An evaluation of medicinal plants used in South Africa and Lesotho for uterotonic contractile purposes
- Authors: Smit, Inge
- Date: 2016
- Subjects: Traditional medicine -- South Africa Traditional medicine -- Lesotho
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/15232 , vital:40256
- Description: Background One of the leading cause of maternal mortality globally is postpartum haemorrhage (PPH), which mainly occur in developing countries. By identifying traditional medicinal plants that is used by Traditional birth attendants we can analysis the plants for cyclotides which contain uterotonic properties and a wide variety of other properties. The indigenous knowledge of traditional medicinal plants need to be preserved and scientifically proven to ensure future drug development and continued use of these plants. Cyclotides can be used as a backbone to develop novel drugs in that cyclotides are very stable proteins. Methods: Ten plants were identified that are commonly used to prevent or treat postpartum haemorrhage. The plant samples were collected, prepared and dried in South Africa. The plants were analysed in Austria. The plants underwent extraction of one gram of each plant was analysed using: Matrix-Assisted Laser desorption Ionization time-of-flight Mass Spectrometry (MALDI-TOF-MS); Tandem Mass Spectrometry and Analysis by High-performance Liquid Chromatography (HPLC). Results None of the ten plants analysed showed the presence of cyclotides. It is important to report negative results, because it informs the academic fraternity and could be entered in a global data base of results. The plants analysed is known to be used by Traditional Birth Attendants for the treatment or prevention of postpartum haemorrhage. Conclusion All the plants analysed are commonly used to prevent and treat PPH. The fact that no cyclotides were found do not dispute the practical use of these plants to prevent and treat PPH. There continue to be a gap in what uterotonic properties these plants contain and should be further investigated.
- Full Text:
- Date Issued: 2016
- Authors: Smit, Inge
- Date: 2016
- Subjects: Traditional medicine -- South Africa Traditional medicine -- Lesotho
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10353/15232 , vital:40256
- Description: Background One of the leading cause of maternal mortality globally is postpartum haemorrhage (PPH), which mainly occur in developing countries. By identifying traditional medicinal plants that is used by Traditional birth attendants we can analysis the plants for cyclotides which contain uterotonic properties and a wide variety of other properties. The indigenous knowledge of traditional medicinal plants need to be preserved and scientifically proven to ensure future drug development and continued use of these plants. Cyclotides can be used as a backbone to develop novel drugs in that cyclotides are very stable proteins. Methods: Ten plants were identified that are commonly used to prevent or treat postpartum haemorrhage. The plant samples were collected, prepared and dried in South Africa. The plants were analysed in Austria. The plants underwent extraction of one gram of each plant was analysed using: Matrix-Assisted Laser desorption Ionization time-of-flight Mass Spectrometry (MALDI-TOF-MS); Tandem Mass Spectrometry and Analysis by High-performance Liquid Chromatography (HPLC). Results None of the ten plants analysed showed the presence of cyclotides. It is important to report negative results, because it informs the academic fraternity and could be entered in a global data base of results. The plants analysed is known to be used by Traditional Birth Attendants for the treatment or prevention of postpartum haemorrhage. Conclusion All the plants analysed are commonly used to prevent and treat PPH. The fact that no cyclotides were found do not dispute the practical use of these plants to prevent and treat PPH. There continue to be a gap in what uterotonic properties these plants contain and should be further investigated.
- Full Text:
- Date Issued: 2016
Using bioinformatics tools to screen for trypanosomal cathepsin B cysteine protease inhibitors from the SANCDB as a novel therapeutic modality against Human African Trypanosomiasis (HAT)
- Authors: Mokhawa, Gaone
- Date: 2016
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/3304 , vital:20470
- Description: Human African Trypanosomiasis (HAT), also known as sleeping sickness, is a fatal chronic disease that is caused by flagellated protozoans, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. HAT is spread by a bite from an infected tsetse fly of the Glosina genus. Up to 60 million people in 36 countries in sub-Saharan Africa are at a risk of infection from HAT with up to 30 000 deaths reported every year. Current chemotherapy for HAT is insufficient since the available drugs exhibit unacceptable side effects (toxicity) and parasite resistance. Novel treatments and approaches for development of specific and more potent drugs for HAT are therefore required. One approach is to target vital proteins that are essential to the life cycle of the parasite. The main interest of this study is to explore Trypanosoma brucei cathepsin B-like protease (TbCatB) structural and functional properties with the primary goal of discovering non peptide small molecule inhibitors of TbCatB using bioinformatics approaches. TbCatB is a papain family C1 cysteine protease which belongs to clan CA group and it has emerged as a potential HAT drug target. Papain family cysteine proteases of Clan CA group of Trypanosoma brucei (rhodesain and TbCatB) have demonstrated potential as chemotherapeutic targets using synthetic protease inhibitors like Z-Phe-Ala-CHN2 to kill the parasite in vitro and in vivo. TbCatB has been identified as the essential cysteine protease of T. brucei since mRNA silencing of TbCatB killed the parasite and resulted in a cure in mice infected with T. brucei while mRNA silencing of rhodesain only extended mice life. TbCatB is therefore a promising drug target against HAT and the discovery and development of compounds that can selectively inhibit TbCatB without posing any danger to the human host represent a great therapeutic solution for treatment of HAT. To understand protein-inhibitor interactions, useful information can be obtained from high resolution protease-inhibitor crystal structure complexes. This study aims to use bioinformatics approaches to carry out comparative sequence, structural and functional analysis of TbCatB protease and its homologs from T. congolense, T, cruzi, T. vivax and H. sapien as well as to identify non-peptide small molecule inhibitors of TbCatB cysteine proteases from natural compounds of South African origin. Sequences of TbCatB (PDB ID: 3HHI) homologs were retrieved by a BLAST search. Human cathepsin B (PDB ID: 3CBJ) was selected from a list of templates for homology modelling found by HHpred. MODELLER version 9.10 program was used to generate a hundred models for T. congolense, T, cruzi and T. vivax cathepsin B like proteases using 3HHI and 3CBJ as templates. The best models were chosen based on their low DOPE Z scores before validation using MetaMQAPII, ANOLEA, PROCHECK and QMEAN6. The DOPE Z scores and the RMSD (RMS) values of the calculated models indicate that the models are of acceptable energy (stability) and fold (conformation). Results from the different MQAPs indicate the models are of acceptable quality and they can be used for docking studies. High throughput screening of SANCDB using AutoDock Vina revealed nine compounds, SANC00 478, 479, 480, 481, 482, 488, 489, 490 and 491, having a strong affinity for Trypanosoma spp. cathepsin B proteases than HsCatB. SANC00488 has the strongest binding to Trypanosoma spp. cathepsin B proteases and the weakest binding to HsCatB protease. Molecular dynamics (MD) simulations show that the complexes between SANC00488 and TbCatB, TcCatB, TcrCatB and TvCatB are stable and do not come apart during simulation. The complex between this compound and HsCatB however is unstable and comes apart during simulation. Residues that are important for the stability of SANC00488-TbCatB complex are Gly328 of the S2 subsite, Phe208, and Ala256. In conclusion SANC00488 is a good candidate for development of a drug against HAT.
- Full Text:
- Date Issued: 2016
- Authors: Mokhawa, Gaone
- Date: 2016
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/3304 , vital:20470
- Description: Human African Trypanosomiasis (HAT), also known as sleeping sickness, is a fatal chronic disease that is caused by flagellated protozoans, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. HAT is spread by a bite from an infected tsetse fly of the Glosina genus. Up to 60 million people in 36 countries in sub-Saharan Africa are at a risk of infection from HAT with up to 30 000 deaths reported every year. Current chemotherapy for HAT is insufficient since the available drugs exhibit unacceptable side effects (toxicity) and parasite resistance. Novel treatments and approaches for development of specific and more potent drugs for HAT are therefore required. One approach is to target vital proteins that are essential to the life cycle of the parasite. The main interest of this study is to explore Trypanosoma brucei cathepsin B-like protease (TbCatB) structural and functional properties with the primary goal of discovering non peptide small molecule inhibitors of TbCatB using bioinformatics approaches. TbCatB is a papain family C1 cysteine protease which belongs to clan CA group and it has emerged as a potential HAT drug target. Papain family cysteine proteases of Clan CA group of Trypanosoma brucei (rhodesain and TbCatB) have demonstrated potential as chemotherapeutic targets using synthetic protease inhibitors like Z-Phe-Ala-CHN2 to kill the parasite in vitro and in vivo. TbCatB has been identified as the essential cysteine protease of T. brucei since mRNA silencing of TbCatB killed the parasite and resulted in a cure in mice infected with T. brucei while mRNA silencing of rhodesain only extended mice life. TbCatB is therefore a promising drug target against HAT and the discovery and development of compounds that can selectively inhibit TbCatB without posing any danger to the human host represent a great therapeutic solution for treatment of HAT. To understand protein-inhibitor interactions, useful information can be obtained from high resolution protease-inhibitor crystal structure complexes. This study aims to use bioinformatics approaches to carry out comparative sequence, structural and functional analysis of TbCatB protease and its homologs from T. congolense, T, cruzi, T. vivax and H. sapien as well as to identify non-peptide small molecule inhibitors of TbCatB cysteine proteases from natural compounds of South African origin. Sequences of TbCatB (PDB ID: 3HHI) homologs were retrieved by a BLAST search. Human cathepsin B (PDB ID: 3CBJ) was selected from a list of templates for homology modelling found by HHpred. MODELLER version 9.10 program was used to generate a hundred models for T. congolense, T, cruzi and T. vivax cathepsin B like proteases using 3HHI and 3CBJ as templates. The best models were chosen based on their low DOPE Z scores before validation using MetaMQAPII, ANOLEA, PROCHECK and QMEAN6. The DOPE Z scores and the RMSD (RMS) values of the calculated models indicate that the models are of acceptable energy (stability) and fold (conformation). Results from the different MQAPs indicate the models are of acceptable quality and they can be used for docking studies. High throughput screening of SANCDB using AutoDock Vina revealed nine compounds, SANC00 478, 479, 480, 481, 482, 488, 489, 490 and 491, having a strong affinity for Trypanosoma spp. cathepsin B proteases than HsCatB. SANC00488 has the strongest binding to Trypanosoma spp. cathepsin B proteases and the weakest binding to HsCatB protease. Molecular dynamics (MD) simulations show that the complexes between SANC00488 and TbCatB, TcCatB, TcrCatB and TvCatB are stable and do not come apart during simulation. The complex between this compound and HsCatB however is unstable and comes apart during simulation. Residues that are important for the stability of SANC00488-TbCatB complex are Gly328 of the S2 subsite, Phe208, and Ala256. In conclusion SANC00488 is a good candidate for development of a drug against HAT.
- Full Text:
- Date Issued: 2016
Community structure and predation impact of carnivorous macrozooplankton in the polar frontal zone (Southern Ocean), with particular reference to chaetognaths
- Authors: Lukáč, Danica
- Date: 2006
- Subjects: Zooplankton -- Antarctic Ocean , Chaetognatha
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5653 , http://hdl.handle.net/10962/d1005336 , Zooplankton -- Antarctic Ocean , Chaetognatha
- Description: The community structure and predation impact of carnivorous macrozooplankton (>2 cm; chaetognaths, medusae, ctenophores and mysids), with particular emphasis on the chaetognaths Eukrohnia hamata and Sagitta gazellae, were investigated during three surveys conducted in late austral summer (April/May) of 2001, 2004 and 2005 in the Polar Frontal Zone in the vicinity of the Prince Edward Islands (46º45’S, 37º50’E), Southern Ocean. The 2001 survey formed part of the Marion Offshore Variability Ecosystem Study (MOVES II), while the 2004 and 2005 surveys formed part of the Dynamics of Eddy Impacts on Marion’s Ecosystem study (DEIMEC III and IV respectively). Macrozooplankton samples were collected using WP-2, RMT-8 and Bongo nets. Results of the hydrographic survey indicated that the region of investigation, the Polar Frontal Zone (PFZ), is an area of high mesoscale variability. During the 2004 survey the Antarctic Polar Front (APF) and the Subantarctic Front (SAF) merged to form an intense frontal feature with subsurface temperature and salinity ranging from 8.5-7.5ºC and 34.15-33.88, respectively. A cyclonic cold core eddy, believed to have been spawned from the APF, was observed during the 2005 survey. Macrozooplankton abundance and biomass ranged from 0 to 43.731 ind. m⁻³, and from 0 to 41.55 mg wwt m⁻³ respectively, during the three surveys. Among the carnivorous macrozooplankton, chaetognaths (Eukrohnia hamata and Sagitta gazellae) were most prominent, contributing up to 85% of the total biomass during all three surveys. Elevated biomass values were found near and within the frontal feature during the 2004 survey, and also along the eddy edge during the 2005 survey. However, hierarchical cluster analysis did not reveal the presence of distinct zooplankton groupings associated with the various water masses encountered during the surveys and this is probably due to the high mesoscale variability in oceanographic conditions that are characteristic of the PFZ. The total average predation impact of the selected carnivorous macrozooplankton during the 2001, 2004 and 2005 surveys accounted for 4.93 ± 6.76%, 0.55 ± 0.51% and 4.88 ± 4.45 of the mesozooplankton standing stock, respectively. S. gazellae had the highest consumption rate in all three surveys, consuming up to 800 g Dwt 1000m⁻³d⁻¹ during the study. Of the two chaetognaths, E. hamata dominated the chaetognath standing stock. The combined abundance and biomass values of E. hamata and S. gazellae ranged from 0 to 43.73 ind. m⁻³ and from 0 to 41.551 mg wwt m⁻³ respectively, during the three surveys. Inter-annual variability in the chaetognath densities was apparent. Highest abundances and biomasses tended to be associated with specific water masses, confirming the existence of a relationship between zooplankton community structure and hydrographic conditions. Generally, about 90% of the chaetognaths contained no food in their guts. S. gazellae consumed a wider variety of prey. Oil droplets occurred in the guts of ≈ 51% of E. hamata. Cannibalism was low in both species, but greater in S. gazellae than E. hamata. During the three surveys, the feeding rate values of E. hamata and S. gazellae went up to 0.48 and 2.099 prey d⁻¹ respectively. S. gazellae also had a greater predation impact on the mesozooplankton standing stock than E. hamata. The mean predation impact of the chaetognaths combined was 0.31 ± 0.291%, 0.52 ± 0.28% and 0.53 ± 0.56% of the mesozooplankton standing stock during the 2001, 2004 and 2005 surveys, respectively. During all three surveys, the majority of individuals (≈ 76%) of the chaetognaths were at stage I maturity, suggesting that during the time of study the chaetognaths were not reproducing. In both species a significant difference (log-linear analysis, p < 0.05) in maturities between the years investigated was observed. In general, there were no differences in lengths and maturities between the different water masses encountered during the surveys. The lengths of E. hamata and S. gazellae ranged from 5 to 24 mm and from 9.4 to 63.6 mm, respectively.
- Full Text:
- Date Issued: 2006
- Authors: Lukáč, Danica
- Date: 2006
- Subjects: Zooplankton -- Antarctic Ocean , Chaetognatha
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5653 , http://hdl.handle.net/10962/d1005336 , Zooplankton -- Antarctic Ocean , Chaetognatha
- Description: The community structure and predation impact of carnivorous macrozooplankton (>2 cm; chaetognaths, medusae, ctenophores and mysids), with particular emphasis on the chaetognaths Eukrohnia hamata and Sagitta gazellae, were investigated during three surveys conducted in late austral summer (April/May) of 2001, 2004 and 2005 in the Polar Frontal Zone in the vicinity of the Prince Edward Islands (46º45’S, 37º50’E), Southern Ocean. The 2001 survey formed part of the Marion Offshore Variability Ecosystem Study (MOVES II), while the 2004 and 2005 surveys formed part of the Dynamics of Eddy Impacts on Marion’s Ecosystem study (DEIMEC III and IV respectively). Macrozooplankton samples were collected using WP-2, RMT-8 and Bongo nets. Results of the hydrographic survey indicated that the region of investigation, the Polar Frontal Zone (PFZ), is an area of high mesoscale variability. During the 2004 survey the Antarctic Polar Front (APF) and the Subantarctic Front (SAF) merged to form an intense frontal feature with subsurface temperature and salinity ranging from 8.5-7.5ºC and 34.15-33.88, respectively. A cyclonic cold core eddy, believed to have been spawned from the APF, was observed during the 2005 survey. Macrozooplankton abundance and biomass ranged from 0 to 43.731 ind. m⁻³, and from 0 to 41.55 mg wwt m⁻³ respectively, during the three surveys. Among the carnivorous macrozooplankton, chaetognaths (Eukrohnia hamata and Sagitta gazellae) were most prominent, contributing up to 85% of the total biomass during all three surveys. Elevated biomass values were found near and within the frontal feature during the 2004 survey, and also along the eddy edge during the 2005 survey. However, hierarchical cluster analysis did not reveal the presence of distinct zooplankton groupings associated with the various water masses encountered during the surveys and this is probably due to the high mesoscale variability in oceanographic conditions that are characteristic of the PFZ. The total average predation impact of the selected carnivorous macrozooplankton during the 2001, 2004 and 2005 surveys accounted for 4.93 ± 6.76%, 0.55 ± 0.51% and 4.88 ± 4.45 of the mesozooplankton standing stock, respectively. S. gazellae had the highest consumption rate in all three surveys, consuming up to 800 g Dwt 1000m⁻³d⁻¹ during the study. Of the two chaetognaths, E. hamata dominated the chaetognath standing stock. The combined abundance and biomass values of E. hamata and S. gazellae ranged from 0 to 43.73 ind. m⁻³ and from 0 to 41.551 mg wwt m⁻³ respectively, during the three surveys. Inter-annual variability in the chaetognath densities was apparent. Highest abundances and biomasses tended to be associated with specific water masses, confirming the existence of a relationship between zooplankton community structure and hydrographic conditions. Generally, about 90% of the chaetognaths contained no food in their guts. S. gazellae consumed a wider variety of prey. Oil droplets occurred in the guts of ≈ 51% of E. hamata. Cannibalism was low in both species, but greater in S. gazellae than E. hamata. During the three surveys, the feeding rate values of E. hamata and S. gazellae went up to 0.48 and 2.099 prey d⁻¹ respectively. S. gazellae also had a greater predation impact on the mesozooplankton standing stock than E. hamata. The mean predation impact of the chaetognaths combined was 0.31 ± 0.291%, 0.52 ± 0.28% and 0.53 ± 0.56% of the mesozooplankton standing stock during the 2001, 2004 and 2005 surveys, respectively. During all three surveys, the majority of individuals (≈ 76%) of the chaetognaths were at stage I maturity, suggesting that during the time of study the chaetognaths were not reproducing. In both species a significant difference (log-linear analysis, p < 0.05) in maturities between the years investigated was observed. In general, there were no differences in lengths and maturities between the different water masses encountered during the surveys. The lengths of E. hamata and S. gazellae ranged from 5 to 24 mm and from 9.4 to 63.6 mm, respectively.
- Full Text:
- Date Issued: 2006
The effect of elevated temperature on the nutrient requirements of rainbow trout, Salmo gairdneri (Pisces : Salmonidae) and the development of "least cost" feeds for trout production in South Africa
- Authors: McEwan, Anthony Graham
- Date: 1988
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:21150 , http://hdl.handle.net/10962/6606
- Description: A review of trout metabolism, ingested energetic pathways, essential dietary nutrient requirements and the effect of water temperature on trout physiology identified the need to determine the effect of elevated temperatures (>18oC) on the nutrient requirements of rainbow trout. This review led to the hypothesis that as the temperature exceeds the optimum the growth potential of trout decreases with a theoretical concomitant decrease in the protein requirement. However, the increased metabolic rates of the fish should be reflected by an increased demand for lipids. The experiments designed to test this hypothesis revealed that at temperatures in excess of 18 oC the protein requirement for small (4.5g) and larger (>25g) juvenile rainbow trout are 40 and 35% respectively. This represents a decrease of 10% for the small juveniles and no change for larger juveniles compared to their requirements at optimum temperatures. The lipid requirements for the small as well as the larger juveniles increased by approximately 5 percent, to between 20 and 23 percent, compared to the requirement at optimum temperatures. Consequently the hypothesis was accepted. A review of practical diet formulation is presented along with a description of the experiments conducted to test several "least cost" diets under South African conditions. Recommendations that winter and summer diets be formulated and that the trout producers manufacture their own feeds are made. The most appropriate diet formulated and tested effected a 21 to 29.9 percent saving compared to the currently available feeds in South Africa.
- Full Text:
- Date Issued: 1988
- Authors: McEwan, Anthony Graham
- Date: 1988
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:21150 , http://hdl.handle.net/10962/6606
- Description: A review of trout metabolism, ingested energetic pathways, essential dietary nutrient requirements and the effect of water temperature on trout physiology identified the need to determine the effect of elevated temperatures (>18oC) on the nutrient requirements of rainbow trout. This review led to the hypothesis that as the temperature exceeds the optimum the growth potential of trout decreases with a theoretical concomitant decrease in the protein requirement. However, the increased metabolic rates of the fish should be reflected by an increased demand for lipids. The experiments designed to test this hypothesis revealed that at temperatures in excess of 18 oC the protein requirement for small (4.5g) and larger (>25g) juvenile rainbow trout are 40 and 35% respectively. This represents a decrease of 10% for the small juveniles and no change for larger juveniles compared to their requirements at optimum temperatures. The lipid requirements for the small as well as the larger juveniles increased by approximately 5 percent, to between 20 and 23 percent, compared to the requirement at optimum temperatures. Consequently the hypothesis was accepted. A review of practical diet formulation is presented along with a description of the experiments conducted to test several "least cost" diets under South African conditions. Recommendations that winter and summer diets be formulated and that the trout producers manufacture their own feeds are made. The most appropriate diet formulated and tested effected a 21 to 29.9 percent saving compared to the currently available feeds in South Africa.
- Full Text:
- Date Issued: 1988
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