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- Eriksson, Anna, et al.
(författare)
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The novel tyrosine kinase inhibitor AKN-028 has significant antileukemic activity in cell lines and primary cultures of acute myeloid leukemia
- 2012
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 2, s. e81-
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Tidskriftsartikel (refereegranskat)abstract
- Aberrantly expressed tyrosine kinases have emerged as promising targets for drug development in acute myeloid leukemia (AML). We report that AKN-028, a novel tyrosine kinase inhibitor (TKI), is a potent FMS-like receptor tyrosine kinase 3 (FLT3) inhibitor (IC50=6 nM), causing dose-dependent inhibition of FLT3 autophosphorylation. Inhibition of KIT autophosphorylation was shown in a human megakaryoblastic leukemia cell line overexpressing KIT. In a panel of 17 cell lines, AKN-028 showed cytotoxic activity in all five AML cell lines included. AKN-028 triggered apoptosis in MV4-11 by activation of caspase 3. In primary AML samples (n=15), AKN-028 induced a clear dose-dependent cytotoxic response (mean IC50 1 μM). However, no correlation between antileukemic activity and FLT3 mutation status, or to the quantitative expression of FLT3, was observed. Combination studies showed synergistic activity when cytarabine or daunorubicin was added simultaneously or 24 h before AKN-028. In mice, AKN-028 demonstrated high oral bioavailability and antileukemic effect in primary AML and MV4-11 cells, with no major toxicity observed in the experiment. In conclusion, AKN-028 is a novel TKI with significant preclinical antileukemic activity in AML. Possible sequence-dependent synergy with standard AML drugs and good oral bioavailability has made it a candidate drug for clinical trials (ongoing).
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| 5. |
- Rådestad, I., et al.
(författare)
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Evaluation of care after stillbirth in Sweden based on mothers' gratitude
- 2011
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Ingår i: British journal of midwifery. - 0969-4900 .- 2052-4307. ; 19:10, s. 646-652
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Tidskriftsartikel (refereegranskat)abstract
- Caring routines in many countries for parents following the death of a baby have shifted over the last 40 years, from initial recommendations that parents should not see their baby, to the opposite in present day. This study aims to describe mothers' gratitude for the actions taken by health professionals in connection with the birth of their child. The study also examines whether the aspects of care for which they were grateful differed between mothers whose children died before and after 1990. Data was collected from 799 women via a questionnaire posted on the homepage of the Swedish National Infant Foundation. Women who gave birth to a stillborn child after 1990 expressed gratefulness more often than women who gave birth to a stillborn child before 1990, for several reasons including the help received in creating memories of their baby. The motherswere thankful for being supported in their motherhood, and that the staff encouraged them to see, hold and be with their baby.
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- Widén, Cecilia, et al.
(författare)
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Erythrocyte antioxidant protection of rose hips (Rosa spp.)
- 2012
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Ingår i: Oxidative Medicine and Cellular Longevity. - : Landes Bioscience / Hindawi Publishing Corporation. - 1942-0900 .- 1942-0994. ; , s. 621579-
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Tidskriftsartikel (refereegranskat)abstract
- Rose hips are popular in health promoting products as the fruits contain high content of bioactive compounds. The aim of this study was to investigate whether health benefits are attributable to ascorbic acid, phenols, or other rose-hip-derived compounds. Freeze-dried powder of rose hips was preextracted with metaphosphoric acid and the sample was then sequentially eluted on a C18 column. The degree of amelioration of oxidative damage was determined in an erythrocyte in vitro bioassay by comparing the effects of a reducing agent on erythrocytes alone or on erythrocytes pretreated with berry extracts. The maximum protection against oxidative stress, 59.4±4.0% (mean ± standard deviation), was achieved when incubating the cells with the first eluted meta-phosphoric extract. Removal of ascorbic acid from this extract increased the protection against oxidative stress to 67.9±1.9%. The protection from the 20% and 100% methanol extracts was 20.8±8.2% and 5.0±3.2%, respectively. Antioxidant uptake was confirmed by measurement of catechin by HPLC-ESI-MS in the 20% methanol extract. The fact that all sequentially eluted extracts studied contributed to protective effects on the erythrocytes indicates that rose hips contain a promising level of clinically relevant antioxidant protection.
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| 7. |
- Abrikosov, Igor, et al.
(författare)
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Importance of Thermally Induced Magnetic Excitations in First-principles Simulations of Elastic Properties of Transition Metal Alloys
- 2012
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Ingår i: Solid State Phenomena. - 1012-0394 .- 1662-9779. ; 190, s. 291-294
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the importance of accounting for the complex magnetic ground state and finite temperature magnetic excitations in theoretical simulations of structural and elastic properties of transition metal alloys. Considering Fe72Cr16Ni12 face centered cubic (fcc) alloy, we compare results of first-principles calculations carried out for ferromagnetic and non-magnetic states, as well as for the state with disordered local moments. We show that the latter gives much more accurate description of the elastic properties for paramagnetic alloys. We carry out a determination of the magnetic ground state for fcc Fe-Mn alloys, considering collinear, as well as non-collinear states, and show the sensitively of structural and elastic properties in this system to the detailed alignment between magnetic moments. We therefore conclude that it is essential to develop accurate models of the magnetic state for the predictive description of properties of transition metal alloys.
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| 10. |
- Gebhardt, T., et al.
(författare)
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The influence of additions of Al and Si on the lattice stability of fcc and hcp Fe-Mn random alloys
- 2011
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 23:24, s. 246003-
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the influence of additions of Al and Si on the lattice stability of face-centred-cubic (fcc) versus hexagonal-closed-packed (hcp) Fe-Mn random alloys, considering the influence of magnetism below and above the fcc Neel temperature. Employing two different ab initio approaches with respect to basis sets and treatment of magnetic and chemical disorder, we are able to quantify the predictive power of the ab initio methods. We find that the addition of Al strongly stabilizes the fcc lattice independent of the regarded magnetic states. For Si a much stronger dependence on magnetism is observed. Compared to Al, almost no volume change is observed as Si is added to Fe-Mn, indicating that the electronic contributions are responsible for stabilization/destabilization of the fcc phase.
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