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PubMed1980

Dextran sulphate induced arthritis in rabbits.

Persistent effects of a short course of intra-articular dextran sulphate, dextrans, or chondroitin sulphate were examined in rabbit knees. Only dextran sulphate produced gross arthritis, associated with high synovial acid phosphatase and beta-glucuronidase activities. Synovial degradative capacity in synovium-cartilage cocultures was increased 2-fold by dextran sulphate and 1.5-fold by chondroitin sulphate treatments. Stimulation of cartilage breakdown in vitro paralleled the content of synovial marker enzyme at death of the animal, but the 2 responses could be dissociated.

Animals↗

PubMed1992

Effect of intravenous iron-dextran (Imferon) infusion on antigen induced monarticular arthritis in rabbits.

The effect of intravenously infused iron-dextran (Imferon) on the progression of antigen induced monarticular arthritis in rabbits was studied. A rapid deposition of iron and apoferritin in the synovia of arthritis joints occurred after infusion of iron-dextran during either the acute or chronic phases of the disease. This coincided with the appearance of catalytic (bleomycin reactive) iron in the synovial fluid. There was no evidence, however, for an exacerbation of the antigen induced arthritis as a result of the iron-dextran, and synovial and bleomycin reactive iron concentrations decreased with time after administration, indicating a redistribution of the synovial iron load. Thus although intravenously infused iron-dextran appears to 'prime' the rabbit arthritic joint transiently with the potential for iron stimulated oxygen free radical damage, other factors may determine its occurrence.

Animals↗

PubMed1979

Effect of dextran sulphates on thrombin activity.

To clarify the action of dextran sulphate, a heparin analogue, in the clotting of fibrinogen by thrombin, determinations were carried out on the clotting activity, the release of fibrinopeptides from fibrinogen, and the hydrolytic activity of thrombin against a peptide chromogenic substrate in the absence or presence of antithrombin III (heparin cofactor). It was shown that dextran sulphate itself inhibited thrombin activity, and its inhibition was dependent on the molecular weight and the sulphur content of the dextran sulphate. Although heparin markedly enhanced the antithrombin activity of antithrombin III, dextran sulphate did not activate antithrombin III.

Antithrombin III↗

PubMed1977

Synthesis of soluble dextran-hemoglobin complexes of different molecular sizes.

Experimental conditions were defined that determined the synthesis of dextran-hemoglobin complexes through the alklation of hemoglobin by N-bromoacetylaminoethylaminodextran. Using appropriate concentrations of the two reactants, over 90% yield of dextran-hemoglobin was obtained for dextrans of average molecular weight of 200 000 110000, 70000, 400000, and 20000. Extensive viscosity increase due to crosslinking could be avoided, and a large molar excess of dextran over hemoglobin made unnecessary, under the optimal conditions.

Dextrans↗

PubMed1990

Evaluation of Gd-DTPA-labeled dextran as an intravascular MR contrast agent: imaging characteristics in normal rat tissues.

Dextran covalently linked to moieties of gadolinium diethylenetriamine pentaacetic acid (DTPA), for use as a macromolecular, intravascular blood pool marker for contrast material-enhanced magnetic resonance (MR) imaging was characterized by means of physicochemical and relaxivity measurements and MR imaging in healthy rats. Dextran labeled with 15 Gd-DTPA moities (molecular weight of approximately 75,000 d) had a T1 relaxivity at 0.25 T and 37 degrees C of 157.1 mmol-1.sec-1 per molecule and 10.5 mmol-1.sec-1 per gadolinium atom, more than twice that of unbound Gd-DTPA. Osmolality was 300-350 mOsm/kg at a gadolinium concentration of 0.01 mmol/L. Tissue enhancement was essentially linearly related to injected dose in the gadolinium dose range of 0.01-0.05 mmol/kg of body weight. Approximate typical enhancement values over baseline for normal tissues at 10 minutes after a gadolinium dose of 0.05 mmol/kg were as follows: cardiac muscle, adrenal gland, and liver, 40%-50%; lungs, 160%-200%; renal cortex, 130%; renal medulla, 240%; spleen, 75%; muscle, 15%; and brain, 5%-10%. Projection-subtraction images showed that dextran-(Gd-DTPA)15 remained intravascular for at least 1 hour after injection. The prolonged and easily appreciated levels of tissue enhancement with dextran-(Gd-DTPA)15, at a gadolinium dose less than that routinely used in Gd-DTPA, indicate further evaluation of this macromolecular marker.

Animals↗

PubMed1986

Antishock effects of corticosterone on dextran-induced shock in rats.

To study the effects of glucocorticoid on the shock state, dextran-induced shock in rats was used as an experimental model system. The rats were divided into three groups, viz., control (group A), adrenalectomized (group B), and adrenalectomized corticosterone supplemented (2 mg/rat for 4 days; group C), and 5% dextran solution was given intravenously to each rat. In group B, remarkable increases in the histamine levels in both plasma and the paw cutaneous tissue, hemoconcentration, and intractable hypotension were observed. Most rats in group B died during the shock experiment without showing any recovery when the cannulas were inserted into the left carotid artery for the measurement of blood pressure. But in group C, most rats eventually survived and recovered to a normal state within 2 h, so that corticosterone clearly ameliorated the shock state of adrenalectomized rats by dextran administration. These results suggested that the ameliorating effects of corticosterone in the dextran-induced shock states are due to the acceleration of the rate of clearance of circulating chemical mediators that are represented by histamine and are due to the alteration of overall responsiveness of the animals to a complex array of factors that threaten the status of the animals, as represented by the amelioration of the vascular activity.

Adrenalectomy↗

PubMed1978

Dextran as a radioactive microsphere suspending agent: severe hypotensive effect in rat.

The effects of different commercially available radioactive microsphere suspending solutions were studied on the cardiovascular hemodynamics of male, Sprague-Dawley rats. Single left ventricular injections of carbonized radioactive microspheres (15 +/- 5 micron diam) totaling 850,000 spheres, suspended in 10% dextran (mol wt, 73,000) solution with Tween, caused reductions in arterial pressure (control, 101; postinjection, 74 mmHg; P less than 0.001), with no change in heart rate. Identical injections made with isotonic saline solution plus Tween had no effect on either heart rate or arterial pressure. Independent studies were conducted to examine the effects of 1-ml injections of four suspending solutions without microspheres on the cardiovascular hemodynamics of rats. Isotonic saline had no hemodynamic effect, and isotonic saline plus Tween decreased only heart rate. Ten percent dextran soluton with Tween decreased arterial pressure, heart rate, peak left ventricular systolic pressure, and left ventricular end-diastolic pressure. Similar changes occurred when dextran solution without Tween was administered. These data demonstrate that 10% dextran solution used as a microsphere suspending agent induces a severe hypotensive response in rats. Furthermore, injections of up to 850,000 microspheres in isotonic saline solution do not alter arterial pressure in the rat.

Animals↗

PubMed1992

Systemic and regional O2 delivery and uptake in bled dogs given hypertonic saline, whole blood, or dextran.

The mechanisms by which small volumes of hypertonic saline in dextran (HSD) resuscitate bled dogs are incompletely understood but may include a pulmonary osmolar reflex. A known negative effect of HSD is hemodilution that reduces O2-carrying capacity. Our goals in this study were to ascertain whether the putative osmotic reflex redistributed blood flow between muscle and gut and whether O2 delivery (DO2) was adequate at systemic and regional levels. Left hindlimb muscle and a segment of ileum were vascularly isolated in three groups (n = 8) of anesthetized dogs that were then bled to mean arterial pressure (MAP) of 40 mmHg for 30 min. At that point, all shed blood (approximately 40 ml/kg) was returned in the blood group (BLD); 20 ml/kg of Dextran 70 was given to the dextran group (DEX); and 5 ml/kg of 7.5% NaCl in dextran was given to the HSD group. MAP and cardiac output were restored to acceptable levels in all but was poorly maintained in HSD. The fall in hematocrit (41 to 25%) in HSD was matched by that in DEX (42 to 22%), so that DO2 only reached approximately 55% of that in BLD. Nevertheless, systemic and regional O2 uptakes were similar; O2 debt and repayment did not differ; and lactate metabolism was alike in all groups. O2 extraction did have to increase to near maximum in HSD, however. Other than a transient increase to muscle, HSD had no special effect on distribution of cardiac output. HSD was efficacious as a short-term resuscitative measure but did encroach markedly on O2 transport reserves.

Animals↗

PubMed1992

Effects of hypertonic saline and dextran 70 resuscitation on microvascular permeability after burn.

Administration of hyperosmolar fluids to burn patients has been proposed as a means of decreasing resuscitative fluid volume and, subsequently, wound edema accumulation. To test this hypothesis, canine hindpaw lymph flow (QL) and lymph (CL) and plasma (CP) total protein concentrations were measured, and capillary filtration coefficient (Kf) was calculated before and for 6 h after a 5-s 100 degrees C footpaw scald. Scald was followed 30 min later by bolus infusion (4 ml/kg) of 7% saline or 6% Dextran 70 or the two in combination. Before scald, venous pressure was elevated until a minimal CL/CP was reached. The reflection coefficient (sigma d) was calculated by the formula: 1-minimal CL/CP. Scald increased QL, CL/CP, and Kf, but sigma d was decreased (P less than 0.05). Compared with burn alone, 7% saline exacerbated burn-induced increases in QL and Kf. In contrast, infusion of Dextran 70 did not exacerbate these changes in QL or Kf. Perhaps more importantly, Dextran 70 may have attenuated the increase in CL/CP and reduced edema formation in the burned hindpaw. However, the addition of 7% saline to the dextran eliminated these beneficial effects.

Animals↗

PubMed1983

Determination of postglomerular permselectivity to neutral dextrans in the dog.

The single-pass multiple-indicator-dilution (MID) technique was used to analyze postglomerular capillary permeability. Anesthetized mongrel dogs (n = 13) during mannitol diuresis received a pulse injection of 125I-albumin (plasma reference), [14C]inulin (glomerular reference), creatinine (interstitial reference), and a homogeneous [3H]dextran molecular weight marker 6,000-12,000 dalton in the left renal artery. Simultaneous left renal venous outflow and right and left urine were rapidly sampled. Left urine recoveries of creatinine, [14C]inulin, and [3H]dextran were identical, indicating no glomerular solute flux limitation. Progressive precession of the [14C]inulin and [3H]dextran renal vein curves relative to creatinine indicated increasing postglomerular limitation to solute flux proportional to molecular size. The postglomerular solute extraction (EPG) (renal vein upslope indicator/125I-albumin) varied inversely with postglomerular renal plasma flow (F), indicating diffusion limitation. Ouabain infusion into the left renal artery significantly reduced Na reabsorption but did not alter the EPG of [14C]inulin or [3H]dextran. Permeability-surface (PS) area products calculated from EPG and F ranged from 4.86 +/- 0.89 to 0.97 +/- 0.25 (SD) cm X s-1 X 100 g-1 for indicators 5,000-12,000 dalton. [14C]Inulin PS products remained constant for F greater than or equal to 2.50 ml X s-1 X 100 g kidney-1. PS[3H]dextran/PS[14C]In (n = 20, F greater than or equal to 2.5 ml X s-1) was used to calculate an effective postglomerular capillary pore radius, r = 55.5 +/- 7.6 (SD) A.

Animals↗

PubMed1992

Increased negativity of interstitial fluid pressure in rat trachea in dextran anaphylaxis.

This study shows that, in rat trachea, dextran anaphylaxis is associated with increased negativity of interstitial fluid pressure (Pif) as measured with sharpened glass capillaries (tip diameter 3-7 microns) connected to a servo-controlled counterpressure system. Experiments were carried out in pentobarbital-anesthetized Wistar-Møller rats. Pif in the control situation was -2.5 +/- 0.38 (SD) mmHg. The mean pressure in animals killed 2 min after initiation of the anaphylactic reaction by injection of 1 ml of 10% Dextran 70 in 0.9% NaCl was -10.3 +/- 2.6 mmHg. In another experimental series, interstitial fluid volume was measured after dextran administration but without inducing circulatory arrest. Interstitial fluid volume increased from 0.94 +/- 0.16 to 1.56 +/- 0.42 ml/g dry wt after 10 min to 1.57 +/- 0.30 and 1.10 +/- 0.27 ml/g dry wt after 30 and 60 min, respectively. The increased negativity in Pif in tracheal mucosa in the early phase of dextran anaphylaxis will markedly increase the transcapillary net filtration pressure in the initial phase of edema development.

Anaphylaxis↗

PubMed2004

Presynaptic calcium measurements at physiological temperatures using a new class of dextran-conjugated indicators.

Presynaptic calcium (Ca(pre)) has been studied extensively because of its role in triggering and modulating neurotransmitter release. Although calcium regulation and calcium-driven processes can be strongly temperature dependent, technical difficulties have limited most studies of Ca(pre) to temperatures well below the physiological range. Here we assessed the use of membrane-permeant acetoxymethyl (AM) indicators and dextran-conjugated indicators for measuring Ca(pre) at physiological temperatures. A comparison of these two types of indicators loaded into parallel fibers of rat cerebellar slices revealed striking differences. AM indicators were rapidly extruded from axons and presynaptic terminals and therefore cannot be used for long-term measurements at high temperatures. In contrast, dextran-conjugated indicators were retained within parallel fibers and are therefore well suited to measuring Ca(pre) at physiological temperatures. The limited number of dextran indicators available prompted us to synthesize three new indicators that show peak emission in the red (575-600 nm). These indicators allow for simultaneous use of multiple calcium indicators that can be readily distinguished on the basis of excitation and emission wavelengths, use of excitation and emission wavelengths that are relatively insensitive to tissue autofluorescence, and measurements in systems with expression of green fluorescent protein (GFP). Thus we find that dextran-conjugated indicators are well suited to long-term recordings of Ca(pre) at physiological temperatures and that the development of new red indicators greatly extends their utility.

Animals↗

PubMed2000

Augmentative effect of polyethylene glycol, polyvinyl alcohol and dextran on thyroid-stimulating antibody stimulated cAMP production in FRTL-5 cells and CHO cells expressing human TSH receptor.

Previously we reported the augmentative effect of nonionic hydrophilic polymers such as polyethylene glycol (PEG), polyvinyl alcohol (PVA) and dextran on thyroid-stimulating antibody (TSAb) activity in porcine thyroid cell assays. We examined whether a similar phenomenon occurs in FRTL-5 thyroid cells and CHO cells expressing the human (h) TSH receptor (CHO-hTSHR cells). As with porcine thyroid cells, PEG 22.5% precipitated crude IgG from serum of patients with Graves' disease, significantly increased cAMP production as compared with PEG 12.5% precipitated crude IgG in both FRTL-5 cells and CHO-hTSHR cells. PEG 5% augmented purified-TSAb-IgG-stimulated cAMP production in both cell assays. TSAb activities and positivity by the direct assay using whole serum (0.05 ml) in the presence of 5% PEG in untreated Graves' patients were significantly increased as compared with the absence of 5% PEG. The augmentative effects of PVA 10% or dextran T-70 10% on TSAb-IgG-stimulated cAMP production were also observed in both cell assays. PVA 10% did not augment TSH-stimulated cAMP production in spite of weak augmentation by dextran 10% in both cell assays. Lack of the augmentative effects of PEG 5%, PVA 10% and dextran 10% on cAMP produced by GTPgammaS, forskolin and pituitary adenylate cyclase activating polypeptide was observed in both cell assays. The augmentative effects of these polymers in both cell assays similar to porcine thyroid cells suggest that there is no apparent species specificity among human, porcine and rat thyroid cells as far as TSH receptor linked cAMP production in cell membranes existed.

Animals↗

PubMed1982

Effect of dextran infusion on left atrial size in normal subjects.

The purpose of this study was to evaluate left atrium dimension during acute volume loading. Low molecular weight dextran solution (1,000 ml) was continuously infused in 10 subjects without cardiac disease. Measurements of pulmonary arterial, capillary wedge, right atrial and systemic blood pressures, cardiac output, heart rate and M-mode left atrial maximum diameter were made in basal conditions and after 250, 500, 750 and 1,000 ml of dextran. In 4 subjects a two-dimensional echocardiogram was also obtained in the short axis and four-chamber views. Dextran produced the following changes (mean values +/- standard deviation) in haemodynamic variables: right atrial and wedge pressures increased from 3.2 +/- 1.55 to 12.3 +/- 3.08 mm Hg (p less than 0.001) and from 6.9 +/- 1.45 to 20.6 +/- 3.44 mm Hg (p less than 0.001), respectively. Stroke volume increased from 70.5 +/- 31.6 to 86.6 +/- 24.6 ml/beat (p less than 0.05). Heart rate increased from 81.0 +/- 15.8 to 95.0 +/- 12.3 beats/min (p less than 0.05). Left atrial maximum diameter showed a slight increase after 500 ml of dextran (from 39.5 +/- 4.1 to 43.6 +/- 5.0 mm, p less than 0.05). It did not further increase by continuing the infusion up to 1,000 ml despite the marked increase in wedge pressure. The results show that left atrial size is partly independent of haemodynamic changes and that the compliance of the left atrium is relatively low. This finding is consistent with the common clinical observation that the left atrium is only slightly enlarged in acute mitral insufficiency.

Adult↗

PubMed1984

Electron microscopic study of the peritoneal kinetics of iron dextran during peritoneal dialysis in the rabbit.

Iron dextran, an electron-dense tracer, was given intravenously (100 mg of iron/100 g of body weight) to 8 normal rabbits to study its movement from the plasma to the peritoneal cavity during peritoneal dialysis. The dialysate infused at 75 ml/kg contained 1.5 g/dl of glucose in 4 animals and 4.25 g/dl in the remainder. Peritoneal dialysis was discontinued and the peritoneum was fixed in vivo at various times (20-120 min) after the injection of the iron dextran. Large amounts of tracer were detected in the effluent after draining the peritoneal cavity. Electron microscopic examination of the mesentery showed particles of iron dextran in the endothelial cells of small vessels (capillaries and venules) the interstitium and the mesothelial cells adjacent to vessels irrespective of the dialysate concentration or duration of dialysis. Tracer was not clearly demonstrated in the interendothelial or intermesothelial spaces. In the mesothelial cells, the particles were found exclusively in (small, elongated or large) vesicles, while in the endothelial cells they were both in vesicles and free in the cytoplasm. Our findings suggest that during the 20- to 120-min period after intravenous administration, the intracellular transport of iron dextran, depends on either moving vesicles or the presence of pre-existing tunnels in the mesothelial cells of rabbit mesentery.

Animals↗

PubMed1993

Effect of low-molecular-weight dextran on proteolytic and nonproteolytic lysosomal enzymes in isolated segments of rat proximal tubule.

Dextrans undergo glomerular filtration and are taken up by endocytosis into lysosomes of proximal tubule cells. We measured the activities of the intralysosomal proteolytic enzymes cathepsin B and L and the nonproteolytic acid phosphatase in microdissected segments of rat proximal tubules by means of fluorescent ultramicroassays. Cathepsin activities were increased following dextran injection in a dose-dependent manner. Cathepsin stimulation was not dextran-specific since enhanced proximal albumin uptake also increased cathepsin activities. Acid phosphatase remained almost unchanged. We conclude that increased proximal tubule uptake of macromolecules is accompanied by a rather specific stimulation of proteolytic enzymes in the lysosomes. For proteins this constitutes an adequate response to increased protein uptake to maintain the steady state between uptake and catabolism of proteins in lysosomes. For the nondigestible dextran the cathepsin induction is an inadequate response. Since lysosomal cathepsins are involved in breakdown of intracellular proteins, it is conceivable that the increased activities reflect increased cellular autophagy leading to proximal tubule damage.

Acid Phosphatase↗

PubMed1978

Glucans and dextrans in rats and man.

Intracutaneous injections of three glucan contaminants of invert sugar solutions and crude cane sugar into human skin produced localised wheals and erythema reactions. These glucans of molecular weight between 12,000 and 1,400,000 were also active on intradermal injection into both dextran-sensitive and dextran-resistant rats, and, like dextrans, were active on subcutaneous injection into dextran-sensitive animals.

Animals↗

PubMed1980

Clinical dextrans lack mitogenic activity for normal human lymphocytes in vitro.

In vitro studies on mitogenic stimulation of lymphocytes from a panel of normal volunteers revealed no transformation in response to the presence of dextran 40, 70, 110 or 150 at concentrations ranging from 0.8 to 8,000 microgram/ml. High molecular weight native dextran B512 was mitogenic in 1 individual only. In addition, neither Leuconostoc-derived nor fermentation medium-derived moieties, sometimes present in clinical dextrans, were implicated as lymphocyte mitogens. It is concluded on the basis of these findings that clinical dextrans of average molecular weight 40,000--150,000 are not B- or T-cell mitogens.

Dextrans↗