bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a limited sampling method used to determine the bioequivalence of highly variable drugs with long half‐lives
Authors: Jackson Andre J. 
Published: August 2002

AbstractThe usefulness of a limited sampling method (LSM) to determine the bioequivalence of highly variable drugs with long half‐lives was investigated. The LSM uses multiple linear regression of observed drug plasma concentrations versus area under the curve (AUC) or Cmax (peak plasma concentration) to obtain a best set of coefficients, concentration times and intercept based upon the regression coefficient, R2, to predict the selected pharmacokinetic parameter (i.e. AUC or Cmax). The LSM, used successfully in clinical settings, has also been suggested for data analysis of in vivo bioequivalence studies. Because the method has not yet been thoroughly tested under many conditions likely to be encountered in bioequivalence studies, a further investigation of the method's applicability to bioequivalence determination was undertaken. In the present study, training and test data sets incorporating various levels of intrasubject variability in clearance (CL) with different ratios for fraction absorbed (Fa) of test and reference drug formulations were used to further evaluate the applicability of the limited sampling method (LSM) to the evaluation of bioequivalence for drugs with long half‐lives of elimination. Both simulated (a one‐compartment pharmacokinetic (PK) model with first‐order elimination) and experimental data were used in the study. The results indicated that the determination of bioequivalence using the LSM was significantly influenced by the ratio of Fa(test)/Fa(reference) and by the level of intrasubject error (variability) in CL. Therefore, use of the LSM to determine bioequivalence of drugs with long half‐lives and highly variable in CL seems suitable only for formulations that have point estimates of Fa(test)/Fa(reference) within the range of 0.9–1.10. Because the Fa ratio range would have to be verified through use of observed data obtained from a pilot study, the practical utility of the LSM in the determination of bioequivalence would be severely limited. Copyright © 2001 John Wiley & Sons, Ltd.
Biomedical applications of capillary electrophoresis with laser‐induced fluorescence detection
Authors: Páez Ximena , Hernández Luis 
Published: August 2002

AbstractCapillary electrophoresis (CE) is a high‐efficiency analytical technique that has had a great impact as a tool in biomedical research, clinical and forensic practice in the last ten years. Only in one of the applications, the DNA analysis, it has had an explosive exponential growth in the last few years. This impact is expressed in an enormous amount of CE articles and many reviews. The CE advantages with respect to other analytical techniques: the required very small sample volume, rapid analysis, great resolution power and low costs, have made this technique ideal for the analysis of a numerous endogenous and exogenous substances present in biological fluids. The different modes of CE have been coupled to different detection techniques such as UV‐absorbance, electrochemical, mass spectrometry and laser‐induced fluorescence detection (LIFD) to detect different nature and molecular size separated analytes. This review focuses mostly on the applications of CE–LIFD, to measure drugs and endogenous neuroactive substances such as amino acids and monoamines, especially in microdialysis samples from experimental animals and humans. CE–LIFD trends are discussed: automated faster analysis with capillary array systems, resolution power improvement, higher detection sensitivity, and CE systems miniaturization for extremely small sample volume, in order to make CE easier and affordable to the lab bench or the clinical bed. Copyright © 2001 John Wiley & Sons, Ltd.
Analysis and screening of combinatorial libraries using mass spectrometry
Authors: Shin Young Geun , van Breemen Richard B. 
Published: August 2002

AbstractMass spectrometry is a highly selective and high throughput analytical technique that is ideally suited for the identification and purity determination of large numbers of compounds prepared using combinatorial chemistry or for the dereplication of natural products. Compounds may be characterized based on molecular weight, elemental composition and structural features based on fragmentation patterns. When coupled to a separation technique such as high‐performance liquid chromatography (HPLC) or capillary electrophoresis, mass spectrometric applications may be expanded to include analysis of complex mixtures. However, the slower speed of the separation step reduces the throughput of the analysis. This review concerns the application of mass spectrometry to the characterization of combinatorial libraries and the screening of library and natural product mixtures. Strategies to enhance the throughput of LC–MS are discussed including fast HPLC and parallel LC–MS. Also, mass spectrometry‐based screening methods are described including frontal affinity chromatography–mass spectrometry, gel permeation chromatography LC–MS, direct electrospray mass spectrometry of receptor–ligand complexes, affinity chromatography–mass spectrometry, and pulsed ultrafiltration mass spectrometry. Copyright © 2001 John Wiley & Sons, Ltd.
NF‐κB DNA‐binding activity after high peak power pulsed microwave (8.2 GHz) exposure of normal human monocytes
Authors: Natarajan Mohan , Vijayalaxmi  , Szilagyi Maria , Roldan Francis N. , Meltz Martin L. 
Published: August 2002

AbstractThe hypothesis investigated is that exposure of a mammalian cell to high peak power pulsed RF, at the frequency of 8.2 GHz, can result in the activation of an important eukaryotic transcriptional regulator, nuclear factor kappa B (NF‐κB). This DNA‐binding protein controls genes involved in long term cellular regulation. The selection of 8.2 GHz was based on the availability of a high peak power pulsed RF transmitter. In these studies, triplicate cultures of human monocytes (Mono Mac‐6) were exposed to the pulsed wave radiation. The peak to average power ratio was 455:1 (2.2 μs pulse width and pulse repetition rate of 1000 pulses/s). The average power density at the position of exposure was 50 W/m2, and the mean SAR at the bottom of the culture flask was 10.8 ± 7.1 W/kg. The FDTD analysis indicated that 10% of the cells had an SAR of 22–29 W/kg. The cells were exposed continuously for 90 min at 37 °C, reincubated at this temperature, and harvested 4 h postexposure. The nuclear extracts were analyzed by electrophoretic mobility shift assay. The results showed a profound increase (3.6‐fold) in the DNA binding activity of NF‐κB in monocytes at 4 h after the pulsed RF exposure compared to sham irradiated controls. Competition experiments with cold NF‐κB‐ specific oligonucleotides confirmed the specificity of the DNA binding activity. These results provide evidence that high peak power pulsed radiofrequency radiation can perturb the cell and initiate cell signaling pathways. However, at this point, we are not prepared to advocate that the cause is a nonthermal mechanism. Because of the broad distribution of SAR's in the flask, experiments need to be performed to determine if the changes observed are associated with cells exposed to high or low SARs. Bioelectromagnetics 23:271–277, 2002. © 2002 Wiley‐Liss, Inc.
No effects of pulsed radio frequency electromagnetic fields on melatonin, cortisol, and selected markers of the immune system in man
Authors: Radon K. , Parera D. , Rose D.‐M. , Jung D. , Vollrath L. 
Published: August 2002

AbstractThere is growing public concern that radio frequency electromagnetic fields may have adverse biological effects. In the present study eight healthy male students were tested to see whether or not radio frequency electromagnetic fields as used in modern digital wireless telecommunication (GSM standard) have noticeable effects on salivary melatonin, cortisol, neopterin, and immunoglobulin A (sIgA) levels during and several hours after exposure. In a specifically designed, shielded experimental chamber, the circularly polarized electromagnetic field applied was transmitted by an antenna positioned 10 cm behind the head of upright sitting test persons. The carrier frequency of 900 MHz was pulsed with 217 Hz (average power flux density 1 W/m2). In double blind trials, each test person underwent a total of 20 randomly allotted 4 hour periods of exposure and sham exposure, equally distributed at day and night. The results obtained show that the salivary concentrations of melatonin, cortisol, neopterin and sIgA did not differ significantly between exposure and sham exposure. Bioelectromagnetics 22:280–287, 2001. © 2001 Wiley‐Liss, Inc.
AMP‐activated protein kinase: the energy charge hypothesis revisited
Authors: Hardie D. Grahame , Hawley Simon A. 
Published: August 2002

AbstractThe AMP‐activated protein kinase cascade is a sensor of cellular energy charge, and its existence provides strong support for the energy charge hypothesis first proposed by Daniel Atkinson in the 1960s. The system is activated in an ultrasensitive manner by cellular stresses that deplete ATP (and consequently elevate AMP), either by inhibiting ATP production (e.g., hypoxia), or by accelerating ATP consumption (e.g., exercise in muscle). Once activated, it switches on catabolic pathways, both acutely by phosphorylation of metabolic enzymes and chronically by effects on gene expression, and switches off many ATP‐consuming processes. Recent work suggests that activation of AMPK is responsible for many of the effects of physical exercise, both the rapid metabolic effects and the adaptations that occur during training. Dominant mutations in regulatory subunit isoforms (γ2 and γ3) of AMPK, which appear to increase the basal activity in the absence of AMP, lead to hypertrophy of cardiac and skeletal muscle respectively. BioEssays 23:1112–1119, 2001. © 2001 John Wiley & Sons, Inc.
Control of developmental timing by small temporal RNAs: a paradigm for RNA‐mediated regulation of gene expression
Authors: Banerjee Diya , Slack Frank 
Published: August 2002

AbstractHeterochronic genes control the timing of developmental programs. In C. elegans, two key genes in the heterochronic pathway, lin‐4 and let‐7, encode small temporally expressed RNAs (stRNAs) that are not translated into protein. These stRNAs exert negative post‐transcriptional regulation by binding to complementary sequences in the 3′ untranslated regions of their target genes. stRNAs are transcribed as longer precursor RNAs that are processed by the RNase Dicer/DCR‐1 and members of the RDE‐1/AGO1 family of proteins, which are better known for their roles in RNA interference (RNAi). However, stRNA function appears unrelated to RNAi. Both sequence and temporal regulation of let‐7 stRNA is conserved in other animal species suggesting that this is an evolutionarily ancient gene. Indeed, C. elegans, Drosophila and humans encode at least 86 other RNAs with similar structural features to lin‐4 and let‐7. We postulate that other small non‐coding RNAs may function as stRNAs to control temporal identity during development in C. elegans and other organisms. BioEssays 24:119–129, 2002. © 2002 Wiley Periodicals, Inc.
How do features of sensory representations develop?
Authors: Kaas Jon H. , Catania Kenneth C. 
Published: August 2002

AbstractSensory representations in the brainstem and cortex have a number of features that support the idea that neural activity patterns are important in their development. Many of these features vary across species in ways that could result from perturbances in the balance of the effects of activity patterns and position‐dependent gene expression. (1) Most notably, disruptions or septa in sensory maps often reflect actual discontinuities in the receptor sheet, and the discontinuities may be reflected in a series of interconnected maps. Species with different disruption patterns in sensory sheets have different matching disruption patterns in the sensory maps and variant individuals and strains of the same species have matching variations in the receptor disruption patterns and their sensory maps. (2) In addition, mutations that misdirect some of the retinal afferents from one side of the brain to the other create new sensory maps that preserve continuities in the altered pattern of input, while creating new structural discontinuities. (3) Furthermore, functionally different classes of afferents that are mixed in the receptor sheet often segregate to activate separate populations of target cells. (4) Finally, early developing portions of receptor sheets may gain more than their share of territory in sensory maps. These and other variable features of sensory maps are most readily accommodated by theories that involve roles for instruction by evoked and spontaneous neural activity patterns. BioEssays 24:334–343, 2002. ©2002 Wiley Periodicals, Inc.
Mid‐IR microspectroscopic imaging of breast tumor tissue sections
Authors: Fabian H. , Lasch P. , Boese M. , Haensch W. 
Published: August 2002

AbstractIR microspectroscopic imaging is a relatively new approach for the examination of tissue sections. In contrast to standard light microscopy based procedures, the IR approach requires neither sample staining nor fixation. The IR spectra of breast tumor tissue sections are obtained via a microscope equipped with a focal plane array detector. This enabled the simultaneous collection of individual mid‐IR spectra from thousands of different sample positions with a spatial resolution near the diffraction limit. The analysis of the IR data reveals a high sensitivity of the IR approach toward changes in tissue biochemistry and variations in breast tissue architecture. Moreover, the data demonstrate the need for collecting spectra with high spatial resolution at the level of individual cells. This minimizes problems associated with tissue microheterogeneity and is an essential prerequisite for future studies aimed at developing IR microspectroscopic imaging as a complement to present diagnostic tools for breast cancer. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 354–357, 2002
Spatially resolved IR microspectroscopy of single cells
Authors: Lasch Peter , Pacifico Anthony , Diem Max 
Published: August 2002

AbstractFourier transform IR (FTIR) microspectroscopy at a spatial resolution of 18 μm was used to study skin fibroblasts and giant sarcoma cells. Both cell lines were derived from the same patient; they were metabolically active and in the exponentially growing phase. The IR spectra were acquired for the nuclei and cytosol of untreated cells, cells washed with ethanol, and cells treated with RNase or DNase. A comparison of the spectra of the two cell lines yielded only insignificant spectral differences, indicating that IR spectroscopy monitors the overall cell activity rather than specific signs of cancer. © 2002 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 67: 335–338, 2002
Thiosulphate improves yield of hydrogen production from glucose by the immobilized formate hydrogenlyase system of Escherichia coli
Authors: Nandi R. , Dey S. , Sengupta S. 
Published: August 2002

AbstractEscherichia coli cells with formate hydrogenlyase activity that were immobilized in agar beads produced hydrogen from glucose at the approximate yield of 0.6 mole of hydrogen per mole. Succinate or thiosulphate added to glucose increased hydrogen production two‐fold. Thiosulphate did not increase the rate of hydrogen production but reduced the consumption of glucose for the same amount of hydrogen produced compared to control. Oxaloacetate and traces of pyruvate instead of succinate accumulated at the end when thiosulphate was present. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 492–494, 2001.
Microbial synthesis of p‐hydroxybenzoic acid from glucose
Authors: Barker Jessica L. , Frost J. W. 
Published: August 2002

AbstractA series of recombinant Escherichia coli strains have been constructed and evaluated for their ability to synthesize p‐hydroxybenzoic acid from glucose under fed‐batch fermentor conditions. The maximum concentration of p‐hydroxybenzoic acid synthesized was 12 g/L and corresponded to a yield of 13% (mol/mol). Synthesis of p‐hydroxybenzoic acid began with direction of increased carbon flow into the common pathway of aromatic amino acid biosynthesis. This was accomplished in all constructs with overexpression of a feedback‐insensitive isozyme of 3‐deoxy‐D‐arabino‐heptulosonic acid 7‐phosphate synthase. Expression levels of enzymes in the common pathway of aromatic amino acid biosynthesis were also increased in all constructs to deliver increased carbon flow from the beginning to the end of the common pathway. A previously unreported inhibition of 3‐dehydroquinate synthase by L‐tyrosine was discovered to be a significant impediment to the flow of carbon through the common pathway. Chorismic acid, the last metabolite of the common pathway, was converted into p‐hydroxybenzoic acid by ubiC‐encoded chorismate lyase. Constructs differed in the strategy used for overexpression of chorismate lyase and also differed as to whether mutations were present in the host E. coli to inactivate other chorismate‐utilizing enzymes. Use of overexpressed chorismate lyase to increase the rate of chorismic acid aromatization was mitigated by attendant decreases in the specific activity of DAHP synthase and feedback inhibition caused by p‐hydroxybenzoic acid. The toxicity of p‐hydroxybenzoic acid towards E. coli metabolism and growth was also evaluated. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 76: 376–390, 2001.
Numerical simulation of convective and diffusive transport effects on a high‐pressure‐induced inactivation process
Authors: Hartmann Chr. , Delgado A. 
Published: August 2002

AbstractHigh‐pressure‐induced conversions, such as the inactivation of enzymes or of microorganisms, are dependent on the applied pressure and the temperature of the process. The former can be considered to be a spatially homogeneous quantity, while the latter, being a transport quantity, varies over space and time. Here we question whether the uniformity of a high‐pressure conversion can be disturbed by convective and conductive heat and mass transport conditions. Enzyme inactivation is taken as a model process for a high‐pressure conversion. To cover a broad range of parameters and to consider scale‐up effects, the investigation is based on mathematical modeling and numerical simulation for different sizes of the pressure chamber and different solvent viscosities. Apart from viscosity, the physical properties of the enzyme solutions are assumed to be identical in all cases. Therefore, matrix effects other than that of viscosity are excluded. Moreover, the authors postulate that viscosity solely acts on the continuum mechanical scale of momentum exchange but not on the molecular scale on the inactivation kinetics. It has been found that nonuniform thermal conditions can strongly influence the result of a high‐pressure process. A variation of the activity retention between 28% and 48% can be observed after 20 minutes for a 0.8‐L high‐pressure chamber and a matrix fluid with a viscosity comparable to that of edible oils. The same process carried out in a 6.3‐L device leads to an activity retention that varies between 16% and 40%. From the analysis of the time scales for the inactivation and for hydrodynamic and thermal compensation, it can be deduced that a nonuniform activity retention has to be expected if the inactivation time scale is larger than the hydrodynamic time scale and smaller than the thermal compensation time scale. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 94–104, 2002
Improving biomaterial properties of collagen films by chemical modification
Authors: Tiller Joerg C. , Bonner Gary , Pan Li‐Chun , Klibanov Alexander M. 
Published: August 2002

AbstractFilms of bovine collagen were chemically modified with the goal of improving their biomaterial properties. The modified films were investigated with respect to their affinity to fibroblast and endothelial cells, as well as their antibacterial properties tested by adhesion of Staphylococcus aureus. Modifications that only change the net charge of collagen, such as acetylation, succinylation, and treatment with glutaraldehyde (all increase the negative charge), and amination with ethylenediamine (EDA), N,N‐dimethyl‐EDA (DMEDA), or butylamine (all increase the positive charge), did not dramatically alter the mammalian cell attachment to the film. In contrast, derivatization of collagen using methoxypoly(ethylene glycol) (PEG) diminished the attachment of fibroblasts by 98 ± 1% and of endothelial cells by more than 99% compared to unmodified collagen. Moreover, the rate of growth of fibroblasts dropped by 97 ± 1% and that of endothelial cells by 88 ± 3% as a result of PEGylation of collagen. Adhesion of S. aureus cells also plummeted by 93 ± 2% as a result of this PEGylation. With these antifouling properties, PEG‐collagen may be a promising coating material for coronary stents. Sub‐ sequent derivatization of PEG‐collagen with EDA or DMEDA abolished its mammalian cell‐repelling ability, whereas bacterial cell repulsion was partially retained: for example, DMEDA‐modified PEG‐collagen exhibits up to a 5‐fold lower bacterial adhesion than collagen. It is worth noting that a material that allows mammalian cell attachment but reduces bacterial adhesion could be useful as an implant or coating. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 73: 246–252, 2001.
Identification of novel polyphenol oxidase inhibitors by enzymatic one‐pot synthesis and deconvolution of combinatorial libraries
Authors: de la Gôutte Jérome Tricand , Khan Jeffrey A. , Vulfson Evgeny N. 
Published: August 2002

AbstractThe feasibility of enzymatic synthesis of combinatorial libraries using multifunctional starting materials [i.e., 2,4‐dihydroxy‐N‐(2‐hydroxyethyl)benzamide, 1; 4‐hydroxyphenethyl alcohol, 2; 3,5‐dihydroxybenzyl alcohol, 3; and 4‐hydroxybenzyl alcohol, 4] with six vinyl esters, in a one‐pot reaction, was investigated. Candida antarctica lipase was employed as a biocatalyst. The resulting 24‐compound library contained all the expected species with no significant bias toward particular combinations of substrates. As expected, the library contained a substance(s) that showed significant inhibition of polyphenol oxidase, which was used as a model target. The deconvolution was accomplished via resynthesis of ten partial libraries, which were prepared with either an equimolar mixture of the four alcohols and a single vinyl ester, or a single alcohol and equimolar mixture of the activated esters. Analysis of the inhibition pattern observed with these partial libraries suggested that 4‐hydroxybenzyl benzoate (4e) should be the most potent inhibitor. This conclusion was confirmed by the preparation and comparison of all 24 components of the initial library. Finally, it was shown that 4e was a competitive inhibitor of polyphenol oxidase, with a Ki of 40 μM. This value compared favorably with a Ki of 400 μM, which was determined for parent phenol 4. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 93–99, 2001.