DFT and electrochemical studies on nortriptyline oxidation sites

A study on the possible sites of oxidation and epoxidation of nortriptyline was performed using electrochemical and quantum chemical methods; these sites are involved in the biological responses (for example, hepatotoxicity) of nortriptyline and other similar antidepressants. Quantum chemical studies and electrochemical experiments demonstrated that the oxidation and epoxidation sites are located on the apolar region of nortriptyline, which will useful for understanding the molecule`s activity. Also, for the determination of the compound in biological fluids or in pharmaceutical formulations, we propose a useful analytical methodology using a graphite-polyurethane composite electrode, which exhibited the best performance when compared with boron-doped diamond or glassy carbon surfaces.

Structural and morphological studies on SiOxNy thin films

In this work, the structure and morphology of silicon oxynitride films deposited by the PECVD technique were studied. The films were deposited under two different conditions: (a) SiOxNy with chemical compositions varying from SiO2 to Si3N4 via the control of a N2O + N-2 + SiH4 gas mixture, and (b) Si-rich SiOxNy films via the control of a N2O + SiH4 gas mixture. The analyses were performed using X-ray near edge spectroscopy (XANES) at the Si-K edge, transmission electron microscopy (TEM) and Rutherford backscattering spectroscopy (RBS). For samples with chemical composition varying from SiO2 to Si3N4, the diffraction patterns obtained by TEM exhibited changes with the chemical composition, in agreement with the XANES results. For silicon-rich silicon oxynitride samples, the formation of a-Si clusters was observed and the possibility of obtaining Si nanocrystals after annealing depending on the composition and temperature was realized. (C) 2007 Elsevier B.V. All rights reserved.

Clinical and biochemical studies in mucopolysaccharidosis type II carriers

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers` and non-carriers` values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

Morphological and autoradiographic studies on the corneal and limbal epithelium of rabbits

The investigation was centered on the morphological features of the conjunctiva-cornea transition (limbus) of the rabbit eye and the proliferative behavior of its epithelium. The eyes were processed for examination with light and electron microscopy, as well as for autoradiography after intravitreal injection of [H-3]thymidine ([H-3]TdR). At the sites of extraocular muscle insertion, the vascularization of the stroma extended to the peripheral cornea, and the limbal epithelium was thin with its basal stratum made up by clear cuboidal cells. In between the muscle insertions, the cuboidal clear cells, as well as the stroma blood vessels; were scarce. At the light microscope level, the basement membrane was distinct in the cornea but not in the limbus or the conjunctiva. Autoradiographs demonstrated that, at the limbus, the basal cells migrated very quickly to the suprabasal region and remained there up to the 28-day interval. Labeled cells were identified in all epithelial layers of the cornea, including the basal one, at 21 and 28 days but not in the limbal basal clear cells. The rate of renewal of conjunctival epithelium was similar to that observed for the transition with scarce clear cells. The high-resolution autoradiographs demonstrated that the basal cuboidal clear limbal cells exhibit a quick renewal and that they are not label-retaining cells. These latter ones were detected all over the corneal epithelium and in the suprabasal layers of the limbus up to 28 days, in physiological conditions, without the need of stimulation by damage to the corneal epithelium.

Stereological and allometric studies on neurons and axo-dendritic synapses in the superior cervical ganglia of rats, capybaras and horses

The superior cervical ganglion (SCG) in mammals varies in structure according to developmental age, body size, gender, lateral asymmetry, the size and nuclear content of neurons and the complexity and synaptic coverage of their dendritic trees. In small and medium-sized mammals, neuron number and size increase from birth to adulthood and, in phylogenetic studies, vary with body size. However, recent studies on larger animals suggest that body weight does not, in general, accurately predict neuron number. We have applied design-based stereological tools at the light-microscopic level to assess the volumetric composition of ganglia and to estimate the numbers and sizes of neurons in SCGs from rats, capybaras and horses. Using transmission electron microscopy, we have obtained design-based estimates of the surface coverage of dendrites by postsynaptic apposition zones and model-based estimates of the numbers and sizes of synaptophysin-labelled axo-dendritic synaptic disks. Linear regression analysis of log-transformed data has been undertaken in order to establish the nature of the relationships between numbers and SCG volume (V(scg)). For SCGs (five per species), the allometric relationship for neuron number (N) is N=35,067xV (scg) (0.781) and that for synapses is N=20,095,000xV (scg) (1.328) , the former being a good predictor and the latter a poor predictor of synapse number. Our findings thus reveal the nature of SCG growth in terms of its main ingredients (neurons, neuropil, blood vessels) and show that larger mammals have SCG neurons exhibiting more complex arborizations and greater numbers of axo-dendritic synapses.

TL, OSL and ESR studies on beryllium oxide

Electron spin resonance (ESR) studies were carried out to identify the defect centres responsible for the thermoluminescence (TL) and optically stimulated luminescence (OSL) processes in BeO phosphor. Two defect centres were identified in irradiated BeO phosphor by ESR measurements, which were carried out at room temperature and these were assigned to an O(-) ion and Al(2+) centre. The O(-) ion (hole centre) correlates with the main 190 degrees C TL peak. The Al(2+) centre (electron centre), which acts as a recombination centre, also correlates to the 190 degrees C TL peak. A third centre, observed during thermal annealing studies, is assigned to an O(-) ion and is related to the high temperature TL at 317 degrees C. This centre also appears to be responsible for the observed OSL process in BeO phosphor. (c) 2010 Elsevier B.V. All rights reserved.

Kinetic and Crystallographic Studies on Glyceraldehyde-3-Phosphate Dehydrogenase from Trypanosoma cruzi in Complex with Iodoacetate

Kinetic and crystallographic studies on the formation of the complex between iodoacetate and the enzyme glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi were conducted in order to investigate the mechanistic and structural basis underlying enzyme inactivation. The crystallographic complex reveal important structural features useful for the design of novel inhibitors.

2D QSAR and similarity studies on cruzain inhibitors aimed at improving selectivity over cathepsin L

Hologram quantitative structure-activity relationships (HQSAR) were applied to a data set of 41 cruzain inhibitors. The best HQSAR model (Q(2) = 0.77; R-2 = 0.90) employing Surflex-Sim, as training and test sets generator, was obtained using atoms, bonds, and connections as fragment distinctions and 4-7 as fragment size. This model was then used to predict the potencies of 12 test set compounds, giving satisfactory predictive R-2 value of 0,88. The contribution maps obtained from the best HQSAR model are in agreement with the biological activities of the study compounds. The Trypanosoma cruzi cruzain shares high similarity with the mammalian homolog cathepsin L. The selectivity toward cruzam was checked by a database of 123 compounds, which corresponds to the 41 cruzain inhibitors used in the HQSAR model development plus 82 cathepsin L inhibitors. We screened these compounds by ROCS (Rapid Overlay of Chemical Structures), a Gaussian-shape volume overlap filter that can rapidly identify shapes that match the query molecule. Remarkably, ROCS was able to rank the first 37 hits as being only cruzain inhibitors. In addition, the area under the curve (AUC) obtained with ROCS was 0.96, indicating that the method was very efficient to distinguishing between cruzain and cathepsin L inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

Enzyme kinetics, structural analysis and molecular modeling studies on a series of Schistosoma mansoni PNP inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the development of novel drugs against schistosomiasis, a neglected tropical disease that affects about 200 million people worldwide. In the present work, enzyme kinetic studies were carried out in order to determine the potency and mechanism of inhibition of a series of SmPNP inhibitors. In addition to the biochemical investigations, crystallographic and molecular modeling studies revealed important molecular features for binding affinity towards the target enzyme, leading to the development of structure-activity relationships (SAR).

Quantum-chemical, NMR and X-ray diffraction studies on (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane

Time-averaged conformations of (+/-)-1-[3,4-(methylenedioxy)phenyl]-2-methylaminopropane hydrochloride (MDMA, ""ecstasy"") in D(2)O, and of its free base and trifluoroacetate in CDCl(3), were deduced from their (1)H NMR spectra and used to calculate their conformer distribution. Their rotational potential energy surface (PES) was calculated at the RHF/6-31G(d,p), 133LYP/6-31G(d,p), B3LYP/cc-pVDZ and AM1 levels. Solvent effects were evaluated using the polarizable continuum model. The NMR and theoretical studies showed that, in the free base, the N-methyl group and the ring are preferentially trans. This preference is stronger in the salts and corresponds to the X-ray structure of the hydrochloride. However, the energy barriers separating these forms are very low. The X-ray diffraction crystal structures of the anhydrous salt and its monohydrate differed mainly in the trans or cis relationship of the N-methyl group to the a-methyl, although these two forms interconvert freely in solution. (C) 2007 Elsevier Inc. All rights reserved.

Microcystins -LA, -YR, and -LR action on neutrophil migration

Microcystins (MCs) produced by some freshwater cyanobacterial species possess potent liver toxicity as evidenced by acute neutrophil infiltration. Here, we investigate the ability of three structurally distinct toxins (MC-LA, MC-LR, and MC-YR) to evoke neutrophil recruitment per se and their effects on migration pathways. Intravital Microscopic Studies showed that topical application of only MC-LR enhanced the numbers of rolling and adhered leukocytes in the endothelium of postcapillary mesenteric venules. The latter effects may be dependent upon induction of the synthesis and expression Of L-selectin and beta(2)-integrin in neutrophils, as assessed by flow cytometry and RT-PCR, respectively. Conversely, the three toxins promoted direct locomotion of neutrophils and enhanced their migration in response to NO, as measured by Boyden chamber assays, and increased intracellular calcium, a messenger in the chemotaxic process. In conclusion, our results show that MCs act on specific pathways of neutrophil recruitment, indicating their potential effect on neutrophils activation. (C) 2009 Elsevier Inc. All rights reserved.

Discrepancies among ecological, household, and individual data on fruits and vegetables consumption in Brazil

Information on fruits and vegetables consumption in Brazil in the three levels of dietary data was analyzed and compared. Data about national supply came from Food Balance Sheets compiled by the FAO; household availability information was obtained from the Brazilian National Household Budget Survey (HBS); and actual intake information came from a large individual dietary intake survey that was representative of the adult population of São Paulo city. All sources of information were collected between 2002 and 2003. A subset of the HBS, representative of São Paulo city, was used in our analysis in order to improve the quality of the comparison with actual intake data. The ratio of national supply to household availability of fruits and vegetables was 2.6 while the ratio of national supply to actual intake was 4.0. The discrepancy ratio in the comparison between household availability and actual intake was smaller, 1.6. While the use of supply and availability data has advantages, as lower cost, must be taken into account that these sources tend to overestimate actual intake of fruits and vegetables.

Synchrotron X-ray powder diffraction and extended X-ray absorption fine structure spectroscopy studies on nanocrystalline ZrO(2)-CaO solid solutions

The crystal structure and the local atomic order of a series of nanocrystalline ZrO(2)-CaO solid solutions with varying CaO content were studied by synchrotron radiation X-ray powder diffraction and extended X-ray absorption fine structure (EXAFS) spectroscopy. These samples were synthesized by a pH-controlled nitrate-glycine gel-combustion process. For CaO contents up to 8 mol%, the t' form of the tetragonal phase (c/a > 1) was identified, whereas for 10 and 12 mol% CaO, the t '' form (c/a=1; oxygen anions displaced from their ideal positions in the cubic phase) was detected. Finally, the cubic phase was observed for solid solutions with CaO content of 14 mol% CaO or higher. The t'/t '' and t ''/cubic compositional boundaries were determined to be at 9 (1) and 13 (1) mol% CaO, respectively. The EXAFS study demonstrated that this transition is related to a tetragonal-to-cubic symmetry change of the first oxygen coordination shell around the Zr atoms.

Electrochemical and spectroscopic studies of ethanol oxidation on Pt stepped surfaces modified by tin adatoms

Ethanol oxidation on platinum stepped surfaces vicinal to the (111) pole modified by tin has been studied to determine the role of this adatom in the oxidation mechanism. Tin has been slowly deposited so that the initial stages of the deposition take place on the step, and deposition on the terrace only occurs when the step has been completely decorated. Voltammetric and chronoamperometric experiments demonstrate that tin on the step catalyzes the oxidation. The maximum enhancement is found when the step is completely decorated by tin. FTIR experiments using normal and isotopically labeled ethanol have been used to elucidate the effect of the tin adatoms in the mechanism. The obtained results indicate that the role of tin is double: (i) when the surface has sites capable of breaking the C-C bond of the molecule, that is, when the step sites are not completely covered by tin, it promotes the oxidation of CO formed from the molecular fragments to CO(2) through a bifunctional mechanism and (ii) it catalyzes the oxidation of ethanol to acetic acid.

Mapping the Contemporary Studies on Alliances and Strategic Networks

The competition among the companies depends on the velocity and efficience they can create and commercialize knowledge in a timely and cost-efficient manner. In this context, collaboration emerges as a reaction to the environmental changes. Although strategic alliances and networks have been exploited in the strategic literature for decades, the complexity and continuous usage of these cooperation structures, in a world of growing competition, justify the continuous interest in both themes. This article presents a scanning of the contemporary academic production in strategic alliances and networks, covering the period from January 1997 to august 2007, based on the top five journals accordingly to the journal of Citation Report 2006 in the business and management categories simultaneously. The results point to a retraction in publications about strategic alliances and a significant growth in the area of strategic. networks. The joint view of strategic alliances and networks, cited by some authors a the evolutionary path of study, still did not appear salient. The most cited topics found in the alliance literature are the governance structure, cooperation, knowledge transfer, culture, control, trust, alliance formation,,previous experience, resources, competition and partner selection. The theme network focuses mainly on structure, knowledge transfer and social network, while the joint vision is highly concentrated in: the subjects of alliance formation and the governance choice.