The Feasibility of Imaging Myocardial Ischemic/Reperfusion Injury Using \u3csup\u3e99m\u3c/sup\u3eTc-labeled Duramycin in a Porcine Model

When pathologically externalized, phosphatidylethanolamine (PE) is a potential surrogate marker for detecting tissue injuries. 99mTc-labeled duramycin is a peptide-based imaging agent that binds PE with high affinity and specificity. The goal of the current study was to investigate the clearance kinetics of 99mTc-labeled duramycin in a large animal model (normal pigs) and to assess its uptake in the heart using a pig model of myocardial ischemia–reperfusion injury. Methods The clearance and distribution of intravenously injected 99mTc-duramycin were characterized in sham-operated animals (n = 5). In a closed chest model of myocardial ischemia, coronary occlusion was induced by balloon angioplasty (n = 9). 99mTc-duramycin (10–15 mCi) was injected intravenously at 1 hour after reperfusion. SPECT/CT was acquired at 1 and 3 hours after injection. Cardiac tissues were analyzed for changes associated with acute cellular injuries. Autoradiography and gamma counting were used to determine radioactivity uptake. For the remaining animals, 99mTc-tetrafosamin scan was performed on the second day to identify the infarct site. Results Intravenously injected 99mTc-duramycin cleared from circulation predominantly via the renal/urinary tract with an α-phase half-life of 3.6 ± 0.3 minutes and β-phase half-life of 179.9 ± 64.7 minutes. In control animals, the ratios between normal heart and lung were 1.76 ± 0.21, 1.66 ± 0.22, 1.50 ± 0.20 and 1.75 ± 0.31 at 0.5, 1, 2 and 3 hours post-injection, respectively. The ratios between normal heart and liver were 0.88 ± 0.13, 0.80 ± 0.13, 0.82 ± 0.19 and 0.88 ± 0.14. In vivo visualization of focal radioactivity uptake in the ischemic heart was attainable as early as 30 min post-injection. The in vivo ischemic-to-normal uptake ratios were 3.57 ± 0.74 and 3.69 ± 0.91 at 1 and 3 hours post-injection, respectively. Ischemic-to-lung ratios were 4.89 ± 0.85 and 4.93 ± 0.57; and ischemic-to-liver ratios were 2.05 ± 0.30 to 3.23 ± 0.78. The size of 99mTc-duramycin positive myocardium was qualitatively larger than the infarct size delineated by the perfusion defect in 99mTc-tetrafosmin uptake. This was consistent with findings from tissue analysis and autoradiography. Conclusion 99mTc-duramycin was demonstrated, in a large animal model, to have suitable clearance and biodistribution profiles for imaging. The agent has an avid target uptake and a fast background clearance. It is appropriate for imaging myocardial injury induced by ischemia/reperfusion

Evolution of a fluorinated green fluorescent protein

The fluorescence of bacterial cells expressing a variant (GFPm) of the green fluorescent protein (GFP) was reduced to background levels by global replacement of the leucine residues of GFPm by 5,5,5-trifluoroleucine. Eleven rounds of random mutagenesis and screening via fluorescence-activated cell sorting yielded a GFP mutant containing 20 amino acid substitutions. The mutant protein in fluorinated form showed improved folding efficiency both in vivo and in vitro, and the median fluorescence of cells expressing the fluorinated protein was improved {approx}650-fold in comparison to that of cells expressing fluorinated GFPm. The success of this approach demonstrates the feasibility of engineering functional proteins containing many copies of abiological amino acid constituents

О работе конференции "Лекарственные средства Республики Беларусь"

ЗДРАВООХРАНЕНИЕ РЕСПУБЛИКИ БЕЛАРУСЬЛЕКАРСТВАКОНГРЕСС

Anatomy of the inferior orbital fissure: Implications for endoscopic cranial base surgery

Considering many approaches to the skull base confront the inferior orbital fissure (IOF) or sphenomaxillary fissure, the authors examine this anatomy as an important endoscopic surgical landmark. In morphometric analyses of 50 adult human dry skulls from both sexes, we divided the length of the IOF into three segments (anterolateral, middle, posteromedial). Hemotoxylin- and eosin-stained sections were analyzed. Dissections were performed using transnasal endoscopy in four formalin-fixed cadaveric cranial specimens (eight sides); three endoscopic approaches to the IOF were performed.IOF length ranged from 25 to 35 mm (mean 29 mm). Length/width of the individual anterolateral, middle, and posteromedial segments averaged 6.46/5, 4.95/3.2, and 17.6/ 2.4 mm, respectively. Smooth muscle within the IOF had a consistent elationship with several important anatomical landmarks. The maxillary introstomy,total ethmoidectomy approach allowed access to the posteromedial segment of the fissure. The endoscopic modified, medial maxillectomy approach allowed access to the middle and posterior-medial segment. The Caldwell-Luc approach allowed complete exposure of the IOF. The IOF serves as an important anatomic landmark during endonasal endoscopic approaches to the skull base and orbit. Each of the three segments provides a characteristic endoscopic corridor, unique to the orbit and different fossas surrounding the fissure.Fil: de Battista, Juan Carlos. University of Cincinnati; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Anatomia Normal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zimmer, Lee A.. University of Cincinnati; Estados UnidosFil: Theodosopoulos, Philip V.. University of Cincinnati; Estados UnidosFil: Froelich, Sebastien C.. University of Cincinnati; Estados UnidosFil: Keller, Jeffrey T.. University of Cincinnati; Estados Unidos. Mayfield Clinic; Estados Unido

Random billiards with wall temperature and associated Markov chains

By a random billiard we mean a billiard system in which the standard specular reflection rule is replaced with a Markov transition probabilities operator P that, at each collision of the billiard particle with the boundary of the billiard domain, gives the probability distribution of the post-collision velocity for a given pre-collision velocity. A random billiard with microstructure (RBM) is a random billiard for which P is derived from a choice of geometric/mechanical structure on the boundary of the billiard domain. RBMs provide simple and explicit mechanical models of particle-surface interaction that can incorporate thermal effects and permit a detailed study of thermostatic action from the perspective of the standard theory of Markov chains on general state spaces. We focus on the operator P itself and how it relates to the mechanical/geometric features of the microstructure, such as mass ratios, curvatures, and potentials. The main results are as follows: (1) we characterize the stationary probabilities (equilibrium states) of P and show how standard equilibrium distributions studied in classical statistical mechanics, such as the Maxwell-Boltzmann distribution and the Knudsen cosine law, arise naturally as generalized invariant billiard measures; (2) we obtain some basic functional theoretic properties of P. Under very general conditions, we show that P is a self-adjoint operator of norm 1 on an appropriate Hilbert space. In a simple but illustrative example, we show that P is a compact (Hilbert-Schmidt) operator. This leads to the issue of relating the spectrum of eigenvalues of P to the features of the microstructure;(3) we explore the latter issue both analytically and numerically in a few representative examples;(4) we present a general algorithm for simulating these Markov chains based on a geometric description of the invariant volumes of classical statistical mechanics

A RISC-V Vector Processor With Simultaneous-Switching Switched-Capacitor DC-DC Converters in 28 nm FDSOI

This work demonstrates a RISC-V vector microprocessor implemented in 28 nm FDSOI with fully integrated simultaneous-switching switched-capacitor DC-DC (SC DC-DC) converters and adaptive clocking that generates four on-chip voltages between 0.45 and 1 V using only 1.0 V core and 1.8 V IO voltage inputs. The converters achieve high efficiency at the system level by switching simultaneously to avoid charge-sharing losses and by using an adaptive clock to maximize performance for the resulting voltage ripple. Details about the implementation of the DC-DC switches, DC-DC controller, and adaptive clock are provided, and the sources of conversion loss are analyzed based on measured results. This system pushes the capabilities of dynamic voltage scaling by enabling fast transitions (20 ns), simple packaging (no off-chip passives), low area overhead (16%), high conversion efficiency (80%-86%), and high energy efficiency (26.2 DP GFLOPS/W) for mobile devices

Transient developmental imbalance of cortical interneuron subtypes presages long-term changes in behavior

Cortical GABAergic interneurons are generated in large numbers in the ganglionic eminences and migrate into the cerebral cortex during embryogenesis. At early postnatal stages, during neuronal circuit maturation, autonomous and activity-dependent mechanisms operate within the cortex to adjust cell numbers by eliminating naturally occurring neuron excess. Here, we show that when cortical interneurons are generated in aberrantly high numbers—due to a defect in precursor cell proliferation during embryogenesis—extra parvalbumin interneurons persist in the postnatal mouse cortex during critical periods of cortical network maturation. Even though cell numbers are subsequently normalized, behavioral abnormalities remain in adulthood. This suggests that timely clearance of excess cortical interneurons is critical for correct functional maturation of circuits that drive adult behavior

Analysis of Fourier transform valuation formulas and applications

The aim of this article is to provide a systematic analysis of the conditions such that Fourier transform valuation formulas are valid in a general framework; i.e. when the option has an arbitrary payoff function and depends on the path of the asset price process. An interplay between the conditions on the payoff function and the process arises naturally. We also extend these results to the multi-dimensional case, and discuss the calculation of Greeks by Fourier transform methods. As an application, we price options on the minimum of two assets in L\'evy and stochastic volatility models.Comment: 26 pages, 3 figures, to appear in Appl. Math. Financ

Systematic Study on Fluorine-doping Dependence of Superconducting and Normal State Properties in LaFePO1-xFx

We have investigated the fluorine-doping dependence of lattice constants, transports and specific heat for polycrystalline LaFePO1-xFx. F doping slightly and monotonically decreases the in-plane lattice parameter. In the normal state, electrical resistivity at low temperature is proportional to the square of temperature and the electronic specific heat coefficient has large value, indicating the existence of moderate electron-electron correlation in this system. Hall coefficient has large magnitude, and shows large temperature dependence, indicating the low carrier density and multiple carriers in this system. Temperature dependence of the upper critical field suggests that the system is a two gap superconductor. The F-doping dependence of these properties in this system are very weak, while in the FeAs system (LaFeAsO), the F doping induces the large changes in electronic properties. This difference is probably due to the different F-doping dependence of the lattice in these two systems. It has been revealed that a pure effect of electron doping on electronic properties is very weak in this Fe pnictide compound.Comment: 8 pages, 5 figures, accepted for publication in J. Phys. Soc. Jp