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Burgess J.L.,University of Arizona | Kurzius-Spencer M.,University of Arizona | Poplin G.S.,University of Arizona | Littau S.R.,University of Arizona | And 4 more authors.
Journal of Exposure Science and Environmental Epidemiology | Year: 2014

Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium positively associated with sputum AAT (P=0.004 and P=0.002, respectively). In analyses stratified by town, these relationships remained significant only in Ajo, with the higher arsenic exposure. Reduction in AAT may be a means by which arsenic induces respiratory disease, and selenium may protect against this adverse effect. © 2014 Nature America, Inc. Source

Peltier-Pain P.,Danish University Of Pharmaceutical Science | Singh S.,University of Kentucky | Thorson J.S.,University of Kentucky
ChemBioChem | Year: 2015

The characterization of TDP-α-D-glucose dehydrogenase (AtmS8), TDP-α-D-glucuronic acid decarboxylase (AtmS9), and TDP-4-keto-α-D-xylose 2,3-dehydratase (AtmS14), involved in Actinomadura melliaura AT2433 aminodideoxypentose biosynthesis, is reported. This study provides the first biochemical evidence that both deoxypentose and deoxyhexose biosynthetic pathways share common strategies for sugar 2,3-dehydration/reduction and implicates the sugar nucleotide base specificity of AtmS14 as a potential mechanism for sugar nucleotide commitment to secondary metabolism. In addition, a re-evaluation of the AtmS9 homologue involved in calicheamicin aminodeoxypentose biosynthesis (CalS9) reveals that CalS9 catalyzes UDP-4-keto-α-D-xylose as the predominant product, rather than UDP-α-D-xylose as previously reported. Cumulatively, this work provides additional fundamental insights regarding the biosynthesis of novel pentoses attached to complex bacterial secondary metabolites. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Jamt R.E.G.,University of Oslo | Gjelstad A.,University of Oslo | Eibak L.E.E.,University of Oslo | Oiestad E.L.,Norwegian Institute of Public Health | And 4 more authors.
Journal of Chromatography A | Year: 2012

For the first time, electromembrane extraction (EME) of six basic drugs of abuse from undiluted whole blood and post mortem blood in a totally stagnant system is reported. Cathinone, methamphetamine, 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-methamphet-amine (MDMA), ketamine and 2,5-dimethoxy-4-iodoamphetamine (DOI) were extracted from the whole blood sample, through a supported liquid membrane (SLM) consisting of 1-ethyl-2-nitrobenzene (ENB) immobilized in the pores of a hollow fiber, and into an aqueous acceptor solution inside the lumen of the hollow fiber. The SLM acts as a barrier with efficient exclusion of all macromolecules and acidic substances in the sample. Due to the application of the electrical field, only the cationic compounds of interest are extracted efficiently across the membrane, thus providing extremely clean extracts for analysis with liquid chromatography-mass spectrometry, LC-MS. Recoveries in the range 10-30% were obtained from 80μl whole blood within 5min extraction time and an applied voltage of 15V across the SLM. The optimized technique was tested on real forensic whole blood samples taken from three forensic autopsy cases and on five forensic whole blood samples from living persons. The results were in agreement with the analysis using standard sample preparation methods (liquid-liquid extraction) performed on the same samples by Norwegian Institute of Public Health (NIPH), Division of Forensic Toxicology and Drug Abuse Research. Evaluation data were acceptable, with limit of detections (LODs) in the range 40-2610pg/mL, well below concentrations associated with drug abuse; linearites in the range between 10 and 250ng/mL with r 2 values above 0.9939, and with repeatability (RSD) of 7-32%. © 2011 Elsevier B.V. Source

Tobgay T.,JDW NR Hospital | Tandin,JDW NR Hospital | Rai M.,Essential Drugs Programme | Rai M.,DBL Institute for Health Research and Development | And 3 more authors.
Asian Biomedicine | Year: 2010

Background: The emergence of antibiotic resistance is a complex problem contributed by the interplay of various parties such as prescribers, patients or health settings. In particular, prescribers play a vital role in the use of antibiotics both in rational prescribing of drugs and influencing patients on the appropriate use. Objectives: Determine the appropriateness of the higher generation antibiotics (cephalosporin and flouroquonolone groups) in the out-patient setting of Bhutan hospitals. Materials and method: A cross-sectional study was conducted in three referral hospitals of Bhutan where the prescriptions were collected from the pharmacy. All prescriptions containing higher generation antibiotics were selected based on the appropriateness using a modified Medication Appropriateness Index. Three hundred thirty three prescriptions containing higher generation antibiotics were analyzed. Results: The use of antibiotics was common with 37.1% of the prescriptions containing antibiotics out of which 14% were higher generation antibiotics. When assessed on the appropriateness of the prescription, 55.9% of the prescriptions containing higher generation antibiotics were prescribed inappropriately. In addition, only 47.1% of the prescriptions had appropriate indications for higher generation antibiotics. Conclusion: There is a widespread inappropriate use of higher generation antibiotics in Bhutan. Source

Roberts G.W.,Repatriation General Hospital | Quinn S.,Flinders University | Druskeit T.,Danish University Of Pharmaceutical Science | Helboe T.,Danish University Of Pharmaceutical Science | And 2 more authors.
Journal of Pharmacy Practice and Research | Year: 2013

Background: Guidelines recommend re-initiating postoperative warfarin at the previous maintenance dose. This results in prolonged re-establishment of a therapeutic international normalised ratio (INR). Modelling warfarin initiation and subsequent INR response using previously published data indicated that re-initiation with twice the maintenance dose for 3 days may provide a rapid alternative. Aim: To compare the time to a stable therapeutic INR for conventional maintenance dose re-initiation of warfarin with a loading dose strategy. Method: Warfarin maintenance doses were adjusted by using the standardised maintenance dose - a theoretical dose resulting in an INR of 2.5. The test group was re-initiated on warfarin doses twice their standardised maintenance dose on Days 1, 2 and 3 and on Day 4 reverted to their maintenance dose. The guideline group was re-initiated on warfarin doses equivalent to their standardised maintenance dose on these days. Results: The test group (n = 17) achieved a therapeutic INR more rapidly than the guideline group (n = 23; p < 0.001) with median times to therapeutic INR of 3 and 6 days respectively. After 3 doses the test group INR on Day 4 was in the therapeutic range (2.1±0.4) and signifi cantly higher than the guideline group (1.7±0.5; p = 0.002). No patient in the test group experienced an elevated INR (maximum INR 3.3). Conclusion: INR response to the warfarin re-initiation dose was dependent on the magnitude of the induction dose relative to the maintenance dose. The loading dose strategy achieved a stable therapeutic INR more rapidly than conventional practice. Prospective investigation in surgical patients is needed to confi rm its clinical applicability. Source

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