vincristine sulfate

From crude extracts to purified fractions: Tracking sulfate preservation, antioxidant loss, and nanostructures by X-ray scattering of Hokkaido brown algae fucoidans.

Kumagai Yuya Y, Mune Martin Alain Mune MAM, Akita Shingo S, Sajeevan Shilja S et al.

Fucoidan shows promise for food and therapeutic applications; however, inadequate purification leads to inconsistent composition and over-claimed bioactivity. This study rigorously fractionated eight brown algae species from Hokkaido, Japan, using anion-exchange chromatography to generate three primary fractions (FN1, FN2, and FN3). While fractionation enriched sulfate content, it resulted in a >90% reduction in measured antioxidant activity. Multivariate analysis identified the interaction between sulfate and saccharide contents as the principal determinant of this residual activity. Makombu-derived FN3 was then enzymatically digested, treated with activated charcoal, and ultrafiltered to yield FN3 UF, which contained 48.9% sulfate and negligible glucuronic acid, as determined by high-performance anion-exchange chromatography with pulsed amperometric detection. Overall results suggest that the high activity typically reported is largely extrinsic, driven by co-extracted impurities, whereas the true intrinsic activity is trace (~1 μg/mg). Synchrotron small-angle X-ray scattering revealed that this refinement triggers an expansion of the Bragg distance from 12.6 nm (alginate-rich FN1) to 21.7 nm (sulfated FN3), providing the first direct physical evidence that sulfate-driven electrostatic repulsion governs fucoidan's nanostructural organization in solution. These findings establish a previously undocumented physical baseline, proving that rigorous chemical refinement is a mandatory prerequisite for reliable structure-function evaluations of fucoidan.

Exploratory Study on Colistin Sulfate Pharmacokinetics and Safety in Critically Ill Elderly Patients.

Xu Aochao A, Xiong Xiaomiao X, Zhang Na N, Qu Geping G et al.

The rise of multidrug-resistant Gram-negative bacteria has made polymyxins vital last-line therapies. However, its pharmacokinetics in elderly patients remain poorly characterized, which hinders dosing optimization to balance efficacy and toxicity risks in this vulnerable population. A prospective, single-center observational study was conducted in elderly (≥65) intensive care unit (ICU) patients who received colistin sulfate therapy. Blood samples were collected prior and post-dose time points. Plasma concentrations of colistin sulfate were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic (PK) parameters were calculated via non-compartmental analysis. Treatment-emergent adverse events and laboratory parameters were systematically recorded for safety evaluation. Thirteen patients with MDR gram-negative infections were included and all received colistin sulfate-based combination therapy; 84.6% achieved anti-infective efficacy. Compared with previously reported data in healthy individuals at 50 MIU q12h, elderly patients demonstrated significantly higher AUC0-12h (9.62 ± 3.58 vs. 5.33 ± 0.71 mg·h/L, p < 0.05), prolonged T1/2 (25.84 ± 25.19 vs. 4.53 ± 1.22 h, p < 0.05), and larger Vd (87.57 ± 74.40 vs. 17.32 ± 2.52 L, p < 0.05). Target attainment(AUC0-24h/MIC ≥ 50) probability was ≥ 80% only at MIC ≤ 0.25 mg/L, dropping to ≤ 20% at MIC ≥ 0.5 mg/L. Serum creatinine elevations occurred during colistin therapy and returned to baseline after discontinuation 7-14 days, while liver function parameters remained stable throughout. Colistin sulfate therapy in critically ill elderly ICU patients demonstrates elevated systemic exposure with reversible nephrotoxicity, necessitating pharmacokinetic-guided dosing strategies individualized to renal function, therapeutic drug monitoring, and clinical severity.

csRNA and heparan sulfate : cell surface ribonucleoproteins regulate HS-mediated signaling.

Li Jinlin J, Ling Jiaxin J

Structural characterization, in vitro anticoagulant, and antiplatelet activities of a Distolasterias nipon dermatan sulfate-like polymer with a distinctive sulfation pattern.

Filshtein Alina P AP, Belova Vlada S VS, Taran Ilya V IV, Kokoulin Maxim S MS

A novel dermatan sulfate-like polysaccharide (DNP) was isolated from the body walls of the starfish Distolasterias nipon. Its structure was elucidated using chemical methods and 2D NMR spectroscopy, revealing a backbone of →4)-α-L-IdopA-(1→3)-β-D-GalpNAc-(1→, with the α-L-iduronic acid residues predominantly 2,3-di-O-sulfated, alongside 2-O- and 3-O-monosulfated variants, and the β-D-GalpNAc residues 4-O-sulfated. Functional assays showed that DNP prolongs thrombin time (TT) comparable to heparin and more potently than enoxaparin (Clexane®), whereas its effect on activated partial thromboplastin time (APTT) is less pronounced. The anticoagulant activity of DNP is characterized by antithrombin-dependent thrombin inhibition and moderate suppression of factor Xa. Furthermore, the polysaccharide does not induce platelet aggregation nor interfere with physiological ADP-mediated pathways, but it inhibits ristocetin-induced aggregation. These findings identify D. nipon as a source of a dermatan sulfate structurally distinct from those found in other starfishes and invertebrates, and characterized by an antithrombin-dependent anti-IIa/anti-Xa profile and additional antiplatelet properties.