| 1. |
- Alamidi, Daniel, et al.
(författare)
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T1 Relaxation Time in Lungs of Asymptomatic Smokers.
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers.
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| 2. |
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| 3. |
- Berg, Tove, et al.
(författare)
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Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.
- 2014
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Ingår i: Pharmacology research & perspectives. - : Wiley. - 2052-1707. ; 2:4, s. e00054-
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Tidskriftsartikel (refereegranskat)abstract
- This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters.
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| 6. |
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| 7. |
- Bohman, Hannes, 1965-, et al.
(författare)
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Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders : a pilot study using non-invasive high frequency ultrasound
- 2010
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Ingår i: World Journal of Biological Psychiatry. - : Informa Healthcare. - 1562-2975 .- 1814-1412. ; 11:1, s. 71-75
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Tidskriftsartikel (refereegranskat)abstract
- Background. Growing evidence indicates that depression is an important risk factor for coronary heart disease. Thus, the aim of the present study has been to investigate if young women with adolescent onset and recurrent depressive disorders have signs of carotid intima and media changes already at the age of 30. Methods. Fifteen subjects with adolescent onset recurrent depressive disorders, mean age 31.5 years, were compared to 20 healthy women with a mean age of 39.6 years. The thickness of carotid artery intima and media was assessed, using non-invasive high-frequency ultrasound (25MHz). Results. The subjects with recurrent depressive disorders had significantly thicker carotid intima, significantly thinner carotid media and significantly higher intima/media ratio despite the fact that they were about 10 years younger than the healthy women. Hypertension, obesity or smoking could not explain the results. Conclusion. Already at the age of 30, subjects with recurrent depressive disorders with adolescent onset do have early signs of carotid intima and media changes, indicating a less healthy artery wall, despite otherwise no clinical signs of cardiovascular disease.
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| 8. |
- Broberg, Marita, 1973, et al.
(författare)
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Cell swelling precedes seizures induced by inhibition of astrocytic metabolism.
- 2008
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Ingår i: Epilepsy Res.. - : Elsevier BV. - 0920-1211. ; 80:2-3, s. 132-41
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Tidskriftsartikel (refereegranskat)abstract
- It is currently unknown what processes take place at the interface between non-ictal and ictal activity during seizure initiation. In this study, using paralysed awake rats, we focally inhibited astrocytic metabolism with fluorocitrate (FC), causing seizures. We measured changes in electroencephalogram (EEG) (0-300 Hz), and extracellular ion-concentrations during ictal onsets defining possible relationships with impedance-determined cell swelling. In animals showing ictal activity (69%) there were spike-wave discharges, spike-wave discharges followed by spreading depression and spreading depression without any discharges. In a high proportion of spike-wave discharges (>95%), just prior to the first spike-wave discharge, there was a decrease in the volume of the extracellular space. Following the initiation of cell swelling and prior to discharges, there were increases in high-frequency (150-300 Hz) EEG activity, increases in extracellular potassium- and decreases in extracellular calcium-concentrations. We suggest that EEG and ionic changes are not causative of cell swelling. Cell swelling due to metabolic failure in astrocytes at the injected site may release excitatory amino acids. At the same time, our results suggest ion homeostasis is not maintained and increased neuronal excitability and synchronisation occur. These could be the drivers changing normal brain activity into ictal activity.
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| 9. |
- Broberg, Marita, 1973, et al.
(författare)
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Spreading depression: Evidence of five electroencephalogram phases.
- 2014
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Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 92:10, s. 1384-1394
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Tidskriftsartikel (refereegranskat)abstract
- Spreading depression (SD), a self-propagating wave of astroglial and neuronal depolarization, is an accompaniment of several neurological disorders including epilepsy. Its well-described features are initial depolarization, followed by EEG flattening. In this in vivo study in awake animals, the relationship of SDs to epileptiform activity was re-examined. We assessed SDs generated by mechanical stimulation and by metabolic inhibition with fluorocitrate. In addition to identifying prolonged EEG depression, we identified two periods, one prior to and another during depression, characterized by increases in power of specific frequencies that were sometimes associated with epileptiform discharges. The first period was characterized by ripple activity close to the induction site (88% of SDs with intracortical electrodes). The second period was characterized by localized low-frequency spikes (100% with dural screw electrodes, 65% with intracortical electrodes). By using fluorocitrate to induce SDs, the initial period was also characterized by runs of spikes (52%). Finally, with SDs induced by both methods, there was a period at the end of depression when additional, unprovoked SDs occurred (20%). Five stages of SD were defined by these phenomena, in the order: excitation, depression, excitation, depression, SD, with metabolic inhibition enhancing the expression of epileptiform spiking.
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