Effect of Plasma Argon Pretreatment on the Surface Properties of AZ31 Magnesium Alloy.

Climate change has evidenced the need to reduce carbon dioxide emissions into the atmosphere, and so for transport applications, lighter weight alloys have been studied, such as magnesium alloys. However, they are susceptible to corrosion; therefore, surface treatments have been extensively studied. In this work, the influence of argon plasma pretreatment on the surface properties of an AZ31 magnesium alloy focus on the enhancement of the reactivity of the surface, which was examined by surface analysis techniques, electrochemical techniques, and gravimetric measurements. The samples were polished and exposed to argon plasma for two minutes in order to activate the surface. Contact angle measurements revealed higher surface energy after applying the pretreatment, and atomic force microscopy showed a roughness increase, while X-Ray photoelectron spectroscopy showed a chemical change on the surface, where after pretreatment the oxygen species increased. Electrochemical measurements showed that surface pretreatment does not affect the corrosion mechanism of the alloy, while electrochemical impedance spectroscopy reveals an increase in the original thickness of the surface film. This increase is likely associated with the high reactivity that the plasma pretreatment confers to the surface of the AZ31 alloy, affecting the extent of oxide formation and, consequently, the increase in its protection capacity. The weight loss measurements support the effect of the plasma pretreatment on the oxide thickness since the corrosion rate of the pretreated AZ31 specimens was lower than that of those that did not receive the surface pretreatment.

Evaluation of limited-sampling strategies to calculate AUC(0-24) and the role of CYP3A5 in Chilean pediatric kidney recipients using extended-release tacrolimus.

Background: Kidney transplantation (KTx) requires immunosuppressive drugs such as Tacrolimus (TAC) which is mainly metabolized by CYP3A5. TAC is routinely monitored by trough levels (C0) although it has not shown to be a reliable marker. The area-under-curve (AUC) is a more realistic measure of drug exposure, but sampling is challenging in pediatric patients. Limited-sampling strategies (LSS) have been developed to estimate AUC. Herein, we aimed to determine AUC(0-24) and CYP3A5 genotype in Chilean pediatric kidney recipients using extended-release TAC, to evaluate different LSS-AUC(0-24) formulas and dose requirements. Patients and methods: We analyzed pediatric kidney recipients using different extended-release TAC brands to determine their trapezoidal AUC(0-24) and CYP3A5 genotypes (SNP rs776746). Daily TAC dose (TAC-D mg/kg) and AUC(0-24) normalized by dose were compared between CYP3A5 expressors (*1/*1 and *1/*3) and non-expressors (*3/*3). We evaluated the single and combined time-points to identify the best LSS-AUC(0-24) model. We compared the performance of this model with two pediatric LSS-AUC(0-24) equations for clinical validation. Results: Fifty-one pharmacokinetic profiles were obtained from kidney recipients (age 13.1 ± 2.9 years). When normalizing AUC(0-24) by TAC-D significant differences were found between CYP3A5 expressors and non-expressors (1701.9 vs. 2718.1 ng*h/mL/mg/kg, p < 0.05). C0 had a poor fit with AUC(0-24) (r 2 = 0.5011). The model which included C0, C1 and C4, showed the best performance to predict LSS-AUC(0-24) (r 2 = 0.8765) and yielded the lowest precision error (7.1% ± 6.4%) with the lowest fraction (9.8%) of deviated AUC(0-24), in comparison to other LSS equations. Conclusion: Estimation of LSS-AUC(0-24) with 3 time-points is an advisable and clinically useful option for pediatric kidney recipients using extended-release TAC to provide better guidance of decisions if toxicity or drug inefficacy is suspected. The different CYP3A5 genotypes associated with variable dose requirements reinforce considering genotyping before KTx. Further multi-centric studies with admixed cohorts are needed to determine the short- and long-term clinical benefits.

Ostwald Ripening and Antibacterial Activity of Silver Nanoparticles Capped by Anti-Inflammatory Ligands.

Silver nanoparticles (AgNPs) have been extensively studied during recent decades as antimicrobial agents. However, their stability and antibacterial activity over time have yet to be sufficiently studied. In this work, AgNPs were coated with different stabilizers (naproxen and diclofenac and 5-chlorosalicylic acid) in different concentrations. The suspensions of nanostructures were characterized by transmission electron microscopy, UV-Vis and FT-IR spectroscopic techniques. The antibacterial activity as a function of time was determined through microbiological studies against Staphylococcus aureus. The AgNPs show differences in stabilities when changing the coating agent and its concentration. This fact could be a consequence of the difference in the nature of the interaction between the stabilizer and the surface of the NPs, which were evaluated by FT-IR spectroscopy. In addition, an increase in the size of the nanoparticles was observed after 30 days, which could be related to an Ostwald maturation phenomenon. This result raises new questions about the role that stabilizers play on the surface of NPs, promoting size change in NPs. It is highly probable that the stabilizer functions as a growth controller of the NPs, thus determining an effect on their biological properties. Finally, the antibacterial activity was evaluated over time against the bacterium Staphylococcus aureus. The results showed that the protective or stabilizing agents can play an important role in the antibacterial capacity, the control of the size of the AgNPs and additionally in the stability over time.

The Effect of the Addition of Copper Particles in High-Density Recycled Polyethylene Matrices by Extrusion.

In this study, the effect of the recycling process and copper particle incorporation on virgin and recycled pellet HDPE were investigated by thermo-chemical analysis, mechanical characterization, and antibacterial analysis. Copper particles were added to pellet HDPE, virgin and recycled, using a tabletop single screw extruder. Some copper particles, called copper nano-particles (Cu-NPs), had a spherical morphology and an average particle size near 20 nm. The others had a cubic morphology and an average particle size close to 300 nm, labeled copper nano-cubes (Cu-NCs). The thermo-chemical analysis revealed that the degree of crystallization was not influenced by the recycling process: 55.38 % for virgin HDPE and 56.01% for recycled HDPE. The degree of crystallization decreased with the addition of the copper particles. Possibly due to a modification in the structure, packaging organization, and crystalline ordering, the recycled HDPE reached a degree of crystallization close to 44.78% with 0.5 wt.% copper nano-particles and close to 36.57% for the recycled HDPE modified with 0.7 wt.% Cu-NCs. Tensile tests revealed a slight reduction in the tensile strength related to the recycling process, being close to 26 MPa for the virgin HDPE and 15.99 MPa for the recycled HDPE, which was improved by adding copper particles, which were near 25.39 MPa for 0.7 wt.% copper nano-cubes. Antibacterial analysis showed a reduction in the viability of E. coli in virgin HDPE samples, which was close to 8% for HDPE containing copper nano-particles and lower than 2% for HDPE having copper nano-cubes. In contrast, the recycled HDPE revealed viability close to 95% for HDPE with copper nano-particles and nearly 50% for HDPE with copper nano-cubes. The viability of S. aureus for HDPE was lower than containing copper nano-particles and copper nano-cubes, which increased dramatically close to 80% for recycled HDPE with copper nano-particles 80% and 75% with copper nano-cubes.

[Evaluation dosing intravenous voriconazole three times a day vs twice daily for the treatment of invasive aspergillosis in immunocompromised children: therapeutic drugs monitoring and safety]. / Evaluación de la dosificación de voriconazol intravenoso tres veces al día vs dos veces al día para el tratamiento de aspergilosis invasora en niños inmunocomprometidos: monitorización terapéutica y seguridad.

BACKGROUND: Voriconazole is the antifungal of choice for the treatment of invasive aspergillosis (IA). Plasma concentrations (PCs) > 1 µg / mL llave been associated with better therapeutic results which have not always been achieved during treatment in immunocompromised children. In the necessity to initiate early and effective therapy for the infection, it is relevant to establish the voriconazole administration regimen that is associated with optimal PCs in this population. AIM: To compare the PC and safety of intravenous (IV) voriconazole, dosed BID and TID in immunocompromised children with indication of antifungal treatment. METHOD: Retrospective observational study since January 2015 until July 2018 in a highly complex pediatric hospital in Santiago of Chile, in patients aged 0 to 17 years who received treatment with IV voriconazole. Those with renal replacement therapy, liver failure and / or renal failure were excluded. Trough PCs were compared between a group with BID dosing regimen versus another group with TID administration. Adverse reactions were evaluated in both groups. RESULTS: 137 trough PCs were obtained in 76 children, with a median age of 9 years (0-17 years) in the BID group and 9 years (0-16) in the TID group with a median weight of 27 kg (6-83 kg) and 28 kg (9.3-60 kg), respectively. Patients < 12 years old exposed to TID dosages are 4.65 times (OR: 4.65, 95% CI 1.93-11.2) more likely to have PC > 1 gg/mL compared to BID administration (p = 0.001). Eight adverse reactions were reported, mainly photophobia, with no significant difference found between the BID and TID groups. CONCLUSION: TID dosages are associated with a greater probability of obtaining adequate exposure to voriconazole in patients < 12 years old compared to BID dosages, with a low frequency of adverse reactions.

Evaluación de la dosificación de voriconazol intravenoso tres veces al día vs dos veces al día para el tratamiento de aspergilosis invasora en niños inmunocomprometidos: monitorización terapéutica y seguridad / Evaluation dosing intravenous voriconazole three times a day vs twice daily for the treatment of invasive aspergillosis in immunocompromised children: therapeutic drugs monitoring and safety

INTRODUCCIÓN: Voriconazol es el antifúngico de elección para el tratamiento de la aspergilosis invasora (AI). Concentraciones plasmáticas (CPs) > 1 μg/mL se han asociado a mejores resultados terapéuticos, las que no siempre se alcanzan durante el tratamiento en niños inmunocomprometidos. Dada la necesidad de iniciar una terapia precoz y efectiva de la infección, es relevante establecer el régimen de administración de voriconazol que se asocie con CPs óptimas en esta población. OBJETIVO: Comparar las CPs y seguridad de voriconazol intravenoso (IV), dosificado BID y TID en niños inmunocomprometidos con indicación de tratamiento antifúngico. MÉTODO: Estudio observacional retrospectivo de enero de 2015 a julio de 2018 en un hospital pediátrico de alta complejidad de Santiago de Chile, en pacientes de 0 a 17 años que recibieron tratamiento con voriconazol IV. Se excluyeron aquellos con terapia de reemplazo renal, falla hepática y/o falla renal. Se compararon las CPs valles entre un grupo con régimen de dosificación BID y otro grupo con administración TID. Se evaluaron las reacciones adversas en ambos grupos. RESULTADOS: Se obtuvieron 137 CPs valles en 76 niños, con una mediana de edad de 9 años (0-17 años) en el grupo BID y 9 años (0-16 años) en el grupo TID, con una mediana de peso de 27 kg (6-83 kg) y 28 kg (9,3-60 kg), respectivamente. Resultados: Pacientes 1 gg/mL en comparación con la administración BID (p = 0,001). Se reportaron ocho reacciones adversas, principalmente fotofobia, sin encontrarse diferencias significativas entre grupo BID y TID. CONCLUSIÓN: Dosificaciones TID están asociadas a una mayor probabilidad de obtener una adecuada exposición a voriconazol en pacientes < 12 años en comparación a dosificaciones BID, con baja frecuencia de reacciones adversas.

BACKGROUND: Voriconazole is the antifungal of choice for the treatment of invasive aspergillosis (IA). Plasma concentrations (PCs) > 1 μg / mL llave been associated with better therapeutic results which have not always been achieved during treatment in immunocompromised children. In the necessity to initiate early and effective therapy for the infection, it is relevant to establish the voriconazole administration regimen that is associated with optimal PCs in this population. AIM: To compare the PC and safety of intravenous (IV) voriconazole, dosed BID and TID in immunocompromised children with indication of antifungal treatment. METHOD: Retrospective observational study since January 2015 until July 2018 in a highly complex pediatric hospital in Santiago of Chile, in patients aged 0 to 17 years who received treatment with IV voriconazole. Those with renal replacement therapy, liver failure and / or renal failure were excluded. Trough PCs were compared between a group with BID dosing regimen versus another group with TID administration. Adverse reactions were evaluated in both groups. RESULTS: 137 trough PCs were obtained in 76 children, with a median age of 9 years (0-17 years) in the BID group and 9 years (0-16) in the TID group with a median weight of 27 kg (6-83 kg) and 28 kg (9.3-60 kg), respectively. Patients 1 gg/mL compared to BID administration (p = 0.001). Eight adverse reactions were reported, mainly photophobia, with no significant difference found between the BID and TID groups. CONCLUSION: TID dosages are associated with a greater probability of obtaining adequate exposure to voriconazole in patients < 12 years old compared to BID dosages, with a low frequency of adverse reactions.

Effect of pH on the Electrochemical Behavior of Hydrogen Peroxide in the Presence of Pseudomonas aeruginosa.

The influence of pH on the electrochemical behavior of hydrogen peroxide in the presence of Pseudomonas aeruginosa was investigated using electrochemical techniques. Cyclic and square wave voltammetry were used to monitor the enzymatic activity. A modified cobalt phthalocyanine (CoPc) carbon electrode (OPG), a known catalyst for reducing O2 to H2O2, was used to detect species resulting from the enzyme activity. The electrolyte was a sterilized aqueous medium containing Mueller-Hinton (MH) broth. The open-circuit potential (OCP) of the Pseudomonas aeruginosa culture in MH decreased rapidly with time, reaching a stable state after 4 h. Peculiarities in the E / I response were observed in voltammograms conducted in less than 4 h of exposure to the culture medium. Such particular E/I responses are due to the catalase's enzymatic action related to the conversion of hydrogen peroxide to oxygen, confirming the authors' previous findings related to the behavior of other catalase-positive microorganisms. The enzymatic activity exhibits maximum activity at pH 7.5, assessed by the potential at which oxygen is reduced to hydrogen peroxide. At higher or lower pHs, the oxygen reduction reaction (ORR) occurs at higher overpotentials, i.e., at more negative potentials. In addition, and to assess the influence of bacterial adhesion on the electrochemical behavior, measurements of the bacterial-substrate metal interaction were performed at different pH using atomic force microscopy.

The effect of Staphylococcus aureus on the electrochemical behavior of porous Ti-6Al-4V alloy.

Ti-6Al-4V alloy has been widely investigated for biomedical applications due to its low density, high specific strength, and favorable corrosion resistance. However, some reported failures have imposed a challenge to improve bone regeneration and fixation, as well as antibacterial properties. A further opportunity for solving this problem is the introduction of porosity. However, this can induce metallic release and corrosion product formation. In this work, a Ti-6Al-4V alloy was exposed to Hank's solution, sterilized and inoculated with Staphylococcus aureus at 37 °C. Surface analysis was carried out by SEM-EDS and XPS. Electrochemical measurements were also performed using chronopotentiometry at open circuit potential, polarization curves, and electrochemical impedance spectroscopy. After exposure, FE-SEM showed some colonies of S. aureus on the sample with 22% porosity. However, XPS analysis revealed that the presence of bacterium influenced the composition of the oxide layer, even more drastically with the increase in added porosity. Moreover, the impedance analysis showed De Levie's behavior, revealing a reduction of pore resistance and modulus of the impedance in the low frequency range in inoculated medium, and polarization curves showed that the passivity potential range was decreased, whereas the passivity current increased in the presence of the S. aureus.

Capping of silver nanoparticles by anti-inflammatory ligands: Antibacterial activity and superoxide anion generation.

Silver nanoparticles (AgNPs) have been widely recognized as antibacterial agents. However, its stability and activity over time have been poorly studied. In this work, the properties and characteristics of differently stabilized AgNPs were evaluated during a span of time. The surface capping agents were diclofenac (d), and ketorolac (k), which currently are used as anti-inflammatory in human medicine. On evaluating the size variation over time, it was observed that the AgNPs-k are the most stable, unlike the non-capped nanoparticles agglomerate and precipitate. UV-Vis spectroscopy analysis showed that the absorbance during time decreases for the three types of nanoparticles, but the decrease is less marked for the two types of anti-inflammatory-capped AgNPs. The rapid loss of the optical prop- erties of bare AgNPs, is mainly due to oxidation, agglomeration, and precipitation of this nanoparticles. The potential cytotoxicity of the AgNPs, evaluated through the formation of the superoxide anion using XXT, showed that both, AgNPs-k and AgNPs-d, generate the radical anion when the samples are irradiated with UV light at 365 nm. This effect appears associated with the capping agents, since the bare nanoparticles did not promote the formation of the superoxide anion. The antibacterial activity of the AgNPs throughout time, against two microorganisms (Escherichia coli and Staphylococcus aureus), was also evaluated. The results showed that capping agents played a decisive role in the antibacterial ability of AgNPs and also in enhancing the antibacterial activity over time.

Surface Functionalization of an Aluminum Alloy to Generate an Antibiofilm Coating Based on Poly(Methyl Methacrylate) and Silver Nanoparticles.

An experimental protocol was studied to improve the adhesion of a polymeric poly(methyl methacrylate) coating that was modified with silver nanoparticles to an aluminum alloy, AA2024. The nanoparticles were incorporated into the polymeric matrix to add the property of inhibiting biofilm formation to the anticorrosive characteristics of the film, thus also making the coating antibiocorrosive. The protocol consists of functionalizing the surface through a pseudotransesterification treatment using a methyl methacrylate monomer that bonds covalently to the surface and leaves a terminal double bond that promotes and directs the polymerization reaction that takes place in the process that follows immediately after. This results in more compact and thicker poly(methyl methacrylate) (PMMA) coatings than those obtained without pseudotransesterification. The poly(methyl methacrylate) matrix modified with nanoparticles was obtained by incorporating both the nanoparticles and the methyl methacrylate in the reactor. The in situ polymerization involved combining the pretreated AA2024 specimens combined with the methyl methacrylate monomer and AgNps. The antibiofilm capacity of the coating was evaluated against P. aeruginosa, with an excellent response. Not only did the presence of bacteria decrease, but the formation of the exopolymer subunits was 99.99% lower than on the uncoated aluminum alloy or the alloy coated with unmodified poly(methyl methacrylate). As well and significantly, the potentiodynamic polarization measurements indicate that the PMMA-Ag coating has a good anticorrosive property in a 0.1-M NaCl medium.

Stability of Antibacterial Silver Carboxylate Complexes against Staphylococcus epidermidis and Their Cytotoxic Effects.

The antibacterial effects against Staphylococcus epidermidis of five silver carboxylate complexes with anti-inflammatory ligands were studied in order to analyze and compare them in terms of stability (in solution and after exposure to UV light), and their antibacterial and morphological differences. Four effects of the Ag-complexes were evidenced by transmission electronic microscopy (TEM) and scanning electronic microscopy (SEM): DNA condensation, membrane disruption, shedding of cytoplasmic material and silver compound microcrystal penetration of bacteria. 5-Chlorosalicylic acid (5Cl) and sodium 4-aminosalicylate (4A) were the most effective ligands for synthesizing silver complexes with high levels of antibacterial activity. However, Ag-5Cl was the most stable against exposure UV light (365 nm). Cytotoxic effects were tested against two kinds of eukaryotic cells: murine fibroblast cells (T10 1/2) and human epithelial ovarian cancer cells (A2780). The main objective was to identify changes in their antibacterial properties associated with potential decomposition and the implications for clinical applications.

Copper-polymer nanocomposites: An excellent and cost-effective biocide for use on antibacterial surfaces.

The development of polymer nanocomposites with antimicrobial properties has been a key factor for controlling or inhibiting the growth of microorganisms and preventing foodborne diseases and nosocomial infections. Commercially available antibacterial products based on silver-polymer are the most widely used despite the fact that copper is considerably less expensive. The incorporation of copper nanoparticles as antibacterial agents in polymeric matrices to generate copper-polymer nanocomposites have presented excellent results in inhibiting the growth of a broad spectrum of microorganisms. The potential applications in food packaging, medical devices, textiles and pharmaceuticals and water treatment have generated an increasing number of investigations on preparing copper based nanocomposites and alternative polymeric matrices, as potential hosts of nano-modifiers. This review presents a comprehensive compilation of previous published work on the subject, mainly related to the antimicrobial activity of copper polymer nanocomposites. Within all the phenomenology associated to antibacterial effects we highlight the possible mechanisms of action. We discuss the differences in the susceptibility of Gram negative and positive bacteria to the antibacterial activity of nanocomposites, and influencing factors. As well, the main applications of copper polymer-metal nanocomposites are described, considering their physical and chemical characteristics. Finally, some commercially available copper-polymer nanocomposites are described.