Adolescent pregnancy: a community engaged participatory approach to design and implement an educational intervention
- Authors: Siruma, Amanda Tatenda
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54656 , vital:26597
- Description: Millennium Development Goal (MDG) 5 focuses on improving maternal health, due to global acknowledgment that no woman should have to die as a result of complications during pregnancy and childbirth. Adolescents have an increased risk of maternal death compared with older women. Adolescent pregnancy also poses a threat to the empowerment of young girls by mitigating their physical, educational, social, and economic development. In this context, maternal health promotion strategies which inclusively target adolescents are crucial, not only in improving maternal health outcomes, but also in optimising the overall transition of adolescent girls to adulthood. This study was a first time collaborative partnership of the Faculty of Pharmacy and Community Engagement Office of Rhodes University with the Angus Gillis Foundation (a non-profit community development organisation), and community participants of Glenmore and Ndwayana, two rural communities in the Eastern Cape. The aim of this study was to identify the maternal health issue of most concern to community participants and to design and implement an appropriate educational intervention for a suitable target group. During the baseline phase of this study, ten focus group discussions (FGDs) were conducted with 76 community stakeholders. Semi-structured interviews (SSIs) were conducted with two Sisters-in-Charge from each Primary Health Care (PHC) facility in the study setting. Data on the stock status of World Health Organization (WHO) identified lifesaving priority medicines for women’s health was also collected at both PHCs. Thereafter, pre- and posteducational interventions SSIs with female adolescent participants were conducted. The educational intervention was followed up with the development of a booklet on reproductive health. FGD participants identified adolescent pregnancy as the maternal health issue of most concern. They also highlighted challenges in service delivery of ambulance services for expectant mothers in urgent need of transportation to a referral hospital. A majority of preintervention SSI participants indicated coercion from both younger and older men as a factor influencing early sexual debut amongst adolescent girls in their communities. Despite availability in the PHCs, challenges in accessing contraceptives were highlighted by the participants. Additionally, a number of sexually active adolescent girls defaulted on their next allocated visit to the PHC due to myths regarding use of oral and injectable contraceptives. During the educational intervention sessions, participants recognised knowledge gaps regarding reproductive health issues and the influence of peer pressure as constraining factors in preventing adolescent pregnancy. During the post-intervention phase, participants highlighted that the educational intervention of this study had provided a forum to discuss ways of preventing adolescent pregnancy. The educational booklet developed is intended to serve as a resource tool of the educational programme on prevention of adolescent pregnancy, which is expected to be incorporated into the Angus Gillis Foundation’s existing ‘Positive Health’ Programme. The results of this study show that community-based participatory research facilitated the identification of the maternal health issue of most concern to these communities. Working synergistically with key stakeholders in designing and implementing an educational intervention for preventing adolescent pregnancy provides a good foundation for future up scaling and sustainability of this educational programme.
- Full Text:
- Date Issued: 2014
- Authors: Siruma, Amanda Tatenda
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54656 , vital:26597
- Description: Millennium Development Goal (MDG) 5 focuses on improving maternal health, due to global acknowledgment that no woman should have to die as a result of complications during pregnancy and childbirth. Adolescents have an increased risk of maternal death compared with older women. Adolescent pregnancy also poses a threat to the empowerment of young girls by mitigating their physical, educational, social, and economic development. In this context, maternal health promotion strategies which inclusively target adolescents are crucial, not only in improving maternal health outcomes, but also in optimising the overall transition of adolescent girls to adulthood. This study was a first time collaborative partnership of the Faculty of Pharmacy and Community Engagement Office of Rhodes University with the Angus Gillis Foundation (a non-profit community development organisation), and community participants of Glenmore and Ndwayana, two rural communities in the Eastern Cape. The aim of this study was to identify the maternal health issue of most concern to community participants and to design and implement an appropriate educational intervention for a suitable target group. During the baseline phase of this study, ten focus group discussions (FGDs) were conducted with 76 community stakeholders. Semi-structured interviews (SSIs) were conducted with two Sisters-in-Charge from each Primary Health Care (PHC) facility in the study setting. Data on the stock status of World Health Organization (WHO) identified lifesaving priority medicines for women’s health was also collected at both PHCs. Thereafter, pre- and posteducational interventions SSIs with female adolescent participants were conducted. The educational intervention was followed up with the development of a booklet on reproductive health. FGD participants identified adolescent pregnancy as the maternal health issue of most concern. They also highlighted challenges in service delivery of ambulance services for expectant mothers in urgent need of transportation to a referral hospital. A majority of preintervention SSI participants indicated coercion from both younger and older men as a factor influencing early sexual debut amongst adolescent girls in their communities. Despite availability in the PHCs, challenges in accessing contraceptives were highlighted by the participants. Additionally, a number of sexually active adolescent girls defaulted on their next allocated visit to the PHC due to myths regarding use of oral and injectable contraceptives. During the educational intervention sessions, participants recognised knowledge gaps regarding reproductive health issues and the influence of peer pressure as constraining factors in preventing adolescent pregnancy. During the post-intervention phase, participants highlighted that the educational intervention of this study had provided a forum to discuss ways of preventing adolescent pregnancy. The educational booklet developed is intended to serve as a resource tool of the educational programme on prevention of adolescent pregnancy, which is expected to be incorporated into the Angus Gillis Foundation’s existing ‘Positive Health’ Programme. The results of this study show that community-based participatory research facilitated the identification of the maternal health issue of most concern to these communities. Working synergistically with key stakeholders in designing and implementing an educational intervention for preventing adolescent pregnancy provides a good foundation for future up scaling and sustainability of this educational programme.
- Full Text:
- Date Issued: 2014
An investigation of the potential anti-diabetic (insulinomimetic) activity of anti-oxidant compounds derived from Sargassum heterophyllum
- Authors: Nyambe, Mutenta Nsokolo
- Date: 2014
- Subjects: Sargassum , Diabetes -- Chemotherapy , Diabetes -- Africa , Antioxidants -- Therapeutic use , Marine algae , Endemic plants -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3874 , http://hdl.handle.net/10962/d1021020
- Description: In Africa, non-communicable diseases such as diabetes mellitus have been generally neglected. This problem has worsened over the years owing to continuous threats from infectious diseases such as HIV/AIDS, tuberculosis and malaria. Despite this, statistics have shown that by 2030, the African region will have the highest proportional increase in diabetes prevalence. Over 80% of all diabetic deaths occur in developing countries probably not only due to poor equity of access to medication but also due to limited efficacy and side effects associated with the commonly available anti-diabetic agents. Therefore, this creates the desperate need for the development of new anti-diabetic agents that are more efficacious and can be sourced from within the continent. With oxidative stress as a suggested mechanism underlying the cause of diabetes mellitus and diabetic complications, the discovery of natural anti-oxidants that prevent free radical mediated damage is important for developing new treatment strategies. Marine algae have been identified as good sources for natural anti-oxidants. Unfortunately, very few studies have embarked on the discovery of marine-derived anti-oxidant compounds with potential anti-diabetic activity. In this project, we investigated the potential anti-oxidant activity of the South African endemic algae Stypopodium multipartitum, Dictyopterus ligulata, Cystophora fibriosa, Bifurcariopsis capensis, Sargassum sp. and Sargassum heterophyllum. From these studies, Sargassum heterophyllum yielded prenylated compounds, the main compound being sargahydroquinoic acid (3.6) and the carotenoid metabolite fucoxanthin (3.8), which are in part responsible for the radical scavenging activity of the crude extract. Sargahydroquinoic acid (3.6) and fucoxanthin (3.8) also exhibited significant anti-inflammatory activity. Sargaquinoic acid (3.1), sargachromenoic acid (3.9) and sarganaphthoquinoic acid (3.10) were then semi-synthesized from sargahydroquinoic acid (3.6) and their in-vitro cytotoxicity profiles evaluated using Chang Liver, HT-29, Caco-2 and 3T3-L1 cell lines prior to antidiabetic testing. From the semi-synthetic derivatives, sargachromenoic acid (3.9) exhibited the most potent anti-oxidant activity (IC₅₀ = 6.99 μg/mL). After the evaluation of antidiabetic activity using 3T3-L1 preadipocyte differentiation, sarganaphthoquinoic acid (3.10) showed the most potent insulinomimetic activity at 1.19 μM by inducing a PPARγ response similar to that of rosiglitazone at 1 μM.
- Full Text:
- Date Issued: 2014
- Authors: Nyambe, Mutenta Nsokolo
- Date: 2014
- Subjects: Sargassum , Diabetes -- Chemotherapy , Diabetes -- Africa , Antioxidants -- Therapeutic use , Marine algae , Endemic plants -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3874 , http://hdl.handle.net/10962/d1021020
- Description: In Africa, non-communicable diseases such as diabetes mellitus have been generally neglected. This problem has worsened over the years owing to continuous threats from infectious diseases such as HIV/AIDS, tuberculosis and malaria. Despite this, statistics have shown that by 2030, the African region will have the highest proportional increase in diabetes prevalence. Over 80% of all diabetic deaths occur in developing countries probably not only due to poor equity of access to medication but also due to limited efficacy and side effects associated with the commonly available anti-diabetic agents. Therefore, this creates the desperate need for the development of new anti-diabetic agents that are more efficacious and can be sourced from within the continent. With oxidative stress as a suggested mechanism underlying the cause of diabetes mellitus and diabetic complications, the discovery of natural anti-oxidants that prevent free radical mediated damage is important for developing new treatment strategies. Marine algae have been identified as good sources for natural anti-oxidants. Unfortunately, very few studies have embarked on the discovery of marine-derived anti-oxidant compounds with potential anti-diabetic activity. In this project, we investigated the potential anti-oxidant activity of the South African endemic algae Stypopodium multipartitum, Dictyopterus ligulata, Cystophora fibriosa, Bifurcariopsis capensis, Sargassum sp. and Sargassum heterophyllum. From these studies, Sargassum heterophyllum yielded prenylated compounds, the main compound being sargahydroquinoic acid (3.6) and the carotenoid metabolite fucoxanthin (3.8), which are in part responsible for the radical scavenging activity of the crude extract. Sargahydroquinoic acid (3.6) and fucoxanthin (3.8) also exhibited significant anti-inflammatory activity. Sargaquinoic acid (3.1), sargachromenoic acid (3.9) and sarganaphthoquinoic acid (3.10) were then semi-synthesized from sargahydroquinoic acid (3.6) and their in-vitro cytotoxicity profiles evaluated using Chang Liver, HT-29, Caco-2 and 3T3-L1 cell lines prior to antidiabetic testing. From the semi-synthetic derivatives, sargachromenoic acid (3.9) exhibited the most potent anti-oxidant activity (IC₅₀ = 6.99 μg/mL). After the evaluation of antidiabetic activity using 3T3-L1 preadipocyte differentiation, sarganaphthoquinoic acid (3.10) showed the most potent insulinomimetic activity at 1.19 μM by inducing a PPARγ response similar to that of rosiglitazone at 1 μM.
- Full Text:
- Date Issued: 2014
Development and assessment of sustained release stavudine loaded microparticles
- Authors: Zindove, Chiedza Cathrine
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54722 , vital:26603
- Description:
Stavudine (D4T) has been used as first line treatment for HIV/AIDS and is part of highly active anti retroviral treatment (HAART). It is an affordable medicine and its use is beneficial in resource limited settings. However D4T exhibits dose dependent side effects that may lead to non-adherence in patients. This study was undertaken to formulate, develop and manufacture a dosage form that could reduce dose dependent side effects by decreasing the dose of D4T but still exhibit antiretroviral (ARV) activity. The use of sustained release (SR) formulations of D4T that ensure constant levels of the D4T in the body would not only optimize therapy but also reduce the incidence of side effects thereby increasing patient adherence. SR microparticles containing 30mg D4T were manufactured and loaded into size 3 hard gelatine capsules prior to analysis. The D4T microparticles were manufactured by microencapsulation using non-aqueous oil-in-oil solvent evaporation approach. D4T-excipient, excipient-excipient interactions and D4T purity were assessed using Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Copolymers synthesized from acrylic and methacrylic acid esters viz., Eudragit® RSPO and S100 were used as rate retardant materials and the effect of microcrystalline cellulose (Avicel® PH102) on the microparticles was also investigated. Magnesium stearate was used as a droplet stabilizer and n-hexane was added to harden the microspheres formed in a liquid paraffin continuous phase. The microparticles were optimized using a Box Behnken design and Response Surface Methodology (RSM). The microparticles were characterized in terms of their flow properties and encapsulation efficiency (% EE), in addition to visualization of the surface morphology with Scanning Electron Microscopy. In vitro D4T release studies were performed using USP Apparatus III in media of different pH and the samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection that had been developed and optimized using a Central Composite Design (CCD). The method was validated according to ICH guidelines. The IR spectra and DSC thermographs revealed that D4T exhibited thermal stability and there was no evidence of D4T-excipient and excipient-excipient interactions. The microparticles that were produced were white, free flowing and were obtained in a high yield with high encapsulation efficiency. Scanning Electron Microscopy studies revealed that the microparticles were spherical and porous in nature. In vitro D4T release extended to 12 hours and the mechanism of release was established using model dependent methods by fitting the data to a Zero order, First order, Higuchi and Hixson Crowell model. It was observed that the mechanism of D4T release was diffusion-controlled and that the data was best fitted to the Higuchi model with correlation coefficients > 0.9. The release mechanism was confirmed using the Korsmeyer-Peppas model that revealed that most of the formulations exhibited anomalous transport kinetics with the release exponent, n, ranging from 0.5
- Full Text:
- Date Issued: 2014
- Authors: Zindove, Chiedza Cathrine
- Date: 2014
- Language: English
- Type: text , Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/54722 , vital:26603
- Description:
Stavudine (D4T) has been used as first line treatment for HIV/AIDS and is part of highly active anti retroviral treatment (HAART). It is an affordable medicine and its use is beneficial in resource limited settings. However D4T exhibits dose dependent side effects that may lead to non-adherence in patients. This study was undertaken to formulate, develop and manufacture a dosage form that could reduce dose dependent side effects by decreasing the dose of D4T but still exhibit antiretroviral (ARV) activity. The use of sustained release (SR) formulations of D4T that ensure constant levels of the D4T in the body would not only optimize therapy but also reduce the incidence of side effects thereby increasing patient adherence. SR microparticles containing 30mg D4T were manufactured and loaded into size 3 hard gelatine capsules prior to analysis. The D4T microparticles were manufactured by microencapsulation using non-aqueous oil-in-oil solvent evaporation approach. D4T-excipient, excipient-excipient interactions and D4T purity were assessed using Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Copolymers synthesized from acrylic and methacrylic acid esters viz., Eudragit® RSPO and S100 were used as rate retardant materials and the effect of microcrystalline cellulose (Avicel® PH102) on the microparticles was also investigated. Magnesium stearate was used as a droplet stabilizer and n-hexane was added to harden the microspheres formed in a liquid paraffin continuous phase. The microparticles were optimized using a Box Behnken design and Response Surface Methodology (RSM). The microparticles were characterized in terms of their flow properties and encapsulation efficiency (% EE), in addition to visualization of the surface morphology with Scanning Electron Microscopy. In vitro D4T release studies were performed using USP Apparatus III in media of different pH and the samples were analysed using a validated High Performance Liquid Chromatographic (HPLC) method with ultraviolet (UV) detection that had been developed and optimized using a Central Composite Design (CCD). The method was validated according to ICH guidelines. The IR spectra and DSC thermographs revealed that D4T exhibited thermal stability and there was no evidence of D4T-excipient and excipient-excipient interactions. The microparticles that were produced were white, free flowing and were obtained in a high yield with high encapsulation efficiency. Scanning Electron Microscopy studies revealed that the microparticles were spherical and porous in nature. In vitro D4T release extended to 12 hours and the mechanism of release was established using model dependent methods by fitting the data to a Zero order, First order, Higuchi and Hixson Crowell model. It was observed that the mechanism of D4T release was diffusion-controlled and that the data was best fitted to the Higuchi model with correlation coefficients > 0.9. The release mechanism was confirmed using the Korsmeyer-Peppas model that revealed that most of the formulations exhibited anomalous transport kinetics with the release exponent, n, ranging from 0.5
- Full Text:
- Date Issued: 2014
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
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