Typical Half-lives Research Articles

Nanomolar E-Selectin Antagonists with Prolonged Half-Lives by a Fragment-Based Approach

Selectins, a family of C-type lectins, play a key role in inflammatory diseases (e.g., asthma and arthritis). However, the only millimolar affinity of sialyl Lewis(x) (sLe(x)), which is the common tetrasaccharide epitope of all physiological selectin ligands, has been a major obstacle to the development of selectin antagonists for therapeutic applications. In a fragment-based approach guided by NMR, ligands binding to a second site in close proximity to a sLe(x) mimic were identified. A library of antagonists obtained by connecting the sLe(x) mimic to the best second-site ligand via triazole linkers of different lengths was evaluated by surface plasmon resonance. Detailed analysis of the five most promising candidates revealed antagonists with K(D) values ranging from 30 to 89 nM. In contrast to carbohydrate-lectin complexes with typical half-lives (t(1/2)) in the range of one second or even less, these fragment-based selectin antagonists show t1/2 of several minutes. They exhibit a promising starting point for the development of novel anti-inflammatory drugs.

Ketorolac tromethamine: stereo‐specific pharmacokinetics and single‐dose use in postoperative infants aged 2–6 months

We determined the postoperative pharmacokinetics (PK), safety, and analgesic effects of ketorolac in 14 infants (aged <6 months) receiving a single intravenous (IV) administration of racemic ketorolac or placebo. Information on the PK of ketorolac in infants is limited. Unblinded studies suggest ketorolac may be useful in infants. This double-blinded, placebo-controlled study enrolled 14 infants (aged <6 months) postoperatively. At 6-18 h after surgery, infants were randomized to receive placebo, 0.5 mg·kg(-1), or 1 mg·kg(-1) ketorolac IV. All infants received morphine sulfate as needed for pain control. Blood was collected up to 12-h postdosing. Analysis used noncompartmental and compartmental population modeling methods. In addition to noncompartmental and empirical Bayes PK modeling, data were integrated with a previously studied data set comprising 25 infants and toddlers (aged 6-18 months). A two-compartmental model described the comprehensive data set. The population estimates of the R (+) isomer were (%CV): central volume of distribution 1130 (10%) ml, peripheral volume of distribution 626 (25%) ml, and clearance from the central compartment 7.40 (8%) ml·min(-1). Those of the S (-) isomer were 1930 (15%) ml, 319 (58%) ml, and 39.5 (13%) ml·min(-1). Typical elimination half-lives were 191 and 33 min, respectively. There was a trend for increased clearance and central volume with increasing age and weight. The base model suggested that clearance of the S (-) isomer was weakly related to age; however, when body size adjustment was added to the model, no covariates were significant. Safety assessment showed no changes in renal or hepatic function tests, surgical drain output, or continuous oximetry between groups. Cumulative morphine administration showed large inter-patient variability and was not different between groups. Stereo-isomer-specific clearance of ketorolac in infants (aged 2-6 months) shows rapid elimination of the analgesic S (-) isomer as reported in infants aged 6-18 months. No adverse effects were seen after a single IV ketorolac dose.

Field application of a tailored catalyst for hydrodechlorinating chlorinated hydrocarbon contaminants in groundwater

Catalytic hydrodechlorination via Pd catalysts is an efficient way to destroy chlorinated hydrocarbon compounds (CHCs) in aqueous systems. However, its application in groundwater suffers from rapid catalyst deactivation, e.g. by sulfur poisoning and interference with biological processes, such as growth of sulfate-reducing bacteria. In this paper we describe the application of a tailored catalyst for groundwater remediation in a full-scale field installation. The catalyst (Pd on a hydrophobic zeolite Y) was operated in a flow-through mode over 2 years and showed sustained removal efficiencies. Typical half-lives for CHC reduction were between 1.5 and 3min. As the addition of the reductant hydrogen results in favorable conditions for sulfate-reducing bacteria, the system was periodically flushed with a dilute H2O2 solution to prevent the growth of this type of bacteria. With this it could be shown, that a catalytic method with noble metals for the direct reductive destruction of chlorinated contaminants in groundwater can be operated over extended periods of time with sustained efficiencies.

Reductive Dechlorination of Trichloroethene and Carbon Tetrachloride Using Iron and Palladized-Iron Cathodes

This research investigated the effectiveness of electrochemical reduction for removing trichloroethylene (TCE) and carbon tetrachloride (CT) from dilute aqueous solutions. The kinetics, reaction mechanisms, and current efficiencies for TCE and CT reduction were investigated using flow-through, iron electrode reactors and with amperometric measurements of reduction rates. The electrode reactors were operated over a range of flow rates, pH, ionic strength, dissolved oxygen concentration, and working electrode potentials. Typical reduction half-lives for TCE and CT in the iron reactor were 9.4 and 3.7 min, respectively. The addition of palladium as an electrocatalyst at a level of 1 mg of Pd per m2 of electrode surface area increased the reaction rates by a factor of 3. When operated continuously, reaction rates in the palladized-iron reactor were stable over a 9-month period of operation, indicating that there was no loss of palladium from the electrode. In both the iron and Pd−iron reactors, TCE was reduce...

Natural Protection of Spring and Well Drinking Water Against Surface Microbial Contamination. I. Hydrogeological Parameters

The fate and transport of microbes in groundwater are controlled by physicochemical characteristics of the microbe and of the groundwater/aquifer media. Key characteristics of the microbe include size, inactivation (die-off) rate, and surface electrostatic properties. Key properties of the groundwater/aquifer system include flow velocity, aquifer grain (or pore) size, porosity, solid organic carbon content, temperature, pH, and other chemical characteristics of water and mineral composition. Because of size and surface electrical properties, viruses are much more mobile in groundwater than Cryptosporidium and Giardia (which are about 100 times or more larger than viruses). The inactivation or die-off rate is usually the most important factor governing how far microbes can migrate in significant numbers in groundwater. Typical half-lives of microbes in groundwater range from a few hours to a few weeks. Examples of maximum reported migration distances of microbes in groundwater include: bacteria, 600 m in a sandy aquifer; viruses., 1000 to 1600 m in channeled limestones and 250 to 408 m in glacial silt-sand aquifers; Cryptosporidium and Giardia, no confirmed reports found of significant migration distances. Investigations by the EPA have indicated that distances of 210 to 325 m away from septic tanks are necessary to achieve with high confidence an 11 order of magnitude reduction in virus concentrations.

Electron transfer between a quinohemoprotein alcohol dehydrogenase and an electrode via a redox polymer network

A quinohemoprotein alcohol dehydrogenase (QH-EDH) from Comamonas testosteroni was immobilized on an electrode in a redox polymer network consisting of a polyvinylpyridine partially n-complexed with osmiumbis-(bipyridine)chloride. The enzyme effectively transfers electrons to the electrode via the polymer. An average maximum catalytic current of 11 μA cm −2 was observed with 1-propanol as the substrate. The maximum activity of the enzyme electrode (current density) for primary alcohols is independent of the type of substrate in contrast with the activity of the free enzyme. Affinity constants of the immobilized QH-EDH for different substrates are comparable with the values found for the free enzyme. Typical half-lives for the immobilized enzyme electrodes are in the order of 5 h.

Environmental photochemistry of PCDDs. Part I. Kinetics and quantum yields of the photodegration of 1,2,3,4,7-penta- and 1,2,3,4,7,8-hexachlorodibenzo- [formula omitted]-dixin in aqueous acetontrile

For the determination of the quantum yields of 1,2,3,4,7-pentachlorodibenzo- p -dioxin ( 1 ) and 1,2,3,4,7,8-hexachlorodibenzo- p -dioxin ( 2 ), ten Pyrex glass photochemical cells were constructed and their correction factors determined. Quantum yields at 313 nm for 1 and 2 in aqueous acetonitrile (4:6 v/v) were (9.781 ± 2.376) 10 −5 and (1.096 ± 0.020) × 10 −4, respectively. These quantum yields and the measured absorption spectra were used to estimate the environmental phototransformation first-order rate constants and photochemical half-lives of 1 and 2 in water under conditions of variable sunlight intensity during various seasons from solar intensity data available in the literature. In summer, typical half-lives for the phototransformation of 1 and 2 , respectively, near the surface of water bodies at 40° north latitude would be 364 ± 88 and 151 ± 3 h; whilst such values in winter would be 1257 ± 309 and 518 ± 10 h.

No. 2 fuel oil compounds in Mytilus edulis

Mytilus edulis contaminated by a brief 2-d exposure to a slick from a No. 2 fuel oil spill in the Cape Cod Canal, Massachusetts, USA were sampled six times during an 86-d post-spill period to study the rate of release of fuel oil compounds under field conditions. Detailed measurements of compounds by high resolution glass capillary gas chromatography and quantitative glass capillary gas chromatography-mass spectrometry-computer systems analyses provided a more comprehensive examination of release rates of different types of compounds. Biological half-lives were calculated for selected compounds for the first 21 d during which the release rates were exponential. Typical half-lives were n-alkanes, 0.2–0.8 d; pristane, 1.5 d; C-2 (dimethyl or ethyl) napthalenes, 0.9 d; methyl phenanthrenes, 1.7 d. Changes in relative ratios of C-2 phenanthrenes during the release period were observed. The evidence available to date strongly supports the role of molecular weight and accompanying properties of water solubility as the main controlling factors in the rate of release of fuel oil compounds by M. edulis. However, the data for the rapid release of n-alkanes and C-2 phenanthrenes also indicate molecular type and molecular configuration as additional key factors. The data from this study are compared and contrasted to data from short term experimental studies in the laboratory, longer term studies from chronic exposure conditions, and data from two other oil spills with longer term exposure.

Numerical Experiments on the Decay of Three-Body Systems

AbstractNumerical results are presented for calculations of stellar three-body systems. Among the triple systems with similar initial separations between each of the stars, the equal-mass systems are most stable with typical half-lives of about 40 crossing times. In the other extreme, systems with a very small total angular momentum or a large mass difference have half-lives of only about 10 crossing times. The escaping star is usually the lightest one, while the escape probability for the heaviest star approaches zero when its mass exceeds the combined mass of the other two stars by more than a factor of about 5. The final binary becomes very eccentric (ē ≳ 0.8) when the three stars are restricted to a plane and do not have a very high total angular momentum, or when the total angular momentum is very small.