Mani, Augustine and the vision of God

Contribution to ‘Augustine and Manichaean Christianity’, the First South African Symposium on Augustine of Hippo, University of Pretoria, 24−26 April 2012. Prof. Dr Iain Gardner is participating as research fellow of Prof. Dr Hans van Oort, Professor Extraordinarius in the Department of Church History and Polity of the Faculty of Theology at the University of Pretoria, Pretoria, South Africa.Scan this QR code with your smart phone or mobile device to read online.The recovery of the text of the Manichaean daily prayers provides an opportunity to consider how their recitation and practice may have influenced the young Augustine. It is argued that the prayers focused the mental and indeed physical gaze of the believer on the manifestation of God in this present reality, and through that upon the transcendent eternal world of future hope. If one accepts that Augustine as a Manichaean catechumen would have partaken in this most basic of the community’s religious duties then one must consider what effect this could have had on the development of his own striking and influential teachings about the vision of God. The article discusses evident allusions to this Manichaean practice in Augustine’s writings, and suggests that its influence continued through his later life despite his disavowal of his former faith. In particular, attention is drawn to similarities between the Manichaean ‘new aeon’ and the ‘heaven of heaven’ in Augustine’s writings, where the pure of heart can look forward to unmediated contemplation of God.http://www.hts.org.zaam2013mn201

Posterior Shoulder Dislocation due to an Unusual Injury Mechanism

Peer reviewedPublisher PD

The Implants used for Intramedullary Fixation of Distal Fibula Fractures : A Review of Literature

Peer reviewedPostprin

Novel in vitro and mathematical models for the prediction of chemical toxicity

The focus of much scientific and medical research is directed towards understanding the disease process and defining therapeutic intervention strategies. Whilst the scientific basis of drug safety has received relatively little attention, despite the fact that adverse drug reactions (ADRs) are a major health concern and a serious impediment to development of new medicines. Toxicity issues account for ~21% drug attrition during drug development and safety testing strategies require considerable animal use. Mechanistic relationships between drug plasma levels and molecular/cellular events that culminate in whole organ toxicity underpins development of novel safety assessment strategies. Current in vitro test systems are poorly predictive of toxicity of chemicals entering the systemic circulation, particularly to the liver. Such systems fall short because of 1) the physiological gap between cells currently used & human hepatocytes existing in their native state, 2) the lack of physiological integration with other cells/systems within organs, required to amplify the initial toxicological lesion into overt toxicity, 3) the inability to assess how low level cell damage induced by chemicals may develop into overt organ toxicity in a minority of patients, 4) lack of consideration of systemic effects. Reproduction of centrilobular & periportal hepatocyte phenotypes in in vitro culture is crucial for sensitive detection of cellular stress. Hepatocyte metabolism/phenotype is dependent on cell position along the liver lobule, with corresponding differences in exposure to substrate, oxygen & hormone gradients. Application of bioartificial liver (BAL) technology can encompass in vitro predictive toxicity testing with enhanced sensitivity and improved mechanistic understanding. Combining this technology with mechanistic mathematical models describing intracellular metabolism, fluid-­‐flow, substrate, hormone and nutrient distribution provides the opportunity to design the BAL specifically to mimic the in vivo scenario. Such mathematical models enable theoretical hypothesis testing, will inform the design of in vitro experiments, and will enable both refinement and reduction of in vivo animal trials. In this way, development of novel mathematical modelling tools will help to focus and direct in vitro and in vivo research, and can be used as a framework for other areas of drug safety science

Topical ocular pharmacokinetics and bioavailability for a cocktail of atenolol, timolol and betaxolol in rabbits

Ocular bioavailability after eye drops administration is an important, but rarely determined, pharmacokinetic parameter. In this study, we measured the pharmacokinetics of a cocktail of three beta blockers after their topical administration into the albino rabbit eye. Samples from aqueous humour were analysed with LC-MS/MS. The pharmacokinetic parameters were estimated using compartmental and non-compartmental analyses. The ocular bioavailability was covering broad range of values: atenolol (0.07 %), timolol (1.22%, 1.51%) and betaxolol (3.82%, 4.31%). Absolute ocular bioavailability presented a positive trend with lipophilicity and the values showed approximately 60-fold range. The generated data enhances our understanding for ocular pharmacokinetics of drugs and may be utilized in pharmacokinetic model building in ophthalmic drug development.Peer reviewe

Ocular intracameral pharmacokinetics for a cocktail of timolol, betaxolol and atenolol in rabbits

The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three β-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC–MS/MS to determine drug concentrations. Pharmacokinetic parameters were obtained using a compartmental fitting approach, and the estimated clearance, volume of distribution, and half-life values were the following: atenolol (6.44 μL/min, 687 μL, and 73.87 min), timolol (19.30 μL/min, 937 μL, and 33.64 min), and betaxolol (32.20 μL/min, 1421 μL, and 30.58 min). Increased compound lipophilicity (atenolol < timolol < betaxolol) resulted in higher clearance and volume of distributions in the aqueous humor. Clearance of timolol and betaxolol is about 10 times higher than the aqueous humor outflow, demonstrating the importance of other elimination routes (e.g., uptake to iris and ciliary body and subsequent elimination via blood flow)

Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail : Tissue exposures in the rabbit eye

Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUCiris-ciliary body than AUCaqueous humor, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.Peer reviewe

Benefits Transfer and the Aquatic Environment: An Investigation into the Context of Fish Passage Improvement

We present findings from a choice experiment investigating improvements in the aquatic environment from mitigation of barriers to fish passage. Implemented at a local and national level, results reveal positive preferences for increased numbers of fish species as well as fish abundance. In addition, we examine if in this case the willingness to pay estimates are suitable for direct transfer between national and local settings. For both samples, we consider the extent to which stated attribute non-attendance impacts estimates of willingness to pay and the potential ability of researchers to transfer values between contexts. Implications of the use of benefit transfer within this policy context are discussed in light of our findings

Adherence to prescribed medications in patients with heart failure – insights from liquid chromatography-tandem mass spectrometry-based urine analysis

Aims: None of the existing studies on adherence have directly measured levels of medications (or their metabolites) in patients with heart failure. Methods and Results: We used liquid chromatography-tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4 to 6 weeks after hospitalisation with heart failure. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only 7 out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed heart failure drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients. Conclusion: Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in 1 of 5 patients evaluated 4 to 6 weeks after hospitalisation with heart failure