| 1. |
- Sjöberg Lind, Ylva, et al.
(författare)
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Circulating levels of persistent organic pollutants (POPs) are associated with left ventricular systolic and diastolic dysfunction in the elderly
- 2013
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 123, s. 39-45
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE:Major risk factors for congestive heart failure (CHF) are myocardial infarction, hypertension, diabetes, atrial fibrillation, smoking, left ventricular hypertrophy (LVH) and obesity. However, since these risk factors only explain part of the risk of CHF, we investigated whether persistent organic pollutants (POPs) might also play a role.METHODS:In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, left ventricular ejection fraction, (EF), E/A-ratio and isovolumic relaxation time (IVRT), were determined by echocardiography and serum samples of 21 POPs were analyzed in serum measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 998 subjects all aged 70 years.RESULTS:In this cross-sectional analysis, high levels of several of the polychlorinated biphenyls (PCB congeners 99, 118, 105, 138, 153, and 180) and octachlorodibenzo-p-dioxin (OCDD) were significantly related to a decreased EF. Some POPs were also related to a decreased E/A-ratio (PCBs 206 and 209). All the results were adjusted for gender, hypertension, diabetes, smoking, LVH and BMI, and subjects with myocardial infarction or atrial fibrillation were excluded from the analysis.CONCLUSIONS:Circulating levels of POPs were related to impairments in both left ventricular systolic and diastolic function independently of major congestive heart failure risk factors, suggesting a possible role of POPs in heart failure.
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| 2. |
- Sjöberg Lind, Ylva, et al.
(författare)
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Persistent organic pollutants and abnormal geometry of the left ventricle in the elderly
- 2013
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 31:8, s. 1547-1553
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Tidskriftsartikel (refereegranskat)abstract
- Background:Established risk factors for left ventricular hypertrophy (LVH) are hypertension, diabetes, and obesity. However, as these risk factors explain only part of the variation in left ventricular mass, we investigated whether persistent organic pollutants (POPs) might also play a role in LVH, because exposure to polychlorinated biphenyl 126 induced cardiac growth in rats.Methods:In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), left ventricular mass index (LVMI), relative wall thickness (RWT), and geometric groups of LVH, were determined by echocardiography and 21 POPs were measured by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS) in 1016 individuals aged 70 years. All individuals with a history of myocardial infarction were excluded from analysis (n=72).Results:Several of the POPs were related to abnormal left ventricular geometry before adjustment for established risk factors, but lost in significance following adjustment. However, the pesticide hexachlorobenzene (HCB) levels were significantly related to RWT, and concentric left ventricular remodeling, also following adjustment for sex, blood pressure, antihypertensive treatment, diabetes, and BMI (Pandlt;0.0001).Conclusion:In this cross-sectional study, circulating levels of HCB were related to increased wall thickness of the left ventricle and concentric left ventricular remodeling, independently of LVH risk factors, suggesting a role of this environmental contaminant in abnormal growth of the left ventricle.
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| 3. |
- Rönn, Monika, et al.
(författare)
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Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344 rats
- 2013
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 303:1, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Prenatal exposure to bisphenol A (BPA) has been shown to induce obesity in rodents. To evaluate if exposure also later in life could induce obesity or liver damage we investigated these hypothesises in an experimental rat model.METHODS: From five to fifteen weeks of age, female Fischer 344 rats were exposed to BPA via drinking water (0.025, 0.25 or 2.5mgBPA/L) containing 5% fructose. Two control groups were given either water or 5% fructose solution. Individual weight of the rats was determined once a week. At termination magnetic resonance imaging was used to assess adipose tissue amount and distribution, and liver fat content. After sacrifice the left perirenal fat pad and the liver were dissected and weighed. Apolipoprotein A-I in plasma was analyzed by western blot.RESULTS:No significant effects on body weight or the weight of the dissected fad pad were seen in rats exposed to BPA, and MRI showed no differences in total or visceral adipose tissue volumes between the groups. However, MRI showed that liver fat content was significantly higher in BPA-exposed rats than in fructose controls (p=0.04). BPA exposure also increased the apolipoprotein A-I levels in plasma (p<0.0001).CONCLUSION: We found no evidence that BPA exposure affects fat mass in juvenile fructose-fed rats. However, the finding that BPA in combination with fructose induced fat infiltration in the liver at dosages close to the current tolerable daily intake (TDI) might be of concern given the widespread use of this compound in our environment.
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| 4. |
- Rönn, Monika, et al.
(författare)
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Quantification of total and visceral adipose tissue in fructose-fed rats using water-fat separated single echo MRI
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:9, s. E388-E395
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to setup a rodent model for modest weight gain and an MRI-based quantification of body composition on a clinical 1.5 T MRI system for studies of obesity and environmental factors and their possible association. Design and Methods: Twenty-four 4-week-old female Fischer rats were divided into two groups: one exposed group (n=12) and one control group (n 12). The exposed group was given drinking water containing fructose (5% for 7 weeks, then 20% for 3 weeks). The control group was given tap water. Before sacrifice, whole body MRI was performed to determine volumes of total and visceral adipose tissue and lean tissue. MRI was performed using a clinical 1.5 T system and a chemical shift based technique for separation of water and fat signal from a rapid single echo acquisition. Fat signal fraction was used to separate adipose and lean tissue. Visceral adipose tissue volume was quantified using semiautomated segmentation. After sacrifice, a perirenal fat pad and the liver were dissected and weighed. Plasma proteins were analyzed by Western blot. Results: The weight gain was 5.2% greater in rats exposed to fructose than in controls (P=0.042). Total and visceral adipose tissue volumes were 5.2 cm(3) (P=0.017) and 3.1 cm(3) (P=0.019) greater, respectively, while lean tissue volumes did not differ. The level of triglycerides and apolipoprotein A-I was higher (P=0.034, P=0.005, respectively) in fructose-exposed rats.
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| 5. |
- Wikgren, Mikael, et al.
(författare)
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Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE epsilon 3/epsilon 3 Subjects
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E epsilon 4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 epsilon 3/epsilon 3 carriers; 28 epsilon 4 carriers) aged 49-79 yr. Leukocyte telomere length correlated inversely with left (r(s) = -0.465; p = 0.011), right (r(s) = -0.414; p = 0.025), and total hippocampus volume (r(s) = -0.519; p = 0.004) among APOE epsilon 3/epsilon 3 carriers, but not among epsilon 4 carriers. However, the epsilon 4 carriers fit with the general correlation pattern exhibited by the epsilon 3/epsilon 3 carriers, as epsilon 4 carriers on average had longer telomeres and smaller hippocampi compared with epsilon 3/epsilon 3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain.
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| 6. |
- Abrikosov, Igor, et al.
(författare)
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Phase Stability and Elasticity of TiAlN
- 2011
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Ingår i: Materials. - : MDPI. - 1996-1944. ; 4:9, s. 1599-1618
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Tidskriftsartikel (refereegranskat)abstract
- We review results of recent combined theoretical and experimental studies of Ti1−xAlxN, an archetypical alloy system material for hard-coating applications. Theoretical simulations of lattice parameters, mixing enthalpies, and elastic properties are presented. Calculated phase diagrams at ambient pressure, as well as at pressure of 10 GPa, show a wide miscibility gap and broad region of compositions and temperatures where the spinodal decomposition takes place. The strong dependence of the elastic properties and sound wave anisotropy on the Al-content offers detailed understanding of the spinodal decomposition and age hardening in Ti1−xAlxN alloy films and multilayers. TiAlN/TiN multilayers can further improve the hardness and thermal stability compared to TiAlN since they offer means to influence the kinetics of the favorable spinodal decomposition and suppress the detrimental transformation to w-AlN. Here, we show that a 100 degree improvement in terms of w-AlN suppression can be achieved, which is of importance when the coating is used as a protective coating on metal cutting inserts.
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| 7. |
- Dahlén, Elsa, 1975-
(författare)
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Markers of subclinical atherosclerosis and arterial stiffness in type 2 diabetes
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Type 2 diabetes is a common disease with increased mortality and morbidity due to cardiovascular disease (CVD). This thesis is based on three studies that evaluated traditionally used and emerging risk markers to identify individuals with high-risk of developing CVD in middle-aged men and women with type 2 diabetes. One study was conducted to compare the equivalence between two different ultrasound techniques to measure intima-media thickness since IMT was used to evaluate subclinical atherosclerosis as a surrogate endpoint.Methods: Data from the cohort study, cardiovascular risk in type 2 diabetes – a prospective study in primary care (CARDIPP) was used in paper I, III and IV. In paper I, baseline data from the first 247 subjects was analysed. Associations between traditionally measured lipids, apolipoproteins, glycaemic control and low-grade inflammation and IMT were analysed.In paper III, the full baseline cohort, with data from 761 subjects from the CARDIPP study was cross-sectionally analysed regarding correlations between abdominal obesity measured as waist circumference (WC) and sagittal abdominal diameter (SAD), inflammatory markers and IMT and pulse wave velocity (PWV). In paper IV, the associations reported in paper I and III were prospectively investigated with data from the first year of follow-up four years after the baseline investigations in CARDIPP-revisited.In paper II a study was performed on 24 young healthy subjects, both men and women. IMT was measured in the common carotid artery (CCA) and in the abdominal aorta (AA), by two skilled ultrasonographers, with 2 different ultrasound techniques in a randomised order.Results: ApoB/apoA-I ratio (r=0.207, p=0.001), apoB (r=0.166, p=0.009) and non HDLcholesterol (nHDL-c) (0.129, p=0.046) correlated with IMT.In CCA IMT was equivalent using B-mode- and M-mode respectively. However in AA, IMT was 11.5% thicker using B-mode.Abdominal obesity were significantly correlated with; IL-6 and CRP (both p<0.001, WC and SAD respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001 WC and SAD respectively). Adjusting for age, sex, treatment with statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, SAD (p=0.047) but not WC, remained associated with IMT.There were significant correlations between apoB (r=0.144, p=0.03) and CRP (r=0.172, p=0.009) measured at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r=0.130, p=0.049), WC (r=0.147, p=0.027) and SAD (r=0.184, p=0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p=0.036).Conclusions: There was a significant association between apoB/apoA-I ratio and IMT. The association was independent of conventional lipids, CRP, glycaemic control and use of statins. Both SAD and WC were associated with inflammation, atherosclerosis and arterial stiffness. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC. Prospectively; apoB and CRP, but not LDL-cholesterol predicted increased subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.The two different ultrasound techniques, B-mode and M-mode, measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.
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| 8. |
- Dunberger, Gail, et al.
(författare)
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Cancer survivors' perception of participation in a long-term follow-up study.
- 2013
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Ingår i: Journal of medical ethics. - : BMJ. - 1473-4257 .- 0306-6800. ; 39:1, s. 41-5
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Tidskriftsartikel (refereegranskat)abstract
- Every year medical researchers make contact with a large number of cancer survivors with the aim of evaluating cancer treatment. For this reason we decided to investigate how Swedish cancer survivors perceived their participation in research studies focusing on the long-term consequences of being a survivor of gynaecological or urinary bladder cancer. Data were collected by means of two study-specific postal questionnaires, both consisting of questions covering physical symptoms, well-being and the experience of being a cancer survivor. Both questionnaires also included questions evaluating the participants' experience of being research subjects. The questionnaires were developed in close co-operation with cancer survivors. The study population consisted of 1068 cancer survivors. Of these, 95% (n=1003) reported that they thought the study was valuable and 54% (n=559) that they had been positively affected by participating. Four per cent (n=39) expressed that they had been negatively affected by their participation in the study. The vast majority of the cancer survivors thought that participating in their particular study was valuable.
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| 9. |
- Hedner, Thomas, et al.
(författare)
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Stora förändringar i den globala läkemedelsindustrin
- 2012
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Ingår i: Läkartidningen. - Stockholm. - 0023-7205 .- 1652-7518. ; 109:7, s. 324-325
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Den globala läkemedelsindustrin är under kraftig för- ändring. Under de senaste tio åren har 300 000 arbets- tillfällen lagts ner i »Big Pharma«. I stället utvecklas mindre, kreativa och »öppna« innovationsnätverk och organisationsstrukturer för att ta fram nya läkemedel, skriver Thomas Hedner och medförfattare.
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| 10. |
- Lind, Hans, et al.
(författare)
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High temperature phase decomposition in TixZryAlzN
- 2014
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Ingår i: AIP Advances. - : American Institute of Physics (AIP). - 2158-3226. ; 4:12, s. 127147-1-127147-9
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Tidskriftsartikel (refereegranskat)abstract
- Through a combination of theoretical and experimental observations we study the high temperature decomposition behavior of c-(TixZryAlzN) alloys. We show that for most concentrations the high formation energy of (ZrAl)N causes a strong tendency for spinodal decomposition between ZrN and AlN while other decompositions tendencies are suppressed. In addition we observe that entropic effects due to configurational disorder favor a formation of a stable Zr-rich (TiZr)N phase with increasing temperature. Our calculations also predict that at high temperatures a Zr rich (TiZrAl)N disordered phase should become more resistant against the spinodal decomposition despite its high and positive formation energy due to the specific topology of the free energy surface at the relevant concentrations. Our experimental observations confirm this prediction by showing strong tendency towards decomposition in a Zr-poor sample while a Zr-rich alloy shows a greatly reduced decomposition rate, which is mostly attributable to binodal decomposition processes. This result highlights the importance of considering the second derivative of the free energy, in addition to its absolute value in predicting decomposition trends of thermodynamically unstable alloys.
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