Prehospital Thrombolysis: A Manual from Berlin

In acute ischemic stroke, time from symptom onset to intervention is a decisive prognostic factor. In order to reduce this time, prehospital thrombolysis at the emergency site would be preferable. However, apart from neurological expertise and laboratory investigations a computed tomography (CT) scan is necessary to exclude hemorrhagic stroke prior to thrombolysis. Therefore, a specialized ambulance equipped with a CT scanner and point-of-care laboratory was designed and constructed. Further, a new stroke identifying interview algorithm was developed and implemented in the Berlin emergency medical services. Since February 2011 the identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of this ambulance, a stroke emergency mobile (STEMO). On arrival, a neurologist, experienced in stroke care and with additional training in emergency medicine, takes a neurological examination. If stroke is suspected a CT scan excludes intracranial hemorrhage. The CT-scans are telemetrically transmitted to the neuroradiologist on-call. If coagulation status of the patient is normal and patient''s medical history reveals no contraindication, prehospital thrombolysis is applied according to current guidelines (intravenous recombinant tissue plasminogen activator, iv rtPA, alteplase, Actilyse).Thereafter patients are transported to the nearest hospital with a certified stroke unit for further treatment and assessment of strokeaetiology. After a pilot-phase, weeks were randomized into blocks either with or without STEMO care. Primary end-point of this study is time from alarm to the initiation of thrombolysis. We hypothesized that alarm-to-treatment time can be reduced by at least 20 min compared to regular care.     

Growth, regeneration and shade tolerance of the Wild Service Tree (Sorbus torminalis (L.) Crantz) in aged oak coppice forests

Sorbus torminalis L. (Crantz) is a rare species in Central European forests with very limited quantitative information on its regeneration and growth dynamics. Since coppicing is no longer practiced in the most parts of Central Europe, it is unclear whether S. torminalis, which has usually a shorter end height than companion species, can persist in high forest systems. Here, we quantified species frequency on three 1 ha sample plots of former oak coppice forest. To determine whether S. torminalis regenerated continuously and how it might compete with oaks, the age of 80 trees was determined, and diameter and height growth were reconstructed for the 20 largest trees by stem analysis. To assess its shade tolerance, photosynthesis was measured for leaves located in high and low light conditions. Dendrochronological data demonstrated that, over the last 80 years, continuous recruitment of S. torminalis occurred. Growth patterns and photosynthesis measurements suggest that S. torminalis is a highly shade-tolerant species. We conclude that abandonment of coppicing in these forests does not threaten the status of S. torminalis, which can persist beneath the canopy of oaks.     

Relationship of 5-HTTLPR Polymorphism with Various Factors of Pain Processing: Subjective Experience,Motor Responsiveness and Catastrophizing

Although serotonin is known to play an important role in pain processing, the relationship between the polymorphism in 5-HTTLPR and pain processing is not well understood. To examine the relationship more comprehensively, various factors of pain processing having putative associations with 5-HT functioning were studied, namely the subjective pain experience (pain threshold, rating of experimental pain), catastrophizing about pain (Pain Catastrophizing Scale = PCS) and motor responsiveness (facial expression of pain). In 60 female and 67 male participants, heat pain stimuli were applied by a contact thermode to assess pain thresholds, supra-threshold ratings and a composite score of pain-relevant facial responses. Participants also completed the PCS and were grouped based on their 5-HTTLPR genotype (bi-allelic evaluation) into a group with s-allele carriers (ss, sl) and a second group without (ll). S-allele carriers proved to have lower pain thresholds and higher PCS scores. These two positive findings were unrelated to each other. No other difference between genotype groups became significant. In all analyses, “age” and “gender” were controlled for. In s-allele carriers the subjective pain experience and the tendency to catastrophize about pain was enhanced, suggesting that the s-allele might be a risk factor for the development and maintenance of pain. This risk factor seems to act via two independent routes, namely via the sensory processes of subjective pain experiences and via the booster effects of pain catastrophizing.     

Binding of Lassa virus perturbs extracellular matrix-induced signal transduction via dystroglycan

The arenavirus Lassa virus (LASV) causes a severe haemorrhagic fever with high mortality in man. The cellular receptor for LASV is dystroglycan (DG). DG is a ubiquitous receptor for extracellular matrix (ECM) proteins, which cooperates with β1 integrins to control cell-matrix interactions. Here, we investigated whether LASV binding to DG triggers signal transduction, mimicking the natural ligands. Engagement of DG by LASV resulted in the recruitment of the adaptor protein Grb2 and the protein kinase MEK1 by the cytoplasmic domain of DG without activating the MEK/ERK pathway, indicating assembly of an inactive signalling complex. LASV binding to cells however affected the activation of the MEK/ERK pathway via α6β1 integrins. The virus-induced perturbation of α6β1 integrin signalling critically depended on high-affinity LASV binding to DG and DG's cytoplasmic domain, indicating that LASV-receptor binding perturbed signalling cross-talk between DG and β1 integrins.     

Novel antiviral strategies to combat human Arenavirus infections

Arenaviruses merit significant attention both as tractable model systems to study acute and persistent viral infections, and as clinically important human pathogens. Evidence indicates that LCMV remains present in the USA and Europe and capable of causing significant morbidity in infected individuals, likely being a neglected human pathogen. Moreover, new arenaviruses are being discovered in the Americas on the average of one every three years, with some of them causing severe hemorrhagic fever. In addition, weaponized forms of these viruses pose a real threat as agents of bioterrorism. Therefore, it is important to develop effective vaccines and better antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced Arenavirus infections. The development of arenavirus reverse genetic systems is allowing investigators to conduct a detailed molecular characterization of the viral cis-acting signals and trans-acting factors that control each of the steps of the Arenavirus life cycle, including RNA synthesis, packaging and budding. We will discuss how this new knowledge is facilitating the establishment of novel assays to identify and characterize compounds capable of interfering with specific steps of the virus life cycle. Likewise, the ability to generate predetermined specific mutations within the arenavirus genome, and analyze their phenotypic expression, would significantly contribute to the elucidation of arenavirus-host interactions, including the bases of their ability to persist, as well as to cause severe HF (hemorrhagic fever) disease in humans. These approaches could also lead to the development of novel potent and safe Arenavirus vaccines.     

Mitochondrial potassium channels: from pharmacology to function

Mitochondrial potassium channels, such as ATP-regulated or large conductance Ca2+ -activated and voltage gated channels were implicated in cytoprotective phenomenon in different tissues. Basic effects of these channels activity include changes in mitochondrial matrix volume, mitochondrial respiration and membrane potential, and generation of reactive oxygen species. In this paper, we describe the pharmacological properties of mitochondrial potassium channels and their modulation by channel inhibitors and potassium channel openers. We also discuss potential side effects of these substances.     

Non-Newtonian Behavior of Blood in Oscillatory Flow

Sinusoidal oscillatory flow of blood and of aqueous glycerol solutions was produced in rigid cylindrical tubes. For aqueous glycerol, the amplitude of the measured pressure gradient wave form conformed closely to that predicted by Womersley's theory of oscillatory flow, up to Reynolds numbers approaching 2000. Blood differed significantly from aqueous glycerol solutions of comparable viscosity, especially at low frequencies and high hematocrits. As frequency increased, the hydraulic impedance of blood decreased to a minimum at a frequency of about 1-2 CPS, increasing monotonically at higher frequencies. The dynamic apparent viscosity of blood, calculated from Womersley's theory, decreased with increasing flow amplitude. The reactive component of the hydraulic impedance increased with frequency as predicted by theory; the resistive component decreased with increasing frequency, differing from the resistance of a Newtonian fluid which increased with frequency.