Influence of Solvents on the Oxidation Kinetics of Aldehydic Group Compounds by Diethylammonium Chloro-chromate

The redox studies of some compounds containing aldehydic functional groups by diethyl ammonium chloro-chromate (DEACC) in dimethyl sulfoxide leading a product forming to acid of correspondimg order. Reactions are found to be in unit order with oxidant while a fractional order (less than unity) was found w.r.t. reductants. The redox reactions are influenced with acid, the acid dependence is governed by this equation: kobs = a + b[H+].. When isomeric form of aldehyde, that is Me-CDO is oxidised with the same oxidant it was observed a considerable K.I.E. (Deuterium effect; kH/kD = 05.69 at 298 K). The reaction of Acetaldehyde was done in various non aqueous medium, soluble or miscible in DMSO. The effect of solvent is studied fitting our data in the solvent model of Taft's and Swain's applied for this purpose.. Rate constants are correlating very well with already reported Taft’s values of *; further the reaction constants are negative in nature. Suitable mechanism involving are proposed with transfer of hydride ion..

Intra-articular hyaluronic acid: dependence of the effect on molecular weight

The article discusses the patient management with knee osteoarthritis according to the ESCEO 2019 algorithm. The focus is on the second stage in the persistence of osteoarthritis signs. The article pays attention to the means based on hyaluronic acid for intra-articular injection. It also provides the study analysis that proved the anti-inflammatory mechanism of action of hyaluronic acid-based drugs during intraarticular administration, as well as the study results in which histology data indicated that hyaluronic acid prevents cartilage degradation and can promote its regeneration. These researches show that repeated injections of hyaluronic acid are not only effective, but also safe. In the literature, there is evidence that during treatment, the time to endoprosthesis increases, as well as the need for taking NSAIDs and opioids decreases. The article discusses the molecular weight of hyaluronic acid, providing research data confirming the greatest efficacy of hyaluronic acid with medium and high molecular weight. KEYWORDS: osteoarthritis, knee joints, hyaluronic acid, intraarticular injection. FOR CITATION: Filatova Yu.S., Gawert V.R. Intra-articular hyaluronic acid: dependence of the effect on molecular weight. Russian Medical Inquiry. 2021;5(3):156–161. DOI: 10.32364/2587-6821-2021-5-3-156-161.

Novel Silyl Ether-Based Acid-Cleavable Antibody-MMAE Conjugates with Appropriate Stability and Efficacy

Antibody-drug conjugate (ADC) is a novel efficient drug delivery system that has been successfully used in clinical practice, and it has become a research hotspot in the anti-tumor drug field. Acid-cleavable linkers were first used in clinical ADCs, but their structural variety (e.g., hydrazone and carbonate) is still limited, and their stability is usually insufficient. Designing novel acid-cleavable linkers for the conjugation of the popular cytotoxin monomethyl auristatin E (MMAE) has always been a significant topic. In this paper, we generate a novel, silyl ether-based acid-cleavable antibody-MMAE conjugate, which skillfully achieves efficient combination of amino-conjugated MMAE with the acid-triggered silyl ether group by introducing p-hydroxybenzyl alcohol (PHB). The stability, acid-dependence cleavage, effective mechanism, efficacy and safety of the resulting ADC were systematically studied; the results show that it exhibits a significant improvement in stability, while maintaining appropriate efficacy and controlled therapeutic toxicity. This strategy is expected to expand a new type of acid-cleavable linkers for the development of ADCs with highly potent payloads.

Thermodynamic parameters for the complexation of technetium(IV) with EDTA

Technetium-99 is a high yield (~6% fission yield) fission product and long-lived (2.13×105 year half-life) component of nuclear waste that will be disposed of in a geological repository. Some 99Tc has been released into the environment due to nuclear fuel and weapon production activities at sites such as Hanford, WA. Strongly complexing ligands such as ethylenediamine-N,N,N′,N′-tetraacetic acid (EDTA) are known to increase Tc(IV) solubility and mobility in environmental systems and an accurate quantification of the complexation of Tc(IV) with EDTA is important for predicting its behavior in a geological repository. A liquid–liquid extraction system utilizing 0.2 M TOPO in dodecane was used to measure the stability constants of Tc(IV)-EDTA in 0.50 m NaNO3 at variable temperatures (14.0±0.1, 25.0±0.1, and 32.0±0.1°C). The acid dependence of the apparent stability constants in the pCH range of 2.00–2.70 indicated the formation of TcO(EDTA)2− (logβ101=17.9±0.3, 25.0±0.1°C) and a protonated complex TcO(H)(EDTA)− (logβ111=20.5±0.1, 25.0±0.1°C). The associated thermodynamic parameters ΔrG101=−101.7±0.4 kJ·mol−1, ΔrH101=−47±9 kJ·mol−1, ΔrS101=179±36 J·mol−1·K−1, ΔrG111=−117.2±0.3 kJ·mol−1, ΔrH111=−23±5 kJ·mol−1, and ΔrS111=315±63 J·mol−1·K−1 (0.50 m NaNO3, 25.0±0.1°C) were determined by van’t Hoff analysis. The formation of each Tc(IV)–EDTA complex is exothermic and present favorable entropy terms.

Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse

This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

Inhibitory Humoral Responses to the Plasmodium falciparum Vaccine Candidate EBA-175 Are Independent of the Erythrocyte Invasion Pathway

ABSTRACTPlasmodium falciparumutilizes multiple ligand-receptor interactions for invasion. The invasion ligand EBA-175 is being developed as a major blood-stage vaccine candidate. EBA-175 mediates parasite invasion of host erythrocytes in a sialic acid-dependent manner through its binding to the erythrocyte receptor glycophorin A. In this study, we addressed the ability of naturally acquired human antibodies against the EBA-175 RII erythrocyte-binding domain to inhibit parasite invasion ofex vivoisolates, in relationship to the sialic acid dependence of these parasites. We have determined the presence of antibodies to the EBA-175 RII domain by enzyme-linked immunosorbent assay (ELISA) in individuals from areas of Senegal where malaria is endemic with high and low transmission. Using affinity-purified human antibodies to the EBA-175 RII domain from pooled patient plasma, we have measured the invasion pathway as well as the invasion inhibition of clinical isolates from Senegalese patients inex vivoassays. Our results suggest that naturally acquired anti-EBA-175 RII antibodies significantly inhibit invasion of Senegalese parasites and that these responses can be significantly enhanced through limiting other ligand-receptor interactions. However, the extent of this functional inhibition by EBA-175 antibodies is not associated with the sialic acid dependence of the parasite strain, suggesting that erythrocyte invasion pathway usage by parasite strains is not driven by antibodies targeting the EBA-175/glycophorin A interaction. This work has implications for vaccine design based on the RII domain of EBA-175 in the context of alternative invasion pathways.

Aerosol dynamics simulations on the connection of sulphuric acid and new particle formation

We have performed a series of simulations with an aerosol dynamics box model to study the connection between new particle formation and sulphuric acid concentration. For nucleation either activation mechanism with a linear dependence on the sulphuric acid concentration, kinetic mechanism with a squared dependence on the sulphuric acid concentration or ternary H2O-H2SO4-NH3 nucleation was assumed. The aim was to study the factors that affect the sulphuric acid dependence during the early stages of particle growth, and specifically to find conditions which would yield the linear dependence between the particle number concentration at 3–6 nm and sulphuric acid, as observed in field experiments. The simulations showed that the correlation with sulphuric acid may change during the growth from nucleation size to 3–6 nm size range, the main reason being the size dependent growth rate between 1 and 3 nm. In addition, the assumed size for the nucleated clusters had a crucial impact on the sulphuric acid dependence at 3 nm. A linear dependence between the particle number concentration at 3 nm and sulphuric acid was achieved, when activation nucleation mechanism was used with a low saturation vapour pressure for the condensable organic vapour, or with nucleation taking place at ~2 nm instead of ~1 nm. Simulations with activation, kinetic and ternary nucleation showed that ternary nucleation reproduces too steep dependence on sulphuric acid as compared to the linear or square dependence observed in field measurements.