189 research outputs found
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Circulating Omegaâ3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study
Background: Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omegaâ3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results: In the communityâbased Cardiovascular Health Study, 3660 participants aged â„65 underwent brain MRI in 1992â1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992â1993 and related to crossâsectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest longâchain omegaâ3 PUFA quartile. Higher longâchain omegaâ3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediateâchain omegaâ3 PUFA alphaâlinolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alphaâlinolenic acid intake. Conclusions: Among older adults, higher phospholipid longâchain omegaâ3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of longâchain omegaâ3 PUFAs, on brain health in later life. The role of plantâderived alphaâlinolenic acid in brain health requires further investigation
Associations between long chain polyunsaturated fatty acids and cardiovascular lipid risk factors in youth with type 1 diabetes: SEARCH Nutrition Ancillary Study
In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Î5 and Î6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D)
Cruciferous vegetable feeding alters UGT1A1 activity: diet- and genotype-dependent changes in serum bilirubin in a controlled feeding trial.
Chemoprevention by isothiocyanates from cruciferous vegetables occurs partly through up-regulation of phase-II conjugating enzymes, such as UDP-glucuronosyl-transferases (UGT). UGT1A1 glucuronidates bilirubin, estrogens, and several dietary carcinogens. The UGT1A1*28 polymorphism reduces transcription compared to the wild-type, resulting in decreased enzyme activity. Isothiocyanates are metabolized by glutathione-S-transferases (GST); variants may alter isothiocyanate clearance, such that response to crucifers may vary by genotype. We evaluated, in a randomized, controlled, cross-over feeding trial in humans (n=70), 3 test diets, (single- and double-âdoseâ cruciferous and cruciferous plus apiaceous) compared to a fruit-and-vegetable-free basal diet. We measured serum bilirubin concentrations on days 0, 7, 11 and 14 of each 2-week feeding period to monitor UGT1A1 activity, and determined effects of UGT1A1*28 and GSTM1/GSTT1-null variants on response. Aggregate bilirubin response to all vegetable-containing diets was statistically significantly lower compared to the basal diet (p<0.03 for all). Within each UGT1A1 genotype, lower bilirubin concentrations were seen in: *1/*1 in both single and double-dose cruciferous diets compared to basal (p<0.03 for both); *1/*28 in double-dose cruciferous and cruciferous plus apiaceous compared to basal, and cruciferous plus apiaceous compared to single-dose cruciferous (p<0.02 for all); and *28/*28 in all vegetable-containing diets compared to basal (p<0.02 for all). Evaluation of the effects of diet stratified by GST genotype revealed some statistically significant genotypic differences however, the magnitude was similar and not statistically significant between genotypes. These results may have implications for altering carcinogen metabolism through dietary intervention, particularly among UGT1A1*28/*28 individuals
Modulation of human serum glutathione S-transferase-A1/2 concentration by cruciferous vegetables in a controlled feeding study is influenced by GSTM1 and GSTT1 genotypes
Glutathione S-transferases (GST) detoxify a wide range of carcinogens. Isothiocyanates (ITC), from cruciferous vegetables, are substrates for, and inducers of GST. GST variants may alter ITC clearance such that response to crucifers varies by genotype. In a randomized cross-over trial, we tested the hypothesis that changes in serum GSTA1/2 concentration in response to cruciferous vegetable feeding depends on GSTM1/GSTT1 genotype. Thirty-three men and 34 women (age 20-40 yr), ate four 14-day controlled diets: basal (vegetable-free), basal supplemented with 2 different doses of crucifers, (single-âdoseâ and double-âdoseâ) and single-dose cruciferous-plus-apiaceous vegetables, fed per kg body weight. Fasting bloods from days 0, 7, 11, and 14 of each diet period were analyzed for serum GSTA1/2 by ELISA. GSTA1/2 increased with single- and double-dose cruciferous compared to basal diet (10% and 13%, respectively; P = 0.02 and 0.004), but cruciferous-plus-apiaceous did not differ from basal (P = 0.59). Overall, GSTA1/2 was higher in GSTM1-null/GSTT1-null than GSTM1+/GSTT1+ individuals (4198 ± 338 and 3372 ± 183 pg/ml; P = 0.03). The formal interaction of genotype-by-diet was not statistically significant, but the GSTA1/2 increase during the single-dose cruciferous diet was among GSTM1-null/GSTT1-null individuals (by 28%; P = 0.008), largely explained by GSTM1-null/GSTT1-null men (by 41%; P = 0.01). GSTA1/2 increased during the double-dose cruciferous diet in both GSTM1-null/GSTT1-null men (by 35 %; P = 0.04) and GSTM1+/GSTT1+ men (by 26%; P = 0.01), but not in women. In summary, cruciferous vegetable supplementation increased GSTA1/2, but the effect was most marked in GSTM1-null/GSTT1-null men
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Associations of Plasma Phospholipid and Dietary Alpha Linolenic Acid With Incident Atrial Fibrillation in Older Adults: The Cardiovascular Health Study
Background: Few studies have examined the relationship of αâlinolenic acid (ALA 18:3nâ3), an intermediateâchain essential nâ3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF). Methods and Results: The study population included participants from the Cardiovascular Health Study, a communityâbased longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar. Conclusions: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF
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Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: The Cardiovascular Health Study
Background: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF. Methods and Results: The study population included 2899 participants from the Cardiovascular Health Study, a communityâbased longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the longâchain saturated fatty acidsâpalmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)âwith incident AF. During a median of 11.2 years of followâup, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top and bottom quartiles were 0.76 (95% CI: 0.61, 0.95) for 18:0; 0.78 (95% CI: 0.63, 0.97) for 20:0; 0.62 (95% CI: 0.50, 0.78) for 22:0; and 0.68 (95% CI: 0.55, 0.85) for 24:0. Conclusions: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longerâchain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk
Insulin-Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone : Receptor Binding Specificity
Insulin, insulin-like growth factors 1 and 2 (IGF-1 and -2, respectively), and their receptors (IR and IGF-1R) are the key elements of a complex hormonal system that is essential for the development and functioning of humans. The C and D domains of IGFs (absent in insulin) likely play important roles in the differential binding of IGF-1 and -2 to IGF-1R and to the isoforms of IR (IR-A and IR-B) and specific activation of these receptors. Here, we attempted to probe the impact of IGF-1 and IGF-2 D domains (DI and DII, respectively) and the IGF-2 C domain (CII) on the receptor specificity of these hormones. For this, we made two types of insulin hybrid analogues: (i) with the C-terminus of the insulin A chain extended by the amino acids from the DI and DII domains and (ii) with the C-terminus of the insulin B chain extended by some amino acids derived from the CII domain. The receptor binding affinities of these analogues and their receptor autophosphorylation potentials were characterized. Our results indicate that the DI domain has a more negative impact than the DII domain does on binding to IR, and that the DI domain Pro-Leu-Lys residues are important factors for a different IR-A versus IR-B binding affinity of IGF-1. We also showed that the additions of amino acids that partially "mimic" the CII domain, to the C-terminus of the insulin B chain, change the binding and autophosphorylation specificity of insulin in favor of the "metabolic" IR-B isoform. This opens new venues for rational enhancement of insulin IR-B specificity by modifications beyond the C-terminus of its B chain
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Plasma Phospholipid TransâFatty Acids Levels, Cardiovascular Diseases, and Total Mortality: The Cardiovascular Health Study
Background: While selfâreported transâfatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (tâ16:1n9, total tâ18:1, and cis/transâ(c/tâ), t/câ and t/tâ18:2) and cardiovascular disease (CVD) or total mortality are not well established. Methods and Results: We evaluated 2742 adults in the Cardiovascular Health Study, aged 74±5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and nonâCVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 personâyears, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/tâ18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95% CI=1.04 to 1.44, Pâtrend=0.01), CVD mortality (HR=1.40, 95% CI=1.05 to 1.86, Pâtrend=0.02), and total CHD (HR=1.39, 95% CI=1.06 to 1.83, Pâtrend=0.01). t/câ18:2 was positively related to total mortality (HR=1.19, Pâtrend=0.05), total CHD (HR=1.67, Pâtrend=0.002), and nonfatal CHD (HR=2.06, Pâtrend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither tâ16:1n9 nor tâ18:1 was significantly associated with total mortality or CVD, nor was c/tâ18:2 if we excluded early cases. Conclusions: Among circulating TFAs, t/tâ18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/câ18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially tâ18:2 isomers
Plasma Nutrient Biomarkers Are Associated with Waist-to-Height Ratio in Youth with Type 1 Diabetes
Background: Plasma fatty acids (FAs) and micronutrients have been associated with central obesity in adults; however, previous studies of these associations in adults have yielded mixed results. In addition, no comparable research has been conducted among youth with type 1 diabetes (T1D)
Comparing nuclear power trajectories in Germany and the UK: from âregimes' to âdemocraciesâ in sociotechnical transitions and Discontinuities
This paper focuses on arguably the single most striking contrast in contemporary major energy politics in Europe (and even the developed world as a whole): the starkly differing civil nuclear policies of Germany and the UK. Germany is seeking entirely to phase out nuclear power by 2022. Yet the UK advocates a ânuclear renaissanceâ, promoting the most ambitious new nuclear construction programme in Western Europe.Here,this paper poses a simple yet quite fundamental question: what are the particular divergent conditions most strongly implicated in the contrasting developments in these two countries. With nuclear playing such an iconic role in historical discussions over technological continuity and transformation, answering this may assist in wider understandings of sociotechnical incumbency and discontinuity in the burgeoning field ofâsustainability transitionsâ. To this end, an âabductiveâ approach is taken: deploying nine potentially relevant criteria for understanding the different directions pursued in Germany and the UK. Together constituted by 30 parameters spanning literatures related to socio-technical regimes in general as well as nuclear technology in particular, the criteria are divided into those that are âinternalâ and âexternalâ to the âfocal regime configurationâ of nuclear power and associated âchallenger technologiesâ like renewables.
It is âinternalâ criteria that are emphasised in conventional sociotechnical regime theory, with âexternalâ criteria relatively less well explored. Asking under each criterion whether attempted discontinuation of nuclear power would be more likely in Germany or the UK, a clear picture emerges. âInternalâ criteria suggest attempted nuclear discontinuation should be more likely in the UK than in Germanyâ the reverse of what is occurring.
âExternalâ criteria are more aligned with observed dynamics âespecially those relating to military nuclear commitments and broader âqualities of democracyâ. Despite many differences of framing concerning exactly what constitutes âdemocracyâ, a rich political science literature on this point is unanimous in characterising Germany more positively than the UK. Although based only on a single case,a potentially important question is nonetheless raised as to whether sociotechnical regime theory might usefully give greater attention to the general importance of various aspects of democracy in constituting conditions for significant technological discontinuities and transformations. If so, the policy implications are significant. A number of important areas are identified for future research, including the roles of diverse understandings and specific aspects of democracy and the particular relevance of military nuclear commitmentsâ whose under-discussion in civil nuclear policy literatures raises its own questions of democratic accountability
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