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

Disease spread through animal movements: a static and temporal network analysis of pig trade in Germany

Background: Animal trade plays an important role for the spread of infectious diseases in livestock populations. As a case study, we consider pig trade in Germany, where trade actors (agricultural premises) form a complex network. The central question is how infectious diseases can potentially spread within the system of trade contacts. We address this question by analyzing the underlying network of animal movements. Methodology/Findings: The considered pig trade dataset spans several years and is analyzed with respect to its potential to spread infectious diseases. Focusing on measurements of network-topological properties, we avoid the usage of external parameters, since these properties are independent of specific pathogens. They are on the contrary of great importance for understanding any general spreading process on this particular network. We analyze the system using different network models, which include varying amounts of information: (i) static network, (ii) network as a time series of uncorrelated snapshots, (iii) temporal network, where causality is explicitly taken into account. Findings: Our approach provides a general framework for a topological-temporal characterization of livestock trade networks. We find that a static network view captures many relevant aspects of the trade system, and premises can be classified into two clearly defined risk classes. Moreover, our results allow for an efficient allocation strategy for intervention measures using centrality measures. Data on trade volume does barely alter the results and is therefore of secondary importance. Although a static network description yields useful results, the temporal resolution of data plays an outstanding role for an in-depth understanding of spreading processes. This applies in particular for an accurate calculation of the maximum outbreak size.Comment: main text 33 pages, 17 figures, supporting information 7 pages, 7 figure

Quantum simulator for the Schwinger effect with atoms in bi-chromatic optical lattices

Ultra-cold atoms in specifically designed optical lattices can be used to mimic the many-particle Hamiltonian describing electrons and positrons in an external electric field. This facilitates the experimental simulation of (so far unobserved) fundamental quantum phenomena such as the Schwinger effect, i.e., spontaneous electron-positron pair creation out of the vacuum by a strong electric field.Comment: 4 pages, 2 figures; minor corrections and improvements in text and in figures; references adde