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PubMed1995

Labeling of polypeptides with technetium-99m using a dextran spacer.

Radioimmunoscintigraphy and other forms of scintigraphy are becoming increasingly important as tools in detection and evaluation of cancer diseases. Several radionuclides can be considered as radiolabel; however, 99mTc may be the most suitable because of easy availability and near ideal physical properties. This study describes how dextran is coupled to a monoclonal anticytokeratin antibody, epidermal growth factor, and somatostatin through stable amine bonds. The dextran moiety could then be labeled with 40-62 MBq of 99mTc. The labeling efficiency was 60-94%, determined by gel filtration or TLC. The specific binding could be considerably preserved after the dextranation, the antibody retained > 90% of its activity, epidermal growth factor bound with > 90% specificity to receptor-expressing tumor cells, and somatostatin showed approximately 40% specific binding to rat adrenal homogenates. Because somatostatin only has a transient half-like in vivo, the in vivo plasma half-life of somatostatin-dextran was tested in normal female Sprague-Dawley rats. The result showed a strong enhancement of the plasma half-life that was dependent on two compartments, 4 and 8 h.

Animals↗
PubMed1994

Treatment with dextran-conjugated anti-IgD delays the development of autoimmunity in MRL-lpr/lpr mice.

The onset of clinical disease in autoimmune MRL-lpr/lpr mice is preceded by a switch from predominantly IgM production to IgG production. Previous studies have shown that IgG autoantibodies play a central role in the development of life-threatening glomerulonephritis in this strain. Delaying or preventing the switch from IgM to IgG production might therefore be of therapeutic benefit. We previously documented similarities in the B cell repertoire expressed by young MRL-lpr/lpr mice and normal mice treated with the polyclonal activator LPS. Recent in vivo studies indicate that cross-linking membrane IgM or IgD can suppress LPS-dependent IgG production in normal animals. These observations led us to examine whether membrane cross-linking could also lower serum IgG levels in MRL-lpr/lpr mice. Lupus-prone animals were treated with multivalent anti-IgD conjugated to high m.w. dextran. This anti-IgD dextran conjugate was previously shown to reduce IgG production in LPS-stimulated normal animals. Treatment of young lupus-prone MRL-lpr/lpr mice resulted in a significant reduction in the total number of B cells secreting IgG and lower serum titers of IgG anti-DNA and IgG anti-histone autoantibodies. Anti-IgD dextran treatment also delayed the development of glomerulonephritis and improved survival. Thus, anti-IgD dextran interfered with autoantibody-dependent disease progression, perhaps by inhibiting the switch from IgM to IgG autoantibody production.

Age Factors↗
PubMed1994

Acute effects of intravascular absorption of 32% dextran 70 on blood coagulation, electrolytes and arterial blood gas.

Thirty-two percent dextran 70 is used to help visualize the uterine cavity during hysteroscopy and is also used intraperitoneally to prevent adhesions. We measured serum electrolytes, serum osmolarity, hematocrit, arterial blood gas and coagulation profile in 11 patients receiving dextran 70 while undergoing hysteroscopy. Dextran 70 had no significant effect on prothrombin time, partial thromboplastin time, thrombin time, fibrinogen level or serum osmolarity. There was a significant decrease in hematocrit, serum sodium and oxygen tension of arterial blood (PaO2). The decrease in sodium and hematocrit suggested hemodilution. This study demonstrated that 32% dextran 70 had a minimal effect on the majority of laboratory parameters measured.

Absorption↗
PubMed1995

Interactions of HIV-1 envelope glycoproteins with derivatized dextrans.

The present study demonstrates that derivatized dextrans, such as carboxylmethyl dextran benzylamide and carboxymethyl dextran benzylamide sulfonate, specifically interact with HIV-1 envelope glycoproteins (rgp160 and rgp41) with significantly higher affinities than those observed for dextran sulfate (MW 8 kDa). These results suggest the possible involvement in HIV infectivity of surface membrane molecules which may bind the virus at pre or post-CD4 binding steps. They also suggest the possible use of these compounds in anti-HIV therapy.

Amino Acid Sequence↗
PubMed1979

Opposite effects of dextrans substituted with sulfhydryls or mercury on tumor growth.

Macromolecular dextrans carrying substituents terminated by sulfhydryl groups or terminated by aromatic amines effectively inhibit the growth of a fibrosarcoma and of a mammary adenocarcinoma in a syngeneic mouse model. These compounds have no or very low toxicity to animals and are nontoxic to fibrosarcoma cells in vitro. Small-molecular-weight compounds carrying the same substituents as the above dextrans are without any effect on the growth of these tumors. A dextran substituted with mercury-containing side chains is growth promoting for the same fibrosarcoma in mice at doses which are nontoxic for these animals. However, the mercury-containing compound is toxic to fibrosarcoma cells in vitro. It is hypothesized that these nonpermeating macromolecules do not directly influence the tumor cells in animals but modulate the natural system of defense against tumors; cells of that system are stimulated or poisoned by the substituted dextrans.

Animals↗
PubMedDate not supplied

Parenteral iron dextran therapy: a review.

Iron dextran was introduced more than 30 yr ago for the parenteral treatment of iron deficiency anemia that is refractory to oral therapy. Iron dextran is a preparation of ferric hydroxide complexed with a low molecular weight fraction of dextran. Iron deficiency anemia is one of the most common nutritional deficiency diseases and occurs worldwide secondary to inadequate dietary iron, usually with excessive gastrointestinal blood losses. Repletion of iron stores is often complicated by intolerance to oral iron supplementation and may require parenteral iron. Parenteral iron can be administered via the intramuscular or intravenous route either directly or as an additive to total parenteral nutrition. Both routes of administration can cause various side effects and a test dose is recommended before therapeutic administration to assess the risk for anaphylaxis. Although the efficacy and safety of parenteral iron dextran have been convincingly demonstrated, supplementation may be contraindicated in the setting of infection.

Anemia, Iron-Deficiency↗
PubMed1993

Prehospital resuscitation of hypotensive trauma patients with 7.5% NaCl versus 7.5% NaCl with added dextran: a controlled trial.

Small volume infusions of hypertonic saline combined with dextran are very effective in resuscitating animals that have been subjected to hemorrhagic shock, and seem to be effective in resuscitating trauma patients with severe injuries. In this study, the contribution of the dextran component was investigated in a prospective, three-armed, double-blind, randomized trial. Trauma patients transported by ambulance to the hospital with a systolic blood pressure of 90 mm Hg or less were given 250 mL of (1) normal saline (NS); (2) 7.5% NaCl (HS, for hypertonic saline); or (3) 7.5% NaCl in 6% dextran 70 (HSD). Infusion of the study solution was followed by administration of conventional isotonic fluids as the patients' conditions indicated. By predetermined hypothesis, the observed survival rates in the three treatment groups were compared with the predicted survival rates from the TRISS methodology. The 7.5% NaCl solution significantly improved upon the predicted survival for the entire cohort and for high-risk patients when compared with the survival estimates from the TRISS methodology. The addition of a colloid, in the form of 6% dextran 70, did not offer any additional benefit, at least in this setting of rapid urban transport.

Adult↗
PubMed1975

Coagulation changes in baboons during acute experimental hemoglobinemia and dextran infusion.

Evidence of disseminated intravascular coagulation (DIC) was dought in normal baboons infused with autologous hemolyzed whole blood, preceded or followed by infusion of dextran (molecular weight, 70,000). Mean peak plasma hemoglobin following a rapid single injection was 370 mg/100 ml in 2 animals and 1,236 mg/100 ml in 1 animal, while levels during continuous 5 hour infusion in 2 animals averaged 326 and 474 mg/100 ml, respectively. Dextran infusion immediately preceded hemoglobin injection in 2 baboons and followed hemoglobin injection by 1 1/2 and 2 1/2 hours, respectively, in 2 baboons. Coagulation studies showed a moderate although significant fall in platelet count with prolongation of the partial thromboplastin time following hemoglobin infusion, and shortening of the thrombin time after dextran. Fibrin degradation products developed in four of five experiments after hemolysate injection. The induction of acute experimental hemoglobinemia results, therefore, in the development of coagulation changes consistent with milk DIC. Preliminary infusion of dextran (molecular weight, 70,000) may facilitate this response by either initiating the development or impeding the clearance of fibrin degradation products.

Acute Disease↗
PubMed1995

Absorption of iron dextran from the peritoneal cavity of rats.

We investigated the absorption rate and acute toxicities of intraperitoneal iron dextran in rats. Eighteen Sprague-Dawley rats were divided into three groups (n = 6). The animals were given standard 1.5% Dianeal (group 1) or 1.5% Dianeal containing iron in a concentration of 2 mg/L (group 2) or 10 mg/L (group 3) as iron dextran. First, a predialysis blood sample was obtained, and 25 mL of the designated dialysis solution was instilled into the peritoneal cavity. After a 6-hour cycle the dialysate was drained, and a postdialysis blood sample and specimen of the peritoneum were obtained. The iron concentrations of the dialysis solution, the dialysate, and both serum samples were determined. Histological samples were processed by hematoxylin and eosin and Prussian blue stain. Results of the iron concentration (mg/L) of the dialysis solution, the dialysate, and the percent of the absorbed iron were as follows: group 1: 0.00, 0.20 +/- 0.15, N/A; group 2: 2.24, 0.66 +/- 2.8, 73.8 +/- 11.0; group 3: 9.84, 2.12 +/- 0.62, 80.8 +/- 5.7. The serum iron concentration did not change. No abnormal findings were found histologically. More than 70% of the iron dextran was absorbed from the peritoneal cavity of the rats during a 6-hour peritoneal dialysis exchange. Intraperitoneal iron dextran may be an alternative route of iron delivery.

Absorption↗
PubMed1995

Anaphylactic reactions to high molecular weight dextran during hysteroscopic surgery.

Dextran solutions are used for plasma expanders, thromboembolic prevention, and as a distention and irrigating fluid for various endoscopic procedures. High-molecular-weight dextrans are accompanied by significant side effects including pulmonary edema, allergic reactions, renal failure, and altered coagulation profiles. The following is a case report of an allergic reaction to 32% Dextran-70 during a hysteroscopic examination and biopsy of a 67-year-old woman. A discussion follows outlining the adverse effects of high viscosity dextrans alerting the anesthetist to the possibilities of intraoperative complications.

Aged↗
PubMed1995

99Tcm-dextran: a potential inflammation-seeking radiopharmaceutical.

The aim of this study was to test whether 99Tcm-dextran can be used for imaging inflammation. An in vivo inflammation model was prepared by intramuscular (i.m.) injection of Freund's complete adjuvant to the thigh of five rabbits. Serial imaging of the animals was done with 99Tcm-dextran for 2 weeks following the onset of inflammation. The radiotracer was seen to concentrate selectively in the lesion, with a mean target-to-nontarget ratio of 3.01 (range 2.74-3.15) from day 4 onwards. The area of scintiscan abnormality increased with time and was more marked than the physical appearance of the lesion. In two rabbits, the tracer was also seen to localize at the site of injection of the anaesthesia in the normal thigh. The best time to image was found to be 2-4 h after 99Tcm-dextran administration. It would appear that abnormally increased capillary permeability in the inflamed area results in enhanced uptake of the macromolecule. We conclude that 99Tcm-dextran is a potential inflammation-seeking radiotracer, though it needs to be evaluated further.

Animals↗
PubMed1995

Dextran and hydroxyethyl starch interfere with fibrinogen assays.

We studied the haemostatic and volume effects of synthetic plasma substitutes and Ringer's solution in 48 surgical patients and found that the measured fibrinogen concentrations of patients receiving either dextran or hydroxyethyl starch (HES) were significantly higher than those predicted by the dilutional effects. The groups given Ringer's solution showed no apparent disproportion between fibrinogen concentration and plasma volume change. The results suggested that the presence of artificial colloids might interfere with the indirect fibrinogen assay used in the study. The method of analysis was based on light scattered from the reaction mixture during prothrombin time (PT) measurement. To test the hypothesis, plasma was obtained from nine volunteers to prepare 20, 40 and 60% dilutions in normal saline, 6% dextran 70, 6% HES 120/0.7 or 6% HES 200/0.5 solutions. Fibrinogen was measured on a ACL-300R coagulometer by two indirect methods, PT derived and the Clauss method. Relative concentrations were compared by analysis of variance and Sheffé's multiple comparisons. Dilutions containing either dextran or HES gave significantly higher values (P < 0.001) than samples diluted with normal saline. We conclude that the results of indirect fibrinogen assays should be interpreted cautiously, when HES or dextran is used for volume replacement. This may be particularly true when hypofibrinogenaemia is encountered after extensive use of synthetic colloids during massive transfusion.

Dextrans↗
PubMed1977

Effect of dextran and induced thrombocytopenia on the lysability of ex vivo thrombi in dogs.

The lysability of thrombi and clots was studied in intact and thrombocytopenic dogs. The thrombi were formed in ex vivo in rotating. Chandler loops, the clots were formed in plastic tubes. Infustion of dextran 70 to the intact dogs was followed by a significant increase in the lysability of the thrombi but not of the clots. Thrombocytopenia caused an increase in the lysability of both thrombi and clots. After infusion of dextran to thrombocytopenic dogs a further increase was noted in the lysability of thrombi but not of clots. The results indicate that dextran and induced thrombocytopenia increase the lysability of thrombi by different mechanisms. The different behaviour between thrombi and clots is probably due to the difference in structure between them particularly with regard to the distribution of platelets. It is suggested that dextran decreased the thrombus statility by impairing the platelet surface function.

Animals↗
PubMed1979

Selective effects of anti-Ia serum and complement treatment upon polyclonal B lymphocyte responses to dextran sulfate and lipopolysaccharide.

Subpopulations of B lymphocytes have been shown to vary in their expression of Ia alloantigens and polyclonal responsiveness to thymic independent antigens. We have demonstrated that the polyclonal B cell antibody response to dextran sulfate is less sensitive to removal of Ia-positive cells than is the response to LPS. This is a consistent finding whether alloantibody and complement (C) pretreatment is directed toward cells bearing Ia antigens coded for by the entire I region or by the I-A or I-E subregions. Heterogeneity appears to exist within the dextran sulfate-sensitive population in that using high antibody; cell ratios during antibody and C-mediated cell selection results in an inhibition of the proliferative but not the antibody response. This result may indicate a differential expression of Ia antigens on dextran sulfate-sensitive B cells that respond by proliferation versus those cells that produce antibody. Alternatively, proliferative responses to dextran sulfate may be more dependent upon Ia-positive accessory cells than is the polyclonal antibody response.

Animals↗
PubMed1997

Kinetics of hepatic accumulation of dextrans in isolated perfused rat livers.

The role of various processes (uptake, release, metabolism, and excretion) in the hepatic accumulation of dextrans was investigated in isolated perfused rat livers (IPRLs). Single-pass IPRLs were infused with fluorescein-dextran (FD) with a molecular weight (MW) of 70,000 (FD-70) for 15, 30, 45, or 60 min, and inlet and outlet samples and livers were collected. In addition, two groups of livers were infused with FD-70 for 60 min, followed by 30 or 60 min of drug-free perfusion. The concentrations of the macromolecule in the samples were measured by a size exclusion chromatographic method. Similar, but limited, experiments were also conducted for FDs with MWs of 4,000 (FD-4) and 150,000 (FD-150). In addition, the metabolism of all three FDs were investigated using liver homogenates. Because of low hepatic extraction, the concentrations of dextrans in the inlet and outlet perfusates were almost the same during the entire perfusion. However, liver concentrations increased almost linearly during the infusion of FD-70 (0-60 min) and declined slowly thereafter (60-120 min). The apparent hepatic extraction ratio (Eapp) values, estimated directly from the concentrations of FDs in the liver, were MW dependent; Eapp of FD-4 (0.124% +/- 0.015%) was significantly (p < 0.05) less than that for FD-70 (0.677% +/- 0.193%) or FD-150 (0.711% +/- 0.022%). The metabolism and biliary excretion of all FDs were negligible during the perfusion time. The mean residence time of FD-70 in the liver, estimated by nonlinear regression analysis of experimental data, was 248 min. These studies define the role of various processes involved in the slow (but substantial) and MW dependent hepatic accumulation of dextrans.

Animals↗
PubMedDate not supplied

Chronic administration of iron dextran into the peritoneal cavity of rats.

OBJECTIVE: To determine the influence of chronic iron dextran administrations into the peritoneal cavity of rats on function and anatomy of the peritoneal membrane, as well as on erythropoiesis and serum iron. DESIGN: Prospective randomized animal study. SETTING: Animal laboratory. ANIMALS: 36 Sprague-Dawley rats. INTERVENTIONS: The rats were divided into three groups (n = 12). The animals were given standard 1.5% Dianeal (control group) or 1.5% Dianeal containing iron dextran in a concentration of 2 mg/L [low-dose group (LDG)] or 10 mg/L [high-dose group (HDG)]. MAIN OUTCOME MEASURES: On the 8th day, at 3 months, and at 6 months a 2-hour peritoneal equilibration test (PET) and blood tests including hematocrit, serum iron, and total iron-binding capacity (TIBC) were done. After the final PET at 6 months, the peritoneal membrane was evaluated by gross inspection and by light microscopy. RESULTS: Hematocrit and serum iron levels increased only in the HDG and LDG. Peritoneal transport of small solutes decreased significantly in the HDG compared to baseline. All cases of the HDG group revealed peritoneal adhesions and fibrosis around the peritoneal catheter as well as massive iron deposits on the peritoneum. Similar but less pronounced changes were found in the LDG. CONCLUSIONS: These findings suggest an efficient absorption of iron from the peritoneal cavity of rats, however, dialysate iron dextran concentrations of 2 mg/L or greater are toxic to the peritoneal membrane. Therefore, future studies should be performed to determine the minimal effective and nontoxic iron dextran concentrations for intraperitoneal administration.

Animals↗
PubMed1997

Erythrocyte depletion of human umbilical cord blood using dextran sedimentation.

We report on the results of a study using high molecular weight dextran for depletion of red blood cells (RBCs) from cord blood. Our technique achieved efficient RBC depletion by sedimentation without a significant loss in haemopoietic stem cells. Cord blood units were fractionated for erythrocyte depletion by unit gravity sedimentation in 3 per cent high molecular weight dextran. Dextran sedimentation enabled recovery of more than 80 per cent of the total nucleated cells present and 100 per cent mononuclear cell (MNC) recovery as compared to unfractionated cord blood. A four-fold increase in the colony forming unit-granulocyte macrophage (CFU-GM) number per 2 x 10(5) cells was observed after dextran treatment suggesting that this step also resulted in the enrichment of stem cells.

Blood Component Removal↗
PubMed1997

Potentiation of C1 inhibitor by glycosaminoglycans: dextran sulfate species are effective inhibitors of in vitro complement activation in plasma.

Activation of the complement system may contribute to the pathogenesis of many diseases. Hence, an effective inhibitor of complement might be useful to reduce tissue damage. Some glycosaminoglycans (GAG), such as heparin, are known to inhibit the interaction of C1q with activators and the assembly of the classical and the alternative pathway C3 convertases. Furthermore, they may potentiate C1 inhibitor-mediated inactivation of C1s. To search for potential complement inhibitors, we systematically investigated the complement inhibitory properties of various synthetic and naturally occurring GAG (dextran sulfates 500,000 and 5,000, heparin, N-acetylheparin, heparan sulfate, dermatan sulfate, and chondroitin sulfates A and C). First, we assessed the effect of GAG on the second-order rate constant of the inactivation of C1s by C1 inhibitor. This rate constant increased 6- to 130-fold in the presence of the GAG, dextran sulfate being the most effective. Second, all tested GAG were found to reduce deposition of C4 and C3 on immobilized aggregated human IgG (AHG) and to reduce fluid phase formation of C4b/c and C3b/c in recalcified plasma upon incubation with AHG. Dextran sulfate again was found to be most effective. We conclude that GAG modulate complement activation in vitro and that the low molecular weight dextran sulfate (m.w. 5000) may be a candidate for pharmacologic manipulation of complement activation via potentiation of C1 inhibitor.

Complement Activation↗