Biomedical subjects

S L Cooper

Publications and source records attributed to S L Cooper.

At least 37 records · Page 2Linked to original sources

PubMed1999

Neutrophil adhesion on polyurethanes preadsorbed with high molecular weight kininogen.

Interaction of biomaterials with blood components including neutrophils is responsible for some of the clinical complications that have occurred in cardiopulmonary bypass, hemodialysis, and ventricular assist procedures. The possibility of inhibiting the initial adhesion of neutrophils to biomaterials has been studied extensively, but the problem remains unsolved. In this study, we investigated the effect of HK adsorption on polyurethane, a widely used component of extracorporeal and intracorporeal devices. HK and HKa were allowed to adsorb on 4 different charged polyurethanes: noncharged (PU), cationic (NR(4)), anionic (SO(3)), and zwitterionic (GPC) polyurethanes. The effect of kininogen adsorption on neutrophil adhesion, the surface density of the adsorbed kininogen, and the exposure of HK domains 3 and 5 (D(3) and D(5H)), which are responsible for the binding of HK to the neutrophil integrin alpha(m)beta(2) or Mac-1, were examined. On PU, NR(4), and SO(3), kininogen adsorption reached 80% of monolayer coverage when 100 pmol/mL or higher concentration of protein solutions were used. The NR(4) surface adsorbed the most kininogen along with a high exposure of D(3) and D(5H). The availability of D(3) and D(5H) allowed neutrophils to bind to the surface via the Mac-1 receptor; thus, on the NR(4) surface, adsorbed kininogens lost their antiadhesive property, which resulted in a high degree of neutrophil adhesion. Increasing Mac-1 expression by exposure to fMLP increased the neutrophil adhesion on this surface. In contrast, exposure of D(3) and D(5H) on SO(3) was significantly less, because HK binds to anionic surfaces with similar protein sequences used for cell binding. This low binding site exposure preserved the antiadhesive property of HK. GPC was resistant to neutrophil adhesion even in the absence of adsorbed kininogens because of its phosphorylcholine moiety. Thus, both SO(3) coupled with kininogen (or kininogen peptides) and GPC have the potential to markedly reduce neutrophil adhesion to biomaterial devices.

Adsorption↗

PubMed1999

Aprotinin inhibits thrombin formation and monocyte tissue factor in simulated cardiopulmonary bypass.

BACKGROUND: Aprotinin reduces perioperative bleeding after open heart surgery, primarily by inhibiting fibrinolysis. In addition, the drug has both procoagulant and anticoagulant effects that involve complex reactions of coagulation proteins and cells that are incompletely understood. This study tests the hypothesis that aprotinin has an anticoagulant effect on the extrinsic coagulation pathway. METHODS: Human heparinized blood was recirculated through a membrane oxygenator with and without high concentrations of aprotinin (18.4 microM). Serial plasma samples were obtained at intervals up to 240 minutes. RESULTS: Aprotinin significantly reduced the progressive increase in prothrombin fragments (F1.2) and thrombin-antithrombin complex beginning immediately. Aprotinin also significantly reduced monocyte expression of tissue factor and Mac-1. Aprotinin did not significantly reduce factor VII or factor VIIa. CONCLUSIONS: During simulated cardiopulmonary bypass, aprotinin immediately inhibits kallikrein and thrombin formation via the intrinsic coagulation pathway. Later, aprotinin inhibits monocyte expression of tissue factor and the extrinsic coagulation pathway. The ability of aprotinin to inhibit monocyte tissue factor provides a means to reduce thrombin formation in blood aspirated from the wound during open heart surgery.

Antithrombin III↗

PubMed1999

Surface properties and hemocompatibility of alkyl-siloxane monolayers supported on silicone rubber: effect of alkyl chain length and ionic functionality.

Self-assembled monolayers of alkylsiloxanes supported on poly(dimethylsiloxane) (PDMS) rubber were used as model systems to study the relation between blood compatibility and surface composition. The inner lumen of PDMS tubes were first treated with an oxygen plasma. The resultant oxidized surfaces were post-derivatized by reaction with alkyltrichlorosilanes to form the monolayer films. The alkyl chain lengths used were slightly longer than in a previous study, and this may alter the phase-state of the monolayer from liquid-like to crystalline. The chemical properties of the monolayer were controlled by varying the chemical composition of the alkyltrichlorosilanes used. Terminal functionalities included -CH3, -CF3, -COOH, -SO3H and -(CH2CH2O)4OH. Surface derivatization was verified with static contact angle measurements and X-ray photoelectron spectroscopy. Blood compatibility was evaluated using a canine ex vivo arterio-venous series shunt model. Surfaces grafted with hydrophobic head groups such as -CH3 and -CF3 were significantly less thrombogenic than the surfaces composed of ionic head groups such as -COOH and -SO3H. Surfaces enriched in -(CH2CH2O)4OH had an intermediate thrombogenicity. Silastic pump grade tubing and polyethylene tubing, used as controls, were found to be the least thrombogenic of all the surfaces tested.

Animals↗

PubMed1999

The effect of high molecular weight kininogen on neutrophil adhesion to polymer surfaces.

The adhesion of neutrophils on a biomaterial surface depends on the surface chemistry of the material and the cell, as well as the composition and conformation of adsorbed protein and the adherence of other cells when the biomaterial is exposed to circulating blood. In this study, HK and HKa were allowed to adsorb on three different polyurethanes: underivatized (PU-base), quaternized (PU-NR4), sulfonated (PU-SO3). The effect of kininogen adsorption on the degree of neutrophil adhesion was examined. The surface density of the adsorbed protein was also investigated. The PU-NR4 surface adsorbed the most HK and HKa and had the high degree of neutrophil adhesion. Although the surface density of adsorbed HK and HKa on the PU-SO3 surface, the degree of neutrophil on adhesion was significantly lower when compared to the PU-NR4 and PU-base surfaces. HK and HKa contain binding sites for both anionic surfaces and neutrophils in the same domain (D5H). When adsorbed to the anionic PU-SO3 surfaces, HK and HKa did not have the neutrophil binding sites available and therefore, exhibited an anti-adhesive effect. In contrast, the neutrophil binding domains D3 and DsH of adsorbed kininogens were available on the PU-NR4 and PU-base surfaces. Thus, adsorbed kininogens on these two surfaces lost their anti-adhesive property and this led to a high degree of neutrophil adhesion.

Adsorption↗

PubMed1999

Bacterial adhesion to functionalized polyurethanes.

The effect of fibrinogen and high molecular weight kininogen on bacterial adhesion to functionalized polyurethanes was studied. Glass slides were coated with different polyurethanes, including Pellethane, sulfonated Pellethane, phosphonated Pellethane, a zwitterionic phosphonated polyurethane, and quaternized amine polyurethanes. The polymer-coated glass squares were exposed to radiolabelled S. aureus. When comparing adhesion to bare polyurethanes, it was found that adhesion was lowest on the phosphonated Pellethane and the zwitterionic phosphonated polyurethane while highest on the methyl quaternized polyurethanes. Fibrinogen-mediated adhesion was studied by first exposing the polymers to increasing concentrations of canine fibrinogen before incubating them with S. aureus. All the polymers except the quaternized amine polyurethanes exhibited at least ten-fold increases in bacterial adhesion as the fibrinogen treatment concentration was increased from 0.0 to 10.0 microg ml(-1). The quaternized amine polyurethanes maintained their relatively high amount of bacterial adhesion regardless of the fibrinogen concentration. The effect of two-chain high molecular weight kininogen (TCHMWK) on fibrinogen-mediated bacterial adhesion was assessed by exposing the polymers to 1.0 microg ml(-1) fibrinogen followed by two different concentrations of TCHMWK. Decreases in bacterial adhesion were observed on all the polymers except the quaternized amine polyurethanes, which again retained their relatively high amount of bacterial adhesion.

Animals↗

PubMed1998

Influence of thrombus components in mediating Staphylococcus aureus adhesion to polyurethane surfaces.

The role of protein and cellular components of thrombi in mediating bacterial adhesion on artificial surfaces was investigated in this study. The attachment of Staphylococcus aureus on polyurethane surfaces was observed directly using an automated video microscopy system. Surfaces were preconditioned with components of platelet-fibrin thrombi, including fibrinogen, thrombin, plasma, and isolated platelets. Experiments were performed in a radial flow chamber, and attachment rate constants were compared on the preconditioned surfaces in an effort to understand the complex relationship that exists between bacterial infection and thrombosis on synthetic biomaterials. Preadsorption of fibrinogen to surfaces significantly increased S. aureus adhesion compared to those preadsorbed with albumin alone while the presence of fibrin dramatically increased bacterial attachment compared to plasma preadsorbed surfaces. While the presence of adherent platelets also increased bacterial attachment, fibrin appeared to play a larger role in mediating bacterial adhesion on polyurethane surfaces. Striking results were obtained on the zwitterionic phosphonated polyurethane for a number of pretreatment conditions with regard to decreased bacterial adhesion and fibrinogen deposition.

Bacterial Adhesion↗

PubMed1998

Three noncontiguous peptides comprise binding sites on high-molecular-weight kininogen to neutrophils.

The binding of high-molecular-weight kininogen (HK) to neutrophils (polymorphonuclear leukocytes, PMN) is required for the stimulation of aggregation and degranulation by human plasma kallikrein as well as the displacement of fibrinogen from this cell surface. The putative receptor for HK is the leukocyte integrin alphaMbeta2, and domains 3 (D3) and 5 (D5) of HK form its binding site. To further map the binding sites on HK for PMN, we used D3 recombinant exon products and designed peptides from D3 and D5. In D3, a heptapeptide, Leu271-Ala277, from exon 7 product, and a peptide, Cys333-Cys352, from exon 9 product can inhibit binding of kininogen to PMN. Two contiguous peptides from D5 in the histidine-glycine-rich region, Gly442-Lys458 and Phe459-Lys478, each inhibit the binding of HK to PMN. This study has thus delineated three noncontiguous surface-oriented sequences on HK, which together comprise all or most of the binding site for human PMN.

Amino Acid Sequence↗

PubMed1997

Quantitative comparison of shear-dependent Staphylococcus aureus adhesion to three polyurethane ionomer analogs with distinct surface properties.

Bacterial adhesion is a central step in infection on biomaterial surfaces; however, the relation between biomaterial surface properties and adhesion remains poorly understood. To quantitatively determine the relationship among polyurethane surface properties, protein coating, and adhesion, we have compared attachment and detachment kinetics of Staphylococcus aureus on three different novel polyurethanes with different protein coatings. Rate constants for attachment or detachment were measured as a function of shear rate in a well-defined laminar flow field. The tested polyurethanes included a relatively hydrophobic-base polyether urethane and hydrophilic anionomer and cationomer analogs of the base material. Materials were tested bare, or coated with human fibrinogen, plasma, or albumin. The results suggest that the presence of fibrinogen or plasma greatly enhance the attachment rate constants and decrease the detachment rate constants on all materials. The most extreme differences among the different materials were observed on the bare materials, with the base polyurethane being most resistant to both attachment and detachment. However, except for a reduced attachment rate constant on the plasma-coated sulfonated polyurethane, few differences in the rate constants were observed among protein-coated materials, suggesting the primary role of surface properties is masked by the presence of the adsorbed protein layer.

Bacterial Adhesion↗

PubMed1997

Physical property analysis and bacterial adhesion on a series of phosphonated polyurethanes.

Glycerophosphorylcholine (GPC) was incorporated as the chain extender in a series of poly(tetramethylene oxide)-based polyurethane block copolymers. In order to determine the feasibility of use of these polyurethanes in biomedical devices, the effects of GPC incorporation on physical properties were studied. The effect of soft-segment molecular weight was also investigated. Biocompatibility of these materials was studied with regard to bacterial adhesion and protein deposition. Tensile testing showed that as GPC content increased, elongation at break decreased, while Young's modulus increased. Differential scanning calorimetry (DSC) results showed slightly decreased glass transition temperatures (Tgs) with increasing GPC content, indicating increased phase separation. Dynamic mechanical analysis (DMA) confirmed the decrease in Tg and the increase in rubbery plateau modulus with increasing GPC content. Water absorption was also increased with GPC content. Decreased bacterial adhesion was found on the GPC-containing materials compared to other functionalized polyurethanes. These experiments were carried out in a radial flow chamber utilizing automated video microscopy. Bacterial attachment was found to be lower on the GPC-containing polyurethanes both in the absence of and after pre-adsorption with plasma proteins.

Bacterial Adhesion↗

PubMed1997

Drug use management in board and care facilities.

The purpose of this study was to describe medication management in board and care facilities throughout Minnesota. A triangulation of data collection methods was used, including mail questionnaires (N = 98 facilities), telephone interviews (N = 64 facilities), and site visits (N = 15 facilities). Major issues examined included characteristics of board and care facilities, staffing, residents, and drug management systems. Results showed that staff in 86% of the board and care facilities surveyed provided medication storage, 83% gave medication reminders, and 69% administered medications to one or more residents. Site visits revealed a wide diversity in the characteristics of managers and their attitudes toward medication administration.

Activities of Daily Living↗

PubMed1996

Role of leucocytes in coagulation induced by artificial surfaces: investigation of expression of Mac-1, granulocyte elastase release and leucocyte adhesion on modified polyurethanes.

Thrombus formation on artificial surfaces can be viewed as the sequential and concomitant involvement of protein adsorption, platelet reactions, activation of the coagulation system, participation of complement, fibrinolytic and kallikrein-kinin systems, and the interaction of cellular elements. This study examines the activation of leucocytes on a series of well-characterized polyurethanes with different ionic groups [sulphonate groups (negatively charged); quaterinary amine groups (positively charged)], in terms of adhesion, degranulation and cell surface integrin receptor expression. Leucocyte adhesion was monitored with radiolabelled neutrophils and scanning electron microscopy (SEM), degranulation by measurement of human neutrophil elastase using an indirect enzyme-linked immunosorbent assay and cell surface expression of the integrin receptor Mac-1, using fluorescent-activated cell sorting (FACS). Our results indicate a trend towards enhanced adhesion and degranulation with respect to the negatively charged polyurethane. Similar results were observed with respect to the integrin Mac-1 from recovered adherent cells. The findings of enhanced adhesion and spreading, Mac-1 up-regulation and granulocyte elastase release from the negatively charged sulphonated polyurethane indicate the potential of leucocytes to contribute towards thrombus formation on such surfaces.

Biocompatible Materials↗

PubMed1996

Neutrophil adhesion on surfaces preadsorbed with high molecular weight kininogen under well-defined flow conditions.

The adhesion of neutrophils and other leukocytes to biomaterial surfaces is an important phenomenon in the host response to biomaterials because the number of adherent leukocytes is often related to the inflammatory response after implantation. After adhering to biomaterial surfaces, other leukocyte reactions, such as phagocytosis, respiratory burst, and protease release, may occur and result in the deterioration of the implanted biomaterial and injury to peripheral tissue. This study of neutrophil adhesion quantitatively characterizes neutrophil adhesion under well-defined laminar flow conditions using a radial flow chamber. In this rheologically well-defined system, the fluid shear rate on the surface varies continuously with radial position. This allows the study of shear-dependent behavior of neutrophil adhesion. Exploiting the variable shear rate in the radial flow chamber, the kinetics of neutrophil adhesion was obtained using automated video microscopy and image analysis to recursively acquire cell counts from multiple fields in different radial positions, and to quantify the surface density of neutrophil as a function of time. Neutrophil adhesion was studied on glass preadsorbed with fibrinogen and high-molecular-weight kininogen (HK). At a shear rate of 20 s-1, the number of adherent cells on the preadsorbed fibrinogen surface was similar to that on bare glass, and the number of adherent cells on the HK surface was less than 10% of that on the bare glass. We conclude that surfaces preadsorbed with HK are anti-adhesive to neutrophils.

Adsorption↗

PubMed1996

Bacterial adhesion to polyurethane surfaces in the presence of pre-adsorbed high molecular weight kininogen.

The factors which affect the adherence of a bacteria cell to the surface of a biomaterial include the surface chemistry of the cell and material, as well as the composition of the adsorbed protein layer when the biomaterial is exposed to circulating blood. In an effort to better understand the mechanisms by which bacteria adhere to such surfaces, and specifically to determine the effects of high molecular weight kininogen on bacterial adhesion, experiments were performed in which the attachment of Staphylococcus aureus was directly observed on glass and on a series of functionalized polyurethanes. These surfaces had been pre-adsorbed with various concentrations of high molecular weight kininogen and fibrinogen. Attachment was observed using a radial flow chamber, in which shear stress varied inversely with radial distance. Protein adsorption studies were also performed using 125I labeled fibrinogen to investigate the relationship between surface chemistry, protein adsorption, and bacterial attachment. Bacterial attachment was significantly decreased when the glass surface was pre-adsorbed with high molecular weight kininogen--either alone, or following adsorption of fibrinogen. High molecular weight kininogen thus exhibited anti-adhesive effects. On polyurethane surfaces pre-adsorbed with fibrinogen, kininogen, and albumin, the highest bacterial attachment was found on the base polyurethane, while significant decreases were seen on the hydrophilic polyurethanes. In addition, it was found that the surface with the least bacterial attachment and fibrinogen deposition was the polyurethane with pendant phosphonate groups.

Adsorption↗

PubMed1996

Nafamostat mesilate, a broad spectrum protease inhibitor, modulates platelet, neutrophil and contact activation in simulated extracorporeal circulation.

Activation of humoral and cellular participants in inflammation enhances the risk of postoperative bleeding and multiple organ damage in cardiopulmonary bypass (CPB). We now compare the effects of heparin alone in combination with nafamostat mesilate (NM), a protease inhibitor with specificity of trypsin-like enzymes, in an extracorporeal circuit which simulates CPB. NM significantly inhibits the release of platelet beta-thromboglobulin (beta TG) at 60 and 120 min. Platelet counts do not differ. ADP-induced aggregation decreases in circuits with NM, which is due to a direct effect of NM on platelet function. NM prevents any significant release of neutrophil elastase; at 120 min, plasma elastase-alpha 1-antitrypsin complex is 0.16 micrograms/ml in the NM group and 1.24 micrograms/ml in the control group. NM completely inhibits formation of complexes of C1 inhibitor with kallikrein and FXIIa. NM does not alter markers of complement activation (C1-C1-inhibitor complex and C5b-9), or indicators of thrombin formation (F1.2). However, at 120 min, thrombin activity as measured by release of fibrinopeptide A is significantly decreased. The data indicate that complement activation during CPB correlates poorly with neutrophil activation and that either kallikrein or FXIIa or both may be more important agonists. The ability of NM to inhibit two important contact system proteins and platelet and neutrophil release raises the possibility of suppressing the inflammatory response during clinical CPB.

Anticoagulants↗

PubMed1995

Surface and blood-contacting properties of alkylsiloxane monolayers supported on silicone rubber.

Self-assembled monolayers of alkylsiloxanes supported on polydimethyl siloxane (PDMS) rubber were used as model systems to study the relation between blood compatibility and surface chemistry. The inner lumen of PDMS tubes was first treated with an oxygen plasma. The resultant oxidized surfaces were postderivatized by reacting them with alkyltrichlorosilanes to form the monolayer films. The chemical properties of the monolayers were controlled by varying the head-group chemical compositions. Surface derivatization was verified using variable-angle X-ray photoelectron spectroscopy (XPS or ESCA). Blood compatibility was evaluated using a canine ex vivo arteriovenous series shunt model. Surfaces grafted with hydrophobic head-groups as -CH3 and -CF3 had significantly lower platelet and fibrinogen deposition than the surfaces composed of hydrophilic groups such as -CO2CH3, -(CH2CH2O)3COCH3, and -(OCH2CH2)3OH.

Animals↗

PubMed1995

Studies on the tumor-promoting activity of polyurethanes: depletion of inhibitory action of metabolic cooperation on the surface of a polyalkyleneurethane but not a polyetherurethane.

Methanol extracts prepared from three polyetherurethanes (PEUs), namely PU4, PU6, and PU8, which were synthesized using 4,4'-diphenylmethanediisocyanate, poly(tetramethylene oxide), and 1,4-butanediol, showed an inhibitory action on the gap-junctional intercellular communication in a V79 metabolic cooperation (MC) test system. However, the inhibitory potentials of methanol extracts did not correlate with the tumorigenic potential of the polyurethanes in 1-year rat implantation studies. When the MC test was carried out using glass dishes partly coated with low molecular weight PEU, the inhibitory activity was clearly detected on the surface of the polyurethane coating but not on that of the noncoated glass area. The inhibitory activity of the three PEUs investigated using polyurethane-coated dishes correlated with the values of the polyurethane's tumorigenic potential in the rat implantation study. Various polyurethanes containing polybutadiene (PBD), hydrogenated polybutadiene (HPBD), or a fluoropolyether glycol (FPEG) as the soft segment were also tested using coated dishes in the MC assay. The threshold inhibitory response of FPEG-PU was 10-fold less than that of PU4, and neither PBD-PU nor HPBD-PU showed any inhibition in the MC test system. Both the FPEG and aliphatic soft segment containing polyurethanes decreased, and had minimal influence on the gap junctional intercellular communication. Thus, the tumor-promoting potential of PBD-PU, HPBD-PU, and FPEG-PU was considered to be lower than those of the PEUs based on these in vitro test results.

Animals↗

PubMed1995

Surface characterization and ex vivo blood compatibility study of plasma-modified small diameter tubing: effect of sulphur dioxide and hexamethyldisiloxane plasmas.

The development of a small diameter artificial vascular graft or prosthesis is limited by rapid thrombus formation and subsequent embolization upon blood contact. Plasma surface modification was employed to modify the inner surface of small diameter low density polyethylene (LDPE) tubing without varying the outer surface chemistry and physical properties of the tubing. A sulphur dioxide (SO2) plasma was used to form sulphonate functionality on the surface. In addition, a hexamethyldisiloxane (HMDSO) plasma and different gas flow ratios of SO2-HMDSO gas mixture plasmas were used to form ultrathin polysiloxane-like coatings inside the LDPE tubing. X-ray photoelectron spectroscopy (XPS) indicated that the inner surface of the tubing can be modified uniformly with this treatment. In addition, XPS results showed that the percentage of sulphur atoms bound to two or three oxygen atoms (sulphone or sulphonate) increased with the SO2-HMDSO mass flow rate ratio. The blood compatibility of the plasma-modified model materials was evaluated using an ex vivo canine arteriovenous shunt model. Similar thrombogenicity was observed comparing the untreated control and the surfaces modified by HMDSO plasma and SO2-HMDSO gas mixture plasmas, despite the differences in surface chemistry. The SO2 plasma-modified surface, which is the most hydrophilic as measured by the captive bubble contact angle measurement technique, was more thrombogenic than the untreated control. This may be attributed to the combined effect of the surface chemistry and surface hydrophilicity.

Animals↗

PubMed1995

Effect of sulphonate incorporation on in vitro leucocyte adhesion to polyurethanes.

A series of poly(tetramethylene oxide)-based polyurethane block copolymers was synthesized with varying levels of sulphonate ion incorporated in the hard segment block. Static in vitro adhesion of polymorphonuclear leucocytes (PMNs) on the underivatized and propyl sulphonate-grafted polyurethanes was investigated. The effect of plasma proteins on PMN adhesion to the polymers was also examined. The number of adherent cells on the sulphonated polyurethane surfaces was significantly higher than on the underivatized polyurethane under all conditions. The adherent PMNs on sulphonated polyurethanes showed increased cell spreading compared to the underivatized base polyurethane. Increasing the level of sulphonate incorporation from 5 to 17 mol% had no effect on the extent of cell adhesion. The presence of preadsorbed proteins generally led to a decrease in the number of adherent PMNs on the surfaces. However, the presence of plasma proteins in the suspension medium had no effect on the degree of leucocyte adhesion to the sulphonated polyurethanes.

Absorption↗