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Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with tense ascites. Results of a randomized study.

Forty-one patients with cirrhosis and tense ascites were randomized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g for each 1000 ml of ascites removed) (group I = 20 patients) or paracentesis with albumin (6 g for each 1000 ml of ascites) (group II = 21 patients). The basal clinical features, laboratory data, and plasma renin activity were similar in both groups. The volume of ascites removed was 12.9 +/- 4.4 and 10.9 +/- 3.7 liters in group I and II, respectively (n.s.). No significant changes were observed in liver and renal function tests, KPTT, platelet count, factor VIII, serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups, except for a decrease in bilirubin in group I and a transient increase of serum albumin in group II. Four patients developed complications in each group, mainly hyponatremia, while one patient in each group developed renal impairment. One patient from group I died with hepatic encephalopathy. Moreover, the probability of survival and readmission to the hospital because of tense ascites were similar in both groups of patients during the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient treated. These results indicate that repeated large volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites. However, due to its reduced cost, paracentesis with Dextran 70 may be considered the treatment of choice in cirrhotic patients with tense ascites without liver cancer and renal failure.

Ascites↗

The role of low molecular weight dextran on platelet pulmonary trapping during endotoxin-induced shock.

In vivo behaviour of Indium-111-labelled platelets were followed simultaneously in the lungs, liver, spleen and kidneys in 16 adult sheep which were exposed to intravenous injection of endotoxin (10 micrograms/kg body wt.). The effects on the respiratory function and the central hemodynamics were also followed. Eight sheep received, 30 min after the endotoxin challenge, continuous intravenous infusion of low molecular weight dextran during 4 h while the other eight animals served as controls. A marked pulmonary and hepatic platelet sequestration was observed during and just after the endotoxin infusion and was followed by a marked platelet disaggregation within 30 min in both the groups. Three hours after the endotoxin a second wave of platelet sequestration occurred in the control animals, both in the lungs and in the liver, but no such increase was seen in the low molecular weight dextran-treated group. Within the kidneys only minor changes occurred during the experiment period. In the spleen, however, there was a decrease in platelet sequestration after endotoxin in both groups. Less marked hemodynamic and respiratory alterations occurred in the dextran-treated group compared to the controls. It was concluded that low molecular weight dextran decreases sequestration of platelets in the lungs and in the liver of sheep during endotoxic shock.

Animals↗

Effects of dextran-linked chloromercuribenzoic acid on insulin release from microdissected pancreatic islets.

Insulin release in response to dextran-linked p-chloromercuribenzoic acid was studied in microdissected pancreatic islets of non-inbred ob/ob-mice. No contamination of the dextran-linked mercurial with free chloromercuribenzoic acid was detected before or after the incubation with islets. In comparison with free mercurial, of the same thiol-blocking activity, the dextran-linked compound had a weak insulin-releasing action with a different dose vs. response relationship. The dextran-linked mercurial had no demonstrable effect on the islet content of cyclic AMP. The results support the hypothesis that free organic mercurials mainly stimulate insulin release by blocking thiol ground that are embedded within the beta-cell plasma membranes beneath their surfaces.

Animals↗

Intracellular labeling of cat spinal neurons using a tetramethylrhodamine-dextran amine conjugate.

Tetramethylrhodamine-dextran is a highly fluorescent neuroanatomical tracer that, in its 10,000 MW form, has seen widespread use as a sensitive anterograde tract-tracing label. We report here the use of a lower molecular weight tetramethylrhodamine-dextran (3000 MW; Molecular Probes, OR) as an in vivo intracellular marker of locomotor-related spinal neurons. In the paralyzed, decerebrate cat preparation, fictive locomotion was evoked by electrical stimulation of the mesencephalic locomotor region. Extracellular and intracellular potentials of rhythmically active spinal neurons were recorded using microelectrodes filled with 2% tetramethylrhodamine-dextran (3000 MW) in 0.9% saline (impedance 5-20 Mohm). Following impalement and electrophysiological characterization, neurons were iontophoretically injected for 2-30 min with 3-10 nA of pulsed positive current. Animals were then perfused 30 min to 7 h postinjection with a variety of paraformaldehyde- and glutaraldehyde-containing fixatives. After tissue sectioning, more than 90% of the injected neurons were recovered. Choline acetyltransferase-immunoreactivity could be demonstrated in a subpopulation of tetramethylrhodamine-dextran-labeled neurons. This technique, in addition to producing high-quality electrodes, has the advantages of rapid yet extensive filling of neuronal processes, no tissue processing prior to visualization, and compatibility with immunohistochemistry.

Animals↗

Quantitative determination of dextran-naproxen ester pro-drugs with varying molecular weights and degrees of substitution in biological media by means of high-performance size exclusion chromatography with fluorescence detection.

A high-performance size exclusion chromatographic procedure using a Nucleosil Diol column and fluorescence detection has been developed for the determination of dextran-naproxen ester pro-drugs with varying molecular weights and degrees of substitution in aqueous buffer solutions and biological media in the presence of the parent drug. The effect of several variables on the chromatographic behaviour of the compounds is discussed. Linear standard calibration curves were constructed for all the dextran derivatives incubated in whole blood and urine (human and rabbit), rabbit liver homogenate and human synovial fluid. In whole blood, the detection limit (lambda ex = 330 nm, lambda em = 360 nm) for a dextran T-70 pro-drug with a degree of substitution (DS) of 10.6 was found to be 2 micrograms ml-1 after applying a 20-micrograms sample to the column. The assay has been used in stability studies and determination of plasma concentration-time profiles after intravenous administration to rabbits of dextran-naproxen ester pro-drugs.

Animals↗

Investigations into the physicochemical properties of dextran small particulate gadolinium oxide nanoparticles.

RATIONALE AND OBJECTIVES: Relatively few studies involving the physicochemical properties of crystalline, nanometer-sized particulate gadolinium complexes have been reported. This is in part because of the challenges associated with making nanoparticulate gadolinium suspensions that are stable in aqueous solution. Small particulate gadolinium oxide (SPGO) and SPGO embedded in albumin microspheres (gadolinium oxide albumin microspheres, GOAM), have been used experimentally as prototype contrast agents for multimodality imaging. MATERIALS AND METHODS: In the present study, an initial attempt was made to better solubilize SPGO, prevent particle aggregation, and investigate the physicochemical properties of dextran SPGO relevant to its use as a high-field magnetic resonance contrast agent in aqueous solution. RESULTS: Dextran SPGO demonstrates regular crystalline lattices and has a gadolinium oxide electron diffraction pattern consistent with that of published X-ray powder diffraction (XPD) patterns. The subtraction XPD pattern of dextran SPGO shows diffraction angles and intensities similar, but not identical, to that of published Gd2O3 diffraction patterns. High r2/r1 ratios and magnetic susceptibility studies indicate dextran SPGO can be classified as a superparamagnetic compound. Enhanced relaxivity is observed at high magnetic field strength; largely because of solubilization of SPGO via the surface adherent carbohydrate. Perhaps also contributing to the observed relaxivity enhancement is the ideal lattice structure of the central gadolinium oxide crystal and the effects of sonochemical preparation on nanoparticle physicochemical properties. CONCLUSIONS: It is anticipated that these studies will help provide a basis for the development of novel nanoparticulate contrast agent platforms capable of improving T1 and T2/T2* contrast for high-field magnetic resonance imaging and molecular imaging.

Contrast Media↗

Tissue reactions of in situ formed dextran hydrogels crosslinked by stereocomplex formation after subcutaneous implantation in rats.

In this study, the in vivo biocompatibility of physically crosslinked dextran hydrogels was investigated. These hydrogels were obtained by mixing aqueous solutions of dextran grafted with L-lactic acid oligomers and dextran grafted with D-lactic acid oligomers. Gelation occurs due to stereocomplex formation of the lactic acid oligomers of opposite chirality. Since gelation takes some time, in situ gel formation is possible with this system. A number of sterilization methods was evaluated for their effect on the chemical and physical properties of the hydrogel. It was shown that of the investigated options (filtration, gamma irradiation, dry-heat and autoclaving) dry-heat sterilization was the preferred method to prepare sterile gels suitable for in vivo evaluations. Two types of stereocomplex gels were prepared and implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 30 days. A mild ongoing foreign body reaction was observed characterized by infiltration of macrophages. Giant cells were only scarcely formed and the low numbers of lymphocytes showed that priming of the immune system is hardly involved. Importantly, the gels fully degraded in vivo within 15 days, which is in good agreement with the in vitro degradation behaviour of these gels. In conclusion, stereocomplexed dextran-oligolactic gels showed good biocompatibility which makes them suitable candidates for the design of controlled release devices for pharmaceutically active proteins.

Absorbable Implants↗

Degradation behavior of dextran hydrogels composed of positively and negatively charged microspheres.

This paper reports on the degradation behavior of in situ gelling hydrogel matrices composed of positively and negatively charged dextran microspheres. Rheological analysis showed that, once the individual microspheres started to degrade, the hydrogel changed from a mainly elastic to a viscoelastic network. It was shown with gels composed of equal amounts of cationic and anionic microspheres, that both a higher crosslink density of the particles and a decrease in water content of the hydrogels resulted in a slower degradation, ranging from 65 to 140 days. Dispersions containing cationic, neutral or anionic microspheres completely degraded within 30, 55 or 120 days, respectively. The microspheres were loaded with rhodamine-B-dextran and degradation was studied with confocal microscopy and fluorescence spectroscopy. After a lag time of 3 days rhodamine-B-dextran started to release from the positive microspheres with a 50% release after 16 days. In contrast, release of rhodamine-B-dextran from the negative microspheres started after 10 days with a 50% release after 36 days. The faster degradation of the positively charged microspheres as compared to the negatively charged microspheres is attributed to stabilization of the transition state in the hydrolysis process by the protonated tertiary amine groups present in the cationic microspheres. On the other hand, the presence of negatively charged groups causes repulsion of hydroxyl anions resulting in a slower degradation. Combining the oppositely charged microspheres in different ratios makes it possible to tailor the network properties and the degradation behavior of these hydrogels, making them suitable for various applications in drug delivery and tissue engineering.

Anions↗

Phase-transition and aggregation characteristics of a thermoresponsive dextran derivative in aqueous solutions.

Grafting of poly(N-vinylcaprolactam) side chains onto a hydrophilic dextran backbone was found to provide the dextran with new, thermoresponsive properties in aqueous solutions. Depending on its solution concentration, the resulting dextran derivative could exhibit a temperature-induced phase-transition and critical transition temperature (T(c)). Different anions and cations of added salts, including five potassium salts and five alkali-metal chlorides, were observed to influence the T(c) value of its aqueous solution. Except for potassium iodide, all added salts were found to lower the T(c) value. The addition of the surfactant, cationic cetyltrimethylammonium bromide or anionic sodium dodecyl sulfate, resulted in an increase of the T(c) value. With the help of the Coomassie Brilliant Blue dye as a polarity probe, the formation of hydrophobic aggregates above the T(c) was revealed for this new dextran derivative in aqueous solution.

Caprolactam↗

A novel model to study bacterial adherence to the transplanted airway: inhibition of Burkholderia cepacia adherence to human airway by dextran and xylitol.

BACKGROUND: Lung infection with Burkholderia cepacia complex before lung transplantation in patients with cystic fibrosis is a major risk factor for decreased post-operative survival rates compared with those of patients colonized with the more common opportunistic pathogen Pseudomonas aeruginosa. Because adherence to mucosal surfaces is an important initial step in infection, we investigated the use of non-toxic neutral polysaccharides and a sugar alcohol to prevent adherence of B cepacia complex to allograft airway epithelium. METHODS: We used human airway explants prepared from donor tracheobronchial tissue to test the effect of dextrans and xylitol in inhibiting the binding of Burkholderia cepacia complex. We used immunofluorescence and electron microscopy to determine the distribution of bacteria in the explants. RESULTS: Burkholderia cepacia complex bound to the explants and was found only in the surface mucus layer. Dextran 40 kd applied before adding the bacteria decreased the number of bound organisms by 80% to 99%. Smaller molecular mass dextrans (4 and 20 kd) were ineffective. Xylitol inhibited bacterial binding by 67% to 85%. Both agents seemed to decrease the thickness of the surface mucus, suggesting that they may indirectly inhibit bacterial binding by removing adherent surface mucus. CONCLUSIONS: Treating donor lungs with dextran 40 kd or xylitol before (and possibly after) surgery may inhibit the adherence of Burkholderia cepacia complex to airways and may prevent or decrease subsequent infection of the allografts.

Bacterial Adhesion↗

Release of bioactive BMP from dextran-derived microspheres: a novel delivery concept.

Recent developments of biotechnology have produced a great variety of protein and bioactive drugs. For these drugs to be used therapeutically, suitable drug delivery systems have become increasingly essential. Dextran-derived biomaterials have been considered to be compatible matrices for protein and bioactive drugs because of their hydrophilic properties and ability to control drug dissolution and permeability. A novel class of dextran-glycidylmethacrylate (Dex-GMA)/poly(ethylene glycol) (PEG) microspheres were designed and synthesized by polymerization of Dex-GMA emulsified in an aqueous PEG solution. Dex-GMA was prepared by substituting the hydroxyl groups in Dex by GMA. The drug loading and in vitro drug release was evaluated by routine procedure and the biological activity of BMP-loaded microspheres was studied by experimental cytology methods. Recombinant human bone morphogenetic protein-2 (rhBMP-2) were entrapped in dextran-derived microspheres quantitatively and with full preservation of their biological activity. In vitro release kinetics indicated that dextran-derived microspheres could retain rhBMP-2 in a variable manner depending on the preparation and degradation of the microspheres. The release profiles of rhBMP-2 from microspheres as a function of time showed that rhBMP-2 releasing kinetics in vitro fitted to first-order and Higuchi equations. The release profile in vitro was in accord with two phases kinetics law and more than 60% drug were released during 20 days. Cytology studies showed rhBMP-2 microspheres have good biological effects on cultured periodontal ligament cells, and could achieve a longer action time than concentration of rhBMP-2 solution. These properties make those microspheres interesting osteo-conductive BMP carriers, allowing to decrease the amount of implanted factor required for tissue regeneration.

Alkaline Phosphatase↗

Prevention of interfacial inactivation of enzymes by coating the enzyme surface with dextran-aldehyde.

Interactions between soluble enzymes and interfaces of organic solvent drops or gas bubbles have a very negative effect on the operational stability of the soluble enzymes. In this study, the formation of a hydrophilic shell around the enzyme has been attempted using dextran-aldehyde which would prevent the interaction between enzyme and hydrophobic interfaces with minimal modification of the enzyme surface. After optimizing the size of the dextran (that was found to play a critical role), three different enzymes (glucose oxidase, d-amino acid oxidase, and trypsin) have been conjugated with dextran-aldehyde and their stability towards organic-aqueous and air-liquid interfaces has been evaluated. The treatment itself proved to be very low-cost in terms of activity and was highly stabilizing for the three enzymes assayed. The conjugated preparation of the three assayed enzymes remained fully active in the presence of air-liquid interfaces for at least 10h. However, the unmodified enzymes lost more than 50% of activity within the first hour of the experiments except for trypsin which kept 38% activity after 12h while the trypsin dextran-aldehyde conjugate maintained 100% enzyme activity. Similar results were achieved in the presence of stirred organic solvent-aqueous buffer biphasic system, although in this case some activity was lost by the action of the soluble portion of the organic solvent. In fact, this treatment seems to be also effective to improve the resistance to the action of organic solvent.

Aldehydes↗

APTS-labeled dextran ladder: a novel tool to characterize cell layer tightness.

The aim of this work was the development of an easy manageable analytic system for describing tightness of cell layers in a molecular size dependent manner, which is more precise than currently used ones. Dextrans were labeled by reductive amination with fluorescent 1-aminopyrene-3,6,8-trisulfonate (APTS). This mixture, including internal standard diazepam, was used for transport studies, which were accomplished with an established transwell blood-brain barrier model culturing an immortalized porcine brain microvascular endothelial cell line (PBMEC/C1-2). Samples were analyzed by fluorescence measurements, capillary electrophoresis and RP-LC. Following this approach, a permeability pattern could be achieved including each single fraction from APTS, APTS-glucose to APTS-dextran consisting of 31 glucose units. Permeability coefficients were calculated and ranged from 16.38+/-3.79 microm/min for APTS to 6.07+/-1.23 microm/min for the APTS-dextran with 31 glucose units (diazepam: 67.97+/-7.32 microm/min). All in all, the developed APTS-dextran ladder is an useful tool to characterize cell layer tightness--especially to describe paracellular transport ways and leakiness status of the blood-brain barrier over time--applying a wide range from smaller to larger molecules at the same time in order to refine, e.g. TEER, sucrose or Evans blue measurements.

Animals↗

Dose-dependent biodistribution of [(99m)Tc]DTPA-mannosyl-dextran for breast cancer sentinel lymph node mapping.

[(99m)Tc]DTPA-mannosyl-dextran is a receptor-binding radiopharmaceutical specifically designed for sentinel lymph node mapping. The purpose of this study was to test the biodistribution and safety of [(99m)Tc]DTPA-mannosyl-Dextran at different molar doses. Twenty-four female breast cancer patients participated in this study. Four groups of 6 patients received an injection of 0.2, 1.0, or 5.0 nmol of [(99m)Tc]DTPA-mannosyl-Dextran or filtered [(99m)Tc]sulfur colloid. The injection site clearance was monitored by dynamic imaging for three hours. Whole body scans were acquired at 2.5 and 12, and lymph nodes were assayed for radioactivity after gamma-guided sentinel lymph node biopsy. Injection site clearance of [(99m)Tc]DTPA-mannosyl-Dextran was not statistically different in a dose-dependent manner. Dose-dependent sentinel node uptake was observed (p = 0.03). There were no clinically significant alterations in laboratory parameters among all dose levels at 4 h or 24 h post injection compared to preoperative levels. Radiation absorbed doses did not differ among the three dose levels, but were lower than filtered [(99m)Tc]sulfur colloid.

Adult↗

Decrease in hematocrit after coronary stent placement and dextran therapy.

In summary, dextran 40, when given after coronary stent placement, results in a marked decrease in hematocrit within 24 hours. Hematocrit often returns to near baseline levels within 48 hours of stopping dextran. This phenomenon most likely reflects dextran-related hemodilution. This hemodilutional decrease in hematocrit is often misinterpreted as acute blood loss and may result in blood transfusion in patients with low baseline hematocrit. However, far less aggressive anticoagulation regimens, which do not include dextran, are under investigation in patients undergoing coronary stent placement.

Angioplasty, Balloon, Coronary↗

Intravenous iron dextran therapy in patients with iron deficiency and normal renal function who failed to respond to or did not tolerate oral iron supplementation.

PURPOSE: To evaluate the safety and effectiveness of using 500-mg doses of iron as intravenous iron dextran after premedication with diphenhydramine, cimetidine, and dexamethasone. SUBJECTS AND METHODS: We treated 135 iron-deficient adults (26 men, 109 women) with normal renal function (serum creatinine level </=1.5 mg/dL or blood urea nitrogen level </=26 mg/dL) who could not be treated adequately with oral iron supplements due to gastrointestinal symptoms (59%), inadequate hematologic response (39%), severe anemia (19%), or noncompliance (4%). Some patients had more than one reason for treatment. Resolution of iron deficiency was defined as the restoration of transferrin saturation, serum ferritin level, anemia, and abnormal erythrocyte indexes to normal or baseline values. RESULTS: Before treatment with iron dextran, patients had a mean (+/- SD) transferrin saturation of 8% +/- 5%, a median serum ferritin level of 11 ng/mL, and a mean hemoglobin level of 10 +/- 2 g/dL. Ninety-two percent were anemic; 60% had unrecognized or untreated causes of anemia other than iron deficiency. We administered 285 iron dextran infusions (median 2, mean 2 infusions per patient; range 1 to 7). Eighty-seven percent of patients had no adverse reaction; 13% had mild reactions, especially arthralgias and myalgias. No patient had an anaphylaxis-like reaction. Fifty-four (40%) patients had resolution of iron deficiency, 34 (25%) continue to receive therapy, 36 (27%) returned to the care of their primary physician, and 11 (8%) died before iron repletion could be achieved. CONCLUSIONS: Iron-deficient adults with normal renal function who cannot be treated adequately with oral iron supplements can be treated effectively and safely with this intravenous iron dextran regimen.

Adolescent↗

Is intraperitoneal dextran 70 safe for routine gynecologic use?

The routine use of intraperitoneal 32% dextran 70 has been suggested as an adjuvant to prevent postsurgical pelvic adhesions. Two hundred thirty-four women received an antiadhesion regimen consisting of intraperitoneal 32% dextran 70, dexamethasone, and promethazine. Ten women (4%) experienced spontaneous leakage of the dextran-peritoneal fluid mixture through their abdominal incisions. Painless bilateral swelling of the labia was noted in 18 women (8%). Mild abdominal bloating and weight gain of from 2.5 to 11 pounds were common. No anaphylactic reactions, peritonitis, or wound infections were experienced by any woman. Intraperitoneal dextran 70 appears to be a safe, well-tolerated antiadhesion adjuvant for routine use in gynecologic operations.

Anti-Bacterial Agents↗

Paralysis of the preterm rabbit fetus inhibits the pulmonary uptake of intraamniotic iron dextran.

OBJECTIVE: Whether fetal breathing movements or gasping result in the movement of amniotic fluid substances into the distal airways remains controversial. We evaluated the effect of paralysis of the preterm rabbit fetus on the pulmonary distribution of iron dextran. STUDY DESIGN: Laparotomy was performed on 10 New Zealand White rabbits of 25 days' gestation (term 31 days) under general anesthesia. Fetuses in one uterine horn were given an intramuscular injection of pancuronium (1.5 mg/kg) and fetuses in the other horn were given an equal volume of normal saline solution as controls. A 1 ml volume of iron dextran (100 mg/ml) was injected into the amniotic sac of all fetuses. The laparotomy was closed, and 20 to 24 hours later the fetuses were removed by hysterotomy and assessed for paralysis. Necropsy was performed. Lungs were stained with prussian blue and evaluated histologically for the presence of iron. RESULTS: A total of 92 pups were delivered (49 given pancuronium, 43 given normal saline solution), of which 64 were born alive. There were no differences between groups for live births (31 pancuronium, 33 normal saline solution), pup body weight, or lung weight. Pups given normal saline solution demonstrated more breathing motions, spontaneous movement, and brown (color of iron dextran) stomach contents than did the pups given pancuronium (p < 0.001). At necropsy a greater number of control pups (31/33) had brown lungs grossly compared with pups given pancuronium (2/31, p < 0.001). Lung histologic examination showed that more control pups (29/29) had iron in the trachea and main bronchi compared with pancuronium pups (0/27, p < 0.001), and more control pups (29/29) had iron in the distal lung airways compared with pancuronium pups (0/27, p < 0.001). With use of the Optimas Image Analysis System, iron in the lungs of control pups was found to be equally distributed between right versus left lungs, upper half versus lower half lungs, and anterior versus posterior lung sections. More iron was identified in the central airways than in the periphery (p < 0.001). CONCLUSION: We conclude that paralysis prevents the uptake of iron dextran into the main and distal airways of the rabbit fetus. Although lung fluid production results in a net efflux of fluid, we speculate that fetal breathing movements can result in the movement of fluid into distal airways and potentially provide fetal therapy.

Amniotic Fluid↗