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A fractal analysis of analyte-estrogen receptor binding and dissociation kinetics using biosensors: environmental and biomedical effects.

A fractal analysis is used to model the binding and dissociation kinetics between analytes in solution and estrogen receptors (ERs) immobilized on a sensor chip of a surface plasmon resonance (SPR) biosensor. The influence of different ligands is also analyzed. A better understanding of the kinetics provides physical insights into the interactions, and suggests means by which appropriate interactions (to promote correct signaling) and inappropriate interactions such as with xenoestrogens (to minimize inappropriate and deleterious to health signaling) may be better controlled. The fractal approach is applied to analyte-ER interaction data available in the literature. The units for the different parameters (rate coefficients and affinities) in fractal-type kinetics are different from those obtained in classical kinetics. Numerical values obtained for the binding and the dissociation rate coefficients are linked to the degree of roughness or heterogeneity (fractal dimension, D(f)) present on the biosensor chip surface. In general, the binding and the dissociation rate coefficients are very sensitive to the degree of heterogeneity on the surface. A single-fractal analysis is adequate in some cases. In others (that exhibit complexities in the binding or the dissociation curves) a dual-fractal analysis is required to obtain a better fit. This has biomedical and environmental implications in that the dissociation (and the binding) rate coefficient may be used to alleviate (deleterious effects) or enhance (beneficial effects) by selective modulation of the surface. The affinity values obtained in the analysis are consistent with the numbers required to (a). promote signaling between the correct analyte and the estrogen receptor, and (b). minimize the signaling between xenoestrogens and the estrogen receptor.

Biomedical Technology↗

In vitro toxicology methods: impact on regulation from technical and scientific advancements.

The impressive advancement of technologies in biomedical research, and particularly in the area of in vitro experimental models, has opened up new possibilities related to co-cultures, micromass or stem cell cultures. Engineered cells to study specific targets and/or mechanisms are also available. Moreover, a very subtle approach in the study of toxicological effects is represented by the very recent genomics and proteomics techniques. New mechanistically based methods could be established from all these approaches, which, once validated, could enter the regulatory procedure. So far, in toxicology, only a few in vitro tests are accepted for regulatory purposes, such as those related to corrosion, phototoxicity and absorption. Many others are in the pre-validation or validation phase. An area where in vitro tests play a key role is the genetic toxicology. In this context, the most recent testing strategies and test methods will be presented, with particular attention to the recently updated guidelines for food additives by the EU Scientific Committee on Food. An improvement in the implementation of validated methods could arise from a better coordination on the matter at national and international levels, the harmonisation of different legislations, and a strict control of the national rules in order to make them up-to-date with respect to validated methods.

Animals↗

Pharmaceutical and biomedical applications of enantioseparations using liquid chromatographic techniques.

The chiral separation methods using liquid chromatographic techniques can be divided into two categories: one is a direct method, which is based on a diastereomer formation on stationary phase or in mobile phase. The other is an indirect method, which is based on a diasteromer formation by reaction with a homochiral reagent. The enantiomer separation on a chiral stationary phases followed by derivatization with an achiral reagent is also dealt with this review article as the indirect method. The pharmaceutical and biomedical applications of enantioseparations using the direct and indirect methods have been considered in this review.

Biomedical Technology↗

Selected fundamental aspects of chiral electromigration techniques and their application to pharmaceutical and biomedical analysis.

While capillary electrophoresis has been established as a major enantioseparation technique within the last decade, the potential of capillary electrochromatography is still studied extensively. This review summarizes recent applications of electromigration techniques with regard to the enantioseparation of chiral drugs. The first part discusses the general aspects of migration models and the enantiomer migration order. The application of capillary electrophoresis to chiral pharmaceutical analysis considers recent literature on: (1) chiral resolutions of non-racemic mixtures of enantiomers for the development of assays and the determination of the stereochemical purity of the drugs, (2) chiral separations of compounds in pharmaceutical formulations and products, and (3) enantioseparations of drugs in biological samples. A shorter section devoted to chiral electrochromatography discusses some fundamental aspects as well as the application to the chiral analysis of drugs including bioanalysis.

Biomedical Technology↗

Bioanalytical applications of polyion-sensitive electrodes.

Recent developments in the design and bioanalytical applications of polyion-sensitive electrodes (PSEs) are reviewed. The general electrochemical principles governing the potentiometric response of such polymer membrane-based devices are summarized and new directions for the use of these novel sensors are detailed. These new directions include basic fundamental studies aimed at determining the thermodynamics of polyion extraction into ion exchanger-doped polymeric membranes, new methods to quantitate the anticoagulant drug heparin in whole blood via titrations with polycationic protamine, selective assays of protease activities (and inhibitors of such activities) using natural and synthetic polyionic peptides as substrates, and novel homogeneous immunoassay schemes based on potentiometric polyion detection.

Biology↗

Will the nation need more cardiologists in the future than are being trained now?

This article supports the view that in the future our nation will need more general cardiologists who perform no high-tech procedures than we are currently training. It also addresses the reason graduates of American medical schools, especially women who make up 40% to 50% of the graduating class, are not choosing cardiology fellowship programs as they were previously. A remedy for this serious problem is offered.

Biomedical Technology↗

Segmental anatomy of the temporal bone.

More of us suffer from hearing loss than from visual impairment, coronary artery disease, and cancer combined. Auditory dysfunction is detected in less than one third of newborns afflicted and is underdiagnosed in the elderly. Despite biomedical and technological advances, our understanding of vestibular dysfunction has grown little. Forming part of the lateral and inferior surfaces of the skull, the temporal bone contains the organs of hearing and balance. Diagnosis of diseases in these important regions requires adequate clinical information and a thorough knowledge of normal temporal bone anatomy to recognize abnormal findings when present. This article dissects the temporal bone into segments, describes the relevant radiologic anatomy of each, and discusses the imaging appropriate to specific concerns.

Anatomy, Cross-Sectional↗

Microchip electrophoretic separation systems for biomedical and pharmaceutical analysis.

The application of microchip capillary electrophoresis (CE) systems to biomedical and pharmaceutical analysis is described and reviewed. Fabrication, instrumentation, and operation of the systems are discussed. An overview of applications is presented, covering four main areas: DNA sequencing, genetic analysis, immunoassays, and protein and peptide analysis. These systems have the potential to dramatically change the way that biochemical analyses are performed.

Animals↗

Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications.

This review presents a critical analysis of covalently and ionically crosslinked chitosan hydrogels and related networks for medical or pharmaceutical applications. The structural basis of these hydrogels is discussed with reference to the specific chemical interactions, which dictate gel formation. The synthesis and chemistry of these hydrogels is discussed using specific pharmaceutical examples. Covalent crosslinking leads to formation of hydrogels with a permanent network structure, since irreversible chemical links are formed. This type of linkage allows absorption of water and/or bioactive compounds without dissolution and permits drug release by diffusion. pH-controlled drug delivery is made possible by the addition of another polymer. Ionically crosslinked hydrogels are generally considered as biocompatible and well-tolerated. Their non-permanent network is formed by reversible links. Ionically crosslinked chitosan hydrogels exhibit a higher swelling sensitivity to pH changes compared to covalently crosslinked chitosan hydrogels. This extends their potential application, since dissolution can occur in extreme acidic or basic pH conditions.

Biomedical Technology↗

UK strategy for process qualification/validation: from concept to practical implementation.

In this communication, after a brief review of current requirements of various stages of leucodepletion qualification/validation processes, we provide some practical examples for the usefulness of long term validation programme for process improvement. It is hoped that the experience gained from this process qualification/validation enhances the awareness to key variables that can influence the overall outcome of filtration programme.

Biomedical Technology↗

Reliability and validity of a multi-pad pressure evaluator for pressure ulcer management.

It is often helpful to assess the pressures exerted upon the bony prominences when monitoring the likely outcome of pressure ulcer prevention or treatment. However, in the clinical setting, hard pressure sensors may damage the skin and operational difficulties may influence their reliability and validity. The authors have developed a multi-pad pressure sensor and tested its clinical reliability and validity. The inter-rater and intra-rater reliability were calculated using the coefficient of variation data from 10 patients. After a comparison analysis, the multi-pad was more reliable than a single-pad type pressure sensor. A validation test was conducted in 79 elderly patients. The mean interface pressures recorded among patients who had erythema or stage I pressure ulcers at the sacrum were significantly higher than were the contact pressures measured in patients with no pressure damage. The pressure sensor exhibited satisfactory clinical reliability and validity. Furthermore, it may be that for Japanese elderly patients the maximum pressure that can be tolerated by the tissues around the sacrum may be 40-50 mmHg.

Aged↗

Antisense phosphorothioate oligodeoxyribonucleotide targeted against ICAM-1: synthetic and biological characterization of a process-related impurity formed during oligonucleotide synthesis.

A phosphorothioate-linked oligonucleotide bearing a 3'-terminal phosphorothioate monoester has been synthesized and characterized. This oligonucleotide has been identified as a process-related impurity formed during synthesis of ISIS 2302. Biological properties of the compound have been determined. Based on these data, it can be concluded that this species (3'-TPT) has biological properties similar to parent drug.

Animals↗

Practical quantitative biomedical applications of MALDI-TOF mass spectrometry.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) is used to obtain fast and accurate determinations of molecular mass, but quantitative determinations are generally made by other techniques. In this study we illustrate the practical utility of automated MALDI-TOFMS as a tool for quantifying a diverse array of biomolecules covering an extensive molecular weight range, and present in biological extracts and fluids. Growth hormone was measured in rat pituitary tissue; insulin in human pancreatic tissue; homovanillic acid in human urine; and LVV-hemorphin-7, epinephrine and norepinephrine in human adrenal and pheochromocytoma tissues. Internal standards including compounds of similar molecular weight, structural analogs or isotopomers were incorporated into each analysis. We report on the current practical limitations of quantitative MALDI-TOFMS and highlight some of the potential benefits of this technique as a quantitative tool.

Adrenal Glands↗