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Biomedical subjects

O Larm

Publications and source records attributed to O Larm.

At least 19 recordsLinked to original sources
PubMed2001

Effect in a rat model of heparinized peritoneal dialysis catheters on bacterial colonization and the healing of the exit site.

We performed a prospective, double-blind, randomized study to evaluate whether stable surface heparinization of silicone peritoneal dialysis (PD) catheters prevents bacterial colonization or biofilm formation and improves healing of the exit site. Heparinized catheters were implanted in 20 Sprague-Dawley rats (group H) and non heparinized catheters in another 20 (group C). The PD catheters, constructed of silicon tubing with two polyester cuffs, were patterned after the standard Tenckhoff catheter. A covalent multipoint method of attachment onto polymeric surfaces was used for stable, permanent chemical immobilization of heparin on the PD catheter. Dialysis exchanges (25-mL instillation volume) were performed twice daily for 4 weeks through the permanent catheter. Prophylactic antibiotics were not used. The exit sites were evaluated at 2-week intervals. The extent of biofilm coverage on the intraperitoneal portion of the catheter (obtained at the end of the experiment) was assessed, and sonicated fluid from the catheter tip was cultured for evaluating bacterial colonization of the catheter. Exit-site scores in group H were lower than in group C (p = 0.052) at the end of week 4. Bacterial colonization tended to be less common in group H [2 of 12 catheters (17%)] than in group C [8 of 15 catheters (53%); p = 0.058], but the extent of biofilm, the peritonitis rate, and the inflammation score of tissue adjacent to the cuff were not different between the groups. Those data suggest that heparinized PD catheters can be a practical approach to the prevention of bacterial colonization and can improve healing of the exit site.

Animals↗
PubMed2000

External ventricular drainage catheters: effect of surface heparinization on bacterial colonization and infection.

Surface heparinization of central venous catheters has earlier been shown to reduce the frequency of bacterial colonization and septicaemia. The present study was undertaken to investigate the benefit of surface heparinization of external ventricular drainage (EVD) catheters in relation to bacterial colonization, as measured by bacterial growth and examination by a 16S-rRNA PCR assay, of catheters and of samples of cerebrospinal fluid (CSF). Ninety-eight heparinized and one hundred unheparinized EVD catheters from the same batch of catheters were used. Twenty point five percent of the heparinized and 22.8% (p = 0.63) of the unheparinized EVD catheters were colonized with bacteria. Culture of CSF, which is the definition of clinical infection in this study, yielded growth in 10.3% of patients with heparinized and in 6.3% (p = 0.18) of those with unheparinized catheters. PCR examination yielded positive signal in 31.3% of patients with heparinized catheters and in 37.7% (p = 0.061) of patients without (CSF and catheters). In the subgroup of patients with subarachnoid haemorrhages, there was a tendency, though not statistically significant, towards a lowered frequency of colonization with 23.1% for heparinized and 33.3% (p = 0.31) for unheparinized catheters. PCR examination did not contribute any further to the diagnostic procedure in the patients concerned. The EVD catheters are skin-penetrating devices and contamination from the skin flora is common. Skin cultures, obtained after skin disinfection and insertion of catheters, showed growth of bacteria in 62% of the patients.

Bacteria↗
PubMed1998

A new model to assess staphylococcal adhesion to intraocular lenses under in vitro flow conditions.

Adhesion of staphylococcal cells to intraocular lenses coated with heparin was studied under in vitro flow conditions (280 microl min(-1)) at 37 degrees C. The intraocular lenses were incubated with human cerebrospinal fluid for 1 h or with cerebrospinal fluid including 0.50% plasma for 12 h, prior to bacterial challenge. Two strains of Staphylococcus epidermidis selected for this study, were isolated from biomaterial-associated infections. Bacterial adhesion was quantitated by bioluminescence and visualized by fluorescence microscopy of acridine orange stained bacteria. Surface coating with heparin significantly decreased bacterial adhesion of both strains after incubation with cerebrospinal fluid including 0.50% plasma for 12 h (p = 0.0209). However, no difference in bacterial adhesion was obtained between intraocular lenses with and without heparin, after incubation with cerebrospinal fluid for 1 h (p = 0.327). Microscopy showed that more bacteria were present on intraocular lenses without heparin than on intraocular lenses with heparin. The results show that preincubation with a proteinaceous fluid influences subsequent bacterial adhesion to the polymer surface. The results suggest that IOLs with heparin coating may be less prone to bacterial adhesion under perfusion conditions after surface conditioning in human CSF with 0.50% plasma and a preincubation period of 12 h. Heparin coating might be a valuable tool to decrease implant-associated bacterial endophthalmitis.

Acridine Orange↗
PubMed1998

Immobilised heparin accelerates the healing of human wounds in vivo.

Locally produced growth factors are of great importance in wound healing in human skin. Wound fluid from chronic wounds contains low concentrations of growth factors possibly because of rapid degradation as a result of the high concentration of proteases. Many growth factors involved in wound healing bind to heparin and are thereby stabilised and activated. We have recently shown that heparin in combination with chitosan stimulates re-epithelialisation in an in vitro model of human wound healing. In the present study we investigated the effects of a chitosan-heparin membrane on wound healing in 10 split-thickness graft donor sites in human skin. The chitosan-heparin membrane stimulated healing of the donor sites both when judged macroscopically in a blinded fashion and when biopsy specimens from the treated and untreated parts of the wound were investigated microscopically. We hypothesise that the beneficial effects of the chitosan-heparin membrane result from slow release of heparin into the wound area which protects locally produced growth factors. The result is increased stabilisation and concentration of growth factors in the wound area, which stimulate healing. We believe that these results may be important in the treatment of wounds that are reluctant to heal.

Biocompatible Materials↗
PubMed1997

Heparin-chitosan complexes stimulate wound healing in human skin.

The effect of heparin ionically linked to chitosan on the stimulation of re-epithelialisation of full thickness wounds in human skin was investigated in an in vitro model. After seven days of incubation, heparin-chitosan gel stimulated 9/10 of the full thickness wounds to re-epithelialise compared with only 3/10 of the wounds that were covered with chitosan gel or membrane, and none of the wounds incubated without gel or membrane or with heparin solution alone. Both dermal and epidermal cells were viable after the incubation time. Furthermore, the stimulatory effect of the heparin-chitosan complexes depended on the concentration of heparin in the complex. We hypothesise that these effects are caused by stabilisation and activation of growth factors that bind to immobilised heparin.

Biocompatible Materials↗
PubMed1996

Surface heparinization of central venous catheters reduces microbial colonization in vitro and in vivo: results from a prospective, randomized trial.

OBJECTIVE: To evaluate in vitro and in vivo the efficacy of covalent end point-attached heparin to single-lumen polyurethane central venous catheters in reducing microbial adherence and colonization. DESIGN: In vitro study: A controlled bench study. In vivo study: A prospective, randomized, double-blind, clinical trial. SETTING: Intensive care unit in a 1200-bed teaching hospital. INTERVENTIONS: In vitro study: Adhesion of 17 radiolabeled clinical isolates of Staphylococci to catheters was examined in vitro. In vivo study: The outcome of heparinized and control catheters was compared in vivo in patients receiving long-term parenteral nutrition. Fifty-five adult patients were prospectively, blindly randomized to heparinized or control central venous catheters. The catheters, removed on clinical grounds, were analyzed with semiquantitative and quantitative cultures. Blood cultures were done at catheter removal. MEASUREMENTS AND MAIN RESULTS: In vitro study: Coagulase-negative Staphylococci adhered less in vitro to heparinized catheters than to control catheters (p < .05). In vivo study: Among 32 central venous catheters, or patients who completed the study, catheter-associated bacteremia or fungemia was observed in five patients in the control group (n = 19) and in no patient with a heparinized catheter (n = 13) (p = .047). Four of 13 catheters in the heparin group were colonized compared with 14 of 19 in the control group (p = .03). Coagulase-negative Staphylococci were the most frequent microorganisms in both groups. The numbers of organisms found on colonized catheters were larger in the control group than in the heparin group. CONCLUSIONS: Covalent end point surface heparinization appears to have a great impact on both in vitro and in vivo bacterial colonization of central venous catheters. Such heparinization can be a practical and economical approach to the prevention of catheter-associated bacteremia or fungemia.

Adult↗
PubMed1995

Helicobacter pylori interacts with heparin and heparin-dependent growth factors.

The pathogenic bacterium Helicobacter pylori, which causes active, chronic type B gastritis and peptic ulcer disease, and increases the risk for development of gastric cancer, could tentatively interfere with growth factors and growth factor receptors of importance for the gastroduodenal mucosa, e.g. heparin-binding FGFs (fibroblast growth factors). H. pylori binds FGF with an extremely strong affinity (3.8 x 10(-12)M), and also heparan sulfate and heparin with higher affinity (Kd 9 x 10(-9)M) than FGFs bind to heparin (10(-8) - 10(-9)M). FGF receptors are also dependent on heparin for their activation. Heparan sulfate binding proteins (HSBP) are exposed on and shed from the surface of H. pylori, which often are localised close to the epithelial stem cells in the gastroduodenal glands. H. pylori could thus efficiently interfere with growth factors and growth factor receptors, tentatively resulting in disturbance of the delicate balance that control the renewal, maintenance and repair of the gastroduodenal mucosa. This mode of action has previously not been considered, but may constitute part of its pathogenic mechanisms. Such a dynamic mode of action of H. pylori may explain the reason for that infected victims may either suffer from gastrointestinal symptoms or lack clinical evidence of disease or discomfort.

Fibroblast Growth Factor 1↗
PubMed1994

Adherence of coagulase-negative staphylococci to heparin and other glycosaminoglycans immobilized on polymer surfaces.

The adherence of clinical isolates of staphylococci to surfaces immobilized with various glycosaminoglycans (GAGs) was studied. In general, cells of strains of coagulase-negative (CNS) staphylococci showed a greater adherence to polyethylene surfaces than did cells of Staphylococcus aureus, as studied by bioluminescence. When the surface was heparinized, the adherence of staphylococcal cells decreased, but CNS cells still adhered in greater numbers than did cells of S. aureus. The adherence of CNS to serum-coated heparinized surfaces was of the same magnitude, or increased compared with nonheparinized surfaces. When the surfaces were preadsorbed with different proteins with known heparin-binding domains, i.e., vitronectin, fibronectin, laminin, or collagen, the S. epidermidis cells showed higher binding to heparinized surfaces than to nonheparinized ones, and also in greater numbers than did other staphylococcal cells. Different CNS strains showed a greater ability to agglutinate polystyrene beads immobilized with heparin than did S. aureus. The adherence of S. epidermidis strain 3380 to polyethylene coated with various GAGs such as heparin and chondroitin, dextran, dermatan, and heparan sulfate was shown to be pH-dependent, with the highest adherence at pH 7.2. This may indicate that CNS have the ability to bind to other domains of host proteins when they are adsorbed to heparinized surfaces, versus to nonheparinized ones.

Bacterial Adhesion↗
PubMed1994

Adhesion of coagulase-negative staphylococci and adsorption of plasma proteins to heparinized polymer surfaces.

Protease treatment of cells of coagulase-negative staphylococci reduced the adhesion of bacteria to heparinized polyethylene preadsorbed with serum. Fibronectin (Fn), fibrinogen (Fg), vitronectin, complement factor C3c, plasminogen, laminin and to a low extent albumin were detected on tridodecylmethylammonium chloride (TDMAC)-heparinized polyvinyl chloride (PVC) catheters extirpated from the circulation of patients. Using a perfusion model we show that during the first hours of perfusion with human plasma, Fn and Vn dominate, whereas after 22 h of perfusion Fg is the dominant protein. Field emission scanning electron microscopy and atomic force microscopy studies on TDMAC-heparinized catheters as well as on end-point attached heparinized PVC catheters indicate that quantitatively more Fg than Fn is exposed on these surfaces after prolonged exposure (> 22 h) to human plasma.

Adsorption↗
PubMed1993

Modification of the complement binding properties of polystyrene: effects of end-point heparin attachment.

In recent years, conjugation of heparin to biomaterials has been shown to improve its biocompatibility. The purpose of the present work was to compare complement activation and binding of C3 to unmodified and heparin-treated polystyrene surfaces of microtitre plates. When polystyrene was incubated with human serum, C3 was deposited on the surface by both adsorption and binding dependent on activation of the classical (CPW) and alternative (APW) pathways. After end-point attachment of heparin, significant C3 deposition, although at reduced levels, occurred only by CPW-mediated mechanisms, while adsorption and APW-mediated binding were strongly reduced. Generally, the modified surface bound lower amounts of protein, e.g. serum albumin and IgG, than the unmodified. By contrast, it had increased affinity for C1q which leads to binding of C1 and activation of complement via the CPW. Nevertheless, the net effect of the surface modification on the complement reaction was an overall reduction of C3 binding due to obliteration of APW. This can be related to an enhanced factor H/I-dependent down-regulation of C3b and to the lowered protein-adsorbing property of the surface, both of which have inhibitory effects on APW and on the C3 shunt-dependent activation of the complement system.

Complement Activation↗
PubMed1992

Surface-heparinized neonatal ECMO circuit--an experimental animal study.

The present experiment examined the capacity of the Carmeda Bioactive Surface to prevent clot formation in an ECMO circuit designed for neonatal use. The Terumo Capiox oxygenator was used in the seven experiments. Mongrel dogs were perfused with veno-arterial bypass at a low flow rate of 200 ml/min. Without any blood heparinization, the circuit was totally occluded within a few hours. With a very low heparin infusion (10 IUxkg -1xh -1) extracorporeal blood flow could be maintained despite some clots forming in the oxygenator. With a small bolus injection of heparin (20 IU/kg) and a low continuous heparin infusion (20 IUxkg -1xh -1) the ECMO circuit showed negligible clotting. With better haemodynamic design of the device in combination with a thrombo-resistant surface, it may be possible to decrease the need for blood heparinization in the neonatal ECMO circuit.

Animals↗
PubMed1988

Monoclonal antibodies specific for oligosaccharides prepared by partial nitrous acid deamination of heparin.

Monoclonal antibodies were raised against a conjugate between heparin oligosaccharides and human serum albumin. The oligosaccharides were prepared by partial nitrous acid degradation of heparin and were coupled to human serum albumin by reductive amination. Characterization of the antibodies secreted by one of the resulting clones showed that they recognize a determinant present in the oligosaccharide antigen, but not in intact heparin, nor in a variety of related polysaccharides. Degradation of heparin by nitrous acid generates a 2,5-anhydro-D-mannose residue at the reducing end of the resulting oligosaccharides, and it is concluded that this structure is essential for interaction with the antibodies. Reduced oligosaccharides (containing a terminal anhydromannitol residue) are also active. After gel chromatography of partially degraded heparin, the smallest components capable of binding to the antibodies were found in a tetrasaccharide fraction. Affinity chromatography on immobilized monoclonal antibodies separated this tetrasaccharide fraction into distinct populations of binding and nonbinding species. Structural analysis showed that the tetrasaccharide fraction that bound to the monoclonal antibodies contained one single component with the structure IdoA(2-OSO3)-GlcNSO3 (6-OSO3)-IdoA(2-OSO3)-aManR(6-OSO3), whereas the fraction that did not bind to the antibodies contained a mixture of different structures.

Animals↗
PubMed1988

Influence of blood flow and the effect of protamine on the thromboresistant properties of a covalently bonded heparin surface.

Polyethylene tubings, 2-mm inner diameter and the length of 1 m, untreated or furnished with a covalently bonded heparin surface layer, were inserted as arteriovenous shunts bilaterally in dogs. By compressing the middle part, the initial blood flow was adjusted to 10 or 40 mL/min. The thrombogenicity of the tubings was assessed by the patency of the shunts and by assaying the generation of fibrinopeptide A (FPA) in arterial blood and in blood after its passage through the shunts. In untreated shunts clotting rapidly occurred preceded by high FPA generation in blood passing through the shunts. The blood flow in heparinized shunts remained unchanged throughout the test period. At the low flow rate a certain degree of FPA generation in the shunts occurred. At the high flow rate no changes in FPA levels occurred. The function of the heparin surface is thus flow rate dependent. Systematic heparinization and subsequent neutralization with protamine or administration of protamine alone did not interfere with the function of the heparin surface.

Animals↗
PubMed1987

Antithrombin III binding to surface immobilized heparin and its relation to F Xa inhibition.

The mode of F Xa inhibition was investigated on a thromboresistant surface with end-point attached partially depolymerized heparin of an approximate molecular weight of 8000. Affinity chromatography revealed that one fourth of the heparin used in surface coating had high affinity for antithrombin III (AT). The heparin surface adsorbed AT from both human plasma and solutions of purified AT. By increasing the ionic strength in the AT solution the existence of high and low affinity sites could be shown. The uptake of AT was measured and the density of available high and low affinity sites was found to be in the range of 5 and 11 picomoles/cm2, respectively. Thus the estimated density of biologically active high and low affinity heparin respectively would be 40 and 90 ng/cm2. The heparin coating did not take up or exert F Xa inhibition by itself. With AT adsorbed on both high and low affinity heparin the surface had the capacity to inhibit several consecutive aliquots of F Xa exposed to the surface. When mainly high affinity sites were saturated with AT the inhibition capacity was considerably lower. It was demonstrated that the density of AT on both high and low affinity heparin determines the F Xa inhibition capacity whereas the amount of AT on high affinity sites limits the rate of the reaction. This implies that during the inhibition of F Xa there is a continuous surface-diffusion of AT from sites of a lower class to the high affinity sites where the F Xa/AT complex is formed and leaves the surface. The ability of the immobilized heparin to catalyze inhibition of F Xa is likely to be an important component for the thromboresistant properties of a heparin coating with non-compromised AT binding sequences.

Animals↗
PubMed1987

The protective effect of beta 1-3D-glucan-derivatized plastic beads against Escherichia coli infection in mice.

Pretreatment with beta-1,3-D-glucan-derivatized plastic beads conferred strong protection against Escherichia coli infection in mice. The protective effect showed a dose-response relationship to the amount of beads injected and was dependent on the time point of the injection relative to the infection with E. coli. A similar protection could be obtained in nude mice. Experiments with radioactively labelled bacteria as well as beads indicated a systemic effect of the beads. Macrophages extracted from animals treated with glucan plastic beads appeared highly stimulated. This was also true of cells that did not contain beads and presumably therefore not glucan, which seems to indicate a soluble stimulatory factor.

Animals↗