With great appreciation, I would like to accentuate the substantial contributions of the following people who made this project possible: To Dr. CMT Fourie (my supervisor), Prof. JM van Rooyen (my co–supervisor) and Prof. AE Schutte (my co–supervisor) whose gracious advise, patient guidance, commitment and support have enabled me to plan, analyse, interpret and write this project in a scientific manner. It has been an educational experience for me, thank you. To Mr. LS Wyldbore for the language editing of this dissertation. I thank all the participants, researchers, field workers and supporting staff of the PURE study. The financial assistance of the National Research Foundation (DAAD–NRF) towards this research is hereby acknowledged. A special thanks to my parents, sister, Albert, family and friends, thank you for the never–ending love, support, patience and understanding that you gave me throughout this project. Last, but not the least, a special thank to God for giving me the opportunity, talent, determination and endurance to complete this project. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

With great appreciation, I would like to accentuate the substantial contributions of the following people who made this project possible: To Dr. CMT Fourie (my supervisor), Prof. JM van Rooyen (my co–supervisor) and Prof. AE Schutte (my co–supervisor) whose gracious advise, patient guidance, commitment and support have enabled me to plan, analyse, interpret and write this project in a scientific manner. It has been an educational experience for me, thank you. To Mr. LS Wyldbore for the language editing of this dissertation. I thank all the participants, researchers, field workers and supporting staff of the PURE study. The financial assistance of the National Research Foundation (DAAD–NRF) towards this research is hereby acknowledged. A special thanks to my parents, sister, Albert, family and friends, thank you for the never–ending love, support, patience and understanding that you gave me throughout this project. Last, but not the least, a special thank to God for giving me the opportunity, talent, determination and endurance to complete this project. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

There is a global rise in the use of herbal products in combination with allopathic medicines, while most patients do not inform their health care providers of the use of these natural products. Both pharmacodynamic and pharmacokinetic interactions between herbal products and conventional drugs must be avoided for the wellbeing of the patient. Increasing evidence from in vitro and in vivo studies indicate that changed drug pharmacokinetics by co-administered herbs may be attributed to modulation of efflux drug transporters such as P-glycoprotein (P-gp). Garlic (Allium sativum), lemon (Citrus limonum) and beetroot (Beta vulgaris) are widely used by human immunodeficiency virus (HIV) patients, especially following the pronouncement by a former President of South Africa and the Ministers of Health at that time who promoted the use of these botanicals in HIV patients. The aim of this study was to measure the bi-directional in vitro transport of indinavir, a protease inhibitor, in the presence of crude extracts and pure phytoconstituents of A. sativum (L-alliin and diallyl disulphide), C. limonum (hesperidin and eriocitrin) and B. vulgaris (betaine monohydrate and ß-carotene) across excised porcine intestinal tissue in Sweetana-Grass diffusion chambers. In the negative control group, the transport of indinavir alone (200 M) was determined with no modulator added. In the positive control group, the transport of indinavir was determined in the presence of verapamil (100 M), a known P-gp related efflux inhibitor. The control experiments were used to indicate that the effects of the test compounds were caused by their action and not by chance interferences or external factors. Samples collected at pre-determined time intervals were analysed by means of a validated high performance liquid chromatography (HPLC) method and the transport was expressed as the apparent permeability coefficient (Papp) and the transepithelial flux (J) from which the efflux ratio (ER) and the net flux (Jnet) values were calculated. Statistical analysis was used to compare the results of the test compounds with the control groups in order to indicate significant differences. The mean ER value for indinavir in the negative control group was 1.41 ± 0.170 and in the positive control group it was 0.56 ± 0.0426. Statistically significant (p < 0.05) inhibition of indinavir efflux as indicated by reduced ER values was obtained for L-alliin (ER = 0.280 ± 0.030), diallyl disulphide (ER = 0.505 ± 0.034) and ß-carotene (ER = 0.664 ± 0.075). Inhibition of indinavir efflux will lead to increased transport and therefore a potentially higher bioavailability. Statistically significant (p < 0.05) promotion of indinavir efflux as indicated by increased ER values was obtained for C. limonum crude extract (ER = 5.551 ± 0.575) and hesperidin (ER = 3.385 ± 0.477), which potentially may lead to lower bioavalability. B. vulgaris crude extract (p = 0.8452), betaine monohydrate (p = 0.9982), A. sativum crude extract (p = 0.7161) and eriocitrin (p = 0.4431) displayed no statistically significant effect compared to the negative control group on indinavir transport across excised porcine intestinal tissue. The results from this study demonstrate that L-alliin, diallyl disulphide and ß-carotene have an inhibitory effect on indinavir efflux, which may significantly increase indinavir plasma levels after oral administration. C. limonum crude extract and hesperidin promote indinavir efflux, which may significantly reduce indinavir plasma levels. These pharmacokinetic interactions between certain drugs and plant extracts may negatively affect the anti-retroviral treatment of HIV patients, but deliberate and controlled inclusion of L-alliin, diallyl disulphide and ß-carotene in dosage forms may possibly cause more effective delivery of protease inhibitors after oral administration resulting in less frequent dosing intervals. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

There is a global rise in the use of herbal products in combination with allopathic medicines, while most patients do not inform their health care providers of the use of these natural products. Both pharmacodynamic and pharmacokinetic interactions between herbal products and conventional drugs must be avoided for the wellbeing of the patient. Increasing evidence from in vitro and in vivo studies indicate that changed drug pharmacokinetics by co-administered herbs may be attributed to modulation of efflux drug transporters such as P-glycoprotein (P-gp). Garlic (Allium sativum), lemon (Citrus limonum) and beetroot (Beta vulgaris) are widely used by human immunodeficiency virus (HIV) patients, especially following the pronouncement by a former President of South Africa and the Ministers of Health at that time who promoted the use of these botanicals in HIV patients. The aim of this study was to measure the bi-directional in vitro transport of indinavir, a protease inhibitor, in the presence of crude extracts and pure phytoconstituents of A. sativum (L-alliin and diallyl disulphide), C. limonum (hesperidin and eriocitrin) and B. vulgaris (betaine monohydrate and ß-carotene) across excised porcine intestinal tissue in Sweetana-Grass diffusion chambers. In the negative control group, the transport of indinavir alone (200 M) was determined with no modulator added. In the positive control group, the transport of indinavir was determined in the presence of verapamil (100 M), a known P-gp related efflux inhibitor. The control experiments were used to indicate that the effects of the test compounds were caused by their action and not by chance interferences or external factors. Samples collected at pre-determined time intervals were analysed by means of a validated high performance liquid chromatography (HPLC) method and the transport was expressed as the apparent permeability coefficient (Papp) and the transepithelial flux (J) from which the efflux ratio (ER) and the net flux (Jnet) values were calculated. Statistical analysis was used to compare the results of the test compounds with the control groups in order to indicate significant differences. The mean ER value for indinavir in the negative control group was 1.41 ± 0.170 and in the positive control group it was 0.56 ± 0.0426. Statistically significant (p < 0.05) inhibition of indinavir efflux as indicated by reduced ER values was obtained for L-alliin (ER = 0.280 ± 0.030), diallyl disulphide (ER = 0.505 ± 0.034) and ß-carotene (ER = 0.664 ± 0.075). Inhibition of indinavir efflux will lead to increased transport and therefore a potentially higher bioavailability. Statistically significant (p < 0.05) promotion of indinavir efflux as indicated by increased ER values was obtained for C. limonum crude extract (ER = 5.551 ± 0.575) and hesperidin (ER = 3.385 ± 0.477), which potentially may lead to lower bioavalability. B. vulgaris crude extract (p = 0.8452), betaine monohydrate (p = 0.9982), A. sativum crude extract (p = 0.7161) and eriocitrin (p = 0.4431) displayed no statistically significant effect compared to the negative control group on indinavir transport across excised porcine intestinal tissue. The results from this study demonstrate that L-alliin, diallyl disulphide and ß-carotene have an inhibitory effect on indinavir efflux, which may significantly increase indinavir plasma levels after oral administration. C. limonum crude extract and hesperidin promote indinavir efflux, which may significantly reduce indinavir plasma levels. These pharmacokinetic interactions between certain drugs and plant extracts may negatively affect the anti-retroviral treatment of HIV patients, but deliberate and controlled inclusion of L-alliin, diallyl disulphide and ß-carotene in dosage forms may possibly cause more effective delivery of protease inhibitors after oral administration resulting in less frequent dosing intervals. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

The effects of HIV/AIDS and subsequent opportunistic infections and/or associated conditions on the development of infected children are substantial. Considerable delays and/or disorders in communication development have been noted in the HIV/AIDS infected child, as well as the need for Early Communication Intervention (ECI) services for this population. A dearth of locally relevant data regarding the speech, language and hearing development of HIV/AIDS infected children within the South African context currently exists. The objective of this study was to describe the characteristics of a group of HIV/AIDS infected children being managed at an outreach clinic of regional hospital in Gauteng. A cross-sectional, retrospective, non-experimental, descriptive, quantitative research design was used in this study. The main objective was achieved by analysing the clinic records of 203 children infected with HIV/AIDS between the ages of 0 – 5 years 11months through the use of a pre-designed checklist. A questionnaire completed by four medical doctors practicing at the HIV/AIDS clinic within the hospital was also used. This allowed for the perceptions and practices of the medical doctors to be described. Results revealed that the majority HIV/AIDS infected children being managed at the outreach clinic were significantly immunocompromised and diagnosed with Stage III or Stage IV HIV/AIDS infection. Furthermore, results indicated the presence of several opportunistic infections and HIV/AIDS associated conditions (such as Tuberculosis, Candidiasis and Encephalopathy). A positive finding was that 76% of the HIV/AIDS infected children (n=153) were receiving Highly Active Antiretroviral Therapy (HAART) at the time of data collection. The most outstanding finding was that very few of the children with HIV/AIDS being managed at the outreach clinic were recorded as having speech, language and/or hearing delays and/or disorders. Similarly, referrals to other professionals as recorded in the children’s hospital records seemed to be limited to Social Workers and Dietitians, with only one child recorded as being referred to a Speech-Language Therapist and Audiologist for further management. It was unclear whether more children were in fact referred for additional intervention by other professionals and this was simply not recorded in the children’s records, or whether these referrals were in fact not made. Results from the questionnaires completed by the medical doctors working with the pediatric HIV/AIDS population within the outreach clinic were significant. Findings indicated that the majority of the respondents believed that HIV/AIDS infected infants were more at risk for developmental and communicative delays and/or disorders than the general population, and that this population would likely benefit from Speech-Language Therapy and/or Audiology intervention services. Respondents indicated that medical doctors working with the pediatric HIV/AIDS population were often not adequately informed regarding the effects of HIV/AIDS on communication development and that they would benefit from further training in this regard. The need for further research regarding the characteristics of the pediatric HIV/AIDS population, particularly on a larger sample, was described. This would assist in the development of a guideline for ECI service delivery for children infected with HIV/AIDS. The need for further training of other professionals regarding the effects that HIV/AIDS has on the communication development of the infected child, to assist with necessary referrals and teamwork, was also highlighted. AFRIKAANS : Suid-Afrika is een van die lande ter wêreld, wat die hoogste voorkoms van Menslike Immuniteitsgebrekvirus/ Verworwe Immuniteitsgebreksindroom (MIV/VIGS), toon - met die pediatriese populasie op die voorfront van hierdie epidemie. Die effek wat MIV/VIGS en opeenvolgende opportunistiese infeksies en/of ander geassosieerde toestande op die ontwikkeling van kinders het, is verreikend. Internasionale literatuur beskryf agterstande en/of akwykings in die kommunikasie ontwikkeling van kinders wat met MIV/VIGS geinfekteer is. Die behoefte vir Vroeë Kommunikasie Intervensie (VKI) vir hierdie populasie word ook gemeld. Daar bestaan egter slegs ‘n beperkte hoeveelheid relevante, plaaslike literatuur met betrekking tot die spraak-, taal- en gehoorontwikkeling van kinders met MIV/VIGS binne die Suid-Afrikaanse konteks. Die doelwit van hierdie studie was om die kenmerke van ‘n groep kinders, wat met MIV/VIGS besmet is en by ‘n streekshospitaal in Gauteng behandel word, te beskryf. ‘n Kwantitatiewe, nie-eksperimentele, terugwerkende, dwarsdeurige, beskrywende navorsingsontwerp is gebruik. Die hoofdoelwit was bereik deur die kliniekrekords van kinders wat met MIV/VIGS besmet is, te analiseer deur van ‘n vooraf-ontwerpte merklys gebruik te maak. Data is ook ingesamel deur middel van vraelyste wat deur mediese dokters, wat by MIV/VIGS klinieke binne die hospitale werk, voltooi is. Dit het toegelaat dat die persepsies en praktyke van die mediese dokters ook beskryf kon word. Resultate het getoon dat die meerderheid kinders met MIV/VIGS, wat by klinieke behandel word, se immuunsisteme ernstig onderdruk was en dat hulle met stadium III of stadium IV van MIV/VIGS gediagnoseer was. Die resultate het verder ook die voorkoms van verskeie opportunistiese infeksies en MIV/VIGS geassosieerde toestande aangedui. ‘n Positiewe bevinding was dat 76% van die kinders (n=153), wat met MIV/VIGS geinfekteer was, tydens die proses van data-insameling reeds Hoogsaktiewe Antiretrovirale Terapie (HAART) ontvang het. Die mees uitstaande bevinding was dat slegs ‘n geringe hoeveelheid kinders met MIV/VIGS by die kliniek, as met ‘n agterstand en/of afwyking in spraak, taal en/of gehoor, aangeteken is. Beperkte verwysings na ander professionele persone is ook in die kliniekrekords opgemerk. Verwysings was beperk tot Maatskaplike Werkers en Dieëtkundiges. Daar was slegs een aantekening van ‘n kind wat vir behandeling na ‘n Spraak- en Taalterapeut en Oudioloog verwys is. Dit is egter onduidelik of daar werklik meer verwysings na ander professionele persone gemaak is, maar net nie in die kinders se kliniekrekords aangedui is nie, of dat daar werklik min verwysings na ander professionele dissiplines gemaak is. Bykomend, was die resultate van voltooide vraelyste deur mediese dokters, wat met die pediatriese MIV/VIGS populasie in die kliniek werk, insiggewend. Bevindings dui aan dat die meerderheid proefpersone, wat aan die studie deelgeneem het, van mening is dat kinders wat met MIV/VIGS besmet is wel ‘n hoër risiko toon vir ontwikkelings- en kommunikasie agterstande en/of afwykings in vergeleke met die algemene populasie. Die proefpersone is verder ook van mening dat hierdie populasie wel van spraak- en taalterapie en/of oudiologiese intervensie sal baatvind. Proefpersone het verder aangedui dat mediese dokters, wat met die pediatriese MIV/VIGS populasie werk, nie ten volle ingelig is omtrent die effek van MIV/VIGS op kommunikasie ontwikkeling en dat hulle van verdere opleiding sal baatvind. Die behoefte vir verdere navorsing in die veld van pediatriese MIV/VIGS en kommunikasie ontwikkeling, binne die Suid-Afrikaanse konteks, word in hierdie studie beskryf. Dit sal as riglyn vir VKI dienslewering aan hierdie populasie dien. Daar is ook ‘n groot behoefte vir verdere opleiding van ander mediese professionele persone met betrekking tot pediatriese MIV/VIGS en die effek wat die op die kind se kommunikasie ontwikkeling het. / Dissertation (MCommunication Pathology)--University of Pretoria, 2010. / Speech-Language Pathology and Audiology / unrestricted