For any conformational analysis based on spectroscopic data, both the amount of data extracted and the accuracy of the theoretical relation between data and conformation are key. In this presentation, new developments for both the measurement of 1 H- 1 H J -couplings and their use for conformational analysis of five-membered rings will be discussed.
Many pathogens such as Vibrio cholerae use tripartite ATP-independent periplasmic TRAP transporters to scavenge N-acetyl- neuraminic acid sialic acid from host organisms. The sialic acid is then incorporated into the bacterial cell wall, as a disguise to protect against detection by the human immune system. Hyperpolarization by dissolution DNP provides a route to enhancing 13C MR sensitivity by more than four orders of magnitude on a wide range of small molecules. However, many potential applications of dDNP metabolomics, drug discovery, etc.
- Systematic Reviews in the Social Sciences: A Practical Guide!
- The Britannica Guide to Modern China!
- Myelodysplastic syndromes.
Using structural biology derived predictions 1 , a-Synuclein is shown to form non-toxic intrinsically disordered monomers and non-toxic fibrils, This membraneless compartment, formed by phase separation, has liquid properties and has been shown for several viruses in vivo [1,2]. Measles virus MeV is the cause of measles, it infects T-cells and macrophage cells, belongs to Paramyxoviridae family.
Its genome consists of non-segmented Electron paramagnetic resonance EPR is the method of choice to investigate and quantify paramagnetic states in e. Common EPR spectrometers use microwave mw resonators, where the sample is inserted. Here, we present an improved design of a Spectral overlap, even at high field, is a problem generally encountered in many EPR studies.
In the specific case of bulk-heterojunction BHJ organic solar cells OSCs , the paramagnetic species of interest are light-induced radicals which are created as a pair after charge transfer at the interface between the donor polymer and molecular acceptor regions making up the BHJ blend. Hence, the Recent work has shown that this protein can phase separate into liquid droplets and gels in vitro, properties that have vast implications for the mechanism of heterochromatin formation and regulation in cells.
Despite the tremendous We report an in-situ, non-invasive approach to quantify oxygen partial pressure in microfluidic lab-on-a-chip LoC devices. LoC systems provide a versatile platform to culture biological systems. As they allow a detailed control over the growth conditions, LoC devices are finding increasing applications in the culture of cells, tissues and other biological systems . This talk will focus on one class of cyclic peptides known as cyclotides, which are topologically unique in that they have a head-to-tail cyclized Magnetic resonance observes spin transitions whose frequencies depend on magnetic field because spin is associated with magnetic moment.
Allowed transitions involve a unit change of the magnetic quantum number. If the magnetic quantum number is not a good quantum number, other transitions can be partially allowed. Bile or gall is a dark green to yellowish brown fluid, produced by the liver of most vertebrates and aids the digestion of lipids in the small intestine. Bile salts are complex molecules that tend to form micellar aggregates in solutions if their Understanding the mechanisms of membrane proteins entails complementing static structures with the conformational changes in the structure.
Recent advances in Double Electron-Electron Resonance DEER spectroscopy along with computational methods to generate restrained models of proteins are enabling unprecedented insights into the conformational dynamics of active transporters. My laboratory This technique, originally developed for low magnetic fields, has been shown to be applicable at high fields, opening new avenues in materials and life sciences.
In this presentation we will review some recent advances from high magnetic field Diffusion MRI is today used in clinical routine for detecting stroke and grading prostate tumors, as well as in clinical research studies of for instance neurological diseases and normal brain development. The overwhelming majority of the diffusion MRI measurements are performed with motion encoding by the most basic form of the pulsed-gradient spin echo sequence from the mids, which is The recently introduced CLIP-COSY experiment providing homonuclear correlation spectrum with high quality clean in-phase multiplets expedites the assignment of scalar coupled proton spin network, aiding the structure elucidation of small- and medium-sized molecules.
The resolution of COSY spectra is, however, limited by the inherently small chemical shift dispersion of proton Microfluidics is a well-established technique to process, synthesize and analyse small amounts of materials for chemical, biological, medical, and environmental applications. Telomerase maintains the DNA at the ends of linear chromosomes, thereby preventing genomic instability. Its catalytic core is a non-coding Hsp70s are ubiquitous chaperones tasked with safeguarding proteins throughout their entire lifecycle, from synthesis to degradation, and are thus critical for maintaining protein-homeostasis.
The ATPase cycle of Hsp70s, which is allosterically coupled to the binding and release of their substrates, is, in turn, regulated by a large set of dedicated co-chaperones consisting of In the last few years microwave driven dynamic nuclear polarization DNP has become the method of choice to enhance signal intensities in a variety magic angle spinning MAS NMR experiments.
In particular, because of the large signal enhancements, it is used to address a variety of important chemical, biological and physical questions that are otherwise inaccessible. Despite the success of Telomeres are specialized structures located at the ends of linear chromosomes essential for cell viability and genome integrity. Their protective function is due to the formation of the Shelterin complex, that caps the end of the DNA. BiP is the only member of the Hsp70 chaperone family in the human endoplasmic reticulum 1.
Its chaperone activity is driven by ATP binding and hydrolysis that trigger the conformational change regulating the docking and undocking of its nucleotide-binding domain NBD and substrate-binding domain SBD. To achieve its many functions, BiP is regulated by several co-chaperones including the The structural organization of the interface characterizing binding, assembly and recognition of biomolecules on inorganic surfaces has attracted considerable attention in the domains of catalysis and prebiotic chemistry.
In the context of origins-of-life chemistry, this study is focused on the catalytic effect of a silica surface on amino acids condensation, more precisely on two amino acids, Nanobodies i. We propose here the use of spin-labeled nanobodies as conformational reporters of wild type unlabeled proteins via DEER spectroscopy. Recent developments in magnetic flux tailoring techniques paved the way for NMR in high pressure diamond anvil cells at multi-megabar pressures.
These structures have been Nuclear magnetic resonance NMR , one of the most powerful analytical techniques in chemistry and life science, is typically limited to macroscopic volumes due to its inherent low sensitivity. This excludes NMR spectroscopy from analysis of microscopic samples sizes such as in single-cell biology or in microfluidic applications.
In recent years, it has been shown that NMR signals can be Nuclear Magnetic Resonance NMR Spectroscopy is a unique tool to study complex systems such as biological macromolecules due to its ability to probe molecular structure and dynamics at atomic resolution and on a wide range of timescales.
During the last decades major progresses have been made towards the description of biomolecular dynamics and protein folding. However, fundamental questions Electron paramagnetic resonance EPR distance measurements provide highly accurate and precise geometric constraints. These have made valuable contributions to studies of the structures and conformations of biomolecules. Recently, application of double-histidine dHis motifs, coupled with Cu II spin-labels has shown promise in even higher precision distance Anisotropic NMR parameters become increasingly important in organic structure elucidation for the determination of conformations and relative configuration of natural products, synthesized compounds and catalysts.
The use of lyotropic liquid crystals from helically chiral polymers is especially The protein Upstream-of-N-Ras Unr is a highly conserved and abundant RNA binding protein with elevated expression levels in several cancer types. Here, it is supposed to bind certain mRNAs to regulate their translation. In all hitherto publications Despite the central importance of the binding of chaperones to unfolded substrates, the structural basis of their interaction remains poorly understood.
The scarcity of structural data on complexes between chaperones and NMR is a major tool in metabolomics thanks to its non-destructive and highly reproducible character. NMR metabolomics include untargeted analysis where spectral fingerprints are analyzed with statistical tools to highlight potential biomarkers, and targeted methods which aim at accurately quantifying multiple metabolites.
Most studies rely on 1D NMR which suffers from ubiquitous spectral These acetylation sites have been linked to processing and folding of nascent H3 and play an integral role in replication- and repair-coupled nucleosome assembly. Rtt is unique in its activation, performed by two structurally unrelated histone Electron-nuclear double resonance ENDOR and dynamic nuclear polarization DNP are two techniques based on polarization transfer between electron and nuclear spins.
Despite differences in the experimental realization, their similarities rely on the detailed mechanism of hyperfine interactions. We report on design of solid-state NMR probes for the 1. We will discuss strategy for making higher-field solid-state NMR probes for materials and biological applications, while It is generated by the internal dynamics of methyl groups resulting in negative enhancement and inverted Aiming at the design of an allosteric modulator of the neonatal Fc receptor FcRn —Immunoglobulin G IgG interaction, we developed a new methodology including NMR fragment screening, X-ray crystallography, and magic-angle-spinning MAS NMR at kHz after sedimentation, exploiting very fast spinning of the nondeuterated soluble 42 kDa receptor construct to obtain resolved proton-detected 2D So-called phase-space representations such as Wigner functions, are a powerful tool for representing quantum states and characterizing their time evolution in the case of infinite-dimensional quantum systems and have been widely used in quantum optics and beyond.
Continuous phase spaces have also been studied for the finite-dimensional quantum systems of individual spins. However, much less Hereby we present a systematic study performed at different magnetic fields on model systems doped with nitroxide radical Biofilms are implicated in serious infectious diseases and have emerged as a target for anti-infectives. Our research program is inspired by the challenge and importance of elucidating chemical structure and function in complex biological systems and we strive to transform our discoveries into new therapeutic strategies.
We have introduced new approaches integrating solid-state NMR with A broad effort is underway to improve the sensitivity of nuclear magnetic resonance through the use of dynamic nuclear polarization DNP. Nitrogen-vacancy NV centers in diamond offer an appealing platform because these paramagnetic defects show efficient optical pumping at room temperature. This presentation focuses on the spin dynamics of NVs coupled to substitutional nitrogen the so NMR spectroscopy presents a non-invasive detection technique for molecular structure elucidation and dynamic effect analyses.
In general NMR applications, spectral resolution is the key index determining the availability of resulting spectra. Due to limited chemical shift ranges and appended J coupling splittings, conventional 1H NMR spectra are subject to spectral congestions in complex We have employed various NMR techniques to reach the goal and some results will be presented.
The water and proton dynamics in Nafion polymer Applications of advanced solid-state NMR methods for probing intermolecular interactions, notably hydrogen bonding are presented: Homonuclear 1H-1H double-quantum DQ experiments reveal proximities typically under 3. Recent breakthroughs in optical and electron microscopy have changed the fields of Cell and Structural Biology in a most profound manner, with ever more detailed information about the inner workings of cells becoming available. Complementary to the advancements, novel in situ methods are beginning to emerge as powerful tools in Cellular Structural Biology.
Here, I discuss how recent HBV infection causes a severe liver infectious disease and has become a global problem affecting human health. At least million people are chronically infected with HBV, with an estimated , deaths per year from HBV associated hepatocellular carcinoma, mainly in Asia. Current clinical strategy We have recently shown how the bulk of proton-free inorganic solids can be hyperpolarized using dynamic nuclear polarization, resulting in sensitivity enhancements in MAS experiments. Structural investigation of nucleic acids is usually carried out either in diluted buffered solutions or on crystals of these biomolecules.
These environments markedly differ from the native one in which these molecules are found, where effects as macromolecular crowding or intermolecular interactions can play a significant role on the conformation. The difficulty to automate data acquisition and analysis of complex protein spectra has been one of the major bottlenecks for the widespread use of NMR spectroscopy in structural biology. Biological tissue biopsies are often heterogeneous in cell type and structure and the recognition of this heterogeneity is crucial for many diagnostic studies.
For example, differentiation between involved and uninvolved tissue is paramount for the determination of exact tumour margins [DeFeo et al. Identification of chronic kidney disease patients at risk of progressing to end-stage renal disease ESRD is essential for treatment decision-making and clinical trial design.
Here, we show that proton nuclear magnetic resonance NMR spectroscopy of blood plasma specimens together with techniques from machine learning improves the currently best performing kidney failure risk equation, the Understanding how proteins fold into stable structures without external assistance remains one of the major open questions in biophysics. The ability of NMR to report atomic resolution structural information for both folded and unfolded proteins makes it a uniquely powerful to study protein folding. However, typical experiment times of hours to days are incompatible with the typical Increasing evidence suggests that the highly complex and dynamic environment of the cell interior and its physiochemical setting imposes critical control on cellular functions, which is hardly reproducible under in vitro conditions.
In-cell solution-state NMR can track such structural and dynamical interactions at the atomic level provided that proteins or other molecular units are small and Nuclear magnetic resonance NMR spectroscopy and magnetic resonance imaging MRI are powerful and versatile methods in modern chemistry and biology fields.
Nevertheless, they suffer from intrinsically limited sensitivity due to the low nuclear spin polarization at ambient temperature. One of the promising methods to overcome this limitation is dynamic nuclear polarization DNP that Solid-state NMR is a very flexible and powerful technique for the elucidation of geometry and dynamics information on a variety of samples. However, there is still a need to overcome sensitivity and resolution aspects along with the necessity to carry out multidimensional experiments in a short span of time.
In order to overcome these challenges, we have made use of two approaches. It makes it possible to run, in minutes, experiments that would take weeks, or simply would not be possible otherwise because they are too insensitive. Acute Respiratory Distress Syndrome ARDS , as characterized by the onset of clinically significant hypoxemia and diffuse pulmonary infiltrates, has been a challenge to the critical care physicians due to high death toll rate. The molecular mechanisms that regulate genome organization in the mammalian interphase nucleus are largely unclear. At the interface between the nuclear membrane and chromatin, the inner nuclear envelope contains both nucleoskeleton filaments lamins and transmembrane proteins NETs.
Lamins tether heterochromatin to the nuclear envelope and modulate chromosome territory positions. In this presentation I will discuss various implementations of multiple detection experiments for accelerating assignment, structure determination and relaxation measurements in the solid state NMR. Methods will include multiple receiver variants of time-shared TSAR experiments for obtaining long distance restraints, 1 H-detected and 13 C-detected experiments for spectral Resistance to antibiotics is a growing health concern worldwide.
Antimicrobial peptides AMPs present an alternative to conventional antibiotics but details of their mechanism of action and the basis for differences in their potency observed between different bacterial strains remain unclear. Structural information is crucial for defining the molecular mechanism by which these peptides We have developed experimental methods for initiating nonequilibrium structural conversion processes e. When combined with low-temperature dynamic nuclear polarization, In particular, this improvement opens new avenues for the study of fast dynamical processes such as chemical reactions, with a time resolution smaller than a second.
DDNP has proven of particular interest The accessible free energy landscape is a generic property of proteins, which determines both their protein folding pathways and their biological function. This landscape can be explored by determining the thermodynamic stability of proteins at different pressures and temperatures. We combine these variations with NMR spectroscopy to gain molecular resolution. For two proteins apoKti11  Protein folding is usually driven by the hydrophobic core while the role of the surface residues is considered to be marginal.
Intimately ligated to protein folding, protein stability establishes the energy required to unfold a protein and the equilibrium populations of the folded and unfolded conformations at a given temperature. Proteins from halophilic organisms challenge this concept Increased dietary consumption of sugar has been implicated in a number of clinical pathologies, including obesity and other metabolic diseases.
In this study, we have investigated the metabolism of these two types of sugar in SfXL glioblastoma and Double helix is the most known structure of DNA. It can account for transfer of genetic information. However, DNA can fold into a wide range of structures that are associated with its unique biological roles and functions. An extraordinary feature of brain function is the encoding of information at multiple spatial and temporal scales, going from the cellular level in the form of action potentials to coordinated activity over billions of neurons spanning large parts of the brain, if not the entire brain, to achieve perception and behavior.
Bridging and spanning these multiple scales of organization is an THz ESR under multi-extreme conditions, which covers the frequency region between 0. Firstly, we will show our recent developments of the torque magnetometry 3 and mechanically Conventional reception of NMR signals relies on electrical amplification of the electromotive force caused by nuclear induction. In general, the signals cannot be transported without noise being added through the process of amplification before being acquired. Here, we report a different approach that potentially leads to much less noise added through signal transduction.
The idea is to Algorithmic cooling is a relatively new method to increase overall spin-polarization in NMR, which is based on manipulations of coupled slow-relaxing and fast-relaxing spins. The method enables increasing the magnetization of slow-relaxing spin by using the ability of fast-relaxing spins to pump entropy into the environment. Here, we suggest a new method to increase spin polarization by using Here we examine its use for imaging pregnancy-related Water and other polar molecules are known to absorb electromagnetic radiation and the absorption is particularly strong in the mm-Wave mmW range.
Metal surfaces are also becoming increasingly lossy. While large samples can However, determining the metabolic fluxes within the system remains technically challenging due to both the complexity of the metabolic network and the sophisticated methods required to analyse the complex spectra derived from NMR and mass spectrometry. Here we present three tools to aid We showed that R12 forms a unique quadruplex structure and reduces a level of the abnormal prion protein, PrPSc, in the mouse neuronal cells, implying its therapeutic potential as to prion diseases 1,2.
In the highest-field NMR magnets currently However, at the present time, it is difficult to generate a programmable sequence of phase-coherent narrow-band pulses Current NMR methods for studying proteins are primarily focused on backbone resonances and on methyl bearing side chains. In contrast, NMR of aromatic side chains has been less pursued although these moieties form a large portion of the hydrophobic protein cores. This is in part due to the complexity of aromatic side-chain spectra, which appear in a narrow and crowded spectral region The smaller chemical shift dispersion and the pairwise interaction among all the abundant nuclear spins of the molecule renders 1H NMR spectrum highly complex, severely hindering the straightforward analysis and the accurate determination of homo- and hetero- nuclear scalar couplings.
The inherent insentitivy of NMR technique poses additional challenge. We have manipulated the spin dynamics The glucocorticoid receptor GR binds steroid hormones, leading to structural rearrangements that drive DNA binding, recruitment of coregulator proteins, and ultimately gene regulation. Different receptor-ligand complexes have distinct interactions with coregulators, resulting in differential gene regulation.
The allosteric mechanism within the ligand-binding domain LBD has remained In this context this lecture will give recent examples from our journey of pushing MR boundaries. We will Many limitations of state-of-the-art drug screening by nuclear magnetic resonance NMR can be overcome by means of high-throughput hyperpolarization. Screening techniques must be GPCRs belong to a family of ca. Activation of the individual receptor proteins is initiated via extracellular stimuli, such as photon uptake, or binding of small molecules, peptides, proteins, ions, lipids etc.
This initial stimulus leads to Beta-detected NMR is up to 10 orders of magnitude more sensitive than conventional NMR, because it is based on the detection of beta-particles from hyperpolarized short-lived nuclei. Our project aims at applying it for the first time to liquid samples relevant in chemistry and biology, thus extending its use from nuclear structure and material science studies in solid environments. Nuclear shielding is considered independent of the magnetic field strength when analysing NMR experiments. However, already in , Ramsey proposed on theoretical grounds that this may not be valid for heavy nuclei.
Here we present experimental evidence for the direct field dependence of shielding, using 59 Co shielding in Co acac 3 dissolved into chloroform as an Electron and nuclear spins in diamond have long coherence and relaxation times at room temperature, making them a promising platform for applications such as biomedical and molecular imaging and nanoscale magnetic field sensing. While the optically-active nitrogen-vacancy NV defect has received a great deal of attention, the substitutional nitrogen or P1 center also exhibits long Reversibly photo-switchable fluorescent proteins RSFPs are important tools for microscopy and other biotechnological applications.
Hyperpolarization allows one to increase the NMR sensitivity by several orders of magnitude. The main drivers behind the development of hyperpolarization techniques are their biomedical applications. For example, the inhalation of hyperpolarized noble gases, such as Xe and 3 He, enables functional imaging of lung diseases.
However, highly specialized Xe Rheo NMR has been applied to investigate the effect of external shear on the aggregation and on the chain dynamics of polymers. A Couette cell with the polymer melt or solution in the gap is applied. To get further insight, oscillating rotation in addition to continuous rotation has been applied. An in-house built rheo NMR system using a servo motor, avoiding any vibrations has been used on a With the advent of site-specific isotope labeling and deuteration, the study of local dynamics in biological macromolecules, has reached levels of unprecedented accuracy.
There are, however, many cases in e. While classical carbonbased solid-state NMR techniques are often possible, they nevertheless suffer from low A large ribonucleoprotein complex called the ribosome is responsible for several steps of protein synthesis in all organisms. In bacteria, regulation of translation begins at initiation. Despite the availability of structural information, we still lack a clear understanding of how the ribosome encounters folded mRNA structures during translation initiation.
A general mechanism for initiation Hyperpolarized water produced by dissolution dynamic nuclear polarization dDNP has recently been shown to enable the detection of hyperpolarized spectra of proteins with up to fold improvement in signal amplitudes. With this dDNP approach, novel insights can be gained into solvent accessible surfaces, ligand interactions, and complex protein geometries. Examples of applications to We present our recent progress in implementing an improved readout scheme for the nitrogen-vacancy NV center's spin-state combining resonant excitation at low 4 Kelvin temperature with spin-to-charge conversion.
Resonant excitation exploits that the optical excitation spectrum at low temperature has sufficiently narrow linewidths[1,2] to selectively address the spin-sublevels. Magnetic Resonance Imaging at ultra-high field strengths T provides both opportunities and challenges for non-invasive imaging of biological specimens. As low sensitivity is the most common drawback of MRI applications, the most apparent opportunity of ultra-high field imaging manifests itself by an augmentation in the Signal-to-Noise ratio SNR.
To this end, using similar RF coils, Higher magnetic fields lead to higher sensitivity and higher resolution. Reaching higher fields is key to study biomolecular systems of increasing complexity. Yet, higher fields are not optimal for all applications of NMR, neither for all nuclei. For instance, the chemical shift anisotropies of carbon nuclei in many chemical entities, or that of fluorine lead to transverse relaxation Background and aim: Acidosis and low-oxygen status are hallmarks of solid tumors.
Acidification in extracellular space in solid tumors reflects a shift of cellular metabolism for tumors. Thus, visualization of extracellular pH pHe is useful to understand the pathophysiological status of tumors. A method of three-dimensional 3D pHe mapping of murine tumors using electron paramagnetic Sensitivity and resolution have been the two important traits in NMR of biomolecules. With the advent of cryogenically cooled probed and non-uniform sampling methods, the battle of sensitivity and resolution has to be revisited.
The large gyromagnetic ratio of 1H it is nemesis when dealing high molecular weight systems since Magnetic resonance MR is one of the most important techniques for characterizing compositions, structure and dynamics of molecules. Over the past several years, quantum sensing with Nitrogen-Vacancy NV center has opened a new door for magnetic resonance spectroscopy of a single molecule.
In my talk, I will mainly introduce several new experimental results on both of methods and biology SABRE has many applications, ranging from biomedical to high precision measurements. To achieve the full potential, we investigated key steps in spin physics, chemistry, and engineering. Specifically, we 1 engineered membrane The nitrogen-vacancy NV centre in diamond is an optically addressable single spin-1 electronic system with relatively long coherence persisting at room temperature, making it ideal for a range of nanoscale quantum sensing applications.
The NV system is sensitive to local magnetic and electric fields, as well as material properties such as strain and temperature. An exciting direction is the Proteins are inherently dynamic, exhibiting conformational freedom on many timescales, 1 implicating structural rearrangements that play a major role in molecular interaction, thermodynamic stability and biological function. Intrinsically disordered proteins IDPs represent extreme examples where flexibility defines molecular function. IDPs exhibit highly heterogeneous local and Consequently much effort has been ventured to improve the application of diffusion measurements in NMR .
In this work we introduce a pulse sequence that enables the spectroscopist to perform DOSY experiments in a matter of tens Nanodiamonds NDs are a subject of increased application interest based on the possibilities of their use in medical imaging  and as drug delivery systems [2, 3]. Fluorescent NDs are addressed as they emit single-photon luminescence due to a number of optically sensitive paramagnetic defects, particularly nitrogen-vacancy centres.
The knowledge on how the defect types and distribution in In this research flavin-binding LOV domain, which is a blue light receptor, can receive an electron from a short distance appr. This electron is the core of Signal Amplification By Reversible Exchange SABRE is a method based on the transfer of parahydrogen p-H 2 polarization to the substrate nuclei due to the constant exchange of p-H 2 and ligands over metallic Ir center of metal-organic complex.
Generated levels of polarization provide the higher signal of the ligand. In this contribution, we present a simple analytical fitting approach based upon a power-law model of the segmental orientation autocorrelation function OACF , by the way of which an effective power-law time scaling exponent and the amplitude of the OACF can be estimated from multiple-quantum MQ NMR data at any given temperature .
This obviates the use of the time-temperature In many organic compounds where it is covalently bound, the 35 Cl nucleus Double Quantum NMR is a well-established method to study spatial proximities and local molecular dynamics in solid samples. In many cases, more or less restricted local dynamics of polymer chains has been analyzed.
Here we studied the local packing of phosphate groups during the crystallization of precise polyethylene obtained from acrylic diene metathesis ADMET polycondensation with Most materials are heterogeneous on the millimeter resolution of magnetic resonance imaging MRI in the sense that they are comprised of multiple microscopic domains with different chemical and diffusional properties. Consequently, the measured MRI signal on the voxel scale is highly unspecific as it originates from the average of the signals arising from these domains.
An unexpected great challenge in dDNP  has recently emerged with the use of ultra-shielded DNP magnets; the preservation of hyperpolarization during transfer from one ultra-shielded magnet to the other in ultra-low field regions, as magnetization not only relaxes but can be wiped-out in a non-adiabatic process. Short-lived and low-abundance enzyme intermediate complexes represent a mainstream of transient protein complexes in enzyme catalysis and signal transductions. Many transient and unstable protein intermediate complexes are generated in real-time reactions or non-equilibrium conditions, however, resonance assignments of these unstable complexes are a challenge and structural determination of The automation of NMR structure determination remains a significant bottleneck towards increasing the throughput and accessibility of NMR as a structural biology tool to study proteins.
The chief barrier currently is that obtaining NMR assignments at sufficient levels of completeness to accurately define the structures by conventional methods requires a significant amount of spectrometer time It is known that cobalt exhibits polymorphism: it exists in both hcp and fcc phases. Synthesis method and other thermodynamic conditions are known to play a role in determining the phase composition of cobalt nanoparticles.
In this work, we have studied the phase composition of the cobalt nanoparticles synthesized using two different solvents water and ethanol. XRD measurements confirm the NMR is a primary method of measurement that provides quantitative results without the need of a standard of the same measurand. The use of a NMR spectroscopy is an efficient method for obtaining quantitative data on the fractional 13 C enrichment of metabolic intermediates or end-products.
In biosynthetically directed fractional 13 C labelling using uniformly 13 C labelled carbon source, the biomass becomes 13 C labelled in a metabolic flux distribution dependent manner and the cleavage and Exchange processes with the solvent may reveal useful information about intrinsically disordered proteins and their interactions. We introduce a new method to evaluate amide proton exchange rates that relies on the creation of a triple spin order state, i.
This spin state is left free to evolve in a variable mixing time during which it undergoes To examine bonding nature of fluorine ligands in a metal coordinated system, 19 F high-resolution solid-state NMR has been applied to TiF 4 , which bears both bridging and terminal fluorines. By referring to the calculated isotropic shifts using DFT, the observed 12 isotropic signals were assigned to 12 crystallographically different fluorines 6 terminal F T and The fundamental importance of protein-glycan recognition calls for specific and sensitive high-resolution methods for detailed analysis.
Binding of small molecules to proteins is often monitored by observing 1 H NMR resonances of the ligands due to the inherent high sensitivity of 1 H detection. Ligand-observed schemes may, however, fail, because of spectral overlap, if Radio-frequency signals can be up-converted to the optical regime through electromechanical and optomechanical couplings .
Towards realization of practical EMO NMR, we present here the design and fabrication of a compact rf-to-light transducer that can be installed inside Cyanobacteriochromes CBCRs , proteins responsible for detection of light in cyanobacteria, are special not only because of their comparatively simple architecture, but also because they show an astonishing broad spectral variability. Metabolic syndrome MetS is a cluster of metabolic abnormalities that generate an increased risk in the onset of cardiovascular disease CVD , liver disease, type 2 diabetes and chronic kidney disease.
The large diversity of nucleic acid structures can be expanded even further by the introduction of metal-mediated base pairs in which base pairs are generated by coordination to metal ions instead or in addition to hydrogen bonds. Using crystallography, information about the two meta-stable states Pr and Pfr, has been gained. This series of discrete structural changes is believed to be responsible for phytochrome intracellular signaling. However, the structural characteristics of these meta-stable states remains to Direct interaction between intrinsically disordered proteins is often difficult to be characterized hampering the elucidation of their binding mechanism.
Particularly challenging are the cases of extreme fuzziness of the complex, which is now appearing as a common interaction mode,requiring new models for their description. In practice, the classic homo-nuclear 2D J-resolved spectroscopy , generally suffers from phase-twist lineshape and field inhomogeneity effects, thus rendering its potential applications limited. Here, a NMR spectroscopy is a nondestructive characterization technique that provides detailed information on molecular structures with incomparable specificity.
With NMR, it is possible to observe chemical reactions, detect chemical substances, and to determine concentrations. Commercial NMR devices are usually bulky, expensive and power hungry. To change this situation, our approach uses integrated Recently, the function of proteins is much more attract attention and measurement of high-pressure NMR about proteins showed many remarkable results in this field.
A signature trait of NMR spectroscopy is its limited sensitivity due to low, field-dependent polarisation across spin states. Several hyperpolarisation methods have been developed to overcome this barrier, however, such techniques typically require expensive and complex instrumentation. The introduction of Parahydrogen p-H 2 based methodologies, however, provide pathways for Dissolution dynamic nuclear polarization D-DNP is currently the subject of many new developments in view of boosting the sensitivity of nuclear magnetic resonance spectroscopy NMR and imaging MRI.
Most D-DNP probes are designed for one or two nuclei at most. The investigation of multiple nuclei, therefore, requires manufacturing a number of different costly probes. In addition, changing Electron-nuclear double resonance ENDOR spectroscopy is the method of choice for detecting magnetic nuclei in biomolecules which contain an unpaired electron spin is. However, due to its low gyromagnetic ratio, the detection of deuterium couplings is a particular challenge for ENDOR spectroscopy. New subtype-selective tool compounds are required to Fitting a weighted sum of exponentials to a noisy exponential decay is an ill-posed problem.
In the T 2 relaxation context, it leads to non-unique solutions because different sets of relaxation times and amplitudes give identical least-square distance between the model and the experimental data. Conventional data analysis combine a non-negative least squares NNLS algorithm In modern organic and medicinal chemistry, fluorine is commonly used to enhance the chemical properties of molecules in many desirable ways: it may delay the metabolism of the molecule, reduce the toxicity of aromatic groups, or increase the bioavailability.
The hyperpolarization of biologically relevant molecules for signal-enhanced magnetic resonance detection holds great promise for studying biological processes in vitro and in vivo. Being important metabolites as well as the building blocks of peptides, the canonical amino acids are promising targets for hyperpolarization, and a number of parahydrogen based strategies have been Abstract: We present the design of a portable one-sided low cost system for EPR applications that uses a new shimming approach to achieve the required homogeneity.
The proposed permanent magnet offers an open geometry enabling non-destructive EPR measurements on arbitrarily large objects. It has been designed, simulated and optimized using the finite element method. The system is based on Electron Paramagnetic Resonance EPR in single crystals is used to study paramagnetic intermediates at the active-site of an enzyme to fully resolve the magnitudes and orientations of the g-, hyperfine, and quadrupole tensors.
The electronic structure, when combined with X-ray crystallography, is related to a proposed molecular geometry to gain a better understanding of the catalytic NMR spectra provides indispensable information such as chemical shift and scalar coupling which plays a pivotal role in molecular structure determination and analysis.
Unfortunately, it is often difficult to extract proton-proton scalar coupling since signals are often hidden in overcrowded regions in conventional 1D NMR spectroscopy. Hence, the gradient-encoded selective refocusing method The atomic There exists a number of experimental methods which provide homodecoupled pure-shift 1H NMR spectra. However, this often leads to very time-consuming experiments . The problem with time rises, when a series of pure-shift proton spectra This gives a boost in resolution as multiplets in a spectrum collapse into singlets. The techniques rely on echo-type pulse sequences with selective pulses.
In between the pulses, a short chunk of an FID is acquired. The whole FID is then constructed from these chunks. The type The combination of a phase-modulated PM saturation pulse and symmetry-based dipolar recoupling into a rotational-echo saturation-pulse double-resonance RESPDOR sequence has been employed to measure 1 H- 14 N distances. Such a measurement is challenging owing to the quadrupolar interaction of 14 N nucleus and the intense 1 H- 1 H homonuclear This small missetting has no significant impact on the overall spectral resolution, but is sufficient Accurately determined conformations of biological agents are valuable assets in drug discovery.
The use of NMR to study the range of Unambiguous characterization of different acid sites in zeolites is of great importance in heterogeneous catalysis. The zeolites are well known for the decades for their excellent properties as adsorbents and catalysts. The large-scale application of these materials is ensured by petroleum chemistry as a part of fuel cracking catalysts FCC for gasoline production and hydrockacking catalysts HCK for diesel due to their thermal stability, strong acidity, and developed specific surface area.
A main To overcome the inherently low signal-to-noise ratio that usually hampers a wider application, we present an alternative approach to prepolarized ULF MRS, employing Conventional methods for determining crosslink densities CLDs in elastomers, such as equilibrium swelling of vulcanizates using the Flory-Rehner equation , and stress-strain measurements using the Mooney-Rivlin equation lack phase-specific distinction of crosslink densities in elastomer blends . NMR spectroscopy offers better solutions to overcome these limitations, but studies The aggregation of beta-amyloid peptides is closely associated with Alzheimer's disease.
We have used different chemical devices such as liposomes and reverse micelles to encapsulate the residue beta-amyloid peptides so that the spatial confinement could lead to the formation of nonfibrillar aggregates of beta-amyloid peptides. These on-pathway beta-sheet intermediates were used to seed the The protein family of small GTPases controls cellular processes by acting as a binary switch between an active and an inactive state.
The most prominent family members are H Ras, N Ras, and K Ras isoforms, which are highly related and frequently mutated in cancer. Bisphenols are widespread in modern life because of their industrial application as plasticisers. Bisphenol A BPA is the best Phase-alternating decoupling XiX [1,2] is one of the simplest and efficient high-power decoupling methods in solid-state NMR for faster MAS frequencies.
We present variations of this heteronuclear decoupling sequences with improved performance based on numerical calculations of the second-order cross terms . Amyloids are involved in various pathologies but also display different adaptive functional roles in animals, fungi and bacteria. Numerous proteins can adopt the amyloid fold, pointing to its adaptability to high sequence variability; yet amyloid propensity is also highly Despite the growing interest in their pathogenesis, no existing method can capture aggregate nucleation and subsequent growth at atomic resolution in real time.
In this study, we have recently established high-sensitivity Rheo-NMR spectroscopy that enables us to detect atomic-level This article is committed to developing a portable method for accurate detection of human blood glucose by low field nuclear magnetic resonance technology. A portable NMR apparatus magnetic field frequency: 26 MHz was constructed by manufacturing a miniature NMR probe for micro sample detection and integrated with a lightweight permanent magnet and an electronic control system.
In order to Recently the phenomenon of Liquid-Liquid Phase Separation LLPS has gained great interest among the scientific community given its participation in the formation of membraneless organelles that play crucial roles in the cellular environment 1. Great efforts are currently devoted to its structural and functional characterization. However, obtaining structural information at the molecular level We introduce an efficient, yet easy to use, homonuclear dipolar recoupling scheme by employing a chirp pulse or a train of chirp pulses.
This method is useful for generating cross peaks between any sites that possess small, medium, or large To determine the saturation factor of the electron spin, the 1 H paramagnetic shift as a function of the microwave power was measured as previously reported . We could show that the Intrinsically disordered proteins IDPs are abundant in eukaryotic proteomes and act at the heart of fundamental cellular processes such as cell cycle control and signal transduction.
The aberrant function of IDPs is therefore associated with severe diseases such as cancers and neurodegenerative diseases. Protein functions are mediated via motions, therefore a detailed characterization of Tc toxins are 1. The complex consists of three subunits: the 1. The inversion is to solve the Fredholm integral equation of the first kind with non-negative constraints, which is known as an ill-posed problem. In this paper, a novel method is presented for NMR inversion based on the regularization method.
The proposed objective function can transform the The ability to select the signal passing through chosen coherence pathways is a powerful feature of NMR. Nuclear singlet states are coherent states that have effective spin 0. Despite being NMR silent, singlet states can be Among other factors, the sensitivity of Magnetic Resonance Imaging MRI is limited by the low polarization of the sample investigated.
Enhancing the polarization offers several orders of magnitude in signal enhancement. In comparison to e. Dynamic Nuclear Polarization DNP , para-hydrogen pH 2 based approaches are less cost intensive, scale well and offer high At the functional level m6A plays an important role in many biological processes . In plants MTA and Chocolate is obtained from cocoa bean Theobroma Cocoa , which is previously fermented by microbial activity transforming it reaches until characteristic odour and flavour. This process is developed in three stages: 1st Alcoholic fermentation, whereby sugars of husk and bean are consumed first 48 h, aprox , 2nd Acidogenic fermentation, where the alcohol yielded is consumed and it produces This spectroscopic technique has much potential, since it extends the time-scale of ESR spectroscopy toward slower processes e.
Selective anion binding to a catalytic host is a promising topic on the route to develop systems triggering catalytic activity. In this regard, cooperative hydrogen bonding by multiple 1,2,3-triazoles establishes a suitable environment for different anions. On this basis, the asymmetric dearomatization of quinolines was successfully introduced by anion binding catalysis . However, the Oxidative stability of oils is an important quality issue especially during deep-fat frying process.
It is well known that lipid oxidation can lead to changes in functional, sensory, and nutritive values and even the safety of fried foods. Extracts of many plants have been reported to have varying degrees of antioxidant activities, which increase the oxidative stability of fats and oils Proteins in biological environments exist as part of crowded mixtures. Characterizing protein self-interactions vs cross-interactions in such complex systems in situ is challenging, but is required for adequate system description.
Glycosylation and spontaneous modifications are critical quality attributes of protein therapeutics that can impact drug efficacy and safety. Therefore they need to be tightly monitored during production, formulation and storage. Mass spectrometry and fluorescence-detected chromatography are currently the dominating methods for the analysis of post-translational modifications PTMs including The functions of lubricant base oil are largely correlated to its structure and composition, which are however very difficult to be measured simultaneously by current analytical methods.
Mass spectroscopy could get quantitative group composition of base oil, but it is deficient in characterization of structures with branches. On the other hand, conventional NMR method is not only suffered from The aim of a metabolic study is the differentiation of biological populations by their metabolite composition. Even in a simple model the assessment of large numbers of samples is mandatory to produce statistically meaningful data. This requirement becomes even larger in the analysis of metabolite progression, for example in disease development, or mixtures of commodities, for example the Pulmonary compliance is an important index for evaluating the function of the lung, which could reflect the pulmonary ability to stretch and expand.
Hyperpolarized Xe MR is a powerful tool in quantifying the microstructure and function of the lung in vivo, and it has unique advantages in measuring the gas volume in the lung. In this study, a proof-of-concept method was proposed HFOV is currently considered to be contraindicated in obstructive airway disease with prolonged time constants due to the risk of dynamic airtrapping. This could give rise to circulatory and ventilatory compromise and barotrauma. In distinct to current opinion, we showed that small airway disease can safely and successfully be managed with HFOV. Ventilatory strategy should be directed to open up the small airways and keep them open with sufficiently high mean airway pressures 'the open airway strategy' similar to the 'open lung strategy' in diffuse alveolar disease.
Permissive hypercapnia may be used to reduce pressure swings as much as possible, leading to less shear stress on lung tissue, without influencing airway recruitment. Further dynamic airtrapping can be prevented with the use of longer expiratory than inspiratory times and with prevention of spontaneous breathing. Although marked hyperinflation was present in all our patients prior to transition, no airleaks developed during HFOV. Nitric oxide was added and oxygenation improved immediately. All patients survived without residual lung disease. Crit Care Med , Thompson MW, Bates JN, Klein JM: Treatment of respiratory failure in an infant with bronchopulmonary dysplasia with respiratory syncytial virus using inhaled nitric oxide and high frequency ventilation.
Acta Paediatr , Introduction: In acute respiratory distress syndrome ARDS change from supine SP to prone position can improve gas exchange by recruiting alveoli situated in dorsal dependent. The aim of this study was to investigate the effect of prone position PP after application of high fractional inspired oxygen hFiO2 , inverse ratio ventilation IRV , positive end exspiratory pressure PEEP.
Renal failure of these two non-responders was not treated by HF. Improvement of oxygenation index was independent of duration in supine before the begin prone position range 6 to h. Conclusion: Starting prone position seems to mark a U-turn for oxygenation for the majority of patients with severe ARDS, while application of high fractional inspired oxygen, inverse ratio ventilation, positive end exspiratory pressure as well as kinetic therapy and hemofiltration do not necessarily improve oxygenation. The timing of this non invasive technique primarily depends on the decision to turn the patient from supine to prone.
We recommend prone position in ARDS as soon as possible to reduce lung injury and complications resulting of mechanical ventilation. P36 The effect of the pulmonary time constant on the cough peak flow rate at two different inflation pressures: a bench test model. Supramaximal flow is characteristic of the cough manoeuvre and is thought to be the result of dynamic compression of collapsible airways.
We investigated the effect of changing the pulmonary time constant on the peak flow rate produced by an in vitro cough manoeuvre. We used a prototype artificial cough generator and a simplified lung-airway model. The model consisted of a compliant bag with a resistor internal diameter 3 mm to 7 mm that emptied through a collapsible tube.
The resulting range of emptying time constants to ms included those found in vivo to ms. The lung-airway model was inflated to one of two pressures 31 cmH2O or 55cmH2O and then compressed within a glass container to a pressure of 45 cmH2O. A mechanically-operated glottis opened rapidly and the resultant flow was measured by a pneumotachograph. The cough peak flow rate CPFR was.
The results from this bench-test model suggest that the pulmonary time constant has a profound effect on the magnitude of the cough peak flow rate. Mechanics and gas exchange can in be studied with a computer-controlled ventilator. When setting PEEP, frequency, I:E ratio, and minute ventilation or inspi-ratory pressure the physician needs to assimilate the information of the physiological profile and all clinical information to assure an adequate gas exchange at a non-traumatic ventilation.
In COPD the task is to ventilate at the lowest possible volume and airway pressure. The complexity of the physiology and ventilator settings makes it impossible to figure out what is the ideal pattern of ventilation in order to reach the immediate therapeutic goals defined by the physician. However, on the basis of an adequate mathematical physiological profile, a computer can by simulation prognosticate what would be the consequences of alternative modes of ventilation.
Through repeated simulations the physician can search a mode of ventilation that leads to his goals. Computer simulation can be used to: a increase the understanding of various patterns of ventilation in disease. In left diagram the total pressure in the ventilator Pvent , the tracheal pressure Ptr and the alveolar, i.
The pressures were, however, very high. By repeated simulations it was possible to identify a setting which dramatically would reduce the pressures without changing PaCO2. P38 Clinical evaluation of a new closed loop ventilation mode: adaptive supportive ventilation ASV. ASV may adjust mandatory breath rate, I:E ratio, and inspiratory pressure of mandatory breaths. Galileo assesses the pt by measuring dynamic compliance and expiratory time constant.
Methods: Ninteen post-operative pts requiring MV were studied. Vent settings by physician were noted and each pt was placed on those settings or ASV randomly. Data were compared using student's t-test. Results: 19 pts 14 male were studied. Initial 'test breaths' during ASV were well tolerated. Mean IBW was Mean age was Table 1 reveals set and measured ventilator parameters for both study periods. Respiratory rate was higher during ASV. VE, TI, and Paw were unchanged between study periods. No pt suffered any adverse events from derangements in ventilation or acid-base balance.
Table 3 reveals heart rate and mean arterial pressure during each study period. There were no clinical changes to any measured vital sign between the two study periods. Determination of vent settings made by the machine have been suggested Intern Care Med , Our results suggest that ASV as startup mode of ventilation is acceptable and comparable to physician determined ventilator settings. Gas exchange during ASV is equivalent to physician determined ventilation. VT during ASV is more consistent with 'lung protective' strategy 7.
Introduction: Excess body weight increases the risk of death from any cause and from cardiovascular disease in adults . In the majority of population studies, the relationship of BMI to mortality is a U-shaped curve, with increased risk in the lowest and highest percentiles of the distribution.
The results of an interim analysis are presented in this abstract. Maximal IAP and lactate levels were recorded within the first 72 h. Results: The percentage of female patients was Raised IAP was present in 71 patients The Table lists the parameters studied in patients with high and normal IAP. With a cut-off at 12 IAP had Conclusion: The interim results of an ongoing prospective clinical trial show that increased IAP can be expected in about It seems to be a predictor of mortality and causes a considerable extra-cost and prolonged ICU-stay.
There is no U-shaped concave mortality curve associated with BMI, on the contrary, patients with higher BMI had lower mortality compared to patients within the first BMI quartile, and this is in accordance with the results from others . Results of a pilot study. Crit Care , 3 suppl 1 :P40 on the diaphragm causes a pattern of restrictive lung disease with.
Introduction: It is well known that IAPs above mmHg Finally this results in diminished chest wall compliance causing increase peak and plateau alveolar pressures. The rise in pressure difficult ventilation and weaning. The respiratory system can be. Since the diaphragm is coupled to the abdominal wall any increase in IAP may therefore affect chest wall and lung compliance . By calculation of static V-P curves it has been shown in animal and human studies that abdominal and subsequently chest wall compliance goes up after abdominal decompression and this correlates well with the volume recruited .
Recent studies looking at compliance in primary and secondary ARDS found that the latter presents with preserved lung but decreased chest wall compliance and PEEP allows to recruit lung units markedly [1,2]. In this pilot study we wanted to sort out if there is a correlation between IAP and Pflex. Methods: Over a 2 month period measurements were performed in 11 patients. The number of measurements in each patient was There were three patients with primary and three with secondary ARDS, and three patients had secondary ALI according to the definitions given by the American-European consensus conference.
As suspected the correlation was worse in. We propose this simple strategy for determination of best PEEP in ALI instead of the more time consuming, not generally accepted and not without risk calculation of Pflex with the super syringe method. Before being used for clinical purposes, the results of this pilot study need to be validated in a multicentre trial. P41 Determination of the best volume of perfluorocarbone to ensure partial liquid ventilation in the pig with ARDS. Introduction: Partial liquid ventilation consists of filling the residual functional capacity with perfluorocarbon PFC , while providing tidal volume by conventional ventilation.
Several studies have shown that smaller volumes of PFC allow significant improvement in ventilation parameters during experimental ARDS. To date no study has compared several small volumes of PFC. At this point ARDS was. The animals were then split into four groups of four, with a control group being given continuous positive pressure ventilation CPPV without PFC. Blood gases and ventilation parameters: peak inspiratory pressure, tidal volume and pulmonary compliance were recorded every 15 min. After a few minutes, the compliance increase significatly.
Lung compliance increase to satifac-torys values All the animals in the control. The fact that a low dose does not have long-lasting effects might be due to faster evaporation of the product and a drop in its efficiency. P42 Cardiorespiratory effects of inhaled nitric oxide during acute hypercapnia with and without correction of blood pH in acute respiratory failure in piglets.
Objective: To evaluate the effects of inhaled nitric oxide on gas exchange and hemodynamic data during acute hypercapnia with uncorrected and corrected blood-pH. Interventions: After induction of anesthesia, tracheostomy and controlled mechanical ventilation animals were instrumented with two central venous catheters, a pulmonary artery and two arterial catheters, and an ultrasonic flow probe around the pulmonary artery.
Acute respiratory failure was induced by the infusion of oleic acid 0. Tidal volume was reduced to. Tham infusion was used to correct pH. At each PaCO2-period the animals were ventilated with and without inhaled nitric oxide 10 ppm. Measurements and results: Continuous hemodynamic monitoring included right atrial, mean pulmonary artery and mean systemic arterial pressures, and continuous flow recording at the pulmonary artery. In addition, airway pressures, tidal volumes, lung compliance and airway resistance, arterial and mixed venous blood gases were measured.
Data were obtained with and without inhalation. Conclusion: Acute hypercapnia resulted in a significant increase in pulmonary artery pressure and pulmonary vascular resistance without significantly influencing oxygenation and cardiac output. Inhaled nitric oxide significantly reduced pulmonary hypertension induced by acute hypercapnia and significantly improved oxygenation during normocapnia and acute hypercapnia with and without acidosis.
P43 Cardiorespiratory effects of inhaled nitric oxide and moderate hypercapnia in an experimental model of single ventricle. Objective: To evaluate the effects of inhaled nitric oxide and moderate hypercapnia on hemodynamics and gas exchange in an experimental model of single ventricle. Interventions: After induction of anesthesia, tracheostomy and controlled mechanical ventilation animals were instrumented with two central venous catheters and two arterial catheters. After a midline sternotomy the animals were placed on cardiopulmonary bypass and subjected to atrial septectomy, patch closure of the tri-cuspid valve, and creation of a 4 mm systemic to pulmonary arterial shunt.
Before weaning from cardiopulmonary bypass ultrasonic flow probes were placed around the pulmonary artery and the descending aorta. In addition a pulmonary artery catheter was inserted into the pulmonary artery via the right ventricle. Tidal volume was reduced to induce hypercapnia, inspiratory time and PEEP were adjusted to achieve constant mean airway pressures Paw. Measurements and results: Continuous hemodynamic monitoring included right atrial, mean pulmonary artery and mean systemic arterial pressures, and continuous flow recordings at the pulmonary artery and the descending aorta.
In addition, arterial and central venous blood gases were measured.
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Data were obtained at baseline, normocapnia with and without NO-inhalation and 2 levels of hypercapnia and are given in the Table. Conclusion: The creation of this experimental model of single ventricle resulted in a significant decrease in oxygen saturations and mean arterial pressure. Moderate hypercapnia resulted only in minimal changes in pulmonary artery pressure, pulmonary vascular resistance, and oxygen saturations. Inhaled nitric oxide decreased pulmonary artery pressure and resistance associated a slight increase in oxygen saturations.
Introduction: Inhaled nitric oxide NO causes selective pulmonary vasodilation. In experiment, pulmonary arteries were shown to be primary site of NO effect. One hour test of 20 ppm NO was performed and in 3 patients NO was additionally increased to 40 ppm with the primary aim to improve oxygenation. Pressure curves during pulmonary artery occlusion were recorded in duplicate before and with NO and the more representative one was used for pulmonary capillary pressure PCP estimation .
Statistics: non-parametrical Wilcoxon test for two related samples and simple correlation when appropriate. Results: In 1 patient a marked decrease in mPAP was measured 15mmHg , in other 4 patients the drop was marginal. Conclusion: When effective in lowering pulmonary pressures, inhaled NO seems to act primarily on the arterial component of transpulmonal vascular resistance.
P45 Correlation of lung mechanics with saturated phosphatidylcholine ratios and surfactant protein A in bronchoalveolar lavage fluid from infants with RSV induced respiratory failure. Aim: Infants with respiratory syncytial virus RSV induced respiratory failure have been shown to be deficient in surfactant, both in quantity and ability to reduce surface tension.
Theoretical evidence suggests that surfactant may have a role in maintaining patency of small airways, which has implications for RSV bronchi-olitis. In addition, a minimum ratio of surfactant protein A SPA to fully saturated dipalmitoylphosphatidylcholine DPPC must be present for surfactant to be fully functional. Methods: Nineteen infants were studied, median age 7 weeks range weeks , median weight 4 kg range kg.
BALs were taken within 24 h of commencing mechanical ventilation. BAL surfactant phospholipid composition was detected by elec-trospray ionization mass spectrometry, and SPA levels by enzyme-linked immunosorbent assay. Results: The median interquartile range values for compliance were 0. Conclusion: Surfactant containing higher ratios of saturated phos-phatidylcholine has a role in maintaining compliance and small airway patency in RSV infected infants.
These findings have implications for exogenous surfactant supplementation in this disease. P46 Experimental study on prevention of simulated high altitude ALI by tetramethylpyrazine in dogs. Tel: ; E-mail: jshaw public. Twenty-one hybird dogs were randomly divided into acute lung injury ALI treated and control groups at simulated high altitude environment of m. All animals were sacrificed after 6h. The increase in production of. These results demonstrated that the early treatment with TMP could inhibit the decrease in the WBC count, and reduce the accumulation of leukocytes in the lungs.
P47 Effects of Cl-inhibitor and rSP-C surfactant on oxygenation and histology in rats with lavage-induced acute lung injury. Introduction: The acute respiratory distress syndrome ARDS is characterized by diffuse injury to the endothelial and epithelial surfaces of the lung leading to severe respiratory failure. Alterations in the surfactant system and activation of the contact system of coagulation are major contributors to the pathophysiol-ogy of ARDS. C1-inhibitor C1-INH is the main inhibitor of contact activation and the only known inhibitor of classical pathway complement activation.
The aim of this study was to investigate the effects of C1-inhibitor administration and rSP-C surfactant application on oxygenation and lung histology in an ARDS-model. Methods: Thirty-six male Sprague Dawley rats were subjected to repetitive lung lavage with isotonic saline solution. Three experimental groups and two control groups were studied: Group 1 and 2 served as controls without any treatment. Animals of group 1 were sacrificed 60min after the last lavage procedure p.
Blood gases were determined. All animals of group were sacrificed at min p. Results: At min p. Hyaline membrane formation was significantly reduced in group 4 and 5. The severity of intraalveolar hemorrhage and edema were significantly reduced in group 3 and highest in group 4. Conclusion: Surfactant application was effective in improving pO2 which was related to the reduction of hyaline membrane formation. C1-INH administration had no significant effect on pO2 and hyaline membrane formation but was effective in reducing PMN infiltration, intraalveolar hemorrhage and edema formation.
P48 Inhibition of pulmonary microvascular chemokine production by human Laktoferrin and Phosphatidylethanolamine. Chemokines, a large family of structurally related chemotactic cytokines, are essential for the migration of leukocytes during inflammatory processes. In other experiments, cell impermeable PE, Cyclooxygenase-.
These findings may have clinical implications in the treatment of acute lung injury during sepsis. P49 Lipid peroxidation, antioxidant status and selenium levels in patients requiring prolonged ventilatory support. Introduction: Recently free oxygen radicals have been implicated as possible mediators of respiratory muscle dysfunction, particularly diaphragm fatigue. The aim of the study was to evaluate lipid peroxidation, antioxidant status and selenium levels in patients with sepsis requiring ventilatory support and during weaning.
Methods: After institutional approval 40 critically ill patients were prospectively studied during ventilatory support and weaning, three patients due to death were excluded. All patients were weaned according to standard weaning protocol. Blood samples were drawn daily and collected until analysis. Malondialdehyde MDA serum levels, total glutathion GSH , glutathion-peroxi-dase GPX and superoxid-dismutase SOD activity in erythro-cytes and serum selenium levels were estimated at the time of admission to ICU T1 , on the last day of full ventilatory support T2 , on the day when weaning was started T3 and on the first day of spontaneous ventilation T4.
Discussion: Prolonged ventilatory support and weaning longer than 3 days were associated with higher MDA levels and lower GPX levels, also selenium levels were insignificantly lower in patients with prolonged ventilatory support. The clinical importance of these findings needs to be further studied.
Objective: To determine primary endogenous pneumonia effect on severe burn patient mortality and to establish the associated factors with primary endogenous pneumonia. Intervention: Collection of data on surveillance samples from throat and rectum on admission and afterwards twice weekly, and primary endogenous pneumonia during the intensive care unit stay. Statistical analysis: The variables potentially related to mortality were age, sex, total body surface burn area, full-thickness burn.
Comparison between groups was performed using Wilcoxon test or Fisher's exact test when appropriate. Results: Thirty-one patients fulfilled the criteria of analysis. Inhalation injury was identified on 13 patients. Mean stay was 28 days Fourteen patients developed 19 pneumonias: 12 primary endogenous, six secondary endogenous and one exogenous.
The causative microorganisms were 14 Staphylococcus aureus, three Haemophilus influenzae, two Streptococcus pneumoniae, one Pseudomona aeruginosa and one Acinetobacter spp. Increasing the number of cases 56 patients , both variables were statistically significant in the uni-variate analysis, but were not statistically significant in the multi-variate analysis.
At present we are continuing the study to know the factors associated with morbidity and mortality in severe burn patients. The isolated pathogens were predominantly Staphylococcus aureus. Primary endogenous pneumonia in severe burn patients may be associated with mortality, but is necessary collecting more cases to show it. SM is a potentially dangerous organism because of its resistance to many antibiotics. We present here an outbreak of mucoid phenotype SM pneumonia four cases and respiratory tract colonisation three cases. Our review of literature revealed only one case report of pneumonia characterised as mucoid phenotype .
Chest X-ray showed an infiltrative shadow in the right lower lobe and bilateral pleural effusion was detected on CT. Treatment with ticarcilline plus clavulonic acid to which the isolates was susceptible was initiated. One-day later chest X-. Ciprofloxacine was added to the treatment. Subsequent SM isolates rapidly developed antimicrobial resistance to antibiotics. A significant number of both infected and colonised patients had severe systemic diseases and tracheotomy, they were mechanically ventilated and receiving broad spectrum antibiotics before isolation of SM.
SM is emerging as an important nosocomial pathogen in critically ill ICU patients and should no longer be regarded as a harmless bacillus in ICU. P52 Selective decontamination of the digestive tract influences the acquisition of Helicobacter pylori among intensive care nurses.
Introduction: H. Exposure to H. The routine use of selective decontamination of the digestive tract SDD at an intensive care unit suppresses H. It was questioned whether as a consequence, a decreased exposure of H. Methods: The H. Both the intensive care nurses and controls were included on a voluntary basis. Persons using proton pump inhibitors were excluded. The prevalence of H. In group III the prevalence of H. The mean age in the three groups was Conclusion: The prevalence of H. Acquisition of H. P53 Factors predicting the etiologic pathogens in intensive care patients with early-onset pneumonia.
Wytsmanstreet 14, Brussels, Belgium. The aim was to examine whether the etiologic pathogen in ICU-patients with early-onset pneumonia could be predicted by specific patient characteristics. Material and methods: Data provided by the ICUs participating in the national surveillance programme for nososcomial infections in ICUs between January and June were examined. For the most frequently isolated pathogens in early-onset pneumonia, associated patient characteristics at admission were identified. Independence of association was verified by multivariate analysis using logistic regression.
Results: Seventy hospitals reported cases of early-onset pneumonia, The most frequently isolated pathogens were S. Factors associated with S. No patient characteristics were found to be predictive for infection with E. After multivariate analysis, S. For S.
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Patient characteristics at admission, such as duration of prior hospital stay, prior antibiotic use and patient severity score, are important factors in predicting the most probable etiologic pathogen and may be helpful in decision-making with regard to empirical antimicrobial therapy for early-onset pneumonia in ICUs. P54 Nosocomial infection: main cause in development of septic complications in surgical postoperative patients.
E-mail marga sps-elsys. Introduction: In this first attempt to prove the main cause of septic complications in postoperative ICU patients in Bulgaria's biggest hospital more than beds we analyzed all patient admitted in general ICU during 5 year period Methods: We provided a standard bacterial monitoring of all body media tracheal tubes, urinary tract, blood, central venous lines, sputum and surgical wounds. According to bacterial growth we divided patients into three groups. The Group 1 included patiens without any bacterial growth. Group 2 included patients with nosocomial infection. Group 3 included patients with secondary surgical endogenous infections.
Results: Of all patients during these 5 years, we include those From Group 2 we obtained following positive. The dominating pathogens in cultures were: from tracheal tubes: Acinetobacter spp. In Group 3 we obtained samples from surgical wounds and drainage tubes.
The dominating pathogens were the same as in other body media Acinetobacter spp. Conclusion: The nosocomial infection remains the main cause of septic complications in postoperative ICU patients and its emergence in ICU further rises There is also increase in secondary endogenous surgical infection. We noted P. P55 Nosocomial pneumonia and bacteremia in intensive care: results from the Belgian national surveillance, A total of 31 patients were included for the analysis.
The number of ventilator-associated pneumonias per ventilation-days was The predominant micro-organisms were Pseudomonas aeruginosa recovered in Bacteremia was reported in 2. Five percent of bacteremia occurred within the first 48 h.
The device-adjusted primary bacteremia rate was 3. The five predominant micro-organisms in primary bacteremia were Staphylococcus epidermidis in The frequent participation to the national surveillance led to an important national database that allows to study the risk factors of ICU-acquired infections, to identify areas for prevention and to improve the inter-ICU comparability of infection rates according to the risk profile of the different ICU populations.
International comparisons remain a delicate matter by lack of internationally standardised surveillance methods. P56 Protected specimen brush bronchoscopically directed versus unprotected tracheal aspirate in patients with ventilator associated pneumonia. Abate Hospital. Objectives: Bacterial resistance to antimicrobial treatment is actually one of the most debated issue in medical field.
Therefore, it is important to dispose a diagnostic procedure to allow an aimed antimicrobial treatment. Unprotected tracheal aspirate UTA is the most widely used sampling technique to assess pulmonary infection even though known to have a high sensivity and a low specificity . Protected specimen brush bronchoscopically directed PSB is a procedure that purpose a higher specificity .
The aim of the study is to compare both methods for the diagnosis of pneumonia in ICU. Materials and methods: 70 consecutive patients admitted to an 8-bed general ICU over a period of 18 months, intubated and mechanically ventilated . Above all it is to underline that microorganism most frequently represented in UTA and not detected by PSB were in sequence:. Candida spp, Pseudomonas aeruginosas, Staphylococcus aureus. No complications were reported during the procedures. Antimicrobial therapy based on PSB data was started, leading to a good clinical response and favourable outcome.
Conclusion: PSB is a reliable and safe method useful to investigate pulmonary infections. High specificity of the technique allows to aim antibiotic therapy, so reducing the risk of inducing resistance to molecule still effective with a consequent optimization of expenses. In consideration of UTA elevated vpn, this method could represent a first diagnostic step followed in case of positiveness by PSB. Chest , SS. Criteria for evaluating diagnostic techniques.
Chest , Suppl 1 : SS. Objective: To know infection incidence, pathogenesis and microorganisms on severe burns patients. Intervention: Collection of data on surveillance samples from throat and rectum on admission and afterwards twice weekly, and infections during the intensive care unit stay.
The infections were diagnosed according to the CDC criteria. Twenty-two patients developed 59 infections: 28 primary endogenous, 27 secondary endogenous and four exogenous. The causative microorganisms were: 14 Staphylococcus aureus, three Haemophilus influenzae, two Streptococcus pneumoniae, one Pseudomona aeruginosa and one Acinetobacter spp. Eight patients had nine urinary tract infections: eight primary endogenous and one secondary endogenous. The pathogens were: six Escherichia coli, three Streptococcus faecalis and one Serratia.
Nine patients developed 10 burn wound infections: one primary endogenous, eight secondary endogenous and one exogenous. The causative microorganisms were: six Staphylococcus aureus, three Pseudomona aeruginosa, one Escherichia coli, one Acinetobacter spp, one Proteus and one Klebsiella. Fourteen patients had 21 bloodstream infections: seven primary endogenous, 12 secondary endogenous and two exogenous. The pathogens were: nine Staphylococcus aureus, four coagulase-nega-tive staphylococcus, two Streptococcus faecalis, one Streptococcus faecium, three Escherichia coli, two Pseudmona aeruginosa, and one Candida spp.
The isolated pathogens were predominantly gram positive coccus, except in urinary tract infections. On the ather hand, infection, one of the most important complications of CVC must always be thought. Infections due to CVC are attributed to colonization of microorganisms at the tip of CVC and then their migration to the circulation. In our study , we planned to determine the colonization ratio of microorganisms at the tip of CVC and analyse the agents of infection.
Method: We evaluated the data obtained from 40 CVC that we could send to the laboratory in a year. The insetion sites of CVC were V. CVC were inserted under sterile condition by using sterile gloves and surgical drapes. The duration of catheterization was 8. Central venous pressure measurements and fluid administrations were made by the nurses under sterile conditions. Fluid administration sets were changed two times a week. Approximately 2 cm to the tip of each with drawn CVC is sended to the laboratory of microbiology in a sterile tube for culture-antibiogram analysis.
The agents were: Acinetobacter spp. We determined no agent of infection in the others 34 catheters. Discussion: Infection rate was less compared to previous reports and was similar to the results of the study by Nahidh et al. Then we concluded that the ratio of infections due to colonization at the tip of CVC may be decreased by daily care of catheters made under sterile conditions.
Department of Anesthesiology, Northwestern University, E. Introduction: Central venous access is an integral part of patient care. The dilemma was whether to insert an introducer or multilumen catheter for access. However, the Advanced Venous Access device A. The object of this study was to compare maximal flow rates of this new device with other introducers utilizing the Haemonetics Rapid Infusion System R.
Test methods: Devices tested with the traditional system were: Baxter A. The test system has been described previously. The RIS was set up in a manner to continually infuse fluids through the device using a cut-off pressure of mmHg to judge maximum flow. Devices were tested with PA catheters 7. Results for the A. Results: In the traditional I. Figure 1 below shows flow rate results for the RIS system. Discussion: In all categories, the Advanced venous Access device delivered higher flows than the other introducers.
Therefore, the A. It now gives us the ability to monitor the circulation and infuse fluids with fewer venous punctures. Introduction: In last years the nosocomial ICU fungal infections are assuming a greater impact with increasing morbidity, mortality and cost. A better outcome is correlated with an earlier treatment.
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Objectives: The aim of the study was to assess the accuracy of simple not expensive biochemical and haematologic parameters to predict the change of fungal colonisation to a status of fungemia. Materials and methods: Three-year retrospective study with ICU medical and surgical non-neutropenic patients. The study group consisted of 90 patients with fungal documentation, 37 patients were excluded for insufficient data.
We considered two groups. Alkaline phosph. Age, SAPSII in first 24 h, alkaline phosphatase, lactate dehydroge-nase, blood lactate, pH, bicarbonate, leukocytes, and platelets were evaluated in all patients the 3 days preceding fungal documentation. We compared biochemical and haematologic results in group 1 and group 2 trying to identify a different profile and evaluated the predictive value of the different parameters.
Results are presented as media and standard deviation. We found significant statistical difference with bicarbonate, and platelet count when comparing the two groups. We also observed an increasing blood level on alkaline phosphate in fungemic patients. Conclusion: In our study, variations on bicarbonate, platelet count and alkaline phosphatase are predictive of fungemia in previous colonised patients. However, further observations, analyses, are needed and perhaps involving larger patient numbers to evaluate the clinical utility of these findings.
P61 Fluconazole prophylaxis of systemic candida infection in non-neutropenic critically ill patients: a prospective randomized study. Introduction: Systemic candida infection has been associated with increased morbidity and mortality in patients requiring intensive care. Fluconazole F is the preferred therapy in Candida albicans infection. The aim of the study was to evaluate effect of daily prophylactic fluconazole administration on the incidence of systemic candida infection. Methods: After institutional approval 38 critically ill patients were prospectively studied.
In 18 patients group F presumptive fluconazole therapy after admission was started in daily dose mg intravenously until discharge or evidence of systemic candida infection, which was treated using standard dosage. Control group C consisted of 20 patients. Apache II, candida colonization, selected risk factors for candidemia central venous and urinary catheters, parenteral nutrition, corticosteroids therapy, broad-spectrum antibiotics, H2-receptor antagonists , length of ICU and hospital stay, ventilatory days, incidence of candida albicans and non albicans candida species were recorded.
The cultures from nasopharynx, trachea, urine, stool and blood stream were taken. Conclusion: There were no significant differences in incidence of candida colonization and proportion of albicans v. Hospital and ICU stay and length of ventilatory support were nonsignificantly longer in group F. Clinical usefulness of early fluconazole prophylaxis needs to be further evaluated. In a retrospective ongoing study, the incidence of nosocomial can-didemia among patients pts admitted to a tertiary-care teaching hospital bed capacity ; 78 beds for intensive care units, ICUs was evaluated together with causative pathogens, potential risk factors, antifungal treatment, and crude mortality.
During the primary study period November October there were episodes of candidemia occurring in pts median age 62 years, range The overall incidence of candidemia was The underlying diseases were the following: solid or hematological malignancies 43 pts , major abdominal surgery 30 pts , cardiovascular diseases 18 pts , trauma 17 pts , other diseases 28 pts. In addition, the mortality of pts infected by C. In conclusion, the incidence of nosocomial candidemia was high during the primary phase of the study; most of our pts with candidemia had severe underlying diseases and were hospitalized in ICUs.
The number of fungal positive blood cultures did not influence the crude mortality, confirming that a single bood culture shuld not be dismissed as benign transient candidemia. On the contrary, about two-third of our pts did not receive an adequate antifungal treatment and the majority of them died. Herpes Simplex Virus HSV infection may cause different disorders in patients hospitalized in intensive care.
Bronchoalveolar lavage BAL is a procedure performed almost as a routine in patients with unexplained respiratory insufficiency in our department. During the last 10 years, HSV has been isolated frequently from the respiratory tract at our 30 beds intensive care unit. The objectives of this retrospective study were to define risk factors of the population in whom HSV virus was isolated. HSV was isolated by culture on shell vials and identified by immunofluorescence after staining with monoclonal antibodies or by the conventional culture and cytopathogenic effect on Vero-cells.
The mean age of the patients was 62 years range from 16 to The majority of. The role of immunosuppression, previously recognized as a risk factor for herpes infection, was not confirmed in this study: only Striking is that Daily chest X-rays from 2 days before till 2 days after virus isolation were reviewed blindly by the same radiologist. Isolation of HSV in respiratory samples from critically ill patients is therefore more frequent than previously known.
Whether these isolates contribute to illness and its evolution remains to be determined. P64 Preliminary validation of new prognostic scoring system in patients with invasive meningococcal disease. Benese 13, 99 Pilsen, Czech Republic. E-mail: Kasal fnplzen. Introduction: Invasive meningococcal disease IMD caused by an invasive strain of Neisseria meningitidis group C:2a:P1,2,P1,5 and lately by an invasive strain group B:2a:P1,2 as well appeared in the Czech republic in and completely changed severity of the disease.
Incidence and severity of the disease in the West Bohemian region is the highest in our country. We have published preliminary results of our several studies of prediction factors of this disease. Haemocoagulopathy seemed to be of great and reliable prediction value. Purpose of the study: Prospectively to develop and preliminarily validate a model for the probability of hospital death in patients with meningococcal invasive disease.
A preliminary model was developed on the base of 82 patients data. Logistic regression was used for the development of the model, which was evaluated by the receiver operating characteristic ROC analysis. The mortality rate preliminary validation as the outcome was studied. Studied group characteristics: Unlike previous studies we studied now the group of patients with IMD treated in the whole West Bohemian region. The area under the ROC curve is 0. By the substitution to the next equation enables simply calculate the preliminary validated prediction. Tel: ; E-mail: philiph ulth.
Background: A principle feature of Gram negative sepsis is the rapid onset of profound shock. The failure of anti-endotoxin antibodies to produce significant improvement in outcome  and the profound hypocalcaemia we have observed in meningococcal sepsis led us to re-evaluate the possible aetiologies of shock in Gram negative infection. Objective: To test the hypothesis that Gram negative organisms directly or indirectly may be capable of proteolytic breakdown of albumin thus explaining in part the aetiology of shock and hypocalcaemia seen in severe Gram negative sepsis.
Methods: Urine was collected from patients with severe meningo-coccal sepsis 11 and from controls including patients admitted to intensive care 2 and patients with known proteinuria 4. Albumin was also incubated with. Results: Multiple albumin fragments were detected in urine collected from patients with meningococcal sepsis. Similar in vitro studies with homogenates of N. No albumin cleavage products were detected in the urine of control patients.
Conclusion: This study suggests that in meningococcal sepsis there is release into the circulation of protease s which cleave albumin. We were not able to distinguish whether the protease action was of exogenous or endogenous origin. This may have profound significance for the treatment of meningococcal sepsis. The HA-1A Sepsis Study Group: Treatment of gram negative bacteraemia and septic shock with HA-1A human monoclonal antibody against endotoxin: a randomised, double blind placebo-controlled trial. N Engl. P66 Continuous infusion versus intermittent administration of meropenem in critically ill patients: a pilot study.
Department of Internal Medicine I, Div. E-mail: florian. This prospective crossover study compares the pharmacokinetics of meropenem administered by continuous infusion with intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose followed by a 3g continuous infusion CI over 24 h or as intermit-.
Each regimen was performed over a period of 2 days followed by a cross over to the alternative regimen for the same time. Maximum and minimum serum concentration of meropenem Cmax, Cmin and total meropenem clearance. Cltot for IA were In both treatment groups meropenem serum concentrations remained above the minimal inhibitory concentration for the most important bacterial strains all the time.
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P67 Clearance of meropenem during continuous renal replacement therapy in critically ill patients. Meropenem is a new carbapenem antibiotic with a broad spectrum of activity against Gram-positive and Gram-negative strains including P-lactamase producers. Thus, it is particularly useful in intensive care patients pts with septic complications due to unknown pathogens. The present study was conducted to evaluate the phar-macokinetic properties of meropenem in nine critically ill patients treated by continuous venovenous hemofiltration CVVH. All pts received one single dose of 1 g meropenem intravenously.
High-flux polysulfone membranes Diafilter, Amicon, Ireland were used as dialyzer. Meropenem serum concentrations as well as filtrate aliquots were determined by high-performance liquid chromatography. Peak serum concentrations were The post-to-pre hemodialysis ratio was 0. The calculated pharmacokinetic parameters were: half-life 2. No side effects were seen.
Based upon these data we conclude that patients with severe infections on CVVH can be treated effectively with 1 g meropenem every 8 h. Often a new drug is licensed for use in the critically ill before its pharmacokinetic profile has been fully described. In particular information relating to the amount removed by continuous renal replacement therapies, such as haemofiltration, is sparse.
This relates to the difficulties associated with patient recruitment and standardisation for in vivo studies. This study describes the removal of meropenem, a broad spectrum antibiotic, by an in vitro model of haemofiltration and compares the data with that obtained in a previous in vivo investigation . Ultrafiltration rates were manipulated using a peristaltic pump attached to the ultrafiltration line.
Pre-membrane, post-membrane and ultrafiltration samples were collected from the model at timed intervals, employing three different UFR rates. Meropenem concentrations were measured by HPLC and used to calculate the drugs' sieving coefficient S and filter clearance FCL , using standard equations . The results were then compared to values obtained from a previous in vivo study  employing a similar membrane Hospal, Multiflow A mean. The results of this study suggest that the in vitro model is capable of providing accurate meropenem filter clearance data.
Although further validation of this model using a range of drugs is required, this preliminary work suggests that, in the absence of in vivo pharmacokinetic information, extracorporeal drug clearance determined using an in vitro model could be used to aid prescribing in patients receiving haemofiltration. Crit Care Med in press.
Bickley SK: Drug dosing during continuous arteriovenous hemofiltration. Clin Pharm ; Introduction: The bactericidal activity of P-lactam antibiotics on gram-negative bacilli is related to the time that concentrations of antibiotic in tissues and plasma exceed a certain threshold. The effect is maximal and constant at relatively low concentrations four times the MIC of the organism.
The dosing regime should maintain these serum levels for the entire dosing interval, as there is no significant post-antibiotic effect. Pharmacokinetic data from healthy patients may not be adequate in the critically ill. Objectives: To determine if the current recommended regimen for ceftriaxone maintains adequate serum concentrations for antibacterial efficacy in critically ill patients. Plasma ceftriaxone concentration time curves.
Methods: We administered ceftriaxone in the maximum recommended dose 2 g daily IV to 10 intensive care patients without renal or hepatic failure. Plasma samples were taken at timed intervals over 24 h with a further trough sample taken on day 4. Results: The pharmacokinetics were different to reported data in healthy subjects. Vd However, there was large inter-patient variability in drug.
There was no clinical predictor of which patients would have low plasma concentrations. Conclusion: Because of large inter-patient variability in critically ill patients, the recommended dosing regimen for ceftriaxone may result in sub-optimal tissue concentrations and loss of bactericidal efficacy in some patients.
This may be overcome by more frequent boluses or possibly by continuous infusion. We observed that the administration of vancomycin V is sometimes accompanied by pruritus, a clinical sign which appears a few minutes after the beginning of V infusion and lasts soon after V administration has been stopped. Generally it is not associated with a cutaneous rash. The aim of this study was to evaluate the hemodynamic behaviour which follows the appearance of pruritus. Method: We studied 45 patients undergoing elective coronary surgery.
The inclusion criteria consisted of stable hemodynamics without i. The hemodynamic data were collected before the administration of V time 1 , 15 min time 2 and 30 min time 3 after the beginning of V infusion, and 15 min after the administration of V has been stopped time 4. The patients were divided into two groups: group A who had pruritus during V infusion, and group B who did not.
Results: Group A included 17 patients, group B 28 patients. In patients of group B the hemody-namic data did not change significantly at the four times of the study Table.
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No patient showed a cutaneous rash throughout the study. Discussion: The analysis of our data points out that in patients who showed pruritus during the administration of vancomycin, SVRI went down. This vasodilating effect was offset by the increase in CI. As a result MSP was well maintained. Certainly this compensation was possible because the patients studied were.
But we would like to know what would happen if pruritus appears in patients with hypovolemia? Probably the compensatory mechanism would not be so effective and hypotension could occur. We conclude that pruritus which follows the administration of vancomycin can be considered an alarm-bell indicating a condition of peripheral vasodilatation, and must lead us to evaluate the patient in order to detect the hypovolemic state and to compensate for it before continuing the infusion of vancomycin.
Introduction: Remote organ injury, as evidenced by loss of functional capillaries and impaired microvascular function, has been demonstrated in a resuscitated normotensive h chronic model of intra-abdominal sepsis [1,2]. Our objective has been to develop an acute intra-abdominal model of sepsis which can be used to observe the temporal evolution of this remote microvascular dysfunction. Methods: Twenty-eight male Sprague Dawley rats were randomised to either sham SH laparotomy or modified caecal liga-tion and perforation CLP and divided into three experimental groups.
Haemodynamic variables were monitored for 4-h post laparotomy in all animals. Blood cultures from all CLP animals were positive for a combination of E. There were no differences in haemody-namics or arterial blood gases between CLP or SH animals at different time points. However, there were significant differences in white blood cell count WBC's , blood lactate and stopped capillary flow CD stop density measurements between the groups Table.
Conclusion: In this acute model of sepsis remote organ damage occurs early and is equivalent to that seen at 24 h. Therapies aimed at MODS prevention need to be commenced at the first possible opportunity. Lam C, et al. J Clin Invest , Gill R, et al. Respir Crit Care Med , :A NOx levels were significantly higher in the group that died than in the group that survived. TGF-P levels were significantly higher in the sepsis-alone group than in the septic shock group. TGF-P levels were significantly higher in the group that survived than in the group that died.
Journal of Perinatal Medicine
Twenty-one Two Conclusion: NO is involved in the pathogenesis of septic shock. Whereas NO seems to be one factor behind the decreased responsiveness of the circulation to adrenergic stimulation in septic shock, the role of NO in increased vascular permeability is less clear. In a former study  we have shown that although NO production increased after LPS there was no increased extravasation of albumin in a wide variety of rat tissues examined; on the contrary clearance was decreased in the entire gastrointestinal tract.
In this study tissue extravasation was examined after administration of the nitric oxide synthase inhibitor L-NAME. Methods: Anaesthetised Wistar rats were given E. As an indicator of NO production methemoglobin metHb was measured in the beginning and end of experiments. The tissue clearance of albumin was studied over the last 2h of the experiment by means of a double isotope method .
Tissue plasma clearance for albumin increased in the NAME-group in skin, skeletal muscle and heart and decreased in testes as compared to controls. No differences in gastrointestinal albumin clearance were detected between groups, however in heart, skeletal muscle and skin albumin extravasation was increased. We conclude that this is most likely due to changes in regional hemodynamics with locally increased capillary pressures leading to increased albumin filtration in certain tissues only. In the majority of tissues no differences were found.
P74 Loss of erythrocyte deformability during systemic sepsis is prevented by nitric oxide synthase inhibition.