Ph.D., Faculty of Science, University of the Witwatersrand, 2011 / The ABCB1 gene encodes P-glycoprotein, a transmembrane protein that regulates the efflux of drugs in the cells and may affect the response to antiretroviral drugs. ABCB1 polymorphisms affect the function or expression of P-gp. The 3435T allele has been associated with decreased protein production, but is in linkage disequilibrium with other polymorphisms. HIV is prevalent in Southern Africa, and characterization of ABCB1 variation may provide insight into its role in antiretroviral immune response. The aim was to determine if there was any association between ABCB1 variation, relative mRNA levels and immune response. Seven known polymorphisms were characterized for linkage disequilibrium and haplotype analysis, regions upstream of the gene were sequenced for bioinformatic analysis, the relative amounts of mRNA were determined, and CD4+ and viral load data was analyzed for association. Sequencing revealed six novel variations: T-137G, C-233T and G-298A upstream of exon 1, T108G and G153A in exon 2, and A111G in intron 26. The frequencies of the -129T (0.85), 1236T (0.70), 2677G (0.77), IVS 25+3050G (0.86), IVS 25+5231T (0.51), 3435C (0.88) and IVS 26+80T (0.89) polymorphisms were different and LD was lower compared to other populations. The haplotype frequencies were different to other populations and the genetic structure was probably a result of multiple recombination or mutation events. The viral load counts at the second measurement after baseline (time point 2) were significantly different from baseline for the 2677GG and 2677GA genotypes, and the -129T allele was associated with a lower proportional decrease in viral load at 8 the second measurement. The IVS 25+3050GG, 3435CC and IVS 26+80TT genotypes have been associated with lower mean relative mRNA levels. In conclusion, the genetic structure of the southern African populations is different from other populations and that genetic association and functional studies derived from other populations would be irrelevant in this population. A larger sample size and functional studies would be required to attempt to resolve the molecular mechanisms of the ABCB1 gene and to confirm the findings of association between ABCB1 polymorphisms and immune response.

No description available.

No description available.

No description available.

by Kwok-Ping Ho. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1980. / Bibliography: leaves 111-118.

No description available.

Addiction is a complex social phenomenon resulting from psychological and physiological dependence. The aim of the study was to create a clinical impression of the lived experiences of cocaine dependents. A transcendental phenomenological approach was used to elicit the essence of addiction as experienced by the participants. Theoretical sampling ensured relevant participants were selected through haphazard sampling procedures. Data was collected through the use of biographical questionnaires and individual, semi-structured interviews with three cocaine dependents. Data was processed according to the four phenomenological principles epoche, phenomenological reduction, imaginative variation and synthesis using Tesch’s eight steps. The essence of cocaine dependency is contained in the psychological experiences of the drug which define and perpetuate that addiction. The psychological addiction develops prior to physical dependence resulting in an entrenched addiction before treatment is sought by the cocaine dependents.

In the present study, the influence of various drug pretreatments will be investigated in the rabbit in an attempt to (a) define the pharmacological mechanism of action of pipradrol in its mediation of hyperthermia and (b) observe the effects of these pretreatments on the behavioral effect of pipradrol. Although pipradrol is no longer of clinical utility, it is hoped that the results of this study may provide more information for its use in future studies as a pharmacological tool.

Made available in DSpace on 2014-11-10T11:09:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-14Bitstream added on 2014-11-10T11:57:54Z : No. of bitstreams: 1 000794313.pdf: 2112932 bytes, checksum: 238260035927357487cc849464653a8e (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O Transtorno do Espectro Alcoólico Fetal – TEAF refere-se ao grupo de manifestações apresentadas pelos indivíduos expostos ao consumo materno de álcool na gestação, que inclui déficit no crescimento, dismorfismos faciais, alterações estruturais no SNC e neurodesenvolvimentais. Dentre as alterações observadas, a habilidade para a narração oral de histórias tem sido descrita como uma habilidade prejudicada nestes indivíduos. Estudos anteriores nesta direção, contemplando, principalmente, os aspectos microestruturais da narrativa, reportaram os prejuízos semânticos apresentados por essa população. O objetivo deste estudo foi caracterizar a narrativa oral de história de indivíduos com diagnóstico de TEAF, a partir de aspectos macroestruturais (elementos típicos da narrativa de história e o nível de coerência global) e microestruturais da narrativa (produtividade e complexidade linguística). Assim, foram propostos três objetivos específicos, a saber: comparar os aspectos macro e microestruturais da narrativa oral de história dos indivíduos com TEAF e desenvolvimento típico de linguagem; comparar os aspectos macro e microestruturais da narrativa oral de história dos subgrupos clínicos com TEAF, estabelecidos a partir do “4 Digit Diagnostic Code” ; e investigar se há relação entre os aspectos macro e microestruturais da narrativa oral de história e o nível de comprometimento dos indivíduos com TEAF, a partir da pontuação das principais características clínicas que definem o diagnóstico dos subgrupos clínicos do TEAF no “4 Digit Diagnostic Code”. Participaram deste estudo 20 indivíduos com diagnóstico de TEAF (GA), de ambos os gêneros,com idade cronológica entre 6 e 16 anos, que foram comparados a 20 indivíduos com desenvolvimento típico de linguagem (GC), semelhantes aos indivíduos com TEAF, segundo o gênero, idade e nível socioeconômico. A narrativa oral foi eliciada por meio do... / The Fetal Alcohol Spectrum Disorders – FASD refers to group of manifestations presented by individuals exposed to maternal alcohol consumption during the pregnancy which includes growth deficit, facial dimorphisms, structural and neurodevelopment changes. Among the observed changes, the ability for oral storytelling has been described as an impaired ability in these individuals. Previous studies in this direction focusing mainly the microstructural aspects of the narrative, reported the semantic impairments presented by this population. The goal of this study was to characterize the oral narrative story of individuals diagnosed with FASD from the macrostructural (typical story narrative elements and the overall coherence) and microstructural aspects of the narrative (productivity and linguistic complexity). Thus, three specific goals were proposed: (1) To compare the aspects macro and microstructural of the oral narrative story of individuals with FASD and the typical development of the language, (2) To compare the macro and microstructural aspects of the oral narrative story of clinical subgroups with FASD, established from the “4 Digit Diagnostic Code” and (3) To investigate if there is relationship between the macro and microstructural aspects of the oral narrative story and the level of commitment of the individuals with FASD, from the score of the main clinical features that define the clinical subgroups diagnose of FASD in the “4 Digit Diagnostic Code”. There were in this study 20 individuals with FASD (AG), from both gender, with ages from 6 to 16, they were compared to 20 individuals with typical language development (CG), similar to the FASD individuals, gender, age and socioeconomic level. The oral narrative was elicited by the book “Frog, where are you?”. The results indicated that the individuals with FASD presented statistically significant differences compared to their pairs, in the macrostructural...

Made available in DSpace on 2014-06-11T19:29:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-02Bitstream added on 2014-06-13T19:38:41Z : No. of bitstreams: 1 ramos_cm_me_botfm.pdf: 872774 bytes, checksum: 872c5e3919250784d15ad40694098724 (MD5) / O consumo de drogas lícitas e ilícitas é considerado um grande problema de saúde pública, não somente por sua alta frequência, mas devido aos inúmeros prejuízos à saúde, principalmente entre a população mais jovem. O grande desafio é realizar o reconhecimento dos fatores que levam os adolescentes a usarem e abusarem das drogas para melhor direcionar as ações de prevenção e auxiliar no desenvolvimento de políticas púbicas nessa área. Desta forma, o presente trabalho teve como objetivo estimar a prevalência do uso de substâncias psicoativas entre estudantes do ensino fundamental e médio de escolas públicas e privadas de um município do interior paulista, bem como identificar os possíveis fatores associados ao uso de drogas. No ano de 2002 foi realizado o primeiro levantamento, portanto este é considerado o segundo levantamento e traz comparações importantes referentes ao uso de drogas após 10 anos. Teve como população alvo os estudantes do 8º e 9º ano do ensino fundamental, 1º, 2º e 3º ano do ensino médio. Trata-se de um estudo transversal, que contou com a aplicação de um questionário estruturado, previamente testado, individual, anônimo, de autopreenchimento e com participação facultativa. O teste de diferença entre proporções foi utilizado para estabelecer diferenças comparativas entre as análises dos anos de 2002 e 2012, e foram realizadas análises univariadas, utilizando-se o teste Qui-quadrado de Pearson, e análises multivariadas (regressão logística), com utilização do teste Qui-quadrado de Wald. Todos os testes tiveram nível de significância de 5%. Dentre os resultados, cerca de 56% pertence ao sexo feminino, faixa etária de 12 a 19 anos, com idade média de 14,86 (±1,52) anos, e 62,13% matriculados no ensino médio. De acordo com o uso de drogas na vida, o uso de álcool foi maior entre o sexo feminino (p=0,000) e o consumo... / The consumption of licit and illicit drugs is considered a major public health problem, not only for its high frequency, but due to the numerous health hazards, especially among the younger population. The challenge is to identify of the factors that lead the adolescents to use and abuse drugs to better target the primary prevention and assist in the development of pubic policy in this area. Thus, this study aimed to estimate the prevalence of substance use among students in elementary and secondary education in public and private schools of a city in the interior as well as identify possible factors associated with drug use. In 2002 we performed the first survey, so this is the second survey and brings important comparisons related to drug use after 10 years. Target population was students in the 8th and 9th grade of elementary school, 1st, 2nd and 3rd year of high school. It is a cross-sectional study, which included the application of a structured questionnaire, previously tested, individual, anonymous, self-administered and voluntary participation. The test of difference between proportions was used to establish differences between the comparative analysis of the years 2002 and 2012, and univariate analyzes were performed, using the chi-square test, and multivariate analysis (logistic regression), using the Chi-square Wald. All tests had a significance level of 5%. Among the results, about 56% are female, aged 12-19 years with a mean age of 14,86 (±1,52) years, and 62.13% enrolled in high school. According to drug use in life, alcohol use was higher among females (p=0,000) and the tobacco use was higher among males (p=0,040). For drug use in the past 30 days, alcohol consumption was not statistically significant and tobacco use was higher among males (p=0,014). The highest prevalence of illicit substances, both in life and in the last 30 days, in both sexes was marijuana... (Complete abstract click electronic access below)