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PubMedDate not supplied

Acute and subacute toxicity of 7.5% hypertonic saline-6% dextran-70 (HSD) in dogs. 2. Biochemical and behavioral responses.

7.5% Hypertonic saline-6% Dextran-70 (HSD) is currently being evaluated in our laboratory as a resuscitation solution for the treatment of hypovolemia at a dose of 4 ml kg-1 body weight. A few reports of dextran toxicity, particularly of the kidney, have been cited in the literature, so the present study evaluated the acute and subacute toxicity of HSD administered i.v. to beagle dogs. In the acute toxicity studies animals were infused with a single dose of HSD, or its components of hypertonic saline (HS) or Dextran-70 (D-70), at the maximum tolerated dose (MTD: 20 ml kg-1). Controls received Ringers lactate (RL). In the HSD-infused dogs, transient but significant increases in serum alanine (ala) aminotransferase (AT), aspartate (asp) AT and alkaline phosphatase (AP) were observed for the first 72 h. In most cases this increase was also observed in the HS group. In the subacute studies, dogs were infused daily with the MTD of the above test solutions. Serum ala AT activity was 2-3-fold higher in the HSD than the RL group for the first 3 days. Again, a similar effect was observed in the HS group. Slight, transient increases in asp AT and AP activity were also observed in the HSD group. Higher lactate dehydrogenase (LDH) activity was only observed at Day 14 in dogs infused with the MTD of HSD or HS. In both studies, no adverse effects on blood urea nitrogen (BUN) or serum creatinine were observed and other transient changes in serum parameters were attributable to hemodilution induced by HSD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Evaluation of the local irritation potential of hypertonic saline-dextran (HSD) in mice and rabbits.

Recent questions have renewed concerns regarding possible irritation associated with intravenous (i.v.) injection of 7.5% hypertonic saline (HS) or hypertonic saline-dextran (HSD: 7.5% NaCl and 6% Dextran-70). This study investigated local injection site irritation associated with i.v., paravenous (p.v.), intramuscular (i.m.) and subcutaneous (s.c.) injection of HSD or its individual components. Mice (n=10 per group per time point) and rabbits (n=10 per group per time point) were infused i.v. with the maximum tolerated dose (28 or 20 ml kg(-1), respectively) of HSD, HS, Dextran-70 (D-70) or lactated Ringer's solution (LR). Animals were observed at 1,2 and 4 h after injection and then twice daily until euthanized on day 3 or 14. In irritation studies, 24 rabbits were randomized to receive the four fluids and they were evaluated histologically at 4, 24, 48 or 72 h after i.v., p.v., i.m. or s.c. infusion. The sites were observed immediately after injection, at 4 h and then twice daily until euthanasia. In surviving mice, bruising of the tail was observed in 6/18 and 5/19 animals in the HSD and HS groups, respectively, compared with 0/20 animals in the D-70 or LR groups. Sloughing of the tail was eventually observed in two HSD-infused and three HS-infused mice, compared with none in the other groups. More bruises, hematomas and blebs were observed after i.v. or s.c. injection of HS and D-70 than LR or HSD in the rabbit irritation studies, but the differences among groups were not statistically significant. In the acute toxicity study in rabbits, bruising at the site of injection was observed in 7/20 and 5/14 surviving animals from the HSD and HS groups, respectively, but none was observed in the LR or D-70 groups. These data suggest that, if infused over 5-10 min into a peripheral or central vein, a therapeutic dose of HSD (4 ml kg(-1)) should not induce any greater inflammation on the vein than LR. However, if significant extravasation of hypertonic fluid occurs, the possibility of localized, focal necrosis might be expected to occur.

Animals↗
PubMed2004

Biocompatibility of chemoenzymatically derived dextran-acrylate hydrogels.

The biocompatibility of chemoenzymatically generated dextran-acrylate hydrogels has been evaluated in vitro, using human foreskin fibroblasts, and in vivo, by subcutaneous and intramuscular implantation in Wistar rats for up to 40 days. In vitro tests show that hydrogel extracts only minimally reduced (<10%) the mitochondrial metabolic activity of fibroblasts. Direct contact of the hydrogels with cells induced a cellular proliferation inhibition index (CPII) of 50-80%, compared with a control, whereas through indirect contact, the CPII values were <16%, suggesting that the high CPII values achieved in the direct assay test were likely due to mechanical stress or limitations in oxygen diffusion. Hence, the hydrogels were noncytotoxic. Moreover, cell-material interaction studies show that these hydrogels were nonadhesive. Finally, histologic evaluation of tissue response to subcutaneous and intramuscular implants showed acceptable levels of biocompatibility, as characterized by a normal cellular response and the absence of necrosis of the surrounding tissues of the implant. In the first 10 days, the foreign-body reaction in the intramuscular implantation was more severe than in subcutaneous implantation, becoming identical after 30 days. In both cases, dextran hydrogels did not show signs of degradation 6 weeks postimplantation and were surrounded by a thin fibrous capsule and some macrophages and giant cells. This response is typical with a number of nondegradable biocompatible materials. These results indicate that dextran hydrogels are biocompatible, and may have suitable applications as implantable long-term peptide/protein delivery systems or scaffolds for tissue engineering.

Acrylates↗
PubMed1994

Mechanism of the enhancement effect of n-octyl-beta-D-thioglucoside on the transdermal penetration of fluorescein isothiocyanate-labeled dextrans and the molecular weight dependence of water-soluble penetrants through stripped skin.

To clarify the mechanism of the enhancing effect of n-octyl-beta-D-thioglucoside (OTG), which acts as a potent enhancer for skin penetration of peptides and water-soluble penetrants, the in vitro penetration of macromolecules [fluorescein isothiocyanate-labeled dextrans (FTIC-dextrans)] was evaluated with hairless rat skin and stripped skin. The FITC-dextrans (MW, 4400, 9600, and 69,000 Da, referred to as FD-4, FD-10, and FD-70, respectively) penetrated more easily in the presence of OTG (1.5%), with high fluxes equivalent to those through stripped skin. This result indicated that the enhancement effect of OTG on the penetration of macromolecules through the stratum corneum was extensive, and the barrier function of the corneum was nearly eliminated by the OTG treatment. OTG significantly solubilized the stratum corneum proteins and ceramides during the initial time stage. Scanning electron microscopic observations demonstrated that OTG treatment dramatically changed the cell membrane (i.e., exfoliation of cell membranes and dissociation of adherent cornified cells), suggesting a significant disturbance of the cohesive laminae and barrier functions. The extent of dissociation of cell membranes increased with treatment time, without significant changes in the cell junctions. These results clarify that the enhancement mechanism of OTG was different from that of laurocapram and other lipophilic enhancers. The permeability of polar solutes with differing molecular sizes (MW, 180-69,000 Da) through stripped skin was size dependent (r = 0.997, p < 0.001). However, the viable epidermis and dermis restricted the penetration of macromolecules, such as FD-70.

Animals↗
PubMed1992

Osmotic complications of low-molecular-weight dextran therapy in free flap surgery.

Low-molecular-weight dextran is utilized by many microsurgeons after free tissue transfer for its beneficial effects on the microcirculation. While it is generally felt to have a low rate of complications, severe complications secondary to dextran's osmotic effects may occur. We report here on two cases in which therapy with low-molecular-weight dextran was strongly implicated as a causative factor in major complications. These cases and their background are reviewed. Guidelines for the safe administration of this agent in patients post free-tissue transfer are discussed.

Acute Kidney Injury↗
PubMed1988

Dextran-magnetite: a contrast agent for sodium-23 MRI.

Dextran-magnetite, a superparamagnetic compound, is a powerful relaxation reagent for sodium. Administered intravenously, it is confined mainly to the vasculature and eliminates the signal from plasma sodium, a significant component of the tissue sodium signal. Applications of dextran-magnetite for in vivo sodium imaging of a normal rat and rats with a tumor and experimentally induced peripheral edema are shown. Our results indicate that dextran-magnetite may be useful for improving tumor detection and for imaging of edema. To our knowledge, this is the first report of a contrast agent suitable for sodium magnetic resonance imaging.

Adenocarcinoma↗
PubMed1997

Protective effect of dextran sulfate and heparin on adult rat cardiomyocytes damaged by free radicals.

Studies in our laboratory have demonstrated that addition of polyanions, heparin or dextran sulfate, to endothelial cell cultures decrease free radical injury. To determine if these polyanions had a similar effect on cardiomyocytes, models of free radical injury were produced in adult rat cardiomyocyte cultures by: (1) addition of hydrogen peroxide; (2) exposure to hypoxia followed by reoxygenation; or (3) exposure to medium conditioned by endothelial cells that were damaged by hypoxia-reoxygenation. All three procedures significantly decreased cell viability as measured by trypan blue exclusion and increased release of enzymes, lactate dehydrogenase and creatine kinase, into cell medium when compared to control cultures. Addition of dextran sulfate or heparin to medium (5 microg/ml) prior to cell injury significantly increased cell viability and decreased release of enzymes when cells were damaged by the above protocols. Heparin was significantly less protective than dextran sulfate when cells were injured by hydrogen peroxide or hypoxia-reoxygenation but not when conditioned medium from damaged endothelial cells was added to cardiomyocytes. These results indicate that polyanions are protective of cardiomyocytes as well as endothelium. This protective effect may contribute to the beneficial effects of heparin on the cardiovascular system.

Animals↗
PubMed2001

Influence of high molecular dextrans on lung function in an ex vivo porcine lung model.

BACKGROUND: Extracellular preservation solutions utilizing high molecular agents can reduce intracellular edema during ischemia/reperfusion in lung transplantation. A solution of 40,000 dalton molecular weight (DMW) has already been clinically established (Perfadex). However, it is unclear whether dextrans of this particular size represent the optimal additive for lung preservation solutions. MATERIALS AND METHODS: In a new ex vivo porcine lung model, lungs were each preserved with low-potassium solutions containing 5% dextran with 90,000 DMW (Dex 90) and 160,000 DMW (Dex 160) and with Perfadex (40,000 DMW). After 24 h of cold ischemia, reperfusion was performed employing a roller pump with a pulsatile module. Lungs were perfused with deoxygenated perfusate and ventilated with room air. The oxygenation capacity (Delta pO(2)), peak inspiratory pressure (PIP), and mean pulmonary artery pressure (PAP) were monitored for 60 min. Net weight gain (NWG) and wet-to-dry ratio (W/D ratio) were determined. Free-radical generation was assessed by measuring malondialdehyde (MDA) at 10, 30, and 50 min. RESULTS: PIP and PAP increased in all groups significantly during reperfusion. However, Dex 160-perfused lungs exhibited significantly higher values than those with Dex 90 and Perfadex. Perfadex showed the highest Delta pO(2) throughout the entire reperfusion, while Delta pO(2) was slightly reduced in Dex 160 and significantly lower in Dex 90. In Perfadex the lowest water content was observed assessed by NWG and W/D ratio. The highest MDA values were observed in Dex 90, followed by Dex 160, while the lowest values were seen in Perfadex. CONCLUSIONS: Preservation of the lung with Perfadex exhibited superior postischemic function in contrast to preservation solutions containing dextrans with a higher molecular weight.

Animals↗
PubMed1993

Microscopic visualization of the retina by angiography with high-molecular-weight fluorescein-labeled dextrans in the mouse.

Methods currently available for the examination of the retinal vasculature of laboratory animals have significant drawbacks. Fluorescein angiography of rodent eyes is hampered by a poor view of the peripheral retina and difficulty in performing fundus photography. Methods of staining or filling retinal vessels are unreliable, labor-intensive, or have high backgrounds. We have developed a novel technique that is quick, simple, and accurate. Fluorescein-labeled 2 million molecular weight dextrans are used to fill the retinal vasculature of mice in vivo, followed by removal of the retina, fixation in paraformaldehyde, and examination of the vascular pattern in whole mount preparations by fluorescence microscopy. We found that fluorescein and fluorescein-labeled low-molecular-weight dextrans (40,000-500,000) are not suitable as they leak out of the vasculature to stain the entire retina in whole mount preparations. By contrast, fluorescein-labeled 2 million molecular weight dextrans remain in the vasculature for many months without diffusion or decay. Under low magnification, the entire retinal vasculature can be visualized at one time. By focusing from one plane to another, the superficial, connecting, or deep vascular layers are delineated. The background fluorescence is very low. We have successfully used this technique in over 20 mice per day to document retinal angiogenesis in a model of oxygen-induced proliferative retinopathy.

Animals↗
PubMed1978

Dextran receptors as immunogens in caries prophylaxis.

1) Immunization of rats with dextran receptors appears to confer resistance to development of caries. 2) A significant negative correlation between antiserum titers and caries scores is observed in immunized rats. 3) Antiserum specific for dextran receptors does not inhibit in vitro adherence of live bacteria in sucrose supplemented media. 4) Free receptors can bind to dextran, thereby inhibiting its ability to induce bacterial agglutination.

Animals↗
PubMed1987

Critical oxygen delivery levels during shock following normoxic and hyperoxic haemodilution with fluorocarbons or dextran.

Fluosol-DA 20% (FDA), an emulsion of fluorocarbons in a glucose electrolyte solution can deliver physiologically significant amounts of oxygen (O2) to the tissues and improve ischaemic hypoxia. To investigate its effect on critical oxygen delivery level (QO2c), four groups of six phenobarbitone anaesthetised air-ventilated splenic clamped mongrel dogs were haemodiluted to a haematocrit (Hct) of 25%; two groups with FDA and two with 6% dextran solution. Oxygen consumption (VO2) was derived from expired gas measurement and analysis, or by using a spirometer and carbon dioxide absorption. Whole body O2 flux (QO2) was calculated from mixed venous and arterial O2 contents and the Fick-derived cardiac output. QO2 was progressively decreased by haemorrhaging in steps of 1.5-2.5 ml per kg. Hct was kept at 25% using packed cells. VO2/QO2 pairs were calculated at each step and QO2c was determined for each animal by least squares fitting of data with 2 straight lines. Analyses of variance were performed. QO2c was significantly less in the FDA and O2 (F+O) group than either the dextran and O2 (D+O) or dextran and air (D+A) groups. Analysis of O2 extraction at QO2c, which effectively normalized results for differences in resting, VO2, had significantly better extraction in the FDA and air (F+A) than the D+A group. When fluorocarbon- and plasma-dissolved oxygen was subtracted, the O2 extraction in the F+A group was significantly better than in the D+A and F+O groups. The results imply that normoxic FDA haemodilution in animals respiring air can improve O2 delivery and that hyperoxia interferes with this process.

Animals↗
PubMedDate not supplied

Diffusion of dextrans and microspheres in the human amniotic basement membrane model.

The human amniotic basement membrane model was utilized to determine diffusion ratios of dextrans and beads according to size selectivity. Diffusion through both intact and denuded amnions was determined after 24 and 72 h. Four neutrally charged fluorescein isothiocyanate labeled dextrans, having molecular weights of 17,900, 42,000, 71,200 and 156,000, diffused through the amnion. The amnion functioned as a sieve in that the passage of dextrans was increasingly restricted as molecular weight increased. In contrast, uncharged latex microspheres (1.05 micron +/- 0.07 micron (SD] and fluorescent carboxylated microspheres (1.57 micron +/- 0.13 micron (SD] failed to pass through the amnion. Light and electron microscopy revealed no preformed channels through which the 1.05 micron microspheres could pass through the amnion. Statistical analysis of cross-sectional thickness of individual and similarly treated amnions (intact or denuded) showed a difference in thickness (P = 0.05).

Amnion↗
PubMed1992

Long-term experience with extracorporeal low-density lipoprotein cholesterol removal by dextran sulfate cellulose adsorption.

Patients with familial hypercholesterolemia have a high incidence of coronary heart disease due to diet- and drug-resistant, elevated low-density lipoprotein cholesterol (LDL-C). Five patients with familial hypercholesterolemia and diet- and drug-resistant LDL-C greater than 230 mg/dl were treated by LDL apheresis using dextran sulfate cellulose adsorption (Liposorber System LA-15, Kaneka). Plasma separation was by 0.5-m2 polysulfone hollow fiber filter. Two columns containing 150 ml of dextran sulfate cellulose alternately adsorbed LDL and were regenerated by 4.1% saline. The five patients received a total of 360 treatments at 7-day intervals. The treated plasma volume per session was 4.1 +/- 0.4 l. Postapheresis values compared with preapheresis were: total cholesterol, 40%; LDL-C, 28%; VLDL-C, 65%; HDL-C, 95%; triglycerides, 70%; white blood cells, 116%; platelets, 87%; C3 complement, 79%; fibrinogen, 64%; albumin, 94%. The decrease in HDL-C per treatment was not significant. The safety parameters showed only slight changes. The initial LDL of 436 +/- 172 mg/dl decreased to mean pre-apheresis levels of between 150 and 100 mg/dl. The anti-atherogenic HDL increased in three and remained unchanged in two patients. Adverse events like hypotension, angina pectoris, and technical problems occurred in 11 of the 360 treatments. Long-term treatment of patients with diet- and drug-resistant familial hypercholesterolemia by extracorporeal dextran sulfate cellulose adsorption is effective and safe.

Adult↗
PubMed1979

Preoperative normovolaemic haemodilution with dextran 70 as a thromboembolic prophylaxis in total in hip replacement.

The effect of preoperative normovolaemic haemodilution with dextran 70 in 57 patients undergoing total hip replacement for osteoarthritis, was evaluated with respect to the production of thrombosis and pulmonary embolism. The patients were randomly allocated to one group undergoing preoperative haemodilution and one control group receiving 500 ml dextran 70 during operation and again on the second postoperative day. Before operation blood was replaced by dextran 70 to lower the hematocrit to between 25 and 30. The blood drained from the patients was used to replace blood lost at operation. Between 10 and 14 days after operation the patients were examined by perfusion lung scan, chest radiography and bilateral phlebography. Twelve patients also had 133Xe ventilation scans. The incidence of deep vein thrombosis in the two groups did not differ significantly. Pulmonary embolism was significantly decreased in the preoperative haemodilution group. One patient in the control group had clinical symptoms of, and died from, pulmonary embolism.

Aged↗
PubMed1987

Real time observations of polylysine, dextran and polyethylene glycol induced mutual adhesion of erythrocytes held in suspension in an ultrasonic standing wave field.

A technique which enables cells to be observed in suspension for times of the order of minutes (employing acoustic radiation forces in a 1 MHz ultrasonic standing wave field) is described. Video recordings of the mutual adhesion of human erythrocytes in suspension have been analysed. Concave-ended cell doublets and linear rouleaux developed in 0.5-1.5% w/v Dextran T500 by a gradual (2.5-17 s) increase in the area of cell contact over the cell cross-section. The concave-ended rouleaux form was not seen in polylysine or in polyethylene glycol. In 5-7% dextran and in 20 micrograms/ml polylysine mutual adhesion was a two stage process. Cells first form a strong local contact which persists (without apparently growing in area) for a number of seconds following which the cell surfaces move suddenly to form a spherical doublet. The average initial contact time and engulfment time for cells in 7% Dextran T500 are 18 and 2.7s, respectively. The corresponding values for cells in 20 micrograms/ml, 14 kDa, polylysine are 2.7 and 0.3s. There was no initial contact delay during spherical doublet formation in 1 mg/ml polylysine. Electron microscopy showed that the intercellular seam for spherical doublets formed with all three agglutinating molecules was bent in a wavy lambda approximately equal to 4 micron) profile. The thickness of the intercellular space varied in a spatially periodic way (lambda approximately equal to 0.8 microns) for cells in polylysine. Examples of periodic intercellular spaces were seen by light microscopy in polyethylene glycol induced clumps. The role of interfacial instability in the adhesion processes is discussed.

Cell Adhesion↗
PubMed1984

Distribution of exudated FITC-dextrans in experimental vasogenic brain edema produced by a focal cryogenic injury.

Mice were subjected to cortical cryogenic brain injury, and FITC-dextrans (mol. wt. 20,000 or 150,000) were injected intravenously (i.v.). After a survival period of 4 h the distribution of the FITC-dextrans was determined by a histotechnical procedure described recently ( Hultstr öm et al. 1982a ). This technique is based on freeze-drying and vapor fixation to immobilize the tracer and to provide tissue fixation. In and around the cryogenic injury both tracers leaked out of the cortical and the leptomeningeal vessels and spread into the brain parenchyma. They were seen as multiple, closely apposed droplets of fluorescent material best recognized by fluorescence microscopy under high magnification. The tracers were also taken up by neuronal perikarya and in glial cell nuclei of, presumably, astrocytic origin. Our study shows that the FITC-dextran technique can be used for experimental studies on the vasogenic form of brain edema. The patterns formed by the extravasated tracers have qualitative similarities to those produced by other more commonly used tracers, such as fluorochrome-labeled serum proteins and peroxidase.

Animals↗
PubMed1991

Factors influencing transient expression in cytotoxic T cells following DEAE dextran-mediated gene transfer.

A number of transfection protocols have been tested for the introduction of exogenous DNA into cytotoxic T cells. These included electroporation, lipofection, calcium phosphate coprecipitation, polybrene-assisted gene transfer, and DEAE dextran-mediated transfer. Only the latter gave significant and reproducible transfection efficiencies coupled with low toxicity. The DEAE dextran protocol was optimized for the transfection of a transcription reporter construct pRSVcat into a cloned cytotoxic cell line. Among the parameters investigated were cell density, amount of input DNA, concentration of DEAE dextran, DNA adsorption time, temperature, use of permeabilization and expression facilitators, and recovery time. The optimized protocol was then used to demonstrate the presence of cis-acting regulatory regions in the 5'-flanking sequences of two cytotoxic cell-specific serine protease genes and, in addition, was shown to be applicable to other cloned T-cell lines.

Adsorption↗
PubMed1985

[Hemorrhagic pancreatitis: effect of dextran 40 and plasma on microcirculation disorders of the pancreas].

A dog model was used to measure the hemodynamic changes occurring during acute pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. Continuous measurements of pancreatic blood flow, cardiac output, mean arterial blood pressure and pancreatic oxygen consumption were made under normal conditions and during acute pancreatitis. All animals received 100 ml of saline/h during the time of observation. Three methods of therapy then were instituted in the dogs starting 30 min after induction of pancreatitis. 10 dogs served as controls (saline 100 ml/h); in 6 dogs additionally 15 ml/kg plasma was infused over 45 min and 6 dogs received 1.5 ml/kg Dextran 40/h continuously. Hemorrhagic pancreatitis was characterized by a fall in cardiac output and mean arterial pressure and the development of severe impairment of the pancreatic microcirculation with early reduction of pancreatic blood flow followed by a fall in pancreatic oxygen consumption. Administration of plasma produced a significant increase in cardiac output; however, blood pressure and pancreatic blood flow remained low. Low-molecular weight Dextran has no influence on cardiac output, but significantly improved the blood pressure and leads to a normalization in pancreatic blood flow and oxygen consumption. These results suggest that low-molecular weight Dextran appears to reverse the impairment of microcirculation and hypoxia of the pancreas and limits the progression from edematous to hemorrhagic pancreatitis and irreversible pancreatic damage.

Animals↗