| 1. |
- Ahlner, J, et al.
(författare)
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CYP2D6, serotonin and suicide
- 2010
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Ingår i: Pharmacogenomics. - 1744-8042. ; 11:7, s. 903-905
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Isacsson, G., et al.
(författare)
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Antidepressant medication prevents suicide in depression
- 2010
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 122:6, s. 454-460
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increasing use of antidepressants. To investigate on the individual level the hypothesis that antidepressant medication was a causal factor. Method: Data on the toxicological detection of antidepressants in 18 922 suicides in Sweden 1992-2003 were linked to registers of psychiatric hospitalization as well as registers with sociodemographic data. Results: The probability for the toxicological detection of an antidepressant was lowest in the non-suicide controls, higher in suicides, and even higher in suicides that had been psychiatric inpatients but excluding those who had been in-patients for the treatment of depression. Conclusion: The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.
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| 3. |
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| 4. |
- Jornil, J, et al.
(författare)
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A poor metabolizer of both CYP2C19 and CYP2D6 identified by mechanistic pharmacokinetic simulation in a fatal drug poisoning case involving venlafaxine
- 2013
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Ingår i: Forensic Science International. - : Elsevier. - 0379-0738 .- 1872-6283. ; 226:1-3, s. E26-E31
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Tidskriftsartikel (refereegranskat)abstract
- We present a fatal drug poisoning case involving venlafaxine (VEN). The deceased took his medication regularly (including 150 mg VEN twice daily), and nothing in the case or autopsy findings pointed towards suicide. The toxicological assessment concluded that the cause of death was most likely due to a poisoning with a combination of VEN, oxycodone and ethanol, and the manner of death was considered to be an accident. The blood concentration of VEN was high (4.5 mg/kg), and the ratio of the VEN metabolite O-desmethylvenlafaxine (ODV) to VEN was exceptionally low (0.006). Mechanistic pharmacokinetic simulations suggested that the low metabolite ratio was the result of combined poor metabolizer (PM) status of cytochrome P450 (CYP) 2C19 and CYP2D6. This hypothesis was confirmed by genetic analysis. Simulations revealed that it was likely that the combined missing CYP2D6 and CYP2C19 activity would cause higher concentrations of VEN, but the simulations also suggested that there could be additional reasons to explain the high VEN concentration found in this case. Thus, it seems likely that the potentially toxic VEN concentration was caused by reduced metabolic capacity. The simulations combined with genotyping were considered very useful in this fatal drug poisoning case.
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| 5. |
- Weininger, Ulrich, et al.
(författare)
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Protein conformational exchange measured by H-1 R-1 rho relaxation dispersion of methyl groups
- 2013
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Ingår i: Journal of Biomolecular NMR. - : Springer Verlag (Germany). - 0925-2738 .- 1573-5001. ; 57:1, s. 47-55
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Tidskriftsartikel (refereegranskat)abstract
- Activated dynamics plays a central role in protein function, where transitions between distinct conformations often underlie the switching between active and inactive states. The characteristic time scales of these transitions typically fall in the microsecond to millisecond range, which is amenable to investigations by NMR relaxation dispersion experiments. Processes at the faster end of this range are more challenging to study, because higher RF field strengths are required to achieve refocusing of the exchanging magnetization. Here we describe a rotating-frame relaxation dispersion experiment for H-1 spins in methyl (CHD2)-C-13 groups, which improves the characterization of fast exchange processes. The influence of H-1-H-1 rotating-frame nuclear Overhauser effects (ROE) is shown to be negligible, based on a comparison of R (1 rho) relaxation data acquired with tilt angles of 90A degrees and 35A degrees, in which the ROE is maximal and minimal, respectively, and on samples containing different H-1 densities surrounding the monitored methyl groups. The method was applied to ubiquitin and the apo form of calmodulin. We find that ubiquitin does not exhibit any H-1 relaxation dispersion of its methyl groups at 10 or 25 A degrees C. By contrast, calmodulin shows significant conformational exchange of the methionine methyl groups in its C-terminal domain, as previously demonstrated by H-1 and C-13 CPMG experiments. The present R (1 rho) experiment extends the relaxation dispersion profile towards higher refocusing frequencies, which improves the definition of the exchange correlation time, compared to previous results.
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