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Sucrose-stimulated release of FITC-dextran into the bile in the dynamics of its storage and elimination from the liver.

Stimulation of release of FITC-dextran endocytosed in the liver by an injection of hypertonic sucrose led to the appearance of a less pronounced and prolonged peak (with the maximum at min 15-25) at later terms after injection of the marker (30 days). Biliary release of FITC-dextran was 4-9-fold accelerated on days 1-14 in comparison with the constitutive release, and after 30 days it was accelerated 19-fold, which reflects high capacity of the long storage compartment to stimulated release of FITC-dextran into the bile.

Animals↗

Bowman-Birk inhibitor concentrate reduces colon inflammation in mice with dextran sulfate sodium-induced ulcerative colitis.

Bowman-Birk inhibitor concentrate (BBIC) is a soybean extract enriched in the Bowman-Birk inhibitor, a protein protease inhibitor. The Bowman-Birk inhibitor can inhibit proteases released from inflammation mediating cells and suppress superoxide anion radical secretion from immunocytes. This study investigates the ability of Bowman-Birk inhibitor concentrate to inhibit colon inflammation in the dextran sulfate sodium model of ulcerative colitis, an inflammatory bowel disease. When compared to mice on a standard diet, mice given food supplemented with 0.5% BBIC during and after dextran sulfate sodium treatment showed suppression of three of four scored histopathological inflammation criteria (P < 0.01), total histopathological score (P < 0.01), a 15% lower mortality rate (P < 0.01), and a delayed onset of mortality. We conclude that dietary Bowman-Birk inhibitor concentrate can beneficially affect dextran sulfate sodium-treated mice and may be useful in the treatment of human inflammatory bowel diseases, particularly ulcerative colitis.

Animals↗

Streptococcus mutans binding to solid phase dextran mediated by the glucan-binding protein C.

Streptococcus mutans GbpC is a wall-anchored surface protein which is involved in dextran-dependent aggregation. The GbpC phenotype is observed only in cells grown under stress conditions. In order to detect the GbpC protein of S. mutans, we isolated the wall fraction following digestion of the cell wall of this organism by N-acetylmuramidase, and detected the GbpC protein from S. mutans cells by western analysis with anti-GbpC serum. Interestingly, S. mutans cells exhibiting the negative dextran(alpha-1,6 glucan)-dependent aggregation (ddag) phenotype expressed the protein and could bind to immobilized dextran.

Bacterial Adhesion↗

Pharmacokinetic profile of epidural meperidine with and without dextran 70.

To evaluate the effect of dextran 70 on the kinetics of epidural meperidine, 10 female patients anesthetized with nitrous oxide and halothane were studied. Meperidine, 1 mg.kg-1, was administered epidurally in either 10 ml dextran 70 in saline solution (group I) or 10 ml saline solution (group II, control subjects). Plasma concentration of meperidine was determined for 10 hours after its administration with GC. Meperidine plasma concentration-time curves could be best resolved into three exponential terms with a lag time in both groups of patients. The disposition kinetics were described adequately by a three-compartment model. This study demonstrated that apart from a significantly longer lag time and smaller k10 (apparent first-order rate constant for elimination of meperidine from the central compartment), the addition of dextran did not alter significantly the kinetic parameters of epidural meperidine.

Adult↗

Oxygen-binding and immunological properties of complexes between dextran and animal haemoglobins.

Complexes of dextran 20 000 with haemoglobins of sheep, rabbit, dog, bovine and human origin were prepared through alkylation of haemoglobin by N-bromoacetylaminoethylamino-dextran. The yields were uniformly high. Complex-formation in each case was accompanied by the disappearance of reactive thiol groups on the haemoglobin, and by an increase in the affinity of the haemoglobin for oxygen. The immunological properties of dog, rabbit and sheep dextran-haemoglobin were investigated in both homologous and heterologous species. The complexes were found to be non-immunogenic in the homologous species. In heterologous species the anti-haemoglobin response induced by each complex was generally of a similar level to that induced by the haemoglobin alone.

Animals↗

Effect of dextran on synthesis, secretion and deposition of type III procollagen in cultured human fibroblasts.

When subconfluent cultures of primary human skin fibroblasts are incubated for 20 h in the presence of 5% neutral dextran, the newly synthesized procollagens are shifted from the medium into the pericellular matrix fraction. This is accompanied by an overall decrease by 30-50% in the secretion rates of these proteins, as indicated by the incorporation of tritiated proline into collagenase-sensitive macromolecules and by radioimmunoassays for the propeptide regions of type I and III procollagens. Inhibition of tyrosine sulphation in newly formed type III procollagen by NaClO3 does not change the distribution of this protein between the medium and matrix fractions either in the presence or in the absence of the polymer. Processing of type III procollagen at its N-terminus is incomplete in this situation, irrespective of whether the protein is present mainly in the medium or in the pericellular matrix. The concentrations of the mRNAs for the pro alpha 1(I)- and pro alpha 1(III)-chains of procollagens and for actin were monitored for up to 20 h; in the dextran-treated cultures these are not different from the corresponding concentrations in control cultures, indicating that the rapid down-regulation of the synthesis of type I and III procollagens in response to the enhanced pericellular matrix deposition induced by dextran is not due to transcriptional mechanisms.

Blotting, Northern↗

Desulphation of dextran sulphate during kidney ultrafiltration.

The renal clearance of [3H]dextran sulphate by the isolated perfused rat kidney was associated with desulphation of the molecule, as demonstrated by ion-exchange and affinity chromatography of material resident in both glomeruli and urine samples. This process also occurred in vivo. The molecular size distribution of glomerular dextran sulphate in the perfused kidney was indistinguishable from that in the perfusate, and although urinary material was smaller it remained macromolecular. Sulphatase activity was not detected in urine or in the perfusate of perfused kidneys, but was detected in glomerular and non-glomerular cortex fractions isolated by a sieving procedure. The identification of significant biochemical changes to dextran sulphate demonstrates that it does not function as an inert transport probe, and supports the concept of cellular involvement in the process of renal charge selectivity.

Animals↗

Effects of aniso-osmolarity and hydroperoxides on intracellular pH in isolated rat hepatocytes as assessed by (2',7')-bis(carboxyethyl)-5(6)-carboxyfluorescein and fluorescein isothiocyanate-dextran fluorescence.

Freshly isolated rat hepatocytes were plated for 4-6 h and either loaded with (2',7)-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) or allowed to endocytose fluorescein isothiocyanate (FITC)-coupled dextran in order to study the effects of aniso-osmotic exposure and oxidative stress on cytosolic (pHcyt) and apparent vesicular pH (pHves) by single-cell fluorescence recordings. In the presence of normo-osmotic (305 mosmol/l) medium pHcyt was 7.23 +/- 0.03 (n = 108), whereas an apparent pH of 6.07 +/- 0.02 (n = 156) was found in the vesicular compartment accessible to endocytosed FITC-dextran. Substitution of 60 mM NaCl against 120 mM raffinose had no effect on pHcyt or apparent pHves, whereas addition of NH4Cl increased both pHcyt and apparent pHves. Hypo-osmotic cell swelling lowered pHcyt, whereas simultaneously apparent pHves increased. These effects were rapidly reversible upon re-institution of normo-osmotic media. Similarly, an increase of apparent pHves was observed when cell swelling was induced by Ba2+, glutamine or histidine. Conversely, hyperosmotic cell shrinkage due to addition of NaCl or raffinose led to a cytosolic alkalinization and a vesicular acidification. Both, H2O2 (0.2 mmol/l) and t-butyl-hydroperoxide (0.2 mmol/l) were without effect on pHcyt, but lowered apparent pHves by about 0.2 pH units. Ba2+ (1 mmol/l) diminished the acidifying effect of the hydroperoxides by about 50%. Pretreatment of the cells with colchicine, but not with lumicolchicine, largely abolished the effects of aniso-osmolarity and hydroperoxides on pHves. The data suggest that hepatocellular hydration affects the proton gradients built up across the membranes of endocytotic FITC-dextran-accessible compartments in a microtubule-dependent way. They further suggest that hydroperoxides induce vesicular acidification in a colchicine- and Ba(2+)-sensitive way. Because hydroperoxides induce Ba(2+)-sensitive cell shrinkage [Hallbrucker, Ritter, Lang, Gerok and Häussinger (1992) Eur. J. Biochem. 211, 449-458], the results are compatible with the view that hydroperoxide-induced cell shrinkage mediates vesicular acidification. It is concluded that modulation of vesicular pH by the hepatocellular hydration state may play a role in triggering some metabolic changes in response to cell swelling/shrinkage.

Ammonium Chloride↗

Fractional dextran and protein clearances in glomerulonephritis and in diabetic nephropathy.

The renal clearance of dextran and protein of different molecular sizes has been measured in 42 proteinuric patients with diabetes and glomerulonephritis. In both patient groups the fractional low molecular (radii 3.0-3.6 nm) dextran clearances were significantly decreased whereas the fractional high molecular (radii 5.1-7.8 nm) dextran clearances were increased as compared with the controls. A porosity/charge index was constructed by calculating the ratio of fractional clearances of neutral to anionic macromolecules (theta D3.6/theta ALB, theta D5.1/theta IgG). In diabetic patients the relation between the fractional clearances of neutral and anionic macromolecules was dependent on glomerular filtration rate. It seems likely that the altered glomerular permeability in diabetic nephropathy is associated with a decrease of charge as renal function deteriorates. In glomerulonephritis the process is different and there is a high degree of variation from case to case.

Adolescent↗

Effects of a hypertonic saline solution and dextran 70 combination in the treatment of diarrhoeic dehydrated calves.

Thirty dehydrated diarrheic calves aged 2-45 days were used to study the effects of small volume intravenous 7.2% hypertonic saline and 6% dextran 70 solution in combination with alkalinising oral fluids and to compare this therapy with the large volume intravenous isotonic saline with alkalinising oral fluid treatment. This study included a total of 30 diarrhoeic dehydrated calves aged 2-45 days. After routine clinical and haematological examinations, the calves were allotted to two treatment groups. Isotonic saline solution (32 ml/kg, i.v.) with an oral electrolyte solution (22 ml/kg, p.o.) were administered to group I (control), and the combination of 7.2% hypertonic saline in 6% dextran 70 solutions (HSD) (4 ml/kg, i.v.) with an oral electrolyte solution (50 ml/kg, p.o.) were administered to group II (test). Additionally, an oral electrolyte solution (50 ml/kg, p.o.) was readministered to both groups at 12 h of the study. The clinical and haematological examinations of all calves were performed both before and after the treatment at the 1/2, 1, 2, 4, 12 and 24 h. The capillary refill time, peripheral pulse quality, dehydration degrees, mental status, haematocrit rates, haemoglobin and plasma values after treatment were found to be statistically different compared with the values before treatment. In comparison with group I, group II is observed to have shorter capillary refill time at 1, 4 and 12 h (P < 0.001) and better peripheral pulse quality at 1/2 (P < 0.05), 1, 2, 4 and 12 h (P < 0.001). Moreover, the degree of dehydration in group II, was significantly improved at 2 (P < 0.01), 4 and 12 h. Results of the study indicated that administration of low volumes of hypertonic sodium chloride and dextran 70 solution combinations with oral electrolyte solutions was concluded as quicker, practical, economical and most importantly an effective way for the treatment of dehydrated diarrhoeic calves.

Administration, Oral↗

Toxicity of parenteral iron dextran therapy.

Parenteral iron dextran is efficacious and safe for iron repletion in patients with iron-deficiency anemia. The risk for developing reactions to parenteral iron infusion can be attenuated if patients are carefully selected. Patients with underlying autoimmune disease, malnutrition with indolent infection, and risk for iron overload syndromes should be carefully monitored for complications. Further, the rate of infusion and the route of administration of iron dextran play roles in the risk of adverse reactions. The purpose of this review is to identify and elucidate the mechanisms of the acute and chronic toxicities associated with parenteral iron dextran use.

Anemia, Iron-Deficiency↗

Processing of major ABO-incompatible bone marrow for transplantation by using dextran sedimentation.

BACKGROUND: Various open and semi-closed methods are used for red cell (RBC) depletion and hematopoietic progenitor cell (HPC) enrichment of bone marrow (BM) in vitro, but with variable efficacy. A simple, efficient, and safe method using dextran 110k was developed. STUDY DESIGN AND METHODS: An equal volume of 4.5-percent dextran was applied to major ABO-incompatible BM in transfer bags and sedimentation was allowed for 30 minutes. RBCs, nucleated cells (NCs), and mononuclear cells (MNCs) from BM allografts before and after dextran sedimentation (DS) were counted. Flow cytometry, short-term cultures, and long-term cultures were performed to assay the respective recovery of CD34+ cells, colony-forming units (CFUs), and long-term culture-initiating cells (LTC-ICs). RESULTS: Sixteen BM collections were processed. The mean volume was 666 mL (range, 189-1355 mL). The mean +/-1 SD post-DS NC, MNC, CD34+ cell, and CFU counts per kg of the recipient's body weight were 4.11 +/-1.74 x 10(8), 8.98 +/- 3.68 x 10(7), 2.90 +/- 1.95 x 10(6), and 2.03 +/- 2.01 x 10(5), respectively, with the corresponding post-DS recovery being 90.6 percent, 90 percent, 92.4 percent, and 100.8 percent. The numbers of LTC-ICs in cultures (up to 12 weeks) of pre-DS and post-DS samples of five BM allografts were comparable (p = 0.91). Residual RBCs were 5.1 +/- 4.6 (0.1-14) mL with depletion of 96.5 +/- 3.2 percent. There was no significant difference in the mean absolute RBC count in post-DS BM allografts and in four ficoll-treated BM allografts (8.09 x 10(10) vs. 4.9 x 10(9); p = 0.206) and in eight major ABO-incompatible peripheral blood HPC collections (8.09 x 10(10) vs. 9.81 x 10(10); p = 0.87). No posttransplant hemolysis was encountered. Engraftment occurred at 22 +/- 7 days, which is similar to that of four transplants with ficoll-treated BM allografts (22 +/- 9; p = 0.611) and 54 unprocessed BM allografts (19 +/- 6; p = 0.129). CONCLUSION: DS is an efficient method of depleting RBCs in major ABO-incompatible BM allografts without significant loss of HPCs.

ABO Blood-Group System↗

An evaluation of iron-dextran supplementation in piglets administered by injection on the first, third or fourth day after birth.

The aims of the study were to evaluate the effect of iron-dextran injection given on the first, third or fourth day after birth on haematology in piglets. An advanced automated blood analyser; Technicon H*1, which performs a complete blood cell count and leukocyte differential counts was used to analyse the blood. Six litters of Norwegian Landrace x Yorkshire piglets were included in the study. The day after birth (day 1), half of the piglets in each litter (split litters) were injected subcutaneously with 180 mg iron as iron-dextran (1.5 ml Idofer). The untreated piglets from two of the litters were injected with the same amount of iron-dextran on day 3, and those from the remaining four litters on day 4. The piglets were weighed and blood samples collected on days 1, 3 or 4, 7, 14 and 21. Erythropoiesis, but not leukocyte count, responded to injection on day 1 compared with injection on the third or fourth day. The difference between groups in haematological parameters was greatest on day 7. The two groups of piglets treated on day 1 had a haemoglobin concentration (Hb) +/-SD of 92 g litre-1(+/-9) and 94 g litre-1(+/-9), and the piglets treated on day 3 had a Hb of 81 g litre-1(+/-7) and the one treated on day 4 had a Hb of 78 g litre-1(+/-7) on day 7. On days 14 and 21 there were no differences between groups. This study indicates that some piglets were anaemic and responded to subcutaneous iron injection on day 1.

Animals↗

Acute renal failure in a healthy young adult after dextran 40 infusion for external-ear reattachment surgery.

Dextran 40 is used to improve the microcirculation after certain surgical procedures. We report a rare case of acute anuric renal failure in a healthy young adult after administration of dextran 40 to improve the microcirculation following ear-reattachment surgery. The renal failure was subsequently reversed by plasmapheresis and intensive care support. Although rare in the young and fit, the risk of developing acute anuric renal failure exists with administration of dextran 40 and appropriate monitoring is essential.

Acute Kidney Injury↗

Tumour embolization of the Vx2 rabbit head and neck cancer model with Dextran hydrogel and Holmium-poly(L-lactic acid) microspheres: a radionuclide and histological pilot study.

INTRODUCTION: Intra-arterial embolization of unresectable malignant tumours with biodegradable microspheres is an effective way of selective anti-tumour therapy. Promising candidates are Dextran hydrogel (Dex) microspheres for chemo-embolization and Holmium-166 poly(L-lactic acid) (166HoPLA) microspheres for radio-embolization. This study was performed to investigate the distribution of intra-arterially injected microspheres both in vivo and histologically in order to establish an optimal size of particles for embolization of head and neck tumours. MATERIAL: Twenty rabbits with Vx2 auricular tumours were embolized via the caudal auricular artery with 4 different batches of microspheres: Radioactive (166)HoPLA microspheres sieved between 20 and 50 microm and Dextran hydrogel microspheres sieved between 20 and 100 microm (Dex20), 30 and 100 microm (Dex30) or 50 and 100 microm (Dex50). Dex20 and Dex50 microspheres were labelled with 99mTechnetium in six cases. METHODS: The average particle size of the microspheres was determined. The proportion of microspheres entrapped in the tumour was measured with a gamma camera. The distribution of microspheres around the primary tumour and spill of particles over into lungs or other organs was analysed from histological sections. RESULTS: The mean particle diameter varied from 19 to 66 microm: (166)HoPLA 19+/-11 microm, Dex20 40+/-19 microm, Dex30 50+/-19 microm, Dex50 66+/-21 microm. The 19 microm(166)HoPLA particles proved inadequate for embolization as 51% spilled over into the lungs, whereas over 95% of the 40-66 microm Dex microspheres were retained within the primary tumour area. Particle density in lung tissues proved significantly lower for the Dex50 group. Stray emboli to the brain occurred in two rabbits. CONCLUSION: The results of this investigation show that both Dextran hydrogel and holmium-166 poly(L-lactic acid) microspheres are potential candidates for embolization of head and neck cancer. In future studies, arterio-arteriolar anastomoses which might confound treatment should be identified and occluded. Particles with a number weighted mean diameter of at least 40 microm and a volume weighted mean size up to 70 microm should be used.

Analysis of Variance↗

[The metabolism of organ cultures of cornea in TC 199 with added dextran 500 or hydroxyethyl starch 450].

Pig corneas were stored at room temperature for 20 days in TC 199 culture medium supplemented with 10% pig blood serum, antibiotics, and to reduce swelling with 10% Dextran 500 or 10% hydroxyethyl starch HAES 450. The high molecular weight of these additions, 500,000 and 450,000 Daltons respectively, prohibited swelling by their osmotic pressure. The water content of the cultured corneas was 80.6 +/- 0.5% with HAES 450 and 76.4 +/- 2.0% with Dextran 500. The epithelial cells of the cultured cornea rounded and desquamated after 12 to 16 days of culture. The endothelium showed vacuoles. The metabolism of the cultured corneas was measured by glucose and lactate levels in the epithelium, the stroma, and the medium as well as by the glycogen, ATP, and ADP content in the corneal epithelium. The cultured corneas consumed reasonable amounts of glucose and produced lactate. The glycogen content and the ATP levels decreased slightly, but the ATP/ADP ratio showed a good energy state. In the cultures containing HAES 450 the entire system was flooded with glucose released from hydroxyethyl starch. The Dextran 500 culture system could prove suitable for culturing human donor material without swelling.

Adenosine Diphosphate↗

The effect of low molecular weight dextran on platelet deposition onto prosthetic materials.

Low molecular weight dextran (LMD) has recently been shown in a randomized, multicenter trial to improve early patency in difficult lower extremity vascular bypass. The question remained as to whether this effect was due to plasma volume expansion by LMD or to its effects on platelets and coagulation. To analyze this we have studied the effects of LMD on platelet-graft interactions using an ex vivo baboon shunt. Indium 111-labeled autologous platelet deposition on expanded polytetrafluoroethylene and knitted Dacron grafts was monitored at a flow rate of 25 ml/min for 21/2 hours. LMD was given by intravenous bolus at a dose of 5 ml/kg and was followed by a continuous infusion of 10 ml/hr. Flow through the shunt was started after the initial dextran bolus. Control studies were performed in a similar manner without dextran. An additional series of experiments was performed with a 5 to 10 ml/kg bolus of 5% human serum albumin to analyze the contribution of plasma volume expansion to platelet deposition in this model. The results revealed a significant (p less than 0.05) reduction in platelet deposition on both graft materials with the LMD infusion. No difference was seen between the control group and the albumin group. These studies provide direct in vivo evidence of the antiplatelet effect of LMD.

Albumins↗

A chemically modified dextran inhibits smooth muscle cell growth in vitro and intimal in stent hyperplasia in vivo.

PURPOSE: Intimal smooth muscle cell (SMC) hyperplasia is a main component of the arterial wall response to injury. We have investigated the capacity of a water-soluble nonanticoagulant functionalized dextran (E9) in inhibition of SMC growth in vitro and in vivo. METHODS: E9 was obtained with chemical substitutions with anionic and hydrophobic groups on the dextran backbone. SMC proliferation (cell counting, thymidine uptake, cell cycle analysis) was followed in culture in the presence of E9. Western blot analysis against phosphorylated mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinase 1/2, and assessment of MAPK activity on serum-stimulated SMCs also were investigated. Binding/displacement experiments, electron microscopy, and cell fractionations were used to follow the binding and internalization of radiolabeled and fluorescentlabeled E9. New Zealand white rabbit iliac arteries were injured with balloon dilatation and stent deployment. Animals were treated for 14 days with saline solution or E9 (5 mg/kg injected subcutaneously, twice daily). Morphometric analyses were carried out in each group (n = 6 arteries, 18 sections). RESULTS: Nonanticoagulant E9 inhibited SMC proliferation in vitro. Tyrosine phosphorylation of MAPK 1/2 and MAPK activity were inhibited with E9 within 5 minutes of incubation. The binding and rapid cytoplasmic internalization of the synthetic compound was evidenced, but, in contrast to heparin, we did not detect any nuclear localization of the antiproliferative E9. In the in vivo model, qualitative modifications of neointimal structure with a thinner fibrocellular neointima were noticed after E9 treatment. Morphometric analyses of stented arteries in E9-treated animals indicated an important reduction (P <.01) of intimal growth: 33% and 45% for intimal area and intima/media ratio, respectively. CONCLUSION: Cytoplasmic internalization of the synthetic polysaccharide correlated to the SMC growth inhibition that involved the MAPK pathway. In vivo inhibition of intimal instent hyperplasia with this nonanticoagulant derived dextran is shown providing a new candidate for a potential selective treatment of SMC proliferation.

Animals↗