Plasma tPA-Activity and Progression of Cerebral White Matter Hyperintensities in Lacunar Stroke Patients

Introduction

Tissue plasminogen activator (tPA)-activity and plasminogen activator inhibitor type 1 (PAI-1) antigen are considered to be haemostasis-related markers of endothelial activation and relate to presence of cerebral white matter hyperintensities (WMH) as was earlier shown in a cross-sectional study. We investigated whether tPA-activity and PAI-1 levels are associated with WMH progression in a longitudinal study.

Methods

In 127 first-ever lacunar stroke patients in whom baseline brain MRI and plasma levels of tPA-activity and PAI-1-antigen were available, we obtained a 2-year follow-up MRI. We assessed WMH progression by a visual WMH change scale. We determined the relationship between levels of tPA-activity and PAI-1 and WMH progression, by logistic regression analysis.

Results

Plasma tPA-activity was associated with periventricular WMH progression (OR 2.36, 95% CI 1.01–5.49, with correction for age and sex and baseline presence of WMH), but not with deep or any (periventricular and/or deep) WMH progression. PAI-1 levels were lower in patients with WMH progression, but these results were not significant.

Conclusion

We found a relationship between plasma tPA-activity and progression of periventricular WMH. More research is needed to determine whether there is a (direct) role of tPA in the development and progression of WMH.     

ESM-1 silencing decreased cell survival,migration, and invasion and modulated cell cycle progression in hepatocellular carcinoma

Amino Acids - Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate. The aim of this study was to...     

Human transformations of the Wadden Sea ecosystem through time: a synthesis

Todays Wadden Sea is a heavily human-altered ecosystem. Shaped by natural forces since its origin 7,500 years ago, humans gradually gained dominance in influencing ecosystem structure and functioning. Here, we reconstruct the timeline of human impacts and the history of ecological changes in the Wadden Sea. We then discuss the ecosystem and societal consequences of observed changes, and conclude with management implications. Human influences have intensified and multiplied over time. Large-scale habitat transformation over the last 1,000 years has eliminated diverse terrestrial, freshwater, brackish and marine habitats. Intensive exploitation of everything from oysters to whales has depleted most large predators and habitat-building species since medieval times. In the twentieth century, pollution, eutrophication, species invasions and, presumably, climate change have had marked impacts on the Wadden Sea flora and fauna. Yet habitat loss and overexploitation were the two main causes for the extinction or severe depletion of 144 species (~20% of total macrobiota). The loss of biodiversity, large predators, special habitats, filter and storage capacity, and degradation in water quality have led to a simplification and homogenisation of the food web structure and ecosystem functioning that has affected the Wadden Sea ecosystem and coastal societies alike. Recent conservation efforts have reversed some negative trends by enabling some birds and mammals to recover and by creating new economic options for society. The Wadden Sea history provides a unique long-term perspective on ecological change, new objectives for conservation, restoration and management, and an ecological baseline that allows us to envision a rich, productive and diverse Wadden Sea ecosystem and coastal society.     

Endothelial Transient Receptor Potential Conical Channel (TRPC)-3 Activation Induces Vasogenic Edema Formation in the Rat Piriform Cortex Following Status Epilepticus

Transient receptor potential canonical channel (TRPC) is a nonselective cation channel permeable to Ca²⁺, which express in many cell types, including neurons. However the alterations in TRPC receptor expressions in response to status epilepticus (SE) have not been explored. Therefore, the present study was designated to elucidate the roles of TRPC3 in neuronal death and vasogenic edema within the rat piriform cortex (PC) following SE. In non-SE animals, TRPC3 immunoreactivity was abundantly detected in the PC. Following SE, TRPC3 immunoreactivity was increased in neurons. Furthermore, TRPC3 expression was detected in endothelial cells that did not contain it in non-SE animals. Loss of SMI-71 (a blood–brain barrier antigen) immunoreactivity was also observed in TRPC3 positive endothelial cells. In addition, FJB positive neurons and vasogenic edema were noticeably detected in the PC. To directly determine whether TRPC3 activation is correlated to SE-induced vasogenic edema formation and neuronal damages in the PC, the effect of Pyr-3 (a TRPC3 antagonist) on SE-induced insults were investigated. Pyr-3 infusion effectively attenuated vasogenic edema in the PC as compared to the vehicle. Therefore, our findings indicate that TRPC3 activation/overexpression induced by SE may involve BBB disruption and neuronal damages in the rat PC following SE. Therefore, the present study was TRPC3 may play an important role in SE-induced vasogenic edema formation through BBB disruptions in the rat PC.     

Horizontal Transfer of Archaeal Genes into the Deinococcaceae: Detection by Molecular and Computer-Based Approaches

Members of the Deinococcaceae (e.g., Thermus, Meiothermus, Deinococcus) contain A/V-ATPases typically found in Archaea or Eukaryotes which were probably acquired by horizontal gene transfer. Two methods were used to quantify the extent to which archaeal or eukaryotic genes have been acquired by this lineage. Screening of a Meiothermus ruber library with probes made against Thermoplasma acidophilum DNA yielded a number of clones which hybridized more strongly than background. One of these contained the prolyl tRNA synthetase (RS) gene. Phylogenetic analysis shows the M. ruber and D. radiodurans prolyl RS to be more closely related to archaeal and eukaryal forms of this gene than to the typical bacterial type. Using a bioinformatics approach, putative open reading frames (ORFs) from the prerelease version of the D. radiodurans genome were screened for genes more closely related to archaeal or eukaryotic genes. Putative ORFs were searched against representative genomes from each of the three domains using automated BLAST. ORFs showing the highest matches against archaeal and eukaryotic genes were collected and ranked. Among the top-ranked hits were the A/V-ATPase catalytic and noncatalytic subunits and the prolyl RS genes. Using phylogenetic methods, ORFs were analyzed and trees assessed for evidence of horizontal gene transfer. Of the 45 genes examined, 20 showed topologies in which D. radiodurans homologues clearly group with eukaryotic or archaeal homologues, and 17 additional trees were found to show probable evidence of horizontal gene transfer. Compared to the total number of ORFs in the genome, those that can be identified as having been acquired from Archaea or Eukaryotes are relatively few (approximately 1%), suggesting that interdomain transfer is rare.     

Effect of feedback on test ordering behaviour of general practitioners.

OBJECTIVE--To assess the effect of feedback on the test ordering behaviour of general practitioners. DESIGN--Comparison of requests at two diagnostic centres, and internal comparison between tests which were discussed in feedback and tests which were not. SETTING--A diagnostic centre in Maastricht giving feedback and another elsewhere in the Netherlands (laboratory A) not giving feedback. SUBJECTS--All 85 general practitioners in the region of Maastricht, and all general practitioners in the region of laboratory A. MAIN OUTCOME MEASURES--Numbers of tests requested by general practitioners. RESULTS--Requests at the Maastricht diagnostic centre decreased soon after the onset of feedback whereas there was a persistent increase in requests at laboratory A. Tests that were discussed showed the strongest decrease (maximum 40%), though tests that were not discussed decreased as well (maximum 27%). CONCLUSIONS--Feedback on diagnostic requests may exert a strong influence on request behaviour. Four years after the onset of feedback the effects were still noticeable.