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- Bulanova, Daria, et al.
(författare)
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Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
- 2017
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.
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- Elming, Sten-åke, et al.
(författare)
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The drift of the Fennoscandian and Ukrainian Shields during the Precambrian : a Palaeomagnetic analysis
- 1993
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Ingår i: Tectonophysics. - : Elsevier BV. - 0040-1951 .- 1879-3266. ; 223:3-4, s. 177-198
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Tidskriftsartikel (refereegranskat)abstract
- A revised Precambrian (2.85-0.6 Ga) Apparent Polar Wander Path (APWP) for the Fennoscandian Shield, based on a new compilation and analysis of data, is presented. In fitting the APW path to successive Grand Mean Palaeomagnetic poles (GMPs), we applied the spherical spline technique originally developed by Jupp and Kent in 1987. The position and orientation of the Fennoscandian Shield during 2.85-0.6 Ga was determined from the GMPs. Major palaeoclimatological findings are used to constrain the palaeomagnetic interpretation of palaeolatitudes. The general drift of Fennoscandia, from relatively high latitudes in the late Archaean-Early Proterozoic to nearly equatorial latitudes in the Middle Proterozoic, correlates with palaeoclimatological indications that a period of cold climate was followed by one of warm climate during this time interval. From the continuous APWP the APW velocities and latitudinal drift velocities of the shield were calculated. An accumulated APW curve was also calculated. The palaeomagnetic data are irregularly distributed and some periods are rather poorly represented. This means that the calculated velocities can sometimes be artifacts of sampling. Late Archaean and Early Proterozoic (2.85-1.90 Ga) data are too sparse to make these calculations meaningful and velocity calculations are therefore restricted to data of 1.90 Ga and younger ages. The accumulated APW curve shows a number of linear segments with varying slopes, indicating sudden changes in drift rate. During the Middle Proterozoic (1.90-1.35 Ga) there was a period when the rate of APW was constant and low and that of latitudinal drift also was low. This pattern changed at ca. 1.35 Ga, and the following Middle-Late Proterozoic period can be described by rapid APW and strongly fluctuating drift velocities. Jotnian rifting and the intrusion of numerous dyke swarms (at ca. 1.25 Ga) correlate with this shift in rate. These changes are attributed to changes in plate configuration. A new database for the Ukrainian Shield is also presented, and GMPs in the 2.32-1.20 Ga range are defined. The database is still inadequate and the comparison of the Ukrainian and Fennoscandian drift histories is therefore tentative. Similarities in position, latitudinal drift and rotation during the Early-Middle Proterozoic are, nevertheless, evident. A close relationship between the shields in this period is consistent with the low APW rate of Fennoscandia, indicating that Fennoscandia may have been part of a larger continent, including the Ukraine, at that time. At ca. 1.2 Ga, the latitudinal position of Ukraine differed significantly from that of Fennoscandia, suggesting that the large shield split up between ca. 1.35 and 1.2 Ga. This would explain the change in APW rate at 1.35 Ga. The subsequent increase in rate was due to a reduction in the size of the shield. The discrepancy in palaeopositions of Fennoscandia and Ukraine at 1.2 Ga led Mikhailova and Kravchenko to suggest a late Precambrian time (1.07-0.57 Ga) for the accreation of Fennoscandia to the East European Platform (EEP). This may be correct as the rate of APW for Fennoscandia decreased in the late Precambrian, reflecting such a consolidation.
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- Lahdentausta, L, et al.
(författare)
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The Use of Serum MMP-9 and TIMP-1 in Acute Coronary Syndrome
- 2018
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Ingår i: Journal of cardiovascular translational research. - : Springer Science and Business Media LLC. - 1937-5395 .- 1937-5387. ; 11:6, s. 526-527
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Liuba, P., et al.
(författare)
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Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass surgery of piglets
- 2011
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Ingår i: Cardiology in the Young. - 1467-1107. ; 21:S1, s. 70-70
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Konferensbidrag (refereegranskat)abstract
- Introduction: Cardiopulmonary bypass (CPB) surgery remains associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully clarified. Abnormalities in coronary flow and function have beensuggested to play an important role. A few prior studies suggested protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A prior to CPB surgery. Methods: Barrier-bred piglets (10-12 kg, n=20) were subjected to CPB with (n=10) or without (n=10) antegrade administration for 20 minutes of cardioplegic solution. Prior to surgery, half of animals from each group received 10-minute i.v. infusion of 100 mg/kg cyclosporine A. Left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, respectively. Results: Coronary peak flow velocity (cPFV) rose significantly after surgery, especially in cardioplegia group (p0.4). There was no difference in systolic myocardial function between groups at any timepoint. Conclusions: Cardioplegia during CPB surgery of piglets was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, intracoronary pretreatment with cyclosporine had no observable protective effect on coronary circulation or arrhythmia vulnerability after CPB surgery.
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| 8. |
- Liuba, Petru, et al.
(författare)
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Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice
- 2000
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Ingår i: Circulation. - 1524-4539. ; 102:9, s. 1039-1044
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E-knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation. METHODS AND RESULTS: Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of N:(G)-nitro-L-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P:<0.05 and P:<0.01, respectively). When administered together with L-NAME, diclofenac enhanced the relaxation of the L-NAME-pretreated aortas in infected mice at 2 weeks (P:<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (P:<0.1). No intimal thickening was detected at either time point. CONCLUSIONS: C pneumoniae impairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. These findings further support the role of C pneumoniae infection in atherosclerosis development.
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- Odermarsky, M., et al.
(författare)
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Human Leucocyte Antigen, Infections and Systemic Inflammatory Biomarkers in Early Atherosclerosis in Children and Adolescents with Type 1 Diabetes
- 2015
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Ingår i: Cardiology in the Young. - 1467-1107. ; 25:Suppl. 1, s. 33-33
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Konferensbidrag (refereegranskat)abstract
- Background: This prospective study focuses on factors associated with arterial damage in children with type 1 diabetes (T1D). Materials and Methods: Eighty children and adolescents with T1D (mean age 15, range: 8-20 yrs; mean diabetes duration 7, range: 0.5 to 19 years) were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. HLA genotypes were determined in dried spots of peripheral blood by polymerase chain reaction followed by hybridization assay. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results: cIMT progression (% change of cIMT from baseline) correlated inversely with the % changes of both CAC (p = 0.04, r=−0.3, n=62) and FMD (p=0.03, r=−0.3, n=67). RTI frequency correlated significantly with cIMT progression irre- spective of age, diabetes duration, BMI, and HbA1c (p=0.03, r=0.3, in multivariate analysis). When patients were divided in relation to DQ2/8 genotype and RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with CRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions: Diabetes-risk genotype DQ2/8 and inflammation con- tribute to vascular changes in children and adolescents with T1D.
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