The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Tom Eirik Mollnes - One of the best experts on this subject based on the ideXlab platform.
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Artificial Surface-Induced Inflammation Relies on Complement Factor 5: Proof From a Deficient Person
The Annals of thoracic surgery, 2011Co-Authors: Grethe Bergseth, John D. Lambris, Tom Eirik Mollnes, Knut Tore LappegårdAbstract:Background Exposing blood to Artificial Surfaces results in an inflammatory response, including complement activation and cytokine release. The aim of this investigation was to study complement-dependency and independency in Artificial Surface-induced inflammation in human whole blood from a patient with a genetic deficiency of complement factor 5 (C5). Methods Whole blood from a C5-deficient patient, C5 protein reconstituted blood, and blood from a control subject was used. The complement inhibitor compstatin (C3 inhibitor) and a C5a receptor antagonist were used to block complement. Blood was circulated in closed loops of polyvinyl chloride tubing. Leukocyte CD11b expression and release of granule enzymes (myeloperoxidase, elastase, lactoferrin), cytokines (interleukins, chemokines, and growth factors; n=27) as well as complement activation were measured after incubation. Results In C5-deficient blood, there was no formation of the terminal complement complex, as opposed to reconstituted or control blood. Release of granule enzymes was partly dependent on C3, revealed by a compstatin-dependent effect in C5-deficient blood, and partly C5a-dependent as evident from the reconstitution and control blood. The chemokines interleukin-8 and monocyte chemoattractant protein-1 were also highly complement dependent, the effect being C5a-mediated, whereas platelet-derived and vascular endothelial growth factors were partly complement dependent. Interferon-γ increased in a complement-independent manner, whereas the rest of the cytokines did not respond to the Surface. Leukocyte expression of CD11b was only marginally increased in deficient blood exposed to the Surface, whereas reconstitution induced a considerable, C5a-dependent increase, comparable with that of the control. Conclusions The polyvinyl chloride Surface induced a defined inflammatory response, which largely depended on C5.
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The Artificial Surface-induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent.
Journal of biomedical materials research. Part A, 2008Co-Authors: Knut Tore Lappegård, John D. Lambris, Johan Riesenfeld, Grethe Bergseth, Anne Pharo, Paola Magotti, Tom Eirik MollnesAbstract:Exposing blood to an Artificial Surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the Artificial Surface-induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth-factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the Surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL-1β, TNFα and IL-6 were not induced, although IL-6, as well as IL-15 and IL-17 increased if the Surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin-coated PVC Surface was used as negative control and completely abolished the whole inflammatory response. The Artificial Surface PVC markedly induced a broad spectrum of chemokines and growth-factors, which was largely dependent on activation of complement.
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Differential Effect of Heparin Coating and Complement Inhibition on Artificial Surface-Induced Eicosanoid Production
The Annals of thoracic surgery, 2005Co-Authors: Knut Tore Lappegård, John D. Lambris, Johan Riesenfeld, Ole-lars Brekke, Grethe Bergseth, Tom Eirik MollnesAbstract:Background Contact between blood and Artificial Surfaces induces an inflammatory response including activation of leukocytes and platelets, as well as complement and other plasma cascade systems. In the present study we investigated the roles of complement and Surface modification in polyvinyl chloride-induced synthesis of eicosanoids (arachidonic acid metabolites). Methods Human whole blood was incubated in rotating loops of polyvinyl chloride or heparin-coated polyvinyl chloride tubing for 4 hours. Plasma concentrations of the eicosanoids leukotriene B4, prostaglandin E2 and thromboxane B2 were quantified. Results Polyvinyl chloride induced a substantial increase in leukotriene B4, prostaglandin E2, and thromboxane B2. Inhibition of complement activation by the complement factor 3 binding peptide compstatin or blockade of the complement factor 5a receptor with a specific antagonist significantly and specifically inhibited the synthesis of leukotriene B4, whereas thromboxane B2 and prostaglandin E2 synthesis were apparently complement independent. The increase in all three mediators was significantly reduced by the heparin coating. Indomethacin abolished the increase of the cyclooxygenase products prostaglandin E2 and thromboxane B2, but had no effect on the increase of the lipoxygenase product leukotriene B4, consistent with the specificity of indomethacin for the cyclooxygenase and confirming the specificity of complement inhibition. Conclusions Polyvinyl chloride-induced increase in all three eicosanoids was attenuated by heparin coating, whereas complement inhibition selectively reduced the synthesis of leukotriene B4.
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Artificial Surface induced cytokine synthesis effect of heparin coating and complement inhibition
The Annals of Thoracic Surgery, 2004Co-Authors: Knut Tore Lappegård, Johan Riesenfeld, Grethe Bergseth, Michael Fung, Tom Eirik MollnesAbstract:Abstract Background Contact between blood and Artificial Surfaces induces an inflammatory response including activation of leukocytes and platelets, as well as complement and other plasma cascade systems. In the present study we investigated the roles of complement and Surface modification in polyvinylchloride-induced cytokine production. Methods Human whole blood was incubated in rotating loops of polyvinylchloride or heparin-coated polyvinylchloride tubing for 4 hours. Plasma concentrations of the cytokines tumor necrosis factor α, interleukin (IL) 1β, IL-6, IL-8, IL-10, and monocyte chemoattractant protein 1 (MCP-1) were quantified. Results Polyvinylchloride induced a substantial increase in IL-8 and MCP-1, which was abolished by cycloheximide, indicating that they were synthesized during incubation. Interleukin 8 synthesis was completely complement-dependent since it was abolished by neutralizing antibodies to factor D and complement factor 5, as well as by a complement factor 5a receptor antagonist. Monocyte chemoattractant protein 1 synthesis was reduced by approximately half the amount by the complement inhibitors. Heparin-coated polyvinylchloride efficiently prevented synthesis of both IL-8 and MCP-1. Addition of recombinant human complement factor 5a to blood incubated in heparin-coated polyvinylchloride restored IL-8 and MCP-1 production completely and partly, respectively. In contrast to IL-8 and MCP-1, tumor necrosis factor α, IL-1β, interleukin 6 and IL-10 increased only marginally. A minor but significant increase in IL-1β was complement-dependent, whereas a similar increase in IL-10 was completely prevented by heparin-coated polyvinylchloride. No significant changes were observed for tumor necrosis factor α and IL-6. Conclusions Polyvinylchloride induced a marked increase in IL-8 and MCP-1, in contrast to a marginal increase in tumor necrosis factor α, IL-1β, IL-6, and IL-10. The increase in IL-8 and MCP-1 was prevented by heparin-coated polyvinylchloride. Interleukin 8 production was totally complement-dependent and mediated by complement factor 5a.
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Effect of complement inhibition and heparin coating on Artificial Surface–induced leukocyte and platelet activation
The Annals of thoracic surgery, 2004Co-Authors: Knut Tore Lappegård, John D. Lambris, Johan Riesenfeld, Grethe Bergseth, Michael Fung, Vibeke Videm, Tom Eirik MollnesAbstract:Abstract Background Exposure of blood to Artificial Surfaces, as in cardiopulmonary bypass, induces an inflammatory response involving complement, leukocyte and platelet activation. To elucidate the specific role of complement in this process, studies were performed on blood circulated in polyvinyl chloride tubing in the absence and presence of complement inhibitors. Parallel experiments were performed with heparin-coated polyvinyl chloride tubing, which is known to prevent complement and cell activation. Methods A novel experimental model was used, based on human whole blood anticoagulated with lepirudin. Complement activation products, myeloperoxidase, lactoferrin, and thrombospondin were quantified in enzyme immunoassays. Leukocyte CD11b expression and leukocyte-platelet conjugates were detected by flow cytometry. Results Increased levels of C3 activation products, alternative pathway convertase, and the terminal SC5b-9 complex, combined with unchanged levels of C1rs–C1-inhibitor complexes and marginal changes in C4 activation demonstrated that complement was activated through the alternative pathway. Granulocyte and monocyte CD11b expression and granulocyte-platelet conjugate formation were efficiently attenuated by blocking either factor D, C3, C5, or C5a receptor. In contrast, monocyte-platelet conjugate formation and release of myeloperoxidase, lactoferrin, and thrombospondin were not reduced by complement inhibition. Heparin-coated polyvinyl chloride tubing efficiently reduced all inflammatory markers studied, except for C1rs–C1-inhibitor complexes, which increased, consistent with the enhancing effect of heparin on C1-inhibitor function. This effect did not, however, reduce fluid-phase classic pathway activation induced by heat-aggregated immunoglobulin G. Conclusions Leukocyte and platelet activation in response to Artificial materials occur by mechanisms that vary in their dependence on complement. Heparin coating precludes both the complement-dependent and complement-independent reactions.
Dimiter Vlaev - One of the best experts on this subject based on the ideXlab platform.
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detecting filter cake pathologies in solid liquid filtration semi tech scale demonstrations using electrical resistance tomography ert
Chemical Engineering Journal, 2000Co-Authors: Dimiter Vlaev, Mi Wang, Tom Dyakowski, Uce GrieveAbstract:Abstract Solid–liquid filtration monitoring by means of a single inexpensive 16-element ring sensor array for electrical resistance tomography (ERT) is described. The high sensitivity of the UMIST Mark 1b-E data acquisition system led to the unexpected finding that this tomography array can detect movement of the liquid level during filtration. This degree of sensitivity was also capable of detecting any tilt of the filter assembly, so that pathological behaviour due to malfunction or accidental displacement of the filter support plate could also be identified. Moreover, illustrative distortions of a filter cake formed by Artificial Surface depressions were readily observed in tomograms reconstructed by linear back projection. It is concluded that ERT has great potential for instrumenting and detecting ‘pathological’ behaviour of filtration processes in the pharmaceutical and fine chemicals industries.
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Detecting filter-cake pathologies in solid–liquid filtration: semi-tech scale demonstrations using electrical resistance tomography (ERT)
Chemical Engineering Journal, 2000Co-Authors: Dimiter Vlaev, R. Mann, Mi Wang, Tom Dyakowski, Bruce GrieveAbstract:Abstract Solid–liquid filtration monitoring by means of a single inexpensive 16-element ring sensor array for electrical resistance tomography (ERT) is described. The high sensitivity of the UMIST Mark 1b-E data acquisition system led to the unexpected finding that this tomography array can detect movement of the liquid level during filtration. This degree of sensitivity was also capable of detecting any tilt of the filter assembly, so that pathological behaviour due to malfunction or accidental displacement of the filter support plate could also be identified. Moreover, illustrative distortions of a filter cake formed by Artificial Surface depressions were readily observed in tomograms reconstructed by linear back projection. It is concluded that ERT has great potential for instrumenting and detecting ‘pathological’ behaviour of filtration processes in the pharmaceutical and fine chemicals industries.
Knut Tore Lappegård - One of the best experts on this subject based on the ideXlab platform.
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Artificial Surface-Induced Inflammation Relies on Complement Factor 5: Proof From a Deficient Person
The Annals of thoracic surgery, 2011Co-Authors: Grethe Bergseth, John D. Lambris, Tom Eirik Mollnes, Knut Tore LappegårdAbstract:Background Exposing blood to Artificial Surfaces results in an inflammatory response, including complement activation and cytokine release. The aim of this investigation was to study complement-dependency and independency in Artificial Surface-induced inflammation in human whole blood from a patient with a genetic deficiency of complement factor 5 (C5). Methods Whole blood from a C5-deficient patient, C5 protein reconstituted blood, and blood from a control subject was used. The complement inhibitor compstatin (C3 inhibitor) and a C5a receptor antagonist were used to block complement. Blood was circulated in closed loops of polyvinyl chloride tubing. Leukocyte CD11b expression and release of granule enzymes (myeloperoxidase, elastase, lactoferrin), cytokines (interleukins, chemokines, and growth factors; n=27) as well as complement activation were measured after incubation. Results In C5-deficient blood, there was no formation of the terminal complement complex, as opposed to reconstituted or control blood. Release of granule enzymes was partly dependent on C3, revealed by a compstatin-dependent effect in C5-deficient blood, and partly C5a-dependent as evident from the reconstitution and control blood. The chemokines interleukin-8 and monocyte chemoattractant protein-1 were also highly complement dependent, the effect being C5a-mediated, whereas platelet-derived and vascular endothelial growth factors were partly complement dependent. Interferon-γ increased in a complement-independent manner, whereas the rest of the cytokines did not respond to the Surface. Leukocyte expression of CD11b was only marginally increased in deficient blood exposed to the Surface, whereas reconstitution induced a considerable, C5a-dependent increase, comparable with that of the control. Conclusions The polyvinyl chloride Surface induced a defined inflammatory response, which largely depended on C5.
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The Artificial Surface-induced whole blood inflammatory reaction revealed by increases in a series of chemokines and growth factors is largely complement dependent.
Journal of biomedical materials research. Part A, 2008Co-Authors: Knut Tore Lappegård, John D. Lambris, Johan Riesenfeld, Grethe Bergseth, Anne Pharo, Paola Magotti, Tom Eirik MollnesAbstract:Exposing blood to an Artificial Surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the Artificial Surface-induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth-factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the Surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL-1β, TNFα and IL-6 were not induced, although IL-6, as well as IL-15 and IL-17 increased if the Surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin-coated PVC Surface was used as negative control and completely abolished the whole inflammatory response. The Artificial Surface PVC markedly induced a broad spectrum of chemokines and growth-factors, which was largely dependent on activation of complement.
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Differential Effect of Heparin Coating and Complement Inhibition on Artificial Surface-Induced Eicosanoid Production
The Annals of thoracic surgery, 2005Co-Authors: Knut Tore Lappegård, John D. Lambris, Johan Riesenfeld, Ole-lars Brekke, Grethe Bergseth, Tom Eirik MollnesAbstract:Background Contact between blood and Artificial Surfaces induces an inflammatory response including activation of leukocytes and platelets, as well as complement and other plasma cascade systems. In the present study we investigated the roles of complement and Surface modification in polyvinyl chloride-induced synthesis of eicosanoids (arachidonic acid metabolites). Methods Human whole blood was incubated in rotating loops of polyvinyl chloride or heparin-coated polyvinyl chloride tubing for 4 hours. Plasma concentrations of the eicosanoids leukotriene B4, prostaglandin E2 and thromboxane B2 were quantified. Results Polyvinyl chloride induced a substantial increase in leukotriene B4, prostaglandin E2, and thromboxane B2. Inhibition of complement activation by the complement factor 3 binding peptide compstatin or blockade of the complement factor 5a receptor with a specific antagonist significantly and specifically inhibited the synthesis of leukotriene B4, whereas thromboxane B2 and prostaglandin E2 synthesis were apparently complement independent. The increase in all three mediators was significantly reduced by the heparin coating. Indomethacin abolished the increase of the cyclooxygenase products prostaglandin E2 and thromboxane B2, but had no effect on the increase of the lipoxygenase product leukotriene B4, consistent with the specificity of indomethacin for the cyclooxygenase and confirming the specificity of complement inhibition. Conclusions Polyvinyl chloride-induced increase in all three eicosanoids was attenuated by heparin coating, whereas complement inhibition selectively reduced the synthesis of leukotriene B4.
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Artificial Surface induced cytokine synthesis effect of heparin coating and complement inhibition
The Annals of Thoracic Surgery, 2004Co-Authors: Knut Tore Lappegård, Johan Riesenfeld, Grethe Bergseth, Michael Fung, Tom Eirik MollnesAbstract:Abstract Background Contact between blood and Artificial Surfaces induces an inflammatory response including activation of leukocytes and platelets, as well as complement and other plasma cascade systems. In the present study we investigated the roles of complement and Surface modification in polyvinylchloride-induced cytokine production. Methods Human whole blood was incubated in rotating loops of polyvinylchloride or heparin-coated polyvinylchloride tubing for 4 hours. Plasma concentrations of the cytokines tumor necrosis factor α, interleukin (IL) 1β, IL-6, IL-8, IL-10, and monocyte chemoattractant protein 1 (MCP-1) were quantified. Results Polyvinylchloride induced a substantial increase in IL-8 and MCP-1, which was abolished by cycloheximide, indicating that they were synthesized during incubation. Interleukin 8 synthesis was completely complement-dependent since it was abolished by neutralizing antibodies to factor D and complement factor 5, as well as by a complement factor 5a receptor antagonist. Monocyte chemoattractant protein 1 synthesis was reduced by approximately half the amount by the complement inhibitors. Heparin-coated polyvinylchloride efficiently prevented synthesis of both IL-8 and MCP-1. Addition of recombinant human complement factor 5a to blood incubated in heparin-coated polyvinylchloride restored IL-8 and MCP-1 production completely and partly, respectively. In contrast to IL-8 and MCP-1, tumor necrosis factor α, IL-1β, interleukin 6 and IL-10 increased only marginally. A minor but significant increase in IL-1β was complement-dependent, whereas a similar increase in IL-10 was completely prevented by heparin-coated polyvinylchloride. No significant changes were observed for tumor necrosis factor α and IL-6. Conclusions Polyvinylchloride induced a marked increase in IL-8 and MCP-1, in contrast to a marginal increase in tumor necrosis factor α, IL-1β, IL-6, and IL-10. The increase in IL-8 and MCP-1 was prevented by heparin-coated polyvinylchloride. Interleukin 8 production was totally complement-dependent and mediated by complement factor 5a.
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Effect of complement inhibition and heparin coating on Artificial Surface–induced leukocyte and platelet activation
The Annals of thoracic surgery, 2004Co-Authors: Knut Tore Lappegård, John D. Lambris, Johan Riesenfeld, Grethe Bergseth, Michael Fung, Vibeke Videm, Tom Eirik MollnesAbstract:Abstract Background Exposure of blood to Artificial Surfaces, as in cardiopulmonary bypass, induces an inflammatory response involving complement, leukocyte and platelet activation. To elucidate the specific role of complement in this process, studies were performed on blood circulated in polyvinyl chloride tubing in the absence and presence of complement inhibitors. Parallel experiments were performed with heparin-coated polyvinyl chloride tubing, which is known to prevent complement and cell activation. Methods A novel experimental model was used, based on human whole blood anticoagulated with lepirudin. Complement activation products, myeloperoxidase, lactoferrin, and thrombospondin were quantified in enzyme immunoassays. Leukocyte CD11b expression and leukocyte-platelet conjugates were detected by flow cytometry. Results Increased levels of C3 activation products, alternative pathway convertase, and the terminal SC5b-9 complex, combined with unchanged levels of C1rs–C1-inhibitor complexes and marginal changes in C4 activation demonstrated that complement was activated through the alternative pathway. Granulocyte and monocyte CD11b expression and granulocyte-platelet conjugate formation were efficiently attenuated by blocking either factor D, C3, C5, or C5a receptor. In contrast, monocyte-platelet conjugate formation and release of myeloperoxidase, lactoferrin, and thrombospondin were not reduced by complement inhibition. Heparin-coated polyvinyl chloride tubing efficiently reduced all inflammatory markers studied, except for C1rs–C1-inhibitor complexes, which increased, consistent with the enhancing effect of heparin on C1-inhibitor function. This effect did not, however, reduce fluid-phase classic pathway activation induced by heat-aggregated immunoglobulin G. Conclusions Leukocyte and platelet activation in response to Artificial materials occur by mechanisms that vary in their dependence on complement. Heparin coating precludes both the complement-dependent and complement-independent reactions.
Bruce Grieve - One of the best experts on this subject based on the ideXlab platform.
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Detecting filter-cake pathologies in solid–liquid filtration: semi-tech scale demonstrations using electrical resistance tomography (ERT)
Chemical Engineering Journal, 2000Co-Authors: Dimiter Vlaev, R. Mann, Mi Wang, Tom Dyakowski, Bruce GrieveAbstract:Abstract Solid–liquid filtration monitoring by means of a single inexpensive 16-element ring sensor array for electrical resistance tomography (ERT) is described. The high sensitivity of the UMIST Mark 1b-E data acquisition system led to the unexpected finding that this tomography array can detect movement of the liquid level during filtration. This degree of sensitivity was also capable of detecting any tilt of the filter assembly, so that pathological behaviour due to malfunction or accidental displacement of the filter support plate could also be identified. Moreover, illustrative distortions of a filter cake formed by Artificial Surface depressions were readily observed in tomograms reconstructed by linear back projection. It is concluded that ERT has great potential for instrumenting and detecting ‘pathological’ behaviour of filtration processes in the pharmaceutical and fine chemicals industries.
Uce Grieve - One of the best experts on this subject based on the ideXlab platform.
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detecting filter cake pathologies in solid liquid filtration semi tech scale demonstrations using electrical resistance tomography ert
Chemical Engineering Journal, 2000Co-Authors: Dimiter Vlaev, Mi Wang, Tom Dyakowski, Uce GrieveAbstract:Abstract Solid–liquid filtration monitoring by means of a single inexpensive 16-element ring sensor array for electrical resistance tomography (ERT) is described. The high sensitivity of the UMIST Mark 1b-E data acquisition system led to the unexpected finding that this tomography array can detect movement of the liquid level during filtration. This degree of sensitivity was also capable of detecting any tilt of the filter assembly, so that pathological behaviour due to malfunction or accidental displacement of the filter support plate could also be identified. Moreover, illustrative distortions of a filter cake formed by Artificial Surface depressions were readily observed in tomograms reconstructed by linear back projection. It is concluded that ERT has great potential for instrumenting and detecting ‘pathological’ behaviour of filtration processes in the pharmaceutical and fine chemicals industries.
