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[Hemorheologic changes in preoperative hemodilution during total hip replacement. Randomized study comparing hydroxyethyl starch 200,000/0.62 (HES) and a dextran 60,000].

Hemodilution can be used to save blood transfusion during total hip replacement. We have carried out a randomized study to compare the hemorheological effects of two plasma substitutes: a hydroxyethylstarch 200,000/0.62 versus a dextran 60,000. Twenty-two patients were hemodiluted with 20 mk/kg of either substitute, just after the spinal anesthesia. Whereas the hematocrit have fallen by 30% in the two groups, significant differences are observed about hemorheological parameters. The plasma viscosity express a greater increase at hour 4 in the dextran group. The whole blood viscosities are more increased in the dextran group at hour 4 and 24. The erythrocyte aggregation is decreased in the HES group at hour 4 and 24, but is increased in the dextran group. The fibrinogen is more increased in the dextran group at day 7. In spite of similar hemodilutions, the two substitutes express different hemorheological effects with a favourable role of HES on erythrocyte aggregation and blood viscosities. This can improve the microcirculation and decrease the activation of the endothelial cells, reducing the inflammatory reaction.

Adult↗

Effect of low molecular weight heparin, dextran and their combinations on experimental venous thrombosis in rabbits.

An experimental model based on the combination of endothelial damage and flow reduction was used to induce jugular vein thrombosis in rabbits. The effect on thrombosis of a low molecular weight heparin (LMWH [Fragmin]), dextran 70, placebo and their combination was studied in a double-blind fashion with actual doses used in clinical thromboprophylaxis. Saline and polygeline were used as placebo in the control group. Four groups with 120 isolated vein segments in 60 animals were studied for presence of thrombus formation, occlusive thrombi and thrombus weights. Dextran reduced the thrombus weights (p = 0.048) and the formation of occlusive thrombi (p = 0.01), but not the formation of thrombi when compared with the placebo control group. Similarly, LMWH reduced the thrombus weights (p = 0.046), the formation of thrombi (p = 0.007) and occlusive thrombi (p = 0.0001). Compared with the LMWH group the group treated with the combination of LMWH and dextran was found to reduce the frequency of occlusive thrombi (p = 0.03) and numerically, but not significantly, further reduce the overall frequency of thrombosis (p = 0.18) and thrombus weights (p = 0.11). The results are consistent with an augmentation of the antithrombotic effect of LMWH by dextran 70. The need for further evaluation of the combined efficacy of LMWH and dextran is apparent from this study.

Animals↗

Use of dextran beads for live analysis of the nuclear division and nuclear envelope breakdown/reformation cycles in the Drosophila embryo.

We employ fluorescently labeled dextran beads to follow cycles of nuclear division and nuclear envelope breakdown in living Drosophila embryos. When injected into syncytial Drosophila embryos, 3000 mol wt fluorescently labeled dextran beads concentrate in the interphase nucleus. Through confocal microscopy, undisrupted multiple cycles of nuclear division are readily followed. In contrast, 40,000 mol wt fluorescently labeled dextran beads concentrate in the cytoplasm and enter the nucleus only after nuclear envelope breakdown during prophase. Once the nuclear envelope reforms during telophase, these large dextran beads are again excluded from the nuclei. The complementary behavior of the large and small dextran beads makes them applicable to a broad range of cellular studies. We employ the 40,000 mol wt fluorescein-labeled beads, in combination with rhodamine-labeled histones, to demonstrate that nuclear envelope breakdown occurs about 3.5-4.0 minutes prior to the initiation of anaphase.

Animals↗

Study of the interaction of dextran and enoxaparin on haemostasis in humans.

The effect on haemostatic variables by dextran 70, enoxaparin and their combinations, given in doses of 500 ml i.v. and 40 mg s.c. respectively, was studied in a randomised cross-over fashion in twelve healthy male volunteers. Antifactor-IIa activity, antifactor-Xa activity, APTT, factor VIII, vWF, bleeding time and blood counts were analysed over a 24-h period. Dextran alone did not affect antifactor-IIa activity and antifactor-Xa activity. No difference in antifactor-IIa and antifactor-Xa activity was found for Amax, tmax, AUC0-8 h and AUC0-24 h in the groups treated with enoxaparin or the combination of enoxaparin and dextran. Only minor changes in APTT were observed without statistical significance between the treatment groups. Factor VIII did not change significantly in the three treatment groups. However, vWF was significantly reduced in the dextran and the dextran/enoxaparin group (p = 0.046 and 0.01 respectively) but no difference was found between the two groups. Bleeding time was not significantly increased four hours after administration of the test substances and no difference was found between the individual treatment groups. Our findings indicate that dextran can be combined with enoxaparin, when used in thromboprophylactic doses, without increased risk for bleeding.

Adult↗

Preservation of competent rabbit lung function after 30 hours of storage with a low-potassium dextran solution.

BACKGROUND: The goal of organ preservation is maintenance of physiologic functions during extended extracorporeal storage. METHODS: This study was designed to evaluate the efficacy of using low-potassium (4 mmol/L) dextran (1%) solution on lung function after 30 hours hypothermic (10 degrees C) storage and to compare this with lung function after no storage. With low-potassium dextran solution rabbit lungs were flushed (10 degrees C, 40 ml/kg, 60 cm H2O), excised, inflated (with room air), and either not stored (control; no preservation; n = 9) or stored in low-potassium dextran solution (10 degrees C) 30 hours (experimental group; n = 9). RESULTS: During the flush the infusion pressure and pulmonary vascular resistance for the two groups did not differ (17.56 +/- 1.3 versus 16.74 +/- 1.5 mm Hg/ml/sec). After either no preservation or after 30 hours of storage, the lungs were first reperfused with low-potassium dextran solution (37 degrees C) for 4 minutes and then with blood (37 degrees C) for 30 minutes at 100 ml/min. During the reperfusion period the mean pulmonary artery pressure and end-inspiratory airway pressure for the control and experimental groups did not differ. After reperfusion the wet and dry weights of the left lung were determined. The wet/dry ratio for the two groups did not differ (5.32 +/- 2.20 versus 4.70 +/- 2.70, respectively). CONCLUSIONS: These data suggest that cold flush, cold storage, and initial warm perfusion with low-potassium dextran solution crystalloid preserve lung function after 30 hours of storage.

Animals↗

Serum anti-dextran antibodies in IgA nephropathy.

Abnormally high humoral responses have been described in IgA nephropathy (IgAN), towards antigens commonly involved in infectious events or food intolerance. Here we report a comparative analysis of humoral responses to a common environmental antigen, dextran B 512, present both in nonpathogenic microorganisms and normal diet. Dextran-specific IgG, IgA and IgM were assayed using an ELISA method in serum samples from 121 patients with IgAN, 40 controls and 32 patients with biopsy-proven renal diseases different from IgAN. Among the latter, 17 were transplant recipients. Anti-dextran IgG antibodies were found significantly (p < 0.05) more frequently and at higher levels in IgAN patients than in patients with other renal diseases. Anti-dextran IgA were at significantly (p < 0.05) higher levels in IgAN patients than in controls or untransplanted NIgAN patients. However, similarly elevated levels of anti-dextran IgA were found in IgAN patients and transplanted patients with other renal diseases. These data confirm that IgA and IgG responses towards common antigens are elevated in IgAN, possibly as a consequence of the pathogenesis of this disease rather than because of renal impairment. Moreover, since the same degree of dysregulation was noted in the control group of transplanted patients whose initial diagnosis was not IgAN, these data favour the hypothesis of a global dysregulation of the IgA system in IgAN, yielding enhanced humoral immune responses to possible pathogens and diet antigens.

Adult↗

Iron metabolism and oxidative stress during acute and chronic phases of experimental inflammation: effect of iron-dextran and deferoxamine.

Iron overload induces a rise in lipid peroxidation, but there are no data on the effects of iron administered in vivo on the production of free radicals by inflammatory cells. Further, there is lack of agreement about the benefits of deferoxamine (Dfx) in the treatment of anemia and oxidative stress during inflammation and chronic diseases. In this study, iron-dextran (Fe-dextran) or Dfx was administered subcutaneously during the acute and chronic phases of carrageenan-induced granuloma. Several parameters related to iron metabolism, inflammatory cell activity, and lipid peroxidation were measured in liver, plasma, and the inflammatory exudate. Treatment with Fe-dextran increased iron content in plasma and in stores, increased production of superoxide anion (O2-) by inflammatory cells and lipid peroxidation, and also altered the inflammatory process. Dfx mobilized iron from stores without modifying essential parameters related to anemia or to the level of lipid peroxidation induced by inflammation. We conclude that treatment with Fe-dextran had a beneficial effect on recovery from the anemia of inflammation. Nevertheless, the high levels of loosely-bound iron found after Fe-dextran treatment in plasma and in exudate contribute to the increase in oxidative stress. Dfx treatment had no effect on anemia or on lipid peroxidation.

Acute Disease↗

[The effect of phenol derivatives on the antimutagenic activity of dextran].

The effects of dextran + hydrazine or amino derivative of dibunol and of dextran + cystafos derivatives with different degree of modification of their molecules on the mutagenic activity of gamma irradiation were studied using the micronucleus test in polychromatophilic erythrocytes of the mouse bone marrow. The effects of these compounds on differentiation of the erythroid series has also been studied. The mutagenic activity of gamma irradiation was most markedly inhibited by the copolymer dextran and the amino derivative dibunol. The optimal structure of copolymers was 1 heterocyclic link per 3 non-oxidized links of dextran, while the increasing number of active links in the dextran molecule insignificantly enhanced its antimutagenic effect. The studied compounds effectively protected erythropoiesis.

Animals↗

Falsely decreased total serum calcium concentration associated with iron dextran injection.

We cared for a patient in whom iron dextran administration interfered with the determination of total serum calcium concentration. An unexpected elevation in serum phosphorus concentration also occurred after the iron dextran infusion. A MEDLINE search from 1966 to present was conducted, and the manufacturer of the iron dextran was contacted for information related to these findings. Several drugs and diseases were found that may decrease serum calcium and increase phosphorus concentrations. We found one anecdotal citation of iron dextran interfering with serum calcium concentrations, but no reports of interference with serum phosphorus concentrations. Doses of iron dextran in excess of 250 mg may cause a false decrease in total calcium concentration more than 4 hours after the infusion is completed. A false increase in serum phosphorus concentrations after the infusion requires further investigation.

Antiviral Agents↗

Hematologic and erythropoietin responses to iron dextran in the hemodialysis environment.

OBJECTIVE: To investigate the hematologic and economic advantages of using iron dextran as the sole supplemental agent to safely increase and maintain hematocrit levels and iron availability while optimizing erythropoietin dosing in patients on chronic hemodialysis. DESIGN: Iron dextran 100 mg (2 ml) was administered i.v. slow push, undiluted three times per week, sometime during the last 30 minutes of each hemodialysis treatment, until a total required ml (determined by using the package insert's formula) was attained. Maintenance doses of either 25 or 50 mg per week (dependent upon body weight) were administered ongoing to compensate for dialytic and gastrointestinal blood losses. The analysis duration was 12 months. SAMPLE/SETTING: A prospective analysis was performed on 13 clinically stable hemodialysis outpatients in a rural community hospital-based dialysis facility (mean age 56.4 years ranging from 24-76; sample included 9 males, 4 females). METHODS: The means and medians were calculated for each variable: hematocrit, ferritin, transferrin saturation, and erythropoietin dose. A one-tailed paired student t test was performed on doses of erythropoietin at -1 and 6 months, -1 and 9 months, and -1 and 12 months. Cost per patient of iron dextran loading dose and maintenance, as well as cost savings from actual erythropoietin dose reductions, were calculated at 3, 9, and 12 months. Cost savings reflected the cost of iron dextran. RESULTS: After 6 months on the protocol, erythropoietin doses decreased an average of 3100 units per patient with an 8% increase in hematocrit and 66% and 78% increase in transferrin saturation and ferritin, respectively. Based on averages in actual reduced erythropoietin dosing, a savings of +5,070 per patient per year was realized. CONCLUSIONS: This analysis found the use of iron dextran in the hemodialysis setting to be an effective and economic means to maintain hematocrit values and iron availability while optimizing erythropoietin dosing.

Adult↗

Effect of high-molecular weight dextran macromolecules on low-flow ischemia and reperfusion of the large colon in horses.

OBJECTIVE: To evaluate the effect of high-molecular weight (MW) dextran macromolecules on low-flow ischemia and reperfusion of the large colon in horses. DESIGN: Horses subjected to low-flow ischemia and reperfusion of the large colon were treated with either 0.9 NaCl (group 1, n = 6) or high-MW dextran (group 2, n = 6) solutions. ANIMALS: 12 adults horses. PROCEDURE: Horses were subjected to 3 hours' low-flow ischemia followed by 3 hours' reperfusion. A dose of either 0.9% NaCl or a 6% solution of high-MW (250,000) dextran (10 ml/kg of body weight) was administered i.v., 30 minutes prior to reperfusion. Hemodynamic variables were recorded at 30-minute intervals. Systemic arterial and colonic venous blood were collected for determination of PCV, plasma total protein, and whole blood lactate concentrations, and for blood gas and oximetry analyses. Histologic examination of large-colon biopsy specimens was performed. RESULTS: Mean arterial pressure was greater in group-2 horses, compared with group-1 horses, from 3 to 3.25 hours, but there were no significant differences between groups for any of the other hemodynamic variables. Compared with baseline values, colonic blood flow was significantly lower from 0.5 to 3 hours and was significantly greater from 3.25 to 6 hours. Arterial and colonic venous PCV were significantly lower than baseline values from 3 to 3.25 hours, and at 3 hours, respectively, in group-2 horses. These values were significantly lower in group-2 horses, from 3 to 6 and 3 to 5 hours, respectively. There was significant mucosal necrosis, hemorrhage, edema, and neutrophil infiltration in horses of both groups; however, there were no significant differences between the 2 groups. CONCLUSIONS: High-MW dextran did not protect the colonic mucosa from low-flow ischemia and reperfusion; there were no deleterious effects on colonic mucosa or on systemic hemodynamic or metabolic variables. CLINICAL RELEVANCE: Reperfusion with high-MW dextran solution probably would not protect the large colon from ischemia-reperfusion injury associated with large-colon volvulus.

Animals↗

Isolation of a cell line insensitive to growth-restricting action of dextran sulfate from 3t6 cells.

In the medium containing dextran sulfate, 3T6 cells stopped growth at almost monolayer stage and showed decreased saturation density. This action of dextran sulfate is referred to as a growth restriction. About 70% of untreated 3T6 cells formed piled-up colonies whereas the remaining 30% formed monolayer colonies. Fraction of the latter increased with increasing concentration of dextran sulfate in the medium. Cell lines sensitive and insensitive to the growth-restricting action of the compound were cloned from colonical culture of the wild type cells. Sensitive cells showed a slightly less saturation density than the wild type cells in the presence of dextran sulfate. Insensitive cells grown in dextran sulfate medium showed almost the same growth rate and saturation density as the untreated wild type cells grown in the absence of the compound.

Animals↗

Dextran anaphylactoid reaction in Sprague-Dawley CFY rats.

From a closed colony of randomly-bred Sprague-Dawley CFY rats about 23% failed to respond to intravenous dextran with the characteristic generalized anaphylactoid reaction, but still exhibited an inflammatory response when dextran was given into the foot pad. Brother-sister mating of rats showing the most expressed generalized reaction (reactor rats) yielded good responder offsprings, while the non-reactors had descendants completely unresponsive to systemic dextran. Brother-sister mating of selected non-reactor rats led to a gradual decrease in dextran paw oedema in the subsequent generations, and after the third mating, a complete local non-reactivity developed. In these rats the intradermal injection of dextran failed to increase vascular permeability, while the inflammatory response evoked by histamine, 5-HT, bradykinin, and compound 48/80 remained unchanged as compared to that of the reactor animals. These result show that the anaphylactoid reaction in Sprague-Dawley CFY rats is under genetic control.

Anaphylaxis↗

Effects of dextran on the molecular structure and tensile behaviour of human fibrin.

Characteristic changes induced by dextran during the conversion of fibrinogen to fibrin have previously been shown to be associated with profound alterations in morphology of fibrin. However, whether dextran is incorporated into the fibrin molecule and whether morphological changes are associated with alterations in mechanical behaviour of formed fibrin was unclear. The investigations described show that the fibrin made in the presence of dextran has a shortened syneresis time, a lowered modulus of elasticity, an increased elongation and diminished ultimate strength at break. The molecular composition of fibrin clots remains unaltered despite the altered mechanical properties and morphological changes. Furthermore, dextran is not incorporated into the fibrin structure in any appreciable quantity. It is suggested that these several effects of dextran on clot morphology, tensile behaviour and kinetics of fibrin formation arise from increased forces of attraction between fibrin molecules such that fibrin chains are held together by weak secondary cross-links rather than by stronger primary cross-links which are hidden within the thicker fibrin chain bundles.

Binding Sites↗

Estimation of antibodies specific for dextran.

Methods are described for the isolation and characterization of picogram quantities of anti-dextran antibodies. 14C-dextrans produced by using the dextransucrases of Leuconostoc mesenteroides strains B1355 and B512 were used in a radioimmunoassay. The specificity of this assay was verified by using cell cytoplasmic lysates from mouse plasmacytomas, J558 (anti-alpha 1 leads to 3 dextran) and W3129 (anti-alpha 1 leads to 6 dextran). Dextran produced by strain B1355 and insolubilized with epichlorohydrin was used as an immunoabsorbent.

Animals↗

The prevention of postoperative deep vein thrombosis and pulmonary embolism with low dose subcutaneous heparin and dextran.

The standard low dose of heparin for the prevention of deep venous thrombosis in patients who are operated upon is 5,000 units administered subcutaneously two hours before operation and at eight or 12 hourly intervals for the next seven days. Heparin in low doses can at present be recommended as an effective agent in the prevention of deep venous thrombosis in patients over the age of 40 years who are undergoing a major abdominothoracic or gynecologic operation. There is reasonable evidence that heparin in low doses also offers a satisfactory protection against fatal pulmonary embolism for patients at high risk after general abdominothoracic operations. The evidence of the effectiveness of low doses of heparin in the prevention of deep venous thrombosis is less well established in other patients and particularly those at high risk, as after urologic and hip operations. This important distinction is to be made in terms of the population at risk and the efficacy of heparin in low doses. Considering the evidence so far available, it appears that the postoperative state in which dextran has been shown to reduce the incidence of phlebographically confirmed deep venous thrombosis most convincingly is after orthopedic operations. Major orthopedic operations are precisely the type in which the superiority of heparin in low doses is controversial. Unless proved otherwise, dextran 70 in an infusion of 500 to 1,000 milliliters of a 6 per cent solution started before operation and 500 milliliters the following and next three alternate days may be the agent of choice in preventing deep venous thrombosis in major orthopedic operations. Using this scheme, the prophylaxis of postoperative deep venous thrombosis appears equally effective with dextran 70 as with oral anticoagulants. Whether the protection offered by dextran 70 will also prevent fatal and nonfatal pulmonary embolism is still an open question. Low doses of heparin and dextran do not expose patients to serious risks of bleeding after operation, and with the recommended doses of the latter drug, other untoward effects are rare. At the doses recommended, neither of these two drugs requires laboratory monitoring.

Abdomen↗

ESTIMATION OF THE LOW-DENSITY (BETA) LIPOPROTEINS OF SERUM IN HEALTH AND DISEASE USING LARGE MOLECULAR WEIGHT DEXTRAN SULPHATE.

Studies have been made of the factors affecting the specificity of the interaction between high molecular weight dextran sulphate and low-density lipoproteins, both in pure solution and in serum. The results have been used in the development of a simple assay method for the serum concentration of low-density lipoproteins in small volumes of serum. The results obtained by this assay procedure have been found to correlate acceptably with parallel estimations of low-density lipoproteins by an ultracentrifugal technique and by paper electrophoresis. The technique has been applied to a survey of serum levels of these proteins in a normal population. The results have been compared with data in the literature. Satisfactory agreement was found between mean levels, matched for age and sex, between the dextran sulphate method and those methods based ultimately on chemical estimation of one or more components of the isolated lipoproteins. A systematic difference was observed when the dextran sulphate method was compared with estimates based on analytical ultracentrifugation or turbidimetry using amylopectin sulphate.Some indication of the range of application of the dextran sulphate method in clinical chemistry is provided.

Aging↗

The detection of estrogen receptors in gynecologic tumors using immunoperoxidase and the dextran-coated charcoal assay.

The dextran-coated charcoal receptor assay for demonstrating functional estrogen and progesterone receptors was used to evaluate the receptor content of gynecological tumors. An immunocytochemical method, the immunoperoxidase antiperoxidase method, that may detect estrogen receptors, was also employed on the same specimens utilizing sections from formalin-fixed paraffin embedded blocks. The results by the two methods were compared and were correlated with the state of differentiation of the tumors. According to the dextran-coated charcoal method, two cases of well differentiated endometrial adenocarcinoma were strongly positive for both estradiol and progesterone receptors, and three moderately differentiated cases contained lesser amounts of both types of receptors. Six cases of undifferentiated adenocarcinoma ranged from no detectable receptors to very high values, while of five cases of squamous cell carcinoma of the cervix, only two were positive for estradiol receptors by the dextran-coated charcoal method. Staining of tissue sections from these same cases using the immunoperoxidase method, demonstrated a positive correlation to the dextran-coated charcoal assay for estrogen receptors. The Dextran-coated charcoal method is presently being used clinically as a screening measure for statistical probability of a patient's response to hormone therapy. The degree of positive correlation shown here suggests that use of the immunoperoxidase method may have further potential for diagnostic and clinical use, and merits further investigation.

Adenocarcinoma↗