No description available.

Publicación a texto completo no autorizada por el autor / Trata sobre el problema del Síndrome Ascítico (SA) en la avicultura. En pollos de engorde este problema es de importancia mundial, en especial en aquellos países que tienen una crianza de producción de pollos de engorde sobre los 1300 m.s.n.m.; siendo la causa principal de muerte en pollos criados en altura. También se presenta a nivel del mar cuando las condiciones ambientales generan una deficiencia de oxígeno en el interior de los galpones; debido a la pobre ventilación y al aumento de gases como el amoniaco, además las micotoxinas dañan el hígado y riñón interfiriendo con el retorno venoso y agravando el cuadro; a esto se suma que el pollo de engorde ha sido mejorado genéticamente con el pasar de los tiempos para producir pollos con mayor ganancia de peso y masa muscular, en el menor tiempo posible. Este mejoramiento genético hace que este tipo de ave tenga una mayor demanda metabólica con un mayor consumo de oxígeno. La baja temperatura y menor presión de oxigeno existente en las regiones altas, exige un mayor gasto cardiaco y mayor demanda de O2, desencadenando hipoxia, que es la principal causa que da origen al síndrome ascítico; el cual se caracteriza por un incremento de la resistencia al flujo sanguíneo en la circulación arteriolar pulmonar, que conduce a una hipertensión arterial pulmonar, dificultad del retorno venoso, hipertrofia del ventrículo derecho y en la mayoría de los casos insuficiencia cardiaca derecha que culmina con la muerte del pollo de engorde. Es por eso que el presente trabajo tiene por objetivo establecer los factores, mecanismos fisiológicos compensatorios y las descompensaciones que ocasionan el SA en pollos de engorde; y los métodos orientados a disminuir la mortalidad por el SA como son el manejo ambiental y la restricción alimenticia; y así disminuir las pérdidas económicas anuales para los avicultores de varios países del mundo. / Trabajo de suficiencia profesional

Purpose: Hypoxia in colorectal cancer (CRC) and gastroesophageal cancer (GEC) decreases tumour responsiveness to radio and chemotherapy leading to cancer progression and poor prognosis. This is the first study to utilise [18F]FAZA hypoxia radiotracer in patients with CRC and GEC. Methods: Six patients (mean age 68±8 years, 2 males and 4 females) with CRC and 4 patients diagnosed with GEC (mean age 65 years, 3 males and 1 female) were included in the study. [18F]FAZA was synthesised at the John Mallard Scottish PET Centre. After injection with 370 MBq of [18F]FAZA, PET/CT images with 60 min dynamic scan were acquired. In addition, 15 min static scans 2 hr post injection were performed. 3D PET images were reconstructed iteratively using an ordered subset expectation maximization (OSEM) method and fused to the corresponding low-dose CT images. [18F]FAZA uptake parameters including maximum standard uptake value (SUVmax), tumour-to-muscle ratio (T/M), tumour-to-bowel ratio (T/B) and volume of interest (VOI) were measured. Results: 4 out 6 patients with CRC (66%) showed clear uptake of [18F]FAZA in the primary tumour. The mean tumour SUVmax was 2.2±0.91 (range 1.12 - 3.71). The tumour SUVmax was significantly higher compared with muscle and bowel (t(5) =3.11, P=0.03), (t(5) =3.08, P=0.03), respectively. However, tumour SUVmean didn't differ significantly compared with muscle and bowel (t(5) =2.41 , P=0.06), (t(5) =2.46 , P=0.06) respectively. The mean tumour to muscle ratio (T/M) ratio was 1.89±0.64 (range 1.10 - 2.87), while the mean tumour to normal bowel (T/B) was 1.92±0.64 (range 1.08 - 2.74). However, [18F]FAZA did not accumulate in any of the tumours found in patients with GEC. Conclusions: [18F]FAZA PET/CT imaging is suitable and feasible for detecting CRC hypoxic tumour regions with image quality that can be used in clinical practice.

The inter-tissue metabolic responses to hypoxia were determined in lungfish (Protopterus aethiopicus), and trout (Salmo gairdneri). Lungfish respond to hypoxia with a reduction in metabolic rate. It was intended to determine which tissue, or tissues exhibit decreased metabolic rates during hypoxia, and then compare the results with the metabolic reactions observed in trout, which are not reported to reduce metabolic rate during hypoxia. The metabolic potentials of the heart, brain, white muscle and liver in the African lungfish were estimated using enzymatic data. Metabolic effects of a 12 hr submergence were monitored using metabolite measurements. Heart was the most oxidative tissue, but also showed the greatest anaerobic potential. The brain displayed relatively low oxidative capabilities. White muscle remained almost inert. Although high energy phosphate concentrations in brain and heart did not fall during submergence, glycolysis was activated as indicated by cross-over plots, depletion of endogenous glycogen stores, and lactate accumulation. Blood-tissue lactate and glucose gradients indicated (1) that the heart and brain released lactate throughout submergence, (2) that after 12 hr of submersion the brain and heart were probably obtaining all their required glucose from the blood (3) that the liver released glucose throughout submergence, and (4) the white muscle was metabolically isolated from the rest of the body during submergence. The lack of measurable changes in white muscle metabolite concentrations coupled with the low enzyme activities leads to the suggestion that the most significant adaptation to hypoxia in these fishes may not be the capacity for increased anaerobic energy production. Instead, it is likely that the ability of the muscle to prevent the activation of glycolysis during hypoxic dysoxia is the key to the animal's survival. Histochemical and ultrastructural studies were done on the axial musculature of the lungfish. The small wedge of red coloured muscle evident upon gross examination was shown by histochemical demonstrations of lactate and succinate dehydrogenases, of adenosine triphosphatases, and of lipid to be composed of a mosaic of red and intermediate fibres. Respectively, these fibres measured 23.6 and 34.3 microns in average diameter. The bulk of the myotome is composed of white fibres having an average diameter of 67.3 microns. Mitochondrial density, capillarity and lipid content were very low for all fibres. These data suggest that the axial musculature is geared primarily for anaerobic function. The relatively large percentage of white muscle indicates that the overall metabolic rate of the axial muscle is low. The capacity of the muscle to exist with a reduced rate of ATP turnover (as was suggested above) may be related to the large proportion of white fibres present in the myotome. Tissue metabolites were measured in a hypoxia sensitive organism, the Rainbow trout (Salmo qairdneri), before and after exposure for 3 hr to inspired oxygen tensions of 20 torr (at 4°C). There were small changes in the brain but the energy status was maintained. The red muscle was the least affected. White muscle creatine phosphate was depleted. Various data indicate that the white muscle is the major user of glycolytic substrates and the major producer of lactate. The heart is stressed as indicated by a decline in glycogen, ATP, CrP, and the total adenylate pool. The liver exhibited declines in every indicator of metabolic homeostasis. The liver concentrations of glycogen did not decline. The fact that anaerobic glycolysis has been activated in the white muscle, while the muscle remains in metabolic communication with the other tissues via the blood, supports the suggestion that the metabolism of the white muscle will have a pronounced effect on the metabolic status of the whole animal. The trout is maintaining its rate of oxygen uptake while activating anaerobic glycolysis in the attempt to maintain 'normal' rates of energy utilization. The turnover rates of glucose and lactate were measured in trout subjected to the same hypoxic stress as above. Glucose turnover did not change while lactate turnover increased from 2.8 ± 0.4 µmoles/min./kg to 20.6 ± 6.8 µmoles/min./kg. The lack of increase in glucose turnover was attributed to the observation that liver glycogen concentrations do not change and so there is no increase in glucose flux. The increase in lactate turnover emphasizes the fact that anaerobic glycolysis is activated and that some tissues are oxidizing lactate. The problem of when a cell becomes hypoxic and the reactions of the cell to that stress is addressed. The cell (tissue, organ, animal) has two options if oxygen supply drops to a level which prevents oxidative metabolism from supplying all of the requirements for ATP synthesis. The cell may exhibit a decline in requirements, in which case the rate of ATP production need not be as high as in the oxidative state or, conversely, anaerobic energy production may increase in the attempt to maintain ATP production rates. The lungfish muscle appears to be capable of the former, thus preserving substrates for other tissues and reducing the rate of end-product formation. The trout white muscle, on the other hand, exerts a major influence upon the other tissues when the animal is stressed with hypoxia. The term 'energy conformer' is applied to animals which do not maintain oxygen uptake in the face of a declining supply, and which allow ATP production to decline concomittantly by not activating glycolysis to a marked degree. An energy regulator would activate glycolysis in the attempt to maintain oxidative rates of ATP production. The trout is more of an energy regulator than is the lungfish with the main difference in this capacity being in the white muscle. / Science, Faculty of / Zoology, Department of / Graduate

The soil-nematode Caenorhabditis elegans survives oxygen deprivation (anoxia < 0.001 kPa of O2, 0% O2) by entering into a state of suspended animation during which cell cycle progression at interphase, prophase and metaphase stage of mitosis is arrested. I conducted cell biological characterization of embryos exposed to various anoxia exposure times, to demonstrate the requirement and functional role of spindle checkpoint gene san-1 during brief anoxia exposure. I conducted a synthetic lethal screen, which has identified genetic interactions between san-1, other spindle checkpoint genes, and the kinetochore gene hcp-1. Furthermore, I investigated the genetic and cellular mechanisms involved in anoxia-induced prophase arrest, a hallmark of which includes chromosomes docked at the nuclear membrane. First, I conducted in vivo analysis of embryos carried inside the uterus of an adult and exposed to anoxic conditions. These studies demonstrated that anoxia exposure prevents nuclear envelope breakdown (NEBD) in prophase blastomeres. Second, I exposed C. elegans embryos to other conditions of mitotic stress such as microtubule depolymerizing agent nocodazole and mitochondrial inhibitor sodium azide. Results demonstrate that NEBD and chromosome docking are independent of microtubule function. Additionally, unlike anoxia, exposure to sodium azide causes chromosome docking in prophase blastomeres but severely affects embryonic viability. Finally, to identify the genetic mechanism(s) of anoxia-induced prophase arrest, I conducted extensive RNA interference (RNAi) screen of a subset of kinetochore and inner nuclear membrane genes. RNAi analysis has identified the novel role of 2 nucleoporins in anoxia-induced prophase arrest.

Neurovascular injuries are leading causes of disability implicated in neurological dysfunction. Much of the Central Nervous System (CNS) homeostasis depends on concerted signaling between neurons, glial cells, and vasculature–the neurovascular unit (NVU). Neurovascular injuries disrupt the NVU causing hypoxia, ischemia, neuroinflammation, and neuronal death. Much of the neuroinflammatory responses associated with neurovascular injuries have been characterized, but the contribution of specific signaling pathways from the injured endothelium to inflammatory response remains to be established. To understand vascular-glial communication in the context of vascular injury, the Troy lab has used a mouse model of retinal vascular injury, retinal vein occlusion (RVO). The retina is a CNS enclosed tissue that allows live visualization of vascular and neuronal condition upon injury, genotype, and/or treatment. Previous studies in the laboratory determined that non-apoptotic expression of endothelial caspase-9 (EC Casp9) was key for the development of retinal edema, capillary ischemia, and neuronal death. Caspases are known for their role in mediating cell death, but how and if glial cells orchestrated outcomes remain unknown. This thesis work aimed to investigate the role of caspase-9 signaling in vascular-glial communication and its contribution to pro-inflammatory cytokine levels and neurodegeneration in neurovascular injury. To answer this, we first optimized the mouse model of RVO and profiled the levels of caspases in RVO retinas treated or untreated with a caspase-9 inhibitor using immunohistochemistry. Then, we used tamoxifen inducible endothelial and astroglial caspase-9 KO lines, subjected them to RVO and measured glial changes, cytokine levels, capillary ischemia, retinal edema, neuronal death, and vision dysfunction. We first found that RVO induces a range of cell-specific levels of caspases and that inhibition of caspase-9 specifically modulated the levels of endothelial caspase-9 and 8, neuronal caspase-9, 7, and 6, astroglial caspase-6, and leukocytic caspase-9 and 7. Our studies also suggest that endothelial caspase-9 induces a decrease in reactive microglia, inflammatory cytokines, cleaved- caspase-6 and GFAP cleavage in astrocytes. EC Casp9 deletion also altered changes in GFAP, nestin and AQP4 levels in Müller glia. Through investigating an astroglial caspase-9 KO, we discovered that astroglial caspase-9 could be upstream of astroglia caspase-6. Additionally, we found that astroglial caspase-9 loss protected hypoxic retinas from capillary ischemia but not from retinal edema nor neuronal death. Lastly, we used an optokinetic test to study the potential role of endothelial and astroglial caspase-9 in RVO-induced vision disfunction. Our results indicate that removing caspase-9 from endothelial cells or astrocytes protected contrast sensitivity damage in visual function one day post-RVO. In sum, the present thesis work demonstrates that endothelial and astroglial caspase-9 signaling can lead to inflammation and worsening of visual function in neurovascular injury.

No description available.

The brain of fish, as in other vertebrates, is responsible for many functions basic to life and is also thought to be an anoxia-sensitive tissue. Therefore, during anoxia, the maintenance of energy within the brain is of paramount importance to the survival of the animal. Studies concerning energy levels and storage and the use of anaerobic metabolism in fish brains following exposure to anoxia are lacking. Rainbow trout (<u>Salmo gairdneri</u>) and brown bullhead catfish (<u>Ictalurus nebulosus</u>) occupy ecologically distinct habitats. Their tolerance of anoxia is different; trout survived l2 minutes while bullhead survived 62 minutes in anoxic water. Brains from control and anoxiaâ exposed trout and bullheads were analyzed using enzymatic assays and high pressure liquid chromatography (HPLC). Control bullhead brains had higher concentrations of glycogen, ATP, CrP, and glucose than control trout. With anoxia, bullheads showed a significant decrease in ATP, CrP, and glycogen with no change noted for glucose, ketone bodies (betaâ hydroxybutyrate and acetoacetate), or alternative anaerobic endproducts (succinate, alanine, propionate, isobutyrate, isovalerate, and ethanol). Lactic acid increased two-fold with anoxia. The bullhead was able to generate ATP by depleting its CrP stores and through classical anaerobic glycolysis. Death was most likely due to an inability to maintain ATP levels. Catfish may survive anoxia longer than trout in part due to greater fuel stores. Rainbow trout brain stored approximately one sixth the amount of glycogen as bullheads. With anoxia, these stores were depleted but there was no significant decrease in ATP, CrP, or glucose; the alternative endproducts also did not change. There was a l00% increase in lactic acid, suggesting that anaerobic glycolysis helped maintain ATP levels. Death may be due to factors other than ATP depletion such as lactic acid injury and increased intracellular free calcium. / Master of Science

INTRODUÇÃO: A ventilação não-invasiva consiste na aplicação de pressão positiva na via aérea do paciente através de máscaras e interfaces sem a utilização de uma cânula intratraqueal. A presença da cânula na traquéia e outros fatores relacionados à ventilação invasiva convencional são responsáveis por diversas complicações. O uso da ventilação não-invasiva e o desenvolvimento de estudos sobre o tema têm aumentado nos últimos anos, com o objetivo de prevenir ou amenizar as complicações da ventilação invasiva. Em grupos selecionados de pacientes adultos, a ventilação nãoinvasiva é responsável pela diminuição da necessidade de intubação, mortalidade e custos hospitalares. Em pediatria, o número de estudos ainda é reduzido. OBJETIVOS: 1) Descrever os aspectos gerais relacionados ao uso da ventilação não-invasiva (interfaces, ventiladores, modos, pressões, tempo de uso e cuidados) em crianças e adolescentes com insuficiência respiratória aguda. 2) Avaliar a eficácia e a efetividade do uso da ventilação não-invasiva em crianças e adolescentes com insuficiência respiratória aguda. 3) Descrever as complicações da ventilação não-invasiva em crianças e adolescentes com insuficiência respiratória aguda. METODOLOGIA: Foi realizada uma revisão sistemática da literatura nas seguintes bases de dados: Medline, Lilacs, Embase e Colaboração Cochrane, no período de 1966 a maio de 2006, utilizando os seguintes termos: ventilação não-invasiva, CPAP, BIPAP, falha respiratória aguda, hipoxemia e hipercapnia. Os desfechos analisados incluíam: necessidade de intubação, mortalidade, efeitos sobre a oxigenação e ventilação. RESULTADOS: Das 120 publicações encontradas, 11 foram incluídas nesta revisão, sendo um ensaio clínico randomizado, uma revisão sistemática e nove séries de casos, envolvendo um total de 145 pacientes. A ventilação não-invasiva acarretou melhora clínica, e gasométrica dos pacientes. Apenas quatro, dos cento e quarenta e cinco pacientes, morreram. A maioria dos estudos, porém, não tinha grupo controle, o que impossibilitou uma análise da relação causal entre a ventilação não-invasiva em estudo e os efeitos encontrados. CONCLUSÕES: Devido ao reduzido número de ensaios clínicos randomizados, os dados mais atuais sugerem que a ventilação não-invasiva é ainda uma terapia experimental para crianças com IRtA / INTRODUCTION: The non invasive ventilation consists of the application of positive pressure in the airway of the patient through masks and interfaces without the use of a traqueal cannula. The presence of the cannula in the trachea and other factors related to the conventional invasive ventilation is responsible for diverse complications. The use of the non invasive ventilation and the development of studies on the subject have increased in the last years, with the objective to prevent and to brighten up the complications of the invasive ventilation. In selected groups of adult patients use of non invasive ventilation provides effective respiratory support while avoiding the need for endotracheal intubation and mortality decrease. OBJECTIVES: 1) Describe the general aspects related to the use of the non invasive ventilation (interfaces, fans, ways, pressures, time of use and cares) in children and adolescents with acute respiratory insufficience. 2) Avaliar the efficacy and the effectiveness of the use of the non invasive ventilation in children and adolescents with acute respiratory insufficience. 3) Describe the complications of the non invasive ventilation in children and adolescents with acute respiratory insufficience. METHODOLOGY: The medology consisted of a systematic review of literature on non invasive ventilation. The research was performed using: Medline, Lilacs, Embase and Cochrane Collaboration in the period of 1966 to the May of 2006, using the following terms: non invasive ventilation, CPAP, BIPAP, acute respiratory failure, hipoxemia and hipercapnia. The outcomes evaluted were: necessity of endotracheal intubation, mortality, effect on the oxygenation and ventilation. RESULTS: Of the 120 publications founded, 11 were to analyse the eficacy of the non invasive ventilation in the treatment of acute respiratory failure in pediatric patients. Of the 11 clinical trials, one was systematic review, one was randomized clinical trial and six were case series, involving a total of 145 patients. A decrease in respiratory rate, heart rate and an improvment in oxigenation and ventilation were related in all patients. Only four patients (4/145) died. However, the majority of the studies did not have control group what it disabled an analysis of the causal relation enters the non invasive ventilation in study and the outcomes evaluated. CONCLUSIONS:Because the reduced number of randomizaded clinical trials, the current data suggest that the non invasive ventilation is still an experimental therapy for children with acute respiratory failure

INTRODUÇÃO: A ventilação não-invasiva consiste na aplicação de pressão positiva na via aérea do paciente através de máscaras e interfaces sem a utilização de uma cânula intratraqueal. A presença da cânula na traquéia e outros fatores relacionados à ventilação invasiva convencional são responsáveis por diversas complicações. O uso da ventilação não-invasiva e o desenvolvimento de estudos sobre o tema têm aumentado nos últimos anos, com o objetivo de prevenir ou amenizar as complicações da ventilação invasiva. Em grupos selecionados de pacientes adultos, a ventilação nãoinvasiva é responsável pela diminuição da necessidade de intubação, mortalidade e custos hospitalares. Em pediatria, o número de estudos ainda é reduzido. OBJETIVOS: 1) Descrever os aspectos gerais relacionados ao uso da ventilação não-invasiva (interfaces, ventiladores, modos, pressões, tempo de uso e cuidados) em crianças e adolescentes com insuficiência respiratória aguda. 2) Avaliar a eficácia e a efetividade do uso da ventilação não-invasiva em crianças e adolescentes com insuficiência respiratória aguda. 3) Descrever as complicações da ventilação não-invasiva em crianças e adolescentes com insuficiência respiratória aguda. METODOLOGIA: Foi realizada uma revisão sistemática da literatura nas seguintes bases de dados: Medline, Lilacs, Embase e Colaboração Cochrane, no período de 1966 a maio de 2006, utilizando os seguintes termos: ventilação não-invasiva, CPAP, BIPAP, falha respiratória aguda, hipoxemia e hipercapnia. Os desfechos analisados incluíam: necessidade de intubação, mortalidade, efeitos sobre a oxigenação e ventilação. RESULTADOS: Das 120 publicações encontradas, 11 foram incluídas nesta revisão, sendo um ensaio clínico randomizado, uma revisão sistemática e nove séries de casos, envolvendo um total de 145 pacientes. A ventilação não-invasiva acarretou melhora clínica, e gasométrica dos pacientes. Apenas quatro, dos cento e quarenta e cinco pacientes, morreram. A maioria dos estudos, porém, não tinha grupo controle, o que impossibilitou uma análise da relação causal entre a ventilação não-invasiva em estudo e os efeitos encontrados. CONCLUSÕES: Devido ao reduzido número de ensaios clínicos randomizados, os dados mais atuais sugerem que a ventilação não-invasiva é ainda uma terapia experimental para crianças com IRtA / INTRODUCTION: The non invasive ventilation consists of the application of positive pressure in the airway of the patient through masks and interfaces without the use of a traqueal cannula. The presence of the cannula in the trachea and other factors related to the conventional invasive ventilation is responsible for diverse complications. The use of the non invasive ventilation and the development of studies on the subject have increased in the last years, with the objective to prevent and to brighten up the complications of the invasive ventilation. In selected groups of adult patients use of non invasive ventilation provides effective respiratory support while avoiding the need for endotracheal intubation and mortality decrease. OBJECTIVES: 1) Describe the general aspects related to the use of the non invasive ventilation (interfaces, fans, ways, pressures, time of use and cares) in children and adolescents with acute respiratory insufficience. 2) Avaliar the efficacy and the effectiveness of the use of the non invasive ventilation in children and adolescents with acute respiratory insufficience. 3) Describe the complications of the non invasive ventilation in children and adolescents with acute respiratory insufficience. METHODOLOGY: The medology consisted of a systematic review of literature on non invasive ventilation. The research was performed using: Medline, Lilacs, Embase and Cochrane Collaboration in the period of 1966 to the May of 2006, using the following terms: non invasive ventilation, CPAP, BIPAP, acute respiratory failure, hipoxemia and hipercapnia. The outcomes evaluted were: necessity of endotracheal intubation, mortality, effect on the oxygenation and ventilation. RESULTS: Of the 120 publications founded, 11 were to analyse the eficacy of the non invasive ventilation in the treatment of acute respiratory failure in pediatric patients. Of the 11 clinical trials, one was systematic review, one was randomized clinical trial and six were case series, involving a total of 145 patients. A decrease in respiratory rate, heart rate and an improvment in oxigenation and ventilation were related in all patients. Only four patients (4/145) died. However, the majority of the studies did not have control group what it disabled an analysis of the causal relation enters the non invasive ventilation in study and the outcomes evaluated. CONCLUSIONS:Because the reduced number of randomizaded clinical trials, the current data suggest that the non invasive ventilation is still an experimental therapy for children with acute respiratory failure