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| 2. |
- Cibis, Merih, et al.
(författare)
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The Effect of Spatial and Temporal Resolution of Cine Phase Contrast MRI on Wall Shear Stress and Oscillatory Shear Index Assessment
- 2016
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:9, s. e0163316-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Wall shear stress (WSS) and oscillatory shear index (OSI) are associated with atherosclerotic disease. Both parameters are derived from blood velocities, which can be measured with phase-contrast MRI (PC-MRI). Limitations in spatiotemporal resolution of PC-MRI are known to affect these measurements. Our aim was to investigate the effect of spatiotemporal resolution using a carotid artery phantom. Methods A carotid artery phantom was connected to a flow set-up supplying pulsatile flow. MRI measurement planes were placed at the common carotid artery (CCA) and internal carotid artery (ICA). Two-dimensional PC-MRI measurements were performed with thirty different spatiotemporal resolution settings. The MRI flow measurement was validated with ultrasound probe measurements. Mean flow, peak flow, flow waveform, WSS and OSI were compared for these spatiotemporal resolutions using regression analysis. The slopes of the regression lines were reported in %/mm and %/100ms. The distribution of low and high WSS and OSI was compared between different spatiotemporal resolutions. Results The mean PC-MRI CCA flow (2.5 +/- 0.2mL/s) agreed with the ultrasound probe measurements (2.7 +/- 0.02mL/s). Mean flow (mL/s) depended only on spatial resolution (CCA:-13%/ mm, ICA:-49%/mm). Peak flow (mL/s) depended on both spatial (CCA:-13%/mm, ICA:17%/ mm) and temporal resolution (CCA:-19%/100ms, ICA:-24%/100ms). Mean WSS (Pa) was in inverse relationship only with spatial resolution (CCA:-19%/mm, ICA:-33%/mm). OSI was dependent on spatial resolution for CCA (-26%/mm) and temporal resolution for ICA (-16%/100ms). The regions of low and high WSS and OSI matched for most of the spatiotemporal resolutions (CCA: 30/30, ICA: 28/30 cases for WSS; CCA: 23/30, ICA: 29/30 cases for OSI). Conclusion We show that both mean flow and mean WSS are independent of temporal resolution. Peak flow and OSI are dependent on both spatial and temporal resolution. However, the magnitude of mean and peak flow, WSS and OSI, and the spatial distribution of OSI and WSS did not exhibit a strong dependency on spatiotemporal resolution.
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| 3. |
- Eriksson, Ulf J., et al.
(författare)
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Pathogenesis of diabetes-induced congenital malformations
- 2000
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Ingår i: Upsala Journal of Medical Sciences. - 0300-9734 .- 2000-1967. ; 105:2, s. 53-84
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Tidskriftsartikel (refereegranskat)abstract
- The increased rate of fetal malformation in diabetic pregnancy represents both a clinical problem and a research challenge. In recent years, experimental and clinical studies have given insight into the teratological mechanisms and generated suggestions for improved future treatment regimens. The teratological role of disturbances in the metabolism of inositol, prostaglandins, and reactive oxygen species has been particularly highlighted, and the beneficial effect of dietary addition of inositol, arachidonic acid and antioxidants has been elucidated in experimental work. Changes in gene expression and induction of apoptosis in embryos exposed to a diabetic environment have been investigated and assigned roles in the teratogenic processes. The diabetic environment appears to simultaneously induce alterations in several interrelated teratological pathways. The complex pathogenesis of diabetic embryopathy has started to unravel, and future research efforts will utilize both clinical intervention studies and experimental work that aim to characterize the human applicability and the cell biological components of the discovered teratological mechanisms.
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| 4. |
- Eriksson, Ulf J, et al.
(författare)
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Teratogenicity of 3-deoxyglucosone and diabetic embryopathy
- 1998
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 47:12, s. 1960-1966
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Tidskriftsartikel (refereegranskat)abstract
- The increased rate of embryonic dysmorphogenesis in diabetic pregnancy is correlated with the severity and duration of the concurrent hyperglycemia during early gestation. Whole embryo culture was used to investigate a possible association of hyperglycemia-induced disturbances of embryo development with tissue levels of the three alpha-oxoaldehydes: glyoxal, methylglyoxal, and 3-deoxyglucosone (3-DG). Rat embryos exposed to high glucose levels in vitro showed severe dysmorphogenesis and a 17-fold increased concentration of 3-DG compared with control embryos cultured in a low glucose concentration. Exogenous 3-DG (100 micromol/l) added to the medium of control cultures yielded an increased embryonic malformation rate and a 3-DG concentration similar to that of embryos cultured in high glucose. Addition of superoxide dismutase (SOD) to the culture medium decreased the malformation rates of embryos exposed to either high glucose or high 3-DG levels, but it did not decrease the high embryonic 3-DG concentrations caused by either agent. Our results implicate the potent glycating agent 3-DG as a teratogenic factor in diabetic embryopathy. In addition, the anti-teratogenic effect of SOD administration appears to occur downstream of 3-DG formation, suggesting that 3-DG accumulation leads to superoxide-mediated embryopathy.
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| 5. |
- Miller, V., et al.
(författare)
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Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study
- 2017
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 390:10107, s. 2037-2049
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Tidskriftsartikel (refereegranskat)abstract
- Background The association between intake of fruits, vegetables, and legumes with cardiovascular disease and deaths has been investigated extensively in Europe, the USA, Japan, and China, but little or no data are available from the Middle East, South America, Africa, or south Asia. Methods We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality. Findings Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3.91 (SD 2.77) servings per day. During a median 7.4 years (5.5-9.3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0.90, 95% CI 0.74-1.10, p(trend) = 0.1301), myocardial infarction (0.99, 0.74-1.31;p(trend) = 0.2033), stroke (0.92, 0.67-1.25;p(trend) = 0.7092), cardiovascular mortality (0.73, 0.53-1.02; p(trend) = 0.0568), non-cardiovascular mortality (0.84, 0.68-1.04; p trend = 0.0038), and total mortality (0.81, 0.68-0.96; p(trend) < 0.0001). The HR for total mortality was lowest for three to four servings per day (0.78, 95% CI 0.69-0.88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality. Interpretation Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day).
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| 6. |
- Pettersen, T., et al.
(författare)
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Sex differences in incidence of self-reported adverse drug reactions after percutaneous coronary intervention
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:Supplement_2
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDespite experiencing adverse drug reactions (ADRs) more often than men, the proportion of women participating in clinical drug trials is low. Thus, evidence for sex differences in the incidence of ADRs is limited.AimTo determine sex differences in incidence of self-reported ADRs after percutaneous coronary intervention (PCI). Further, to determine whether receiving information about ADRs is associated with sex.MethodsCONCARDPCI is a prospective multicentre cohort study (N=3417) conducted at seven referral PCI centres in two Nordic countries. Clinical data were collected from patients’ medical records. Socio-demographic characteristics were obtained by self-report after PCI. Two questions from the Heart Continuity of Care Questionnaire (HCCQ) were used to determine if information about potential ADRs was received before hospital discharge. De novo created questions were used to determine if patients reported ADRs from prescribed therapy. Questionnaires were distributed two- (T1), six- (T2), and twelve months (T3) after hospital discharge to assess the incidence of self-reported ADRs in a longitudinal perspective. Logistic regression was utilised to scrutinize the aims, reported as odds ratios (ORs) with 95% confidence intervals (CIs).ResultsPatients were predominantly male (78%), with a mean age of 65 years (SD 11). Female patients were older (68, SD 10). Acute coronary syndrome was the most frequent cause of admission for PCI (62%). At T1, 2656 of the included patients responded to the questions from the HCCQ. Of these, 1019 patients (39%) reported being informed of potential ADRs from prescribed therapy, 1075 patients (42%) reported not having been informed, 511 patients (20%) reported ‘Hard to decide’, and 51 (2%) reported ‘Not applicable’. Patients reporting ‘Hard to decide’ or ‘Not applicable’ were excluded from further analysis. Women were less likely to receive information than men (OR 0.58, CI 0.45 – 0.75, p<0.001). For the total study population, 42%, 49% and 40% reported ADRs at T1-T3 respectively. After adjusting for sociodemographic and clinical variables, the incidence of self-reported ADRs were significantly higher in women compared to men at T1 (OR 1.71, CI 1.36 – 2.15, p<0.001), T2 (OR 1.89, CI 1.49 – 2.38, p<0.001), and T3 (OR 1.79, CI 1.40 – 2.28, p<0.001).ConclusionWomen report significantly more ADRs from prescribed therapy than men after PCI. However, they are less likely to receive information about potential ADRs compared to men. Efforts to improve communication on ADRs and gender equity should be a priority.
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| 7. |
- Svensson, Kristian, et al.
(författare)
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The paternal allele of the H19 gene is silenced in a stepwise manner duringearly mouse development: the acetylation status of histones mya be involved in the generation of variegated expression patter
- 1998
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Ingår i: Development. - 0950-1991 .- 1477-9129. ; 125:1, s. 61-69
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Tidskriftsartikel (refereegranskat)abstract
- Transcriptional silencing can reflect heritable, epigenetic inactivation of genes, either singly or in groups, during the life-time of an organism. This phenomenon is exemplified by parent-of-origin-specific inactivation events (genomic imprinting) for a subset of mammalian autosomal genes, such as H19. Very little is known, however, about the timing and mechanism(s) of silencing of the paternal H19 allele during mouse development. Using a novel in situ approach, we present evidence that the silencing of the paternal H19 allele is progressive in the trophectodermal lineage during early mouse development and generates variegated expression patterns. The silencing process apparently involves recruitment of histone deacetylases since the mosaic paternal-specific H19 expression reappears in trichostatin A-treated mouse conceptuses, undergoing in vitro organogenesis. Moreover, the paternal H19 alleles of PatDup.d7 placentas, in which a region encompassing the H19 locus of chromosome 7 is bipaternally derived, partially escape the silencing process and are expressed in a variegated manner. We suggest that allele-specific silencing of H19 share some common features with chromatin-mediated silencing in position-effect variegation.
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| 8. |
- Wentzel, Parri, et al.
(författare)
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Induction of embryonic dysmorphogenesis by high glucose concentration, disturbed inositol metabolism, and inhibited protein kinase C activity
- 2001
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Ingår i: Teratology. - : Wiley. - 0040-3709 .- 1096-9926. ; 63:5, s. 193-201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to a diabetic environment causes excess reactive oxygen species (ROS), decreased prostaglandin E(2) (PGE(2)) concentration, and increased embryonic maldevelopment. The aim of the present work was to study whether embryonic dysmorphogenesis is also dependent on alterations of inositol and associated intracellular metabolites. METHODS: Day 9 rat embryos were cultured for 24 or 48 hr and evaluated for gene expression. Day 10 and day 11 embryos from normal and diabetic rats were also examined. RT-PCR was used to study embryonic gene expression of protein kinase C (PKC) and cytosolic phospholipase A(2) (cPLA(2)). RESULTS: Embryos exposed to 30 mmol/L glucose (30G), 500 or 750 micromol/L of scyllo-inositol (500SI or 750SI) had higher malformation score than control embryos cultured in 10 mmol/L glucose (10G). Adding 1.6 mmol/L inositol to the 30G or 750SI culture medium partly corrected these embryos, and completely normalized 500SI embryonic development. Adding 0.5 mmol/L N-acetylcysteine (NAC) or 280 nmol/L PGE(2) protected, and failed to protect, the SI-exposed embryos, respectively. 10G embryos exposed to the PKC inhibitor GF-109203X displayed dose-dependent dysmorphogenesis. Addition of 1.6 mmol/L inositol or 0.5 mmol/L NAC to the PKC-inhibitor-exposed 10G embryos largely normalized the outcome, whereas PGE(2) again failed to protect embryonic development. 30G culture tended to decrease the expression of cPLA(2) after 24 hr in vitro. We also found decreased mRNA levels of cPLA(2) in offspring of diabetic rats on gestational day 10 and of PKC on day 11, as compared with normal offspring. CONCLUSIONS: High glucose concentration causes dysmorphogenesis in embryos by an interaction of oxidative stress and inositol depletion.
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| 9. |
- Bertram, Melanie Y., et al.
(författare)
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Reducing the sodium content of high-salt foods : Effect on cardiovascular disease in South Africa
- 2012
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Ingår i: SAMJ South African Medical Journal. - Pretoria : South African Medical Association. - 0256-9574 .- 2078-5135. ; 102:9, s. 743-745
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Tidskriftsartikel (refereegranskat)abstract
- Background. Average salt intake in South African (SA) adults, 8.1 g/day, is higher than the 4 - 6 g/day recommended by the World Health Organization. Much salt consumption arises from non-discretionary intake (the highest proportion from bread, with contributions from margarine, soup mixes and gravies). This contributes to an increasing burden of hypertension and cardiovascular disease (CVD). Objectives. To provide SA-specific information on the number of fatal CVD events (stroke, ischaemic heart disease and hypertensive heart disease) and non-fatal strokes that would be prevented each year following a reduction in the sodium content of bread, soup mix, seasoning and margarine. Methods. Based on the potential sodium reduction in selected products, we calculated the expected change in population-level systolic blood pressure (SBP) and mortality due to CVD and stroke. Results. Proposed reductions would decrease the average salt intake by 0.85 g/person/day. This would result in 7 400 fewer CVD deaths and 4 300 less non-fatal strokes per year compared with 2008. Cost savings of up to R300 million would also occur. Conclusion. Population-wide strategies have great potential to achieve public health gains as they do not rely on individual behaviour or a well-functioning health system. This is the first study to show the potential effect of a salt reduction policy on health in SA.
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| 10. |
- Bhavadharini, B., et al.
(författare)
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Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries
- 2020
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Ingår i: Bmj Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study. Methods The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In thecross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). Forthe prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes). Results In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend<0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend<0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome. Conclusions Higher intake of whole fat (but not low fat) dairy was associated with alower prevalenceof MetS and most of its component factors, and with alower incidenceof hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes.
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