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Legal regulation of experimental animals handling This thesis deals with the legal regulation of experimental animals handling and their protection in international law, European union law and national law. Its goal is to complexly capture current legislation in this field, point out unsystematic or otherwise unsuitable institutes and propose means of their change. The core of the thesis is a description and an analysis of relevant parts of the Act on Animal Protection Against Cruelty, directives and regulations of the European Union and international treaties. Furthermore the thesis includes a treatise on the legal status of an animal, a brief introduction into ethical issues of animal experiments, historical evolution of relevant legal regulation and questions of administrative and criminal liability in the field of experimental animals handling.

Modelos matemáticos são utilizados como ferramentas na avaliação da mecânica respiratória para a compreensão da fisiologia e patologias do sistema respiratório. A presente pesquisa visou avaliar, através da aplicação de modelos matemáticos, a mecânica respiratória em camundongos submetidos à metacolina. Deu-se ênfase no modelo linear de compartimento único e suas variantes não lineares. Camundongos C57BL/6 (n = 8) foram traqueostomizados, ventilados mecanicamente (flexiVent, SCIREQ, Canadá) e perturbações em volume foram aplicadas para a modelagem do sistema respiratório. O protocolo experimental foi elaborado de forma a se analisar a variação dos parâmetros respiratórios durante a aplicação do agente broncoativo e também se verificou a divisão do sinal quasi-senoidal em expirações e inspirações durante a técnica de oscilação forçada (FOT) com perturbação de frequência 2,5 Hz. Com base nisso, uma rotina computacional própria foi desenvolvida para a análise dos experimentos realizados no ventilador mecânico e foram pesquisadas as vantagens e desvantagens dos modelos matemáticos aplicados. Os resultados demonstraram um aumento no desvio padrão dos parâmetros do modelo linear unicompartimental e suas variantes não lineares após a aplicação do broncoconstritor. Acredita-se que esta grande variação nos parâmetros esteja relacionada com o enrijecimento do parênquima e da heterogeneidade da ventilação pulmonar após a utilização da droga. Devido à correlação dos parâmetros do modelo com a fisiologia ocorrer somente no modelo linear, acredita-se que este ainda é o mais indicado na avaliação da mecânica respiratória e as variantes não lineares seriam indicadas como opção em casos onde o modelo linear é incapaz de realizar ajustes adequados ou para informações complementares. / Mathematical models are used as tools in the assessment of respiratory mechanics for the understanding of the physiology and pathologies of the respiratory system. This study aimed to assess the respiratory mechanics by applying mathematical models in mice subjected to challenges with methacholine. Emphasis was placed on linear single-compartment model and its nonlinear variants. C57BL/6 mice (n = 8) were tracheostomized, mechanically ventilated (flexiVent, SCIREQ, Canada) and disturbances in volume were applied to the modeling of the respiratory system. The experimental protocol was developed in order to analyze the variation of respiratory parameters during the application of the bronchoactive agent. The division of quasisinusoidal signal in expirations and inspirations during the forced oscillation technique (FOT) with frequency perturbation of 2.5 Hz was also observed. Based on that, a proper computational routine was developed in order to analyze the experiments in the mechanical ventilator and the advantages and disadvantages of the applied mathematical models. The results demonstrated an increase in the standard deviation of the linear single-compartment model and its nonlinear variants parameters after the application of bronchoconstrictor. It is believed that this large variation in the parameters relates to the parenchyma stiffening and to the heterogeneity of pulmonary ventilation after the use of the drug. Due to the fact that the correlation between the model parameters and the physiology occurred only in the linear model, it is believed that this is still the most suitable model in the assessment of respiratory mechanics. Nonlinear variations of the single-compartment model would be indicated only as an option, for example, in cases where the linear model is incapable of performing appropriate fits or when additional information about the respiratory system is required.

Modelos matemáticos são utilizados como ferramentas na avaliação da mecânica respiratória para a compreensão da fisiologia e patologias do sistema respiratório. A presente pesquisa visou avaliar, através da aplicação de modelos matemáticos, a mecânica respiratória em camundongos submetidos à metacolina. Deu-se ênfase no modelo linear de compartimento único e suas variantes não lineares. Camundongos C57BL/6 (n = 8) foram traqueostomizados, ventilados mecanicamente (flexiVent, SCIREQ, Canadá) e perturbações em volume foram aplicadas para a modelagem do sistema respiratório. O protocolo experimental foi elaborado de forma a se analisar a variação dos parâmetros respiratórios durante a aplicação do agente broncoativo e também se verificou a divisão do sinal quasi-senoidal em expirações e inspirações durante a técnica de oscilação forçada (FOT) com perturbação de frequência 2,5 Hz. Com base nisso, uma rotina computacional própria foi desenvolvida para a análise dos experimentos realizados no ventilador mecânico e foram pesquisadas as vantagens e desvantagens dos modelos matemáticos aplicados. Os resultados demonstraram um aumento no desvio padrão dos parâmetros do modelo linear unicompartimental e suas variantes não lineares após a aplicação do broncoconstritor. Acredita-se que esta grande variação nos parâmetros esteja relacionada com o enrijecimento do parênquima e da heterogeneidade da ventilação pulmonar após a utilização da droga. Devido à correlação dos parâmetros do modelo com a fisiologia ocorrer somente no modelo linear, acredita-se que este ainda é o mais indicado na avaliação da mecânica respiratória e as variantes não lineares seriam indicadas como opção em casos onde o modelo linear é incapaz de realizar ajustes adequados ou para informações complementares. / Mathematical models are used as tools in the assessment of respiratory mechanics for the understanding of the physiology and pathologies of the respiratory system. This study aimed to assess the respiratory mechanics by applying mathematical models in mice subjected to challenges with methacholine. Emphasis was placed on linear single-compartment model and its nonlinear variants. C57BL/6 mice (n = 8) were tracheostomized, mechanically ventilated (flexiVent, SCIREQ, Canada) and disturbances in volume were applied to the modeling of the respiratory system. The experimental protocol was developed in order to analyze the variation of respiratory parameters during the application of the bronchoactive agent. The division of quasisinusoidal signal in expirations and inspirations during the forced oscillation technique (FOT) with frequency perturbation of 2.5 Hz was also observed. Based on that, a proper computational routine was developed in order to analyze the experiments in the mechanical ventilator and the advantages and disadvantages of the applied mathematical models. The results demonstrated an increase in the standard deviation of the linear single-compartment model and its nonlinear variants parameters after the application of bronchoconstrictor. It is believed that this large variation in the parameters relates to the parenchyma stiffening and to the heterogeneity of pulmonary ventilation after the use of the drug. Due to the fact that the correlation between the model parameters and the physiology occurred only in the linear model, it is believed that this is still the most suitable model in the assessment of respiratory mechanics. Nonlinear variations of the single-compartment model would be indicated only as an option, for example, in cases where the linear model is incapable of performing appropriate fits or when additional information about the respiratory system is required.

Background: The main focus of the dissertation is the use of nanofibrous biodegradable materials for the healing support of intestinal anastomoses in colorectal surgery. The altered healing process of intestinal anastomosis leads to several types of local complications. Anastomotic leakage is one of the most feared ones. Severe anastomotic leakage causes peritonitis, sepsis and is a life-threatening condition. Reoperation is necessary in many cases, bringing the need for intensive care, and hospital stays prolongation. Extensive peritoneal adhesions are another source of postoperative complications. These adhesions are a frequent cause of bowel obstruction and abdominal discomfort and are the most common reason for readmission after colorectal procedures. Nanofibrous biodegradable materials showed positive effects on the healing process in various locations. We aimed to develop and perfect a biodegradable patch for both prevention of anastomotic leakage and the formation of extensive peritoneal adhesions. Methods: We conducted 3 subsequential experiments on porcine models. In Experiment A, we managed to develop polycaprolactone and polylactic acid- polycaprolactone copolymer nanofibrous patches and applied them on anastomoses on the small porcine intestine. The animals were observed for 3 weeks....

Possibilities of Portal Vein Reconstruction during Surgical Treatment of Pancreatic Cancer - Experiment on a Large Animal Introduction: Pancreatic cancer is a fatal malignancy that is known as one of the leading causes of cancer mortality worldwide. The only potentially curative treatment is radical surgical resection. Because of the lack of early symptoms, the diagnosis is usually made in advanced stages of the disease. In the majority of patients, the tumor is already locally advanced or it has distant metastases at the time of diagnosis. Pancreatic cancer tends to infiltrate the portal vein (PV) or the superior mesenteric vein (SMV). Nowadays, resection of infiltrated parts of PV/SMV is recommended in specialized centers. There are several established techniques of PV/SMV reconstruction. The use of allogeneic venous grafts seems to be a method with minimal risk of adverse effects but there is only limited experience with these grafts. The optimal anatomical origin of allogeneic venous grafts for PV/SMV reconstruction remains unknown. Aims: The aim of this experiment was to compare two types of allogeneic venous grafts used for PV reconstruction in a large animal model of pancreatico- duodenectomy. These grafts were harvested from the systemic venous system (inferior caval vein grafts - IVC grafts) and...

A experimentação animal é uma prática extremamente incorporada à ciência biomédica moderna, com raízes desde a Antiguidade, mas que foi cada vez mais se desenvolvendo, adquirindo características bem definidas. O animal não humano, no contexto da experimentação, é um ser vulnerado, enclausurado dentro de uma estrutura muito bem definida, que mantém um discurso focado na excelência do modelo do animal na pesquisa e testes, com o objetivo de garantir a manutenção dessas práticas. No entanto, ao analisarmos os dados científicos obtidos com a experimentação animal, que visa primariamente um possível benefício humano, assim como as argumentações éticas relativas ao respeito à vida e ao sofrimento do animal envoltas nesta situação, a argumentação ética prepondera sobre uma base científica cuja eficácia é também extremamente questionável. Partindo de uma análise crítica da aplicação do modelo animal como padrão da pesquisa científica e da concepção ética do reconhecimento da vulnerabilidade do animal não humano na experimentação, propomos que esta reflexão colabore com políticas públicas que incentivem e implementem as técnicas substitutivas ao uso de animais não humanos em pesquisa, testes da indústria e ensino na área biomédica no Brasil. / Animal experimentation is an extremely convenient inserted in modern biomedical science, with roots from antiquity, but it was increasingly developing, acquiring well-defined characteristics. The non-human animal in the context of trials is a hacked being, enclosed within a well defined structure that holds a speech focused on excellence in animal model in research and testing, with the goal of maintaining these practices. However, when analyzing the scientific data obtained from animal experiments, which primarily targets a possible human benefit, as well as the ethical arguments concerning respect for life and the suffering of animals wrapped in this situation, the ethical argument outweighs scientific basis whose effectiveness is also extremely questionable. Based on a critical analysis of the application of animal model as the standard of scientific research and the ethical conception of recognition of the vulnerability of non-human animal experimentation, we propose that this reflection collaborate with public policies that encourage and implement the substitute for use of non-human animals in research, testing and education industry in Brazil biomedical techniques.

A experimentação animal é uma prática extremamente incorporada à ciência biomédica moderna, com raízes desde a Antiguidade, mas que foi cada vez mais se desenvolvendo, adquirindo características bem definidas. O animal não humano, no contexto da experimentação, é um ser vulnerado, enclausurado dentro de uma estrutura muito bem definida, que mantém um discurso focado na excelência do modelo do animal na pesquisa e testes, com o objetivo de garantir a manutenção dessas práticas. No entanto, ao analisarmos os dados científicos obtidos com a experimentação animal, que visa primariamente um possível benefício humano, assim como as argumentações éticas relativas ao respeito à vida e ao sofrimento do animal envoltas nesta situação, a argumentação ética prepondera sobre uma base científica cuja eficácia é também extremamente questionável. Partindo de uma análise crítica da aplicação do modelo animal como padrão da pesquisa científica e da concepção ética do reconhecimento da vulnerabilidade do animal não humano na experimentação, propomos que esta reflexão colabore com políticas públicas que incentivem e implementem as técnicas substitutivas ao uso de animais não humanos em pesquisa, testes da indústria e ensino na área biomédica no Brasil. / Animal experimentation is an extremely convenient inserted in modern biomedical science, with roots from antiquity, but it was increasingly developing, acquiring well-defined characteristics. The non-human animal in the context of trials is a hacked being, enclosed within a well defined structure that holds a speech focused on excellence in animal model in research and testing, with the goal of maintaining these practices. However, when analyzing the scientific data obtained from animal experiments, which primarily targets a possible human benefit, as well as the ethical arguments concerning respect for life and the suffering of animals wrapped in this situation, the ethical argument outweighs scientific basis whose effectiveness is also extremely questionable. Based on a critical analysis of the application of animal model as the standard of scientific research and the ethical conception of recognition of the vulnerability of non-human animal experimentation, we propose that this reflection collaborate with public policies that encourage and implement the substitute for use of non-human animals in research, testing and education industry in Brazil biomedical techniques.

Die Störung der intestinalen Mikrozirkulation gilt als ein kardinaler Mechanismus für die Entwicklung des Multiorganversagens bei Sepsis. Da das Intestinum für mikrozirkulatorische Studien klinisch kaum zugänglich ist, wurden die Auswirkungen einer Therapie mit den antioxidativen Substanzen Oxypurinol und U-74389G (Lazaroid) bzw. den vasoaktiven Substanzen Iloprost (Prostacyclin-Analogon) und Dopexamin auf die intestinale Mikrozirkulation und die systemische Mediatorfreisetzung in einem Tiermodell mit moderater und hoher Endotoxin-Belastung untersucht. Die intravitalmikroskopische Untersuchung der Kapillarperfusion in der Muskularisschicht bei Endotoxinämie erbrachte eine Verbesserung durch Oxypurinol- und Dopexamingabe. Die Perfusion der Mukosa konnte vor allem durch eine Iloprostapplikation gesteigert werden. Die Endotoxin-induzierte, intestinale Leukozytenadhärenz wurde insbesondere durch die Behandlung mit den antioxidativen Substanzen vermindert. Beide therapeutischen Optionen bewirkten eine ca. 60 %ige Reduktion der initialen Tumornekrosefaktor-alpha-Freisetzung in der Versuchsreihe mit der niedrigeren Endotoxin-Dosis. Parallel dazu konnte anhand von Malondialdehyd-Analysen gezeigt werden, dass Oxypurinol und U-74389G wirksam die intestinale, Radikal-induzierte Lipidperoxidation verringerten. Der intestinale mikrovaskuläre Blutfluss konnte durch beide vasoaktiven Substanzen - sowohl bei moderater als auch bei erhöhter Endotoxin-Dosierung - signifikant gesteigert werden. Die Ergebnisse beider Teilstudien bestätigten, dass sowohl reaktive Sauerstoffspezies als auch eine inadäquate Perfusion in der Mikrozirkulation wesentliche pathogenetische Faktoren bei Endotoxinämie bzw. Sepsis darstellen und entsprechende Therapieformen indiziert und effektiv sind. Eine kombinierte Gabe beider Substanzklassen erscheint daher sinnvoll und sollte in weiteren tierexperimentellen und klinischen Studien evaluiert werden. / The disturbance of the intestinal microcirculation is regarded as a pivotal mechanism in the development of multiorgan failure related to sepsis. Since the intestine is clinically not accessible for microcirculatory studies, the effects of a therapy with the antioxidants oxypurinol and U-74389G (lazaroid) as well as the vasoactive substances iloprost (a prostacyclin analogue) and dopexamine on the intestinal microcirculation and the systemic mediator release was studied in an animal model with moderate and high endotoxin challenge. The intravital microscopic examination of the capillary perfusion in the muscularis layer of the intestine during endotoxemia revealed an improvement by administration of oxypurinol and dopexamine. The perfusion of the mucosa could be increased by iloprost administration. The amount of the endotoxin induced, intestinal leukocyte adherence was especially decreased by the treatment with the antioxidants. Both therapeutic options caused a 60 % reduction in the initial tumor necrosis factor-alpha-release in the experiments with the lower endotoxin dose. Malondialdehyde analyses showed that oxypurinol and U-74389G reduced effectively the intestinal, radical-induced lipid peroxidation. The intestinal microvascular blood flow could be significantly increased by both vasoactive substances - as well as with moderately than also with elevated endotoxin-dosage. The results of the study confirmed that both reactive oxygen-species as well as an inadequate perfusion in the microcirculation represent essential pathogenetic factors during endotoxemia as well as sepsis and index corresponding therapy-forms and participates effective. A combined offering both substance-classes appears therefore meaningfully and should be evaluated in further experimental and clinical studies.