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Advances in Anti-inflammatory Therapy explores the cutting-edge in anti-inflammation therapy in clear and concise language, with insights from academia and industry. Sections cover key regulatory pathways that mediate acute and chronic inflammation and disease onset. Further chapters are devoted to advanced anti-inflammatory pharmaceuticals, including chemical moieties, pharmacophores, APIs, natural products, herbal therapies, molecular nanomedicine and advanced drug delivery vectors. Systematically planned chapters and illustrations enable potential readers to gain essential insights on the most recent advancements in the field. Arranged with systematic chapters covering a broad range of inflammatory diseases, discussions on past, current and future therapeutics and advanced anti-inflammatory pharmaceuticals, this book will be useful to a wide range of researchers, especially medicinal chemists, drug design experts, and biological and translational researchers working in the field of inflammation.

Barrie Rathbone,1 Janusz Jankowski,2 Michael Rathbone31University Hospitals of Leicester, Leicester, 2Sir James Black Professor Queen Mary University of London, 3St George's University of London, London, United KingdomAbstract: Esophageal cancer is the sixth commonest cause of cancer death worldwide. It predominantly occurs in two histological types, ie, squamous cell carcinoma and adenocarcinoma, each with its own distinct geographical distribution and natural history. The incidence of esophageal adenocarcinoma is rising, as is that of its precursor lesion, Barrett's esophagus, which consists of metaplastic change in the squamous mucosa of the esophagus in response to damage by gastroesophageal reflux disease. The principal risk factors for esophageal cancer are cigarette smoking and alcohol consumption, reflux disease, and obesity. In tumors without local invasion or distant metastases, surgery remains the treatment option of choice, although there are considerable differences of opinion regarding the roles of chemotherapy and radiotherapy. A wide variety of endoscopic treatments are available for dysplastic lesions and palliation. Despite the availability of increasingly complex imaging modalities and expensive and possibly ineffective attempts at screening, the evidence base is conflicted and the prognosis remains poor. However, from a recent large systematic review, three clear recommendations can be made, ie, use of endoscopic resection for high grade dysplasia, use of radiofrequency ablation for residual premalignant lesions, and, finally, prevention of risk factors for cancer, such as smoking, alcohol consumption, and obesity.Keywords: cancer, Barrett's, esophagus, squamous cell carcinoma, adenocarcinoma

The purpose of this article is to critically discuss the tragedy that occurred between 11 and 16 August 2012 at the Lonmin Mine in Marikana, South Africa. Although the events leading up to the Marikana massacre were complex and not one single factor was responsible for the tragedy we will focus on the philosophical and anthropological aspect that may have influenced the breakdown of engagement between the management of Lonmin and workers. It will be argued that this breakdown may have been the result of reductionist anthropological trends that arise in capitalism. These trends selectively utilize modern economic principles to advance the profit motive of business and dehumanises workers. This dehumanisation is clear in the view of workers by the Lonmin management and breakdown of communication. In order to provide an alternative anthropology the philosophy of Paul Ricoeur with special reference to his work Fallible man (1986) is explored and applied as an alternative anthropology for the reductionist trends related to labour that sporadically arise in capitalism. This offers a balanced view that incorporates the aim of responsible business to make profit with that of a sustainable labour market. Die doel van hierdie artikel is om 'n kritiese bespreking te doen van die tragedie wat tussen 11 en 16 Augustus 2012 afgespeel het by die Lonmin-myn in Marikana, Suid-Afrika. Hoewel die gebeure wat aanleiding gegee het tot die Marikana-slagting kompleks is en nie gereduseer kan word tot een enkele faktor wat verantwoordelik was vir die tragedie nie, sal ons fokus op die filosofiese en antropologiese aspekte wat gelei het tot die ineenstorting van die kommunikasie tussen die bestuur van Lonmin en die werkers. Daar sal aangevoer word dat hierdie ineenstorting die gevolg kon wees van reduksionistiese antropologiese neigings wat binne die raamwerk van kapitalisme ontwikkel. Hierdie neigings maak op 'n selektiewe basis gebruik van modern ekonomiese beginsels om die winsmotief van besighede te bevorder, en dit lei tot die ontmensliking van die werker. Hierdie ontmensliking is duidelik sigbaar uit die oogpunt van die werkers teenoor die agtergrond van die Lonmin-bestuur en die ineenstorting van kommunikasie tussen die partye. Om 'n alternatiewe antropologie voor te stel, word ondersoek ingestel na die filosofie van Paul Ricoeur, met spesifieke verwysing na sy werk Fallible man (1986) en dit word toegepas as 'n alternatiewe antropologie vir die reduksionistiese neigings wat saamhang met arbeid soos wat dit sporadies in kapitalisme opduik. Dit bied 'n gebalanseerde gesigspunt wat die doel van verantwoordelike besighedspraktyke (om wins te maak) inkorporeer met 'n volhoubare arbeidsmark.

Biblical scholarship from the African context provides possible new and creative perspectives for the interpretation of the Tower of Babel narrative because of uniquely African questions that structure the interpretative process. These unique questions relate to the cultures of African people, the injustice of colonialism, apartheid and so forth. The problem is that some of these new perspectives are influenced by rationalism that may result in reductionist interpretations of the Tower of Babel narrative. This is clear in the African cultural hermeneutics of Solomon Avotri and Black African hermeneutics of emeritus arch-bishop Desmond Tutu. The contemporary move among some biblical scholars from the African context that focus on the interaction between scholarly and non-scholarly interpreters of the Bible is an attempt to address the problems associated with rationalism. The art of Azaria Mbatha will be used to illustrate the potential of this contemporary move.

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Guanosine has long been known as an endogenous purine nucleoside deeply involved in the modulation of several intracellular processes, especially G-protein activity. More recently, it has been reported to act as an extracellular signaling molecule released from neurons and, more markedly, from astrocytes either in basal conditions or after different kinds of stimulation including hypoxia. Moreover, in vivo studies have shown that guanosine plays an important role as both a neuroprotective and neurotrophic agent in the central nervous system. Specific high-affinity binding sites for this nucleoside have been found on membrane preparations from rat brain. The present study was undertaken to investigate the distribution and metabolic profiles of guanosine after administering the nucleoside to gain a better understanding of the biological effects of this potential drug candidate. Rats were given an intraperitonal (i.p.) injection of 2, 4, 8 or 16 mg/kg of guanosine combined with 0.05% of [3H]guanosine. Plasma samples were collected 7.5, 15, 30, 60 and 90 min after the guanosine-mixture administration and analyzed by either a liquid scintillation counter or by HPLC connected to a UV and to an on-line radiochemical detector to measure the levels of guanosine and its metabolic products guanine, xanthine and uric acid. The levels of guanosine, guanine and xanthine were also measured in brain, lung, heart, kidney and liver tissue homogenates at the defined time points after the injection of 8 mg/kg of the guanosine-mixture. We found that the levels of radioactivity in plasma increased linearly in a dose- and time-dependent manner. Guanosine was widely distributed in all tissues examined in the present study, at almost twice its usual levels. In addition, guanine levels dramatically increased in all the organs. Interestingly, enzymatic analysis of the plasma samples showed the presence of a soluble purine nucleoside phosphorylase, a key enzyme in the purine salvage pathway and nucleoside catabolism. Since guanosine has been shown to be neuroprotective and astrocytes have been reported to play critical roles in mediating neuronal survival and functions in different neurodegenerative disorders, we also performed uptake and release experiments using primary cultures of rat brain astrocytes. Astrocytes actively and specifically take up both guanosine and guanine and release the respective nucleotides which, in turn, undergo breakdown extracellularly. The high levels of guanine found in the culture medium following astrocyte preloading with guanosine indicates that guanine should also be considered as a potential signaling molecule able to mediate, at least in part, the biological effects that, until now, have been ascribed to guanosine. These findings indicate that newly synthesized guanosine/guanine-based analogues could represent a novel therapeutic approach to neurodegenerative disorders and support the evidence that astrocytes could represent novel, promising therapeutic targets in brain diseases. Copyright © by BIOLIFE, s.a.s.

Herbal plants are a great alternative source of medicine for various diseases. Various countries or a particular ethnic group have their own herbal-based treatment methods that have been in practice since antiquity. Herbal extracts prepared from medicinal plants and their isolated single compounds have been studied for their protective role against vascular inflammation/atherosclerosis using in vitro cell line and in vivo animal models with promising outcomes. Due to the advancement in drug delivery system, it is now possible to formulate herbal-based molecules into liquid crystalline nanoparticles, solid lipid nanoparticles, and so on to increase their stability, uptake by cells, improve bioavailability, and efficacy. In this chapter, we highlight various herbal extracts and chemical constituents as a potential preventive approach for vascular inflammation. Further, we have also discussed the advancement in drug delivery technology in targeting atherosclerosis with some study demonstrating the advantage of formulating novel drug delivery system

MCom (Management Accountancy), North-West University, Potchefstroom Campus The aim, and principal objective, of this study was to explore and document the phenomenon of institutional isomorphism at professional accounting schools at universities in South Africa (hereafter referred to as “accounting schools”), from the perspective of institutional theory. It should be noted that this study, being a phenomenological research effort, was based on the idiosyncratic construction of the lived experiences of a relatively limited number of participations, and not on the generalised reduction of a larger population group. Following a phenomenological research approach, a comprehensive study of research literature relating to the phenomenon was conducted to construct a theoretical framework of institutional theory, professions, universities and the concept of power. In addition, a literature study was done on the accounting profession in South Africa from a historical context, the interrelation between the accounting profession and universities in South Africa and, as indication of its legitimacy, notable instances of criticism recorded against the accounting profession in South Africa. Data was collected by way of obtaining responses from 11 participants - mainly through semi-structured interviews - of whom eight are currently academics at accounting schools, two are international academics and one participant who could provide a more objective perspective regarding the relationship between SAICA and accounting schools at South African universities. An analysis of documents and textual data provided additional data on inter alia the curricular composition of a selection of accounting degree offerings at South African and international universities; the professional qualifications of academics from two accounting schools, the SAICA framework for accrediting accounting degree programmes and the current professional syllabi of SAICA and CIMA. Based on the phenomenological analysis performed, five distinct themes to the phenomenon explored were identified: the accreditation by professional accounting bodies of accounting schools; the curricular composition of accounting degree offerings at South African universities; the appointment of accounting academics at South African universities by virtue of their professional qualification, as opposed to academic qualifications; the examinations of professional accounting bodies, as attempted by students from accredited accounting schools; and research practices by academics at accounting schools. This study concluded that, although accreditation to SAICA is sought voluntarily, due to its unique education model and dominance in the South African professional accounting field, some participants to the study deemed it unviable not to be accredited at SAICA, which ultimately led to conforming behaviour amongst accredited accounting schools in homogenised and isomorphic practices. This isomorphic behaviour is further entrenched by the deemed importance (as regarded by several of the participants to this study) of the results of the SAICA ITC examinations, seemingly as a measure of a respective accounting school’s quality of education and the legitimacy attributed to it. In respect of the curricular alignment of degree offerings by accounting schools to the professional syllabi of professional accounting bodies, the assimilation of behaviour due to the pressure that the participants to the study experienced in respect of the accreditation to SAICA was interpreted as being coercive in nature. In contrast the assimilated curricular adjustments implemented by several accounting schools in South Africa - in response to the professional syllabus change by CIMA in 2019 – was interpreted as normative in nature, as the respective accounting schools were at ease with, but not necessarily obliged, to adapt to the professional syllabus set by CIMA. The appointment of accounting academics at South African universities by virtue of their professional qualification, as opposed to academic qualifications, cannot be attributed to a coercive relationship between professional accounting bodies and accounting schools at South African universities, but can rather be ascribed to mimetic isomorphism amongst these schools. Furthermore, whereas a perceived lack of involvement by South African accounting academics in research activities, could also not be attributed to a coercive relationship between professional accounting bodies and accounting schools, but rather as a result of resource allocation in favour of an emphasis placed on teaching and the focus of these accounting schools to yield successful results in professional accounting examinations, the seeming - although slow - isomorphic shift towards a higher research focus amongst accounting schools at South African universities could be regarded as mimetic in nature. Masters

PhD (Philosophy), North-West University, Potchefstroom Campus A neoliberal global economic system is driven by a political rationality that creates and/or exaggerates socio-economic challenges such as economic inequality. South Africa has adopted some of the neoliberal characteristics and implemented a political rationality that is reflected in its policies and reaction to socio-economic crises. Economic challenges are often approached from quantitatively relying on economic figures and measures to understand and overcome these challenges. This approach oversimplifies socio-economic problems and often leads to the escalation of these problems. In response to this, a more dynamic, multi-dimensional approach is needed. Amartya Sen’s capability approach is one avenue of a multi-dimensional approach that will address this. Sen’s capability approach provides a multi-dimensional understanding of economic inequality. Sen is also critical of the utilitarian approach to understanding economic development and socio-economic challenges. However, Sen’s capability approach still tries to work from within the neoliberal economic system to change its economic and political approaches and policies. I argue that Herbert Marcuse’s concept of false needs not only demonstrates why a new rationality is required to overcome challenges such as economic inequality, but also supplements Sen by giving us an alternative rationality to develop a more dynamic approach to an economy that services the concerns, inequalities and needs of all citizens. A revolution of the quantitative understanding of well-being within neoliberalism is necessary to develop a new economic system that is directed towards a multi-dimensional human development that promotes a qualitative approach to well-being. I argue that a new generation in South Africa is inspired though art and memory to challenge and transform the current neoliberal rationality. Moreover, South Africans are in search of a new rationality and Marcuse’s theories offer the alternative. Doctoral

MA (Philisophy), North-West University, Potchefstroom Campus The purpose of this article is to undertake a philosophical reflection of the South African social grant system from the perspective of the gift as presented by Marcel Mauss, Alasdair John Milbank, Jean-Luc Marion and Jacques Derrida. Mauss’s and Milbank’s view of the gift is based on reciprocity and a circular economy that highlights a reductionist understanding of the gift and possibly of the social grant system. On the other hand, Marion’s saturated gift emphasises givenness as a transcendent phenomenon that moves beyond the donor-receiver relationship and may end in a mystical theology. The aneconomics of Derrida will be presented as an alternative to these reductions as a function of the appearance of the other. The appearance of the other interrupts economic circularity and opens the possibility of hospitality. Masters

Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation of A2A receptor reduced the overexpression of the EMT-related markers, mainly through the cAMP-dependent PKA pathway, as confirmed by cell pre-treatment with Myr-PKI. Both A1 and P2Y1 receptor stimulation exacerbated the TGF-β1-driven effects, which were reduced by cell pre-treatment with the MAPK inhibitor PD98059, according to the increased ERK1/2 phosphorylation upon receptor activation. The effects induced by P2Y11 receptor activation were oppositely modulated by PKA or MAPK inhibition, in line with the dual nature of the Gs- and Gq-coupled receptor. Differently, P2X7 receptor induced, per se, similar and not additive effects compared to TGF-β1, after prolonged cell exposure to BzATP. These results suggest a putative role of purine receptors as target for anti-fibrotic agents.

MA (Philosophy), North-West University, Potchefstroom Campus, 2017 A philosophical inquiry is conducted regarding the view of Jacques Derrida (1930 – 2004) on deconstruction with emphasis on the argument that deconstruction is always already present in some texts as far as metaphors are concerned. The various underlying concepts which form part of deconstruction are investigated – concepts like fragmentation, advanced fragmentation, dissemination and discontinuity. A case study follows in which emphasis is placed on the way in which deconstruction as textual process or dynamic functions in two short short stories of Breyten Breytenbach titled Kersverhaal and Kersverhaal 2 specifically with regard to metaphors. The finding made in this study is that metaphors like “blindness”, “the frame” and “consciousness of the unconscious” are functioning parts of deconstruction. It was subsequently found that deconstruction itself possibly functions metaphorically as an “decentric circle”. Through the ages metaphors have been researched by various philosophers and therefore a short review is given on the views of Plato, Aristotle, Kant, Nietzsche and Ricoeur. It was concluded that the views of these five thinkers are not totally suitable for a philosophical inquiry into metaphors specifically with regard to Breytenbach. However, Derrida’s approach has been found to be quite suitable for an inquiry into Breytenbach’s two short short stories, since both Derrida’s and Breytenbach’s approaches suggest strong elements of deconstruction. Both Derrida and Breytenbach place emphasis on spontaneous expression in literary-aesthetical texts, with specific regard to the role that the human unconscious plays. They both also have a critical view of traditions and therefore this study also focuses on the role that colours traditionally played, compared to the role colours like white and black play in Breytenbach’s Kersverhaal and Kersverhaal 2 – especially as a result of ethnocentrism in the historic, social and political background of South Africa. The prominent metaphors “blindness”, “the frame” and “consciousness of the unconscious”, which form part of the functioning of deconstruction, function analogically in the two texts of Breytenbach; especially concerning the way in which fragmentation, advanced fragmentation, dissemination and discontinuity function within these texts. Accordingly it is also illustrated in which way reconstruction plays a role as a parallel process of deconstruction in the two texts. In spite of the fact that deconstruction is an advantageous textual process or dynamic, there are certain flaws and/or limitations. Consequently attention is also paid to the presence of logocentric constructs like historicism, irrationalism and postmodernism / poststructuralism within the functioning of deconstruction. In the end the critical-philosophical reassessment of deconstruction and metaphors is successful, regardless of certain flaws and/or limitations of deconstruction. Masters

MPhil, North-West University, Potchefstroom Campus, 2016 The Marikana massacre in August 2012 at the Lonmin mine was primarily a consequence of the modern economic philosophy and its embedded reductionist anthropology, as it manifests in the South African context. This reductionist view of people ignores what is at the core of being human — to be recognised and respected as an individual. A perceived complete lack of respect by Lonmin for its workers was a major cause of the Marikana massacre. Paul Ricoeur’s more comprehensive philosophical anthropology, as an alternative, opens up new possibilities in addressing the current dysfunctional view of labour and its dire consequences. Lack of respect for the person is inherent in the modern global economic philosophy and its implied reductionist anthropology. Ricoeur on the other hand, cannot even contemplate personhood without respect. With the unfairness of our economic system and the destruction of the middle class leading to unprecedented levels of social unrest, it is indeed time to embrace a new economic philosophy based on a more comprehensive anthropology. Masters

The need for more rapid onset of action and improved absorption of medications has resulted in great development of drug delivery technologies. Transmucosal drug delivery offers a convenient route of administration for a variety of clinical indications. Unfortunately, the wide variability in structure of the oral mucosal tissues could constitute a key factor in drug penetration and absorption. To circumvent this obstacle and to increase the drug flux through the mucosal membranes, different approaches to permeation enhancement are used. This chapter describes the most significant aspects of the physical techniques widely used such as sonophoresis, iontophoresis, and electroporation. These physical methods are extensively used to enhance drug permeation through the skin, nevertheless, they have some infrequent applications on the mucosae of the oral cavity despite are very promising. In the future, these methods could be further developed and improved.

Guanosine has many trophic effects in the CNS, including the stimulation of neurotrophic factor synthesis and release by astrocytes, which protect neurons against excitotoxic death. Therefore, we questioned whether guanosine protected astrocytes against apoptosis induced by staurosporine. We evaluated apoptosis in cultured rat brain astrocytes, following exposure (3 h) to 100 nM staurosporine by acridine orange staining or by oligonucleosome, or caspase-3 ELISA assays. Staurosporine promoted apoptosis rapidly, reaching its maximal effect (approximately 10-fold over basal apoptotic values) in 18-24 h after its administration to astrocytes. Guanosine, added to the culture medium for 4 h, starting from 1 h prior to staurosporine, reduced the proportion of apoptotic cells in a concentration-dependent manner. The IC50 value for the inhibitory effect of guanosine is 7.5 x 10(-5) M. The protective effect of guanosine was not affected by inhibiting the nucleoside transporters by propentophylline, or by the selective antagonists of the adenosine A1 or A2 receptors (DPCPX or DMPX), or by an antagonist of the P2X and P2Y purine receptors (suramin). In contrast, pretreatment of astrocytes with pertussis toxin, which uncouples Gi-proteins from their receptors, abolished the antiapoptotic effect of guanosine. The protective effect of guanosine was also reduced by pretreatment of astrocytes with inhibitors of the phosphoinositide 3-kinase (PI3K; LY294002, 30 microM) or the MAPK pathway (PD98059, 10 microM). Addition of guanosine caused a rapid phosphorylation of Akt/PKB, and glycogen synthase kinase-3beta (GSK-3beta) and induced an upregulation of Bcl-2 mRNA and protein expression. These data demonstrate that guanosine protects astrocytes against staurosporine-induced apoptosis by activating multiple pathways, and these are mediated by a Gi-protein-coupled putative guanosine receptor.

Rat brain astrocyte and microglia cultures express different members of ATP-binding-cassette (ABC) proteins. RT-PCR analysis showed that astrocytes are equipped with P-glycoprotein (mdr1a, mdr1b), multidrug resistance-associated-protein (mrp1, mrp4, mrp5) and cystic fibrosis transmembrane conductance regulator (CFTR). No transcripts for mrp5 and CFTR were detected in microglia. The ABC protein functional activities are shown by the following results: (i) cyclosporin A (50 microM), verapamil (50 microM), probenecid (1 mM) or sulfinpyrazone (2 mM) enhanced [3H]vincristine accumulation; (ii) cyclosporin A or verapamil but not probenecid or sulfinpyrazone enhanced [3H]digoxin accumulation; (iii) glibenclamide (100 microM) inhibited 36Cl efflux from astrocytes. ATP release from glial cells was inhibited by the pretreatment with ABC protein inhibitors indicating that ABC proteins are involved in nucleotide efflux from glial cells which represent the main source of cerebral extracellular purines.