ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS)☆☆☆

https://www.cell.com/cell/pdf/0092-8674(92)90471-N.pdf

Homeobox genes and axial patterning

Jeffrey L. Anderson, MD, FACC, FAHA, Chair 

Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect 

Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1]

Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1]

Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1]

Nancy M

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.

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Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) 

Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR) 

ABI
: ankle-brachial index

/pdf/2016-esc-eas-guidelines-for-the-management-of-dyslipidaemias-3oe2qnm09b.pdf

2016 ESC/EAS Guidelines for the Management of Dyslipidaemias

ALL-trans retinoic acid (RA) is well known as a biologically active form of vitamin A and a teratogen1-8. The identification of nuclear receptors for this ligand9-11 suggests strongly that it is an endogenous signal molecule, and measurements of RA12 and teratogenic manipulations13-15 suggest further that RA is a mor-phogen specifying the anteroposterior axis during limb development. Besides the limb, RA and other retinoids affect development of other organs, including the central nervous system (CNS)4,6,7,16-18. None of these other effects has been investigated in detail. Our purpose here was to begin analysing the effects of RA on CNS development in Xenopus laevis. We find that RA acts on the developing CNS, transforming anterior neural tissue to a posterior neural specification. These and other19 findings raise the possibility that RA mediates an inductive interaction regulating anteroposterior differentiation within the CNS. Following recent reports implicating transforming growth factor-β2-like20,21 and fibroblast growth factor-like factors21,22 in mesoderm induction, this indicates that a different type of signal molecule (working through a nuclear receptor, not a plasma membrane receptor) might mediate inductive cell interactions during early embryonic development.

Retinoic acid causes an anteroposterior transformation in the developing central nervous system.

OBJECTIVE - This meta-analysis was undertaken to obtain insight regarding the shape and strength of the relationship between alcohol consumption and the risk of type 2 diabetes, the effects of adjustment for confounders, and the effect of modification by type 2 diabetes definition, sex, and BMI. RESEARCH DESIGN AND METHODS - The 15 original prospective cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average, were followed for 12 years. RESULTS - After pooling the data, a U-shaped relationship was found. Compared with nonconsumers, the relative risk (RR) for type 2 diabetes in those who consumed ≤6 g/day alcohol was 0.87 (95% CI 0.79-0.95). For the moderate consumption ranges of 6-12, 12-24, and 24-48 g/day, RRs of 0.70 (0.61-0.79), 0.69 (0.58-0.81), and 0.72 (0.62-0.84) were found, respectively. The risk of type 2 diabetes in heavy drinkers (≥48 g/day) was equal to that in nonconsumers (1.04 [0.84-1.29]). In general, nonsignificant trends for larger RR reduction associated with moderate alcohol consumption were observed for women compared with men, for crude compared with multivariate-adjusted analyses, and for studies that used self-reports instead of testing for type 2 diabetes definition. No differences in RR reductions were found between individuals with low or high BMI. CONCLUSIONS - The present evidence from observational studies suggests an ∼30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction is observed in consumers of ≥48 g/day. © 2005 by the American Diabetes Association.

/pdf/moderate-alcohol-consumption-lowers-the-risk-of-type-2-56emaubiw7.pdf

Moderate alcohol consumption lowers the risk of type 2 diabetes: A meta-analysis of prospective observational studies

http://ernaehrungsdenkwerkstatt.de/fileadmin/user_upload/EDWText/TextElemente/Ernaehrungswissenschaft/Naehrstoffe/Saettigung_Biomarker_deGraaf_AJCN_79_946_2004.pdf

Biomarkers of satiation and satiety

Objective: To investigate the dose-response relationship between cholesterol lowering and three different, relatively low intake levels of plant sterols (0.83, 1.61, 3.24 g/d) from spreads. To investigate the effects on lipid-soluble (pro)vitamins. Design: A randomized double-blind placebo controlled balanced incomplete Latin square design using five spreads and four periods. The five study spreads included butter, a commercially available spread and three experimental spreads fortified with three different concentrations of plant sterols. Subjects: One hundred apparently healthy normocholesterolaemic and mildly hypercholesterolaemic volunteers participated. Interventions: Each subject consumed four spreads, each for a period of 3.5 week. Results: Compared to the control spread, total cholesterol decreased by 0.26 (CI: 0.15-0.36), 0.31 (CI: 0.20-0.41) and 0.35 (CI: 0.25-0.46) mmol/L, for daily consumption of 0.83, 1.61 and 3.24 g plant sterols, respectively. For LDL-cholesterol these decreases were 0.20 (CI: 0.10-0.31), 0.26 (CI: 0.15-0.36) and 0.30 (CI: 0.20-0.41). Decreases in the LDL/HDL ratio were 0.13 (CI: 0.04-0.22), 0.16 (CI: 0.07-0.24) and 0.16 (CI: 0.07-0.24) units, respectively. Differences in cholesterol reductions between the plant sterol doses consumed were not statistically significant. Plasma vitamin K1 and 25-OH-vitamin D and lipid standardized plasma lycopene and alpha-tocopherol were not affected by consumption of plant sterol enriched spreads, but lipid standardized plasma (alpha + beta)-carotene concentrations were decreased by about 11 and 19% by daily consumption of 0.83 and 3.24 g plant sterols in spread, respectively. Conclusions: The three relatively low dosages of plant sterols had a significant cholesterol lowering effect ranging from 4.9-6.8%, 6.7-9.9% and 6.5-7.9%, for total, LDL-cholesterol and the LDL/HDL cholesterol ratio, respectively, without substantially affecting lipid soluble (pro)vitamins. No significant differences in cholesterol lowering effect between the three dosages of plant sterols could be detected. This study would support that consumption of about 1.6 g of plant sterols per day will benefically affect plasma cholesterol concentrations without seriously affecting plasma carotenoid concentrations. Sponsorship: Unilever Research Vlaardingen, NL

Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects

Retinoids (vitamin A and its metabolites) are suspected of regulating diverse aspects of growth, differentiation, and patterning during embryogenesis, but many questions remain about the identities and functions of the endogenous active retinoids involved. The pleiotropic effects of retinoids may be explained by the existence of complex signal transduction pathways involving diverse nuclear receptors of the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families, and at least two types of cellular retinoic acid binding proteins (CRABP-I and -II). The different RARs, RXRs, and CRABPs have different expression patterns during vertebrate embryogenesis, suggesting that they each have particular functions. Another level at which fine tuning of retinoid action could occur is the metabolism of vitamin A to active metabolites, which may include all-trans-retinoic acid, all-trans-3,4-didehydroretinoic acid, 9-cis-retinoic acid, and 14-hydroxy-4,14-retroretinol. Formation of the metabolite all-trans-4-oxo-retinoic acid from retinoic acid was considered to be an inactivation pathway during growth and differentiation. We report here that, in contrast, 4-oxo-retinoic acid is a highly active metabolite which can modulate positional specification in early embryos. We also show that this retinoid binds avidly to and activates RAR beta, and that it is available in early embryos. The different activities of 4-oxo-retinoic acid and retinoic acid in modulating positional specification on the one hand, and growth and differentiation on the other, interest us in the possibility that specific retinoid ligands regulate different physiological processes in vivo.

H.F.J. Hendriks

Papers

Retinoic acid causes an anteroposterior transformation in the developing central nervous system.

Moderate alcohol consumption lowers the risk of type 2 diabetes: A meta-analysis of prospective observational studies

Biomarkers of satiation and satiety

Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects

The retinoid ligand 4-oxo-retinoic acid is a highly active modulator of positional specification