Introduction: Across the world the incidence of the metabolic syndrome increases annually at an alarming rate. Two conditions associated with this are obesity and hypertension (high blood pressure). Both have negative health and lifestyle consequences, numerous studies on adrenergic receptor (AR) gene polymorphisms in various population groups have proved, although not exclusively, that these polymorphisms may be positively associated with susceptibility to and progression of obesity and hypertension. The AR encoding genes are attractive targets for such studies because the ARs, as part of the sympathetic nervous system, perform important functions like vasoconstriction, vasodilation, lipolysis and influence the heart's contraction. These functions accentuate the possible role of AR gene polymorphisms in the onset or progression of obesity and hypertension. Obesity is a health concern especially among black South African women. The prevalence of obesity (BMI > 30 kg/m2) in the North-West province of South Africa is high: 28.6%. The POWIRS (Profile of Obese Women with the Insulin Resistance syndrome) study was conducted in 2003 on 102 black South African female volunteers to search for possible associations of the p2-AR Gln27Glu and p3-AR Trp64Arg polymorphisms with parameters of the carbohydrate and lipid metabolism, the index of insulin resistance (HOMA-IR), body mass index (BMI) and body fat % (Schutte et al., 2005). To our knowledge, this was the first study of its kind in South Africa and which led to this study and dissertation. Objectives: The objectives of this study were to: • Determine the incidence of the following polymorphisms in (a) 102 black South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; (b) 115 white South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; Gln27Glu; B3-AR: Trp64Arg; • identify possible diplotypes and haplotypes in the study groups; • take relevant physiological parameters (measured in the POWIRS studies) into account in the search for possible associations of these polymorphisms, diplotypes and haplotypes with obesity and high blood pressure as characteristics of the metabolic syndrome; • compare the black and the white study groups with regards to the above mentioned objectives. Methods: DNA was isolated from blood spots on Guthrie cards (collected during the POWIRS studies) and the respective AR gene regions amplified by polymerase chain reaction (PCR). After restriction enzyme digestion, the DIVA fragments were separated by agarose gel electrophoresis. Genotypic findings were examined along with measured physiological parameters (measured during the POWIRS studies) and statistically processed. Area under the curve (AUC) analysis was performed on parameters measured during the oral glucose tolerance test. Diplotype and haplotype analyses were also performed on both subject groups. Results: The minor allele frequencies for both groups were calculated and compared to that reported in other published studies. For the black group, the minor allele frequencies were: 84% (B1-AR Ser49Gly), 16% (B2-AR Gln27Glu), 49% (B2-AR Arg16Gly) and 28% (B3-AR Trp64Arg) and for the white group: 94%, 46%, 50% and 7% respectively. The AUC differed in almost every instance of comparison, but was within normal ranges. Only a few significant differences were identified when the measured physiological parameters were compared between the genotypes, diplotypes and haplotypes in each group, most of which were found to be within normal ranges. When the two groups of test subjects were compared, only minimal differences were observed, most of which were still found to be well within normal ranges. Conclusions: Although no associations were identified between the separate investigated AR gene polymorphisms, diplotypes or haplotypes and obesity and hypertension or high blood pressure, indications are present that they may act as contributors to risk factors for the onset and progression of these characteristics of the metabolic syndrome. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.

Diffuse large B-cell lymphoma (DLBCL), which is the most common type of lymphoma, is characterised by its aggressiveness and poor outcome without adequate treatment and also for its biological and clinical heterogeneity. It is therefore highly desirable to gain a more profound understanding of the underlying biology of the disease, as well as predictive factors for the guidance of treatment. The studies presented here attempt to gain an overall grasp on DLBCL, from the epidemiological level down to the genomic level. The tumour microenvironment consists of both tumour cells and normal infiltrating cells in a delicate interplay. By assessing the number of infiltrating mast cells (MCs) in the microenvironment, a correlation between low numbers of MCs and poorer prognosis of DLBCL was found. However, malignant cells are not only affected by environmental conditions but also by intrinsic factors, such as small non-coding microRNAs. A low expression level of microRNA-129 was found to correlate with poor survival of DLBCL and the finding remained significant even for rituximab-treated patients. An even smaller intracellular genomic unit is one single nucleotide. The single nucleotide polymorphism 309 (SNP309) is a T to G change in the promotor region of MDM2, a regulatory protein in the p53 pathway, which results in increased transcription of MDM2 and thus decreased levels of p53. It was found that homozygous T allele patients had longer overall survival, as well as disease-specific survival and disease-free survival. However, treatment with rituximab eliminated the predictive value of the SNP309 polymorphism. In the last project presented in this thesis we used epidemiological methods to analyse all DLBCL cases diagnosed 2000-2013 in Sweden. Here it was possible to categorically show that higher age is an adverse prognostic factor, and most importantly, this starts from a young age. In conclusion, within this thesis I have applied different laboratory and analysis techniques to examine DLBCL biology in relation to the clinic. I have identified potential new prognostic markers, contributed to an enhanced understanding of DLBCL biology and described epidemiological data from one of the largest DLBCL cohorts ever presented. All of these aspects provide important information for a deeper understanding of the disease DLBCL.

Introduction: Across the world the incidence of the metabolic syndrome increases annually at an alarming rate. Two conditions associated with this are obesity and hypertension (high blood pressure). Both have negative health and lifestyle consequences, numerous studies on adrenergic receptor (AR) gene polymorphisms in various population groups have proved, although not exclusively, that these polymorphisms may be positively associated with susceptibility to and progression of obesity and hypertension. The AR encoding genes are attractive targets for such studies because the ARs, as part of the sympathetic nervous system, perform important functions like vasoconstriction, vasodilation, lipolysis and influence the heart's contraction. These functions accentuate the possible role of AR gene polymorphisms in the onset or progression of obesity and hypertension. Obesity is a health concern especially among black South African women. The prevalence of obesity (BMI > 30 kg/m2) in the North-West province of South Africa is high: 28.6%. The POWIRS (Profile of Obese Women with the Insulin Resistance syndrome) study was conducted in 2003 on 102 black South African female volunteers to search for possible associations of the p2-AR Gln27Glu and p3-AR Trp64Arg polymorphisms with parameters of the carbohydrate and lipid metabolism, the index of insulin resistance (HOMA-IR), body mass index (BMI) and body fat % (Schutte et al., 2005). To our knowledge, this was the first study of its kind in South Africa and which led to this study and dissertation. Objectives: The objectives of this study were to: • Determine the incidence of the following polymorphisms in (a) 102 black South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; (b) 115 white South African female volunteers and calculate the minor allele frequency: B1-AR: Ser49Gly; B2-AR: Arg16Gly; Gln27Glu; B3-AR: Trp64Arg; • identify possible diplotypes and haplotypes in the study groups; • take relevant physiological parameters (measured in the POWIRS studies) into account in the search for possible associations of these polymorphisms, diplotypes and haplotypes with obesity and high blood pressure as characteristics of the metabolic syndrome; • compare the black and the white study groups with regards to the above mentioned objectives. Methods: DNA was isolated from blood spots on Guthrie cards (collected during the POWIRS studies) and the respective AR gene regions amplified by polymerase chain reaction (PCR). After restriction enzyme digestion, the DIVA fragments were separated by agarose gel electrophoresis. Genotypic findings were examined along with measured physiological parameters (measured during the POWIRS studies) and statistically processed. Area under the curve (AUC) analysis was performed on parameters measured during the oral glucose tolerance test. Diplotype and haplotype analyses were also performed on both subject groups. Results: The minor allele frequencies for both groups were calculated and compared to that reported in other published studies. For the black group, the minor allele frequencies were: 84% (B1-AR Ser49Gly), 16% (B2-AR Gln27Glu), 49% (B2-AR Arg16Gly) and 28% (B3-AR Trp64Arg) and for the white group: 94%, 46%, 50% and 7% respectively. The AUC differed in almost every instance of comparison, but was within normal ranges. Only a few significant differences were identified when the measured physiological parameters were compared between the genotypes, diplotypes and haplotypes in each group, most of which were found to be within normal ranges. When the two groups of test subjects were compared, only minimal differences were observed, most of which were still found to be well within normal ranges. Conclusions: Although no associations were identified between the separate investigated AR gene polymorphisms, diplotypes or haplotypes and obesity and hypertension or high blood pressure, indications are present that they may act as contributors to risk factors for the onset and progression of these characteristics of the metabolic syndrome. / Thesis (M.Sc. (Biochemistry))--North-West University, Potchefstroom Campus, 2007.

Polymorphic crystal forms in food fats contribute to physical characteristics of the fats and consequently to their performance in fat based foods. In the present study the phase transitions associated with polymorphism behavior of common food fats were investigated. The polymorphism of butters, margarines, cocoa butter and cocoa butter products were determined and the effects of certain ingredients and conditions of temperature were studied. The following polymorphic forms were detected: sub-alpha, alpha, beta' , beta'3, beta' 2, beta, beta2, and beta1; however, not all forms were observed in all fats. Margarines contained beta' and beta forms depending on their fat constituents, while butter, cocoa butter, and fat blends consisted of alpha, beta' and beta; only the beta' form of butter showed a sharp melting point. Rapeseed oil exhibited alpha, beta1 and beta 2 forms, depending on the degree of hydrogenation. / DSC measurements of fat blends were correlated with viscosity index measurements from Universal Material Testing Machine (UMTM) using a single cycle, back extrusion technique. A correlation of R2 = 0.70 (p = 0.95) was obtained. Viscosity index decreased as temperature increased, suggesting a possible relationship between viscosity index and solid fat fraction. This suggests that viscosity index could be a potential indicator of food fat textural properties which are evaluated by DSC. (Abstract shortened by UMI.)

No description available.

No description available.

Several pseudopolymorphic forms of sodium naproxen were crystallized from methanol-water and ethanol-water solutions, including hydrated and alcohol-solvated forms. Results showed that the transitions of the pseudopolymorphic forms occur at temperatures that depend upon the solvent concentration. Results also revealed that water activity is a controlling factor for the transitions because regardless of which alcohol solvent mixture was used. The heats of solution for each pseudopolymorph were estimated by fitting the solubility data with the van't Hoff equation. The stability of hydrated forms over solvated forms at higher temperatures was proven for enantiotropic systems from a thermodynamic cycle. A 1:1 methanol-solvated form of sodium naproxen was discovered and fully characterized using a variety of analytical techniques. For further analysis, a single crystal was performed and revealed a two to three ratio solvate of sodium naproxen to methanol. The 1.5 solvate was shown to not be representative of the entire sample, but still provided insight into the bonding of the methanol solvent in sodium naproxen. Additionally, the ability of sodium naproxen to solvate with other alcohol solvents was explored, specifically looking at comparisons between pure ethanol, 1-propanol, 2-propanol, 1-butanol, and isobutanol solvents. It was shown that as the size of the alcohol increases and/or branching increases the ability to solvate decreases in relation to the molar amount of the alcohol present in the crystal structure. Additionally larger, branched alcohols required more energy to desolvate.

<p>The aim of this study was to investigate the forensic usefulness of various Y-chromosome short tandem repeat loci among South African sub-populations. Three different sets of Y-chromosome short tandem repeat loci were chosen for investigation.</p>

Spectroscopy is increasingly used to investigate and monitor the solid state forms of pharmaceutical materials and products. Spectroscopy�s speed, nondestructive sampling, compatibility with fibre optics and safety also make it attractive for in-line monitoring. In this thesis, the spectroscopic techniques Fourier transform Raman spectroscopy, terahertz pulsed spectroscopy and second harmonic generation were used to characterise and quantify polymorphism and crystallinity of pharmaceutical compounds. Where possible, the multivariate analysis technique partial least squares was used for quantitative analysis. Fourier transform Raman spectroscopy detects polarisability changes mainly associated with molecular vibrations. Terahertz pulsed spectroscopy is a new spectroscopic technique that operates between the infrared and microwave regions of the electromagnetic spectrum and detects dipole moment changes mainly associated with crystalline phonon vibrations in the solid state. Second harmonic generation is a nonlinear optical phenomenon that depends on the dipole moment in crystals and crystal symmetry. Several materials capable of existing in different solid state forms were used. FT-Raman spectroscopy was able to differentiate carbamazepine forms I and III, enalapril maleate forms I and II and γ-crystalline and amorphous indomethacin. Combined with partial least squares the technique could quantify binary mixtures of CBZ forms I and III with a limit of detection as low as 1%, and mixtures of enalapril maleate with a limit of detection of as low as 2%. Terahertz pulsed spectroscopy obtained very different spectra for carbamazepine forms I and III, enalapril maleate forms I and II, γ-crystalline and amorphous indomethacin, crystalline and supercooled thermotropic liquid crystalline fenoprofen calcium, three forms of lactose, and five forms of sulphathiazole. At present the modes in the spectra cannot be attributed to specific phonon modes. Quantitation of binary mixtures of different forms of a compound using partial least squares analysis usually resulted in a limit of detection of about 1%. Second harmonic generation was used to quantify binary mixtures of different forms of enalapril maleate and lactose, as well as binary mixtures of enalapril maleate form II and polyvinylpyrrolidone. A quantitative relationship was present for each of the mixtures, however the limits of detection were usually above 10%. The high value is probably due to the machine being a prototype and univariate analysis associated with a single output variable. Future improvements to the apparatus and measurement parameters are likely to reduce the limits of detection. Ranitidine hydrochloride polymorphs could also be differentiated using second harmonic generation, however γ-crystalline and amorphous indomethacin and forms I and III of carbamazepine could not. The methods used in this thesis were successfully used for qualitative and quantitative analysis of polymorphism and crystallinity of pharmaceutical compounds. TPS and SHG are useful additions to the range of experimental techniques that can be used to investigate and monitor properties of pharmaceutical solids.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 4 uppsatser.