Maria Bergquist - Academia.edu (original) (raw)

Uploads

Papers by Maria Bergquist

Research paper thumbnail of 68Ga Labeled TNF-± For Localization Of Experimental Ventilator Induced Lung Inflammation

B95. DIAGNOSING AND MANAGING VENTILATOR INDUCED LUNG INJURY, 2010

Research paper thumbnail of Matrix Metalloproteinases -8 and -9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study

PLOS ONE, 2015

Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation an... more Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Plasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.

Research paper thumbnail of Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung

Critical care medicine, Jan 5, 2015

PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung ... more PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Prospective laboratory investigation. University animal research laboratory. Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were...

Research paper thumbnail of No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist

Journal of applied physiology (Bethesda, Md. : 1985), Jan 30, 2014

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hyper... more Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and non-response is common. A better understanding of the mechanisms by which INO acts, may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, non-ventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsis-like condition (infusion of endotoxin) were blunted by INO 40ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (E...

Research paper thumbnail of Molecular Imaging In An Animal Model Of ARDS: Rethinking The Lung-Protective Mechanical Ventilation Strategy

D24. THE VILLAIN BEHIND VENTILATOR-INDUCED LUNG INJURY, 2012

Research paper thumbnail of Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma

BMC Pulmonary Medicine, 2014

Background: Improvements in asthma diagnosis and management require deeper understanding of the h... more Background: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL).

Research paper thumbnail of Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock

Journal of Infection, 2014

Objectives: It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis... more Objectives: It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis. The aim of the present study was to investigate if glucocorticoid receptor (GR) expression and function is impaired in lipopolysaccharide (LPS) induced shock, and whether the time point for start of glucocorticoid treatment affects the outcome. Methods: Male C57BL/6J mice were administered LPS i.p. and GR expression and binding ability in blood and spleen leukocytes were analysed by flow cytometry. GR translocation was analysed using Image Stream technique. The effect of dexamethasone treatment started 2 h before or 2, 12 or 36 h after LPS administration on survival was studied. Results: Despite increased GR expression in neutrophils after LPS administration, the GR binding capacity was reduced. In addition, GR translocation was decreased in neutrophils and T lymphocytes from endotoxic mice at 12 h compared to control animals. Dexamethasone treatment improved survival only when started early (2 h) after LPS administration. Conclusion: The decreased glucocorticoid responsiveness displayed by neutrophils, in combination with their increased numbers, may explain why survival is increased only when dexamethasone treatment is given early during LPS induced shock.

Research paper thumbnail of Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction without affecting endogenous pulmonary nitric oxide production

Intensive Care Medicine, 2012

Research paper thumbnail of Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia

Critical Care, 2013

Introduction: We hypothesized that mechanical ventilation per se increases abdominal edema and in... more Introduction: We hypothesized that mechanical ventilation per se increases abdominal edema and inflammation in sepsis and tested this in experimental endotoxemia.

Research paper thumbnail of Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis

Journal of Infection, 2013

Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesiz... more Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesized that failure to respond to steroid therapy may be caused by decreased expression and/or function of glucocorticoid receptors (GR) and studied this in a mouse model of Staphylococcus aureus sepsis. The impact of timing of dexamethasone treatment was also investigated. Male C57BL/6J mice were intravenously inoculated with S. aureus and GR expression and binding ability in blood, spleen and lymph nodes were analysed by means of flow cytometry. GR translocation was analysed using Image Stream. Septic mice were administered dexamethasone at 22, 26, 48, 72 and 96 h after inoculation and body weight, as a sign of dehydration, was observed. GR expression was decreased in septic animals, but not the ligand binding capacity. GR translocation was decreased in septic mice compared to control animals. Early dexamethasone treatment (22 and 26 h) improved clinical outcome as studied by weight gain compared to when treatment was started at later time points (48, 72 and 96 h). Our data provide evidence that GR expression is progressively decreased in experimental sepsis and that dexamethasone has a decreased ability to translocate into the cell nucleus. This may explain why steroid treatment is only beneficial when administered early in sepsis and septic shock.

Research paper thumbnail of 68Ga Labeled TNF-± For Localization Of Experimental Ventilator Induced Lung Inflammation

B95. DIAGNOSING AND MANAGING VENTILATOR INDUCED LUNG INJURY, 2010

Research paper thumbnail of Matrix Metalloproteinases -8 and -9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study

PLOS ONE, 2015

Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation an... more Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Plasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.

Research paper thumbnail of Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung

Critical care medicine, Jan 5, 2015

PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung ... more PET with [F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Prospective laboratory investigation. University animal research laboratory. Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were...

Research paper thumbnail of No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist

Journal of applied physiology (Bethesda, Md. : 1985), Jan 30, 2014

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hyper... more Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and non-response is common. A better understanding of the mechanisms by which INO acts, may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, non-ventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsis-like condition (infusion of endotoxin) were blunted by INO 40ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (E...

Research paper thumbnail of Molecular Imaging In An Animal Model Of ARDS: Rethinking The Lung-Protective Mechanical Ventilation Strategy

D24. THE VILLAIN BEHIND VENTILATOR-INDUCED LUNG INJURY, 2012

Research paper thumbnail of Comprehensive multiplexed protein quantitation delineates eosinophilic and neutrophilic experimental asthma

BMC Pulmonary Medicine, 2014

Background: Improvements in asthma diagnosis and management require deeper understanding of the h... more Background: Improvements in asthma diagnosis and management require deeper understanding of the heterogeneity of the complex airway inflammation. We hypothesise that differences in the two major inflammatory phenotypes of asthma; eosinophilic and neutrophilic asthma, will be reflected in the lung protein expression profile of murine asthma models and can be delineated using proteomics of bronchoalveolar lavage (BAL).

Research paper thumbnail of Glucocorticoid receptor function is decreased in neutrophils during endotoxic shock

Journal of Infection, 2014

Objectives: It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis... more Objectives: It remains unclear whether glucocorticoid treatment can improve the outcome of sepsis. The aim of the present study was to investigate if glucocorticoid receptor (GR) expression and function is impaired in lipopolysaccharide (LPS) induced shock, and whether the time point for start of glucocorticoid treatment affects the outcome. Methods: Male C57BL/6J mice were administered LPS i.p. and GR expression and binding ability in blood and spleen leukocytes were analysed by flow cytometry. GR translocation was analysed using Image Stream technique. The effect of dexamethasone treatment started 2 h before or 2, 12 or 36 h after LPS administration on survival was studied. Results: Despite increased GR expression in neutrophils after LPS administration, the GR binding capacity was reduced. In addition, GR translocation was decreased in neutrophils and T lymphocytes from endotoxic mice at 12 h compared to control animals. Dexamethasone treatment improved survival only when started early (2 h) after LPS administration. Conclusion: The decreased glucocorticoid responsiveness displayed by neutrophils, in combination with their increased numbers, may explain why survival is increased only when dexamethasone treatment is given early during LPS induced shock.

Research paper thumbnail of Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction without affecting endogenous pulmonary nitric oxide production

Intensive Care Medicine, 2012

Research paper thumbnail of Mechanical ventilation worsens abdominal edema and inflammation in porcine endotoxemia

Critical Care, 2013

Introduction: We hypothesized that mechanical ventilation per se increases abdominal edema and in... more Introduction: We hypothesized that mechanical ventilation per se increases abdominal edema and inflammation in sepsis and tested this in experimental endotoxemia.

Research paper thumbnail of Expression of the glucocorticoid receptor is decreased in experimental Staphylococcus aureus sepsis

Journal of Infection, 2013

Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesiz... more Glucocorticoid treatment in septic shock remains controversial after recent trials. We hypothesized that failure to respond to steroid therapy may be caused by decreased expression and/or function of glucocorticoid receptors (GR) and studied this in a mouse model of Staphylococcus aureus sepsis. The impact of timing of dexamethasone treatment was also investigated. Male C57BL/6J mice were intravenously inoculated with S. aureus and GR expression and binding ability in blood, spleen and lymph nodes were analysed by means of flow cytometry. GR translocation was analysed using Image Stream. Septic mice were administered dexamethasone at 22, 26, 48, 72 and 96 h after inoculation and body weight, as a sign of dehydration, was observed. GR expression was decreased in septic animals, but not the ligand binding capacity. GR translocation was decreased in septic mice compared to control animals. Early dexamethasone treatment (22 and 26 h) improved clinical outcome as studied by weight gain compared to when treatment was started at later time points (48, 72 and 96 h). Our data provide evidence that GR expression is progressively decreased in experimental sepsis and that dexamethasone has a decreased ability to translocate into the cell nucleus. This may explain why steroid treatment is only beneficial when administered early in sepsis and septic shock.