Ion-trapping, microsomal binding, and unbound drug distribution in the hepatic retention of basic drugs

This study investigated the relative contribution of ion-trapping, microsomal binding, and distribution of unbound drug as determinants in the hepatic retention of basic drugs in the isolated perfused rat liver. The ionophore monensin was used to abolish the vesicular proton gradient and thus allow an estimation of ion-trapping by acidic hepatic vesicles of cationic drugs. In vitro microsomal studies were used to independently estimate microsomal binding and metabolism. Hepatic vesicular ion-trapping, intrinsic elimination clearance, permeability-surface area product, and intracellular binding were derived using a physiologically based pharmacokinetic model. Modeling showed that the ion-trapping was significantly lower after monensin treatment for atenolol and propranolol, but not for antipyrine. However, no changes induced by monensin treatment were observed in intrinsic clearance, permeability, or binding for the three model drugs. Monensin did not affect binding or metabolic activity in vitro for the drugs. The observed ion-trapping was similar to theoretical values estimated using the pHs and fractional volumes of the acidic vesicles and the pK(a) values of drugs. Lipophilicity and pK(a) determined hepatic drug retention: a drug with low pK(a) and low lipophilicity (e.g., antipyrine) distributes as unbound drug, a drug with high pK(a) and low lipophilicity (e.g., atenolol) by ion-trapping, and a drug with a high pK(a) and high lipophilicity (e.g., propranolol) is retained by ion-trapping and intracellular binding. In conclusion, monensin inhibits the ion-trapping of high pK(a) basic drugs, leading to a reduction in hepatic retention but with no effect on hepatic drug extraction.

Impact of pre-existing sulfate on retention of imported chloride and nitrate in variable charge soil profiles

In variable charge soils, anion retention and accumulation through adsorption at exchange sites is a competitive process. The objectives of this study in the wet tropics of far north Queensland were to investigate (i) whether the pre-existing high sulphate in variable charge soils had any impact on the retention of chloride and nitrate, derived mostly from the applied fertilizer; and (ii) whether chloride competed with nitrate during the adsorption processes. Soil cores up to 12.5 m depth were taken from seven sites, representing four soil types, in the Johnstone River Catchment. Six of these sites had been under sugarcane (Saccharum officinarum-S) cultivation for at least 50 years and one was an undisturbed rainforest. The cores were segmented at 1.0 m depth increments, and subsamples were analysed for nitrate-N, cation (CEC)- and anion-exchange capacities (AEC), pH, exchangeable cations (Ca, Mg, K, Na), soil organic C (SOC), electrical conductivity (EC), sulphate-S, and chloride. Sulphate-S load in 1-12 m depth under cropping ranged from 9.4 to 73.9 t ha(-1) (mean= 40 t ha(-1)) compared with 74.4 t ha(-1) in the rainforest. Chloride load under cropping ranged from 1.5 to 9.6 t ha(-1) (mean= 4.9 t ha(-1)) compared to 0.9 t ha(-1) in the rainforest, and the nitrate-N load from 113 to 2760 kg ha(-1) (mean = 910 kg ha(-1)) under cropping compared to 12 kg ha(-1) in the rainforest. Regardless of the soil type, the total chloride or nitrate-N input in fertilisers was 7.5 t ha(-1), during the last 50 years. Sulphate-S distribution in soil profiles decreased with depth at >2 m, whereas bulges of chloride or nitrate-N were observed at depths >2 m. This suggests that chloride or nitrate adsorption and retention increased with decreasing sulphate dominance. Abrupt decreases in equivalent fraction of sulphate (EFSO4), at depths >2 m, were accompanied by rapid increases in equivalent fraction of chloride (EFCl), followed by nitrate (EFNO3). The stepwise regression for EFCl and EFNO3 indicated that nitrate retention was reduced by the pre-existing sulphate and imported chloride, whereas only sulphate reduced chloride adsorption. The results indicate that chloride and nitrate adsorption and retention occurred, in the order chloride>nitrate, in soils containing large amounts of sulphate under approximately similar total inputs of N- and Cl-fertilisers. (C) 2004 Elsevier B.V. All rights reserved.

Engagement and retention of participants in a physical activity website

Background. Websites have the potential to deliver enhanced versions of targeted and tailored physical activity programs to large numbers of participants. We describe participant engagement and retention with a stage-based physical activity website in a workplace setting. Methods. We analyzed data from participants in the website condition of a randomized trial designed to test the efficacy of a print- vs. website-delivered intervention. They received four stage-targeted e-mails over 8 weeks, with hyperlinks to the website. Both objective and self-reported website use data were collected and analyzed. Results. Overall, 327 were randomized to the website condition and 250 (76%) completed the follow-up survey. Forty-six percent (n = 152) visited the website over the trial period. A total of 4,114 hits to the website were recorded. Participants who entered the site spent on average 9 min per visit and viewed 18 pages. Website use declined over time; 77% of all visits followed the first e-mail. Conclusions. Limited website engagement, despite the perceived usefulness of the materials, demonstrates possible constraints on the use of e-mails and websites in delivering health behavior change programs. In the often-cluttered information environment of workplaces, issues of engagement and retention in website-delivered programs require attention. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved.

Hydrodynamics and mass transfer coefficient in activated sludge aerated stirred column reactor: Experimental analysis and modeling

The aerated stirred reactor (ASR) has been widely used in biochemical and wastewater treatment processes. The information describing how the activated sludge properties and operation conditions affect the hydrodynamics and mass transfer coefficient is missing in the literature. The aim of this study was to investigate the influence of flow regime, superficial gas velocity (U-G), power consumption unit (P/V-L), sludge loading, and apparent viscosity (pap) of activated sludge fluid on the mixing time (t(m)), gas hold-up (epsilon), and volumetric mass transfer coefficient (kLa) in an activated sludge aerated stirred column reactor (ASCR). The activated sludge fluid performed a non-Newtonian rheological behavior. The sludge loading significantly affected the fluid hydrodynamics and mass transfer. With an increase in the UG and P/V-L, the epsilon and k(L)a increased, and the t(m), decreased. The E, kLa, and tm,were influenced dramatically as the flow regime changed from homogeneous to heterogeneous patterns. The proposed mathematical models predicted the experimental results well under experimental conditions, indicating that the U-G, P/V-L, and mu(ap) had significant impact on the t(m) epsilon, and k(L)a. These models were able to give the tm, F, and kLa values with an error around +/- 8%, and always less than +/- 10%. (c) 2005 Wiley Periodicals, Inc.

Simulated rainwater effects on anion exchange capacity and nitrate retention in Ferrosols

Nitrate (NO3) accumulations (up to 1880 kg NO3-N/ha for a 12-m profile) in the soils of the Johnstone River catchment (JRC) may pose a serious environmental threat to the Great Barrier Reef lagoon if the NO3 were released. The: leaching of artificial rainwater through repacked soil columns was investigated to determine the effect of low NO3/low ionic strength inputs on the NO3 Chemistry of the JRC profiles. Repacked soil columns were used to simulate the 11.5-m profiles, and the soil solution anion and cation concentrations were monitored at 10 points throughout the soil column. As the rainwater was applied, NO3 leached down the profile, with substantial quantities exiting the columns. Anion exchange was discounted as the major mechanism of NO3 release due to the substantial net loss of anions from the system (up to 2740 kg NO3-N/ha over the experimental period). As the soils were dominated by variable charge minerals, the effect of changing pH and ionic strength on the surface charge density was investigated in relation to the release of NO3 from the exchange. It was concluded that the equilibration of the soil solution with the low ionic strength rainwater solution resulted in a lessening of both the positive and negative surface charge. Nitrate was released into the soil solution and subsequently leached due to the lessening of the positive surface charge. Loss of NO3 from the soil profile was slow, with equivalent field release times estimated to be tens of years. Although annual release rates were high in absolute terms (up to 175 kg NO3-N/ha.year), they are only slightly greater than the current loss rates from fertilised sugarcane production (up to 50 kg NO3-N/ha.year). In addition to this, the large-scale release of NO3 from the accumulations will only occur until a new equilibrium is established with the input rainwater solution.

W/O microemulsions for ocular delivery: Evaluation of ocular irritation and precorneal retention

Water-in-oil microemulsions (w/o ME) capable of undergoing a phase-transition to lamellar liquid crystals (LC) or bicontinuous ME upon aqueous dilution were formulated using Crodarnol EO, Crill 1 and Crillet 4, an alkanol or alkanediol as cosurfactant and water. The hypothesis that phase-transition of ME to LC may be induced by tears and serve to prolong precomeal retention was tested. The ocular irritation potential of components and formulations was assessed using a modified hen's egg chorioallantoic membrane test (HET-CAM) and the preocular retention of selected formulations was investigated in rabbit eye using gamma scintigraphy. Results showed that Crill 1, Crillet 4 and Crodamol EO were non-irritant. However, all other cosurfactants investigated were irritant and their irritation was dependent on their carbon chain length. A w/o ME formulated without cosurfactant showed a protective effect when a strong irritant (0.1 M NaOH) was used as the aqueous phase. Precorneal clearance studies revealed that the retention of colloidal and coarse dispersed systems was significantly greater than an aqueous solution with no significant difference between ME systems (containing 5% and 10% water) as well as o/w emulsion containing 85% water. Conversely, a LC system formulated without cosurfactant displayed a significantly greater retention compared to other formulations. (c) 2005 Elsevier B.V. All rights reserved.

Development of a non-intrusive heat transfer coefficient gauge and its application to high pressure die casting Effect of the process parameters

A heat transfer coefficient gauge has been built, obeying particular rules in order to ensure the relevance and accuracy of the collected information. The gauge body is made out of the same materials as the die casting die (H13). It is equipped with six thermocouples located at different depths in the body and with a sapphire light pipe. The light pipe is linked to an optic fibre, which is connected to a monochromatic pyrometer. Thermocouples and pyrometer measurements are recorded with a data logger. A high pressure die casting die was instrumented with one such gauge. A set of 150 castings was done and the data recorded. During the casting, some process parameters have been modified such as piston velocity, intensification pressure, delay before switch to the intensification stage, temperature of the alloy, etc.... The data was treated with an inverse method in order to transform temperature measurements into heat flux density and heat transfer coefficient plots. The piston velocity and the initial temperature of the die seem to be the process parameters that have the greatest influence on the heat transfer. (c) 2005 Elsevier B.V. All rights reserved.

Estimation of water retention curve from mercury intrusion porosimetry and van Genuchten model

The water retention curve (WRC) is a hydraulic characteristic of concrete required for advanced modeling of water (and thus solute) transport in variably saturated, heterogeneous concrete. Unfortunately, determination by a direct experimental method (for example, measuring equilibrium moisture levels of large samples stored in constant humidity cells) is a lengthy process, taking over 2 years for large samples. A surrogate approach is presented in which the WRC is conveniently estimated from mercury intrusion porosimetry (MIP) and validated by water sorption isotherms: The well-known Barrett, Joyner and Halenda (BJH) method of estimating the pore size distribution (PSD) from the water sorption isotherm is shown to complement the PSD derived from conventional MIP. This provides a basis for predicting the complete WRC from MIP data alone. The van Genuchten equation is used to model the combined water sorption and MIP results. It is a convenient tool for describing water retention characteristics over the full moisture content range. The van Genuchten parameter estimation based solely on MIP is shown to give a satisfactory approximation to the WRC, with a simple restriction on one. of the parameters.

Hydrodynamics and mass transfer coefficient in three-phase air-lift reactors containing activated sludge

This study was to investigate the impacts of operating conditions and liquid properties on the hydrodynamics and volumetric mass transfer coefficient in activated sludge air-lift reactors. Experiments were conducted in internal and external air-lift reactors. The activated sludge liquid displayed a non-Newtonian rheological behavior. With an increase in the superficial gas velocity, the liquid circulation velocity, gas holdup and mass transfer coefficient increased, and the gas residence time decreased. The liquid circulation velocity, gas holdup and the mass transfer coefficient decreased as the sludge loading increased. The flow regime in the activated sludge air-lift reactors had significant effect on the liquid circulation velocity and the gas holdup, but appeared to have little impact on the mass transfer coefficient. The experimental results in this study were best described by the empirical models, in which the reactor geometry, superficial gas velocity and/or power consumption unit, and solid and fluid properties were employed. (c) 2006 Elsevier B.V. All rights reserved.

Extrusion of mixtures of starch and D-limonene encapsulated with beta-cyclodextrin: Flavour retention and physical properties

d-Limonene was encapsulated with beta-cyclodextrin to improve its retention during pre-added flavour starch extrusion. The objective of this work was to determine the effect of processing condition on the flavour retention and extrudate properties. Corn starch containing five levels of beta-cyclodextrin-d-limonene capsules (0-5%) were extruded at five different maximum barrel temperatures (133-167 degrees C) and screw speeds (158-242 rpm) using a twin screw extruder. The effect of these parameters on the flavour retention, expansion, texture, colour difference (Delta E), Water Absorption Index, Water Solubility Index, and residence time distribution (RTD) were investigated. Barrel temperature and capsule level predominantly influenced flavour retention and extrudate properties, while screw speed primarily affected extruder performances such as torque, die pressure, specific mechanical energy and RTD. (c) 2005 Elsevier Ltd. All rights reserved.

Relationship between bicarbonate retention and bone characteristics in broiler chickens

Determination of the bicarbonate retention factor (BRF) is an important step during development of the indicator amino acid oxidation technique for use in a new model. A series of 4-h oxidation experiments were performed to determine the BRF of broilers aged 7, 14, 21, 28, 35, and 42 d using 4 birds per age group. A priming dose of 1.2 mu Ci of (NaHCO3)-C-14, followed by eight half-hourly doses of 1 mu Ci of (NaHCO3)-C-14 were given orally to each of 4 birds per age. The percentage of 14 C dose expired by the bird at a steady state was measured. These birds, as well as 12 additional birds matched for age and BW, were killed, and femur bone mineral density was measured by quantitative computed tomography to determine the relationship between bone development and bicarbonate retention at each age. There was a correlation (r = 0.50; P < 0.05) between total cross-sectional femur bone mineral density and bicarbonate retention at each age. A prediction equation (Y = 6.95 x 10(-2) X - 3.51 x 10(5)X(2) + 27.58; P < 0.0001, R-2 = 0.79) where Y = bicarbonate retention and X = BW was generated to predict Y as a function of X. Bicarbonate retention values peaked at 28 d, during the stage of the most rapid bone deposition and the highest growth rate. A constant BRF was found from 1,900 to 2,700 g of BW of 35.15 +/- 1.095% (mean SEM). This retention factor will allow the accurate correction of oxidation of C-14-labeled substrates in broilers of different ages and BW in future indicator amino acid oxidation studies.

Retention, adherence and compliance: Important considerations for home- and group-based resistance training programs for older adults

Reports on the efficacy of physical activity intervention trials usually only include discussion of the primary outcomes. However, assessing factors such as participant retention, adherence and compliance can assist in the accurate interpretation of the overall impact of a program in terms of reach and appeal. A quasi-randomised trial was carried out to assess and compare retention and adherence rates, and compliance with, a twice weekly resistance training program provided either individually at home or in a group format. Retirement villages (n=6) were assigned to either 'Have A Try' (HAT, home-based) or 'Come Have A Try' (CHAT, group-based); both programs included nine strength and two balance exercises. The program involved a 20-week Intervention Phase a 24-week Maintenance Phase and a 20-week On-going Maintenance Phase. One hundred and nineteen participants (mean age 80 +/- 6 years) were recruited (HAT = 38, CHAT = 81). There was no difference in retention rates at the end of the Intervention Phase, but significantly more HAT than CHAT participants had dropped out of the study (p < 0.01) after the Maintenance Phase and the On-going Maintenance Phase. During the Intervention Phase, over half the HAT and CHAT participants completed >= 75% of the prescribed activity sessions, but adherence was significantly greater in CHAT than HAT during the Maintenance Phase (p < 0.01). Participants in CHAT were significantly more compliant than HAT participants (p < 0.05). Both home- and group-based formats were successful over the short-term, but, in retirement villages, the group program had better adherence and compliance in the longer-term. (c) 2006 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Water balance in goats subjected to feed restriction

The effect of feed restriction on water balance and nutrient utilization was investigated in individually penned Boer x Saanen kids. Twenty-two male Boer x Saanen kids with an initial average live weight (LW) of 15 kg were used. Seven kids were slaughtered at the beginning of the experiment (reference animals) and the remainders were allocated to one of the three treatments (0, 30 and 60% restriction) and therefore there were five kids per treatment. The feed intake for the 0% restriction treatment animals determined the intake for the animals in the 30 and 60% restriction treatment. When the animals in the 0% restriction treatment group reached 25 kg LW, the animals in the 30 and 60% restriction treatment groups were also slaughtered. There was a negative relationship between DMI and water intake. The digestibility coefficients for DM, OM, carbohydrates, ash, ether extract, energy, NDF, ADF and lignin did not differ between treatments, whereas the digestibility coefficient for CP was different between treatment groups. The highest metabolic water production was in animals in the 0% restriction treatment group. No significant differences were observed in the composition of gastro-intestinal tract contents of the goats in the different treatments. Lower water retention was found in the animals in the 60% restriction treatment group. The study showed that feed restriction affected water intake, CP digestibility and water retention in the body of the kid goats. This experiment demonstrated that DM:water intake ratio changed when severe feed restriction was applied (60% restriction) and water was freely available. It shows a different pattern of behaviour of penned goats, particularly if feed intake is restricted and perhaps caution is needed to extrapolate results from nutritional and physiological trials in pens to goats at pasture. (c) 2005 Elsevier BX All rights reserved.