183 research outputs found
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
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
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
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
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