Efeito da hiperprolactinemia induzida pela metoclopramida na glândula lacrimal: estudo experimental

OBJETIVO: avaliar as alterações morfológicas promovidas pela hiperprolactinemia induzida pela metoclopramida na glândula lacrimal de camundongas durante a fase de proestro e gestação. MÉTODOS: 40 camundongas adultas foram divididas em dois grupos: CTR1 (controle) e MET1 (tratadas com metoclopramida). Após 50 dias, metade dos animais de cada grupo foram sacrificados por decapitação. Os restantes foram acasalados, constituindo os grupos controle prenhe (CTR2) e metoclopramida prenhe (MET2), que foram sacrificadas no 6º dia de gestação. O sangue foi coletado e submetido à dosagem hormonal dos níveis de estradiol e de progesterona por quimioluminescência. Em seguida as glândulas lacrimais foram removidas, fixadas em formol a 10% e processadas segundo metodologia histológica para inclusão em parafina, sendo as lâminas coradas pelo HE. A análise morfométrica foi realizada com o programa AxionVision (Carl Zeiss), medindo-se os volumes celulares e nucleares das células acinares. RESULTADOS: os volumes nuclear e celular das glândulas lacrimais dos grupos experimentais MET1 (152,2±8,7; 6,3±1,6 µm³) e MET2 (278,3±7,9; 27,5±0,9 µm³) mostraram-se reduzidos em relação aos grupos controles CTR1 (204,2±7,4; 21,9±1,3 µm³) e CTR2 (329,4±2,2; 35,5±2,0 µm³). Houve redução dos níveis hormonais de estrogênio e de progesterona nos animais que receberam metoclopramida em comparação com os respectivos controles (CTR1: estradiol = 156,6±42,2 pg/ml; progesterona = 39,4±5,1 ng/ml; MET1: estradiol = 108,0±33,1 pg/ml; progesterona = 28,0±6,4 ng/ml; CTR2: estradiol = 354,0±56,0 pg/ml; progesterona = 251,0±56,0 ng/ml; MET2: estradiol = 293,0±43,0 pg/ml, progesterona = 184,0±33,0 ng/ml). CONCLUSÃO: a hiperprolactinemia induzida pela metoclopramida produziu sinais de diminuição na atividade das células da glândula lacrimal tanto em camundongas prenhes quanto não prenhes. Este efeito está possivelmente relacionado com a redução da produção hormonal de estrogênio e progesterona.

Gravidez e disfunção lacrimal

OBJETIVO: Verificar a prevalência de disfunção lacrimal em grávidas, comparando-a com a de mulheres não grávidas. Correlacionar achados de diminuição do filme lacrimal com antecedentes obstétricos. MÉTODOS: Foram entrevistadas 150 mulheres grávidas e 150 não grávidas para avaliação da presença de sintomas de secura ocular e antecedentes obstétricos. Os dois grupos foram submetidos ao teste de Schirmer I e a um questionário para sintomas de olho seco. Pacientes com colagenoses, uso de medicamentos associados à secura de mucosas, hepatite C e infecção por vírus da imunodeficiência humana, inflamação intraocular prévia ou cirurgia ocular foram excluídas. Os dados obtidos foram analisados por testes de Χ2 e Fisher quanto às variáveis nominais, e pelo t de Student e Mann-Whitney quando numéricos. A significância adotada foi de 5%. RESULTADOS: Os dois grupos não diferiram quanto aos sintomas relacionados à secura ocular. O valor absoluto do teste de Schirmer foi igual nos dois grupos, tanto para olho direito (p=0,3) como esquerdo (p=0,3). Todavia, as mulheres grávidas tiveram maior prevalência de disfunção lacrimal em pelo menos um olho (p=0,004). A ocorrência de disfunção lacrimal nos dois grupos (pacientes e controles) estava associada a maior número de gestações a termo por paciente (p=0,04), mas não com número de abortos (p=0,9), nem com o tempo da gravidez (p=0,5). CONCLUSÕES: Mulheres grávidas têm mais disfunção lacrimal do que não grávidas. Nos dois grupos a prevalência de disfunção lacrimal é mais alta em mulheres com maior paridade.

Experimental analysis of the flow between stay and guide vanes of a pump-turbine in pumping mode

An experimental study was conducted in a pump-turbine model in pumping mode, in order to characterize the flow field structure in the region between stay and guide vanes, using mainly the laser-Doppler anemometry in a two-color and back-scattered light-based system. The structure of the steady and unsteady flow was analyzed. The measurements were performed at three operation points. The obtained data provide appropriate boundary conditions and a good base of validation for numerical codes, and for the understanding of main loss mechanisms of this complex flow.

Energy-efficient control strategies for variable speed driven parallel pumping systems based on pump operation point monitoring with frequency converters

The pumping processes requiring wide range of flow are often equipped with parallelconnected centrifugal pumps. In parallel pumping systems, the use of variable speed control allows that the required output for the process can be delivered with a varying number of operated pump units and selected rotational speed references. However, the optimization of the parallel-connected rotational speed controlled pump units often requires adaptive modelling of both parallel pump characteristics and the surrounding system in varying operation conditions. The available information required for the system modelling in typical parallel pumping applications such as waste water treatment and various cooling and water delivery pumping tasks can be limited, and the lack of real-time operation point monitoring often sets limits for accurate energy efficiency optimization. Hence, alternatives for easily implementable control strategies which can be adopted with minimum system data are necessary. This doctoral thesis concentrates on the methods that allow the energy efficient use of variable speed controlled parallel pumps in system scenarios in which the parallel pump units consist of a centrifugal pump, an electric motor, and a frequency converter. Firstly, the suitable operation conditions for variable speed controlled parallel pumps are studied. Secondly, methods for determining the output of each parallel pump unit using characteristic curve-based operation point estimation with frequency converter are discussed. Thirdly, the implementation of the control strategy based on real-time pump operation point estimation and sub-optimization of each parallel pump unit is studied. The findings of the thesis support the idea that the energy efficiency of the pumping can be increased without the installation of new, more efficient components in the systems by simply adopting suitable control strategies. An easily implementable and adaptive control strategy for variable speed controlled parallel pumping systems can be created by utilizing the pump operation point estimation available in modern frequency converters. Hence, additional real-time flow metering, start-up measurements, and detailed system model are unnecessary, and the pumping task can be fulfilled by determining a speed reference for each parallel-pump unit which suggests the energy efficient operation of the pumping system.

Regulation of the renal proximal tubule second sodium pump by angiotensins

For several years it was believed that angiotensin II (Ang II) alone mediated the effects of the renin-angiotensin system. However, it has been observed that other peptides of this system, such as angiotensin-(1-7) (Ang-(1-7)), present biological activity. The effect of Ang II and Ang-(1-7) on renal sodium excretion has been associated, at least in part, with modulation of proximal tubule sodium reabsorption. In the present review, we discuss the evidence for the involvement of Na+-ATPase, called the second sodium pump, as a target for the actions of these compounds in the regulation of proximal tubule sodium reabsorption.

Inhibition of the sarcoplasmic reticulum Ca2+ pump with thapsigargin to estimate the contribution of Na+-Ca2+ exchange to ventricular myocyte relaxation

Relaxation in the mammalian ventricle is initiated by Ca2+ removal from the cytosol, which is performed by three main transport systems: sarcoplasmic reticulum Ca2+-ATPase (SR-A), Na+-Ca2+ exchanger (NCX) and the so-called slow mechanisms (sarcolemmal Ca2+-ATPase and mitochondrial Ca2+ uptake). To estimate the relative contribution of each system to twitch relaxation, SR Ca2+ accumulation must be selectively inhibited, usually by the application of high caffeine concentrations. However, caffeine has been reported to often cause changes in membrane potential due to NCX-generated inward current, which compromises the reliability of its use. In the present study, we estimated integrated Ca2+ fluxes carried by SR-A, NCX and slow mechanisms during twitch relaxation, and compared the results when using caffeine application (Cf-NT) and an electrically evoked twitch after inhibition of SR-A with thapsigargin (TG-TW). Ca2+ transients were measured in 20 isolated adult rat ventricular myocytes with indo-1. For transients in which one or more transporters were inhibited, Ca2+ fluxes were estimated from the measured free Ca2+ concentration and myocardial Ca2+ buffering characteristics. NCX-mediated integrated Ca2+ flux was significantly higher with TG-TW than with Cf-NT (12 vs 7 µM), whereas SR-dependent flux was lower with TG-TW (77 vs 81 µM). The relative participations of NCX (12.5 vs 8% with TG-TW and Cf-NT, respectively) and SR-A (85 vs 89.5% with TG-TW and Cf-NT, respectively) in total relaxation-associated Ca2+ flux were also significantly different. We thus propose TG-TW as a reliable alternative to estimate NCX contribution to twitch relaxation in this kind of analysis.

The Fluid Structure Interaction Analysis of a Peristaltic Pump

The thesis work models the squeezing of the tube and computes the fluid motion of a peristaltic pump. The simulations have been conducted by using COMSOL Multiphysics FSI module. The model is setup in axis symmetric with several simulation cases to have a clear understanding of the results. The model captures total displacement of the tube, velocity magnitude, and average pressure fluctuation of the fluid motion. A clear understanding and review of many mathematical and physical concepts are also discussed with their applications in real field. In order to solve the problems and work around the resource constraints, a thorough understanding of mass balance and momentum equations, finite element concepts, arbitrary Lagrangian-Eulerian method, one-way coupling method, two-way coupling method, and COMSOL Multiphysics simulation setup are understood and briefly narrated.

A low concentration of ouabain (0.18 µg/kg) enhances hypertension in spontaneously hypertensive rats by inhibiting the Na+ pump and activating the renin-angiotensin system

We investigated the effects of low ouabain concentrations on systolic (SAP) and diastolic (DAP) arterial pressures and on pressor reactivity in 3-month-old male spontaneously hypertensive rats (SHR). Arterial blood pressure (BP) and pressor reactivity to phenylephrine (PHE) were investigated before and after 0.18 μg/kg ouabain administration (N = 6). The influence of hexamethonium (N = 6), canrenone (N = 6), enalapril (N = 6), and losartan (N = 6) on ouabain actions was evaluated. Ouabain increased BP (SAP: 137 ± 5.1 to 150 ± 4.7; DAP: 93.7 ± 7.7 to 116 ± 3.5 mmHg; P<0.05) but did not change PHE pressor reactivity. Hexamethonium reduced basal BP in control but not in ouabain-treated rats. However, hexamethonium + ouabain increased DAP sensitivity to PHE. Canrenone did not affect basal BP but blocked ouabain effects on SAP. However, after canrenone + ouabain administration, DAP pressor reactivity to PHE still increased. Enalapril and losartan reduced BP and abolished SAP and DAP responses to ouabain. Enalapril + ouabain reduced DAP reactivity to PHE, while losartan + ouabain reduced SAP and DAP reactivity to PHE. In conclusion, a small dose of ouabain administered to SHR increased BP without altering PHE pressor reactivity. Although the renin-angiotensin system (RAS), Na+ pump and autonomic reflexes are involved in the effects of ouabain on PHE reactivity, central mechanisms might blunt the actions of ouabain on PHE pressor reactivity. The effect of ouabain on SAP seems to depend on the inhibition of both Na+ pump and RAS, whereas the effect on DAP seems to depend only on RAS.

Benefits of gas driven ground source heat pump systems

This thesis studies energy efficiencies and technical properties of gas driven ground source heat pumps and pump systems. The research focuses on two technologies: gas engine driven compressor heat pump and thermally driven gas absorption heat pump. System consist of a gas driven compressor or absorption ground source heat pump and a gas condensing boiler, which covers peak load. The reference system is a standard electrically powered compressor heat pump with electric heating elements for peak load. The systems are compared through primary energy ratios. Coefficient of performances of different heat pump technologies are also compared. At heat pump level, gas driven heat pumps are having lower coefficient of performances as compared with corresponding electric driven heat pump. However, gas heat pumps are competitive when primary energy ratios, where electricity production losses are counted in, are compared. Technically, gas heat pumps can potentially achieve a slightly higher temperatures with greater total energy efficiency as compared to the electric driven heat pump. The primary energy ratios of gas heat pump systems in relation to EHP-system improves when the share of peak load increases. Electric heat pump system's overall energy efficiency is heavily dependent on the electricity production efficiency. Economy as well as CO2-emissions were not examined in this thesis, which however, would be good topics for further study.

Design of the sensorless pressure control system for a centrifugal pump

This thesis investigates the pressure-based control of a variable-speed-driven pump system in the case of existing output pressure measurement and in the case of sensorless system, where the actual output pressure value is calculated with the steady state estimator.

Control of multi-actuator system by an electrically driven hydraulic pump-motor

The awareness and concern of our environment together with legislation have set more and more tightening demands for energy efficiency of non-road mobile machinery (NRMM). Integrated electro-hydraulic energy converter (IEHEC) has been developed in Lappeenranta University of Technology (LUT). The elimination of resistance flow, and the recuperation of energy makes it very efficient alternative. The difficulties of IEHEC machine to step to the market has been the requirement of one IEHEC machine per one actuator. The idea is to switch IEHEC between two actuators of log crane using fast on/off valves. The control system architecture is introduced. The system has been simulated in co-simulation using two different software. The simulated responses of pump-controlled system is compared to the responses of the conventional valve-controlled system.

The overexpression of the efflux pump Tpo1 leads to the bleomycin resistance in Saccharomyces cerevisiae.

La bléomycine est un antibiotique cytotoxique, son potentiel génotoxique est plus important quand elle est utilisée en combinaison avec des agents antinéoplasiques sur le cancer testiculaire, que sur les autres types qui développent souvent une résistance envers la drogue. Notre but consiste alors de mettre en évidence ce mécanisme de résistance en utilisant l’organisme modèle Saccharomyces cerevisiae. Nous avons démontré au sein de notre laboratoire, que les levures délétées au niveau de leur coactivateur transcriptionnel Imp2, présentent une hypersensibilité à la bléomycine, en raison de son accumulation toxique dans la cellule. Ceci suggère que Imp2 pourrait réguler l’expression d’une ou de plusieurs pompes à efflux, capables d’expulser la bléomycine à l’extérieur de la cellule. Pour tester notre hypothèse, nous avons recherché des suppresseurs multicopies capables de restaurer la résistance à la bléomycine chez le mutant imp2, et c’est ainsi que nous avons identifié l'activateur transcriptionnel Yap1. Ce dernier se lie à une région spécifique localisée au niveau du promoteur et permet d’activer l'expression d'un sous-ensemble de gènes, codant pour des pompes à efflux, impliquées dans la résistance aux drogues. Selon la littérature, au moins 27 pompes à efflux ont été identifiées chez la levure Saccharomyces cerevisiae, certaines d’entre elles disposent du site de liaison pour Yap1, tels que Qdr3, Tpo2 et Tpo1. Afin de déterminer si une de ces pompes expulse la bléomycine, nous avons créé des mutations simples et doubles en combinaison avec IMP2, aussi nous avons verifié si les mutants étaient sensibles à la drogue et enfin, nous avons testé si la surexpression de Yap1 pouvait restaurer le phénotype sauvage chez ces mutants, via l’activation de pompes à efflux.

Femtosecond pump-probe study of the spreading and recurrence of a vibrational wave packet in Na_2

The motion of a vibrational wave packet in the bound A(^1 \summe^+_u) electronic state of the sodium dimer is detected in a femtosecond pump/probe molecular beam experiment. For short times harmonic motion is seen in the total ion yield of Na^+_2 as a function of delay time between the two laser pulses. The spreading of the wave packet results in the loss of the periodic variation of the ion signal. For longer delay times (47 ps) the wave packet regains its initial form which is reflected in the revival structure of the Na^+_2 signal. Time-dependent quantum calculations reproduce the measured effects.

Discrete demand side control performance under dynamic building simulation: a heat pump application

This study presents the findings of applying a Discrete Demand Side Control (DDSC) approach to the space heating of two case study buildings. High and low tolerance scenarios are implemented on the space heating controller to assess the impact of DDSC upon buildings with different thermal capacitances, light-weight and heavy-weight construction. Space heating is provided by an electric heat pump powered from a wind turbine, with a back-up electrical network connection in the event of insufficient wind being available when a demand occurs. Findings highlight that thermal comfort is maintained within an acceptable range while the DDSC controller maintains the demand/supply balance. Whilst it is noted that energy demand increases slightly, as this is mostly supplied from the wind turbine, this is of little significance and hence a reduction in operating costs and carbon emissions is still attained.

Interactions between the physical soil environment and a horizontal ground coupled heat pump, for a domestic site in the UK

There is currently an increased interest of Government and Industry in the UK, as well as at the European Community level and International Agencies (i.e. Department of Energy, American International Energy Agency), to improve the performance and uptake of Ground Coupled Heat Pumps (GCHP), in order to meet the 2020 renewable energy target. A sound knowledge base is required to help inform the Government Agencies and advisory bodies; detailed site studies providing reliable data for model verification have an important role to play in this. In this study we summarise the effect of heat extraction by a horizontal ground heat exchanger (installed at 1 m depth) on the soil physical environment (between 0 and 1 m depth) for a site in the south of the UK. Our results show that the slinky influences the surrounding soil by significantly decreasing soil temperatures. Furthermore, soil moisture contents were lower for the GCHP soil profile, most likely due to temperature-gradient related soil moisture migration effects and a decreased hydraulic conductivity, the latter as a result of increased viscosity (caused by the lower temperatures for the GCHP soil profile). The effects also caused considerable differences in soil thermal properties. This is the first detailed mechanistic study conducted in the UK with the aim to understand the interactions between the soil, horizontal heat exchangers and the aboveground environment. An increased understanding of these interactions will help to achieve an optimum and sustainable use of the soil heat resources in the future. The results of this study will help to calibrate and verify a simulation model that will provide UK-wide recommendations to improve future GCHP uptake and performance, while safeguarding the soil physical resources.