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Comparison of gleptoferron with iron dextran for anemia prevention in young pigs.

Gleptoferron, a sterile aqueous colloidal solution of beta-ferric oxyhydroxide and dextran glucoheptonic acid, was compared with iron dextran for the prevention of Fe deficiency anemia in young pigs. Using 26 litters, pigs (within each litter) were randomly allotted to one of three treatments: 1) control (no Fe), 2) iron dextran (200 mg) and 3) gleptoferron (200 mg). Blood was collected at 0, 10, 21 and 50 d post-treatment for red blood cell count (RBC), hematocrit (HCT), hemoglobin (HGB) concentration, serum Fe concentration (Fe) and serum Fe-binding capacity (IBC). At 21 d, 30 pigs (one pig/treatment from each of 10 litters) were killed to determine milligrams nonheme Fe (NHFe) in liver and spleen, bile IBC and concentrations of bile and fecal Fe. There were no differences (P greater than .05) between Fe sources in 3- or 8-wk body weight or in any of the blood or tissue characteristics. In contrast, control pigs gained less (P less than .05) weight and had lower (P less than .05) RBC, HGB, HCT, serum Fe and liver and spleen NHFe than those that received iron dextran or gleptoferron. Serum IBC was greater (P less than .05) for the control than for Fe-treated pigs. These results demonstrate that the iron from iron dextran and gleptoferron is used with similar efficiency for anemia prevention in young pigs.

Anemia, Hypochromic↗

The distribution of dextran macromolecules in the glomeruli of normal and nephrotoxic rats.

The incorporation of intravenously injected dextran molecules (molecular weight 500,000 & 2,000,000) by the glomeruli of laboratory rats was studied by electron microscopy. In normal rats some dextran molecules were observed 12 minutes after injection in vesicles and invaginations of both endothelial and mesangial cells. Rats with nephrotoxic serum nephritis showed extensive separation of endothelial cells from the glomerular basement membrane. These subendothelial spaces contained irregular granular material, cytoplasmic extensions of mesangial cells and, in animals injected with dextran, dense accumulations of dextran molecules. There was no apparent difference in distribution of the two test samples of dextran. These findings demonstrated the involvement of both endothelial and mesangial cells in the glomerular localization of circulating material and indicated that immunologically inactive macromolecules can be incorporated into subendothelial deposits following immunological injury to the glomerulus.

Animals↗

Anti-neutrophil serum attenuates dextran sulfate sodium-induced colonic damage in the rat.

BACKGROUND: The role of neutrophils in experimental colonic damage induced by dextran sulfate sodium is uncertain. We test the hypothesis that neutrophils are of pathogenic significance and anti-neutrophil serum will attenuate the colonic damage induced by oral dextran sulfate sodium in rats. METHODS: Rabbit anti-rat neutrophil serum (anti-neutrophil serum) or control rabbit serum was administered to, and circulating neutrophil count was monitored in, rats before and during feeding of dextran sulfate sodium or regular rat diet for 2 weeks. Histologic features of mucosal damage were evaluated in hematoxylin and eosin-stained proximal and distal colonic sections by a blinded observer. RESULTS: Oral dextran sulfate sodium induces weight loss, diarrhea, peripheral neutrophilia, and colonic damage. Anti-neutrophil serum induced neutropenia and significantly attenuated the weight loss, the neutrophil infiltration in the colon, and the mucosal necrosis and pathologic index in the distal colon. CONCLUSION: The data showing that anti-neutrophil serum attenuates distal colonic mucosal injury induced by dextran sulfate sodium support the hypothesis that neutrophils play a pathogenic role in this model of colonic mucosal damage.

Animals↗

Incidence of acute oligoanuric renal failure in dextran 40 treated patients with acute ischemic stroke stage III or IV.

Two hundred eleven patients with acute ischemic stroke, stage III or IV, received daily intravenous infusion of 500-1000 mL low-molecular dextran (dextran 40) over a period of 4 days. In 10 cases (4.7%) acute renal failure, associated with dextran infusion, could be observed; oligoanuria occurred after a mean time of 4 (3-6) days. The incidence of dextran-induced acute renal failure was significantly higher in patients with a preexisting reduction of glomerular filtration rate below 30 mL/min/1.73 m2 (p < 0.005). Five of the patients (50%) with acute renal failure died within 4-12 days after the hemodilution therapy with dextran 40; this high lethality was due to nonrenal complications.

Acute Disease↗

The effect of nimodipine and dextran on axonal function and blood flow following experimental spinal cord injury.

There is evidence that posttraumatic ischemia is important in the pathogenesis of acute spinal cord injury (SCI). In the present study spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, and motor and somatosensory evoked potentials (MEP and SSEP) were recorded to evaluate whether the administration of nimodipine and dextran 40, alone or in combination, could increase posttraumatic SCBF and improve axonal function in the cord after acute SCI. Thirty rats received a 53-gm clip compression injury on the cord at T-1 and were then randomly and blindly allocated to one of six treatment groups (five rats in each). Each group was given an intravenous infusion of one of the following over 1 hour, commencing 1 hour after SCI: placebo and saline; placebo and dextran 40; nimodipine 0.02 mg/kg and saline; nimodipine 0.02 mg/kg and dextran 40; nimodipine 0.05 mg/kg and saline; and nimodipine 0.05 mg/kg and dextran 40. The preinjury physiological parameters, including the SCBF at T-1 (mean +/- standard error of the mean: 56.84 +/- 4.51 ml/100 gm/min), were not significantly different (p greater than 0.05) among the treatment groups. Following SCI, there was a significant decrease in the SCBF at T-1 (24.55 +/- 2.99 ml/100 gm/min; p less than 0.0001) as well as significant changes in the MEP recorded from the spinal cord (MEP-C) (p less than 0.0001), the MEP recorded from the sciatic nerve (MEP-N) (p less than 0.0001), and the SSEP (p less than 0.002). Only the combination of nimodipine 0.02 mg/kg and dextran 40 increased the SCBF at T-1 (43.69 +/- 6.09 ml/100 gm/min; p less than 0.003) and improved the MEP-C (p less than 0.0001), MEP-N (p less than 0.04), and SSEP (p less than 0.002) following SCI. With this combination, the changes in SCBF were significantly related to improvement in axonal function in the motor tracts (p less than 0.0001) and somatosensory tracts (p less than 0.0001) of the cord. This study provides quantitative evidence that an increase in posttraumatic SCBF can significantly improve the function of injured spinal cord axons, and strongly implicates posttraumatic ischemia in the pathogenesis of acute SCI.

Animals↗

Dextran potentiation of the canine lymphocyte response to plant mitogens (38515).

Peripheral blood lymphocytes from Beagle dogs were separated using a dextran sedimentation technique. Lymphocyte cultures were stimulated by the plant mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), both in the presence of dextran and after dextran had been removed from the medium. It was found that dextran acted synergistically with both PHA and PWN and greatly potentiated the mitogenic response of the lymphocytes. The routine use of dextran in separating blood lymphocytes for culture purposes should be reevaluated in light of these findings.

Animals↗

Erythrocytes sedimentation profiles under gravitational field as determined by He-Ne laser. VII. Influence of dextrans, albumin and saline on cellular aggregation and sedimentation rate.

The erythrocytes sedimentation profiles (ESP) of normal blood and of blood mixed with saline, albumin (7%), and various molecular weight dextrans of different concentrations, at various height and widths of the sample holder are determined. These observations show that the sedimentation characteristics of the erythrocytes depend on the influence of these substitutes on the plasma and cellular constituents. The normalised aggregation and the sedimentation rate, as determined from these profiles, show that the dextran 40 and dextran 70 retard the erythrocytes sedimentation, for high molecular weight it is similar to that of normal blood and is the maximum for saline. This change for high molecular weight dextrans could be attributed to the enhanced aggregation tendency of erythrocytes and for saline to the enhanced sedimentation due to decrease in the viscosity and density of suspending medium. The influence of the various concentrations of dextrans on these parameters has been determined.

Albumins↗

Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis.

OBJECTIVES: To assess the benefits in terms of reductions in the risks of deep vein thrombosis (DVT) and of pulmonary embolism (PE), and hazards in terms of major bleeding, of: (i) mechanical compression; (ii) oral anticoagulants; (iii) dextran; and (iv) regional anaesthesia (as an alternative to general anaesthesia) in surgical and medical patients. DATA SOURCES: Electronic databases, search of Antithrombotic Trialists' Collaboration database, contact with trialists and manufacturers. REVIEW METHODS: All trials identified as fitting the selection criteria were independently assessed. The primary outcomes were DVT, PE and major bleeding events, and proximal venous thrombosis (PVT) and fatal PE were secondary outcomes. Trials were subdivided into those that had assessed a method as the only means of thromboprophylaxis ('monotherapy') and those that had assessed the effects of adding a method to another form of thromboprophylaxis ('adjunctive therapy'). RESULTS: Mechanical compression methods reduced the risk of DVT by about two-thirds when used as monotherapy and by about half when added to a pharmacological method. These benefits were similar irrespective of the particular method used (graduated compression stockings, intermittent pneumatic compression or footpumps) and were similar in each of the surgical groups studied. Mechanical methods reduced the risk of PVT by about half and the risk of PE by two-fifths. Oral anticoagulants, when used as monotherapy, reduced the risk of DVT and of PVT by about half, and this protective effect appeared similar in each of the surgical groups studied. There was an apparently large four-fifths reduction in the role of PE, but not only was the magnitude of this reduction statistically uncertain, but also pulmonary embolism was reported by a minority of trials, so it may be subject to selection bias. Oral anticoagulant regimens approximately doubled the risk of major bleeding and appeared less effective at preventing DVT than heparin regimens, although were associated with less major bleeding. Dextran reduced the risk of DVT and of PVT by about half, again irrespective of the type of surgery, but too few studies had reported PE to provide reliable estimates of effect on this outcome. Dextran appeared to be less effective at preventing DVT than the heparin regimens studied. Dextran was associated with an increased risk of bleeding, but too few bleeds had occurred for the size of this excess risk to be estimated reliably. Compared with general anaesthesia, regional anaesthesia reduced the risk of DVT by about half, and this benefit appeared similar in each of the surgical settings studied. Regional anaesthesia was associated with less major bleeding than general anaesthesia. CONCLUSIONS: In the absence of a clear contraindication (such as severe peripheral arterial disease), patients undergoing a surgical procedure would be expected to derive net benefit from a mechanical compression method of thromboprophylaxis (such as graduated compression stockings), irrespective of their absolute risk of venous thromboembolism. Patients who are considered to be at particularly high risk of venous thromboembolism may also benefit from a pharmacological thromboprophylactic agent, but since oral anticoagulant and dextran regimens appear less effective at preventing DVT than standard low-dose unfractionated heparin or low molecular weight heparin regimens, they may be less suitable for patients at high risk of venous thromboembolism, even though they are associated with less bleeding. Whenever feasible, the use of regional anaesthesia as an alternative to general anaesthesia may also provide additional protection against venous thromboembolism. There is little information on the prevention of venous thromboembolism among high-risk medical patients (such as those with stroke), so further randomised trials in this area would be helpful.

Administration, Oral↗

Prevention of hypotension after spinal anesthesia for cesarean section: dextran 40 versus lactated Ringer's solution.

BACKGROUND: This study was designed to compare the efficacy of 10% dextran 40 with lactated Ringer's (LR) solution in reducing the incidence and severity of hypotension after spinal anesthesia for Cesarean section. METHODS: Sixty ASA grade I patients scheduled for Cesarean section were randomized into two groups in a double-blind fashion to receive either 500 ml of dextran 40 or 1000 ml of LR solution prior to induction of spinal anesthesia. RESULTS: The incidence of hypotension was 16 in 30 (53.3%) in the LR solution group and 8 in 30 (26.7%) in the dextran group (P < 0.05). The required dose of ephedrine for treatment of hypotension was significantly greater in the LR solution group than in the dextran group (15.5 mg versus 3.2 mg, P < 0.05). Neonatal outcome, as determined by Apgar score, was good and similar in both groups. CONCLUSIONS: We concluded that 500 ml of dextran 40 is more effective than 1000 ml of lactated Ringer's solution in reducing the incidence of hypotension induced by spinal anesthesia.

Adult↗

The adsorptive properties of hydroxyapatite to albumin, dextran and lipids.

Hydroxyapatite is widely utilized as a component in dental hygiene agents. The ability to adsorb and remove dental plaque adhering to tooth surfaces is recognized as an important property of hydroxyapatite particles. In this study, the adsorptive ability of hydroxyapatite was evaluated based on its adsorptive amount and adsorptive strength. The adsorptive amount was determined by measuring the weight of albumin, dextran and lipids adsorbing to hydroxyapatite. The adsorptive strength was determined by measuring the weights of albumin and dextran remaining adsorbed after rinsing. Similar procedures were performed in control experiments using calcium hydrogen phosphate dihydrate, alumina and sericite. The results showed that the weights of albumin and dextran adsorbed to hydroxyapatite were 1.4 +/- 0.13 and 1.6 +/- 0.30 times higher than that to calcium hydrogen phosphate dihydrate. The weight of lipids adsorbed to hydroxyapatite was much higher than that to alumina and sericite. The percentages of weight loss of albumin and dextran were 2.3 +/- 1.7% and 5.3 +/- 2.0% for hydroxyapatite and 27 +/- 6.8% and 19 +/- 11% for calcium hydrogen phosphate dihydrate after one rinse. It is concluded that hydroxyapatite is a better adsorbent than calcium hydrogen phosphate dihydrate, alumina and sericite with respect to adsorbing albumin, dextran and lipids.

Adsorption↗

IgA anti-dextran B1355 responses.

Injection of mice bearing the Ig-1a allotype with dextran B1355 results in an IgM antibody response that is generally regarded as thymus independent. Moreover, the antibody is directed to alpha[1,3] determinants on dextran B1355 and shares cross-reacting idiotypic determinants with a lambda 1 IgA (J558) myeloma protein as well as a lambda 1 IgM (MOPC 104E) myeloma protein. In this study, we show that BALB/c (Ig-1a) mice injected with dextran B1355 produced highly significant IgA anti-dextran responses with specificity directed to the alpha[1,3] epitope. Kinetics of the IgA anti-dextran response in BALB/c mice paralleled kinetics of the IgM response. However, the magnitude of the IgA response was markedly T cell dependent and age dependent.

Aging↗

[Hypersensitivity reaction associated with the use of Dextran 70 (Hiscon) in Hysteroscopy (author's transl)].

A hypersensitivity reaction to Dextran 70 during hysteroscopy for removal of an implanted Dalkon Shield is reported. The patient had not been exposed to Dextran previously and the hypersensitivity reaction was controlled by the administration of Benadryl, Solu-cortef and Phenergan. Since Dextran 70 is especially useful for hysteroscopy when bleeding is anticipated the possibility of enought Dextran uptake in the blood stream to cause a hypersensitivity reaction must be kept in mind during hysteroscopies with Dextran 70.

Adult↗

Modulation of trichosanthin antigenicity by coupling to dextran.

Trichosanthin (TCS) is a plant-derived type I ribosome-inactivating protein with a wide spectrum of biological and pharmacological activities. Recently, it was covalently coupled to dextran in order to prolong its half-life in plasma. The major biological activities were generally retained but at lower potency. The immunogenicity of the dextran-trichosanthin (DX-TCS) was compared to that of TCS itself in this study. The results showed that mice immunized with TCS produced 8 times as much TCS-reactive IgE than those immunized with DX-TCS. However, both TCS and DX-TCS immunization produced similar titers of TCS-reactive IgG. A trace of dextran-reactive IgG was detected in mice immunized with DX-TCS. Thus, coupling of TCS to dextran reduced its antigenicity but slightly enhanced that of dextran, and the conjugate elicited less IgE than TCS.

Adjuvants, Immunologic↗

Comparison of top and bottom loading of a dextran gradient for rat pancreatic islet purification.

Rat pancreatic islet yields obtained with dextran gradient purification were compared after suspending the digest into either the top or the bottom layer of the gradient. A 5-layer discontinuous gradient was used, which consisted of 16 ml 31% dextran as bottom layer, overlayered with 25%, 23%, 20% and 11% dextran (4 ml each). When the digest of 1 rat pancreas was suspended into the top layer of the gradient, the total number of islets obtained from the 11-20, 20-23 and 23-25% interfaces was 862 +/- 38, 240 +/- 39 and 54 +/- 5, respectively. From this gradient, also 1409 +/- 81 islets were retrieved from the bottom layer (i.e., exocrine pellet). In contrast, when the pancreas digest was suspended into the bottom layer of the gradient, 1964 +/- 63, 435 +/- 42, and 177 +/- 34 islets were obtained from the successive interfaces, and only 50 +/- 20 islets from the exocrine pellet. The total islet volume obtained from the two uppermost interfaces was 3.46 +/- 0.31 microliters after top-loading, and 4.93 +/- 0.16 microliters after bottom-loading (n = 7, p < 0.01). When the islets retrieved from one bottom loaded gradient were transplanted into either 1 (n = 6) or 2 (n = 9) diabetic recipients, glucose levels normalized in all instances. We therefore conclude that a bottom-loaded dextran gradient separates islets from exocrine tissue effectively, resulting in significantly higher islet yields than obtained with a top-loaded dextran gradient.

Animals↗

Detection of gastric and colonic sentinel nodes through endoscopic administration of 99mTc-DTPA-mannosyl-dextran in pigs.

UNLABELLED: The purpose of this study was to develop a method for the endoscopic administration of a radiopharmaceutical for sentinel node detection and to characterize its uptake by gastric and colonic sentinel nodes. (99m)Tc-Diethylenetriaminepentaacetic acid (DTPA)-mannosyl-dextran is a new radiotracer labeled with (99m)Tc and composed of multiple units of mannose attached to the polymeric backbone, dextran. METHODS: Gastric and colonic lymph node detection was studied in 4 fasting and anesthetized pigs. A flexible video endoscope was inserted into the rectum and positioned in the lower colon or advanced down the esophagus into the stomach. A standard endoscopic sclerotherapy needle and sheath filled with 0.9% saline was then loaded with 0.2 mL of a 7.4-MBq 1:1 (v/v) mixture of isosulfan blue and (99m)Tc-DTPA-mannosyl-dextran (7.4 MBq, 0.3 nmol). The needle and sheath were passed through the biopsy channel, and the radiotracer/dye solution (0.1 mL) was injected in a tangential fashion into the submucosa. Within 5-10 min after injection, all radioactive or blue lymph nodes were excised, assayed for radioactivity, and noted for color. Distal lymph nodes were also excised, assayed, and noted for color. RESULTS: (99m)Tc-DTPA-mannosyl-dextran uptake by colonic sentinel nodes (n = 4) ranged from 0.54% to 2.4% of the injected dose; all radioactive nodes were stained blue. The uptake for all (n = 3) distal nodes ranged from 0.001% to 0.005%, and none of these nodes were stained blue. Uptake by gastric sentinel nodes (n = 6) ranged from 0.13% to 4.50%; all radioactive nodes were stained blue. The range for distal nodes was 0.001% to 0.050%; no distal nodes were stained blue. In 2 pigs, each gastric injection produced 2 hot and blue lymph nodes. CONCLUSION: Within 10 min of a gastric and colonic submucosal injection, (99m)Tc-DTPA-mannosyl-dextran demonstrated high sentinel node uptake and high concordance with isosulfan blue.

Animals↗

Treatment of cirrhotic tense ascites with Dextran-40 versus albumin associated with large volume paracentesis: a randomized controlled trial.

Intravenous albumin infusion prevents complications after large-volume paracentesis (LVP), particularly paracentesis-induced circulatory dysfunction (PCD), and improves patient survival. However, albumin is expensive. We compared a low-molecular weight dextran (Dextran-40) with albumin in treating LVP in cirrhotic patients with tense ascites. Sixty-nine cirrhotic patients were included and 96 LVPs were performed. Any repeat punctures on the same patient were at least three months apart. Patients were randomized to receive either i.v. Dextran-40 infusion (Group I, n = 48) or i.v. albumin infusion after LVP (Group II, n = 48). Clinical, biochemical, and hormonal evaluations were done before and after LVP. Patients were followed up for the detection of any recurrence of ascites or complications. The two groups were similar in age, sex, and etiology of cirrhosis, and in the volumes of ascites recovered. Significant decreases in mean arterial pressure were observed in both groups 24 and 48 h after LVP. Urine volumes increased significantly at 24 h in both groups (p < 0.05), but remained high only in Group I. Plasma renin activity and aldosterone concentrations increased in both groups 48 h after LVP, but they were more marked in Group I. Complications developed in 17 % of patients treated with Dextran-40 and in 23 % treated with albumin (p > 0.05). Ascites recurrence rates and survival were similar in the two groups. In conclusion, Dextran-40 was thus not as efficacious as albumin for preventing PCD.

Aged↗

The effect of renal arterial infusion of albumin and dextran on tubular fluid reabsorption in the dog.

Albumin or Dextran solutions of varying concentration were infused into the renal artery of hydropenic dogs. Their effect on urine flow, sodium excretion, creatinine and PAH clearance, single nephron GFR, fractional and absolute fluid reabsorption in the proximal convolution, reabsorptive t1/2, and hydrostatic pressures in the proximal tubules and adjacent capillaries was compared with a similar infusion of isotonic saline solution. Six, 9, 12, 18 and 25% albumin and 6% Dextran solution did not significantly change the measured parameters. Infusion of 9 and 12% Dextran solution elicited a decrease in water and sodium excretion as well as absolute and fractional proximal tubular fluid reabsorption to a 5% level of significance. Infusion of 18% Dextran was accompanied by a marked decrease in total and proximal reabsorption combined with a decline of GFR, PAH clearance, and hydrostatic pressures in tubules and peritubular capillaries. The results do not support the hypothesis of a direct action of oncotic pressure on tubular fluid reabsorption; the above described effects of Dextran seem to be accounted for by its other "pharmacological" effect.

Absorption↗

Human factor XII (Hageman factor) autoactivation by dextran sulfate. Circular dichroism, fluorescence, and ultraviolet difference spectroscopic studies.

The first event leading to the activation of the plasma kallikrein-kinin system is the surface-dependent conversion of factor XII to an active enzyme. Factor XII autoactivation was investigated using dextran sulfate as a soluble activating surface, and the significance of aggregation and the nature of the conformational change were examined by ultraviolet difference spectroscopy, fluorescence and circular dichroism. Results indicate that DS500 (500-kDa dextran sulfate) induces aggregation of factor XII. Analysis of the binding data suggests that 165-192 factor XII molecules can bind to one DS500 chain, while a 1:1 stoichiometry is observed with 5-kDa dextran sulfate. The interaction of factor XII and dextran sulfate is a biphasic process. It is initiated by a fast contraction of the molecule upon binding, as revealed by an apparent increase in organized secondary structures, and then followed by a slow relaxation process during cleavage and subsequent activation. Overall, the results are consistent with a model in which factor XII undergoes conformational changes upon binding to the activating surface. The rapidity of autoactivation in the presence of DS500, as opposed to 5-kDa dextran sulfate, implies that aggregation provides a special mechanism whereby proteolytic cleavage is accomplished efficiently when factor XII molecules are bound side by side on the DS500 molecule.

Circular Dichroism↗