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Analytical applications and implications of intramolecular micelle-mimetic ionene aggregates.

The synthesis and relevant properties of some cationic polyelectrolytes of the [x,y]-ionene type (i.e., molecules consisting of dimethylammonium charge centers interconnected by alternating alkyl chain segments containing x and y methylene groups) are described. Such hydrophobic ionenes can form intramolecular aggregates and function as micelle-mimetic agents since they mimic the key properties of traditional surfactant micelles (such as hexadecyltrimethylammonium bromide) in many respects. However, the ionenes possess certain important advantages over surfactant micelles. For example, aqueous ionene-containing solutions exhibit much less foaming and analyte molecules can be extracted and recovered from their solutions by use of organic solvents. In this work, some applications of the ionenes in analytical chemistry, such as their use as mobile phase additives for thin-layer chromatographic and capillary electrophoretic separations, as fluorescence enhancement agents, and as a means to catalyze slow spectroscopic derivatization reactions are demonstrated. In addition, other potential advantages concerning the utilization of the micelle-mimetic ionenes in chemical analysis applications are mentioned.

Cations↗

Nitrogen absorption, translocation and distribution from urea applied in autumn to leaves of young potted apple (Malus domestica) trees.

We studied the absorption, assimilation, translocation and distribution of nitrogen (N) from urea applied in autumn to leaves of 1-year-old potted Fuji/M26 apple (Malus domestica Borkh) trees. In early October, all leaves of each tree were painted with either 3% urea (enriched to 10 atom % with 15N) or water (control trees). Four trees were harvested before the treatment and N and amino acid contents were determined. Four trees from each treatment were harvested at 2, 4, 7, 10, 15 and 20 days after urea or water application. Total N, amino acids and 15N in leaves, bark, xylem, shank and roots were analyzed to determine uptake and mobilization of N from urea. Most uptake of 15N by leaves occurred during the first 2 days following application of urea. The mean rate of absorption during these 2 days was 0.29 g m-2 day-1. Amino acids in leaves, bark and roots increased significantly after urea application compared with control values. The highest concentrations of amino acids in leaves and bark occurred 4 days after application, whereas the highest concentrations of amino acids in roots occurred 10 days after application. Total 15N content in leaves peaked 2 days after urea application and then decreased, whereas 15N content in roots and bark increased throughout the experiment. Total 15N content in xylem and shank was low. Leaves absorbed 35% of the 15N applied as urea, and 63.6% of absorbed 15N was translocated out of leaves within 20 days after urea application. We conclude that N from urea was converted to amino acids in leaves after foliar application in autumn, and roots and bark were the main sinks of N from urea applied to leaves.

Absorption↗

Development and validation of a method for determination of caffeine in diuretic tablets and capsules by high-performance thin-layer chromatography on silica gel plates with a concentration zone using manual spotting and ultraviolet absorption densitometry.

A new quantitative method using silica gel high-performance thin-layer chromatography plates with channels and a concentration zone, manual application of standards and samples, development with methanol-ethyl acetate (15 + 85) mobile phase, and ultraviolet absorption densitometry is reported for the determination of caffeine in diuretic pharmaceutical preparations. Tablet and capsule products containing potassium salicylate, acetaminophen, and salicylamide as active ingredients were analyzed to test the applicability of the new method, and precision, accuracy, linearity, limits of detection and quantitation, and selectivity were validated. The milligrams of caffeine in each tablet ranged from 48.0 to 51.0, and the milligrams in each capsule from 37.9 to 40.3. Within-day precision was 1.48 and 1.78% (n=6), and interday precision 0.723 and 1.26% (n=5) for analysis of 2 tablets and 2 capsules, respectively. Accuracy validation of the tablet and capsule results produced errors of 1.0 and 1.9% for spiked blank analyses and 2.6 and 3.5% for standard addition analyses, respectively. A comparative study using a caffeine standard solution and a multicomponent analgesic tablet solution containing caffeine, acetaminophen, and acetylsalicylic acid showed that manual application on the concentration zone, instrumental application on the concentration zone, and instrumental application on the silica gel gave quite similar results in terms of number of theoretical plates, resolution, limit of detection, and linearity.

Acetaminophen↗

Quantitation of the nitrosamine 2-ethylhexyl-4-(N-methyl-N-nitrosoamino) benzoate (NPABAO) in sunscreen products.

We have devised a method to quantitate the nitrosamine, 2-ethylhexyl-4-(N-methyl-N-nitrosoamino) benzoate (NPABAO), in commercial products containing the sunscreen ingredient, Padimate O. The method involves a minimum of cleanup steps to afford a nonaqueous extract from product emulsions suitable for analysis by a liquid chromatograph interfaced to a thermal energy analyzer (LC/TEA). The method is applicable to lotions, creams, and gels. Oils are normally soluble in the mobile phase and can be analyzed directly on the LC/TEA without additional cleanup procedures. The method has a minimum detectable limit of about 30 ppb and yields greater than 80% recovery. It is highly reproducible and generates no NPABAO artifactually prior to quantitation on the LC/TEA. Application of the method to 22 different commercial product formulas disclosed that the level of NPABAO in each of the products is below 250 ppb, with 18 of the products containing less than 100 ppb. Of interest was the observation that musk ketone, a common fragrance constituent, produces a false-positive TEA response that can interfere with accurate analysis of NPABAO content in typical commercial products.

Aniline Compounds↗

Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy.

After its successful application to the treatment of acute Pb poisoning, Ca disodium EDTA came into routine clinical use for diagnosis and treatment of subacute and chronic Pb poisoning. Despite widespread use, few definitive conclusions have emerged about the sources of Pb mobilized by Ca disodium EDTA. Furthermore, the possibility that mobilized Pb may be redistributed has been suggested. The current studies indicate that the standard therapeutic protocol for Ca disodium EDTA has little impact on critical organs such as brain and liver and moreover, that diagnostic Ca disodium EDTA chelation may even increase the concentration of Pb in these tissues. After a 3 to 4 month exposure to Pb acetate in drinking water, different groups of rats received daily i.p. injections of saline (control), 75 or 150 mg/kg of Ca disodium EDTA for either 1, 2, 3, 4 or 5 days and were then sacrificed 24 hr after the final injection. Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver. Levels in both brain and liver declined with subsequent Ca disodium EDTA injections, but no net loss from either tissue occurred over the 5-day treatment period despite a decline in blood Pb levels and a marked enhancement of urinary Pb excretion. These findings stress the need for further investigation of Ca disodium EDTAs effects and for parallel evaluation of alternate chelating agents, and suggest that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.

Animals↗

A novel dynamic approach for automatic microsampling and continuous monitoring of metal ion release from soils exploiting a dedicated flow-through microdialyser.

In this paper, a novel concept is presented for automatic microsampling and continuous monitoring of metal ions in soils with minimum disturbance of the sampling site. It involves a hollow-fiber microdialyser that is implanted in the soil body as a miniaturized sensing device. The idea behind microdialysis in this application is to mimic the function of a passive sampler to predict the actual, rather than potential, mobility and bioavailability of metal traces. Although almost quantitative dialysis recoveries were obtained for lead (> or = 98%) from aqueous model solutions with sufficiently long capillaries (l > or = 30 mm, 200 microm i.d.) at perfusion rates of 2.0 microL min(-1), the resistance of an inert soil matrix was found to reduce metal uptake by 30%. Preliminary investigation of the potential of the microdialysis analyser for risk assessment of soil pollution, and for metal partitioning studies, were performed by implanting the dedicated probe in a laboratory-made soil column and hyphenating it with electrothermal atomic absorption spectrometry (ETAAS), so that minute, well-defined volumes of clean microdialysates were injected on-line into the graphite furnace. A noteworthy feature of the implanted microdialysis-based device is the capability to follow the kinetics of metal release under simulated natural scenarios or anthropogenic actions. An ancillary flow set-up was arranged in such a way that a continuous flow of leaching solution--mild extractant (10(-2) mol L(-1) CaCl2), acidic solution (10(-3) mol L(-1) HNO3), or chelating agent (10(-4) or 10(-2) mol L(-1) EDTA)--was maintained through the soil body, while the concentration trends of inorganic (un-bound) metal species at the soil-liquid interface could be monitored at near real-time. Hence, relevant qualitative and quantitative information about the various mobile fractions is obtained, and metal-soil phase associations can also be elucidated. Finally, stimulus-response schemes adapted from neurochemical applications and pharmacokinetic studies are to be extended to soil research as an alternative means of local monitoring of extraction processes after induction of a chemical change in the outer boundary of the permselective dialysis membrane.

Journal Article↗

Cyclam complexes and their applications in medicine.

Cyclams are 14-membered tetraamine macrocycles which bind strongly to a wide range of metal ions. Medical interest has centred on clinical trials of a bicyclam for the treatment of AIDS and for stem cell mobilization, and on adducts with Tc and Cu radionuclides for diagnosis and therapy. Other potential applications particularly for Cr, Mn, Zn, and Ru cyclams are also emerging. We discuss in this critical review the mechanism of metal complexation, stability of metal cyclams and their structures, with particular emphasis on the variety of configurational states which metal cyclams can adopt. Understanding the factors which control the thermodynamics and kinetics of the interconversion of configurational states of metallo-cyclams may be a key factor in designing novel cyclam derivatives for future use in medicine.

Animals↗

An application of flexible constraints in Monte Carlo simulations of the isobaric--isothermal ensemble of liquid water and ice Ih with the polarizable and flexible mobile charge densities in harmonic oscillators model.

The method of flexible constraints was implemented in a Monte Carlo code to perform numerical simulations of liquid water and ice Ih in the constant number of molecules, volume, and temperature and constant pressure, instead of volume ensembles, using the polarizable and flexible mobile charge densities in harmonic oscillators (MCDHO) model. The structural and energetic results for the liquid at T=298 K and rho=997 kg m(-3) were in good agreement with those obtained from molecular dynamics. The density obtained at P=1 atm with flexible constraints, rho=1008 kg m(-3), was slightly lower than with the classical sampling of the intramolecular vibrations, rho=1010 kg m(-3). The comparison of the structures and energies found for water hexamers and for ice Ih with six standard empirical models to those obtained with MCDHO, show this latter to perform better in describing water far from ambient conditions: the MCDHO minimum lattice energy, density, and lattice constants were in good agreement with experiment. The average angle HOH of the water molecule in ice was predicted to be slightly larger than in the liquid, yet 1.2% smaller than the experimental value.

Journal Article↗

An HPLC method for the quantitation of quinidine and its metabolites in plasma: an application to a quinidine-phenytoin drug interaction study.

A rapid and simple method is described for the separation of quinidine (Q), its metabolites 3-hydroxyquinidine (30HQ) and 2'oxoquinidinone (QD) as well as the quinidine salt contaminant, dihydroquinidine (DHQ) in plasma by high pressure liquid chromatography (HPLC). A silica column was used with methanol: 1 N ammonium nitrate: 2 N ammonium hydroxide (28:1:1 v/v) as the mobile phase to separate the compounds and a fluorescence spectrophotometer for detection. Application of this method is demonstrated by the analysis of human plasma samples collected from a volunteer during a phenytoin-quinidine drug interaction study.

Chromatography, High Pressure Liquid↗

Anomalous mobility of Brownian particles in a tilted symmetric sawtooth potential.

Overdamped motion of Brownian particles in a 1D periodic system with a simple symmetric sawtooth potential subjected to both unbiased thermal noise and spatially nonhomogeneous three-level colored noise is considered analytically. Upon application of a tilting force the particles exhibit anomalous transport properties, namely, absolute negative mobility, negative differential mobility, and the phenomenon of hypersensitive differential response. It is established that the mobility (differential mobility included) depends nonmonotonically on the parameters (switching rate, amplitude, and temperature) of nonequilibrium and thermal noises. The necessary conditions for various anomalous transport properties are found.

Journal Article↗

Development of a hand dynamometer for the control of manually applied forces.

OBJECTIVE: The aim of the study was to develop a prototype tool capable of providing instantaneous feedback about manually applied forces, and to use it to determine (1) whether force constancy can be maintained during different application postures and (2) whether sensitivity to stiffness using the tool is different from sensitivity when assessing stiffness with the hands. METHODS: Subjects were students and staff in a health sciences faculty. A series of grade II and IV mobilizing forces were delivered using a mobilizing tool, a modified JAMAR dynamometer fitted with a molded handle. Forces were executed without feedback at application points on a plinth that were near, midway, and far from the body. Thereafter, discrimination between elastic stiffness was determined with hands alone or using the tool. RESULTS: Force was maintained at grade II when the point of application was moved away from the body, but attempts to replicate grade IV mobilization forces in similar postures showed a decrease despite increased effort. Variation in force produced was substantial both within and between subjects. Stiffness discrimination was not significantly different whether hands or the tool was used. CONCLUSION: There is substantial variation in manually applied forces that could be controlled if instantaneous force readout was available. Reports of hand injury in manual therapists motivate further development of devices that maintain sensitivity and allow for control of applied force and spread the load over a greater surface area on the hands.

Equipment Design↗

Effects of discrimination by sex and race on the early careers of British medical graduates during 1981-7.

OBJECTIVE: To examine the possible effects of discrimination by sex and race on the career patterns of doctors up to six years after qualifying. DESIGN: Postal questionnaire follow up survey. PARTICIPANTS: 1572 Doctors who graduated from five British medical schools in 1981, 1983, and 1985, including 587 women and 131 doctors from ethnic minorities. MAIN OUTCOME MEASURES: Reported success rates of applications for training posts. RESULTS: Comparison of the career patterns of women and men yielded no evidence of discrimination against women in competition for posts. In contrast, there were striking differences in career patterns between graduates of native European origin and those of ethnic minority origin. Graduates from ethnic minorities reported lower success rates and more difficulty in obtaining house officer posts, registrar posts, and places in vocational training schemes in general practice. Most of this discrimination seemed to occur at the stage of shortlisting for interview. Graduates from ethnic minorities were more likely than graduates of native European origin to have experienced spells of unemployment while seeking work. They were also more likely to have changed their original choice of career because of difficulty in obtaining suitable training posts or unfavourable career prospects. CONCLUSIONS: Discrimination against ethnic minorities occurs in the competition for training posts among graduates from British medical schools. There was no evidence of discrimination against women graduates. Shortlisting procedures based on objective scoring systems may help to ensure equality of opportunity in future.

Career Mobility↗

Simple and efficient fabrication of room temperature stable electride: melt-solidification and glass ceramics.

Electrides are ionic compounds in which electrons act as anions. These compounds are expected to have interesting properties arising from their exotic structure. The fatal drawbacks of the thermal and chemical instability of organic electrides were resolved by the synthesis of a room temperature (RT) stable electride using single crystalline 12CaO.7Al2O3 (C12A7) with a nanoporous structure and the chemical treatments for a long duration. However, an innovative fabrication method is obviously required for practical applications such as cold electron-emitter and thermionic devices. Herein we report a simple synthesis for polycrystalline C12A7 electrides with a moderate electronic conductivity via a strongly reducing C12A7 "melt", i.e., direct solidification of the melt or crystallization of the transparent glass. Generation of carrier electrons and precipitation of the C12A7 phase from the strongly reducing melt and glass are likely associated with the incorporation of carbon-related anions for stabilizing the C12A7 phase and keeping the mobile electrons in C12A7. These findings will be broadly utilized for applications by mass production in a desired shape and dimension, facilitating the research of electrides.

Journal Article↗

Military and government applications of human-machine communication by voice.

This paper describes a range of opportunities for military and government applications of human-machine communication by voice, based on visits and contacts with numerous user organizations in the United States. The applications include some that appear to be feasible by careful integration of current state-of-the-art technology and others that will require a varying mix of advances in speech technology and in integration of the technology into applications environments. Applications that are described include (1) speech recognition and synthesis for mobile command and control; (2) speech processing for a portable multifunction soldier's computer; (3) speech- and language-based technology for naval combat team tactical training; (4) speech technology for command and control on a carrier flight deck; (5) control of auxiliary systems, and alert and warning generation, in fighter aircraft and helicopters; and (6) voice check-in, report entry, and communication for law enforcement agents or special forces. A phased approach for transfer of the technology into applications is advocated, where integration of applications systems is pursued in parallel with advanced research to meet future needs.

Aircraft↗

Recent advances in enantioseparations of peptides by capillary electrophoresis.

The present review summarizes peptide enantioseparations by capillary electrophoresis with the focus on recent developments. These include the application of new chiral selectors and systematic studies involving series of di- and tripeptides with either common features or with a variety of structures. One section emphasizes mechanistic aspects of the migration order of the enantiomers in cyclodextrin-assisted chiral separations with respect to the complexation constants and the mobilities of the transient diastereomeric complexes. In addition, short paragraphs on the application of chiral capillary electrophoresis to the determination of the stereochemical purity of peptidomimetics and on chiral separations of peptides by capillary electrochromatography have also been included.

Cyclodextrins↗

The importance of three-dimensional brachytherapy treatment planning for nasopharyngeal carcinoma.

High dose rate (HDR) intracavitary brachytherapy is now more frequently incorporated into treatment programmes for patients with persistent and recurrent nasopharyngeal carcinoma (NPC). However, many centres still employ two-dimensional (2-D) image reconstruction for applicators with a three-dimensional (3-D) orientation. In this study, we introduced the use of a mobile modified Nucletron reconstruction box inside the brachytherapy suite for image reconstruction and quality assurance. Three-dimensional reconstruction of the applicators' configurations proved possible and the dose distributions generated by the 2-D and 3-D image reconstructions could be compared. Thirty-one applications were included in this part of the analysis. The results showed that, based on the 2-D planning method, the reference doses were under-prescribed by 1%-10% in all except one patient, whose dose was over-prescribed by 3%. The evaluated doses to the floor of the sphenoid, which was shown to be significant for subsequent local control, was shown to be underestimated by up to 19% or overestimated by 18%, with an average of 5.9% dose underestimation. With this system, the reliability of the anchoring techniques was verified by posttherapy radiographs. Any catheter displacement of more than 1 mm was counted as a failure. Nine of the 43 verified applications were classified as failures, although six of nine catheter displacements measured < or = 2.5 mm. We recommend the routine use of a modified reconstruction box for 3-D image reconstruction for dose calculation and prescription in the treatment of NPC with HDR intracavitary brachytherapy. Quality assurance programmes should be included as an integral part of any HDR treatment; their importance cannot be overemphasized.

Brachytherapy↗

Immunobiology of allogeneic peripheral blood mononuclear cells mobilized with granulocyte-colony stimulating factor.

The use of mobilized peripheral blood (PB) stem cells for autologous transplantation initially generated much enthusiasm because of enhanced engraftment in comparison to marrow stem cells and avoidance of general anesthesia for the donor. Its application to the allogeneic setting seemed inevitable. For obvious ethical reasons, allogeneic donors are mobilized with cytokines only, mainly granulocyte colony-stimulating factor (G-CSF). Results from preliminary studies suggest that in comparison to standard bone marrow transplants, outcomes such as engraftment, host-versus-graft reaction, graft-versus-host disease, graft-versus-leukemia and immunological reconstitution may be different. Surprisingly, G-CSF, previously recognized as a late acting lineage-specific factor for neutrophil production, not only disrupts homeostasis between stem cells and their microenvironment, but also induces significant quantitative and qualitative changes in the accessory cell compartment, affecting lymphocytes, monocytes, natural killer, dendritic, and stromal cells. Furthermore, mobilization of huge numbers of non-professional antigen presenting cells (CD34+ stem cells) amplifies the tolerizing potential of PB stem cell grafts. Thus, G-CSF mobilization provides PB transplants with different immunobiologic properties in comparison to standard bone marrow grafts. Whether these immunobiologic differences will lead to better transplant outcomes remains to be shown through much awaited results of large randomized clinical trials.

Bone Marrow Transplantation↗