In situ Fourier transform infrared reflection absortion spectroscopy study of adenine adsorption on gold electrodes in basic media

In situ Fourier transform infrared reflection absortion spectroscopy (FT-IRRAS) has been used in the external (SNIFTIRS method) and the internal (ATR-SEIRAS) reflection configurations to determine the pH influence, in the neutral and basic range, on the adsorption of adenine on Au(111) and gold nanofilm electrodes from D2O and H2O solutions. In D2O solutions, the main adsorbate band around 1640 cm−1,due to a ring stretching mode, shows different characteristics in the spectra collected at pH values at which the neutral and the basic adenine forms predominate in solution. The analysis of these differences, in comparison with the respective spectra of adenine in solution, permits us to conclude that both forms of adenine can adsorb chemically. The high sensitivity of the ATR-SEIRAS method has been used to analyze the contribution to the spectra of each form of adsorbed adenine as a function of the pH of the solution. The pKa2 obtained for the adsorbed species from this analysis is almost coincident with the pKa2 reported for adenine in solution, indicating that the coordination to the electrode and the second acid-base equilibrium involves different atoms of the adenine molecule. This result confirms the previously proposed adsorption model for adenine, implying the bonding of adenine to the electrode by the amine nitrogen (N10) and either the ring nitrogens N1 or N7, while the second acid-base equilibrium of adenine involves the ring nitrogen N9. Comparison of the 3400-3600 cm−1 region of the ATR-SEIRAS spectra of adenine obtained in H2O solutions at different pH values, which corresponds to the characteristic–OH stretching mode of the interfacial water molecules, permits us to discard the co-adsorption of water molecules in neutral and basic media, contrary to the case of adenine adsorption from acid media.Financial support from the Spanish Ministry of Science and Technology (CTQ2010-19823 and a FPU-grant to JAM), from the Junta de Andalucia (PAI FQM202) and University of Alicante

Embalagem plástica para flocão de milho biofortificado.

Devido a carência de micronutrientes que são essenciais para a saúde, vem sendo desenvolvido no Brasil produtos biofortificados. O objetivo desse estudo foi levantar informações sobre os efeitos de quatro tipos de embalagem e do tipo de acondicionamento (com e sem vácuo), na perda de qualidade de flocão de milho biofortificado. Os resultados mostraram que em todas as embalagens avaliadas houve preservação dos carotenoides, tendo um destaque para o PETmet/PEBD com vácuo que teve uma maior retenção do teor de carotenoides pró-vitamina A e maior preservação da cor.22 a 26 de outubro de 2017

Cholesterol levels affect the performance of aunps-decorated thermo-sensitive liposomes as nanocarriers for controlled doxorubicin delivery

Stimulus-responsive liposomes (L) for triggering drug release to the target site are particularly useful in cancer therapy. This research was focused on the evaluation of the effects of cholesterol levels in the performance of gold nanoparticles (AuNPs)-functionalized L for controlled doxorubicin (D) delivery. Their interfacial and morphological properties, drug release behavior against temperature changes and cytotoxic activity against breast and ovarian cancer cells were studied. Langmuir isotherms were performed to identify the most stable combination of lipid components. Two mole fractions of cholesterol (3.35 mol% and 40 mol%, L1 and L2 series, respectively) were evaluated. Thin-film hydration and transmembrane pH-gradient methods were used for preparing the L and for D loading, respectively. The cationic surface of L allowed the anchoring of negatively charged AuNPs by electrostatic interactions, even inducing a shift in the zeta potential of the L2 series. L exhibited nanometric sizes and spherical shape. The higher the proportion of cholesterol, the higher the drug loading. D was released in a controlled manner by diffusion-controlled mechanisms, and the proportions of cholesterol and temperature of release media influenced its release profiles. D-encapsulated L preserved its antiproliferative activity against cancer cells. The developed liposomal formulations exhibit promising properties for cancer treatment and potential for hyperthermia therapy.Ministerio de Ciencia e Innovación CTQ2014- 57515-C2-

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Evidences of adenine–thymine Interactions at gold electrodes interfaces as provided by in-situ infrared spectroscopy

The co-adsorption of complementary DNA bases adenine and thymine on gold thin-film electrodes from 0.1 M HClO4 solutions in H2O and D2O is studied by surface-enhanced infrared absorption spectroscopy in the attenuated total reflection mode (ATR-SEIRAS). The comparison of the spectra in the range 1750–1550 cm− 1 for co-adsorbed adenine and thymine at controlled potentials to those of the individual adsorbed bases shows the enhancement of the signals associated to the vibration modes of adenine and the inhibition of those of thymine. The results can be explained by invoking the rearrangement of both molecules on the electrode surface in order to facilitate the Watson–Crick (W–C) and/or Hoogsteen (HG) interactions between the bases. The co-adsorption seems to be a cooperative process in which a low surface concentration of each base can induce the rearrangement of the complementary base molecules on the surface.Financial support from Ministerio de Educación y Ciencia (Spain) (Projects CTQ2010-19823 and CTQ2009-13142 and a FPU-grant to JA), Junta de Andalucía (Grupo FQM202) and Generalitat Valenciana (ACOMP/2011/200) are greatly acknowledged

Tautomerism of adsorbed thymine on gold electrodes: an in situ surface-enhanced infrared spectroscopy study

The adsorption of thymine on gold electrodes has been studied by ATR-SEIRAS in situ spectroscopy at three pH values (1, 7 and 12), in order to analyse the tautomeric equilibrium of deprotonated thymine in the adsorbed state. The anionic form which is deprotonated in nitrogen N1 (N1 tautomer) and the one deprotonated in nitrogen N3 (N3 tautomer) are considered. The spectroscopic results have been interpreted in the light of DFT ab-initio calculations of both tautomeric forms adsorbed on gold surfaces. The basis sets 6-311 + +G(d,p) for C, H, O and N atoms and LANDL2DZ for Au atoms have been used. The electrode surface has been simulated as an unreconstructed Au(111) surface of 19 atoms. The preponderance of each tautomer of adsorbed thymine as a function of pH has been inferred from the analysis of the spectral signals in the 1500–1800 cm−1 wavenumber region related mostly to stretching modes of the carbonyl groups. It has been found that the adsorbed N3 tautomer predominates in the case of adsorption from acid media while the N1 tautomer predominates in the adsorption from basic media but the adsorption of both forms have been distinguished in the experiments from neutral media. Moreover, the plausible changes in the orientation of the two adsorbed tautomers with the electric field have been determined by analysing the relative intensities of the characteristic CH stretching signals in the 2800–3300 cm−1 spectral region. It is proposed that the N3 tautomer undergoes changes in the interaction sites with the metal and in the molecular plane orientation on the electrode as the electric potential is increased, but the N1 tautomer molecule keeps the interaction sites while the molecular plane slightly rotates to facilitate the electrostatic interaction with the field.Financial support from the Spanish Ministry of Economy and Competitiveness (CTQ2014-57515-C2-1-R and CTQ-2013-44083-P) and from the Junta de Andalucia (PAI FQM202) is gratefully acknowledged

Electrostatics affects formation of Watson-Crick complex between DNA bases in monolayers of nucleolipids deposited at a gold electrode surface

Chronocoulometry was applied to determine charge in a monolayer of nucleolipid (1,2-dipalmitoyl-sn‑glycero-3-(cytidine diphosphate)) deposited at a gold electrode surface. The immersion method was used to measure the potential of zero charge of the interface (Epzci), which is a sum of charge on the monolayer of the nucleolipid and charge on the gold surface. Photon polarization infrared reflection absorption spectroscopy (PM-IRRAS) was used to determine formation of the Watson-Crick complex between terminal cytidine moiety of the nucleolipid and guanine (its complementary base) added to the solution. The combination of electrochemical and spectroscopic studies allowed one to demonstrate that the Watson-Crick complex is formed when the interface is positively charged. The potential applied to the electrode affects not only the complex formation but also orientation of the cytosine moiety. The complex is formed when the cytosine moiety is oriented assuming a small angle with respect to the electrode surface.Ministerio de Ciencia e Innovación CTQ2014-57515-C2-1-R, RED2018-102412-TJunta de Andalucía FQM202Natural Sciences and Engineering Research Council of Canada (NSERC) RG-0395

Mixed monolayer of a nucleolipid and a phospholipid has improved properties for spectroelectrochemical sensing of complementary nucleobases

A mixed monolayer of 1,2-dipalmitoyl-sn-glycero-3-(cytidine diphosphate) nucleolipid (DG-CDP) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was transferred from the air–water interface onto an gold (1 1 1) electrode surface using the Langmuir-Schaeffer (horizontal touch) technique. Compression isotherms were recorded for the monolayer spread at the air–water interface. These measurements demonstrated that the mixture composition 7:3 of DG-CDP:DPPC displayed reduced repulsive interactions between polar heads and ideal packing of acyl chains. Chronocoulometric experiments were performed to demonstrate stability of this film at the gold–solution interface. Photon polarization modulation infrared reflection absorption spectroscopy showed that the tilt angle of the acyl chains is slightly higher, and the chains are less twisted in the mixed than in the pure nucleolipid monolayer. In the mixed film, the tilt of the cytosine moiety (the sensing element of the monolayer) assumes a large angle with respect to the surface normal, even when the monolayer becomes detached from the gold surface. The mixed monolayer has improved properties for future applications for detection of guanine, its complementary base.Ministerio de Ciencia e Innovación CTQ2014-57515-C2-1-R, RED2018-102412-TJunta de Andalucía FQM202Natural Sciences and Engineering Research Council of Canada (NSERC) RG-0395