Vaccination plays a very important part in daily life. It is essential to get vaccinated at an early age. The conventional parented method used is not always effective and not cost efficient. It requires qualified personnel and sterile conditions for administration of the vaccines. The aim of this study was to investigate the effect of chitosan, N-trimethyl chitosan chloride (TMC) and Emzaloid™ particles on the local and systemic immune response of mice after oral vaccination with Diphtheria toxoid (DT). The different formulations used were chitosan microparticles (± 10 µm), chitosan nanoparticles (± 400 nm), TMC microparticles (± 5 µm), Emzaloid microparticles (± 4 µm) and Emzaloid nanoparticles (± 500 nm). All of these formulations proved to be very good delivery systems and can entrap large amounts of the antigen. Balb/c mice were used to determine the local and systemic immune response of these formulations. The mice were vaccinated orally on three consecutive days in week 1 and 3 with 40 Lf DT per week with a total volume of 300 µl. Blood samples were taken from the mice and analysed for a systemic immune response (IgG). The same mice were used to determine the local immune response (IgA). Faeces were collected from each mouse on day 1, 3, 4, 6, 14 and 20 for analysis. An enzyme-linked immunosorbent assay (ELISA) was used to determine IgG and IgA titers. It can be concluded that chitosan nanoparticles was the only formulation with a higher response than that of the currently used vaccine. Emzaloid nanoparticles showed no significant difference in response when compared to the currently used vaccine. All the other formulations showed a much smaller response than that of the conventional method of vaccination. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Tuberculosis has for decades been the leading cause of death, worldwide, originating from merely one infectious matter i.e. the bacilli Mycobacterium tuberculosis (MTB). It is killing approximately 1.5 million people every year. The World Health Organization (WHO) estimates that 2 billion people might be infected by this specific bacterium, and that there emerges about 9 million new, active cases of TB each year. The aim with this thesis is to elucidate the possibilities and the difficulties with two new drugs against susceptible and resistant, latent and replicating strains of M. tuberculosis. A search for relevant articles on Pub Med, through the university library, was undertaken and approximately 35 articles were found. These articles were read; facts were sorted out and used for this paper. Figures were found through Creative Commons. The two new drugs discussed in this paper are TMC 207 and PA-824. They have two different mechanisms of action, and additionally and most importantly, that differ from the drugs used as first-line and second-line options. TMC 207 targets the mycobacterial ATP synthase. PA-824, a pro-drug, targets the cell wall synthesis and in addition causes respiratory poisoning, through the release of nitric oxide. The different mechanisms are vital in order to combat emerging resistance, due to various missense mutations in specific genes in the bacilli. The bactericidal activity of the drugs against mycobacteria is high, promising a successful cure for MDR (multi drug resistant)/XDR (extensively drug resistant) patients. The median survival is 4.1 years for MDR patients and 2.9 years for XDR patients, with currently available treatments. This is noticeably worse than some cancer prognoses. Perhaps with these drugs there is even a possibility of shortening the treatment time. The adverse events are mild to moderate, for both drugs. This is another additive advantage, since the toxicity of the drugs will be minimal and hopefully tolerable, and most importantly will bring about treatment commitment and the sought elimination of the disease. However, as with all new drugs the outcomes are still to be proven in real settings, the complex fields (in low- and middle income countries, with difficult TB cases), and with complicated cases (e.g. HIV co-morbidity) during a longer period of time. Reporting and evaluating the outcomes is crucial, since whatever is displayed from the drug consumption and the effects of it can lead to alterations in regimens, doses and treatment commitment.

El informe describe la Construcción de Obras de Arte en el Corredor Vial Interoceánico Sur Perú – Brasil Tramo 3: Puente Inambari en la Región Madre de Dios límite con Cuzco, hasta la ciudad fronteriza Iñapari con Brasil. En las obras de arte que menciono: Defensa Ribereña, Cunetas de Drenaje revestida en concreto y en césped respectivamente, Cuneta de Drenaje Urbano, Veredas Urbanas, Otras Obras de Arte (Pases Vehiculares, Pases Peatonales, Dispositivos de Amortiguamiento y Encausamiento de Alcantarillas); se define cada una de ellas, los materiales que se utilizan, y se explica el proceso constructivo. Se ve la importancia de la utilización de equipos de última generación en la topografía (estación total, GPS) y en el estudio de suelos (densímetro nuclear), entre otros, haciendo uso además de programas de computación asociados a estos. Además se hace una descripción del monitoreo de los trabajos realizados, supervisión de campo, programación e informe, reuniones semanales de coordinación y por último se hace mención al departamento de Seguridad y Salud que tienen el objetivo principal de garantizar las condiciones de seguridad y salvaguardar la vida, la integridad física y bienestar de los trabajadores en general. The report describes the Construction Works of Art in South Interoceanic Highway Peru - Brazil Section 3: Bridge Inambari in the Madre de Dios region bordering Cuzco, to the border town with Brazil Iñapari. In works of art that I mention: Riverfront Defense, Drainage Ditches lined with concrete and grass respectively Cuneta Urban Drainage, Urban Trails, Other Works of Art (Vehicle Passes, Passes Pedestrian, damping devices and Sewer Indictment) defined each of them, the materials used, and explains the construction process. We see the importance of using the latest equipment in the topography (total station, GPS) and the study of soils (nuclear densimeter), among others, also using computer programs associated with them. Besides a description of monitoring the work, field supervision, scheduling and reporting, weekly coordination meetings, and finally referred to the Health and Safety department with the primary aim of ensuring the security and safeguarding life, physical integrity and welfare of workers in general.

No description available.

L'hydrogène moléculaire est la molécule la plus simple et la plus répandue dans l'Univers. Elle se présente sous deux formes, ortho- et para- H$_2$, correspondant aux différents alignements des spins de ses deux noyaux. Le rapport ortho/para de H$_2$ est un paramètre essentiel pour comprendre les processus collisionnels inélastiques et réactifs dans les milieux astrophysiques moléculaires. Dans cette thèse, nous nous sommes intéressés à la détermination de ce rapport dans les nuages sombres, régions où H$_2$ ne peut pas être observée directement. Dans ce but, nous avons utilisé la molécule de formaldéhyde (H$_2$CO) dont l'excitation rotationnelle dans ces sources est dominée par les collisions avec H$_2$. Une transition particulière a été choisie pour cette étude : la raie à 6 cm (4,8 GHz) de ortho-H$_2$CO observée en absorption devant le fond diffus cosmologique. Si des études précédentes ont montré que cette absorption (antimaser) peut être expliquée par des effets collisionnels, aucune n'a étudié jusqu'à présent l'impact des formes ortho- et para-H$_2$ sur l'absorption. Nous présentons, dans un premier temps, nos calculs haute-précision des taux d'excitation rotationnelle entre (ortho-,para-)H$_2$CO et (ortho-,para-)H$_2$. Nous montrons qu'il existe des différences significatives sur les taux de collisions selon le type de projectiles, et en particulier qu'il existe des différences entre ortho- et para-H$_2$. Nous présentons ensuite l'utilisation de ces taux dans un modèle de transfert radiatif afin de reproduire les observations que nous avons menées au Green Bank Telescope sur la transition a 6 cm de ortho-H$_2$CO en direction de 3 nuages sombres (B68, L134N et TMC-1). Nous montrons que les différences dans les taux de collisions calculés avec ortho- et para-H$_2$ ont un impact significatif sur les simulations, nous permettant ainsi d'apporter des contraintes sur la valeur du rapport ortho/para de H$_2$ dans ces milieux. Nous traitons en particulier l'exemple de B68, prototype de c\oe ur pre-stellaire.

Previous studies have demonstrated that chitosan and its derivative, N-trimethyl chitosan chloride (TMC) are effective and safe absorption enhancers to improve mucosal delivery of macromolecular drugs including vaccines. Furthermore, chitosan and TMC can easily form microparticles and nanoparticles, which have the ability to encapsulate large amounts of antigens. Emzaloid™ technology has proven in the past to be an effective delivery system for numerous drugs. Emzaloids can entrap, transport and deliver large amounts of drugs including vaccines. In this study, the ability of chitosan microparticles and nanoparticles, TMC microparticles as well as micrometer and nanometer range Emzaloids to enhance both the systemic and mucosal (local) immune response against diphtheria toxoid (DT) after nasal administration in mice was investigated. The above mentioned formulations were prepared and characterised according to size and morphology. DT was then associated to the chitosan microparticles and nanoparticles as well as TMC microparticles to determine the antigen loading and release. It was found that the loading efficacy of the formulations was 88.9 %, 27.74 % and 63.1 % respectively, and the loading capacity of the formulations was 25.7 %, 8.03 % and 18.3 %. DT loaded and unloaded (empty) chitosan microparticles and nanoparticles, TMC microparticles, micrometer and nanometer range Emzaloids as well as DT in phosphate buffered saline (PBS) were administered nasally to mice. Mice were also vaccinated subcutaneous with DT associated to alum as a positive control. All mice were vaccinated on three consecutive days in week 1 and boosted in week 3. Sera was analysed for anti- DT IgG and nasal lavages were analysed for anti-DT IgA using an enzyme linked imrnunosorbent assay (ELISA). In the study conducted to determine the systemic (IgG) and local (IgA) immune responses it was seen that DT associated to all the experimental formulations produced a systemic immune response. The said formulations produced a significantly higher systemic immune response when compared to the formulation of DT in PBS. Furthermore, the mice vaccinated with DT associated to the TMC formulations showed a much higher systemic immune response than the mice that were vaccinated subcutaneously with DT associated to alum, whereas the other formulations produced systemic immune responses that were comparable to that of DT associated to alum. It was also found that DT associated to the experimental formulations produced a local immune response, however only DT associated to TMC microparticles produced a consistent local immune response. It can be concluded from the in vivo experiments that the TMC formulations, moreover, the TMC microparticles is the most effective and promising formulation for the nasal delivery of vaccines. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

Previous studies have demonstrated that chitosan and its derivative, N-trimethyl chitosan chloride (TMC) are effective and safe absorption enhancers to improve mucosal delivery of macromolecular drugs including vaccines. Furthermore, chitosan and TMC can easily form microparticles and nanoparticles, which have the ability to encapsulate large amounts of antigens. Emzaloid™ technology has proven in the past to be an effective delivery system for numerous drugs. Emzaloids can entrap, transport and deliver large amounts of drugs including vaccines. In this study, the ability of chitosan microparticles and nanoparticles, TMC microparticles as well as micrometer and nanometer range Emzaloids to enhance both the systemic and mucosal (local) immune response against diphtheria toxoid (DT) after nasal administration in mice was investigated. The above mentioned formulations were prepared and characterised according to size and morphology. DT was then associated to the chitosan microparticles and nanoparticles as well as TMC microparticles to determine the antigen loading and release. It was found that the loading efficacy of the formulations was 88.9 %, 27.74 % and 63.1 % respectively, and the loading capacity of the formulations was 25.7 %, 8.03 % and 18.3 %. DT loaded and unloaded (empty) chitosan microparticles and nanoparticles, TMC microparticles, micrometer and nanometer range Emzaloids as well as DT in phosphate buffered saline (PBS) were administered nasally to mice. Mice were also vaccinated subcutaneous with DT associated to alum as a positive control. All mice were vaccinated on three consecutive days in week 1 and boosted in week 3. Sera was analysed for anti- DT IgG and nasal lavages were analysed for anti-DT IgA using an enzyme linked imrnunosorbent assay (ELISA). In the study conducted to determine the systemic (IgG) and local (IgA) immune responses it was seen that DT associated to all the experimental formulations produced a systemic immune response. The said formulations produced a significantly higher systemic immune response when compared to the formulation of DT in PBS. Furthermore, the mice vaccinated with DT associated to the TMC formulations showed a much higher systemic immune response than the mice that were vaccinated subcutaneously with DT associated to alum, whereas the other formulations produced systemic immune responses that were comparable to that of DT associated to alum. It was also found that DT associated to the experimental formulations produced a local immune response, however only DT associated to TMC microparticles produced a consistent local immune response. It can be concluded from the in vivo experiments that the TMC formulations, moreover, the TMC microparticles is the most effective and promising formulation for the nasal delivery of vaccines. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2005.

No description available.

This diploma thesis deals with the preparation and characterization of negatively charged catanionic vesicular systems and their combination with selected polycations. The catanionic vesicular system was prepared by mixing of two oppositely charged surfactants SDS and CTAB. The negative charge as well as the stability of the vesicular system was provided by the incorporation of phosphatidic acid. Polycations, DEAE and TMC, have been selected for use in a pharmaceutical applications. Characterization of the prepared systems was performed by measuring DLS and ELS. The results indicate that we were able to prepare stable negatively charged vesicles that were eligible to non-covalently interact with selected polycations.

Features recently added to the nuclear reaction software TALYS allow the use of the GEF model as a fission fragment generator. GEF generates data for fission fragment yields, total excitation energy (TXE), total kinetic energy (TKE) and individual fragment excitation energies (E*) with their standard deviations through Monte Carlo simulations for TALYS. In this work a framework named McPUFF was developed to couple GEF and TALYS and study the propagation of uncertainties in fission fragment data. The GEF model has a set of 94 parameters which were changed in order to produce perturbed output data. Both GEF and TALYS were modified to allow implementation of the Total Monte Carlo (TMC) method which is a method for handling the propagation of uncertainties throughout the simulation process. The developed framework allows the user to control aspects of the nuclear reaction using a set of input files. It is designed to be fast and memory efficient, performing simulations in parallel and storing all results in an object structure. A demonstration of the framework for the neutron induced fission of 235U, 238U and 239Pu was performed. Randomly perturbed sets of fission fragment data were created by GEF and fed into TALYS for simulation of the evaporation process using a Hauser-Feshbach statistical model. The impact that the perturbation of parameters in GEF has on results from TALYS were investigated for prompt particle multiplicity and energy. The results showed that a perturbation of parameter values in GEF by 3 percent has significant effects on values for fission observables produced by TALYS. The TALYS results for 235U showed an uncertainty for prompt neutron multiplicity of σn = 0.16 neutrons with an uncertainty for the neutron energy of σϵn = 0.03 MeV. The corresponding values for the uncertainty of the prompt γ-ray multiplicity were σγ = 0.10 γ-rays with an uncertainty for the γ-ray energy of σϵγ = 0.02 MeV. An investigation of how changes in the angular momentum of the fission fragments affects the evaporation process in GEF and TALYS was performed through the perturbation of the GEF parameter Jscaling. The results highlighted the need to scrutinize the handling of angular momentum in TALYS.