference was statistically significant at p = 0.051 by two-tailed Wilcoxon analysis. The difference between survival of dextran treated and control catheters increased if patients who received intraperitoneal doxorubicin were factored out (p = 0.035 by two-tailed Wilcoxon analysis). Plasma and peritoneal dextran levels were measured on 9 courses in 8 patients. Dextran was detectable in the peritoneal cavity up to 7 days after administration. The "apparent half-life" of dextran 70 in the peritoneal cavity was 36 hours. Plasma dextran concentrations increased for 2 days following i.p. administration and then decreased with an apparent half-life of 36 hours. One patient experienced chills and another had an anaphylactoid reaction following administration of the dextran. This study suggests that i.p. administration of 32% dextran 70 may be an effective means of minimizing peritoneal catheter failures.

Adult↗

PubMed2003

Dextran modulates microvascular permeability: effect in isotonic and hypertonic solutions.

Hypertonic saline solutions with Dextran (HSD) have been advocated for rapid restoration of intravascular volume. Dextran is thought to increase the duration of action of hypertonic saline (HS) by selectively partitioning the water in the vascular space that has been drawn out of cells by HS. The goal of this study was to define the microvascular permeability modulating activity of Dextran in both isotonic and hypertonic solutions. We hypothesized that Dextran would decrease hydraulic permeability (Lp). Using the modified Landis micro-occlusion technique, single rat mesenteric venules were perfused with either normal Ringers (NR) with 135 mM NaCl or HS with 185 mM NaCl. In sequential cannulations of the venules, 1%, 2%, and 3% of Dextran was added to the NR perfusion (n = 6) and the HS perfusion (n = 6). The Lp was measured at baseline and after perfusion with each Dextran concentration. Baseline Lp measurements for NR and HS solutions were 1.01 +/- 0.034 and 5.14 +/- 1.02, respectively. In the NR group, the 2% and 3% Dextran decreased permeability below baseline levels to 0.79 +/- 0.028 (P < 0.0001) and 0.66 +/- 0.028 (P < 0.0001), respectively. In the HS group, the 2% and 3% Dextran decreased permeability to 1.65 +/- 0.53 (P < 0.0001) and 0.99 +/- 0.2 (P < 0.0001), respectively. All values for Lp are x10(-7) cm s(-1) x cm H2O(-1). The addition of Dextran to isotonic and hypertonic solutions results in a decrease in microvessel permeability. This effect is more pronounced with the perfusion of hypertonic solutions. The results demonstrate the oncotic potential of Dextran and its ability to hold water in the vascular space. Dextran may have a beneficial effect when used for resuscitation with HS by decreasing microvascular permeability and augmenting intravascular volume.

Animals↗

PubMed1992

Use of blue dextran for measuring changes in perfused vascular surface area in lungs.

We investigated the uptake and efflux of Blue Dextran in the isolated perfused rabbit lung. Blue Dextran is a high-molecular-weight glucose polymer (original mol wt 2 x 10(6) g/mol) containing covalently bonded Reactive Blue 2 dye (approximately mmol/g dextran). This blue dye is known for its high binding affinity to a wide variety of proteins, with a particularly high affinity for serum albumin. In isolated rabbit lungs perfused with a protein-free perfusate, both bolus injection and recirculation of Blue Dextran revealed a rapid saturable uptake. Once the lungs were loaded with Blue Dextran, efflux of the Blue Dextran accumulated in the lungs could be induced by addition of bovine serum albumin (BSA) to the recirculating perfusate. The amount of BSA-induced efflux of Blue Dextran from the lung was independent of perfusate flow. When the left pulmonary artery was ligated after the lungs had been loaded with Blue Dextran, the dye-induced BSA efflux was only about 50% of normal. Release of the ligature so that both lungs were perfused resulted in efflux of the remaining Blue Dextran. The combination of high airway pressure and low flow also reduced the dye efflux, and the effect was reversed by reducing the airway pressure. With the assumption that the high average molecular weight of Blue Dextran confines this molecule to interaction with proteins on the vascular surface, the results of this study suggest that Blue Dextran uptake and its BSA-induced efflux are proportional to the perfused vascular surface area in the lung.

Animals↗

PubMed1993

Safety of dextran in relation to other colloids--ten years experience with hapten inhibition.

OBJECTIVE: The effects of hapten inhibition with dextran 1 (molecular weight: 1,000 D, Promit), which is in use since 1982 for the prevention of severe dextran-induced anaphylactic reactions (DIAR) caused by immune complexes, were studied. DESIGN: Spontaneous reports to the manufacturer and to the WHO database INTDIS regarding adverse reactions to clinical dextran after preinjection of dextran 1 and to dextran 1 alone were collected from 1983 to 1992. During this period a total of 5.1 million doses of dextran 1 were sold in 15 countries. INTERVENTIONS: Analysis of pre- and post-reaction titers of dextran-reactive antibodies (DRA) was made in most Scandinavian reports. RESULTS: The incidence of severe DIAR (grades III-V) to clinical dextran after the prophylactic use of hapten inhibition was approximately 1/200,000 patients receiving dextran 1. In Sweden, where reporting of severe adverse drug reactions is mandatory, the incidence was approximately 1/70,000, indicating a 35-fold reduction. Only 2 fatal reactions were reported, an incidence of 1/2.5 million doses, indicating a 90-fold reduction. Both these occurred in patients with extremely high titers of DRA. Side effects to dextran 1, mostly mild, were reported in approximately 1 case per 100,000 doses. These side effects were not antibody mediated. CONCLUSIONS: The above findings, together with other recent safety profile data, suggest that dextran with hapten inhibition has possibly become the safest plasma substitute in current clinical practice.

Adverse Drug Reaction Reporting Systems↗

PubMed1998

Improved clearability of cystic fibrosis sputum with dextran treatment in vitro.

Most patients with cystic fibrosis (CF) are infected by Pseudomonas aeruginosa. Dextran exhibits anti-adhesive effects in preventing attachment of P. aeruginosa to epithelial cells (1). The initial purpose of this study was to evaluate the potential of dextran to alter the rheology and ciliary transportability of CF sputum prior to initiation of a clinical trial in patients with CF. Sputum samples were collected from 25 patients with CF not receiving rhDNase therapy for use in in vitro testing. Aliquots of CF sputum were treated with 10% vol. Ringer's or the same volume of Dextran 4000 to give a final concentration of 0.4% (4 mg/ml) or 4% (40 mg/ml) dextran in the sputum. Dog mucus samples were collected from seven healthy, anesthetized dogs from the endotracheal tube cuff. Aliquots of dog mucus were subjected to the same concentrations of dextran as the CF sputum. All treated samples were incubated for 30 min at 37 degrees C, and their rheologic properties (viscoelasticity) were evaluated by magnetic microrheometry. For 17 of the sputum samples, frog palate mucociliary transportability was determined from sputum movement on the ciliated, mucus-depleted frog palate, relative to native frog mucus control. Spinnability (cohesiveness) was evaluated by the filancemeter technique for eight sputum samples. Overall, whether for CF sputum or healthy dog mucus, Dextran 4000 treatment significantly reduced viscoelasticity and increased predicted mucociliary and cough clearability. Direct measurements of sputum mucociliary clearability on frog palate increased significantly with 0.4% dextran and 4% dextran compared with saline control. Sputum spinnability (cohesiveness) decreased significantly with both dextran concentrations, too. The effects on viscoelasticity and spinnability were greater at 4% than at 0.4%. There was a significant positive correlation between spinnability and viscoelasticity, and negative relationships between spinnability and both forms of clearability as predicted from viscoelastic measurements. This study suggests that treatment with Dextran 4000 can reduce the crosslink density and cohesiveness of CF and improve mucociliary and cough clearability. Dextran 4000 is an inexpensive and nontoxic agent that may be of benefit in patients with CF lung disease and perhaps in other respiratory disease where mucus retention is an important feature.

Adolescent↗

PubMed2004

Influence of molecular weight on intracameral dextran movement to the posterior segment of the mouse eye.

PURPOSE: Uveoscleral outflow provides a potential pathway to the posterior segment for drug delivery. In this study, the influence of molecular weight on the intraocular distribution of dextran molecules after intracameral injection in the mouse eye was investigated. METHODS: The anterior chambers of the eyes of 64 anesthetized NIH Swiss mice were perfused with various fluorescent dextran solutions (10, 40, 70, and 500 kDa) at 500 nL/min for 10 minutes. At 10, 20, or 60 minutes after the initiation of the anterior chamber perfusion, the mice were killed and tissue obtained for evaluation by fluorescence microscopy. RESULTS: Each of the different molecular weight dextrans were visible in the anterior chamber of the mouse eye after the termination of the experiments. The 10-kDa dextran was observed in the supraciliary space and the supraciliary sclera after 10 minutes and in the anterior sclera after 60 minutes of perfusion. The 40-kDa dextran was detected in the supraciliary space and the anterior sclera after 10 minutes and in the anterior choroid and sclera after 20 and 60 minutes, but not in the posterior segment. The 70-kDa dextran was observed in the supraciliary space and anterior choroid after 10 minutes. After 20 minutes, it was visible in the equatorial choroid. After 60 minutes, it was observed in the posterior choroid. The 500-kDa dextran was observed in the supraciliary space and the anterior choroid after 10 minutes and in the supraciliary sclera at 20 minutes. At 60 minutes, 500-kDa dextran was observed in the equatorial choroid, but not farther toward the posterior. CONCLUSIONS: The influence of molecular weight on the redistribution of macromolecules from the anterior chamber to the posterior globe in the mouse eye appears to be similar to primate eyes. These similarities include passage of all size dextrans through the proximal uveoscleral pathway, the dependence of the extent of posterior movement on the size of the dextran, and the absence of large dextran entry into the distal uveoscleral pathway.

Animals↗

PubMed2002

Impact of iron dextran on polymorphonuclear cell function among hemodialysis patients.

BACKGROUND: Polymorphonuclear cell (PMN) dysfunction and the increased use of parenteral iron may be important contributory factors to bacterial infections among patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). We compared the in vitro impact of a commonly used parenteral iron preparation, iron dextran, on PMN function and viability between a group of HD patients with normal iron indices and healthy subjects. METHODS: Eleven patients with ESRD on HD and 10 healthy subjects were studied. PMN harvested from heparinized blood were incubated with iron dextran (0 - 20 mM) in culture medium (RPMI) for 24 hours at 37 degrees C with 5% CO2 following which function and viability were assessed by flow cytometry using appropriate fluorescent labels. RESULTS: Unstimulated, S. aureus and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated hydrogen peroxide (H2O2) production was significantly higher in PMN unexposed to iron dextran from HD patients compared to those from healthy subjects. Iron dextran had no impact on unstimulated PMN H2O2 production in either group. In the healthy group, the only significant change occurred with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) stimulation, where cells exposed to 0.2 and 2.0 mM iron dextran produced less H2O2 relative to PMN unexposed to iron dextran (p < 0.05). In the HD group, all concentrations of iron dextran significantly attenuated H2O2 production stimulated by S. aureus, fMLP and PMA compared to PMN unexposed to iron dextran. Although PMN phagocytosis decreased with exposure to increasing concentration of iron dextran in both healthy subjects and HD patients, these changes did not achieve statistical significance. No significant changes in PMN viability or apoptosis were seen in either group after exposure to iron dextran. CONCLUSIONS: These results indicate that iron dextran, a standard parenteral iron preparation, attenuates PMN function in HD patients with normal iron indices at clinically relevant concentrations. Further studies are required to evaluate and compare the impact of newer preparations of parenteral iron, such as iron sucrose and ferric gluconate, on PMN function.

Adult↗

PubMed1985

An immunochemical study of the combining site specificities of C57BL/6J monoclonal antibodies to alpha (1----6)-linked dextran B512.

This is the first report of an immunochemical study of the combining site specificities of a set of monoclonal antibodies to dextran B512 from C57BL/6J mice. The results confirm previous observations on antidextran combining sites and reveal specificities not seen earlier extending the observed repertoire of antibody combining sites to the single alpha (1----6)-linked glucosyl antigenic determinant. Eight C57BL/6J anti-dextran B512 hybridomas, four IgM,kappa and four IgA,kappa, were produced by PEG fusion of immune spleen cells with the nonproducer myeloma cell line P3X63Ag8 6.5.3. Antibody combining site specificities were determined by quantitative precipitin assays with 14 dextrans. Native dextrans with high percentages of linear alpha (1----6)-linked glucoses, similar to the immunogen B512, were the best precipitinogens; dextrans with alternating alpha (1----3), alpha (1----6) linkages, and highly branched dextrans were less effective. All antibodies precipitated with a synthetic, unbranched alpha (1----6)-linked dextran, suggesting their combining sites were "groove-like" and directed toward internal sequences of alpha (1----6)-linked residues, rather than "cavity-like" and directed toward a nonreducing terminal glucose. Two of the IgA hybridomas gave biphasic precipitin curves with dextran B512; this was shown to be due to differences in the precipitability of IgA monomers and polymers. Differences were observed in the reactivities of several dextrans considered previously to be structurally similar, and a newly proposed structural model of dextran B1299S was assessed. Quantitative precipitin inhibition studies with alpha (1----6)-linked isomaltosyl (IM) oligosaccharides, IM2 to IM9, showed that maximum inhibition was reached with IM6 or IM7, consistent with earlier estimates of the upper limit for the sizes of anti-B512 combining sites. Two IgM hybridomas showed a unique pattern, with inhibition being obtained only with IM5 or larger IM oligosaccharides. Association constants of the antidextrans for dextran B512 and for IM7, determined by affinity gel electrophoresis, ranged from 10(2) to 10(4) ml/g, comparable to earlier findings with antidextrans and other anticarbohydrate antibodies.

Animals↗

PubMed2026

Structural and physicochemical characterisation of branched dextrans produced by an active α-(1→2) branching sucrase from Apilactobacillus kunkeei PDER37.

Recently, branching sucrases encoded in the genomes of certain Lactic Acid Bacteria (LAB) strains have become novel enzymes to obtain branched α-glucans. In this study an active α-(1 → 2) branching sucrase from Apilactobacillus kunkeei PDER37 was expressed, characterised and distinct branched dextrans was obtained with reactions under different sucrose: dextran ratio. Structural characterisation by 1H and 13C NMR analysis demonstrated the branching of the dextran with (1 → 2)-linked α-d-glucose units with no alteration in the final structure depending on sucrose: dextran ratio (D0) but this ratio was effective for the determination of the molecular weights of the branched dextrans (D1, D2 and D3). FTIR analysis further supported the dextran structures and suggested the higher accumulation of the α-Glc units in the branched dextrans. Thermal characterisation of the branched dextrans obtained by TGA and DSC analysis suggested the increased hygroscopicity of the branching units. Both SEM and AFM analysis demonstrated more porous chain like structures in the branched dextrans. This study provides valuable information on the role of active α-(1 → 2) branching sucrase (BS37) for the production of branched dextrans with potential increased physicochemical status applicable for food and other industries.

Dextrans↗

PubMed1986

The role of lymphocytes, macrophages and interferon in the depression of drug metabolism by dextran sulfate.

Cytochrome P-450-mediated drug biotransformation is depressed by many immune stimulants. We have shown that such depression caused by the immune stimulant dextran sulfate is mediated by Kupffer cells. The purpose of this study is to determine if other cells of the immune system or a cellular product such as interferon are involved in the depressive action of dextran sulfate on drug metabolism. Plasma samples taken from mice treated with dextran sulfate contained no detectable interferon, yet hepatic cytochrome P-450 was significantly depressed, suggesting that interferon did not mediate the depression of drug metabolism by dextran sulfate. Administration of cyclophosphamide or antilymphocyte serum to mice prior to dextran sulfate to markedly decrease lymphocyte populations did not prevent the depressive actions of dextran sulfate on cytochrome P-450, suggesting that the lymphocyte population was not involved in the dextran sulfate mediated depression. Preincubation of dextran sulfate with peritoneal macrophages prior to incubation with hepatocytes significantly depressed hepatocyte cytochrome P-450 content, while dextran sulfate alone had no direct effect on hepatocyte cytochrome P-450 content. These results further support the hypothesis that macrophages play a major role in the depression of cytochrome P-450 by dextran sulfate.

Adjuvants, Immunologic↗

PubMedDate not supplied

Anti-HIV activity of dextran sulphate as determined under different experimental conditions.

Dextran sulphate is a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1). Its anti-HIV-1 activity has been investigated under varying experimental conditions. MT-4 cells were infected with HIV-1 at different multiplicities of infection (MOI), and treated with either dextran sulphate, 3'-azido-2',3'-dideoxythymidine (AZT), or anti-HIV-1 serum obtained from an ARC patient. Dextran sulphate suppressed HIV-1 replication (as monitored by viral antigen expression) when the MOI was 0.01 or 0.1. It was ineffective at an MOI of 1.0. The anti-HIV-1 serum was only partially effective at an MOI of 0.01 and ineffective at an MOI of 0.1 or 1.0. AZT proved effective at all three MOIs. Co-cultures of uninfected and HIV-1-infected MT-4 cells were protected against destruction by dextran sulphate at a concentration of 10 and 100 micrograms/ml. To fully suppress viral antigen expression a concentration of 100 micrograms/ml was needed. When used at this concentration, a 1-h contact of dextran sulphate with the cells during the virus adsorption period sufficed to suppress HIV-1 antigen expression. In this sense, dextran sulphate behaved like the anti-HIV-1 serum. Dextran sulphate also behaved like OKT-4A in that they both inhibited HIV-1 attachment to the MT-4 cells, whereas OKT-4 failed to do so. However, dextran sulphate did not affect the binding of OKT-4A to the cells. The present results support the concept that dextran sulphate owes its anti-HIV-1 activity mainly to inhibition of virus binding to its target cells. The anti-HIV-1 activity of dextran sulphate is highly dependent on its sulphate content.

Antibodies, Monoclonal↗

PubMed2002

Neutral and DEAE dextrans as tracers for assessing lung microvascular barrier permeability and integrity.

Steady-state lymph-to-plasma concentration ratios (L/Ps) of neutral dextrans, cationic DEAE dextrans, and endogenous proteins were determined under normal and increased permeability conditions in six unanesthetized yearling sheep prepared with chronic lung lymph fistulas. Fluorescent dextrans with radii ranging from 1 to 30 nm were intravenously infused, and after 24 h, perilla ketone (PK) was given to alter permeability while the dextran infusion was maintained. Plasma and lymph samples were collected before and after PK administration and analyzed for dextran and protein concentrations after high-performance liquid chromatography size separation. Under both baseline and increased permeability conditions, DEAE dextrans had higher L/Ps than neutral dextrans of similar size but lower L/Ps than proteins of similar size. Comparison of L/Ps before and after PK revealed that the percentage change in permeability for neutral and DEAE dextrans was significantly larger than that for proteins. These results suggest that 1) the pulmonary microvascular barrier behaves as a net negative barrier, 2) some transport mechanisms for proteins and dextrans are different, and 3) neutral and cationic dextrans are more sensitive markers than proteins of the same size for assessing changes in pulmonary capillary permeability.

Animals↗

PubMed2000

Synthesis and characterization of dextran-methacrylate hydrogels and structural study by SEM.

The objectives of this study were to develop a simple and reproducible method for the preparation of the hydrogel precursor dextran-methacrylate and to conduct a visual observation of the interior structure of the swollen dextran-methacrylate hydrogel with minimum artifacts. A dextran-methacrylate hydrogel precursor was synthesized by reacting dextran with methacrylic anhydride in the presence of triethylamine as a catalyst. The effects of reaction time, temperature, concentration, and catalyst amount were studied to obtain a wide range of degree of substitution (DS) in dextran by methacrylate. The dextran-methacrylate synthesized showed an enhanced solubility in water and common organic solvents. UV irradiation of dextran-methacrylate by a long-wave UV lamp (365 nm) generated a photocrosslinked hydrogel. This dextran-methacrylate hydrogel showed a range of swelling ratio from 67 to 227% and exhibited an increase in swelling ratio with a decrease in methacrylate substitution. The pH of the swelling media did not affect the swelling behavior of the dextran-methacrylate hydrogels at all the degrees of substitution used. Special cryofixation and cryofracturing techniques were used to prepare aqueous swollen dextran-methacrylate hydrogel samples for SEM observation of their surface and interior structures. A unique three-dimensional porous structure was observed in the swollen hydrogel but was absent in the unswollen hydrogel. Different pore sizes and morphologies between the surface and the interior of swollen hydrogels also were observed.

Biocompatible Materials↗

PubMed1996

Glomerular processing of dextran sulfate during transcapillary transport.

The fractional clearance of dextran sulfate across the glomerular capillary wall in the isolated perfused kidney is shown to be dependent on the concentration of dextran sulfate in the perfusate and the degree of sulfate substitution on dextran sulfate. While normal charge selectivity is apparent at low dextran sulfate perfusate concentrations, the nature of the concentration dependence of the fractional clearance clearly eliminates charge-electrostatic interactions as being responsible. A strong correlation has been experimentally established between fractional clearance and the degree of desulfation of dextran sulfate found in the urine. The correlation was further established through the demonstration that the lysosomotropic agent NH4Cl partially inhibits charge selectivity as well as desulfation. The glomerular cellular processing of the dextran sulfate was further studied through dextran sulfate-mediated release of metabolically labeled glomerular heparan sulfate. A model of glomerular capillary wall transport, invoking endothelial cell processing of dextran sulfate, is proposed to explain the differences between the fractional clearance of dextran and dextran sulfate.

Ammonium Chloride↗