Summary Melanoma is the main cause of death in skin cancers. Despite combating with early detection, resection and post-operative therapy, melanoma treatment remains unsuccessful and investigations ...into other forms of adjuvant therapy such as photodynamic therapy (PDT) are prudent. This study proposes that depigmentation i.e. the removal of the free radical scavenging pigment, melanin, in melanotic melanoma cells increases their susceptibility to PDT-induced cell death. Two human melanoma cell lines: one pigmented (Mel-1) and one amelanotic (A375 ) cell lines were used. Kojic acid (KA), a tyrosinase-specific inhibitor, was optimised to 6 μg/ml and shown to quantifiably inhibit melanin synthesis after a 3-day exposure. PDT on these cells resulted in a 3.82 fold increase of intracellular ROS production which correlated to 11% increase in cell death susceptibility compared to untreated controls. Moreover, cells allowed to regain their pigment failed to return to normal even after 72 h thus proving the effectiveness of PDT. Using a DPPH* assay, the results confirmed the scavenging properties of melanin (IC50 18.30 μg/ml) proving that this pigment may be one of the reasons for melanoma chemoresistance. Overall this study shows that pigment plays an important role in the efficacy of adjunctive PDT treatment and its removal enhances cell death susceptibility in melanomas.
In Memoriam: Adib Jarrar Davids, M., Fakhry; Mazarweh, Gehad
International journal of applied psychoanalytic studies,
December 2017, Letnik:
14, Številka:
4
Journal Article
After emerging from its troubled past, postapartheid South Africa adopted a democratic constitution and cosmopolitanism as path to a peaceful future. Cosmopolitanism, once a vibrant tradition at the ...turn of the 19th century, disappeared from the apartheid historical canon and memory due to the colonial practice of forced removals. The apartheid fallacy that forced removals were necessary because of urban slum conditions and public health reasons obscured its ideological and economic reasons. Apartheid narratives and traumatic memories of forced removals continue in the postapartheid era and mitigate against the establishment of a nonracial, cosmopolitan society. Notwithstanding the dominance of negative memories, a productive, decolonised version of forced removals can make a positive contribution to social cohesion. This paper offers a multiple historical case study of three pre-apartheid cosmopolitan spaces that were destroyed by the Group Areas Act as framework to suggest how ideology critique can be employed as a decolonising pedagogy. A critical notion of cosmopolitanism is appropriated, using the notion of production of space to explain the role of political and social engineering in the making of place during the colonial-apartheid period. Recommendations suggest how to integrate cosmopolitanism, segregation, and forced removals with ideology critique as decolonising pedagogy in teacher education curriculum spaces.
Lipopolysaccharide (LPS), a well-conserved cell wall component of Gram positive bacteria, exerts its toxic effects via inducing oxidative and pro-inflammatory responses. Red palm oil (RPO) is a ...unique natural product with a balanced ratio of saturated and unsaturated fatty acids, with reported antioxidant and anti-inflammatory effects. In this study, we assess the protective effect and mechanistic action of RPO using a lipopolysaccharide (LPS)-induced hepatic injury model. Male Wistar rats were assigned into four groups (10 animals/group): normal control (NC), RPO, LPS and RPO + LPS. Animals in the RPO and RPO + LPS groups were administered RPO (200 μL/day) for 28 days. On the 27th day of experiment, animals in LPS and RPO + LPS groups were injected with LPS (0.5 mg/kg body weight). Animals were sacrificed 24 h later, and blood and liver tissues harvested for biochemical and molecular analysis. RPO resolved hepatic histological dysfunction induced by LPS, and lowered alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transferase activities in the serum. Hepatic malondialdehyde and conjugated dienes, as well as pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6 and TNFα were significantly diminished (p < 0.05) by RPO pre-treatment. Activity of hepatic antioxidant enzymes including superoxide dismutase, glutathione reductase, glutathione peroxidase, as well as glutathione redox status (GSH:GSSG), and markers of antioxidant capacity that decreased as a result of LPS injection were improved by RPO pre-treatment. Mechanistically, RPO up-regulated mRNA expression of redox sensitive transcription factor Nrf2 and its downstream targets GCL and HO-1, while also suppressing the expression of NFκβ and associated inflammatory protein, Iκβ kinase (IκKβ). In conclusion, this study highlights the ameliorating effects of RPO against LPS-induced hepatic injury and revealed the Nrf2/GCL/HO-1 and NFκβ signaling axis as potential contributing mechanisms.
This article investigates common understandings and practices of a group of supervisors assessing students during the Teaching Practicum in South Africa. In the light of this context and the need for ...a constructivist approach to develop students to be able to teach in diverse contexts, the question that the research intends to answer is as follows: What are the common foci of supervisors as reflected in their teaching practicum assessment reports? A randomly mixed sample of 33 narrative reports, taken from 5 supervisors was analysed to gain insight into the assessment report. Findings are presented as five assessment discourses and an argument is presented for the Teaching Practicum assessment to shift towards a student-oriented developmental approach that is neither hierarchical nor judgmental but aims at serving students' professional development that meets the challenges of culturally diverse societies.
Chemicals capable of lightening the skin – variously known as skin-bleaching, skin-lightening, depigmenting, skin-evening and skin-brightening agents – are among the most commonly used skin ...preparations in the world. Globally, Africa reportedly exhibits a high prevalence of skin lightener use. In this review, we provide both clinical and social perspectives on skin lightener use in Africa, with particular emphasis on South Africa. We narratively explore the timeline associated with skin lightener use in South Africa and attempt to interweave the social rhetoric of this specific paradigm. Despite the risks associated with exposing the skin to known constituents of these formulations, such as hydroquinone and mercury, chronic use continues. In spite of legislation banning hydroquinone and mercury in cosmetics in South Africa, these ingredients are present in widely available products. We recommend better implementation of policies and greater ethical responsibility of multinational cosmetic companies in addition to the initiation of a system of random product testing and penalties that could improve industry compliance.
Significance:
There is a high prevalence of skin lightener use in Africa.
Despite legislation banning harmful compounds, these compounds are still used in skin lightening formulations.
There is an urgent need to implement policies and recommendations for preventing the influx and illicit sale and use of untested skin lighteners.
Diesel Exhaust Particles (DEP) have been reported to be mainly responsible for most of the toxic effects of air pollution probably via a mechanism that involves induction of oxidative stress and ...proinflammatory response. Rooibos (Aspalathus linearis) and Honeybush (Cyclopia species) are widely used due to their health promoting effects. This study examined the effect of Rooibos tea and Honeybush on the prooxidative and proinflammatory effects of standard reference material (SRM) 2975 DEP in human skin fibroblasts and immortalized keratinocyte cell lines. The cells were either exposed to different concentrations (5-50 μg/ml) of DEP for 4 h or pre-treated with 40 and 60 μg/ml of fermented (FR) or green (GR) Rooibos or fermented Honeybush (FH) for 6 h prior to 4 h exposure to 10 μg/ml DEP. Exposure to DEP caused a significant decrease in cell viability, and increase in LDH leakage, ROS production, oxidative stress biomarkers and proinflammatory cytokines in both cell lines compared to control. However, the presence of the extracts significantly (p < 0.001) attenuate these effects. This study highlights the potential of FR, GR and FH in protecting against DEP-induced oxidative stress and proinflammatory effect in fibroblasts and keratinocytes probably.
Abstract
Background: There is a need to determine the feasibility of conducting studies of chronic diseases among large cohorts of African patients. One aim of the South African feasibility study was ...to determine the prevalence of chronic kidney disease (CKD) and its association with cardiovascular disease (CVD) risk factors among school teachers.
Methods: In a cross-sectional survey of 489 teachers we captured data on demographics, CVD risk factors, anthropometry and blood pressure. Serum glucose, creatinine, cholesterol and urine protein/creatinine ratio was measured. Glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease study equations.
Results: The mean (± standard deviation) age of the participants was 46.3 ± 8.5 years, with 70.3% being female and 74.6% of mixed ethnicity. The crude prevalence of CKD using the CKD-EPI equation was 6.1% while the age-adjusted prevalence was 6.4% (95% confidence interval 3.2–9.7%). CKD was associated with the presence of diabetes and higher diastolic blood pressures.
Conclusions: In our study population of relatively young, working individuals CKD was common, clinically silent and associated with cardiovascular risk factors. The long-term complications of CKD are serious and expensive to manage and this, therefore, constitutes an important public health problem for South Africa.
The resistance of pigmented human melanomas over their unpigmented counterparts to a number of therapies has suggested that the presence of intracellular melanin plays a role in rendering these cells ...less susceptible to cell death, probably through the ability of this pigment to act as an intracellular antioxidant, thus neutralizing chemotherapeutic‐induced ROS (reactive oxygen species). PDT (photodynamic therapy) was recently suggested as an attractive, adjunctive therapy owing to its cellular specificity and limited side effects. In the present study, we propose that first depigmenting melanomas with a reversible TYR (tyrosinase) inhibitor such as PTU (phenylthiourea) increases their susceptibility to HYP‐PDT (hypericin‐mediated PDT). Pigmented UCT Mel‐1 (University of Cape Town melanoma cell line 1) and unpigmented (A375) melanomas were first characterized with respect to their TYR activities and melanin quantities and then treated with a TYR inhibitor for 48 h. Cell viability assays after treatment with 3 μM HYP‐PDT showed a significant increase in cell death in depigmented melanomas compared with untreated melanomas that returned to the level of untreated melanoma cells on removing the TYR inhibitor. The present study supports the hypothesis that combining the inhibition of melanogenesis with PDT should be explored as a valid therapeutic target for the management of advanced melanoma.
Abstract Metastatic malignant melanoma remains one of the most dreaded skin cancers worldwide. Numerous factors contribute to its resistance to hosts of treatment regimes and despite significant ...scientific advances over the last decade in the field of chemotherapeutics and melanocytic targets, there still remains the need for improved therapeutic modalities. Photodynamic therapy, a minimally invasive therapeutic modality has been shown to be effective in a number of oncologic and non-oncologic conditions. Using second-generation stable, lipophilic photosensitizers with optimised wavelengths, PDT may be a promising tool for adjuvant therapy in combating melanoma. Potential targets for PDT in melanoma eradication include cell proliferation inhibition, activation of cell death and reduction in pro-survival autophagy and a decrease in the cellular melanocytic antioxidant system. This review highlights the current knowledge with respect to these characteristics and suggests that PDT be considered as a good candidate for adjuvant treatment in post-resected malignant metastatic melanoma. Furthermore, it suggests that primary consideration must be given to organelle-specific destruction in melanoma specifically targeting the melanosomes – the one organelle that is specific to cells of the melanocytic lineage that houses the toxic compound, melanin. We believe that using this combined knowledge may eventually lead to an effective therapeutic tool to combat this highly intractable disease.
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