Background: Each year, thousands of patients around the world receive a new heart through heart transplant surgery. This is a lifesaving action and is most common among people with a heart disease that has led to a severe and non-treatable heart failure, for instance cardiomyopathy. But the process of receiving a new heart comes with challenges and the patients can experience emotional and physical difficulties. Aim: The aim of this study was to illuminate adult patients' experiences after heart transplantation. Method: A literature-based study was conducted and fourteen scientific qualitative articles were analyzed with a qualitative approach. Results: After analyzing the results, three main themes emerged; "To receive someone else's heart", "Learning how to live" and "To experience difficult emotions". Each main theme had three significant subthemes. The findings showed that a diversity of experiences arose among the patients after undergoing heart transplant surgery. They experienced gratitude, faith, concern, existential thoughts and sadness. They expressed support and the pursuit of gaining control in daily life as meaningful and essential. But they also had to handle limitations in their lives concerning the medical treatment, the continuous follow-ups and the diet restrictions. Conclusion: As a nurse it is fundamental to see the heart transplant patient as a unity and a unique person. Thus it is important to notice the patients' psychological difficulties that can arise after heart transplantation and not only observe the physical problems. Communicate with the patients in a motivating and caring way and try to understand their individual experiences of the situation in order to promote their health. In that way we can lay a valuable foundation for nursing.

Diabetes is a major health problem worldwide, and there is substantial interest in developing xenogeneic islet transplantation as a potential treatment. The potential to relieve the demand on an inadequate supply of human pancreata is dependent upon the efficiency of techniques for isolating and culturing islets from the source pancreata. Porcine islets are favored for xenotransplantation, but mature pigs (>2 years) present logistic and economic challenges, and young pigs (3-6 months) have not yet proven to be an adequate source. In this study, islets were isolated from 20 juvenile porcine pancreata (similar to 3 months; 25 kg Yorkshire pigs) immediately following procurement or after 24 h of hypothermic machine perfusion (HMP) preservation. The resulting islet preparations were characterized using a battery of tests during culture in silicone rubber membrane flasks. Islet biology assessment included oxygen consumption, insulin secretion, histopathology, and in vivo function. Islet yields were highest from HMP-preserved pancreata (2,242 +/- 449 IEQ/g). All preparations comprised a high proportion (>90%) of small islets (<100 mu m), and purity was on average 63 +/- 6%. Morphologically, islets appeared as clusters on day 0, loosely disaggregated structures at day 1, and transitioned to aggregated structures comprising both exocrine and endocrine cells by day 6. Histopathology confirmed both insulin and glucagon staining in cultures and grafts excised after transplantation in mice. Nuclear staining (Ki-67) confirmed mitotic activity consistent with the observed plasticity of these structures. Metabolic integrity was demonstrated by oxygen consumption rates=175 +/- 16 nmol/min/mg DNA, and physiological function was intact by glucose stimulation after 6-8 days in culture. In vivo function was confirmed with blood glucose control achieved in nearly 50% (8/17) of transplants. Preparation and culture of juvenile porcine islets as a source for islet transplantation require specialized conditions. These immature islets undergo plasticity in culture and form fully functional multicellular structures. Further development of this method for culturing immature porcine islets is expected to generate small pancreatic tissue-derived organoids termed "pancreatites," as a therapeutic product from juvenile pigs for xenotransplantation and diabetes research.

Two major problems preventing the clinical application of pancreatic islet transplantation were investigated. The problem of allograft rejection was studied in rats, made diabetic by streptozotocin treatment. It was shown that DA rats given LEW renal allografts and treated with cyclosporine accepted their grafts, and subsequently developed a strain-specific unresponsive state that allowed successful transplantation of LEW islets without further immunosuppression, whilst BN islets were rejected normally. The effect was demonstrated to be independent of the site of islet transplantation, and, once an islet allograft had been accepted, it was possible to remove the original renal allograft without affecting the transplanted islets. The effect was shown to apply to another strain combination (LEW into PVG), and also to animals made unresponsive to renal allografts by another method (donor-specific blood transfusion). The problem of separation of adequate numbers of viable islets from the pancreas was studied in the rat, dog, pig and human. To aid the investigation, supravital staining techniques were developed, using neutral red to identify the islets, and fluorescein diacetate and ethidium bromide to assess islet viability. A variety of islet isolation techniques were investigated, and a new technique for isolation of islets from the dog pancreas, yielding up to 160,000 islets from 1 pancreas with a maximum purity of 80%, was developed. The structural integrity and in vitro function of the isolated islets was demonstrated, but it was not possible to prevent diabetes by autotransplantation of islets to the portal vein of pancreatectomised dogs. A method for isolation of islets from the human pancreas was developed from that used in the dog, yielding up to 80,000 islets from a whole pancreas, with a maximum purity of 40%. The technique was shown to be both simple and reliable. The structural integrity and in vitro function of the isolated islets was demonstrated, and the viability of the islets proven by successful transplantation under the kidney capsule of nude mice.

Battlefield retinal laser injury is an infrequent but potentially devastating cause of irreversible blindness. Resultant laser-induced photoreceptor death may occur by necrosis or apoptosis, the latter which is a form of programmed cell death that may be physiological or pathological. Though necrosis cannot be prevented, apoptosis may be inhibited under certain conditions. Therefore, following retinal laser injury, specific treatment aims to target apoptotic photoreceptors and may take the form of neuroprotection or cell replacement. The primary aim of this thesis was to construct an in vivo model in which to observe the effects of retinal laser exposure on cone photoreceptor apoptosis. Current methodology to determine the effects involves histological techniques and is therefore limited to being cross-sectional. An in vivo model would permit longitudinal study to observe the cone response to injury using clinically relevant applications, including fundus autofluorescence imaging. Such a construct would enable more sensitive evaluation of new therapies which would be of direct translational relevance. The secondary aim was to investigate potential therapeutic options for retinal laser injury by pharmacological means in the form of CNTF or cell transplantation. To identify the possible molecular signals involved in neurotrophic factor-induced photoreceptor cell survival, apoptotic gene expression was investigated focusing on those genes modulated by the CNTF pathway.

The main aims of this thesis are to assess the efficiency of the current bankruptcy system in Oman and to offer specific proposals for bankruptcy reform to be adopted by the Omani legislator. Where appropriate, in proposing solutions for various issues lessons will be taken from the experience of both England and the US. This thesis consists of six chapters. The first chapter is a general introduction to the thesis which outlines the structure and scope of the study. Chapter Two critically explores the main theories underpinning bankruptcy law across the world. The aim of this exploration is to provide a general understanding of the policies underpinning bankruptcy laws and to establish the view of this thesis. Chapter Three discusses the experience of England and the US by identifying the main differences and similarities between bankruptcy proceedings in these jurisdictions; such discussion is necessary as a basis for determining the possibility of taking lessons from these developed bankruptcy regimes. Chapter Four provides a critical analysis of the current bankruptcy regime in Oman and outlines the key features of this regime. This chapter also discusses in detail the main issues with the current bankruptcy regime. This discussion includes: (1) the definition of bankruptcy; (2) the qualification of persons administering bankruptcy processes (3) ranking of creditors; (4) position of employees; (5) available alternatives under the current regime; and (6) the effect of declaration of bankruptcy on existing contracts. Chapter Five outlines the possibility of legal transplants and why it is desirable for Oman to adopt some of the bankruptcy principles that are found in England and the US. However, to avoid the risk of rejection of such transplants, this thesis will highlight the necessity of assessing the functionality and workability of western bankruptcy principles before transplanting them. This chapter also offers a proposal for future bankruptcy reform in Oman. Such reforms include having a clear statutory mandate, making bankruptcy law certain and predictable, and establishing a bankruptcy regime that encourage the rehabilitation of viable enterprises instead of liquidating them. Chapter Six is the overall conclusion of this thesis which explains the main ideas discussed and highlights the main contributions made by this study.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

86 Abstract - Transplantation Act: ethical and legal aspects. Theory and practice in the Czech Republic in comparison to the legal regulation in Germany Transplantations and related issues form an important part of medical law which is constantly developing. Currently it is a widely debated topic because there is lack of organs for donation, thus current supply can't satisfy all the demanding donees. It is a problem where the ethic, legal, medical and economic factors meet so there is no easy solution for majority of difficulties associated with transplantations. This diploma thesis focuses on contemporary legislation of organ and tissue donation and transplantations in Czech Republic which is mainly based on transplantation law and several legally binding international agreements. The aim of the thesis is a comprehensive evaluation of the current legislation and its comparison with the same legal branch in Germany. The work will also point out some of the shortcomings associated with the transplantation law and proposal of possible solution. Thanks to the comparison the thesis comes to a conclusion that the Czech transplantation law is relatively of high quality, but there are still imperfections which haven't been erased even by the approved amendatory act. However with relation to the German...

This thesis sought to investigate novel methods for protecting the liver from ischaemia reperfusion injury in the context of liver transplantation. Research in the heart, brain and kidneys has suggested that hypoxia inducible factor (HIF) may play a key role in the delayed phase of ischaemic preconditioning and can protect organs for up to 3 days. However, although there is good evidence for the potential of HIF to protect organs from ischaemia, the HIF pathway still presents some what of a paradox because it targets both pro-death (e.g. BNIP3,NIX) as well as pro-survival genes (e.g. HO-I, EPO). HIF is primarily controlled by 3 oxygen dependent prolyl hydroxylases (PHD 1 , PHD2, PHD3), and inhibition of these prolyl hydroxylases leads to HIF activation. It was hypothesised that differential inhibition of PHD 1,2 or 3 may result in selective gene regulation and may confer greater or less protection against ischaemia reperfusion injury. To investigate this hypothesis mouse embryonic fibroblasts (MEFs) were isolated from PHDl, 2, and 3 knock-out (KO) embryos and compared to MEFs derived from WT littermate controls. In these MEFs, cell growth and proliferation, as well as cell survival following exposure to anoxia and inducers of apoptosis was studied. The principal findings were that PHD2 is the dominant regulator of HIF in normoxia. PHD2 knock-out MEFs exhibited glycolytic metabolism and had a lower oxygen consumption compared to wild-type MEFs. Gene array studies confirmed the dominant role of PHD2 but also demonstrated that PHD 1 upregulates a number of HIF target genes, albeit to a lesser extent than PHD2. There were no differences, however, in susceptibility to hypoxic injury in the PHDl, 2, and 3 knock-out MEFs compared to wild-type controls. A further aim of the study was to investigate whether prolyl hydroxylase inhibition using dimethyloxalyglycerine (DMOG) may protect the liver in a rodent model of ischaemia reperfusion injury. DMOG effectively upregulated HIF and IllF target genes. Serum transaminases (AST and AL T) were significantly lower in the DMOG treated animals compared to the normal saline treated controls 24 hours following ischaemia. This protection was similar to the protection conferred by surgically induced ischaemic preconditioning. This thesis provides important insights into the individual function of the prolyl hydroxylases and provides preliminary evidence that prolyl hydroxylase inhibitors may be useful in the treatment of ischaemia reperfusion injury in liver transplantation.

Orientador: Joaquim Mansano Garcia / Coorientador: Marina Ragagnin de lima / Banca: Luisa Cunha Carneiro / Resumo: A necessidade de uma metodologia mais prática para transferência de embriões em tempo fixo em rebanhos de gado de corte, para que se torne mais proveitoso, tem aumentado ao longo dos anos. O presente estudo avaliou a taxa de concepção e gestação de embriões produzidos in vitro transferidos a fresco, vitrificados ou congelados em um rebanho nelore de corte. Doadoras Nelore (n= 20) de um mesmo rebanho foram previamente selecionadas para serem submetidas a ovum pick up em dia aleatório do ciclo estral. Oócitos foram recuperados e selecionados para maturação in vitro por 24 horas a 38,5°C com 5% CO2 e 95% de humidade do ar. Para fertilização in vitro, sêmen da mesma partida, de um touro pré-selecionado da raça Nelore foi utilizado. Após 6 dias de cultivo in vitro, os embriões na fase de blastocisto foram aleatoriamente selecionados para serem transferidos a fresco, vitrificados ou congelados. As transferências foram realizadas em novilhas e vacas do mesmo rebanho das doadoras. As taxas de concepção, aos 30 dias, para os embriões transferidos a fresco, vitrificados ou congelados e transferidos depois do reaquecimento foram, respectivamente, de 37,64 ± 11,20%, 24,09 ± 2,34% e 16,21 ± 10,23%. As taxas de concepção, aos 30 dias, considerando a categoria da receptora, novilha ou vaca foi de 23,02 ± 3,42% e 31,06 ± 4,62%, respectivamente. O estudo mostrou que o método de congelação lenta, para transferência direta utilizado, não consegue resultados similares aos transferidos à... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The necessity of a more practical fixed time embryo transfer method in beef cattle herds, in order to make it more usable, has grown over the years. The present study compared the conception and pregnancy rates of in vitro produced embryos transferred fresh, vitrified or slow frozen in an nelore beef herd. Nelore donors (n=20) were previously selected to be submitted to ovum pickup on a random day of estrous cycle. Oocytes were recovered and selected for in vitro maturation for 24 hours at 38,5°C with 5% CO2 and 95% air humidity. For in vitro fertilization, semen, from the same batch, of one pre-selected Nelore bull was used. After 6 days of in vitro cultivation, embryos on blastocysts stage were randomly selected to be transferred either fresh, vitrified or frozen. The transfer procedures were conducted on heifers and cows of the same herd of the donors. Conception rates, at 30 days, for fresh transferred, vitrified and frozen transferred embryos were, respectively, 37,64 ± 11,20%, 24,09 ± 2,34% and 16,21 ± 10,23%. Conception rates, at 30 days, considering animal category of the recipients, heifer or cow were 23,02 ± 3,42% e 31,06 ± 4,62%, respectively. This study showed that the slow freezing, for direct transfer method used, can't achieve similar results (p= 0,0078) as the fresh transferred on Nelore herds, and vitrification still has to be the cryopreservation method for embryos on Nelore herds. It was used a significance of p<0,05. / Mestre

8 ABSTRACT Author: Bc. Lucie Moravcová Supervisor: MUDr. Vít Řeháček Charles University, Faculty of Pharmacy in Hradec Králové Title of master's thesis: Kidney transplantation: donor-recipient pairing in University Hospital Hradec Králové Background: The aim of this study was to determine HLA, blood group, age and sex match in donor-recipient pairing in kidney transplantation. HLA alleles of deceased donors were typed in Transfusion Department of the University Hospital Hradec Králové. Methods: Donor's HLA-A*, HLA-B* and HLA-DRB1* alleles were typed by PCR - SSP method. Complex data evaluating and processing was then performed. Results: 97 deceased donors were tested between 2013 and 2018. A total of 98 kidneys received from them were subsequently transplanted to 98 recipients in University Hospital Hradec Králové. 60,2 % of the donors were men, 63,3 % of the recipients were men. Most of the donors, as well as the recipients, were 51-70 years old (50,0 % and 59,2 %, respectively). The most common diagnoses in the group of deceased donors were associated with brain damage (66,3 %), the most common cause of renal failure in the group of recipients was chronic inflammatory kidney disease (41,8 %). All 98 transplantations (100,0 %) were AB0 compatible. 74 transplantations (75,5 %) were RhD compatible. 5...