Towards the creation of the next generation of biomedical implants that effectively integrate in tissues, understanding cell behaviour at the material-host interface to control and optimize the biological outcome is a crucial endeavour. It is now well known that the nanoscale surface properties of biomaterials play a significant role in directing the activity of adherent cells at the implant-host tissue interface. A variety of cellular functions, ranging from adhesion and proliferation to differentiation along specific lineages, are guided by the nanoscale topographical and physicochemical features of the substrate. This evidence reaffirms the role of surface features on eliciting an enhanced response of cells towards improved biological outcomes (e.g., bone integration) of implanted biomaterials. In this context, Titanium (Ti) and its alloys are popular biomaterials widely used in orthopedic, dental, and cardiovascular applications. In particular, in the field of osseointegrated devices, chemical treatments of titanium, specifically oxidative nanopatterning (i.e., a simple yet effective treatment with a H₂SO₄/H₂O₂ solution), have shown to be a promising strategy for guiding and controlling the fate of relevant cells (e.g., osteoblasts, stem cells), thereby achieving the ability to direct the biological response towards the desired outcome. In this context, the sponge-like nanoporous surface resulting from oxidative nanopatterning of titanium allows direct surface cueing to bone cells. It also has the capacity to selectively regulate cell behaviour, modulate the expression of crucial determinants of cell activity, and offers the potential to harness the power of stem cells. However, the mechanisms that control how cells sense and respond to these nanometric cues are still elusive. A novel strategy to elucidate them takes inspiration from in-vivo protocols, where "knock-out" animal models are used to determine the role of a specific gene. Based on this, I propose an original approach aimed at investigating cell response under conditions known to affect specific cellular processes, thereby determining whether these activities can be rescued by direct cueing by the substrate, ultimately elucidating their implication in responding to a given nanostructured substrate. In particular, hyperglycemic culturing conditions often used to mimic diabetes in-vitro are known to exert detrimental effects on the proliferation and differentiation of osteoblasts, and thereby could be an excellent opportunity to test whether the nanometric surface features resulting from oxidative nanopatterning of titanium also possess the ability to compensate to the cell-level changes caused by higher levels of glucose. This would ultimately demonstrate a direct effect of the substrate on these events and help us understand the mechanisms involved in cell-biomaterial interactions. To address this challenge, I propose to investigate the response of human MG-63 osteoblastic cells to nanoporous titanium under hyperglycemic conditions. The goal is, therefore, to understand whether direct nanotopographical cueing at the nanoscale can rescue MG-63 cells from the effects of hyperglycemia, thereby casting new light on the mechanisms underlying the interactions between this widely used cell line and nanoporous titanium. In parallel, results from my work aim at providing new fundamental evidence to interpret results from that body of literature that uses high glucose content as a way to mimic the osseointegration of biomaterials in diabetic conditions.

No description available.

Bacteria of the radiation resistant genus 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 have a high resistance to the lethal and mutagenic effects of many DNA damaging agents, however, the mechanisms involved in the response of these bacteria to oxidative stress are poorly understood. To investigate antioxidant enzyme responses in 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp., the types of catalase and superoxide dismutase (SOD) produced by these bacteria were identified by visualization of the enzyme activities on non-denaturing polyacrylamide gels (PAGE) and the growth inhibition of selected strains by various concentrations of hydrogen peroxide and paraquat (a superoxide generating agent) was tested. 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp. were found to be more resistant to hydrogen peroxide and more sensitive to paraquat than 𝘌𝘴𝘤𝘩𝘦𝘳𝘪𝘤𝘩𝘪𝘢 𝘤𝘰𝘭𝘪 K12. They possess relatively high levels of catalase and exhibit similar electrophoretic patterns on catalase zymograms compared to 𝘌. 𝘤𝘰𝘭𝘪, but all the tested strains produce only one SOD except 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘳𝘢𝘥𝘪𝘰𝘱𝘩𝘪𝘭𝘶𝘴 which produces two. The two catalases of 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴 were found to be regulated independently. Cultures of 𝘋. 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴, when pretreated with sublethal levels of hydrogen peroxide, became relatively resistant to the lethal effects of H₂O₂ and exhibited higher levels of catalase than untreated control cultures. The pretreated cells were also relatively resistant to UV-and γ-ray-mediated lethality. These results suggest that 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp. possess inducible defense mechanisms against the deleterious effects of oxidants and ionizing and UV radiation. The resistance to the lethal effects of hydrogen peroxide and UV radiation can not be induced by pretreatment with sublethal levels of hydrogen peroxide in 𝘋. 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴 rec30 mutant. Effects of manganese and magnesium on the growth and catalase activity of 𝘋. 𝘳𝘢𝘥𝘪𝘰𝘥𝘶𝘳𝘢𝘯𝘴 were determined. Homology between 𝘌. 𝘤𝘰𝘭𝘪 catalase and SOD genes and those of 𝘋𝘦𝘪𝘯𝘰𝘤𝘰𝘤𝘤𝘶𝘴 sp. was tested by Southern blot analysis using previously cloned genes from 𝘌. 𝘤𝘰𝘭𝘪. / Thesis / Master of Science (MS)

Parkinson's disease (PD) is a chronic, progressive disorder of the central nervous system that affects approximately 1.5 million Americans. One of the principal pathological features of PD is dopamine deficiency in the substantia nigra of the brain. A key enzyme that has been associated with the neurodegeneration seen in PD is monoamine oxidase-B (MAO-B). Several inhibitors of this enzyme have resulted in neuroprotection in the mouse model of PD. One such compound is 7-nitroindazole (1). This thesis describes the synthesis and MAO activity of several indazolyl and benzimidazolyl prodrugs that are designed to release an enzyme inhibitor in the affected brain area. These studies have provided information regarding the nucleophilic aromatic substitutions of the ambident nucleophiles under consideration. We have also discovered a compound that releases the enzyme inhibitor upon bioactivation by MAO. These results as well as a MPTP mouse study with the aforementioned compound are detailed within. / Master of Science

No description available.

During peak lactation female mammals reach a limit in their maximal sustained energy intake (SusEI). The causes of such limits is disputed. In this thesis, I examined the causes of the limits on SusEI at peak lactation, and then explored the consequences of such limits for reproductive performance. Finally I tested a possible physiological mechanism that may underpin the trade-off between reproduction and somatic protection (the oxidative stress theory). To answer these questions, I studied reproductive performance and oxidative stress in two lines of mice previously selected for high and low food intake (MH and ML, respectively). I found that these mice reached a plateau in their food intake around day 13 of lactation. In support of the heat dissipation limits theory, reproductive performance in the MH mice was significantly higher than that of the ML mice. Oxidative damage is expected to be higher among lactating individuals. Moreover, lactating mice with greater reproductive performance are also predicted to experience more oxidative damage. By measuring multiple-markers of oxidative damage and protection in different tissues, I found that lactation resulted in reduced oxidative damage in both brain and serum. Additionally, it did not increase oxidative damage to proteins and DNA in liver. Moreover, multiple measures of oxidative stress in the mammary gland were not significantly different between mice with different reproductive effort. Furthermore, I found that lactating mice with greater reproductive performance (litter size and litter mass) had reduced protein damage in their livers and upregulated protection (HSP70) in their brains. These results were inconsistent with the oxidative stress theory. Finally, I employed a novel approach to assess oxidative stress differences with metabolomics analysis. I found that lactation resulted in significant differences in the metabolome. By focusing on the metabolites that are related to vi oxidative stress, I found that most of these metabolites measured in livers and brains were not affected by lactation which provides more evidence against the oxidative stress theory. My results provide support for the heat dissipation theory as a mechanism explaining the limits on reproductive performance. Moreover it provides comprehensive information against oxidative stress as a mediator of life history trade-offs.

In sperm chromatin, DNA exists in a highly condensed state reaching a final volume roughly twenty times that of a somatic nucleus. For the vast majority (>90%) of sperm DNA in mammals, somatic-like histones are first replaced by transition proteins which in turn are replaced by arginine-rich protamines. This near crystalline organization of the DNA in mature sperm is thought crucial for both the transport and protection of genetic information since all DNA repair mechanisms are shut down. Recent studies show that increased DNA damage is linked to dysfunctions in replacing histones with protamines resulting in mispackaged DNA. This increased DNA damage correlates not only to infertility but also impacts normal embryonic development. This damage is currently poorly characterized, but is known to involve oxidative base damage by reactive oxygen species (ROS). Using a variety of biophysical methods, the effect of DNA condensation by polycations on the on free radical access and DNA damage in the packaged state was investigated. In Chapter 2, gel electrophoresis was used to quantify the ability of free radicals to damage both unpackaged and packaged DNA. DNA condensed by polycations shows significantly reduced levels of indirect damage from exposure to free radicals. Combining previous work on packaging density, it is also shown that differences in the packaged state, even by a few Angstroms, can result in significantly different degrees of damage to the DNA. In Chapter 3, we investigate the effects of protamine concentration on the ability to condense and protect DNA. Insufficient protamination is known to be a potential source of protamine dysfunction in mammalian sperm chromatin. Using gel retardation assays and UV-Vis studies, we examined the ability for DNA to condense with protamine at varying nitrogen to phosphate (N:P) charge ratios. Initial results on damage as a function of N:P are also discussed. Future work will more quantitatively determine the interrelationship between DNA packaging densities and the resulting accessibility of DNA to reactive oxygen species (ROS).

Background: Myocardial infarction (MI) results in severe biochemical, physiological, and cellular changes that lead to alterations in the structure and function of the myocardium. Oxidative stress potentiates this remodeling response and is associated with progressive worsening of cardiac function. Accordingly, we used a powerful antioxidant-based therapeutic strategy to improve cardiac health and study redox-dependent signaling. Methods: MI was surgically induced in rats by ligating the left anterior descending coronary artery. Subgroups of MI rats received resveratrol (i.p., 10 mg/kg/day for 28 days beginning immediately post-MI). Cardiac histology and biochemical analyses of genes and proteins implicated in cardiac fibrosis, hypertrophy, and apoptosis, and redox-dependent signaling were analyzed. Results: As expected, MI resulted in profound structural changes to the myocardium. Further, we observed a sharp reduction in nuclear factor-erythroid 2-related factor 2 (Nrf2) and Krüppel-like factor 15 (KLF15), factors that are responsible for maintaining the endogenous antioxidant capacity and regulating cardiac gene expression, respectively. It is likely that disruption of normal KLF15 signaling permitted the expression of several cardiac genes associated with progressive cardiac remodeling. Importantly, daily treatment with resveratrol ameliorated cardiac remodeling, improved redox state, restored Nrf2 expression, and up-regulated KLF15 expression. Further, induction of KLF15 signaling following resveratrol treatment is associated with attenuated expression of several genes implicated in cardiac remodeling. Conclusions: Chronic oxidative stress potentiates cardiac remodeling post-infarct, in part, by suppressing Nrf2 and KLF15 expression. Importantly, we demonstrate that normal KLF15 signaling may be rescued with an antioxidant-based therapy, which may be an attractive therapeutic target to support cardiac health post-MI.

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Previous studies in yeast in this laboratory have found carnitine to be both protective against oxidative stress induced by hydrogen peroxide and to increase the detrimental effect of dithiothreitol. These phenotypes were found to be independent of the role of carnitine within the carnitine shuttle. A screen for suppressor mutations for these carnitine-dependent phenotypes identified, among others, Δcho2 and Δopi3. Cho2p and Opi3p catalyse the sequential methylation reactions in the formation of phosphatidylcholine from phosphatidylethanolamine. Therefore, this study aimed to investigate the relationship between choline, phosphatidylcholine and the carnitine phenotypes. Liquid growth assays of Δcho2 and Δopi3 cultures revealed that addition of choline can restore the protective effects of carnitine against hydrogen peroxide. The connection between the cellular phospholipid composition and the carnitine-dependent shuttleindependent phenotypes was also investigated. Analysis of the lipid composition of cells by LCMS showed that Δcho2 and Δopi3 had a largely different lipid composition compared with the wild type, most notably, a reduction in phosphatidylcholine and an increase in triacylglycerol content were observed for both mutants. These changes were reversed by supplementation with choline. However, no effects on the lipid composition of cells in response to carnitine treatment were observed, either when supplemented alone or in combination with DTT and hydrogen peroxide. Carnitine has also been investigated in mammalian systems for its potential to protect cells from oxidative stress, an effect which would be of benefit in various neurodegenerative disorders. Several studies have documented the positive effects of carnitine against oxidative stress in mammalian cells however the mechanism behind this action remains unknown. It is therefore thought that, provided similar effects for carnitine can be shown in mammalian cells as was observed in yeast, it would be beneficial to use yeast as a model system for the study of the molecular changes induced by carnitine. In view of this, the effects of carnitine on toxicity induced by oxidative stress in mammalian neural cells were compared to that which has been observed in yeast. For this purpose the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, a measure of reductive capacity of cells, was used. However, no effects for carnitine were observed in the MTT assay in combination with either dithiothreitol or paraquat. / AFRIKAANSE OPSOMMING: Vorige studies op gis in hierdie laboratorium het bevind dat karnitien beskermend is teenoor oksidatiewe stres wat deur waterstofperoksied geïnduseer word en ook die nadelige effek van ditiotreitol verhoog. Hierdie fenotipes is gevind om onafhanklik te wees van die rol van karnitien binne die karnitien-pendel. Die sifting vir onderdrukker-mutasies van hierdie karnitienafhanklike fenotipes het onder andere Δcho2 en Δopi3 geïdentifiseer. Cho2p en Opi3p kataliseer die opvolgende metileringsreaksies tydens die vorming van fosfatidielcholien vanaf fosfatidieletanolamien. Hierdie studie het dus gepoog om die verhouding tussen cholien, fosfatidielcholien en die karnitienfenotipes te ondersoek. Vloeistofanalises van Δcho2- en Δopi3-kulture het aangedui dat die byvoeging van cholien die beskermende effekte van karnitien teenoor waterstofperoksied kan herstel. Die verband tussen die sellulêre fosfolipiedsamestelling en die karnitienafhanklike pendel-onafhanklike fenotipes is ook ondersoek. Die analise van die lipiedsamestelling van selle deur middel van LCMS het getoon dat Δcho2 en Δopi3 ‘n grootliks verskillende samestelling het in vergelyking met die wilde tipe, en daar is veral ‘n afname in fosfatidielcholien en ‘n verhoging in triasielgliserol-inhoud vir beide mutante waargeneem. Hierdie veranderinge is omgekeer deur aanvulling met cholien. Geen effekte op die lipiedsamestelling van die selle is egter in reaksie op die karnitienbehandelings waargeneem nie, hetsy toe dit alleen aangevul is of in kombinasie met ditiotreitol en waterstofperoksied. Karnitien is ook in soogdierstelsels ondersoek vir sy potensiaal om selle teen oksidatiewe stres te beskerm, ‘n effek wat groot voordeel sal inhou vir verskeie neurodegeneratiewe steurings. Verskeie studies het reeds die positiewe effekte van karnitien teen oksidatiewe stres in soogdierselle opgeteken, hoewel die meganisme agter hierdie werking nog onbekend is. Daar word dus vermoed dat, gegewe dat soortgelyke effekte vir karnitien in soogdierselle getoon kan word as wat in gis waargeneem is, dit voordelig sou wees om gis as ‘n modelsisteem vir die studie van die molekulêre veranderinge wat deur karnitien geïnduseer word, te gebruik. In die lig hiervan is die effekte van karnitien op giftigheid wat deur oksidatiewe stres in soogdiersenuselle geïnduseer is, vergelyk met dít wat in gis waargeneem is. Om hierdie rede is die 3-[4,5-dimetieltiasool-2-iel]-2,5-difeniel tetrasoliumbromied (MTT) essaiëring, ‘n meting van die verminderende kapasiteit van selle, gebruik. Geen effekte vir karnitien is egter met die MTT essaiëring in kombinasie met óf ditiotreitol óf parakwat waargeneem nie.

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Chronic inflammation and immune activation are hallmarks of HIV infection, resulting in chronic oxidative stress with over-utilization of antioxidant defences, which may contribute to the loss of immune cells and faster disease progression. Low levels of antioxidants in HIV- infected individuals have been associated with frequent opportunistic infections and an increased risk of mortality. HIV infection is also associated with on-going and aberrant activation of both the innate and adaptive immune systems. An important aspect of innate immune stimulation is derived from the leakage of lipopolysaccharide (LPS) across the damaged mucosal lining of the gut in early HIV infection. The impact of this innate immune stimulation on the adaptive arm of the immune system, as represented in this study by levels of CD4+ T-cell activation and death, have not been explored previously in untreated HIV infection. Using an integrated approach of immune activation, inflammation, oxidative stress and ameliorating antioxidant intervention for the first time, this thesis reports the impact of inflammatory induced-oxidative stress on CD4+ T-cells in an in vitro HIV model. In a preliminary study, baseline levels of neutrophil respiratory burst as an in vitro indication of immune stimulation were investigated. The relationships between baseline total antioxidant status (TAS), Red blood cell (RBC) antioxidant enzyme activities (catalase, superoxide dismutase & glutathione peroxidase), lipid peroxidation and glutathione redox ratio and other markers of disease in asymptomatic, untreated HIV infection were also explored. The design and optimization of an assay that could determine the effects of LPS-induced oxidative stress on CD4+ T-cells, was a critical part of this study. The development of this assay enabled the measurement of the effects of selected antioxidant interventions N-acetyl cysteine (NAC) and vitamin C, on LPS-induced CD4+ T-cell activation and death. The results were also correlated with CD4 count, viral load and markers of inflammation (fibrinogen & D-dimers) in HIV-infected and uninfected groups. Neutrophils from HIV-infected persons at rest showed a ―primed‖ response to low stimulating agent, bacterial N-formyl peptides (fMLP), which was significantly (P = 0.04) higher than uninfected individuals. There was increased oxidative stress as evidenced by increased catalase activity, malondialdehyde (MDA) and conjugated dienes (CDs) with a corresponding decrease in antioxidant capacity in HIV-infected individuals with lower CD4 count. NAC in combination with vitamin C, significantly (P = 0.0018) reduced activation of CD4+ T-cells to a greater degree than with either antioxidant alone. NAC and vitamin C individually and in combination significantly (P = 0.05, P = 0.012 and P<0.0001) decreased the expression of the markers of apoptosis, Annexin V and 7-amino-actinomycin (7-AAD). Importantly, the antioxidant combination decreased MDA values and significantly (P = 0.01) increased the glutathione redox ratio in the HIV-infected group. Based on these results, the respiratory burst and LPS-induced activation may be important contributing factors in inflammatory-associated oxidative stress in HIV infection and contribute to the depletion of CD4+ T-cells in the asymptomatic stage of HIV infection. These results also indicate the potential inhibitory effects of NAC and vitamin C in combination as agents that may limit immune activation and inflammation-induced oxidative stress. Importantly, the study showed that at this asymptomatic stage, CD4+ T-cells of the HIV-infected group responded similarly to stimulation as the HIV negative group, indicating that antioxidant defences were still functional and that appropriate early intervention at this stage may be protective against oxidative damage to the immune cells. To the best of our knowledge, this study is the first to use an integrated approach involving not only plasma levels of antioxidant status, but also RBC antioxidant enzyme activities, oxidative damage (lipid peroxidation), inflammation, cellular levels of immune activation and potential ameliorating interventions in evaluating the problem of inflammation-induced oxidative stress in HIV infection. Based on the results of this study, it is envisaged that an insight into the immune activation, inflammatory and oxidative stress status of patients will enable long-term profiling of each patient with a view to individualized therapy. This approach may have a direct impact on patient care in resource-limited settings such as sub-Saharan Africa. / AFRIKAANSE OPSOMMING: Chroniese inflammasie en immuunaktivering is kenmerke van MIV-infeksie. Dié twee prosesse lei tot chroniese oksidatiewe stres en oorbenutting van antioksidant verdedigingstelsels, wat lei tot die verlies van die immuun selle en vinniger siektevordering. Lae vlakke van antioksidante in MIV-positiewe individue stem ooreen met gereelde opportunistiese infeksies en 'n verhoogde risiko van mortaliteit. MIV-infeksie word ook geassosieer met langdurige en abnormale aktivering van beide die ingebore en aanpasbare immuunstelsels. 'n Belangrike aspek van ingebore immuun stimulasie in die raamwerk van vroeë MIV-infeksie, is die lekkasie van LPS oor die beskadigde slymvlies voering van die dunderm. Die impak van die ingebore immuun stimulasie op die aanpasbare arm van die immuunstelsel, soos aangetoon in hierdie studie deur die vlakke van CD4 T-sel aktivering en apoptose, is nog nie voorheen ondersoek in onbehandelde MIV-infeksie nie. Met behulp van 'n oorspronklike, geïntegreerde benadering van immuun aktivering, inflammasie, oksidatiewe stres en 'n lae vlak van antioksidant intervensie, lewer hierdie tesis verslag oor 'n in vitro model van inflammasie-geïnduseerde oksidatiewe stres op CD4 T-selle. In 'n voorlopige studie, is basislyn vlakke van die neutrofiel respiratoriese uitbarsting as 'n in vitro aanduiding van immuunstimulasie ondersoek. Die verhoudinge tussen basislyn totale antioksidant status (TAS), rooi bloed sel (RBC) antioksidant ensiemaktiwiteit (katalase, superoksied dismutase, en glutatioon peroksidase), lipied peroksidasie en glutatioon redoks-verhouding, asook ander merkers van siektevordering in asimptomatiese, onbehandelde MIV-infeksie is ook ondersoek. Die ontwerp en optimisering van 'n toets wat die effek van LPS-geïnduseerde oksidatiewe stres op CD4 T-selle kan bepaal, was 'n kritieke deel van hierdie studie. Die ontwikkeling van hierdie toets het ook die meting van die effek van toevoeging van twee geselekteerde anti-oksidante, N-asetiel sisteïen (NAC) en vitamien C, op LPS-geïnduseerde CD4 T-sel aktivering en apoptose ondersoek. Die resultate is ook gekorreleer met CD4-telling, virale lading en merkers van inflammasie (fibrinogeen en D-dimere) in groepe met en sonder MIV-infeksie. Neutrofiele van asimptomatiese persone met MIV infeksie, het 'n 'voorbereide' reaksie gehad teen ‗n lae stimulerende agent, bakteriële N-formiel peptied (fMLP), wat beduidend (P = 0,04) hoër was as in individue sonder MIV infeksie. Daar was verhoogde oksidatiewe stres soos bewys deur verhoogde katalase aktiwiteit, malondialdehied (MDA) en gekonjugeerde diëne (CDs), saam met 'n ooreenstemmende afname in anti-oksidant kapasiteit in MIV-positiewe individue met laer CD4-tellings. NAC in kombinasie met vitamien C, het die aktivering van CD4 T-selle beduidend verminder (P = 0,0018), 'n effek wat groter was in vergelyking met elke antioksidant alleen. NAC en vitamien C alleen, en in kombinasie het beduidend die uitdrukking van die merkers van apoptose, Annexin V en 7-AAD verminder (P = 0,05, P = 0.012 en P<0,0001). Wat belangrik is, is dat die afname in MDA waardes as gevolg van antioksidante in kombinasie, 'n beduidende styging in die glutatioon redoks verhouding in die MIV-positiewe groep tot gevolg gehad het. Hierdie resultate het aangetoon dat die respiratoriese uitbarsting en LPS-geïnduseerde aktivering belangrike bydraende faktore mag wees in inflammasie-verwante oksidatiewe stres in MIV-infeksie, wat kan bydra tot die uitputting van CD4 T-selle in die asimptomatiese stadium van MIV-infeksie. Hierdie resultate dui ook aan dat die moontlike inhiberende effekte van NAC en vitamien C in kombinasie, immuun aktivering en geïnduseerde oksidatiewe stres kan beperk. Van belang is die feit dat hierdie studie bewys het dat in die asimptomatiese stadium van MIV-infeksie, CD4 T-selle weens stimulasie dieselfde gereageer het as dié van mense sonder MIV infeksie. Dit het aangedui dat antioksidant verdediging in hierdie stadium nog funksioneel was, en dat 'n toepaslike vroeë intervensie op hierdie stadium beskermend teen immuun-sel oksidatiewe skade kan wees. Tot die beste van ons kennis, is hierdie studie die eerste om 'n geïntegreerde benadering te gebruik, waar plasma vlakke van antioksidant status saam met RBC antioksidant ensiemaktiwiteit, oksidatiewe skade (lipied peroksiidasie), inflammasie, sellulêre vlakke van immuunaktivering, en potensiële beskermende ingrypings ondersoek is in die evaluering van die probleem van oksidatiewe stres in MIV-infeksie wat tot inflammasie lei. Gebaseer op dié resultate, word dit in die vooruitsig gestel dat 'n insig in die status van immuunaktivering, inflammasie, en oksidatiewe stress van pasiënte, dit moontlik sal maak vir langtermyn- beplanning om vir elke pasiënt individuele terapie voor te skryf. Hierdie benadering kan 'n direkte impak op die sorg van pasiënte in hulpbron-beperkte gebiede soos sub-Sahara Afrika hê.