Browsing by Author "Davids, Lester"

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    An investigation into the cellular mechanisms underlying photodynamic rejuvenation in human skin
    (2012) Van Kets, Victoria Louise; Davids, Lester
    Photodynamic Rejuvenation (PDR) is a novel therapy used to treat the signs of skin ageing. It is a promising dermatological therapy due to its less severe side effects and superior results when compared to other chemical treatments. This therapy involves the topical application of a photosensitizing drug (PS) which is activated by a specific wavelength of light to react with oxygen and generate reactive oxygen species (ROS) in the skin. At low levels ROS are able to alter cell signalling and are thought to be the key mediators that reverse the signs of ageing. Dermatologists use this therapy to treat various characteristics of skin ageing such as fine/coarse wrinkles, mottled pigmentation, skin roughness and telangiectasia (small broken blood vessels near the surface of the skin). Initial clinical reports showed success; however, inconsistencies in patient outcomes provide impetus to improve characteristics of current treatment regimes including the PS, light sources, fluences and irradiances. As very little is known about the actual biological mechanism of PDR in human skin cells, the aim of this investigation was to first optimise a protocol using the PS, hypericin, activated with 3 different light sources. Hypericin, an extract from St Johns Wort, is a second generation PS that has many benefits such as low dark cytotoxicity, no carcinogenicity/mutagenicity, high quantum yield and can be activated by several wavelengths of light. We chose three light sources that emitted light within hypericin’s absorbance spectra: two lasers emitted light at 561nm and 632nm and lamps in a UVA transilluminator emitted a light range with a peak at 365nm. Cultured primary human fibroblasts were chosen as the cell model as they are an ideal representation of the dermal layer of the skin. Our results showed that low hypericin concentrations (0.25-0.5μM) at all three wavelengths caused an increase in cell viability. When this increase was investigated in relation to growth or cellular activity, growth curves showed that PDR with all 3 wavelengths had no effect on the cell proliferation rate. To confirm whether ROS was indeed occurring after the therapy, a ROS assay was performed. The yellow laser and UVA transilluminator, which emit light maximally absorbed by hypericin, were used. UVA served as the upper limit for ROS generation as this range of wavelengths is known to cause intracellular ROS. Yellow laseractivated hypericin resulted in a non-significant increase in intracellular ROS which was less than the levels in fibroblasts with UVA activated hypericin. This confirms that PDR using hypericin does generate ROS. As migration is considered inverse to collagen production and increased collagen is a main objective of skin rejuvenation, we studied fibroblast migration after PDR. To assess fibroblast migration in response to yellow laser light activation of hypericin, a scratch assay was used. This PDR protocol showed that migration was significantly slowed after treatment. Our proposal is that our PDR protocol with yellow laser light decreases migration diverting energy to producing collagen.
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    The protective effects of the antioxidant combination of ferulic acid with vitamins C and E against UV-induced photodamage in human skin cells
    (2010) Bone, Emma Lewis; Davids, Lester
    This study assessed the ability of 0.8 mM ferulic acid (FA), in combination with vitamins C and E, to reduce the effect of UVA-induced photodamage in human epidermal (HaCaTs) and dermal skin cells (primary human fibroblasts (HFbs) and murine 3T3 cells). Pretreatment with the FA and vitamins C and E (vEC) combination solution reduced UVAinduced ROS in human fibroblasts while pre-treatment with vEC individually led to a reduction in HaCaTs.
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    The impact of solar ultraviolet radiation on human health in sub-Saharan Africa
    (2012) Wright, Caradee Y; Norval, Mary; Summers, Beverley; Davids, Lester; Coetzee, Gerrie; Oriowo, Matthew O
    Photoprotection messages and 'SunSmart' programmes exist mainly to prevent skin cancers and, more recently, to encourage adequate personal sun exposure to elicit a vitamin D response for healthy bone and immune systems. Several developed countries maintain intensive research networks and monitor solar UV radiation to support awareness campaigns and intervention development. The situation is different in sub-Saharan Africa. Adequate empirical evidence of the impact of solar UV radiation on human health, even for melanomas and cataracts, is lacking, and is overshadowed by other factors such as communicable diseases, especially HIV, AIDS and tuberculosis. In addition, the established photoprotection messages used in developed countries have been adopted and implemented in a limited number of sub-Saharan countries but with minimal understanding of local conditions and behaviours. In this review, we consider the current evidence for sun-related effects on human health in sub-Saharan Africa, summarise published research and identify key issues. Data on the prevalence of human diseases affected by solar UV radiation in all subpopulations are not generally available, financial support is insufficient and the infrastructure to address these and other related topics is inadequate. Despite these limitations, considerable progress may be made regarding the management of solar UV radiation related health outcomes in sub-Saharan Africa, provided researchers collaborate and resources are allocated appropriately.
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    The impact of solar ultraviolet radiation on human health in sub-Saharan Africa
    (2012) Wright, Caradee Y; Norval, Mary; Summers, Beverley; Davids, Lester; Coetzee, Gerrie; Oriowo, Matthew O
    Photoprotection messages and ‘SunSmart’ programmes exist mainly to prevent skin cancers and, more recently, to encourage adequate personal sun exposure to elicit a vitamin D response for healthy bone and immune systems. Several developed countries maintain intensive research networks and monitor solar UV radiation to support awareness campaigns and intervention development. The situation is different in sub-Saharan Africa. Adequate empirical evidence of the impact of solar UV radiation on human health, even for melanomas and cataracts, is lacking, and is overshadowed by other factors such as communicable diseases, especially HIV, AIDS and tuberculosis. In addition, the established photoprotection messages used in developed countries have been adopted and implemented in a limited number of sub-Saharan countries but with minimal understanding of local conditions and behaviours. In this review, we consider the current evidence for sun-related effects on human health in sub-Saharan Africa, summarise published research and identify key issues. Data on the prevalence of human diseases affected by solar UV radiation in all subpopulations are not generally available, financial support is insufficient and the infrastructure to address these and other related topics is inadequate. Despite these limitations, considerable progress may be made regarding the management of solar UV radiation related health outcomes in sub-Saharan Africa, provided researchers collaborate and resources are allocated appropriately.
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    Vitamin C status, oxidative stress, hyperglycaemia and endothelial function in critically ill patients with septic shock : an observational study
    (2014) Katundu, Kondwani; Hill, Lauren; Davids, Lester
    Septic shock is associated with oxidative stress, reduced levels of plasma vitamin C and stress hyperglycaemia – all factors that may influence endothelial, and therefore, organ function. Vitamin C is an important antioxidant in human plasma; and it has been implicated in maintaining normal endothelial function during oxidative stress. The vitamin C status of critically ill patients in South African ICUs has not been well investigated; neither has the relationship between vitamin C status, oxidative stress, hyperglycaemia and endothelial function been studied in this patient group. In a prospective, cross-sectional study investigating these factors in critically ill patients with septic shock on inotropic support, serial blood samples from 25 patients were taken at days zero and one, following inotrope initiation, and on day seven after inotrope cessation. These samples were analysed for plasma vitamin C, thiobarbituric acid-reactive substances (TBARS) - as a biomarker of oxidative stress - and soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin, as markers of endothelial dysfunction. The plasma glucose to vitamin C ratios were also calculated. Daily clinical measures in the patients included Sequential Organ Failure Assessment (SOFA) score, mean arterial blood pressure, blood glucose, fluid balance and inotropic support. The clinical outcomes were recorded.