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Made available in DSpace on 2015-07-22T20:49:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-22. Added 1 bitstream(s) on 2015-08-11T03:26:02Z : No. of bitstreams: 1 Publico-12515.pdf: 978359 bytes, checksum: 3be0798a82267f20204fe25244cbed7d (MD5) / Objetivo: Avaliar a evidência de eficácia e segurança do deferasirox para o tratamento da sobrecarga de ferro relacionada à betatalassemia, doença falciforme e síndrome mielodisplásica, em comparação a outros quelantes de ferro disponíveis no Brasil (desferroxamina e deferiprona). Método: Para síntese da evidência foi realizada busca por relatórios de agências de avaliação de tecnologias em saúde e por revisões sistemáticas no Medline (março 2009). Adicionalmente, foi feita busca por ensaios clínicos para atualização da informação disponível. Das referências identificadas, foi selecionado o trabalho de McLeod (2009), por ser uma revisão sistemática e estudo de avaliação econômica elaborado por uma agência de avaliação de tecnologias em saúde de alta confiabilidade. Considerando o contexto econômico local e a disponibilidade dos medicamentos e insumos laboratoriais, a evidência foi adaptada e avaliada criticamente. Resultados: A evidência encontrada é baseada em três ensaios clínicos, de baixa qualidade metodológica, que avaliaram o uso do deferasirox em relação à desferroxamina. Não foram localizados estudos comparativos entre o deferasirox e a deferiprona. Nos ensaios clínicos identificados, a concentração hepática de ferro (exame não disponível no Brasil) foi considerada como desfecho primário, apesar de na prática clínica a quantidade de ferro ser monitorada pela concentração de ferritina sérica. As mudanças na ferritina sérica revelam-se mais favoráveis em pacientes com betatalassemia e doença falciforme (maior prevalência no Brasil) que receberam desferroxamina, do que aqueles que receberam deferasirox. As informações econômicas levantadas indicam que o deferasirox, em comparação a desferroxamina pode ser uma opção custo-efetiva. Conclusões: Como o deferasirox foi introduzido recentemente no mercado brasileiro e é considerado alternativa de tratamento no sistema público de saúde, informações de farmacovigilância precisam ser monitoradas, principalmente no que se refere ao risco de insuficiência renal, citopenias (agranulocitose e trombocitopenia), além de distúrbios gastrointestinais, hepáticos, renais e sanguíneos. / Objectives: to evaluate the evidence on efficacy and safety regarding deferasirox for treatment of iron overload relating to beta-thalassemia, sickle cell disease and myelodysplastic syndrome, in comparison with other iron chelators available in Brazil (deferoxamine and deferiprone). Methods: to produce a synthesis of the evidence, a search was conducted using reports from HTA agencies and systematic reviews in Medline (March 2009). Additionally, a search for clinical trials was conducted to update the information available. Among the references identified, the study by McLeod (2009) was selected because this was a systematic review and economic evaluation produced by a highly trustworthy HTA agency. Considering the local economic context and the availability of medications and laboratory supplies, the evidence was adapted and critically evaluated. Results: the evidence found was based on three clinical trials of low methodological quality that evaluated the use of deferasirox in relation to deferoxamine. No comparative studies between deferasirox and deferiprone were found. In the clinical trials identified, hepatic iron concentration (a test unavailable in Brazil) was taken to be the primary outcome, although in clinical practice, the iron levels were monitored by means of the serum ferritin concentration. The changes in serum ferritin concentration were more favorable among patients with beta thalassemia and sickle cell disease (highest prevalence in Brazil) who received deferoxamine than among those who received deferasirox. Previous economic evaluation suggests that deferasirox may be a cost-effective strategy. Conclusions: since deferasirox was only recently introduced onto the Brazilian market and is considered to be an alternative for treatment within the public healthcare system, drug surveillance information is required, particularly regarding the risks of kidney failure, cytopenia (agranulocytosis and thrombocytopenia) and gastrointestinal, hepatic, renal and blood disorders. / TEDE / BV UNIFESP: Teses e dissertações

Thesis (MTech (Biomedical Technology))--Cape Technikon, 2003 / Allergic conditions among workers processing seafood are most often related to inhalation of the seafood antigens or via direct unprotected handling of the seafood and its products. This can cause sensitised individuals to suffer from asthma, rhino-conjunctivitis, urticaria and protein contact dermatitis, which are IgE mediated. Food intolerance may also occur which is a non-IgE mediated reaction, however the exact mechanism is yet to be determined. There is therefore a need to develop reliable tests to identify sensitised workers processing seafood. The objective of this study was to prepare specific seafood extracts from raw and cooked lobster; raw and cooked saltwater bony fish species (mackerel, red eye, maasbanker, pilchard and anchovy) and fishmeal dust obtained from a fish-processing factory. These extracts were tested by SDS-Polyacrylamide Gel Electrophoresis to characterise the seafood proteins, and the allergenicity was confirmed by the Western blot technique. Polyclonal IgG antibodies were also successfully generated in rabbits, using the specific seafood extracts isolated from the various species. The second objective was to optimise and standardize an Enzyme Allergosorbent Test (EAST) method to quantify specific IgE antibodies in the sera of factory workers. This EAST was optimised and validated to detect allergen-specific IgE to each of the different fish species and also one crustacean species (rock lobster). Sera from a group of workers were selected and analysed for specific IgE antibodies by the optimised EAST (S) (South African laboratory), and commercial RAST techniques. Analysis was performed for the three most important extracts, pilchard (canned), anchovy, and lobster. The same samples were analysed by EAST (R) in the reference laboratory (Dr Gerald Reese; Paul-Ehrlich-Institute, Germany). The different techniques, and the EAST (R) and the EAST (S) results were compared by using a statistical software package. An EAST method was successfully developed, however, compared to the results obtained by the reference laboratory the sensitivity and specificity was below 80%. The main reason for the low agreement between the two laboratories was the fact that the South African laboratory used a modified EAST method, and different data calculation methods, for categorising positive results. The South African laboratory did not use a kit-based assay and a serum dilution of 1:4 and not 1:2 were used when compared to the reference laboratory. When the EAST results were compared to the RAST results, poor agreement was found due to the fact that canned pilchard was used in the EAST while raw pilchard in the commercial RAST assay. For pilchard, anchovy and lobster EAST, different species were utilized compared to the RAST, and this can also explain the poor level of agreement. Future directions would be to further standardise the EAST method and to introduce reference sera and a standard curve to determine positive results, thereby ensuring more reproducible results between laboratories.

Thesis (DTech (Biomedical Technology))--Cape Technikon, 2001 / Ionising radiation has the ability to induce, inter alia, DNA damage and is well established as a causative agent of carcinogenesis and mutagenesis. The effects of high doses of short duration have been well documented, whereas the effects of continuous exposure to low doses of ionising radiation have not, nor are they as clearly understood and current risk estimates are largely extrapolated from high-dose data of atomic bomb survivors. This study evaluated the clastogenic effects of low dose ionising radiation on a population of bats (Chiroptera) residing in an abandoned monazite mine. Bats were sampled from two areas in the mine, with external radiation levels measuring around 20 µSv/h (low dose) and 100 µSv/h (high dose). A control group of bats was collected from a cave with no detectable radiation above normal background levels. The most frequently encountered genetic event in human malignancy is the alteration of the p53 gene. Mutant p53 proteins have a longer half-life than the wild-type variant and accumulate to high levels in the nucleus of tumour cells. The study showed that not only was there a significant increase in p53 positive cells of radiation exposed bats, but also in the degree of positivity, especially in the cells lining the bronchioles of the lungs. Although experimental studies have shown that exposure to radiation may lead to the onset of fibrosis and an inflammatory response in the lung and other tissues, the magnitude of the dose exposure was not comparable to this study and histological examination of bat lung and liver tissues showed no morphological changes in radiation exposed bats when compared to the control group. It has been documented that chronic radiation exposures may give rise to a number of specific haematological defects which are collectively termed "preleukemia" or myelodysplastic syndrome. Full blood counts on bat samples showed a significant decrease in the MCV indicating microcytic erythrocytes from the radiation exposed bats. Differential counts performed on the peripheral blood of the bats showed a marked neutropenia. Neutrophils also showed marked dysplasia including psuedo-Pelger Huet cells in radiation-exposed bats. Cytochemical analysis using DAB myeIoperoxidase showed that control bats had hypogranular neutrophils andradiation-exposedbats had largely '1granularneutrophils. Bonemarrow biopsies were taken from both control and radiation-exposed bats and evaluated for ceIlularity, granulocyte: lymphocyte: erythrocyte (GLE) ratio and megakaryocyte morphology. A hypocelIular bone marrow, a decreased granulocytic haematopoeisis and dysplastic megakaryocyte morphology were observed in radiation-exposed bats. Mineralisation of bone osteoid was determined using image analysis and showed a highly significant decrease in the bone matrix from radiation-exposed bats. All haematological features observed are congruent with current literature describing secondary (radiation-induced) myelodysplastic syndrome.

With the new capabilities of genetic engineering and such biotechnologies, come added considerations for policy makers. If gene therapy (or even embryo selection) becomes common practice, we must look not only to creating policies that protect the interests of individuals in the legal and social realms, but consideration must also be given to the equality of opportunity in the genetic sense. This additional level brings with it much significance; one can argue that financial disparity is at least theoretically surmountable but it is difficult to account for intentional genetic alterations that would forever give certain individuals a physical advantage over non-enhanced persons. It is with these new boundaries that genetic policy must find itself creating legislation; it is also with these new boundaries that policy will find its greatest hurdles. Given the ever-expanding field of biotechnology and gene therapy, one can hardly expect policy written today to be up-to-date ten, or even two years from now. Instead of focusing, therefore, on specific recommendations, I will center my discussion on a broad framework that outlines the arguments that should be considered when dealing with genetic engineering and public policy. After creating a theoretical structure centered on historical experiences and the philosophical writings of John Rawls, we will delve deeper into the actual possibilities created by genetic engineering and embryo selection. I will further analyze the differences between positive and negative genetic interventions and discuss the consequences of these differences as they should (or should not) affect policy. This particular distinction and the implications of these differences on policy will serve as the bulk of my discussion. / Master of Arts