This master’s thesis is focused on calculation, simulation and experimental verification of electrodynamic forces acting upon movable contact piece of MCCB and experimental current carrying path. A short description of low voltage circuit breakers is briefly discussed in first chapter. Second chapter is focused upon contact system analysis of particular MCCB with thermomagnetic trigger. A hardness of contact materials is briefly described. A detailed analytical calculations were used to determine electrodynamic forces in MCCB. A FEM simulation in ANSYS Maxwell was carried out for comparison with analytical results. An experimental apparatus was designed and built for verification of constriction repulsion force, so called Holm’s force. A series of measurements is subsequently performed on proposed apparatus and results are compared with results from previous chapters.

Pharmacological treatment of neuropathic pain is still insufficient. Methylphenidate, a psychostimulant that increases the dopamine and noradrenaline levels, is commonly used for treating ADHD. There have been reports of changes in patients pain thresholds by ADHD patients treated with methylphenidate. The aim of the study is to examine if methylphenidate can affect peripheral neuropathic pain. Neuropathic pain has been modelled on laboratory rats by chronic constriction of the ischiatic nerve. The effect of methylphenidate on the evoked pain component was evaluated on control animals and on animals with neuropathic pain using reflex (plantar test, vonFrey test) and operanting test (thermal place preference). The effect of methylphenidate on the spontaneous components of pain was evaluated using the methods of conditioned place preference. This study has proven that methylphenidate in an applicable dose of 1 mg/kg has an antialodynic effect but does not act antinociceptively. This study further confirms that methylphenidate in low doses does not act as attractant and has no effect on spontaneous pain. The last part of the study compares the different methods for pain measurement and comes to the conclusion that the plantar test is not an adequate method for evaluating the effect of analgesics...

Chronic kidney disease (CKD) is defined as glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2 for 3 months and is characterized by progressive loss of renal function. The second leading cause of CKD is hypertension. More than half of CKD patients also suffer from hypertension. Arteries and arterioles adjust to the fluctuations in the systematic blood pressure through a mechanism called autoregulation. In the kidneys, autoregulation protects the delicate glomeruli capillaries from high blood pressure and occurs through myogenic constriction (MC). MC refers to contraction of arterioles in response to an increase in the blood pressure. Chronically hypertensive individuals and animal models have an enhanced MC, leading to minimal renal injury despite their elevated blood pressure. Experimental and clinical evidence point to a role for the MC in the pathogenesis of the CKD, however, the mechanism through which preglomerular arterial MC contributes to CKD has not been fully elucidated. This thesis showed that augmented MC in chronically hypertensive animal models was due to increased thromboxane A2 prostaglandin that was not released from the endothelium (Chapter 2). Nevertheless, inhibiting MC while also reducing the blood pressure prevented salt-induced renal injury even though the blood pressure was still not normalized compared to the normotensive controls (Chapter 3). The resulting improvement in renal structure and function could be attributed to the reduction in the blood pressure, albumin, and uromodulin (UMOD) excretion (Chapter 3). UMOD is a kidney-specific glycoprotein that, based on a genome-wide association study have the strongest association to CKD (Chapter 3). Comparing two CKD hypertensive animal models further revealed that CKD progression was independent of the blood pressure and strongly associated with UMOD excretion levels (Chapter 4). Collectively, the data discussed in this thesis demonstrates potential therapeutic targets in CKD hypertensive animal models. / Dissertation / Doctor of Philosophy (PhD)

No description available.

As complicações biliares mais comuns pós-transplante hepático são as estenoses da anastomose, as estenoses não-anastomóticas e as fístulas biliares e podem ocorrer de diferentes modos, de forma isolada ou associada. A origem do enxerto (doador cadáver ou doador vivo) tem influência na incidência de estenose biliar, bem como na resposta ao tratamento endoscópico. A terapêutica endoscópica utilizando-se esfincterotomia, dilatação balonada da estenose e inserção de próteses biliares através da CPRE é utilizada como método inicial de tratamento dessas complicações. Objetivos: Comparar as diferentes técnicas de tratamento endoscópico das estenoses biliares pós-transplante hepático. Método: Foi realizada uma revisão sistemática da literatura e metanálise sendo a busca conduzida nas bases MEDLINE, EMBASE, Scielo - LILACS e Biblioteca Cochrane até junho de 2015. A metanálise foi executada utilizando-se os softwares Review Manager, 2012 (RevMan) versão 5.2 e OpenMetaAnalyst e os cálculos dos desfechos foram feitos comparando-se os resultados dos estudos incluídos utilizando-se a diferença de risco absoluto e adotando-se um intervalo de confiança (IC) de 95%. Os estudos foram agrupados comparando-se transplantes hepáticos com doador cadáver versus doador vivo; dilatação biliar endoscópica com balão exclusiva versus dilatação biliar endoscópica com balão associada à inserção de próteses plásticas e próteses biliares plásticas comparadas à prótese biliar metálica por endoscopia. Os desfechos clínicos analisados foram incidência da estenose biliar, falha do tratamento endoscópico, resolução da estenose, recorrência da estenose e complicações. Resultados: Foram recuperados 1.110 artigos, sendo motivo de análise dez ensaios clínicos, com apenas um Ensaio Clínico Randomizado e nove Ensaios Clínicos não randomizados, dos quais sete foram incluídos na metanálise. Comparando-se doador cadáver e doador vivo observou-se redução da incidência de estenose biliar (p=0,0001), bem como da falha técnica do tratamento endoscópico (p=0,0009) e da recorrência da estenose biliar (p=0,03) nos transplantes realizados com enxertos provenientes de doador cadáver. Dois estudos compararam o tratamento da estenose da anastomose biliar pós-transplante hepático utilizando dilatação com balão exclusiva versus dilatação com balão associada à inserção próteses plásticas e não foram observadas diferenças estatisticamente significantes em relação aos desfechos falha de tratamento, recorrência da estenose ou complicações. Somente o desfecho clínico complicações teve resultado estatisticamente significante na comparação entre prótese metálica autoexpansível versus prótese plástica no tratamento da estenose da anastomose biliar pós-transplante hepático (p= 0.03). Conclusões: O tratamento da estenose biliar anastomótica pós-transplante hepático com prótese metálica foi igualmente efetivo quando comparado ao uso de prótese plástica, mas associou-se a um menor risco de complicações. A comparação entre dilatação com balão exclusiva e dilatação com balão associada à prótese plástica apresentou resultados semelhantes em relação à falha do tratamento endoscópico, complicações e recorrência da estenose. A utilização de enxerto proveniente de doador cadáver reduziu o risco de estenose biliar pós-transplante hepático e o tratamento endoscópico nesse grupo de pacientes, foi mais efetivo quando comparado com as estenoses biliares após transplante com doador vivo / The most common biliary complications after liver transplantation are anastomotic strictures, non-anastomotic strictures and biliary fistulas and they can occur in different fashions, isolated or in combination. Graft source (cadaveric liver donor or living liver donor) has an influence on the incidence of biliary strictures as well as on the response to endoscopic treatment. The endoscopic treatment using sphincterotomy, balloon dilation and insertion of biliary stents by ERCP (Endoscopic Retrograde Cholangiopancreatography) is used as an initial endoscopic approach to treat these complications. Objectives: To compare different endoscopic techniques to treat post-liver transplantation biliary strictures. Method: It was performed a systematic review of the literature and meta-analysis and the search was carried out on MEDLINE, EMBASE, Scielo-LILACS and Cochrane Library databases until June, 2015. The meta-analysis was made using Review Manager, 2012 (RevMan) version 5.2 and OpenMetaAnalyst software and the calculations of the outcomes were made comparing the results from the included papers by using the difference in absolute risks, adopting a confidence interval of 95%. The studies were grouped comparing cadaveric liver donor versus living liver donor grafts; exclusive balloon dilation versus balloon dilation associated with plastic stents insertion; and plastic stents versus totally covered selfexpandable metal stents. The clinical outcomes were biliary stricture incidence, endoscopic treatment failure, stricture resolution, stricture recurrence and complications. Results: There were retrieved 1,100 articles. Ten clinical trials were analyzed, with just one Randomized Clinical Trial and nine Non-Randomized Clinical Trials, out of which seven were included in the meta-analysis. When comparing cadaveric liver donor transplantation to living liver donor transplantation, it was observed a decrease in the incidence of biliary strictures (p=0.0001), as well as in the technical failure rate of the endoscopic treatment (p=0.0009) and in the biliary stricture recurrence (p=0.03) in the cadaveric liver donor graft group. Two studies have compared the treatment of anastomotic biliary strictures after liver transplantation using balloon dilation exclusive to balloon dilation associated with the insertion of plastic stents, and no statistically significant differences in relation to endoscopic treatment failure, stricture recurrence or complications rates were observed. Only the clinical outcome complications had statistically significant result in a comparison between self-expandable metal stents versus plastic stents in the treatment of post-liver transplantation anastomotic biliary strictures (p=0.03). Conclusions: The treatment of post-liver transplantation anastomotic biliary strictures was equally effective when compared the use of self-expandable metal stents to plastic stents, but the use metallic stents was associated with a lower complication risk. The comparison between exclusive balloon dilation to balloon dilation associated with plastic stents presented similar results in relation to endoscopic treatment failure, complications and stenosis recurrence. The use of graft from cadaveric donor reduced the risk of biliary stenosis after liver transplantation and endoscopic treatment of biliary strictures in these patients were more effective when compared to biliary strictures after living liver donor transplantation

A prevalent morphology in the microscopic world of artificial microswimmers, bacteria and viruses is that of a helix. The intriguingly different physics at play at the small scale level make it necessary for bacteria to employ swimming strategies different from our everyday experience, such as the rotation of a helical filament. Bio-inspired microswimmers that mimic bacterial locomotion achieve propulsion at the microscale level using magnetically actuated, rotating helical filaments. A promising application of these artificial microswimmers is in non-invasive medicine, for drug delivery to tumours or microsurgery. Two crucial features need to be addressed in the design of microswimmers. First, the ability to selectively control large ensembles and second, the adaptivity to move through complex conduit geometries, such as the constrictions and curves of the tortuous tumour microvasculature. In this dissertation, a mechanics-based selective control mechanism for magnetic microswimmers is proposed, and a model and simulation of an elastic helix passing through a constricted microchannel are developed. Thereafter, a theoretical framework is developed for the propulsion by stiff elastic filaments in viscous fluids. In order to address this fluid-structure problem, a pertubative, asymptotic, elastohydrodynamic approach is used to characterise the deformation that arises from and in turn affects the motion. This framework is applied to the helical filaments of bacteria and magnetically actuated microswimmers. The dissertation then turns to the sub-bacterial scale of bacteriophage viruses, 'phages' for short, that infect bacteria by ejecting their genetic material and replicating inside their host. The valuable insight that phages can offer in our fight against pathogenic bacteria and the possibility of phage therapy as an alternative to antibiotics, are of paramount importance to tackle antibiotics resistance. In contrast to typical phages, flagellotropic phages first attach to bacterial flagella, and have the striking ability to reach the cell body for infection, despite their lack of independent motion. The last part of the dissertation develops the first theoretical model for the nut-and-bolt mechanism (proposed by Berg and Anderson in 1973). A nut being rotated will move along a bolt. Similarly, a phage wraps itself around a flagellum possessing helical grooves, and exploits the rotation of the flagellum in order to passively travel along and towards the cell body, according to this mechanism. The predictions from the model agree with experimental observations with respect to directionality, speed and the requirements for succesful translocation.

As complicações biliares mais comuns pós-transplante hepático são as estenoses da anastomose, as estenoses não-anastomóticas e as fístulas biliares e podem ocorrer de diferentes modos, de forma isolada ou associada. A origem do enxerto (doador cadáver ou doador vivo) tem influência na incidência de estenose biliar, bem como na resposta ao tratamento endoscópico. A terapêutica endoscópica utilizando-se esfincterotomia, dilatação balonada da estenose e inserção de próteses biliares através da CPRE é utilizada como método inicial de tratamento dessas complicações. Objetivos: Comparar as diferentes técnicas de tratamento endoscópico das estenoses biliares pós-transplante hepático. Método: Foi realizada uma revisão sistemática da literatura e metanálise sendo a busca conduzida nas bases MEDLINE, EMBASE, Scielo - LILACS e Biblioteca Cochrane até junho de 2015. A metanálise foi executada utilizando-se os softwares Review Manager, 2012 (RevMan) versão 5.2 e OpenMetaAnalyst e os cálculos dos desfechos foram feitos comparando-se os resultados dos estudos incluídos utilizando-se a diferença de risco absoluto e adotando-se um intervalo de confiança (IC) de 95%. Os estudos foram agrupados comparando-se transplantes hepáticos com doador cadáver versus doador vivo; dilatação biliar endoscópica com balão exclusiva versus dilatação biliar endoscópica com balão associada à inserção de próteses plásticas e próteses biliares plásticas comparadas à prótese biliar metálica por endoscopia. Os desfechos clínicos analisados foram incidência da estenose biliar, falha do tratamento endoscópico, resolução da estenose, recorrência da estenose e complicações. Resultados: Foram recuperados 1.110 artigos, sendo motivo de análise dez ensaios clínicos, com apenas um Ensaio Clínico Randomizado e nove Ensaios Clínicos não randomizados, dos quais sete foram incluídos na metanálise. Comparando-se doador cadáver e doador vivo observou-se redução da incidência de estenose biliar (p=0,0001), bem como da falha técnica do tratamento endoscópico (p=0,0009) e da recorrência da estenose biliar (p=0,03) nos transplantes realizados com enxertos provenientes de doador cadáver. Dois estudos compararam o tratamento da estenose da anastomose biliar pós-transplante hepático utilizando dilatação com balão exclusiva versus dilatação com balão associada à inserção próteses plásticas e não foram observadas diferenças estatisticamente significantes em relação aos desfechos falha de tratamento, recorrência da estenose ou complicações. Somente o desfecho clínico complicações teve resultado estatisticamente significante na comparação entre prótese metálica autoexpansível versus prótese plástica no tratamento da estenose da anastomose biliar pós-transplante hepático (p= 0.03). Conclusões: O tratamento da estenose biliar anastomótica pós-transplante hepático com prótese metálica foi igualmente efetivo quando comparado ao uso de prótese plástica, mas associou-se a um menor risco de complicações. A comparação entre dilatação com balão exclusiva e dilatação com balão associada à prótese plástica apresentou resultados semelhantes em relação à falha do tratamento endoscópico, complicações e recorrência da estenose. A utilização de enxerto proveniente de doador cadáver reduziu o risco de estenose biliar pós-transplante hepático e o tratamento endoscópico nesse grupo de pacientes, foi mais efetivo quando comparado com as estenoses biliares após transplante com doador vivo / The most common biliary complications after liver transplantation are anastomotic strictures, non-anastomotic strictures and biliary fistulas and they can occur in different fashions, isolated or in combination. Graft source (cadaveric liver donor or living liver donor) has an influence on the incidence of biliary strictures as well as on the response to endoscopic treatment. The endoscopic treatment using sphincterotomy, balloon dilation and insertion of biliary stents by ERCP (Endoscopic Retrograde Cholangiopancreatography) is used as an initial endoscopic approach to treat these complications. Objectives: To compare different endoscopic techniques to treat post-liver transplantation biliary strictures. Method: It was performed a systematic review of the literature and meta-analysis and the search was carried out on MEDLINE, EMBASE, Scielo-LILACS and Cochrane Library databases until June, 2015. The meta-analysis was made using Review Manager, 2012 (RevMan) version 5.2 and OpenMetaAnalyst software and the calculations of the outcomes were made comparing the results from the included papers by using the difference in absolute risks, adopting a confidence interval of 95%. The studies were grouped comparing cadaveric liver donor versus living liver donor grafts; exclusive balloon dilation versus balloon dilation associated with plastic stents insertion; and plastic stents versus totally covered selfexpandable metal stents. The clinical outcomes were biliary stricture incidence, endoscopic treatment failure, stricture resolution, stricture recurrence and complications. Results: There were retrieved 1,100 articles. Ten clinical trials were analyzed, with just one Randomized Clinical Trial and nine Non-Randomized Clinical Trials, out of which seven were included in the meta-analysis. When comparing cadaveric liver donor transplantation to living liver donor transplantation, it was observed a decrease in the incidence of biliary strictures (p=0.0001), as well as in the technical failure rate of the endoscopic treatment (p=0.0009) and in the biliary stricture recurrence (p=0.03) in the cadaveric liver donor graft group. Two studies have compared the treatment of anastomotic biliary strictures after liver transplantation using balloon dilation exclusive to balloon dilation associated with the insertion of plastic stents, and no statistically significant differences in relation to endoscopic treatment failure, stricture recurrence or complications rates were observed. Only the clinical outcome complications had statistically significant result in a comparison between self-expandable metal stents versus plastic stents in the treatment of post-liver transplantation anastomotic biliary strictures (p=0.03). Conclusions: The treatment of post-liver transplantation anastomotic biliary strictures was equally effective when compared the use of self-expandable metal stents to plastic stents, but the use metallic stents was associated with a lower complication risk. The comparison between exclusive balloon dilation to balloon dilation associated with plastic stents presented similar results in relation to endoscopic treatment failure, complications and stenosis recurrence. The use of graft from cadaveric donor reduced the risk of biliary stenosis after liver transplantation and endoscopic treatment of biliary strictures in these patients were more effective when compared to biliary strictures after living liver donor transplantation

No description available.