Reaction of Partially Methylated Polygalacturonic Acid with Iron(III) Chloride and Characterization of a New Mixed Chloride-Polygalacturonate Complex.

We have described a new route for the preparation of partially methylated polygalacturonic acid containing hydrolyzed (acidic) and unhydrolyzed (methyl esterified) carboxylate groups in a ratio of 1:1 (PGA, compound 1), and one of its basic FeIII-salts (compound 2) with a ~1:2 FeIII:GA stoichiometry (GA means galacturonic acid and methylated galacturonic acid units). The partially hydrolyzed pectin was transformed into compound 1 with the use of double ion exchange with a strongly acidic macroreticular sulfonated styrene-divinylbenzene copolymer as a hydrogen ion source. The reaction of compound 1 with FeCl3 resulted in compound 2. Compound 2 has a polymeric nature and contains binuclear FeIII(µ-O)(µ-OH)FeIII core units with two kinds of distorted octahedral iron geometries. The salt-forming acidic and methylated GA units of compound 1 are coordinated to FeIII centers in asymmetric bidentate-chelating and -bridging (via C=O group and glycosidic oxygen) modes, respectively. Two kinds of outer-sphere chloride anions were also detected by XPS in various chemical environments fixed by different sets of hydrogen bonds. We also observed a partial reduction of FeIII into FeII due to the ring-opening of the chain-end GA units of compound 1. This reaction provides a new route to determine the number of chain-ends in compound 2, and with the use of the number of GA units calculated from charge neutrality, the average length of these chains and the average molecular weight were also determined. The average molecular weight of the partially methylated polygalacturonic acid used in the industrial-scale production of commercial anti-anemic iron-polygalacturonate agents was ~50,000 g/mol. Compound 2 was also characterized by IR, Mössbauer, and X-ray photoelectron spectroscopy, and magnetic susceptibility measurements. These results on the structure and average molecular weight of basic iron(III) polygalacturonate provide a tool to design Fe-PGA complexes with tuned iron-releasing properties.

GM-1020: a novel, orally bioavailable NMDA receptor antagonist with rapid and robust antidepressant-like effects at well-tolerated doses in rodents.

The NMDA receptor (NMDAR) antagonist ketamine has shown great potential as a rapid-acting antidepressant; however, its use is limited by poor oral bioavailability and a side effect profile that necessitates in-clinic dosing. GM-1020 is a novel NMDAR antagonist that was developed to address these limitations of ketamine as a treatment for depression. Here, we present the preclinical characterization of GM-1020 alongside ketamine, for comparison. In vitro, we profiled GM-1020 for binding to NMDAR and functional inhibition using patch-clamp electrophysiology. In vivo, GM-1020 was assessed for antidepressant-like efficacy using the Forced Swim Test (FST) and Chronic Mild Stress (CMS), while motor side effects were assessed in spontaneous locomotor activity and on the rotarod. The pharmacokinetic properties of GM-1020 were profiled across multiple preclinical species. Electroencephalography (EEG) was performed to determine indirect target engagement and provide a potentially translational biomarker. These results demonstrate that GM-1020 is an orally bioavailable NMDAR antagonist with antidepressant-like efficacy at exposures that do not produce unwanted motor effects.

Impact of Patient-specific Factors and Spinopelvic Alignment on the Development of Adjacent Segment Degeneration After Short-segment Lumbar Fusion.

STUDY DESIGN: Prospective cross-sectional cohort study. OBJECTIVES: The main purpose of this study was to evaluate the association between demographical, surgery-related and morphologic parameters, and the development or progress of adjacent segment degeneration (ASD) after short-segment lumbar fusions. SUMMARY OF BACKGROUND DATA: ASD is a major long-term complication after lumbar fusions. Possible risk factors are related to the patients' demographics, spinopelvic anatomy, or preoperative lumbar intervertebral disk conditions, but the role of these parameters is still not clear. METHODS: A prospective cross-sectional study of 100 patients who underwent 1- or 2-level open lumbar transforaminal interbody fusions due to a lumbar degenerative pathology was conducted. Demographical, radiologic findings, and magnetic resonance imaging features were analyzed to identify factors associated with ASD in 5-year follow-up. RESULTS: ASD patients showed higher level of pain ( P =0.004) and disability ( P =0.020) at follow-up. In univariate analysis, older age ( P =0.007), upper-level lumbar fusion ( P =0.007), lower L4-S1 lordosis ( P =0.039), pelvic incidence-lumbar lordosis mismatch ( P =0.021), Pfirrmann grade III or higher disk degeneration ( P =0.002), and the presence of disk bulge/protrusion ( P =0.007) were associated with ASD. In multivariate analysis, the presence of major degenerative sign (disk degeneration and/or disk bulge) was the significant predictor for developing ASD (odds ratio: 3.85, P =0.006). CONCLUSION: By examining the role of different patient- and procedure-specific factors, we found that preoperative major degenerative signs at the adjacent segment increase the risk of ASD causing significantly worse outcome after short-segment lumbar fusion. On the basis of our results, adjacent disk conditions should be considered carefully during surgical planning.

Spacer Layer Thickness Dependence of the Giant Magnetoresistance in Electrodeposited Ni-Co/Cu Multilayers.

Electrodeposited Ni65Co35/Cu multilayers were prepared with Cu spacer layer thicknesses between 0.5 nm and 7 nm. Their structure and magnetic and magnetoresistance properties were investigated. An important feature was that the Cu layers were deposited at the electrochemically optimized Cu deposition potential, ensuring a reliable control of the spacer layer thickness to reveal the true evolution of the giant magnetoresistance (GMR). X-ray diffraction indicated satellite reflections, demonstrating the highly coherent growth of these multilayer stacks. All of the multilayers exhibited a GMR effect, the magnitude of which did not show an oscillatory behavior with spacer layer thickness, just a steep rise of GMR around 1.5 nm and then, after 3 nm, it remained nearly constant, with a value around 4%. The high relative remanence of the magnetization hinted at the lack of an antiferromagnetic coupling between the magnetic layers, explaining the absence of oscillatory GMR. The occurrence of GMR can be attributed to the fact that, for spacer layer thicknesses above about 1.5 nm, the adjacent magnetic layers become uncoupled and their magnetization orientation is random, giving rise to a GMR effect. The coercive field and magnetoresistance peak field data also corroborate this picture: with increasing spacer layer thickness, both parameters progressively approached values characteristic of individual magnetic layers. At the end, a critical analysis of previously reported GMR data on electrodeposited Ni-Co/Cu multilayers is provided in view of the present results. A discussion of the layer formation processes in electrodeposited multilayers is also included, together with a comparison with physically deposited multilayers.

Anodic Polymerization of Phenylphenols in Methyl Isobutyl Ketone and Mesityl Oxide: Incorporation of a Cavitand into the Layers Formed for Sensing Phenols in Organic Media.

The electropolymerization of three phenylphenol isomers was studied in methyl isobutyl ketone and mesityl oxide, and the remarkable differences highlighted the importance of the carbon-carbon double bond in mesityl oxide. In the case of each substrate, a brownish deposit formed during the electrooxidation. The obvious difference between the polymers formed from the two solvents was recognized via voltammetric signal enhancement of 4-methoxyphenol and 4-chlorophenol, and it was only observed in the case of mesityl oxide. The experiments highlighted that incorporation of a cavitand with biphenyl groups on the upper rim of the polymers of phenylphenols improved the results to a small extent. The cavitand was, itself, electroactive without any fouling effect. As 2-phenylphenol is by far the cheapest of the three isomers, a cavitand was incorporated into its polymer, which was exploited to solve analytical problems while mesityl oxide was used as solvent. Useful quantifications were achieved in organic solvents; however, it failed under aqueous conditions due to the high hydrophobicity of the deposit. Application of differential pulse voltammetry for 4-methoxyphenol and 4-chlorophenol gave detection limits of 9.28 and 50.8 µM in acetonitrile, respectively. This procedure resulted in the immobilization of cavitand derivatives onto the electrode's surface, and the layer formed offered selective sensing of phenols by electrochemical methods.