Electroanalytical determination of promethazine hydrochloride in pharmaceutical formulations on highly boron-doped diamond electrodes using square-wave adsorptive voltammetry

The electrochemical oxidation of promethazine hydrochloride was made on highly boron-doped diamond electrodes. Cyclic voltammetry experiments showed that the oxidation mechanisms involved the formation of an adsorbed product that is more readily oxidized, producing a new peak with lower potential values whose intensity can be increased by applying the accumulation potential for given times. The parameters were optimized and the highest current intensities were obtained by applying +0.78 V for 30 seconds. The square-wave adsorptive voltammetry results obtained in BR buffer showed two well-defined peaks, dependent on the pH and on the voltammetric parameters. The best responses were obtained at pH 4.0, frequency of 50 s(-1), step of 2 mV, and amplitude of 50 mV. Under these conditions, linear responses were obtained for concentrations from 5.96 x 10(-7) to 4.76 x 10(-6) mol L-1, and calculated detection limits of 2.66 x 10(-8) mol L-1 (8.51 mu g L-1) for peak 1 and of 4.61 x 10(-8) mol L-1 (14.77 mu g L-1) for peak 2. The precision and accuracy were evaluated by repeatability and reproducibility experiments, which yielded values of less than 5.00% for both voltammetric peaks. ne applicability of this procedure was tested on commercial formulations of promethazine hydrochloride by observing the stability, specificity, recovery and precision of the procedure in complex samples. All results obtained were compared to recommended procedure by British Pharmacopeia. The voltammetric results indicate that the proposed procedure is stable and sensitive, with good reproducibility even when the accumulation steps involve short times. It is therefore very suitable for the development of the electroanalytical procedure, providing adequate sensitivity and a reliable method.

Development and Application of a Highly Selective Biomimetic Sensor for Detection of Captopril, an Important Ally in Hypertension Control

A biomimetic sensor is proposed as a promising new analytical method for determination of captopril in different classes of samples. The sensor was prepared by modifying a carbon paste electrode with iron (II) phthalocyanine bis(pyridine) [FePe(dipy)] complex. Amperometric measurements in a batch analytical mode were first carried out in order to optimize the sensor response. An applied potential lower than 0.2 V vs Ag vertical bar AgCl in 0.1 mol L(-1) of TRIS buffer at pH 8.0 provided the best response, with a linear range of 2.5 x 10(-5) to 1.7 x 10(-4) mol L(-1). A detailed investigation of the selectivity of the sensor, employing seventeen other drugs, was also performed. Recovery studies were carried out using biological and environment samples in order to evaluate the sensor`s potential for use with these sample classes. Finally, the performance of the biomimetic sensor was optimized in a flow injection (FIA) system using a wall jet electrochemical cell. Under optimized flow conditions, a broad linear response range, from 5.0 x 10(-4) to 2.5 x 10(-2) mol L(-1), was obtained for captopril, with a sensitivity of 210 +/- 1 mu A L mol(-1).

Ability of Ru complexes for ROMP tuned through a combination of phosphines and amines

Polynorbonerne with high molecular weight was obtained via ring opening metathesis polymerization using catalysts derived from [RuCl(2)(PPh(2)Bz)(2) L] (1 for L = PPh(2) Bz; 2 for L = piperidine) type of complexes when in the presence of ethyl diazoacetate in CHCl(3). The polymer precipitated within a few minutes at 50 degrees C when using 1 with ca. 50% yield ([NBE]/[Ru] = 5000). Regarding 2, for either 30 min at 25 C or 5 min at 50 degrees C, more than 90% of yields are obtained; and at 50 C for 30 min a quantitative yield is obtained. The yield and PDI values are sensitive to the [NBE]/[Ru] ratio. The reaction of 1 with either isonicotinamide or nicotinamide produces six-coordinated complexes of [RuCl(2)(PPh(2)Bz)(2)(L)(2)] type, which are almost inactive and produce only small amounts of polymers at 50 C for 30 min. Thus, we Concluded that the novel complexes show very distinct reactivities for ROMP of NBE. This has been rationalized on account of a combination of synergistic effects of the phosphine-amine ancillary ligands. (C) 2009 Elsevier B.V. All rights reserved.

Busca pelo homem social nas organizações: indícios, constatações, possibilidades

This study approaches the question of organizations in search for competitiveness when globalization, knowledge and technological advances in the First World is a challenge in developing countries. The case study research focus on Bahia Sul ¿ a large organization which belongs to the important sector of paper and cellulose, especially in terms of exports. This study analyses an organization in that underpriviledged situation of a third world country in which the majority of organizational strategies are heavily thrown on people who are simultaneously reduced to instruments for economic results and who are highly demanded in terms of productivity and creativity. Due to that reality, references chosen present two key contrasting concepts. Mass man, going back to Taylor¿s blue collars as well as to Marcel¿s knowledgeable but empty words man, whose abilities do not feet his needs, in contrast with rogerian expectations of person as a mutable and continuously enriched human being and with habermasian position looking for political and decision making participation in work an social situations. Results show a strong presence of mass man, despite his technological knowledge, and scarce indications of the social man and which appears in mere aspirations out of labor situations. Conclusions emphasize a need for coherence between organizational practices in search for competitiveness and expectations on persons¿ performance because they stimulate exchanges in terms of working places for obedience and some material comfort which is aggravated by the fact that any possibility of personal fulfillment is interpreted as only possible in out of work situations. Competitiveness in such a context is not to be expected.

Does location matter to explain loan interest rates? evidence from Brazilian highly concentrad local markets

O setor bancário brasileiro é altamente concentrado. Embora concentração não signifique necessariamente que o mercado se comporta de forma não competitiva, o grau de competição é freqüentemente questionado no país. Utilizando uma base de dados extensiva e única do mercado de crédito brasileiro, este trabalho procura avaliar muitos dos fatores que contribuem para a variação nas taxas de juros cobradas pelos bancos nos diferentes mercados locais em duas categorias de empréstimos. A concentração não é significante ou mesmo associada a taxas de juros mais baixas, em parte devido ao papel dos bancos públicos. O prêmio de default é positivo e significante, e há alguma evidência de imperfeição de mercado. Neste trabalho, analisamos também o comportamento de precificação dos bancos em diferentes regiões do país, e encontramos que a localização é importante para explicar as taxas de juros dos empréstimos.

How the full opening of the capital account to highly liquid financial markets led Latin America to two and a half cycles of ‘mania, panic and crash’

Latin America has recently experienced three cycles of capital inflows, the first two ending in major financial crises. The first took place between 1973 and the 1982 ‘debt-crisis’. The second took place between the 1989 ‘Brady bonds’ agreement (and the beginning of the economic reforms and financial liberalisation that followed) and the Argentinian 2001/2002 crisis, and ended up with four major crises (as well as the 1997 one in East Asia) — Mexico (1994), Brazil (1999), and two in Argentina (1995 and 2001/2). Finally, the third inflow-cycle began in 2003 as soon as international financial markets felt reassured by the surprisingly neo-liberal orientation of President Lula’s government; this cycle intensified in 2004 with the beginning of a (purely speculative) commodity price-boom, and actually strengthened after a brief interlude following the 2008 global financial crash — and at the time of writing (mid-2011) this cycle is still unfolding, although already showing considerable signs of distress. The main aim of this paper is to analyse the financial crises resulting from this second cycle (both in LA and in East Asia) from the perspective of Keynesian/ Minskyian/ Kindlebergian financial economics. I will attempt to show that no matter how diversely these newly financially liberalised Developing Countries tried to deal with the absorption problem created by the subsequent surges of inflow (and they did follow different routes), they invariably ended up in a major crisis. As a result (and despite the insistence of mainstream analysis), these financial crises took place mostly due to factors that were intrinsic (or inherent) to the workings of over-liquid and under-regulated financial markets — and as such, they were both fully deserved and fairly predictable. Furthermore, these crises point not just to major market failures, but to a systemic market failure: evidence suggests that these crises were the spontaneous outcome of actions by utility-maximising agents, freely operating in friendly (‘light-touch’) regulated, over-liquid financial markets. That is, these crises are clear examples that financial markets can be driven by buyers who take little notice of underlying values — i.e., by investors who have incentives to interpret information in a biased fashion in a systematic way. Thus, ‘fat tails’ also occurred because under these circumstances there is a high likelihood of self-made disastrous events. In other words, markets are not always right — indeed, in the case of financial markets they can be seriously wrong as a whole. Also, as the recent collapse of ‘MF Global’ indicates, the capacity of ‘utility-maximising’ agents operating in (excessively) ‘friendly-regulated’ and over-liquid financial market to learn from previous mistakes seems rather limited.

How the full opening of the capital account to highly liquid financial markets led Latin America to two and a half cycles of ‘mania, panic and crash’

Latin America has recently experienced three cycles of capital inflows, the first two ending in major financial crises. The first took place between 1973 and the 1982 ‘debt-crisis’. The second took place between the 1989 ‘Brady bonds’ agreement (and the beginning of the economic reforms and financial liberalisation that followed) and the Argentinian 2001/2002 crisis, and ended up with four major crises (as well as the 1997 one in East Asia) — Mexico (1994), Brazil (1999), and two in Argentina (1995 and 2001/2). Finally, the third inflow-cycle began in 2003 as soon as international financial markets felt reassured by the surprisingly neo-liberal orientation of President Lula’s government; this cycle intensified in 2004 with the beginning of a (purely speculative) commodity price-boom, and actually strengthened after a brief interlude following the 2008 global financial crash — and at the time of writing (mid-2011) this cycle is still unfolding, although already showing considerable signs of distress. The main aim of this paper is to analyse the financial crises resulting from this second cycle (both in LA and in East Asia) from the perspective of Keynesian/ Minskyian/ Kindlebergian financial economics. I will attempt to show that no matter how diversely these newly financially liberalised Developing Countries tried to deal with the absorption problem created by the subsequent surges of inflow (and they did follow different routes), they invariably ended up in a major crisis. As a result (and despite the insistence of mainstream analysis), these financial crises took place mostly due to factors that were intrinsic (or inherent) to the workings of over-liquid and under-regulated financial markets — and as such, they were both fully deserved and fairly predictable. Furthermore, these crises point not just to major market failures, but to a systemic market failure: evidence suggests that these crises were the spontaneous outcome of actions by utility-maximising agents, freely operating in friendly (light-touched) regulated, over-liquid financial markets. That is, these crises are clear examples that financial markets can be driven by buyers who take little notice of underlying values — investors have incentives to interpret information in a biased fashion in a systematic way. ‘Fat tails’ also occurred because under these circumstances there is a high likelihood of self-made disastrous events. In other words, markets are not always right — indeed, in the case of financial markets they can be seriously wrong as a whole. Also, as the recent collapse of ‘MF Global’ indicates, the capacity of ‘utility-maximising’ agents operating in unregulated and over-liquid financial market to learn from previous mistakes seems rather limited.

Functionalization of dendrimers for improved gene delivery to mesenchymal stem cell

Disease, injury, and age problems compromise human quality of life and continuously motivate the search for new and more efficacious therapeutic approaches. The field of Tissue Regeneration and Engineering has greatly evolved over the last years, mainly due to the combination of the important advances verified in Biomaterials Science and Engineering with those of Cell and Molecular Biology. In particular, a new and promising area arose – Nanomedicine – that takes advantage of the extremely small size and especial chemical and physical properties of Nanomaterials, offering powerful tools for health improvement. Research on Stem Cells, the self-renewing progenitors of body tissues, is also challenging to the medical and scientific communities, being expectable the appearance of new and exciting stem cell-based therapies in the next years. The control of cell behavior (namely, of cell proliferation and differentiation) is of key importance in devising strategies for Tissue Regeneration and Engineering. Cytokines, growth factors, transcription factors and other signaling molecules, most of them proteins, have been identified and found to regulate and support tissue development and regeneration. However, the application of these molecules in long-term regenerative processes requires their continuous presence at high concentrations as they usually present short half-lives at physiological conditions and may be rapidly cleared from the body. Alternatively, genes encoding such proteins can be introduced inside cells and be expressed using cell’s machinery, allowing an extended and more sustained production of the protein of interest (gene therapy). Genetic engineering of stem cells is particularly attractive because of their self-renewal capability and differentiation potential. For Tissue Regeneration and Engineering purposes, the patient’s own stem cells can be genetically engineered in vitro and, after, introduced in the body (with or without a scaffold) where they will not only modulate the behavior of native cells (stem cell-mediated gene therapy), but also directly participate in tissue repair. Cells can be genetically engineered using viral and non-viral systems. Viruses, as a result of millions of years of evolution, are very effective for the delivery of genes in several types of cells, including cells from primary sources. However, the risks associated with their use (like infection and immunogenic reactions) are driving the search for non-viral systems that will efficiently deliver genetic material into cells. Among them, chemical methods that are promising and being investigated use cationic molecules as carriers for DNA. In this case, gene delivery and gene expression level remain relatively low when primary cells are used. The main goal of this thesis was to develop and assess the in vitro potential of polyamidoamine (PAMAM) dendrimers based carriers to deliver genes to mesenchymal stem cells (MSCs). PAMAM dendrimers are monodispersive, hyperbranched and nanospherical molecules presenting unique characteristics that make them very attractive vehicles for both drug and gene delivery. Although they have been explored for gene delivery in a wide range of cell lines, the interaction and the usefulness of these molecules in the delivery of genes to MSCs remains a field to be explored. Adult MSCs were chosen for the studies due to their potential biomedical applications (they are considered multipotent cells) and because they present several advantages over embryonic stem cells, such as easy accessibility and the inexistence of ethical restrictions to their use. This thesis is divided in 5 interconnected chapters. Chapter I provides an overview of the current literature concerning the various non-viral systems investigated for gene delivery in MSCs. Attention is devoted to physical methods, as well as to chemical methods that make use of polymers (natural and synthetic), liposomes, and inorganic nanoparticles as gene delivery vectors. Also, it summarizes the current applications of genetically engineered mesenchymal stem cells using non-viral systems in regenerative medicine, with special focus on bone tissue regeneration. In Chapter II, the potential of native PAMAM dendrimers with amine termini to transfect MSCs is evaluated. The level of transfection achieved with the dendrimers is, in a first step, studied using a plasmid DNA (pDNA) encoding for the β-galactosidase reporter gene. The effect of dendrimer’s generation, cell passage number, and N:P ratio (where N= number of primary amines in the dendrimer; P= number of phosphate groups in the pDNA backbone) on the level of transfection is evaluated, being the values always very low. In a second step, a pDNA encoding for bone morphogenetic protein-2, a protein that is known for its role in MSCs proliferation and differentiation, is used. The BMP-2 content produced by transfected cells is evaluated by an ELISA assay and its effect on the osteogenic markers is analyzed through several classical assays including alkaline phosphatase activity (an early marker of osteogenesis), osteocalcin production, calcium deposition and mineralized nodules formation (late osteogenesis markers). Results show that a low transfection level is enough to induce in vitro osteogenic differentiation in MSCs. Next, from Chapter III to Chapter V, studies are shown where several strategies are adopted to change the interaction of PAMAM dendrimers with MSCs cell membrane and, as a consequence, to enhance the levels of gene delivery. In Chapter III, generations 5 and 6 of PAMAM dendrimers are surface functionalized with arginine-glycine-aspartic acid (RGD) containing peptides – experiments with dendrimers conjugated to 4, 8 and 16 RGD units were performed. The underlying concept is that by including the RGD integrin-binding motif in the design of the vectors and by forming RGD clusters, the level of transfection will increase as MSCs highly express integrins at their surface. Results show that cellular uptake of functionalized dendrimers and gene expression is enhanced in comparison with the native dendrimers. Furthermore, gene expression is dependent on both the electrostatic interaction established between the dendrimer moiety and the cell surface and the nanocluster RGD density. In Chapter IV, a new family of gene delivery vectors is synthesized consisting of a PAMAM dendrimer (generation 5) core randomly linked at the periphery to alkyl hydrophobic chains that vary in length and number. Herein, the idea is to take advantage of both the cationic nature of the dendrimer and the capacity of lipids to interact with biological membranes. These new vectors show a remarkable capacity for internalizing pDNA, being this effect positively correlated with the –CH2– content present in the hydrophobic corona. Gene expression is also greatly enhanced using the new vectors but, in this case, the higher efficiency is shown by the vectors containing the smallest hydrophobic chains. Finally, chapter V reports the synthesis, characterization and evaluation of novel gene delivery vectors based on PAMAM dendrimers (generation 5) conjugated to peptides with high affinity for MSCs membrane binding - for comparison, experiments are also done with a peptide with low affinity binding properties. These systems present low cytotoxicity and transfection efficiencies superior to those of native dendrimers and partially degraded dendrimers (Superfect®, a commercial product). Furthermore, with this biomimetic approach, the process of gene delivery is shown to be cell surface receptor-mediated. Overall, results show the potential of PAMAM dendrimers to be used, as such or modified, in Tissue Regeneration and Engineering. To our knowledge, this is the first time that PAMAM dendrimers are studied as gene delivery vehicles in this context and using, as target, a cell type with clinical relevancy. It is shown that the cationic nature of PAMAM dendrimers with amine termini can be synergistically combined with surface engineering approaches, which will ultimately result in suitable interactions with the cytoplasmic membrane and enhanced pDNA cellular entry and gene expression. Nevertheless, the quantity of pDNA detected inside cell nucleus is always very small when compared with the bigger amount reaching cytoplasm (accumulation of pDNA is evident in the perinuclear region), suggesting that the main barrier to transfection is the nuclear membrane. Future work can then be envisaged based on the versatility of these systems as biomedical molecular materials, such as the conjugation of PAMAM dendrimers to molecules able to bind nuclear membrane receptors and to promote nuclear translocation.

Simultaneous analysis of free amino acids and biogenic amines in honey and wine samples using in loop orthophthalaldeyde derivatization procedure

This work presents a RP-HPLC method for the simultaneous quantification of free amino acids and biogenic amines in liquid food matrices and the results of the application to honey and wine samples obtained from different production processes and geographic origins. The developed methodology is based on a pre-column derivatization with o-phthaldialdehyde carried out in the sample injection loop. The compounds were separated in a Nova-Pack RP-C18 column (150 mm × 3.9 mm, 4 μm) at 35 °C. The mobile phase used was a mixture of phase A: 10 mM sodium phosphate buffer (pH 7.3), methanol and tetrahydrofuran (91:8:1); and phase B: methanol and phosphate buffer (80:20), with a flow rate of 1.0 ml/min. Fluorescence detection was used at an excitation wavelength of 335 nm and an emission wavelength of 440 nm. The separation and quantification of 19 amino acids and 6 amines was carried out in a single run as their OPA/MCE derivatives elute within 80 min, ensuring a reproducible quantification. The method showed to be adequate for the purpose, with an average RSD of 2% for the different amino acids; detection limits varying between 0.71 mg/l (Asn) and 8.26 mg/l (Lys) and recovery rates between 63.0% (Cad) and 98.0% (Asp). The amino acids present at the highest concentration in honey and wine samples were phenylalanine and arginine, respectively. Only residual levels of biogenic amines were detected in the analysed samples.

Hydroalumination of seleno acetylenes: a versatile generation and reactions of alpha-aluminate vinyl selenide intermediates in the highly regio and stereoselective synthesis of telluro(seleno)ketene acetals

The hydroalumination of butylseleno acetylenes with DIBAL-H followed by addition of n-butyllithium generated in situ the (Z)-butylseleno vinyl alanates intermediates which were captured with C(4)H(9)TeBr furnishing the (E)-telluro(seleno)ketene acetals exclusively. The isomers with opposite stereochemistry (Z)-telluro(seleno)ketene acetals were obtained by the reduction of phenylseleno acetylenes with lithium di-(isobutyl)-n-butyl aluminate hydride (Zweifel's reagent) followed by reaction of (E)-phenylseleno vinyl alanates intermediates with C(4)H(9)TeBr. (c) 2008 Elsevier Ltd. All rights reserved.

Shiitake (lentinula edodes) production on a sterilized bagasse substrate enriched with rice bran and sugarcane molasses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Protection levels of vaccinated pigeons (Columba livia) against a highly pathogenic newcastle disease virus strain

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)