Identification of potential biogenic chalcones against antibiotic resistant efflux pump (AcrB) via computational study.

The cases of bacterial multidrug resistance are increasing every year and becoming a serious concern for human health. Multidrug efflux pumps are key players in the formation of antibiotic resistance, which transfer out a broad spectrum of drugs from the cell and convey resistance to the host. Efflux pumps have significantly reduced the efficacy of the previously available antibiotic armory, thereby increasing the frequency of therapeutic failures. In gram-negative bacteria, the AcrAB-TolC efflux pump is the principal transporter of the substrate and plays a major role in the formation of antibiotic resistance. In the current work, advanced computer-aided drug discovery approaches were utilized to find hit molecules from the library of biogenic chalcones against the bacterial AcrB efflux pump. The results of the performed computational studies via molecular docking, drug-likeness prediction, pharmacokinetic profiling, pharmacophore mapping, density functional theory, and molecular dynamics simulation study provided ZINC000004695648, ZINC000014762506, ZINC000014762510, ZINC000095099506, and ZINC000085510993 as stable hit molecules against the AcrB efflux pumps. Identified hits could successfully act against AcrB efflux pumps after optimization as lead molecules.Communicated by Ramaswamy H. Sarma.

Design, Material, and Seating Load Effects on In Vitro Fretting Corrosion Performance of Modular Head-Neck Tapers.

BACKGROUND: The short-term corrosion and micromechanical behavior of 32 unique head-neck taper design/material/assembly conditions was tested using an incremental cyclic fretting corrosion (ICFC) test method previously developed. METHODS: Seven materials, design, and simulated surgical parameters were evaluated, each being assigned 2 conditions for testing, using a 27-2 (7 factor, quarter factorial) design of experiments test matrix. The factors explored were (1) seating load, (2) head-neck offset, (3) material combination, (4) taper diameter, (5) taper roughness, (6) angular mismatch/engagement, and (7) taper length. Each sample underwent assembly, ICFC testing, pull off. RESULTS: Low seating load and high head offset correlated with increased fretting corrosion (P < .05). High head offset also contributed to a lower onset load for fretting current and higher micromotion (P < .05). Head subsidence measured over the ICFC test for samples seated at 100 N was significantly higher than samples seated at 4000 N. Micromotion for 12-mm head offsets was statistically higher than samples with a 1.5-mm head offset. A number of interactive effects were observed. For example, samples seated at 4000 N were less sensitive to head offset than samples seated at 100 N in terms of the resulting fretting current. CONCLUSION: Taper locking position, material combination, taper engagement length, taper roughness, and taper dimensions all had weak or no correlation with fretting current and taper micromotion. This test method and experimental design is a versatile means of assessing potential new taper designs in the future.

Material dependent fretting corrosion in spinal fusion devices: Evaluation of onset and long-term response.

Posterior spinal fusion implants include number of interconnecting components, which are subjected to micromotion under physiological loading conditions inducing a potential for fretting corrosion. There is very little known about the fretting corrosion in these devices in terms of the minimum angular displacement (threshold) necessary to induce fretting corrosion or the amount of fretting corrosion that can arise during the life of the implant. Therefore, the first goal was to evaluate the threshold fretting corrosion in three anatomical orientations and second the long-term fretting corrosion for the three different material types of spinal implants under physiological loading conditions. In threshold test, axial rotation exhibited highest changes in open circuit potential (VOCP in mV) and induced fretting currents (Ifrett in µA) for cobalt chrome (ΔVOCP : 24.71 ± 5.53; ΔIfrett : 4.03 ± 0.51) and stainless steel (ΔVOCP : 28.21 ± 6.97; ΔIfrett : 2.98 ± 0.42) constructs whereas it was flexion-extension for titanium constructs (ΔVOCP : 4.51 ± 2.48; ΔIfrett : 0.38 ± 0.12). Long-term test indicated that the titanium (VOCP :101 ± 0.06; Ifrett : 0.07 ± 0.02) and cobalt chrome (VOCP : 140.67 ± 0.04; Ifrett : 0.12 ± 0.05) constructs were more resistant to the fretting corrosion compared to stainless steel (VOCP : -135.33 ± 0.31; Ifrett : 2.63 ± 1.06). © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2858-2868, 2018.

Effect of mixed alloy combinations on fretting corrosion performance of spinal screw and rod implants.

Spinal implants are made from a variety of materials to meet the unique mechanical demands of each application. However, the medical device community has raised concern about mixing dissimilar metals in an implant because of fear of inducing corrosion. There is a lack of systematic studies on the effects of mixing metals on performance of spinal implants, especially in fretting corrosion conditions. Hence, the goal was to determine whether mixing stainless steel (SS316L), titanium alloy (Ti6Al4V) and cobalt chromium (CoCrMo) alloy components in a spinal implant leads to any increased risk of corrosion degradation. Spinal constructs consisting of single assembly screw-connector-rod components were tested using a novel short-term cyclic fretting corrosion test method. A total of 17 alloy component combinations (comprised of SS316L, Ti6Al4V-anodized and CoCrMo alloy for rod, screws and connectors) were tested under three anatomic orientations. Spinal constructs having all SS316L were most susceptible to fretting-initiated crevice corrosion attack and showed higher average fretting currents (∼25 - 30 µA), whereas constructs containing all Ti6Al4V components were less susceptible to fretting corrosion with average fretting currents in the range of 1 - 6 µA. Mixed groups showed evidence of fretting corrosion but they were not as severe as all SS316L group. SEM results showed evidence of severe corrosion attack in constructs having SS316L components. There also did not appear to be any galvanic effects of combining alloys together. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1169-1177, 2017.

Incorporation of Ca and P on anodized titanium surface: Effect of high current density.

This study systematically evaluated the surface and corrosion characteristics of commercially pure titanium (grade 2) modified by plasma electrolytic oxidation (PEO) with high current density. The anodization process was carried out galvanostatically (constant current density) using a solution containing calcium glycerophosphate (0.02mol/L) and calcium acetate (0.15mol/L). The current densities applied were 400, 700, 1000 and 1200mA/cm(2) for a period of 15s. Composition, crystalline structure, morphology, roughness, wettability and "in-vitro" bioactivity test in SBF of the anodized layer were evaluated by X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, profilometry and contact angle measurements. Corrosion properties were evaluated by open circuit potential, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization measurements. The results show that the TiO2 oxide layers present an increase of thickness, porosity, roughness, wettability, Ca/P ratio, and bioactivity, with the applied current density up to 1000mA/cm(2). Corrosion resistance also increases with applied current density. It is observed that for 1200mA/cm(2), there is a degradation of the oxide layer. In general, the results suggest that the anodized TiO2 layer with better properties is formed with an applied current of 1000mA/cm(2).

In vivo oxide-induced stress corrosion cracking of Ti-6Al-4V in a neck-stem modular taper: Emergent behavior in a new mechanism of in vivo corrosion.

In vivo modular taper corrosion in orthopedic total joint replacements has been documented to occur for head-neck tapers, modular-body tapers, and neck-stem tapers. While the fretting corrosion mechanism by which this corrosion occurs has been described in the literature, this report shows new and as yet unreported mechanisms at play. A retrieved Ti-6Al-4V/Ti-6Al-4V neck-stem taper interface, implanted for 6 years is subjected to failure analysis to document taper corrosion processes that lead to oxide driven crack formation on the medial side of the taper. Metallurgical sectioning techniques and scanning electron microscopy analysis are used to document the taper corrosion processes. The results show large penetrating pitting attack of both sides of the taper interface where corrosion selectively attacks the beta phase of the microstructure and eventually consumes the alpha phase. The pitting attack evolves into plunging pits that ultimately develop into cracks where the crack propagation process is one of corrosion resulting in oxide formation and subsequent reorganization. This process drives open the crack and advances the front by a combination of oxide-driven crack opening stresses and corrosion attack at the tip. The oxide that forms has a complex evolving structure including a network of transport channels that provide access of fluid to the crack tip. This emergent behavior does not appear to require continued fretting corrosion to propagate the pitting and cracking. This new mechanism is similar to stress corrosion cracking where the crack tip stresses arise from the oxide formation in the crack and not externally applied tensile stresses.