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Biomedical subjects

G Wei

Publications and source records attributed to G Wei.

117 records · Page 7Linked to original sources

Voltammetric determination of platinum in inorganic complexes and in water, geological and biological matrices using laboratory- and field-based instrumentation.

The extremely sensitive catalytic hydrogen ion reduction wave observed after the formation of a platinum-formazone complex at a mercury electrode in a hydrazine-formaldehyde-H2SO4 medium has been utilised to determine platinum voltammetrically in well characterised platinum inorganic complexes (oxidation states O, II and IV) and in biological, geological and water samples. Experimental conditions have been optimised and sample-treatment procedures for various matrices have been critically evaluated for the quantification of platinum by the standard additions method. The determination of platinum in geological samples by this method has been compared with an inductively coupled plasma mass spectrometric method. Both conventional and portable field-based instrumentation have been used in the studies, and the possibility of developing a field-based method for the determination of platinum has been investigated. Despite the inherent sensitivity of the method, which enables concentrations down to 0.01 p.p.b. to be detected in simple matrices, natural levels in water and biological materials, where matrix effects suppress the voltammetric response, are often below the detection limit.

Animals↗

Application of reverse micelles for the extraction of proteins.

The solubilization of proteins in hydrocarbon solutions of reverse micelles is examined at the aim of establishing whether this process can be utilized for the separation and extraction of proteins. Two techniques of solubilization are considered, the phase transfer of proteins from an aqueous solution into a supernatant micellar solution and the direct extraction of the protein powder into the micellar solution. Basic questions concerning the influence of structural parameters of the proteins, as well as the influence of external parameters (pH, salt concentration) on the specificity of the solubilization process are discussed.

Colloids↗

Characterization of mutations that lie in the promoter-regulatory region for glnA, the structural gene encoding glutamine synthetase.

In enteric bacteria products of nitrogen regulatory genes ntrA, ntrB and ntrC are known to regulate transcription both positively and negatively at glnA, the structural gene encoding glutamine synthetase [L-glutamate:ammonia-ligase (ADP-forming), EC 6.3.1.2]. We have characterized two types of cis-acting mutations in the glnA promoter-regulatory region. One type, which we have called promoter Up [glnAp (Up)], elevates transcription of glnA to high levels without need for ntr-mediated activation but leaves expression sensitive to ntr-mediated repression. The other type renders glnA transcription insensitive to repression but leaves it normally responsive to activation. Properties of the two types of promoter-regulatory mutations suggest that sites for ntr-mediated activation of glnA transcription are functionally distinct from sites for ntr-mediated repression.

Bacterial Proteins↗

Characterization of the highly variable bioavailability of tiludronate in normal volunteers using population pharmacokinetic methodologies.

Currently, the use of classical bioequivalence criteria is being called into question for certain classes of drugs such as bisphosphonates. These compounds typically possess a wide therapeutic index but may be characterized by low and variable absorption. The purpose of this communication was to characterize the highly variable bioavailability of tiludronate using a population pharmacokinetic method (NONMEM program) and compare the results to a standard 2 way cross-over bioequivalence trial in healthy subjects. Over 3500 plasma samples from 153 healthy subjects, representing 12 different clinical trials were pooled for mixed effect modeling purposes (complete data set). These studies, conducted under single and multiple dose conditions, contained all the directly comparable data available in healthy subjects administered a 400 mg dose of tiludronate. A two compartment model with first order absorption was fit to the plasma concentration-time data and a term for relative bioavailability (BA) was included. Intersubject and residual variability were modeled using a constant coefficient of variation (CCV) model. A pilot model development data set was obtained from a 24 subject cross-over bioequivalence study. Population estimates of BA and its associated 90% confidence interval of 1.12 and 0.89-1.35 compared favorably to standard bioequivalence methodology (1.15 and 0.93-1.42, respectively). Since a good fit of predicted and observed plasma concentrations as well as estimates of BA were obtained, a two compartment model with a term for BA was then applied to the complete data set. Under these conditions, BA and its 90% confidence interval were found to be 1.17 and 0.98-1.36. Intersubject variability of 31%, compared with 38% in the pilot model development data set and residual variability of 38% were seen. No differences in absorption characteristics as measured by Ka were found. Good agreement between the population pharmacokinetic parameters were observed when the pilot data set was compared with the full data set. The proposed model was confirmed by creating 10 additional smaller data sets that were matched for the number of subjects given both formulations under single and multiple dose conditions. No change in the estimate of BA was observed under these study conditions. This study demonstrated that population pharmacokinetic methodology can be applied successfully to problematical bioequivalence issues that may occur during the development process. Increasing the number of subjects in the overall analysis did not alter the estimate of BA or its 90% confidence interval, when compared to the original cross-over bioequivalence study. Bayesian approaches can be of value in large clinical trials where typically relatively few plasma samples are obtained from individual subjects.

Biological Availability↗

Modification of vertical OKN and vertical OKAN asymmetry in humans during parabolic flight.

Characteristics of human vertical optokinetic nystagmus (OKN) and afternystagmus (OKAN) were examined by ISCAN imaging system on the ground and on board NASA's KC-135 aircraft in a parabolic flight study. The aircraft produced alternating periods of micro-(ca. 10(-2) G) and hyper-(ca. 1.8 G) gravitoinertial forces. Each phase lasted approximately 20 to 25 s. As compared to the baseline data on the ground, there was a significant increase of downward OKN/OKAN, whereas the upward OKN/OKAN did not change significantly in either micro- or hyper-G. As a consequence, the asymmetry of vertical OKN/OKAN, normally seen on the ground, was lost. It is postulated that the increase of downward OKN/OKAN in non-1-G conditions was governed by two different mechanisms. In micro-G, the normal inhibition effect in 1 G on the downward eye movement mediated by otolith organ activity to vertical velocity storage was removed. In hyper-G, downward OKN/OKAN was facilitated by augmented otolith-ocular reflex because of increased gravitoinertial force, so as to produce enhanced compensatory downward eye movement.

Adult↗