Mini-dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2007. / The purpose of this investigation was to determine the effect of Chamaeleo dilepis dilepis on healthy volunteers (provers), and to record the signs and symptoms produced, so that it may be prescribed to those suffering from similar symptoms as determined by the Law of Similars. A further aim of the investigation was to compare the materia medica of Chamaleo dilepis dilepis as determined by proving symptoms to those remedies yielding the highest numerical value and total number of rubrics on repertorisation of the proving symptoms of Chamaeleo dilepis dilepis. / M

Mini-dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2007. / This study was conducted by administering Chamaeleo dilepis dilepis 30CH to healthy individuals with the aim of eliciting and documenting the resulting mental, emotional and physical symptomology. Chamaeleo dilepis dilepis was chosen as a substance based on it being indigenous to South Africa and as no other members of the Chamaeleonidae species have been proven / M

A dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2008. / Conduct a randomised, double blind, placebo controlled study in order to determine the sphere of action of the imponderable remedy Pink 30CH on healthy volunteers who recorded the signs and symptoms produced in order to determine the substances potential usefulness in a future clinical setting according to the Law of Similars. Determine and highlight the commonalities shared between the symptoms and themes produced by remedy Pink 30CH and the other selected imponderable remedies. In the homoeopathic drug proving of remedy Pink 30CH, provers were uninformed to both the nature of the substance as well as to the potency selected and used for proving purposes. Neither the provers nor the research investigator had any knowledge of who received the verum or the placebo until the end of the proving. Thirty (30) provers were selected after meeting the inclusion criteria of which thirty percent (30%) of the subjects received placebo in a randomised fashion. Verum and placebo were dispensed to the proving body in a set of six (6) powders which were taken sublingually three (3) times daily or until any proving symptoms were experienced. All provers were examined and made to record in their journals before, during and after the administration of the proving substance so as to serve as their own intra-individual controls. At the end of the proving period all journals were then recalled and all proving data recorded was then collated and edited into a repertory and materia medica format, which was then used to formulate a homoeopathic drug picture of the remedy that could be used in future clinical settings. The homoeopathic drug picture thus derived was then analysed with the aim of highlighting the important themes that were elicited during the proving. These symptoms and themes were then related and compared to seven (7) other imponderable remedies: Luna (Moonlight); Magnetis Polus Arcticus (North pole of the magnet); Magnetis Polus Australis (South pole of the magnet); Positronium (Anti-matter); Radium bromatum (Radium bromide); Sol (Sunlight) and X-ray, in order to expand the overall understanding of the commonalities shared by the imponderabilia as an entirety. / M

As the global population increases, estimated to reach 9 billion by the year 2050, global food security becomes a priority. A prominent disease implicated in financial loss to the poultry industry, on a global scale, is infectious bursal disease virus (IBDV). Vaccination against IBDV is sub-optimal and difficult to deliver. Therefore it has been highlighted as a key area for the development of an oral vaccine. A highly conserved capsid protein from IBDV (VP2) was identified, and sub-cloned into a bacterial expression cassette. This protein was fused to a potential carrier protein (cholera toxin B chain), previously shown to mediate the exit from the gut lumen into the lamina propria. However, to allow this antigen to reach the mucosal associated lymphoid tissue, the protein antigen must remain in its native conformation through the stomach. This work developed a delivery system to meet this end. By encapsulation within a fatty acid coated, protein adsorbed-solid core drug delivery system (SCDDS), it was shown that a model protein antigen (GST-GFP) could be protected from low pH (i.e. pH 2.0) and proteases. Protease protection was demonstrated against the exposure of myristic acid coated, GST-GFP adsorbed silica, to both protease K (100 μU, 1hour (100% protection)) as well as a simulated in vitro stomach environment (pepsin (0.2 mg) (100% protection)). Having demonstrated protection from proteases at pH 2.0 and pH7.4, it was then shown that GST-GFP could be released from the myristic acid coated silica at pH 8.8 (consistent with the small intestine). As much as ~15% (15 μg) (w/w) GST-GFP was released from the aforementioned system. The evidence supporting this conclusion was drawn from molar ellipticity calculations that showed the proportion of helical structure in relation to regions of beta sheet remained constant, pre-adsorption and post-release (16.9% α-helix, 20.8% β-sheet, 43.3% random coil). Finally, this work has shown that if a recombinant antigen was fused to cholera toxin B chain (but not shiga toxin B chain), it was capable of mediating transcytotic passage across, differentiated, polarised Caco-2 cells (1/1000th input (10 ng)). In conclusion and based upon the evidence provided above, this system warrants further optimisation and investigation to serve as an oral vaccine delivery system to treat IBDV.

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homeopathy, Durban University of Technology, Durban, South Africa, 2016. / INTRODUCTION: The idea of the memory of water arose in the laboratory of immunologist, Jacques Benveniste in the late 1980s where his research into allergies took him deeper intotrying to find out how the smallest amount of a substance could affect an organism. He experimented with Homeopathy by using highly diluted antibodies in his basophil degranulation test. He observed that highly dilute biological agents were still able to trigger the relevant biological system. (Thomas, 2007) The memory of water is a controversial topic that requires more research to be properly understood and as such, it is the researcher’s aim to gain insight on the memory of water. METHODOLOGY: The purpose of this study was to examine the effect that the preparation of a Homeopathic remedy (Natrum muriaticum) has on water, as its solvent, using the glass stain analysis as outlined by Kroplin (2001). The possible ability of water to hold and store the memory of its solute, sodium chloride, was investigated. The results would be added to the critical reflection on current literature available. In an experimental double blind study, Kroplin’s glass stain method was used to analyse the following:  The mother solution samples.  The 9CH potency samples (within Avogadro’s constant).  The 30CH potency samples (past Avogadro’s constant).  As well as the water sample used to make the remedy as the control. The above four samples were supplied from the following two manufacturers:  Durban University of Technology (DUT) manufactured by the researcher (appendix 2).  Samples manufactured by one commercial homeo-pharmaceutical company, ParcevalPharmaceuticals (appendix 3). This research aimed to investigate, using homeo-pharmaceutical principles (dilution and succussion), the structural influence of a solute on water after the solution is diluted beyond Avogadro’s constant. Repetition of the 5 experiment in week six aimed to investigate the validity of expiry time proposed by the homeopathicpharmacopoeia. RESULTS:  The stained picture patterns took on a consistent form of a starry night and the ‘stars’ seemed to increase in mass with potentisation suggesting that the homeopathic remedy manufacture process affects the outcome of the water’s form.  Overall consistency in picture patterns between both experimenters suggesting minimal observer effect.  The experiment was repeated to test expiry date and these pictures displayed degradation and thus seemed to offer validation towards homeopathic remedy expiration.  Although abstract qualitative results, a notable difference in water control and potentised water samples offer enough evidence for further investigations. / M

No description available.

The prevalence of Type 2 diabetes mellitus (T2DM) has increased dramatically over the past 10 years in Malaysia due to the modernisation of the country. The most recent national health survey revealed that more than 15.2% of Malaysian adults are suffering from the diseases. Insulin treatment has been demonstrated to play a clinically significant role to improve glycaemic control among selected Type 2 diabetes mellitus (T2DM) patients. However, studies from several local hospitals showed that more than half of T2DM patients are reluctant to initiate insulin treatment. There is an increasing trend for the Malaysian healthcare sector to invest in understanding patients’ health experiences. This qualitative study focused on T2DM patients’ insights about their lived-experience of using insulin treatment as part of their diabetes management. This study aimed to understand the facilitators, which encourage patients to accept insulin treatment and also the psychological, social and behavioural barriers to effective diabetes management. Drawing on interview data with 37 participants, the three main barriers to initiate insulin treatment were worries about inability to handle using insulin, a sense of personal failure and negative perceptions of injections due to past experiences. The facilitators that encourage patients to accept insulin treatment were prior exposure to insulin injections, better side effect profile and wanting a better quality of life. However, there were many obstacles faced by T2DM patients when coping with insulin treatment such as the restriction of lifestyle and concerns about social acceptance. In general, knowledge of T2DM and insulin treatment are still lacking among the Malaysians interviewed in this study. There are still many distorted beliefs and misconceptions about insulin among T2DM patients. At the same time, patients’ concerns and beliefs regarding insulin use are greatly influenced by their experience and support from others. Many participants felt embarrassed and self-conscious when self-injecting insulin in public places. They felt that the Malaysian public often associate the use of injections to drug abuse. Social stigma is one key point, which leads to poor adherence to insulin treatment. Thus it is crucial to increase public awareness about insulin treatment in order to help these patients to be more comfortable about injecting, and also to encourage other people to be more open minded towards insulin treatment. Apart from raising public awareness, there is a need to empower T2DM patients with adequate knowledge through early, simplified, tailored education focusing on the disease nature and the role of insulin. Making them more aware of their health condition and the uses of modern insulin devices at an early stage will better prepare them mentally for insulin therapy.

Adverse drug reactions remain a major health issue with delayed type hypersensitivity reactions developing in a high number of individuals. The cellular immunological processes that underlie drug-specific responses in hypersensitive patients have been previously described; however the involvement of the humoral immune system has not been studied in great detail. Consequently, this thesis explores the nature of the piperacillin-specific B cell response in hypersensitive patients and compares the cellular and humoral immune response that develops in patients with cystic fibrosis (CF) exposed to repeated courses of the drug. Initial studies involved characterization of B cell proliferation, B cell phenotype and the nature of total and drug-specific IgG antibody secretions using peripheral blood mononuclear cells (PBMC) from hypersensitive patients. For comparison PBMCs from 2 groups of individuals were assessed: piperacillin naïve healthy volunteers and piperacillin tolerant patients with CF. ELISA, and ELISpot were used to detect piperacillin-specific B cells responses and IgG secretion. T lymphocyte proliferation was assessed with the lymphocyte transformation test (LTT). T lymphocytes from hypersensitive patients, but not tolerant patients or naïve donors were stimulated to proliferate in the presence of the drug. The peak concentration for T cell activation was 1 mM. Phenotypic assessment of hypersensitive patients B-cells revealed an increase in CD19+CD27+ expression in response to piperacillin treatment in vitro. IgG secreting immortalized B-cell lines also expressed a pure CD19+CD27+ phenotype. Piperacillin stimulation of hypersensitive patient PBMC also led to an increase in the secretion of IgG. In contrast, IgG secretion was not detectable following piperacillin stimulation of PBMC from tolerant patients and healthy controls. Western blotting and mass spectrometric methods were applied to characterize -lactam-protein covalent binding. Bovine serum albumin (BSA) binding was time- and concentration-dependent with hapten densities (i.e., the extent of selective lysine residue modification) and anti-piperacillin antibody binding affinity increasing with increasing molar ratios. Lysine residues in BSA at positions 4, 12, 131, 132, 136, 211, 431, 524, and 537 were modified by piperacillin. Epitope profiles also showed similar lysine residues were modified with amoxicillin, benzylpenicillin and flucloxacillin though the extent of ionisation at each site of modification was drug-dependent. A hapten inhibition ELISA used to assess the specificity of the antidrug antibodies revealed the total antibody binding to aztreonam, amoxycillin, benzylpenicillin and penicillin V BSA adducts. This indicates a lack of cross-reactivity with piperacillin-specific IgG antibodies. Subsequently, LTT and ELISA were employed to screen the piperacillin-specific T cell response and IgG antibodies during piperacillin therapy. It was established that piperacillin-specific T cells were detectable on and following clinical diagnosis of hypersensitivity. Moreover, piperacillin-specific T cell responses were detected in a small number of patients currently classified as drug tolerant. A significant difference in piperacillin-specific IgG was observed when plasma form LTT positive and negative blood samples were compared. LTT positivity was associated with higher levels of piperacillin-specific IgG. Furthermore, a significant decrease in piperacillin-specific IgG was seen 24 h post-desensitisation (graded drug challenge). Piperacillin-specific T cell clones isolated from hypersensitive patients were used to explore the effect of plasma bearing anti-piperacillin IgG on the T cell response. Eleven piperacillin-specific CD4+ and CD8+ T-cell clones were generated from 2 hypersensitive patients. All clones were stimulated to proliferate with piperacillin in a concentration-dependent manner. IFN-γ and IL-5 secretion was seen to predominate following piperacillin stimulation. There were no differences in piperacillin-specific T-cell proliferation when piperacillin-specific antibody bearing plasma and plasma from naive volunteers were compared. However, attenuation in IFN-γ secretion was observed with plasma bearing anti-piperacillin antibodies alone. Collectively, the data presented in this thesis begins to describe the different components of the drug-specific humoral and cellular immune response that develops in piperacillin hypersensitive patients with CF.

In recent years, a number of reports have focused on the use of polyesters in drug delivery due to their intrinsic biocompatibility and biodegradability. In this thesis, aliphatic polyesters were synthesized by polycondensation reaction and ring opening polymerization reactions. The properties of the polymers and drug delivery potential of the resultant materials were evaluated. In the polycondensation reactions, a series of aliphatic polyesters of similar molecular weight were synthesized by reacting 1,10-decanediol with different ratios of succinic acid/phenylsuccinic acid and the effects of phenyl group side-chain substitution on polymer properties was investigated. A solvent-free melt polycondensation method using scandium (III) triflate as catalyst at an industrially relevant temperature (120 °C) was used. As the phenyl content increased, the polymers changed from semicrystalline to amorphous in state. The loading capability of polymers was checked by formulating nanoparticles containing coumarin 6 as a fluorescent dye analogue of active drugs. A polymer with a 70/30 ratio of succinic acid and phenylsuccinic acid showed the highest dye loading among the set of materials synthesised. This polymer was found to be degradable over time under selected experimental conditions. Amphiphilic block co-polymers from the PluronicTM class were used to stabilize, in PBS, nanoparticles formed from these polyesters by nanoprecipitation routes. The metabolic activity, cell membrane integrity and lysosomal functions of C3A cells dosed with the polymers were determined to observe the cytocompatibility of the highest dye-loaded nanoparticles. Activity relative to undosed C3A cells was retained at more than 80% in the all of the assays. Imaging of Pluronic coated and uncoated nanoparticles in C3A cells suggested that both types of the nanoparticles were endocytosed in the early stage of the study (within 10 min). The internalization of nanoparticles was increased progressively over the study time. These results indicated the possible utility of the selected polymers in diagnostic and delivery applications. Ring opening polymerization (ROP) reactions were used for the synthesis of a diblock (mPEG-b-PεDL) and a triblock (PεDL-b-PEG-b-PεDL) copolymer from a seven membered ε-decalactone (ε-DL) monomer obtained from renewable sources. A diblock (mPEG-b-PεDL) copolymer was compared with structurally similar mPEG-b-PCL copolymer synthesized via ROP of ε-caprolactone (ε-CL) monomer, which can be considered as a non-renewable monomer. A six membered δ-decalactone (δ-DL) was also used for the synthesis of a diblock copolymer (mPEG-b-PδDL) to compare the reaction kinetics and properties of the copolymers. The copolymers were prepared via bulk polymerisation using 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) as a metal-free catalyst to replace the conventionally used stannous octoate [Sn(Oct)2]. A higher polymerization efficiency was achived with TBD compared to Sn(Oct)2 catalyst. However, a notable difference in the reaction temperature required for ε-DL and δ-DL polymerization was observed. The comparison with a structural analogue, i.e. ε-CL, demonstrated that the ε-DL polymerization was inhibited due to the presence of the alkyl chain of ε-DL monomer. However, a higher reaction time (12 h for TBD and 24 h for Sn(Oct)2) in CROP of ε-DL was addressed by using microwave based ring opening polymerization (MROP) reaction. The MROP was adopted as a ‘green’ and cheap heating method alternative to conventional heating (CROP) for the synthesis of mPEG-b-PεDL diblock copolymers using TBD as a catalyst. All the reactions were conducted in bulk. The MROP was designed based on the dielectric properties of all the reacting materials, as it was found that ε-DL monomers showed good absorption of MW radiation (tanδ>0.5). Accordingly, MROP resulted in a higher rate of ε-DL polymerization compared to CROP but comparison of the synthesis of mPEG-b-PCL copolymer by MROP indicated that the presence of the alkyl chain in ε-DL monomer significantly reduced the rate of polymerization. The synthesized mPEG-b-PεDL copolymer was investigated as a potential drug delivery vehicle for solubilization and controlled delivery of indomethacin. The indomethacin loading and release from mPEG-b-PεDL micelles (amorphous core) was compared against well-established mPEG-b-PCL micelles (semicrystalline core). The drug-polymer compatibility was also determined through a predictive computational approach to access the drug solubilisation (or drug loading) into hydrated micelles. The micelles were prepared by solvent evaporation method and characterized for size, morphology, indomethacin (IND) loading and release. Both of the micelle formulations showed a uniform distribution of spherical micelles with size <60 nm. However, a significantly higher size of empty mPEG-b- PεDL micelle was observed compared to mPEG-b-PCL micelles. A higher compatibility of the drug was predicted with PCL core as determined by modified Flory-Huggins interaction parameters (sp) using the Hanson solubility parameter (HSP) approach. The compatibility of the drug was determined for both of the segments (hydrophilic and hydrophobic) of the copolymers and found to be in the order of sp (PεDL)> sp (mPEG)> sp (PCL). The predictions suggested that more IND should encapsulate within the micelles with PCL core compared to PDL core, but the IND loading experiments revealed an overall higher loading in PεDL core (6.55 wt%) compared to PCL core (5.39 wt%) (P < 0.05, unpaired student’s t-test). However, consideration of the IND loading per unit volume of the micelles revealed that the PCL cored micelles was able to load 1.5 times more compared to the PεDL cored micelles. This result illustrated the higher compatibility of the IND with PCL core in accordance with the solubility parameter calculations. These data also suggested that the overall higher IND loading in PεDL core was attributable to the amorphous nature of the core which increased the core volume by 1.81 times compared to the PCL core. Drug release studies showed the sustained release pattern from both of the micelle systems although the semicrystalline PCL core (80% drug release in 110 h) was able to release the drug for a longer period compared to PεDL core (80% drug release in 72 h). Cell viability tests demonstrated the cytocompatibility of the mPEG-b-PεDL polymer. The micelles were internalized effectively in the early stages of the study and progressively increased with time. The results of the present thesis suggested that novel aliphatic polyester can be good candidates for the drug delivery applications and further studies can explore the possible applications of these polymers in the biomedical field.

O uso de produtos naturais, principalmente de origem vegetal, na terapêutica medicinal representa a forma mais antiga e difundida de medicação. Ficus pumila, planta amplamente utilizada na ornamentação de muros e paredes, conhecida como hera-miúda ou unha-de-gato, apresenta inúmeras atividades biológicas. Pela população é utilizada como antitumoral, antiinflamatório, tônico e no tratamento de doenças como diabetes e hipertensão. Neste contexto, o presente trabalho teve como objetivo estudar a composição química e as atividades antimicrobiana e antioxidante, além da citotoxicidade de extratos hidroetanólicos de caule, raiz, folhas e frutos secos e frescos de Ficus pumila. Em relação à composição química, os resultados encontrados revelaram a presença de taninos e flavonoides em todos os extratos. O maior teor de compostos fenólicos foi exibido pela raiz seca (724,39 mg AG/g) e o menor pelo caule fresco (84,8 mg AG/g). O maior teor de flavonoides foi apresentado pela folha seca (15,30 mg quercetina/g) e o menor pelo caule seco (1,29 mg de quercetina/g). Os testes microbiológicos indicaram a atividade dos extratos contra Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus e Proteus mirabilis. Os melhores resultados foram exibidos pelos extratos de caule e raiz. Os extratos não apresentaram atividade contra Mycobacterium tuberculosis H37 e Mycobacterium bovis (BCG). A maior atividade antioxidante foi demonstrada pelo extrato de caule fresco (12,81 μg/mL) e a menor pelo extrato de folha fresca (58,56 μg/mL). A avaliação da citotoxicidade frente à cultura celular revelou a ausência de citotoxicidade dos extratos de caule, raiz e fruto nas concentrações testadas. Concluiu-se que Ficus pumila pode ser, no futuro, uma fonte de compostos antioxidantes e antimicrobianos para o desenvolvimento de novos fármacos. / The use of natural products, mainly of vegetable origin in medical therapy is the oldest form of medication and widespread. Ficus pumila plant widely used in the decoration of walls and partitions, known as Ivy - girl or cat's claw, has numerous biological activities. By population is used as antitumor, anti-inflammatory, tonic and also for the treatment for some diseases such as diabetes and hypertension. In this context, the present work aimed to study the chemical composition and antimicrobial and antioxidant activities, beyond the cytotoxicity of hydroethanolic extracts of root, stalk, leaves and dried and fresh fruits of Ficus pumila. Regarding the chemical composition, the results revealed the presence of tannins and flavonoids in all extracts. The higher content of phenolic compounds was screened by dried root (724.39 mg AG / g) and the lowest by the fresh stem (84.8 mg AG/ g). The highest content of flavonoids was presented by drought (15.30 mg quercetin/ g) and the lowest by dry leaf stem (1.29 mg quercetin/ g). Microbiological tests indicated the activity of the extracts against Bacillus subtilis, Bacillus cereus, Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus and Proteus mirabilis. The best results were shown by the extracts of stem and root. The extracts showed no activity against Mycobacterium tuberculosis and Mycobacterium bovis H37 (BCG). The highest antioxidant activity was shown by extracts of fresh stem (12.81 mg/ mL) and lowest for fresh leaf extract (58.56 mg/ mL). The cytotoxicity against the cell culture revealed the absence of cytotoxicity of extracts of root, stalk and fruit concentrations tested. It was concluded that Ficus pumila may be in the future a source of antioxidants and antimicrobial compounds for drug development.