The objectives of these investigations were (1) the purification of MG reductase from sheep liver and (2) studies of some of its characteristics. MG reductase was purified 40 fold and showed a single band on SDS-PAGE. Molecular weight estimations with SDS-PAGE showed a molecular weight of 44,000; although gel filtration with Sephadex G-150 gave a molecular weight of 87,000 indicating that the enzyme might be a dimer. The Km for MG is 1.42 mM and for NADH it is 0.04 mM. The pH optimum for the purified enzyme is pH 7.0. Isoelectric focusing experiments showed a pI of 9.3. In vivo experiments involving rats treated with 3,3',5-triiodothyronine (T_3) and 6-n-propyl-2-thiouracil (PTU) indicated that MG reductase was depressed by T_3 and elevated by PTU.

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.

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.

Bibliography: leaves 193-206. / xiii, 206 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis investigates the effect of femoral stem surface roughness and a collar on the fixation of cemented hip hemi-arthroplasty femoral stems in an in vivo sheep model up to nine months following implantation. Plain radiography, micromotion between prosthesis and bone during mechanical testing and histology are used. / Thesis (Ph.D.)--University of Adelaide, Dept. of Orthopaedics and Trauma, 1997?

Includes bibliographies. / 1 v. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / The present study provides a detailed account of the anatomical and neurohistological structure of the temporomandibular joint (TMJ) in foetal and adult Australian Merino sheep. The purpose is to describe the innervation of the joint and to determine the possible roles of both afferent receptor structures and neuropeptides in the pathophysiology of experimentally induced osteoarthritis. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anatomical Science, 1997

Bibliography: leaves 249-283. / xi, 283 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the hypothesis that cerebrospinal fluid (CSF) is driven from the subarachnoid space into perivascular spaces and the central canal by arterial pulsations and that this is the driving force for the development of non-communicating syringomyelia. Horseradish peroxidase (HRP) is used as a CSF tracer in rats and sheep. A technique for studying the three-dimensional morphology of the human central canal is also developed. / Thesis (Ph.D.)--University of Adelaide, Dept. of Surgery, 1997?

Bibliography: p. 207-236. / 236 p. : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / This thesis examines the systemic and cerebral pharmacokinetics and pharmacodynamics of propofol following rapid administration, using regional pharmacokinetic techniques in a sheep preparation. New methods for measurement of cerebral blood flow, cerebral metabolic rate and depth of anaesthesia are developed and validated. The final studies show that distribution of propofol to the brain is dependent on cardiac output. / Thesis (Ph.D.)--University of Adelaide, Dept. of Anaesthesia and Intensive Care, 1997?

Bibliography: leaves 198-219. / xii, 219 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the effect of implant design on the femoral bone remodelling response in a sheep cemented hip arthroplasty model. The clinical section of the thesis also indicates the importance of biological factors in the femoral bone remodelling response. / Thesis (Ph.D.)--University of Adelaide, Dept. of Orthopaedics and Trauma, 1998

Thesis (Ph.D.)--University of Adelaide, Dept. of Orhtopaedics and Trauma, 1998. / Bibliography: leaves 198-219.

A recently emerging engineering design approach entails studying the brilliant design solutions found in nature with an aim to develop design strategies that mimic the remarkable efficiency found in biological systems. This novel engineering approach is referred to as bio-inspired design. In this context, the present study quantifies the structure-property relations in bighorn sheep (Ovis canadensis) horn keratin, qualitatively characterizes the effects of a tapered spiral geometry (the same form as in a ram’s horn) on pressure wave and impulse mitigation, describes the stress attenuation capabilities and features of a ram’s head, and compares the structures and mechanical properties of some energy absorbent natural materials. The results and ideas presented herein can be used in the development of lightweight, energy absorbent, bio-inspired material designs. Among the most notable conclusions garnered from this research include: Horn keratin behaves in an anisotropic manner similar to a long fiber composite. Moisture content dominates the material behavior of horn keratin more than anisotropy, age, and stress-state. This makes moisture content the most influential parameter on the mechanical behavior of horn keratin. Tapered geometries mitigate the impulse generated by a stress wave due to the convergent boundary and a continually decreasing cross sectional area such that greater uniaxial stresses and subsequent axial deformation arises. Furthermore, the tapered geometry introduces small shear stresses that further decrease the impulse. Spiral geometries attenuate the impulse generated by a stress wave by the introduction of shear stresses along the length of the spiral. These shear stresses introduce transverse displacements that function to lessen the impulse. When both a taper and spiral geometry are used in a design, their synergistic effects multiplicatively reduce the impulse Tough natural materials have a high porosity, which makes them light-weight, while increasing their compressive energy absorption ability. Biomaterials whose functions include protection and energy absorption feature a multiscale, hierarchical, composite structure. The constituent materials are arranged in such ways to achieve a synergistic effect, where the properties of the composite exceed the properties of its constituents. Biological materials are therefore not confined to the law of mixtures.