Adaptação digestiva com duodenal switch parcial em pacientes diabéticos e com IMC<35 Kg/m2. Análise da resposta clínica, laboratorial, enterohormonal e da expressão do gene p53 na mucosa intestinal

O diabetes mellitus tipo 2 (DM2) é uma doença de prevalência crescente na população mundial, sendo associado ao aumento de diversas comorbidades. A relação entre o trato digestivo e o DM2 tem sido fortalecida a partir dos resultados das diferentes cirurgias metabólicas frente à remissão do distúrbio endócrino. Alterações morfológicas hipertróficas no epitélio intestinal são percebidas nos estágios iniciais da doença e parece ter papel primordial na instalação da hiperglicemia crônica. O gene p53 participa ativamente dos processos de regulação do crescimento epitelial intestinal e pode sofrer alteração de sua expressão em estados diabéticos. Objetiva-se avaliar os resultados clínicos e laboratoriais de pacientes DM2 e com índice de Massa Corpórea (IMC) >25 e <35 Kg/m2 submetidos a cirurgia metabólica denominada adaptação digestiva com duodenal switch parcial (DSP) e avaliar o comportamento da expressão do gene p53 na mucosa intestinal no período pré e pós-operatório. Nove pacientes DM2, com IMC<35Kg/m2 foram operados pela técnica DSP. Biópsias de duodeno e íleo foram colhidas no estado diabético (pré e transoperatório respectivamente) e, 3 meses após a cirurgia, através de endoscopia digestiva alta. Foram comparados os dados de evolução antropométrica (IMC) e laboratorial no período pré e pós-operatório. Através do método enzyme-linked immunosorbent assay (ELISA) foram determinados os níveis dos entero-hormônios glucagon-like peptide-1 (GLP-1) e glucose-dependent insulinotropic peptide (GIP), no pré e pós-operatório, em jejum e pós-prandial nos períodos 30',60',90' e 120'. A expressão do gene p53, foi avaliada por real time polymerase chain reaction (qrt-PCR) e western blot, nos dois diferentes momentos. As variáveis: glicemia de jejum e pós-prandial (2 horas), trigliceridemia de jejum, hemoglobina glicada (HbAc1) e peptídeo C foram analisadas. As médias dos parâmetros laboratoriais foram comparadas pela análise multivariada ANOVA e após teste-Tukey. A média de expressão relativa do gene p53 foi comparada nos dois períodos pelo teste t-student. Os resultados evidenciaram que entre maio e dezembro de 2010, nove pacientes (4 homens, 5 mulheres) DM2 e com IMC entre 26 e 34Kg/m2 foram submetidos a DSP. A média de IMC do grupo operado foi de 31,3. Houve queda do IMC média de 23% após um ano. Houve queda significativa (p<0,05) nos níveis de triglicerídeos, glicemia de jejum e pós-prandial (2 horas), HbA1c assim como aumento do peptídeo-C (p<0,05), quando comparados os períodos pré e pós-operatório. Os níveis séricos de GLP-1 foram significativamente maiores no pós-operatório (p<0,05), tanto em jejum como pós-prandial sendo que houve diminuição dos níveis de GIP, contudo sem significância estatística. O gene p53 sofreu aumento significativo de sua expressão relativa (qrt-PCR)(p<0,05) no período pós-operatório na mucosa duodenal e uma tendência de aumento no íleo, contudo sem significância estatística. A análise da expressão ao nível proteico foi bem sucedida somente no íleo, também mostrando tendência de aumento. Concluí-se que a DSP foi capaz de controlar satisfatoriamente o DM2 em pacientes com IMC<35 Kg/m2. Houve aumento da secreção de GLP-1 e tendência de diminuição do GIP. Houve aumento da expressão do p53 na mucosa intestinal, no período pós-operatório, após o controle do diabetes, quando comparada ao período pré-operatório.

Efeitos da desnutrição calórica ou protéica durante a lactação na susceptibilidade à nicotina durante a adolescência de camundongos

A desnutrição durante o desenvolvimento produz alterações permanentes em diferentes sistemas de neurotransmissores, o que pode gerar modificações na respostas a drogas psicoativas. Apesar dos efeitos da desnutrição precoce no sistema colinérgico serem bem conhecidas, não existem evidências que demonstrem efeitos relacionados a susceptibilidade aos efeitos da nicotina. Assim, o objetivo deste estudo foi investigar os efeitos da restrição protéica ou calórica durante a lactação de camundongos na susceptibilidade aos efeitos desta droga. Considerando que estudos demonstram que o consumo de tabaco freqüentemente se inicia na adolescência, investigamos neste período, os efeitos da nicotina no teste de campo aberto (CA), teste da preferência condicionada por lugar (CPP) e teste da preferência pela nicotina (PPN). Estudos sugerem que o estresse pode alterar a susceptibilidade ao uso de drogas, por isso foram avaliados os níveis séricos de corticosterona, o conteúdo de catecolaminas da medula adrenal e enzimas desta via. As mães foram randomicamente divididas nos seguintes grupos: 1) Grupo Controle (GC)- dieta padrão (23% de proteína); 2) Grupo Restrição Protéica (RP)- dieta isoenergética (8% de proteína) e 3) Grupo Restrição Calórica (RC)- dieta padrão em quantidade restrita (média de ingestão do grupo RP). A desnutrição abrangeu o período do segundo dia de vida pós-natal (PN2) até o desmame (PN21) e em PN30, foram realizados os testes comportamentais. Após o término dos testes de OP e CPP, os animais foram decapitados e o sangue e a adrenal coletados para análises endócrinas. Os animais do grupo RP e RC apresentaram menor ganho de peso e menor conteúdo de gordura retroperitoneal quando comparados aos animais GC. No teste CA, a administração de nicotina produziu um aumento da atividade locomotora nos animais GC e RP, o que não foi observado nos animais RC A desnutrição levou a uma diminuição do conteúdo de catecolaminas da adrenal em PN30. No teste CPP, apenas o GC e RC apresentaram padrão de condicionamento. Em relação ao teste da PPN, o grupo CG apresentou aumento no padrão de consumo de nicotina, o que não foi visto nos grupos RC e RP. A nicotina não afetou a função adrenal dos grupos programados. Estes resultados sugerem que a desnutrição durante a lactação ameniza os efeitos da nicotina durante a adolescência e que as alterações comportamentais dependem do padrão de desnutrição.

Human use pharmaceuticals in the estuarine environment: a survey of the Chesapeake Bay, Biscayne Bay, and Gulf of the Farallones

The assessment of emerging risks in the aquatic environment is a major concern and focus of environmental science (Daughton and Ternes, 1999). One significant class of chemicals that has received relatively little attention until recently are the human use pharmaceuticals. In 2004, an estimated 2.6 billion prescriptions were written for the top 300 pharmaceuticals in the U.S. (RxList, 2005). Mellon et al. (2001) estimated that 1.4 million kg of antimicrobials are used in human medicine every year. The use of pharmaceuticals is also estimated to be on par with agrochemicals (Daughton and Ternes, 1999). Unlike agrochemicals (e.g., pesticides) which tend to be delivered to the environment in seasonal pulses, pharmaceuticals are continuously released through the use/excretion and disposal of these chemicals, which may produce the same exposure potential as truly persistent pollutants. Human use pharmaceuticals can enter the aquatic environment through a number of pathways, although the main one is thought to be via ingestion and subsequent excretion by humans (Thomas and Hilton, 2004). Unused pharmaceuticals are typically flushed down the drain or wind up in landfills (Jones et al. 2001).

Anti-grazing properties of the toxic dinoflagellate Karlodinium veneficum during predator-prey interactions with the copepod Acartia tonsa

Karlodinium veneficum (syn. Karlodinium micrum, Bergholtz et al. 2006; J Phycol 42:170–193) is a small athecate dinoflagellate commonly present in low levels in temperate, coastal waters. Occasionally, K. veneficum forms ichthyotoxic blooms due to the presence of cytotoxic, hemolytic compounds, putatively named karlotoxins. To evaluate the anti-grazing properties of these karlotoxins, we conducted food removal experiments using the cosmopolitan copepod grazer Acartia tonsa. Wild-caught, adult female A. tonsa were exposed to 6 monoalgal or mixed algal diets made using bloom concentrations of toxic (CCMP 2064) and non-toxic (CSIC1) strains of K. veneficum. Ingestion and clearance rates were calculated using the equations of Frost (1972). Exposure to the toxic strain of K. veneficum did not contribute to an increased mortality of the copepods and no significant differences in copepod mortality were found among the experimental diets. However, A. tonsa had significantly greater clearance and ingestion rates when exposed to a monoalgal diet of the non-toxic strain CSIC1 than when exposed to the monoalgal diet of toxic strain CCMP 2064 and mixed diets dominated by this toxic strain. These results support the hypothesis that karlotoxins in certain strains of K. veneficum deter grazing by potential predators and contribute to the formation and continuation of blooms.

Challenges in the Silent Aircraft engine design

The Silent Aircraft Initiative goal is to design an aircraft that is imperceptible above background noise outside the airport boundary. The aircraft that fulfils this objective must also be economically competitive with conventional aircraft of the future and therefore fuel consumption and mechanical reliability are key considerations for the design. To meet these ambitious targets, a multi-fan embedded turbofan engine with boundary layer ingestion has been proposed. This configuration includes several new technologies including a variable area nozzle, a complex high-power transmission system, a Low Pressure turbine designed for low-noise, an axial-radial HP compressor, advanced acoustic liners and a low-speed fan optimized for both cruise and off-design operation. These technologies, in combination, enable a low-noise and fuel efficient propulsion system but they also introduce significant challenges into the design. These challenges include difficulties in predicting the noise and performance of the new components but there are also challenges in reducing the design risks and proving that the new concepts are realizable. This paper presents the details of the engine configuration that has been developed for the Silent Aircraft application. It describes the design approach used for the critical components and discusses the benefits of the new technologies. The new technologies are expected to offer significant benefits in noise reduction without compromising fuel burn. However, more detailed design and further research are required to fully control the additional risks generated by the system complexity.

Performance of a Boundary Layer Ingesting (BLI) propulsion system

This paper presents an assessment of the performance of an embedded propulsion system in the presence of distortion associated with boundary layer ingestion. For fan pressure ratios of interest for civil transports, the benefits of boundary layer ingestion are shown to be very sensitive to the magnitude of fan and duct losses. The distortion transfer across the fan, basically the comparison of the stagnation pressure non-uniformity downstream of the fan to that upstream of the fan, has a major role in determining the impact of boundary layer ingestion on overall fuel burn. This, in turn, puts requirements on the fidelity with which one needs to assess the distortion transfer, and thus the type of models that need to be used in such assessment. For the three-dimensional distortions associated with fuselage boundary layers ingested into a subsonic diffusing inlet, it is found that boundary layer ingestion can provide decreases in fuel burn of several per cent. It is also shown that a promising avenue for mitigating the risks (aerodynamic as well as aeromechanical) in boundary layer ingestion is to mix out the flow before it reaches the engine face.

An advanced multi-configuration stator well cooling test facility

Optimisation of cooling systems within gas turbine engines is of great interest to engine manufacturers seeking gains in performance, efficiency and component life. The effectiveness of coolant delivery is governed by complex flows within the stator wells and the interaction of main annulus and cooling air in the vicinity of the rim seals. This paper reports the development of a test facility which allows the interaction of cooling air and main gas paths to be measured at conditions representative of those found in modern gas turbine engines. The test facility features a two stage turbine with an overall pressure ratio of approximately 2.6:1. Hot air is supplied to the main annulus using a Rolls-Royce Dart compressor driven by an aero-derivative engine plant. Cooling air can be delivered to the stator wells at multiple locations and at a range of flow rates which cover bulk ingestion through to bulk egress. The facility has been designed with adaptable geometry to enable rapid changes of cooling air path configuration. The coolant delivery system allows swift and accurate changes to the flow settings such that thermal transients may be performed. Particular attention has been focused on obtaining high accuracy data, using a radio telemetry system, as well as thorough through-calibration practices. Temperature measurements can now be made on both rotating and stationary discs with a long term uncertainty in the region of 0.3 K. A gas concentration measurement system has also been developed to obtain direct measurement of re-ingestion and rim seal exchange flows. High resolution displacement sensors have been installed in order to measure hot running geometry. This paper documents the commissioning of a test facility which is unique in terms of rapid configuration changes, non-dimensional engine matching and the instrumentation density and resolution. Example data for each of the measurement systems is presented. This includes the effect of coolant flow rate on the metal temperatures within the upstream cavity of the turbine stator well, the axial displacement of the rotor assembly during a commissioning test, and the effect of coolant flow rate on mixing in the downstream cavity of the stator well. Copyright © 2010 by ASME.

La reproducción de la merluza en el Mar Argentino (Merlucciidae, Meluccius merluccius hubbsi) : 2. La reproducción de la merluza y su relación con otros aspectos biológicos de la especie

The paper deals with the spawning cycle of the hake, Merluccius merluccius hubbsi in the fishing area of the Argentine fleet, SW Atlantic (35°- 46° L. S.: 53°- 63° L.W.; 30-160 fathoms depth). It was made on the basis of the weekly sampling of the commercial catch in the period January 1965 - March 1968. The results have been compared with those of the exploratory surveys made by the United Nations Fisheries Development Program (República Argentina - FAO). The histological study, which was made with 741 specimens, was most intensive in females than in males. The results have been compared with the sexual stage determinations of both sexes in the total samples during the period before mentioned. The conclusions are: 1. The analysis of the ovocytes frequency distributions showed a period of resting or slow recuperation (April - August) with a mode of 120 ~k and one of rapid transformation (October - December) from 120 μ tíll 830 ~k. After December it appears again the mode of 120 ~k which indicated the reserve stock. 2. The maturity factor shows in both sexes a period of low values , 0,52 to 2% (April - September) and, another with higher values (October - March). In the first period the values are concentrated, while in the second one a large dispersion is observed produced by the rapidity of the growth process of the gonads. It is more evident between November and December. 3. The liver weight variations, compared with the degree of ingestion and the values of the maturity factor, in time, demonstrated that: a) after two periods of abundant ingestion (March - April and October- November) there are two increases of the liver index; b) the increase of the Iiver index has a direct relation to the maturity factor; c) at the end of the summer season, when the values of the maturity factor decrease, those of the liver index are still high. This demonstrates that the hake does not arrive exhausted at the end of the spawning season and that a rapid recuperation for a new spawning by part of the stock is possible. 4. Females predominate in the samples during most of the year. In the period October - December, when sexual activation occurs, as it is demonstrated by the high values of the maturity factor, proportions are nearly 1 :1, and males at times are more numerous than females. 5. The analisys of the advaneed maturity stages, in relation to total length shows that in the hake, Iike in other fishes, the largest ones mature first. This applies for both sexes. 6. The study of the maturity factor values and the sexual stages of the samples allows the recognition of two spawning periods, the main one in summer (October - March) and another in winter (June - July). 7. Part of the summer spawners, with a rapid recuperation, should be able to spawn again in winter. This indicates that the hake population, acording to our samples, has two different possibilities of spawning. 8. After analysis of the frequency percentages composition of mature specimens it is concluded that during the summer season, when hake is fished in shallow waters and in a wide area (38°– 43° L.S.) the fleet is fishing on the spawning stocks. Some winter spawners specimens have been found at 37°- 38° L.S. and in waters of more than 100 fathoms depth. 9. A new maturity scale of seven stages is proposed, instead of the one of six stages now in use. The new added stage corresponds to the postspawners during its resting period.

Rain igestion in axial flow compressors at part speed

New experimental work is reported on the effects of water ingestion on the performance of an axial flow compressor. The background to the work is the effect that heavy rain has on an aeroengine compressor when operating in a "descent idle" mode, i.e., when the compressor is operating at part speed and when the aeromechanical effects of water ingestion are more important than the thermodynamic effects. Most of our existing knowledge in this field comes from whole engine tests. The current work provides the first known results from direct measurements on a stand-alone compressor. The influence of droplet size on path trajectory is considered both computationally and experimentally to show that most rain droplets will collide with the first row of rotor blades. The water on the blades is then centrifuged toward the casing where the normal airflow patterns in the vicinity of the rotor tips are disrupted. The result of this disruption is a reduction in compressor delivery pressure and an increase in the torque required to keep the compressor speed constant. Both effects reduce the efficiency of the machine. The behavior of the water in the blade rows is examined in detail, and simple models are proposed to explain the loss of pressure rise and the increase in torque. The measurements were obtained in a low speed compressor, making it possible to study the mechanical (increase in torque) and aerodynamic (reduction in pressure rise) effects of water ingestion without the added complication of thermodynamic effects. Copyright © 2008 by ASME.

Experimental investigation of turbine stator well rim seal, reingestion and interstage seal flows using gas concentration techniques and displacement measurements

Gas turbine engine performance requires effective and reliable internal cooling over the duty cycle of the engine. Life predictions for rotating components subject to the main gas path temperatures are vital. This demands increased precision in the specification of the internal air system flows which provide turbine stator well cooling and sealing. This in turn requires detailed knowledge of the flow rates through rim seals and interstage labyrinth seals. Knowledge of seal movement and clearances at operating temperatures is of great importance when prescribing these flows. A test facility has been developed at the University of Sussex, incorporating a two stage turbine rated at 400 kW with an individual stage pressure ratio of 1.7:1. The mechanical design of the test facility allows internal cooling geometry to be rapidly re-configured, while cooling flow rates of between 0.71 CW, ENT and 1.46 C W, ENT, may be set to allow ingress or egress dominated cavity flows. The main annulus and cavity conditions correspond to in cavity rotational Reynolds numbers of 1.71×106< Reφ <1.93×106. Displacement sensors have been used to establish hot running seal clearances over a range of stator well flow conditions, allowing realistic flow rates to be calculated. Additionally, gas seeding techniques have been developed, where stator well and main annulus flow interactions are evaluated by measuring changes in gas concentration. Experiments have been performed which allow rim seal and re-ingestion flows to be quantified. It will be shown that this work develops the measurement of stator well cooling flows and provides data suitable for the validation of improved thermo-mechanical and CFD codes, beneficial to the engine design process. Copyright © 2011 by Rolls-Royce plc.

An investigation into numerical analysis alternatives for predicting reingestion in turbine disc rim cavities

Reliable means of predicting ingestion in cavities adjacent to the main gas path are increasingly being sought by engineers involved in the design of gas turbines. In this paper, analysis is to be presented that results from an extended research programme, MAGPI, sponsored by the EU and several leading gas turbine manufactures and universities. Extensive use is made of CFD modelling techniques to understand the aerodynamic behaviour of a turbine stator well cavity, focusing on the interaction of cooling air supply with the main annulus gas. The objective of the study has been to benchmark a number of CFD codes and numerical techniques covering RANS and URANS calculations with different turbulence models in order to assess the suitability of the standard settings used in the industry for calculating the mechanics of the flow travelling between cavities in a turbine through the main gas path. The modelling methods employed have been compared making use of experimental data gathered from a dedicated two-stage turbine rig, running at engine representative conditions. Extensive measurements are available for a range of flow conditions and alternative cooling arrangements. The limitations of the numerical methods in calculating the interaction of the cooling flow egress and the main stream gas, and subsequent ingestion into downstream cavities in the engine (i.e. re-ingestion), have been exposed. This has been done without losing sight of the validation of the CFD for its use for predicting heat transfer, which was the main objective of the partners of the MAGPI Work- Package 1 consortium. Copyright © 2012 by ASME.

Food web of benthic macro invertebrates in a large Yangtze River-connected lake: the role of flood disturbance

This Study was conducted in Lake Dongtinghu, a large river-connected lake on the Yangtze River flood-plain, China. Our goal was to determine trophic relationships among benthic macroinvertebrates, as well as the effects of flood disturbance on the benthic food web of a river-connected lake. Macroinvertebrates in the lake fed mainly on detritus and plankton (both zooplankton and phytoplankton). Food web Structure in Lake Dongtinghu was characterized by molluscs as the dominant group, low connectance, high level of omnivory. based oil detritus and primary production, and most ingestion concentrating on a few links. Our analyses showed that flood disturbance is an important factor affecting the benthic food web in Lake Dongtinghu. The numbers of species and functional feeding groups (FFGs), and the density and biomass of macroinvertebrates decreased significantly during flooding. Connectance was higher during the flood season than in other seasons, indicating that floods have a strong effect on connectance in this Yangtze River-connected lake. Flood effects on the benthic web were also evident in the decrease of niche overlaps within and anion, FFGs. Our results provide useful information regarding biodiversity conservation on the Yangtze floodplain. Reconstructing and maintaining natural and regular flow regimes between Yangtze lakes and the river is essential for restoration of macroinvertebrates on the floodplain.

The influence of boundary conditions on tip leakage flow

Most of the current understanding of tip leakage flows has been derived from detailed cascade experiments. However, the cascade model is inherently approximate since it is difficult to simulate the boundary conditions present in a real machine, particularly the secondary flows convecting from the upstream stator row and the relative motion of the casing and blade. This problem is further complicated when considering the high pressure turbine rotors of aero engines, where the high Mach numbers must also be matched in order to correctly model the aerodynamics and heat transfer. More realistic tests can be performed on high-speed turbines, but the experimental fidelity and resolution achievable in such set-ups is limited. In order to examine the differences between cascade models and real-engine behavior, the influence of boundary conditions on the tip leakage flow in an unshrouded high pressure turbine rotor is investigated using RANS calculations. This study examines the influence of the rotor inlet condition and relative casing motion. A baseline calculation with a simplified inlet condition and no relative endwall motion exhibits similar behavior to cascade studies. Only minor changes to the leakage flow are induced by introducing either a more realistic inlet condition or relative casing motion. However when both of these conditions are applied simultaneously the pattern of leakage flow is very different, with ingestion of flow over much of the early suction surface. The paper explores the physical processes driving this change and the impact on leakage losses and modeling requirements. Copyright © 2013 by ASME.

Microcystin accumulation in freshwater bivalves from Lake Taihu, China, and the potential risk to human consumption

The potential risk through ingestion of microcystins (MC) in contaminated mollusks has not been well studied. The present paper studied seasonal changes of MC content (determined by liquid chromatography-mass spectrometry) in various organs of three species of bivalves (Cristaria plicata, Hyriopsis cumingii, and Lamprotula leai) in Lake Taihu, China, where toxic cyanobacterial blooms occurred. Coinciding with peaks of seston MC (maximum, 5.7 mu g/L) and MC in cyanobacterial blooms (maximum, 0.534 mg/g), most organs showed sharp MC peaks during the summer, indicating both fast uptake and fast depuration by bivalves. Because hepatopancreas and intestine had considerably higher MC content than other organs, they are the most dangerous for human consumption. Both the present and previous studies show that the hepatopancreatic MC and total tissue MC often are correlated in various aquatic invertebrates. During the peak of the cyanobacterial blooms, C. plicata had higher hepatopancreatic MC content than the other bivalves, whereas H. cumingii had higher intestinal MC content than the other bivalves. Estimated daily intakes for humans from the consumption of whole tissues of the three bivalves were 0.48 to 0.94 mu g MC-LR equivalent/kg body weight (12- to 23.5-fold the tolerable daily intake value proposed by the World Health Organization), which indicates a high risk for humans consuming these bivalves.

Bioaccumulation of the hepatotoxic microcystins in various organs of a freshwater snail from a subtropical Chinese lake, Taihu lake, with dense toxic microcystis blooms

In this paper, we describe the seasonal dynamics of three common microcystins (MCs MC-RR, MC-YR, and MC-LR) in the whole body, hepatopancreas, intestine, gonad, foot, remaining tissue, and offspring of a freshwater snail, Bellamya aeruginosa, from Gonghu Bay of Lake Taihu, China, where dense toxic Microcystis blooms occur in the warm seasons. Microcystins were determined by liquid chromatography electrospray ionization mass spectrum. Microcystin (MC-RR + MC-YR + MC-LR) content of the offspring and gonad showed high positive correlation, indicating that microcystins could transfer from adult females to their young with physiological connection. This study is the first to report the presence of microcystins in the offspring of the adult snail. The majority of the toxins were present in the intestine (53.6%) and hepatopancreas (29.9%), whereas other tissues contained only 16.5%. If intestines are excluded, up to 64.3% of the toxin burden was allocated in the hepatopancreas. The microcystin content in the intestine, hepatopancreas, and gonad were correlated with the biomass of Microcystis and intracellular and extracellular toxins. Of the analyzed foot samples, 18.2% were above the tolerable daily microcystin intake recommended by the World Health Organization (WHO) for human consumption. This result indicates that public health warnings regarding human ingestion of snails from Taihu Lake are warranted. In addition, further studies are needed to evaluate the occurrence by Microcystis in relation to spatial and temporal changes in water quality.