The antioxidative properties of two series of new phenolic, amphiphilic compounds were evaluated using the chemiluminescence (CL) method. 2,2'-Azobis (2-amidinopropane) dihydrochloride (AAPH) was ...used as a source of free radicals, to obtain high and prolonged CL. Three different kinds of buffers (organic and inorganic) were tested. The CL level varied only slightly depending on the buffer but increased significantly with the pH. Twelve newly synthesised compounds were compared with butylated hydroxytoluene (BHT), a commercially used antioxidant. The new antioxidants included two classes of quaternary ammonium salts with a phenol substituent functioning as an antioxidant. The salts were synthesised by quaternarization of pyrrolidine ethyl esters of dihydrocinnamic acid by n-alkoxymethyl bromides (PYA-n) or quaternarization of 2-dimethylaminoethyl esters by n-alkyl bromides (PPA-n). All the tested compounds quenched CL proportionally to their concentrations. In our experimental conditions 8.5 microM BHT quenched 50% of the CL. The PYA and PPA compounds had IC50 two to six times lower than BHT. CL inhibition was proportional to the pH for all antioxidants. The relationships between the structure and activity of the tested compounds are discussed.
Clinical trials of fostamatinib in patients with rheumatoid arthritis showed blood pressure (BP) elevation using clinic measurements. The OSKIRA-ambulatory BP monitoring trial assessed the effect of ...fostamatinib on 24-hour ambulatory systolic BP (SBP) in patients with active rheumatoid arthritis. One hundred thirty-five patients were randomized to fostamatinib 100 mg twice daily (bid; n = 68) or placebo bid (n = 67) for 28 days. Ambulatory, clinic, and home BPs were measured at baseline and after 28 days of therapy. Primary end point was change from baseline in 24-hour mean SBP. Fostamatinib increased 24-hour mean SBP by 2.9 mm Hg (P = .023) and diastolic BP (DBP) by 3.5 mm Hg (P < .001) versus placebo. Clinic/home-measured BPs were similar to those observed with ambulatory BP monitoring. After treatment discontinuation (1 week), clinic BP values returned to baseline levels. Fostamatinib induced elevations in 24-hour mean ambulatory SBP and DBP. BP elevations resolved with fostamatinib discontinuation.
There is a large body of evidence that atomic nuclei can undergo octupole distortion and assume the shape of a pear. This phenomenon is important for measurements of electric-dipole moments of atoms, ...which would indicate CP violation and hence probe physics beyond the standard model of particle physics. Isotopes of both radon and radium have been identified as candidates for such measurements. Here, we have observed the low-lying quantum states in \(^{224}\)Rn and \(^{226}\)Rn by accelerating beams of these radioactive nuclei. We report here additional states not assigned in our 2019 publication. We show that radon isotopes undergo octupole vibrations but do not possess static pear-shapes in their ground states. We conclude that radon atoms provide less favourable conditions for the enhancement of a measurable atomic electric-dipole moment.
There is sparse direct experimental evidence that atomic nuclei can exhibit stable pear shapes arising from strong octupole correlations. In order to investigate the nature of octupole collectivity ...in radium isotopes, electric octupole (\(E3\)) matrix elements have been determined for transitions in \(^{222,228}\)Ra nuclei using the method of sub-barrier, multi-step Coulomb excitation. Beams of the radioactive radium isotopes were provided by the HIE-ISOLDE facility at CERN. The observed pattern of \(E\)3 matrix elements for different nuclear transitions is explained by describing \(^{222}\)Ra as pear-shaped with stable octupole deformation, while \(^{228}\)Ra behaves like an octupole vibrator.
Objective
SB5 is a biosimilar agent for adalimumab (ADA). The aim of this study was to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of SB5 in comparison with reference ADA ...in patients with rheumatoid arthritis (RA).
Methods
In this phase III, randomized, double‐blind, parallel‐group study, patients with moderately to severely active RA despite treatment with methotrexate were randomized 1:1 to receive SB5 or reference ADA at a dosage of 40 mg subcutaneously every other week. The primary efficacy end point was the response rate based on the American College of Rheumatology 20% improvement criteria (ACR20) at week 24 in the per‐protocol set (completer analysis). Additional end points included efficacy, PK, safety, and immunogenicity assessments.
Results
Of the 544 patients randomized to receive a study drug, the full analysis set comprised 542 patients (269 in the SB5 group, 273 in the reference ADA group) and the per‐protocol set comprised 476 patients (239 receiving SB5, 237 receiving reference ADA). The ACR20 response rate at week 24 in the per‐protocol set was equivalent between those receiving SB5 and those receiving reference ADA (72.4% and 72.2%, respectively); the difference in the ACR20 response rate (0.1%, 95% confidence interval −7.83%, 8.13%) was within the predefined equivalence margin (±15%). Similar results were seen in the full analysis set (missing data being considered a nonresponse). The SB5 and reference ADA treatment groups were comparable across other end points, including the ACR 50% and ACR 70% improvement response rates, Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate, PK data, incidence of treatment‐emergent adverse events, and the antidrug antibody response. Subgroup analyses showed that the efficacy and safety of SB5 and reference ADA were comparable regardless of antidrug antibody status.
Conclusion
The ACR20 response rate at week 24 was equivalent between patients treated with the biosimilar agent SB5 and those treated with reference ADA. SB5 and reference ADA were both well tolerated, with comparable safety profiles, in patients with RA.
Abstract
Since its discovery in 2019, multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been identified. This study investigates virus spread and associated ...pathology in the upper and lower respiratory tracts of Syrian golden hamsters at 4 days post intranasal SARS-CoV-2 Omicron infection, in comparison to infection with variants of concern (VOCs) Gamma and Delta as well as ancestral strain 614 G. Pathological changes in the upper and lower respiratory tract of VOC Omicron infected hamsters are milder than those caused by other investigated strains. VOC Omicron infection causes a mild rhinitis with little involvement of the olfactory epithelium and minimal lesions in the lung, with frequent sparing of the alveolar compartment. Similarly, viral antigen, RNA and infectious virus titers are lower in respiratory tissues of VOC Omicron infected hamsters. These findings demonstrate that the variant has a decreased pathogenicity for the upper and lower respiratory tract of hamsters.
Time-resolved pulse radiolysis, utilizing short pulses of high-energy electrons from accelerators, is an effective method for rapidly generating free radicals and other transient species in solution. ...Combined with fast time-resolved spectroscopic detection (typically in the ultraviolet/visible/near-infrared), it is invaluable for monitoring the reactivity of species subjected to radiolysis on timescales ranging from picoseconds to seconds. When used for polymer solutions, pulse radiolysis can be coupled with light-scattering detection, creating a powerful tool for kinetic and mechanistic analysis of processes like degradation or cross-linking of macromolecules. Changes in the light scattering intensity (LSI) of polymer solutions are indicative of alterations in the molecular weight and/or in the radius of gyration, i.e., the dimensions and shape of the macromolecules. In addition to other detection methods, LSI technique provides a convenient tool to study radiation-induced alterations in macromolecules as a function of time after the pulse. Pulse radiolysis systems employing this detection mode have been so far constructed to follow light scattered at a single angle (typically the right angle) to the incident light beam. Here we present an advanced pulse radiolysis & multi-angle light-scattering-intensity system (PR-MALLS) that has been built at IARC and is currently in the phase of optimization and testing. Idea of its design and operation is described and preliminary results for radiation-induced degradation of pullulan as well as polymerization and crosslinking of poly(ethylene glycol) diacrylate are presented. Implementation of the proposed system provides a novel research tool, which is expected to contribute to the expansion of knowledge on free-radical reactions in monomer- and polymer solutions, by delivering precise kinetic data on changes in molecular weight and size, and thus allowing to formulate or verify reaction mechanisms. The proposed method is universal and can be applied for studying both natural and synthetic polymers. The developed system can be also valuable in studies of the border of biology and medicine, especially on radical reactions of biopolymers and their conformational transitions. Furthermore, capability to follow fast changes in mass and dimensions of nanobjects may be of significant importance for nanoscience and nanotechnology.
•Pulse radiolysis with multi-angle light scattering detection.•Radiation-induced degradation of pullulan.•Radiation-induced polymerization and cross-linking of poly(ethylene oxide) diacrylate.
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