The Use of Hexokinase 2-Displacing Peptides as an Anti-Neoplastic Approach for Malignant Peripheral Nerve Sheath Tumors.

Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas that can arise both sporadically and in patients with the genetic syndrome Neurofibromatosis type 1 (NF1). Prognosis is dismal, as large dimensions, risk of relapse, and anatomical localization make surgery poorly effective, and no therapy is known. Hence, the identification of MPNST molecular features that could be hit in an efficient and selective way is mandatory to envision treatment options.

Label-free sensing of cells with fluorescence lifetime imaging: The quest for metabolic heterogeneity.

Molecular, morphological, and physiological heterogeneity is the inherent property of cells which governs differences in their response to external influence. Tumor cell metabolic heterogeneity is of a special interest due to its clinical relevance to tumor progression and therapeutic outcomes. Rapid, sensitive, and noninvasive assessment of metabolic heterogeneity of cells is a great demand for biomedical sciences.

4-Dialkylamino-2,5-dihydroimidazol-1-oxyls with Functional Groups at the Position 2 and at the Exocyclic Nitrogen: The pH-Sensitive Spin Labels.

Local acidity and electrostatic interactions are associated both with catalytic properties and the adsorption activity of various materials, and with the vital functions of biomolecules. The observation of acid-base equilibria in stable free radicals using EPR spectroscopy represents a convenient method for monitoring pH changes and the investigation of surface electrostatics, the advantages of which are especially evident in opaque and turbid samples and in porous materials such as xerogels. Imidazoline nitroxides are the most commonly used pH-sensitive spin probes and labels due to the high sensitivity of the parameters of the EPR spectra to pH changes, their small size, and their well-developed chemistry.

Comparative Analysis of Behavioral Reactions and Morphological Changes in the Rat Brain After Exposure to Ionizing Radiation with Different Physical Characteristics.

The aim of this research was to study behavioral reactions and morphological changes in the brain of adult female Sprague Dawley rats after exposure to 170 MeV and 70 MeV protons and gamma radiation (60Co) at a dose of 1 Gy. The analysis of the behavioral reactions in the T-maze showed that exposure to ionizing radiation with different LETs led to an increase in number of repeated entries into the arms of the maze in the spontaneous alternation test. In the Open Field test a decrease in overall motor activity in the group of irradiated animals (70 MeV protons at the Bragg peak) was observed.

High fidelity triangular sweep of the magnetic field for millisecond scan EPR imaging.

Linearity of the magnetic field sweep is important for high resolution continuous wave EPR imaging. Driving the field with triangular wave function is the most efficient way to scan EPR projections. However, the magnetic field sweep profile can be significantly distorted during fast millisecond projection scan.

Development of an L-band resonator optimized for fast scan EPR imaging of the mouse head.

Purpose: To develop a novel resonator for high-quality fast scan electron paramagnetic resonance (EPR) and EPR/NMR co-imaging of the head and brain of mice at 1.25 GHz.

Methods: Resonator dimensions were scaled to fit the mouse head with maximum filling factor.

New phenazine based anolyte material for high voltage organic redox flow batteries.

Herein, we report the synthesis and investigation of a novel phenazine derivative M1 with oligomeric ethylene glycol ether substituents as a promising anolyte material for non-aqueous organic redox flow batteries (RFBs). The designed material undergoes a reversible and stable reduction at -1.72 V vs.

Algebraic reconstruction of 3D spatial EPR images from high numbers of noisy projections: An improved image reconstruction technique for high resolution fast scan EPR imaging.

A novel method for reconstructing 3D spatial EPR images from large numbers of noisy projections was developed that minimizes mean square error between the experimental projections and those from the reconstructed image. The method utilizes raw projection data and zero gradient spectrum to account for EPR line shape and hyperfine structure of the paramagnetic probe without the need for deconvolution techniques that are poorly suited for processing of high noise projections. A numerical phantom was reconstructed for method validation.

Interrogation of tumor metabolism in tissue samples ex vivo using fluorescence lifetime imaging of NAD(P)H.

Exploring metabolism in human tumors at the cellular level remains a challenge. The reduced form of metabolic cofactor NAD(P)H is one of the major intrinsic fluorescent components in tissues and a valuable indicator of cellular metabolic activity. Fluorescence lifetime imaging (FLIM) enables resolution of both the free and protein-bound fractions of this cofactor, and thus, high sensitivity detection of relative changes in the NAD(P)H-dependent metabolic pathways in real time.

In Vivo Extracellular pH Mapping of Tumors Using Electron Paramagnetic Resonance.

An electron paramagnetic resonance (EPR)-based method for noninvasive three-dimensional extracellular pH mapping was developed using a pH-sensitive nitroxyl radical as an exogenous paramagnetic probe. Fast projection scanning with a constant magnetic field sweep enabled the acquisition of four-dimensional (3D spatial +1D spectral) EPR images within 7.5 min.

Maintenance of redox balance by antioxidants in hemolymph of the greater wax moth Galleria mellonella larvae during encapsulation response.

The lipid peroxidation process in hemocytes, activities of phenoloxidase and key enzymatic antioxidants (superoxide dismutase, glutathione-S-transferase, catalase) and nonenzymatic antioxidants (thiols, ascorbate) in hemolymph of the greater wax moth Galleria mellonella L. (Lepidoptera: Pyralidae) were studied during the encapsulation process of nylon implants. It has been established that as soon as 15 min after piercing a cuticle with the implant, a capsule is formed on its surface.

A 750-MHz Electronically Tunable Resonator Using Microstrip Line Couplers for Electron Paramagnetic Resonance Imaging of a Mouse Tumor-Bearing Leg.

Objective: The purpose of this work was to develop an electronically tunable resonator operating at 750 MHz for continuous-wave electron paramagnetic resonance (CW-EPR) imaging of a mouse tumor-bearing leg.

Methods: The resonator had a multi-coil parallel-gap structure with a sample space of 16 mm in diameter and 20 mm in length. Microstrip line couplers were used in conjunction with varactor diodes to enable resonance frequency adjustment and to reduce the nonlinear effects of the varactor diodes.

Fast backprojection-based reconstruction of spectral-spatial EPR images from projections with the constant sweep of a magnetic field.

In this paper, we introduce a procedure for the reconstruction of spectral-spatial EPR images using projections acquired with the constant sweep of a magnetic field. The application of a constant field-sweep and a predetermined data sampling rate simplifies the requirements for EPR imaging instrumentation and facilitates the backprojection-based reconstruction of spectral-spatial images. The proposed approach was applied to the reconstruction of a four-dimensional numerical phantom and to actual spectral-spatial EPR measurements.

Feasibility of in vivo three-dimensional T mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging.

Objectives: The aim of this study was to demonstrate the feasibility of in vivo three-dimensional (3D) relaxation time T mapping of a dicarboxy-PROXYL radical using continuous-wave electron paramagnetic resonance (CW-EPR) imaging.

Materials And Methods: Isotopically substituted dicarboxy-PROXYL radicals, 3,4-dicarboxy-2,2,5,5-tetra(H)methylpyrrolidin-(3,4-H)-(1-N)-1-oxyl (H,N-DCP) and 3,4-dicarboxy-2,2,5,5-tetra(H)methylpyrrolidin-(3,4-H)-1-oxyl (H-DCP), were used in the study. A clonogenic cell survival assay was performed with the H-DCP radical using squamous cell carcinoma (SCC VII) cells.

Effect of Sterical Shielding on the Redox Properties of Imidazoline and Imidazolidine Nitroxides.

The oxidant properties of the series of 2,2,5,5-tetraalkyl imidazoline and imidazolidine nitroxides were investigated. An increase in the number of bulky alkyl substituents leads to a decrease in the rate of reduction with ascorbate, which makes the electrochemical reduction potential more negative and shifts the equilibrium in the mixture of nitroxide and reference hydroxylamine (3-carboxy-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-1-oxyl-1-(15)N) toward the starting compounds. The effect of structural factors on these reactions was analyzed by means of multiple regression using the Fujita steric constant Es and the inductive Hammett constant σI.

Functional electron paramagnetic resonance imaging of ischemic rat heart: Monitoring of tissue oxygenation and pH.

Purpose: Electron paramagnetic resonance (EPR) imaging in the spectral-spatial domain with application of soluble paramagnetic probes provides an opportunity for spatially resolved functional measurements of living objects. The purpose of this study was to develop EPR methods for visualization of oxygenation and acidosis of ischemic myocardium.

Methods: EPR oxygen measurements were performed using isotopically substituted (2) H,(15) N-dicarboxyproxyl.

Cardiopulmonary bypass duration as predictor of immediate results after cardiac surgery.

It was analyzed the results of treatment of 152 patients who underwent heart valve surgery. Depending on cardiopulmonary bypass (CPB) duration patients were divided into 4 groups: the 1st--up to 90 min, the 2nd--90-120 min, the 3rd--120-180 min, the 4th--more than 180 min. Severity of initial comorbidities was comparable in all groups.

Phosphonated trityl probes for concurrent in vivo tissue oxygen and pH monitoring using electron paramagnetic resonance-based techniques.

Previously we proposed the concept of dual function pH and oxygen paramagnetic probes based on the incorporation of ionizable groups into the structure of persistent triarylmethyl radicals, TAMs (J. Am. Chem.

Oxidation of adenosine and inosine: the chemistry of 8-oxo-7,8-dihydropurines, purine iminoquinones, and purine quinones as observed by ultrafast spectroscopy.

Oxidative damage to purine nucleic acid bases proceeds through quinoidal intermediates derived from their corresponding 8-oxo-7,8-dihydropurine bases. Oxidation studies of 8-oxo-7,8-dihyroadenosine and 8-oxo-7,8-dihydroinosine indicate that these quinoidal species can produce stable cross-links with a wide variety of nucleophiles in the 2-positions of the purines. An azide precursor for the adenosine iminoquinone has been synthesized and applied in ultrafast transient absorption spectroscopic studies.

Synthesis of a chiral C2-symmetric sterically hindered pyrrolidine nitroxide radical via combined iterative nucleophilic additions and intramolecular 1,3-dipolar cycloadditions to cyclic nitrones.

A sterically hindered bis-spirocyclic C(2)-symmetric chiral pyrrolidine-type nitroxide has been successfully synthesized starting from an l-tartaric derived nitrone. Starting from a pyrrolidine flanked by two methylene groups, complete quaternization of the two α-carbon atoms has been accomplished through iteration of completely regio- and stereoselective intramolecular cycloaddition reactions and organometallic additions to key nitrone intermediates, formed in turn by oxidation procedures. This method appears to be very useful for building up bulky spirocyclic moieties adjacent to a nitroxide group and provides an important supplementation to traditional methods of nitroxide synthesis.

Dual-function pH and oxygen phosphonated trityl probe.

Triarylmethyl radicals (TAMs) are used as persistent paramagnetic probes for electron paramagnetic resonance (EPR) spectroscopic and imaging applications and as hyperpolarizing and contrast agents for magnetic resonance imaging (MRI) and proton-electron double-resonance imaging (PEDRI). Recently we proposed the concept of dual-function pH and oxygen TAM probes based on the incorporation of ionizable groups into the TAM structure ( J. Am.

Electron paramagnetic resonance monitoring of ischemia-induced myocardial oxygen depletion and acidosis in isolated rat hearts using soluble paramagnetic probes.

A new low-field electron paramagnetic resonance approach for noninvasive measurements of myocardial oxygen tension and tissue acidity was developed. The approach was applied to monitor myocardial pO(2) and pH in a model of global no-flow ischemia (30 min) and reperfusion in isolated perfused rat hearts. The myocardial oxygen measurements were performed using deuterated Finland trityl radical probe.

[Generation of reactive oxygen species and activity of antioxidants in larva hemolymph of galleria mellonella (L.) (lepidoptera: piralidae) at development of process of encapsulation].

Activities of enzymatic antioxidants (superoxide dismutase, glutathione-S-transferase, and catalase) have been determined in hemocytes and generation of reactive oxygen species (ROS) has been studied in lymph of larvae of the wax moth Galleria mellonella at development of the process of encapsulation of nylon implants. It has been established that as soon as 15 min after piercing of cuticle with implant the capsule is formed on its surface. The active melanization of the capsule has been shown to last for 4 h.