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Item Antidepressant activity of Zembrin alone and combined with desipramine in flinders sensitive line rats(North-West University, 2021-12) Polile, R PIntroduction: People with major depressive disorder and comorbid anxiety disorders tend to have poor response to treatment compared to patient with major depressive disorder alone. The standardized extract of Sceletium tortuosum (Zembrin®) is a multi-model serotonin reuptake transporter (SERT) and phosphodiesterase (PDE) 4B inhibitor that may be a promising novel therapy for patients with depression, either as monotherapy or as an augmentation strategy in poor responders. Therefore, investigation into its therapeutic potential alone following sub-chronic treatment and in combination with a known standard antidepressant is required. Aim of the study: To assess the dose-related antidepressant- and anxiolytic-like effects of Zembrin® (ZEM) in the Flinders Sensitive Line (FSL) rats, a genetic model of depression, alone and as an adjunctive treatment with low-dose desipramine (DMI), and correlation with altered regional brain monoamines and phosphodiesterase 4B expression. Material and methods: For confirmation of the model, 12 male Flinders Resistant Line (FRL) rats and 12 male FSL rats (control group) were treated with saline for 14 days via oral gavage. Seven groups (n =12) of male FSL rats were treated with a 3-tier dose of ZEM (10, 25 & 30 mg/kg/day), and a 2-tier dose of DMI (15 & 30 mg/kg/day) for 14 days via oral gavage to establish predictive validity. To assess augmentation potential, ZEM (10 & 30 mg/kg/day), was combined with a low dose of DMI (15 mg/kg/day) over 14 days. Following treatment, depressive- like behaviour was assessed in the Forced Swim Test (FST), and anxiety-like behaviour was assessed in the Open Field Test (OFT) and Elevated Plus Maze (EPM). The behavioural assessment was followed by analyses of cortical and hippocampal monoamines and PDE4B levels. Results: Depressive-like behaviour was significantly increased in FSL rats versus Flinders Resistant Line (FRL) control rats. DMI (15 & 30 mg/kg/day) significantly decreased immobility and increased struggling behaviour in the FST. ZEM (10, 25 & 30 mg/kg/day) showed no antidepressant-like properties in the FST versus SAL (saline) treated FSL rats. Similarly, combinations of ZEM+DMI showed no antidepressant-like properties in FST versus FSL saline treated rats. ZEM-10+DMI-15 and ZEM-30+DMI-15 showed no antidepressant-like effects in FSL rats versus DMI-15 treated rats. ZEM- ABSTRACT ABSTRACT ii 10+DMI-15 and ZEM-30+DMI-15 significantly reduced immobility in the FST in FSL rats versus ZEM- (10 & 30 mg/kg/day) monotherapies. FSL rats did not demonstrate anxiety in either the OFT or EPM versus FRL rats. There was significantly increased cortical norepinephrine (NE) levels in FRL rats versus FSL saline control, nevertheless, the hippocampal serotonin (5-HT) levels were reduced in the FRL rats versus FSL saline control. In the DMI-30 treated rats, hippocampal and cortical NE levels were reduced versus FSL saline rats, whereas the hippocampal NE levels were reduced in DMI-15 versus FSL saline rats. ZEM-30 significantly increased frontal cortical NE and 5-HT levels versus the FSL saline control group. Neither DMI (15 mg/kg/day) nor ZEM (10 & 30 mg/kg/day) monotherapies reduced cortical and hippocampal PDE4B levels in FSL rats versus SAL FSL control group. However, ZEM-10+DMI-15 and ZEM-30+DMI-15 combination therapies significantly reduced hippocampal PDE4B levels versus FSL SAL treated rats. ZEM-30+DMI-15 significantly increased cortical PDE4B levels versus FSL SAL treated rats. Conclusions: FSL rats showed distinct depressive- like characteristics versus FRL controls. DMI alone reverse depressive-like behavioural characteristics in FSL rats. We were unable to confirm the antidepressant-like effects of ZEM in this study, either alone or in combination with DMI. These results may be model-related. Nevertheless, studies on hippocampal PDE4 levels do lend some support for the augmentation potential of ZEM as an add-on therapy for patients responding poorly to standard antidepressants, especially where specific actions on the hippocampal PDE4B are required. Combination of ZEM with antidepressants i.e., NRIs may be depressogenic displaying increased cortical PDE4B levels. However, further work is needed.Item Antidepressant activity of Zembrin alone and combined with desipramine in flinders sensitive line rats(North-West University, 2021-12) Polile, R P; Lekhooa, Makhotso; Harvey, Brian H; Steyn, StephanIntroduction: People with major depressive disorder and comorbid anxiety disorders tend to have poor response to treatment compared to patient with major depressive disorder alone. The standardized extract of Sceletium tortuosum (Zembrin®) is a multi-model serotonin reuptake transporter (SERT) and phosphodiesterase (PDE) 4B inhibitor that may be a promising novel therapy for patients with depression, either as monotherapy or as an augmentation strategy in poor responders. Therefore, investigation into its therapeutic potential alone following sub-chronic treatment and in combination with a known standard antidepressant is required. Aim of the study: To assess the dose-related antidepressant- and anxiolytic-like effects of Zembrin® (ZEM) in the Flinders Sensitive Line (FSL) rats, a genetic model of depression, alone and as an adjunctive treatment with low-dose desipramine (DMI), and correlation with altered regional brain monoamines and phosphodiesterase 4B expression. Material and methods: For confirmation of the model, 12 male Flinders Resistant Line (FRL) rats and 12 male FSL rats (control group) were treated with saline for 14 days via oral gavage. Seven groups (n =12) of male FSL rats were treated with a 3-tier dose of ZEM (10, 25 & 30 mg/kg/day), and a 2-tier dose of DMI (15 & 30 mg/kg/day) for 14 days via oral gavage to establish predictive validity. To assess augmentation potential, ZEM (10 & 30 mg/kg/day), was combined with a low dose of DMI (15 mg/kg/day) over 14 days. Following treatment, depressive- like behaviour was assessed in the Forced Swim Test (FST), and anxiety-like behaviour was assessed in the Open Field Test (OFT) and Elevated Plus Maze (EPM). The behavioural assessment was followed by analyses of cortical and hippocampal monoamines and PDE4B levels. Results: Depressive-like behaviour was significantly increased in FSL rats versus Flinders Resistant Line (FRL) control rats. DMI (15 & 30 mg/kg/day) significantly decreased immobility and increased struggling behaviour in the FST. ZEM (10, 25 & 30 mg/kg/day) showed no antidepressant-like properties in the FST versus SAL (saline) treated FSL rats. Similarly, combinations of ZEM+DMI showed no antidepressant-like properties in FST versus FSL saline treated rats. ZEM-10+DMI-15 and ZEM-30+DMI-15 showed no antidepressant-like effects in FSL rats versus DMI-15 treated rats. ZEM- ABSTRACT ABSTRACT ii 10+DMI-15 and ZEM-30+DMI-15 significantly reduced immobility in the FST in FSL rats versus ZEM- (10 & 30 mg/kg/day) monotherapies. FSL rats did not demonstrate anxiety in either the OFT or EPM versus FRL rats. There was significantly increased cortical norepinephrine (NE) levels in FRL rats versus FSL saline control, nevertheless, the hippocampal serotonin (5-HT) levels were reduced in the FRL rats versus FSL saline control. In the DMI-30 treated rats, hippocampal and cortical NE levels were reduced versus FSL saline rats, whereas the hippocampal NE levels were reduced in DMI-15 versus FSL saline rats. ZEM-30 significantly increased frontal cortical NE and 5-HT levels versus the FSL saline control group. Neither DMI (15 mg/kg/day) nor ZEM (10 & 30 mg/kg/day) monotherapies reduced cortical and hippocampal PDE4B levels in FSL rats versus SAL FSL control group. However, ZEM-10+DMI-15 and ZEM-30+DMI-15 combination therapies significantly reduced hippocampal PDE4B levels versus FSL SAL treated rats. ZEM-30+DMI-15 significantly increased cortical PDE4B levels versus FSL SAL treated rats. Conclusions: FSL rats showed distinct depressive- like characteristics versus FRL controls. DMI alone reverse depressive-like behavioural characteristics in FSL rats. We were unable to confirm the antidepressant-like effects of ZEM in this study, either alone or in combination with DMI. These results may be model-related. Nevertheless, studies on hippocampal PDE4 levels do lend some support for the augmentation potential of ZEM as an add-on therapy for patients responding poorly to standard antidepressants, especially where specific actions on the hippocampal PDE4B are required. Combination of ZEM with antidepressants i.e., NRIs may be depressogenic displaying increased cortical PDE4B levels. However, further work is needed.Item Exploring perceived factors of nurse midwives regarding postpartum depression in Quthing hospital, Lesotho(National University of Lesotho, 2024-08) Maloleka, NtsehisengBackground: Despite the increasing awareness of Postpartum Depression (PPD) worldwide, health providers continue to ignore the impact of PPD on the mother and child during the postnatal period. Nurse-midwives are the first care providers and have contact with women during pregnancy and after birth. They must be able to identify women at risk and those who already have PPD and educate women and their relatives about PPD and risk factors. Purpose: The purpose of this study was to explore perceived factors of nurse midwives regarding PPD in Quthing District. Methodology: This study used a qualitative, descriptive, explorative, and contextual design. Data collection was conducted through individual interviews and data saturation was reached on the ninth participant. An audio - recorder was used to record interviews from purposefully selected participants. The study participants were nurse-midwives working at Quthing Hospital in the Quthing District. The data organization was done, followed by transcribing the audio data into text, and lastly thematic data analysis. Results: Thematic analysis of the data resulted in themes and sub-themes. The six themes which emerged from the study findings are empowerment, stigma, screening /assessment of PPD, family support, lack of resources and home visits. Participants had different perceived factors regarding PPD at Quthing District. Conclusion: The nurses-midwives’ perceived factors regarding PPD were expressions of empowerment, stigma, screening /assessment of PPD, family support, lack of resources and home visits. The research findings have significant implications for decision-makers and policymakers to solve problems in maternal mental health service provision. Nurse-midwives perceived that they could be better supported to carry out their important work by having access to continued education, training, and mentorship regarding PPD.Item Assessment of water quality, soil degradation and water purification ability of Khubelu wetland in Mokhotlong Lesotho, and the implications of climate change(University of South Africa, 2020-04) George, Antoinette MaetiPalustrine wetlands in Lesotho are vulnerable to vegetation loss due to overgrazing and the nature of the topography, the latter leading to gully erosion exacerbated by a degraded soil structure. Degraded soils are not able to adsorb pollutants; neither can they support vegetation growth. The presence of degraded soils in wetlands thus contributes towards leaching of pollutants into nearby streams and groundwater resources. Khubelu wetland (which was the focus of this study) is a palustrine wetland that discharges water into the Khubelu stream in Lesotho. The water purification function of this wetland is pertinent since Khubelu River is one of the tributaries at the headwaters of the shared Orange-Senqu basin. This function is threatened by vegetation loss and soil degradation through overgrazing and environmental conditions like extreme climatic variations. Consequently, water released into adjacent streams from the wetland could be of low quality, further putting at risk the health of this ecosystem and users of these streams due to toxicity caused by the polluted water from the wetland. With predicted floods and/or droughts and intense heat, water temperatures may rise by up to 70% in the 21st century according to researchers. It is believed that floods would lead to shorter residence time of water within wetlands, washing away soil with pollutants into surrounding streams before any geochemical processes that would sequester them occurs. Droughts on the other hand would lead to failure of dilution of polluted waters. Excessive evaporation due to intense heat would also leave pollutant-concentrated water behind. Since these wetlands are the headwaters of an international river, the problem of water pollution and deteriorated water resources might be regional. The main aim of the study was to characterise the extent of soil degradation and water quality in the Khubelu wetland and assess the water purification ability in an endeavour to understand the role the wetland plays in the quality of water in rivers and streams fed by the Khubelu wetland, and also to understand how changes in climate would impact on the wetland characteristics. In situ analyses of soil and water were done followed by sampling of the same for further analysis in the laboratory using standard methods. Surface water samples were collected from two sampling points in the Khubelu stream, whereas water in the wetland was sampled from seven piezometers installed in the wetland. Three replicates of water samples were collected from each sampling point monthly over a period of one year. The water properties determined included pH, v Electrical Conductivity (EC), Dissolved Oxygen (DO), Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), cations (magnesium, calcium, potassium and sodium), Total Dissolved Solids (TDS), nitrates, phosphates and chlorides. The data generated from these analyses were subjected to various statistical tests and the Water Quality Index (WQI) of the wetland and stream waters determined. The water quality drinking standards were preferred in this study since the major beneficiaries of the stream that emanates from the wetland are human populace. Prediction of water quality in the wetland in light of the changing climate was done using the Water Evaluation and Planning (WEAP) model. Soil samples were collected from the upper, middle and lower areas of the wetland, referred to as upstream, midstream and downstream of the wetland in the report, at the same sites where the piezometers were installed. At each site, three sampling points were identified two metres apart from each other and samples collected at depths of 15 cm, 30 cm and 45 cm at each site. The soil samples were then characterised for their texture, pH, Electrical Conductivity (EC), Cation Exchange Capacity (CEC), Total Carbon (TC), Total Nitrogen (TN), Organic Matter (OM), exchangeable calcium, magnesium, potassium and sodium, and available phosphorus, using standard procedures. The soil data generated were then subjected to data analyses and the Chemical Degradation Index (CDI) of the wetland soils determined. Determination of the wetland’s potential to purify water was done by assessing its ability to retain nutrients, pollutants and sediments. Results obtained in this study showed that the wetland and stream water had circumneutral pH with values that ranged from 6.32 -7.69. The values for Na, Ca, K, Mg, TDS, NO3, Cl and DO in the wetland and stream waters were below the WHO drinking water standards thresholds of 200 mg/l for Na and Ca, 12 mg/l for K, 150 mg/l for Mg, 50 mg/l for TDS 50 mg/l for NO3, 5 mg/l for DO and BOD, and 250 mg/l for Cl. Food and Agricultural Organisation (FAO) water standards for livestock drinking were: EC: <1.5 mS/cm (Excellent); 1.5 – 5.0 mS/cm (very satisfactory); < 250 mg/l of Mg for cows, 400 mg/l for beef cattle, and 500 mg/l for adult sheep. SA Irrigation water quality standards were also used, and it was determined that pH was within the acceptable threshold of 6.5 – 8.4, 70 mg/l for sodium and 0.4 mS/cm for EC. EC of 0.41 mS/cm to 1.12 mS/cm in the wetland and 0.67 mS/cm to 2.11 mS/cm in the stream was above the SA irrigation vi water quality standards. Other water properties such as PO4 (0.06-1.26 mg/l in stream and 0.17-0.61 mg/l in wetland), and COD (10.00 to 55.00 mg/l in stream and 48-140.80 mg/l in the wetland) were above the WHO permissible limits. The water quality in the Khubelu wetland and stream ranged from very poor to unsuitable for drinking, with WQI values of 107 for the stream and 93 for the wetland. Water quality simulation along the Khubelu stream using the WEAP model shows that by the year 2025, BOD as one of the water quality parameters, would be high, with DO declining further especially if temperature increases and precipitation decreases. The wetland had sandy and acidic soils, with the TC and TN content of the soil decreasing with depth. The CDI value for the soil was 3.29. Regarding potential to reduce sediments, nutrients and organic pollutants, the wetland scored 7.09, 5.39 and 7.39 out of 10, respectively. This implies that there is moderate potential for the wetland to purify water that is discharged into the stream. The study concludes that the stream and wetland water qualities are unsuitable for human consumption and usable for livestock drinking. However, there might be some risks associated with evaporation that would leave the water saline. The wetland water presents a threat to the water quality of the receiving stream. However, the wetland has moderate potential to retain sediments, nutrients and toxic organics. This potential is threatened by a predicted decrease in precipitation and increase in temperature since oxygen-depleting contaminants and other pollutants whose behaviour in the environment are influenced by climate are highly likely to increase in concentrations in both the wetland and the stream. There is therefore a threat to the supply of water of good quality to the Senqu catchment, which supplies neighbouring countries (South Africa, Namibia and Botswana). Similar studies to this one need to be carried out for other wetlands in Lesotho on a regular basis to come up with data that would aid policy development that seeks to protect water resources.Item Exploring perceived factors of nurse midwives regarding postpartum depression in Quthing hospital, Lesotho(National University of Lesotho, 2024-08) Maloleka, NtsehisengBackground: Despite the increasing awareness of Postpartum Depression (PPD) worldwide, health providers continue to ignore the impact of PPD on the mother and child during the postnatal period. Nurse-midwives are the first care providers and have contact with women during pregnancy and after birth. They must be able to identify women at risk and those who already have PPD and educate women and their relatives about PPD and risk factors. Purpose: The purpose of this study was to explore perceived factors of nurse midwives regarding PPD in Quthing District. Methodology: This study used a qualitative, descriptive, explorative, and contextual design. Data collection was conducted through individual interviews and data saturation was reached on the ninth participant. An audio - recorder was used to record interviews from purposefully selected participants. The study participants were nurse-midwives working at Quthing Hospital in the Quthing District. The data organization was done, followed by transcribing the audio data into text, and lastly thematic data analysis. Results: Thematic analysis of the data resulted in themes and sub-themes. The six themes which emerged from the study findings are empowerment, stigma, screening /assessment of PPD, family support, lack of resources and home visits. Participants had different perceived factors regarding PPD at Quthing District. Conclusion: The nurses-midwives’ perceived factors regarding PPD were expressions of empowerment, stigma, screening /assessment of PPD, family support, lack of resources and home visits. The research findings have significant implications for decision-makers and policymakers to solve problems in maternal mental health service provision. Nurse-midwives perceived that they could be better supported to carry out their important work by having access to continued education, training, and mentorship regarding PPD.Item Evaluation of factors affecting the implementation of HIV/AIDS treatment guidelines in Lesotho(North-West University, 2020-05) Ramathebane, MVTitle: Evaluation of factors affecting the implementation of HIV/AIDS treatment guidelines in Lesotho Lesotho has the second-highest prevalence of HIV-infection in the world (MOH, 2017).The successful implementation of HIV/AIDS treatment guidelines has a potentially optimal impact on HIV/AIDS management (Kripke et al., 2016). Therefore, there is a need to evaluate the factors affecting the implementation of the fifth edition of the 2016 HIV/AIDS treatment guidelines by focusing on the implementation process, drivers and barriers in Lesotho (Damschroder et al., 2009:50; Fixsen et al., 2005). It is also essential to formulate an implementation framework to implement the HIV/AIDS treatment guidelines suitable for Lesotho and other resource-limited settings. The specific research objectives of the study include: • To explore current HIV/AIDS treatment guideline implementation processes in Lesotho. • To investigate how the implementation drivers may affect the implementation of current HIV/AIDS treatment guidelines in Lesotho. • To identify barriers to the implementation of HIV/AIDS treatment guidelines in Lesotho. • To develop a framework for the implementation of HIV/AIDS treatment guidelines in resource-limited countries such as Lesotho. A cross-sectional study was implemented in the public healthcare sector of Lesotho. The study population consisted of healthcare professionals from the HIV/AIDS programme (N=5), the District Health Management Team (DHMT) (N=30) and the primary healthcare (PHC) facilities (N=330). Researcher-designed, structured questionnaires were completed during face-to-face interviews with the HIV/AIDS programme and DHMT healthcare professionals. Self-administered questionnaires were completed by healthcare professionals at the PHC facilities. Data collection took place between May and December 2018. A total of five healthcare professionals at the HIV/AIDS programme, 27 at the DHMT and 116 at the PHC facilities participated in the study. Process-related results indicate that an implementation plan was available, as reported by all healthcare professionals at the HIV/AIDS programme (n=5), DHMT 9 (33.3%) and PHC facilities 8 (9.4%). PHC managers also indicated that they had copies of the 2016 HIV/AIDS treatment guidelines 70 (80.5%) and reported daily use 60 (69.0%). The iii results show that PHC managers 50 (57.5%) confirmed that patient care and treatment were given according to the HIV/AIDS treatment guidelines. The results related to implementation drivers show that all healthcare professionals at the HIV/AIDS programme (n=5), 55.6% (n=15) at the DHMT and 75.9% (n=22) at the PHC level as well as 52.3% (n=45) of PHC managers were trained regarding changes made to the 2016 HIV/AIDS treatment guidelines. Healthcare professionals at the HIV/AIDS programme (n=5) indicated that they supervised DHMT healthcare professionals on a quarterly basis. DHMT healthcare professionals 23 (88.5%) indicated that they supervised PHC managers at the PHC facilities. PHC managers 52 (61.2%) also supervised healthcare professionals regarding the treatment of HIV/AIDS through the use of treatment guidelines. Feedback was provided after every supervision at all levels; this was confirmed by healthcare professionals at the HIV/AIDS programme (n=5) and the DHMT 23 (85.2%), and PHC managers 54 (65.9%). The following implementation barriers were identified by healthcare professionals at all levels: personnel-related (lack of different types of personnel at PHC facilities), knowledge and competency (insufficient management skills and insufficient communication skills), resource-related (no or unreliable internet access and no or unreliable e-mail services) and financially-related (lack of funds to acquire highly technologic health information systems and lack of budget for new posts for healthcare personnel). It can, therefore, be concluded that there was an implementation plan, even though it was not fully distributed – PHC managers confirmed that patient care and treatment was carried out according to the HIV/AIDS treatment guidelines. It can also be concluded that training regarding changes made to the 2016 HIV/AIDS treatment guidelines took place at all levels; however, not all healthcare professionals at the DHMT and the PHC were trained. It can also be concluded that supervision and feedback were provided, which is a strength that can be built on. The implementation barriers identified in Lesotho will assist decision-makers in future healthcare planning to prevent possible barriers to the implementation of forthcoming HIV/AIDS treatment guidelines. Decision-makers will have to focus specifically on identified personnel-related, knowledge and competency, resource-related and financially-related barriers. An implementation framework was also formulated based on the literature and the empirical results of the implementation processes, drivers and barriers.Item Non-communicable disease management in the public health system of Lesotho(North-West University, 2021-07) Maja, Lineo JThe general aim of the study was to investigate and propose a model for the optimal disease management of non-communicable diseases (NCDs) in the public health system of Lesotho. To achieve this general aim, specific aims were formulated: (i) to assess the public health system in Lesotho in terms of health service delivery to patients with hypertension, diabetes mellitus, asthma and epilepsy in different healthcare facilities; (ii) to assess the role of the pharmacist in the national, district and primary healthcare (PHC) levels in the health system of Lesotho concerning the management of hypertension, diabetes mellitus, asthma, and epilepsy, and to (iii) develop a potential non-communicable disease (NCD) management structure emphasising the role of the pharmacist in hypertension, diabetes mellitus, asthma and epilepsy management in Lesotho. To attain the aims for the study, a literature review about chronic disease management models and the health system of Lesotho was performed, followed by an empirical investigation into the human resources, medication and medical devices, health management and information system (HMIS), healthcare financing, health infrastructure and equipment, and role of the pharmacist at the national, district and PHC levels of Lesotho’s public health system using self-administered structured questionnaires. The study followed a cross-sectional design. The study population included all employees in managerial positions and/or those in acting managerial positions at the Pharmaceutical Directorate, NCD unit, District Health Management Teams (DHMTs), outpatient departments (OPDs) in district hospitals, and the healthcare centres involved in the management of NCDs during the study period. Data were collected from December 2018 to June 2019. Six managers at the Ministry of Health (MOH), nine managers at DHMTs, 16 managers at OPDs, and 86 managers at healthcare centres participated in the study. Because of the low overall response rate (28.9%) and variance in the number of responses to questions, data were analysed descriptively. The results of this study portray the perception of the managers on the management of NCDs. Assessment of the public health system in Lesotho in terms of health service delivery showed that some health facilities in Lesotho’s public health system had pharmacists, pharmacy technicians, nurses, medical doctors, nursing assistants, public health nurses and community health workers (CHWs). Some of these health workers performed health promotion activities within their community. Some public health facilities collaborated with private health facilities on NCD management; however, some public health facilities did not collaborate with traditional healers. Public health facilities mainly had medicines and equipment used in the management xii of NCDs and some health workers were trained on how to use this equipment. However, some of the pharmaceutical and non-pharmaceutical staff at health facilities were not trained in drug and medical supply management, indicating a need for NCDs’ health service delivery strengthening. Assessment of the role of the pharmacist in the different PHC levels showed that pharmacists at the national, district and the PHC levels (except in healthcare centres) had roles to perform in the prevention and management of NCDs; thus, they work as part of a healthcare team at different levels of Lesotho’s health system. Finally, to develop the proposed NCD management structure for Lesotho's public health system, the results on perceptions of respondents on the management of NCDs in the public health system of Lesotho and literature review about chronic disease management models and the health system of Lesotho were integrated. In conclusion, the different elements of the health system of Lesotho need strengthening. Also, the proposed structure could be used to improve the already existing structure and also serve as baseline for further research on certain aspects of the public health system of Lesotho.Item Harnessing herb-drug interactions for enhanced oral delivery of anti-HIV and antimalarial drugs using colloidal formulations(Tswane University of Technology, 2020-10) Kheoane, Poloko StephenProblem: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and malaria infect and kill a large population globally. Most of the current clinically used anti-HIV and antimalarial drugs have low bioavailability, either due to poor solubility and permeability, rapid clearance from anatomical reservoirs and poor retention at their site of action (e.g. by the p-glycoprotein efflux system), and extreme first-pass metabolism (e.g. by the cytochrome P450 enzymes). Hence, new approaches such as the incorporation of plant-derived absorption enhancers (PDAEs) into dosage forms, and exploration of nanocarriers as novel dosage forms, are needed and may provide a viable means that could improve the bioavailability of both anti-HIV and antimalarial drugs. Methods and procedures: Luminescent-based assay systems were used to screen for the effective inhibitory concentrations of the selected PDAEs against both p-glycoprotein and cytochrome P450 in vitro. Thereafter, an everted gut sac model was utilized to further screen for the effective concentrations of PDAEs combinations. Liposomes loaded with efavirenz or mefloquine as well as placebos were prepared using a thin-lipid film hydration technique and characterized for their entrapment efficiency, particle size, zeta potential, in vitro drug release, and in vitro drug permeability. Liposomes were further investigated for their biocompatibility (safety) with liver using H-4-II-E liver cells in vitro. Finally, the everted gut sac model was used for the drug transport studies across an intestinal membrane ex vivo. Drug analyses were performed using UV/Vis spectrophotometer for the entrapment efficiency, in vitro drug release, and in vitro drug permeability studies while high-performance liquid chromatography (HPLC) was used for the ex vivo studies. Main findings: Quercetin and curcumin had the most significant (p < 0.05) inhibitory vii effects on both p-glycoprotein and cytochrome P450 at concentrations of 75 μM and 100 μM, respectively. Drug-loaded liposomes prepared using l-α-phospatidylcholine, dioleoyl (DOPC) and cholesterol (CHOL) (1:1 mol/mol) as well as liposomes made of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), CHOL and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (4:6:26 mol/mol/mol) exhibited better results in terms of their entrapment efficiency, particle size, zeta potential, in vitro drug release and permeability. Furthermore, these liposomes were biocompatible (safe) with liver cells. However, drugs and/or liposomes were unable to permeate through the porcine intestinal tissue, possibly due to high protein binding capacities of efavirenz and mefloquine. Conclusions: The DOPC:CHOL liposomes and the DSPC:CHOL:DPPC liposomes could provide a useful nanoformulation platform, which could ensure sustained release of both anti-HIV and antimalaria drugs. However, these dosage forms need further investigation using in vivo studies that could rectify the effect of protein binding, which was not investigated in this study.