Cholesterol absorption and synthesis related to low density lipoprotein metabolism during varying cholesterol intake in men with different apoE phenotypes

The aim of the present study was, first, to investigate whether cholesterol (C) absorption, enhanced by cholesterol feeding, was related to synthesis of cholesterol, serum level of low density lipoprotein (LDL)-C, and receptor activity for LDL apolipoprotein (apo) B in healthy men. Secondly, we were interested in whether apolipoprotein E (apoE) phenotypes contributed to cholesterol and LDL apoB metabolism under these conditions. We studied 29 home-living men aged 55 +/- 1 (mean +/- SE) years on a low-fat, low cholesterol (208 +/- 13 mg/day) diet followed by a low-fat high cholesterol (878 +/- 38 mg/day) diet during 5 weeks. Cholesterol feeding increased total cholesterol, LDL-C, high density lipoprotein (HDL)-C, and LDL apoB levels from 10% to 13% (P less than 0.05) and bile acid production and cholesterol turnover by 16% (P less than 0.05), decreased the fractional catabolic rate (FCR) for LDL apoB by 10% (P less than 0.05) and cholesterol absorption efficiency by 8% (P less than 0.05), while cholesterol synthesis only tended to decrease. During the cholesterol feeding, LDL-C was positively related to apoB production rate and cholesterol absorption efficiency (P less than 0.05), and negatively related to bile acid and cholesterol synthesis (P less than 0.05) and FCR for LDL apoB, which, in turn, was negatively related to cholesterol absorption efficiency and positively to bile acid synthesis. ApoE phenotype was positively related to TC, LDL-C, and LDL apoB levels and negatively to FCR for LDL apoB. The increase of the LDL-C level by the high cholesterol intake was positively correlated with LDL-C on high cholesterol diet and apoE phenotypes, so that the increase was 7% in apoE2 (ns), 11% in apoE3 (P less than 0.05), and 18% in apoE4 (P less than 0.05); the increase of bile acid synthesis was significant only in subjects with apoE2. Moreover, the increase of LDL-C was positively related to the absolute amount of dietary cholesterol absorbed and negatively to FCR for LDL apoB. The findings suggest that the higher the LDL-C level, the higher is the absorption efficiency of cholesterol and production of LDL apoB, and the lower is the removal of LDL apoB and synthesis of both bile acids and cholesterol, and the more frequently the subjects had epsilon 4 allele. The nonresponsiveness to dietary cholesterol was dependent on low LDL-C level, apoE2 phenotype, and effective bile acid synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of reaction conditions on the oxidation of veratryl alcohol catalyzed by cobalt salen-complexes

Cobalt salen-type [salen=N,N′-bis(salicylidene)ethylenediamine] complexes 1–6 were studied as catalysts for dioxygen activation in the oxidation of veratryl alcohol in basic aqueous conditions. The complexes Co(salen) (1), Co(CH₃salen) (2) [CH₃salen=N,N′-bis(methylsalicylidene)ethylenediamine], Co(4OHsalen) (3) [4OHsalen=N,N′-bis(4-hydroxosalicylidene)ethylenediamine], Co(sulfosalen) (4) [sulfosalen=N,N′-bis(5-sulfonatosalicylidene)ethylenediamine], Co(acacen) (5) [acacen=N,N′-bis(acetylacetone)ethylenediamine) and Co(N-Me-salpr) (6) [N-Me-salpr=bis(salicylideniminato-3-propyl)methylamine] were chosen to examine the influence of ligand structure on the catalytic activity. The effect of reaction conditions on the oxidation of veratryl alcohol was studied by varying temperature, pH, time or the nature and amount of the axial base needed to enhance the activity of complexes 1–5. The catalytic behaviour of the studied complexes was shown to be very depended on the applied conditions and distinct differences could be observed among the complexes. In all reactions, veratraldehyde was the only product observed. The unsubstituted complex 1 was the most efficient catalyst in the studied system achieving turnover numbers of up to 28 at 80 °C and pH 12.5.     

Quantified factory worker: field study of a web application supporting work well-being and productivity

Cognition, Technology & Work - The work on the factory floor is gradually changing to resemble knowledge work due to highly automated manufacturing machines. In the increasingly automated work...     

Absorption and metabolic fate of dietary3H-squalene in the rat

The absorption and metabolic fate of dietary squalene were investigated on the rat by administering a single oral dose of³H-squalene and¹⁴C-cholesterol. Experiments on rats with cannulated thoracic duct revealed that³H-squalene was, like¹⁴C-cholesterol, absorbed through the lymphatic vessels and that ca. 20% of absorbed³H-squalene was cyclized to sterols during the transit through the intestinal wall. Feces contained³H-sterols, indicating that newly synthesized mucosal sterols had been secreted into the gut lumen. In intact animals,³H-squalene appeared in the circulation more rapidly than¹⁴C-cholesterol and did not persist to any significant extent in the squalene-rich adipose and muscle tissues. The increase in dietary squalene load (8–48 mg) decreased the absorption percentage of³H-squalene (45–26%) but did not affect the absorption of¹⁴C-cholesterol (47%). Determination of fecal steroids revealed that during the first days absorbed³H-squalene was eliminated to a significantly higher extent than¹⁴C-cholesterol as fecal bile acids (34% vs 11%). The experiments indicate that the rat intestine has a marked capacity for absorbing dietary squalene and that the absorbed squalene is preferentially converted to bile acids in the liver.     

The regiospecific position of 18∶1 cis and trans monoenoic fatty acids in milk fat triacylglycerols

TAG of butterfat were fractionated according to the type and degree of unsaturation into six fractions by silver-ion HPLC. The fractions containing TAG with either cis-or trans-monoenoic FA were collected and fractionated further by reversed-phase HPLC to obtain fractions containing cis TAG of ACN:DB (acyl carbon number:double bonds) 48∶1, 50∶1, and 52∶1 as well as trans 48∶1, 50∶1, and 52∶1. The FA compositions of these fractions were elucidated by GC. The MW distribution of each fraction was determined by ammonia negative-ion CI-MS. Each of the [M-H]⁻ parent ions was fractionated further by collision-induced dissociation with argon, which gave information on the location of cis-and trans-FA between the primary and secondary positions of TAG. The results suggest that the sn-positions of the monoenoic cis-and trans-FA depend on the two other FA present in the molecule. With 14∶0 FA in the TAG molecule, the 18∶1 FA in the sn-2 position are mostly present as cis-isomers. When there is no 14∶0 in the TAG molecule, the trans-18∶1 isomers seem to be more common in the sn-2 position. Also when other long-chain FA are present, the trans-isomers are more likely to be located in the secondary (sn-2) position.     

Changes in content of microbially available phosphorus,assimilable organic carbon and microbial growth potential during drinking water treatment processes

There are regions where microbial growth in drinking water is limited by phosphorus instead of organic carbon. In phosphorus limited waters small changes in phosphorus concentration significantly affect microbial growth. We studied how water treatment processes in waterworks affect the availability of microbial nutrients and microbial growth potential in drinking water. The nutrients studied were assimilable organic carbon (AOCpotential) and microbially available phosphorus (MAP) which both were quantified by bioassays. Chemical coagulation, commonly used in surfacewater works, effectively removed AOCpotential and MAP. In contrast to activated carbon filtration, ozonation increased the concentrations of AOCpotential and MAP, and also microbial growth potential. In most of the drinking waters, microbial growth was limited by phosphorus, and microbial growth potential correlated with the MAP concentration. Microbial growth potential was lowest in drinking waters produced from surface waters with efficient treatment technique and highest in less treated ground waters.     

Artificial reconstruction of two cryptic angucycline antibiotic biosynthetic pathways

Genome-sequencing projects have revealed that Streptomyces bacteria have the genetic potential to produce considerably larger numbers of natural products than can be observed under standard laboratory conditions. Cryptic angucycline-type aromatic polyketide gene clusters are particularly abundant. Sequencing of two such clusters from Streptomyces sp. PGA64 and H021 revealed the presence of several open reading frames that could be involved in processing the basic angucyclic carbon skeleton. The pga gene cluster contains one putative FAD-dependant monooxygenase (pgaE) and a putatively bifunctional monooxygenase/short chain alcohol reductase (pgaM), whereas the cab cluster contains two similar monooxygenases (cabE and cabM) and an independent reductase (cabV). In this study we have reconstructed the biosynthetic pathways for aglycone synthesis by cloning and sequentially expressing the angucycline tailoring genes with genes required for the synthesis of the unmodified angucycline metabolite-UWM6-in Streptomyces lividans TK24. The expression studies unequivocally showed that, after the production of UWM6, the pathways proceed through the action of the similar monooxygenases PgaE and CabE, followed by reactions catalysed by PgaM and CabMV. Analysis of the metabolites produced revealed that addition of pgaE and cabE genes directs both pathways to a known shunt product, rabelomycin, whereas expression of all genes from a given pathway results in the production of the novel angucycline metabolites gaudimycin A and B. However, one of the end products is most probably further modified by endogenous S. lividans TK24 enzymes. These experiments demonstrate that genes that are either inactive or cryptic in their native host can be used as biosynthetic tools to generate new compounds.     

Trade-off analysis approach for interactive nonlinear multiobjective optimization

When solving multiobjective optimization problems, there is typically a decision maker (DM) who is responsible for determining the most preferred Pareto optimal solution based on his preferences. To gain confidence that the decisions to be made are the right ones for the DM, it is important to understand the trade-offs related to different Pareto optimal solutions. We first propose a trade-off analysis approach that can be connected to various multiobjective optimization methods utilizing a certain type of scalarization to produce Pareto optimal solutions. With this approach, the DM can conveniently learn about local trade-offs between the conflicting objectives and judge whether they are acceptable. The approach is based on an idea where the DM is able to make small changes in the components of a selected Pareto optimal objective vector. The resulting vector is treated as a reference point which is then projected to the tangent hyperplane of the Pareto optimal set located at the Pareto optimal solution selected. The obtained approximate Pareto optimal solutions can be used to study trade-off information. The approach is especially useful when trade-off analysis must be carried out without increasing computation workload. We demonstrate the usage of the approach through an academic example problem.