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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
21

Estudo do Envolvimento da Bioactivação Metabólica no Efeito Hiponatrémico da 3,4 - Metilenodioximetanfetamina (Ecstasy)

Silva, Daniel Gomes Esteves da 24 September 2008 (has links)
Mestrado em Controlo de Qualidade / MSc in Quality Control / A 3,4-metilenodioximetanfetamina (MDMA; ecstasy ), tal como outras anfetaminas, tem sido considerada por muitos como sendo uma droga segura . No entanto estão descritas na literatura muitas respostas de toxicidade, reacções adversas e mortes relacionadas com a sua ingestão recreativa. Um dos seus efeitos adversos, potencialmente fatal, é a hiponatrémia. Este efeito foi relacionado com alterações na secreção da hormona antidiurética (ADH, AVP ou arginina-vasopressina) desencadeadas pela MDMA. A hiponatrémia foi apontada como causa possível para numerosas intoxicações severas e por vezes fatais decorrentes da ingestão desta droga. Estudos recentes in vivo, em humanos saudáveis do sexo masculino, e in vitro, em hipotálamo isolado de rato, demonstraram que a bioactivação metabólica da MDMA, nomeadamente a desmetilenação seguida pela O-metilação do catecol resultante, é crucial para a libertação da AVP quer in vivo quer in vitro. Para a avaliação da contribuição desta via metabólica para a expressão in vivo do efeito de hiponatrémia causado pela ingestão da MDMA, é crucial quantificar estes metabolitos e relacionar o perfil metabólico com a magnitude do efeito hiponatrémico. Com este objectivo, foi desenvolvido e validado um método de GC-MS/MS para a quantificação da MDMA e dos seus principais metabolitos, metilenodioxianfetamina (MDA), 4-hidroxi-3-metoxianfetamina (HMA) e 4-hidroxi-3-metoximetanfetamina (HMMA), no plasma e na urina. Para melhor compreender a influência da MDMA e da sua bioactivação na secreção da AVP foram realizados estudos in vivo em ratos Wistar machos e fêmeas, aos quais foi administrada MDMA na dose 20 mg/kg. Nos estudos realizados 1 hora após a administração de MDMA foram avaliados os níveis plasmáticos de AVP e as concentrações plasmáticas da MDMA e dos metabolitos MDA, HMA e HMMA. Com estas quantificações foi possível observar, nos ratos de ambos os géneros, o aumento estatisticamente significativo dos níveis de AVP em relação aos animais controlo, ao mesmo tempo que não se detectaram correlações estatisticamente significativas entre os níveis de AVP a MDMA e os metabolitos MDA, HMA e HMMA. Nos estudos realizados 24 horas após a administração de MDMA foram avaliados os níveis plasmáticos e urinários de AVP e as concentrações urinárias de MDMA, MDA, HMA e HMMA. Os resultados destas determinações demonstraram que apesar de não se detectarem diferenças significativas nas concentrações plasmáticas de AVP entre os animais tratados e os animais controlo, existem diferenças estatisticamente significativas para as concentrações urinárias de AVP, verificando-se que os animais tratados com MDMA apresentam concentrações urinárias de AVP superiores. Além disso verificou-se também que os animais tratados excretaram menos urina relativamente à água ingerida, mostrando o efeito anti-diurético desencadeado pela AVP. Neste estudo foram também estabelecidas correlações positivas e estatisticamente significativas entre os níveis de AVP e as concentrações de MDMA, MDA, HMA e HMMA. A correlação com maior significado estatístico foi estabelecida com o metabolito HMMA. Estes resultados permitiram pela primeira vez demonstrar a secreção da AVP em ratos após a administração da MDMA. Com estes estudos foi possível observar, in vivo, não só as alterações da secreção da AVP induzidas pela MDMA mas também as consequências dessas alterações nomeadamente na resposta antidiurética e o envolvimento desta resposta no efeito de hiponatrémia. Finalmente foi possível observar a contribuição da bioactivação metabólica para a secreção de AVP. Estes resultados permitem assim compreender melhor o envolvimento da MDMA e do seu metabolismo na resposta hiponatrémica. / Although considered as safe drugs by many, exaggerated responses and deaths have been reported due to 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse. One of the adverse effects associated with ecstasy intoxications is hyponatremia that has been related with a disruption on the release of the antidiuretic hormone (ADH or arginine-vasopressin) and pointed out as the possible cause of numerous severe and fatal intoxications after intake of this drug. Recent in vivo studies with human healthy volunteers and also in vitro studies performed with rat isolated hypothalamus have shown that the metabolic bioactivation of MDMA, namely its demethylenation followed by O-methylation of the resulting cathecol metabolite are crucial for the release of ADH both in vivo and in vitro. For the evaluation of the contribution of this metabolic pathway to the in vivo expression of the hyponatremic effect of MDMA it is crucial to quantify these metabolites, and to relate the metabolic profile with the magnitude of the hyponatremic effect. For this purpose, a GC-MS/MS method was developed to quantify MDMA and its main metabolites: methylenedioxyamphetamine (MDA), 4-hydroxy-3- methoxyamphetamine (HMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in plasma and urine. To better understand the influence of MDMA and its metabolic bioactivation in the secretion of AVP in vivo studies were performed with male and female Wistar rats, the MDMA dose tested was 20 mg/kg. In the studies preformed 1 hour after the MDMA administration the plasmatic levels of AVP and the plasmatic concentrations of MDMA, MDA, HMA and HMMA were evaluated. The plasmatic concentrations of AVP obtained with the treated animals were compared with the concentrations obtained with the controls showing a statistically significant increase of AVP levels in the animals treated with MDMA. Correlations between the MDMA, MDA, HMA and HMMA and the AVP plasmatic levels were also preformed. No significant correletions were obtained. In the studies preformed 24 hours after the administration of MDMA the urinary and plasmatic levels of AVP were evaluated. The concentration of MDMA, MDA, HMA and HMMA were determined in plasma and urine. It was also established the ratio between the volume of ingested water and the volume of excreted urine. The plasmatic and urinary AVP concentrations obtained in the treated animals were compared with the concentrations obtained from the controls. This compairison showed significant increases of the urinary AVP levels in the treated animals. The evaluation of the correlations between the urinary concentrations of AVP and the urinary concentrations of MDMA, MDA, HMA and HMMA showed significant correlations between AVP and MDMA, MDA, HMA and HMMA. The evaluation of the ratio between the volume of ingested water and the volume of excreted urine showed that the treated animals excreted less urine in comparison with the ingested water. The studies performed with urines collected 24 hours after MDMA administration have shown significant positive correlations between AVP and the concentrations of MDMA, MDA, HMA and HMMA. The strongest correlation was established between the concentrations of HMMA and AVP. With this study it was possible to confirm the in vivo changes in the AVP secretion profile and relate those changes with the levels of MDMA, MDA, HMA and HMMA. It was also shown for the first time the induction of the secretion of AVP in male and female rats, one hour after the administration of MDMA. The consequent antidiuretic effect can be related with the hiponatremic effect.
22

Controlo de Qualidade de PCR - Controlo interno e HACCP

Oliveira, Ana Elisabete Pereira Correia de 04 June 2009 (has links)
Mestrado em Controlo de Qualidade / MSc in Quality Control
23

Avaliação da actividade antitumoral e investigação de potencial actividade estrogénica / antiestrogénica de xantonas e flavonas

Camões, Ana Catarina Dias Gonçalves Sobral 09 January 2008 (has links)
Mestrado em Controlo de Qualidade / MSc in Quality Control / Aiming for new compounds with antitumor activity, the synthesis of prenylated xanthones and prenylated and geranylated flavones was recently achieved on CEQOFFUP. In this work the potential antitumor activity of these compounds in three tumor cell lines, namely MCF-7 (human breast cancer cells expressing estrogen receptors (ER+)), MDA-MB-231 (human breast cancer cells non expressing estrogen receptors (ER-)) and NCI-H460 (non-small cell lung cancer) was evaluated. Structure-activity relationships were established highlighting the influence of prenylation and geranylation. Concerning xanthones, prenylation of 3,4-dihydroxyxanthone (XXIX) furnished more potent and selective derivates for MCF-7 (ER+) cells than the original oxygenated xanthone. Xanthone derivate XP13 showed the strongest inhibitory effect on the growth of breast adenocarcinoma cell line ER+, MCF-7 (GI50 = 5,3 M). Thus, potential estrogenic/antiestrogenic properties were investigated for this compound. No proliferative effect at low concentrations was observed for XP13 in experiments performed in steroid-free medium (RPMI-SFM). However, when high concentrations of XP13 were used, this prenylated xanthone inhibit cancer cell growth in a dose-dependent manner, being more active on MCF-7 (ER+) cell line than on MDA-MB-231 (ER -) cell line. This antiproliferative effect was not influenced by the culture medium (steroid (RPMI) or steroid-free medium (RPMI-SFM)). From these results it can be inferred that XP13 does not directly act on the estrogen receptor, suggesting that it could interfere with other signaling pathways. Moreover, XP13 enhanced the growth inhibitory action of 4-hydroxytamoxifen (4-OHT, XIV), a partial antiestrogen in estrogen sensitive breast cancer cells. Concerning flavone derivates, none of the six flavones investigated, that were resulted from prenylation and geranylation of baicalein (BAIC, XIX), presented a higher cytotoxic effect on all tumor cellular lines (MCF-7 (ER+), MDA-MB-231 (ER -) and NCI-H460) when compared to the original oxygenated flavone BAIC (XIX). However, monoprenylation in C(7) conduced to a flavone (FP2) with a selective inhibitory effect on the growth of MCF-7 (ER+) cells. Possible estrogenic/antiestrogenic properties were investigated for this compound. It was verified that in steroid-free medium (RPMI-SFM) experiments, FP2 presented a biphasic effect in vitro growth on the ER-positive MCF-7 cell line. Although at low concentrations this flavone has stimulated cell growth, at high concentrations a cell growth inhibition was observed. Then, the effect of FP2 in combination with E2 was examinated. Results showed that FP2 suppressed at low concentrations, the mitogenic effect enhanced by estrogenic stimulation, suggesting a competition for ERs. Also, the FP2 cancer cell growth inhibitory effect on MCF-7 (ER+) cells was stronger when assed in steroid free medium, i.e., in the absence of estrogenic stimulation. These results suggest a direct involvement of estrogen receptor in the proliferative/antiproliferative effect of flavone FP2. Moreover, FP2 enhanced the growth inhibitory action of partial (4-OHT, XIV) and pure (ICI 182,780, XII) antiestrogens in estrogen sensitive breast cancer cells. These results were consistent with previous reports of prenylated flavones and disclose for prenylated xanthones effects compatible with antiestrogenic activity. Thus, the present work represents a promising contribution for the prevention and treatment of hormone-dependent breast cancer.
24

Complementary Medicines in Hospitals - a Focus on Surgical Patients and Safety

Braun, Lesley Anne, lgbraun@bigpond.net.au January 2007 (has links)
This study aimed to determine how CMs used by surgical patients are managed in the hospital system by doctors and pharmacists and what patient and practitioner influences affect this management. Research design and method Five systematic reviews were conducted to investigate the peer-reviewed literature for information about Australians use of CM; overseas and Australian doctors and CM; surgical patients use of CM and safety information about CMs in surgery as a basis to design and conduct three surveys. Surveys of hospital doctors, pharmacists and surgical patients were used to obtain measurement of people's attitudes, perceptions, behaviours and usage of CMs. For healthcare practitioners, knowledge of complementary medicines (CMs), past training, current practice and interest in future practice of complementary therapies (CTs) and education was also investigated. Approximately 50% of surgical patients reported taking CMs in the 2 weeks prior to surgery and approximately 50% of these patients intended to continue use in hospital. The most commonly used CMs were: fish oil supplements, multivitamins, vitamin C and glucosamine supplements as well as some CMs considered to potentially increase bleeding risk or induce drug interactions. It was not uncommon for CMs to be used at the same time as prescription medicines. Most surgical patients in general self-prescribe their CMs or have them recommended by family and friends whereas medical practitioners were the main prescribers to cardiac surgery patients. Nearly 60% of patients using CMs in the 2 weeks prior to admission did not tell hospital staff about use. The main reason for non-disclosure was not being asked about use whereas fear of a negative response was rarely a concern. The most common sources of information surgery patients refer to were GPs, pharmacists and health food stores. Hospital doctors and pharmacists did not routinely refer to information sources about CMs safety. The majority of doctors and pharmacists did not routinely ask patients about CMs, or record usage information. They had little training and knowledge of the evidence of commonly used CMs and lacked confidence in dealing with CMs-related issues. Their attitude to CMs is moderately negative and many are wary of safety, efficacy and cost-effectiveness issues. The majority of practitioners considered some CTs as potentially useful, particularly acupuncture, massage and meditation whereas the medicinal CTs and chiropractic were considered potentially harmful. Most practitioners were interested in future education about CMs and CTs and some would consider practising CTs. Personal usage of CTs was low although there was substantial interest in receiving future treatment. Despite many strategically orientated initiatives developed in Australia to promote evidence based medicine (EBM) and quality use of medicines (QUM), it appears that CMs have been largely ignored and overlooked in the practice of Medicine and Pharmacy within the hospital system. Furthermore, it appears that in regards to CMs a 'don't ask, don't tell, don't know' culture exists within hospitals and that evidence based patient-centred care and concordance is not being achieved and potentially patient safety and wellbeing is being compromised.
25

Consumers' expectations of over-the-counter medicine : location of sale

Lo, Ya-Ning 30 August 2006
Over-the counter (OTC) medicines are used commonly for treating minor illnesses. Even though most Canadians believe that OTC medicines are safe and effective, they can pose some risk through side effects and interactions if people do not take them with due care. With notable exceptions, people in Canada can purchase OTC medicines from pharmacies or non-pharmacy outlets such as convenience stores. Global trends in medicine-related legislation are leading to more of these products ending up in retail outlets other than pharmacies. Therefore, understanding public attitudes involving OTC medicine is becoming more and more important. Public expectations of OTC medicines in relation to location of sale were investigated in this study. It was hypothesized that the product buying public would perceive medicines differently based on where they are sold. <p>Adult Saskatoon residents over 18 years old (n = 2547) were randomly selected from a telephone registry. Advance letters were initially mailed to them, followed by a ten page questionnaire and two reminder letters. Non-response letters were only sent to subjects who did not reply after two reminders. Subjects were asked to indicate what attributes (effectiveness, safety, potency, side effect propensity, price, etc.) they would expect from OTC medicines depending on where they were purchased pharmacies versus convenience stores. The usable response rate was 57.5 percent. Almost every participant (96.1 percent) had bought OTC medicines from pharmacies. Most respondents (80.7 percent) were aware that OTC medicines could be purchased in convenience stores; however, only 42.2 percent of respondents had purchased OTC medicines from such locations. Significantly different expectations for the two locations were seen for product variety and quality, price, and ability to get help. Pharmacies should have a better selection of products and be of better quality than these OTC medicines sold in convenience stores. Public expectations for OTC product potency, safety, effectiveness, propensity for side effects, and package information did not differ across locations. The findings of this study suggest that location of sale has minimal effect on Saskatoon residents expectations of OTC medicines along clinical attributes. Saskatoon residents also appear to have healthy attitudes regarding OTC medicines and realize care is needed during their use. This may have implications in how people use such products after they are purchased and may be important for how they are scheduled for the Canadian marketplace.
26

Consumers' expectations of over-the-counter medicine : location of sale

Lo, Ya-Ning 30 August 2006 (has links)
Over-the counter (OTC) medicines are used commonly for treating minor illnesses. Even though most Canadians believe that OTC medicines are safe and effective, they can pose some risk through side effects and interactions if people do not take them with due care. With notable exceptions, people in Canada can purchase OTC medicines from pharmacies or non-pharmacy outlets such as convenience stores. Global trends in medicine-related legislation are leading to more of these products ending up in retail outlets other than pharmacies. Therefore, understanding public attitudes involving OTC medicine is becoming more and more important. Public expectations of OTC medicines in relation to location of sale were investigated in this study. It was hypothesized that the product buying public would perceive medicines differently based on where they are sold. <p>Adult Saskatoon residents over 18 years old (n = 2547) were randomly selected from a telephone registry. Advance letters were initially mailed to them, followed by a ten page questionnaire and two reminder letters. Non-response letters were only sent to subjects who did not reply after two reminders. Subjects were asked to indicate what attributes (effectiveness, safety, potency, side effect propensity, price, etc.) they would expect from OTC medicines depending on where they were purchased pharmacies versus convenience stores. The usable response rate was 57.5 percent. Almost every participant (96.1 percent) had bought OTC medicines from pharmacies. Most respondents (80.7 percent) were aware that OTC medicines could be purchased in convenience stores; however, only 42.2 percent of respondents had purchased OTC medicines from such locations. Significantly different expectations for the two locations were seen for product variety and quality, price, and ability to get help. Pharmacies should have a better selection of products and be of better quality than these OTC medicines sold in convenience stores. Public expectations for OTC product potency, safety, effectiveness, propensity for side effects, and package information did not differ across locations. The findings of this study suggest that location of sale has minimal effect on Saskatoon residents expectations of OTC medicines along clinical attributes. Saskatoon residents also appear to have healthy attitudes regarding OTC medicines and realize care is needed during their use. This may have implications in how people use such products after they are purchased and may be important for how they are scheduled for the Canadian marketplace.
27

Engineering design cycle of curriculum and apparatus for encapsulating medicine design project

Garcia, Heather Rachelle 29 November 2012 (has links)
The goal of this work is to modify an existing course module on engineering better medicines to produce a more engaging physiologically realistic and pedagogically sound curriculum. The original module explored drug delivery using a one-compartment model, which examined only the dissolution of medicine; the module relied on a traditional teacher lead pedagogy. The curriculum modifications include engineering a two-compartment model students use to test the medicines they design, incorporating both dissolution and transfer to the blood and project based learning strategies have been added to produce a student centered project. The purpose of these modifications is to produce a curriculum successful in providing a diverse group of students, both male and female, of all socioeconomic backgrounds as well as ethnic and cultural groups with a positive engineering experience. / text
28

Modelling the Clinical and Economic Outcomes of Variations in Intensity of Valsartan-Centric Regimens for Hypertension

Al Shayban, Dhfer Mahdi D. January 2015 (has links)
Purposes: The purpose of this study was threefold. First, to examine how both the effectiveness of valsartan centric regimens and the patient-related factors affect the control rates of the Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and combined SBP/DBP; specifically for Belgian patients with a history of failed or intolerant anti-hypertensive treatment. Secondly, to assess the effectiveness of valsartan treatment groups and the related factors concerning a patients' total cardiovascular risk (TCVR) residuals. Lastly, to attempt to estimate the cost avoidance factor associated with taking varying levels of valsartan treatment doses. Methodology: This research took the form of a secondary-data analysis study, focusing on the analysis of data collected primarily from seven prospective studies conducted between 2004 and 2009, covering different regimens of valsartan. The variants of valsartan doses given to patients included: valsartan monotherapy (80mg or 160 mg); a combination of valsartan with hydrochlorothiazide (HCTZ) (80 mg and 12.5mg, 160mg and 12.5 mg, or 160mg and 25mg); and a combination of valsartan with amlodipine (80mg and 5mg, 160mg and 5mg, or 160mg and 10mg). We applied Bailey's approach, using Kaplan-Meier curves to estimate the distribution of treatment intensity at which the target rates of SBP, DBP and SBP/DBP were achieved. The treatment intensity was calculated by dividing the daily dose prescribed to a patient by the maximum daily recommended dose of that particular drug variant. The outcomes provided by Bailey's approach included the control rates of SBP, DBP and combined SBP/DBP, in addition to the reduction in TCVR residuals. Another aspect of our methodology was the use of a simulation method to estimate the cost avoidance by using valsartan treatment groups. We used OCED data to compare health indicators between the US and Belgium in order to estimate the ratio enabling us to calculate the cost of hypertension per patient per year. This cost was then used in the simulation method to calculate the cost avoidance of using varying levels of the treatment intensity of valsartan regimens. Results: A total of 17,683 patients were included in this study, contributed to by 3,434 physician-investigators. The mean age of the population was 63.63 + 11.83 years, with a mean BMI of 28.45 + 3.13 kg/m^2 and 47.7% of the population was male and the vast majority of the total population was Caucasian (98%). As a baseline the total population who had controlled SBP, DBP and combined SBP/DBP were 1358, 5301 and 1091 respectively. The total population who were categorized as low added risk TCVR, moderate added risk TCVR, high added risk TCVR, and very high added risk TCVR were 192; 3,721; 3,888 and 9,362 respectively. Overall, there was a statistically significant increase in the proportion of patients with controlled SBP, DBP and combined SBP/DBP after 90 days of starting on valsartan-centric regimens (p<0.001). Both older age and the presence of diabetes were associated with a lower control rate of SBP, DBP and combined SBP/DBP (P<0.05). High adherence to valsartan-centric regimens was associated with an increase in the control rates of blood pressure. Substantial reductions in total cardiovascular risk, particularly in the very high added-risk category was observed 5,852 times (33.1%) (P<0.001) and an increase in the low added risk TCVR 3,331 times (18.9%) (p<0.001). The associated cost avoidance with varying levels of treatment intensity were dose related. The cost avoidance associated with the treatment intensity levels of 0.25, 0.5, 0.75, 1.0 and 1.5 were $261,164; $2,403,188; $6,384,142; $8,702,272 and $10,230,321, respectively. Conclusion: The different levels of the treatment intensity of valsartan-centric regimens were effective in increasing the control rates of SBP, DBP and combined SBP/DBP in the real practice for patients whose prior treatment failed. Not only did valsartan regimens improve the BP control rate, they also reduced the TCVR residuals. Additionally, substantial cost avoidance was found to be associated with the use of higher levels of treatment intensity. These results may support the idea that intensive anti-hypertensive treatment may be associated with higher clinical and economic benefits for both patients and payers. However, more research might be needed to validate our results and to address the questions of adverse effects that may be associated with intensive anti-hypertensive therapy and the economic consequences of treating any such effects.
29

Effects of a prostaglandin precursor, gamma-linolenic acid (GLA), on malignant cells in vitro and in vivo.

Ramchurren, Nirasha. January 1985 (has links)
Recent studies have shown that the proliferation of various human and murine tumour lines can be inhibited by the addition of gamma-linolenic acid (GLA) to the culture medium. These findings are consistent with the proposal put forward by Horrobin (1980) that malignant cells lack the enzyme/ A 6 desaturase; which is responsible for the conversion of linoleic acid (LA) to GLA. Since GLA is a prostaglandin (PG) precursor/ inadequate conversion of LA to GLA would result in decreased production of PGs/ particularly PGEi/ which has been shown to have an inhibitory effect on cell growth. Provision of GLA to enzyme deficient malignant cells should therefore bypass this blockade/ increase PGET synthesis and thus "normalise malignant cells". This study was performed to examine further the effects of exogenous GLA on growth of malignant cells in vitro and in vivo. Cells of the continuous murine sarcoma (M52B) line and primary cultures of non malignant fibroblasts were used to investigate effects of GLA in vitro. Cultures were exposed to either single or multiple doses of a range of concentrations of GLA. Radioimmunoassay (RIA) was performed to compare the amounts of PGE and PGF released into the medium by GLA treated and control M52B cultures and thus determine whether the addition of GLA in vitro significantly affected production of these PGs. Athymic BALB/c mice and immunocompetent BALB/c and Biozze mice as well as mice of the "Onderstepoort Strain" were used in various in vivo studies. Tumours were induced by the subcutaneous inoculation of approximately 1 x 106 cells of either the M52B line (into immunocompetent and athymic mice) or human breast carcinoma (NUB 1) line (into athymic mice). Take rates and latent periods were recorded. GLA treatment was initiated after tumours were established. In one study the fatty acid in hydrogenated coconut oil (HCO), which contains no PG precursors/ was administered parenterally (100 ug/ml/day) to Biozze mice. Control mice were either untreated or injected with HCO only. In another study, BALB/c mice and mice of the "Onderstepoort Strain" had their diet supplemented with GLA (in the form of EPO) to an extent of 3.5%. Control mice consumed either standard laboratory chow only or, chow supplemented with either 35% sunflower seed oil (SSO) or 35% HCO/ neither of which contain GLA. All diets were supplied ad libitum. Tumour sizes were measured every 48 hours and at the end of each experiment at which time tumours were excised and examined histologically. GLA was found to produce inhibitory and toxic effects on growth of both M52B cells and non malignant fibroblasts in vitro/ although the effect in the latter was observed only with high concentrations of the fatty acid. The inhibition of malignant cell growth was concentration dependant and was positively related to the duration of exposure to the fatty acid. Prior to death/ cells treated with GLA accumulated vii paranuclear granules which were shown histochemically to be lipid in nature. Electron microscopy confirmed the presence of large lipid deposits. Cultured M52B cells treated with GLA also released more PGE and PGF into the medium than did cells not exposed to the fatty acid. However, analysis of results using the Mann Whitney U test showed these differences to be statistically non significant for both PGE and PGF on two tailed tests. In contrast to the inhibition of M52B cell growth observed in vitro, growth of solid M52B sarcomas and NUB 1 carcinoma xenografts in athymic mice was apparently unaffected by administration of dietary GLA. Analysis of data using an unpaired student's t-test showed that the differences in tumour volumes between control and treated groups were not statistically significant either before or at the end of the experiment. While the inhibition of malignant cell growth caused by GLA in vitro was consistent with Horrobin's proposal that malignant cells may lack this PG precursor, whether or not these actions are mediated by the PGs remains obscure. Although an increase in PGE production by M52B cells was observed following GLA treatment, besides this increase being statistically non significant, it was not possible to determine whether this was due to PGE, (as suggested by Horrobin) or PGE2. It is possible that the effect produced in vitro was due to some factor other than raised PGE production, for example a non-specific fat-overload effect or a change in cell membrane fluidity. The lack of effect of GLA on tumour growth in vivo may have been due to inadequate delivery of the fatty acid to the tumour site. However, whatever the mechanism of action of GLA in vitro/ since oral GLA was supplemented to the maximum tolerated extent and produced no effect in immunodeficient mice inyiyo, it would seem that in a similar clinical situation oral doses which would be practical may be ineffective. / Thesis (M.Sc.)-University of Natal, Durban, 1985.
30

Marketing Medicines: Conceptualizing Cultural Identity and Livelihood among Market Vendors in Asunción, Paraguay

Millman, Heather 16 April 2012 (has links)
This thesis investigates the ways in which the selling and utilizing of medicinal plant remedies in Asunción, Paraguay intersects with conceptualizations of Paraguayan cultural identity, traditional gendered knowledge systems, and with the socioeconomic realities of vendors and consumers. Engaging with anthropological theories of the political economy of health, cultural identity, and the socioeconomics of women workers in Latin America, it explores how the use of indigenous healthcare practices engages with notions of Paraguayan identity and traditional knowledge, including the transmission of gendered knowledge. Through data collected in semi-structured interviews with market vendors of medicinal plants in Asunción, this thesis investigates the connections between indigeneity and land, cultural and symbolic identity and food, and the livelihoods of medicinal plant vendors, in order to argue that the selling of these traditional plant medicines in the local markets of Asunción solidifies Paraguayan identity by providing daily affordable access to consumable symbols of “Paraguayanness.” / Social Sciences and Humanities Research Council of Canada

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