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Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab') 2 antibody fragments targeting MMPs detects colitis induced colonic fibrosis. Mice were administered 2% dextran sulfate sodium treated water for 1 cycle (inflamed) or 3 cycles (fibrotic), or were untreated (control). Colonic and kidney collagen, innate cytokine, MMPs and fecal MPO concentrations were analyzed by multiplex/ELISA. α-pro-MMP-9 F(ab') 2 fragments were engineered and conjugated to 89 Zr for PET imaging, ex-vivo Cherenkov analysis and bio-distribution. Colonic innate cytokine concentrations and fecal myeloperoxidase were increased in inflamed mice but not fibrotic mice, while collagen concentrations were increased in fibrotic mice. MMPs were increased in inflamed mice, but only pro-MMP-9 remained increased in fibrotic mice. 89 Zr-pro-MMP-9 F(ab') 2 uptake was increased in the intestine but also in the kidney of fibrotic mice, where collagen and pro-MMP-9 concentrations were increased. 89 Zr-pro-MMP-9 F(ab') 2 detects colitis induced intestinal fibrosis and associated kidney fibrosis.

Introduction: The demand for Gallium-68 ( 68 Ga) for labelling PET radiopharmaceuticals has increased over the past few years. 68 Ga is obtained through the decayed parent radionuclide 68 Ge using commercial 68 Ge/ 68 Ga generators. The principal limitation of commercial 68 Ge/ 68 Ga generators is that only a limited and finite quantity of 68 Ga (<1.85 GBq at start of synthesis) may be accessed. The focus of this study was to investigate the use of a low energy medical cyclotron for the production of greater quantities of 68 Ga and to develop an automated and rapid procedure for processing the product., Methods: Enriched ZnCl 2 was electrodeposited on a platinum backing using a NH 4 Cl (pH 2-4) buffer. The Zn target was irradiated with GE PETtrace 880 at 35 μA and 14.5 and 12.0 MeV beam energy. The irradiated Zn target was purified using octanol resin on an automated system., Results: Following the described procedure, 68 Ga was obtained in 6.30 ± 0.42 GBq after 8.5 min bombardment and with low radionuclidic impurities ( 66 Ga (<0.005%) and 67 Ga (<0.09%)). Purification on a single octanol resin gave 82% recovery with resulting [ 68 Ga]GaCl 3 obtained in 3.5 mL of 0.2 M HCl. [ 68 Ga]GaCl 3 production from irradiation to final product was <45 min. To highlight the utility of the automated procedure, [ 68 Ga]Ga-DOTA-TATE labelling was incorporated to give 1.56 GBq at EOS of the labelled peptide with RCY of >70%., Conclusions: A straightforward procedure for producing 68 Ga on a low energy medical cyclotron was described. Current efforts are focus on high activity production and radiolabelling using solid target produced 68 Ga., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Coordination polymers and discrete metallo-supramolecular assemblies of hexaaryl[3]radialene compounds exhibit intriguing structures with short anion to π-centroid distances in the solid-state. Furthermore, these [3]radialene compounds display useful photophysical and electrochemical properties that make them ideal as potential platforms for anion receptors. In this study, hexafluoro[3]radialene was optimized to the MP2/aug-cc-pVTZ level of theory, and its complexes with halide anions were optimized to HF/6-31G++(d,p), MP2/6-31G++(d,p), M06-2X/6-31G++(d,p), and M06-2X/6-311G++(d,p) levels of theory. Hexafluoro[3]radialene was shown to have properties (large positive Qzz and areas of positive electrostatic surface potential) comparable to other compounds that show anion-π interactions. The interaction energies of complexes of hexafluoro[3]radialene with halide anions were calculated and found to be favorable and equivalent to those of fluorinated aromatic compounds. A series of synthetically accessible hexaaryl[3]radialenes were optimized to HF/6-31G++(d,p) theory and their complexes with halides optimized to the M06-2X/6-31G++(d,p) level of theory. The calculated properties of the electron-deficient hexaaryl[3]radialenes also show large positive Qzz quadrupole moments and two areas of positive potential; at the [3]radialene core and the acidic aryl hydrogen atoms. The interaction energies of the complexes of hexaaryl[3]radialenes and halide anions were found to follow the trend F(-) > Cl(-) ≈ Br(-) and correlate with the electron-deficient nature of the [3]radialene. Close contacts were observed between the anion and the radialene core and the aryl hydrogen atoms, suggesting a combination of anion-π and hydrogen bonding is important. Mass spectrometry was used to experimentally observe the complexes of a number of hexaaryl[3]radialenes with F(-), Cl(-), and Br(-) predicted computationally. Anion-[3]radialene complexes were successfully detected, and the stability of the complexes in tandem MS/MS experiments was found to support the computational results.

The syntheses of three new [3]radialenes - hexakis(3,5-dimethylpyrazolyl)-, hexakis(3-cyanophenyl)-, and hexakis(3,4-dicyanophenyl)[3]radialene (1-3) - are reported. Compound 3 is obtained in five steps with an excellent yield of 76% in the key step. Compared to that, the respective steps of the syntheses of 1 and 2 result in lower yields. All compounds adopt a double bladed propeller conformation in solution. Compound 3 is considerably more electron deficient than previously reported hexaaryl[3]radialenes, with reduction potentials of -0.06 and -0.45 V in CH(2)Cl(2). The compounds mostly display red fluorescence with large Stokes shifts.

The sterol and fatty acid content of mycelium from germinating basidiospores of Cronartium fusiforme was determined. The mycelium contained stigmast-7-enol, fungisterol, and possibly stigmasta-5,7-dienol. No ergosterol was detected. The mycelium contained the expected fatty acids and low relative proportions of 9,10-epoxyoctadecanoic acid. The absence of ergosterol, and presence of the epoxy C18 acid and sterols typical of certain rust spores may be used for a relatively rapid confirmation of rust fungi in culture. Based on these chemical criteria, yeast-like cells isolated from the cultures of germinating basidiospores appear not to be C. fusiforme.

The first appearance of mitotic figures in reactivatinig buds of 1-year-old ash seedlings is in leaf primordia. The occurrence of mitotic figures then progresses sequentially to the procambial cells and finally to the cambium at the base of the bud. Milotic reactivation of the cambium in progressively more proximal regions of the stem is slow, proceeding at a maximal rate of 6 centimeters per day.

Transport of indoleacetic acid-1(14)C following application to the buds of intact white ash (Fraxinus americana L.) shoots proceeds at a velocity of about 1.3 centimeters per hour in actively growing seedlings, but only 0.3 centimeter per hour in dormant seedlings. The rapid movement is metabolically controlled, and at 1 C or in a nitrogen environment it is reduced to 0.2 centimeter per hour, suggesting that the slower movement is due to diffusion. The transport profile for growing shoots shows a logarithmic decrease in activity in stems treated for 3 hours. However, over longer treatment intervals, especially after 12 hours, a steady state of recoverable activity occurs in the more basal stem segments. Cold-treated shoots acquire the capacity for rapid transport 7 days after they are placed into favorable growing conditions, at which time dormancy callose disappears from the phloem, respiratory activity of the stem tissue increases, and mitotic reactivation occurs in the bud. Following shoot reactivation, the velocity and amount of exogenously supplied indoleacetic acid transported remained relatively uniform until the onset of the succeeding dormant period. Five per cent, or less, of the applied tracer moves into the shoot, with substantial portions remaining as indoleacetic acid.

In excised embryos of Fraxinus ornus, the first macroscopic sign of germination is a curvature near the root apex. Histological studies show that this curvature is due to cell elongation on the convex side and is accompanied by cell division. Metabolic changes, manifested by the disintegration of protein bodies and tissue differentiation, also occur during this time. In embryos treated with phleomycin cell division is completely inhibited but elongation, root hair formation, disintegration of protein bodies, and differentiation are still detectable. Phleomycin also drastically inhibits the formation of chlorophylls and the fresh weight increase of embryos.