Introduction: Neutrophilic granulocytes represent the first line of defense against microorganisms. Granulocytes phagocytose microorganisms and specifically synthesize oxygen radicals against them, which eventually kills the invaders. Methods: Neutrophilic granulocytes were isolated from peripheral blood of healthy volunteer donors. Putative interference of new-generation antibiotics with neutrophil function was tested using a collection of granulocyte-stimulating agents and Amplex™ Red-based plate assay and flow cytometry-based respiratory burst assays. In addition, phagocytosis of E. coli, IL-8 production, bactericidal activity, and CD62L expression of granulocytes were evaluated. Results: Of note, we found that the two glycopeptide antibiotics dalbavancin and teicoplanin inhibited ROS production upon granulocyte activation via different signaling pathways in a dose-dependent manner. Dalbavancin also blocked the PMA-induced shedding of CD62L. In contrast, the oxazolidinone antibiotics tedizolid and linezolid had no effect on neutrophil function, while the combination of ceftazidime/avibactam dose dependently inhibited the fMLP/Cytochalasin B-induced granulocyte burst in a dose-dependent manner. Additionally, we showed that dalbavancin and teicoplanin as well as sulfametrole/trimethoprim and ceftazidime/avibactam inhibited baseline and PMA-induced IL-8 production by neutrophilic granulocytes. Moreover, dalbavancin impaired the bactericidal activity of neutrophilic granulocytes. Conclusion: We here identified hitherto unknown inhibitory effects of several classes of antibiotics on the effector functions of neutrophilic granulocytes.

01 Jan 2023·Annals of Hematology

CD19 CAR T-cell infusion during severe COVID-19 acute respiratory distress syndrome in large B-cell lymphoma

Letter

Author: Lobmeyr, Elisabeth ; Traby, Ludwig ; Staudinger, Thomas ; Knaus, Hanna ; Buchtele, Nina ; Schellongowski, Peter ; Vossen, Matthias ; Staber, Philipp B ; Wohlfarth, Philipp ; Rabitsch, Werner ; Worel, Nina

In general, the COVID-19-related mortality rate in patients with hematol. malignancies remains high and is even more pronounced after stem-cell and CAR T-cell therapies.Optimal timing of transplantation and cell therapy needs to be emphasized even more during this ongoing pandemic.

01 Jun 2022·Journal of Molecular Structure

Synthesis, characterization, molecular modeling against EGFR target and ADME/T analysis of novel purine derivatives of sulfonamides

Author: Bhat, Mashooq A. ; Tuzun, Burak ; Ali Khan, Azmat ; Naglah, Ahmed M. ; Alsaif, Nawaf A.

A novel series of purine derivatives containing sulfonamide moiety I [R = NH, CH₂CH₂NH, NHSO₂, etc.; R¹ = SO₂OH, SO₂NH₂, SO₂NC(NH)₂, etc.] were synthesized in good yield by the single-step reaction method.The chem. activities of the mols. at the B3LYP, HF, M062X level 3-21 g, 6-31 g, and SDD basis were set with the Gaussian package program.The biol. activities of the mols. against the epidermal growth factor receptor (EGFR) proteins (PDB ID: 1M17 and 2ITN) were compared with the Maestro Mol. modeling platform by Schrodinger.Compound I [R = NH; R¹ = SO₂NH-2-4,5-dimethyloxazole] had the highest value in all basis sets, according to the numerical value of the HOMO parameter.The interactions of compound I [R = NH; R¹ = SO₂NH-2-4,5-dimethyloxazole] with Epidermal Growth Factor Receptor ID: 1M17 and ID: 2ITN proteins, presented the highest activity.Finally, ADME/T anal. was performed to examine the drug properties of the mols.

100 Deals associated with Sulfametrole

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