Due to the immuncompromised status of AIDS patients, secondary infections and malignancies are common. Conditions secondary to AIDS for which patients require treatment include Karposi's sarcoma (treated with methotrexate), varicella-zoster (treated with antivirals such as acyclovir) and herpes simplex (also treated with antivirals like acyclovir or idoxuridme). However the clinical efficacy of these drugs is limited by poor skin permeability. Few reports, however, have dealt with the delivery of low molecular weight hydrophilic drugs from these vesicles (El Maghraby et al, 2000). The aim of our study was to investigate in vitro permeation of methotrexate, acyclovir and idoxuridine across human epidermal membrane from elastic liposomes. The intent was to establish whether formulation of these hydrophilic drugs into elastic liposomes would enhance their skin permeation parameters. We developed and validated high-performance liquid chromatographic techniques for quantitative analysis of methotrexate, idoxuridine and acyclovir. Elastic liposomes were prepared from various phospholipids- phosphatidylcholine 78.6%; phosphatidylcholine 50%; hydrogenated phosphatidylcholine 90%; phosphatidylcholine 95% and surfactants - sodium cholate, sodium deoxycholate, Span 20, 40, 60, 80. These vesicles were characterised by transmission electron microscopy. The solubilities of methotrexate, acyclovir and idoxuridine were determined. Phospholipon G (95% phosphatidylcholine) was chosen for the preparation of the liposomes with different surfactants. Permeation of methotrexate, acyclovir and idoxuridme from these vesicles across human epidermal membrane was investigated. Flux values for methotrexate, acyclovir and idoxuridine values (J) obtained by curve-fitting of data using Easyplot were compared to those obtained by linear regression. We used Student's t-test to determine statistically significant differences in the flux values of the formulations. A computer program http://www.physics.csbsju.edu/stats/ttest- bulk-form.html was used for this purpose. Our results indicate that there are no statistically significant differences between flux values from elastic liposomes and saturated aqueous solutions. / Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2004.

An isobaric flow loop added to the Gas Hydrate And Sediment Test Laboratory Instrument (GHASTLI) is being investigated as a means of rapidly forming methane hydrate in watersaturated sand from methane dissolved in water. Water circulates through a relatively warm source chamber, dissolving granular methane hydrate that was pre-made from seed ice, then enters a colder hydrate growth chamber where hydrate can precipitate in a water-saturated sand pack. Hydrate dissolution in the source chamber imparts a known methane concentration to the circulating water, and hydrate particles from the source chamber entrained in the circulating water can become nucleation sites to hasten the onset of hydrate formation in the growth chamber. Initial results suggest hydrate grows rapidly near the growth chamber inlet. Techniques for establishing homogeneous hydrate formation throughout the sand pack are being developed.

We have conducted an experimental investigation of the solubility and speciation of Mo in HCl-, NaCl-, and NaOH-bearing water vapour, and of the partitioning of Mo between coexisting aqueous liquid and vapour at 300 to 370°C and up to saturated pressure. Our results indicate that Mo concentration is enhanced in HCl-bearing water vapour at fHCl > 0.1 bar, and in NaOH-saturated water vapour, but is unaffected by the presence of NaCl. This suggests that Mo speciates as MoO3·nH2O in water vapour at equilibrium with NaCl or fHCl < 0.1 bar. The dependence of SigmafMo on fHCl at higher acidity points to the formation of Mo oxychloride (MoO2Cl 2). For the system MoO3-NaOH-H2O, log Sigma fMo increases with increasing fH2O, and with log SigmafNa in a ratio of 0.28+/-0.4, but Sigma fNa does not change with increasing fH2O. This suggests the formation of a small proportion of sodium molybdate (Na 2MoO4) in addition to MoO3·nH2O. Our partitioning experiments show that at lower temperature and fluid density, Mo partitions more strongly into the liquid than the vapour, but the Mo concentration in the vapour increases as the temperature-pressure conditions approach those of the critical point of water (374°C and 221 bar), surpassing that in the liquid at ∼360°C. The results of our experiments indicate that both the liquid and vapour phases may be important for the transport of Mo in porphyry ore-forming systems, and that vapour-phase solubility is enhanced in high fHCl magmatic gases.

No description available.

Pt, Rh and chromite solubility in basalt-rhyolite mixtures at 1400°C, 0.1 MPa, FMQ +3.4 and FMQ (fayalite-magnetite-quartz-buffer) is presented. Melt samples were equilibrated on Pt90Rh10 loops and in chromite crucibles for up to 100 hours. Pt/Rh solubility decreased 20 and 7-fold respectively, progressing to rhyolitic compositions. Cr solubility decreased 3-fold (FMQ+3.4) and 4-fold (FMQ) over the same compositional interval. At FMQ+3.4, reduced Cr solubility, compared to FMQ, reflects Cr3+ and Fe3+ exchange, stabilizing Fe3+-rich spinel. As SiO2 increases, decreasing Pt/Rh and Cr solubility is interpreted to result from low abundances of non-bridging oxygens and lack of octahedral sites for Cr3+.Numerically simulated diffusive exchange between basalt and rhyolite predicts rapid alloy saturation at high fO2, but undersaturated mixtures at low fO2. Magma mixing produced Fe3+-rich spinel at high fO2; chromite undersaturation occurs near FMQ. Combined chromite and Pt-rich alloy saturation does not appear to result from magma mixing near FMQ.

Pt, Rh and chromite solubility in basalt-rhyolite mixtures at 1400°C, 0.1 MPa, FMQ +3.4 and FMQ (fayalite-magnetite-quartz-buffer) is presented. Melt samples were equilibrated on Pt90Rh10 loops and in chromite crucibles for up to 100 hours. Pt/Rh solubility decreased 20 and 7-fold respectively, progressing to rhyolitic compositions. Cr solubility decreased 3-fold (FMQ+3.4) and 4-fold (FMQ) over the same compositional interval. At FMQ+3.4, reduced Cr solubility, compared to FMQ, reflects Cr3+ and Fe3+ exchange, stabilizing Fe3+-rich spinel. As SiO2 increases, decreasing Pt/Rh and Cr solubility is interpreted to result from low abundances of non-bridging oxygens and lack of octahedral sites for Cr3+.Numerically simulated diffusive exchange between basalt and rhyolite predicts rapid alloy saturation at high fO2, but undersaturated mixtures at low fO2. Magma mixing produced Fe3+-rich spinel at high fO2; chromite undersaturation occurs near FMQ. Combined chromite and Pt-rich alloy saturation does not appear to result from magma mixing near FMQ.

No description available.

No description available.

RNA m5C methyltransferases are a group of enzymes that catalyze the transfer of a methyl group to a cytosine nucleotide of RNA. Only two of these enzymes have been well characterized: Fmu from E. coli and Trm4p from S. cerevisiae. YNLO22c is one of three ORFs identified in S. cerevisiae that have homology with both known and putative RNA m5C methyltransferases, but its encoded protein, YNLO22p, has not been confirmed to have enzyme activity. Verifying that YNLO22c encodes an RNA m5C methyltransferase will require adequate amounts of soluble YNLO22p for enzyme assays. A bacterial expression plasmid for YNLO22c was developed, but the result was insoluble protein. Therefore, several methods known to improve protein solubility were tested to develop a system in which a sufficient amount of soluble YNLO22p could be produced. Results of this study found that coexpression of YNLO22c with chaperone proteins can provide sufficient quantities of soluble YNLO22p. / Department of Biology

Azithromycin, an azalide and member of the macrolide group, is a broad spectrum antimicrobial, representing one of the bestselling antimicrobials worldwide. It is derived from erythromycin and exhibits improved acidic stability as a result of its structural modifications. The stable solid form of azithromycin is its dihydrate, although it also naturally occurs in its metastable forms, i.e. the monohydrate and anhydrate. Because azithromycin is poorly soluble in water, its absorption from the gastro-intestinal tract is negatively influenced, which ultimately affects its bioavailability following oral administration (37 %). Polymorphic (monohydrates and dihydrates) and anhydrous forms of azithromycin were screened and investigated. One anhydrous form also proved to be amorphous, which shifted the focus of this study from polymorphism to amorphism. An amorphous glassy azithromycin was subsequently prepared and fully characterised to present its solid state profile. The stability of this amorphous glassy form was established at a high temperature and relative humidity over a period of four weeks. Exposure to increased relative humidity (up to 95 %) and increased water content (up to 50 %) also served as stability indicating tests. Its solubility in various aqueous media was determined. A solid dosage form (tablet), containing the azithromycin glass, was prepared, whereafter these tablets were subjected to dissolution studies in different aqueous media. The stability of azithromycin glass in tablet form was determined over a period of three months. The permeability of azithromycin glass across excised pig intestinal tissue was further established at various pH values. This amorphous glassy form of azithromycin (AZM-G) proved to be very stable at high temperature and relative humidity, whilst also remaining stable after prolonged exposure to 95 % of relative humidity, as it only adsorbed moisture onto its surface. Water content (up to 50 %) had no plasticising effect on azithromycin glass. It demonstrated a significantly higher water solubility (339 % improvement) in comparison with the commercially available azithromycin dihydrate and was it also 39 % more soluble in phosphate buffer (pH 6.8) than its dihydrate counterpart. The prepared azithromycin glass tablets showed a promising dissolution profile in water, due to the improved water solubility of this glass form. The transport of azithromycin glass at higher pH values (6.8 and 7.2) across the membrane proved to be significantly higher than that of azithromycin dihydrate, thus also illustrating its pH dependence for its transport across pig intestinal tissue. The improved water solubility of the azithromycin glass, together with its faster dissolution rate, its superior stability and its increased permeability, may ultimately result in a higher azithromycin bioavailability following oral administration. These research outcomes hence give rise to the need for investigating the effect of administering lower dosages of azithromycin and to determine whether the same antimicrobial efficacy would possibly be achieved, due to maintaining the same tissue concentration levels at these lower dosages. / Thesis (PhD (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013