Serum Bile Acids in Repaired Tetralogy of Fallot: A Marker for Liver and Heart?

Background and Aims

Patients with repaired tetralogy of Fallot may develop chronic right ventricular dysfunction and hepatic congestion over time. We hypothesized that bile acid metabolism is altered in repaired tetralogy of Fallot patients and therefore sought to correlate right ventricular indices with serum bile acid levels.

Methods

Indexed right ventricular end diastolic volume, as assessed by cardiac magnetic-resonance imaging, was classified as <100ml/m² (Group 1, n = 5), 100–150ml/m² (Group 2, n = 18), and >150ml/m² (Group 3, n = 6) in 29 patients with repaired tetralogy of Fallot. Pulmonary regurgitation fraction and right ventricular ejection fraction were calculated. The serum bile acid profile, including 15 species, in these patients was determined by liquid chromatography coupled with mass spectrometry.

Results

Serum bile acid levels increased from Group 1 to Group 3 (2.5 ± 0.7; 4.1 ± 2.5; 6.0 ± 2.8 μmol/l, respectively) with significantly increased bile acid values in Group 3 compared to Group 1 (p≤0.05). In Group 3, but not in Group 1 and 2, a significant increase in glycine-conjugated bile acids was observed. Pulmonary regurgitation fraction increased (12 ± 1; 28 ± 16; 43 ± 3%, Groups 1–3, respectively) and right ventricular ejection fraction decreased (48.4 ± 6.4; 48.5 ± 6.5; 42.1 ± 5.3%, Groups 1–3, respectively) with rising indexed right ventricular end diastolic volume.

Conclusions

These preliminary results suggest that serum bile acid levels are positively correlated with indexed right ventricular end-diastolic volume in patients with repaired tetralogy of Fallot; however, this needs to be confirmed in a larger patient cohort.     

Ein Diplopode (Tausendfüßler i. e. S.) aus den lakustrinen Karbonaten des Nördlinger Rieses (Miozän,Süddeutschland): Morphologie und Integumentstruktur

An eugnath diplopode is described from Miocene lacustrine carbonates of the impact crater Nördlinger Ries. A further systematic classification is impossible, because gonopodes, which are the most important taxonomic characteristics, are not preserved. The primary calcite-impregnated integument has been dolomitized with structural preservation. In fractures, a differentiation of endo-and exocuticle is visible by distinct ultrastructures. The epicuticle is not preserved. Concentric arched structures, which display the orientation of former chitin-protein-microfibres, are preserved by the arrangement of dolomite crystallites. Concerning the diagenetic history of the Ries-lake-carbonates this is an argument for an early, near-surface dolomitization.     

Kin groups in closely spaced capercaillie leks

We quantified the genetic structure among 58 capercaillie (Tetrao urogallus) from three closely spaced leks in boreal Russia using ten microsatellite loci. We did not find significant structuring with respect to lek membership in an overall analysis. However, all but one individual could be strongly assigned to one of two genetic clusters, which we interpret as reflecting different local lineages or extended family groups. There was evidence for structuring among some clusters within leks, and one smaller lek consisted of nine out of ten males from one cluster, which could reflect kin biasing of lek membership. One cluster was apparently outperforming the other, since nine out of ten juveniles sampled belonged to it.     

Transport and metabolism of exogenously applied gibberellins to Malus domestica Borkh. cv. Jonagold

The radio-labeled gibberellins GA₁, GA₃,GA₄, and GA₇ were applied to intact developing applefruits (Malus domestica Borkh. cv. Jonagold) during theperiod when GAs are suggested to inhibit flower bud induction for the followingyear. Radioactivity from these compounds was found to be transported intoadjacent tissues as there are pedicels and bourses (4%). Application topedicels, after removal of the fruits, enhanced the transport into adjacentbourses up to 11%. The bud-carrying lateral bourse shoots contained onlyminor amounts of radioactivity on average 0.4% in both cases. Theseexport rates were identical, 1 or 5 days after application.After application of the corresponding deuterium-labeled GAs and analyses bymass spectrometry the specific metabolization of GA₁ toGA₁ 13-O-glucoside and of GA₃ to GA₃13-O-glucoside was demonstrated. Additional metabolites of GA₁ andGA₃ were not detected. After fruit application of GA₃ theratio of GA₃ to GA₃ 13-O-glucoside was found to be 1:2 inthe fruit. Pedicel application led to ratios of 1:4 and 1:5, respectively, inthe pedicel and in the adjacent bourse. After the application of GA₄and GA₇, neither glucosylation products nor other GA-like metabolitescould be identified.This is the first report of the metabolism of GAs to GA 13-O-glucosides indeveloping apple fruits. The possible function of the GAs as a signal in flowerbud formation for the following year is discussed.     

Trophoblast-like human choriocarcinoma cells serve as a suitable in vitro model for selective cholesteryl ester uptake from high density lipoproteins.

As human choriocarcinoma cells display many of the biochemical and morphological characteristics reported for in utero invasive trophoblast cells we have studied cholesterol supply from high density lipoproteins (HDL) to these cells. Binding properties of 125I-labeled HDL subclass 3 (HDL3) at 4 degrees C were similar for BeWo, JAr, and Jeg3 choriocarcinoma cell lines while degradation rates at 37 degrees C were highest for BeWo. Calculating the selective cholesteryl ester (CE)-uptake as the difference between specific cell association of [3H]CE-labeled HDL3 and holoparticle association of 125I-labeled HDL3 revealed that in BeWo cells, the selective CE-uptake was slightly lower than holoparticle association. However, the pronounced capacity for specific cell association of [3H]CE-HDL3 and selective [3H]CE-uptake in excess of HDL3-holoparticle association, and cAMP-mediated enhanced cell association of [3H]CE-HDL3 in JAr and Jeg3 suggested the scavenger receptor class B, type I (SR-BI) to be responsible for this pathway. Abundant expression of SR-BI (but not SR-BII, a splice variant of SR-BI) could be observed in JAr and Jeg3 but not in BeWo cells using RT-PCR, Northern and Western blot analysis, and immunocytochemical technique. Adenovirus-mediated overexpression of SR-BI in all three choriocarcinoma cell lines resulted in an enhanced capacity for cell association of [3H]CE-HDL3 (20-fold in BeWo; fivefold in JAr and Jeg3). The fact that exogenous HDL3 remarkably increases proliferation in JAr and Jeg3 supports the notion that selective CE-uptake and subsequent intracellular generation of cholesterol is coupled to cellular growth. From our findings we propose that JAr and Jeg3 cells serve as a suitable in vitro model to study selective CE-supply to human placental cells.     

NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells

In this study we have investigated the role of a specific corepressor of EGR-1, NAB2, to down-regulate vascular endothelial growth factor (VEGF)-induced gene expression in endothelial cells and to inhibit angiogenesis. Firstly, we show a reciprocal regulation of EGR-1 and NAB2 following VEGF treatment. During the initial phase EGR-1 is rapidly induced and NAB2 levels are down-regulated. This is followed by a reduction of EGR-1 and a concomitant increase of NAB2. Secondly, using the tissue factor gene as a readout for VEGF-induced and EGR-1-regulated gene expression we demonstrate that NAB2 can completely block VEGF-induced tissue factor reporter gene activity. Thirdly, by adenovirus-mediated expression we show that NAB2 inhibits up-regulation of tissue factor, VEGF receptor-1, and urokinase plasminogen activator mRNAs even when a combination of VEGF and bFGF is used for induction. In addition, NAB2 overexpression significantly reduced tubule and sprout formation in two different in vitro angiogenesis assays and largely prevented the invasion of cells and formation of vessel-like structures in the murine Matrigel model. These data suggest that NAB2 regulation represents a mechanism to guarantee transient EGR-1 activity following exposure of endothelial cells to VEGF and that NAB2 overexpression could be used to inhibit signals involved in the early phase of angiogenesis.     

Apparatus and mechanism of photosynthetic oxygen evolution: a personal perspective*

This historical minireview describes basic lines of progress in our understanding of the functional pattern of photosynthetic water oxidation and the structure of the Photosystem II core complex. After a short introduction into the state of the art about 35 years ago, results are reviewed that led to identification of the essential cofactors of this process and the kinetics of their reactions. Special emphasis is paid on the flash induced oxygen measurements performed by Pierre Joliot (in Paris, France) and Bessel Kok (Baltimore, MD) and their coworkers that led to the scheme, known as the Kok-cycle. These findings not only unraveled the reaction pattern of oxidation steps leading from water to molecular oxygen but also provided the essential fingerprint as prerequisite for studying individual redox reactions. Starting with the S. Singer and G. Nicolson model of membrane organization, attempts were made to gain information on the structure of the Photsystem II complex that eventually led to the current stage of knowledge based on the recently published X-ray crystal structure of 3.8 A resolution in Berlin (Germany).With respect to the mechanism of water oxidation, the impact of Gerald T. Babcock's hydrogen abstractor model and all the considerations of electron/proton transfer coupling are outlined. According to my own model cosiderations, the protein matrix is not only a 'cofactor holder' but actively participates by fine tuning via hydrogen bond networks, playing most likely an essential role in water substrate coordination and in oxygen-oxygen bond formation as the key step of the overall process.