Wim Buurman - Academia.edu (original) (raw)

Papers by Wim Buurman

Gastroenterology, May 1, 2011

PubMed, Feb 1, 1991

In this study the interaction of endotoxemia and ischemic organ injury was investigated in a rat ... more In this study the interaction of endotoxemia and ischemic organ injury was investigated in a rat model. Animals received lipopolysaccharide to induce endotoxemia and were simultaneously subjected to renal ischemia. If only renal ischemia was induced, moderate azotemia occurred and all animals survived. Lipopolysaccharide treatment caused neither renal failure nor death. However, rats with both endotoxemia and renal ischemia showed severe azotemia, and 50% of the animals died within 48 hours. The observed mortality rate is unlikely related to renal failure since animals subjected to bilateral nephrectomy did not die within 48 hours after treatment with lipopolysaccharide. To further exclude the role of renal failure in the enhanced effect of endotoxemia, experiments were performed in which ischemic kidneys were excised from littermates and were placed in the abdomens of lipopolysaccharide-treated animals. A similar effect was observed: 50% of the animals died within 48 hours. Azotemia did not occur. Since tumor necrosis factor (TNF) is an important cytokine involved in endotoxemia-induced morbidity and death, we studied the role of TNF in our model. Plasma levels of TNF were increased during endotoxemia. Concomitant renal ischemic injury did not influence the concentration of TNF. When animals were treated with recombinant TNF and were subsequently subjected to renal ischemic injury, again a 50% mortality was observed, a rate similar to that in lipopolysaccharide-treated animals. We conclude that the sensitivity to endotoxemia is enhanced by tissue necrosis and may lead to death in the experimental model used in this study.

The Journal of Urology, Sep 1, 2014

Immunopharmacology and Immunotoxicology, 1989

Heavy metals administered to animals, at doses which appear relatively innoxious by themselves, e... more Heavy metals administered to animals, at doses which appear relatively innoxious by themselves, enhance susceptibility to endotoxin. The mechanisms which underly this phenomenon are not yet fully understood. In this study we investigated the role of the cytokine Tumour Necrosis Factor (TNF), an important mediator of the effects of endotoxin, in this phenomenon. First it was studied whether lead enhances sensitivity of mice to endotoxin and to TNF. Lead appeared to enhance sensitivity to both endotoxin and TNF resulting in mortality of mice at low endotoxin and TNF doses. Next we studied the influence of lead on serum TNF levels after stimulation by endotoxin. Lead treated mice showed lower TNF blood levels two hours after injection of endotoxin and lead. Six and eight hours after injection TNF levels of lead treated mice were higher compared to those of mice injected with endotoxin only. In the last part of our investigation, we studied the influence of a monoclonal hamster anti TNF antibody on the effect of combined lead-endotoxin exposure. Administration of the antibody prevents lethality completely. Our data indicate that TNF plays a central role in the phenomenon of the enhanced susceptibility of animals to endotoxin after exposure to lead. The enhanced susceptibility to endotoxin is caused by an enhanced susceptibility to TNF and possibly by a prolonged exposure to a higher level of TNF.

European Journal of Gastroenterology & Hepatology, Dec 1, 1999

International Journal of Obesity, Feb 1, 2002

Current Opinion in Clinical Nutrition and Metabolic Care, Sep 1, 2007

In clinical research, increased permeability has been scrutinized as a potential indicator of the... more In clinical research, increased permeability has been scrutinized as a potential indicator of the severity of gastrointestinal disease and as a potential cause of the perpetuation of severe inflammatory activity in infectious states. This review discusses old and recent epidemiological and clinical evidence to establish whether increased permeability in sepsis is a sequel or a cause of multiple organ failure. In addition, old and new evidence linking inflammation and permeability in abnormal gastrointestinal anatomy and function to liver abnormalities in susceptible patients will be reviewed. Intestinal permeability has been found to be increased in several gastrointestinal diseases but not to be a very good marker of the severity of disease. Evidence is put forward supporting the claim that increased intestinal permeability is part of generalized leakiness of tight junctions in multiple organ failure and to play a less strong role as a primary event in its pathogenesis. Endemic malnutrition has been shown to be caused by interplay between malnutrition and intestinal inflammation. Recently experimental evidence has been put forward suggesting that enteral fat has anti-inflammatory effects on the intestine via the autonomic nervous system. Old clinical and new epidemiological evidence links intestinal inflammation, disruption of the enterohepatic cycle of bile acids, and liver disease. The implications of the described findings are that inflammatory activity, locally induced by abnormal intestinal anatomy and disruption of the bile acid pool, or systemically by severe and uncontrolled inflammation/infection, should be the focus of treatment or research. In addition, the connection between intestinal inflammation and liver disease should be investigated.

Medicine and Science in Sports and Exercise, Dec 1, 2012

Gastroenterology, Feb 1, 1990

Gastroenterology, May 1, 2010

Frontiers in Physiology, Sep 8, 2014

Scandinavian Journal of Immunology, Oct 1, 1990

TNF plays a central role in septic shock induced by endotoxin or Gram‐negative bacteria. Zymosan ... more TNF plays a central role in septic shock induced by endotoxin or Gram‐negative bacteria. Zymosan can elicit a septic shock‐like syndrome in rodents in the absence of endotoxin. TNF and IL‐6 release in mice treated with zymosan was investigated. One hour after intraperitoneal zymosan injection, maximal TNF levels were measured in serum, followed by IL‐6 peak levels 1 h later. Treatment with a monoclonal antibody against TNF lowered zymosan‐induced mortality from 63 to 11.6%, while maximal IL‐6 levels were lowered by about 40%.Mechanisms triggering zymosan‐induced cytokine release in murine macrophages were analysed in vitro. Cytokine release was only slightly triggered by uncoated zymosan particles. Thirty‐nine per cent of TNF release by macrophages appeared to be triggered by zymosan‐bound activated complement. Maximal TNT release also required the presence of natural antibodies against zymosan and zymosan‐activated scrum. In contrast, maximal 11–6 release was reached upon stimulation with zymosan‐activated serum only, while the presence of zymosan particles lowered this response.We conclude that TNF is a crucial mediator m zymosan‐induced shock. TNF release can be induced by different immunological pathways, without the need for the direct presence of endotoxins. Although IL‐6 release during septic shock is partly dependent on TNF. in vitro trigger mechanisms for IL‐6 and TNF differ remarkably.

International Journal of Obesity, Dec 1, 2001

Annals of Surgery, Feb 1, 2011

Journal of Immunology, May 1, 2013

In the autoimmune disease myasthenia gravis (MG), autoantibodies against the muscle AChR are main... more In the autoimmune disease myasthenia gravis (MG), autoantibodies against the muscle AChR are mainly produced by both short- and long-lived plasma cells, which are resistant to standard immunosuppressive drugs (i.e. glucocorticoids). A novel therapy to eliminate plasma cells is the proteasome inhibitor bortezomib, which is used to treat patients with multiple myeloma (MM, a plasma cell malignancy). Previously, we demonstrated that bortezomib also reduced autoantibody titers in an animal model of MG (Gomez, A. M. J. Immunol. 2011). The thymus of MG patients is frequently enriched in germinal centers and contains plasma cells that produce autoantibodies in vitro, even after irradiation (which depletes B and T lymphocytes). We studied the in vitro effects of bortezomib in cultured thymus cells from MG patients undergoing therapeutic thymectomy. Treatment with a single dose of bortezomib blocked the production of these pathogenic autoantibodies, reduced the total IgG levels and eliminated plasma cells. Ultrastructural signs of apoptosis were detected in plasma cells as early as 8 h after addition of bortezomib; at 24 h, no plasma cells could be detected. Moreover, we demonstrated that the minimum concentration of bortezomib that eliminates plasma cells in vitro is 60-fold lower than the peak concentration found in MM patients treated with bortezomib, suggesting that low doses might be effective for eliminating plasma cells in patients with antibody-mediated autoimmune diseases.

Perfusion, Mar 1, 2005

This prospective randomized clinical pilot study was conducted to evaluate a recently introduced ... more This prospective randomized clinical pilot study was conducted to evaluate a recently introduced reduced volume CPB system that is coated with the biopassive Xcoating. Twenty-two patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB), either with a fully heparin-coated CPB circuit (control, n=11) or with an Xcoating coated condensed extra-corporeal circuit (CondECC, n=11), were included. We examined activation of the complement system (C3bc and C4bc), activation of neutrophils (BPI), the acute phase response (interleukin (IL)-6, and acute phase proteins (LBP, AGP, and CRP)), myocardial tissue injury (troponin T), hemolysis (free hemoglobin (FHb)), and clinical outcome parameters. Preoperative risk profiles were identical for both patient groups. All patients went through the procedure without major complications and were discharged from the hospital. FHb and BPI levels at the end of pump support (p < 0.01) and at 15 min after the administration of protamine (p < 0.05) were significantly higher in the control group. In addition, FHb levels were still significantly elevated upon arrival on the cardiothoracic intensive care unit (CICU) in the control group (p < 0.05). C3bc and C4bc, acute phase proteins, IL-6, and troponin T concentrations, and clinical outcome variables were identical in both patient groups. In conclusion, the evaluated condensed extracorporeal circuit is a flexible and multifunctional CPB sytem that offers safe procedures. Furthermore, the results indicate improved biocompatibility of this option for extracorporeal circulation.

Gastroenterology, May 1, 2011

PubMed, Feb 1, 1991

In this study the interaction of endotoxemia and ischemic organ injury was investigated in a rat ... more In this study the interaction of endotoxemia and ischemic organ injury was investigated in a rat model. Animals received lipopolysaccharide to induce endotoxemia and were simultaneously subjected to renal ischemia. If only renal ischemia was induced, moderate azotemia occurred and all animals survived. Lipopolysaccharide treatment caused neither renal failure nor death. However, rats with both endotoxemia and renal ischemia showed severe azotemia, and 50% of the animals died within 48 hours. The observed mortality rate is unlikely related to renal failure since animals subjected to bilateral nephrectomy did not die within 48 hours after treatment with lipopolysaccharide. To further exclude the role of renal failure in the enhanced effect of endotoxemia, experiments were performed in which ischemic kidneys were excised from littermates and were placed in the abdomens of lipopolysaccharide-treated animals. A similar effect was observed: 50% of the animals died within 48 hours. Azotemia did not occur. Since tumor necrosis factor (TNF) is an important cytokine involved in endotoxemia-induced morbidity and death, we studied the role of TNF in our model. Plasma levels of TNF were increased during endotoxemia. Concomitant renal ischemic injury did not influence the concentration of TNF. When animals were treated with recombinant TNF and were subsequently subjected to renal ischemic injury, again a 50% mortality was observed, a rate similar to that in lipopolysaccharide-treated animals. We conclude that the sensitivity to endotoxemia is enhanced by tissue necrosis and may lead to death in the experimental model used in this study.

The Journal of Urology, Sep 1, 2014

Immunopharmacology and Immunotoxicology, 1989

Heavy metals administered to animals, at doses which appear relatively innoxious by themselves, e... more Heavy metals administered to animals, at doses which appear relatively innoxious by themselves, enhance susceptibility to endotoxin. The mechanisms which underly this phenomenon are not yet fully understood. In this study we investigated the role of the cytokine Tumour Necrosis Factor (TNF), an important mediator of the effects of endotoxin, in this phenomenon. First it was studied whether lead enhances sensitivity of mice to endotoxin and to TNF. Lead appeared to enhance sensitivity to both endotoxin and TNF resulting in mortality of mice at low endotoxin and TNF doses. Next we studied the influence of lead on serum TNF levels after stimulation by endotoxin. Lead treated mice showed lower TNF blood levels two hours after injection of endotoxin and lead. Six and eight hours after injection TNF levels of lead treated mice were higher compared to those of mice injected with endotoxin only. In the last part of our investigation, we studied the influence of a monoclonal hamster anti TNF antibody on the effect of combined lead-endotoxin exposure. Administration of the antibody prevents lethality completely. Our data indicate that TNF plays a central role in the phenomenon of the enhanced susceptibility of animals to endotoxin after exposure to lead. The enhanced susceptibility to endotoxin is caused by an enhanced susceptibility to TNF and possibly by a prolonged exposure to a higher level of TNF.

European Journal of Gastroenterology & Hepatology, Dec 1, 1999

International Journal of Obesity, Feb 1, 2002

Current Opinion in Clinical Nutrition and Metabolic Care, Sep 1, 2007

In clinical research, increased permeability has been scrutinized as a potential indicator of the... more In clinical research, increased permeability has been scrutinized as a potential indicator of the severity of gastrointestinal disease and as a potential cause of the perpetuation of severe inflammatory activity in infectious states. This review discusses old and recent epidemiological and clinical evidence to establish whether increased permeability in sepsis is a sequel or a cause of multiple organ failure. In addition, old and new evidence linking inflammation and permeability in abnormal gastrointestinal anatomy and function to liver abnormalities in susceptible patients will be reviewed. Intestinal permeability has been found to be increased in several gastrointestinal diseases but not to be a very good marker of the severity of disease. Evidence is put forward supporting the claim that increased intestinal permeability is part of generalized leakiness of tight junctions in multiple organ failure and to play a less strong role as a primary event in its pathogenesis. Endemic malnutrition has been shown to be caused by interplay between malnutrition and intestinal inflammation. Recently experimental evidence has been put forward suggesting that enteral fat has anti-inflammatory effects on the intestine via the autonomic nervous system. Old clinical and new epidemiological evidence links intestinal inflammation, disruption of the enterohepatic cycle of bile acids, and liver disease. The implications of the described findings are that inflammatory activity, locally induced by abnormal intestinal anatomy and disruption of the bile acid pool, or systemically by severe and uncontrolled inflammation/infection, should be the focus of treatment or research. In addition, the connection between intestinal inflammation and liver disease should be investigated.

Medicine and Science in Sports and Exercise, Dec 1, 2012

Gastroenterology, Feb 1, 1990

Gastroenterology, May 1, 2010

Frontiers in Physiology, Sep 8, 2014

Scandinavian Journal of Immunology, Oct 1, 1990

TNF plays a central role in septic shock induced by endotoxin or Gram‐negative bacteria. Zymosan ... more TNF plays a central role in septic shock induced by endotoxin or Gram‐negative bacteria. Zymosan can elicit a septic shock‐like syndrome in rodents in the absence of endotoxin. TNF and IL‐6 release in mice treated with zymosan was investigated. One hour after intraperitoneal zymosan injection, maximal TNF levels were measured in serum, followed by IL‐6 peak levels 1 h later. Treatment with a monoclonal antibody against TNF lowered zymosan‐induced mortality from 63 to 11.6%, while maximal IL‐6 levels were lowered by about 40%.Mechanisms triggering zymosan‐induced cytokine release in murine macrophages were analysed in vitro. Cytokine release was only slightly triggered by uncoated zymosan particles. Thirty‐nine per cent of TNF release by macrophages appeared to be triggered by zymosan‐bound activated complement. Maximal TNT release also required the presence of natural antibodies against zymosan and zymosan‐activated scrum. In contrast, maximal 11–6 release was reached upon stimulation with zymosan‐activated serum only, while the presence of zymosan particles lowered this response.We conclude that TNF is a crucial mediator m zymosan‐induced shock. TNF release can be induced by different immunological pathways, without the need for the direct presence of endotoxins. Although IL‐6 release during septic shock is partly dependent on TNF. in vitro trigger mechanisms for IL‐6 and TNF differ remarkably.

International Journal of Obesity, Dec 1, 2001

Annals of Surgery, Feb 1, 2011

Journal of Immunology, May 1, 2013

In the autoimmune disease myasthenia gravis (MG), autoantibodies against the muscle AChR are main... more In the autoimmune disease myasthenia gravis (MG), autoantibodies against the muscle AChR are mainly produced by both short- and long-lived plasma cells, which are resistant to standard immunosuppressive drugs (i.e. glucocorticoids). A novel therapy to eliminate plasma cells is the proteasome inhibitor bortezomib, which is used to treat patients with multiple myeloma (MM, a plasma cell malignancy). Previously, we demonstrated that bortezomib also reduced autoantibody titers in an animal model of MG (Gomez, A. M. J. Immunol. 2011). The thymus of MG patients is frequently enriched in germinal centers and contains plasma cells that produce autoantibodies in vitro, even after irradiation (which depletes B and T lymphocytes). We studied the in vitro effects of bortezomib in cultured thymus cells from MG patients undergoing therapeutic thymectomy. Treatment with a single dose of bortezomib blocked the production of these pathogenic autoantibodies, reduced the total IgG levels and eliminated plasma cells. Ultrastructural signs of apoptosis were detected in plasma cells as early as 8 h after addition of bortezomib; at 24 h, no plasma cells could be detected. Moreover, we demonstrated that the minimum concentration of bortezomib that eliminates plasma cells in vitro is 60-fold lower than the peak concentration found in MM patients treated with bortezomib, suggesting that low doses might be effective for eliminating plasma cells in patients with antibody-mediated autoimmune diseases.

Perfusion, Mar 1, 2005

This prospective randomized clinical pilot study was conducted to evaluate a recently introduced ... more This prospective randomized clinical pilot study was conducted to evaluate a recently introduced reduced volume CPB system that is coated with the biopassive Xcoating. Twenty-two patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB), either with a fully heparin-coated CPB circuit (control, n=11) or with an Xcoating coated condensed extra-corporeal circuit (CondECC, n=11), were included. We examined activation of the complement system (C3bc and C4bc), activation of neutrophils (BPI), the acute phase response (interleukin (IL)-6, and acute phase proteins (LBP, AGP, and CRP)), myocardial tissue injury (troponin T), hemolysis (free hemoglobin (FHb)), and clinical outcome parameters. Preoperative risk profiles were identical for both patient groups. All patients went through the procedure without major complications and were discharged from the hospital. FHb and BPI levels at the end of pump support (p < 0.01) and at 15 min after the administration of protamine (p < 0.05) were significantly higher in the control group. In addition, FHb levels were still significantly elevated upon arrival on the cardiothoracic intensive care unit (CICU) in the control group (p < 0.05). C3bc and C4bc, acute phase proteins, IL-6, and troponin T concentrations, and clinical outcome variables were identical in both patient groups. In conclusion, the evaluated condensed extracorporeal circuit is a flexible and multifunctional CPB sytem that offers safe procedures. Furthermore, the results indicate improved biocompatibility of this option for extracorporeal circulation.