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Half-lives
Kinds of Half-lives Selected AbstractsMeasurement of dissociation rate of biomolecular complexes using CEELECTROPHORESIS, Issue 3 2009Peilin Yang Abstract Fluorescence anisotropy (FA), non-equilibrium CE of equilibrium mixtures (NECEEM) and high-speed CE were evaluated for measuring dissociation kinetics of peptide,protein binding systems. Fyn-SH3-SH2, a protein construct consisting of the src homology 2 (SH2) and 3 (SH3) domain of the protein Fyn, and a fluorescein-labeled phosphopeptide were used as a model system. All three methods gave comparable half-life of,53,s for Fyn-SH3-SH2:peptide complex. Achieving satisfactory results by NECEEM required columns over 30,cm long. When using Fyn-SH2-SH3 tagged with glutathione S -transferase (GST) as the binding protein, both FA and NECEEM assays gave evidence of two complexes forming with the peptide, yet neither method allowed accurate measurement of dissociation rates for both complexes because of a lack of resolution. High-speed CE, with a 7,s separation time, enabled separation of both complexes and allowed determination of dissociation rate of both complexes independently. The two complexes had half-lives of 22.0±2.7 and 58.8±6.1,s, respectively. Concentration studies revealed that the GST-Fyn-SH3-SH2 protein formed a dimer so that complexes had binding ratios of 2:1 (protein-to-peptide ratio) and 2:2. Our results demonstrate that although all methods are suitable for 1:1 binding systems, high-speed CE is unique in allowing multiple complexes to be resolved simultaneously. This property allows determination of binding kinetics of complicated systems and makes the technique useful for discovering novel affinity interactions. [source] Choosing natural enemies for conservation biological control: use of the prey detectability half-life to rank key predators of Colorado potato beetleENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2010Matthew H. Greenstone Abstract Determining relative strengths of trophic links is critical for ranking predators for conservation biological control. Molecular gut-content analysis enables ranking by incidence of prey remains in the gut, but differential digestive rates bias such rankings toward predators with slower rates. This bias can be reduced by indexing each predator's half-life to that of the middle-most half-life in a predator complex. We demonstrate this with data from key species in the predator complex of Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), comprising adults and immatures of four taxonomically diverse species. These animals display order-of-magnitude variation in detectability half-life for the cytochrome oxidase I DNA sequence of a single CPB egg: from 7.0 h in larval Coleomegilla maculata (DeGeer) (Coleoptera: Coccinellidae) to 84.4 h in nymphal Perillus bioculatus (Fabricius) (Hemiptera: Pentatomidae). The raw species-specific incidence of L. decemlineata DNA in the guts of 351 field-collected predators ranged from 11 to 95%, ranking them as follows: C. maculata adults < Lebia grandis Hentz (Coleoptera: Carabidae) adults < Podisus maculiventris (Say) (Hemiptera: Pentatomidae) adults < P. maculiventris nymphs < P. bioculatus adults < P. bioculatus nymphs. Half-life adjustment reorders the rankings: C. maculata adults < P. bioculatus adults < P. bioculatus nymphs < P. maculiventris nymphs < L. grandis adults < P. maculiventris adults. These changes in status demonstrate the value of half-life-adjusted molecular gut-content data for ranking predators. This is the first study to measure prey detectability half-lives for the key arthropod predators of a major insect pest, and to use them to evaluate the relative impact of all adults and immatures in this predator complex. [source] Environmental factors affecting the levels of legacy pesticides in the airshed of Delaware and Chesapeake Bays, USAENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2010Anubha Goel Abstract Organochlorine insecticides and their degradation products contribute to toxicity in Chesapeake Bay, USA, sediments and affect the reproductive health of avian species in the region; however, little is known of atmospheric sources or temporal trends in concentrations of these chemicals. Weekly air (n,=,265) and daily rain samples (n,=,494) were collected over 2000 to 2003 from three locations in the Delmarva Peninsula, USA. Pesticides were consistently present in the gas phase with infrequent detection in the particle phase. Hexachlorocyclohexanes (HCHs) and cis - and trans -chlordane were detected most frequently (95,100%), and cis - and trans -nonachlor, oxychlordane, heptachlor, heptachlor epoxide, dieldrin, and 1-chloro-4-[2,2-dichloro-1-(4-chlorophenyl)ethenyl]benzene (4,4,-DDE) were also detected frequently. The highest mean air concentrations were for dieldrin (60,84,pg/m3), ,-HCH (37,83,pg/m3), and 4,4,-DDE (16,80,pg/m3). Multiple regression analyses of air concentrations with temperature and wind conditions using modified Clausius-Clapeyron equations explained only 30 to 60% of the variability in concentration for most chemicals. Comparison of the air concentrations and enthalpy of air,surface exchange values at the three sites indicate sources of chlordanes and ,-HCH sources are primarily from long-range transport. However, examination of chlordane isomer ratios indicates some local and regional contributions, and ,-HCH, 4,4,-DDE, dieldrin, heptachlor, heptachlor epoxide, and oxychlordane also have local or regional sources, possibly from contaminated soils. Median rain sample volumes of 1 to 3 L led to infrequent detections in rain; however, average measured concentrations were 2 to 10 times higher than in the Great Lakes. Dissipation half-lives in air were well below 10 years for all chemicals and below published values for the Great Lakes except dieldrin, which did not decline during the sample period. Environ. Toxicol. Chem. 2010;29:1893,1906. © 2010 SETAC [source] Factors affecting the degradation of pharmaceuticals in agricultural soils,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2009Sara C. Monteiro Abstract Pharmaceuticals may be released to the soil environment through the application of biosolids to land. To understand those factors affecting the persistence of pharmaceuticals in the soil environment, the present study was performed to assess the effects of soil type, the presence of biosolids, and the impact of chemical mixture interactions on the degradation of three pharmaceuticals: naproxen, carbamazepine, and fluoxetine. Single-compound studies showed that naproxen degraded in a range of soils with half-lives ranging from 3.1 to 6.9 d and in biosolids with a half-life of 10.2 d. No relationships were observed between degradation rate and soil physicochemical properties and soil bioactivity. For naproxen, addition of biosolids to soils reduced the degradation rate observed in the soil-only studies, with half-lives in the soil-biosolid systems ranging from 3.9 to 15.1 d. Carbamazepine and fluoxetine were found to be persistent in soils, biosolids, and soil-biosolid mixtures. When degradation was assessed using a mixture of the three study compounds and the sulfonamide antibiotic sulfamethazine, the degradation behavior of fluoxetine and carbamazepine was similar to that observed in the single compound studies (i.e., no degradation). However, the degradation rate of naproxen in soils, biosolids, and soil-biosolid systems spiked with the mixture was significantly slower than in the single-compound studies. As degradation studies for risk assessment purposes are performed using single substances in soil-only studies, it is possible that current risk assessment procedures will underestimate environmental impacts. Further work is therefore warranted on a larger range of substances, soils, biosolid types, and chemical mixtures to better understand the fate of pharmaceuticals in terrestrial systems. [source] Disposition of perfluorinated acid isomers in sprague-dawley rats; Part 1: Single doseENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2009Jonathan P. Benskin Abstract Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 ,g/kg body weight perfluorooctane sulfonate (C8F17SO3,, PFOS), perfluorooctanoic acid (C7F15CO2H, PFOA), and perfluorononanoic acid (C8F17CO2H, PFNA) and 30 ,g/kg body weight perfluorohexane sulfonate (C6F13SO3,, PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m -PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure,property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples. [source] Disposition of perfluorinated acid isomers in sprague-dawley rats; Part 2: Subchronic doseENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2009Amila O. De Silva Abstract Two major industrial synthetic pathways have been used to produce perfluorinated acids (PFAs) or their precursors: Telomerization and electrochemical fluorination (ECF). Products of telomer and ECF origin can be distinguished by structural isomer profiles. A mixture of linear and branched perfluoroalkyl isomers is associated with ECF. Telomer products characteristically consist of a single perfluoroalkyl geometry, typically linear. In biota, it is unclear if the isomer profile is conserved relative to the exposure medium and hence whether PFA isomer profiles in organisms are useful for distinguishing environmental PFA sources. A companion study suggested isomer-specific disposition following a single oral gavage exposure to rats. To confirm these findings under a more realistic subchronic feeding scenario, male and female rats were administered PFA isomers by diet for 12 weeks, followed by a 12-week depuration period. The diet contained 500 ng/g each of ECF perfluorooctanoate (PFOA, ,80% n -PFOA), ECF perfluorooctane sulfonate (PFOS, ,70% n -PFOS), and linear and isopropyl perfluorononanoate (n - and iso -PFNA). Blood sampling during the exposure phase revealed preferential accumulation of n -PFOA and n -PFNA compared to most branched isomers. Female rats depurated all isomers faster than males. Both sexes eliminated most branched perfluorocarboxylate isomers more rapidly than the n -isomer. Elimination rates of the major branched PFOS isomers were not statistically different from n -PFOS. Two minor isomers of ECF PFOA and one branched PFOS isomer had longer elimination half-lives than the n-isomers. Although extrapolation of these pharmacokinetics trends in rats to humans and wildlife requires careful consideration of dosage level and species-specific physiology, cumulative evidence suggests that perfluorocarboxylate isomer profiles in biota may not be suitable for quantifying the relative contributions of telomer and ECF sources. [source] Enantiomeric composition of chiral polychlorinated biphenyl atropisomers in dated sediment coresENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2007Charles S. Wong Abstract ,Enantiomer fractions (EFs) of seven chiral poly chlorinated biphenyls (PCBs) were measured in dated sediment cores of Lake Hartwell (SC, USA) and Lake Ontario (USA) to detect, quantify, and gain insight regarding microbial reductive dechlorination of PCBs in lake sediments with high and low concentrations, respectively. Lake Hartwell sediments had high total PCBs (5,60 ,g/g), with significantly nonracemic EFs that generally were consistent with those from previous laboratory microcosm reductive dechlorination experiments using sediments from these sites. Thus, stereoselective reductive dechlorination had occurred in situ, including at total PCB concentrations of less than the threshold of approximately 30 to 80 ,g/g suggested as being necessary for reductive dechlorination. Enantiomer fractions of PCBs 91, 95, 132, and 136 in Lake Hartwell cores were significantly correlated both with concentrations of those individual congeners and with total PCB concentration for some sites. This result indicates that enantioselective microbial dechlorination activity increases with higher concentrations within sediments for these congeners. Enantiomer composition reversed with depth for PCBs 91, 132, and 176, suggesting that multiple microbial populations may be present within the same core that are enantioselectively dechlorinating PCBs. Such observations indicate that concentration and time are not the only factors affecting biotransformation, complicating prediction of enantioselectivity. Comparison of EFs with dates suggested biotransformation half-lives of approximately 30 years, which is on the same time scale as sequestration by burial. In contrast, Lake Ontario sediments (maximum total PCBs, 400 ng/g) had racemic or near-racemic amounts of most congeners throughout the core profile, which is consistent with achiral indicators suggesting no microbial biotransformation within Lake Ontario sediments. Thresholds for reductive dechlorination may exist, but they would be at concentrations of less than 30 to 80 ,g/g. [source] Dietary accumulation of hexabromocyclododecane diastereoisomers in juvenile rainbow trout (Oncorhynchus mykiss) I: Bioaccumulation parameters and evidence of bioisomerizationENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2006Kerri Law Abstract Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to three diastereoisomers (,, ,, ,) of hexabromocyclododecane (C12H18Br6) via their diet for 56 d followed by 112 d of untreated food to examine bioaccumulation parameters and test the hypothesis of in vivo bioisomerization. Four groups of 70 fish were used in the study. Three groups were exposed to food fortified with known concentrations of an individual diastereoisomer, while a fourth group were fed unfortified food. Bioaccumulation of the ,-diastereoisomer was linear during the uptake phase, while the ,- and ,-diastereoisomers were found to increase exponentially with respective doubling times of 8.2 and 17.1 d. Both the ,- and the ,-diastereoisomers followed a first-order depuration kinetics with calculated half-lives of 157 ± 71 and 144 ± 60 d (±1 × standard error), respectively. The biomagnification factor (BMF) for the ,-diastereoisomer (BMF = 9.2) was two times greater than the ,-diastereoisomer (BMF = 4.3); the large BMF for the ,-diastereoisomer is consistent with this diastereoisomer dominating higher-trophic-level organisms. Although the BMF of the ,-diastereoisomer suggests that it will biomagnify, it is rarely detected in environmental samples because it is present in small quantities in commercial mixtures. Results from these studies also provide evidence of bioisomerization of the ,- and ,-diastereoisomers. Most importantly, the ,-diastereoisomer that was recalcitrant to bioisomerization by juvenile rainbow trout in this study and known to be the dominant diastereosiomer in fish was bioformed from both the ,- and the ,-diastereoisomers. To our knowledge, this is the first report of bioisomerization of a halogenated organic pollutant in biota. [source] Dissipation kinetics and mobility of chlortetracycline, tylosin, and monensin in an agricultural soil in Northumberland County, Ontario, CanadaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2006Jules C. Carlson Abstract A robust high-throughput method was refined to extract three growth-promoting antibiotics, tylosin (TYL), chlortetracycline (CTC), and monensin (MON), from soil. Analysis was performed by electrospray liquid chromatography tandem mass spectrometry. Soil dissipation rate studies were performed in a farm field soil for antibiotics applied with and without manure. Tylosin, CTC, and MON followed first-order dissipation kinetics with half-lives of 4.5, 24, and 3.3 d, respectively, with the addition of manure and 6.1, 21, and 3.8 d, respectively, without manure. Manure application significantly increased TYL dissipation rate, perhaps because of the introduced microbial flora, but had no significant effect on CTC or MON. Monensin dissipation half-life was found to be much shorter in the field study than in a controlled laboratory study, perhaps because of differences in microbial communities. The antimicrobials were not highly mobile. Chlortetracycline was the only antibiotic detected at 25 to 35 cm depth and only up to 2% of the initial concentration in a sandy loam soil. These antibiotics are therefore expected to degrade primarily in agricultural soils before moving to greater depths or to groundwater in significant concentrations in most agricultural systems. [source] A new biodegradation prediction model specific to petroleum hydrocarbonsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2005Philip Howard Abstract A new predictive model for determining quantitative primary biodegradation half-lives of individual petroleum hydrocarbons has been developed. This model uses a fragment-based approach similar to that of several other biodegradation models, such as those within the Biodegradation Probability Program (BIOWIN) estimation program. In the present study, a half-life in days is estimated using multiple linear regression against counts of 31 distinct molecular fragments. The model was developed using a data set consisting of 175 compounds with environmentally relevant experimental data that was divided into training and validation sets. The original fragments from the Ministry of International Trade and Industry BIOWIN model were used initially as structural descriptors and additional fragments were then added to better describe the ring systems found in petroleum hydrocarbons and to adjust for nonlinearity within the experimental data. The training and validation sets had r2 values of 0.91 and 0.81, respectively. [source] Photodegradation of common environmental pharmaceuticals and estrogens in river waterENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2005Angela Yu-Chen Lin Abstract Photodegradation rates of five pharmaceuticals (gemfibrozil, ibuprofen, ketoprofen, naproxen, and propranolol) and of four estrogens (estriol, estrone [E1], 17,-estradiol [E2], and 17,-ethinylestradiol [EE2]), which are common contaminants in the aquatic environment, were measured in both purified and river water at environmentally relevant concentrations (1,2 ,g/L) and different oxygen concentrations. Solutions were irradiated with a xenon arc lamp (765 W/m2; 290 nm < , < 700 nm) and analyzed using a high-performance liquid chromatography-tandem mass spectrometry method with electrospray ionization for pharmaceuticals and atmospheric pressure photoionization for estrogens. In river water, half-lives were 4.1 h for ketoprofen, 1.1 min for propranolol, 1.4 h for naproxen, 2 to 3 h for estrogens, and 15 h for gemfibrozil and ibuprofen. In air-saturated purified water, rates generally were slower except for that of ketoprofen, which reacted with a half-life of 2.5 min. Naproxen, propranolol, and E1 reacted with half-lives of 1.9, 4.4, and 4.7 h, respectively. The EE2, estriol, E2, gemfibrozil, and ibuprofen reacted with half-lives of 28.4, 38.2, 41.7, 91.4, and 205 h, respectively. The presence of oxygen doubled the direct photolysis rates of naproxen and propranolol. In nonautoclaved river water, 80% of E2 rapidly biotransformed to E1 within less than 20 min, whereas all other compounds remained stable over 22 h. [source] Toxicokinetics of sediment-associated polybrominated diphenylethers (flame retardants) in benthic invertebrates (Lumbriculus variegatus, oligochaeta)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2004Matti T. Leppänen Abstract Polybrominated diphenylethers (PBDEs) are ubiquitous environmental contaminants showing rapid temporal increase in some sample types. The compounds are known to biomagnify in aquatic food webs and are assumed to archive into sediments and soils. Currently, no direct evidence indicates whether sediment-associated PBDEs are available for biota. The aim of the present study was to explore the uptake and elimination of two common congeners (47 and 99) in sediment-inhabiting invertebrates to shed light on possible bioavailability of sediment-associated PBDEs. Two clean lake sediments were spiked with environmentally relevant concentrations of 14C-labeled tetra- and pentabromo diphenylether, and oligochaetes (Lumbriculus variegatus) were exposed for three or four weeks to allow kinetic accumulation calculations. Subsequent depuration tests were performed after three weeks of exposure to obtain depuration rates. Both congeners were clearly bioavailable, and only slight differences in steady-state tissue concentrations were found between the four sediment-ingesting oligochaete treatments (biota sediment accumulation factors [BSAFs], 3.0,3.7). The tetrabromo diphenylether-exposed oligochaetes that did not ingest sediment had clearly lower influx rates (0.1 vs 1,3 nmol h -1) than sediment-ingesting worms. Also, the estimated BSAF (1.8) was statistically different from that of the sediment-ingesting oligochaetes. These findings support the significance of feeding behavior in bioaccumulation of very hydrophobic organic contaminants. Depuration of both congeners was biphasic, indicating two kinetically different compartments in L. variegatus. Compartment A made up 73 to 92% of total radioactivity in tissues and had relatively fast depuration rates (half-lives, 10.5,47.5 h); the smaller compartment B had very slow depuration rates. No significant biotransformation of PBDEs was evident. The present study clearly demonstrates that the sediment-associated PBDEs, like other hydrophobic organic contaminants of environmental concern, are not totally sequestered from sediment-inhabiting oligochaetes and are subject to trophic transfer. [source] The potential for estradiol and ethinylestradiol degradation in english riversENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2002Monika D. Jürgens Abstract Water samples were collected in spring, summer, and winter from English rivers in urban/industrial (River Aire and River Calder, Yorkshire, UK) and rural environments (River Thames, Oxfordshire, UK) to study the biodegradation potential of the key steroid estrogen 17,-estradiol (E2) and its synthetic derivate ethinylestradiol (EE2). Microorganisms in the river water samples were capable of transforming E2 to estrone (E1) with half-lives of 0.2 to 9 d when incubated at 20°C. The E1 was then further degraded at similar rates. The most rapid biodegradation rates were associated with the downstream summer samples of the River Aire and River Calder. E2 degradation rates were similar for spiking concentrations throughout the range of 20 ng/L to 500 ,g/L. Microbial cleavage of the steroid ring system was demonstrated by release of radiolabeled CO2 from the aromatic ring of E2 (position 4). When E2 was degraded, the loss of estrogenicity, measured by the yeast estrogen screen (YES) assay, closely followed the loss of the parent molecule. Thus, apart from the transient formation of E1, the degradation of E2 does not form other significantly estrogenic intermediates. The E2 could also be degraded when incubated with anaerobic bed sediments. Compared to E2, EE2 was much more resistant to biodegradation, but both E2 and EE2 were susceptible to photodegradation, with half-lives in the order of 10 d under ideal conditions. [source] Potential for octylphenol to biodegrade in some english riversENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2000Andrew C. Johnson Abstract To study octylphenol biodegradation, samples of river water and sediments were taken from the Aire and Calderr vers in the United Kingdom, running through urban/industrial areas, as well as the Thames River running through a more rural area. Using laboratory microcosms, half-lives of 7 to 50 d were obtained for the water samples, with most curves fitting a zero-order reaction. The Calder River was sampled at four separate points along a 45-km length, encompassing rural to increasingly urban/industrial reaches. Little degradation was observed in the sample from the upland/rural reach, while half-lives of 8 to 13 d were seen in the more urban/industrial reaches. Mineralization of the phenyl ring, detected by evolution of 14CO2 from ring-labeled octylphenol, was only observed in water from the Calder River sample. Degradation rate was similar for a range of concentrations from 0.3 to 100 ,,g/L when tested with river water from the Thames River. No degradation was observed over 83 d when bed sediments were spiked with octylphenol and incubated under anaerobic conditions. [source] Use of a bench-top photochemical reactor and solid-phase microextraction to measure semivolatile organic compound-hydroxyl radical rate constantsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2000Mary Jo Bernhard Abstract It is increasingly important to be able to measure semivolatile organic compound-hydroxyl (SOC-OH) radical rate constants and estimate semivolatile organic compounds' (SOCs) atmospheric half-lives because of potential for atmospheric long-range transport. We have used a bench-top photochemical reactor, along with solid-phase microextraction (SPME) and ethyl nitrite, to successfully measure the rate constants of naphthalene, linalool, biphenyl, and phenanthrene with hydroxyl (OH) radical. Biphenyl and phenanthrene underwent wall loss in the reactor. The wall loss rates were determined and were used to correct the measured gas-phase rate constants. The reaction rate constants for naphthalene, linalool, biphenyl, and phenanthrene with OH radical, in our bench-top system at 295 ± 3 K, were determined to be 2.73 ± 0.37 × 10,11, 1.93 ± 0.24 × 10,10, 7.44 ± 1.9 × 10,12, 1.73 ± 0.21 × 10,11 (cm3/molecule/s), respectively, and were in excellent agreement with previous studies and model predictions. Based on the range of experimental and predicted rate constants for these reactants and an estimated average OH concentration in the atmosphere, the atmospheric half-lives of these SOCs are significantly less than 2 d. This indicates that the global presence of these compounds in the atmosphere is primarily due to regional sources and not to atmospheric long-range transport. This study shows that bench-top reactors, combined with corrections for reactant wall loss and simplified analytical tools (such as solid-phase microextraction), can be used to measure SOC-OH rate constants. [source] Reversible transition between active and dormant microbial states in soilFEMS MICROBIOLOGY ECOLOGY, Issue 2-3 2001John Stenström Abstract The rate of respiration obtained in the substrate-induced respiration (SIR) method can be divided into the respiration rate of growing (r) and non-growing (K) microorganisms. The fraction of r is generally small (5,20%) in soils with no recent addition of substrates, but can be 100% in soils with high substrate availability. This suggests that substrate availability determines the proportion of biomass between these groups, and implies that transitions between them can take place reversibly. These hypotheses were tested by adding three different amounts of glucose which induced first-order, zero-order, and growth-associated respiration kinetics to three soils at four pre-incubation times (4, 12, 27, and 46 days) before the SIR measurement. An abiotic flush of CO2 in the SIR measurement was detected and corrected for before data analysis. Accumulated CO2 -C over 4 days after glucose addition, corrected for the respiration in unamended controls, corresponded to 41,50% mineralization of the glucose-C, and the relative amount mineralized by each soil was independent of the glucose amount added. The high glucose concentration gave an increased SIR, which reverted to the initial value within 27,46 days. In a specific sample, the maximum respiration rate induced during the pre-incubation, and the amount of organisms transformed from the K to the r state, as quantified in respiration rate units in the SIR measurement, were identical to each other, and these parameters were also highly correlated to the initial glucose concentration. The K,r transition was very fast, probably concurrent with the instantaneous increase in the respiration rate obtained by the glucose amendment. Thereafter, a slow first-order back-transition from the r to the K state ensued, with half-lives of 12, 23, and 70 days for the three soils. The results suggest the existence of community-level controls by which growth within or of the whole biomass is inhibited until it has been completely transformed into the r state. The data also suggest that the microbial specific activity is not related to the availability of exogenous substrate in a continuous fashion, rather it responds as a sharp transition between dormant and fully active. Furthermore, the inherent physiological state of the microbial biomass is strongly related to its history. It is proposed that the normal dynamics of the soil microbial biomass is an oscillation between active and dormant physiological states, while significant growth occurs only at substantial substrate amendment. [source] Dextropropoxyphene withdrawal from a French university hospital: impact on analgesic drug consumptionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2009Sabine Gaubert Abstract Dextropropoxyphene is a weak opioid analgesic, widely used as a step 2 analgesic (according to WHO classification) in combination with peripheral analgesics, mainly paracetamol. Recent data have underlined its poor analgesic efficacy (in comparison with paracetamol), risks of serious adverse drug reactions (i.e. hepatic reactions, hallucinations, abuse, withdrawal symptoms, hypoglycaemia), possible lethality after overdose, its risk of accumulation in patients with renal failure or in elderly people and some pharmacokinetic insufficiencies (i.e. different half-lives for dextropropoxyphene and paracetamol). Taking into account these data, the drug committee of the Toulouse University Hospital (France) decided to withdraw dextropropoxyphene from the hospital formulary since 1 June 2005. The aim of our study was to investigate the consequences of this withdrawal by comparing use of analgesic drugs in Toulouse University Hospital before (2004) and after (2006) dextropropoxyphene withdrawal (using defined daily dose for 1000 hospitalization-days as the unit measure). Before withdrawal, dextropropoxyphene (in combination with paracetamol) was the second most used analgesic drug after paracetamol alone. After dextropropoxyphene withdrawal, total consumption of analgesic drugs decreased by 4.6% (2006 vs. 2004). There was a 28% decrease in consumption of step 2 analgesics [with an increase in oral tramadol and a slight decrease in codeine (in combination with paracetamol)]. During the same period, step 1 analgesic consumption increased by 11% (mainly paracetamol) and that of step 3 analgesics slightly decreased (,8%). These results show that dextropropoxyphene withdrawal was not associated with a marked switch in prescriptions towards other analgesic drugs. This paper underlines the interest of a hospital-based drug committee to promote rational drug use. Finally, the present data allow us to discuss putative misuse of dextropropoxyphene. [source] Home management of haemophiliaHAEMOPHILIA, Issue 2 2004J. M. Teitel Summary., The demonstrated benefits of home care for haemophilia include improved quality of life, less pain and disability, fewer hospitalizations, and less time lost from work or school. Although reduced mortality has not been demonstrated, the substantial increase in longevity since the early 1980s correlates with the introduction of home treatment and prophylaxis programmes. These programmes must be designed and monitored by haemophilia treatment centres (HTC), which are staffed with professionals with broad and complementary expertise in the disease and its complications. In return, patients and their families must be willing to accept the reciprocal responsibilities that come from administering blood products or their recombinant equivalents at home. Patients with inhibitors to factors VIII or IX pose special challenges, but these complications do not obviate participation in home care programmes. Home care was an essential prerequisite to the introduction of effective prophylactic factor replacement therapy. Prophylaxis offers significant improvements in quality of life, but requires a substantial commitment. The use of implantable venous access devices can eliminate some of the difficulty and discomfort of peripheral venous access in small children, but brings additional risks. The future holds the promise of factor concentrates for home use that have longer half-lives, or can be administered by alternate routes. Knowledge of patient genotypes may allow treatments tailored to avoid complications such as inhibitor development. Gene therapy trials, which are currently ongoing, will ultimately lead to gene-based treatments as a complement to traditional protein-based therapy. [source] Migraine Headache Recurrence: Relationship to Clinical, Pharmacological, and Pharmacokinetic Properties of TriptansHEADACHE, Issue 4 2003Gilles Géraud MD Background and Objectives.,Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo. Methods.,Clinical data were derived from 31 triptan, placebo-controlled, major efficacy studies used in a previous meta-analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct-comparison in vitro pharmacology study, and the elimination half-life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters. Results.,Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half-life and recurrence were inversely correlated (r = ,1.0, P = .0016). There was also a significant inverse correlation between 5-HT1B receptor potency and recurrence (r = ,0.68, P = .034), but 5-HT1D receptor potency was not correlated with recurrence (r = ,0.20, P = .54). In addition, the binding affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 (P = .53) and for therapeutic gain, ,0.11 (P = .71). Conclusion.,The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence. [source] The half-life of hepatitis B virions,HEPATOLOGY, Issue 5 2006John M. Murray The virion half-life of hepatitis B virus (HBV) is currently estimated at approximately 1 day. This estimate has been obtained from drug perturbation experiments with reverse transcriptase inhibitors. However, the analyses of those experiments have not considered the export of virions produced from preformed mature DNA-containing HBV capsids in infected cells. Data from 3 acutely infected chimpanzees indicates that there is approximately 10-fold more total intracellular HBV DNA than HBV DNA in blood, and therefore the half-life of virions for chimpanzees during acute infection is 10-fold shorter at 3.8 hours than the half-life associated with export of total intracellular HBV DNA. Mathematical model simulations duplicating the viral dynamics observed in drug perturbation experiments suggest a half-life of at most 4.4 hours for HBV virions in chronically infected humans, significantly shorter than current estimates, but consistent with the half-lives of virions for hepatitis C virus and HIV. This faster turnover of HBV in blood indicates a correspondingly higher replication rate and risk of mutation against hepatitis B antiviral therapy. In conclusion, we find the half-life of HBV virions is approximately 4 hours, significantly shorter than current estimates of 1 day. This new value is consistent with virion half-life estimates for HIV and hepatitis C virus. (HEPATOLOGY 2006;44:1117,1121.) [source] Analysis of hepatitis B viral load decline under potent therapy: Complex decay profiles observedHEPATOLOGY, Issue 5 2001Sharon R. Lewin We used a new real-time polymerase chain reaction (PCR)-based assay that is sensitive, has a wide dynamic linear range, and is highly reproducible to quantify hepatitis B virus (HBV) DNA in the serum of infected individuals undergoing potent antiviral therapy. In addition, we made frequent measurements of viral load after initiation of treatment and maintained follow-up to about 12 weeks. To analyze the data we used a new model of HBV decay, which takes into account that existing drug treatments do not completely block de novo infection and the possibility of noncytolytic loss of infected cells. On initiation of therapy, there was a mean delay of 1.6 days followed by a biphasic or muliphasic decay of plasma HBV DNA. The slope of the first phase varied considerably, with one individual having rapid decay, corresponding to a virion half-life of 1 hour, but others showing half-lives of up to 92 hours. Individuals either had a slow second-phase decline (t½ = 7.2 ± 1.2 days) or a flat second phase. Some individuals exhibited a complex "staircase pattern" of decay, with further phases of viral DNA decline and phases with little change in viral load. [source] Dynamic, 3D-Pattern Formation Within Enzyme-Responsive HydrogelsADVANCED MATERIALS, Issue 41 2009Karin S. Straley Dynamic, 3D hydrogel patterns emerge over time in response to cell-secreted enzymes (see image). Composite hydrogels fabricated from engineered proteins exhibit customized half-lives ranging across two orders of magnitude due to slight changes in the primary amino acid sequence. The evolution of internal 3D void structures within these polymeric materials is used to release multiple payload molecules with distinct spatial and temporal delivery profiles. [source] Controlled Growth Factor Delivery for Tissue EngineeringADVANCED MATERIALS, Issue 32-33 2009Prakriti Tayalia Abstract Growth factors play a crucial role in information transfer between cells and their microenvironment in tissue engineering and regeneration. They initiate their action by binding to specific receptors on the surface of target cells and the chemical identity, concentration, duration, and context of these growth factors contain information that dictates cell fate. Hence, the importance of exogenous delivery of these molecules in tissue engineering is unsurprising, considering their importance for tissue regeneration. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and their potential toxicity at high systemic levels, suggest that conventional routes of administration are unlikely to be effective. In this review, we provide an overview of the design criteria for growth factor delivery vehicles with respect to the growth factor itself and the microenvironment for delivery. We discuss various methodologies that could be adopted to achieve this localized delivery, and strategies using polymers as delivery vehicles in particular. [source] Absorption kinetics of oxygen scavengersINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 2 2002Gaurav Tewari The oxygen (O2) absorption kinetics of six commercial O2 scavengers were studied. The scavengers were placed in bags which were filled with 240 mL of air, 4.5 L N2 + 15 mL of air, or 3.5 L CO2 + 9 mL of air. The O2 concentration in each bag was measured at hourly intervals for 8 h. The effects of variability among individual scavengers, initial O2 concentrations of 20% or 500 ppm (0.05%), temperatures of 25, 12, 2 or ,1.5 °C, and scavenger capacity on the O2 absorption rate were determined. In addition, the effect of placing scavengers within over-wrapped trays within bags, was examined. Rates of O2 absorption varied by factors of up to 2 between individual O2 scavengers of the same type, but rates of absorption by groups of four scavengers of the same type were similar. Low temperatures gave longer O2 half-life when compared with those at higher temperatures, e.g. O2 half-lives of 7.1 and 1.0 h at ,1.5 and 25 °C, respectively, were obtained for one scavenger type. Shorter O2 half-lives were obtained in air than in N2 atmospheres at the same temperature, e.g. O2 half-lives of 1.0 and 3.3 h in air and N2 at 25 °C, respectively, were obtained for one scavenger type. The O2 absorption reactions were of first order for both high and low initial O2 concentrations. However, O2 concentration was the primary limiting factor for O2 absorption in atmospheres having O2 concentration of 500 ppm because of the dominance of diffusion. Scavengers, when placed within over-wrapped trays within bags had up to 12 times longer O2 half-lives, indicating that the O2 permeable film acts as an O2 barrier when pack atmosphere has low O2 concentrations. To obtain consistent and reproducible results, it is recommended that multiple scavengers be used in a packaging system. The appropriate number should be based on scavenger type, desired O2 absorption rate, storage temperature, and pack atmosphere (air/N2/CO2). [source] Modelling ecological half-lives for radiocaesium in Norwegian brown trout populationsJOURNAL OF APPLIED ECOLOGY, Issue 1 2000Dag O. Hessen Summary 1.,Models of ecological half-life may be valuable and cost-effective predictive tools for authorities setting restrictions on human consumption of freshwater fish after environmental releases of radioactivity. This work aimed to validate such a model for radioactive caesium (134Cs and 137Cs) in brown trout Salmo trutta populations. Data were drawn from lakes with a wide variability in abiotic and biotic factors and initial caesium load. 2.,In Norway, the highest fallout (more than 150 kBq m,2 of 137Cs) from the Chernobyl accident occurred in Oppland county, in south central Norway. Radioactivity was measured in more than 1800 samples of brown trout in nearly 100 localities in this region during 1986,95. 3.,The back-calculated maximum initial radioactivity on 1 January 1987 showed a strong regional variability (range 443,13 370; average 3855 Bq kg,1). Large variation in initial radioactivity was also recorded on a local scale (within 50 km). 4.,The ecological half-life model for caesium in brown trout populations for 1987,94/95 gave a close fit to real data from all localities with sufficient time series. Predicted half-lives ranged from 1·2 to 4·2 years (average 2·5) but 95% confidence limits were narrow (2·7 and 2·3 years). 5.,The overall variability in radioactivity levels over time was almost entirely related to the initial load and, with few exceptions, 88% of the changes in radioactivity was explained by the simple regression model. Modest variability in ecological half-life was not correlated with initial activity, and no clear effects of water quality or season could be detected. For most lakes, levels of radioactivity in brown trout appeared to be predictable, with high accuracy after a fallout event, without extensive information on population ecology and water quality. However, more detailed work may be required to assess patterns within individual lakes. [source] Retinoic acid regulates the expression of PBX1, PBX2, and PBX3 in P19 cells both transcriptionally and post-translationallyJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Pu Qin Abstract Pre-B cell leukemia transcription factors (PBXs) are important co-factors for the transcriptional regulation mediated by a number of Hox proteins during embryonic development. It was previously shown that the expression of several Pbx genes is elevated in mouse embryo limb buds and embryonal carcinoma P19 cells upon retinoic acid (RA) treatment although the mechanism of this induction is not well understood. In this report, we demonstrate that PBX1a, PBX1b, PBX2, and PBX3 mRNAs and PBX1/2/3 proteins are induced during endodermal and neuronal differentiation of P19 cells in a RAR-dependent subtype-unspecific manner following RA treatment. The increases in both PBX1 mRNA and PBX3 mRNA levels are secondary responses to RA treatment requiring new proteins synthesis while the increase in PBX2 mRNA is a primary response. The RA-dependent increases in PBX1 mRNA, PBX2 mRNA, and PBX3 mRNA levels are likely to be transcriptionally regulated since the stability of these mRNAs does not change. In addition, the half-lives of PBX1/2/3 proteins are significantly extended by RA treatment. Two possible mechanisms could contribute to the stabilization of PBX proteins: PBX proteins associate with RA-dependent increased levels of MEIS proteins, and RA may decrease the proteasome dependent degradation of PBX proteins. © 2004 Wiley-Liss, Inc. [source] Thermal deactivation and inhibition of D -Amino acid oxidase in permeabilized cells of the yeast Trigonopsis variabilisJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 4 2004José A Moreno Abstract The inhibition of D -amino acid oxidase contained in permeabilized cells of the yeast Trigonopsis variabilis by ,-keto acids (pyruvic acid, phenylpyruvic acid and 4-methylthio-2-oxobutanoic acid), products of the transformation of the corresponding D -amino acids, was studied. In all cases, inhibition was of the mixed type and significant differences with respect to the inhibition shown by the enzyme from other sources such as pig kidney or the yeast Rhodotorula gracilis were observed. A study was also made of the thermal deactivation of the enzyme contained in permeabilized cells of T variabilis in the temperature range 30,50 °C in sodium phosphate and Tris hydroxylmethyl aminomethane + CaCl2 buffers. A deactivation mechanism with two steps in series is proposed to account for the variation in activity with time. The results suggest that the enzyme shows greater stability in phosphate buffer, with half-lives between 7.6 days at 30 °C and 8.6 h at 50 °C. Copyright © 2004 Society of Chemical Industry [source] Plant amino acid uptake, soluble N turnover and microbial N capture in soils of a grazed Arctic salt marshJOURNAL OF ECOLOGY, Issue 4 2003Hugh A. L. Henry Summary 1The uptake of free amino acids by the grass Puccinellia phryganodes was investigated in soils of an Arctic coastal salt marsh, where low temperatures and high salinity limit inorganic nitrogen (N) availability, and the availability of soluble organic N relative to inorganic N is often high. 2Following the injection of 13C15N-amino acid, 15N-ammonium and 15N-nitrate tracers into soils, rates of soluble nitrogen turnover and the incorporation of 13C and 15N into plant roots and shoots were assessed. Chloroform fumigation-extraction was used to estimate the partitioning of labelled substrates into microbial biomass. 3Free amino acids turned over rapidly in the soil, with half-lives ranging from 8.2 to 22.8 h for glycine and 8.9 to 25.2 h for leucine, compared with 5.6 to 14.7 h and 5.6 to 15.6 h for ammonium and nitrate, respectively. 15N from both organic and inorganic substrates was incorporated rapidly into plant tissue and the ratio of 13C/15N incorporation into plant tissue indicated that at least 5,11% of 13C15N-glycine was absorbed intact. 4Microbial C and N per unit soil volume were 1.7 and 5.4 times higher, respectively, than corresponding values for plant C and N. Plant incorporation of 15N tracer was 56%, 83% and 68% of the comparable incorporation by soil microorganisms of glycine, ammonium and nitrate ions, respectively. 5These results indicate that P. phryganodes can absorb amino acids intact from the soil despite competition from soil microorganisms, and that free amino acids may contribute substantially to N uptake in this important forage grass utilized by lesser snow geese in the coastal marsh. [source] Information Processing in the Hypothalamus: Peptides and Analogue ComputationJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2006G. Leng Abstract ,Lovers and madmen have such seething brains,/Such shaping fantasies, that apprehend/More than cool reason ever comprehends'(A Midsummer Night's Dream, Act V Scene I) Peptides in the hypothalamus are not like conventional neurotransmitters; their release is not particularly associated with synapses, and their long half-lives mean that they can diffuse to distant targets. Peptides can act on their cells of origin to facilitate the development of patterned electrical activity, they can act on their neighbours to bind the collective activity of a neural population into a coherent signalling entity, and the co-ordinated population output can transmit waves of peptide secretion that act as a patterned hormonal analogue signal within the brain. At their distant targets, peptides can re-programme neural networks, by effects on gene expression, synaptogenesis, and by functionally rewiring connections by priming activity-dependent release. [source] Absorption of polyethylene glycol (PEG) polymers: The effect of PEG size on permeabilityJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2009Hema Gursahani Abstract Polyethylene glycol (PEG) polymers are large amphiphilic molecules that are highly hydrated in solution. To explore the permeability properties of different sized PEG polymers across epithelial membranes in vivo, we examined the absorption of fluorescently labeled PEG conjugates sized 0.55,20 kDa from the lung, since this system provides a reservoir that limits rapid diffusion of molecules away from the site of delivery and enables permeability over longer times to be examined. Following intratracheal delivery in rats, the PEG polymers underwent absorption with first-order kinetics described by single exponential decay curves. PEG size produced a marked influence on the rate of uptake from the lung, with half-lives ranging from 2.4 to 13 h, although above a size of 5 kDa, no further change in rate was observed. PEG size likewise affected retention in alveolar macrophages and in lung tissue; whereas smaller PEG sizes (<2 kDa) were effectively cleared within 48 h, larger PEG sizes (>5 kDa) remained in lung cells and tissue for up to 7 days. These data demonstrate that PEG polymers can be absorbed across epithelial membranes and that PEG size plays a dominant role in controlling the rate and mechanism of absorption. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2847,2856, 2009 [source] | |||||||||||||||||||||||||||||||||||||