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.     

Method of intracranial pressure monitoring and cerebrospinal fluid sampling in swine

Cerebral oedema and encephalopathy have been noted to occur frequently in patients severely ill or dying after trauma, ischaemia, infections or even metabolic disorders. The objective of the present study was to establish continuous monitoring of the intracranial pressure (ICP) and sampling of cerebrospinal fluid (CSF) for further investigations in swine. ICP monitoring was established in eight pigs by using a ventricular drainage system, implemented after paramedian trepanation of the os frontale. CSF and serum samples were taken for measurement of the levels of glucose and protein. Operating time was 21+/-8 min for the trepanation until ICP monitoring was performed. No complications occurred during surgery. Continuous monitoring of ICP and CSF sampling was easy to perform, and without any side-effects in any animal. At autopsy, no iatrogenic lesions were found and monitoring catheters were still in place. For several types of research requiring ICP monitoring and sampling of CSF, this method can be used successfully.     

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.     

Genetic variation and differentiation in captive and wild zebra finches (Taeniopygia guttata)

The zebra finch (Taeniopygia guttata) is a small Australian grassland songbird that has been domesticated over the past two centuries. Because it is easy to breed in captivity, it has become a widely used study organism, especially in behavioural research. Most work has been conducted on domesticated populations maintained at numerous laboratories in Europe and North America. However, little is known about the extent to which, during the process of domestication, captive populations have gone through bottlenecks in population size, leading to inbred and potentially genetically differentiated study populations. This is an important issue, because (i) behavioural studies on captive populations might suffer from artefacts arising from high levels of inbreeding or lack of genetic variation in such populations, and (ii) it may hamper the comparability of research findings. To address this issue, we genotyped 1000 zebra finches from 18 captive and two wild populations at 10 highly variable microsatellite loci. We found that all captive populations have lost some of the genetic variability present in the wild, but there is no evidence that they have gone through a severe bottleneck, as the average captive population still showed a mean of 11.7 alleles per locus, compared to a mean of 19.3 alleles/locus for wild zebra finches. We found significant differentiation between the captive populations (F(ST) = 0.062). Patterns of genetic similarity closely match geographical relationships, so the most pronounced differences occur between the three continents: Australia, North America, and Europe. By providing a tree of the genetic similarity of the different captive populations, we hope to contribute to a better understanding of variation in research findings obtained by different laboratories.     

Conservation of NADPH utilization by chorismate synthase and its implications for the evolution of the shikimate pathway

The shikimate pathway is essential for the biosynthesis of aromatic compounds. The seventh and last step is catalysed by chorismate synthase, which has an absolute requirement for reduced FMN in its active site. There are two classes of this enzyme, which are distinguished according to the origin of the reduced cofactor. Monofunctional chorismate synthases sequester it from the cellular environment whereas bifunctional enzymes can generate reduced FMN at the expense of NADPH. These bifunctional enzymes are found in fungi and the ciliated protozoan Euglena gracilis while all bacterial and plant enzymes are monofunctional. In this study, we introduce an in vivo screen, which is based on a chorismate synthase-deficient Saccharomyces cerevisiae strain, allowing the classification of hitherto uncharacterized chorismate synthases. This analysis revealed that bifunctionality is present in the enzymes of protozoan species. In contrast, all bacterial and plant enzymes tested are monofunctional. In addition, we demonstrate that a monofunctional chorismate synthase confers prototrophy in conjunction with a NADPH : FMN oxidoreductase indicating that bifunctionality is required due to the lack of free reduced FMN in fungal and possibly protozoan species. Interestingly, the distribution of bifunctional chorismate synthase concurs with the presence of a pentafunctional enzyme complex.     

The co-ordinated regulation of iron homeostasis in murine macrophages limits the availability of iron for intracellular Salmonella typhimurium

In being both, a modifier of cellular immune effector pathways and an essential nutrient for microbes, iron is a critical determinant in host-pathogen interaction. Here, we investigated the metabolic changes of macrophage iron homeostasis and immune function following the infection of RAW264.7 murine macrophages with Salmonella typhimurium. We observed an enhanced expression of the principal iron export protein, ferroportin 1, and a subsequent increase of iron efflux in Salmonella-infected phagocytes. In parallel, the expression of haem oxygenase 1 and of the siderophore-binding peptide lipocalin 2 was markedly enhanced following pathogen entry. Collectively, these modulations reduced both the cytoplasmatic labile iron and the ferritin storage iron pool within macrophages, thus restricting the acquisition of iron by intramacrophage Salmonella. Correspondingly, limitation of macrophage iron decreased microbial survival, whereas iron supplementation impaired immune response pathways in Salmonella-infected macrophages (nitric oxide formation and tumour necrosis factor-alpha production) and promoted intracellular bacterial proliferation. Our findings suggest that the enhancement of ferroportin 1-mediated iron efflux, the upregulation of the haem-degrading enzyme haem oxygenase 1 and the induction of lipocalin 2 following infection concordantly aim at withholding iron from intracellular S. typhimurium and to increase antimicrobial immune effector pathways thus limiting pathogen proliferation.     

General patterns of sexual dimorphism in graylings (Thymallus), with a comparison to other salmonid species

Among fishes, salmonids (family Salmonidae) have attracted a great deal of research attention focused on sexual dimorphism and associated selective forces. Most of this research has been directed toward anadromous and mostly semelparous salmon and trout (Oncorhynchus, Salmo), and comparatively little is known about intersexual variability in strictly iteroparous freshwater salmonids. We examined a comprehensive data set of 28 linear morphometric characters in 11 of 15 currently recognised species of grayling (Thymallinae, Thymallus), a genus consisting of iteroparous species only, to identify general patterns of intersexual morphological variability. Overall, we found that all grayling species show common sex-specific traits particularly relating to size dimensions of the dorsal, anal, pelvic and pectoral fins. Although the magnitude of sexual dimorphism differed among species, there was no significant phylogenetic signal associated with these differences across the genus. These results are discussed in terms of the assumed selection pressures driving sexual dimorphism in graylings and are compared to existing knowledge in Salmonidae as a whole where similarities and differences with both Salmoninae and Coregoninae exist. The present study provides the first detailed genus-wide comparison of sexually dimorphic phenotypic characters in graylings, and highlights the need for more large-scale comparative studies in multiple salmonid species to better understand general macroevolutionary trends among this important group of freshwater fishes.