Cardiac Troponin I elevation after epileptic seizure

ABSTRACT: BACKGROUND: Cardiac troponin-I (cTNI) is highly specific biomarker to prove myocardial damage, e.g. in acute coronary syndrome (ACS). However, it occurs in other conditions as well. We therefore analysed cTNI increase in patients after generalized convulsive seizure. Methods and Patients: Consecutive patients admitted with acute generalized convulsive seizure were included in case of cTNI measurement on admission. Among 898 selected cases, 53 patients were referred secondary to our department; in 845 cases cTNI measurements on admission were available. In case of multiple admissions (81 cases), only the first admission entered our analysis. In 17 patients elevated cTNI was determined due to ACS; in one patient a myocarditis was found. 5 patients suffered of relevant renal insufficiency. Finally 741 patients were included in the analysis. A cTNI cut-off level of at least 0.1 ng/ml was considered. Factors associated with a cTNI increase were analysed subsequently. RESULTS: The mean age of the study population (n=741) was 47.8 years (SD+/-18.6), 40.9% were female. In 50 patients (6.7%) a cTNI elevation of unknown origin was found; no obvious cardiac involvement could be detected in these patients who all remained asymptomatic. A vascular risk profile (including at least hypertension, hypercholesterolemia or diabetes) (OR= 3.62; CI: 1.59 to 8.21; p=0.001) and elevated creatine kinase on admission (OR= 2.36; CI: 1.26 to 4.39; p=0.002) were independent factors associated with cTNI release. CONCLUSION: cTNI release occurs in patients with generalized convulsive seizure with predominance in patients with vascular risk profile.     

Intraspecific variation in the magnitude and pattern of flooding-induced shoot elongation in Rumex palustris

Background and Aims

Intraspecific variation in flooding tolerance is the basic pre-condition for adaptive flooding tolerance to evolve, and flooding-induced shoot elongation is an important trait that enables plants to survive shallow, prolonged flooding. Here an investigation was conducted to determine to what extent variation in flooding-induced leaf elongation exists among and within populations of the wetland species Rumex palustris, and whether the magnitude of elongation can be linked to habitat characteristics.

Methods

Offspring of eight genotypes collected in each of 12 populations from different sites (ranging from river mudflats with dynamic flooding regimes to areas with stagnant water) were submerged, and petioles, laminas and roots were harvested separately to measure traits related to elongation and plant growth.

Key Results

We found strong elongation of petioles upon submergence, and both among- and within-population variation in this trait, not only in final length, but also in the timing of the elongation response. However, the variation in elongation responses could not be linked to habitat type.

Conclusions

Spatio-temporal variation in the duration and depth of flooding in combination with a presumably weak selection against flooding-induced elongation may have contributed to the maintenance of large genetic variation in flooding-related traits among and within populations.     

Kinases as targets in the treatment of solid tumors

The protein kinase family, one of the largest gene families in eukaryotes, plays an important role in regulating various cellular processes such as cell proliferation, cell death, cell cycle progression, differentiation and cell survival. Therefore, it is not surprising that the deregulation of many kinases is usually directly linked to cancer development. In all solid tumors, changes in protein kinase expression levels and activities, as well as alterations in the degree of posttranslational modifications can contribute to cancer development. Consequently, the identification of molecular targets and signaling pathways specific to cancer cells is becoming more and more important for cancer drug development and cancer therapies. Inhibition of various protein kinases has already been investigated in many pre-clinical and clinical trials targeting all stages of signal transduction, demonstrating promising results in cancer therapy. Conventional chemotherapeutics are often ineffective as well as harmful; hence a combination of both chemotherapeutics and protein kinase inhibitors may result in new and more successful therapeutic approaches. In this review we focus on protein kinases involved in different signaling pathways and their alterations in solid tumors.     

Multidimensional proteomics of human serum using parallel chromatography of native constituents and microplate technology

A versatile, multidimensional, and non-denaturing proteome separation procedure using microplate technology is presented, yielding a digitized image of proteome composition. In the first dimension, the sample under study is separated into 96 fractions by size exclusion chromatography (SEC). In the second dimension, the fractions of the first dimension are transferred by the liquid-handling device CyBi-Well (CyBio AG, Jena, Germany) to 96 parallel anion exchange chromatography columns. In this way the proteins are conserved in their native states and are distributed in 2400 liquid fractions with high recovery rates and sufficient reproducibility. The resulting fractions are subjected to protein quantitation and identification. Spectrophotometrical and immunological methods and enzyme activity measurements are used for quantitation. To identify proteins, the fractions are subjected to MALDI-MS, and their tryptic digests to both MALDI- and LC-ESI-MS/MS. All preparation steps except the first are applied in parallel to sets of multiples of 96 samples. The procedure may be refined by adding more separation steps and may be adapted to various protein amounts and to various proteomes. Moreover, the method offers the opportunity to investigate functional protein complexes. The method was applied to separate the normal human serum proteome. Within 255 fractions exhibiting the highest protein concentrations, 742 proteins were identified by LC-ESI-MS/MS peptide sequence tags.     

Vascular wall resident progenitor cells: a source for postnatal vasculogenesis

Here, we report the existence of endothelial precursor (EPC) and stem cells in a distinct zone of the vascular wall that are capable to differentiate into mature endothelial cells, hematopoietic and local immune cells, such as macrophages. This zone has been identified to be localized between smooth muscle and adventitial layer of human adult vascular wall. It predominantly contains CD34-positive (+) but CD31-negative (-) cells, which also express VEGFR2 and TIE2. Only few cells in this zone of the vascular wall are positive for CD45. In a ring assay using the fragments of human internal thoracic artery (HITA), we show here that the CD34+ cells of the HITA-wall form capillary sprouts ex vivo and are apparently recruited for capillary formation by tumor cells. New vessels formed by these vascular wall resident EPCs express markers for angiogenically activated endothelial cells, such as CEACAM1, and also for mature endothelial cells, such as VE-cadherin or occludin. Vascular wall areas containing EPCs are found in large and middle sized arteries and veins of all organs studied here. These data suggest the existence of a ;vasculogenic zone' in the wall of adult human blood vessels, which may serve as a source for progenitor cells for postnatal vasculogenesis, contributing to tumor vascularization and local immune response.     

Emergence and maintenance of infectious salmon anaemia virus (ISAV) in Europe: a new hypothesis

The present study describes the use of molecular methods in studying infectious salmon anaemia virus (ISAV), an important pathogen of farmed salmon in Norway, Scotland, the Faeroe Islands, Canada, USA and Chile. The nucleotide sequences of the haemagglutinin gene (HA) from 70 ISAV isolates have been analysed for phylogenetic relationship and the average mutation rate of nucleotide substitutions calculated. The isolates constitute 2 major groups, 1 European and 1 North American group. The isolate from Chile is closely related to the North American isolates. The European isolates can be further divided into 3 separate groups reflecting geographical distribution, time of collection, and transmission connected with farming activity. Based on existing information about infectious salmon anaemia (ISA) and new information emerging from the present study, it is hypothesised that: (1) ISAV is maintained in wild populations of trout and salmon in Europe; (2) it is transmitted between wild hosts mainly during their freshwater spawning phase in rivers; (3) wild salmonids, mainly trout, possibly carry benign wild-type ISAV isolates; (4) a change (mutation) in virulence probably results from deletions of amino acid segments from the highly polymorphic region (HPR) of benign wild-type isolates; (5) ISA emerges in farmed Atlantic salmon when mutated isolates are transmitted from wild salmonids or, following mutation of benign isolates, in farmed salmon after transmission from wild salmonids; (6) farming activity is an important factor in transmission of ISAV between farming sites in addition to transmission of ISAV from wild salmonids to farmed salmon; (7) transmission of ISAV from farmed to wild salmonids probably occurs less frequently than transmission from wild to farmed fish due to lower frequency of susceptible wild individuals; (8) the frequency of new outbreaks of ISA in farmed salmon probably reflects natural variation in the prevalence of ISAV in wild populations of salmonids.     

3-hydroxypropionic acid as a nematicidal principle in endophytic fungi

3- Hydroxypropionic acid was isolated by bioactivity-guided fractionation of extracts obtained from submerged cultures of several endophytic fungi isolated from above-ground plant organs. This compound showed selective nematicidal activity against the plant-parasitic nematode Meloidogyne incognita with LD50 values of 12.5-15 microg/ml. Activity against the saprophytic Caenorhabditis elegans was fivefold lower. No antimicrobial, cytotoxic or phytotoxic effects were observed. Propionic acid and D- and L-lactic acids were not active against either nematode species. Based on morphological features and ITS, 18S and 28S rDNA analyses, the producing strains were identified as Phomopsis phaseoli isolated from the leaf of a tropical tree, and four strains of Melanconium betulinum isolated from twigs of Betula pendula and B. pubescens in Germany. This is the first report of 3-hydroxypropionic acid in fungi, and of the nematicidal activity of this metabolite.     

Defects in cytokinesis,actin reorganization and the contractile vacuole in cells deficient in RhoGDI

Rho GDP-dissociation inhibitors (RhoGDIs) modulate the cycling of Rho GTPases between active GTP-bound and inactive GDP-bound states. We identified two RhoGDI homologues in DICTYOSTELIUM: GDI1 shares 51-58% similarity to RhoGDIs from diverse species. GDI2 is more divergent (40-44% similarity) and lacks the N-terminal regulatory arm characteristic for RhoGDI proteins. Both are cytosolic proteins and do not relocalize upon reorganization of the actin cytoskeleton. Using a two-hybrid approach, we identified Rac1a/1b/1c, RacB, RacC and RacE as interacting partners for GDI1. Cells lacking GDI1 are multinucleate, grow slowly and display a moderate pinocytosis defect, but rates of phagocytosis are unaffected. Mutant cells present prominent actin-rich protrusions, and large vacuoles that are continuous with the contractile vacuole system. The actin polymerization response upon stimulation with cAMP was reduced, but the motile behavior toward the chemoattractant was unaffected. Our results indicate that GDI1 plays a central role in the regulation of signal transduction cascades mediated by Rho GTPases.