Low Molecular Weight Dextran Research Articles

Effect of contrast medium versus low-molecular-weight dextran for intracoronary optical coherence tomography in renal insufficiency.

Low-molecular-weight dextran (LMWD) is considered a safe alternative to contrast media to displace blood during optical coherence tomography (OCT) imaging, but concerns remain. The purpose of this study was to investigate whether using LMWD for OCT protects against kidney injury in patients with renal insufficiency compared with contrast media. We retrospectively identified 474 patients with renal insufficiency (estimated glomerular filtration rate < 60ml/min/1.73 m2) who underwent OCT during coronary angiography or percutaneous coronary intervention; 110 patients with LMWD plus contrast medium (LMWD group) and 364 patients with contrast medium exclusively (Contrast group). We evaluated differences between the two groups and performed propensity score-matched subgroup comparisons. Compared with the Contrast group, the LMWD group had worse baseline renal function, higher prevalence of diabetes mellitus and percutaneous coronary intervention history, higher C-reactive protein and N-terminal pro B-type natriuretic peptide levels, lower hemoglobin levels, and lower left ventricular ejection fraction. The median total volume of contrast medium in the Contrast group was 230.0ml vs. 61.8ml of LMWD in addition to 164.0ml of contrast medium in the LMWD group. Renal function was consistently impaired in the LMWD group within 5days, at 1-month, and 1-year follow-up (P < 0.001). Two propensity score-matched analyses adjusted for either total volume used or contrast media volume consistently indicated a trend toward worsening renal function in the LMWD group at the 1-year follow-up. No protective benefit for renal function from using LMWD instead of contrast media for OCT was observed in patients with renal insufficiency.

ILB\xae resolves inflammatory scarring and promotes functional tissue repair

Fibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions and vascular diseases leave tissues susceptible to unresolved inflammation, fibrogenesis, loss of function and scarring. There has been limited clinical success with therapies for inflammatory and fibrotic diseases such that there remains a large unmet therapeutic need to restore normal tissue homoeostasis without detrimental side effects. We investigated the effects of a newly formulated low molecular weight dextran sulfate (LMW-DS), termed ILB®, to resolve inflammation and activate matrix remodelling in rodent and human disease models. We demonstrated modulation of the expression of multiple pro-inflammatory cytokines and chemokines in vitro together with scar resolution and improved matrix remodelling in vivo. Of particular relevance, we demonstrated that ILB® acts, in part, by downregulating transforming growth factor (TGF)β signalling genes and by altering gene expression relating to extracellular matrix dynamics, leading to tissue remodelling, reduced fibrosis and functional tissue regeneration. These observations indicate the potential of ILB® to alleviate fibrotic diseases.

Low Molecular Weight Dextran Sulfate (ILB®) Administration Restores Brain Energy Metabolism Following Severe Traumatic Brain Injury in the Rat.

Traumatic brain injury (TBI) is the leading cause of death and disability in people less than 40 years of age in Western countries. Currently, there are no satisfying pharmacological treatments for TBI patients. In this study, we subjected rats to severe TBI (sTBI), testing the effects of a single subcutaneous administration, 30 min post-impact, of a new low molecular weight dextran sulfate, named ILB®, at three different dose levels (1, 5, and 15 mg/kg body weight). A group of control sham-operated animals and one of untreated sTBI rats were used for comparison (each group n = 12). On day 2 or 7 post-sTBI animals were sacrificed and the simultaneous HPLC analysis of energy metabolites, N-acetylaspartate (NAA), oxidized and reduced nicotinic coenzymes, water-soluble antioxidants, and biomarkers of oxidative/nitrosative stress was carried out on deproteinized cerebral homogenates. Compared to untreated sTBI rats, ILB® improved energy metabolism by increasing ATP, ATP/ adenosine diphosphate ratio (ATP/ADP ratio), and triphosphate nucleosides, dose-dependently increased NAA concentrations, protected nicotinic coenzyme levels and their oxidized over reduced ratios, prevented depletion of ascorbate and reduced glutathione (GSH), and decreased oxidative (malondialdehyde formation) and nitrosative stress (nitrite + nitrate production). Although needing further experiments, these data provide the first evidence that a single post-injury injection of a new low molecular weight dextran sulfate (ILB®) has beneficial effects on sTBI metabolic damages. Due to the absence of adverse effects in humans, ILB® represents a promising therapeutic agent for the treatment of sTBI patients.

Enzymatic degradation of aqueous dextrans as affected by initial molecular weight and concentration

Dextrans with different initial molecular weights (IMW) ranging from 3.86 × 104 Da to 2.15 × 106 Da were enzymatically degraded by dextranase enzyme. The changes in weight-average molecular weight (Mw), polydispersity index (D value) and the percentage of 104–105 Da fragment of aqueous dextran were examined during 0–120 min enzymatic degradation. Results showed that the Mw of all dextran samples decreased with increasing enzymatic time. A significant molecular weight degradation occurred in dextran samples that had a higher IMW and at an early degradation stage. With increasing the degradation time, the percentage of the 104–105 Da in four dextran samples (Dex-270, Dex-1000, Dex-2000 and Dex-F) showed a remarkable growth at the beginning of the treatment (0–50 min). Experimental data indicated that all dextran samples (with different IMW and at different concentration) followed a second-order degradation kinetics. This study demonstrated a great potential for further production of low molecular weight dextrans with a more homologous molecular weight.

Safety and Clinical Outcomes of Using Low-Molecular-Weight Dextran During Islet Autotransplantation in Children.

The objective of this study was to evaluate potential safety and clinical benefit of low-molecular-weight dextran (dextran) use in patients undergoing total pancreatectomy with islet auto transplantation (TPIAT). We evaluated 124 children undergoing TPIAT at a single institution, either with (n = 72) or without (n = 52) perioperative dextran infusion. Data on islet graft function and postoperative complications were collected through electronic medical records and patient-reported outcomes from research questionnaires. Islet graft failure was less likely at 1 year (odds ratio, 0.186; 95% confidence interval, 0.04-0.65) and 2 years (odds ratio, 0.063; 95% confidence interval, 0.003-0.35) post-TPIAT in the dextran group. This finding remained significant at 2 years in multivariate logistic regression modeling adjusting for islet mass, body surface area, and sex. Likewise, in multivariate regression, the odds of partial islet graft function were higher at 1 and 2 years in the dextran group. Dextran use was overall safe, although it did lead to a higher incidence of postoperative bleeding requiring blood transfusions (P < 0.001). These findings suggest that dextran use may increase the likelihood for sustained post-TPIAT islet graft function, potentially mitigating severity of postoperative diabetes for these children.

Dextran deposition in reticuloendothelial organs in hemodialysis patients: A forgotten adverse effect of low‐molecular weight dextran

We present two autopsy cases of refractory ascites/hydrothorax associated with systemic deposition of low-molecular weight dextran that had been used in hemodialysis over an extended period. The most striking autopsy findings in both cases were dense accumulation of dextran-laden macrophages in sinusoids of reticuloendothelial organs. These accumulated macrophages seemed to have disturbed blood and lymph flow. Based on these findings, we concluded that the persistent ascites and hydrothorax were attributable to systemic deposition of dextran, especially the accumulation of dextran-laden macrophages in the reticuloendothelial organs. We suggest that dextran solution should immediately be designated as contraindicated for hemodialysis patients.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention With Low-Molecular-Weight Dextran - Effect on Renal Function.

The excessive volume of contrast needed is a significant limitation of optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI). Low-molecular-weight dextran (LMWD) has been used for OCT image acquisition instead of contrast media. This study compared the effects of OCT-guided PCI using LMWD on renal function and clinical outcomes to those of intravascular ultrasound (IVUS)-guided PCI. In all, 1,183 consecutive patients who underwent intracoronary imaging-guided PCI were enrolled in this single-center, retrospective, observational study. After propensity score matching, 133 pairs of patients were assigned to undergo either OCT-guided PCI using LMWD or IVUS-guided PCI. There was no significant change from baseline in the primary endpoint, serum creatinine concentrations, after the procedure in either group. There were no significant differences between the OCT and IVUS groups in the volume of contrast medium, the incidence of contrast-induced nephropathy (1.5% vs. 2.3%; P=0.65), and major adverse cardiovascular events (MACE) at 30 days (2.3% vs. 6.0%; P=0.12) and 12 months (2.3% vs. 3.0%; P=0.70) after the procedure. Kaplan-Meier analysis at the 12-month follow-up revealed no significant difference in the incidence of MACE between the 2 groups (P=0.75). OCT-guided PCI using LMWD did not negatively affect renal function and achieved similar short- and long-term clinical outcomes to IVUS-guided PCI.

Inhibition of glycogen synthase kinase 3β improves cognitive function in aged mice by upregulating claudin presences in cerebral endothelial cells.

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, is widely distributed in mammalian brains. Since GSK-3β plays a vital role in the development of neurodegenerative disorders, the present study was designed to investigate the role of GSK-3β in the blood-brain barrier (BBB) permeability in aged mice. Morris water maze test was used to examine mouse cognitive function. BBB permeability was examined by the leakage of fluorescence signals of low-molecular weight dextran. GSK-3β inhibitor, 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), was administrated in aged mice and in cultured mouse brain microvascular endothelial cells (bEnd.3). Compared with young mice, aged mice had increased leftover signals of dextran in the hippocampus and a lower score in the maze test, suggesting that aged mice have abnormal leakage of BBB and cognitive dysfunction. The protein expression of Toll-like receptor 4 (TLR4) was increased, whereas the protein expressions of junction proteins (claudin1 and claudin5) were reduced in endothelial cells of BBB in aged mice. Phosphorylated level of serine 9, an inhibitory residue in GSK-3β protein, was decreased. TDZD-8 treatment downregulated TLR4 protein expression, upregulated claudin1 and claudin5 protein expressions, and significantly improved cognitive function in aged mice. In bEnd.3 cells, TDZD-8 treatment reduced TLR4 expression and increased claudin5 expression in cells stimulated with lipopolysaccharides. In conclusion, the inhibition of GSK-3β activity downregulates aging-induced TLR4 expression and restores the BBB integrity, resulting in the improvement of cognitive function in aged mice.

Possible use of low-molecular weight dextran as adjuvant for erector spinae plane block procedure.

Possible use of low-molecular weight dextran as adjuvant for erector spinae plane block procedure.

Influence of Dextransucrase of Weissella Cibaria Nitcsk4 on Low Molecular Weight Dextran Yield: a Statistical Approach using Mixed Level Taguchi Design and Artificial Neural Network

In the present study, the influence of dextransucrase of Weissella cibaria NITCSK4 (DSWc4), sucrose concentration, and reaction temperature on the yield of low molecular weight dextran (LMWD-DexWc4) was investigated using mixed level Taguchi design and back propagation neural network (BPNN). BPNN model with three neurons in a hidden layer generated a low mean squared error (MSE). The determination coefficients (R2 -value) for ANN and Taguchi models were 0.991 and 0.998, respectively. Considering absolute average deviation (AAD) and MSE, Taguchi model is more adequate. Among three factors, the percentage yield of low molecular weight of dextran is invariably dependent on the sucrose concentration. The study suggested that a low sucrose concentration (3% w/v), DSWc4 (0.25 IU/ml) and slightly high temperature (35°C) ultimately favored the production of LMWD-DexWc4 (91.639%). LMW-DexWc4 produced by DSWc4 at optimized conditions was analyzed. The weight average molecular weight of LMW-DexWc4 was calculated using M-H expression, found to be 85775 (≈90 kDa). The relative percentage error between the number and weight average molecular weight was found to be less (4.42%). The polydispersity (PD) index of the LMW-DexWc4 was found to be 0.9576 and the value is close to 1. The PD value depicted that the molecular weight distribution of dextran was narrowly dispersed.

Dextran induced acute kidney injury in a patient with dengue haemorrhagic fever

Dextran 40 is a low molecular weight dextran preparation which is used as an adjunctive treatment in hypovolemic shock. At present dextran 40 is mainly used in the clinical practice for management of severe cases of dengue haemorrhagic fever or dengue shock syndrome. Acute kidney injury is a rare adverse reaction of dextran administration. We report a case of dextran induced acute kidney injury complicated with hypertensive encephalopathy during the convalescent phase of the illness. Renal biopsy revealed fine isometric vacuolations of tubular epithelial cells suggestive of osmotic nephrosis.

A Microfluidic Tool for Fine‐Tuning Motion of Soft Micromotors

AbstractMicrofluidics is an ideal tool for the design of self‐assembled micromotors. It allows for easy change of solutions, catalysts, and flow rates, which affect shape, structure, and motion of the resulting micromotors. A microfluidic tool generating aqueous‐two‐phase‐separating droplets of UV‐polymerizable poly(ethylene glycol)diacrylate (PEGDA) and an inert phase, salt, or polysaccharide, is utilized to fabricate asymmetric microbeads. Different molecular weights and branching of polysaccharides are used to study the effect on shape, surface roughness, and motion of the particles. The molecular weight of the polysaccharide determines the roughness of the motors inner surface. Smooth openings are obtained by low molecular weight dextran, while high surface roughness is obtained with a high molecular weight branched polysaccharide. Since roughness plays an important role in bubble pinning, it influences both speed and trajectory. Increasing speeds are obtained with increasing roughness and trajectories ranging from linear, circular to tumble‐and‐run depending on the nature of bubble pinning. This microfluidic tool allows for fine‐tuning shape, structure, and motion by easy change of solutions, catalysts, and flow rates.

Sudden sensorineural hearing loss (SSHL) following a local anesthetic dental procedure

Acute sensorineural hearing loss is an uncommon phenomenon in dentistry. We describe the case of a 79-year-old male who presented with acute sensorineural hearing loss occurring 2 days after a tooth extraction procedure under local anesthesia. Possible mechanisms are discussed. He was treated with vasodilators (Ginaton and Alprostadil Injection) and Mecobalamin injection with benefit. High dose oral steroids (1 mg/kg) and low molecular weight dextran were used.

Low molecular weight dextran production by Leuconostoc mesenteroides strains: Optimization of a new culture medium and the rheological assessments

Strains belonging to genus Leuoconostoc mesenteroides are able to produce dextran exo-polysaccharide. In this study, MRS broth and milk permeate were used for growth of three strains (NRRL B-512F, NCIB 8023 and NRRL B-512) of L. mesenteroides and the growth rate, dextran production, and its rheological properties were studied. Evaluation of molecular weight by high-performance size exclusion chromatography system showed that dextran produced in milk permeate had a lower molecular weight (<10000 Dalton) compared to the dextran produced in MRS broth (<40000 Dalton). The viscosity of dextran solution (2%) produced in MRS was 0.005–0.01 Pa.s while in the synthetic medium it was <0.005 Pa.s. Also in our study maximum ratio of growth factor and dextran yield belonged to NRRL B-512F, which was subjected to optimization of fermentation condition for dextran production. For optimization, response surface methodology by using sucrose, milk permeate and yeast extract in 5 levels were used. According to experiments, optimum concentrations for sucrose, milk permeate, and yeast extract were found to be 20, 15, and 15 (g/l), respectively.

Are antithrombotic agents necessary for head and neck microvascular surgery?

The aim of this prospective study was to determine the effect of antithrombotic agents in preventing thrombosis after head and neck reconstructive surgery. A randomized clinical trial of referred patients undergoing free flap surgery between February 2015 and July 2017 was conducted. Four hundred and fifty-four patients were randomly assigned to group A (n=153), administered aspirin and low molecular weight dextran; group B (n=150), administered low molecular weight heparin; and group C (n=151), not administered any antithrombotic agent. Patient demographic characteristics, donor site, thrombosis, haematoma, and flap failure were recorded. Coagulation values including platelet count, prothrombin time, and activated partial thromboplastin time were measured during the perioperative period. Repeated-measures ANOVA and the χ2 test were used for data comparisons. No significant inter-group differences were observed for postoperative microvascular thrombosis (P=0.536) or flap failure (P=0.615) among the three groups. There were more postoperative haematoma revisions in group B than in groups A and C (P=0.032). It is concluded that postoperative antithrombotic agents neither provide a significant improvement in the free flap success rate nor decrease the risk of thrombosis and may increase the risk of haematoma.

Ultrasound-guided mandibular nerve block with local anesthetic and low-molecular weight dextran helps reduce anesthetic requirements for parotidectomy.

Ultrasound-guided mandibular nerve block with local anesthetic and low-molecular weight dextran helps reduce anesthetic requirements for parotidectomy.

Marking Technique for Identification of Optimal Stent Landing Site With Optical Coherence Tomographic Imaging

An 85-year-old man with chronic kidney disease (estimated glomerular filtration rate 28.9 ml/min/1.73 m2) underwent percutaneous coronary intervention with optical coherence tomographic (OCT) guidance (ILUMIEN OPTIS, Abbott Laboratories, Abbott Park, Illinois) using low–molecular-weight dextran

Cell Separation in Aqueous Two-Phase Systems - Influence of Polymer Molecular Weight and Tie-Line Length on the Resolution of Five Model Cell Lines.

The availability of clinical-scale downstream processing strategies for cell-based products presents a critical juncture between basic research and clinical development. Aqueous two-phase systems (ATPS) facilitate the label-free, scalable, and cost-effective separation of cells, and are a versatile tool for downstream processing of cell-based therapeutics. Here, we report the application of a previously developed robotic screening platform, here extended to enable a multiplexed high-throughput cell partitioning analysis in ATPS. We investigated the influence of polymer molecular weight and tie-line length on the resolution of five model cell lines in "charge-sensitive" polyethylene-glycol (PEG)-dextran ATPS. We show, how these factors influence cell partitioning, and that the combination of low molecular weight PEGs and high molecular weight dextrans enable the highest resolution of the five cell lines. Furthermore, we demonstrate that the separability of each cell line from the mixture is highly dependent on the polymer molecular weight composition and tie-line length. Using a countercurrent distribution model we demonstrate that our screenings yielded conditions that theoretically enable the isolation of four of the five cell lines with high purity (>99.9%) and yield.

Surface Modification of Polysaccharide-Based Nanoparticles with PEG and Dextran and the Effects on Immune Cell Binding and Stimulatory Characteristics.

Surface modifications of nanoparticles can alter their physical and biological properties significantly. They effect particle aggregation, circulation times, and cellular uptake. This is particularly critical for the interaction with primary immune cells due to their important role in particle processing. We can show that the introduction of a hydrophilic PEG layer on the surface of the polysaccharide-based nanoparticles prevents unwanted aggregation under physiological conditions and decreases unspecific cell uptake in different primary immune cell types. The opposite effect can be observed with a parallel-performed introduction of a layer of low molecular weight dextran (3.5 and 5 kDa) on the particle surface (DEXylation) that encourages the nanoparticle uptake by antigen-presenting cells like macrophages and dendritic cells. Binding of DEXylated particles to these immune cells results in an upregulation of surface maturation markers and elevated production of proinflammatory cytokines, reflecting cell activation. Hence, DEXylated particles can potentially be used for passive targeting of antigen presenting cells with inherent adjuvant function for future immunotherapeutic applications.

Derivatization of Dextran for Multiply Charged Ion Formation and Electrospray Ionization Time-of-Flight Mass Spectrometric Analysis.

We present the use of a simple, one-pot derivatization to allow the polysaccharide dextran to carry multiple positive charges, shifting its molecular weight distribution to a lower m/z range. We performed this derivatization because molecular weight measurements of polysaccharides by mass spectrometry are challenging because of their lack of readily ionizable groups. The absence of ionizable groups limits proton abstraction and suppresses proton adduction during the ionization process, producing mass spectra with predominantly singly charged metal adduct ions, thereby limiting the detection of large polysaccharides. To address this challenge, we derivatized dextran T1 (approximately 1 kDa) by attaching ethylenediamine, giving dextran readily ionizable, terminal amine functional groups. The attached ethylenediamine groups facilitated proton adduction during the ionization process in positive ion mode. Using the low molecular weight dextran T1, we tracked the number of ethylenediamine attachments by measuring the mass shift from underivatized to derivatized dextran T1. Using electrospray ionization time-of-flight mass spectrometry, we observed derivatized dextran chains ranging from two to nine glucose residues with between one and four attachments/charges. Our success in shifting derivatized dextran T1 toward the low m/z range suggests potential for this derivatization as a viable route for analysis of high molecular weight polysaccharides using electrospray ionization time-of-flight mass spectrometry. Graphical Abstract ᅟ.