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Biomedical subjects

D A Russell

Publications and source records attributed to D A Russell.

At least 19 recordsLinked to original sources
PubMed2001

Observation of stimulated electron-acoustic-wave scattering.

A diffraction-limited laser interacts with a plasma whose conditions are uniform on the scale of the focused laser spot. Two distinct, narrow waves are observed in the backscattered spectrum with phase velocities of v(phi)/v(e) = 1.4+/-0.08 and 4.2+/-0.1, where v(e) is the electron thermal speed. The high-velocity wave is ordinary stimulated Raman scattering (SRS) from a Langmuir wave. The low-velocity wave corresponds to stimulated scattering from an electron-acoustic wave (SEAS), and implies strong electron trapping. Previous SRS data from low-density plasmas are reinterpreted in terms of SEAS.

Journal Article↗
PubMed2001

3/2omega0 radiation from the laser-driven two-plasmon decay instability in an inhomogeneous plasma.

We present the results of the first reduced model simulations of the nonlinear development of the two-plasmon decay instability in an inhomogeneous plasma, including properties of the 3/2 harmonic emission. A sharp increase in radiation and Langmuir turbulence fluctuation levels occurs above a threshold laser intensity that depends on initial fluctuation levels. We study the competition between the linear propagation of Langmuir waves in the density gradient and the nonlinear saturation due to the Langmuir decay instability. The secondary decay Langmuir waves can provide the dominant source of the radiation and are essential to explain experiments.

Journal Article↗
PubMed2001

Functional, biochemical and genetic diversity of prokaryotic nitrate reductases.

Prokaryotic nitrate reduction can serve a number of physiological roles and can be catalysed by a number of biochemically distinct nitrate reductases. Three distinct nitrate reductase classes can be indentified in prokaryotes, NAS, NAR and NAP. NAS is located in the cytoplasmic compartment and participates in nitrogen assimilation. NAR is usually a three-subunit complex anchored to the cytoplasmic face of the membrane with its active site located in the cytoplasmic compartment and is involved in anaerobic nitrate respiration. NAP is a two-subunit complex, located in the periplasmic compartment, that is coupled to quinol oxidation via a membrane anchored tetraheme cytochrome. It shows considerable functional flexibility by participating in anaerobic respiration or redox energy dissipation depending on the organism in which it is found. The members of all three classes of enzymes bind the bis-molybdopterin guanine dinucleotide cofactor at the active site, but they differ markedly in the number and nature of cofactors used to transfer electrons to this site. Analysis of prokaryotic genome sequences available at the time of writing reveals that the different nitrate reductases are phylogenetically widespread.

Amino Acid Sequence↗
PubMed2001

Risedronate pharmacokinetics and intra- and inter-subject variability upon single-dose intravenous and oral administration.

PURPOSE: To determine the pharmacokinetics and absolute bioavailability of risedronate after single-dose oral administration of 30 mg risedronate as a tablet and an aqueous solution, and 0.3 mg risedronate as an intravenous infusion. METHODS: This study was a randomized, three-treatment, four-period, partial replicate crossover study involving 33 healthy volunteers. Treatments were administered 7 weeks apart, and the third treatment was repeated during the fourth period. Serum and urine were collected over 72 hours and 672 hours, respectively. RESULTS: Following intravenous administration, renal clearance accounted for 87% of total clearance, with 65% of the dose excreted within 24 hours and 85% of the dose excreted within four weeks. The absolute bioavailability was approximately 0.62% after both oral formulations, and the relative bioavailability of the tablet compared with the oral solution was 104%. The rate and extent of absorption from the two formulations were bioequivalent based on the range proposed for highly variable drugs. Intrasubject variability following oral administration was 50-80%, and was primarily associated with absorption. CONCLUSION: The majority of the total clearance after intravenous administration of risedronate was renal clearance, indicating that only a small percentage of a systemic dose is potentially incorporated, or "cleared," into bone. The absolute bioavailability of orally administered risedronate is approximately 0.6%, and is independent of formulation. Variability in the pharmacokinetics following oral administration is primarily associated with intrasubject variability in absorption.

Administration, Oral↗
PubMed2000

High-yield production of a human therapeutic protein in tobacco chloroplasts.

Transgenic plants have become attractive systems for production of human therapeutic proteins because of the reduced risk of mammalian viral contaminants, the ability to do large scale-up at low cost, and the low maintenance requirements. Here we report a feasibility study for production of a human therapeutic protein through transplastomic transformation technology, which has the additional advantage of increased biological containment by apparent elimination of the transmission of transgenes through pollen. We show that chloroplasts can express a secretory protein, human somatotropin, in a soluble, biologically active, disulfide-bonded form. High concentrations of recombinant protein accumulation are observed (>7% total soluble protein), more than 300-fold higher than a similar gene expressed using a nuclear transgenic approach. The plastid-expressed somatotropin is nearly devoid of complex post-translational modifications, effectively increasing the amount of usable recombinant protein. We also describe approaches to obtain a somatotropin with a non-methionine N terminus, similar to the native human protein. The results indicate that chloroplasts are a highly efficient vehicle for the potential production of pharmaceutical proteins in plants.

Blotting, Western↗
PubMed2000

Development of perfluorocarbon tracer technology for underground leak location.

A method has been developed for the atmospheric sampling and analysis of four perfluorocarbon tracer (PFT) compounds simultaneously at the parts per trillion (ppt) level. PFTs were pre-concentrated using adsorbent tube air sampling. Analysis was achieved by thermal desorption (TD) and gas chromatography (GC) with electron capture detection (ECD). Efficient separation of the PFTs from the other sample constituents was achieved by use of a capillary porous layer open tubular (PLOT) GC column without the need to cool the GC oven to sub-ambient temperatures using liquid coolants (M. de Bortoli and E. Pecchio, J. High Resolut. Chromatogr., 1985, 8, 422) or for a catalytic destruction step to remove interferents (T. W. D'Ottavio, R. W. Goodrich and R. N. Dietz, Environ. Sci. Technol., 1986, 20, 100). Results from test field trials with two volatile PFTs that were buried to simulate an underground leaking cable were successful. The PFTs were detected above ground level to pinpoint the leak position. The highest tracer concentrations were detected within 1 m of the simulated leak positions 2 days after tracer burial. The developed technology was applied to an oil leaking high voltage electricity cable. One PFT was added to the cable oil which enabled detection of the oil leak to within 3 m. The reported method has many advantages over currently used leak detection methods and could, in the future, be applied to the detection of underground leaks in a variety of cables and pipes.

Chromatography, Gas↗
PubMed2000

Optical biosensing of nitrite ions using cytochrome cd1 nitrite reductase encapsulated in a sol-gel matrix.

Nitrite is an important human health and environmental analyte. As such, the European Union (EU) has imposed a limit for nitrite in potable water of 0.1 mg l-1 (2.18 microM). In order to develop an optical biosensing system for the determination of nitrite ions in environmental waters, cytochrome cd1 nitrite reductase has been extracted and purified from the bacterium Paracoccus pantotrophus. The protein has been spectroscopically characterised in solution and important kinetic parameters of nitrite reduction of the cytochrome cd1 enzyme, i.e., Km, Vmax and kcat have been determined. The influence of pH on the activity of the cytochrome cd1 has been investigated and the results suggest that this enzyme can be used for the determination of nitrite in the pH range 6-9. Biosensing experiments with the cytochrome cd1 in solution suggested that the decrease in intensity of the absorption band associated with the d1 haem (which is the nitrite binding site), at 460 nm, with increasing nitrite concentrations would enable the measurement of this analyte with the optimum limit of detection. The cytochrome cd1 has been encapsulated in a bulk sol-gel monolith with no structural changes observed and retention of enzymatic activity. The detection of nitrite ions in the range 0.075-1.250 microM was achieved, with a limit of detection of 0.075 microM. In order to increase the speed of response, a sol-gel sandwich thin film structure was formulated with the cytochrome cd1. This structure enabled the determination of nitrite concentrations within ca. 5 min. The sol-gel sandwich entrapped cytochrome cd1 enzyme was found to be stable for several months when the films were stored at 4 degrees C.

Biosensing Techniques↗
PubMed2000

Effect of renal function on risedronate pharmacokinetics after a single oral dose.

AIMS: To determine the relationship between risedronate pharmacokinetics and renal function. METHODS: Risedronate was administered to adult men and women (n=21) with various degrees of renal function (creatinine clearance 15-126 ml min-1 ) as a single oral dose of 30 mg. Serum samples were obtained for 72 h after dosing, and urine samples were collected for 72 h after dosing and then periodically for 6 weeks. Risedronate concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). Risedronate serum concentration-time and urinary excretion rate-time profiles were analysed simultaneously using nonlinear regression. RESULTS: Renal clearance and volume of distribution were linearly related to creatinine clearance (r2=0.854, P<0.001; and r2=0.317, P<0.01, respectively). Decreases in predicted renal clearance and volume of distribution of 82 and 69%, respectively, were observed when creatinine clearance decreased from 120 to 20 ml min-1. A 64% decrease in predicted oral clearance was observed when creatinine clearance decreased from 120 to 20 ml min-1 (P=0.064). Iohexol clearance, a predictor of renal function, produced similar results to those observed with creatinine clearance. Risedronate was well tolerated by the study population. CONCLUSIONS: Risedronate renal clearance was significantly related to a decrease in renal function. There was a consistent reduction in oral clearance with a decrease in creatinine clearance. However, based on the regression analysis, generally no dosage adjustment appears to be necessary for most patients with mild or moderate renal impairment (creatinine clearance >20 ml min-1 ).

Administration, Oral↗
PubMed1999

Feasibility of antibody production in plants for human therapeutic use.

From the description above, the diversity of antibodies as a class of potential therapeutic agents is weighed against the constraints of developing any therapeutic molecule. Although much of this limit is specific to the antibody design, plant-based production systems have a potential to impact commercialization by making larger volume products manageable, with lower up-front capital requirements. Due to their novel glycosylation pattern (Faye et al. 1989), plants at present may not create antibodies with all the functions of mammalian-glycosylated antibodies (Wright and Morrison 1994). This is not a limit for all current products. Success is dependent on fusing the efficient agriculture infrastructure with the narrow tolerances required for a drug production system. Further validation of plants as a production system will come as more therapeutics from plants follow the corn-produced material through human clinical trials.

Antibodies, Monoclonal↗
PubMed1999

Optical biosensing of nitric oxide using the metalloprotein cytochrome c'.

The metalloprotein cytochrome c' was extracted and purified from the bacterium Paracoccus denitrificans in order to develop a specific biosensing system for nitric oxide (NO). The metalloprotein was encapsulated in a porous silicate sol-gel glass to enable spectroscopic changes in the haem centre as a function of NO ligation to be quantified using absorption measurements. Spectroscopic evidence suggested that, between 2 and 4 d after encapsulation, the cytochrome c' protein changed conformation in the locality of the haem moiety, possibly from a five to a six coordinate haem centre. Such conformational changes were also observed when the cytochrome c' was stored in solution, although over a 2-3 month period. The conformational changes occurring in the protein altered the spectral characteristics of the reduced, oxidised and nitrosyl complex of the cytochrome c' and appear to change the binding affinity of the protein towards NO. However, the encapsulated (reconformed) cytochrome c' was shown to retain its selectivity towards NO with good reproducibility (seven consecutive measurements of NO produced an intensity value with a relative standard deviation of 0.28%). An NO calibration curve, using the in situ release of NO from the donor diethylamine NONOate, was obtained for the encapsulated cytochrome c' with an approximate working range of 10-400 mumol l-1.

Biosensing Techniques↗
PubMed1999

The effect of dosing regimen on the pharmacokinetics of risedronate.

AIMS: To examine the effect of timing of a risedronate dose relative to food intake on the rate and extent of risedronate absorption following single-dose, oral administration to healthy male and female volunteers. METHODS: A single-dose, randomized, parallel study design was conducted with volunteers assigned to four treatment groups (31 or 32 subjects per group, 127 subjects total). Each subject was orally administered 30 mg risedronate. Group 1 was fasted for 10 h prior to and 4 h after dosing (fasted group); Groups 2 and 3 were fasted for 10 h and were dosed 1 and 0.5 h, respectively, before a high-fat breakfast; and Group 4 was dosed 2 h after a standard dinner. Blood and urine samples were collected for 168 h after dosing. Pharmacokinetic parameters were estimated by simultaneous analysis of risedronate serum concentration and urinary excretion rate-time data. RESULTS: Extent of risedronate absorption (AUC and Ae ) was comparable (P=0.4) in subjects dosed 2 h after dinner and 0.5 h before breakfast; however, a significantly greater extent of absorption occurred when risedronate was given 1 or 4 h prior to a meal (1.4- to 2.3-fold greater). Administration 0.5, 1, or 4 h prior to a meal resulted in a significantly greater rate of absorption (Cmax 2.8-, 3.5-, and 4.1-fold greater, respectively) when compared with 2 h after dinner. CONCLUSIONS: The comparable extent of risedronate absorption when administered either 0.5-1 h before breakfast or 2 h after an evening meal support previous clinical studies where risedronate was found to have similar effectiveness using these dosing regimens. This flexibility in the timing of risedronate administration may provide patients an alternative means to achieve the desired efficacy while maintaining their normal daily routine.

Absorption↗
PubMed1999

Significant differences in estradiol bioavailability from two similarly labelled estradiol matrix transdermal systems.

OBJECTIVE: To compare the bioavailabilities of estradiol delivered by two transdermal estradiol matrix systems; Alora and Evorel. STUDY DESIGN: A single-center, open-label, randomized, two-period cross-over study in 33 postmenopausal women. The subjects received two successive 84-h applications of either Alora or Evorel (each labelled to deliver 50 micrograms/day 17 beta-estradiol) in a randomized sequence. Serial serum samples, collected over the 84-h period following the application of the second patch, were analyzed for estradiol using a validated radioimmunoassay method. RESULTS: The fluctuation index produced by Evorel was significantly higher than that produced by Alora (Evorel, 135%; Alora, 76%; p < 0.0005). In addition, the estradiol baseline-corrected area under the curve for Evorel was significantly lower than that for Alora (Alora, 2871.8 pg h/ml; Evorel, 1870.6 pg h/ml; p < 0.0005). Both patches were found to be generally well tolerated. CONCLUSION: Alora delivered a higher, more consistent concentration of estradiol into the systemic circulation over the entire dosing interval than did Everol. Although the full clinical significance of these findings is currently unknown, this study demonstrates that there are significant differences in estradiol delivery from these two products, although they are labelled with the same nominal delivery rate.

Administration, Cutaneous↗
PubMed1998

Risedronate gastrointestinal absorption is independent of site and rate of administration.

PURPOSE: Two studies were conducted to compare the absorption of risedronate administered as a solution to three different gastrointestinal sites (study A) and to determine the extent of absorption of risedronate solution administered by rapid and slow infusion to the second part of the duodenum (study B). METHODS: Each study was designed as a single-dose, crossover (three periods, study A; two periods, study B) trial in healthy male subjects, with a 14-day washout period between dosing. Subjects fasted overnight before drug administration and for 4 hours after drug administration. In study A, a risedronate solution of 40 mg in 30 mL of water was administered directly into the stomach, the second part of the duodenum, or the terminal ileum over 1 minute via a nasoenteral tube in a three-period crossover design. In study B, a risedronate solution of 40 mg in 30 mL of water was administered directly into the second part of the duodenum over 1 minute and over 1 hour in a randomized, two-period crossover design. Serum and urine samples were obtained for 48 hours after dosing for risedronate analysis. RESULTS: Eight subjects completed each study. No statistically significant site-specific differences in any pharmacokinetic parameter were observed (study A). Based on the area under the serum concentration-time profile and the amount of drug excreted in the urine unchanged, the extent of risedronate absorption did not differ significantly following a rapid or a slow infusion (study B). Only minor symptomatic complaints were reported by subjects, such as headaches and body aches. CONCLUSIONS: These studies indicate that the rate and extent of risedronate absorption are independent of the site of administration along the gastrointestinal tract, and that the extent of absorption is not affected by the rate of administration.

Area Under Curve↗
PubMed1997

Tumour-localizing and tumour-photosensitizing properties of zinc(II)-octapentyl-phthalocyanine.

Zn(II)-octapentyl-phthalocyanine (ZnOPPc), incorporated into a Cremophor oil emulsion, was found to be a highly selective tumour-targeting agent (50-fold larger concentration in the tumour than in the peritumoral tissue) when injected at a dose of 1.46 mumol (kg body weight)-1 in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The pharmacokinetic properties of this phthalocyanine were closely similar to those found for the analogous octadecyl derivative, whereas the unsubstituted Zn(II)-phthalocyanine showed a lower efficiency and selectivity of tumour targeting than the octaalkyl-substituted phthalocyanines. Irradiation of the ZnOPPc-loaded tumour with 620-700 nm light 24 h after injection caused a significant delay of tumour growth with a gradual shrinkage of the neoplastic mass; the damage involved important contributions from both random necrosis and apoptosis of malignant cells.

Animals↗
PubMed1997

Tissue-specific expression in transgenic maize of four endosperm promoters from maize and rice.

The tissue-specific, developmental, and genetic control of four endosperm-active genes was studied via expression of GUS reporter genes in transgenic maize plants. The transgenes included promoters from the maize granule-bound starch synthase (Waxy) gene (zmGBS), a maize 27 kDa zein gene (zmZ27), a rice small subunit ADP-glucose pyrophosphorylase gene (osAGP) and the rice glutelin 1 gene (osGT1). Most plants had a transgene expression profile similar to that of the endogenous gene: expression in the pollen and endosperm for the zmGBS transgene, and endosperm only for the others. Histological analysis indicated expression initiated at the periphery of the endosperm for zmGBS, zmZ27 and osGT1, while osAGP transgene activity tended to start in the lower portion of the seed. Transgene expression at the RNA level was proportional to GUS activity, and did not influence endogenous gene expression. Genetic analysis showed that there was a positive dosage response with most lines. Activity of the zmGBS transgene was threefold higher in a low starch (shrunken 2) genetic background. This effect was not seen with zmZ27 or osGTI transgenes. The expression of the transgenes is discussed relative to the known behaviour of the endogenous genes, and the developmental programme of the maize endosperm.

Blotting, Southern↗
PubMed1997

Excited state properties of the siderophore pyochelin and its complex with zinc ions.

The critical effects of pH on the electronic absorption and fluorescence characteristics of the siderophore, pyochelin, are investigated. A single anionic species is shown to be sufficient to explain the data obtained under alkaline conditions. In acidic solutions, several competing ground- and excited-state equilibria are present, which lead to fluorescence emissions from both the protonated form of pyochelin and its phenolate ion. From the spectroscopic data we are also able to show that pyochelin interacts with zinc ions in the ground state via its anionic form, thereby confirming that this siderophore does not bind Fe(III) ions uniquely.

Chromatography, High Pressure Liquid↗
PubMed1996

Peripheral administration of Interleukin-1 Receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat.

We assessed the efficacy of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) on brain injury and edema formation after permanent middle cerebral artery occlusion (MCAo) in the rat. Previous studies showed that low amounts of rhIL-1ra injected directly into the brain significantly decreased infarct size after MCAo or excitotoxic injury in rats. Peripheral administration of rhIL-1ra (100 mg/kg sc at 0, 4, 8, 12, and 18 h after MCAo) significantly inhibited infarct size, by 46% (P < 0.05), measured at 24h. This was greater than the effect of MK801 administered immediately after MCAo (4 mg/kg ip, 0 h) which did not significantly reduce infarct size. rhIL-1ra (100 mg/kg also significantly inhibited cerebral edema formation by 49% (p< 0.05 measured 24 h after MCAo, but did not reduce edema formation measured 2 h after MCAo, but did not reduce edema formation measured 2 h after MCAo. Inhibition of infarction by rhIL-1ra was dependent on dose and time of administration. Together the results demonstrate that peripherally administered rhIL-1ra at high doses is able to mimic the efficacy of low dose of rhIL-1ra administered directly into the brain in a rodent model of stroke and that protection observed with rhIL-1ra was better than that offered by MK801 in this model.

Animals↗