Titanium (Ti) and its alloys have been extensively used as implant materials in orthopedic applications. Nevertheless, implants may fail due to a lack of osseointegration and/or infection. The aim of this in vitro study was to endow an implant surface with favorable biological properties by the dual modification of surface chemistry and nanostructured topography. The application of a nanostructured titanium dioxide (TiO 2 ) coating on Ti-based implants has been proposed as a potential way to enhance tissue-implant interactions while inhibiting bacterial colonization simultaneously due to its chemical stability, biocompatibility, and antimicrobial properties. In this paper, temperature-controlled atomic layer deposition (ALD) was introduced for the first time to provide unique nanostructured TiO 2 coatings on Ti substrates. The effect of nano-TiO 2 coatings with different morphology and structure on human osteoblast and fibroblast functions and bacterial activities was investigated. In vitro results indicated that the TiO 2 coating stimulated osteoblast adhesion and proliferation while suppressing fibroblast adhesion and proliferation compared to uncoated materials. In addition, the introduction of nano-TiO 2 coatings was shown to inhibit gram-positive bacteria ( Staphylococcus aureus ), gram-negative bacteria ( Escherichia coli ), and antibiotic-resistant bacteria (methicillin-resistant Staphylococcus aureus ), all without resorting to the use of antibiotics. Our results suggest that the increase in nanoscale roughness and greater surface hydrophilicity (surface energy) together could contribute to increased protein adsorption selectively, which may affect the cellular and bacterial activities. It was found that ALD-grown TiO 2 -coated samples with a moderate surface energy at 38.79 mJ/m 2 showed relatively promising antibacterial properties and desirable cellular functions. The ALD technique provides a novel and effective strategy to produce TiO 2 coatings with delicate control of surface nanotopography and surface energy to enhance the interfacial biocompatibility and mitigate bacterial infection, and could potentially be used for improving numerous orthopedic implants.
The permeability-glycoprotein (P-gp) efflux transporter is densely expressed at the blood-brain barrier (BBB) and its resultant ‘spare capacity’ requires substantial blockade to increase the uptake of avid substrates. This has blunted the ability of investigators to measure clinically meaningful alterations in P-gp function. This study, conducted in humans, examined two P-gp inhibitors (tariquidar, a known inhibitor, and disulfiram, a putative inhibitor) and two routes of administration (intravenous and oral) to maximally increase brain uptake of the avid and selective P-gp substrate 11C-desmethyl-loperamide (dLop), while avoiding side effects associated with high doses of tariquidar. Methods Forty-two 11C-dLop positron emission tomography (PET) scans were obtained from 37 healthy volunteers. PET was performed with 11C-dLop under five conditions: 1) injected under baseline conditions without P-gp inhibition; 2) injected one hour after IV tariquidar infusion; 3) injected during IV tariquidar infusion; 4) injected after oral tariquidar; and 5) injected after disulfiram. 11C-dLop uptake was quantified with kinetic modeling using metabolite-corrected arterial input function or by measuring the area under the time-activity curve in brain from 10 to 30 minutes. Results Neither oral tariquidar nor oral disulfiram increased brain uptake of 11C-dLop. Injecting 11C-dLop during tariquidar infusion, when plasma tariquidar concentrations reach their peak, resulted in brain uptake of radioligand approximately five-fold greater than baseline. Brain uptake was similar with 2 and 4 mg/kg IV tariquidar; however, the lower dose was better tolerated. Injecting 11C-dLop after tariquidar infusion also increased brain uptake, though higher doses (up to 6 mg/kg) were required. Brain uptake of 11C-dLop increased fairly linearly with increasing plasma tariquidar concentrations, but we are uncertain whether maximal uptake was achieved. Conclusion We sought to increase the dynamic range of P-gp function measured after blockade. Performing 11C-dLop PET during peak plasma concentrations of tariquidar, achieved with concurrent administration of IV tariquidar, resulted in greater P-gp inhibition at the human BBB than delayed administration, and allowed use of a lower, more tolerable dose of tariquidar. Based on prior monkey studies, we suspect that plasma concentrations of tariquidar did not fully block P-gp; however, higher doses of tariquidar would likely be associated with unacceptable side effects.
Purpose We evaluated factors influencing re-operation in tension band and plating of isolated olecranon fractures. Methods Four hundred eighty-nine patients with isolated olecranon fractures who underwent tension band (TB) or open reduction internal fixation (ORIF) from 2003 to 2013 were identified at an urban level 1 trauma centre. Medical records were reviewed for patient information and complications, including infection, nonunion, malunion, loss of function or hardware complication requiring an unplanned surgical intervention. Electronic radiographs of these patients were reviewed to identify Orthopaedic Trauma Association (OTA) fracture classification and patients who underwent TB or ORIF. Results One hundred seventy-seven patients met inclusion criteria of isolated olecranon fractures. TB was used for fixation in 43 patients and ORIF in 134. No statistical significance was found when comparing complication rates in open versus closed olecranon fractures. In a multivariate analysis, the key factor in outcome was method of fixation. Overall, there were higher rates of infection and hardware removal in the TB compared with the ORIF group. Conclusions Our results demonstrate that the dominant factor driving re-operation in isolated olecranon fractures is type of fixation. When controlling for all variables, there is an increased chance of re-operation in patients with TB fixation.
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