Ko Wing Hung. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 129-138). / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Methodology --- p.16 / Chapter Chapter 3 --- Development of Radioimmunoassay --- p.30 / Chapter Chapter 4 --- Coupling of Trichosanthin to Dextran T40 --- p.38 / Chapter Chapter 5 --- Pharmacokinetic Study --- p.49 / Chapter Chapter 6 --- Renal tubular reabsorption of Trichosanthin --- p.63 / Chapter Chapter 7 --- Biological activities of Dextran-Trichosanthin --- p.77 / Chapter Chapter 8 --- Immunological activities of Dextran-Trichosanthin --- p.91 / Chapter Chapter 9 --- General Discussion --- p.124 / References

Thesis (doctoral)--Ludwig Maximilians-Universität zu München, 1979.

In view of its varied concepts and interpretations, and because of the discrepancies produced by the previous utilization of polydispersed dextrans, a study using extremely narrow-range molecular weight dextran fractions was initiated to reevaluate and consolidate some of the aspects of capillary permeability. A portion of the study was performed under decreased barometric pressure in order to clarify further some of the mechanisms involved in particulate transfer across the capillary endothelial membranes. Gel filtration procedures augmented the study as an assessment of the polydispersity effects of the dextrans employed.

by Kin-wai Lee. / Includes bibliographies / Thesis (M.Phil.)--Chinese University of Hong Kong, 1982

by Chan Wah Lun. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 252-260). / Acknowledgments --- p.i / Abstract --- p.ii / Contents --- p.vi / Naming of TCS mutants and modified TCS protein --- p.x / Abbreviations --- p.xi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Physical and chemical properties of Trichosanthin --- p.1 / Chapter 1.2 --- Biological activities of Trichosanthin --- p.3 / Chapter 1.3 --- Renal tubular reabsorption and nephrotoxicity of Trichosanthin --- p.10 / Chapter 1.4 --- Objective and strategies of study --- p.11 / Chapter Chapter 2 --- Materials and methods --- p.19 / Chapter 2.1 --- General Techniques --- p.19 / Chapter 2.2 --- Site directed mutagenesis of Trichosanthin --- p.21 / Chapter 2.3 --- DNA sequencing --- p.37 / Chapter 2.4 --- Overexpression of modified Trichosanthin in E. coli --- p.42 / Chapter 2.5 --- Purification of modified Trichosanthin --- p.43 / Chapter 2.6 --- Breaking of Disulphide bridge between modified TCS --- p.44 / Chapter 2.7 --- Coupling of DX T40 to modified Trichosanthin --- p.44 / Chapter 2.8 --- Biological activities of modified Trichosanthin and Dextran-modified trichosantin conjugates --- p.46 / Chapter 2.9 --- Immunogenicity of modified Trichosanthin and Dextran-trichosanthin conjugates --- p.50 / Chapter 2.10 --- Nephrotoxicity of Trichosanthin and Dextran-trichosanthin conjugates --- p.53 / Chapter Chapter 3 --- Construction of TCS mutants --- p.61 / Chapter 3.1 --- Introduction --- p.61 / Chapter 3.2 --- Method --- p.61 / Chapter 3.3 --- Results --- p.62 / Chapter 3.3.1 --- Construction of K173C mutant --- p.62 / Chapter 3.3.2 --- Construction of R29C mutant --- p.64 / Chapter 3.3.3 --- Construction of K173C R29C double mutant --- p.65 / Chapter 3.4 --- Discussion --- p.66 / Chapter Chapter 4 --- "Expression,Purification and Ribosome- inactivating activities of Modified Trichosanthin proteins" --- p.87 / Chapter 4.1 --- Introduction --- p.87 / Chapter 4.2 --- Method --- p.87 / Chapter 4.3 --- Results --- p.88 / Chapter 4.3.1 --- "Expression, purification and ribosome-inactivating activity of K173C" --- p.88 / Chapter 4.3.2 --- "Expression ,purification and ribosome-inactivating activity of R29C" --- p.89 / Chapter 4.3.3 --- "Expression, purification and ribosome-inactivating activity of K173C R29C" --- p.90 / Chapter 4.4 --- Discussion --- p.91 / Chapter Chapter 5 --- Coupling of Dextran T40 to modified Trichosanthin --- p.108 / Chapter 5.1 --- Introduction --- p.108 / Chapter 5.2 --- Method --- p.109 / Chapter 5.3 --- Results --- p.109 / Chapter 5.3.1 --- Coupling of R29C --- p.109 / Chapter 5.3.2 --- Coupling of K173C --- p.111 / Chapter 5.3.3 --- Coupling of R29CK173C --- p.111 / Chapter 5.4 --- Discussion --- p.111 / Chapter Chapter 6 --- Biological Activities of modified Trichosanthin and Dextran-modified trichosanthin conjugates --- p.128 / Chapter 6.1 --- Introduction --- p.128 / Chapter 6.2 --- Method --- p.128 / Chapter 6.3 --- Results --- p.130 / Chapter 6.3.1 --- In vivo Biological activity- Mid-term abortifacient activity --- p.130 / Chapter 6.3.2 --- In vitro biological activities / Chapter 6.3.2a --- Ribosome-inactivating activity --- p.131 / Chapter 6.3.2b --- Anti-tumour activity --- p.132 / Chapter 6.4 --- Discussion --- p.133 / Chapter Chapter 7 --- Immunogenicity of Dextran-modified trichosanthin conjugates --- p.156 / Chapter 7.1 --- Introduction --- p.156 / Chapter 7.2 --- Method --- p.157 / Chapter 7.3 --- Results / Chapter 7.3.1 --- Immunogenicity without denaturation of protein --- p.158 / Chapter 7.3.2 --- Immunogenicity with denaturation of protein --- p.161 / Chapter 7.4 --- Discussion --- p.162 / Chapter Chapter 8 --- Nephrotoxicity of Trichosanthin and Dextran-Trichosanthin conjugates --- p.199 / Chapter 8.1 --- Introduction --- p.200 / Chapter 8.2 --- Method --- p.202 / Chapter 8.3 --- Results --- p.202 / Chapter 8.3.1 --- Functional study on nephrotoxicity of Trichosanthin --- p.202 / Chapter 8.3.2 --- Morphological study on the nephrotoxicity of Trichosanthin --- p.203 / Chapter 8.3.3 --- The effect of coupling of Dextran T40 on the nephrotoxicity of Trichosanthin --- p.206 / Chapter 8.4 --- Discussion --- p.207 / Chapter Chapter 9 --- General Discussion --- p.244 / References --- p.252

The blood-brain barrier BBB refers to the set of specialized endothelial cells that line the vasculature in the brain and effectively control movement of molecules into and out of the brain. While necessary for proper brain function, the BBB blocks 98% of drugs from entering the brain and is the most significant barrier to developing therapies for neurodegenerative diseases. Active transport allows some specific molecules to cross the BBB, but therapeutic development using this route has had limited success. A number of techniques have been used to bypass the BBB, but are often highly invasive and ineffective. Over the last two decades, a minimally invasive technique to transiently open the BBB has been under development that utilizes transcranial focused ultrasound (FUS) in combination with intravascular microbubble contrast agents. This method is often carried out in conjunction with magnetic resonance imaging (MRI) to guide and assess BBB opening and has been referred to as MRI guided FUS (MRgFUS). Because of the utility of mouse models of neurological disease and the exploratory nature of MRgFUS, systems that allow BBB opening in mice are a useful and necessary tool to develop and evaluate this method for clinical application. In this dissertation project, a custom built, cost-effective FUS system for opening the BBB in mice was developed, with the objective of using this device to deliver therapeutics to the brain. Being a custom device, it was necessary to evaluate the ultrasound output, verify in vivo safety, and anticipate the therapeutic effect. The scope of the work herein consists of the design, construction, and evaluation of system that fulfills these requirements. The final constructed system cost was an order of magnitude less than any commercially available MRgFUS system. At this low price point, the hardware could allow the implementation of the methodology in many more research areas than previously possible. Additionally, to anticipate the therapeutic effect, molecules of pharmacologically-relevant sizes were delivered to brain with a novel, multispectral approach. Results demonstrated that the device was able to safely open the BBB, and macromolecule delivery showed that both molecule size and FUS pressure both influence the amount and distribution of molecules in the brain. Using different ultrasound pressures, the threshold for BBB opening was found to be ≥ 180 kPa (0.13 MI). The threshold for damage was found to be ≥ 420 kPa (0.30 MI), and was minor at this pressure, but extensive for higher pressure (870 kPa, 0.62 MI), in which minor damage was caused by this pressure. Performing a novel implementation of a diffusion model on the fluorescence images of 500, 70, and 3 kDa dextran resulted in calculated diffusion coefficients of 0.032 ± 0.015, 12 ± 6.0, and 0.13 ± 0.094 square microns per second, respectively.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Sept., 2009). Includes bibliographical references.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Sept. 9, 2009). Includes bibliographical references.

Une nouvelle famille de dérivés amphiphiles du dextrane a été obtenue par réaction du dextrane avec le 1,2-époxydodécane en milieu basique. Deux voies de synthèse ont été étudiées. La première en milieu aqueux dispersé n’a permis d’obtenir que des taux de modification faibles (< 10 %) car l’homopolymérisation de l’époxyde est prépondérante. Au contraire, la réaction en milieu organique homogène a permis la synthèse de dérivés dont le taux de modification atteint 164 %. Des émulsions huile dans eau ont été préparées par sonication en présence de plusieurs dérivés hydrosolubles (τ ≤ 25 %). La fraction volumique d’huile (hexadécane ou nujol) est comprise entre 10 % et 50 %. La taille des gouttelettes augmente avec la fraction volumique d’huile mais ne dépend pas du taux de modification du dextrane entre 10 et 25 %. Ces émulsions ont un comportement de gel d’autant plus marqué que la fraction volumique d’huile dispersée augmente. Des émulsions inverses eau : chloroforme, stables pendant au moins 2 mois, ont été obtenues par sonication en présence de dérivés organosolubles (τ = 164 %). Le processus dynamique d’émulsification sous cisaillement a été étudié pour des émulsions directes (hexadécane / eau) dont la fraction volumique d’huile était comprise entre 10 et 60 % et pour différents gradients de vitesse. Un suivi continu in situ de la viscosité des émulsions et du rayon des gouttes formées montre que le temps caractéristique d’émulsification dépend du gradient de vitesse et du rapport des viscosités mais pas de la fraction volumique d’huile dispersée. Dans le cas d’un système newtonien, la viscosité finale et la taille finale des gouttes dépendent du gradient de vitesse appliqué alors qu’elles sont invariantes dans le cas du système non newtonien sur tout l’intervalle exploré / A new family of amphiphilic dextran derivatives was obtained by reaction of 1,2-epoxydodecane on dextran in basic medium. Two reaction procedures were examined. The first one was carried out in biphasic medium but produced only low degrees of hydrophobic substitution. Epoxide homopolymerization was indeed predominant. On the contrary, the reaction in a homogeneous organic medium allowed the synthesis of dextran derivatives with substitution degrees as high as 164 %. Oil-in-water emulsions were prepared by sonication in the presence of different hydrosoluble derivatives (τ ≤ 25 %). Oil volume fraction (hexadecane or nujol) ranged from 10 % to 50 %. The size of the emulsion droplets increased with the oil volume fraction but did not depend on the substitution degree of modified dextran between 10 and 25 %. These emulsions behave like a gel which strengthened with the oil volume fraction. Water-in-oil emulsions (water in chloroform) were obtained by sonication in the presence of organosoluble derivatives (τ = 164 %). They were stable over at least two months.Furthermore, dynamic emulsification process under shear flow was investigated for oil-in-water emulsions (hexadecane in water). The volume fraction of oil ranged from 10 % to 60 % and various shear rates were applied. Simultaneous in situ measurements of viscosity of emulsions and droplet size were performed. The characteristic time of emulsification depended on shear rate and viscosity ratio but was independent of the oil volume. For the newtonian system, final shear stress and final droplet size depended on the applied shear rate while they were invariant in the non newtonian system