This study examined the effect of prolonged differential housing and/or diet following exposure to chronic restraint stress on body weight, body fat weight, body fat composition and corticosterone, glucose, insulin and leptin levels. To this end, male Wistar rats were individually-housed (IH) or pair-housed (PH) and fed a condensed milk diet (CD) or a mushy rat chow diet (MD) for twelve weeks. Subsequently, all rats underwent chronic restraint stress (CRS) for seven hours/day for four weeks. During CRS, only PH rats fed MD continued to gain weight, while growth of the other groups was stunted. Housing and diet impacted on body fat weights, where PH caused increased retrorenal fat (P<0.001) in rats fed MD, while in rats fed CD, PH gave rise to less visceral (P<0.01) and more interscapular (P<0.05) and retrorenal fat (P<0.001). The CD resulted in more retrorenal (P<0.001) and interscapular fat (P<0.05) in PH rats, with more visceral (P<0.001) and retrorenal fat (P<0.01) in IH rats. Housing influenced only the fatty acid profiles of the liver and subcutaneous fat in rats fed CD. The CD caused differing fatty acid profiles of the liver, subcutaneous fat, visceral fat, interscapular fat and muscle in PH rats, while altering the fatty acid profiles of the liver, subcutaneous fat, interscapular fat and muscle in IH rats. Housing and diet did not result in differences in corticosterone, insulin and glucose concentrations, while both resulted in significantly elevated leptin levels in PH rats fed CD. Therefore the types of housing and diet have various effects on body weight and glucose and fat metabolism following chronic stress. This dissertation is dedicated to My dear parents, Jeff and Avril Ackerman, for their on-going support My loving husband, Brandon, for his encouragement, assistance and patience My children, Elazar Tzvi, Sara Esther, Yaakov Yehuda and Rossi Bear who have been my stress alleviators and Idah Rangwato and Annah Sibanda who are my right-hand ladies and have made it possible to complete this dissertation- Thank you!

In rats anaesthetised with enflurane, Iexamined.the response of coccygeal primary afferents fibres to noxious thermal and mechanical stimulation and to innocuous brushing, during transient ischaemia and reperfusion of their receptive fields on the tail. Ischaemia was induced by occluding the blood supply to the tail for 30 min using a tourniquet. I discovered four different groups of afferent fibres, distinguished by conduction velocity and modality, A{3fibres responding to both brush and pinch of their receptive fields showed decreased sensitivity to brush during both ischaemia and reperfusion; Ao fibres responding to pinch were unaffected by either ischaemia or reperfusion, C fibres responding to noxious heat (49· C) and pinch showed hypersensitivity during reperfusion, especially immediately after release of the tourniquet. Another group of C fibres, presumably chemosensitive, became more actiVA during ischaemia and exhibited a 7-fold increase in firing rate during receptive field reperfuslon in the absence of obvious stimuli. These results indicate that during reperfuslon of the rat tail following transient ischaemia, myelinated fibres do not increase their input to the CNS, while C fibres became more active and showed sensitization to noxious stimulation of their receptive fields. The enhanced CNS nociceptive activity which occurs during reperfusion consequently results from both peripheral and. central sensitization. / GR2017

Para a realização de pesquisas científicas biológicas universais e reprodutivas, é fundamental a produção e o fornecimento de animais de laboratório de alta qualidade. Contudo, a qualidade e a saúde desses animais dependem, em grande parte, das instalações disponíveis para a sua produção e alojamento, de forma a garantir a qualidade sanitária e o seu bem-estar, respeitando os princípios éticos que regem a atividade. Nas instalações destinadas a criação, manutenção e experimentação com animais de laboratório são adotadas diretrizes, tanto nacionais como internacionais, para garantir a biossegurança e o bem-estar animal. Além disso, as instalações devem preencher outros requisitos, tais como: a funcionalidade dos ambientes, que devem possibilitar o manejo adequado e eficiente dos animais, facilitando a execução das atividades rotineiras; a climatização ambiental; a instalação de barreiras sanitárias para limitar e impedir o acesso de agentes indesejáveis; o respeito a princípios ergonômicos, para proporcionar um ambiente seguro e o bem-estar dos operadores; a biossegurança, para prevenir, minimizar ou eliminar riscos à saúde do homem e dos animais, a preservação do meio ambiente e a qualidade dos resultados. Dessa forma, o projeto das instalações é de importância vital para que os requisitos mencionados sejam atingidos, com a obtenção de animais sadios, com o mínimo de estresse, proporcionando o bem-estar e reduzindo variações que podem afetar os resultados de pesquisa. Neste documento, é apresentada uma introdução com a importância do suíno na medicina e na experimentação animal, além de alguns parâmetros importantes adotados na construção de instalações destinadas à criação e alojamento desta espécie. Finalmente, é apresentado um projeto conceitual de uma instalação, que reunirá características que representem o estado-da-arte sobre o assunto, para que o espaço destinado ao alojamento dos animais atenda, da melhor maneira, as recomendações sobre aspectos inerentes dos animais de laboratório, com relação à saúde, à alimentação, controle da transmissão de doenças, á adequação das instalações às exigências e às normas internacionais que visam o bem-estar animal. O projeto da instalação reunirá características únicas e inéditas, para que seja possível realizar pesquisas científicas avançadas, contribuindo para o crescimento da ciência nacional, bem como para o desenvolvimento inovador no âmbito da CNEN. / In order to carry out outstanding universal and reproductive biological scientific research, the production and supply of high quality laboratory animals are of fundamental importance. However, the quality and health of these animals depends on a large extent on the facilities available for their production and housing in order to ensure the sanitary quality and their well-being, respecting the ethical principles governing the activity. National and international guidelines for facilities for breeding, maintenance and testing of laboratory animals are aimed, among other things, biosafety and animal welfare. In addition, facilities must meet other requirements, such as: the functionality of the environments, which should allow the proper and efficient management of the animals, facilitating the execution of routine activities; environmental air conditioning; the installation of sanitary barriers to limit and prevent access of undesirable agents; respect for ergonomic principles, to provide a safe environment and the well-being of operators; biosafety, to prevent, minimize or eliminate risks to the health of man and animals, the preservation of the environment and the quality of results. In this way, the design of the facilities is of vital importance in order to achieve the mentioned requirements, obtaining healthy animals with minimum stress, providing well-being and reducing variations that can affect the results of research. This paper presents an introduction to the importance of pig in medicine and animal experimentation, as well as some important parameters adopted in the construction of facilities for breeding and housing of this specie. Finally, a conceptual design of an installation is presented, which will bring up characteristics that represent the state of the art on the subject, so that the space destined to the housing of the animals meets, in the best way, the recommendations on inherent aspects of laboratory animals, with regard to health, food, control transmission of diseases, adaptation of facilities to international requirements and standards for animal welfare. The facilities project will bring also unique and unprecedented features, so that it is possible to carry out scientific cutting-edge research, contributing to the further development of national science, as well as innovative research within CNEN.

Para a realização de pesquisas científicas biológicas universais e reprodutivas, é fundamental a produção e o fornecimento de animais de laboratório de alta qualidade. Contudo, a qualidade e a saúde desses animais dependem, em grande parte, das instalações disponíveis para a sua produção e alojamento, de forma a garantir a qualidade sanitária e o seu bem-estar, respeitando os princípios éticos que regem a atividade. Nas instalações destinadas a criação, manutenção e experimentação com animais de laboratório são adotadas diretrizes, tanto nacionais como internacionais, para garantir a biossegurança e o bem-estar animal. Além disso, as instalações devem preencher outros requisitos, tais como: a funcionalidade dos ambientes, que devem possibilitar o manejo adequado e eficiente dos animais, facilitando a execução das atividades rotineiras; a climatização ambiental; a instalação de barreiras sanitárias para limitar e impedir o acesso de agentes indesejáveis; o respeito a princípios ergonômicos, para proporcionar um ambiente seguro e o bem-estar dos operadores; a biossegurança, para prevenir, minimizar ou eliminar riscos à saúde do homem e dos animais, a preservação do meio ambiente e a qualidade dos resultados. Dessa forma, o projeto das instalações é de importância vital para que os requisitos mencionados sejam atingidos, com a obtenção de animais sadios, com o mínimo de estresse, proporcionando o bem-estar e reduzindo variações que podem afetar os resultados de pesquisa. Neste documento, é apresentada uma introdução com a importância do suíno na medicina e na experimentação animal, além de alguns parâmetros importantes adotados na construção de instalações destinadas à criação e alojamento desta espécie. Finalmente, é apresentado um projeto conceitual de uma instalação, que reunirá características que representem o estado-da-arte sobre o assunto, para que o espaço destinado ao alojamento dos animais atenda, da melhor maneira, as recomendações sobre aspectos inerentes dos animais de laboratório, com relação à saúde, à alimentação, controle da transmissão de doenças, á adequação das instalações às exigências e às normas internacionais que visam o bem-estar animal. O projeto da instalação reunirá características únicas e inéditas, para que seja possível realizar pesquisas científicas avançadas, contribuindo para o crescimento da ciência nacional, bem como para o desenvolvimento inovador no âmbito da CNEN. / In order to carry out outstanding universal and reproductive biological scientific research, the production and supply of high quality laboratory animals are of fundamental importance. However, the quality and health of these animals depends on a large extent on the facilities available for their production and housing in order to ensure the sanitary quality and their well-being, respecting the ethical principles governing the activity. National and international guidelines for facilities for breeding, maintenance and testing of laboratory animals are aimed, among other things, biosafety and animal welfare. In addition, facilities must meet other requirements, such as: the functionality of the environments, which should allow the proper and efficient management of the animals, facilitating the execution of routine activities; environmental air conditioning; the installation of sanitary barriers to limit and prevent access of undesirable agents; respect for ergonomic principles, to provide a safe environment and the well-being of operators; biosafety, to prevent, minimize or eliminate risks to the health of man and animals, the preservation of the environment and the quality of results. In this way, the design of the facilities is of vital importance in order to achieve the mentioned requirements, obtaining healthy animals with minimum stress, providing well-being and reducing variations that can affect the results of research. This paper presents an introduction to the importance of pig in medicine and animal experimentation, as well as some important parameters adopted in the construction of facilities for breeding and housing of this specie. Finally, a conceptual design of an installation is presented, which will bring up characteristics that represent the state of the art on the subject, so that the space destined to the housing of the animals meets, in the best way, the recommendations on inherent aspects of laboratory animals, with regard to health, food, control transmission of diseases, adaptation of facilities to international requirements and standards for animal welfare. The facilities project will bring also unique and unprecedented features, so that it is possible to carry out scientific cutting-edge research, contributing to the further development of national science, as well as innovative research within CNEN.

A rat model of novelty-seeking phenotype predicts vulnerability to nicotine relapse where locomotor reactivity to novelty is used to rank high (HR) versus low (LR) responders. This dissertation examines the neuropeptidergic and structural substrates of the expression of locomotor sensitization to a low dose nicotine challenge and associated social anxiety-like behavior following chronic intermittent nicotine exposure during adolescence in the LRHR phenotype. Data show the long-lasting nature of behavioral sensitization to nicotine and abstinence-related social anxiety-like behavior in nicotine pre-trained HRs compared to saline pre-trained controls. Moreover, this behavior is accompanied by an imbalance between the brain antistress/antianxiety, i.e., neuropeptide Y (NPY), and stress, i.e., corticotrophin releasing factor (CRF) systems in the amygdala. Moreover, a deficit in NPY signaling marked with decreased NPY and increased NPY Y2 receptor (Y2R) mRNA levels is observed in the hip pocampus, along with mossy fiber reorganization in nicotine pre-trained HRs. Furthermore, a Y2R antagonist administered 1 wk of abstinence reverses these behavioral, molecular and morphological effects in nicotine-exposed HRs. Additionally, the role of amygdalar synaptic plasticity in longlasting social withdrawal is also investigated by assessing brain-derived neurotrophic factor (BDNF) and spinophilin mRNA levels in HRs following a behaviorally-sensitizing nicotine regimen. A persistent increase in BDNF and spinophilin mRNA levels in the basolateral amygdala (BLA) is observed in nicotine pre-trained HRs even across a long (3-wk) abstinence spanning into young adulthood. This strongly suggests BDNFmediated long-lasting neuroplasticity within the BLA that may regulate abstinence-related negative affect in HRs. / Moreover, a cannabinoid receptor 1 (CB1R) antagonist, AM251 treatment during a short (1-wk) abstinence is ineffective in reversing social anxiety, nicotine-induced neuroplasticity and the neuropeptidergic changes in the amygdala, although it is effective in reversing the expression of locomotor sensitization to challenge nicotine even following a long (3-wks) abstinence. Furthermore, the identical AM251 treatment given during the late phase of a long (3-wk) abstinence further augments social withdrawal and associated BLA plasticity in nicotine pre-trained HRs. These findings implicate neuropeptidergic and neuroplastic changes in the hippocampus and the amygdala in vulnerability to the long-lasting behavioral effects of nicotine in the novelty-seeking phenotype. / by Cigdem Aydin. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

Although much more work needs to be done to elucidate the functional roles of FSH and LH in fish reproduction, the preset study provides a relatively comprehensive study for us to understand the potential roles of FSH and LH during ovarian development in fish, especially the importance of FSH. / At the same time, functional studies were carried out to examine and compare bioactivities of the CHO-derived zfFSH and zfLH in zebrafish ovary, which is the major part of the present project. The following aspects were covered to investigate the actions of zfFSH and zfLH: steroidogenesis and folliculogenesis. / Both recombinant zfGTHs stimulated activin betaA expression but slightly suppressed activin betaB expression. During short-term treatment, zfFSH and zfLH exhibited similar stimulatory effects on activin betaA expression; the effect of zfLH became more prominent after 24 h treatment while zfFSH had little effect. / Previously, our laboratory had established two stable Chinese hamster ovary (CHO) cell lines expressing recombinant zebrafish FSH (zfFSH) and LH (zfLH). However, the production yields are very low. Therefore, the present study tried to adopt the yeast Pichia pastoris as another bioreactor to produce recombinant zfFSH and zfLH. Two different forms of expression vectors for a native form and a fusion form carrying a His-tag, respectively, were constructed for each hormone. Their bioactivities were monitored and confirmed by receptor-based reporter gene assays as well as ovarian fragment incubation. As expected, the native form exhibited much higher activities than the fusion form. / The pituitary gonadotropins (GTHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are the key hormones controlling vertebrate reproduction. Although the two gonadotropins have been characterized in numerous teleost species, our understanding of their biological functions remains rather limited. This is largely due to the lack of pure form of homologous gonadotropins and inadequate understanding of gonadal physiology in most species studied as well as species variation of hormone actions. The present study aims at systematically investigating the functional roles of FSH and LH in the ovary using zebrafish as the model. Zebrafish is becoming more and more popular as the model of reproductive and developmental studies due to several advantages. First, though its body size is small, its ovary is relatively large and available all the year around. Second, zebrafish spawns everyday and its development is fast. Last but not least, its bioinformatics information is tremendous compared to other fish models. / We investigated the effects of zfFSH and zfLH on steroidogenesis by examining the regulation of aromatase by these two hormones. Aromatase catalyzes the conversion of androgens into estrogens during steroidogenesis. Both recombinant zfGTHs stimulated the aromatase expression during short-term treatment (8 h) in ovarian fragment culture, with zfFSH much more potent than zfLH. However, zfFSH continued to exhibit powerful effect on aromatase expression after 24 h treatment while zfLH had little effect at all. The stimulatory effect of zfFSH on aromatase expression was time-, dose- and stage-dependent and was also confirmed by in vivo study. Furthermore, it was also zfFSH but not zfLH that significantly stimulated StAR protein expression during short-term treatment. StAR protein is critical to steroidogenesis by facilitating the movement of cholesterol across the mitochondrial membrane. / zfLH was found to be able to induce GVBD in zebrafish, as demonstrated in other fish species. However, our preliminary data showed that zfFSH was also involved in this process. To our knowledge, this is the first time to demonstrate that homologous FSH induces GVBD in teleosts. / Yu, Xiaobin. / Adviser: Wei Ge. / Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: . / Thesis submitted in: December 2008. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 152-181). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Tan, Sijiao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 118-136). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract (in English) --- p.iii / Abstract (in Chinese) --- p.vi / List of Abbreviations --- p.viii / Table of Contents --- p.x / Chapter CHAPTER 1 --- INTRODUCTION / Chapter 1.1 --- Frying --- p.1 / Chapter 1.1.1 --- General introduction of frying --- p.1 / Chapter 1.1.2 --- Physical and chemical changes of oils during frying --- p.2 / Chapter 1.1.2.1 --- Physical changes --- p.2 / Chapter 1.1.2.2 --- Chemical changes --- p.5 / Chapter 1.1.2.2.1 --- Hydrolysis --- p.5 / Chapter 1.1.2.2.2 --- Oxidation --- p.5 / Chapter 1.1.2.2.3 --- Polymerization --- p.6 / Chapter 1.1.3 --- Frying oil selection --- p.11 / Chapter 1.1.4 --- Quality control of frying oil --- p.11 / Chapter 1.2 --- Selection of experiment oil --- p.13 / Chapter 1.2.1 --- Lard as a cholesterol-containing animal fat --- p.13 / Chapter 1.2.2 --- Corn oil as a healthy vegetable oil --- p.14 / Chapter 1.3 --- Current studies on frying oils --- p.18 / Chapter 1.4 --- Atherosclerosis and cholesterol metabolism --- p.19 / Chapter 1.4.1 --- Atherosclerosis --- p.19 / Chapter 1.4.2 --- Cholesterol metabolism and related regulating factor --- p.23 / Chapter 1.5 --- Animal model selection --- p.29 / Chapter CHAPTER 2 --- OBEJECTIVES --- p.30 / Chapter CHAPTER 3 --- MATERIALS AND METHODS / Chapter 3.1 --- Sample lard and corn oil preparation --- p.31 / Chapter 3.2 --- Diet preparation --- p.34 / Chapter 3.3 --- Animals --- p.36 / Chapter 3.4 --- Sample collection --- p.36 / Chapter 3.5 --- GC analysis of fatty acid composition in fresh and fried experiment oil samples --- p.37 / Chapter 3.6 --- Determination of plasma cholesterol and organ cholesterol --- p.41 / Chapter 3.7 --- "Determination of hamster fecal neutral and acidic sterols, corn oil phytosterol content" --- p.44 / Chapter 3.7.1 --- Determination of fecal neutral sterols --- p.44 / Chapter 3.7.2 --- Determination of fecal acidic sterols --- p.45 / Chapter 3.7.3 --- Determination of phytosterol content in corn oil --- p.46 / Chapter 3.8 --- "Determination of composition and concentration of liver triglycerides, total free fatty acids and phospholipids" --- p.51 / Chapter 3.9 --- Statistics --- p.54 / Chapter CHAPTER 4 --- RESULTS IN FRIED LARD EXPERIMENT / Chapter 4.1 --- Fatty acid composition and cholesterol content of experiment lard --- p.55 / Chapter 4.2 --- Body weight and food intake --- p.55 / Chapter 4.3 --- Relative organ weight --- p.55 / Chapter 4.4 --- "Plasma total cholesterol, triglycerides and HDL- cholesterol" --- p.60 / Chapter 4.5 --- Organ cholesterol --- p.60 / Chapter 4.6 --- Fecal neutral sterol output --- p.64 / Chapter 4.7 --- Fecal acidic sterol output --- p.64 / Chapter 4.8 --- Effect of fried lard on cholesterol balance in hamster --- p.64 / Chapter 4.9 --- "Effect of fried lard on hepatic triglycerides, free fatty acids and phospholipids concentration in hamster" --- p.68 / Chapter 4.10 --- Correlation between serum HDL cholesterol and liver cholesterol --- p.76 / Chapter 4.11 --- Correlation between serum HDL cholesterol and kidney cholesterol --- p.76 / Chapter 4.12 --- Correlation between serum TG and liver TG --- p.76 / Chapter CHAPTER 5 --- RESULTS OF FRIED CORN OIL EXPERIMENT / Chapter 5.1 --- Fatty acid composition and phytosterol content of experiment corn oil --- p.80 / Chapter 5.2 --- Body weight and food intake --- p.80 / Chapter 5.3 --- Relative organ weight --- p.84 / Chapter 5.4 --- Plasma total cholesterol，triglycerides and HDL- cholesterol --- p.84 / Chapter 5.5 --- Organ cholesterol --- p.87 / Chapter 5.6 --- Fecal neutral sterol and phytosterol output --- p.87 / Chapter 5.7 --- Fecal acidic sterol output --- p.92 / Chapter 5.8 --- Effect of fried corn oil on cholesterol balance and phytosterol balance in hamsters --- p.92 / Chapter 5.9 --- "Effect of fried corn oil on hepatic triglycerides, free fatty acids and phospholipids concentration in hamster" --- p.97 / Chapter 5.10 --- Correlation between serum HDL cholesterol and liver cholesterol --- p.105 / Chapter 5.11 --- Correlation between serum HDL cholesterol and kidney cholesterol --- p.105 / Chapter 5.12 --- Correlation between serum TG and liver TG --- p.105 / Chapter CHAPTER 6 --- DISCUSSION --- p.109 / Chapter CHAPTER 7 --- CONCLUSION --- p.117 / REFERENCE --- p.118

Addenda page on inside back cover. Bibliography: leaves 153-176. Mucopolysaccharideosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is an autosomal recessive lysosomal storage disease, with a prevalence in Australia of 1 in 114,000. MPS IIIA is caused by a deficiency of the lysosomal enzyme sulphamidase which is needed together with other exohydrolases and a N-acetyltransferase to break down the glycosaminoglycan heparan sulphate to sulphate and monosaccharides. Patients are characterised by severe central nervous systems degeneration together with mild somatic involvement; this disproportionate correlation is unique amongst the mucopolysaccharidoses. Features include severe behavioural disturbances, such as hyperactivity and aggressiveness, coarse hair and mild hepatosplenomegaly. Death is usually in the mid- to late-teenage years. Enzyme replacement therapy by intravenous administration of recombinant human NS (rhNS) has been proposed as a potential therapy for MPS IIIA. This thesis suggests that rhNS, entering the brain in the first few weeks of life, is able to retard the behaviour and learning difficulties in MPS IIIA mice.

Purpose: To develop an approach to formulating an injectable solution containing both hydrophilic and lipophilic drugs for subcutaneous administration. Based on the literature survey, isotropic medium chain mono-and diglyceride (MCMDG) systems were chosen for study. For this purpose, analytical methods were developed and validated. In vitro assessments of the MCMDG systems, and in vitro release and in vivo studies were conducted. Methods: The phase diagrams of the isotropic MCMDG systems were constructed with systems comprising two and three components. The isotropic region was examined by visual inspection and confirmed using polarized light microscopy. Viscosities of formulations were measured. The validated HPLC assay methods were developed for determination of levamisole and abamectin in liquid formulations and in sheep plasma. The HPLC assay was capable of evaluating stability of abamectin and levamisole in liquid formulations. Solubilities of levamisole hydrochloride or levamisole phosphate and abamectin were determined in the isotropic MCMDG formulations using a HPLC assay method. Stabilities of levamisole phosphate and abamectin were conducted in the isotropic MCMDG formulations at 60�C for 10 days. In vitro release studies for levamisole phosphate were carried out for selected formulations using modified Franz diffusion cells. Based on stability and in vitro release studies, one formulation (MCMDG/propylene glycol (PG):glycerol formal (GF), 20/20:60 % w/w) was selected for a preliminary in vivo study. The selected MCMDG/PG:GF (20/20:60) formulation containing both levamisole phosphate and abamectin was injected subcutaneously into sheep, and the injection site was examined after subcutaneous injection. Pharmacokinetic profiles were determined. A correlation between in vitro fraction released (FR) and in vivo fraction absorbed (FA) for levamisole phosphate from the MCMDG/PG:GF (20/20:60) formulation was assessed. Results: The isotropic systems of the MCMDG systems containing two or three components were characterized through phase diagrams and viscosity. The solubility of the levamisole hydrochloride in the isotropic MCMDG/sesame oil/water formulations was higher in the absence of abamectin than in combination with abamectin. Solubility of levamisole phosphate was higher in the MCMDG system containing GF or PG compared to the MCMDG/SO/water system. The isotropic MCMDG/PG:GF systems allowed preparations of levamisole phosphate/abamectin solution dose forms containing more than the usual dosage of levamisole. Stability of both levamisole phosphate and abamectin in MCMDG/PG:GF formulations was higher compared with MCMDG/PG:GF/water formulations. Levamisole phosphate degraded in the presence or absence of abamectin in the MCMDG/PG:GF (20/20:60) formulation at 60�C for 10 days. Abamectin alone was found to be stable in the formulation at 60�C for 10 days. In vitro release of levamisole phosphate from water and the MCMDG formulations tested displayed first-order kinetics. Water from the receptor compartment was observed to pass through the membrane into the donor compartment. Therefore, an advancing layer of turbidity occurred in the donor phase. A highly significant decrease in release rate of levamisole phosphate was obtained in MCMDG/GP:GF (20/20:60) formulation compared to water and the other formulations. Pharmacokinetic studies of subcutaneous injection of MCMDG/PG:GF 20/20:60) formulation showed the tmax values of 2.2 h and 4.2 days for levamisole phosphate and abamectin, respectively. The Cmax was 0.94 [mu]g/ml for levamisole phosphate and 6.24 ng/ml for abamectin while the formulation displayed the AUC value was 5.2 [mu]g�h�ml⁻1 for levamisole phosphate and 84.7 ng�day�ml⁻1 for abamectin. No inflammatory reaction was observed at the injection site. Linear regression analysis showed that a significant relationship between the FR (in vitro) and FA for the subcutaneously injected formulation. Conclusion: The study carried out in this thesis introduces a new approach to formulating an injectable solution of the isotropic MCMDG/PG:GF systems containing both levamisole (hydrophilic drug) and abamectin (lipophilic drug) for subcutaneous administration, and presents the development of the HPLC assay methods for determination of levamisole and abamectin in liquid MCMDG formulations and plasma, in order to investigate in vitro and in vivo release from the isotropic MCMDG/PG:GF formulations. The MCMDG/PG:GF formulations may represent an alternative to the more traditional formulations for both lipophilic and hydrophilic drugs.

Copies of author's previously published articles inserted inside back cover. / Bibliography: leaves 137-179. / x, 179, [26] leaves, [28] leaves of plates : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The aims of this study are to determine whether latent HSV genomes are a result of viral DNA amplification in the PNS during the establishment phase and to investigate the relationship between HSV DNA copy number and viral transcriptional activity during latent infection of the PNS. In order to map the distribution of viral nucleic acid sequences in latently infected sensory ganglia, experiments are undertaken using a mouse model that makes novel use of the segmental sensory innervation of flank skin. / Thesis (Ph.D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1995?