Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects

Background/Aims: Ursodeoxycholic acid ( UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers ( 5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during ( days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment ( p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy

Haben die Konzentrationen von Interleukin 6, Procalcitonin und CRP bei Intensivpatienten während des ersten Fieberanstieges eine prognostische Bedeutung?

Serum levels of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) were measured in 38 critically ill patients immediately after an increase in body temperature above 38.3 degrees C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison to healthy control subjects. However, only IL-6 levels were significantly higher (p&lt;0.05) in nonsurvivors compared with survivors. Sensitivity, specificity, positive, and negative predictive values for survival were higher for IL-6 in comparison to levels of PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 compared to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of prognosis and mortality in patients with the onset of fever

Contribution of socioeconomic status, stature and birth weight to obesity in Sub-Saharan Africa: cross-sectional data from primary school-age children in Cameroon

Background: The pattern of obesity in relation to socioeconomic status is of public health concern. This study investigates whether the association between height and obesity in children is affected by their socioeconomic background. It also explores the relationship between high birth weight and obesity. Methods: School children, (N = 557; 5 to 12 years old) were recruited from randomly selected primary schools in a cross-sectional study including 173 rural and 384 urban children in the North West Region of Cameroon. Socioeconomic status (SES) and birth weight were obtained using a self administered questionnaire. Anthropometric measures included height, weight, BMI, waist circumference and percentage body fat. These measures were transformed into age and sex-standardized variables. Then participants were divided according to quartiles of height SDS. Results: The highest frequencies of overweight/obesity (18.8%), abdominal overweight/obesity (10.9%) and high body fat/obesity (12.3%) were observed among the tallest children from a high socioeconomic background. Univariate analyses indicate that children of high SES (39.9%), fourth height quartile (33.1%) and of high birth weight (54.8%) were significantly (p&lt;0.001) more likely to be overweight/obese. Multivariate analyses showed high SES (OR 8.3, 95% CI 3.9 - 15.4), fourth height quartile (OR 9.1, 95% CI 3.4 - 16.7) and high birth weight (OR 0.1, 95% CI 0.06 - 0.2) as independent predictors of overweight/obesity. Conclusions: This study confirms that children coming from a high socioeconomic background and being tall are at particular risk of becoming obese

Suppression of the Nuclear Factor Eny2 Increases Insulin Secretion in Poorly Functioning INS-1E Insulinoma Cells

Eny2, the mammalian ortholog of yeast Sus1 and drosophila E(y)2, is a nuclear factor that participates in several steps of gene transcription and in mRNA export. We had previously found that Eny2 expression changes in mouse pancreatic islets during the metabolic adaptation to pregnancy. We therefore hypothesized that the protein contributes to the regulation of islet endocrine cell function and tested this hypothesis in rat INS-1E insulinoma cells. Overexpression of Eny2 had no effect but siRNA-mediated knockdown of Eny2 resulted in markedly increased glucose and exendin-4-induced insulin secretion from otherwise poorly glucose-responsive INS-1E cells. Insulin content, cellular viability, and the expression levels of several key components of glucose sensing remained unchanged; however glucose-dependent cellular metabolism was higher after Eny2 knockdown. Suppression of Eny2 enhanced the intracellular incretin signal downstream of cAMP. The use of specific cAMP analogues and pathway inhibitors primarily implicated the PKA and to a lesser extent the EPAC pathway. In summary, we identified a potential link between the nuclear protein Eny2 and insulin secretion. Suppression of Eny2 resulted in increased glucose and incretin-induced insulin release from a poorly glucose-responsive INS-1E subline. Whether these findings extend to other experimental conditions or to in vivo physiology needs to be determined in further studies

Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia:New treatments and clinical guidance

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) &gt;10 mmol/L (&gt;400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy - both pharmacologic intervention and lipoprotein apheresis (LA) - is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.</p

Guidelines On Diabetes, Pre-Diabetes, And Cardiovascular Diseases: Executive Summary.The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).

Guidelines and Expert Consensus documents aim to present management and recommendations based on all of the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient, suffering from a specific condition, taking into account not only the impact on outcome, but also the risk benefit ratio of a particular diagnostic or therapeutic procedure. The ESC recommendations for guidelines production can be found on the ESC website†. In brief, the ESC appoints experts in the field to carry out a comprehensive and critical evaluation of the use of diagnostic and therapeutic procedures and to assess the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined below. Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. If necessary, the document is revised once more to be finally approved by the Committee for Practice Guidelines and selected members of the Board of the ESC. The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have, which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements