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Papers by Mårten Sandberg
Biochemical Journal
A newly designed cyclic AMP (cAMP) analogue, , and 8-(p-chlorophenylthio)-cAMP (8-pCPT-cAMP) were... more A newly designed cyclic AMP (cAMP) analogue, , and 8-(p-chlorophenylthio)-cAMP (8-pCPT-cAMP) were compared with respect to their chemical and biological properties in order to assess their potential as activators of the cAMP-dependent protein kinases (cAMP-PK) in intact cells. Sp-5,6-DCl-cBiMPS was shown to be both a potent and specific activator of purified cAMP-PK and of cAMP-PK in platelet membranes, whereas 8-pCPT-cAMP proved to be a potent activator of cAMP-PK and cyclic-GMP-dependent protein kinase (cGMP-PK) both as purified enzymes and in platelet membranes. Sp-5,6-DCl-cBiMPS was not significantly hydrolysed by three types of cyclic nucleotide phosphodiesterases, whereas 8-pCPT-cAMP (and 8-bromo-cAMP) was hydrolysed to a significant extent by the Ca2+/calmodulin-dependent phosphodiesterase and by the cGMP-inhibited phosphodiesterase. The apparent lipophilicity, a measure of potential cell-membrane permeability, of Sp-5,6-DCI-cBiMPS was higher than that of 8-pCPT-cAMP. Extracellular application of Sp-5,6-DCl-cBiMPS to intact human platelets reproduced the pattern of protein phosphorylation induced by prostaglandin E1, a cAMP-increasing inhibitor of platelet activation. In intact platelets, Sp-5,6-DCl-cBiMPS was also more effective than 8-pCPT-cAMP in inducing quantitative phosphorylation of the 46/50 kDa vasodilator-stimulated phosphoprotein (VASP), a major substrate of cAMP-PK in platelets. As observed with prostaglandin E1, pretreatment of human platelets with Sp-5,6-DCl-cBiMPS prevented the aggregation induced by thrombin. The results suggest that Sp-5,6-DCl-cBiMPS is a very potent and specific activator of cAMP-PK in cell extracts and intact cells and, in this respect, is superior to any other cAMP analogue used for intact-cell studies. In contrast with 8-pCPT-cAMP, Sp-5,6-DCl-cBiMPS can be used to distinguish the signal-transduction pathways mediated by cAMP-PK and cGMP-PK.
Molecular Pharmacology
The role of the cGMP-dependent protein kinase (cGK) and one of its major substrates, the vasodila... more The role of the cGMP-dependent protein kinase (cGK) and one of its major substrates, the vasodilator-stimulated phosphoprotein (VASP), in the regulation of a receptor-evoked calcium response was investigated. The human type I beta cGK was stably transfected in human embryonic kidney 293 cells and Swiss mouse 3T6 fibroblasts, which contained significant or no detectable levels of the focal adhesion protein VASP, respectively. Western blot analysis and protein kinase activity measurements demonstrated an 8-fold overexpression of cGK-I beta in 293 cells (7-fold in 3T6 cells), representing an intracellular cGK concentration of 0.33 microM. In experiments with intact 293 cells expressing cGK-I beta, beta-phenyl-1,N2-etheno-cGMP and 8-(p-chlorophenylthio)-cGMP were capable of converting up to 30-40% of the 46-kDa VASP to its 50-kDa phospho- form, equivalent to results observed with cGMP analogs that cause a marked inhibition of the stimulated Ca2+ transient in intact human platelets. In c...
Acta anaesthesiologica Scandinavica, Jan 17, 2015
Anaesthesiologists from Oslo University Hospital have transported patients with severe oxygenatio... more Anaesthesiologists from Oslo University Hospital have transported patients with severe oxygenation failure with inhaled nitric oxide (usually 20 ppm) from other hospitals to a tertiary care centre since 2002 in an effort to reduce the number of patients that otherwise would require transport with ongoing extracorporeal membrane oxygenation. The aim of this study was to evaluate the patient safety during transport with inhaled nitric oxide. All patient transports with ongoing nitric oxide treatment undertaken from 2003 to 2012 were identified in the transport database. The frequency of adverse events and their impact on patient safety were studied in addition to response to inhaled nitric oxide and adjusted intensive care treatment and time aspects of the transports. Information about in-hospital treatment and survival were extracted from the hospital patient records. Adverse events were recorded in 12 of the 104 transports. Seven of the adverse events were due to malfunctioning tech...
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2009
Dear Sir, I read with interest the recently published paper by Rehn and coworkers about field tri... more Dear Sir, I read with interest the recently published paper by Rehn and coworkers about field triage in trauma . The topic is interesting and improved quality of the work and information flow from the scene-of-the-accident to the emergency department can save lives. However, some of the conclusions drawn by the authors can be challenged.
Scandinavian journal of trauma, resuscitation and emergency medicine, 2015
Physicians in prehospital care must be proficient in critical care procedures. Procedure proficie... more Physicians in prehospital care must be proficient in critical care procedures. Procedure proficiency requires a combination of training, experience and continuous clinical exposure. Most physicians in helicopter emergency medical service (HEMS) in Norway are well-trained and experienced anaesthesiologists, but we know little about their exposure to critical care procedures in the prehospital arena. This knowledge is required to plan clinical training and in-hospital practice to maintain core competences for a HEMS physician. We collected survey data on critical care procedures performed by physicians at three HEMS bases in Norway for a one-year period. To correct for differences in duty time between physicians, the expected number of procedures performed in a full time engagement at each HEMS base was calculated. Data was analysed using descriptive statistics and expected procedure volume at each base was compared using one-way between group analysis of variance. We received data fr...
Journal of Steroid Biochemistry, 1987
Scandinavian journal of trauma, resuscitation and emergency medicine, 2015
Despite numerous studies on prehospital airway management, results are difficult to compare due t... more Despite numerous studies on prehospital airway management, results are difficult to compare due to inconsistent or heterogeneous data. The objective of this study was to assess advanced airway management from international physician-staffed helicopter emergency medical services. We collected airway data from 21 helicopter emergency medical services in Australia, England, Finland, Hungary, Norway and Switzerland over a 12-month period. A uniform Utstein-style airway template was used for collecting data. The participating services attended 14,703 patients on primary missions during the study period, and 2,327 (16 %) required advanced prehospital airway interventions. Of these, tracheal intubation was attempted in 92 % of the cases. The rest were managed with supraglottic airway devices (5 %), bag-valve-mask ventilation (2 %) or continuous positive airway pressure (0.2 %). Intubation failure rates were 14.5 % (first-attempt) and 1.2 % (overall). Cardiac arrest patients showed signific...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 25, 2008
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 10, 1999
Phosphodiesterases are enzymes that catalyze the degradation of the cyclic nucleotides, cyclic AM... more Phosphodiesterases are enzymes that catalyze the degradation of the cyclic nucleotides, cyclic AMP and cyclic GMP, to the corresponding 5' nucleotide monophosphates. Ten different phosphodiesterase families have been described to date. These enzymes exist as homodimers and there is structural similarity between the different families. However, they differ in several respects like selectivity for cyclic nucleotides, sensitivity for inhibitors and activators, physiological roles and tissue distribution. Interest in these enzymes has increased tremendously, both within the medical community and in the general public as a consequence of sildenafil (Viagra), the medication recently introduced for the treatment of erectile dysfunction. Sildenafil mediates its effects by inhibiting phosphodiesterase 5. Some biochemical and molecular biological aspects of this enzyme are presented here. To achieve satisfactory erection, normal penile innervation is required. Nitrogen monoxide, the trans...
Biochemical Journal
A newly designed cyclic AMP (cAMP) analogue, , and 8-(p-chlorophenylthio)-cAMP (8-pCPT-cAMP) were... more A newly designed cyclic AMP (cAMP) analogue, , and 8-(p-chlorophenylthio)-cAMP (8-pCPT-cAMP) were compared with respect to their chemical and biological properties in order to assess their potential as activators of the cAMP-dependent protein kinases (cAMP-PK) in intact cells. Sp-5,6-DCl-cBiMPS was shown to be both a potent and specific activator of purified cAMP-PK and of cAMP-PK in platelet membranes, whereas 8-pCPT-cAMP proved to be a potent activator of cAMP-PK and cyclic-GMP-dependent protein kinase (cGMP-PK) both as purified enzymes and in platelet membranes. Sp-5,6-DCl-cBiMPS was not significantly hydrolysed by three types of cyclic nucleotide phosphodiesterases, whereas 8-pCPT-cAMP (and 8-bromo-cAMP) was hydrolysed to a significant extent by the Ca2+/calmodulin-dependent phosphodiesterase and by the cGMP-inhibited phosphodiesterase. The apparent lipophilicity, a measure of potential cell-membrane permeability, of Sp-5,6-DCI-cBiMPS was higher than that of 8-pCPT-cAMP. Extracellular application of Sp-5,6-DCl-cBiMPS to intact human platelets reproduced the pattern of protein phosphorylation induced by prostaglandin E1, a cAMP-increasing inhibitor of platelet activation. In intact platelets, Sp-5,6-DCl-cBiMPS was also more effective than 8-pCPT-cAMP in inducing quantitative phosphorylation of the 46/50 kDa vasodilator-stimulated phosphoprotein (VASP), a major substrate of cAMP-PK in platelets. As observed with prostaglandin E1, pretreatment of human platelets with Sp-5,6-DCl-cBiMPS prevented the aggregation induced by thrombin. The results suggest that Sp-5,6-DCl-cBiMPS is a very potent and specific activator of cAMP-PK in cell extracts and intact cells and, in this respect, is superior to any other cAMP analogue used for intact-cell studies. In contrast with 8-pCPT-cAMP, Sp-5,6-DCl-cBiMPS can be used to distinguish the signal-transduction pathways mediated by cAMP-PK and cGMP-PK.
Molecular Pharmacology
The role of the cGMP-dependent protein kinase (cGK) and one of its major substrates, the vasodila... more The role of the cGMP-dependent protein kinase (cGK) and one of its major substrates, the vasodilator-stimulated phosphoprotein (VASP), in the regulation of a receptor-evoked calcium response was investigated. The human type I beta cGK was stably transfected in human embryonic kidney 293 cells and Swiss mouse 3T6 fibroblasts, which contained significant or no detectable levels of the focal adhesion protein VASP, respectively. Western blot analysis and protein kinase activity measurements demonstrated an 8-fold overexpression of cGK-I beta in 293 cells (7-fold in 3T6 cells), representing an intracellular cGK concentration of 0.33 microM. In experiments with intact 293 cells expressing cGK-I beta, beta-phenyl-1,N2-etheno-cGMP and 8-(p-chlorophenylthio)-cGMP were capable of converting up to 30-40% of the 46-kDa VASP to its 50-kDa phospho- form, equivalent to results observed with cGMP analogs that cause a marked inhibition of the stimulated Ca2+ transient in intact human platelets. In c...
Acta anaesthesiologica Scandinavica, Jan 17, 2015
Anaesthesiologists from Oslo University Hospital have transported patients with severe oxygenatio... more Anaesthesiologists from Oslo University Hospital have transported patients with severe oxygenation failure with inhaled nitric oxide (usually 20 ppm) from other hospitals to a tertiary care centre since 2002 in an effort to reduce the number of patients that otherwise would require transport with ongoing extracorporeal membrane oxygenation. The aim of this study was to evaluate the patient safety during transport with inhaled nitric oxide. All patient transports with ongoing nitric oxide treatment undertaken from 2003 to 2012 were identified in the transport database. The frequency of adverse events and their impact on patient safety were studied in addition to response to inhaled nitric oxide and adjusted intensive care treatment and time aspects of the transports. Information about in-hospital treatment and survival were extracted from the hospital patient records. Adverse events were recorded in 12 of the 104 transports. Seven of the adverse events were due to malfunctioning tech...
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 2009
Dear Sir, I read with interest the recently published paper by Rehn and coworkers about field tri... more Dear Sir, I read with interest the recently published paper by Rehn and coworkers about field triage in trauma . The topic is interesting and improved quality of the work and information flow from the scene-of-the-accident to the emergency department can save lives. However, some of the conclusions drawn by the authors can be challenged.
Scandinavian journal of trauma, resuscitation and emergency medicine, 2015
Physicians in prehospital care must be proficient in critical care procedures. Procedure proficie... more Physicians in prehospital care must be proficient in critical care procedures. Procedure proficiency requires a combination of training, experience and continuous clinical exposure. Most physicians in helicopter emergency medical service (HEMS) in Norway are well-trained and experienced anaesthesiologists, but we know little about their exposure to critical care procedures in the prehospital arena. This knowledge is required to plan clinical training and in-hospital practice to maintain core competences for a HEMS physician. We collected survey data on critical care procedures performed by physicians at three HEMS bases in Norway for a one-year period. To correct for differences in duty time between physicians, the expected number of procedures performed in a full time engagement at each HEMS base was calculated. Data was analysed using descriptive statistics and expected procedure volume at each base was compared using one-way between group analysis of variance. We received data fr...
Journal of Steroid Biochemistry, 1987
Scandinavian journal of trauma, resuscitation and emergency medicine, 2015
Despite numerous studies on prehospital airway management, results are difficult to compare due t... more Despite numerous studies on prehospital airway management, results are difficult to compare due to inconsistent or heterogeneous data. The objective of this study was to assess advanced airway management from international physician-staffed helicopter emergency medical services. We collected airway data from 21 helicopter emergency medical services in Australia, England, Finland, Hungary, Norway and Switzerland over a 12-month period. A uniform Utstein-style airway template was used for collecting data. The participating services attended 14,703 patients on primary missions during the study period, and 2,327 (16 %) required advanced prehospital airway interventions. Of these, tracheal intubation was attempted in 92 % of the cases. The rest were managed with supraglottic airway devices (5 %), bag-valve-mask ventilation (2 %) or continuous positive airway pressure (0.2 %). Intubation failure rates were 14.5 % (first-attempt) and 1.2 % (overall). Cardiac arrest patients showed signific...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 25, 2008
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 10, 1999
Phosphodiesterases are enzymes that catalyze the degradation of the cyclic nucleotides, cyclic AM... more Phosphodiesterases are enzymes that catalyze the degradation of the cyclic nucleotides, cyclic AMP and cyclic GMP, to the corresponding 5' nucleotide monophosphates. Ten different phosphodiesterase families have been described to date. These enzymes exist as homodimers and there is structural similarity between the different families. However, they differ in several respects like selectivity for cyclic nucleotides, sensitivity for inhibitors and activators, physiological roles and tissue distribution. Interest in these enzymes has increased tremendously, both within the medical community and in the general public as a consequence of sildenafil (Viagra), the medication recently introduced for the treatment of erectile dysfunction. Sildenafil mediates its effects by inhibiting phosphodiesterase 5. Some biochemical and molecular biological aspects of this enzyme are presented here. To achieve satisfactory erection, normal penile innervation is required. Nitrogen monoxide, the trans...