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equilibrated in NADH.
Conclusion The structure of ENR shows a striking similarity with the
epimerases and short-chain alcohol dehydrogenases, in particular,
3α,20β-hydroxysteroid dehydrogenase (HSD). The similarity with HSD
extends to the conservation of a catalytically important lysine that
stabilizes the transition state and to the use of a tyrosine as a base
â with subtle modifications arising from differing requirements of the
reduction chemistry.
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[34]Triclosan: release from transdermal adhesive formulatio...
International Journal of Pharmaceutics
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[35]Triclosan: release from transdermal adhesive formulations and in
vitro permeation across human epidermal membranes Original Research
Article
International Journal of Pharmaceutics, Volume 235, Issues 1-2, 20
March 2002, Pages 229-236
Paula Chedgzoy, Gareth Winckle, Charles M. Heard
Abstract
Malarial resistance is an escalating global problem and consequently
new and more efficacious treatments to combat malaria are urgently
needed. The transdermal delivery of anti-malarials may provide an
effective alternative or adjunct to conventional regimens. Triclosan is
widely used as an anti-bacterial agent and it has recently been
demonstrated that this compound has anti-malarial properties. Its high
lipophilicity makes it a potential candidate for delivery across the
skin and this paper examines in vitro the potential for the transdermal
delivery of triclosan from âdrug-in-glueâ formulations. Model patches
were prepared using DuroTak® 2287, 2516 and 2051 acrylic polymer
adhesives loaded with 0, 30 and 50 mg per 0.785 cm^â2 triclosan and
dissolution was measured over a 12-h period. There was no apparent
difference between the adhesives at the 30 mg patch loading, but at 50
mg, the trend for increased release was 2051>2516>2287. No significant
burst effect was apparent. Patches of 50 mg per 0.785 cm^2 were then
used to determine the permeation of triclosan across heat-separated
human epidermal membranes in Franz diffusion cells, over a period of 48
h. The above general trend was reflected in the steady state flux
values obtained: 2051:16.91 μg cm^â2 h^â1 (S.E.M. 1.29), 2516:15.05 μg
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were cultivated in MM with eugenol, vanillin, or protocatechuate as the
sole carbon source, the substrates were completely converted to an
unknown substance. To identify this product, we isolated it from the
culture supernatant of mutant SK6190 grown in MM with eugenol. The
light brownish crystals we obtained exhibited a blurred melting point
of 114 to 150°C. The isolated substance was soluble in HO, methanol,
ethyl acetate, and diethylether. Its mass spectrum showed a molecular
ion at m/z 186. From these results along with the data obtained from
1H NMR (four protons) and 13C NMR (seven carbon atoms) spectra and
the infrared spectrum (OH group[s], three carbonyl bands), the
molecular formula was found to be CHO. The 1H NMR spectrum of
the substance showed an ABXZ spin system (J[AB] = 16.6 Hz, J[AX] = 8.0
Hz, J[BX] = 3.2 Hz) at 2.680, 3.207, and 5.566 ppm, with an allylic
coupling (2.1 Hz) between the X proton and the olefinic proton at 6.678
ppm. These findings established the structure fragments shown in Fig.
Fig.7.7. The 13C NMR spectrum showed seven signals at 173.1,
172.6, 163.7, 160.1, 127.0 ( [pc-E00C.gif] CH) 80.6 (CH), and 37.9
(CH) ppm. Correlations between 1H and 13C extracted from the HMQC
spectrum are shown in Fig. Fig.7.7. Because the protons at C-3
are diastereotopic, an asymmetrically substituted carbon atom must be
in the direct neighborhood. C-1 must be part of a double bond with a
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concentration or for testing when residual disinfectant levels are less
than 0.2 mg/liter in finished waters (4). This method, as well as
other HPC methods, such as membrane filtration or spread plating, may
be also used to collect data for internal purposes (nonreporting). All
the methods (1) for testing of heterotrophic bacteria require
time-consuming preparation of media and can be difficult to read.
Recently, the SimPlate total plate count method for determining the
most probable number (MPN) of microorganisms in food was developed by
IDEXX Laboratories, Westbrook, Maine (3), and approved by the
Association of Official Analytical Chemists (AOAC) International
Research Institute (2). The formulation was modified to allow for
the detection of heterotrophic bacteria in water. The test known as
SimPlate for HPC medium contains substrates that are hydrolyzed by
microbial enzymes to release 4-methylumbelliferone, which fluoresces
blue under a long-wavelength (365-nm) 6-W UV light after incubation for
48 h at 35°C. The bacteria are detected as fluorescent wells on the
SimPlate. The bacterial density of a water sample is determined by
determining the number of positive wells and by using the MPN table
provided for SimPlate. This format will allow a MPN/milliliter value up
to 738 without any dilution. The objective of this study was to compare
the performance of SimPlate and the HPC pour plate method (1) for
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