On the Aromatic Stabilization of Fused Polycyclic Aromatic Hydrocarbons.

The thermodynamic properties and band gap energies were evaluated for six ortho- and peri-fused polycyclic aromatic hydrocarbons (PAHs): triphenylene; benzo[a]pyrene; benzo[e]pyrene; perylene; benzo[ghi]perylene; coronene. The standard molar enthalpies of formation in the crystalline state and the standard molar enthalpies of sublimation were measured by high precision combustion calorimetry and Knudsen effusion methodology, respectively. The combination of the molar enthalpies of formation in the crystalline state with the respective enthalpies of sublimation was used to evaluate the energetics of the progressive peri-fusion of the aromatic moieties from triphenylene to coronene aiming to investigate the hypothetical superaromaticity character of coronene. The linear trend of the enthalpy of formation in crystalline and gaseous phases in the series (from benzo[e]pyrene to coronene) is an irrefutable indication of a non-superaromaticity character of coronene. High accurate thermodynamic properties of sublimation (volatility, enthalpy, and entropy of sublimation) were derived by the measurement of vapor pressures as a function of temperature, using a Knudsen/quartz crystal effusion methodology. Furthermore, the π-electronic conjugation of these compounds was explored by evaluation of the optical band gaps along with this series of compounds. The morphology of perylene, benzo[ghi]perylene, and coronene thin films, deposited by physical vapor deposition onto transparent conductive oxide substrates (ITO and FTO), was used to analyze the nucleation and growth mechanisms. The morphologies observed were found to be related to the cohesive energy and entropy of the bulk.

Understanding the electronic properties of BaTiO3 and Er3+ doped BaTiO3 films through confocal scanning microscopy and XPS: the role of oxygen vacancies.

Photonic and electronic properties exist inherently in ferroelectric barium titanate (BaTiO3); severe luminescence quenching also exists due to the insufficient confinement of excitons. In this sense, high optical emission can only be achieved by its chemical and structural modification. Thin BaTiO3 and Er:BaTiO3 films were grown by the spin coating method on a glass substrate at room temperature. Self-trapping of excitons in the thin BaTiO3 film and its structural modification due to the doping with Er3+ ions (Er:BaTiO3) are verified using scanning confocal fluorescence microscopy (SCFM), where self-trapping excitons never occured in its pure state. By thermal treatment and doping (BaTiO3 and Er:BaTiO3) we obtained localization of the excitons, which would further induce lattice strain around the surface defects, to accommodate the self-trapped excitons. With such a self-trapped state, the structure of BaTiO3 generates broadband emission of several overlapping bands between 1.95 and 2.65 eV at room temperature, while the structure Er:BaTiO3 showed defined emission bands at 2.24 and 2.35 eV, with very weak contributions of the emission due to the self-trapping state. The influence of the variation of the excitation wavelength using 1PE and 2PE on the emission bands of BaTiO3 and Er:BaTiO3 is also investigated. The results of enhanced emission bands suggest a clear dependence of the emission intensity on the excitation energy, where a ∼3 fold enhancement in emission has been demonstrated under Er3+ (1.55 eV) excitation, which can be attributed to effective energy transfer between the Er3+ ions. As a result, it is concluded that the developed BaTiO3 and Er:BaTiO3 can pave the way for future photonic devices.

Key amino acid residues of the AGT1 permease required for maltotriose consumption and fermentation by Saccharomyces cerevisiae.

AIMS: The AGT1 gene encodes for a general α-glucoside-H+ symporter required for efficient maltotriose fermentation by Saccharomyces cerevisiae. In the present study, we analysed the involvement of four charged amino acid residues present in this transporter that are required for maltotriose consumption and fermentation by yeast cells. METHODS AND RESULTS: By using a knowledge-driven approach based on charge, conservation, location, three-dimensional (3D) structural modelling and molecular docking analysis, we identified four amino acid residues (Glu-120, Asp-123, Glu-167 and Arg-504) in the AGT1 permease that could mediate substrate binding and translocation. Mutant permeases were generated by site-directed mutagenesis of these charged residues, and expressed in a yeast strain lacking this permease (agt1∆). While mutating the Arg-504 or Glu-120 residues into alanine totally abolished (R504A mutant) or greatly reduced (E120A mutant) maltotriose consumption by yeast cells, as well as impaired the active transport of several other α-glucosides, in the case of the Asp-123 and Glu-167 amino acids, it was necessary to mutate both residues (D123G/E167A mutant) in order to impair maltotriose consumption and fermentation. CONCLUSIONS: Based on the results obtained with mutant proteins, molecular docking and the localization of amino acid residues, we propose a transport mechanism for the AGT1 permease. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results present new insights into the structural basis for active α-glucoside-H+ symport activity by yeast transporters, providing the molecular bases for improving the catalytic properties of this type of sugar transporters.

Copper(II) complex-loaded castor oil-based nanostructured lipid carriers used against Mycobacterium tuberculosis : Development, characterisation, in vitro and in vivo biological assays.

A copper(II) complex-loaded castor oil-based nanostructured lipid carrier was evaluated to enhance the poor water solubility of antimicrobial compounds, improving their biological properties and antimicrobial activity against Mycobacterium tuberculosis. Nanostructured lipid carriers were composed of the castor oil, polyoxyethylene 40 stearate and caprylic/capric triglyceride, poloxamer 407, cetyltrimethylammonium bromide and three different copper(II) complexes. The systems were ultrasonicated at an amplitude of 8% for 20 min and an ice bath was used throughout the procedure. The blank nanostructured lipid carrier (F5) and nanostructured lipid carriers loaded with copper(II) complex 1, 2 and 3 (F5.1, F5.2 and F5.3, respectively) for 45 days presented values of mean diameter, poly dispersity index and zeta potential ranging from 186 to 199 nm, 0.14 to 0.2 and 24 to 30 mV, respectively. Atomic force microscopy indicated that the nanostructured lipid carriers were distributed at the nanoscale, corroborating the mean diameter data. Differential scanning calorimetry determined the melting points of the constituents of the nanostructured lipid carriers. The antimicrobial activity of copper(II) complexloaded F5 against M. tuberculosis H37Rv showed better anti-tuberculosis activity than the free complexes. In vivo biological assays of complex-loaded F5 demonstrated reduced toxicity. Our results suggest that nanostructured lipid carriers could be a potential nanotechnological strategy to optimise tuberculosis treatment.

Curcumin-loaded cationic solid lipid nanoparticles as a potential platform for the treatment of skin disorders.

Curcumin (CUM) possesses therapeutic activity against diverse skin disorders (SD); however, its clinical use faces many challenges related to physicochemical and bioavailability characteristics, that can be solve designing a new drug delivery system for CUM to treat SD. Cationic solid lipid nanoparticles (CSLN) were developed and physicochemically analyzed. The ingredients and methods adopted in this study promoted the successful preparation of CSLN with a monodispersed particle size of 218.4-238.6 nm and a polydispersity index of 0.156-0.350. A differential scanning calorimetric assay demonstrated that CUM was incorporated. The atomic force microscopy images showed uniform spherical particles, and light scattering technique confirmed the size of the particles. The zeta potential of the CSLN was +23.1 to +30.1 mV, which is important in targeting the drug to the diseased tissue that presents unregulated apoptosis. All formulations behaved as controlled drug delivery systems of CUM, as demonstrated by an in vitro drug release study, which delayed the start of drug release from formulations. At the end of the experiment, the formulations had released 14.74-21.23% of the incorporated CUM. In conclusion, the results suggest the potential of this CSLN as a controlled CUM delivery system for the treatment of SD.

Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms.

Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.

Three-dimensional analysis of jaw kinematic alterations in patients with chronic TMD - disc displacement with reduction.

The study investigated whether chronic TMD patients with disc displacement with reduction (DDR), performing non-assisted maximum jaw movements, presented any changes in their mandibular kinematics with respect to an age-matched control group. Moreover, it was examined whether jaw kinematics and a valid clinic measure of oro-facial functional status have significant associations. Maximum mouth opening, mandible protrusion and bilateral laterotrusions were performed by 20 patients (18 women, 2 men; age, 18-34 years) and 20 healthy controls (17 women, 3 men; age, 20-31 years). The three-dimensional coordinates of their mandibular interincisor and condylar reference points were recorded by means of an optoelectronic motion analyser and were used to quantitatively assess their range of motion, velocity, symmetry and synchrony. Three functional indices (opening-closing, mandibular rototranslation, laterotrusion - right and left - and protrusion) were devised to summarise subject's overall performance, and their correlation with the outcome of a clinical protocol, the oro-facial myofunctional evaluation with scores (OMES), was investigated. TMD patients were able to reach maximum excursions of jaw movements comparable to healthy subjects' performances. However, their opening and closing mandibular movements were characterised by remarkable asynchrony of condylar translation. They had also reduced jaw closing velocity and asymmetric laterotrusions. The functional indices proved to well summarise the global condition of jaw kinematics, highlighting the presence of alterations in TMD-DDR patients, and were linearly correlated with the oro-facial functional status. The jaw kinematic alterations seem to reflect both oro-facial motor behaviour adaptation and a DDR-related articular impairment.

The universal growth rate behavior and regime transition in adherent cell colonies.

In this work, we used five cell lineages, cultivated in vitro, to show they follow a common functional form to the growth rate: a sigmoidal curve, suggesting that competition and cooperation (usual mechanisms for systems with this behavior) might be present. Both theoretical and experimental investigations, on the causes of this behavior, are challenging for the research field; since the sigmoidal form to the growth rate seems to absorb important properties of such systems, e.g., cell deformation and statistical interactions. We shed some light on this subject by showing how cell spreading affects the radius behavior of the growing colonies. Doing numerical time derivatives of the experimental data, we obtained the growth rates. Using reduced variables for the time and rates, we obtained the collapse of all colonies growth rates onto one curve with sigmoidal shape. This suggests a universal-type behavior, with regime transition related to a morphological transition of adherent cell colonies.

Iron oxide nanostructured electrodes for detection of copper(II) ions.

Iron oxide nanostructured (ION) electrodes were assembled layer-by-layer onto ITO-coated glass substrates and their structure, morphology, and electrochemical properties were investigated, the latter aiming at the development of a chemical sensor for Cu2+. The electrodes were built by immersing the substrate alternately into an aqueous colloidal suspension of positively charged magnetite nanoparticles (np-Fe3O4, 8 nm) and an aqueous solution of anionic sodium sulfonated polystyrene (PSS). The adsorbed amount of both materials was monitored ex-situ by UV-vis spectroscopy and it was found to increase linearly with the number of deposition cycles. The resulting films feature a densely-packed structure of magnetite nanoparticles, as suggested by AFM and Raman spectroscopy, respectively. Cyclic voltammograms of electrodes immersed in acetate buffer (pH 4.6) displayed three electrochemical events that were tentatively ascribed to the reduction of Fe(III) oxy-hydroxide to magnetite, reduction of maghemite to magnetite, and finally oxidation of magnetite to maghemite. The effect of np-Fe3O4/PSS bilayers on the ION electrode performance was to increase the anodic and cathodic currents produced during electrochemical oxidation-reduction of the Fe(CN)(3-/4-) redox couple. With more bilayers, the ION electrode provided higher anodic/cathodic currents. Moreover, the redox couple exhibited a quasi-reversible behavior at the ION electrode as already observed with other working electrode systems. Fitting of voltammetry data provided the apparent electron transfer constants, which were found to be higher in ION electrodes for both redox couples (Fe(CN)(3-/4-) and Cu(2+/0)). By means of differential pulsed anodic stripping voltammetry, the ION electrodes were found to respond linearly to the presence of Cu2+ in aqueous samples in the range between 1.0 and 8.0 x 10(-6) mol x L(-1) and displayed a limit of detection of 0.3 x 10(-8) mol x L(-1). The sensitivity was - 0.6µA/µmol x L(-1). In standard addition and recovery experiments performed with tap water the recovery was about 102%-119%. In similar experiments conducted with ground and instant coffee samples the recovery was 92.5% and 103%, respectively. Furthermore, the ION electrodes were almost insensitive to the presence of common interfering ions, such as Zn2+, Mn2+, Ni2+, and Fe3+, even at concentrations ten times higher than that of Cu2+.

Basic ingredients for mathematical modeling of tumor growth in vitro: cooperative effects and search for space.

Based on the literature data from HT-29 cell monolayers, we develop a model for its growth, analogous to an epidemic model, mixing local and global interactions. First, we propose and solve a deterministic equation for the progress of these colonies. Thus, we add a stochastic (local) interaction and simulate the evolution of an Eden-like aggregate by using dynamical Monte Carlo methods. The growth curves of both deterministic and stochastic models are in excellent agreement with the experimental observations. The waiting times distributions, generated via our stochastic model, allowed us to analyze the role of mesoscopic events. We obtain log-normal distributions in the initial stages of the growth and Gaussians at long times. We interpret these outcomes in the light of cellular division events: in the early stages, the phenomena are dependent each other in a multiplicative geometric-based process, and they are independent at long times. We conclude that the main ingredients for a good minimalist model of tumor growth, at mesoscopic level, are intrinsic cooperative mechanisms and competitive search for space.

The effect of fermented milk on the deciduous enamel in the presence and absence of fluoride: in vitro study.

AIM: This study assessed the effect of fermented milk on the enamel of primary teeth in the presence and absence of fluoride. METHODS: Sixty enamel blocks (4X4 mm) underwent surface microhardness analysis (Knoop). The blocks were randomly distributed into 5 groups of 12 samples in each group according to the following treatments: Group 1) pH cycling and fermented milk (control); Group 2) pH cycling and dentifrice; Group 3) pH cycling and fermented milk and dentifrices; Group 4) varnish and pH cycling and fermented milk; Group 5) varnish and pH cycling and fermented milk and dentifrice. After the treatments, new microhardness determination was carried out and the surface microhardness change ratio was calculated (%SMH). The data were submitted to the Shapiro-Wilk normality test, ANOVA test, Tukey's test and paired t-test (P<0.05). RESULTS: It was observed that after treatment, all groups showed statistically significant reduction (P<0.05) for initial surface microhardness. Group 1 showed the lowest microhardness (73.01±9.68 KNH) compared to groups 2, 3 and 4. Group 5 (172.5±45.89KNH) showed a greater surface microhardness than Group 4 (122.0±22.33 KNH). CONCLUSION: It was concluded that the fermented milk adversely altered the microhardness of the samples and that fluorine contributes to a smaller reduction in the microhardness change ratio (SMH%). The combined solution of toothpaste with fluoride varnish provided a lower surface microhardness reduction of the samples.

Temperature-dependent Raman study of thermal parameters in CdS quantum dots.

We report on the strong temperature-dependent thermal expansion, α(D), in CdS quantum dots (QDs) embedded in a glass template. We have performed a systematic study by using the temperature-dependent first-order Raman spectra, in CdS bulk and in dot samples, in order to assess the size dependence of α(D), and where the role of the compressive strain provoked by the glass host matrix on the dot response is discussed. We report the Grüneisen mode parameters and the anharmonic coupling constants for small CdS dots with mean radius R âˆ¼ 2.0 nm. We found that γ parameters change, with respect to the bulk CdS, in a range between 20 and 50%, while the anharmonicity contribution from two-phonon decay channel becomes the most important process to the temperature-shift properties.

Seminal parameters and field fertility of cryopreserved donkey jack semen after insemination of horse mares.

REASONS FOR PERFORMING STUDY: As mule production is often concentrated in remote areas of the world, a simplified semen cryopreservation protocol is required. AIM: To compare the seminal parameters of cryopreserved donkey semen in lactose-EDTA and lactose-yolk extenders and the fertility rates on horse mares. METHODS: TRIAL 1: Sperm total and progressive motility, vigour (scale 0-5), morphology (major and minor defects) and plasma membrane integrity (HOST) were evaluated in 25 ejaculates from 5 donkey jacks immediately after collection (raw), after chilling to 5°C (chilled) and after freezing/thawing. The semen was mixed with skimmed-milk extender, centrifuged, and then re-suspended in lactose-EDTA or lactose-yolk extender. Semen was loaded into 0.5 ml straws and chilled to 5°C for 1 h, after which samples were either evaluated (chilled semen) or placed above liquid nitrogen for 20 min prior to immersion. Seminal parameters were evaluated by ANOVA and Tukey's test. TRIAL 2: Cryopreserved semen from 3 males was used to inseminate 53 mares at 60 oestrous cycles randomly assigned to lactose-yolk (n = 30 cycles) or lactose-EDTA (n = 30 cycles) extenders. Pregnancy diagnosis was performed 15 and 25 days post ovulation. The pregnancy rates were compared using Chi-squared tests. RESULTS: TRIAL 1: No significant differences were evident in any seminal parameters between extenders after either chilling or cryopreservation. Total and progressive motility were significantly (P<0.05) lower in cryopreserved semen than raw and chilled semen for both extenders. TRIAL 2: Pregnancy rates did not significantly differ between extenders (lactose-EDTA extender 53.33 and 43.33%; lactose-yolk 50.0 and 46.66% for Days 15 and 25 post ovulation, respectively). CONCLUSIONS: Cryopreservation of donkey semen using the simplified lactose-yolk extender resulted in similar seminal parameters and fertility rates when compared to lactose-EDTA extender. POTENTIAL RELEVANCE: Lactose-yolk extender may be advocated as a simple, easy to prepare extender, for use in geographically isolated enterprises producing mules throughout the world.

HLA-G polymorphism influences the susceptibility to HCV infection in sickle cell disease patients.

Despite its well known monogenic etiopathogenesis, sickle cell disease (SCD) is characterized by a striking variability of clinical presentation. There is growing evidence that genetic factors may be involved in this variability. Human leukocyte antigen (HLA)-G is a non-classical HLA molecule which was shown to be expressed at sites of inflammation and in inflammatory diseases. Besides its large and highly polymorphic promoter region, the 3' UTR region seems also to play an important role on regulating HLA-G expression. We investigated the influence of the 14 pb (rs1704) and the +3142 (rs1063320) HLA-G polymorphisms in 93 SCD patients in order to evaluate its potential role on clinical parameters. Twenty-one patients presented an HCV infection. Among all SCD patients 16 (22.2%) were homozygous for the +3142C genotype, none of them hepatitis C (HCV) positive. Controlling for blood transfusions in the last year, the C allele represented a dose dependent protection effect for HCV infection (PR = 0.41; 95% CI: 0.24-0.71). The +3142C allele was also underrepresented among patients with history of respiratory-tract infections. Our results support a role of the +3142 polymorphism in the susceptibility to infections, in particular to HCV infection, and suggest a possible interference of the HLA-G molecule in the response to infections, among SCD patients.

Detection of charge distributions in insulator surfaces.

Charge distribution in insulators has received considerable attention but still poses great scientific challenges, largely due to a current lack of firm knowledge about the nature and speciation of charges. Recent studies using analytical microscopies have shown that insulators contain domains with excess fixed ions forming various kinds of potential distribution patterns, which are also imaged by potential mapping using scanning electric probe microscopy. Results from the authors' laboratory show that solid insulators are seldom electroneutral, as opposed to a widespread current assumption. Excess charges can derive from a host of charging mechanisms: excess local ion concentration, radiochemical and tribochemical reactions added to the partition of hydroxonium and hydronium ions derived from atmospheric water. The last factor has been largely overlooked in the literature, but recent experimental evidence suggests that it plays a decisive role in insulator charging. Progress along this line is expected to help solve problems related to unwanted electrostatic discharges, while creating new possibilities for energy storage and handling as well as new electrostatic devices.

Electronic band effects on the spin disorder resistivity of Gd(4)(Co(1-x)Cu(x))(3) compounds.

We present a study of the spin disorder resistivity ([Formula: see text]) and the electronic specific heat coefficient (γ) in Gd(4)(Co(1-x)Cu(x))(3) compounds, with x = 0.00, 0.05, 0.10, 0.20 and 0.30. The experimental results show a strongly nonlinear dependence of [Formula: see text] on the average de Gennes factor (G(av)) which, in similar intermetallic compounds, is usually attributed to the existence of spin fluctuations on the Co 3d bands. Values of γ were found around 110 mJ mol(-1) K(-2) for the Gd(4)(Co(1-x)Cu(x))(3) compounds, much larger than 38.4 mJ mol(-1) K(-2) found for the isostructural nonmagnetic Y(4)Co(3) compound. Using a novel type of analysis we show that the ratio [Formula: see text] follows a well-defined linear dependence on G(av), which is expected when appropriate dependencies with the effective electron mass are taken into account. This indicates that band structure effects, rather than spin fluctuations, could be the main cause for the strong electron scattering and γ enhancement observed in the Gd(4)(Co(1-x)Cu(x))(3) compounds. A discussion on relevant features of magnetization and electrical resistivity data, for the same series of compounds, is also presented.

Effects of confinement on the electron-phonon interaction in Al(0.18)Ga(0.82)As/GaAs quantum wells.

Photoluminescence measurements at different temperatures have been performed to investigate the effects of confinement on the electron-phonon interaction in GaAs/AlGaAs quantum wells (QWs). A series of samples with different well widths in the range from 150 up to 750 Å was analyzed. Using a fitting procedure based on the Pässler-p model to describe the temperature dependence of the exciton recombination energy, we determined a fit parameter which is related to the strength of the electron-phonon interaction. On the basis of the behavior of this fit parameter as a function of the well width thickness of the samples investigated, we verified that effects of confinement on the exciton recombination energy are still present in QWs with well widths as large as 450 Å. Our findings also show that the electron-phonon interaction is three times stronger in GaAs bulk material than in Al(0.18)Ga(0.82)As/GaAs QWs.

Analysis of the association of polymorphism in the osteoprotegerin gene with susceptibility to chronic kidney disease and periodontitis.

BACKGROUND AND OBJECTIVE: Chronic kidney disease (CKD) is a complex disorder, which results in several complications involving disturbance of mineral metabolism. Periodontal disease is an infectious disease that appears to be an important cause of systemic inflammation in CKD patients. Periodontal disease is characterized by clinical attachment loss (CAL) caused by alveolar bone resorption around teeth, which may lead to tooth loss. Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. Polymorphisms are the main source of genetic variation, and single nucleotide polymorphisms (SNPs) have been reported as major modulators of disease susceptibility. The aim of this study was to investigate the association of a polymorphism located at position -223 in the untranslated region of the OPG gene, previously known as -950, with susceptibility to CKD and periodontal disease. MATERIAL AND METHODS: A sample of 224 subjects without and with CKD (in hemodialysis) was divided into groups with and without periodontal disease. The OPG polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: No association was found between the studied OPG polymorphism and susceptibility to CKD or periodontal disease. CONCLUSION: It was concluded that polymorphism OPG-223 (C/T) was not associated with CKD and periodontal disease in a Brazilian population. Studies on other polymorphisms in this and other genes of the host response could help to clarify the involvement of bone metabolism mediators in the susceptibility to CKD and periodontal disease.

Comparative bioavailability of three ibuprofen formulations in healthy human volunteers.

OBJECTIVE: To assess the bioequivalence of three ibuprofen formulations (Test formulation: ibuprofen (400 mg capsule) manufactured by Cardinal Health Brasil 402 Ltda. (Sorocaba, Brazil) and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. (SA poundo Paulo, Brazil); Reference formulation (1): ibuprofen (AdvilA(R); 2 A 200 mg coated tablet) from Wyeth-Whitehall Ltda. (Itapevi, Brazil); Reference formulation (2): ibuprofen (AliviumA; 8 ml A 50 mg/ml solution) from Schering Plough S.A. (Rio de Janeiro, Brazil)) in 24 healthy volunteers of both sexes. METHODS: The study was conducted using an open, randomized, three-period crossover design with at least 5-day washout interval. Plasma samples were obtained over a 24-h period. Plasma ibuprofen concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with negative ion electrospray ionization using multiple reaction monitoring (MRM). The following pharmacokinetic parameters were obtained from the ibuprofen plasma concentration vs. time curves: AUC(last), AUC(trunctmax), AUC(inf) and C(max). RESULTS: The limit of quantification for ibuprofen was 0.1 microg A ml(1). The geometric mean with corresponding 90% confidence interval (CI) for Test/Reference (1) percent ratios were 114.24% (90% CI = 105.67, 123.50%) for C(max), 98.97% (90% CI = 94.69, 103.44%) for AUC(last) and 99.40% (90% CI = 95.21, 103.78%) for AUC(inf). The geometric mean and respective 90% confidence interval (CI) for Test/Reference (2) percent ratios were 108.38% (90% CI = 100.19, 117.25%) for C(max), 100.79% (90% CI = 96.39, 105.40%) for AUC(last) and 101.26% (90% CI = 96.94, 105.77%) for AUC(inf); t(max) for the 400 mg Test capsule was shorter than that for the 2 A 200 mg Reference (1) tablets (p < 0.002). CONCLUSION: Since the 90% CI for AUC(last), AUC(inf) and Cmax ratios were within the 80 - 125% interval proposed by the US FDA, it was concluded that ibuprofen formulation manufactured by Cardinal Health Brasil 402 Ltda. and licensed to Boehringer Ingelheim do Brasil Quim. e Farm. Ltda. is bioequivalent to the AdvilA and AliviumA formulations with regard to both the rate and the extent of absorption.