Binding of endothelin to plasma proteins and tissue receptors: effects on endothelin determination, vasoactivity, and tissue kinetics

AbstractIn vitro binding of (3-[125I]Tyr)-endothelin-1 ([125I]ET-1) and (3-[125I]Tyr)-big ET-1(1–38) ([125I]big ET-1) to plasma proteins of healthy humans, cardiac patients and normotensive and hypertensive rats was investigated by equilibrium dialysis. Binding of both tracers was similar in plasma from healthy humans, patients with congestive heart failure, and following myocardial infarction (∼60%), and marginally higher in rat plasmas (∼70%). Binding of [125I]ET-1 to human plasma could be explained by binding to human serum albumin. Endogenous plasma ET-1 levels were ∼9 pg/ml in healthy humans, and ∼12–16 pg/ml in cardiac patients; big ET-1 concentrations were approximately two- to threefold higher. ET-1 bound to plasma protein was partly lost in column extraction. In rat isolated perfused hearts, the coronary dilator and constrictor potency of exogenous free and albumin-bound ET-1 was similar, whereas the kinetics of endogenous ET-1 was impeded by tight binding to ET receptors. The data indicate that binding of ET-1 to plasma proteins is without effect on peptide vasoactivity, but binding to tissue receptors greatly impedes its tissue kinetics

Rettungsdienststrukturen neu denken – Ergebnisse der Expertenworkshops „Logistik in der präklinischen Notfallversorgung“ [Rethinking emergency medical services (EMS)—results of an interdisciplinary expert panel on logistics in EMS]

Die rettungsdienstliche Struktur in Deutschland stellt eine Versorgung auf sehr hohem Niveau sicher. Dennoch ist es notwendig, die vorhandenen Strukturen zu überdenken und für die Zukunft zu härten. Nicht nur vor dem Hintergrund stetig steigender Einsatzzahlen, sondern auch wegen der Herausforderungen der Personalgewinnung und der Alterung der Bevölkerung sollten Reformen im Rettungsdienst dringend angegangen werden. Hier kann der Rettungsdienst viel von der Mathematik und gerade vom Bereich „operations research“ lernen. Dieser Fachbereich beschäftigt sich explizit mit der Verbesserung von logistischen Herausforderungen, die der Rettungsdienst ohne Frage ist. In der vorliegenden Arbeit berichten die Autorinnen und Autoren über die ersten Ergebnisse zweier Workshops zum Thema „Logistik in der präklinischen Versorgung“ und möchten damit die Diskussion im Rettungsdienst auf breiter Basis anregen sowie Verbesserungspotenziale und Herausforderungen für die verschiedenen Akteure in der präklinischen Behandlung herausarbeiten, aber auch erste Ideen zu Lösungsansätzen liefern

Quantifying coronary sinus flow and global LV perfusion at 3T

<p>Abstract</p> <p>Background</p> <p>Despite the large availability of 3T MR scanners and the potential of high field imaging, this technical platform has yet to prove its usefulness in the cardiac MR setting, where 1.5T remains the established standard. Global perfusion of the left ventricle, as well as the coronary flow reserve (CFR), can provide relevant diagnostic information, and MR measurements of these parameters may benefit from increased field strength. Quantitative flow measurements in the coronary sinus (CS) provide one method to investigate these parameters. However, the ability of newly developed faster MR sequences to measure coronary flow during a breath-hold at 3T has not been evaluated.</p> <p>Methods</p> <p>The aim of this work was to measure CS flow using segmented phase contrast MR (PC MR) on a clinical 3T MR scanner. Parallel imaging was employed to reduce the total acquisition time. Global LV perfusion was calculated by dividing CS flow with left ventricular (LV) mass. The repeatability of the method was investigated by measuring the flow three times in each of the twelve volunteers. Phantom experiments were performed to investigate potential error sources.</p> <p>Results</p> <p>The average CS flow was determined to 88 ± 33 ml/min and the deduced LV perfusion was 0.60 ± 0.22 ml/min·g, in agreement with published values. The repeatability (1-error) of the three repeated measurements in each subject was on average 84%.</p> <p>Conclusion</p> <p>This work demonstrates that the combination of high field strength (3T), parallel imaging and segmented gradient echo sequences allow for quantification of the CS flow and global perfusion within a breath-hold.</p

Swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs

The purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. Samples were obtained from patients 60 years of age or above who were newly admitted to Sorlandet Hospital Arendal, Norway. The patients were interviewed for current symptoms of a respiratory tract infection. Using rayon swabs and nylon flocked swabs, comparable sets of mucosal samples were harvested from the nasopharynx and the oropharynx. The samples were analysed using real-time polymerase chain reaction (PCR) methods. A total of 223 patients (mean age 74.9 years, standard deviation [SD] 9.0 years) were swabbed and a virus was recovered from 11% of the symptomatic patients. Regardless of the sampling site, a calculated 4.8 times higher viral load (95% confidence interval [CI] 1.3–17, p = 0.017) was obtained using the nylon flocked swabs as compared to the rayon swabs. Also, regardless of the type of swab, a calculated 19 times higher viral load was found in the samples from the nasopharynx as compared to the oropharynx (95% CI 5.4–67.4, p < 0.001). When swabbing for respiratory viruses in elderly patients, nasopharyngeal rather than oropharyngeal samples should be obtained. Nylon flocked swabs appear to be more efficient than rayon swabs

Taqman Real-Time PCR Detects Avipoxvirus DNA in Blood of Hawaìi `Amakihi (Hemignathus virens)

Margaret E. M. Farias et al...Background Avipoxvirus sp. is a significant threat to endemic bird populations on several groups of islands worldwide, including Hawaìi, the Galapagos Islands, and the Canary Islands. Accurate identification and genotyping of Avipoxvirus is critical to the study of this disease and how it interacts with other pathogens, but currently available methods rely on invasive sampling of pox-like lesions and may be especially harmful in smaller birds. Methodology/Principal Findings Here, we present a nested TaqMan Real-Time PCR for the detection of the Avipoxvirus 4b core protein gene in archived blood samples from Hawaiian birds. The method was successful in amplifying Avipoxvirus DNA from packed blood cells of one of seven Hawaiian honeycreepers with confirmed Avipoxvirus infections and 13 of 28 Hawaìi `amakihi (Hemignathus virens) with suspected Avipoxvirus infections based on the presence of pox-like lesions. Mixed genotype infections have not previously been documented in Hawaìi but were observed in two individuals in this study. Conclusions/Significance We anticipate that this method will be applicable to other closely related strains of Avipoxvirus and will become an important and useful tool in global studies of the epidemiology of Avipoxvirus.Funding for this study was provided by: U.S. Geological Survey, Pacific Island Ecosystems Research Center (biology.usgs.gov/pierc/); U.S. Geological Survey Wildlife (biology.usgs.gov/wter/) and Invasive Species (biology.usgs.gov/invasive/) Programs; National Science Foundation (DEB0083944, www.nsf.gov); NIH/NCRR IDeA Networks of Biomedical Research Excellence (INBRE), P20RR016467 (http://www.ncrr.nih.gov/research_infrast​ructure/institutional_development_award/​idea_networks_of_biomedical_research_exc​ellence/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Development of a Flow-Trough Microarray based Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification Assay for the Detection of European Bunyaviruses

It is suspected that apart from tick-borne encephalitis virus several additional European Arboviruses such as the sandfly borne Toscana virus, sandfly fever Sicilian virus and sandfly fever Naples virus, mosquito-borne Tahyna virus, Inkoo virus, Batai virus and tick-borne Uukuniemi virus cause aseptic meningo-encephalitis or febrile disease in Europe. Currently, the microarray technology is developing rapidly and there are many efforts to apply it to infectious diseases diagnostics. In order to arrive at an assay system useful for high throughput analysis of samples from aseptic meningo-encephalitis cases the authors developed a combined multiplex ligation-dependent probe amplification and flow-through microarray assay for the detection of European Bunyaviruses. These results show that this combined assay indeed is highly sensitive, and specific for the accurate detection of multiple viruses

The Early Clinical Features of Dengue in Adults: Challenges for Early Clinical Diagnosis

Dengue infection in adults has become increasingly common throughout the world. As most of the clinical features of dengue have been described in children, we undertook a prospective study to determine the early symptoms and signs of dengue in adults. We show here that, overall, dengue cases presented with high rates of symptoms listed in the WHO 1997 or 2009 classification schemes for probable dengue fever thus resulting in high sensitivities of these schemes when applied for early diagnosis. However, symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding were less frequently reported in older adults. This trend resulted in reduced sensitivity of the WHO classification schemes in older adults even though they showed increased risks of hospitalization and severe dengue. Instead, we suggest that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. This could be useful for early clinical diagnosis in older adults so that they can be monitored and treated for severe dengue, which is especially important when an antiviral drug becomes available

Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma

<p>Abstract</p> <p>Background</p> <p>The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease.</p> <p>Methods</p> <p>We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR.</p> <p>Results</p> <p>Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma).</p> <p>Conclusions</p> <p>The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.</p