Interaction mechanism of oseltamivir phosphate with bovine serum albumin: multispectroscopic and molecular docking study.

Oseltamivir phosphate (OP) is an antiviral drug with potential risks to human health due to overuse, leading to serious consequences such as gastrointestinal disturbances, abnormal neuropsychiatric symptoms, and sudden death. Therefore, gaining an in-depth understanding of its interaction with proteins is crucial. We investigated the interaction between OP and bovine serum albumin (BSA) utilizing multispectral methods (i.e., fluorescence, ultraviolet absorption, circular dichroism) combined with molecular docking techniques. Fluorescence spectroscopy indicated that OP quenched BSA fluorescence by forming the OP-BSA complex. The Stern-Volmer constants (KSV) between OP and BSA were determined to be 3.06 × 103 L/mol, 2.36 × 103 L/mol, and 1.86 × 103 L/mol at 293 K, 298 K, and 303 K, respectively. OP occupies exclusively one binding site on BSA, and the fluorescent probe displacement measurements revealed that this is BSA site I. Thermodynamic data (∆H, ∆S, and ∆G) obtained by fitting the van't Hoff equation were - 77.49 kJ/mol, -176.54 J/(mol∙K), and - 24.88 kJ/mol, respectively, suggesting that hydrogen bonding and van der Waals forces mainly participate in OP-BSA complex stabilization. Moreover, the reaction occurs spontaneously at room temperature. Synchronous fluorescence spectra indicated that OP interacts with tryptophan residue of BSA. The results of ultraviolet (UV) and 3D fluorescence spectroscopy indicated that the OP-BSA complex formation altered the microenvironment around amino acid residues. Circular dichroism spectra revealed that the addition of OP decreased the α-helix content of BSA by 7.13%. Docking analysis confirmed that OP binds to BSA site I through hydrogen bonding with amino acids VAL342, SER453, and ASP450. Finally, ADMET studies were conducted to explore the pharmacokinetics of OP as an antiviral drug.

Effect of Surgeon Volume on Mechanical Complications after Resection Arthroplasty with Articulating Spacer.

Two-stage revision with an antibiotic-loaded cement articulating spacer is a standard treatment for chronic prosthetic knee infection (PKI); however, mechanical complications can occur during the spacer period. There is limited evidence on the association between surgeon volume and mechanical complications after resection arthroplasty (RA) using an articulating spacer. This study aimed to compare the rates of mechanical complications and reoperation after RA with articulating spacers by surgeons with high volumes (HV) and low volumes (LV) of RA performed and analyzed the risk factors for mechanical failure. The retrospective study investigated 203 patients treated with PKIs who underwent RA with articulating spacers and were divided according to the number of RAs performed by the surgeons: HV (≥14 RAs/year) or LV (<14 RAs/year). Rates of mechanical complications and reoperations were compared. Risk factors for mechanical complications were analyzed. Of the 203 patients, 105 and 98 were treated by two HV and six LV surgeons, respectively. The mechanical complication rate was lower in HV surgeons (3.8%) than in LV surgeons (36.7%) (p < 0.001). The reoperation rate for mechanical complications was lower in HV surgeons (0.9%) than in LV surgeons (24.5%) (p < 0.001). Additionally, 47.2% of patients required hinge knees after mechanical spacer failure. Medial proximal tibial angle < 87°, recurvatum angle > 5°, and the use of a tibial spacer without a cement stem extension were risk factors for mechanical complications. Based on these findings, we made the following three conclusions: (1) HV surgeons had a lower rate of mechanical complications and reoperation than LV surgeons; (2) mechanical complications increased the level of constraint in final revision knee arthroplasty; and (3) all surgeons should avoid tibial spacer varus malalignment and recurvatum deformity and always use a cement stem extension with a tibial spacer.

Medullary-Sparing Antibiotic Cement Articulating Spacer Reduces the Rate of Mechanical Complications in Advanced Septic Hip Arthritis: A Retrospective Cohort Study.

Antibiotic cement articulating spacers eradicate infection during a two-stage revision for advanced septic hip arthritis (ASHA); however, mechanical complications have been reported. We hypothesized that the rate of mechanical complications would be lower in medullary-sparing (MS) than in non-medullary-sparing (n-MS) articulating spacers. A retrospective study of ASHA using n-MS or MS spacers was conducted between 1999 and 2019. The rate of mechanical complications and reoperation and risk factors for mechanical complications were analyzed. The cohort included 71 n-MS and 36 MS spacers. All patients were followed up for 2 years. The rate of spacer dislocation was lower in MS (0%) than in n-MS spacers (14.1%; p = 0.014). The reoperation rate for mechanical complications was lower in MS (0%) than in n-MS spacers (12.7%; p = 0.019). The rate of a diaphyseal stem during reimplantation was lower in MS (0%) than in n-MS spacers (19.4%; p = 0.002). The identified risk factors for n-MS spacer dislocation were postoperative under-restored femoral head diameter ≥3 mm, femoral offset ≥3 mm, and surgical volume (≤6 resection arthroplasties per year). Both spacers controlled infection. However, MS spacers had a lower spacer dislocation and reoperation rate and avoided the diaphyseal stem during reimplantation. We recommend using MS spacers to restore native femoral head diameter and femoral offset when ASHA is treated by surgeons with lower surgical volumes.