Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice.

BACKGROUND: Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. METHODS: Murine bone marrow-derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry. RESULTS: In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group. CONCLUSIONS: Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase-dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 2: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 1: Radiation Physics and Radiation Biology: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Developed in Collaboration With Mended Hearts.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.

CRF-PEPICO: Double velocity map imaging photoelectron photoion coincidence spectroscopy for reaction kinetics studies.

Photoelectron photoion coincidence (PEPICO) spectroscopy could become a powerful tool for the time-resolved study of multi-channel gas phase chemical reactions. Toward this goal, we have designed and tested electron and ion optics that form the core of a new PEPICO spectrometer, utilizing simultaneous velocity map imaging for both cations and electrons, while also achieving good cation mass resolution through space focusing. These optics are combined with a side-sampled, slow-flow chemical reactor for photolytic initiation of gas-phase chemical reactions. Together with a recent advance that dramatically increases the dynamic range in PEPICO spectroscopy [D. L. Osborn et al., J. Chem. Phys. 145, 164202 (2016)], the design described here demonstrates a complete prototype spectrometer and reactor interface to carry out time-resolved experiments. Combining dual velocity map imaging with cation space focusing yields tightly focused photoion images for translationally cold neutrals, while offering good mass resolution for thermal samples as well. The flexible optics design incorporates linear electric fields in the ionization region, surrounded by dual curved electric fields for velocity map imaging of ions and electrons. Furthermore, the design allows for a long extraction stage, which makes this the first PEPICO experiment to combine ion imaging with the unimolecular dissociation rate constant measurements of cations to detect and account for kinetic shifts. Four examples are shown to illustrate some capabilities of this new design. We recorded the threshold photoelectron spectrum of the propargyl and the iodomethyl radicals. While the former agrees well with a literature threshold photoelectron spectrum, we have succeeded in resolving the previously unobserved vibrational structure in the latter. We have also measured the bimolecular rate constant of the CH2I + O2 reaction and observed its product, the smallest Criegee intermediate, CH2OO. Finally, the second dissociative photoionization step of iodocyclohexane ions, the loss of ethylene from the cyclohexyl cation, is slow at threshold, as illustrated by the asymmetric threshold photoionization time-of-flight distributions.

Visualizing competing intersystem crossing and internal conversion with a complementary measurement.

A complementary measurement method based on a home-built double-sided velocity map imaging setup is introduced. This method can simultaneously obtain time-resolved photoelectron imaging and fragment ion imaging. It has been successfully applied to investigate the ultrafast dynamics of the second singlet electronically excited state (S2) in m-xylene. Time-resolved photoelectron and ion signals derived from the initial populated S2 state are tracked following two-photon absorption of a pump pulse. Time-of-flight mass spectra (TOFMS) show that there are dominant parent ions and one fragment ions with methyl loss during such a process. According to the measured photoelectron images and fragment ions images, transient kinetic energy distributions and angular distributions of the generated photoelectrons and fragments are obtained and analyzed. Compared to stand-alone photoelectron imaging, the obtained fragment ion imaging is powerful for further understanding the mechanisms especially when the dissociation occurs during the pump-probe ionization. Two competing channels intersystem crossing T3←S2 and internal conversion S1←S2 are attributed to the deactivation of the S2 state. A lifetime of ∼50 fs for the initially excited S2 state, of ∼276 fs for the secondary populated S1 state, and of 5.76 ps for the T3 state is inferred.

Bone formation in mono cortical mandibular critical size defects after augmentation with two synthetic nanostructured and one xenogenous hydroxyapatite bone substitute - in vivo animal study.

OBJECTIVES: Healing characteristics as well as level of tissue integration and degradation of two different nanostructured hydroxyapatite bone substitute materials (BSM) in comparison with a deproteinized hydroxyapatite bovine BSM were evaluated in an in vivo animal experiment. MATERIAL AND METHODS: In the posterior mandible of 18 minipigs, bilateral mono cortical critical size bone defects were created. Randomized augmentation procedures with NanoBone(®) (NHA1), Ostim(®) (NHA2) or Bio-Oss(®) (DBBM) were conducted (each material n = 12). Samples were analyzed after five (each material n = 6) and 8 months (each material n = 6). Defect healing, formation of soft tissue and bone as well as the amount of remaining respective BSM were quantified both macro- and microscopically. RESULTS: For NHA2, the residual bone defect after 5 weeks was significantly less compared to NHA1 or DBBM. There was no difference in residual BSM between NHA1 and DBBM, but the amount in NHA2 was significantly lower. NHA2 also showed the least amount of soft tissue and the highest amount of new bone after 5 weeks. Eight months after implantation, no significant differences in the amount of residual bone defects, in soft tissue or in bone formation were detected between the groups. Again, NHA2 showed significant less residual material than NHA1 and DBBM. DISCUSSION: We observed non-significant differences in the biological hard tissue response of NHA1 and DBBM. The water-soluble NHA2 initially induced an increased amount of new bone but was highly compressed which may have a negative effect in less stable augmentations of the jaw.

Approaches to enhancing radiation safety in cardiovascular imaging: a scientific statement from the American Heart Association.

Education, justification, and optimization are the cornerstones to enhancing the radiation safety of medical imaging. Education regarding the benefits and risks of imaging and the principles of radiation safety is required for all clinicians in order for them to be able to use imaging optimally. Empowering patients with knowledge of the benefits and risks of imaging will facilitate their meaningful participation in decisions related to their health care, which is necessary to achieve patient-centered care. Limiting the use of imaging to appropriate clinical indications can ensure that the benefits of imaging outweigh any potential risks. Finally, the continually expanding repertoire of techniques that allow high-quality imaging with lower radiation exposure should be used when available to achieve safer imaging. The implementation of these strategies in practice is necessary to achieve high-quality, patient-centered imaging and will require a shared effort and investment by all stakeholders, including physicians, patients, national scientific and educational organizations, politicians, and industry.

Emerging role of cardiovascular CT and MRI in the evaluation of stroke.

OBJECTIVE. The purposes of this article are to explore the potential for use of CT angiography and MRI and to highlight data suggestive of their usefulness in specific cardiovascular abnormalities. CONCLUSION. The evaluation of stroke requires comprehensive assessment of potential stroke mechanisms, including cardiac sources. Despite an exhaustive search for secondary causes, the precise cause of many strokes remains unknown (cryptogenic). It is well recognized, however, that some of these potential causes occur as a result of embolism from the heart or great vessels. Thus, echocardiography, in particular transesophageal echocardiography, is instrumental in a careful assessment of cardiac causes in selected individuals. Unfortunately, transesophageal echocardiography is invasive, and some patients may have relative or absolute contraindications. Cardiovascular CT angiography and MRI have growing potential compared with conventional cardiovascular echography.

Isomer-specific product detection of gas-phase xylyl radical rearrangement and decomposition using VUV synchrotron photoionization.

Xylyl radicals are intermediates in combustion processes since their parent molecules, xylenes, are present as fuel additives. In this study we report on the photoelectron spectra of the three isomeric xylyl radicals and the subsequent decomposition reactions of the o-xylyl radical, generated in a tubular reactor and probed by mass selected threshold photoelectron spectroscopy and VUV synchrotron radiation. Franck-Condon simulations are applied to augment the assignment of elusive species. Below 1000 K, o-xylyl radicals decompose by hydrogen atom loss to form closed-shell o-xylylene, which equilibrates with benzocyclobutene. At higher temperatures relevant to combustion engines, o-xylylene generates styrene in a multistep rearrangement, whereas the p-xylylene isomer is thermally stable, a key point of difference in the combustion of these two isomeric fuels. Another striking result is that all three xylyl isomers can generate p-xylylene upon decomposition. In addition to C8H8 isomers, phenylacetylene and traces of benzocyclobutadiene are observed and identified as further reaction products of o-xylylene, while there is also some preliminary evidence for benzene and benzyne formation. The experimental results reported here are complemented by a comprehensive theoretical C8H8 potential energy surface, which together with the spectroscopic assignments can explain the complex high-temperature chemistry of o-xylyl radicals.

Improving material properties of a poloxamer P407 hydrogel-based hydroxyapatite bone substitute material by adding silica-A comparative in vivo study.

The structure and handling properties of a P407 hydrogel-based bone substitute material (BSM) might be affected by different poloxamer P407 and silicon dioxide (SiO2) concentrations. The study aimed to compare the mechanical properties and biological parameters (bone remodeling, BSM degradation) of a hydroxyapatite: silica (HA)-based BSM with various P407 hydrogels in vitro and in an in vivo rat model. Rheological analyses for mechanical properties were performed on one BSM with an SiO2-enriched hydrogel (SPH25) as well on two BSMs with unaltered hydrogels in different gel concentrations (PH25 and PH30). Furthermore, the solubility of all BSMs were tested. In addition, 30 male Wistar rats underwent surgical creation of a well-defined bone defect in the tibia. Defects were filled randomly with PH30 (n = 15) or SPH25 (n = 15). Animals were sacrificed after 12 (n = 5 each), 21 (n = 5 each), and 63 days (n = 5 each). Histological evaluation and histomorphometrical quantification of new bone formation (NB;%), residual BSM (rBSM;%), and soft tissue (ST;%) was conducted. Rheological tests showed an increased viscosity and lower solubility of SPH when compared with the other hydrogels. Histomorphometric analyses in cancellous bone showed a decrease of ST in PH30 (p = .003) and an increase of NB (PH30: p = .001; SPH: p = .014) over time. A comparison of both BSMs revealed no significant differences. The addition of SiO2 to a P407 hydrogel-based hydroxyapatite BSM improves its mechanical stability (viscosity, solubility) while showing similar in vivo healing properties compared to PH30. Additionally, the SiO2-enrichment allows a reduction of poloxamer ratio in the hydrogel without impairing the material properties.

Real-time observation of ultrafast internal conversion in ethylbenzene by femtosecond time-resolved photoelectron imaging.

The ultrafast dynamics of the second singlet electronically excited state (S2) in ethylbenzene has been studied by femtosecond time-resolved photoelectron imaging. The time evolution of the photoelectron signal can be well described by a biexponential decay: a rapid relaxation pathway with a time constant of 60 ( ± 9) fs and a longer-lived channel on a timescale of 2.58 ( ± 0.22) ps. The rapid relaxation is ascribed to the ultrafast internal conversion from the S2 state to the vibrationally hot S1 state. This internal conversion process has been observed in real time. The slow photoelectron signal reflects the depopulation of secondarily populated high vibronic S1 state.

Unimolecular reaction mechanism of an imidazolin-2-ylidene: an iPEPICO study on the complex dissociation of an Arduengo-type carbene.

The photoionization and dissociative photoionization of Im(iPr)2, 1,3-diisopropylimidazolin-2-ylidene, was investigated by imaging photoelectron photoion coincidence (iPEPICO) with vacuum ultraviolet (VUV) synchrotron radiation. A lone-pair electron of the carbene carbon atom is removed upon ionization and the molecular geometry changes significantly. Only 0.5 eV above the adiabatic ionization energy, IEad =7.52±0.1 eV, the carbene cation fragments, yielding propene or a methyl radical in parallel dissociation reactions with appearance energies of 8.22 and 8.17 eV, respectively. Both reaction channels appear at almost the same photon energy, suggesting a shared transition state. This is confirmed by calculations, which reveal the rate-determining step as hydrogen-atom migration from the isopropyl group to the carbene carbon center forming a resonance-stabilized imidazolium ion. Above 10.5 eV, analogous sequential dissociation channels open up. The first propene-loss fragment ion dissociates further and another methyl or propene is abstracted. Again, a resonance-stabilized imidazolium ion acts as intermediate. The aromaticity of the system is enhanced even in vertical ionization. Indeed, the coincidence technique confirms that a real imidazolium ion is produced by hydrogen transfer over a small barrier. The simple analysis of the breakdown diagram yields all the clues to disentangle the complex dissociative photoionization mechanism of this intermediate-sized molecule. Photoelectron photoion coincidence is a promising tool to unveil the fragmentation mechanism of larger molecules in mass spectrometry.

Radiation dose in cardiac imaging: how should it affect clinical decisions?

OBJECTIVE: The purpose of this article is to discuss whether and how the risks of exposure to ionizing radiation should affect clinical decision making in patients with known or suspected cardiovascular disease. CONCLUSION: Although the prevalence of cardiovascular disease and frequency of diagnostic testing has risen dramatically, cardiovascular mortality has declined. Earlier and more accurate detection of cardiovascular disease may play an important role. Concerns regarding excessive radiation exposure from cardiovascular imaging have been raised. Efforts to reduce exposure have included selection of appropriate patients for cardiovascular testing, technologic advances, educational resources, and a directed patient-centered approach to testing.

Ultrafast imaging of electronic relaxation in o-xylene: a new competing intersystem crossing channel.

The ultrafast dynamics of the second singlet electronically excited state (S2) in o-xylene was investigated by femtosecond time-resolved photoelectron imaging. A new competing relaxation channel of the S2 state was observed and assigned to the T3 ← S2 intersystem crossing. Interestingly, it is found that the relaxation via this channel occurs on a comparable femtosecond timescale as the S1 ← S2 internal conversion. A lifetime of ~60 fs for the initially excited S2 state, of 540 (±17) fs for the secondary populated S1 state, and of 7.23 (±0.21) ps for the T3 state could be inferred.

3,3,3-Trifluoro-2-hydr-oxy-2-(trifluoro-meth-yl)propionic acid.

In the title perfluorinated hy-droxy-isobutyric acid derivative, C4H2F6O3, the mol-ecule shows approximately Cs symmetry. The carb-oxy group is nearly coplanar with the C-OH moiety and the O=C-C-O(H) torsion angle is 5.5 (2)°. An intra-molecular O-H⋯O hydrogen bond occurs. In the crystal, O-H⋯O hydrogen bonds connect the mol-ecules into supra-molecular chains along the a-axis direction.

rac-3,3,3-Trifluoro-lactic acid.

THE TITLE COMPOUND (SYSTEMATIC NAME: rac-3,3,3-trifluoro-2-hy-droxy-propanoic acid), C3H3F3O3, is a fluorinated derivative of lactic acid. The O=C-C-O(H) torsion angle is 13.26 (15)°. In the crystal, O-H⋯O hydrogen bonds and C-H⋯O contacts connect the mol-ecules into sheets perpendicular to the c axis.

2,4-Dichloro-benzyl 2-meth-oxy-benzoate.

In the title compound, C15H12Cl2O3, the aromatic rings make a dihedral angle of 10.78 (4)°. In the molecule, there is a short C-H⋯O contact. In the crystal, C-H⋯O contacts connect the mol-ecules into C(7)C(8) chains along the b axis. The shortest inter-centroid distance between two benzoic acid aromatic systems is 3.7416 (8) Å.

2-(4-Chloro-phen-yl)-2-oxoethyl naphthalene-1-carboxyl-ate.

In the title compound, C19H13ClO3, an ester of 1-naphthoic acid with an aromatic alcohol, the least-squares planes defined by the C atoms of the respective aromatic systems enclose an angle of 77.16 (3)°. In the crystal, C-H⋯O contacts connect the mol-ecules into undulating sheets parallel to the bc plane.