Novel in silico-designed estradiol analogues are cytotoxic to a multidrug-resistant cell line at nanomolar concentrations

PURPOSE : 2-Methoxyestradiol (2ME) is a promising anticancer agent that disrupts the integrity and dynamics of the spindle network. In order to overcome the pharmacokinetic constraints of this compound, a panel of sulphamoylated estradiol analogues were in silico-designed by our laboratory. In this study, we analysed the potential of each analogue to induce cell death on a panel of cancer cell lines. Moreover, the mechanism of action of the most effective compounds was determined. METHODS : Cytotoxicity screening of the compounds and intermediates was performed on five different cancer cell lines to determine IG50 values. An in vitro tubulin polymerization assay was done to determine the effect of the drugs on tubulin polymerization while their intracellular effects on the microtubule network were assessed by immunofluorescence microscopy. RESULTS : IG50 calculations showed that the sulphamoylated analogues induce cytotoxicity at nanomolar concentrations in all cell lines, including the P-glycoprotein pump overexpressing multidrug-resistant uterine sarcoma cell line. The non-sulphamoylated compounds were only cytotoxic at micromolar ranges, if at all. The sulphamoylated compounds inhibited pure tubulin polymerization in a dose-dependent manner and induced microtubule destruction in cells after 24-h exposure. CONCLUSION : Results revealed that the novel sulphamoylated 2ME derivatives have potential as anti-cancer drugs, possibly even against chemoresistant cancer cells. These compounds disrupt the intracellular microtubule integrity which leads to mitotic block of the cells.The Research Development Programme of the University of Pretoria (RDP AOV840), the South African Medical Association (SAMA), the National Research Foundation (NRF Project # 86475, N00465, N00375, N00591), the Research Committee of the Faculty of Health Sciences, University of Pretoria (RESCOM), CANSA (AOV741, AOW228) and the Medical Research Council (MRC AOW110).http://link.springer.com/journal/2802016-02-28hb201

African Communitarianism and Difference

There has been the recurrent suspicion that community, harmony, cohesion, and similar relational goods as understood in the African ethical tradition threaten to occlude difference. Often, it has been Western defenders of liberty who have raised the concern that these characteristically sub-Saharan values fail to account adequately for individuality, although some contemporary African thinkers have expressed the same concern. In this chapter, I provide a certain understanding of the sub-Saharan value of communal relationship and demonstrate that it entails a substantial allowance for difference. I aim to show that African thinkers need not appeal to, say, characteristically Euro-American values of authenticity or autonomy to make sense of why individuals should not be pressured to conform to a group’s norms regarding sex and gender. A key illustration involves homosexuality

An evaluation of the state of wellness amongst medical aid company employees in South Africa

Huidige navorsing op die gebied van welstand in die werkplek is gefragmenteer en vereis ’n holistiese, geïntegreerde en stelselmatige begrip van werknemerwelstand sodat gesondheiden welstandsorg doeltreffend bestuur kan word. Die toenemende las van nie-oordraagbare toestande in Suid-Afrika beklemtoon die noodsaaklikheid van voorkomingstrategieë soos welstandprogramme. Die werkomgewing bied ’n ideale plek, aangesien ’n groot deel van die bevolking geteiken word, insluitende diegene wie se lewenstyl verbeter moet word. Hierdie studie is dus daarop gemik om verskeie gesondheid- en welstandkomponente onder werknemers van ’n mediesefondsmaatskappy te evalueer in ’n poging om risikogebiede te identifiseer wat verdere ingryping vereis. Die deelnemers het bestaan uit 140 werknemers van ’n mediesefondsmaatskappy wat ten minste 40 h per week werk. Hulle is onderwerp aan ’n welstandassesseringsbattery bestaande uit antropometrieke, gesondheidverwante en fisieke kapasiteitmetings. Die resultate toon dat ingryping nodig is betreffende alkohol- en dwelmgebruik, dieetgewoontes, hartgesondheid, liggaamsamestelling, spieruithouvermoë, kardiorespiratoriese uithouvermoë en individuele persepsies van die maatskappy. Dié studie het resultate opgelewer wat die bevindings van baie vorige navorsing op hierdie gebied staaf. Die trefwydte van welstandprogramme op die Suid-Afrikaanse bevolking is egter beperk. Die sukses van welstandprogramme wat fisieke aktiwiteit beklemtoon, is goed gedokumenteer in hoë-inkomstelande, met bewys van die ekonomiese voordele en opbrengs op belegging. Gevolglik word daar aangevoer dat die toepassing van welstandprogramme ’n positiewe uitwerking op die Suid-Afrikaanse werkmag sal hê.Current research in the area of wellness in the workplace is fragmented and requires a holistic, integrated and systemic understanding of employee wellness in order for health and wellness care to be effectively managed. The growing burden of noncommunicable conditions in South Africa highlights the necessity for prevention strategies such as wellness programmes to be implemented. The workplace provides an ideal setting as a large proportion of the population will be targeted, including those who require lifestyle improvement. Therefore this study sought to evaluate various health and wellness components among employees of a medical aid company in an attempt to identify risk areas which require further intervention. Participants were 140 employees of a medical aid company who work a minimum of 40 h per week and who were subjected to a wellness assessment battery, consisting of anthropometrical, health-related and physical capacity measurements. The results indicate that intervention is required in terms of alcohol and drug usage, dietary habits, heart health, body composition, muscular endurance, cardiorespiratory endurance, and individual perceptions towards the company. This study produced results which corroborate the findings of a great deal of previous research in this field. However, the scope for applying wellness programmes to the South African population is limited. The success of wellness programmes which emphasise physical activity has been well documented in high-income countries, with evidence of economic benefits and return on investment. And so it is proposed that implementation of wellness programmes will have a positive effect on the South African workforce.http://www.satnt.ac.zaam201

Addiction in the Light of African Values: Undermining Vitality and Community

In this article I address the question of what makes addiction morally problematic, and seek to answer it by drawing on values salient in the sub-Saharan African philosophical tradition. Specifically, I appeal to life-force and communal relationship, each of which African philosophers have at times advanced as a foundational value, and spell out how addiction, or at least salient instances of it, could be viewed as unethical for flouting them. I do not seek to defend either vitality or community as the best explanation of when and why addiction is immoral, instead arguing that each of these characteristically African values grounds an independent and plausible account of that. I conclude that both vitalism and communalism merit consideration as rivals to accounts that Western ethicists would typically make, according to which addiction is immoral insofar as it degrades rationality or autonomy, as per Kantianism, or causes pain or dissatisfaction, à la utilitarianism

Relationships, intimacy and desire in the lives of lesbian, gay and bisexual youth in South Africa

This article answers the following questions: how do nine lesbian, gay and bisexual (LGB) young people in South Africa understand and talk about relationships, intimacy, and desire; what does this understanding and talk tell us about gender and sexuality in South Africa; and how useful is the metaphor of the ‘closet’ to understand how LGB youth talk about relationships, intimacy and desire? At the time of the study, they were between 16 and 19 years old and attending school in grades 10 to 12. We used in-depth interviews, which were more like conversations, where primarily open-ended questions focused on these young people’s experiences, and found that relationships of love and care, the desire for love and intimacy, and the ability to exist alongside and for others pervade these young people’s lives. In this regard, employing postcolonial and Southern theory we argue that the youth use the concept of the closet, but that they understand it differently. We also argue that the concept of the closet may not accurately capture the particular positions that youth occupy in society because the concept of the closet suggests separation rather than engagement. The notion of being separate from the surrounding community is anathema to and contradicts these nine young people’s worldviews and those of the communities in which they live

Interlending Services: Trends, Languages, and use for Collection Development at North-West University

This paper uses the bibliometrics methods to analyse the interlending service trends, language and collection development at the North-West University. The results show that despite some challenges, ILS services at the NWU decreased. More than 98.5% of all documents requested are in English language followed by Setswana and Afrikaans. Out of the 535 books requested by the Mafikeng Campus, 138 were added to the collection of the library. These results point to a need for academic libraries in Africa to adopt strategies for the development of African languages. The results support the continued use of ILS data for collection development purposes