Effect of phospholipids and bile acids on cholesterol nucleation time and vesicular/micellar cholesterol in gallbladder bile of patients with cholesterol stones

Supersaturation and rapid nucleation of cholesterol in bile are of key importance in the pathogenesis of cholesterol gallstones. While the effects of bile acids and phospholipids on cholesterol saturation of bile have been extensively studied, their influence on the cholesterol nucleation time has not been compared. We, therefore, investigated whether increases of bile acid or phospholipid concentrations in bile by in vitro supplementation affect the cholesterol nucleation time. Bile samples were obtained at surgery from patients with cholesterol gallstones. Prior to the nucleation assay the bile samples were divided into 0.5-ml aliquots and supplemented with 1.25, 2.5, 5.0, and 10.0 mumol/ml of different phosphatidylcholines (PC-dimyristoyl, PC- dipalmitoyl, PC-distearoyl, and extracted biliary PCs) or with 5.0, 10.0, and 20.0 mumol/ml of bile acids (glycine or taurine conjugates of cholic acid, deoxycholic acid, or chenodeoxycholic acid). The increase of phosphatidylcholine or bile acid concentration decreased the mean cholesterol saturation index to a similar extent (PC: 0.1-0.3; BA: 0.1- 0.2). Supplementations of bile with increasing amounts of synthetic or biliary PCs caused a marked prolongation of the nucleation time in bile from 1.5 +/- 0.2 up to > or = 21 days or 2.5 +/- 0.7 up to > or = 21 days. Concurrently, biliary cholesterol was shifted from vesicles to mixed micelles and the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered. In contrast, the addition of bile acids to gallbladder bile did not affect the cholesterol nucleation time (2.2 +/- 0.3 days), the percentage of vesicular cholesterol, or the cholesterol/phospholipid ratio of vesicles and micelles

Die geskiedenis van die ontwikkeling van die termiese gemaksone-konsep

The impact of the local climate on the indoor climate of buildings and in­door thermal comfort has long been understood, intuitively as well as qualitatively. With the advent of heating and cooling technologies, it became important to define a comfort target that was initially assumed to be a dry ball air temperature. As a result of (conflicting) climate chamber and field studies this point has to be broadened to a thermal comfort zone, valid for a statistical population. The thermal comfort zone had to be further described by dimensions as contained in the bioclimatic/psychrometric charts. This is reflected in the present ISO standard. An improvement on this is the adaptive model that defines thermal comfort as the resultant of physiological reactions as well as expectations built on previous experience. An improvement on the latter accepts the fact that a person plays an important role in creating thermal preferences. Finally it appears that a climate for thermal comfort is not the same as one for productivity.*This article is written in Afrikaan

The Impact of the Global Economic Crisis on Support for Democracy

This contribution provides a brief introduction into the second part of this HSR Special Issue. It informs about an ongoing project on the development of democracy in seven countries, five 'new' and two 'established' democracies. The five new democracies are Chile, South Korea, Poland, South Africa and Turkey. They are compared to Sweden and Germany. The five new democracies are located in different world regions and have different cultural and historical backgrounds. The contribution provides basic economic and political information on these countries. It also describes the common data base used by the six contributions: two surveys of members of parliament conducted in 2007 and 2013 as well as waves 5 and 6 of the World Values Survey conducted at about the same time. The common focus of all six contributions is the analysis of change in political legitimacy between 2007 and 2013

Fibronectin in human gallbladder bile: cholesterol pronucleating and/or mucin "link" protein?

Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal formation and crystal growth in bile. A recent study suggests that fibronectin is such a pronucleator in bile. Fibronectin also seems to closely interact with intestinal mucin. Since biliary mucin plays an important role in gallstone formation, such an interaction in bile may be of relevance in cholesterol gallstone formation. To more clearly elucidate the role of fibronectin in cholesterol gallstone disease, we measured the concentration of fibronectin in native bile of cholesterol gallstone patients and checked its influence on the cholesterol nucleation time of model bile. We further looked for a molecular interaction between biliary fibronectin and gallbladder mucin. We found that fibronectin is present in gallbladder bile of gallstone patients in low concentrations (2.6 +/- 1.2 micrograms/ml). Bile fibronectin did not interact with gallbladder mucin. Moreover, in a wide range of concentrations fibronectin had no influence on the nucleation time of model bile. We conclude that fibronectin does not seem to play a major role in cholesterol gallstone disease

Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease

There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gall-stone formation and mitigate biliary pain in gall-stone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gall-bladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 × 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05±0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94±0.27 versus 0.93±0.32 mg/ml) or total protein (5.8±0.9 versus 6.4±1.3 mg/ml), cholesterol saturation (1.3±0.2 versus 1.5±0.2), or nucleation time (2.0±3.0 versus 1.5±2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9±0.6 versus 5.6±1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content. Since mucus glycoproteins are major determinants of bile viscosity, an alteration in mucin macromolecular composition may conceivably cause the indomethacin-induced decrease in biliary viscosity and explain the beneficial effects of nonsteroidal anti-inflammatory drugs in gallstone disease

Authentication and authorisation in entrusted unions

This paper reports on the status of a project whose aim is to implement and demonstrate in a real-life environment an integrated eAuthentication and eAuthorisation framework to enable trusted collaborations and delivery of services across different organisational/governmental jurisdictions. This aim will be achieved by designing a framework with assurance of claims, trust indicators, policy enforcement mechanisms and processing under encryption to address the security and confidentiality requirements of large distributed infrastructures. The framework supports collaborative secure distributed storage, secure data processing and management in both the cloud and offline scenarios and is intended to be deployed and tested in two pilot studies in two different domains, viz, Bio-security incident management and Ambient Assisted Living (eHealth). Interim results in terms of security requirements, privacy preserving authentication, and authorisation are reported

Genome-wide analysis of growth phase-dependent translational and transcriptional regulation in halophilic archaea : research article

Background Differential expression of genes can be regulated on many different levels. Most global studies of gene regulation concentrate on transcript level regulation, and very few global analyses of differential translational efficiencies exist. The studies have revealed that in Saccharomyces cerevisiae, Arabidopsis thaliana, and human cell lines translational regulation plays a significant role. Additional species have not been investigated yet. Particularly, until now no global study of translational control with any prokaryotic species was available. Results A global analysis of translational control was performed with two haloarchaeal model species, Halobacterium salinarum and Haloferax volcanii. To identify differentially regulated genes, exponentially growing and stationary phase cells were compared. More than 20% of H. salinarum transcripts are translated with non-average efficiencies. By far the largest group is comprised of genes that are translated with above-average efficiency specifically in exponential phase, including genes for many ribosomal proteins, RNA polymerase subunits, enzymes, and chemotaxis proteins. Translation of 1% of all genes is specifically repressed in either of the two growth phases. For comparison, DNA microarrays were also used to identify differential transcriptional regulation in H. salinarum, and 17% of all genes were found to have non-average transcript levels in exponential versus stationary phase. In H. volcanii, 12% of all genes are translated with non-average efficiencies. The overlap with H. salinarum is negligible. In contrast to H. salinarum, 4.6% of genes have non-average translational efficiency in both growth phases, and thus they might be regulated by other stimuli than growth phase. Conclusions For the first time in any prokaryotic species it was shown that a significant fraction of genes is under differential translational control. Groups of genes with different regulatory patterns were discovered. However, neither the fractions nor the identity of regulated genes are conserved between H. salinarum and H. volcanii, indicating that prokaryotes as well as eukaryotes use differential translational control for the regulation of gene expression, but that the identity of regulated genes is not conserved For 70 H. salinarum genes potentiation of regulation was observed, but for the majority of regulated genes either transcriptional or translational regulation is employed

Diagnostic accuracy of coronary artery stenosis and thrombosis assessment using unenhanced multiplanar 3D post-mortem cardiac magnetic resonance imaging.

BACKGROUND A 3D sequence was introduced to unenhanced post-mortem cardiac magnetic resonance imaging (PMCMR) to enable multiplanar coronary artery image analysis and to investigate its diagnostic accuracy for the diagnosis of coronary artery stenosis and thrombosis. MATERIALS AND METHODS N = 200 forensic cases with suspected coronary artery pathology underwent 3 Tesla PMCMR (sequence used: T2 weighted transversal 3D turbo spin echo) before autopsy. Main coronary artery stenosis and thrombosis were assessed in PMCMR by multiplanar image analysis by two observers. Coronary artery histology was determined as the gold standard and compared to PMCMR. Sensitivity, specificity, negative (NPV) and positive predictive values (PPV) with 95% confidence intervals were calculated. RESULTS For all coronary arteries combined, sensitivity was 75% (PPV 73%) for the diagnosis of stenosis and 72% (PPV 71%) for the diagnosis of thrombosis. Specificity was 92% (NPV 90%) for correct diagnosis of non-existing stenosis and 97% (NPV 97%) for non-existing thrombosis. Sensitivity for correct diagnosis of different degrees of stenosis ranged between 67% and 80% (PPVs 67-82%); specificity ranged between 96% and 99% (NPVs 96-99%). CONCLUSION Multiplanar PMCMR coronary artery stenosis and thrombosis assessment based on an unenhanced T2 weighted 3D sequence provide moderate sensitivity and high specificity for the diagnosis of coronary artery stenosis and/or thrombosis. Hence, 3D T2w PMCMR cannot reliably detect existing coronary artery stenosis and thrombosis but may be particularly useful for the exclusion of stenosis or thrombosis of the main coronary arteries