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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Combination vasoactive medication use in asphyxiated newborn piglets

Manouchehri, Namdar Unknown Date
No description available.
2

Combination vasoactive medication use in asphyxiated newborn piglets

Manouchehri, Namdar 11 1900 (has links)
With asphyxia, newborns may suffer cardiogenic shock with myocardial dysfunction and dysregulation of vasomotor tone resulting in multiorgan dysfunction. Vasoactive medications are often administered with limited evidence directing clinicians regarding the use of high-dose monotherapy with dopamine relative to combination treatment with dopamine and a second different agent. We hypothesized that the treatment of hypoxia-reoxygenated newborn piglets with combinations of vasoactive medications would improve systemic and regional hemodynamics. Instrumented newborn piglets were subjected to hypoxia-reoxygenation with subsequent infusion of high-dose dopamine or moderate-dose dopamine and one of epinephrine, milrinone or levosimendan. Treatment with high-dose dopamine improved systemic and mesenteric perfusion. The addition of low-dose epinephrine showed some benefits regarding pulmonary hypertension and should a non-catecholamine agent be added to dopamine, milrinone is preferred to levosimendan given benefits to mesenteric perfusion. We conclude that the selection of appropriate vasoactive medical therapy should be directed by the clinical effects desired. / Experimental Surgery
3

Searching for the optimal radiotherapy treatment time, dose and fractionation - the role of hypoxia and reoxygenation : A modelling study

Lindblom, Emely January 2014 (has links)
The search for the optimal choice of treatment time, dose and fractionation regimen is one of the major challenges in radiation therapy. Several aspects of the radiation response of tumours and normal tissues give different indications of how the parameters defining a fractionation schedule should be altered relative to each other which often results in contradictory conclusions. For example, the increased sensitivity to fractionation in late-reacting as opposed to early-reacting tissues indicates that a large number of fractions is beneficial, while the issue of accelerated repopulation of tumour cells starting at about three weeks into a radiotherapy treatment would suggest as short overall treatment time as possible. Another tumour-to-normal tissue differential relevant to the sensitivity as well as the fractionation and overall treatment time is the issue of tumour hypoxia and reoxygenation. The tumour oxygenation is one of the most influential factors impacting on the outcome of many types of treatment modalities. Hypoxic cells are up to three times as resistant to radiation as well oxygenated cells, presenting a significant obstacle to overcome in radiotherapy as solid tumours often contain hypoxic areas as a result of their poorly functioning vasculature. Furthermore, the oxygenation is highly dynamic, with changes being observed both from fraction to fraction and over a time period of weeks as a result of fast and slow reoxygenation of acute and chronic hypoxia. With an increasing number of patients treated with hypofractionated stereotactic body radiotherapy (SBRT), the clinical implications of a substantially reduced number of fractions and hence also treatment time thus have to be evaluated with respect to the oxygenation status of the tumour. The perhaps most promising tool available for the type of study aiming at determining the optimal SBRT approach with respect to fractionation is radiobiological modelling. With clinically-derived tissue-specific radiobiological parameters and well-established survival models, in silico modelling offers a wide range of opportunities to test various hypotheses with respect to time, dose, fractionation and details of the tumour microenvironment. Any type of radiobiological modelling study intended to provide a realistic representation of a clinical tumour should therefore take into account details of both the spatial and temporal tumour oxygenation. This thesis, consisting of papers I-III and a summary, presents the results of three-dimensional radiobiological modelling of the response of tumours with heterogeneous oxygenation to various radiation qualities, fractionation schemes, oxygenation levels and dynamics using different survival models. The results of this work indicate that hypoxia and its dynamics play a major role in the outcome of both photon and carbon ion radiotherapy, and that neglecting the oxygenation status of tumours treated with SBRT may compromise the treatment outcome substantially. Continued to include clinical studies on the impact of hypoxia on the treatment outcome in lung cancer patients treated with SBRT, this project will hopefully advance the evolution towards routinely incorporating functional imaging of hypoxia into treatment planning. This is ultimately expected to result in increased levels of local control with more patients being cured from their cancer.
4

Surrogates, In-Vitro, and Clinical Investigations into the Safety and Effectiveness of Anesthesia

Niklewski, Paul J. January 2013 (has links)
No description available.
5

Ischemic Preconditioning Protects Adult Rat Cardiomyocytes Against Necrosis but not Apoptosis, via Activation of PKG

Caligtan, Marc J. 01 January 2005 (has links)
The role of cyclic guanosine monophosphate (cGMP) dependent protein kinase (PKG) in necrotic and apoptotic pathways of many cell types is well established; however its role in the ischemic preconditioning (IPC) of cardiomyocytes is not clearly defined. In the current study, we assessed the hypothesis that PKG protects against cell death following ischemidreperfusion injury in myocytes subjected to IPC. Freshly isolated adult rat ventricular myocytes were subjected to IPC by incubating in ischemic buffer for 30 minutes (min) followed by incubation in normal medium for 30 min. Prolonged simulated ischemia (SI) was created by incubating myocytes in the ischemic buffer for 90 min and reoxygenation (RO) for 120 min in the normal medium. Necrosis was determined by trypan blue exclusion and apoptosis was assessed by TUNEL assay. IPC reduced necrosis as shown by significant decrease in trypan blue positive cells as compared to virgin non-preconditioned myocytes subjected to SI and RO alone (p<.01). Similarly, the number of TUNEL positive myocytes following SI and 18 hrs of RO were significantly reduced in the IPC group. Treatment with PKG inhibitor, KT5832 (2pM) completely abolished the protection against necrosis by IPC. However, KT5832 failed to abolish the protective affect of IPC against apoptosis. Furthermore, myocytes infected with an adenoviral construct of PKG-la (1 x 1 o4 particles/cell) significantly reduced the number of trypan blue and TUNEL positive cells. These results suggest that the PKG signaling pathway plays an essential role in the preconditioning of myocytes against necrosis following SI / RO injury. Furthermore, while the overexpression of PKG protects myocytes against necrosis, as well as apoptosis, IPC may not induce a sufficient level of PKG during 18 hours of RO to induce protection against apoptosis.
6

Avaliação de metodologias para a determinação indireta do coeficiente de reoxigenação superficial (K2) / Evaluation of methods for the indirect determination of the surface reoxygenation coefficient (K2)

Gonçalves, Julio Cesar de Souza Inácio 24 September 2012 (has links)
O coeficiente de reoxigenação superficial (K2) é o parâmetro mais importante dos modelos matemáticos usados para simular a qualidade da água em rios. Ele quantifica indiretamente a capacidade de um corpo dágua recuperar-se, em termos de concentração de oxigênio dissolvido, após receber cargas poluidoras. Técnicas de previsão foram criadas para estimar o valor desse coeficiente, mas obtiveram sucesso apenas parcial; algumas são imprecisas e outras são dispendiosas. Esse trabalho traz contribuições teóricas e experimentais acerca de metodologias para a determinação indireta do coeficiente de reoxigenação superficial. Os estudos foram realizados em um tanque hidrodinâmico agitado por jatos e planejados de forma a avaliar a existência de correlações entre o fenômeno de reoxigenação superficial e os fenômenos físicos associados às novas metodologias de previsão do K2 propostas nesse trabalho. O resfriamento de um sólido metálico, o decaimento da concentração de sólidos totais dissolvidos (STD) em esferas perfuradas com minibrocas de 0,4 e 0,5 mm de diâmetro e a variação da componente vertical da velocidade junto à superfície livre foram os fenômenos físicos investigados. Modelos matemáticos foram produzidos através de análises de regressão linear entre os parâmetros K2 e o coeficiente de transferência térmica (Kt), associado ao resfriamento do sólido metálico; K2 vs. H (profundidade da água no tanque) e o coeficiente de transferência de massa por convecção (hm), associado ao decaimento de STD; e K2 e a taxa de dissipação de energia cinética turbulenta por unidade de massa (&#949;), associada à intensidade turbulenta junto à superfície livre. Os resultados revelaram que há uma forte correlação entre o K2 e os parâmetros associados aos fenômenos físicos aqui investigados, com coeficientes de correlação acima de 0,9. A aplicabilidade dos modelos obtidos é restrita às condições hidrodinâmicas nas quais os ensaios foram realizados, uma vez que não há base teórica e nem experimental indicando que as relações entre os fenômenos sejam constantes e independentes da turbulência. Sugere-se que validações em campo, com desenvolvimento de métodos específicos, sejam um próximo passo em pesquisas futuras para que se possa atribuir utilidade definitiva às metodologias aqui estudadas. / The surface reoxygenation coefficient (K2) is the most important parameter in the water quality mathematical modelling in streams. It indirectly measures the ability of a water mass recover quality after a release of wastewater. Predictive techniques have been produced for estimating K2, but they achieved only partial success; some are inaccurate and others are expensive. This work includes contributions from experimental and theoretical studies about methods for the indirect determination of the surface reoxygenation coefficient. Studies were carried out in a jet-agitated vessel and were planned to assess the correlations between surface reoxygenation and physical phenomena, which are related to the new methods for the prediction of K2. The cooling of a solid metal, total dissolved solids (TDS) concentration decay, vertical component velocity near the free surface were the physical phenomena investigated. Mathematical models have been produced using linear regression analysis between K2 and thermal transfer coefficient (Kt), associated with the solid metal cooling; K2 vs. H (depth of the water in the vessel) and mass transfer coefficient by convection (hm), associated with the TDS concentration decay; and K2 and turbulence kinetic energy dissipation rate (&#949;), associated with the vertical component velocity near the free surface. Results revealed that there is a strong correlation between K2 and the physical parameters here investigated, statistically confirmed by correlation coefficients above 0,9. The applicability of the approach used here is limited to hydrodynamic conditions in which the tests were performed, once there is no theoretical basis, or experimental, indicating that the relations between the physical parameters are constant and independent of the turbulence level. It is suggested that field tests with the development of specific methods are a next step for future research, rendering useful the methods studied here.
7

Placental Oxidative Stress in Preeclampsia

Vanderlelie, Jessica, n/a January 2006 (has links)
Affecting 6-8% of all pregnancies, preeclampsia is the leading cause of maternal morbidity in the western world and is charactensed by hypertension, proteinuria, edema and platelet aggregation. Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy, with the only therapies being bed rest, pharmacological symptom management and if necessary early delivery. Oxidative stress plays an important role in the pathophysiology of preeclampsia, resulting from defective trophoblast invasion, reductions in placental perfusion and placental hypoxia/reoxygenation. The inability of endogenous antioxidant systems up regulated in normal pregnancy, to control increased levels of oxidative stress, is suggested as a possible factor in the feed forward generation of reactive oxygen species and placental oxidative stress. That in turn may stimulate increased syncytiotrophoblast apoptosis, endothelial cell activation and the maternal hyper immune response characteristic of preeclampsia. Analysis of the research literature revealed that previous evaluations of placental oxidation and antioxidant enzyme activity in preeclampsia were by no means comprehensive, and exhibited significant inter-study variations. It was the aim of this thesis to clarify the placental oxidative state and the endogenous antioxidant activity of glutathione peroxidase, thioredoxin reductase, thioredoxin and superoxide dismutase in human placentae in an attempt to determine if variations in antioxidant function were due to changes in gene expression or protein oxidation. The findings reported in this thesis indicate the presence of increased levels of oxidative stress in the preeclamptic placenta, associated with significant reductions in antioxidant enzyme capacity. Quantitative real-time PCR analysis of placental samples revealed that deceases in antioxidant capacity in the placenta are more likely to be related to the significant oxidative burden within the tissue rather than reductions in gene expression. A number of animal models exist to investigate components of preeclampsia pathophysiology, however the ability of these models to mimic the oxidative and antioxidant features of preeclampsia remains unclear. The exposure of pregnant rats to N(G)-nitro-L-arginine methyl ester is a widely used model of endothelial cell dysfunction during preeclampsia. It was the aim of this thesis to determine the biochemical characteristics of this model in an attempt to assess its effectiveness in mimicking oxidative changes in the preeclamptic placenta. Although this model is capable of producing a syndiome in rats similar to the disorder in terms of physiology, this is not manifest in terms of placental biochemistry. The importance of selenium in the synthesis of selenobased antioxidants such as glutathione peroxidase and thioredoxin reductase is well documented. Increasing demand for selenium by the developing fetus may be linked to reductions in selenium status during pregnancy. Considering preeclampsia is associated with significant reductions in selenium status it may be hypothesised that reductions in antioxidant function may be linked to selenium inadequacy. The modulation of dietary selenium in pregnant rats was used to determine the importance of selenium during pregnancy and its effect on antioxidant function and placental oxidative stress. The results of this analysis revealed that selenium deficiency causes a pregnancy specific condition similar to preeclampsia. This condition was found to be associated with increased placental oxidative stress and significant reductions in the systemic activity of selenobased antioxidants that could be modified through selenium supplementation. In summary, data obtained in this thesis indicate that placental oxidative stress and reduced antioxidant enzyme activity play a significant role in the pathogenesis of preeclampsia. These studies support the hypothesis that antioxidant sufficiency is crucial in the maintenance of oxidative balance and that antioxidant dysfunction may result in damage to the placenta and the progression of the disease. These novel data further our understanding of the pathophysiology of preeclampsia and provide new insight into the pathogenesis of clinical complications exhibited in this condition, suggesting antioxidant therapy as a possible means for improving the health outcomes of both mother and baby.
8

The role of hypoxia-inducible factor-1 in hyperthermia-induced tumor reoxygenation and therapy resistance

Moon, Eui Jung January 2010 (has links)
<p>Imbalance between oxygen consumption and supply often makes tumors hypoxic (Bristow and Hill 2008). Tumor hypoxia is significantly correlated with aggressive tumor growth, ineffective response to radiation and chemotherapy, and as a result, poor patient prognosis. Hyperthermia (HT) is a strong adjuvant treatment to overcome these challenges of tumor hypoxia because it causes tumor reoxygenation at temperatures lower than 43ºC (Song, Park, and Griffin 2001). However, the detailed molecular mechanisms of how HT enhances tumor oxygenation have not been elucidated. Here we determine that 1 hour HT activates hypoxia-inducible factor-1 (HIF-1) and its downstream targets, vascular endothelial growth factor (VEGF), lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase 1 (PDK1) in tumors. Consistent with HIF-1 activation and upregulation of its downstream genes, HT also enhances tumor perfusion/vascularization and decreases oxygen consumption rates. As a result, tumor hypoxia is reduced after HT suggesting that these physiological changes contribute to HT-induced tumor reoxygenation. Since HIF-1 is a potent regulator of tumor vascularization and metabolism, our findings suggest that HIF-1 plays a role in HT-induced tumor reoxygenation by transactivating its downstream targets. Mechanistically, we demonstrate that NADPH oxidase-mediated reactive oxygen species (ROS) production upregulates HIF-1 after HT. Further, we determine that this pathway is initiated by increased transcription of NADPH oxidase-1 (NOX1) through the ERK pathway.</p><p>A major research effort at Duke focuses on combinations of HT and doxorubicin in the treatment of locally advanced breast and other cancers. Thus, we investigated whether there are HIF-1 responses to doxorubicin treatment. We reveal that doxorubicin also activates HIF-1. Unlike HT, doxorubicin-induced HIF-1 promotes persistent tumor angiogenesis. We also reveal that the signal transducer and activator of transcription 1 (STAT1)/inducible nitric oxide synthase (iNOS) pathway causes HIF-1&#945; accumulation in an oxygen-independent manner. We show that activated STAT1 upregulates iNOS expression and promotes nitric oxide (NO) production in tumor cells resulting in HIF-1&#945; stabilization. We further determine that both iNOS inhibitor, 1400W and STAT1 inhibitor, epigallocatechin-3-gallate (EGCG) significantly decrease intracellular NO production and suppress doxorubicin-induced normoxic HIF-1&#945; accumulation.</p><p>HIF-1 is often considered a promising therapeutic target because of its role in tumor progression (Semenza 2003) and therapy resistance (Moeller et al. 2004). However, our findings suggest that HIF-1 plays a pleiotropic role in response to HT and chemotherapy. Therefore, to preferentially take advantage of HT-induced HIF-1 activation and also to suppress its deleterious effects induced by chemotherapy or as we have previously reported, by radiation (Moeller et al. 2004), HIF-1 inhibition needs to be carefully regulated in a time-sensitive manner to achieve optimal therapeutic effects.</p> / Dissertation
9

Experimental Study of Air-Water Flow Properties on Low-Gradient Stepped Cascades

Toombes, Luke Unknown Date (has links)
Stepped cascades are recognised for both aeration potential and energy dissipation, and have been employed in hydraulic structures for over 3,500 years. Yet little detailed information exists on their performance, especially pertaining to low-gradient cascades. This study presents a detailed investigation of both the macro and micro-scale flow properties on a low-gradient cascade (3.4º slope). Research is conducted on two large-size physical models: a 24m long multi-step cascade (10× 2.4m long steps), and a single-step model with identical step height and length. The large size of the model allows near full-scale data acquisition under controlled flow conditions, minimising potential scale effects. The study comprises three distinct components: 1. A global investigation of the general flow properties of nappe flow on a low-gradient, multi-step cascade. Unforeseen three-dimensional characteristics of the flow, including supercritical shockwaves and sidewall standing-waves downstream of nappe impact, are identified and examined by the study. Although comparable to similar phenomena at channel bends and expansions, these have not been previously described on stepped cascades. Energy dissipation on the cascade is investigated, and is found to be over twice that observed for a smooth chute of similar gradient. 2. A complete characterisation of the air-water structure of flow in a nappe regime. Significant outcomes of the analysis include: ⊕ Air-concentration Distribution: The air-concentration distribution at the lower nappe of the free-falling jet shows good agreement with an analytical solution of the diffusion equation. The experimental results from the study, and a reanalysis of existing data, indicate a distinct relationship between the turbulent diffusivity in the shear layer and distance from the step brink. This contradicts earlier investigations that assumed constant diffusivity. Strong aeration of the flow, with a large volume of spray, occurs downstream of the nappe impact. Depth-averaged air concentrations of 40% to 50% are observed within the spray region, decreasing towards the downstream end of the step. ⊕ Velocity Distribution: A theoretical analysis of the momentum transfer process imparts an improved understanding of the momentum transfer and velocity redistribution within the free-falling jet. An analytical solution based on twodimensional wake flow is developed, superseding existing solutions based upon a monophase free-mixing layer. ⊕ Bubble-frequency Distribution: A quasi-parabolic relationship between bubble frequency and time-average air concentration across a cross-section is observed. A theoretical explanation for the parabolic relationship is developed, and two correction factors are introduced to provide a better representation of the experimental data. ⊕ Air-bubble and Water-droplet Size Distributions: Chord-length distributions are compared with standard probability distributions, showing good agreement with standard Weibull, gamma and log-normal probability distributions within various regions of the flow on the step. A computer model is developed to model interaction between a bubbly transition from water to air and fluctuations of the free surface. 3. A parallel investigation of the oxygen aeration efficiency of a stepped cascade. Measured air-water property data is used to calculate the air-water interface area in bubbly flow, and to estimate the theoretical aeration efficiency of the stepped cascade based upon the integration of the mass transfer equation. The aeration performance of the stepped cascade model is also measured experimentally in terms of dissolved oxygen content. This analysis allows a unique, successful comparison of experimental dissolved oxygen measurements with the numerical integration of the mass transfer equation.
10

Efeitos da pré-exposição ao cobre sobre respostas bioquímicas da anêmona-do-mar Bunodosoma cangicum a hipóxiae reoxigenação

Abujamara, Laís Donini January 2012 (has links)
Dissertação(mestrado) - Universidade Federal do Rio Grande, Programa de Pós–Graduação em Oceanografia Biológica, Instituto de Oceanografia, 2012. / Submitted by Cristiane Gomides (cristiane_gomides@hotmail.com) on 2013-10-11T11:38:27Z No. of bitstreams: 1 Lais.pdf: 937026 bytes, checksum: 99723480330641cd5bc515f0c200b9f0 (MD5) / Approved for entry into archive by Sabrina Andrade (sabrinabeatriz@ibest.com.br) on 2013-10-17T17:16:57Z (GMT) No. of bitstreams: 1 Lais.pdf: 937026 bytes, checksum: 99723480330641cd5bc515f0c200b9f0 (MD5) / Made available in DSpace on 2013-10-17T17:16:57Z (GMT). No. of bitstreams: 1 Lais.pdf: 937026 bytes, checksum: 99723480330641cd5bc515f0c200b9f0 (MD5) Previous issue date: 2012 / Os organismos bentônicos intermareais enfrentam oscilações periódicas nos níveis de oxigênio na água associadas ao ciclo de marés. Durante o recuo da maré, eles ficam expostos ao ar e sujeitos a hipóxia, favorecendo uma redução nas espécies reativas de oxigênio (ERO) e nas defesas antioxidantes. Porém, na reoxigenação há um aumento acentuado na geração de ERO. Para minimizar os prejuízos desse processo, existem mecanismos antecipatórios, tal como o aumento das defesas antioxidantes durante a hipóxia. Por sua vez, o estresse causado por poluentes químicos, como o cobre, pode alterar o padrão destas respostas. Neste estudo foram avaliadas respostas de biomarcadores associados ao estresse oxidativo e metabolismo (capacidade antioxidante total contra radicais peroxil - ACAP, atividade da superóxido dismutase - SOD, concentração de glutationa reduzida - GSH, peroxidação lipídica - LPO e concentração de ATP) na anêmona Bunodosoma cangicum pré-exposta (96 h) ao cobre (6,1 ± 2.7 μg.L-1) e submetida a hipóxia (6 h a 0.5 mgO2.L-1) seguida da reoxigenação (6 h a 7.5 mg O2.L-1). Nas anêmonas controle não foram observadas variações na ACAP, GSH, LPO e ATP. Entretanto, a atividade da SOD aumentou durante a hipóxia. Nas anêmonas pré-expostas ao cobre, a ACAP foi reduzida na hipóxia e reoxigenação. A atividade da SOD não se alterou e a concentração de GSH aumentou no início do experimento, na hipóxia e na reoxigenação. A concentração de ATP diminuiu na reoxigenação, porém a LPO não se alterou em todas as condições experimentais. Estes resultados indicam a existência de mecanismos antecipatórios para prevenção dos efeitos negativos da reoxigenação em B. cangicum e que a exposição ao cobre em concentração ambientalmente relevante afeta negativamente estes mecanismos. / Intertidal benthic organisms are subjected to changes in oxygen availability during the tidal cycle. A hypoxic condition may occur during air exposure, thus favoring a decreased level of oxygen reactive species (ROS) and antioxidant defenses. However, during re-oxygenation a ROS overproduction may occur. Anticipatory mechanisms such as a buildup of antioxidant defenses under hypoxia could be present to avoid a possible oxidative damage occurring during these processes. In turn, chemical stress induced pollutants such as copper may affect the response of these mechanisms. In the present study, the response of biomarkers associated with oxidative stress and energy (total antioxidant capacity against peroxyl radicals - ACAP, superoxide dismutase activity - SOD, lipid peroxidation - LPO, reduced glutathione - GSH, and ATP concentration) were evaluated in the sea anemone Bunadosoma cangicum pre-exposed (96 h) to copper (6.1 ± 2.7 μg.L-1) and submitted to hypoxia (6 h at 5 mg O2.L-1) followed by re-oxygenation (6 h at 7.5 mg O2.L-1). In sea anemones kept under control conditions, ACAP, GSH concentration, LPO and ATP concentration did not change over the experimental time. However, SOD activity was increased under hypoxia. In sea anemones pre-exposed to copper, ACAP was reduced under hypoxia and re-oxygenation. GSH concentration was increased during hypoxia and reoxygenation, while ATP concentration was reduced during re-oxygenation. These findings indicate that B. cangicum shows anticipatory mechanisms to avoid the oxidative stress during re-oxygenation and that pre-exposure to an environmentally relevant concentration of copper affects these mechanisms.

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