Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Simulação do escoamento monofásico em um estágio de uma bomba centrífuga utilizando técnicas de fluidodinâmica computacional

Oil production and exploration techniques have evolved in the last decades in order to increase fluid flows and optimize how the required equipment are used. The base functioning of Electric Submersible Pumping (ESP) lift method is the use of an electric downhole motor to move a centrifugal pump and transport the fluids to the surface. The Electric Submersible Pumping is an option that has been gaining ground among the methods of Artificial Lift due to the ability to handle a large flow of liquid in onshore and offshore environments. The performance of a well equipped with ESP systems is intrinsically related to the centrifugal pump operation. It is the pump that has the function to turn the motor power into Head. In this present work, a computer model to analyze the three-dimensional flow in a centrifugal pump used in Electric Submersible Pumping has been developed. Through the commercial program, ANSYS® CFX®, initially using water as fluid flow, the geometry and simulation parameters have been defined in order to obtain an approximation of what occurs inside the channels of the impeller and diffuser pump in terms of flow. Three different geometry conditions were initially tested to determine which is most suitable to solving the problem. After choosing the most appropriate geometry, three mesh conditions were analyzed and the obtained values were compared to the experimental characteristic curve of Head provided by the manufacturer. The results have approached the experimental curve, the simulation time and the model convergence were satisfactory if it is considered that the studied problem involves numerical analysis. After the tests with water, oil was used in the simulations. The results were compared to a methodology used in the petroleum industry to correct viscosity. In general, for models with water and oil, the results with single-phase fluids were coherent with the experimental curves and, through three-dimensional computer models, they are a preliminary evaluation for the analysis of the two-phase flow inside the channels of centrifugal pump used in ESP systems

Um sistema para estimação da vazão de gás de poços produzindo por Plunger Lift para vaso separador de teste em plataformas de petróleo

This work intends to analyze the behavior of the gas flow of plunger lift wells producing to well testing separators in offshore production platforms to aim a technical procedure to estimate the gas flow during the slug production period. The motivation for this work appeared from the expectation of some wells equipped with plunger lift method by PETROBRAS in Ubarana sea field located at Rio Grande do Norte State coast where the produced fluids measurement is made in well testing separators at the platform. The oil artificial lift method called plunger lift is used when the available energy of the reservoir is not high enough to overcome all the necessary load losses to lift the oil from the bottom of the well to the surface continuously. This method consists, basically, in one free piston acting as a mechanical interface between the formation gas and the produced liquids, greatly increasing the well s lifting efficiency. A pneumatic control valve is mounted at the flow line to control the cycles. When this valve opens, the plunger starts to move from the bottom to the surface of the well lifting all the oil and gas that are above it until to reach the well test separator where the fluids are measured. The well test separator is used to measure all the volumes produced by the well during a certain period of time called production test. In most cases, the separators are designed to measure stabilized flow, in other words, reasonably constant flow by the use of level and pressure electronic controllers (PLC) and by assumption of a steady pressure inside the separator. With plunger lift wells the liquid and gas flow at the surface are cyclical and unstable what causes the appearance of slugs inside the separator, mainly in the gas phase, because introduce significant errors in the measurement system (e.g.: overrange error). The flow gas analysis proposed in this work is based on two mathematical models used together: i) a plunger lift well model proposed by Baruzzi [1] with later modifications made by Bolonhini [2] to built a plunger lift simulator; ii) a two-phase separator model (gas + liquid) based from a three-phase separator model (gas + oil + water) proposed by Nunes [3]. Based on the models above and with field data collected from the well test separator of PUB-02 platform (Ubarana sea field) it was possible to demonstrate that the output gas flow of the separator can be estimate, with a reasonable precision, from the control signal of the Pressure Control Valve (PCV). Several models of the System Identification Toolbox from MATLAB® were analyzed to evaluate which one better fit to the data collected from the field. For validation of the models, it was used the AIC criterion, as well as a variant of the cross validation criterion. The ARX model performance was the best one to fit to the data and, this way, we decided to evaluate a recursive algorithm (RARX) also with real time data. The results were quite promising that indicating the viability to estimate the output gas flow rate from a plunger lift well producing to a well test separator, with the built-in information of the control signal to the PCV

Fases e criticalidade no modelo ashkin - teller de três cores

The usual Ashkin-Teller (AT) model is obtained as a superposition of two Ising models coupled through a four-spin interaction term. In two dimension the AT model displays a line of fixed points along which the exponents vary continuously. On this line the model becomes soluble via a mapping onto the Baxter model. Such richness of multicritical behavior led Grest and Widom to introduce the N-color Ashkin-Teller model (N-AT). Those authors made an extensive analysis of the model thus introduced both in the isotropic as well as in the anisotropic cases by several analytical and computational methods. In the present work we define a more general version of the 3-color Ashkin-Teller model by introducing a 6-spin interaction term. We investigate the corresponding symmetry structure presented by our model in conjunction with an analysis of possible phase diagrams obtained by real space renormalization group techniques. The phase diagram are obtained at finite temperature in the region where the ferromagnetic behavior is predominant. Through the use of the transmissivities concepts we obtain the recursion relations in some periodical as well as aperiodic hierarchical lattices. In a first analysis we initially consider the two-color Ashkin-Teller model in order to obtain some results with could be used as a guide to our main purpose. In the anisotropic case the model was previously studied on the Wheatstone bridge by Claudionor Bezerra in his Master Degree dissertation. By using more appropriated computational resources we obtained isomorphic critical surfaces described in Bezerra's work but not properly identified. Besides, we also analyzed the isotropic version in an aperiodic hierarchical lattice, and we showed how the geometric fluctuations are affected by such aperiodicity and its consequences in the corresponding critical behavior. Those analysis were carried out by the use of appropriated definitions of transmissivities. Finally, we considered the modified 3-AT model with a 6-spin couplings. With the inclusion of such term the model becomes more attractive from the symmetry point of view. For some hierarchical lattices we derived general recursion relations in the anisotropic version of the model (3-AAT), from which case we can obtain the corresponding equations for the isotropic version (3-IAT). The 3-IAT was studied extensively in the whole region where the ferromagnetic couplings are dominant. The fixed points and the respective critical exponents were determined. By analyzing the attraction basins of such fixed points we were able to find the three-parameter phase diagram (temperature £ 4-spin coupling £ 6-spin coupling). We could identify fixed points corresponding to the universality class of Ising and 4- and 8-state Potts model. We also obtained a fixed point which seems to be a sort of reminiscence of a 6-state Potts fixed point as well as a possible indication of the existence of a Baxter line. Some unstable fixed points which do not belong to any aforementioned q-state Potts universality class was also found

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Simulação do escoamento monofásico em um estágio de uma bomba centrífuga utilizando técnicas de fluidodinâmica computacional

Oil production and exploration techniques have evolved in the last decades in order to increase fluid flows and optimize how the required equipment are used. The base functioning of Electric Submersible Pumping (ESP) lift method is the use of an electric downhole motor to move a centrifugal pump and transport the fluids to the surface. The Electric Submersible Pumping is an option that has been gaining ground among the methods of Artificial Lift due to the ability to handle a large flow of liquid in onshore and offshore environments. The performance of a well equipped with ESP systems is intrinsically related to the centrifugal pump operation. It is the pump that has the function to turn the motor power into Head. In this present work, a computer model to analyze the three-dimensional flow in a centrifugal pump used in Electric Submersible Pumping has been developed. Through the commercial program, ANSYS® CFX®, initially using water as fluid flow, the geometry and simulation parameters have been defined in order to obtain an approximation of what occurs inside the channels of the impeller and diffuser pump in terms of flow. Three different geometry conditions were initially tested to determine which is most suitable to solving the problem. After choosing the most appropriate geometry, three mesh conditions were analyzed and the obtained values were compared to the experimental characteristic curve of Head provided by the manufacturer. The results have approached the experimental curve, the simulation time and the model convergence were satisfactory if it is considered that the studied problem involves numerical analysis. After the tests with water, oil was used in the simulations. The results were compared to a methodology used in the petroleum industry to correct viscosity. In general, for models with water and oil, the results with single-phase fluids were coherent with the experimental curves and, through three-dimensional computer models, they are a preliminary evaluation for the analysis of the two-phase flow inside the channels of centrifugal pump used in ESP systems

Ação de polissacarídeos sulfatados de Fucus Vesiculosus na Hemostasia e no sistema complemento

Fucans are a family of sulfated homo and teropolysaccharides respectively, composed mainly of a- (1®2) and a- (1®3) linked by L-fucose residues. Properties such as the ability to act as an anti-contraceptive, to reduce cholesterol levels, and to act as an anti-tumor agent are much related. We have focused our attention on the anticoagulant properties, platelet aggregation, hemorrhagic activity and complement system in vitro of commercial fucoidan (F) and their purified fractions (F1, F2 and F3) from Fucus vesiculosus obtained from fractionation of the fucoidan with different concentrations of acetone 1, 2 and 3v. These compounds were chemically characterized and the fucoidan (F) was modified by desulfation. The anticoagulant activity of the compounds was assessment by activated partial thromboplastin time (APTT) and prothrombine time assay (PT) using citrated normal human plasma. The results of APPT test showed that F, F1 and F2 have high anticoagulants activities 240.0 s (5 µg). The F3 showed 73.7 s in the same concentrations. The results obtained with PT test to F, F1, F2 and F3 were 81.5 s, 120.0 s, 57.1 and 32.5 s respectively with 50 µg. The dessulfated polymer showed a decrease in the anticoagulant activity in these two tests. Platelet aggregation assay was measured turbidimetrically with platelet aggregometer by method of Born. The aggregation platelet with F and fractions F1, F2 and F3 exhibited a two-phase answer in the concentration of 5 mg/mL with maximum aggregation of 76.36 ± 10.3% ; 69.54 ± 9.40%; 75.94 ± 9.01%; 51.13 ± 9.59% respectively. However, was observed a hipoaggregate profile F (15.17 ± 5.2%), F1 (7.40 ± 3.04 %), F2 (19.1 ± 5.41%) and F3 (5.09 ± 3.02%) at 0.1 mg/mL. The hemorrhagic activity assay was carried in Wistar rats and showed that these compounds have low hemorrhagic effect when compared to heparin. The complement system ( alternative pathway was made using non-sensibilized rabbit red blood cells The results of complement system essay showed that F , F2 and F3 have action inhibitory in relation to the group control 0.544, 0.697, 0.622 and 0.958 respectively The results showed that these compounds have action on this system. Interaction of the polisaccharides with proteins C3 and C4 showed that the fraction F1 stimulated the activity assay hemolytic using red blood cells

Análise comparativa entre simuladores de linha de fluxo e diferenças finitas para um reservatório de petróleo submetido a injeção de água

Water injection is the most widely used method for supplementary recovery in many oil fields due to various reasons, like the fact that water is an effective displacing agent of low viscosity oils, the water injection projects are relatively simple to establish and the water availability at a relatively low cost. For design of water injection projects is necessary to do reservoir studies in order to define the various parameters needed to increase the effectiveness of the method. For this kind of study can be used several mathematical models classified into two general categories: analytical or numerical. The present work aims to do a comparative analysis between the results presented by flow lines simulator and conventional finite differences simulator; both types of simulators are based on numerical methods designed to model light oil reservoirs subjected to water injection. Therefore, it was defined two reservoir models: the first one was a heterogeneous model whose petrophysical properties vary along the reservoir and the other one was created using average petrophysical properties obtained from the first model. Comparisons were done considering that the results of these two models were always in the same operational conditions. Then some rock and fluid parameters have been changed in both models and again the results were compared. From the factorial design, that was done to study the sensitivity analysis of reservoir parameters, a few cases were chosen to study the role of water injection rate and the vertical position of wells perforations in production forecast. It was observed that the results from the two simulators are quite similar in most of the cases; differences were found only in those cases where there was an increase in gas solubility ratio of the model. Thus, it was concluded that in flow simulation of reservoirs analogous of those now studied, mainly when the gas solubility ratio is low, the conventional finite differences simulator may be replaced by flow lines simulator the production forecast is compatible but the computational processing time is lower.

Estudo do acoplamento do poço injetor nas simulações de injeção cíclica de vapor

Steam injection is a method usually applied to very viscous oils and consists of injecting heat to reduce the viscosity and, therefore, increase the oil mobility, improving the oil production. For designing a steam injection project it is necessary to have a reservoir simulation in order to define the various parameters necessary for an efficient heat reservoir management, and with this, improve the recovery factor of the reservoir. The purpose of this work is to show the influence of the coupled wellbore/reservoir on the thermal simulation of reservoirs under cyclic steam stimulation. In this study, the methodology used in the solution of the problem involved the development of a wellbore model for the integration of steam flow model in injection wellbores, VapMec, and a blackoil reservoir model for the injection of cyclic steam in oil reservoirs. Thus, case studies were developed for shallow and deep reservoirs, whereas the usual configurations of injector well existing in the oil industry, i.e., conventional tubing without packer, conventional tubing with packer and insulated tubing with packer. A comparative study of the injection and production parameters was performed, always considering the same operational conditions, for the two simulation models, non-coupled and a coupled model. It was observed that the results are very similar for the specified well injection rate, whereas significant differences for the specified well pressure. Finally, on the basis of computational experiments, it was concluded that the influence of the coupled wellbore/reservoir in thermal simulations using cyclic steam injection as an enhanced oil recovery method is greater for the specified well pressure, while for the specified well injection rate, the steam flow model for the injector well and the reservoir may be simulated in a non- coupled way

Repercussões psico-sociais da síndrome dos ovários policísticos: estudo quali-quantitativo

BACKGROUND: Polycystic ovary syndrame (PCOS) has been shown to cause a reduction in quality of life. Little is known on the psychosocial aspects associated with PCOS, especially on women s own experiences regarding the syndrome. Therefore, the aim of this study was to analyze the psychosocial impact of PCOS by measuring the health-related quality of life and exploring the women s own experiences of PCOS. METHODS: A two-phase model of combination of quantitative and qualitative research approaches was conducted, a crass-sectional survey to pravide quantitative data on the quality of life and a qualitative approach to understand the women s experience in relation to the PC OS sympt?ms. For the first phase, 109 women with PC OS and 104 healthy contrais were evaluated with the 36-item short-form health survey (SF-36). Additionally, semi-structured interviews (n=30) were conducted to facilitate in-depth exploration of PC OS women s experience. RESUL TS: PCOS patients showed significant reductions in almost ali SF-36 domains of quality of life when compared with healthy contrais (physical function 76.5:!:20.5 and 84.6:!:15.9, respectively; physical rale function 56.4:!:43.3 and 72.6:!:33.3; general health 55.2:!:21.0 and 62.5:!:17.2; vitality 49.6:!:21.3 and 55.3:!:21.3; social function 55.3:!:32.4 and 66.2:!:26.7; emotional rale function 34.2:!:39.7 and 52.9:!:38.2; mental health 50.6:!:22.8 and 59.2:!:20.2). Thematic analysis revealed reports of feeling abnormal , sadness, afraid and anxiety. These feelings were related to four symptoms commonly experienced by women with PCOS: excess hair grawth; irregular or absent menstruation, infertility and obesity. CONCLUSIONS: Polycystic ovary syndrame impacts women both physically and psychosocially. Owing to this, women with PCOS need not only medical treatment for. the reproductive, esthetic and metabolic repercussions, but also the care of a multidisciplinary team, since PCOS is not just a physical condition, but also an important psychosocial problem that affects various aspects of a woman s life

Análise in vitro da atividade antifúngica e de toxicidade da anfotericina B pré-aquecida

The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also a review of the literature about the new physicochemical and biological properties of this new system was carried out. Afterwards, heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were subsequently diluted at four different concentrations (50mg.L-1, 5mg.L-1, 0.5mg.L-1 and 0.05mg.L-1) to perform the physicochemical study and, then, the pharmacotoxicity assay, in which two cell models were used for the in vitro experiments, Red Blood Cells (RBC) from human donors and Candida parapisilosis (Cp). While potassium (K+) and hemoglobin leakage from RBC were the used parameters to evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K+ leakage and cell survival rate from Cp. The spectral study revealed a slight change on the aggregate peak from 327nm to 323nm for AmB-DOC-H compared to AmB-DOC. Concerning the toxicity, although AmB-DOC and AmB-DOC-H presented different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5mg.L-1) with values tending to zero. However, concerning K+ leakage, both AmB-DOC and AmB-DOC-H, showed similar profile for both cell models, RBC and Cp (p<0,05). AmB-DOC-H and AmB-DOC also revealed similar profile of activity against Cp with equivalent survival rate. In short, the AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as the late one against fungal cell. Therefore, the results highlight the importance of this new procedure as a simple, inexpensive and safe alternative to produce a new kind of micelle system for treatment of systemic fungal infections

Análise comparativa de modelos de maturidade em gerenciamento de projetos: uma contribuição ao estudo da maturidade organizacional em setores de engenharia

The purpose of this dissertation is to formulate guidelines for the improvement of maturity models, or the development of new ones, aiming at its application to project departments. The maturity of project management has become critical for organizations that develop projects and want to stand out in the market they serve. For this purpose, maturity models provide paths in order to guarantee that the institutionalization of project management is achieved in the best possible way. Generally, these models assess the organization, define its current situation in managing projects and propose steps to be performed in the search of more advanced levels of maturity. With the objective of contributing to the improvement of maturity models for specific cases, a bibliographical research was conducted for the preparation of a comparative analysis matrix and performed a case study for application of two maturity models (MMGP and PMMM levels 2 and 3), selected based on criteria found in the literature, in an engineering department of an oil company. The case study supported the realization of a comparative analysis of models, from which guidelines were formulated for improvement. The results showed that thedepartment is evaluated in a medium stage of maturity, recording significant progress in some dimensions assessed. They also found that the results of applying the two models are presented as complementary, although the model is highlighted by the greater depth of MMGP diagnostic, considering many variables in their levels of maturity than model PMMM (levels 2 and 3).Finally, directions have been formulated that contribute to the improvement of maturity models, taking in account the organizational environment in which this work was developed

Uma Fundamentação Intervalar Aplicada à Morfologia Matemática

This work present a interval approach to deal with images with that contain uncertainties, as well, as treating these uncertainties through morphologic operations. Had been presented two intervals models. For the first, is introduced an algebraic space with three values, that was constructed based in the tri-valorada logic of Lukasiewiecz. With this algebraic structure, the theory of the interval binary images, that extends the classic binary model with the inclusion of the uncertainty information, was introduced. The same one can be applied to represent certain binary images with uncertainty in pixels, that it was originated, for example, during the process of the acquisition of the image. The lattice structure of these images, allow the definition of the morphologic operators, where the uncertainties are treated locally. The second model, extend the classic model to the images in gray levels, where the functions that represent these images are mapping in a finite set of interval values. The algebraic structure belong the complete lattices class, what also it allow the definition of the elementary operators of the mathematical morphology, dilation and erosion for this images. Thus, it is established a interval theory applied to the mathematical morphology to deal with problems of uncertainties in images

Caracterização de dois cDNAs homológos e uma AP endonuclease em cana-de-açúcar

The genome of all organisms is subject to injuries that can be caused by endogenous and environmental factors. If these lesions are not corrected, it can be fixed generating a mutation which can be lethal to the organisms. In order to prevent this, there are different DNA repair mechanisms. These mechanisms are well known in bacteria, yeast, human, but not in plants. Two plant models Oriza sativa and Arabidopsis thaliana had the genome sequenced and due to this some DNA repair genes have been characterized. The aim of this work is to characterized two sugarcane cDNAs that had homology to AP endonuclease: scARP1 and scARP3. In silico has been done with these two sequences and other from plants. It has been observed domain conservation on these sequences, but the cystein at 65 position that is a characteristic from the redox domain in APE1 protein was not so conservated in plants. Phylogenetic relationship showed two branches, one branch with dicots and monocots sequence and the other branch with only monocots sequences. Another approach in order to characterized these two cDNAs was to construct overexpression cassettes (sense and antisense orientation) using the 35S promoter. After that, these cassettes were transferred to the binary vector pPZP211. Furthermore, previously in the laboratory was obtained a plant from nicotiana tabacum containing the overexpression cassette in anti-sense orientation. It has been observed that this plant had a slow development and problems in setting seeds. After some manual crossing, some seeds were obtained (T2) and it was analyzed the T2 segregation. The third approach used in this work was to clone the promoter region from these two cDNAs by PCR walking. The sequences obtained were analyzed using the program PLANTCARE. It was observed in these sequences some motives that may be related to oxidative stress response