Isolation, characterization and biomimetic oxidation of selected marine natural products and their analogues
- Authors: Mutsvairo, Tafadzwa
- Date: 2016
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/64685 , vital:28592
- Description: Marine brown algae produce a variety of terpenes with a wide range of biological activities. However, very few phytochemical studies of brown algae have been conducted in South Africa. Therefore, in our continued search for biologically active natural products, we examined the South African brown alga Brassicophycus brassicaeformis. The dichloromethane-methanol extract of B.brassicaeformis was fractionated by silica gel column chromatography followed by normal phase HPLC to give pure four pure compounds which were identified by spectroscopic methods as; fucosterol, fucoxanthin and two monogalactosyldiacylglycerol lipids. Many potential drug molecules such as natural products have failed to reach the market due to poor pharmacokinetic and metabolic profiles despite having potent biological activity. Therefore the importance of early drug metabolism studies in the drug development process is clear. A biomimetic oxidation model was used for in vitro drug metabolism studies to predict any possible metabolites that could be produced by these natural products. Two biomimetic oxidation models catalyzed by two water soluble metalloporphyrins as biomimics of cytochrome P450, in the presence of two terminal oxidants either hydrogen peroxide or iodobenzene diacetete were successfully developed. The models were applied to a range of natural products. The oxidation of the quinone natural products, sargahydroquinoic acid, and lapachol was most easily achieved by metalloporphyrins employed in this study.
- Full Text:
- Date Issued: 2016
- Authors: Mutsvairo, Tafadzwa
- Date: 2016
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/64685 , vital:28592
- Description: Marine brown algae produce a variety of terpenes with a wide range of biological activities. However, very few phytochemical studies of brown algae have been conducted in South Africa. Therefore, in our continued search for biologically active natural products, we examined the South African brown alga Brassicophycus brassicaeformis. The dichloromethane-methanol extract of B.brassicaeformis was fractionated by silica gel column chromatography followed by normal phase HPLC to give pure four pure compounds which were identified by spectroscopic methods as; fucosterol, fucoxanthin and two monogalactosyldiacylglycerol lipids. Many potential drug molecules such as natural products have failed to reach the market due to poor pharmacokinetic and metabolic profiles despite having potent biological activity. Therefore the importance of early drug metabolism studies in the drug development process is clear. A biomimetic oxidation model was used for in vitro drug metabolism studies to predict any possible metabolites that could be produced by these natural products. Two biomimetic oxidation models catalyzed by two water soluble metalloporphyrins as biomimics of cytochrome P450, in the presence of two terminal oxidants either hydrogen peroxide or iodobenzene diacetete were successfully developed. The models were applied to a range of natural products. The oxidation of the quinone natural products, sargahydroquinoic acid, and lapachol was most easily achieved by metalloporphyrins employed in this study.
- Full Text:
- Date Issued: 2016
Marine biotechnology : evaluation and development of methods for the discovery of natural products from fungi
- Authors: Pather, Simisha
- Date: 2005 , 2013-06-18
- Subjects: Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3839 , http://hdl.handle.net/10962/d1007652 , Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Description: One of the major impediments in the development of marine natural products is the provision of biologically active natural products in sufficient quantity for complete pharmacological evaluation, clinical trials and eventual commercial production. Marine microorganisms show great promise in providing a renewable source of biologically active natural products. The main aim of this study was to develop and evaluate methods for the isolation, identification and cultivation of marine fungi from the South African marine environment for the production of biologically active secondary metabolites. Twenty-four species of fungi were isolated from marine algae collected from the intertidal zone near Port Alfred, South Africa. The fungi were cultivated in small-scale under static and agitated conditions and their crude intra- and extracellular organic extracts were screened by ¹H NMR and a series of bioassays. Using this as a basis, one isolate was selected for further study. By analyses of the lTS1 region of the ribosomal DNA, the fungal isolate was identified as a marine-derived isolate of Eurotium rubrum (Aspergillus ruber). Although E. rubrum has been isolated from the marine environment, no investigations have been undertaken to determine the adaptation of these isolates to the marine environment. In order to optimise productivity, creativity and incubation time, the fungus was cultivated in small-scale using a variety of carbon (glucose, fructose, lactose, sucrose, marmitol and maltose) and nitrogen sources (ammonium tartrate, urea, peptone and yeast extract). An HPLC-DAD method was developed to assess the metabolic creativity and productivity under different fermentation conditions. Distinctive variations in the range and yield of metabolites produced as well as morphology and growth time were observed. The crude extracts from all fermentations were combined and six known compounds were isolated by reversed-phase chromatography and their structures elucidated by spectroscopic techniques. The known compounds were fIavoglaucin, aspergin, isodihydroauroglaucin, isotetrahydroauroglaucin, neoechinuline A and physcion. Neoechinuline A, isodihydroauroglaucin and isotetrahydroauroglaucin showed activity against oesophageal and cervical cancer cell lines.
- Full Text:
- Date Issued: 2005
- Authors: Pather, Simisha
- Date: 2005 , 2013-06-18
- Subjects: Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3839 , http://hdl.handle.net/10962/d1007652 , Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Description: One of the major impediments in the development of marine natural products is the provision of biologically active natural products in sufficient quantity for complete pharmacological evaluation, clinical trials and eventual commercial production. Marine microorganisms show great promise in providing a renewable source of biologically active natural products. The main aim of this study was to develop and evaluate methods for the isolation, identification and cultivation of marine fungi from the South African marine environment for the production of biologically active secondary metabolites. Twenty-four species of fungi were isolated from marine algae collected from the intertidal zone near Port Alfred, South Africa. The fungi were cultivated in small-scale under static and agitated conditions and their crude intra- and extracellular organic extracts were screened by ¹H NMR and a series of bioassays. Using this as a basis, one isolate was selected for further study. By analyses of the lTS1 region of the ribosomal DNA, the fungal isolate was identified as a marine-derived isolate of Eurotium rubrum (Aspergillus ruber). Although E. rubrum has been isolated from the marine environment, no investigations have been undertaken to determine the adaptation of these isolates to the marine environment. In order to optimise productivity, creativity and incubation time, the fungus was cultivated in small-scale using a variety of carbon (glucose, fructose, lactose, sucrose, marmitol and maltose) and nitrogen sources (ammonium tartrate, urea, peptone and yeast extract). An HPLC-DAD method was developed to assess the metabolic creativity and productivity under different fermentation conditions. Distinctive variations in the range and yield of metabolites produced as well as morphology and growth time were observed. The crude extracts from all fermentations were combined and six known compounds were isolated by reversed-phase chromatography and their structures elucidated by spectroscopic techniques. The known compounds were fIavoglaucin, aspergin, isodihydroauroglaucin, isotetrahydroauroglaucin, neoechinuline A and physcion. Neoechinuline A, isodihydroauroglaucin and isotetrahydroauroglaucin showed activity against oesophageal and cervical cancer cell lines.
- Full Text:
- Date Issued: 2005
Medicine use in swallowing-impaired patients: Pharmacists’ knowledge, practice and information needs
- Authors: Masilamoney, Mehrusha
- Date: 2018
- Subjects: Deglutition disorders , Drugs -- Administration , Oral medication -- Administration , Pharmacists -- Practice , South African Pharmacy Council
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/61940 , vital:28086
- Description: Dysphagia, or swallowing impairment, is a growing problem that affects 13.5% of the general population. The ability to swallow is essential for patients taking oral medicines, so this presents a challenge for swallowing-impaired (SI) patients as tablets and capsules will usually require modification prior to ingestion. Pharmacists should play a central role in advising SI patients about their medicine use, as well as problems that may impact on safety, adherence and therapeutic outcome. However, little is known about pharmacists’ level of knowledge, their practice and their information needs when dealing with SI patients and their use of medicines. The aim of this study was to investigate pharmacist knowledge, practice and information needs relating to the support of SI patients and their medicine-related needs. The study design included both quantitative and qualitative methods. A quantitative questionnaire was developed to collect data on the knowledge, practice and information needs of pharmacists and was piloted in 10 pharmacists, which resulted in minor modifications. The questionnaire was converted to a web-based survey and emailed to all pharmacists registered with the South African Pharmacy Council. Two knowledge scores were generated by summating correct responses: knowledge of dysphagia (KOD) and knowledge of medicine use (KOMU) in SI patients. Correlation analysis was used to investigate the strength of the relationship between specific variables with KOD and KOMU using the Pearson correlation coefficient. Qualitative semi-structured interviews were conducted with pharmacists from community, hospital and primary healthcare clinics in both a small town and a major metropole. The aim was to gain deeper understanding of issues arising from the survey, and to explore preferences for topic-specific information materials. All interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyse the data. A total of 439 pharmacists responded to the survey, with 67% being females.The mean KOD score out of a maximum score of 10 was 6.1 ± 1.8. KOD was inadequate (<5) in just over one-third (37.8%) of pharmacists. The mean KOMU score achieved (maximum score 17) was 9.4 ± 2.0, with inadequate knowledge (<10) being established in just over two-thirds of pharmacists (70.8%). Age, length of registration as a pharmacist, and years of practice in a setting with direct patient interaction were significantly but weakly correlated with KOMU, whereas KOD showed no significant association with these variables. Qualification significantly influenced both KOD and KOMU; the highest group with adequate knowledge had either a Masters or a PharmD degree. Fewer than half the pharmacists (44%) never ask patients about their swallowing ability, and most (86%) reported no knowledge of locally available viscosity enhancers. Almost all pharmacists were interested in receiving information materials on assisting SI patients with their medicine use. Three major themes emerged from the semi-structured interviews. Pharmacists recognised their knowledge deficit and felt that lack of both undergraduate training and formal training during practice, as well as limited exposure to SI patients, were contributing factors. Barriers to their practice with SI patients included lack of time, lack of institutional support and lack of easily accessible references on the pharmacists’ role in supporting medicine use in SI patients. Lastly, most pharmacists were not prepared to take ownership of medicine-related problems in SI patients and had conflicting opinions of the pharmacists’ role, usually shifting the responsibility of medicine use in SI patients to nurses. This is the first study to investigate pharmacist knowledge of medicine use in SI patients. The findings indicate that pharmacists do not have the requisite knowledge when dealing with SI patients and their medicine-taking issues despite being the most highly trained healthcare professionals in this field. Lack of undergraduate training, in-house training and limited exposure to SI patients were reported to contribute to poor knowledge. Current practice revealed that there appears to be poor communication among different healthcare professionals, pharmacists were reluctant to work with and/or train nurses on appropriate medicine use in SI patients, and there appeared to be ambiguity surrounding the role of a pharmacist. This research identified that pharmacists regard this topic to be highly relevant to their everyday practice and are keen to receive more information and training relating to this area of study. Information materials were designed and will be made accessible to all pharmacists registered in South Africa.
- Full Text:
- Date Issued: 2018
Medicine use in swallowing-impaired patients: Pharmacists’ knowledge, practice and information needs
- Authors: Masilamoney, Mehrusha
- Date: 2018
- Subjects: Deglutition disorders , Drugs -- Administration , Oral medication -- Administration , Pharmacists -- Practice , South African Pharmacy Council
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/61940 , vital:28086
- Description: Dysphagia, or swallowing impairment, is a growing problem that affects 13.5% of the general population. The ability to swallow is essential for patients taking oral medicines, so this presents a challenge for swallowing-impaired (SI) patients as tablets and capsules will usually require modification prior to ingestion. Pharmacists should play a central role in advising SI patients about their medicine use, as well as problems that may impact on safety, adherence and therapeutic outcome. However, little is known about pharmacists’ level of knowledge, their practice and their information needs when dealing with SI patients and their use of medicines. The aim of this study was to investigate pharmacist knowledge, practice and information needs relating to the support of SI patients and their medicine-related needs. The study design included both quantitative and qualitative methods. A quantitative questionnaire was developed to collect data on the knowledge, practice and information needs of pharmacists and was piloted in 10 pharmacists, which resulted in minor modifications. The questionnaire was converted to a web-based survey and emailed to all pharmacists registered with the South African Pharmacy Council. Two knowledge scores were generated by summating correct responses: knowledge of dysphagia (KOD) and knowledge of medicine use (KOMU) in SI patients. Correlation analysis was used to investigate the strength of the relationship between specific variables with KOD and KOMU using the Pearson correlation coefficient. Qualitative semi-structured interviews were conducted with pharmacists from community, hospital and primary healthcare clinics in both a small town and a major metropole. The aim was to gain deeper understanding of issues arising from the survey, and to explore preferences for topic-specific information materials. All interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to analyse the data. A total of 439 pharmacists responded to the survey, with 67% being females.The mean KOD score out of a maximum score of 10 was 6.1 ± 1.8. KOD was inadequate (<5) in just over one-third (37.8%) of pharmacists. The mean KOMU score achieved (maximum score 17) was 9.4 ± 2.0, with inadequate knowledge (<10) being established in just over two-thirds of pharmacists (70.8%). Age, length of registration as a pharmacist, and years of practice in a setting with direct patient interaction were significantly but weakly correlated with KOMU, whereas KOD showed no significant association with these variables. Qualification significantly influenced both KOD and KOMU; the highest group with adequate knowledge had either a Masters or a PharmD degree. Fewer than half the pharmacists (44%) never ask patients about their swallowing ability, and most (86%) reported no knowledge of locally available viscosity enhancers. Almost all pharmacists were interested in receiving information materials on assisting SI patients with their medicine use. Three major themes emerged from the semi-structured interviews. Pharmacists recognised their knowledge deficit and felt that lack of both undergraduate training and formal training during practice, as well as limited exposure to SI patients, were contributing factors. Barriers to their practice with SI patients included lack of time, lack of institutional support and lack of easily accessible references on the pharmacists’ role in supporting medicine use in SI patients. Lastly, most pharmacists were not prepared to take ownership of medicine-related problems in SI patients and had conflicting opinions of the pharmacists’ role, usually shifting the responsibility of medicine use in SI patients to nurses. This is the first study to investigate pharmacist knowledge of medicine use in SI patients. The findings indicate that pharmacists do not have the requisite knowledge when dealing with SI patients and their medicine-taking issues despite being the most highly trained healthcare professionals in this field. Lack of undergraduate training, in-house training and limited exposure to SI patients were reported to contribute to poor knowledge. Current practice revealed that there appears to be poor communication among different healthcare professionals, pharmacists were reluctant to work with and/or train nurses on appropriate medicine use in SI patients, and there appeared to be ambiguity surrounding the role of a pharmacist. This research identified that pharmacists regard this topic to be highly relevant to their everyday practice and are keen to receive more information and training relating to this area of study. Information materials were designed and will be made accessible to all pharmacists registered in South Africa.
- Full Text:
- Date Issued: 2018
Microbial water quality monitoring of raw and treated water sources in Harare and the effect of gender in disaster management due to water related disasters
- Authors: Chirenda, Tatenda Grace
- Date: 2017
- Subjects: Drinking water Microbiology Zimbabwe Harare , Heterotrophic bacteria Zimbabwe Harare , Emergency management Zimbabwe Harare , Disasters Social aspects Zimbabwe Harare , Water quality management Zimbabwe Harare , Public health Zimbabwe Harare , Sex role Zimbabwe Harare
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/59156 , vital:27444
- Description: Background - Microbial water quality monitoring is essential to the provision of potable water for domestic use. Unsafe water sources increase the risk of waterborne diseases. There is a need to raise awareness of legislature that supports management of water related disasters. Gender, education, health, and economic vulnerability contribute to the success of disaster management. Aim - This study aimed to investigate the microbial water quality of treated water in the Harare area. The study also researched the microbial water quality monitoring practices in Zimbabwe and how these contribute to the management of water borne diseases. The impact of gender, marriage, education, and disease in disaster management practices in Zimbabwe and South Africa was analysed. Method - Literature review was conducted on microbial water quality monitoring practices in Zimbabwe and legislature that supports disaster management. Practices of disaster management in Zimbabwe, and South Africa were investigated and compared. The perspective of the Harare community on the quality of their potable water was investigated through the use of a questionnaire and water quality testing was conducted using hydrogen sulphide test and R2A based heterotrophic plate count. Raw water supplying Manyame River and tap water in Harare households were assessed for microbial quality. Results and Discussion - Raw water sources were found to be contaminated by faecal matter. Household water sources had no faecal contamination, but tested positive for heterotrophic bacteria. The CFU/ml quantities obtained ranged from 1- 452 CFU/ml for all samples. The WHO guidelines for domestic water sources recommend that domestic water should have no coliforms/100 ml sample. Disaster management protocols were available in disaster prone areas such as the Matabeleland South Province. No guidelines were in place for monitoring microbial water quality as a disaster prevention method. Conclusion - The current state of treated water supplied by the Morton Jaffray Treatment Plant was found to be suitable for domestic use, but not sufficient to meet the Harare population’s needs. The need to push for legislature supporting microbial water quality monitoring was recognised. Initiating public / private partnerships in water distribution and water quality monitoring in Zimbabwe was encouraged.
- Full Text:
- Date Issued: 2017
- Authors: Chirenda, Tatenda Grace
- Date: 2017
- Subjects: Drinking water Microbiology Zimbabwe Harare , Heterotrophic bacteria Zimbabwe Harare , Emergency management Zimbabwe Harare , Disasters Social aspects Zimbabwe Harare , Water quality management Zimbabwe Harare , Public health Zimbabwe Harare , Sex role Zimbabwe Harare
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/59156 , vital:27444
- Description: Background - Microbial water quality monitoring is essential to the provision of potable water for domestic use. Unsafe water sources increase the risk of waterborne diseases. There is a need to raise awareness of legislature that supports management of water related disasters. Gender, education, health, and economic vulnerability contribute to the success of disaster management. Aim - This study aimed to investigate the microbial water quality of treated water in the Harare area. The study also researched the microbial water quality monitoring practices in Zimbabwe and how these contribute to the management of water borne diseases. The impact of gender, marriage, education, and disease in disaster management practices in Zimbabwe and South Africa was analysed. Method - Literature review was conducted on microbial water quality monitoring practices in Zimbabwe and legislature that supports disaster management. Practices of disaster management in Zimbabwe, and South Africa were investigated and compared. The perspective of the Harare community on the quality of their potable water was investigated through the use of a questionnaire and water quality testing was conducted using hydrogen sulphide test and R2A based heterotrophic plate count. Raw water supplying Manyame River and tap water in Harare households were assessed for microbial quality. Results and Discussion - Raw water sources were found to be contaminated by faecal matter. Household water sources had no faecal contamination, but tested positive for heterotrophic bacteria. The CFU/ml quantities obtained ranged from 1- 452 CFU/ml for all samples. The WHO guidelines for domestic water sources recommend that domestic water should have no coliforms/100 ml sample. Disaster management protocols were available in disaster prone areas such as the Matabeleland South Province. No guidelines were in place for monitoring microbial water quality as a disaster prevention method. Conclusion - The current state of treated water supplied by the Morton Jaffray Treatment Plant was found to be suitable for domestic use, but not sufficient to meet the Harare population’s needs. The need to push for legislature supporting microbial water quality monitoring was recognised. Initiating public / private partnerships in water distribution and water quality monitoring in Zimbabwe was encouraged.
- Full Text:
- Date Issued: 2017
Microemulsions : a new perspective in the treatment of paediatric and geriatric tuberculosis patients
- Authors: Wisch, Michael Henry
- Date: 2000
- Subjects: Emulsions (Pharmacy) , Tuberculosis -- Treatment -- South Africa , Tuberculosis in children -- Treatment , Tuberculosis in old age -- Treatment , Tuberculosis -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3805 , http://hdl.handle.net/10962/d1003283 , Emulsions (Pharmacy) , Tuberculosis -- Treatment -- South Africa , Tuberculosis in children -- Treatment , Tuberculosis in old age -- Treatment , Tuberculosis -- Treatment
- Description: Tuberculosis(TB) was declared to be a global emergency in 1993, with South Africa declaring it to be the country’s top health priority in 1996, but ineffective treatment strategies have led to fewer than half of all treated patients in South Africa being cured. At present,paediatric treatment remains a problem, as the antitubercular preparations of rifampicin, isoniazid and pyrazinamide, that are currently available, were not initially designed for the treatment of paediatric TB patients, providing a motivation for this project. The aim of this project is thus the development of a microemulsion dosage form for the oral delivery of RIF(Rifampicin), INH(Isoniazid) and PZA(Pyrazinamide) in combination. RIF, INH and PZA were adequately characterised with reference to the monograph standards referenced and were found to be sufficiently pure to be used in subsequent work. A chromatographic system and conditions were selected and validated as being optimal for HPLC analysis of RIF, INH and PZA in combination, with a drug partitioning method for miglyol 812 developed and validated. Ternary and pseudo-ternary phase diagrams were constructed and reported, all employing miglyol 812 as the lipid. It was undoubtedly the imwitor 308 and crillet 3 combination o/w microemulsion system that proved most successful, maintaining homogeneity on dilution. The microemulsion used in formulation comprised imwitor 308 (27.63%), crillet 3 (27.63%), miglyol 812 23.68%) and water (21.06%). The stability of RIF, INH and PZA was investigated in aqueous solution, miglyol 812, corn oil, 10%m/v cremophor RH, 5%m/v imwitor 308, 10%m/v crillet 3 and 70%m/v sorbitol solution. Trends in the stability assessments conducted on RIF, INH and PZA were noted, with slight variation depending on the formulation component being evaluated. RIF invariably demonstrated temperature and oxidation dependent degradation in all vehicles, with a definite distinction possible between samples stored at 25, 40 and 600C over a 7 day trial period. A definite advantage of storing RIF solutions under nitrogen was observed, with these solutions showing less degradation over the course of the trial, than those stored under air. INH produced a pronounced increase in the degree of degradation of RIF, whereas PZA had a negligible effect on it’s stability. INH proved to be most stable in the 70%m/v sorbitol solution with no significant oxidation or temperature dependent degradation indicated. Temperature dependent degradation was only noticable when INH was in combination with RIF, most significant in crillet 3 solution. PZA was the most stable of the three drugs, remaining relatively unaffected by temperature and the presence of air, independent of the vehicle employed, although the drug remaining did decrease slightly in the presence of RIF.Due to drug dose specifications and solubility limitations, the final formulation assessed, only contained RIF and INH, despite INH and PZA having no significant effect on the stability of each other. The solubility of PZA in the lipid and aqueous components of the microemulsion was not great enough to achieve the required 500 mg/10ml dose, while RIF and INH could achieve the respective 150mg/10ml and 100mg/10ml dose. RIF stability was improved, as anticipated, with the incorporation of RIF into the internal phase decreasing contact with INH which has been shown to affect it’s stability. RIF behaved as predicted, possessing greater stability than shown in the individual formulation components, however, INH did not, being less stable in formulation in the absence of antioxidant, than in it’s presence. A novel microemulsion formulation capable of delivering the incompatible RIF and INH in combination, with numerous microemulsion systems mapped,with the ability of being used for the delivery of other lipophilic drugs and drug combinations, was produced.The final formulation provided valuable information into possible future improvements of the microemulsion to improve drug stability.
- Full Text:
- Date Issued: 2000
- Authors: Wisch, Michael Henry
- Date: 2000
- Subjects: Emulsions (Pharmacy) , Tuberculosis -- Treatment -- South Africa , Tuberculosis in children -- Treatment , Tuberculosis in old age -- Treatment , Tuberculosis -- Treatment
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3805 , http://hdl.handle.net/10962/d1003283 , Emulsions (Pharmacy) , Tuberculosis -- Treatment -- South Africa , Tuberculosis in children -- Treatment , Tuberculosis in old age -- Treatment , Tuberculosis -- Treatment
- Description: Tuberculosis(TB) was declared to be a global emergency in 1993, with South Africa declaring it to be the country’s top health priority in 1996, but ineffective treatment strategies have led to fewer than half of all treated patients in South Africa being cured. At present,paediatric treatment remains a problem, as the antitubercular preparations of rifampicin, isoniazid and pyrazinamide, that are currently available, were not initially designed for the treatment of paediatric TB patients, providing a motivation for this project. The aim of this project is thus the development of a microemulsion dosage form for the oral delivery of RIF(Rifampicin), INH(Isoniazid) and PZA(Pyrazinamide) in combination. RIF, INH and PZA were adequately characterised with reference to the monograph standards referenced and were found to be sufficiently pure to be used in subsequent work. A chromatographic system and conditions were selected and validated as being optimal for HPLC analysis of RIF, INH and PZA in combination, with a drug partitioning method for miglyol 812 developed and validated. Ternary and pseudo-ternary phase diagrams were constructed and reported, all employing miglyol 812 as the lipid. It was undoubtedly the imwitor 308 and crillet 3 combination o/w microemulsion system that proved most successful, maintaining homogeneity on dilution. The microemulsion used in formulation comprised imwitor 308 (27.63%), crillet 3 (27.63%), miglyol 812 23.68%) and water (21.06%). The stability of RIF, INH and PZA was investigated in aqueous solution, miglyol 812, corn oil, 10%m/v cremophor RH, 5%m/v imwitor 308, 10%m/v crillet 3 and 70%m/v sorbitol solution. Trends in the stability assessments conducted on RIF, INH and PZA were noted, with slight variation depending on the formulation component being evaluated. RIF invariably demonstrated temperature and oxidation dependent degradation in all vehicles, with a definite distinction possible between samples stored at 25, 40 and 600C over a 7 day trial period. A definite advantage of storing RIF solutions under nitrogen was observed, with these solutions showing less degradation over the course of the trial, than those stored under air. INH produced a pronounced increase in the degree of degradation of RIF, whereas PZA had a negligible effect on it’s stability. INH proved to be most stable in the 70%m/v sorbitol solution with no significant oxidation or temperature dependent degradation indicated. Temperature dependent degradation was only noticable when INH was in combination with RIF, most significant in crillet 3 solution. PZA was the most stable of the three drugs, remaining relatively unaffected by temperature and the presence of air, independent of the vehicle employed, although the drug remaining did decrease slightly in the presence of RIF.Due to drug dose specifications and solubility limitations, the final formulation assessed, only contained RIF and INH, despite INH and PZA having no significant effect on the stability of each other. The solubility of PZA in the lipid and aqueous components of the microemulsion was not great enough to achieve the required 500 mg/10ml dose, while RIF and INH could achieve the respective 150mg/10ml and 100mg/10ml dose. RIF stability was improved, as anticipated, with the incorporation of RIF into the internal phase decreasing contact with INH which has been shown to affect it’s stability. RIF behaved as predicted, possessing greater stability than shown in the individual formulation components, however, INH did not, being less stable in formulation in the absence of antioxidant, than in it’s presence. A novel microemulsion formulation capable of delivering the incompatible RIF and INH in combination, with numerous microemulsion systems mapped,with the ability of being used for the delivery of other lipophilic drugs and drug combinations, was produced.The final formulation provided valuable information into possible future improvements of the microemulsion to improve drug stability.
- Full Text:
- Date Issued: 2000
Monitoring and evaluation indicators of the HIV & AIDS programme in Grahamstown's public sector health care system
- Authors: Mahasele, Phehello Anthony
- Date: 2011
- Subjects: AIDS (Disease) -- Patients -- Services for -- South Africa -- Grahamstown -- Evaluation HIV-positive persons -- Services for -- South Africa -- Grahamstown -- Evaluation Public health -- South Africa -- Grahamstown -- Evaluation Antiretroviral agents -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3770 , http://hdl.handle.net/10962/d1003248
- Description: South Africa is one of the countries hardest hit with the Human Immunodeficiency Virus (HIV) and Acquired Immuno Deficiency Syndrome (AIDS) epidemic. In response to the epidemic, the South African government adopted the Comprehensive HIV & AIDS Care, Management and Treatment programme strategic plan (CCMT) in 2000 (1) and developed the Operational Plan for CCMT for antiretroviral therapy rollout in 2003 (2). In order to monitor the progress of the implementation of CCMT, the National Department of Health (NDOH) adopted the Monitoring and Evaluation (M & E) framework in 2004 (3). The aim of this study was to assess the HIV & AIDS programme in Grahamstown‘s public sector health care system by using the national M & E indicators of the HIV & AIDS programme. The national M & E framework was used as the data collection tool and available information was collected from various sources such as the District Health Office (DHO), Primary Health Care (PHC) office, accredited antiretroviral sites and the provincial pharmaceutical depot. Group interviews were conducted with key stakeholder health care professionals at the District Health Office, Primary Health Care office, Settlers Hospital and the provincial Department of Health personnel. A one-on-one interview was conducted with the Deputy Director of HIV & AIDS Directorate, monitoring and evaluation in the National Department of Health. Available indicators such as budget and expenditure including antiretroviral procurement; human resources; nutrition-related indicators; prevention care and treatment indicators were collected. A group interview was conducted to document current practices, or where there was a lack of documentation, for indicators such as traditional medicines and pharmacovigilance. Most of the national M & E indicators are not required to be collected or collated by the district because the reporting format designed by the provincial Department of Health is different. Facilities, districts and provinces in South Africa are at different levels of implementation of the antiretroviral programme and hence a common format of the M & E indicators is not used by all provinces. Uniform data collection is not achieved due to human resources‘ constraints and other challenges such as continued use of manual reporting systems by the clinics. Districts are expected to report according to the formats drawn up by the provincial Department of Health (DOH) and there is a lack of awareness regarding the national M & E document amongst the Grahamstown Health Care Professionals. There is a need for training on the use of the M & E national framework so that the HCPs at the primary and secondary levels of the health care system are proficient with the process of M & E, and can provide inputs as well as take ownership of the process. The establishment of an M & E unit in Grahamstown is essential so that data collection and submission of the HIV & AIDS programme in the public sector according to the National M & E framework is addressed. However, despite all constraints and challenges in the public sector health care system in Grahamstown, available human and financial resources are being used effectively to maintain the HIV & AIDS programme.
- Full Text:
- Date Issued: 2011
- Authors: Mahasele, Phehello Anthony
- Date: 2011
- Subjects: AIDS (Disease) -- Patients -- Services for -- South Africa -- Grahamstown -- Evaluation HIV-positive persons -- Services for -- South Africa -- Grahamstown -- Evaluation Public health -- South Africa -- Grahamstown -- Evaluation Antiretroviral agents -- South Africa -- Eastern Cape
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3770 , http://hdl.handle.net/10962/d1003248
- Description: South Africa is one of the countries hardest hit with the Human Immunodeficiency Virus (HIV) and Acquired Immuno Deficiency Syndrome (AIDS) epidemic. In response to the epidemic, the South African government adopted the Comprehensive HIV & AIDS Care, Management and Treatment programme strategic plan (CCMT) in 2000 (1) and developed the Operational Plan for CCMT for antiretroviral therapy rollout in 2003 (2). In order to monitor the progress of the implementation of CCMT, the National Department of Health (NDOH) adopted the Monitoring and Evaluation (M & E) framework in 2004 (3). The aim of this study was to assess the HIV & AIDS programme in Grahamstown‘s public sector health care system by using the national M & E indicators of the HIV & AIDS programme. The national M & E framework was used as the data collection tool and available information was collected from various sources such as the District Health Office (DHO), Primary Health Care (PHC) office, accredited antiretroviral sites and the provincial pharmaceutical depot. Group interviews were conducted with key stakeholder health care professionals at the District Health Office, Primary Health Care office, Settlers Hospital and the provincial Department of Health personnel. A one-on-one interview was conducted with the Deputy Director of HIV & AIDS Directorate, monitoring and evaluation in the National Department of Health. Available indicators such as budget and expenditure including antiretroviral procurement; human resources; nutrition-related indicators; prevention care and treatment indicators were collected. A group interview was conducted to document current practices, or where there was a lack of documentation, for indicators such as traditional medicines and pharmacovigilance. Most of the national M & E indicators are not required to be collected or collated by the district because the reporting format designed by the provincial Department of Health is different. Facilities, districts and provinces in South Africa are at different levels of implementation of the antiretroviral programme and hence a common format of the M & E indicators is not used by all provinces. Uniform data collection is not achieved due to human resources‘ constraints and other challenges such as continued use of manual reporting systems by the clinics. Districts are expected to report according to the formats drawn up by the provincial Department of Health (DOH) and there is a lack of awareness regarding the national M & E document amongst the Grahamstown Health Care Professionals. There is a need for training on the use of the M & E national framework so that the HCPs at the primary and secondary levels of the health care system are proficient with the process of M & E, and can provide inputs as well as take ownership of the process. The establishment of an M & E unit in Grahamstown is essential so that data collection and submission of the HIV & AIDS programme in the public sector according to the National M & E framework is addressed. However, despite all constraints and challenges in the public sector health care system in Grahamstown, available human and financial resources are being used effectively to maintain the HIV & AIDS programme.
- Full Text:
- Date Issued: 2011
Neuroprotective mechanisms of nevirapine and efavirenz in a model of neurodegeneration
- Authors: Zheve, Georgina Teurai
- Date: 2008
- Subjects: HIV infections -- Treatment AIDS (Disease) -- Treatment AIDS dementia complex -- Treatment Nervous system -- Degeneration -- Treatment Melatonin Neurotoxic agents Quinolinic acid
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3807 , http://hdl.handle.net/10962/d1003285
- Description: AIDS Dementia Complex (ADC) is a neurodegenerative disorder implicated in HIV-1 infection that is associated with elevated levels of the neurotoxin, quinolinic acid (QA) which causes a cascade of events to occur, leading to the production of reactive oxygen species (ROS), these being ultimately responsible for oxidative neurotoxicity. In clinical studies, Non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP) have been shown to potentially delay the progressive degeneration of neurons, thus reducing the frequency and neurological deficits associated with ADC. Despite these neuroprotective implications, there is still no biochemical data to demonstrate the mechanisms through which these agents offer neuroprotection. The present study aims to elucidate and further characterize the possible antioxidant and neuroprotective mechanisms of NVP and EFV in vitro and in vivo, using QA-induced neurotoxicity as a model. Research has demonstrated that antioxidants and metal chelators have the ability to offer neuroprotection against free radical induced injury and may be beneficial in the prevention or treatment of neurodegeneration. Hence the antioxidant and metal binding properties of these agents were investigated respectively. Inorganic studies, including the 1, 1-diphenyl-2 picrylhydrazyl (DPPH) assay, show that these agents readily scavenge free radicals in vitro, thus postulating the antioxidant property of these agents. The enhancement of superoxide radical generation and iron mediated Fenton reaction by QA is related to lipid peroxidation in biological systems, the extent of which was assayed using the nitroblue tetrazolium and thiobarbituric acid method respectively. Both agents significantly curtail QA-induced lipid peroxidation and potentially scavenge superoxide anions generated by cyanide in vitro. Furthermore, in vivo results demonstrate the ability of NVP and EFV to protect hippocampal neurons against lipid peroxidation induced by QA and superoxide radicals generated as a consequence thereof. The alleviation of QA-induced oxidative stress in vitro possibly occurs through the binding of iron (II) and / or iron (III), and this argument is further strengthened by the ability of EFV and not NVP to reduce iron (II)-induced lipid peroxidation in vitro directly. In addition the ferrozine and electrochemistry assay were used to measure the extent of iron (II) Fe[superscript 2+] and iron (III) Fe[superscript 3+] chelation activity. Both assays demonstrate that these agents bind iron (II) and iron (III), and prevent redox recycling of iron and subsequent complexation of Fe[superscript 2+] with QA which enhances neuronal damage. Both NNRTIs inhibit the endogenous biosynthesis of QA by inhibiting liver tryptophan 2, 3-dioxygenase activity in vivo and subsequently increasing hippocampal serotonin levels. Furthermore, these agents reduce the turnover of hippocampal serotonin to 5-hydroxyindole acetic acid. NVP and not EFV increase 5-hydroxyindole acetic acid and norepinephrine levels in the hippocampus. The results of the pineal indole metabolism study show that NVP increases the synthesis of melatonin, but decreases N-acetylserotonin, 5-hydroxyindole acetic acid and 5-hydroxytryptophol levels. Furthermore, it shows that EFV decreases 5-hydroxyindole acetic acid and melatonin synthesis. Behavioural studies using a Morris water maze show that the post-treatment of rats with NVP and EFV significantly improves QA-induced spatial memory deficits in the hippocampus. This study therefore provides novel information regarding the neuroprotective mechanisms of NVP and EFV. These findings strengthen the argument that these NNRTIs not only have antiviral effects but possess potential neuroprotective properties, which may contribute to the effectiveness of these drugs in the treatment of ADC.
- Full Text:
- Date Issued: 2008
- Authors: Zheve, Georgina Teurai
- Date: 2008
- Subjects: HIV infections -- Treatment AIDS (Disease) -- Treatment AIDS dementia complex -- Treatment Nervous system -- Degeneration -- Treatment Melatonin Neurotoxic agents Quinolinic acid
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3807 , http://hdl.handle.net/10962/d1003285
- Description: AIDS Dementia Complex (ADC) is a neurodegenerative disorder implicated in HIV-1 infection that is associated with elevated levels of the neurotoxin, quinolinic acid (QA) which causes a cascade of events to occur, leading to the production of reactive oxygen species (ROS), these being ultimately responsible for oxidative neurotoxicity. In clinical studies, Non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP) have been shown to potentially delay the progressive degeneration of neurons, thus reducing the frequency and neurological deficits associated with ADC. Despite these neuroprotective implications, there is still no biochemical data to demonstrate the mechanisms through which these agents offer neuroprotection. The present study aims to elucidate and further characterize the possible antioxidant and neuroprotective mechanisms of NVP and EFV in vitro and in vivo, using QA-induced neurotoxicity as a model. Research has demonstrated that antioxidants and metal chelators have the ability to offer neuroprotection against free radical induced injury and may be beneficial in the prevention or treatment of neurodegeneration. Hence the antioxidant and metal binding properties of these agents were investigated respectively. Inorganic studies, including the 1, 1-diphenyl-2 picrylhydrazyl (DPPH) assay, show that these agents readily scavenge free radicals in vitro, thus postulating the antioxidant property of these agents. The enhancement of superoxide radical generation and iron mediated Fenton reaction by QA is related to lipid peroxidation in biological systems, the extent of which was assayed using the nitroblue tetrazolium and thiobarbituric acid method respectively. Both agents significantly curtail QA-induced lipid peroxidation and potentially scavenge superoxide anions generated by cyanide in vitro. Furthermore, in vivo results demonstrate the ability of NVP and EFV to protect hippocampal neurons against lipid peroxidation induced by QA and superoxide radicals generated as a consequence thereof. The alleviation of QA-induced oxidative stress in vitro possibly occurs through the binding of iron (II) and / or iron (III), and this argument is further strengthened by the ability of EFV and not NVP to reduce iron (II)-induced lipid peroxidation in vitro directly. In addition the ferrozine and electrochemistry assay were used to measure the extent of iron (II) Fe[superscript 2+] and iron (III) Fe[superscript 3+] chelation activity. Both assays demonstrate that these agents bind iron (II) and iron (III), and prevent redox recycling of iron and subsequent complexation of Fe[superscript 2+] with QA which enhances neuronal damage. Both NNRTIs inhibit the endogenous biosynthesis of QA by inhibiting liver tryptophan 2, 3-dioxygenase activity in vivo and subsequently increasing hippocampal serotonin levels. Furthermore, these agents reduce the turnover of hippocampal serotonin to 5-hydroxyindole acetic acid. NVP and not EFV increase 5-hydroxyindole acetic acid and norepinephrine levels in the hippocampus. The results of the pineal indole metabolism study show that NVP increases the synthesis of melatonin, but decreases N-acetylserotonin, 5-hydroxyindole acetic acid and 5-hydroxytryptophol levels. Furthermore, it shows that EFV decreases 5-hydroxyindole acetic acid and melatonin synthesis. Behavioural studies using a Morris water maze show that the post-treatment of rats with NVP and EFV significantly improves QA-induced spatial memory deficits in the hippocampus. This study therefore provides novel information regarding the neuroprotective mechanisms of NVP and EFV. These findings strengthen the argument that these NNRTIs not only have antiviral effects but possess potential neuroprotective properties, which may contribute to the effectiveness of these drugs in the treatment of ADC.
- Full Text:
- Date Issued: 2008
Patient education : the effect on patient behaviour
- Authors: Shiri, Clarris
- Date: 2006
- Subjects: Patient education -- South Africa -- Eastern Cape Patient compliance -- South Africa -- Eastern Cape Hypertension -- Treatment -- South Africa Health care services -- South Africa Community health services -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3790 , http://hdl.handle.net/10962/d1003268
- Description: Evidence suggests that the prevalence of certain non-communicable diseases, such as hypertension, is increasing rapidly, and that patients with these diseases are making significant demands on the health services of the nations in sub-Saharan Africa. However, these countries also face other health-related challenges such as communicable diseases and underdevelopmentrelated diseases. Developing countries like South Africa have limited resources, in terms of man power and financial capital, to address the challenges that they are facing. Non-communicable diseases cannot be ignored and since health care providers cannot meet the challenges, it is worthwhile to empower patients to be involved in the management of their conditions. Patient education is a tool that can be used to enable patients to manage their chronic conditions and thereby reduce the morbidity and mortality rates of these conditions. The aim of this study was to investigate the effect of a patient education intervention on participants’ levels of knowledge about hypertension and its therapy, beliefs about medicines and adherence to anti-hypertensive therapy. The intervention consisted of talks and discussions with all the participants as one group and as individuals. There was also written information given to the participants. Their levels of knowledge about hypertension and its therapy were measured using one-on-one interviews and self-administered questionnaires. Beliefs about medicines were measured using the Beliefs about Medicines Questionnaire (BMQ) whilst adherence levels were measured using pill counts, elf-reports and prescription refill records. The participants’ blood pressure readings and body mass indices were also recorded throughout the study. The parameters before and after the educational intervention were compared using statistical analyses. The participants’ levels of knowledge about hypertension and its therapy significantly increased whilst their beliefs about medicines were positively modified after the educational intervention. There were also increases, though not statistically significant, in the participants’ levels of adherence to anti-hypertensive therapy. Unexpectedly, the blood pressure readings and body mass indices increased significantly. The participants gave positive feedback regarding the educational intervention and indicated a desire for similar programmes to be run continuously. They also suggested that such programmes be implemented for other common chronic conditions such as asthma and diabetes. This study proved that patient education programmes can be implemented to modify patients’ levels of knowledge about their conditions and the therapy, beliefs about medicines and adherence to therapy. However, such programmes need to be conducted over a long period of time since changes involving behaviour take a long time.
- Full Text:
- Date Issued: 2006
- Authors: Shiri, Clarris
- Date: 2006
- Subjects: Patient education -- South Africa -- Eastern Cape Patient compliance -- South Africa -- Eastern Cape Hypertension -- Treatment -- South Africa Health care services -- South Africa Community health services -- South Africa
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: vital:3790 , http://hdl.handle.net/10962/d1003268
- Description: Evidence suggests that the prevalence of certain non-communicable diseases, such as hypertension, is increasing rapidly, and that patients with these diseases are making significant demands on the health services of the nations in sub-Saharan Africa. However, these countries also face other health-related challenges such as communicable diseases and underdevelopmentrelated diseases. Developing countries like South Africa have limited resources, in terms of man power and financial capital, to address the challenges that they are facing. Non-communicable diseases cannot be ignored and since health care providers cannot meet the challenges, it is worthwhile to empower patients to be involved in the management of their conditions. Patient education is a tool that can be used to enable patients to manage their chronic conditions and thereby reduce the morbidity and mortality rates of these conditions. The aim of this study was to investigate the effect of a patient education intervention on participants’ levels of knowledge about hypertension and its therapy, beliefs about medicines and adherence to anti-hypertensive therapy. The intervention consisted of talks and discussions with all the participants as one group and as individuals. There was also written information given to the participants. Their levels of knowledge about hypertension and its therapy were measured using one-on-one interviews and self-administered questionnaires. Beliefs about medicines were measured using the Beliefs about Medicines Questionnaire (BMQ) whilst adherence levels were measured using pill counts, elf-reports and prescription refill records. The participants’ blood pressure readings and body mass indices were also recorded throughout the study. The parameters before and after the educational intervention were compared using statistical analyses. The participants’ levels of knowledge about hypertension and its therapy significantly increased whilst their beliefs about medicines were positively modified after the educational intervention. There were also increases, though not statistically significant, in the participants’ levels of adherence to anti-hypertensive therapy. Unexpectedly, the blood pressure readings and body mass indices increased significantly. The participants gave positive feedback regarding the educational intervention and indicated a desire for similar programmes to be run continuously. They also suggested that such programmes be implemented for other common chronic conditions such as asthma and diabetes. This study proved that patient education programmes can be implemented to modify patients’ levels of knowledge about their conditions and the therapy, beliefs about medicines and adherence to therapy. However, such programmes need to be conducted over a long period of time since changes involving behaviour take a long time.
- Full Text:
- Date Issued: 2006
Pharmaceutical analysis and aspects of the quality control of St. John's Wort products
- Authors: Wild, Tracy Joy
- Date: 2003
- Subjects: Hypericum perforatum , Hypericum perforatum -- Analysis , Hypericum perforatum -- Therapeutic use , Hypericum perforatum -- Physiological effect , Flavonoids -- Analysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3804 , http://hdl.handle.net/10962/d1003282 , Hypericum perforatum , Hypericum perforatum -- Analysis , Hypericum perforatum -- Therapeutic use , Hypericum perforatum -- Physiological effect , Flavonoids -- Analysis
- Description: Most complementary medicines contain a multitude of chemical components, some of which are claimed to contribute to the biological activity of such products. Use of complementary medicines for preventative and therapeutic purposes is increasing rapidly worldwide. Unfortunately, although control of these products is essential to ensure quality, safety, and efficacy, the quality control of most herbal preparations is currently poor to non-existent, with little or no safety and efficacy data required to support the marketing and use of these products. The objective of this study was therefore to develop suitable analytical methods to qualitatively and quantitatively analyse the relevant components (rutin, isoquercitrin, hyperoside, quercitrin, quercetin, kaempferol, hypericin, pseudohypericin and hyperforin) in St John's Wort dosage forms for quality control purposes. A gradient HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm internal diameter (i.d.) column and UV detection, was developed for the separation of six of the relevant flavonoid compounds in St John's Wort, namely rutin, isoquercitrin, hyperoside, quercitrin, quercetin and kaempferol. The development process involved a systematic investigation of gradient conditions, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products. This system provided the necessary accuracy, precision and reproducibility and was associated with several advantages when compared to using standard bore (4.60 mm i.d.) HPLC columns. The method developed is currently the only known method that separates all six relevant flavonoids in a reasonable run time (less than 20 minutes). It is also one of the few methods that has sufficient separation between rutin, isoquercitrin and hyperoside. A qualitative method for the fingerprinting of flavonoid components was also developed, using capillary electrophoresis (CE). CE is a rapidly growing powerful analytical technique for the separation of charged compounds. Micellar electrokinetic chromatography (MEKC) is a very powerful electrophoretic technique that is capable of selectively resolving both neutral and ionic solutes in a single run. A MEKC method suitable for the separation and determination of various flavonoid constituents used as marker compounds in Hypericum perforatum was developed. Investigations into the effect of pH, ionic strength, applied voltage and capillary dimensions on separation were performed. The optimised method was then applied to qualitatively analyse various St John's Wort products on the market. This method was found to be advantageous in that it was simple, cost-effective, required minimal sample preparation and utilised very small quantities of sample. Due to the vast differences in chemical properties between the various marker and active components in St John's Wort, it was necessary to develop separate analytical methods for the flavonoids and for the other three relevant compounds (hypericin, pseudohypericin and hyperforin). An isocratic HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm (i.d.) column and UV detection was developed for the separation of hypericin, pseudohypericin and hyperforin. The development process involved a systematic investigation of buffer molarity, mobile phase composition, pH, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products on the South African market. This system also provided the necessary accuracy, precision and reproducibility, as well as the advantages associated with the use of a narrow bore column as opposed to the use of the more commonly used wider bore columns. This method was validated and used to quantitate these three compounds in various commercial St John's Wort products. By applying this method to liquid chromatography – tandem mass spectrometry (LC-MS-MS), qualitative analyses of the same products was performed to obtain confirmation of the quantitative HPLC results. Mass spectrometry is a powerful detection tool that is more selective and specific than many detection systems used with HPLC. Natural medicines usually constitute a multitude of constituents with much potential interference. In this regard LC-MS-MS is a powerful tool, with its ability to unequivocally identify target analytes regardless of the presence of interferences or complex matrices. ESI-MS-MS was used for the qualitative analysis of the content of the naphthodianthrones and hyperforin in the respective tablet products assayed with HPLC. LC-MS-MS analyses were performed in order to identify the constituents and to verify the specificity of the HPLC method. High inter-product and inter-batch variability was observed for all nine compounds assayed. These quantitative results were confirmed with the respective qualitative analyses. This study confirms the need for strict quality control of herbal medicinal products commercially available to consumers.
- Full Text:
- Date Issued: 2003
- Authors: Wild, Tracy Joy
- Date: 2003
- Subjects: Hypericum perforatum , Hypericum perforatum -- Analysis , Hypericum perforatum -- Therapeutic use , Hypericum perforatum -- Physiological effect , Flavonoids -- Analysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3804 , http://hdl.handle.net/10962/d1003282 , Hypericum perforatum , Hypericum perforatum -- Analysis , Hypericum perforatum -- Therapeutic use , Hypericum perforatum -- Physiological effect , Flavonoids -- Analysis
- Description: Most complementary medicines contain a multitude of chemical components, some of which are claimed to contribute to the biological activity of such products. Use of complementary medicines for preventative and therapeutic purposes is increasing rapidly worldwide. Unfortunately, although control of these products is essential to ensure quality, safety, and efficacy, the quality control of most herbal preparations is currently poor to non-existent, with little or no safety and efficacy data required to support the marketing and use of these products. The objective of this study was therefore to develop suitable analytical methods to qualitatively and quantitatively analyse the relevant components (rutin, isoquercitrin, hyperoside, quercitrin, quercetin, kaempferol, hypericin, pseudohypericin and hyperforin) in St John's Wort dosage forms for quality control purposes. A gradient HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm internal diameter (i.d.) column and UV detection, was developed for the separation of six of the relevant flavonoid compounds in St John's Wort, namely rutin, isoquercitrin, hyperoside, quercitrin, quercetin and kaempferol. The development process involved a systematic investigation of gradient conditions, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products. This system provided the necessary accuracy, precision and reproducibility and was associated with several advantages when compared to using standard bore (4.60 mm i.d.) HPLC columns. The method developed is currently the only known method that separates all six relevant flavonoids in a reasonable run time (less than 20 minutes). It is also one of the few methods that has sufficient separation between rutin, isoquercitrin and hyperoside. A qualitative method for the fingerprinting of flavonoid components was also developed, using capillary electrophoresis (CE). CE is a rapidly growing powerful analytical technique for the separation of charged compounds. Micellar electrokinetic chromatography (MEKC) is a very powerful electrophoretic technique that is capable of selectively resolving both neutral and ionic solutes in a single run. A MEKC method suitable for the separation and determination of various flavonoid constituents used as marker compounds in Hypericum perforatum was developed. Investigations into the effect of pH, ionic strength, applied voltage and capillary dimensions on separation were performed. The optimised method was then applied to qualitatively analyse various St John's Wort products on the market. This method was found to be advantageous in that it was simple, cost-effective, required minimal sample preparation and utilised very small quantities of sample. Due to the vast differences in chemical properties between the various marker and active components in St John's Wort, it was necessary to develop separate analytical methods for the flavonoids and for the other three relevant compounds (hypericin, pseudohypericin and hyperforin). An isocratic HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm (i.d.) column and UV detection was developed for the separation of hypericin, pseudohypericin and hyperforin. The development process involved a systematic investigation of buffer molarity, mobile phase composition, pH, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products on the South African market. This system also provided the necessary accuracy, precision and reproducibility, as well as the advantages associated with the use of a narrow bore column as opposed to the use of the more commonly used wider bore columns. This method was validated and used to quantitate these three compounds in various commercial St John's Wort products. By applying this method to liquid chromatography – tandem mass spectrometry (LC-MS-MS), qualitative analyses of the same products was performed to obtain confirmation of the quantitative HPLC results. Mass spectrometry is a powerful detection tool that is more selective and specific than many detection systems used with HPLC. Natural medicines usually constitute a multitude of constituents with much potential interference. In this regard LC-MS-MS is a powerful tool, with its ability to unequivocally identify target analytes regardless of the presence of interferences or complex matrices. ESI-MS-MS was used for the qualitative analysis of the content of the naphthodianthrones and hyperforin in the respective tablet products assayed with HPLC. LC-MS-MS analyses were performed in order to identify the constituents and to verify the specificity of the HPLC method. High inter-product and inter-batch variability was observed for all nine compounds assayed. These quantitative results were confirmed with the respective qualitative analyses. This study confirms the need for strict quality control of herbal medicinal products commercially available to consumers.
- Full Text:
- Date Issued: 2003
Pharmacodynamics of phenylpropanolamine: aspects of safety and efficacy in humans
- Authors: Petrie, Lauri René
- Date: 1993
- Subjects: Phenylpropanolamine
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3785 , http://hdl.handle.net/10962/d1003263 , Phenylpropanolamine
- Description: Phenylpropanolamine (PPA), a synthetic sympathomimetic amine, is widely used as a nasal decongestant and as an appetite suppressant. Much controversy exists regarding the efficacy of the drug as an anorectic agent, the related adverse reactions caused by the relatively high doses required for appetite suppression and the potential of this drug for abuse. Whilst numerous studies have been carried out to assess the central and cardiovascular safety of PPA and many investigations have been performed to evaluate efficacy in terms of weight loss in humans, there is a relative paucity of information regarding the effects of PPA on appetite and food intake. A pilot trial was conducted to determine the feasiblility of a multidimensional approach to evaluate the safety and efficacy of PPA as ananorectic agent in humans. Eight normotensive caucasian women who were overweight participated in a randomised double-blind cross-over comparison of PPA (75 mg) and placebo and were dosed to steady-state on a 12-hour fixed-dose schedule for a period of eleven weeks. Aspects of efficacy evaluated included the effects of PPA on hunger, appetite and satiety,salivation, macro-nutrient food intake and body weight. Standardised scales were used to quantitatively assess the possible subjective mood and behavioural reinforcing effects of PPA. Supine systolic and diastolic blood pressures were monitored continually throughout the trial. In addition, peak and trough blood samp1es were taken to monitor serum concentrations of PPA reached at steady-state and patient compliance with the dosing schedule. An adaptation of a published reverse-phase high performance liquid chromatographic (HPLC) assay for PPA in serum using U.V. detection at 210 nm is presented. A significant decrease in body weight, salivation, total food intake and carbohydrate consumption was demonstrated following PPA administration. Phenylpropanolamine produced significant decrements in subjective reports of hunger and appetite, whilst apparently having little effect on satiety. No significant changes were observed for blood pressures and PPA did not produce significant mood alterations or behavioural reinforcing effects. The study demonstrates the feasibility of using this muti-faceted approach, with certain design modifications, to evaluate the overall safety and efficacy of PPA as an appetite suppressant.
- Full Text:
- Date Issued: 1993
- Authors: Petrie, Lauri René
- Date: 1993
- Subjects: Phenylpropanolamine
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3785 , http://hdl.handle.net/10962/d1003263 , Phenylpropanolamine
- Description: Phenylpropanolamine (PPA), a synthetic sympathomimetic amine, is widely used as a nasal decongestant and as an appetite suppressant. Much controversy exists regarding the efficacy of the drug as an anorectic agent, the related adverse reactions caused by the relatively high doses required for appetite suppression and the potential of this drug for abuse. Whilst numerous studies have been carried out to assess the central and cardiovascular safety of PPA and many investigations have been performed to evaluate efficacy in terms of weight loss in humans, there is a relative paucity of information regarding the effects of PPA on appetite and food intake. A pilot trial was conducted to determine the feasiblility of a multidimensional approach to evaluate the safety and efficacy of PPA as ananorectic agent in humans. Eight normotensive caucasian women who were overweight participated in a randomised double-blind cross-over comparison of PPA (75 mg) and placebo and were dosed to steady-state on a 12-hour fixed-dose schedule for a period of eleven weeks. Aspects of efficacy evaluated included the effects of PPA on hunger, appetite and satiety,salivation, macro-nutrient food intake and body weight. Standardised scales were used to quantitatively assess the possible subjective mood and behavioural reinforcing effects of PPA. Supine systolic and diastolic blood pressures were monitored continually throughout the trial. In addition, peak and trough blood samp1es were taken to monitor serum concentrations of PPA reached at steady-state and patient compliance with the dosing schedule. An adaptation of a published reverse-phase high performance liquid chromatographic (HPLC) assay for PPA in serum using U.V. detection at 210 nm is presented. A significant decrease in body weight, salivation, total food intake and carbohydrate consumption was demonstrated following PPA administration. Phenylpropanolamine produced significant decrements in subjective reports of hunger and appetite, whilst apparently having little effect on satiety. No significant changes were observed for blood pressures and PPA did not produce significant mood alterations or behavioural reinforcing effects. The study demonstrates the feasibility of using this muti-faceted approach, with certain design modifications, to evaluate the overall safety and efficacy of PPA as an appetite suppressant.
- Full Text:
- Date Issued: 1993
Preparation and evaluation of captopril - ion exchange resin complexes
- Chikukwa, Mellisa Tafadzwa Ruramai
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59146 , vital:27441
- Description: Restricted access-thesis embargoed for 2 years
- Full Text:
- Date Issued: 2017
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/59146 , vital:27441
- Description: Restricted access-thesis embargoed for 2 years
- Full Text:
- Date Issued: 2017
Preparation, characterization and optimization of carbamazepine based pellets prepared by extrusion-spheronization technique
- Authors: Makoni, Kudzai Gabriella
- Date: 2020-04
- Subjects: Carbamazepine , Pharmacokinetics , Anticonvulsants , Drugs -- Controlled release , Drugs -- Dosage forms , Tablets (Medicine) , Drugs -- Administration , High performance liquid chromatography , International Conference on Harmonisation , Experimental design
- Language: English
- Type: Thesis , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/140478 , vital:37893
- Description: Carbamazepine (CBZ) is an oral antiepileptic drug (AED) that is prescribed as a first-line treatment for partial seizures. CBZ is a class II compound according to the Biopharmaceutical Classification System (BCS), hence it exhibits low aqueous solubility and high gastrointestinal tract (GIT) permeability...
- Full Text:
- Date Issued: 2020-04
- Authors: Makoni, Kudzai Gabriella
- Date: 2020-04
- Subjects: Carbamazepine , Pharmacokinetics , Anticonvulsants , Drugs -- Controlled release , Drugs -- Dosage forms , Tablets (Medicine) , Drugs -- Administration , High performance liquid chromatography , International Conference on Harmonisation , Experimental design
- Language: English
- Type: Thesis , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/140478 , vital:37893
- Description: Carbamazepine (CBZ) is an oral antiepileptic drug (AED) that is prescribed as a first-line treatment for partial seizures. CBZ is a class II compound according to the Biopharmaceutical Classification System (BCS), hence it exhibits low aqueous solubility and high gastrointestinal tract (GIT) permeability...
- Full Text:
- Date Issued: 2020-04
Reaction of carbohydrates with the sulphuryl chloride-N, N-dimethyl formamide reagent
- Authors: Mabusela, Wilfred Thozamile
- Date: 1982
- Subjects: Chemical reactions Carbohydrates
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3731 , http://hdl.handle.net/10962/d1001470
- Description: An investigation of the reaction of the sulphuryl chloride-N, N-dimethyl formamide reagent with several carbohydrate compounds, containing free hydroxyl groups, was undertaken, mainly with the view of looking at substitution of the hydroxyl groups with chlorine atoms. The reaction was found to lead to substitution of both primary and secondary hydroxyl groups with chlorine, with inversion of configuration in the latter case. The reagent was further found to effect formylation and chlorosulphation of secondary hydroxyl groups, where nucleophilic substitution by a chlorine was not favourable. Studies involving the methyl pentopyranosides, showed that the reagent was particularly useful in the chlorosulphation and chlorination of sugars, compared with the hexopyranosides.
- Full Text:
- Date Issued: 1982
- Authors: Mabusela, Wilfred Thozamile
- Date: 1982
- Subjects: Chemical reactions Carbohydrates
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3731 , http://hdl.handle.net/10962/d1001470
- Description: An investigation of the reaction of the sulphuryl chloride-N, N-dimethyl formamide reagent with several carbohydrate compounds, containing free hydroxyl groups, was undertaken, mainly with the view of looking at substitution of the hydroxyl groups with chlorine atoms. The reaction was found to lead to substitution of both primary and secondary hydroxyl groups with chlorine, with inversion of configuration in the latter case. The reagent was further found to effect formylation and chlorosulphation of secondary hydroxyl groups, where nucleophilic substitution by a chlorine was not favourable. Studies involving the methyl pentopyranosides, showed that the reagent was particularly useful in the chlorosulphation and chlorination of sugars, compared with the hexopyranosides.
- Full Text:
- Date Issued: 1982
Science engagement with school learners for microbial quality testing of water in Makhanda
- Authors: Nqowana, Thandiswa
- Date: 2020-04
- Language: English
- Type: text , Thesis , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/124754 , vital:35677
- Description: Expected release date-April 2022
- Full Text: false
- Date Issued: 2020-04
- Authors: Nqowana, Thandiswa
- Date: 2020-04
- Language: English
- Type: text , Thesis , Masters , MSc (Pharmacy)
- Identifier: http://hdl.handle.net/10962/124754 , vital:35677
- Description: Expected release date-April 2022
- Full Text: false
- Date Issued: 2020-04
Serotonin binding in vitro by releasable proteins from human blood platelets
- Authors: Heemstra, Valerie Lawrence
- Date: 1984 , 2013-04-10
- Subjects: Serotonin , Serotonin -- Metabolism
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3829 , http://hdl.handle.net/10962/d1007215 , Serotonin , Serotonin -- Metabolism
- Description: Among the substances released from human blood platelets are serotonin and various proteins. It was hypothesized that one of these proteins binds serotonin and that serotonin might be important to the protein's function or that the protein might be important to serotonin's function. Two platelet-specific proteins, platelet factor 4 (PF4) and ß-thromboglobulin ( ßTG) were found to bind serotonin in vitro. Endogenous PF4 was isolated by serotonin-affinity chromatography and was identified by radioimmunoassay. Purified l¹²⁵ I] -PF4 and native PF4 bound to and eluted from a serotonin-affinity column similarly. Ultrafiltration of the homologous protein, (ßTG, with [¹⁴C]-serotonin demonstrated binding of about 8 moles serotonin per mole tetrameric ßTG with a dissociation con stant of about 4 x 10-8ThesisThesis⁻⁸ M. Equilibrium dialysis of PF4 with radiolabelled serotonin was attempted, but no binding constant values were obtained because serotonin apparently bound to the dialysis membrane. Since EDTA was one of the two agents that eluted PF4 from the serotonin-affinity gel, calcium binding by -PF4 was investigated by equilibrium dialysis. Evidence was obtained for positively cooperative binding of calcium ions by PF4. It is concluded that PF4 and ßTG bind serotonin in vitro, that they may also bind in vivo when platelets undergo release, and that the functions of serotonin, PF4 and ßTG may be mediated in part by serotonin-protein associations. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
- Authors: Heemstra, Valerie Lawrence
- Date: 1984 , 2013-04-10
- Subjects: Serotonin , Serotonin -- Metabolism
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3829 , http://hdl.handle.net/10962/d1007215 , Serotonin , Serotonin -- Metabolism
- Description: Among the substances released from human blood platelets are serotonin and various proteins. It was hypothesized that one of these proteins binds serotonin and that serotonin might be important to the protein's function or that the protein might be important to serotonin's function. Two platelet-specific proteins, platelet factor 4 (PF4) and ß-thromboglobulin ( ßTG) were found to bind serotonin in vitro. Endogenous PF4 was isolated by serotonin-affinity chromatography and was identified by radioimmunoassay. Purified l¹²⁵ I] -PF4 and native PF4 bound to and eluted from a serotonin-affinity column similarly. Ultrafiltration of the homologous protein, (ßTG, with [¹⁴C]-serotonin demonstrated binding of about 8 moles serotonin per mole tetrameric ßTG with a dissociation con stant of about 4 x 10-8ThesisThesis⁻⁸ M. Equilibrium dialysis of PF4 with radiolabelled serotonin was attempted, but no binding constant values were obtained because serotonin apparently bound to the dialysis membrane. Since EDTA was one of the two agents that eluted PF4 from the serotonin-affinity gel, calcium binding by -PF4 was investigated by equilibrium dialysis. Evidence was obtained for positively cooperative binding of calcium ions by PF4. It is concluded that PF4 and ßTG bind serotonin in vitro, that they may also bind in vivo when platelets undergo release, and that the functions of serotonin, PF4 and ßTG may be mediated in part by serotonin-protein associations. , KMBT_363 , Adobe Acrobat 9.53 Paper Capture Plug-in
- Full Text:
- Date Issued: 1984
Sorptive and microbial properties of low-cost adsorbents used in the extraction of ciprofloxacin and isoniazid from aqueous solution
- Authors: Dube, Cyril Simbarashe
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/59178 , vital:27450
- Description: This work describes how coal fly ash (FA), kaolinite, perlite, talc and vermiculite were used to remove ciprofloxacin and isoniazid from aqueous solutions. The adsorptive features of the adsorbents were evaluated for ciprofloxacin and isoniazid with regards to the effects of contact time, pH, solid/liquid ratio and antibiotic concentration. All adsorbents were sterilised by dry heat before use to avoid the proliferation of antimicrobial resistance by the bacteria present on the adsorbents during experiments. The regression correlation coefficients indicate that the linearised form of the Langmuir isotherm gives the best fit for the sorption of both antibiotics onto FA and talc, ciprofloxacin onto kaolinite, and isoniazid onto perlite and vermiculite with R2 values ranging from 0.908 - 0.999. The linearised form of the Freundlich isotherm best describes the sorption of ciprofloxacin onto vermiculite and isoniazid onto kaolinite with R2 values of 0.999 for both. The linearised form of the Temkin isotherm best describes the sorption of ciprofloxacin onto perlite with an R2 = 0.997. The values of the Freundlich exponent, 1/n, range from 0.221 - 0.998, indicating a favourable adsorption of ciprofloxacin and isoniazid onto the adsorbents. The heat of sorption, B, calculated from the Temkin plots has values ranging from 0.018 - 10.460 J/mol, indicating a physical adsorption process (physisorption). Adsorption equilibrium on all adsorbents was achieved after 30 min for both antibiotics and the kinetic data obtained conforms best to the pseudo-second order equation with R2 values ranging from 0.998 - 0.999. The removal of ciprofloxacin and isoniazid by all adsorbents except FA was strongly influenced by the pH suggesting that electrostatic interactions play a major role in the adsorption processes. All adsorbents except FA removed showed excellent adsorption of ciprofloxacin from aqueous solutions with all of them achieving removals ranging from 80 - 99%. The adsorbents were less efficient in removing isoniazid and kaolinite gave the highest removal of 55 %. Furthermore, the microbial quality of the adsorbents was investigated and the results revealed that kaolinite, talc, perlite and vermiculite were heavily contaminated with microorganisms. FA was sterile. The fungi isolated from the mineral adsorbents were in concentrations ranging from 2.13 x 106 to 1.25 x 107 CFU/g and were mostly moulds; Penicillium spp., Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Cladosporium spp. and Rhizopus oryzae. One yeast was isolated and was identified as Candida albicans. The bacteria identified were in concentrations ranging from 4.96 x 106 - 1.19 x 109 CFU/g. E. coli, Enterobacter cloacae, Exiguobacterium spp., Pseudomonas aeruginosa, Bacillus spp. and Serratia liquefaciens. The leachability index (LI) values obtained for adsorbents indicated that it is highly unlikely that microorganisms could be leached out of the adsorbents by rain. Heat inactivation of the microorganisms at a 105 °C was totally unsuccessful. However, it was established that a dry heat dose of 160 °C for at least 15 min was sufficient to eradicate all microorganisms present in the adsorbents. The D-values for coliform bacteria from all samples were very similar ranging from 1.7-2.2 min indicating homogeneity in heat resistance by the microorganisms. The Pseudomonas aureginosa isolated had a D-value of 2.2 min. The fungi isolated from the samples had D-values ranging from 2.1-3.2 min.
- Full Text:
- Date Issued: 2017
- Authors: Dube, Cyril Simbarashe
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSC
- Identifier: http://hdl.handle.net/10962/59178 , vital:27450
- Description: This work describes how coal fly ash (FA), kaolinite, perlite, talc and vermiculite were used to remove ciprofloxacin and isoniazid from aqueous solutions. The adsorptive features of the adsorbents were evaluated for ciprofloxacin and isoniazid with regards to the effects of contact time, pH, solid/liquid ratio and antibiotic concentration. All adsorbents were sterilised by dry heat before use to avoid the proliferation of antimicrobial resistance by the bacteria present on the adsorbents during experiments. The regression correlation coefficients indicate that the linearised form of the Langmuir isotherm gives the best fit for the sorption of both antibiotics onto FA and talc, ciprofloxacin onto kaolinite, and isoniazid onto perlite and vermiculite with R2 values ranging from 0.908 - 0.999. The linearised form of the Freundlich isotherm best describes the sorption of ciprofloxacin onto vermiculite and isoniazid onto kaolinite with R2 values of 0.999 for both. The linearised form of the Temkin isotherm best describes the sorption of ciprofloxacin onto perlite with an R2 = 0.997. The values of the Freundlich exponent, 1/n, range from 0.221 - 0.998, indicating a favourable adsorption of ciprofloxacin and isoniazid onto the adsorbents. The heat of sorption, B, calculated from the Temkin plots has values ranging from 0.018 - 10.460 J/mol, indicating a physical adsorption process (physisorption). Adsorption equilibrium on all adsorbents was achieved after 30 min for both antibiotics and the kinetic data obtained conforms best to the pseudo-second order equation with R2 values ranging from 0.998 - 0.999. The removal of ciprofloxacin and isoniazid by all adsorbents except FA was strongly influenced by the pH suggesting that electrostatic interactions play a major role in the adsorption processes. All adsorbents except FA removed showed excellent adsorption of ciprofloxacin from aqueous solutions with all of them achieving removals ranging from 80 - 99%. The adsorbents were less efficient in removing isoniazid and kaolinite gave the highest removal of 55 %. Furthermore, the microbial quality of the adsorbents was investigated and the results revealed that kaolinite, talc, perlite and vermiculite were heavily contaminated with microorganisms. FA was sterile. The fungi isolated from the mineral adsorbents were in concentrations ranging from 2.13 x 106 to 1.25 x 107 CFU/g and were mostly moulds; Penicillium spp., Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, Cladosporium spp. and Rhizopus oryzae. One yeast was isolated and was identified as Candida albicans. The bacteria identified were in concentrations ranging from 4.96 x 106 - 1.19 x 109 CFU/g. E. coli, Enterobacter cloacae, Exiguobacterium spp., Pseudomonas aeruginosa, Bacillus spp. and Serratia liquefaciens. The leachability index (LI) values obtained for adsorbents indicated that it is highly unlikely that microorganisms could be leached out of the adsorbents by rain. Heat inactivation of the microorganisms at a 105 °C was totally unsuccessful. However, it was established that a dry heat dose of 160 °C for at least 15 min was sufficient to eradicate all microorganisms present in the adsorbents. The D-values for coliform bacteria from all samples were very similar ranging from 1.7-2.2 min indicating homogeneity in heat resistance by the microorganisms. The Pseudomonas aureginosa isolated had a D-value of 2.2 min. The fungi isolated from the samples had D-values ranging from 2.1-3.2 min.
- Full Text:
- Date Issued: 2017
Structural studies on the capsular antigens of Escherichia coli serotypes K102 and K47
- Authors: De Bruin, Aletta Hester
- Date: 1991
- Subjects: Escherichia -- Research , Klebsiella -- Research , Enterobacteriaceae -- Research , Antigens -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3754 , http://hdl.handle.net/10962/d1003232 , Escherichia -- Research , Klebsiella -- Research , Enterobacteriaceae -- Research , Antigens -- Research
- Description: The work presented in this thesis forms part of a continuing programme concerned with the structural determination of capsular polysaccharides of some Enterobacteriaceae. Since bacteria of this family are pathogenic to Man, work in this laboratory has focused on the structural elucidation of Klebsiella and, more recently, Escherichia coli ( E. coli) capsular polysaccharides ( K-antigens ). To date, some 74 K-antigens have been distinguished serologically within the genus E. coli and the structures of approximately 70% are known. In general, the K-antigens of the E. coli are characterized by a wide variety of constituent monosaccharides arranged in repeating units. In this thesis the structural elucidation of the capsular polysaccharides of E. coli serotypes 08: KI02: H- and 08: K47: H2 is presented. A variety of chemical techniques has been employed in the structural analysis, and are discussed. The thesis also includes extensive two-dimensional n.m.r. studies on the E. coli KI02 and K47 polysaccharides, as well as on a modified KI02 polymer produced after a lithium-ethylenediamine degradation of the native polysaccharide.
- Full Text:
- Date Issued: 1991
- Authors: De Bruin, Aletta Hester
- Date: 1991
- Subjects: Escherichia -- Research , Klebsiella -- Research , Enterobacteriaceae -- Research , Antigens -- Research
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3754 , http://hdl.handle.net/10962/d1003232 , Escherichia -- Research , Klebsiella -- Research , Enterobacteriaceae -- Research , Antigens -- Research
- Description: The work presented in this thesis forms part of a continuing programme concerned with the structural determination of capsular polysaccharides of some Enterobacteriaceae. Since bacteria of this family are pathogenic to Man, work in this laboratory has focused on the structural elucidation of Klebsiella and, more recently, Escherichia coli ( E. coli) capsular polysaccharides ( K-antigens ). To date, some 74 K-antigens have been distinguished serologically within the genus E. coli and the structures of approximately 70% are known. In general, the K-antigens of the E. coli are characterized by a wide variety of constituent monosaccharides arranged in repeating units. In this thesis the structural elucidation of the capsular polysaccharides of E. coli serotypes 08: KI02: H- and 08: K47: H2 is presented. A variety of chemical techniques has been employed in the structural analysis, and are discussed. The thesis also includes extensive two-dimensional n.m.r. studies on the E. coli KI02 and K47 polysaccharides, as well as on a modified KI02 polymer produced after a lithium-ethylenediamine degradation of the native polysaccharide.
- Full Text:
- Date Issued: 1991
Studies in the thiophenol mediated substitution and reductive dehalogenation of 3 bromoacetylcoumarins
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
- Date Issued: 2017
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
- Date Issued: 2017
Synthesis and structure-activity relationship studies of 1,4-naphthoquinone derivatives as potential anti-trypanosomal agents
- Authors: Chakaingesu, Chikomborero
- Date: 2014
- Subjects: African trypanosomiasis , Trypanosoma brucei , Naphthoquinone , Protozoan diseases , Drugs -- Structure-activity relationships , Millennium Development Goals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3873 , http://hdl.handle.net/10962/d1020959
- Description: Human African Trypanosomiasis (HAT) is an infectious, vector-borne protozoal disease which is amongst the so-called neglected diseases. In 2000, at a summit of the United Nations, eight Millennium Development Goals (MDGs) were set, to be achieved by 2015. MDG 6 states “to combat HIV/AIDS, malaria & other diseases”. With just under 2 years to go before the end of 2015, HAT is still thriving in developing countries. The drugs currently used for the treatment of HAT are in short supply, have severe side effects and those used to treat late stages of the disease are very difficult to administer. The aforementioned challenges call for research into this neglected disease in order to develop new, safe and easy-to-use medicines. Naphthoquinones are a class of compounds shown to possess anti-parasitic activity, amongst a variety of other biological activities, and therefore this pharmacophore was selected for this study. The purpose of this study was to synthesise derivatives of 2,3-dichloro-1,4- naphthoquinone to be tested for anti-trypanosomal activity and thereafter conduct structureactivity relationship studies. A series of reactions were carried out using thiophenol, phenol and aniline nucleophiles to synthesise thioether (-S-), ether (-O-) and amino (-NH-) derivatives of 2,3-dichloro-1,4-naphthoquinone with various halogen or methyl substituents. Purification of the products was carried out by recrystallisation. Nuclear magnetic resonance (NMR), infra-red (IR) and high pressure liquid chromatography coupled to an electro-spray ionisation mass spectrometer (HPLC-ESI-MS) were the analytical methods used for structural confirmation of the products. There were eighteen 1,4-naphthoquinone derivatives that were successfully synthesised using ethanolic solutions. Unfortunately, attempts to synthesise 1,4-naphthoquinones in reactions involving 2-(trifluoro-methyl)aniline and 2-isopropyl-5-methylphenol were unsuccessful, presumably due to steric hindrance by the bulky ortho-substituents. Although the aims of the synthetic procedures were to obtain both mono- and disubstituted products by nucleophilic displacement of the chlorine atom(s) of 2,3-dichloro-1,4- naphthoquinone, only monosubstituted products were obtained from substitution with aniline and phenol nucleophiles. Thiol nucleophiles, however, selectively yielded disubstituted products only. Synthesised naphthoquinone derivatives were tested against Trypanosoma brucei and calculation of the EC₅₀ values from the obtained dose-response curves was carried out using the four parametric equation. All the 1,4-naphthoquinones showed a degree of potency, except compounds 1b, 3c and 3e, which had little or lack of potency. Structure-activity relationship studies (SARs and QSARs) were carried out to determine which structural features or functional group substituents of the naphthoquinone derivatives contribute or take away from the desired anti-trypanosomal activity. It was found that compounds with the best in vitro anti-trypanosomal potencies in the series of analogous 1,4-naphthoquinone derivatives had EC₅₀ values in the range 2.137 to 2.884 μM. The most potent compound in the series was 2-chloro-3-(4-(trifluoromethyl)phenylamino)-1,4- naphthoquinone 1e; but it was 142-fold less potent than the reference standard of melarsoprol.
- Full Text:
- Date Issued: 2014
- Authors: Chakaingesu, Chikomborero
- Date: 2014
- Subjects: African trypanosomiasis , Trypanosoma brucei , Naphthoquinone , Protozoan diseases , Drugs -- Structure-activity relationships , Millennium Development Goals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3873 , http://hdl.handle.net/10962/d1020959
- Description: Human African Trypanosomiasis (HAT) is an infectious, vector-borne protozoal disease which is amongst the so-called neglected diseases. In 2000, at a summit of the United Nations, eight Millennium Development Goals (MDGs) were set, to be achieved by 2015. MDG 6 states “to combat HIV/AIDS, malaria & other diseases”. With just under 2 years to go before the end of 2015, HAT is still thriving in developing countries. The drugs currently used for the treatment of HAT are in short supply, have severe side effects and those used to treat late stages of the disease are very difficult to administer. The aforementioned challenges call for research into this neglected disease in order to develop new, safe and easy-to-use medicines. Naphthoquinones are a class of compounds shown to possess anti-parasitic activity, amongst a variety of other biological activities, and therefore this pharmacophore was selected for this study. The purpose of this study was to synthesise derivatives of 2,3-dichloro-1,4- naphthoquinone to be tested for anti-trypanosomal activity and thereafter conduct structureactivity relationship studies. A series of reactions were carried out using thiophenol, phenol and aniline nucleophiles to synthesise thioether (-S-), ether (-O-) and amino (-NH-) derivatives of 2,3-dichloro-1,4-naphthoquinone with various halogen or methyl substituents. Purification of the products was carried out by recrystallisation. Nuclear magnetic resonance (NMR), infra-red (IR) and high pressure liquid chromatography coupled to an electro-spray ionisation mass spectrometer (HPLC-ESI-MS) were the analytical methods used for structural confirmation of the products. There were eighteen 1,4-naphthoquinone derivatives that were successfully synthesised using ethanolic solutions. Unfortunately, attempts to synthesise 1,4-naphthoquinones in reactions involving 2-(trifluoro-methyl)aniline and 2-isopropyl-5-methylphenol were unsuccessful, presumably due to steric hindrance by the bulky ortho-substituents. Although the aims of the synthetic procedures were to obtain both mono- and disubstituted products by nucleophilic displacement of the chlorine atom(s) of 2,3-dichloro-1,4- naphthoquinone, only monosubstituted products were obtained from substitution with aniline and phenol nucleophiles. Thiol nucleophiles, however, selectively yielded disubstituted products only. Synthesised naphthoquinone derivatives were tested against Trypanosoma brucei and calculation of the EC₅₀ values from the obtained dose-response curves was carried out using the four parametric equation. All the 1,4-naphthoquinones showed a degree of potency, except compounds 1b, 3c and 3e, which had little or lack of potency. Structure-activity relationship studies (SARs and QSARs) were carried out to determine which structural features or functional group substituents of the naphthoquinone derivatives contribute or take away from the desired anti-trypanosomal activity. It was found that compounds with the best in vitro anti-trypanosomal potencies in the series of analogous 1,4-naphthoquinone derivatives had EC₅₀ values in the range 2.137 to 2.884 μM. The most potent compound in the series was 2-chloro-3-(4-(trifluoromethyl)phenylamino)-1,4- naphthoquinone 1e; but it was 142-fold less potent than the reference standard of melarsoprol.
- Full Text:
- Date Issued: 2014
Taste masking of clarithromycin with ion exchange resins
- Authors: Ntemi, Pascal Vitalis
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65178 , vital:28701
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017
- Authors: Ntemi, Pascal Vitalis
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65178 , vital:28701
- Description: Expected release date-May 2019
- Full Text:
- Date Issued: 2017