Orientadores: Paulo Dalgalarrondo, Ines Lessa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-07-22T22:54:47Z (GMT). No. of bitstreams: 1 Lima_ManuelaGarcia_M.pdf: 1740978 bytes, checksum: d632ec9e7aab9111f0336cf8158d9d5d (MD5) Previous issue date: 1997 / Resumo: A esquizotrenía é provavelmente o transtorno mental de mais elevado custo. Atinge cerca de 1 % da população, acomete adultos jovens e 50% a 60% dos pacientes apresentam um curso crôníco e limitante. Os custos da esquizotrenía para a sociedade podem ser divididos em direto (custos de tratamento) e indireto (perda de produtividade). Objetivos: estimar os custos diretos da internação psiquiátrica de pacientes esquizotrêmcos em surto agudo, com ênfase sobre os custos do tratamento farmacológico, e compará-Ios com pacientes portadores de transtorno afetivo bipolar em episódio de mania e também comparar o perfil sócio-demográfico desses dois grupos. Método: utilizou-se o método de capital humano baseado na abordagem de prevalência para a avaliação dos custos diretos do tratamento dos pacientes internados no Serviço de Saúde Df. Cândido Ferreira (Campinas, SP). Resultados: foram avaliados 132 esquizotrênícos (70% homens) e 51 maníacos (47% homens), internados no ano de 1995, com médias de idade de 37 e 39 anos, respectivamente. Houve predominância de solteiros e desempregados no grupo da esquizotrenía (p<0,005). A média de duração da doença foi 12,4 anos para a esquizotrenía e'12,8 anos para a mama (p>O,05). A du,ração média da internação foi 41 dias para a esquizotreníae 28 dias para a mama (p<0,025). O número de internações anteriores foi, em média, 11 e 7 para a esquizotrenía e mama, respectivamente. A remissão completa dos sintomas foi 11 % nos esquizotrênícos e 53% nos maníacos (p<0,005). A média.. por paciente do custo total do tratamento medicamentoso foi R$30,OO. para os esquizotrênícos e R$24,00 para os maníacos e R$0,70 e R$0,80 o custo por dia por paciente. O custo da internação, para o hospital do estudo, foi R$1.974,00 para os esquizotrênícos e R$1.348,OO para os maníacos e o custo para o governo federal foi, respectivamente, R$756,86 e R$516,88; o que corresponde a 1,5% e 1,8% para o primeiro e 4%e 4,6% para o SUS o valor do tratamento medicamentoso em função do custo com a internação. Conclusões: os pacientes esquizofTênicos apresentam um transtorno mental mais grave no que diz respeito ao desempenho social e risco de reinternaçães. Com uma maior duração da internação há um aumento do custo tanto para o tratamento farmacológico como para a internação. Embora o tratamento farmacológico eficaz seja um ponto crucial na prevenção de recaídas, o custo dos medicamentos é apenas uma pequena parcela do montante que é gasto no tratamento da esquizofTenia. Por isso análises de custo-beneficio devem visar novas estratégias no tratamento da esquizofTenia que não seja a internação / Abstract: Schizophrenia is by far the most costly mental illness to be treated. It affects 1% of the population, has a chronic course, and between 50% to 60% of the patients display oniy partial remission or no remission at alI. Thus the economic burden is considerable. The costs of schizophrenia to society can be divided into direct (treatment costs) and indirect costs (lost of productivity). Objectives: to estimate the direct cost treatment of schizophrenic inpatients, in particular pharmacological treatment and compare it with affective disorder patients in manic episodes, also to compare these patient' s sociodemographic profiles. Method: the human capital method based on the prevalence approach was used to evaluate costs. Results: There were 132 schizophrenics (70% men) and 51 manics (47% men) hospitalized in 1995, with a mean age 37 and 39 years, respectively. Single and unemployed status predominated in the schizophrenic group (p<0,005). The mean length ofillness was 12,4 years for schizophrenics and 12,8 years for manics. The mean length of hospital stay was 41 days for schizophrenics and 28 days for manics (p<0,025). The mean prior rehospitalization was 11 and 7 for schizophrenics and manics, respectively. Complete symptoms remission occurred in 11% schizophrenics and 53% manics (p<0,005). The meaÍl total cost of pharmacological treatment per patient was R$30,00 and R$24,00; R$0,70 and R$0,80 the average day cost per eaçh schizophrenic and manic patient, respectively. Hospital cost was R$1.974,00 for schizophrenics and R$1348,00 for manics and hospital cost for federal govemment was R$756,00 and R$516,00; which correspond to 1,5%,hand 1,8% for the first and 4% and 4,6% for the later concemed to drug' treatment in relation to hospital cost. Conclusions: schizophrenics as compared to manics have a more severe disorder in respect to social impairment and are at higher risk for rehospitalization. They have a much longer length of 8 hospital stay which increases phannacological and hospital treatment COSts. LlI u~ treatment cost represents on1y a small percentage of the total cost of schizophrenia treatment. Hence, cost-benefit studies should bear in mind other strategies for the treatment of schizophrenia than hospitalization / Mestrado / Mestre em Saude Mental

Coccidioidomicose consiste em enfermidade causada pelos fungos dimÃrficos do gÃnero Coccidioides â C. immitis e C. posadasii â que acomete o homem e diversos animais como bovinos, ovinos, roedores e cÃes. Restrita ao continente americano, casos da doenÃa vem ocorrendo no Estado do Cearà desde 1995. A infecÃÃo ocorre geralmente por contato inalatÃrio com as estruturas infectantes do fungo presentes no ambiente, os artroconÃdeos. Em sua fase parasitÃria, os microrganismos se apresentam sob a forma de esfÃrulas responsÃveis pelas manifestaÃÃes clÃnicas da doenÃa. A maioria dos casos cursa de forma assintomÃtica, sendo os quadros respiratÃrios os mais comuns em pacientes clinicamente enfermos. O diagnÃstico da doenÃa se baseia em tÃcnicas microbiolÃgicas como pesquisa direta e cultura, porÃm estes procedimentos demandam estrutura especializada â nÃvel de biosseguranÃa III -por tratar-se de microrganismo de classe biolÃgica 3. Abordagem imunolÃgica mostra-se promissora por prescindir da manipulaÃÃo fÃngica e ser exeqÃÃvel em diversos laboratÃrios de rotina micolÃgica. Neste trabalho, objetivou-se traÃar perfil clÃnicolaboratorial dos casos de coccidioidomicose ocorridos no Estado do Cearà entre os anos de 1995 e 2007, alÃm de obter fraÃÃes antigÃnicas a partir do fracionamento de AntÃgeno total de C. posadasii empregÃveis como imunodiagnÃstico da doenÃa. Foram catalogados 19 casos da doenÃa no perÃodo em estudo. Todos os pacientes eram homens jovens com manifestaÃÃes respiratÃrias, com exceÃÃo de um caso. O hÃbito recreativo de caÃar tatus foi relatado por 18 pacientes. A abordagem laboratorial destes casos consistiu em estudo microbiolÃgico, associado a tÃcnicas moleculares, imunolÃgicas, histopatolÃgicas ou de experimentaÃÃo animal. O fracionamento protÃico do AntÃgeno total de C. posadasii originou trÃs fraÃÃes antigÃnicas com teor protÃico distinto, perfil eletroforÃtico diferenciado e imunorreatividade pela tÃcnica de Western blotting. A fraÃÃo 60-90% revelou banda imunorreagente de aproximadamente 30 a 40 KDa reconhecida por soros de coccidioidomicose, porÃm apresentando reatividade cruzada com alguns soros de paciente com histoplasmose. Esta banda protÃica, em estudos posteriores, poderà ser caracterizada e purificada com potencial utilizaÃÃo como ferramenta para o imunodiagnÃstico da doenÃa. / Coccidiodomycosis is a disease caused by dimorphic fungi of the Coccidioides genus â C. immitis and C. posadasii â which afflicts people and various animals, such as cattle, goats, rodents and dogs. It is restricted to the Americas and cases have been reported in the state of Cearà only since 1995. The infection generally results from inhaling the infectious structures arthroconidia -of the fungus. In its parasitic phase, the microorganisms responsible for the clinical signs of the disease have a spherical shape. Most cases are asymptomatic, and respiratory problems are the most common symptoms in patients that are clinically affected. The diseaseâs diagnosis is based on microbiological techniques such as direct examination of clinical specimens and culturing, but these procedures require specialized biosecurity level 3 facilities because the microorganism falls in biological class 3. The immunological approach appears promising because it does not require manipulation of the fungi and can be performed in various laboratories equipped for routine mycological tests. The aim of this work is to outline the clinical and laboratory profile of the cases of coccidiodomycosis that occurred in the state of Cearà between 1995 and 2007 and to report experiments to obtain antigenic fractions from fractioning AntÃgeno total of C. posadasii, as a possible means for immunodiagnosis of the disease. A total of 19 cases of the disease were cataloged in the study period. All the patients were young men with respiratory symptoms, except for one case. All but one of the patients reported they engaged in recreational hunting of armadillos. The laboratory approach in these cases consisted of microbiological examination combined with molecular, immunological, histopathological techniques or animal experiments. The protein fractioning of AntÃgeno total of C. posadasii produced three antigenic fractions with different protein content, electrophoretic profile and immunoreactivity according to the Western blotting technique. The 60-90% fraction showed an immunoreactive band of approximately 30 to 40 KDa, recognizable by sera from patients with coccidiodomycosis, but showed crossreactivity with some sera from patient with histoplasmosis. This protein band, in subsequent studies, can be characterized and purified for potential use as a tool for immunodiagnosis of the disease.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Apesar do empenho do MinistÃrio da SaÃde para a eliminaÃÃo da hansenÃase, o Brasil à o segundo paÃs em nÃmero de casos no mundo, precedido pela Ãndia, e responsÃvel por 80% dos casos no continente americano, sendo o Nordeste do paÃs e, em especial, o Estado do Cearà considerado uma regiÃo de alta endemicidade. De acordo com a classificaÃÃo de Ridley e Jopling, as formas clÃnicas dividem-se em virchowiana, dimorfa-virchowiana, dimorfa-dimorfa, dimorfa-tuberculÃide e tuberculÃide. O trabalho foi realizado com 87 pacientes com hansenÃase, sendo 51,72% do sexo feminino e 48,3% do sexo masculino; destes 87 pacientes, 77,01% vacinados em algum perÃodo da vida entre a infÃncia a adolescÃncia. Os pacientes incluÃdos no estudo encontravam-se nÃo tratados (n=23) ou em tratamento (n=64), apresentando a maioria dos pacientes a hansenÃase pela primeira vez e alguns apresentavam recidiva (n=11). A sorologia de IgG sÃrica anti-PGL1 foi realizada em 83 pacientes, tendo sido as concentraÃÃes de maiores diferenÃas ocorridas entre os grupos com a forma tuberculÃide e dimorfa-tuberculÃide e o grupo com a forma dimorfa-virchowiana. As 87 amostras analisadas foram amplificadas quanto à seqÃÃncia de 171 pb de uma regiÃo altamente conservada dos aminoÃcidos 671-692 do C-terminal no domÃnio intracelular do receptor Toll-like 2 e foi aplicada a tÃcnica de AnÃlise do Polimorfismo Conformacional de Fita Ãnica (SSCP). O perfil eletroforÃtico das amostras testadas encontradas foram de duas e trÃs bandas, mostrando-se necessÃrio o sequenciamento,este apresentou heterozigose marcado pela presenÃa das bases C e T na posiÃÃo C2029T, e alÃm de dois outros perfis de heterozigose nas posiÃÃes C2006T (encontrado em todas as amostras sequenciadas) e T2008G (amostra 82). O trabalho sugere que houve heterozigose na regiÃo do Ãxon 3 do gene do receptor toll-like tipo 2, diferentemente do encontrado por Kang e Chae (2001) o que pode significar que o perfil de suscetibilidade em nossa populaÃÃo à distinta daqueles encontrados na Ãndia e na CorÃia. / Although several efforts from Ministry of Health have been made in order to eliminate leprosy, Brazil is still the second country with the highest number of cases in world after India and is responsible for 80% of the cases in the American continent, the Ceara state situated in the Norheastern region is considered to have high incidence rates of leprosy cases. According to Ridley and Jopling classification, the clinical forms of leprosy can be divided in lepromatous leprosy, borderline lepromatous leprosy, borderline borderline leprosy, borderline tuberculoid leprosy, and tuberculoid leprosy. This work was done with 87 patients with leprosy, being 51.72 % of the female gender and 48.3% of the male gender; from the total of patients, 77.0% had been vaccinated with BCG once in life. All the patients enrolled in the study were not treated (n=23) or in treatment (n=64). Most of the patients had suffered from leprosy for the first time and some (n=11) had suffered from leprosy recidive. The anti-PGL1 serum IgG serology has been performed in 83 patients, and the most significant differences were found comparing the tuberculoid leprosy and borderline tuberculoid leprosy groups with the borderline lepromatous leprosy group. All DNA samples (n=87) were amplified in respect to the 171 bp highly conserved sequence of the aminoacids 671-692 from the C-terminal intra-cellular domain of Toll-like 2 receptor, and they were submitted to a Single Strain Conformation Polymorphism Technique (SSCP). The eletrophoretic profile found of the samples showed two and three bands, it is essential to the sequencing, this showed heterozygosis at position C2029T, and in addition two other sections of heterozygosity at positions C2006T (found in all four sequenced samples) and 2008 (sample 82). The work showed that the heterozygosity found in the gene exon 3 of the tool-like receptor type 2, unlike the one found by Kang and Chae (2001) which may mean that the susceptibility profile from our population is distinct from those found in India and Korea.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / A dengue à a arbovirose mais importante no mundo, causando mais de 100 milhÃes de casos de dengue clÃssico (DC) e mais de 250 mil casos de febre hemorrÃgica da dengue (FHD), anualmente. A infecÃÃo com o vÃrus dengue (DENV), famÃlia Flaviviridae, causa um amplo espectro de manifestaÃÃes clÃnicas que variam desde formas assintomÃticas a quadros graves, potencialmente fatais, como os casos hemorrÃgicos e/ou de choque hipovolÃmico. Na maioria das vezes, a doenÃa se apresenta com sintomas inespecÃficos. Dessa forma, torna-se difÃcil diferenciar a dengue de outros casos febris de natureza infecciosa como leptospirose, febre amarela e outras arboviroses, apenas com base nas manifestaÃÃes clÃnicas iniciais. Diante disso, o objetivo deste estudo foi identificar a etiologia de 82 pacientes com quadro clÃnico semelhante ao de dengue e com resultado negativo no isolamento viral (IV) para o DENV. O IV foi realizado pelo LaboratÃrio Central de SaÃde PÃblica do Cearà (LACEN-CE), em 2008. Neste estudo, as amostras desses pacientes foram avaliadas para dengue por meio da detecÃÃo de anticorpos especÃficos contra o vÃrus pela tÃcnica de IgM-ELISA (PanBio DiagnosticsÂ) e pela reaÃÃo em cadeia da polimerase apÃs transcriÃÃo reversa (RT-PCR). As amostras negativas para dengue foram testadas para a detecÃÃo de anticorpos IgM especÃficos contra bactÃrias do gÃnero Leptospira por ELISA (PanBio DiagnosticsÂ). Foram testadas tambÃm amostras de 73 pacientes quanto a infecÃÃo por hantavirus, atravÃs da detecÃÃo de anticorpos especÃficos (IgM e IgG) contra antÃgenos de hantavÃrus e RT-PCR. Trinta e cinco pacientes (35/82; 42,68%) foram positivos para dengue, sendo que destes, todos foram positivos no IgM-ELISA e 4 foram positivos tambÃm no RT-PCR. Das 47 amostras dengue-negativas, apenas 43 foram testadas para infecÃÃo por Leptospira devido ao volume insuficiente das amostras. Seis pacientes (6/82; 7,32%) foram positivos IgM-ELISA para leptospirose. TrÃs pacientes foram positivos para hantavÃrus, entretanto apenas 1 (1/82; 1,22%) foi positivo no IgM-ELISA e 2, no IgG-ELISA. A infecÃÃo dos 35 (42,68%) pacientes negativos em todos os testes de detecÃÃo de infecÃÃo aguda foi classficada como sÃndrome febril indiferenciada (SFI). Esta à a primeira evidÃncia de infecÃÃo por hantavÃrus no Estado do CearÃ. Essas doenÃas podem causar infecÃÃo clinicamente indistinguÃvel da dengue e, portanto, deveriam ser incluÃdas no diagnÃstico diferencial no contexto dessas sÃndromes febris. / Dengue is the most important arborvirosis in the world, causing approximately 100 millions cases of classical dengue fever (DF) and more than 250.000 of dengue hemorrhagic fever (DHF), annually. The dengue virus (DENV) belongs to the Flaviviridae family and its infection causes a wide clinical spectrum ranging from assymptomatic forms to severe manifestations, potentially fatal, as in hemorrhagic forms or dengue shock syndrome (DSS). Most of times the disease presents inespecific symptoms. Thus, DF is difficult to distinguish from other acute febrile illnesses, including arboviral ones and leptospirosis, based only on clinical criteria. Given this, the aim of this study was to identify the etiology of 82 patients with clinical picture of dengue-like illness, negative in DENV isolation. The virus isolation was done in Laboratorio Central de SaÃde PÃblica do Cearà (LACEN-CE), Brazil, in 2008. In the present study, the serum samples from these patients were evaluated for dengue infection by IgM-ELISA (PanBio DiagnosticsÂ) and RT-PCR, following Lanciotti et alli protocol (1992). Negative samples to dengue infection were tested to leptospirosis by IgM-ELISA (PanBio DiagnosticsÂ). Seventy-three patients were also tested for hantavirus infection by IgM and IgG by ELISA and RT-PCR. Dengue infection was diagnosed in 35 patients (35/82; 42.68%) of which all were positive in IgM-ELISA, and 4 were also positive in RT-PCR. Of 47 (47/82; 57.32%) DENV-negative samples, only 43 were tested to evaluate lesptospiral infection because of insufficient sample volume. Six patients (6/82; 7,32%) were positive to leptospirosis in the IgM-ELISA. Three patients were positives to hantavirus infection, but only 1 (1/82; 1,22%) was positive in the IgM-ELISA and the two others, in the IgG-ELISA. Thirty and five patients (35/82; 42,68%) remained negative em all tests. They were classified as having other febril illness (OFI). To the best of our knowledge, this is the first evidence of hantavirus infection in humans in the state of CearÃ, Brazil. These diseases, including leptospirosis, may cause infection clinically indistinguishable from DF and therefore should be included in the differential diagnosis of febrile illnesses in this setting.

Orientador: Marcelo de Castro Meneghim / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-03T23:48:47Z (GMT). No. of bitstreams: 1 Merotti_FatimaMarrach_M.pdf: 665952 bytes, checksum: 66f210abca09ed98d4dd560b9f67d6bd (MD5) Previous issue date: 2004 / Resumo: A legislação brasileira determina que os locais de crime deverão ser preservados até a conclusão dos exames periciais, com a finalidade de resguardar as características originais da cena do delito, resultando importante fator de elucidação do crime.Vários profissionais fazem parte desse cenário, com destaque para a atuação dos policiais militares, que são os primeiros profissionais a chegarem no local. O objetivo desse estudo foi avaliar o conhecimento dos policiais militares recém-formados (sargentos e soldados), em relação ao local de crime. Foi aplicado um questionário para 856 militares, constituído por 15 questões, abordando aspectos como legislação pertinente, tempo de preservação, importância dos exames periciais e providências a serem tomadas pelos militares. Os resultados mostram que, entre soldados e sargentos, respectivamente, 66,7% e 75,7% sabem que a legislação atinente à preservação de local, está inserida no Código de Processo Penal; entre 74,2% e 75,4% preservam o local de crime o tempo necessário para a conclusão dos exames periciais; entre 95,1% e 96,3% consideram muito importante o exame pericial para a elucidação de um crime e entre 56,0% e 58,1% têm como primeira providência quando chegam ao local de crime, comunicar o fato à autoridade policial (delegado). Conclui-se que a maioria dos militares são conhecedores da legislação pertinente, estão cientes que devem preservar o local de crime até que todo o exame pericial tenha sido concluído, consideram muito importante a execução do exame pericial para o esclarecimento de um delito e como primeira conduta ao chegar ao local de crime, elegem comunicar o fato à autoridade policial para que este tome as providências cabíveis quanto à preservação / Abstract: Brazilian legislation determines that crime scenes must be preserved until the conclusion of the investigation to preserve its original characteristics, resulting in an important factor to elucidate the crime. Many professionals are involved in this scenario, with emphasis in military police, being the first in approaching the crime scene. The aim of this study was to evaluate the knowledge of those military polices recently graduated (sergeants and soldiers) concerning to crime scene. A survey containing 15 items was applied to 856 militaries, including aspects about pertinent legislation, time of preservation, importance of investigations and the taking of necessary steps by militaries. The results show that among soldiers and sergeants, respectively, 66,7%, and 75,7% know that legislation concerning to crime scene preservation is included in the Code of Crime Procedure; 74,2% and 75,4% preserve the crime scene the necessary time for the conclusion of investigations; 95,1% and 96,3% consider very important investigations for the elucidation of the crime and 56,0% and 58,1% have as a priority to communicate the facts to police authorities (police officer) when they approach the crime scene. It was concluded that the most of militaries are concern about pertinent legislation, that they have to preserve the crime scene until the conclusion of the investigation, they consider very important the execution of investigations for the elucidation of crime, and as a primary conduct arriving to the crime scene, they prefer to communicate the facts to police authorities whom will take the necessary steps relating to preservation / Mestrado / Mestre em Odontologia Legal e Deontologia

M.Tech .(Homoeopathy) / The aim of this study was to evaluate the growth rate of germinating Zea Mays seeds subject to the administration of homoeopathically potentised Carbo vegetabilis in the potencies 12CH, 13CH and 14CH. The purpose of the study is to help disprove the popular "placebo effect" explanation as to why homoeopathy works by showing that homoeopathic medicine can have a fundamental effect on a living organism and thereby lend credibility to homoeopathy as a science. This study is of value as previous botanical studies have not attempted to provide an explanation as to how homoeopathic potencies may be acting and have mostly merely demonstrated their effects on cleoptile growth. Six hundred Zea Mays seeds were selected and planted in rolls of germination paper. There were 150 seeds in each of the three test groups as well as in the control group. The control group received distilled water only and the test groups their respective liquid potencies of Carbo vegetabilis, which were prepared using distilled water. The germination rolls were incubated at 24°C in darkness for a total of 135 hours. After 39 hours the germinating seeds were replanted into fresh germination rolls. The process was repeated at 87 hours after the first measurements were taken. The final measurements were taken at 135 hours. Shoot lengths and root lengths were recorded and overall lengths calculated. Mean shoot, root and overall lengths were expressed as percentages ofthe control using bar graphs. At 87 hours the potency that consistently decreased the growth of Zea Mays was the 13CH. The 12CH potency only decreased the shoot growth, whereas the 14CH improved root growth. At 135 hours overall growth was significantly decreased in all the test groups, but most markedly in the 12CH groups where root growth was drastically inhibited. When compared with the 87th hour measurement, the 13CH group showed a 13% increase in shoot growth. Carbo vegetabilis potencies 12CH, 13CH and 14CH were found to significantly influence the growth of germinating Zea Mays seeds.

Mini-dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Homoeopathy at the Durban Institute of Technology, 2002. / Dream provings are considered to be a new era in Homoeopathy and as such are met with a lot of scepticism. They involve getting in touch with the dynamic influence of the remedy and observing this influence on the vital force in the form of symptoms (Dam, 1998: 128). Dreams are a main focus of the proving as they are considered to be the 'royal way to the psycho-dynamic depth of the state of the remedy being proved' (Dam, 1998: 128). The motivations for their acceptance or rejection are both reasonable. To determine if they are provings that should appear in the Materia Medica and Repertory it needed to be seen if they revealed the same features of a remedy that a classical proving provides. / M

M.Sc. / Pentanisia prunelloides belongs to the Rubiaceae family and is distributed in the grasslands of the eastern part of Southern Africa. The plant is an erect perennial herb that grows to be approximately 30 cm in height. It has stout hairy stems sprouting from a tuberous root. This plant produces pale purple flowers in early summer. P. prunelloides extracts are used in traditional medicine for a wide range of ailments such as colds, rheumatism, heartburn and sores. It is also incorporated in many multipurpose traditional medicines. The raw tuber is occasionally chewed to relief heartburn. The root decoctions were reported to have been used in the 1918 influenza pandemic with great success. The use of this plant in ethno-medicine suggests that it has bio-active principles which justify its continued use by different generations. It has shown to have anti-inflammatory, anti-viral and antibacterial properties. As far as the chemical composition is concerned, only palmitic acid was previously isolated. This compound can not account for all the chemotherapeutic properties of P. prunelloides. Thus this study was done to investigate the chemical constituents of P. prunelloides which may be responsible for its use as a medicinal plant. The plant material was collected from different areas in Swaziland and South Africa. Chemical variation screening was conducted using ether/hexane, methanol and boiling water extracts of the tuber and where possible the aerial parts of P. prunelloides. The methanol extracts were the only extracts used for TLC screening and the results showed the presence of terpenoids, saponins, amino acids, carbohydrates and phenolic compounds that were not identified previously. An attempt was made to quantify some of the compounds by means of HPLC and GC/MS. The compounds observed from all the tuber experiments demonstrated a limited level of variation both in quality and quantity within and between natural plant populations. The variation was found to be random and it was not correlated to the geographical distribution of this plant. This was concluded because variation was observed in plants which were from the same locality as well as different localities. iv The chemotypes observed between the tubers from Swaziland and South Africa were related. This means that there was no unique chemotype observed from plants from the two countries as chemotypes overlap. When considering the TLC of medium polarity compound and polar compounds of the aerial parts, three chemotypes were observed. Again these chemotypes were observed within and between natural plant populations. The occurrence of these chemotypes was random and was not correlated to the geographic distribution of the plants. The variations observed could be due to different developmental stages of the plants. The chemistry of P. angustifolia was also investigated and compared to that of P. prunelloides. This was done because these two species are used to treat the same ailments and could be physiologically mistaken for each other. It was established that the two species could be differentiated based on TLC as the two species contain different compounds. The methanol extract was used to isolate three of the major compounds from P. prunelloides. The compounds had different polarities with one compound being non-polar, another having medium polarity and the third one being polar. The structure of the compound with medium polarity was identified to be (–)-epicatechin, a flavanol, while the polar compound was sucrose. The structure of the non-polar compound could not be concluded due to the complex nature of this compound, but it was assumed to be a triterpenoid, or two stereoisomers of the same compound. The methanol extract was also fractionated to get three fractions which were non-polar, medium polar and polar extracts (containing the three isolated compounds respectively). These extracts together with the crude extract were subjected to antibacterial screening. Bioautographic tests did not show any specific zones from the separated compounds to have any significant antibacterial activity. However, the total extract and the non-polar fraction showed the highest activity with the non-polar fraction recording MIC values of not more than 1.25 mg/cm3. It was then assumed that the compounds from P. prunelloides worked additively or in synergy to produce the observed activity. In future more detailed chemical variation studies need to be done to investigate more specific factors such as soil type, age of the plant and seasonal variation. This would give better indications of when the plant has more of the active compounds thus giving a guide about the best harvesting time. Anti-inflammatory and anti-oxidant tests may also prove to be interesting.

The major goal for physicochemical screening of pharmaceuticals is to predict human drug absorption, distribution, elimination, excretion and toxicity. These are all dependent on the lipophilicity of the drug, which is expressed as a partition coefficient i.e. a measure of a drug’s preference for the lipophilic or hydrophilic phases. The most common method of determining a partition coefficient is the shake flask method using octanol and water as partitioning media. However, this system has many limitations when modeling the interaction of ionised compounds with membranes, therefore, unreliable partitioning data for many solutes has been reported. In addition to these concerns, the procedure is tedious and time consuming and requires a high level of solute and solvent purity. Micellar liquid chromatography (MLC) has been proposed as an alternative technique for measuring partition coefficients utilising surfactant aggregates, known as micelles. This thesis investigates the application of MLC in determining micelle-water partition coefficients (logPMW) of pharmaceutical compounds of varying physicochemical properties. The effect of mobile phase pH and column temperature on the partitioning of compounds was evaluated. Results revealed that partitioning of drugs solely into the micellar core was influenced by the interaction of charged and neutral species with the surface of the micelle. Furthermore, the pH of the mobile phase significantly influenced the partitioning behaviour and a good correlation of logPMW was observed with calculated distribution coefficient (logD) values. More interestingly, a significant change in partitioning was observed near the dissociation constant of each drug indicating an influence of ionised species on the association with the micelle and retention on the stationary phase. Elevated column temperatures confirmed partitioning of drugs considered in this study was enthalpically driven with a small change in the entropy of the system because of the change in the nature of hydrogen bonding. Finally, a quantitative structure property relationship was developed to evaluate biological relevance in terms of predicting skin permeability of the newly developed partition coefficient values. This study provides a better surrogate for predicting skin permeability based on an easy, fast and cheap experimental methodology, and the method holds the predictive capability for a wider population of drugs. In summary, it can be concluded that MLC has the ability to generate partition coefficient values in a shorter time with higher accuracy, and has the potential to replace the octanol-water system for pharmaceutical compounds.

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