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PubMed2001

Influence of ferrous iron and ph on carbon tetrachloride degradation by Methanosarcina thermophila.

The influence of environmental conditions on the biological transformation of a contaminant must be well understood to optimize remediation processes. One factor that impacts the biological transformation of carbon tetrachloride (CT) is elemental iron (Fe0). Previous research has shown that Fe0 increases the methanogenic CT degradation rate by providing H2 for cell growth and dechlorination. As Fe0 oxidizes it also increases the pH and Fe2+ levels, which may also impact the biological transformation of CT. Experiments were performed with Methanosarcina thermophila to investigate the influence of these factors on CT degradation. The transformation of CT and CF was greatly influenced by pH, with the rate of CT and CF degradation increasing with increasing pH. After 6 h, > 90% of the CT had been degraded in the treatments containing cells at a pH of 8.5, whereas only about 51% of the CT had been degraded in similar treatments at a pH of 5.5. Fe2+ did not significantly influence the degradation of CT; however, 60% less CF was formed in systems containing cells+Fe2+ than in systems containing cells only. In addition. Fe2+ promoted rapid transformation of CF when added to treatments containing cells. The product distribution after 9 days in all systems containing cells was very similar, with 98.04 +/- 5.46% (two-sided 95% confidence interval) of the originally fed CT present as soluble products. These results show that pH and Fe2+ influence the degradation of CT and CF, although transiently. Because the residence time of contaminants in Fe0 barriers varies with the thickness of the barrier, it is likely that this influence will be important for some flow-through systems. This implies that a combined Fe0/organism remediation system may have previously unrealized advantages (due to pH and Fe2+ changes).

Biodegradation, Environmental↗

PubMed2000

Degradation of short-chain alkyl- and alkanolamines by TiO2- and Pt/TiO2-assisted photocatalysis.

The photooxidation of C2H5NH2, (C2H5)2NH, HOC2H4NH2, (HOC2H4)2NH and (HOC2H4)3N using TiO2 and Pt/TiO2 as photocatalysts has been investigated. A laboratory set up was designed and a study on the influence of the concentration of the photocatalyst, the pH-value and the structure of the amine performed. The photocatalytic process was optimized with respect to the concentrations of the model substances during degradation. The decrease of the amine concentrations was found to be maximum at a pH of 10. The time-dependence of the formation of cationic breakdown products, such as NH3/NH4 and short-chain alkyl- and alkanolamines was studied by analyses with single column ion chromatography. The experimental data show that the photodegradation follows a Langmuir-Hinshelwood kinetic. The mineralization of the model substances also was monitored by measurements of the decrease of the TOC and of the formation of NO2 and NO3. The different mineralization efficiencies for the model substances studied are discussed with regard to their structure and adsorption behaviour on the photocatalyst. A possible breakdown mechanism involving the electrophilic attack of the hydroxyl radical is given. The applicability of the TiO2-assisted photocatalytic degradation of C2H5NH2 and (C2H5)2NH was tested at the pilot plant-scale with real solar radiation. The degradation rates and products obtained were similar to those found in the laboratory experiments.

Amines↗

PubMed1990

Clinical practice guidelines at an HMO: development and implementation in a quality improvement model.

Harvard Community Health Plan (HCHP) is adapting to clinical medicine the managerial principles and methods of quality improvement theory that were originally developed and successfully applied in industrial settings. An essential step in applying the quality improvement cycle to clinical medicine is the setting of standards or specifications for clinical care. HCHP has chosen to focus its standard-setting efforts on the development of clinical algorithms, which provide an excellent basis for specifying and communicating optimal care processes and for evaluating actual clinical care. When implemented effectively, clinical algorithms may improve quality and decrease costs by guiding clinicians toward more standardized, high-quality, cost-effective clinical strategies and by facilitating more valid measurement of clinical process and outcomes. This article describes the evolution, structure, methods, and future agenda of the Algorithm Based Clinical Quality Improvement Process (ABCQIP) at HCHP.

Algorithms↗

PubMed1999

An overview of chemotherapeutic targets for antimalarial drug discovery.

The need for new antimalarials comes from the widespread resistance to those in current use. New antimalarial targets are required to allow the discovery of chemically diverse, effective drugs. The search for such new targets and new drug chemotypes will likely be helped by the advent of functional genomics and structure-based drug design. After validation of the putative targets as those capable of providing effective and safe drugs, targets can be used as the basis for screening compounds in order to identify new leads, which, in turn, will qualify for lead optimization work. The combined use of combinatorial chemistry--to generate large numbers of structurally diverse compounds--and of high throughput screening systems--to speed up the testing of compounds--hopefully will help to optimize the process. Potential chemotherapeutic targets in the malaria parasite can be broadly classified into three categories: those involved in processes occurring in the digestive vacuole, enzymes involved in macromolecular and metabolite synthesis, and those responsible for membrane processes and signalling. The processes occurring in the digestive vacuole include haemoglobin digestion, redox processes and free radical formation, and reactions accompanying haem release followed by its polymerization into haemozoin. Many enzymes in macromolecular and metabolite synthesis are promising potential targets, some of which have been established in other microorganisms, although not yet validated for Plasmodium, with very few exceptions (such as dihydrofolate reductase). Proteins responsible for membrane processes, including trafficking and drug transport and signalling, are potentially important also to identify compounds to be used in combination with antimalarial drugs to combat resistance.

Antimalarials↗

PubMed1999

Design of infection-resistant antibiotic-releasing polymers. II. Controlled release of antibiotics through a plasma-deposited thin film barrier.

In the first paper in this series, we described the methods to synthesize an antibacterial polyurethane (PU) incorporating ciprofloxacin as the releasable antibiotic and poly(ethylene glycol) as the pore-forming agent. Here, we report that a thin, RF-plasma-deposited, n-butyl methacrylate (BMA) overlayer on this drug-loaded PU can act as a rate-limiting barrier to achieve a constant, sustained release of ciprofloxacin. Deposition power and deposition time during the coating process were optimized to give an appropriate crosslinked coating barrier that yielded desirable release rates, above the minimum required killing rate, N(kill). Electron spectroscopy for chemical analysis (ESCA), also known as X-ray photoelectron spectroscopy (XPS), was used to characterize the coating, and its crosslinking degree was indirectly related to the C/O ratio. Increasing either deposition power (10-60 W) or duration (5-25 min) resulted in increased C/O ratios and decreased ciprofloxacin release rates. The correlation between increased C/O ratios and reduced release rates is believed to be due to the increased crosslinking, increased hydrophobicity and increased thickness of the coating. The optimal plasma conditions to attain an appropriate crosslinked plasma-deposited film (PDF) required argon etching, pre-treatment of the matrices with an 80W-BMA plasma for 1 min, followed by immediate BMA plasma deposition at 40 W and 150 mT for 20 min. By using these plasma deposition protocols, we eliminated the initial burst effect, significantly reduced the release rates, and closely approached the zero order release kinetics for at least five days. In this study, we also showed that ESCA could be used as a powerful tool to explain the release behavior of molecules through the plasma-deposited films (PDFs).

Anti-Infective Agents↗

PubMed2000

Glutaraldehyde crosslinked sodium alginate beads containing liquid pesticide for soil application.

This paper presents experimental results on the successful encapsulation of a natural liquid pesticide 'neem (Azadirachta Indica A. Juss.) seed oil' hereafter designated as NSO, using sodium alginate (Na-Alg) as a controlled release (CR) polymer after crosslinking with glutaraldehyde (GA). The NSO-containing beads have been prepared by changing the experimental variables such as the extent of crosslinking and the amount of loading in order to optimize the process variables. The absence of chemical interactions between active ingredients and polymer as well as crosslinking agent was confirmed by FTIR spectral measurements. The SEM data indicated that the structure of the walls of the beads are smooth and nonporous. The swelling results indicated that swelling of the polymeric beads decreases with increasing exposure time to the crosslinking agent. However, no significant variation in swelling was observed with different amounts of NSO loading. In order to understand the crosslinkability and its effect on the NSO release patterns of the beads, an attempt was made to calculate the molar mass between crosslinks using the Flory-Rehner equation. The release data have been fitted to an empirical equation to estimate the kinetic parameters.

Alginates↗

PubMed2001

Ultrasound to decontaminate heavy metals in dredged sediments.

Sediments contaminated with heavy metals due to past disposal practices threaten the environment and require remediation. This study was an attempt to develop a technology to decontaminate heavy metals in dredged sediments using ultrasound coupled with vacuum pressure. A set of laboratory scale experiments were conducted using dredged sediments obtained from New York/New Jersey harbor. This sediment sample is considered as category III, a material that failed to meet USEPA requirements for toxicity or bioaccumulation, and required secure disposal. Acoustic cavitation due to ultrasound energy coupled with vacuum pressure was used to facilitate the removal of chromium (the selected metal contaminant) from the sediments. Full factorial experimental designs were performed to evaluate the above treatment technique and to optimize the processes. Two coupled processes were used to separate and to treat both coarse (Process #1) and fine (Process #2) fractions of sediments. Selected variables for evaluation of Process #1 were ultrasound power, soil-to-water ratio, vacuum pressure and dwell time, and for Process #2 were ultrasound power, soil-to-water ratio and dwell time. Laboratory scale experiments were carried out with various combinations of these parameters according to the factorial design. The optimum removal was found to be 92% with the parameter levels at 1200W power, 1:15 soil-to-water ratio, 15 psi vacuum pressure and 15 min of dwell time. After the application of Process #2 for fine sediments it was found that the fines were separated into silt and clay. Only the silt faction had a considerable metal removal while the clay fraction was insensitive to the treatment. A maximum removal of 83% was obtained for silt fraction when factor levels were at 1200W power, 1:50 soil-to-water ratio and 90 min of dwell time. Further analysis of clay fraction showed that the chromium in clay is immobile and stable. The toxicity characteristic leaching procedure (TCLP) test on clay fraction confirmed that the treated clay fraction is safe to dispose. The study showed that the proposed treatment technique is effective and economical for sediments with lower clay contents.

Cost-Benefit Analysis↗

PubMed1997

Separation of the stereoisomers of the main metabolite of a non-steroidal anti-inflammatory drug, flobufen, by chiral high-performance liquid chromatography.

The major metabolite of a novel non-steroidal anti-inflammatory drug, DL-4-(2',4'-difluorobiphenyl-4-yl)-2-oxo-2-methylbutanoic acid (flobufen, I), namely 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-gamma-butyrolactone (4-dihydroflobufen lactone, III), has four stereoisomers consisting of two racemic pairs of enantiomers. Of three chiral stationary phases tested, Cyclobond I beta-RSP (Astec) (beta-cylodextrin derivatized with R,S-hydroxypropyl) was best able to separate the (+2)(--) racemate, with a liquid phase containing acetonitrile as modifier and triethylamine acetate as buffer. Using the Box-Wilson Central Composite Design for three factors, an optimum combination of pH and concentrations of the modifier and buffer was eventually obtained. A chromatographic response function based on a combination of the Kaiser peak separation function, Pi, and retention time of the second eluting enantiomer, tRL, served as a response criterion for the process of optimization. The optimum conditions developed for the (+2)(--) racemate were also found to be suitable for separating the (+-)(-+) racemate, for which earlier studies had shown the separation to be more facile. Separation of the four stereoisomers of III, for which the chiral chromatographic system optimized in this study is proposed as the second stage, is targeted at a biochemical study of the stereoisomeric metabolism of I.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Influence of different parameters on reconstitution of lyophilized SLN.

Drug-loaded solid lipid nanoparticles (SLN) suitable for parenteral administration were freeze-dried. The lipid matrix Imwitor 900 (concentration, 2.5%) was stabilized with Lipoid E 80 and sodium glycocholate. The influence of different parameters of lyophilization like the protective effect of cryoprotectants, freezing velocity, and thermal treatment was investigated. The results of this study demonstrate that, by optimizing critical process parameters, i.v.-injectable SLN-dispersions can be freeze-dried, preserving their small particle size.

Drug Carriers↗

PubMed2000

Diversity and plasticity in amino acid receptor subunits in the rat auditory brain stem.

Glutamate, gamma aminobutyric acid (GABA) and glycine receptors have different properties depending on the specific subunit combination utilized. The subunit composition of amino acid receptors may help to shape the responses of neurons and can provide a diversity of response properties in different neuronal types and regions. This allows a synaptic fine tuning for an optimization of processing requirements and may also allow for changes in response to changes in input. This article reviews the diversity that has been found in the subunit composition of GABA, glycine, alpha amino-3-hydroxy-5-methyl-4 isoxazole propionic acid and N-Methyl, D-aspartate (NMDA) receptors in the mammalian auditory brain stem and provides new data on how the NMDAR1 glutamate receptor subunit changes as a consequence of deafness. In the latter study, quantitative in situ hybridization was used to assess NMDAR1 mRNA expression in six cell types of the rat cochlear nucleus. A unilateral cochlear ablation was performed and expression determined in the ipsilateral and contralateral cochlear nucleus 5 and 20 days later. Significantly decreased expression, compared to normal, was found 5 days following deafness, in ipsilateral spherical bushy cells, octopus cells and shell neurons, but not in fusiform cells, corn cells or granule cells. At 20 days the expression was not significantly different from normal in any of the six cell types.

Animals↗

PubMed2001

Principles of molecular microbiology testing methods.

Molecular testing methods have the potential to replace many conventional microbiology laboratory assays. Recent refinements in technology have resulted in more user-friendly testing platforms. These platforms are automated and have lowered risks for contamination, decreased costs, and are faster than older platforms. The success of these technologies depends on their successful application to patient care. Quality issues include appropriate specimens for analysis, performance characteristics of different analytical methods, optimal specimen processing, the effects of PCR inhibitors, and false-positive results caused by contaminating nucleic acids. Quality control guidelines for molecular microbiologic diagnostic assays are in their infancy and require further development. Additionally, the problem of "too much" sensitivity (brought on by the extreme sensitivity of these techniques coupled with the potential presence of small numbers of pathogenic organisms in asymptomatic individuals) should be considered. Potential problems when monitoring therapy (because molecular detection techniques do not generally have the ability to determine whether an organism is dead or alive) can also occur. Cost-effective test use, pathogen- or disease-targeted algorithms, and standardized methods will be necessary for the true value of these technologies to be realized. This is especially important, because, unlike traditional culture methods, most molecular microbiology methods are pathogen-specific. Clinicians familiar with the reasons why "pan-culture" (i.e., requesting all culture possibilities at once) is inadvisable should not use the same irrational approach when requesting molecular tests. The clinical usefulness of molecular testing will be maximized as targeted algorithms are developed and an understanding of molecular test ordering patterns is realized. Laboratory technicians and physicians must continue to apply and combine theories of traditional microbiology, clinical chemistry, and general medicine to the understanding and application of molecular diagnostics.

Base Sequence↗

PubMed1997

Validation and application of a solid phase chemistry method for preparation of high effective specific activity technetium-99m radiopharmaceuticals.

Solid phase chemistry with UltraLink Iodoacetyl gel was investigated as a method for removing excess ligand present in preparations of diaminedithiol (DADT) 99mTc radiopharmaceuticals. The process was optimized and tested under 99mTc labeling conditions with 2,2,4,9,9-pentamethyl-4,7-diaza-1,10-decanedithiol (N-methyl-DADT), 1, and 4-(1-(2'-methoxyphenyl) piperazinylbutyl)-2,2,9,9-tetramethyl-4,7-diaza-1,10 -decanedithiol (DADT-4C-MPP), 2, a serotonin receptor-binding ligand. The results illustrated that this gel removed > or = 99.9% excess ligand used in labeling reactions, and was comparable to the level of purification usually obtained by the more labor intensive method of HPLC.

Chromatography, High Pressure Liquid↗

PubMed2002

Inverse finite element characterization of soft tissues.

In this work a tissue aspiration method for the in vivo determination of biological soft tissue material parameters is presented. An explicit axisymmetric finite element simulation of the aspiration experiment is used together with a Levenberg-Marquardt algorithm to estimate the material model parameters in an inverse parameter determination process. An optimal fit of the simulated experiment and the real experiment is sought with the parameter estimation algorithm. Soft biological tissue is modelled as a viscoelastic, non-linear, nearly incompressible, isotropic continuum. Viscoelasticity is accounted for by a quasi-linear formulation. The aspiration method is validated experimentally with a synthetic material. In vivo (intra-operatively during surgical interventions) and ex vivo experiments were performed on human uteri.

Algorithms↗

PubMed1999

Organotypic culture system of chicken retina.

Analysis of developmental mechanisms during neuroembryogenesis, evaluation of toxicological effects and testing of neuroprotheses rely to an increasing extent on in vivo-like in vitro models. We have developed a novel organotypic culture system of the chick retina. Tissue slices of embryonic retinae were immobilized on glass coverslips by a fibrin clot and permanently rotated between the gas and medium phase, resulting in regular formation and the maintenance of the retinal cytoarchitecture. Selection of embryonic stage, slice thickness and specimen processing were optimized for culturing. Scanning electron microscopy revealed degradation during increasing culture periods of the fibrin clot, which was used for initial immobilization of explants on glass coverslips. Simultaneously, retinal cells became exposed on the tissue surface. Even after several weeks in vitro, formation and maintenance of plexiform and nuclear layers was evident as revealed by two specific monoclonal antibodies. Immunocytochemistry employing two additional photoreceptor- and radial Müller-antibodies indicated differentiation of neuronal and glial cells specific for the retina. The organotypic culture system promises to facilitate developmental studies of retinal development. Quantitative evaluation of Na(+)-channel blocker mexiletine impact on the histogenesis of retinal explants proved the organotypic culture system to be a valuable tool also for neurotoxicological investigations.

Animals↗

PubMed1999

Structure-based design of a new class of anti-inflammatory drugs: secretory phospholipase A(2) inhibitors, SPI.

Human non-pancreatic secretory phospholipase A(2) (hnps-PLA(2)) is a group IIA enzyme that is massively over-expressed in a variety of severe inflammatory diseases. The enzyme degrades membrane phospholipids and it has been hypothesized that this activity can lead to a loss of tissue and organ integrity and function. This report overviews efforts directed toward the identification and clinical evaluation of a new class of anti-inflammatory drugs that specifically targets and inhibits the catalytic site of this hydrolytic enzyme. To achieve this goal, structure-based drug design was applied to a lead molecule identified by random high volume screening. Through an iterative process consisting of X-ray structure determination followed by inhibitor modification and testing, the lead compound was improved more than 6000-fold. Detailed information learned from earlier X-ray studies of stable substrate mimics aided this inhibitor improvement process. The optimized drug candidate, LY315920/S-5920, is currently undergoing phase II clinical evaluation. The outcome of studies such as these will define with greater clarity the pathological role of hnps-PLA(2) in human inflammatory diseases.

Acetates↗

PubMed2002

Emerging paradigms of cognition in medical decision-making.

The limitations of the classical or traditional paradigm of decision research are increasingly apparent, even though there has been a substantial body of empirical research on medical decision-making over the past 40 years. As decision-support technology continues to proliferate in medical settings, it is imperative that "basic science" decision research develop a broader-based and more valid foundation for the study of medical decision-making as it occurs in the natural setting. This paper critically reviews both traditional and recent approaches to medical decision making, considering the integration of problem-solving and decision-making research paradigms, the role of conceptual knowledge in decision-making, and the emerging paradigm of naturalistic decision-making. We also provide an examination of technology-mediated decision-making. Expanding the scope of decision research will better enable us to understand optimal decision processes, suitable coping mechanisms under suboptimal conditions, the development of expertise in decision-making, and ways in which decision-support technology can successfully mediate decision processes.

Cognitive Science↗

PubMed2005

Using project management methodology to plan and track inpatient care.

BACKGROUND: Effective care of each patient throughout a hospital admission involves executing a specific set of tasks to produce a favorable outcome within an appropriate time frame. The ProjectRounds methodology, which can be implemented using widely available software, incorporates the principles of project management in planning and control hospital inpatient care. It consists of four stages--clinical assessment, planning, scheduling, and tracking. OVERVIEW OF PROJECTROUNDS AND EXAMPLE: As an example, a 68-year-old-man is admitted with pneumonia. In clinical assessment, the admitting physician uses an assessment tool that prompts her to list all the patient's clinical issues, define the conditions that need to be met to discharge the patient, highlight special problems, and list any consultations, diagnostic tests, and procedures that are planned. In planning, the work breakdown structure--a tabulation of all the tasks in the "project" (the admission)--is created. In scheduling, a project schedule is generated, and in tracking, the clinical team evaluates and monitors the project's course. During interdisciplinary clinical rounds, the progress of the patient's hospital care can be tracked and quantified by employing the percent complete method. Tracking can be used as a "dashboard," providing a concise summary of the care that needs to be and has been rendered to the patient. SUMMARY AND NEXT STEPS: Applying the tenets of project management can optimize the process of providing health care to hospital inpatients.

Aged↗

PubMed2000

Low glycaemic-index foods.

Accumulating data indicate that a diet characterized by low glycaemic-index (GI) foods not only improves certain metabolic ramifications of insulin resistance, but also reduces insulin resistance per se. Epidemiological data also suggest a protective role against development of non-insulin-dependent diabetes mellitus and cardiovascular disease. A major disadvantage in this connection is the shortage of low-GI foods, and many common starchy staple foods, such as bread products, breakfast cereals and potato products, have a high GI. Studies in our laboratory show that it is possible to significantly lower the GI of starchy foods, for example by choice of raw material and/or by optimizing the processing conditions. Such low-GI foods may or may not influence glucose tolerance at a subsequent meal. Consequently, certain low-GI breakfasts capable of maintaining a net increment in blood glucose and insulin at the time of the next meal significantly reduced post-prandial glycaemia and insulinaemia following a standardized lunch meal, whereas others had no 'second-meal' impact. These results imply that certain low-GI foods may be more efficient in modulating metabolism in the long term. Although the literature supports a linear correlation between the GI and insulinaemic index (II) of foods, this is not always the case. Consequently, milk products elicited elevated IIs, indistinguishable from a white bread reference meal, despite GIs in the lower range. This inconsistent behaviour of milk products has not been acknowledged, and potential metabolic consequences remain to be elucidated.

Blood Glucose↗