Gelatin, a natural proteinous polymer, was used to co-electrospin with poly(butylene succinate) (PBS) in order to improve the mechanical properties of PBS membrane and facilitate its applications in biomedical field. The PBS/gelatin blend membranes have narrower distribution of fiber diameter and smoother surface than neat PBS membrane. The contact angles, water absorption rates and water uptakes of the PBS/gelatin blend membranes were measured, showing increased hydrophilicity. The interaction between PBS and gelatin was investigated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). The mechanical properties of PBS/gelatin blend membranes in both dry and wet states were evaluated by uniaxial tensile tests. In the dry state, the PBS/gelatin blend membrane containing 10% gelatin has a 3-times increase in tensile strength without any adverse effect on ductility because of the existence of interaction between the two blend components, little change in crystallinity of PBS, and possible interaction between any adjacent fibers; the tensile strength and elongation at break are even better in the wet state attributed to some gelatin on fiber surfaces, which act as a binder in the presence of water. The potential applications of PBS/gelatin blend membranes were demonstrated by successful immobilization of thrombin, a clinically-used hemostatic drug. The thrombin-loaded membrane could be used for rapid hemostasis.
Multi-resistant Staphylococcus aureus ( S. aureus ) infection is a significant global health concern owing to its high mortality and morbidity rates. Coagulase (Coa), a key enzyme that activates prothrombin to initiate host coagulation, has emerged as a promising target for anti-infective therapeutic approaches. This study identified sinigrin as a potent Coa inhibitor that significantly inhibited S. aureus -induced coagulation at concentration as low as 32 mg/L. Additionally, at a higher concentration of 128 mg/L, sinigrin disrupted the self-protection mechanism of S. aureus . Thermal shift and fluorescence-quenching assays confirmed the direct binding of sinigrin to the Coa protein. Molecular docking analysis predicted specific binding sites for sinigrin in the Coa molecule, and point mutation experiments highlighted the importance of Arg-187 and Asp-222 as critical binding sites for both Coa and sinigrin. In vivo studies demonstrated that the combination of sinigrin with oxacillin exhibited greater antibacterial efficacy than oxacillin alone in the treatment of S. aureus -induced pneumonia in mice. Furthermore, sinigrin was shown to reduce bacterial counts and inflammatory cytokine levels in the lung tissues of S. aureus -infected mice. In summary, sinigrin was shown to directly target Coa, resulting in the attenuation of S. aureus virulence, which suggests the potential of sinigrin as an adjuvant for future antimicrobial therapies.
Ramos-Martín V.,Johnson A.,Livermore J.,McEntee L.,Goodwin J.,Whalley S.,Docobo-Pérez F.,Felton T. W.,Zhao W.,Jacqz-Aigrain E.,Sharland M.,Turner M. A.,Hope W. W.
ObjectivesCoNS are the most common cause of neonatal late-onset sepsis. Information on the vancomycin pharmacokinetics/pharmacodynamics against CoNS is limited. The aim of this study was to characterize vancomycin pharmacokinetic/pharmacodynamic relationships for CoNS and investigate neonatal optimal dosage regimens.MethodsA hollow fibre and a novel rabbit model of neonatal central line-associated bloodstream CoNS infections were developed. The results were then bridged to neonates by use of population pharmacokinetic techniques and Monte Carlo simulations.ResultsThere was a dose-dependent reduction in the total bacterial population and C-reactive protein levels. The AUC/MIC and Cmax/MIC ratios were strongly linked with total and mutant resistant cell kill. Maximal amplification of resistance was observed in vitro at an fAUC/MIC of 200 mg · h/L. Simulations predicted that neonates <29 weeks post-menstrual age are underdosed with standard regimens with respect to older age groups.ConclusionsThe AUC/MIC and Cmax/MIC ratios are the pharmacodynamic indices that best explain total and resistant cell kill in CoNS infection. This suggests that less-fractionated regimens are appropriate for clinical use and continuous infusions may be associated with increased risk of emergence of antimicrobial resistance. This study has provided the pharmacodynamic evidence to inform an optimized neonatal dosage regimen to take into a randomized controlled trial.
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