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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.
41

Avaliação dos efeitos pró apoptóticos da fosfoetanolamina sintética e da formulação lipossomal DODAC/FOS em células de carcinoma espinocelular da cavidade oral / Evaluation of pro apoptotic effects of synthetic phosphoethanolamine and DODAC/FOS liposomal formulation in oral cavity squamous cell carcinoma cells

Larissa Kim Higashi de Carvalho 24 April 2017 (has links)
Os carcinomas de cabeça e pescoço correspondem a 10% de todos dos tumores malignos, destes aproximadamente 40% se manifestam na boca e 90% correspondem ao carcinoma espinocelular. Os principais agentes carcinogênicos relacionados ao câncer bucal são o tabaco e o álcool. A cirurgia é o tratamento de eleição para o carcinoma de boca seguido dos tratamentos quimio e radioterápicos. O uso de lipossomas como vetor de quimioterápicos abre grandes perspectivas para o tratamento do câncer, pois possibilitam maior eficácia, reduzindo a toxicidade e a dosagem do fármaco. Neste projeto foram avaliados os efeitos pró apoptóticos \"in vitro\" da fosfoetanolamina sintética (FOS) e da sua formulação lipossomal DODAC/FOS em duas linhagens celulares de carcinoma espinocelular de língua humano, SCC-9 e SCC-25. A FOS, a formulação lipossomal DODAC/FOS e o carreador DODAC vazio apresentam diferentes significados em seu potencial citotóxico. A FOS aumentou significativamente a formação de lipoperóxidos pela membrana celular nas maiores concentrações estudadas. A análise das fases do ciclo celular mostrou aumento significativo da população de células com DNA fragmentado em ambas as linhagens celulares induzindo a morte celular por apoptose com aumento da expressão de Bad, Bax, citocromo c e diminuição de Bcl-2, como também alterou o potencial elétrico mitocondrial promovendo a ativação da caspase-3. A FOS e a formulação lipossomal DODAC/FOS induziram retração dos filamentos de actina e fragmentação do DNA. O conjunto de resultados mostra que o composto FOS e a sua formulação lipossomal DODAC/FOS atuam nos efeitos citotóxicos e antitumoral promovidos por estes alquilfosfoésteres, sendo capazes de induzir a morte celular por apoptose em diferentes apresentações / Head and neck carcinomas account for 10% of all malignant tumors, approximately 40% of these tumors manifest in the mouth and 90% correspond to squamous cell carcinoma. The main carcinogenic agents related to oral cancer are tobacco and alcohol. Surgery is the treatment of choice for oral carcinoma followed by chemo and radiotherapeutic treatments. The use of liposomes as a vector of chemotherapy offers great prospects for treatment of cancer, as they allow greater efficacy, reducing the toxicity and the dosage of drug. In this project, in vitro pro apoptotic effects of synthetic phosphoethanolamine (Pho-S) and DODAC/Pho-S liposomal formulation were evaluated in two human tongue squamous cell carcinoma cell lines, SCC-9 and SCC-25. Pho-S, DODAC/Pho-S liposomal formulation and the empty DODAC carrier have different meanings in their cytotoxic potential. Pho-S significantly increased the formation of lipoperoxides by cell membrane in higher concentrations studied. Analysis of the cell cycle phases showed a significant increase in the cell population with fragmented DNA in both cell lines inducing apoptosis cell death with increase expression of Bad, Bax, cytochrome c and decrease of Bcl-2, as well as altered the potential mitochondrial activation promoting caspase-3 activation. Pho-S and the DODAC/Pho-S liposomal formulation induced retraction of the actin filaments and DNA fragmentation. The set of results shows that the Pho-S compound and its liposomal formulation DODAC/Pho-S act on the cytotoxic and antitumor effects promoted by these alkylphosphoesters, being able to induce cell death by apoptosis in different presentations
42

Estudo dialélico para caracteres agronômicos em pinhão-manso (Jatropha curcas L.) / Diallel study for agronomic traits in physic nut (Jatropha curcas L.)

Santana, Ulisses Andrade 25 February 2013 (has links)
The physic nut (Jatropha curcas L.) is oilseed species belonging to Euphorbiaceae family with a widespread distribution in tropical regions. The quality and high oil content in seeds, perenicity and rusticity makes this species a potential feedstock for biodiesel production. However, the success of this insertion involves research ranging from the exploration of divergent genetic materials to selection and acquisition of productive cultivars. In this context, this study aimed to assess the combining ability of jatropha access for agronomic traits of interest, as well as information about genetic parameters associated with morphological and agronomic characters, and investigate their correlations. The study was carried out in the Experimental Farm of the UFS during the year 2012 in hybrids of jatropha evaluated up to 24 months. The experimental design was in randomized blocks with three replications and plots with six plants. There were evaluated seed yield (PR), plant height (PH), number of secondary branches (NRS), the number of female flowers (NFF), stem diameter (DC), 100-seed weight (P100 ), branching height (AR) and crown diameter (DCO). The general combining ability (GCA) was significant for the variables PR, DC, NRS and AR (Group 1) and P100 and NRS (Group 2), whereas specific combining ability (SCA) was significant for variables NFF and NRS. The sum of squares due to GCA was higher than the sum of squares due to SCA for the majority of traits, indicating that the additive effects of loci are more important than the dominance effect loci. The genitors JCUFS-04 and JCUFS-05 highlight from the others for concentration of favorable alleles. The consistent estimation of the coefficient of genetic variation allows us to infer the existence of significant genetic variability among hybrids. The characters which more contributed to genetic diversity were NFF (20.99%), DC (16.83%), PR (15.06%), and NRS (14.06). High, significance and positive genotypic correlations were recorded among (NRS), (DC), (DCO) and grain yield (PR). / O pinhão-manso (Jatropha curcas L.) é uma espécie oleaginosa da família Euphorbiaceae com ampla distribuição em regiões tropicais. A qualidade de óleo e alto teor nas sementes, perenicidade e rusticidade fazem desta espécie uma matéria-prima potencial para produção de biodiesel. Todavia, o sucesso desta inserção passa por pesquisas que vão desde a prospecção de materiais genéticos divergentes, até a seleção e obtenção de cultivares produtivos. Nesse contexto, esse trabalho teve por objetivo avaliar a capacidade combinatória de acessos de pinhão-manso, para caracteres de interesse agronômico, bem como, obter informações acerca de parâmetros genéticos associados a caracteres morfo-agronômicos, e investigar a correlação entre estes. O trabalho foi realizado na Fazenda experimental da UFS durante o ano de 2012 em híbridos de pinhão-manso avaliados até os 24 meses de idade. O delineamento experimental empregado foi em blocos casualizados com três repetições e parcelas compostas por seis plantas. Os caracteres avaliados foram rendimento de sementes (PR), altura de planta (AP), número de ramos secundários (NRS), número de flores femininas do racemo floral (NFF), diâmetro de caule (DC), massa de 100 sementes (P100), altura de ramificação (AR) e diâmetro de copa (DCO). A capacidade geral de combinação (CGC) foi significativa para as variáveis PR, DC, NRS e AR (Grupo 1) e para P100 e NRS (Grupo 2), enquanto a capacidade específica de combinação (CEC) foi significativa para as variáveis NFF e NRS. A soma de quadrados devido à CGC foi maior que a soma de quadrados devido à CEC para a maioria dos caracteres, indicando que os locos de efeito aditivo têm maior importância que os locos de efeito dominante. Os genitores JCUFS-04 e JCUFS-05 se destacaram dos demais quanto à concentração de alelos favoráveis. As estimativas consistentes dos coeficientes de variação genética permitem inferir sobre a existência de variabilidade genética significativa entre os híbridos obtidos. Os caracteres que mais contribuíram para a diversidade genética encontrada entre a populações foram, NFF (20,99%), DC (16,83%), PR (15,06%) e NRS (14,06). Altas e significativas correlações genotípicas positivas foram registradas entre (NRS), (DC), (DCO) e o rendimento de grãos (PR).
43

Dexmedetomidina diminui a resposta inflamatória após cirurgia miocárdica sob mini-circulação extracorpórea / Dexmedetomidine decrease the inflammatory response to myocardial surgery under mini cardiopulmonary bypass

Bulow, Neusa Maria Heinzmann 09 March 2013 (has links)
Despite great technological advances in coronary artery bypass grafting (CABG) surgery, there is a high incidence of cardiac dysfunction and neurocognitive deficits in the postoperative period. Preventive measures are essential to reducing these adverse situations that are responsible for significant morbidity and impairment on life quality of these patients. Surgery and cardiopulmonary bypass (CPB) produces important changes in the immune system, directly involved in the incidence of these complications and is credible that anesthesia choice can it modified. We hypothezised that dexmedetomidine, an (α)-2-agonist, could the inflammatory response to CABG and CPB modified. In a prospective and randomized study, we intend to demonstrate the influence of dexmedetomidine (TIVA-DEX group), as a component of a conventional total intravenous anesthesia (TIVA-propofol+sufentanil) in patients undergoing CABG, with mini-CPB, on the behavior of this inflammatory response. The TIVA-DEX group received a continuous infusion of dexmedetomidine associated to a conventional venous anesthesia (continuous infusion of propofol+sufentanil). Intraoperative dosage of cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), gamma interferon (INF-γ) and tumor necrosis factor (TNF-α) were performed, and also C-reactive protein (CRP), creatine phosphokinase (CPK), creatine phosphokinase-MB (CPK-MB), I troponin (cTnI), cortisol and glucose. The occurrence of lipid peroxidation, by the study of thiobarbituric acid reactive substances (TBARS) and the activity of delta-aminolevulinate dehydratase (δ-ALA-D) to oxidative stress verify were also avaliated. Dexmedetomidine induce a significative reduction of IL-1, IL-6, TNF-α and INF-γ, as compared to group that not receive dexmedetomidine. The levels of IL-10 were decreased in both groups along the time, at a similar pattern. Differences between groups on δ-ALA-D activity do not occur and TBARS was higher in TIVA-DEX group. We concluded that dexmedetomidine associated to TIVA was able to reduce plasma levels of proinflammatory cytokines IL-1, IL-6, TNF-α and INF-γ in patients submitted to CABG surgery under mini-CPB, as compared to a conventional TIVA. These results reinforce literature data about dexmedetomidine potentiality as an anti inflammatory agent. / Apesar dos grandes avanços tecnológicos nas cirurgias de revascularização miocárdica (CRM), ocorre uma grande incidência de disfunção cardíaca e déficit neurocognitivo no período pós-operatório. As medidas preventivas são essenciais para a redução destas situações adversas, responsáveis pelo comprometimento da qualidade de vida dos pacientes. A cirurgia e a circulação extra-corpórea (CEC) produzem alterações importantes no sistema imunológico, diretamente envolvidas na incidência das complicações e acredita-se que a escolha anestésica possa modificá-las. Em estudo prospectivo e randomizado, pretendemos demonstrar a influência da dexmedetomidina (grupo AIVT-DEX), um anestésico (α)-2-agonista, associado à anestesia intravenosa total (AIVT) no comportamento da resposta inflamatória em pacientes submetidos à CRM, sob mini-circulação extracorpórea (mini-CEC). O grupo AIVT-DEX recebeu infusão contínua de dexmedetomidina associado à técnica de AIVT convencional e o outro grupo foi submetido à AIVT convencional (infusão contínua de propofol e sufentanil). Os grupos foram comparados pela dosagem plasmática trans-operatória de citocinas, como a interleucina-1(IL-1), a interleucina-6 (IL-6), a interleucina-10 (IL-10), o interferon gama (INF-γ) e o fator de necrose tumoral alfa (TNF-α), bem como a proteína C reativa (PCR), creatinofosfoquinase (CPK), creatinofosfoquinase miocárdio específica (CPK-MB), troponina I (cTnI), cortisol e glicose. A peroxidação lipídica foi avaliada pelo estudo das substâncias reativas ao ácido tiobarbitúrico (TBARS) e a presença de estresse oxidativo pela atividade da enzima delta-aminolevulinato desidratase (δ-ALA-D). O uso da dexmedetomidina induziu redução significativa de IL-1, IL-6, TNF-α e INF-γ se comparado ao grupo sem dexmedetomidina. Houve redução progressiva dos níveis de IL-10 ao longo do tempo, de forma semelhante entre os grupos. Não houve diferença entre os grupos para a atividade da enzima δ-ALA-D e os níveis de TBARS foram maiores no grupo AIVT-DEX. Concluímos que a dexmedetomidina associada à AIVT convencional foi capaz de reduzir os níveis plasmáticos das citocinas pró-inflamatórias IL-1, IL-6, TNF-α e INF-γ em pacientes submetidos à CRM sob mini-CEC, se comparados aos pacientes que receberam apenas a AIVT convencional. Estes resultados reforçam os dados da literatura quanto à potencialidade da dexmedetomidina como agente modulador da resposta inflamatória no período trans- operatório.
44

Development of Advanced Capillary Electrophoresis Techniques with UV and Mass Spectrometry Detection for Forensic, Pharmaceutical and Environmental Applications

Fu, Hanzhuo 01 July 2014 (has links)
Capillary electrophoresis (CE) is a modern analytical technique, which is electrokinetic separation generated by high voltage and taken place inside the small capillaries. In this dissertation, several advanced capillary electrophoresis methods are presented using different approaches of CE and UV and mass spectrometry are utilized as the detection methods. Capillary electrochromatography (CEC), as one of the CE modes, is a recent developed technique which is a hybrid of capillary electrophoresis and high performance liquid chromatography (HPLC). Capillary electrochromatography exhibits advantages of both techniques. In Chapter 2, monolithic capillary column are fabricated using in situ photoinitiation polymerization method. The column was then applied for the separation of six antidepressant compounds. Meanwhile, a simple chiral separation method is developed and presented in Chapter 3. Beta cycodextrin was utilized to achieve the goal of chiral separation. Not only twelve cathinone analytes were separated, but also isomers of several analytes were enantiomerically separated. To better understand the molecular information on the analytes, the TOF-MS system was coupled with the CE. A sheath liquid and a partial filling technique (PFT) were employed to reduce the contamination of MS ionization source. Accurate molecular information was obtained. It is necessary to propose, develop, and optimize new techniques that are suitable for trace-level analysis of samples in forensic, pharmaceutical, and environmental applications. Capillary electrophoresis (CE) was selected for this task, as it requires lower amounts of samples, it simplifies sample preparation, and it has the flexibility to perform separations of neutral and charged molecules as well as enantiomers. Overall, the study demonstrates the versatility of capillary electrophoresis methods in forensic, pharmaceutical, and environmental applications.
45

Engineering Properties, Hydration Kinetics, and Carbon Capture in Sustainable Construction Materials

Tran, Thien Quoc 20 December 2023 (has links)
Concrete, the second most consumed material on earth after water, is a source of environmental problems due to global urbanization. The production of this construction material requires a large amount of natural resources, and portland cement (PC) is responsible for around 8 % of planet-warming CO2 emissions. Producing 1 ton of PC will release roughly 1 ton of CO2 into the atmosphere. In 2021, around 92 million metric tons of PC were produced in the U.S., and a total of 4.4 billion tons were manufactured worldwide. While there was a yearly increase of around 1.5 % in the direct CO2 intensity of cement production from 2015 to 2021, urgent annual declines of 3 % until 2030 are necessary to be in line with the Net Zero Emissions by 2050 Scenario. This dissertation presents different approaches and technologies to offset the CO2 footprint of the production of cement clinker, concrete, and cementitious materials in general. First, this dissertation investigated the possibility of using end-of-life tire (ELT) rubber powder and its zinc-recovered residual (treated ELT rubber) to partially replace fine aggregates of different construction and infrastructure materials including stabilized soft soil (0 %, 10 %, 30 %, and 50 % ELT rubber added by clay volume), portland cement concrete (0 %, 10 %, 20 %, and 30 % ELT rubber added by sand volume), and asphalt concrete (20 % ELT rubber added by sand volume). This work was discussed through aspects of engineering properties and environmental impacts. The results reveal that the ELT rubber had both negative and positive effects on the engineering properties of the three materials while this waste posed a huge leachability of zinc and total organic carbon (TOC) content when being subjected to aqueous environments. However, the findings indicate that all three materials' matrices could effectively immobilize most leachable zinc from the ELT rubber by more than 90 %. Meanwhile, only stabilized soft soil and asphalt concrete could effectively deal with leachable TOC content from ELT rubber, and portland cement concrete needed the addition of silica fume to reduce TOC concentration in its leachate. Second, while previous studies have shown that steel furnace slag (SFS) can stabilize clay soils, the evidence is not clear if the stabilization mechanism is chemical and/or mechanical. This dissertation used isothermal calorimetry (IC) to quantify the heat of hydration of the mixture to assess the chemical aspects of the stabilization. Specifically, kaolin and bentonite clays were each blended with 40 % SFS by mass at water-to-binder ratios ranging from 1.0 to 1.5. The hydration properties of stabilized mixtures using lime or PC were also tested for comparison at the same experimental conditions. The obtained thermal power and total heat curves of stabilized mixtures confirmed that, for the specific SFS in this study, there is a hydration process taking place in clay stabilized by SFS. Relative to lime and PC, the SFS performed similarly in terms of heat of hydration behavior. When blended into clays, SFS provided a more significant heat of hydration behavior than cement, but that was much milder than lime. X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were also employed to qualitatively analyze the mineralogy of the stabilized mixtures. Finally, this dissertation adopted a Digestion-Titration Method (DTM) for the determination of CO2 content in cementitious materials that has been mineralized in the form of calcium carbonate (CaCO3). This method was modified based on tests that were originally developed in the early 1900s. The method uses hydrochloric acid to digest CaCO3 under vacuum conditions. The CO2 released is captured by a barium hydroxide solution, which is then titrated to quantify the amount of CO2 absorbed. A design of experiments approach was used to optimize the experimental conditions. Samples of known CaCO3 content were first evaluated to establish the baseline test performance, and additional tests were performed on portland cement and various rock samples. The results were also compared to TGA, including a discussion to compare the two test methods. The data suggest that the new test method is feasibly applicable to chemically determine the CO2 captured in cementitious materials, and it can be an alternative method for TGA with lower experimental cost and easier access. Overall, it is evident that cement, concrete, and construction materials are essential to the functionality of civilization. Dealing with CO2 emissions and natural resource depletion induced by the production of these construction materials is urgent for sustainable development. Attempts toward construction materials with lower embodied CO2 by using low-carbon aggregates (e.g., waste aggregates, recycled aggregates) and alternative cementitious binders while controlling the environmental effects of the utilized waste materials are currently viable sustainable approaches. In addition, tools or new test methods that can support measuring the effectiveness of these reduced carbon cementitious materials are necessary. This dissertation investigates the feasibility of the use of ELT rubber waste in construction materials to reduce the exploitation of natural resources considering engineering properties and environmental impacts. It also provides a deeper understanding of the hydration behavior of stabilized soil using SFS which is expected to partially or fully replace PC in the material. Experimentally, it develops a chemical test model as an alternative method for TGA with lower experimental cost, less interference, and easier access to determine the CO2 captured in cementitious materials. / Doctor of Philosophy / Concrete, the second most consumed material on earth after water, is a source of environmental problems due to global urbanization. The production of this construction material requires a large amount of natural resources, and portland cement (PC) is responsible for around 8 % of planet-warming CO2 emissions. This dissertation presents different approaches and technologies to offset the CO2 footprint of the production of construction materials (i.e., cement clinker, concrete, and general cementitious materials). First, this dissertation investigated the possibility of using end-of-life tire (ELT) rubber powder in different construction materials including stabilized soft soil, portland cement concrete, and asphalt concrete. This work was discussed through aspects of engineering properties and environmental impacts. The results reveal that the ELT rubber had both negative and positive effects on the engineering properties of the three materials. In return, all three materials' matrices could effectively immobilize most leachable zinc and total organic carbon (TOC) from the ELT rubber, which are detrimental to aquatic animals, plants, and humans. Second, this dissertation used isothermal calorimetry (IC) for the first time to study the heat of hydration of soil stabilized by steel furnace slag (SFS) to assess the chemical aspects of the stabilization. The work compared the hydration behavior of SFS in clayey soil with traditional stabilizers such as lime or portland cement. The results demonstrated that there were chemical reactions taking place during the hydration of stabilized soil using SFS, explaining the improvement in engineering properties of the stabilized soil. Moreover, this dissertation adopted a Digestion-Titration Method (DTM) for the determination of mineralized CO2 content in cementitious materials. The method uses hydrochloric acid to digest CaCO3 under vacuum conditions. The CO2 released is captured by a barium hydroxide solution, which is then titrated to quantify the amount of CO2 absorbed. The data suggest that the new test method is feasibly applicable to chemically determine the CO2 mineralized in cementitious materials, and it can be an alternative method for thermogravimetric analysis with lower experimental cost and easier access. Overall, it is evident that cement, concrete, and construction materials are essential to the functionality of civilization. Dealing with CO2 emissions and natural resource depletion induced by the production of these construction materials is urgent for sustainable development. This dissertation is expected to fill the knowledge gap in carbon neutral construction materials research, including increasing the use of low-carbon aggregates (e.g., waste aggregates, recycled aggregates) and alternative cementitious binders as well as developing new test methods that can support measuring the effectiveness of these reduced carbon cementitious materials.
46

The Effects of Different Soil Amendments on Fertility and Productivity in Organic Farming Systems

Fisher, Scott E. January 2011 (has links)
No description available.
47

Physical and Chemical Parameters of Common Soils in the Central Plateau Region of Haiti

Stewart, Ryan E. 23 May 2012 (has links) (PDF)
Soil degradation is a common occurrence in Haiti that is mainly caused by the cultivation of marginal lands and deforestation, which both contribute to the excessive erosion rate seen in the country today. The Central Plateau of Haiti is a mountainous region in which a majority of the population is rural and practices subsistence agriculture on hillsides and steeply-sloping land. Essential plant nutrients, such as nitrogen (N) and phosphorus (P), are commonly a limiting factor in crop production, yet fertilizer is unavailable or is too expensive for smallholder farmers to purchase. This study was conducted to a) evaluate organic matter and nutrient stocks of various soils in the Central Plateau region, along with other chemical and physical characteristics and b) to evaluate the phosphorus-scavenging ability of commonly-grown crops to isolate those that may benefit subsequent smallholder yields. Soils from four locations in the Central Plateau were assessed for organic matter in labile and non-labile fractions as well as for cation exchange capacity (CEC), total organic carbon (C) and N, pH, texture, and other characteristics. Results indicated that most of the soil (92%) was contained within aggregates, and organic matter was mainly present in stable, slowly-decomposing fractions. Seven species were evaluated in a controlled-environment pot experiment for bulk and rhizosphere soil P and pH, plant dry weight, and above- and below-ground P tissue content as indicators of the species' ability to solubilize P from the soil. Velvet bean (Mucuna pruriens (L.) DC) produced the most biomass and was able to take up the most P, though lablab (Lablab purpureous (L.) Sweet), took up comparable amounts of P. / Master of Science / LTRA-6 (A CAPS program for the Central Plateau of Haiti)
48

Vliv konvenčních kompenzací na volumetrickou přesnost obráběcího stroje / Impact of conventional compensation to the volumetric accuracy of the machine tool

Žák, Zdeněk January 2016 (has links)
This thesis solves the impact of conventional compensation to the volumetric accuracy of the CNC machine. It is therefore a practical research work, where are in the theoretical introduction mentioned requirements for machine tools, the types of errors that can occur on three-axis kinematics, compensation for the control system Siemens Sinumerik 840D sl and devices by means of which are these compensation under the work formed and subsequently verified. In this work can be seen the measured values and graphs from each measurements, a detailed analysis of the results and drawing conclusions from these results.
49

Estudo da disposição cinética da cefuroxima em pacientes submetidos à cirurgia de revascularização do miocárdio com circulação extracorpórea e hipotermia / Cinetic disposition of cefuroxime in coronary artery bypass graft surgery with Cardiopulmonary bypass and hypothermia

Nascimento, Jorge Willian Leandro 07 May 2004 (has links)
A circulação extracorpórea com hipotermia (CEC-H) é um procedimento comumente utilizado em cirurgias cardíacas, que representa um fator de risco para o paciente por promover extensa hemodiluição e profundas alterações fisiológicas. Nestas cirurgias, utiliza-se a cefuroxima como antimicrobiano para profilaxia de infecções, estando sua concentração inibitória mínima (CIM90) na faixa de 4 a 16 µg/mL dependendo da espécie e cepa bacteriana. Vários esquemas posológicos tem sido propostos para a profilaxia com este antimicrobiano. Assim, o objetivo do presente estudo foi investigar a farmacocinética e a disponibilidade sistêmica da cefuroxima, administrada I.V., bolus, na dose de 1,5g a 17 pacientes submetidos à cirurgia cardíaca com ou sem CEC-H. Desenvolveu-se método analítico simples seletivo e sensível em CLAE-UV para determinar a cefuroxima no plasma e tecido subcutâneo destes pacientes. Os resultados evidenciaram que independente das alterações causadas pela CEC-H, obtiveram-se baixas concentrações plasmáticas, inferiores ao CIM90, a partir da 9a hora após a administração da medicação nos dois grupos de pacientes investigados. Esta baixa disponibilidade sistêmica da cefuroxima após administração de 1,5 g pode favorecer o desenvolvimento de infecções pós-cirúrgicas e o desenvolvimento de cepas bacterianas resistentes. Por outro lado, a disposição cinética da cefuroxima foi alterada pela CEC-H, evidenciando-se ligeiro mas significativo prolongamento da meia vida biológica e redução da depuração plasmática nos pacientes submetidos a este procedimento. A ausência de alterações no volume de distribuição está de acordo com a penetração do antibiótico no tecido, uma vez que a quantidade de cefuroxima presente no subcutâneo foi comparável em ambos os grupos de pacientes investigados. Os dados obtidos permitem recomendar mudanças no regime posológico para manter níveis plasmáticos adequados e garantir a profilaxia com cefuroxima. / Cardiopulmonary bypass and hypothermia (HCPB) is a procedure commonly used during heart surgery, representing a risk factor for the patient by promoting extensive hemodilution and profound physiological changes. Cefuroxime is used for the prophylaxis of infection after heart surgery and its minimum inhibitory concentration (MIC90) may vary from 4 to 16 µg/mL depending on the bacterial species and strain. Several dose schemes have been suggested for prophylaxis with this antimicrobial agent. Thus, the objective of the present study was to assess in a comparative manner the systemic availability of cefuroxime administered intravascularly at the dose of 1.5 g in bolus to 17 patients submitted to heart surgery with or without HCPB. An improved, simple, selective and sensitive micromethod based on HPLC-UV is described to determine cefuroxime in plasma and fat tissue. Despite the differences recorded during the study period as a consequence of HCPB, antibiotic concentrations lower than MIC90 were obtained as early as after the 9th h for the surgical patients of the two groups of patients investigated. Thus, the low systemic availability of cefuroxime after the administration of a 1.5 g dose may be the factor responsible for postoperative infections and may favor the development of resistant bacterial strains. By the other hand, cefuroxime kinetic disposition was altered by HCPB showing a slight prolongation of biological half-life e reduction of plasma clearance. Unchanged apparent volume of distribution was according antibiotic tissue penetration since in both groups of patients the amount of cefuroxime obtained was comparable. The data obtained permit us to recommend a change in the dose scheme in order to maintain adequate plasma levels of the drug and thus guarantee prophylaxis with cefuroxime.
50

Efeitos da aprotinina em crianças com cardiopatia congênita acianogênica operadas com circulação extracorpórea / Effects of aprotinin in children with acianogenic congenital heart disease submitted to correction with extracorporeal circulation

Ferreira, Cesar Augusto 22 November 2006 (has links)
Introdução. A Aprotinina parece reduzir o uso de transfusões, o processo inflamatório e o dano miocárdico, pós-CEC. Material e Métodos. Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas à correção de cardiopatia congênita acianogênica, com CEC e divididas em dois grupos, um denominado Controle (n=9) e o outro, Aprotinina (n=10). Neste, a droga foi administrada imediatamente antes da CEC. A resposta inflamatória sistêmica e disfunções hemostáticas e multiorgânicas foram analisadas por marcadores clínicos e bioquímicos. Foram consideradas significantes as diferenças com p<0,05. Resultados. Os grupos foram semelhantes quanto às variáveis demográficas e intra-operatórias, exceto por maior hemodiluição no Grupo Aprotinina. Não houve benefício quanto aos tempos de ventilação pulmonar mecânica, permanência no CTIP e hospitalar, nem quanto ao uso de inotrópicos e função renal. A relação PaO2/FiO2 (pressão parcial de oxigênio arterial/fração inspirada de oxigênio) apresentou queda significativa com 24 h PO, no Grupo Controle. Ocorreu preservação da concentração plaquetária com a Aprotinina enquanto no grupo Controle houve plaquetopenia desde o início da CEC. As perdas sangüíneas foram semelhantes nos dois grupos. No grupo Aprotinina surgiu leucopenia significativa, em CEC, seguida de leucocitose. Fator de necrose tumoral alfa (TNF-) , Interleucinas (IL)-6, IL-8, IL-10, proporção IL-6/IL-10, troponina I cardíaca (cTnI), fração MB da creatinofosfoquinase (CKMB), transaminase glutâmico-oxalacética (TGO) e fração amino-terminal do peptídio natriurético tipo B (NT-proBNP) não apresentaram diferenças marcantes intergrupos. A proporção IL-6/IL-10 PO aumentou no grupo Controle. A lactatemia e acidose metabólica pós-CEC foi mais intensa no grupo Aprotinina. Não houve complicações com o uso da Aprotinina. Conclusão. A Aprotinina não minimizou as manifestações clínicas e os marcadores séricos de resposta inflamatória sistêmica e miocárdicos, mas preservou quantitativamente as plaquetas. / Introduction. Aprotinin seems to reduce the need for transfusion, the inflammatory process and myocardial damage after extracorporeal circulation (ECC). Material and Methods. A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered immediately before ECC and the systemic inflammatory response and hemostatic and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. Results. The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the postoperative ICU and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24 h after surgery in the Control Group. Platelet concentration was preserved with the use of Aprotinin, whereas thrombocytopenia occurred in the Control Group since the beginning of ECC. Blood loss was similar for both groups. Significant leukopenia was observed in the Aprotinin Group during ECC, followed by leukocytosis. Tumor necrosis factor alpha (TNF-), interleukins (IL)-6, IL-8, IL-10, IL-6/IL-10 ratio, cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), glutamic-oxaloacetic transaminase (GOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) ndid not differ significantly between groups.The postoperative IL-6/IL-10 fraction increased significantly in the Control Group. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of Aprotinin. Conclusion. Aprotinin did not minimize the clinical manifestations or serum markers of the inflammatory, systemic and myocardial response, but quantitatively preserved the platelets.

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