Synthesis and biological evaluation of a new class of glycoconjugated disulfides that exhibit potential anticancer properties.

A synthetic strategy, based on the in situ generation of sulfenic acids and their thermolysis in the presence of thiols, was developed for obtaining a collection of polyvalent disulfides in which a benzene scaffold accommodates two or three flexible arms connecting saccharide moieties. Targeting carbohydrate metabolism or carbohydrate-binding proteins may constitute important approaches in the discovery process of new therapeutic anticancer agents. Therefore, a preliminary screening to ascertain the cytostatic/cytotoxic potential of this new class of enantiopure glycoconjugated disulfides has been conducted. Among them, products with two disulfide arms, harbouring galactose rings, induced high levels of apoptosis on U937 histiocytic lymphoma cells, but lower levels of cell death on peripheral blood mononuclear cells from healthy donors. Further experiments indicated that apoptosis induced by these glycoconjugated bis(disulfides) in U937 cells corresponds to the Bcl-2-sensitive, intrinsic form of apoptotic cell death. The bioinvestigation was extended to a panel of human cancer cell lines with different levels of malignancy and resistance to chemotherapeutic agents. Compounds under study proved to induce detectable levels of cell death towards all the tested cancer cell lines.

COVID-19 Neuromuscular Involvement in Post-Acute Rehabilitation.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with muscle and nerve injuries as a consequence of prolonged critical illness or the infection itself. In this study, we evaluated neuromuscular involvement in patients who underwent post-acute intensive rehabilitation after COVID-19. METHODS: Clinical and neurophysiological evaluations, including nerve conduction studies and electromyography, were performed on 21 consecutive patients admitted for rehabilitation after COVID-19. RESULTS: Clinical signs suggesting muscle or nerve involvement (weakness, reduced deep tendon reflexes, impaired sensitivity, abnormal gait) were found in 19 patients. Neurophysiological examinations confirmed neuromuscular involvement in 17 patients: a likely association of critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) was found in 5 patients; CIM alone was found in 4 patients; axonal sensory-motor polyneuropathy was found in 4 patients (CIP in 2 patients, metabolic polyneuropathy in 2 patients); Guillain-Barré syndrome was found in 2 patients (classical demyelinating sensory-motor polyneuropathy and acute motor axonal neuropathy, respectively); peroneal nerve injury was found in 1 patient; and pre-existing L4 radiculopathy was found in 1 patient. CONCLUSIONS: Neuromuscular involvement is a very common finding among patients admitted for rehabilitation after COVID-19, and proper investigation should be conducted when muscle or nerve injury is suspected for adequate rehabilitative strategy planning.

The protonation of polyacrylate in seawater. Analysis of concentration effects.

The protonation of polyacrylate (PAA, MW 2 kDa) was studied potentiometrically at 25 degrees C, in mixed electrolyte aqueous solution simulating the composition of seawater, in the salinity range 30 < or = S < or = 40. The salt composition of different solutions was varied in order to study its effect on apparent protonation constants. Results were analysed using two fairly different approaches: by simple regression analysis on a combination of concentration parameters and salinity, and by canonical correlation analysis. Unexpectedly we found that variations on protonation constants, due to the different relative component concentrations, are fairly low, revealing a sort of buffering capacity of seawater respect to protonation properties of polyacrylate (and likely for other HMW and LMW polycarboxylates). The intrinsic protonation constant of polyacrylate 2 kDa at 25 degrees C and 35 salinity is log K(H*) = log K(int) = 4.399 +/- 0.004. The use of different pH scales and standard seawater compositions is also discussed.

Determination of humic substances in natural waters by cathodic stripping voltammetry of their complexes with iron.

A new voltammetric method is presented for the measurement of humic substances (HS) in natural waters. The method is based on catalytic cathodic stripping voltammetry (CSV) and makes use of adsorptive properties of iron-HS complexes on the mercury drop electrode at natural pH. A fulvic acid standard (IHSS) was used to confirm the voltammetric response (peak potential and sensitivity) for the HS for natural water samples. Optimized conditions included the linear-sweep mode, deposition at -0.1 V, pH buffered at 8 and a scan rate of 50 mV s(-1). At a deposition time of 240 s in the presence of 10 nM iron and 30 mM bromate, the detection limit was 5 microg L(-1) HS in seawater, which could be lowered further by an increase in the bromate concentration, or in the adsorption time. The method was used to determine HS in the Irish Sea which were found to occur at levels between 60 and 600 microg L(-1). The new method is sufficiently sensitive to detect the low HS content in oceanic samples and has implications to the study of iron speciation.