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- Abrahamsson, Pernilla, 1972-
(författare)
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Methodological aspects on microdialysis sampling and measurements
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The microdialysis (MD) technique is widely spread and used both experimentally and in clinical practice. The MD technique allows continuous collection of small molecules such as glucose, lactate, pyruvate and glycerol. Samples are often analysed using the CMA 600 analyser, an enzymatic and colorimetric analyser. Data evaluating the performance of the CMA 600 analysis system and associated sample handling are sparse. The aim of this work was to identify sources of variability related to handling of microdialysis samples and sources of error associated with use of the CMA 600 analyser. Further, to develop and compare different application techniques of the microdialysis probes both within an organ and on the surface of an organ. Material and Methods: Papers I and II are mainly in vitro studies with the exception of the No Net Flux calibration method in paper I where a pig model (n=7) was used to examine the true concentration of glucose and urea in subcutaneous tissue. Flow rate, sampling time, vial and caps material and performance of the analyser device (CMA 600) were examined. In papers III and IV normoventilated anaesthetised pigs (n=33) were used. In paper III, heart ischemia was used as intervention to compare microdialysis measurements in the myocardium with corresponding measurements on the heart surface. In paper IV, microdialysis measurements in the liver parenchyma were compared with measurements on the liver surface in association with induced liver ischemia. All animal studies were approved by the Animal Experimental Ethics Committee at Umeå University Sweden. Results: In paper I we succeeded to measure true concentrations of glucose (4.4 mmol/L) and Urea (4.1 mmol/L) in subcutaneous tissue. Paper II showed that for a batch analyse of 24 samples it is preferred to store microdialysis samples in glass vials with crimp caps. For reliable results, samples should be centrifuged before analysis. Paper III showed a new application area for microdialysis sampling from the heart, i.e. surface sampling. The surface probe and myocardial probe (in the myocardium) showed a similar pattern for glucose, lactate and glycerol during baseline, short ischemic and long ischemic interventions. In paper IV, a similar pattern was observed as in paper III, i.e. data obtained from the probe on the liver surface showed no differences compared with data from the probe in liver parenchyma for glucose, lactate and glycerol concentrations during baseline, ischemic and reperfusion interventions. Conclusion: The MD technique is adequate for local metabolic monitoring, but requires methodological considerations before starting a new experimental serie. It is important to consider factors such as flow rate, sampling time and handling of samples in association with the analysis device chosen. The main finding in this thesis is that analyses of glucose, lactate and glycerol in samples from the heart surface and liver surface reflect concentrations sampled from the myocardium and liver parenchyma, respectively.
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| 2. |
- Amer-Wåhlin, Isis, et al.
(författare)
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Fetal cerebral energy metabolism and electrocardiogram during experimental umbilical cord occlusion and resuscitation.
- 2010
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Ingår i: Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 23:2, s. 158-166
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The purpose of this experimental study was to elucidate alterations in fetal energy metabolism in relation to ECG changes during extreme fetal asphyxia, postnatal resuscitation and the immediate post-resuscitatory phase. Study design. Five near-term fetal sheep were subjected to umbilical cord occlusion until cardiac arrest followed by delivery, resuscitation and postnatal pressure-controlled ventilation. Four sheep served as sham controls and were delivered immediately after ligation of the umbilical cord. Fetal ECG was analysed online for changes of the ST segment. Fetal metabolism was monitored by intracerebral and subcutaneous microdialysis catheters. Results. Fetal ECG reacted on cord occlusion with an increase in the T-wave height followed by changes in intracerebral levels of oxidative parameters. Cerebral lactate/pyruvate ratio and glutamate increased to median (range) of 240 (200-744) and 34.0 (22.6-60.5) mmol/l, respectively; both parameters returned to baseline after resuscitation. Cerebral glucose decreased to 0.1 (0.08-0.12) mmol/l after occlusion and increased above baseline upon resuscitation. In subcutaneous tissue as well as blood the increase in lactate occurred with a delay compared to cerebral levels. Conclusion. The fetal ECG changes related to asphyxia preceded the increase in excitotoxicity as determined by increase in cerebral glutamate during asphyxia. Cerebral lactate increase was superior to subcutaneous lactate increase.
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| 4. |
- Bergström, Sara K., et al.
(författare)
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Screening of microdialysates taken before and after induced liver damage; on-line solid phase extraction-electrospray ionization-mass spectrometry
- 2006
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1120:1-2, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- A novel method is described to follow known and unknown compounds in biological processes using microdialysis sampling and mass spectrometric detection. By implementation of internal standard, desalting/enrichment for the sample work-up, and multivariate data analysis, this methodology is a basis for future applications in early diagnosis of diseases and organ damage, as a complement to the routinely used clinical methods for biological samples. The present study includes screening without specific target analytes, of samples collected by microdialysis from liver of anaesthetized rats before and after local damage to this organ. Sample series were classified by principal component analysis, and the stimulation was identified in the chemical patterns produced by the presented analytical tool.
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| 7. |
- Chaurasia, Chandra S., et al.
(författare)
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AAPS-FDA workshop white paper : microdialysis principles, application and regulatory perspectives
- 2007
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:5, s. 1014-1025
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Tidskriftsartikel (refereegranskat)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.
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| 8. |
- Chaurasia, Chandra S., et al.
(författare)
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AAPS-FDA Workshop White Paper : microdialysis principles, application, and regulatory perspectives
- 2007
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:5, s. 589-603
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Tidskriftsartikel (refereegranskat)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.
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| 9. |
- Ederoth, Per, et al.
(författare)
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Blood-brain barrier transport of morphine in patients with severe brain trauma
- 2004
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 57:4, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. METHODS: Patients with traumatic brain injury, equipped with one to three microdialysis catheters in the brain and one in abdominal subcutaneous fat for metabolic monitoring, were studied. The cerebral catheter locations were classified as 'better' and 'worse' brain tissue, referring to the degree of injury. Morphine (10 mg) was infused intravenously over a 10-min period in seven patients in the intensive care setting. Tissue and plasma morphine concentrations were obtained during the subsequent 3-h period with microdialysis and regular blood sampling. RESULTS: The area under the concentration-time curve (AUC) ratio of unbound morphine in brain tissue to plasma was 0.64 (95% confidence interval 0.40, 0.87) in 'better' brain tissue (P < 0.05 vs. the subcutaneous fat/plasma ratio), 0.78 (0.49, 1.07) in 'worse' brain tissue and 1.00 (0.86, 1.13) in subcutaneous fat. The terminal half-life and T(max) were longer in the brain vs. plasma and fat, respectively. The relative recovery for morphine was higher in 'better' than in 'worse' brain tissue. The T(max) value tended to be shorter in 'worse' brain tissue. CONCLUSIONS: The unbound AUC ratio below unity in the 'better' human brain tissue demonstrates an active efflux of morphine across the blood-brain barrier. The 'worse' brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood-brain barrier.
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