2,524 research outputs found
Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs
Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base
Waking up the gut in critically ill patients
Multiorgan failure frequently develops in critically ill patients. While therapeutic efforts in such patients are often focused on the lungs, on the cardiovascular system as well as on the kidneys, it is important to also consider the functional alterations in gut motility and hormone secretion. Given the central regulatory functions of many gut hormones, such as glucagon-like peptide 1, glucagon-like peptide 2, ghrelin and others, exogenous supplementation of some of these factors may be beneficial under conditions of critical illness. From a pragmatic point of view, the most feasible way towards a restoration of gut hormone secretion in critically ill patients is to provide enteral nutritional supply as soon as possible
Target profiling of an antimetastatic RAPTA agent by chemical proteomics: relevance to the mode of action.
The clinical development of anticancer metallodrugs is often hindered by the elusive nature of their molecular targets. To identify the molecular targets of an antimetastatic ruthenium organometallic complex based on 1,3,5-triaza-7-phosphaadamantane (RAPTA), we employed a chemical proteomic approach. The approach combines the design of an affinity probe featuring the pharmacophore with mass-spectrometry-based analysis of interacting proteins found in cancer cell lysates. The comparison of data sets obtained for cell lysates from cancer cells before and after treatment with a competitive binder suggests that RAPTA interacts with a number of cancer-related proteins, which may be responsible for the antiangiogenic and antimetastatic activity of RAPTA complexes. Notably, the proteins identified include the cytokines midkine, pleiotrophin and fibroblast growth factor-binding protein 3. We also detected guanine nucleotide-binding protein-like 3 and FAM32A, which is in line with the hypothesis that the antiproliferative activity of RAPTA compounds is due to induction of a G2/M arrest and histone proteins identified earlier as potential targets
Clinical Practice Patterns for Hydroxyurea Initiation in Young Children with Sickle Cell Disease
The Molecular Clockwork of the Fire Ant Solenopsis invicta
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Underwriting Apophenia and Cryptids: Are Cycles Statistical Figments of our Imagination?
This paper re-examines the evidence in favour of the existence of underwriting cycles in property and casualty insurance and their economical significance. Using a meta-analysis of published papers in the area of insurance economics, we show that the evidence supporting the existence of underwriting cycles is misleading. There is, in fact, little evidence in favour of insurance cycles with a linear autoregressive character. This means that any cyclicality in firm profitability in the property and casualty insurance industry is not predictable in a classical econometric framework. It follows that pricing in the property and casualty insurance industry is not incompatible with that of a competitive market
Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin
There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters
Ballistic Spin Resonance
The phenomenon of spin resonance has had far reaching influence since its
discovery nearly 70 years ago. Electron spin resonance (ESR) driven by high
frequency magnetic fields has informed our understanding of quantum mechanics,
and finds application in fields as diverse as medicine and quantum information.
Spin resonance induced by high frequency electric fields, known as electric
dipole spin resonance (EDSR), has also been demonstrated recently. EDSR is
mediated by spin-orbit interaction (SOI), which couples the spin degree of
freedom and the momentum vector. Here, we report the observation of a novel
spin resonance due to SOI that does not require external driving fields.
Ballistic spin resonance (BSR) is driven by an internal spin-orbit field that
acts upon electrons bouncing at gigaHertz frequencies in narrow channels of
ultra-clean two-dimensional electron gas (2DEG). BSR is manifested in
electrical measurements of pure spin currents as a strong suppression of spin
relaxation length when the motion of electrons is in resonance with spin
precession. These findings point the way to gate-tunable coherent spin
rotations in ballistic nanostructures without external a.c. fields.Comment: 24 pages, including supplementary material
Electrical half-wave rectification at ferroelectric domain walls
Ferroelectric domain walls represent multifunctional 2D-elements with great
potential for novel device paradigms at the nanoscale. Improper ferroelectrics
display particularly promising types of domain walls, which, due to their
unique robustness, are the ideal template for imposing specific electronic
behavior. Chemical doping, for instance, induces p- or n-type characteristics
and electric fields reversibly switch between resistive and conductive
domain-wall states. Here, we demonstrate diode-like conversion of
alternating-current (AC) into direct-current (DC) output based on neutral
180 domain walls in improper ferroelectric ErMnO. By combining
scanning probe and dielectric spectroscopy, we show that the rectification
occurs for frequencies at which the domain walls are fixed to their equilibrium
position. The practical frequency regime and magnitude of the output is
controlled by the bulk conductivity. Using density functional theory we
attribute the transport behavior at the neutral walls to an accumulation of
oxygen defects. Our study reveals domain walls acting as 2D half-wave
rectifiers, extending domain-wall-based nanoelectronic applications into the
realm of AC technology
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