Aquatic passive sampling of herbicides on naked particle loaded membranes: Accelerated measurement and empirical estimation of kinetic parameters

Water-sampler equilibrium partitioning coefficients and aqueous boundary layer mass transfer coefficients for atrazine, diuron, hexazionone and fluometuron onto C18 and SDB-RPS Empore disk-based aquatic passive samplers have been determined experimentally under a laminar flow regime (Re = 5400). The method involved accelerating the time to equilibrium of the samplers by exposing them to three water concentrations, decreasing stepwise to 50% and then 25% of the original concentration. Assuming first-order Fickian kinetics across a rate-limiting aqueous boundary layer, both parameters are determined computationally by unconstrained nonlinear optimization. In addition, a method of estimation of mass transfer coefficients-therefore sampling rates-using the dimensionless Sherwood correlation developed for laminar flow over a flat plate is applied. For each of the herbicides, this correlation is validated to within 40% of the experimental data. The study demonstrates that for trace concentrations (sub 0.1 mu g/L) and these flow conditions, a naked Empore disk performs well as an integrative sampler over short deployments (up to 7 days) for the range of polar herbicides investigated. The SDB-RPS disk allows a longer integrative period than the C18 disk due to its higher sorbent mass and/or its more polar sorbent chemistry. This work also suggests that for certain passive sampler designs, empirical estimation of sampling rates may be possible using correlations that have been available in the chemical engineering literature for some time.

Comparative pharmacokinetics of metronidazole in camels, sheep and goats

The pharmacokinetics of metronidazole was determined after a single intramuscular (i.m.) dose of 30 mg.kg(-1)-body weight in five camels, sheep and goats. Marked differences were found between the three species in some of the kinetic parameters. For example, the elimination half-lives t(1/2); (h) in camels, sheep and goats were 10.0, 6.21 and 5.87, respectively. The drug maximum concentrations in plasma, C-max (mg.ml(-1)), were 28.3, 54.6 and 54.4 in camels, sheep and goats, respectively. The time to reach C-max, t(max) (h), were 5, 4 and 2 in camels, sheep and goats, respectively. The mean residence times (MRT; h) in camels, sheep and goats were 16.7, 10.8 and 8.64, respectively. In the light of the present kinetic data and known microbial sensitivities of metronidazole, we recommend an i.m. dose of 15 mg.kg(-1) in camels and 10 mg.kg(-1) in sheep and boats. every 12 h.

A dynamic mathematical model for sequential leach bed anaerobic digestion of organic fraction of municipal solid waste

A mathematical model that describes the operation of a sequential leach bed process for anaerobic digestion of organic fraction of municipal solid waste (MSW) is developed and validated. This model assumes that ultimate mineralisation of the organic component of the waste occurs in three steps, namely solubilisation of particulate matter, fermentation to volatile organic acids (modelled as acetic acid) along with liberation of carbon dioxide and hydrogen, and methanogenesis from acetate and hydrogen. The model incorporates the ionic equilibrium equations arising due to dissolution of carbon dioxide, generation of alkalinity from breakdown of solids and dissociation of acetic acid. Rather than a charge balance, a mass balance on the hydronium and hydroxide ions is used to calculate pH. The flow of liquid through the bed is modelled as occurring through two zones-a permeable zone with high flushing rates and the other more stagnant. Some of the kinetic parameters for the biological processes were obtained from batch MSW digestion experiments. The parameters for flow model were obtained from residence time distribution studies conducted using tritium as a tracer. The model was validated using data from leach bed digestion experiments in which a leachate volume equal to 10% of the fresh waste bed volume was sequenced. The model was then tested, without altering any kinetic or flow parameters, by varying volume of leachate that is sequenced between the beds. Simulations for sequencing/recirculating 5 and 30% of the bed volume are presented and compared with experimental results. (C) 2002 Elsevier Science B.V. All rights reserved.

A potential role for isothermal calorimetry in studies of the effects of thermodynamic non-ideality in enzyme-catalyzed reactions

Attention is drawn to the feasibility of using isothermal calorimetry for the characterization of enzyme reactions under conditions bearing greater relevance to the crowded biological environment, where kinetic parameters are likely to differ significantly from those obtained by classical enzyme kinetic studies in dilute solution. An outline of the application of isothermal calorimetry to the determination of enzyme kinetic parameters is followed by considerations of the nature and consequences of crowding effects in enzyme catalysis. Some of those effects of thermodynamic non-ideality are then illustrated by means of experimental results from calorimetric studies of the effect of molecular crowding on the kinetics of catalysis by rabbit muscle pyruvate kinase. This review concludes with a discussion of the potential of isothermal calorimetry for the experimental determination of kinetic parameters for enzymes either in biological environments or at least in media that should provide reasonable approximations of the crowded conditions encountered in vivo. Copyright (C) 2004 John Wiley Sons, Ltd.

Phosphotyrosyl peptides and analogues as substrates and inhibitors of purple acid phosphatases

Purple acid phosphatases are metal-containing hydrolases. While their precise biological role(s) is unknown, the mammalian enzyme has been linked in a variety of biological circumstances (e.g., osteoporosis) with increased bone resorption. Inhibition of the human enzyme is a possible strategy for the treatment of bone-resorptive diseases such as osteoporosis. Previously, we determined the crystal structure of pig purple acid phosphatase to 1.55 Angstrom and we showed that it is a good model for the human enzyme. Here, a study of the pH dependence of its kinetic parameters showed that the pig enzyme is most efficient at pH values similar to those encountered in the osteoclast resorptive space. Based on the observation that phosphotyrosine-containing peptides are good substrates for pig purple acid phosphatase, peptides containing a range of phosphotyrosine mimetics were synthesized. Kinetic analysis showed that they act as potent inhibitors of mammalian and plant purple acid phosphatases, with the best inhibitors exhibiting low micromolar inhibition constants at pH 3-5. These compounds are thus the most potent organic inhibitors yet reported for the purple acid phosphatases. (C) 2004 Published by Elsevier Inc.

Transition-state-theory calculations for reactions of O(3P) with halogenated olefins

The potential energy surfaces for the reactions of atomic oxygen in its ground electronic state, O(P-3), with the olefins: CF2=CCl2 and CF2=CF - CF3, have been characterized using ab initio molecular orbital calculations. Geometry optimization and vibrational frequency calculations were performed for reactants, transition states and products at the MP2 and QCISD levels of theory using the 6-31G(d) basis set. This database was then used to calculate the rate constants by means of Transition-State-Theory. To obtain a better reference and to test the reliability of the activation barriers we have also carried out computations using the CCSD(T)(fc)/6-311Gdagger, MP4(SDQ)(fc)/CBSB4 and MP2(fc)/CBSB3 single point energy calculations at both of the above levels of theory, as well as with the composite CBS-RAD procedure ( P. M. Mayer, C. J. Parkinson, D. M. Smith and L. Radom, J. Chem. Phys., 1998, 108, 604) and a modi. cation of this approach, called: CBS-RAD( MP2, MP2). It was found that the kinetic parameters obtained in this work particularly with the CBS-RAD ( MP2, MP2) procedure are in reasonable agreement with the experimental values. For both reactions it is found that the channels leading to the olefin double-bond addition predominates with respect to any other reaction pathway. However, on account of the different substituents in the alkenes we have located, at all levels of theory, two transition states for each reaction. Moreover, we have found that, for the reactions studied, a correlation exists between the activation energies and the electronic structure of the transition states which can explain the influence of the substituent effect on the reactivity of the halo-olefins.

Disposition kinetics of propranolol isomers in the perfused rat liver

The aim of this study was to define the determinants of the linear hepatic disposition kinetics of propranolol optical isomers using a perfused rat liver. Monensin was used to abolish the lysosomal proton gradient to allow an estimation of propranolol ion trapping by hepatic acidic vesicles. In vitro studies were used for independent estimates of microsomal binding and intrinsic clearance. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a nonparametric method. Kinetic parameters were derived from a physiologically based pharmacokinetic model. Modeling showed an approximate 34-fold decrease in ion trapping following monensin treatment. The observed model-derived ion trapping was similar to estimated theoretical values. No differences in ion-trapping values was found between R(+)- and S(-)- propranolol. Hepatic propranolol extraction was sensitive to changes in liver perfusate flow, permeability-surface area product, and intrinsic clearance. Ion trapping, microsomal and nonspecific binding, and distribution of unbound propranolol accounted for 47.4, 47.1, and 5.5% of the sequestration of propranolol in the liver, respectively. It is concluded that the physiologically more active S(-)- propranolol differs from the R(+)- isomer in higher permeability-surface area product, intrinsic clearance, and intracellular binding site values.

Modeling the molecular weight distribution of block copolymer formation in a reversible addition-fragmentation chain transfer mediated living radical polymerization

Block copolymers have become an integral part of the preparation of complex architectures through self-assembly. The use of reversible addition-fragmentation chain transfer (RAFT) allows blocks ranging from functional to nonfunctional polymers to be made with predictable molecular weight distributions. This article models block formation by varying many of the kinetic parameters. The simulations provide insight into the overall polydispersities (PDIs) that will be obtained when the chain-transfer constants in the main equilibrium steps are varied from 100 to 0.5. When the first dormant block [polymer-S-C(Z)=S] has a PDI of 1 and the second propagating radical has a low reactivity to the RAFT moiety, the overall PDI will be greater than 1 and dependent on the weight fraction of each block. When the first block has a PDI of 2 and the second propagating radical has a low reactivity to the RAFT moiety, the PDI will decrease to around 1.5 because of random coupling of two broad distributions. It is also shown how we can in principle use only one RAFT agent to obtain block copolymers with any desired molecular weight distribution. We can accomplish this by maintaining the monomer concentration at a constant level in the reactor over the course of the reaction. (c) 2005 Wiley Periodicals, Inc.

Design strategies for controlling the molecular weight and rate using reversible addition-fragmentation chain transfer mediated living radical polymerization

Living radical polymerization has allowed complex polymer architectures to be synthesized in bulk, solution, and water. The most versatile of these techniques is reversible addition-fragmentation chain transfer (RAFT), which allows a wide range of functional and nonfunctional polymers to be made with predictable molecular weight distributions (MWDs), ranging from very narrow to quite broad. The great complexity of the RAFT mechanism and how the kinetic parameters affect the rate of polymerization and MWD are not obvious. Therefore, the aim of this article is to provide useful insights into the important kinetic parameters that control the rate of polymerization and the evolution of the MWD with conversion. We discuss how a change in the chain-transfer constant can affect the evolution of the MWD. It is shown how we can, in principle, use only one RAFT agent to obtain a poly-mer with any MWD. Retardation and inhibition are discussed in terms of (1) the leaving R group reactivity and (2) the intermediate radical termination model versus the slow fragmentation model. (c) 2005 Wiley Periodicals, Inc.

Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation

Systemic inflammation is known to affect drug disposition in the liver. This study sought to relate and quantitate changes in hepatic pharmacokinetics of propranolol with changes in hepatic architecture and physiology in adjuvant-treated rats. Transmission electron microscopy was used to assess morphological changes in mitochondria and lysosomes of adjuvant-treated rat livers. The disposition of propranolol was assessed in the perfused rat liver using the multiple indicator dilution technique. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a nonparametric method. Kinetic parameters were derived from a two-phase physiologically based organ pharmacokinetic model. Possible relationships were then explored between the changes in hepatic drug disposition and cytochrome P-450 activity and iron concentration. Adjuvant treatment induced the appearance of mitochondrial inclusions/tubularization and irregularly shaped lysosomes in rat livers. Livers from adjuvant-treated rats had (relative to normal) significantly higher alpha(1)-acid glycoprotein (orosomucoid) and iron tissue concentrations but lower cytochrome P-450 content. The hepatic extraction, metabolism, and ion trapping of propranolol were significantly impaired in adjuvant-treated rats and could be correlated with altered iron store and cytochrome P-450 activity. It is concluded that adjuvant-induced systemic inflammation alters hepatocellular morphology and biochemistry and consequently influences hepatic disposition of propranolol.

Short report: Lack of sex effect on the pharmacokinetics of primaquine

The pharmacokinetics of primaquine have been well defined in male volunteers, but there is little data on the disposition of the drug in women. We compared the kinetics of primaquine in nine male and nine female healthy Australian volunteers after the administration of a single oral dose (30 mg base) of primaquine. No statistical differences were observed in the following kinetic parameters of primaquine between men and women, respectively: maximum plasma concentration (93 +/- 26 and 115 +/- 38 ng/mL; 95% confidence interval [CI] of the mean difference: -55 to 10 ng/mL; P = 0.16), area under the curve (1.1 +/- 0.5 and 1.2 +/- 0.4 mu g.h/mL; 95% CI: -0.6 to 0.3 mu g.h/mL; P = 0.54), and clearance (0.34 +/- 0.12 and 0.39 +/- 0.14 L/h/kg; 95% CI: -0.17 to 0.08 L/h/kg; P = 0.46). The clinical relevance of such findings would suggest that sex does not have to be taken into account as a factor when prescribing primaquine for radical cure or terminal prophylaxis of Plasmodium vivax malaria.

Kinetic model for selective cultivation of microfungi in a microscreen process for food processing wastewater treatment and biomass production

The research was aimed at developing a technology to combine the production of useful microfungi with the treatment of wastewater from food processing. A recycle bioreactor equipped with a micro-screen was developed as a wastewater treatment system on a laboratory scale to contain a Rhizopus culture and maintain its dominance under non-aseptic conditions. Competitive growth of bacteria was observed, but this was minimised by manipulation of the solids retention time and the hydraulic retention time. Removal of about 90% of the waste organic material (as BOD) from the wastewater was achieved simultaneously. Since essentially all fungi are retained behind the 100 mum aperture screen, the solids retention time could be controlled by the rate of harvesting. The hydraulic retention time was employed to control the bacterial growth as the bacteria were washed through the screen at a short HRT. A steady state model was developed to determine these two parameters. This model predicts the effluent quality. Experimental work is still needed to determine the growth characteristics of the selected fungal species under optimum conditions (pH and temperature).