Structural characterization of cholesterol-rich nanoemulsion (LDE).

Cholesterol-rich nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and can concentrate those agents in the neoplastic and inflammatory tissues. This method improves the biodistribution of the drug and reduces toxicity. However, the structural stability of LDE particles, without or with associated drugs, has not been extensively investigated. The aim of the present study is to investigate the structural stability of LDE and LDE associated to paclitaxel, etoposide or methotrexate in aqueous solution over time by small-angle X-ray scattering (SAXS and Ultra SAXS) and dynamic light scattering (DLS). The results show that LDE and LDE associated with those chemotherapeutic agents had reproducible and stable particle diameter, physical structure, and aggregation behavior over 3-month observation period. As estimated from both DLS and Ultra-SAXS methods, performed at pre-established intervals, the average particle diameter of LDE alone was approx. 32 nm, of LDE-paclitaxel was 31 nm, of LDE-methotrexate was 35 nm and of LDE-etoposide was 36 nm. Ultra-SAXS analysis showed that LDE nanoparticles were quasi-spherical, and SAXS showed that drug molecules inside the particles showed a layered-like organization. Formulations of LDE with associated PTX, ETO or MTX were successfully tested in animal experiments and in patients with cancer or with cardiovascular disease, showing markedly low toxicity, good tolerability and possible superior pharmacological action. Our results may be useful for ensuing clinical trials of this novel Nanomedicine tool, by strengthening the knowledge of the structural aspects of those LDE formulations.

Effects of phytosterol supplementation on lipoprotein subfractions and LDL particle quality.

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .

Regular Practice of Physical Activity Improves Cholesterol Transfers to High-Density Lipoprotein (HDL) and Other HDL Metabolic Parameters in Older Adults.

The effects of regular physical activity on two important anti-atherosclerosis functions of high-density lipoprotein (HDL), namely its capacity to receive both forms of cholesterol and its anti-oxidant function, were investigated in this study comparing older adults with young individuals. One-hundred and eight healthy adult individuals were enrolled and separated into the following groups: active older (60-80 yrs, n = 24); inactive older (60-79 yrs, n = 21); active young (20-34 yrs, n = 39); and inactive young (20-35 yrs, n = 24). All performed cardiopulmonary tests. Blood samples were collected in order to assess the following measures: lipid profile, HDL anti-oxidant capacity, paraoxonase-1 activity, HDL subfractions, and lipid transfer to HDL. Comparing active older and active young groups with inactive older and inactive young groups, respectively, the active groups presented higher HDL-C levels (p < 0.01 for both comparisons), unesterified cholesterol transfer (p < 0.01, p < 0.05), and intermediate and larger HDL subfractions (p < 0.001, p < 0.01) than the respective inactive groups. In addition, the active young group showed higher esterified cholesterol transfer than the inactive young group (p < 0.05). As expected, the two active groups had higher VO2peak than the inactive groups; VO2peak was higher in the two younger than in the two older groups (p < 0.05). No differences in unesterified and esterified cholesterol transfers and HDL subfractions were found between active young and active older groups. HDL anti-oxidant capacity and paraoxonase-1 activity were equal in all four study groups. Our data highlight and strengthen the benefits of regular practice of physical activity on an important HDL function, the capacity of HDL to receive cholesterol, despite the age-dependent decrease in VO2peak.

Antioxidant capacity of simplified oxygen heterocycles and proposed derivatives by theoretical calculations.

CONTEXT: Some structural properties can be involved in the antioxidant capacity of several polyphenol derivatives, among them their simplified structures. This study examines the contribution of simplified structure for the antioxidant capacity of some natural and synthetic antioxidants. The resonance structures were related to the π-type electron system of carbon-carbon double bonds between both phenyl rings. Trans-resveratrol, phenyl-benzofuran, phenyl-indenone, and benzylidene-benzofuranone are the best basic antioxidant templates among the simplified derivatives studied here. Additionally, the stilbene moiety was found on the molecules with the best antioxidant capacity. Furthermore, our investigation suggests that these compounds can be used as antioxidant scaffold for designing and developing of new promising derivatives. METHODS: To investigate the structure-antioxidant capacity for sixteen simplified natural and proposed derivatives we have employed density functional theory and used Gaussian 09. Our DFT calculations were performed using the B3LYP functional and the 6-31+G(d,p) basis set. All electron transfer mechanisms were investigated by using values of HOMO, ionization potential, energy affinity, stabilization energies, and spin density distributions.

Changes in lipoproteins associated with lipid-lowering and antiplatelet strategies in patients with acute myocardial infarction.

BACKGROUND: Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. METHODS: Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. RESULTS: Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. CONCLUSIONS: The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.

Main differences between two highly effective lipid-lowering therapies in subclasses of lipoproteins in patients with acute myocardial infarction.

BACKGROUND: Large observational studies have shown that small, dense LDL subfractions are related to atherosclerotic cardiovascular disease. This study assessed the effects of two highly effective lipid-lowering therapies in the atherogenic subclasses of lipoproteins in subjects with ST-segment elevation myocardial infarction (STEMI). METHODS: Patients of both sexes admitted with their first myocardial infarction and submitted to pharmacoinvasive strategy (N = 101) were included and randomized using a central computerized system to receive a daily dose of simvastatin 40 mg plus ezetimibe 10 mg or rosuvastatin 20 mg for 30 days. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) subfractions were analysed by polyacrylamide gel electrophoresis (Lipoprint System) on the first (D1) and 30th days (D30) of lipid-lowering therapy. Changes in LDL and IDL subfractions between D1 and D30 were compared between the lipid-lowering therapies (Mann-Whitney U test). RESULTS: The classic lipid profile was similar in both therapy arms at D1 and D30. At D30, the achievement of lipid goals was comparable between lipid-lowering therapies. Cholesterol content in atherogenic subclasses of LDL (p = 0.043) and IDL (p = 0.047) decreased more efficiently with simvastatin plus ezetimibe than with rosuvastatin. CONCLUSIONS: Lipid-lowering therapy with simvastatin plus ezetimibe was associated with a better pattern of lipoprotein subfractions than rosuvastatin monotherapy. This finding was noted despite similar effects in the classic lipid profile and may contribute to residual cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02428374, registered on 28/09/2014.

Electron scattering processes in steroid molecules via NEGF-DFT: The opening of conduction channels by central oxygen.

We present a careful analysis of the electron transport in a variety of steroid derivatives attached among Au (111) electrodes. Our discussion is based on the non-equilibrium Green's function formalism coupled to the density functional theory, as well as appropriate parameters, such as the current-voltage behavior, differential conductance, rectification ratio, transmittance, the projected density of states, and the corresponding eigenchannels. The systems investigated present antagonistic features. While the cholesterol has no appreciable electrical rectification and works as an insulator, cortisol presents an evident diode-like behavior with an intense micro-ampere current with a strong peak at ca. 0.3 eV. This characteristic is a consequence of the systematic remotion of saturated carbon chains, and the inclusion of oxygen atoms. These results can help to understand biological processes involving these molecules besides designing new devices for applications in molecular electronics.

Alkylated Sesamol Derivatives as Potent Antioxidants.

Sesamol is a phenolic derivative. Its antioxidant activity is low than that of Trolox and depends on benzodioxole moiety. Thus, a molecular modification strategy through alkylation, inspired by natural and synthetic antioxidants, was studied by molecular modeling at the DFT/B3LYP level of theory by comparing the 6-31+G(d,p) and 6-311++G(2d,2p) basis sets. All proposed derivatives were compared to classical related antioxidants such as Trolox, t-butylated hydroxytoluene (BHT) and t-butylated hydroxyanisole (BHA). According to our results, molecular orbitals, single electron or hydrogen-atom transfers, spin density distributions, and alkyl substitutions at the ortho positions related to phenol moiety were found to be more effective than any other positions. The trimethylated derivative was more potent than Trolox. t-Butylated derivatives were stronger than all other alkylated derivatives and may be new alternative forms of modified antioxidants from natural products with applications in the chemical, pharmaceutical, and food industries.

Thermodynamics study of biokerosene from coconut and palm kernel oils and JP-8 aircraft fuels in the gas phase by the DFT method.

In this work, we performed a theoretical density functional theory (DFT) and semi-empirical (PM3) analysis to calculate thermodynamic properties of biokerosene from coconut and palm kernel oils, Jet Propulsion Fuel 8 (JP-8), and mixtures of these fuels. All simulations were performed in thermal equilibrium and for a temperature range of 0.5-1500 K, considering the canonical ensemble model. We predicted the thermal properties energy, enthalpy, enthalpy change, Gibbs free energy, entropy, and specific heat at constant pressure with respect to temperature. In addition, we compared the performances of the DFT functional hybrid B3LYP and the basis set 6-311++G(d,p) and PM3 methods, in order to determine their accuracy for thermodynamic predictions relating to the fuels. Calculations for combustion enthalpy were carried out using the following methods: B3LYP/6-311++G(d,p), B3LYP/6-31+G(d), CBS-QB3, G3, G4, and G3/G4. The results showed good agreement with measured values, indicating that DFT may be a good method to calculate and predict thermodynamic properties of the combustion reactions of kerosene and biokerosene.

Effect of the Electric Field on DNA Bases as Pigments for Nanodevices: A First-Principles Study.

In this work we used Density Functional Theory to simulate the molecular electronics behavior of the nitrogenous bases of human DNA under electric field effects. The results can describe some internal effects in the use of DNA-based as photoconductor or semiconductor nanodevices. For this investigation, calculations were performed to predict structural deformations, HOMO and LUMO orbitals, and thermodynamic properties of each one of the following nitrogenous bases: adenine, thymine, guanine and cytosine. All the quantities were calculated as functions of the electric field. This analysis allows us to verify the influence of the electric field in the molecular geometry of nitrogenous bases, enabling us to determine that adenine, thymine and guanine are those bases most susceptible to presenting substantial deformations when DNA is submitted to the action of an external electric field, while the molecular structure of cytosine is highly resistant to this effect.

Circulating microparticles and central blood pressure according to antihypertensive strategy.

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Sensors Using the Molecular Dynamics of Explosives in Carbon Nanotubes Under External Uniform Electric Fields.

Possessing a simulated sensor device to identify explosives is of extreme interest to the area of public security to fight against terrorism. In light of this, a carbon armchair nanotube was modeled under the action of an external, longitudinal and uniform electric field at an initial temperature of 1 mK simulation, causing the explosive molecules under analysis to rotate through the carbon nanotube, due to an evanescent effect generated from the action of an electric current and magnetic field induced in this system, and thus behaving as a selective temperature sensor and spinning radius for the molecules. For this, molecular dynamics was used to study the physicochemical properties of the molecules' interactions with a carbon nanotube. The following physical properties, as well as the kinetic, potential, and total energy were calculated for the 2,4,6-trinitrotoluene (TNT), triacetone triperoxide (TATP), hexogen (RDX), hexamethylene triperoxide diamine (HMTD), octogen (HMX) and pentaerythritol tetranitrate (PETN) explosives: thermodynamic conditions such as temperature; entropy variation; and distance between the molecules' center of mass from an armchair type carbon nanotube.

Removal of Organic Pollutants Benzene and Phenol Using Nanofiltration: A Molecular Dynamics Study.

Population growth has resulted in an increased demand for clean water. It is known that chemical pollutants such as phenol and benzene often make water unfit for consumption, and can be responsible for the appearance of diseases such as cancer. In this sense, studies aimed at decontaminating water are still necessary. In this study, molecular dynamics simulations were performed to evaluate the abilities of activated charcoal structures to adsorb benzene and phenol; the results of which were evaluated on the basis of root mean square deviations for all systems. The data were collected from the molecular dynamics (MD) trajectories and edited with the grace plotting tool. Visual molecular dynamics software was used to visualize the MD paths, and images were created using the UCSF chimera software. The results show that activated charcoal are viable alternatives for water decontamination by nanofiltration.

Molecular Electronics Including Temperature Effects Based on Dyes Pigments.

In this work we used the Density Functional Theory to study the thermodynamic properties from Brazilein (BZE) and Brazilin (BZI) molecules, main pigments responsible for the red color from Brazil wood. We did a comparison between the two dyes to then know which dye has better resistance to temperature (T ) and external electric field (E) values, aiming their potential to possible applications in solar cells, as excitons trainers. We have found that the BZE molecule becomes less stable after a temperature known as degradation temperature, and therefore enters oxidation state. However, BZE is more stable and more resistant to high temperatures. With respect to the applied external electric field, we find that BZE is more reactive to almost all the applied electric fields, thus more easily converted into energy in the form of electrical work.

Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects?

BACKGROUND: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. OBJECTIVE: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. METHODS: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. RESULTS: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. CONCLUSION: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.

Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects? / O Produto de Acumulação Lipídica está Associado a um Perfil Aterogênico de Lipoproteínas em Indivíduos Brasileiros?

Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.

Resumo Fundamento: O produto de acumulação lipídica (LAP), um instrumento simples e de baixo custo, é um novo biomarcador de acúmulo de gordura central e representa um marcador substituto potencial para o perfil aterogênico de lipoproteínas. No entanto, sua associação com subfrações de lipoproteínas ainda não foi descrita na literatura. Objetivo: Determinar se o LAP pode ser usado como um marcador de tamanho da lipoproteína de baixa densidade (LDL) e de alta densidade (HDL) em indivíduos brasileiros. Métodos: Este estudo transversal incluiu 351 pacientes de ambos os sexos e idade entre 30 e 74 anos. Dados clínicos e sociodemográficos e história familiar de doenças foram avaliados. O tamanho das lipoproteínas, e níveis de colesterol total (CT), lipoproteínas, apolipoproteína AI e B (APO AI/APO B), glicose, ácidos graxos não esterificados (AGNEs) e insulina, e índice de resistência insulínica (HOMA-IR) foram avaliados em amostras de sangue. O LAP foi calculado utilizando-se as fórmulas (circunferência da cintura (cm]-58) × (triglicerídeos[mmol/L]) para mulheres e (circunferência da cintura[cm]-65) × (triglicerídeos [mmol/L]) para homens. Associações entre LAP e parâmetros metabólicos foram testadas por tendência linear (modelo linear generalizado, GLM) antes e após ajustes por fatores de confusão (sexo, idade, tabagismo, uso de estatinas, fibratos e hipoglicemiantes) ao nível de significância de p < 0,05). Resultados: LAP apresentou uma associação positiva com CT, APO B, AGNEs, glicose, insulina, HOMA-IR, e uma associação negativa com HDL-C. Maior acúmulo de gordura central correlacionou-se com maior porcentagem de HDL intermediária e de partículas pequenas de LDL e HDL, e menor porcentagem de HDL grande. O tamanho da LDL também era reduzido em valores de LAP mais elevados. O impacto negativo do LAP foi mantido após ajuste para múltiplas variáveis. Conclusão: o LAP esteve fortemente associado com o perfil aterogênico de subfrações de lipoproteínas, independetemente dos fatores de confusão.

Time-Dependent Density Functional Theory Analysis of Triphenylamine-Functionalized Graphene Doped with Transition Metals for Photocatalytic Hydrogen Production.

The electronic structures and optical properties of triphenylamine-functionalized graphene (G-TPA) doped with transition metals, using water as a solvent, were theoretically investigated to verify the efficiency of photocatalytic hydrogen production with the use of transition metals. This study was performed by Density Functional Theory and Time-dependent Density Functional Theory through Gaussian 09W software, adopting the B3LYP functional for all structures. The 6-31g(d) basis set was used for H, C and N atoms, and the LANL2DZ basis set for transition metals using the Effective Core Potentials method. Two approaches were adopted: (1) using single metallic dopants (Ni, Pd, Fe, Os and Pt) and (2) using combinations of Ni with the other dopants (NiPd, NiPt, NiFe and NiOs). The DOS spectra reveal an increase of accessible states in the valence shell, in addition to a gap decrease for all dopants. This doping also increases the absorption in the visible region of solar radiation where sunlight is most intense (400 nm to 700 nm), with additional absorption peaks. The results lead us to propose the G-TPA structures doped with Ni, Pd, Pt, NiPt or NiPd to be novel catalysts for the conversion of solar energy for photocatalytic hydrogen production, since they improve the absorption of solar energy in the range of interest for solar radiation; and act as reaction centers, reducing the required overpotential for hydrogen production from water.

Intermolecular interactions between DNA and methamphetamine, amphetamine, ecstasy and their major metabolites.

In this work, we carried out a theoretical investigation regarding amphetamine-type stimulants, which can cause central nervous system degeneration, interacting with human DNA. These include amphetamine, methamphetamine, 3,4-Methylenedioxymethamphetamine (also known as ecstasy), as well as their main metabolites. The studies were performed through molecular docking and molecular dynamics simulations, where molecular interactions of the receptor-ligand systems, along with their physical-chemical energies, were reported. Our results show that 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine (ecstasy) present considerable reactivity with the receptor (DNA), suggesting that these molecules may cause damage due to human-DNA. These results were indicated by free Gibbs change of bind (ΔGbind) values referring to intermolecular interactions between the drugs and the minor grooves of DNA, which were predominant for all simulations. In addition, it was observed that 3,4-Dihydroxymethamphetamine (ΔGbind = -13.15 kcal/mol) presented greater spontaneity in establishing interactions with DNA in comparison to 3,4-Methylenedioxymethamphetamine (ΔGbind = -8.61 kcal/mol). Thus, according with the calculations performed our results suggest that the 3,4-Methylenedioxymethamphetamine and 3,4-Dihydroxymethamphetamine have greater probability to provide damage to human DNA fragments.

Insulin Resistance Predicts Atherogenic Lipoprotein Profile in Nondiabetic Subjects.

BACKGROUND: Atherogenic diabetes is associated with an increased cardiovascular risk and mortality in diabetic individuals; however, the impact of insulin resistance (IR) in lipid metabolism in preclinical stages is generally underreported. For that, we evaluated the capacity of IR to predict an atherogenic lipid subfraction profile. METHODS: Complete clinical evaluation and biochemical analysis (lipid, glucose profile, LDL, and HDL subfractions and LDL phenotype and size) were performed in 181 patients. The impact of IR as a predictor of atherogenic lipoproteins was tested by logistic regression analysis in raw and adjusted models. RESULTS: HDL-C and Apo AI were significantly lower in individuals with IR. Individuals with IR had a higher percentage of small HDL particles, lower percentage in the larger ones, and reduced frequency of phenotype A (IR = 62%; non-IR = 83%). IR individuals had reduced probability to have large HDL (OR = 0.213; CI = 0.999-0.457) and had twice more chances to show increased small HDL (OR = 2.486; CI = 1.341-7.051). IR was a significant predictor of small LDL (OR = 3.075; CI = 1.341-7.051) and atherogenic phenotype (OR = 3.176; CI = 1.469-6.867). CONCLUSION: IR, previously DM2 diagnosis, is a strong predictor of quantitative and qualitative features of lipoproteins directly associated with an increased atherogenic risk.