SEARCH · PubMed Health

Results for “Dextrans”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources

PubMed1981

D-Glucosyltransferase of Streptococcus mutans: isolation of two forms of the enzyme that bind to insoluble dextran.

The D-glucosyltransferase from Streptococcus mutans 6715 has been separated into three enzymic fractions that differ in their binding to dextran and in their synthesis of dextran from sucrose. One enzymic fraction (AFF-I) does not bind to insoluble dextran, and it produces an insoluble D-glucan. Fraction AFF-IIU was eluted from a dextran affinity-column by either dextran or urea, whereas fraction AFF-IID was eluted only by dextran. Both of these fractions produce insoluble D-glucans from sucrose.

Chromatography, Affinity↗

PubMed2002

Production of insoluble dextran using cell-bound dextransucrase of Leuconostoc mesenteroides NRRL B-523.

Water-insoluble, cell-free dextran biosynthesis from Leuconostoc mesenteroides NRRL B-523 has been examined. Cell-bound dextransucrase is used to produce cell-free dextran in a sucrose-rich acetate buffer medium. A comparison between the soluble and insoluble dextrans is made for various sucrose concentrations, and 15% sucrose gave the highest amount of cell-free dextran for a given time. L. mesenteroides B-523 produces more insoluble dextran than soluble dextran. The near cell-free synthesis was validated in a batch reactor, by monitoring the cell growth which is a small (10(6)-10(7) CFU/mL) and constant value throughout the synthesis.

Buffers↗

PubMed1979

Role of dextran 70 in microtubal surgery.

Pelvic adhesion formation represents a major problem following fallopian tube surgery for infertility. Intraperitoneal dextran may prevent pelvic adhesions. Extensive personal clinical experience (W. H. U.) with intraperitoneal dextran organ-flotation on completion of tubal and ovarian surgery has appeared to limit adhesions. A specific study was designed to test the validity of this theory. Four randomized groups of rabbits were subjected to bilateral tubocornual division and microsurgical reanastomosis with total hemostasis and pelvic lavage. Routine peritoneal closure was performed on one group, but followed instillation of 30 to 50 ml of normal saline into the peritoneal cavities of the second group, and 30 to 50 ml of 6% dextran 70 into those of the third. Study of fourth group, which received 32% dextran 70 in the peritoneal cavity, was discontinued because of complications. A second laparotomy was performed 4 weeks later for precise assessment and photography of adhesion formation. Each animal was mated 4 weeks after the second operation in order to determine fertility rates. Reduced adhesion formation and increased fertility rates following the instillation of dextran are reported. A role for dextran 70 in infertility surgery is recommended.

Animals↗

PubMed1983

Reduction of postoperative pelvic adhesions with intraperitoneal 32% dextran 70: a prospective, randomized clinical trial.

Infertile women of reproductive age requiring an operation for distal tubal disease, endometriosis, or pelvic adhesions were recruited from nine study centers. Prior to closing the peritoneal cavity, 250 ml of 32% dextran 70 (n = 55) or saline (n = 47) was instilled into the dependent portion of the pelvis; 8 to 12 weeks later, laparoscopy was performed on those patients not pregnant. Patients with severe adnexal adhesions at the initial laparotomy had a greater reduction in adhesions if they received 32% dextran 70. Further, patients with a marked reduction in adhesion formation following the initial laparotomy were found to occur more frequently in the 32% dextran 70-treated group (26 of 51 for 32% dextran 70 versus 12 of 40 for saline; P less than 0.05). During second-look laparoscopy, adhesions were found to occur more frequently in control patients than in 32% dextran 70-treated patients at the following anatomic sites: ovary (P less than 0.05); cul-de-sac (P = 0.017); pelvic side wall (P less than 0.001). Thus, in a prospective, randomized, blinded clinical trial, the intraperitoneal high-molecular-weight dextran was found to reduce postoperative adhesion formation effectively.

Adnexal Diseases↗

PubMed1987

The effect of dextran solution on pulmonary plasma-lymph barrier in awake sheep.

We investigated the effect of dextran solution on lung lymph flow in awake sheep with chronic lung lymph fistulas. Ten percent of dextran (molecular weight 40,000) solution or normal saline were infused at 1000 ml/h for 2 h through left atrial catheter. We measured pulmonary arterial pressure (Ppa), left atrial pressure (Pla), aortic pressure (Psa), cardiac output (CO), oncotic pressures of both plasma (IImv) and lung lymph (IIpmv), lung lymph flow rate (Qlym), and lymph-to-plasma ratio of total protein (L/P). Infusion of dextran solution caused significant increases in Ppa, Pla and CO and decrease in plasma-lung lymph oncotic pressure gradient (IImv-IIpmv), without changes in L/P. Infusion of normal saline caused significant increases in Ppa and Pla and no changes in IImv-IIpmv and CO, and slight decrease in L/P. The calculated filtration coefficients increased by 2.2 fold after dextran infusion and 1.7 fold after normal saline infusion. Moreover, an apparent increase in protein transport across microvessels as evidenced by the normal L/P despite increases in hydrostatic pressure occurred after dextran solution infusion. These results suggest that dextran solution may increase permeability of microvascular wall, as well as effective net pressure gradient across microvessels, both of which result in a large net fluid filtration from microvessels to perimicrovascular compartment.

Animals↗

PubMed1975

Dextran and the prevention of postoperative thromboembolic complications.

1. The purpose of fluid administration is not only the restoration of blood volume but also the normalization of impaired nutritive flow. 2. Plasma oncotic (colloid osmotic) pressure is the only force which can draw water into the circulation. In shock the infusion of colloid solutions is able to normalize nutritive flow and peripheral resistance almost at once. 3. Five per cent solutions of pasteurized plasma protein or albumin and 6 per cent dextran 70 yield a volume expansion corresponding to the amount infused. 4. The decrease in hematocrit produced by the infusion of these three colloidal solutions is accompanied by a decrease in whole blood viscosity resulting in a rise in cardiac output as well as in nutritional tissue flow. 5. Hemodilution improves oxygen supply as long as the hematocrit does not fall below 30 per cent, although normovolemia is the critical requirement. 6. Transmission of viral hepatitis is still the greatest danger of blood transfusion. 7. The use of large amounts of Ringer's lactate is not advised, as this solution does not reduce the total number of units of blood which need to be given. Pulmonary edema may become a problem. 8. Dextrans are best suited to initial volume replacement in shock. They increase plasma volume, improve blood flow, have antithrombotic properties, and are easily available and relatively cheap. Anaphylactoid reactions are rare. 9. Every third patient undergoing general surgery and every other patient having hip surgery develops a deep venous thrombosis. Widespread prophylaxis to prevent thromboembolic complications is mandatory. 10. The antithrombotic properties of dextran are due to a reduction in platelet adhesiveness, a change in fibrin clot structure, and the increased lysability of thrombi and the improvement of blood flow. 11. In a personal controlled, prospective, randomezed trial comparing subcutaneous heparin and intravenous dextran 40, 35.8 per cent of the controls (n=95), 13.2 per cent of the 83 patients in the heparin group, and 20.5 per cent in the dextran group (n=83) developed deep venous thrombosis. The difference between dextran and heparin is not significant; however, both treatment groups show a statistically significant effect compared to the controls.

Blood Coagulation Tests↗

PubMed1977

Is dextran 70 a lymphocyte mitogen?

Dextran 70 ('Lomodex') roduced significant increases in thymidine incorporation in a modified whole-blood method of investigating lymphocyte blastogenesis. This blastogenesis occurred at molar concentrations of 7 X 10(-6) and 7 10(-5). At 7 X 10(-7) mol/l dextran alone did not significantly increase thymidine incorporation; however, when this concentration of dextran was added simultaneously with phytohaemagglutinin there was a significant increase in incorporation. Conversely when dextran was added before P.H.A., thymidine incorporation was decreased. These variable effects indicate that dextran 70 may be a B-cell mitogen. Dextran 70 is widely used and these effects on lymphocyte blastogenesis may be clinically relevant.

B-Lymphocytes↗

PubMed2003

Dextran-binding human plasma antibody recognizes bacterial and yeast antigens and is inhibited by glucose concentrations reached in diabetic sera.

Dextran-binding antibody was isolated in high yield from plasma of all 40 blood donors screened in a South Indian population. The antibody was purified by a single step affinity chromatography on Sephadex G100 using 1-O-methyl alpha-D-glucoside as eluant. Analysis of protein peaks obtained in size exclusion high pressure liquid chromatography (HPLC) revealed dominance of IgG and suggested the presence of polymeric IgA in this antibody. Methyl and para-nitrophenyl alpha-D-glucosides, in contrast to their beta-anomers, were very efficient inhibitors of binding of this antibody to dextran. Galactose and glucose were equally good inhibitors. Among disaccharide inhibitors sucrose was more efficient than maltose or melibiose. Hemoglobin artificially glycosylated to contain covalently-linked glucose or alpha-anomeric galactose was sugar-specifically recognized by this antibody. Galactose moieties in glycoproteins or polysaccharides were, however, not recognized. The dextran-binding antibody bound sugar-specifically to glycoconjugates from yeast (Saccharomyces cerevisiae) and to lipopolysaccharides from Klebsiella and group A Streptococci, but not to lipopolysaccharides from E. coli. Inhibition studies suggested glucose moiety with unsubstituted C2 and C4 and alpha-anomeric C1 as ideal for recognition by the dextran-binding antibody. Concentration of glucose required for 50% inhibition of binding of the purified antibody to polystyrene-coated dextran in phosphate buffered saline was above the glucose concentrations in normal sera, but well below those reached in diabetic sera. Binding of the antibody from dialysed plasma to immobilized dextran was lowered only marginally in presence of glucose at 4.5mM (which nears normal serum glucose concentrations), but substantially in presence of the sugar at 20mM and above which are reached in diabetic sera. If verified in vivo, inhibition of this antibody by high serum glucose may possibly be among reasons for the increased susceptibility of diabetics to infection.

Adolescent↗

PubMed2000

Pathway tracing using biotinylated dextran amines.

Biotinylated dextran amines (BDA) are highly sensitive tools for anterograde and retrograde pathway tracing studies of the nervous system. BDA can be reliably delivered into the nervous system by iontophoretic or pressure injection and visualized with an avidin-biotinylated HRP (ABC) procedure, followed by a standard or metal-enhanced diaminobenzidine (DAB) reaction. High molecular weight BDA (10 k) yields sensitive and exquisitely detailed labeling of axons and terminals, while low molecular weight BDA (3 k) yields sensitive and detailed retrograde labeling of neuronal cell bodies. The detail of neuronal cell body labeling can be Golgi-like. BDA tolerates EM fixation and processing well and can, therefore, be readily used in ultrastructural studies. Additionally, BDA can be combined with other anterograde or retrograde tracers (e.g. PHA-L or cholera toxin B fragment) and visualized either by multi-color DAB multiple-labeling - if permanent labels are desired, or by using multiple simultaneous immunofluorescence - if fluorescence viewing is desired. In the same manner, BDA pathway tracing and neurotransmitter immunolabeling can be combined. Note that BDA pathway tracing can also be combined with anterograde or retrograde labeling with fluorescent dextran amines, if one wishes to exclusively use tracers with the favorable transport properties and sensitivities of dextran amines. In this case, the BDA can be visualized together with the fluorescent dextran amines using fluorescence labeling for the BDA, or the fluorescent dextran amines can be visualized together with the BDA by multicolor DAB labeling via immunolabeling of the fluorescent dextran amines using anti-fluorophore antisera. BDA is, thus, a flexible and valuable pathway tracing tool that has gained widespread popularity in recent years.

Animals↗

PubMed2001

Suspected iron dextran-related adverse drug events in hemodialysis patients.

Despite the use of recombinant erythropoietin, anemia remains a significant problem for patients with end-stage renal disease, in part related to chronic dialysis-related blood loss and resultant iron deficiency. Because oral iron preparations have been relatively ineffective and poorly tolerated in this population, intravenous (IV) iron dextran has been widely prescribed, despite a finite risk for adverse effects associated with its use. We analyzed data from Fresenius Medical Care North America (FMCNA) clinical variance reports to determine the incidence of suspected iron dextran-related adverse drug events (ADEs) and associated patient characteristics, dialysis practice patterns, and outcomes. We used a case-cohort study design, comparing individuals who experienced suspected ADEs with the overall FMCNA population. Among 841,252 IV iron dextran administrations from October 1998 through March 1999, there were 165 reported suspected ADEs, corresponding to an overall rate of 0.000196%, or approximately 20 per 100,000 doses. Forty-three patients (26%) required an independent emergency department evaluation, 18 patients (11%) required hospitalization, and 1 patient (0.6%) died. Dyspnea (43%), hypotension (23%), and neurological symptoms (23%) were the most common major ADEs; nausea (34%), vomiting (23%), flushing (27%), and pruritus (25%) were the most common other ADEs. ADEs were 8.1-fold more common among patients administered Dexferrum (American Regent Laboratories, Inc, Shirley, NY) compared with those administered InFed (Watson Pharmaceuticals, Phoenix, AZ). In summary, serious adverse reactions to IV iron dextran are rare in clinical practice. The risk appears to depend on the specific formulation of IV iron dextran. Otherwise, iron dextran-related ADEs are difficult to predict.

Humans↗

PubMed1996

Randomized cross-over study of adverse reactions and cost implications of intravenous push compared with infusion of iron dextran in hemodialysis patients.

In many dialysis centers, iron dextran is administered by intravenous infusion rather than intravenous push (the method of administration recommended in the package insert) as a possible, but unproven, means to reduce side effects. This study was performed to determine whether there is a difference in adverse reactions between these two methods. Ten iron-deficient hemodialysis patients participated in a randomized, cross-over study of iron dextran 100 mg administered by intravenous push over 2 minutes (undiluted) or as a 30-minute intravenous infusion during the first hour of hemodialysis. Patients received a total of four doses (two by each method during four separate dialysis sessions). Blood pressure and heart rate were monitored pre-dose and at frequent intervals throughout the hemodialysis session following the dose. Patients completed adverse event surveys before and 60 minutes after the dose and prior to the next hemodialysis session. Blood pressure, heart rate, and survey data were analyzed using a Wilcoxon analysis (P </= 0.05 was considered significant). Seven patients received all four doses, two patients received only three doses (one due to missed hemodialysis session and one due to severe diarrhea possibly related to iron dextran), and one patient received only one dose (due to unstable clinical status). No differences in blood pressure, heart rate, or adverse events were observed between the two administration methods. A cost-minimization analysis was performed to compare the costs of each method of iron dextran administration. There were no differences in nursing time or number of syringes and needles used between the two methods. However, cost savings were observed with intravenous push administration because the intravenous tubing and intravenous piggyback were eliminated. Iron dextran can be administered by either intravenous push or intravenous infusion during the first hour of hemodialysis, with no significant differences between the two methods in terms of blood pressure or heart rate. Dialysis programs can minimize iron dextran administration costs by changing to the intravenous push method.

Aged↗

PubMed1998

Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and erythropoietin requirements in hemodialysis patients.

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.

Adult↗

PubMed2001

Effect of poly-L-arginine on the nasal absorption of FITC-dextran of different molecular weights and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats.

The effect of poly-L-arginine (poly-L-Arg) on the in vivo nasal absorption of FITC-dextrans with a mean molecular weight ranging from 4.3 to 167 kDa and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats were studied. When FITC-dextrans were co-administered intranasally with 1.0 w/v% poly-L-Args of different molecular weight (MW, ca. 45.5 and 92 kDa, poly-L-Arg (50) and poly-L-Arg (100)), the bioavailability (F(infinity)) increased markedly compared with that after administration of FITC-dextran alone. However, the F(infinity) decreased exponentially with the increasing molecular weight of FITC-dextrans. There was no significant difference between the enhanced nasal absorption of FITC-dextrans achieved by the co-administration of poly-L-Arg (50) and poly-L-Arg (100). Moreover, the relationship between the F(infinity) and the molecular weight of FITC-dextrans indicated that the molecular weight of protein drugs, which exhibited efficient absorption with poly-L-Arg, was about 20 kDa, when the lower limit of bioavailability for developing a potent transnasal delivery system was assumed to be about 10%. Indeed, the nasal absorption of rhG-CSF, which has a molecular weight of 18.8 kDa, was also increased after co-administration of 1.0 w/v% poly-L-Arg (50) and the F(infinity) was about 11%. It seems likely that poly-L-Arg can be used to provide adequate nasal absorption of various protein drugs which have a molecular weight of about 20 kDa, thereby allowing the successful development of a variety of transnasal drug delivery systems.

Absorption↗

PubMed1995

Effect of dextran and enoxaparin on early ePTFE graft thrombogenicity in sheep.

OBJECTIVES: To evaluate the effect of low molecular weight heparin (LMWH), dextran 70 and their combination on platelet adhesion and fibrinogen uptake in ePTFE grafts in an experimental sheep model. DESIGN: Prospective open study. SETTING: Animal Laboratory of a University Hospital. MATERIALS: Early thrombogenicity of ePTFE grafts was studied after interposition in the two common carotid arteries of 40 adult sheep. The animals received one of four different treatment regimens in a double blind randomised way: enoxaparin and polygeline, saline and dextran 70, enoxaparin and dextran 70 or saline and polygeline (control). The substances were administered i.v. with a total dose of 73 antifactor-Xa U/kg for enoxaparin and 1.0 g/kg for dextran 70. Polygeline and saline were used as placebo substances in equivalent volumes. On one side (random allocation) the carotid blood flow was restricted to 25 ml/min, on the other side it was left unrestricted. CHIEF OUTCOME MEASURES: The following variables were studied: 1) fibrinogen uptake; 2) platelet uptake; 3) early graft patency; 4) blood flow in patient grafts; 5) visible presence of graft thrombus; 6) thrombus weight. MAIN RESULTS: The results verified the importance of adequate blood flow as only 30% of grafts with restricted blood flow in the control group were patent compared with 80% of those with unrestricted blood flow (p = 0.038). Dextran 70, enoxaparin and the combination of the two increased early graft patency (p < 0.05) and reduced thrombus weights (p < 0.05) in grafts with restricted blood flow. The relative number of grafts with thrombus free surface was increased in the unrestricted blood flow situation. CONCLUSIONS: Dextran 70 and enoxaparin appeared to be equally effective in decreasing fibrinogen and platelet uptake in the grafts. Their combination was not significantly more effective although there was a favourable trend.

Animals↗

PubMed2000

Therapeutic effects of an oral adsorbent on acute dextran sulphate sodium-induced colitis and its recovery phase in rats, especially effects of elimination of bile acids in gut lumen.

BACKGROUND: The pathogenesis of inflammatory bowel disease is still unknown. However, it is possible that faecal bile acids influence the clinical course. AIMS: To evaluate the eliminating effects of faecal bile acids by the oral adsorbent on dextran sulphate sodium-induced rat colitis. METHODS: Rats were given 3% dextran sulphate sodium aqueous solution for 7 days, with or without concomitant administration of oral adsorbent, or the rats were given dextran sulphate sodium for 7 days, followed with or without oral adsorbent for 5 days. Macroscopic and microscopic examinations of the colons and measurement of faecal bile acids were performed. The cytotoxicity of bile salts on Caco-2 cells was also evaluated. RESULTS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis. Oral adsorbent was fairly effective in reducing faecal hyodeoxycholic acid concentration. A positive correlation was found between the size of the ulcer area and the faecal hyodeoxycholic acid concentration. In a cell culture study, cytotoxicity of bile acid was parallel with increasing hydrophobicity of the bile acid. However, hyodeoxycholate exhibited severe cytotoxicity, despite its hydrophilic properties. CONCLUSIONS: Oral adsorbent tended to attenuate the dextran sulphate sodium-induced colitis and tended to promote the recovery process. It is possible that bile acids in the gut lumen influence the progression of dextran sulphate sodium-induced colitis and its repair process.

Acute Disease↗

PubMed1995

Dextran sulfate promotes the rapid aggregation of porcine bone-marrow stromal cells.

Despite the fact that cells of the mammalian stromal compartment of bone marrow have been shown to contain multipotential stem cells when studied in diffusion chambers it is notable that the same range of possible phenotypes (e.g., chondrocytic) has not been induced in freshly isolated marrow stromal cells in vitro. To investigate the possible role of glycoconjugates on phenotype expression, the effects of chondroitin sulfate, dermatan sulfate, dextran 500, and dextran sulfate on the cell morphology and differentiation of confluent porcine bone-marrow stromal-cell monolayers were studied. Of these glycosaminoglycan molecules only dextran sulfate induced confluent porcine bone-marrow stromal-cell monolayers to retract into tight, circular cell aggregates. Retraction began within 6 h, was complete after 3-5 days, and was dose dependent. Subsequent removal of dextran sulfate from the culture medium resulted in a return to a monolayer culture. Aggregated cells were essentially nonmitotic but dye exclusion indicated high cell viability. Dexamethasone, ascorbate, and beta-glycerophosphate produced no morphological change within 6 days when administered alone, but increased proliferation and aggregation in dextran sulfate-treated cultures. Immunocytochemistry of monolayer cultures revealed positive staining for type I but not type II collagen and addition of dexamethasone, ascorbate, and beta-glycerophosphate increased type I collagen deposition. In contrast, the centers of dextran sulfate-induced aggregates were positive for type II collagen, whereas type I collagen was only present at the periphery of the aggregates. Further addition of dexamethasone, ascorbate, and beta-glycerophosphate had little effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2003

Effect of dextran as a run buffer additive in drug-protein binding studies using capillary electrophoresis frontal analysis.

The study of drug-protein interactions by capillary electrophoresis frontal analysis requires establishment of a sufficient mobility difference between the mobility of the ligand and protein. The potential utility of dextran as a run buffer additive to manipulate the electrophoretic mobilities of low molecular weight ligands and protein in capillary electrophoresis frontal analysis binding studies was assessed. It was demonstrated that dextran was effective in improving the separation between the ligands warfarin and flurbiprofen and human serum albumin. Separation of ligand and protein increased with the concentration of added dextran (0-7.5% (w/w)), while molecular weight of the additive (70,000-2,000,000) only had a minor effect. The effect of dextran addition on viscosity and electrophoretic and electroosmotic mobilites was systematically studied. Optimal frontal analysis settings were a compromise between achieving satisfactory separation and acceptable analysis times without loss of plateau peak conditions. No effect of dextran upon the drug-human serum albumin interactions could be detected for the model ligands. Introduction of dextran into the electrophoresis buffer expands the applicability of capillary electrophoresis frontal analysis in drug research to binding interactions between proteins and low molecular weight ligands possessing similar electrophoretic mobilities.

Buffers↗

PubMedDate not supplied

Development and in vitro studies of epidermal growth factor-dextran conjugates for boron neutron capture therapy.

A delivery molecule for directed boron neutron capture therapy against epidermal growth factor (EGF) receptor-rich tumors, such as gliomas, squamous carcinomas, and breast cancers, is presented. EGF and sulfhydryl boron hydride (BSH) were covalently coupled to an allylated 70 kDa dextran chain to form a conjugate. Conjugates with low and high substitution rates of BSH, as well as without BSH, were investigated. The conjugate with a low amount of boron had approximately 6 BSH (72 boron atoms) per dextran, while the conjugates with higher amounts had an average substitution of 55 BSH (660 boron atoms) per dextran. The maximum substitution of boron to dextran in a single experiment was over 800 boron atoms. Binding, retention, and internalization of 125I-labeled conjugates were investigated on cultured human glioma cells. Binding of the conjugates was EGF receptor specific, but the amount of BSH coupled to dextran affected specificity, more than the presence of dextran. The nonspecific binding of the conjugates increased with the amount of attached boron. This was partly due to nonspecific adhesion to the plastic in the culture dishes. [125I]EGF-allyldextran with 6 BSH had a binding maximum after 4 h of continuous incubation and thereafter decreased in binding, while [125I]EGF-allyldextran with the higher substitution rate had a slow increase of binding during 24 h. Over 93% of the radioactivity bound to the cells was internalized, but the retention was quite poor. Only one-third of the cell-bound activity was still associated to the cells 4 h after incubation had ended. In conclusion, it is possible to load the conjugates produced with high amounts of boron, and they retained specificity for the EGF receptor and internalized into cultured cells. Theoretical calculations show that about 10(3) boron atoms per EGF-based conjugate are needed to give a satisfactory therapeutic response. These conjugates are within reach of that level.

Boron Neutron Capture Therapy↗