Determinação de açucares em bagaço de palha de cana-de-açúcar por cromatografia líquida de alta eficiência com detecção eletroquímica utilizando eletrodos de nanotubos modificados com óxidos metálicos

Pós-graduação em Química - IQ

Avaliação técnico-econômica da produção de enzimas celulolíticas por fermentação em estado sólido

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo da variabilidade da região codificadora e 3'não traduzida do gene HLA-F no Brasil

Pós-graduação em Patologia - FMB

DESIGN AND ANALYSIS OF MULTIFUNCTIONAL ROBOT FOR NOTES

The elimination of all external incisions is an important step in reducing the invasiveness of surgical procedures. Natural Orifice Translumenal Endoscopic Surgery (NOTES) is an incision-less surgery and provides explicit benefits such as reducing patient trauma and shortening recovery time. However, technological difficulties impede the widespread utilization of the NOTES method. A novel robotic tool has been developed, which makes NOTES procedures feasible by using multiple interchangeable tool tips. The robotic tool has the capability of entering the body cavity through an orifice or a single incision using a flexible articulated positioning mechanism and once inserted is not constrained by incisions, allowing for visualization and manipulations throughout the cavity. Multiple interchangeable tool tips of the robotic device initially consist of three end effectors: a grasper, scissors, and an atraumatic Babcock clamp. The tool changer is capable of selecting and switching between the three tools depending on the surgical task using a miniature mechanism driven by micro-motors. The robotic tool is remotely controlled through a joystick and computer interface. In this thesis, the following aspects of this robotic tool will be detailed. The first-generation robot is designed as a conceptual model for implementing a novel mechanism of switching, advancing, and controlling the tool tips using two micro-motors. It is believed that this mechanism achieves a reduction in cumbersome instrument exchanges and can reduce overall procedure time and the risk of inadvertent tissue trauma during exchanges with a natural orifice approach. Also, placing actuators directly at the surgical site enables the robot to generate sufficient force to operate effectively. Mounting the multifunctional robot on the distal end of an articulating tube provides freedom from restriction on the robot kinematics and helps solve some of the difficulties otherwise faced during surgery using NOTES or related approaches. The second-generation multifunctional robot is then introduced in which the overall size is reduced and two arms provide 2 additional degrees of freedom, resulting in feasibility of insertion through the esophagus and increased dexterity. Improvements are necessary in future iterations of the multifunctional robot; however, the work presented is a proof of concept for NOTES robots capable of abdominal surgical interventions.

STATUS OF BROMETHALIN OUTSIDE THE UNITED STATES

ABSTRACT: Bromethalin has been extensively researched over the past decade in the United States, Switzerland, England, Denmark, and France. United States EPA registrations were received in 1982 and commercial pelleted formulations containing 0.01% bromethalin were developed and introduced in the USA by Ralston Purina (ASSAULT1*) in 1985 and Velsicol (VENGEANCE1*) in 1986. Ciba-Geigy is currently developing new formulations under the tradename DORATIDR for use outside the United States. Bromethalin acute toxicity and 14-day subchronic studies are reviewed and data from recently completed 90-day subchronic studies required for registration outside the US are presented. Pharmacodynamic studies have shown that bromethalin acts as an uncoupler of oxidative phosphorylation, thus interrupting the vital production of ATP necessary to maintain essential metabolic functions. Laboratory and field trial data are presented from Switzerland, France, England, and Denmark that indicate the effectiveness of new bromethalin formulations against anticoagulant resistant and susceptible rodents. A comparative rodenticide pen testing system is described from which test results confirm bromethalin's quick action and feed consumption efficiency when compared to second-generation anticoagulants.

Avaliação técnico-econômica da produção de enzimas celulolíticas por fermentação em estado sólido

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo da variabilidade da região codificadora e 3'não traduzida do gene HLA-F no Brasil

Pós-graduação em Patologia - FMB

Novel aryl beta-aminocarbonyl derivatives as inhibitors of Trypanosoma cruzi trypanothione reductase: binding mode revised by docking and GRIND2-based 3D-QSAR procedures

Trypanothione reductase has long been investigated as a promising target for chemotherapeutic intervention in Chagas disease, since it is an enzyme of a unique metabolic pathway that is exclusively present in the pathogen but not in the human host, which has the analog Glutathione reductase. In spite of the present data-set includes a small number of compounds, a combined use of flexible docking, pharmacophore perception, ligand binding site prediction, and Grid-Independent Descriptors GRIND2-based 3D-Quantitative Structure-Activity Relationships (QSAR) procedures allowed us to rationalize the different biological activities of a series of 11 aryl beta-aminocarbonyl derivatives, which are inhibitors of Trypanosoma cruzi trypanothione reductase (TcTR). Three QSAR models were built and validated using different alignments, which are based on docking with the TcTR crystal structure, pharmacophore, and molecular interaction fields. The high statistical significance of the models thus obtained assures the robustness of this second generation of GRIND descriptors here used, which were able to detect the most important residues of such enzyme for binding the aryl beta-aminocarbonyl derivatives, besides to rationalize distances among them. Finally, a revised binding mode has been proposed for our inhibitors and independently supported by the different methodologies here used, allowing further optimization of the lead compounds with such combined structure- and ligand-based approaches in the fight against the Chagas disease.

A comparative transcriptome analysis reveals expression profiles conserved across three Eimeria spp. of domestic fowl and associated with multiple developmental stages

Coccidiosis of the domestic fowl is a worldwide disease caused by seven species of protozoan parasites of the genus Eimeria. The genome of the model species, Eimeria tenella, presents a complexity of 55-60 MB distributed in 14 chromosomes. Relatively few studies have been undertaken to unravel the complexity of the transcriptome of Eimeria parasites. We report here the generation of more than 45,000 open reading frame expressed sequence tag (ORESTES) cDNA reads of E. tenella, Eimeria maxima and Eimeria acervulina, covering several developmental stages: unsporulated oocysts, sporoblastic oocysts, sporulated oocysts, sporozoites and second generation merozoites. All reads were assembled to constitute gene indices and submitted to a comprehensive functional annotation pipeline. In the case of E. tenella, we also incorporated publicly available ESTs to generate an integrated body of information. Orthology analyses have identified genes conserved across different apicomplexan parasites, as well as genes restricted to the genus Eimeria. Digital expression profiles obtained from ORESTES/EST countings, submitted to clustering analyses, revealed a high conservation pattern across the three Eimeria spp. Distance trees showed that unsporulated and sporoblastic oocysts constitute a distinct clade in all species, with sporulated oocysts forming a more external branch. This latter stage also shows a close relationship with sporozoites, whereas first and second generation merozoites are more closely related to each other than to sporozoites. The profiles were unambiguously associated with the distinct developmental stages and strongly correlated with the order of the stages in the parasite life cycle. Finally, we present The Eimeria Transcript Database (http://www.coccidia.icb.usp.br/eimeriatdb), a website that provides open access to all sequencing data, annotation and comparative analysis. We expect this repository to represent a useful resource to the Eimeria scientific community, helping to define potential candidates for the development of new strategies to control coccidiosis of the domestic fowl. (C) 2011 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Degree of conversion of nanofilled and microhybrid composite resins photo-activated by different generations of LEDs

Objective: This study aimed at evaluating the degree of conversion (DC) of four composite resins, being one nanofilled and 3 microhybrid resins, photo-activated with second- and third-generation light-emitting diodes (LEDs). Material and methods: Filtek (TM) Z350 nanofilled composite resins and Amelogen (R) Plus, Vit-l-escence (TM) and Opallis microhybrid resins were photo-activated with two second-generation LEDs (Radii-cal and Elipar Free Light (TM) 2) and one third-generation LED (Ultra-Lume LED 5) by continuous light mode, and a quartz halogen-tungsten bulb (QHT, control). After 24 h of storage, the samples were pulverized into fine powder and 5 mg of each material were mixed with 100 mg of potassium bromide (KBr). After homogenization, they were pressed, which resulted in a pellet that was evaluated using an infrared spectromer (Nexus 470, Thermo Nicolet) equipped with TGS detector using diffuse reflectance (32 scans, resolution of 4 cm(-1)) coupled to a computer. The percentage of unreacted carbon-carbon double bonds (% C=C) was determined from the ratio of absorbance intensities of aliphatic C=C (peak at 1637 cm-1) against internal standard before and after curing of the specimen: aromatic C-C (peak at 1610 cm-1). Results: The ANOVA showed a significant effect on the interaction between the light-curing units (LCUs) and the composite resins (p<0.001). The Tukey's test showed that the nanofilled resin (Filtek (TM) Z350) and Opallis when photo-activated by the halogen lamp (QTH) had the lowest DC compared with the other microhybrid composite resins. The DC of the nanofilled resin (Filtek (TM) Z350) was also lower using LEDs. The highest degrees of conversion were obtained using the third-generation LED and one of second-generation LEDs (Elipar Free Light (TM) 2). Conclusions: The nanofilled resin showed the lowest DC, and the Vit-l-escence (TM) microhybrid composite resin showed the highest DC. Among the LCUs, it was not possible to establish an order, even though the second-generation LED Radii-cal provided the lowest DC.

Optimized Duration of Clopidogrel Therapy Following Treatment with the Endeavor Zotarolimus-Eluting Stent in Real-World Clinical Practice (OPTIMIZE) Trial: Rationale and design of a large-scale, randomized, multicenter study

Background Current recommendations for antithrombotic therapy after drug-eluting stent (DES) implantation include prolonged dual antiplatelet therapy (DAPT) with aspirin and clopidogrel >= 12 months. However, the impact of such a regimen for all patients receiving any DES system remains unclear based on scientific evidence available to date. Also, several other shortcomings have been identified with prolonged DAPT, including bleeding complications, compliance, and cost. The second-generation Endeavor zotarolimus-eluting stent (E-ZES) has demonstrated efficacy and safety, despite short duration DAPT (3 months) in the majority of studies. Still, the safety and clinical impact of short-term DAPT with E-ZES in the real world is yet to be determined. Methods The OPTIMIZE trial is a large, prospective, multicenter, randomized (1: 1) non-inferiority clinical evaluation of short-term (3 months) vs long-term (12-months) DAPT in patients undergoing E-ZES implantation in daily clinical practice. Overall, 3,120 patients were enrolled at 33 clinical sites in Brazil. The primary composite endpoint is death (any cause), myocardial infarction, cerebral vascular accident, and major bleeding at 12-month clinical follow-up post-index procedure. Conclusions The OPTIMIZE clinical trial will determine the clinical implications of DAPT duration with the second generation E-ZES in real-world patients undergoing percutaneous coronary intervention. (Am Heart J 2012;164:810-816.e3.)

Fermentation medium and oxygen transfer conditions that maximize the xylose conversion to ethanol by Pichia stipitis

The xylose conversion to ethanol by Pichia stipitis was studied. In a first step, the necessity of supplementing the fermentation medium with urea. MgSO(4) x 7H(2)O, and/or yeast extract was evaluated through a 2(3) full factorial design. The simultaneous addition of these three nutritional sources to the fermentation medium, in concentrations of 2.3, 1.0, and 3.0 g/l, respectively, showed to be important to improve the ethanol production in detriment of the substrate conversion to cell. In a second stage, fermentation assays performed in a bioreactor under different K(L)a (volumetric oxygen transfer coefficient) conditions made possible understanding the influence of the oxygen transfer on yeast performance, as well as to define the most suitable range of values for an efficient ethanol production. The most promising region to perform this bioconversion process was found to be between 2.3 and 4.9 h(-1), since it promoted the highest ethanol production results with practically exhaustion of the xylose from the medium. These findings contribute for the development of an economical and efficient technology for large scale production of second generation ethanol. (C) 2011 Elsevier Ltd. All rights reserved.

Molecular measurement of BCR-ABL transcript variations in chronic myeloid leukemia patients in cytogenetic remission

Abstract Background The monitoring of BCR-ABL transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR) has become important to assess minimal residual disease (MRD) and standard of care in the treatment of chronic myeloid leukemia (CML). In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of BCR-ABL gene rearrangements in blood samples from 91 CML patients in chronic phase (CP) who achieved complete cytogenetic remission (CCyR) and major molecular remission (MMR) throughout imatinib treatment. Methods The absolute level of BCR-ABL transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols. Results Based on sequential analysis of BCR-ABL transcripts, the 91 patients were divided into three categories: (A) 57 (62.6%) had no variation on sequential analysis; (B) 30 (32.9%) had a single positive variation result obtained in a single sample; and (C) 4 (4.39%) had variations of BCR-ABL transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of BCR-ABL/BCR ratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the ABL gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5%) patients, and none of whom lost CCyR. Conclusions Despite an increase levels of BCR-ABL/BCR ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of imatinib on the basis of BCR-ABL/BCR% sustained increase and mutational studies is a prudent approach for preserving other therapeutic options in imatinib-resistant patients.

Ultra-structural mapping of sugarcane bagasse after oxalic acid fiber expansion (OAFEX) and ethanol production by Candida shehatae and Saccharomyces cerevisiae

Background Diminishing supplies of fossil fuels and oil spills are rousing to explore the alternative sources of energy that can be produced from non-food/feed-based substrates. Due to its abundance, sugarcane bagasse (SB) could be a model substrate for the second-generation biofuel cellulosic ethanol. However, the efficient bioconversion of SB remains a challenge for the commercial production of cellulosic ethanol. We hypothesized that oxalic-acid-mediated thermochemical pretreatment (OAFEX) would overcome the native recalcitrance of SB by enhancing the cellulase amenability toward the embedded cellulosic microfibrils. Results OAFEX treatment revealed the solubilization of hemicellulose releasing sugars (12.56 g/l xylose and 1.85 g/l glucose), leaving cellulignin in an accessible form for enzymatic hydrolysis. The highest hydrolytic efficiency (66.51%) of cellulignin was achieved by enzymatic hydrolysis (Celluclast 1.5 L and Novozym 188). The ultrastructure characterization of SB using scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman spectroscopy, Fourier transform–near infrared spectroscopy (FT-NIR), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) revealed structural differences before and after OAFEX treatment with enzymatic hydrolysis. Furthermore, fermentation mediated by C. shehatae UFMG HM52.2 and S. cerevisiae 174 showed fuel ethanol production from detoxified acid (3.2 g/l, yield 0.353 g/g; 0.52 g/l, yield, 0.246 g/g) and enzymatic hydrolysates (4.83 g/l, yield, 0.28 g/g; 6.6 g/l, yield 0.46 g/g). Conclusions OAFEX treatment revealed marked hemicellulose degradation, improving the cellulases’ ability to access the cellulignin and release fermentable sugars from the pretreated substrate. The ultrastructure of SB after OAFEX and enzymatic hydrolysis of cellulignin established thorough insights at the molecular level.

Tratamento endovascular dos aneurismas da aorta abdominal com anatomia complexa: resultados preliminares com a segunda geração de endoprótese com arcabouço metálico circular

INTRODUÇÃO: O tratamento endovascular dos aneurismas da aorta abdominal tem revolucionado o tratamento dessa afecção, em decorrência das baixas taxas de morbidade e mortalidade. Apesar dos avanços tecnológicos ocorridos nas endopróteses, ainda existem limitações anatômicas para o emprego da técnica. Este estudo teve por objetivo avaliar os resultados imediatos do tratamento de pacientes portadores de aneurisma da aorta abdominal com anatomia complexa com uma endoprótese de segunda geração. MÉTODOS: Estudo observacional, prospectivo, não-randomizado, realizado em um único centro, em uma série de pacientes submetidos a tratamento endovascular de aneurismas da aorta abdominal infrarrenais complexos, com prótese com arcabouço metálico disposta em anéis (Anaconda - Vascutek, Terumo, Inchinnan, Escócia). Foram avaliados as características clínicas e angiográficas, o sucesso técnico, o sucesso terapêutico, a morbidade e a mortalidade, e a taxa de reintervenção perioperatória. RESULTADOS: Foram analisados, no período de fevereiro de 2010 a dezembro de 2011, 108 pacientes consecutivos portadores de aneurisma da aorta, dos quais 16 eram portadores de aneurisma da aorta abdominal com anatomia complexa tratados com a prótese Anaconda . A média de idade foi de 76 + 7 anos e 75% eram do sexo masculino. Houve sucesso técnico em 94% e êxito terapêutico em 75% dos casos. Ocorreu um óbito no pós-operatório. As complicações perioperatórias mais prevalentes foram sangramento da ferida operatória (2/16) e embolia periférica (2/16). Foram necessárias reintervenções em 12,5% dos pacientes durante o seguimento. CONCLUSÕES: Neste estudo, a segunda geração da endoprótese Anaconda foi efetiva e apresenta resultados imediatos satisfatórios no tratamento do aneurisma da aorta abdominal infrarrenal de anatomia complexa.