Thesis (Ph.D.)--University of Western Australia, 2006.

Thesis (Ph.D.) - University of Queensland, 2002. / Includes bibliography.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

München, Techn. Univ., Diss., 2004.

Frankfurt (Main), Univ., Diss., 2001.

Introdução: O tratamento da hepatite C crônica com intereferon dura de 48 a 72 semanas, dependendo do genótipo. Os efeitos adversos mais prevalentes são dores pelo corpo, sintomas depressivos e piora na qualidade de vida. O tratamento torna o paciente incapacitado para suas tarefas diárias e atrapalha a adesão ao tratamento. Dessa forma, faz-se necessário buscar novas alternativas para minimizar os danos tornando o tratamento menos agressivo ao paciente e diminuindo os sintomas. Objetivo: Foram testadas duas hipóteses. A primeira foi explorar se a estimulação transcraniana por corrente continua (ETCC) seria mais eficaz em pacientes tratados com interferon peguilhado (PegINF) no tratamento da hepatite C crônica do que um placebo-sham para a redução dos sintomas dolorosos avaliados por meio dos níveis de dor e do limiar de dor a pressão. A segunda foi testar se os efeitos da ETCC nos sintomas relacionados ao uso de PegINF estariam relacionados ao processo de neuroplasticidade avaliado por meio dos níveis séricos de BDNF. Métodos: Foram recrutados 28 pacientes com hepatite C crônica, destros, com idades entre 40-74 anos, com escore de dor na escala numérica acima de 4 e com e limitações funcionais para realizar atividades de rotina devido à dor. Estes pacientes foram randomizados para um dos grupos de tratamento – placebo-sham (n=14) ou ETCC ativo (n=14). O tratamento consistiu em uma sessão diária de ETCC durante cinco dias consecutivos com a estimulação de 2mA aplicada na área do córtex motor primário(M1) do lado dominante. Os instrumentos de avaliação utilizados foram questionário para avaliar nível socioeconômico e dados demográficos, Escala Analógica Visual de dor (VAS), Escala do perfil de dor crônica (B-PCP:S) e níveis séricos de BDNF. Resultados: Comparando ETCC ativo com placebo-sham, ETCC ativa apresentou escores de dor significativamente mais baixos de VAS (P<0,003). A interação entre grupo e tratamento não foi significativa (P=0,07). A ETCC ativa resultou em redução da média de dor em 56% em comparação com o placebo-sham (P<0,001). Além disso, em comparação com placebo-sham, ETCC ativa resultou em melhora significativa no limiar de dor por pressão (P = 0,007) e no B-PCP: S (P <0,001), bem como reduziu o numero de doses analgésicas (P <0,03). O grupo da ETCC ativa também teve aumento significativo do BDNF no soro a partir da linha de base que foi de 37,48% (ETCC ativo) em comparação com 1,48% (diminuição do placebo-sham), esta diferença foi significativa (P <0,01). Conclusão: Concluímos que há grande potencial de utilização dessa técnica no tratamento de pacientes com hepatite c crônica, no que diz respeito ao alívio da dor, limiar de dor e diminuição dos níveis de BDNF. / Background: The treatment of chronic hepatitis C with intereferon lasts 48-72 weeks depending on the genotype. The most prevalent adverse effects are body pain, depressive symptoms and poor quality of life. The treatment makes the patient incapacitated for their daily tasks and interfere with treatment adherence. Thus, it is necessary to seek new alternatives to minimize the damage becoming less aggressive treatment to the patient and decreasing symptoms. Objective: Two hypotheses were tested . The first was to test whether transcranial direct current stimulation ( tDCS ) would be more effective in patients treated with interferon pegylated (PegINF) in the treatment of chronic hepatitis C than placebo-sham to reduce painful symptoms assessed by levels of pain and pressure pain threshold. The second was to test whether the effect of the tDCS related to use of PegINF symptoms would be related to the neuroplasticity process evaluated by means of BDNF serum. Methods: We recruited 28 patients with chronic hepatitis C, right-handed, aged 40-74 years, with a pain score on a scale above 4 and with functional limitations to perform routine activities due to pain. These patients were randomized to one of the treatment groups - placebo-sham (n = 14) or active tDCS (n=14). The treatment consisted of a daily session of 2mA tDCS for five consecutive days, applied in the primary motor cortex (M1) of the dominant hand area. The assessment instruments were used questionnaire to assess socioeconomic and demographic data, visual analogue scale for pain (VAS), scale profile of chronic pain (B-PCP:S) and serum BDNF levels. Results: Compared active tDCS with placebo-sham, active tDCS scores showed significantly lower pain VAS (P<0.003). The interaction between group and treatment was not significant (P =0.07). The active tDCS resulted in a reduction in average pain by 56% compared with the placebo -sham (P < 0.001). Moreover, active tDCS compared with placebo-sham, active tDCS resulted in significant improvement in the pain pressure threshold (P = 0.007) and the B -PCP:S (P<0.001) and reduced the number of analgesic doses (P < 0.03). The active tDCS group also had significantly increased BDNF in serum from the baseline that was 37.48 % (active tDCS) compared to 1.48% (reduced placebo-sham), this difference was significant (P < 0.01). Conclusion: We conclude that there is great potential for using this technique in the treatment of patients with chronic hepatitis C, with regard to pain relief, pain threshold and decreased levels of BDNF.

Made available in DSpace on 2014-06-11T19:26:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-18Bitstream added on 2014-06-13T20:34:30Z : No. of bitstreams: 1 nogueira_ct_me_arafcf.pdf: 255888 bytes, checksum: d417d37d80e882645bd66ae985054789 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os perfis metabólicos correlacionam-se com a infecção pelo VHC e são prognósticos da resposta viral em pacientes crônicos. Porém, pouco se sabe a respeito da associação entre perfis lipídicos e carga viral do VHC entre infecções dos genótipos 1, 2 ou 3. Portanto, o objetivo deste trabalho foi estudar a influência da viremia e dos genótipos do VHC sobre o metabolismo lipídico através das variações de lipoproteínas séricas (colesterol total, LDL, HDL, VLDL, triglicérides) e apolipoproteína B (Apo B) em hepatopatas crônicos, avaliando se o VHC predispõe os indivíduos ao aparecimento de complicações vasculares. O grupo amostral constituiu-se de um total de 150 pacientes crônicos do VHC com genótipos 1, 2 ou 3, e de um grupo controle de 20 indivíduos saudáveis (10 homens e 10 mulheres) em idade adulta (20 à 50 anos). Os níveis séricos de HDL (28%), VLDL (26%) e triglicérides (26%) nos portadores crônicos do VHC se mostraram diminuídos em relação ao grupo controle, enquanto os níveis de LDL (25%) e Apo B (29%) se mostraram elevados, resultados que foram mais importantes nos portadores do genótipo 3a. Observou-se correlação positiva entre a viremia e alterações nos níveis de apo B (r = 0,5763) nos portadores do genótipo 1b. Assim, foi pressuposto que o risco de pacientes portadores do VHC desenvolverem complicações vasculares é elevado, pois 1% de redução nos níveis de LDL está associado com uma redução de 2-3% no risco de desenvolvimento de doenças cardíacas, e como cerca de 90% da proteína na LDL se constitui de apo B, sua concentração plasmática indica o número total de partículas potencialmente aterogênicas. Desta forma, o perfil lipídico auxilia no diagnóstico da severidade da infecção hepática causada pelo VHC e ainda atua como um bom sinal prognóstico. / The metabolic profiles correlate with the hepatitis C virus infection and are prognostics for the viral reply in chronic patients. However, little is known regarding the distinguishing association between lipid profiles and hepatitis C viral load in patients carrying genotypes 1, 2 or 3. Therefore, the objective of this work was to study viremia and genotypes on the lipid metabolism through the serum lipoprotein variations (total cholesterol, LDL, HDL, VLDL, triglycerides) and apolipoprotein B (Apo B) in chronic carriers of this infection, evaluating if the HCV premakes the individual to the lipidic disequilibrium and favors the appearance of vascular complications. The amostral group consisted of 150 HCV chronic patients with genotypes 1, 2 or 3, and a control group consisted of 20 healthful individuals (10 men and 10 women) in adult age (20 to 50 years). The levels of HDL (28%), VLDL (26%) and triglycerides (26%) of the HCV chronic patients were lower than the control group, while the LDL levels (25%) and the Apo B levels (29%) were higher. These findings were more significant in the genotype 3a carrying patients. Positive correlation occurred between the viremia and the alterations in the Apo B levels (r = 0.5763) in the genotype 1b carrying patients. Consequently it was inferred that the risk of HCV patients to develop vascular complication is elevated. In general, 1% of reduction in the LDL levels is associated with a reduction of 2-3% in the risk of development of cardiac illnesses, and, as about 90% of the protein in the LDL is constituted of apo B, its plasmatic concentration indicates the total potentially atherogenics particles number. The lipid profile aids in the diagnosis of the severity of the hepatic infection and equally acts as a good signal prognostic, therefore its analysis must be carried through in all the cases of advanced hepatic infection.

Made available in DSpace on 2014-11-10T11:09:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-03-06Bitstream added on 2014-11-10T11:57:26Z : No. of bitstreams: 1 000773465_20150110.pdf: 677474 bytes, checksum: 3ab409c79c33f6f910c52214a6fc684c (MD5) Bitstreams deleted on 2015-01-16T10:37:56Z: 000773465_20150110.pdf,Bitstream added on 2015-01-16T10:38:38Z : No. of bitstreams: 1 000773465.pdf: 1856915 bytes, checksum: 31cff2133ada813ddd49b0c93615b201 (MD5) / Neste trabalho foram investigados a fibroína da seda (silk fibroin, SF) com o peptídeo antigênico da proteína NS5A-1 derivado do vírus da hepatite C (HCV) e nanopartículas de vanadato de ítrio dopadas com európio em filmes nanoestruturados. Dois foram os tópicos abordados: i) interação e organização estrutural do peptídeo com a fibroína. ii) imobilização do peptídeo, da fibroína e nanopartículas em filmes automontados (Layer-by-Layer, LbL), visando estudar a interação específica peptídeo antigênico-anticorpo e a produção de protótipos de imunossensores. As interações fibroína-peptídeo foram estudadas em solução e em filmes LbL pelas técnicas espectroscópicas de dicroísmo circular e luminescência. Os resultados indicaram que há uma mudança conformacional da fibroína em solução para a fibroína em filmes, de aleatória para folha-β, respectivamente, e que o filme de fibroína induz a estrutura secundária do peptídeo que não possui uma conformação bioativa em solução. O crescimento dos filmes LbL foi monitorado por espectroscopia UV-visível, e pôde-se observar um crescimento linear a cada deposição realizada. Além do estudo fundamental das interações a nível molecular, os sistemas foram utilizados para o desenvolvimento de protótipos de imunossensores. A interação peptídeo antigênico-anticorpo foi estudada por medidas de detecção eletroquímica, elétrica e óptica. Para a detecção eletroquímica realizou-se medidas de voltametria cíclica, indicando uma diminuição na corrente quando em presença dos anticorpos anti-HCV e testes em amostras reais soropositivas para o vírus, que indicaram uma maior densidade de elétrons nos voltamogramas referentes às amostras infectadas. A detecção elétrica foi analisada por espectroscopia de impedância elétrica, e observou-se que há um aumento no sinal da capacitância e das perdas dielétricas de acordo com o aumento da concentração... / The present study investigated the silk fibroin (SF) with the antigenic peptide of the NS5A-1 protein of the hepatitis C virus (HCV) and nanoparticles of yttrium vanadate doped with europium immobilized on nanostructured films. Two main topics were explored: i) interaction and structural organization of the peptide with fibroin. ii) immobilization of the peptide together with fibroin and nanoparticles in LbL films (Layer- by- Layer), in order to study the specific interaction peptide antigen-antibody and production of prototype immunosensors. The fibroin-peptide interactions were studied in solution and in LbL films by spectroscopic techniques of circular dichroism and luminescence. The results indicate that there is a conformational change of fibroin in the fibroin solution in film, sheet to random coil-B, respectively, and that the fibroin film induces the secondary structure of the peptide does not possess a bioactive conformation in solution. The growth of the LbL films was monitored by UV-visible spectroscopy, and could observe a linear growth every deposit made. Besides the fundamental study of interactions at the molecular level, the systems were used for the development of prototype immunosensors. The peptide antigen-antibody interaction was studied by electrochemical, electrical and optical detection measures. For electrochemical detection, were made cyclic voltammetry measurements indicating a decrease in current when in the presence of anti-HCV antibodies, and were made tests on real samples seropositive for the virus, which indicated a higher density of electrons in voltammograms respect to infected samples. The electrical detection was analyzed by electrical impedance spectroscopy, and it was observed that there is an increase in the signal of capacitance and the dielectric losses in accordance with the increase in antibody concentration. This increase in signal is higher for films containing smaller number of bilayers and...

This thesis portfolio includes two studies, a qualitative grounded theory of treatment adherence in people who inject drugs (PWID) and a systematic review of staff turnover in substance misuse services. The empirical paper is presented first, the findings of which led to the systematic review. The qualitative interview study arose from observations made within a clinical trial for the treatment of chronic Hepatitis C (HCV). The Chief Investigator of the ERADICATE trial team initially approached the Adult Psychological Therapies Service to investigate what seemed to be an anomaly – patient engagement with HCV treatment had far exceeded expectations. Indeed, positive treatment adherence is not common among PWID. What is more remarkable is participants continued the trial while experiencing the highly aversive side-effects of interferon, a medication known to mimic opioid withdrawal. It is important, if not crucial, to acknowledge the wider socio-cultural context in which this thesis portfolio was produced; the political landscape changed significantly over the course of writing. Divisive judgements about what characteristics make a person worthy and deserving of resources, became more dominant in public discourse and heightened the author’s awareness to these aspects in the data. PWID are among the most marginalised, and stigmatised groups in society. Several of the participants interviewed were homeless and all were at various points on a relapsing trajectory of injecting drug use. Perhaps positive treatment adherence in this population is counter-intuitive because intuition is often based on assumptions derived from implicit biases. Indeed, until 2008, Scottish policy systematically denied HCV treatment to PWID. Due to the assumption that re-infection was inevitable, treatment was seen to be wasteful. Epidemiological studies now show is that public health is significantly improved when PWID are treated, as population prevalence goes down. Completing this thesis led to an examination of fundamental assumptions, not just relating to the participants or the data, but also relating to the question of what Clinical Psychology is. What can we contribute to the science of human behaviour? How does a self-aware mind arise and become autonomous? What leads adults to mentalize and enact their intentionality through particular behaviours, like taking medication? In grappling with these questions, the reader will detect the influence of developmental theorists, Vygotsky, Erikson and Bowlby. Seminal experiments, such as Tronick’s still face (Tronick, 1989)1 and Harlow’s monkeys (Harlow and Zimmerman, 1958)2, alongside newer fields of interpersonal neurobiology and developmental trauma have supplied the soil in which to ground the data gathered in this study. From our earliest days we are designed to absorb stimuli and integrate our perception into a gestalt. When PWID are characterised as “chaotic”, there is a failure to appreciate what this may really reflect: difficulty making sense of internal experience resulting in the absence of order, coherence and meaning. Therefore, the ontological presupposition underlying both the empirical paper and systematic review, is that humans are resilient, relational beings. When the correct conditions and contingencies are in place, our innate propensity to learn and grow can manifest in positive, adaptive behaviour. Narratives are not only ways of seeing the world, but ways of constructing it; we live through and are created by the stories told by others and ourselves (Murray, 2003)3. The public narrative of scepticism that has emerged around scientific endeavour, makes it all the more incumbent upon researchers to carry out their work with personal conviction, integrity and transparency (Rea, 2017, February 22)4. This qualitative analysis was completed with a high level of scientific rigour. Indicators of quality were employed throughout, for example, particular attention was paid to preserving the colloquial expression of participants in transcription and substantiates the authentic representation of their voice. The resultant grounded theory shows that the interpersonal context is a key part of adherence behaviour among PWID. This finding precipitated another question, if good quality relationships are important for patient engagement, how do staff stay engaged in the task of providing consistent, sensitive care on a sustained basis? The current evidence base on supporting and preserving compassion did not substantiate a systematic review, however, the opposite phenomenon, people leaving their jobs has been explored. As Clinical Psychologists we are able to connect with and influence different audiences by skilfully adapting our language. In order to appeal to managers and team leaders, the most pragmatic way of framing staff disengagement, was to examine actual staff turnover as a ‘hard’, concrete outcome. The methodological quality of studies included for review was reasonable in the context of methodological limitations. Findings point to the importance of collective support, good quality relationships and job satisfaction in mitigating against turnover in substance misuse services. This thesis portfolio is a sensitive and pragmatic understanding of engagement in both PWID and staff with the respective systems within which they are embedded. The results are contextualised and oriented toward medical colleagues working in HCV treatment, service leaders and fellow applied psychologists.

Made available in DSpace on 2014-06-11T19:24:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-04-07Bitstream added on 2014-06-13T20:51:48Z : No. of bitstreams: 1 gryninger_g_me_botfm.pdf: 272447 bytes, checksum: 5ed6892f68f886811597fca3fd900973 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / O vírus da hepatite C é uma das principais causas de doença hepática no mundo inteiro. O estudo histopatológico é de grande importância no prognóstico e indicação de tratamento. A coinfecção com o vírus da hepatite B oculta pode agravar a lesão hepática e diminuir a resposta ao tratamento. As citocinas IL-2, INF, TNF- induzem lesão hepática e fibrose. A IL-10 apresenta atividade antiinflamatória e o TGF- induz o desenvolvimento e depósito de matriz extracelular causando fibrose. Este estudo avaliou, em pacientes com HCC, a presença da hepatite B oculta, a dosagem das citocinas IL-2, INF, TNF , TGF e IL-10, correlacionando com o estágio de fibrose em pacientes tratados e não tratados com interferon, comparando também com indivíduos saudáveis. Foram estudados 55 pacientes com HCC crônica, atendidos na Faculdade de Medicina de Botucatu, excluindo-se pacientes imunossuprimidos e gestantes. O grupo controle foi constituído de 20 indivíduos doadores de sangue. O vírus da hepatite B oculto foi pesquisado por de PCR in house, segundo técnica de Kaneno, com limite de detecção menor que 100 cópias/ml. A dosagem de citocinas foi determinada por método de Elisa. A avaliação da fibrose hepática seguiu aquela proposta pela Sociedade Brasileira de Patologia. Os resultados mostraram predominância do gênero masculino, adulto jovem, 36,4% foram usuários de drogas endovenosas e 41,8% haviam sido hemotransfundidos. Nenhum paciente apresentou coinfecção pelo vírus da hepatite B oculto. Na biópsia hepática predominou fibrose leve ou ausência de fibrose (47,2%). As citocinas analisadas não discriminaram o grau de fibrose nos indivíduos com HCC crônica, mesmo quando separados em pacientes que foram submetidos ao tratamento e pacientes que não receberam o tratamento. Não houve também discriminação das citocinas... / The Hepatitis C virus is one of the major causes of hepatic diseases worldwide. Histopathological analyses play a leading role in determining disease outcome and treatment. Co-infection with occult Hepatitis B can aggravate liver injury and diminish treatment response. Cytokines such as IL-2, INF and TNF- induce liver injury and fibrosis. IL-10 has an antiinflamatory action and TGF- induces extracellular matrix development and deposition causing fibrosis. In this study, the presence of occult Hepatitis B and the expression of IL-2, INF, TNF , TGF and IL-10 were assessed in HCC patients and correlated with fibrosis stage in patients treated and non-treated with interferon, as well as healthy individuals. A total of 55 patients with chronic HCC seen at Botucatu Medical School were included. Immunosuppressed or pregnant patients were excluded. The control group consisted of 20 blood donors. The occult Hepatitis B virus was detected by in-house PCR according to the technique of Kaneno with a detection limit < 100 clones/ml. Cytokine levels were determined by the Elisa method. Hepatic fibrosis was assessed as proposed by the Brazilian Society of Pathology. The results showed a predominance of male young adults of whom 36.4% had used endovenous drugs and 41.8% had been hemotransfused. No patient showed occult Hepatitis B co-infection. Hepatic biopsy revealed that fibrosis was either absent or mild in most cases (47.2%). The cytokines under study did not correlate with fibrosis stage in individuals with chronic HCC no matter whether they had or not received treatment. In addition, no correlations with cytokine levels were observed when VHC patients were separated into groups of individuals treated and non-treated with interferon . However, cytokine expressions were significantly increased in all cases in comparison with the control group.