Nontoxic

Distribution by Scientific Domains
Distribution within Chemistry

Terms modified by Nontoxic

  • nontoxic concentration
  • nontoxic dose

  • Selected Abstracts


    Poly(,-caprolactone)- b -poly(ethylene glycol)- b -poly(,-caprolactone) triblock copolymers: Synthesis and self-assembly in aqueous solutions

    JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 4 2007
    Yaqiong Zhang
    Abstract Nontoxic and biodegradable poly(,-caprolactone)- b -poly(ethylene glycol)- b -poly(,-caprolactone) triblock copolymers were synthesized by the solution polymerization of ,-caprolactone in the presence of poly(ethylene glycol). The chemical structure of the resulting triblock copolymer was characterized with 1H NMR and gel permeation chromatography. In aqueous solutions of the triblock copolymers, the micellization and sol,gel-transition behaviors were investigated. The experimental results showed that the unimer-to-micelle transition did occur. In a sol,gel-transition phase diagram obtained by the vial-tilting method, the boundary curve shifted to the left, and the gel regions expanded with the increasing molecular weight of the poly(,-caprolactone) block. In addition, the hydrodynamic diameters of the micelles were almost independent of the investigated temperature (25,55 °C). The atomic force microscopy results showed that spherical micelles formed at the copolymer concentration of 2.5 × 10,4 g/mL, whereas necklace-like and worm-like shapes were adopted when the concentration was 0.25 g/mL, which was high enough to form a gel. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 605,613, 2007 [source]


    A pilot-scale demonstration of a membrane-based absorption- stripping process for removal and recovery of volatile organic compounds

    ENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY, Issue 1 2001
    S. Majumdar
    A new membrane-based continuous absorption-stripping process has been developed to separate gas/vapor mixtures, such as volatile organic compounds (VOCs), from a nitrogen/air stream. Two different hollow fiber membrane modules are needed in this process to remove the VOCs. In the first module, VOC-laden nitrogen/air stream flows through the bore of the hollow fibers. A suitable absorbent liquid with a high solubility for the VOC and essentially no solubility for nitrogen/air is pumped countercurrently over the outside of the fibers. This liquid is an inert, nontoxic, and essentially nonvolatile, organic solvent. The VOCs are effectively removed from nitrogen/air to a very low level and are concentrated in the absorbent for recovery, while the absorbent is regenerated by heating and subjecting it to vacuum in a separate hollow fiber membrane module called the stripping module. A pilot-scale membrane-based absorption-stripping unit was located next to a paint spray booth at Robins Air Force Base, Warner Robins, GA. Tests were performed on slip-streams of real-time air emissions from scheduled intermittent painting operations, so the concentration of VOC in the exhaust air fluctuated with time. The VOC removal efficiency was determined as a function of the feed air flow rate and the absorbent (silicone oil) flow rate. Depending on the gas/liquid flow rates and the inlet VOC concentration, the process successfully removed as much as 95+% of the VOC present. The experimental results have been compared with theoretical predictions. [source]


    Evaluation of sorbent amendments for in situ remediation of metal-contaminated sediments

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2010
    Seokjoon Kwon
    Abstract The present study evaluated sorbent amendments for in situ remediation of sediments contaminated with two divalent metals. A literature review screening was performed to identify low-cost natural mineral-based metal sorbents and high-performance commercial sorbents that were carried forward into laboratory experiments. Aqueous phase metal sorptivity of the selected sorbents was evaluated because dissolved metals in sediment porewater constitute an important route of exposure to benthic organisms. Based on pH-edge sorption test results, natural sorbents were eliminated due to inferior performance. The potential as in situ sediment amendment was explored by comparing the sorption properties of the engineered amendments in freshwater and saltwater (10 PPT salinity estuarine water) matrices. Self-assembled monolayers on mesoporous supports with thiols (Thiol-SAMMSÔ) and a titanosilicate mineral (ATSÔ) demonstrated the highest sorption capacity for cadmium (Cd) and lead (Pb), respectively. Sequential extraction tests conducted after mixing engineered sorbents with contaminated sediment demonstrated transfer of metal contaminants from a weakly bound state to a more strongly bound state. Biouptake of Cd in a freshwater oligochaete was reduced by 98% after 5-d contact of sediment with 4% Thiol-SAMMS and sorbed Cd was not bioavailable. While treatment with ATS reduced the small easily extractable portion of Pb in the sediment, the change in biouptake of Pb was not significant because most of the native lead was strongly bound. The selected sorbents added to sediments at a dose of 5% were mostly nontoxic to a range of sensitive freshwater and estuarine benthic organisms. Metal sorbent amendments in conjunction with activated carbon have the potential to simultaneously reduce metal and hydrophobic contaminant bioavailability in sediments. Environ. Toxicol. Chem. 2010;29:1883,1892. © 2010 SETAC [source]


    An evaluation of logistic regression models for predicting amphipod toxicity from sediment chemistry

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2005
    Jeffrey D. Wetherington
    Abstract An empirical screening level approach was developed to assess the probability of toxicity to benthic organisms associated with contaminated sediment exposure. The study was based on simple logistic regression models (LRMs) of matching sediment chemistry and toxicity data retrieved from a large database of field-collected sediment samples contaminated with multiple chemicals. Three decisions were made to simplify the application of LRMs to sediment samples contaminated with multiple chemicals. First, percent mortality information associated with each sediment sample was condensed into a dichotomous response (i.e., toxic or nontoxic). Second, each LRM assumed that toxicity was attributable to a single contaminant. Third, individual contaminants present at low concentrations were excluded from toxic sediment samples. Based on an analysis of the National Sediment Inventory database, the LRM approach classified 55% of nontoxic sediments as toxic (i.e., false-positives). Because this approach has been used to assess the probability of benthic toxicity as reported by the U.S. Environmental Protection Agency (U.S. EPA), the resultant estimates of potential toxicity convey a misleading impression of the increased hazard that sediments pose to the health of aquatic organisms at many sites in the United States. This could result in important resources needlessly being diverted from truly contaminated sites to evaluate and possibly remediate sediments at uncontaminated sites. [source]


    Predicting the toxicity of chromium in sediments

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2004
    Walter J. Berry
    Abstract Chromium exists in sediments in two oxidation states: Cr(III), which is relatively insoluble and nontoxic, and Cr(VI), which is much more soluble and toxic. Chromium(VI) is thermodynamically unstable in anoxic sediments, and acid-volatile sulfide (AVS) is formed only in anoxic sediments; therefore sediments with measurable AVS concentrations should not contain toxic Cr(VI). If this hypothesis holds true, measuring AVS could form the basis for a theoretically based guideline for Cr in sediments. Ten-day water-only and spiked sediment toxicity tests with the amphipod Ampelisca abdita were performed with Cr(VI) and Cr(III), along with sediments collected from a site contaminated with high concentrations of Cr. In sediments where AVS exceeded analytical detection limits, Cr concentrations in interstitial water were very low (<100 ,g/L) and no significant toxicity to A. abdita was observed. In sediments in which AVS was not significantly greater than zero, Cr concentrations in interstitial waters increased significantly, with greater than 90% of the Cr present as Cr(VI), and mortality of A. abdita was elevated. These results demonstrate that measurements of AVS and interstitial water chromium can be useful in predicting the absence of acute effects from Cr contamination in sediments. [source]


    Impact of perfluorooctanoic acid on fathead minnow (Pimephales promelas) fatty acyl-coa oxidase activity, circulating steroids, and reproduction in outdoor microcosms

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2004
    Ken D. Oakes
    Abstract This study investigates reproductive impairment and biochemical changes in fathead minnow (Pimephales promelas) exposed for 39 d to varying concentrations of perfluorooctanoic acid (PFOA) under microcosm conditions. While the concentrations tested in this study were much higher than those normally found in the environment, no mortality was associated with PFOA exposure. Only modest changes were observed in condition factor and in relative liver and gonad size. Significant declines in circulating plasma steroids were observed, but these were accompanied by only limited increases in time to first oviposition and decreases in overall egg production. Peroxisome proliferation, as quantified by fatty acyl-CoA oxidase (FAO) activity, was elevated with low PFOA concentrations but attenuated with exposure to higher PFOA doses. Little evidence was seen of differential induction of peroxisome-associated enzyme activity with sex. Oxidative stress, as quantified by the 2-thiobarbituric acid reactive substances (TBARS) assay, was only modestly influenced by PFOA exposure and is not a significant consequence of FAO activity in fathead minnow. Perfluorooctanoic acid appears to be relatively nontoxic at environmentally relevant concentrations but may impact biochemical and reproductive endpoints under conditions associated with environmental spills. [source]


    Interlaboratory comparison of a reduced volume marine sediment toxicity test method using the amphipod Ampelisca abdita

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2004
    James A. Ferretti
    Abstract The U.S. Environmental Protection Agency has standardized methods for performing acute marine amphipod sediment toxicity tests. A test design reducing sediment volume from 200 to 50 ml and overlying water from 600 to 150 ml was recently proposed. An interlaboratory comparison was conducted to evaluate the precision of this reduced sediment volume toxicity test method using the marine amphipod Ampelisca abdita. A negative control and three sediment samples of varying degrees of toxicity ranging from low to high were tested by six laboratories. Complete agreement was reached in rank of relative toxicity for all samples tested by five out of six laboratories. Test acceptability for control survival was achieved by all laboratories, and 69% agreement in classification of the sediments as toxic or nontoxic was documented. Coefficients of variation in all test samples were similar to those reported in other interlaboratory studies using marine amphipods. Results of this study indicate that the reduced sediment volume test using A. abdita is a reliable and precise measure of acute toxicity in marine sediment samples. [source]


    Comparison of synthetic surfactants and biosurfactants in enhancing biodegradation of polycyclic aromatic hydrocarbons

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2003
    Randhir S. Makkar
    Abstract Polycyclic aromatic hydrocarbon (PAH) contamination of the environment represents a serious threat to the health of humans and ecosystems. Given the human health effects of PAHs, effective and cost-competitive remediation technologies are required. Bioremediation has shown promise as a potentially effective and low-cost treatment option, but concerns about the slow process rate and bioavailability limitations have hampered more widespread use of this technology. An option to enhance the bioavailability of PAHs is to add surfactants directly to soil in situ or ex situ in bioreactors. Surfactants increase the apparent solubility and desorption rate of the PAH to the aqueous phase. However, the results with some synthetic surfactants have shown that surfactant addition can actually inhibit PAH biodegradation via toxic interactions, stimulation of surfactant degraders, or sequestration of PAHs into surfactant micelles. Biosurfactants have been shown to have many of the positive effects of synthetic surfactants but without the drawbacks. They are biodegradable and nontoxic, and many biosurfactants do not produce true micelles, thus facilitating direct transfer of the surfactant-associated PAH to bacteria. The results with biosurfactants to date are promising, but further research to elucidate surfactant,PAH interactions in aqueous environments is needed to lead to predictive, mechanistic models of biosurfactant-enhanced PAH bioavailability and thus better bioremediation design. [source]


    Molecular Iodine Mediated Preparation of Isothiocyanates from Dithiocarbamic Acid Salts

    EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 12 2009
    Jayashree Nath
    Abstract We have developed a general economical and environmentally benign method for the preparation of isothiocyanates from the corresponding dithiocarbamic acid salts by using cheap and readily available reagent molecular iodine. This is perhaps the most efficient method reported so far for the synthesis of isothiocyanates. The reagent is easily available and nontoxic, and the precipitated sulfur can be removed easily; hence, this method is most suitable for large-scale synthesis.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]


    Identification of crucial residues for the antibacterial activity of the proline-rich peptide, pyrrhocoricin

    FEBS JOURNAL, Issue 17 2002
    Goran Kragol
    Members of the proline-rich antibacterial peptide family, pyrrhocoricin, apidaecin and drosocin appear to kill responsive bacterial species by binding to the multihelical lid region of the bacterial DnaK protein. Pyrrhocoricin, the most potent among these peptides, is nontoxic to healthy mice, and can protect these animals from bacterial challenge. A structure,antibacterial activity study of pyrrhocoricin against Escherichia coli and Agrobacterium tumefaciens identified the N-terminal half, residues 2,10, the region responsible for inhibition of the ATPase activity, as the fragment that contains the active segment. While fluorescein-labeled versions of the native peptides entered E. coli cells, deletion of the C-terminal half of pyrrhocoricin significantly reduced the peptide's ability to enter bacterial or mammalian cells. These findings highlighted pyrrhocoricin's suitability for combating intracellular pathogens and raised the possibility that the proline-rich antibacterial peptides can deliver drug leads into mammalian cells. By observing strong relationships between the binding to a synthetic fragment of the target protein and antibacterial activities of pyrrhocoricin analogs modified at strategic positions, we further verified that DnaK was the bacterial target macromolecule. Inaddition, the antimicrobial activity spectrum of native pyrrhocoricin against 11 bacterial and fungal strains and the binding of labeled pyrrhocoricin to synthetic DnaK D-E helix fragments of the appropriate species could be correlated. Mutational analysis on a synthetic E. coli DnaK fragment identified a possible binding surface for pyrrhocoricin. [source]


    Triplex Au,Ag,C Core,Shell Nanoparticles as a Novel Raman Label

    ADVANCED FUNCTIONAL MATERIALS, Issue 6 2010
    Aiguo Shen
    Abstract Monodispersed, readily-grafted, and biocompatible surface-enhanced Raman spectroscopic (SERS) tagging materials are developed; they are composed of bimetallic Au@Ag nanoparticles (NPs) for optical enhancement, a reporter molecule for spectroscopic signature, and a carbon shell for protection and bioconjugation. A controllable and convenient hydrothermal synthetic route is presented to synthesize the layer-by-layer triplex Au,Ag,C core,shell NPs, which can incorporate the Raman-active label 4-mercapto benzoic acid (4-MBA). The obtained gold seed,silver coated particles can be coated further with a thickness-controlled carbon shell to form colloidal carbon-encapsulated Aucore/Agshell spheres with a monodisperse size distribution. Furthermore, these SERS-active spheres demonstrated interesting properties as a novel Raman tag for quantitative immunoassays. The results suggest such SERS tags can be used for multiplex and ultrasensitive detection of biomolecules as well as nontoxic, in vivo molecular imaging of animal or plant tissues. [source]


    Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma,

    HEPATOLOGY, Issue 6 2006
    Boris Blechacz
    The oncolytic measles virus Edmonston strain (MV-Edm), a nonpathogenic virus targeting cells expressing abundant CD46, selectively destroys neoplastic tissue. Clinical development of MV-Edm would benefit from noninvasive monitoring strategies to determine the speed and extent of the spread of the virus in treated patients and the location of virus-infected cells. We evaluated recombinant MV-Edm expressing carcinoembryonic antigen (CEA) or the human sodium iodide symporter (hNIS) for oncolytic potential in hepatocellular carcinoma (HCC) and efficiency in tracking viruses in vivo by noninvasive monitoring. CD46 expression in human HCC and primary hepatocytes was assessed by flow cytometry and immunohistochemistry. Infectivity, syncytium formation, and cytotoxicity of recombinant MV-Edm in HCC cell lines were evaluated by fluorescence microscopy, crystal violet staining, and the MTS assay. Transgene expression in HCC cell lines after infection with recombinant MV-Edm in vitro and in vivo was assessed by CEA concentration, 125I-uptake, and 123I-imaging studies. Toxicology studies were performed in IfnarKO×CD46 transgenic mice. The CD46 receptor was highly expressed in HCC compared to nonmalignant hepatic tissue. Recombinant MV-Edm efficiently infected HCC cell lines, resulting in extensive syncytium formation followed by cell death. Transduction of HCC cell lines and subcutaneous HCC xenografts with recombinant MV-Edm resulted in high-level expression of transgenes in vitro and in vivo. MV-Edm was nontoxic in susceptible mice. Intratumoral and intravenous therapy with recombinant MV-Edm resulted in inhibition of tumor growth and prolongation of survival with complete tumor regression in up to one third of animals. In conclusion, engineered MV-Edm may be a potent and novel cancer gene therapy system for HCC. MV-Edm expressing CEA or hNIS elicited oncolytic effects in human HCC cell lines in vitro and in vivo, enabling the spread of the virus to be monitored in a noninvasive manner. (HEPATOLOGY 2006;44:1465,1477.) [source]


    Colloidal Route for Preparing Optical Thin Films of Nanoporous Metal,Organic Frameworks

    ADVANCED MATERIALS, Issue 19 2009
    Patricia Horcajada
    Colloids of a highly flexible porous metal-organic framework (MOF) have been prepared using nontoxic and easily removable solvents. Furthermore, a simple dip-coating method for the preparation of optical-quality thin films of the MOF has been developed. The homogeneous thin film exhibits reversible flexibility, as has been proven by environmental ellipsometry. [source]


    Biocompatibility of various root canal filling materials ex vivo

    INTERNATIONAL ENDODONTIC JOURNAL, Issue 8 2008
    R. Scotti
    Abstract Aim, To evaluate the biocompatibility of a resin-based endodontic filler (RealSeal) using the indirect cytotoxicity test. Methodology, Human gingival fibroblasts were cultured ex vivo. Pellets of the materials to be tested were incubated for 24, 48, and 72 h at 37 °C under sterile conditions to obtain their eluates. The fibroblasts were exposed to either diluted (50%) or undiluted eluates for 24 h. A culture medium with foetal calf serum was added to the control wells. Cell viability was estimated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide method. The data concerning cell viability were statistically analyzed using one-way anova test and Bonferroni multiple comparisons test. Results, Eluates obtained after 24 h of incubation with the resin filler did not reduce cellular viability. An increase in cellular viability, as compared with control cells, was observed in the gutta-percha group. The undiluted eluate from the polyether material was cytotoxic, causing an 82 ± 4% decrease in cellular viability. Eluates obtained after 48 h of incubation with the resin filler increased cellular viability, whereas the polyether significantly reduced viability. Gutta-percha did not cause any detectable change. After 72 h of incubation the eluate of the resin filler caused an increase in cellular viability, as did gutta-percha, whereas polyether caused a significant decrease. Conclusions, RealSeal resin filler was nontoxic in this laboratory model. Further investigations are necessary to verify its usefulness in clinical applications. [source]


    Inhibition of biofilms associated with dentures and toothbrushes by tetrasodium EDTA

    JOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2007
    D.A. Devine
    Abstract Aims:, We examined the efficacy of tetrasodium EDTA in eradicating biofilms derived from salivary inocula or pure cultures of Candida albicans on discs of polymethyl methacrylate (PMMA) denture base or on toothbrushes that had been used normally for 4,8 weeks. Its efficiency in virus neutralization was also determined. Methods and Results:, Overnight (16 h) treatment with 4% (w/v) tetrasodium EDTA solution reduced salivary and C. albicans biofilm viable counts by ,99%. Biofilm removal was confirmed using confocal laser scanning microscopy. Presence/absence of sucrose during biofilm formation had no effect on killing efficacy. Prolonged treatment of PMMA with tetrasodium EDTA did not influence subsequent formation of C. albicans biofilms or affect surface roughness of the PMMA, but it reduced subsequent biofilm formation from a salivary inoculum. Infectivities of herpes simplex virus and polio virus suspensions were reduced by >99·99% by treatment for 1 and 2 h, respectively. Conclusions:, Tetrasodium EDTA solution efficiently disinfected toothbrushes and PMMA discs, with the detachment of biofilms, and rapidly neutralized both nonenveloped and enveloped viruses. Significance and Impact of the Study:, Dentures and toothbrushes become contaminated by bacterial biofilms and by viruses. There is a need for disinfection methods that are rapidly effective, cost-effective, nontoxic and easily implemented. These studies indicate that tetrasodium EDTA solution has disinfection applications in the oral care field. [source]


    INFLUENCE OF PULSED ELECTRIC FIELD ON SELENOCYSTEINE CONTENT IN SACCHAROMYCES CEREVISIAE

    JOURNAL OF FOOD BIOCHEMISTRY, Issue 6 2008
    URSZULA PANKIEWICZ
    ABSTRACT Culture of Saccharomyces cerevisiae with sodium selenite addition in medium was treated by pulsed electric fields (PEFs). Amino acids from yeast hydrolysates were separated by means of ion-exchange chromatography on amino acid analyzer according to previously established procedure. Selenocysteine was determined in a form of complex with ninhydrin, applying photometric technique. PEF treatment of S. cerevisiae cells resulted in about threefold content increase of selenium bonded within selenocysteine. PRACTICAL APPLICATIONS Se yeast is an attractive source of Se because of its low cost and its ability to act as a precursor for selenoprotein synthesis. Se yeast can be consumed as such and as a nutritional supplement. Another possibility is to use selenized yeast instead of conventional yeast for baking bread. Bread is generally low in Se, and hence the use of selenized yeast for this purpose could result in higher Se intakes because bread is a common product consumed by many individuals (Dumont et al. 2006). The presented way to enrich the baking yeast in selenium, namely selenomethionine, may be successfully applied in yeast production, because the studied method is a relatively simple, nontoxic and cheap technique for introducing macrocompounds into the yeast cells. Such enriched selenium yeast may be a valuable and safe source of selenium at diet supplementation. [source]


    Poly(ethyleneglycol): A versatile and recyclable reaction medium in gaining access to benzo[4,5]imidazo[1,2- a]pyrimidines under microwave heating

    JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2009
    Shu-Liang Wang
    Polyethylene glycol is found to be a nontoxic and recyclable reaction medium for the microwave-assisted, one-pot, multicomponent reactions of aromatic aldehydes with 2-aminobenzimidazole and 1,2-diphenylethanone in the presence of potassium carbonate. This environmentally friendly microwave protocol offers ease of operation and enables recyclability of reaction media and synthesis of a variety of substituted benzo[4,5]imidazo[1,2- a]pyrimidine derivatives. It is an efficient, promising, and green synthetic strategy to construct benzo[4,5]imidazo[1,2- a]pyrimidine skeleton. J. Heterocyclic Chem. (2009). [source]


    Towards a rational development of anti-endotoxin agents: novel approaches to sequestration of bacterial endotoxins with small molecules

    JOURNAL OF MOLECULAR RECOGNITION, Issue 6 2001
    Sunil A. David
    Abstract Endotoxins, or lipopolysaccharides (LPS), present on the surface of Gram-negative bacteria, play a key role in the pathogenesis of septic shock, a common clinical problem and a leading cause of mortality in critically ill patients, for which no specific therapeutic modalities are available at the present time. The toxic moiety of LPS is a glycolipid called ,lipid A', which is composed of a bisphosphorylated diglucosamine backbone bearing up to seven acyl chains in ester and amide linkages. Lipid A is structurally highly conserved in Gram-negative bacteria, and is therefore an attractive target for developing anti-endotoxin molecules designed to sequester, and thereby neutralize, the deleterious effects of endotoxins. The anionic and amphipathic nature of lipid A enables the interaction of a wide variety of cationic amphiphiles with the toxin. This review describes the systematic evaluation of several structural classes of cationic amphiphiles, both peptides and non-peptidic small molecules, in the broader context of recent efforts aimed at developing novel anti-endotoxin strategies. The derivation of a pharmacophore for LPS recognition has led to the identification of novel, nontoxic, structurally simple small molecules, the lipopolyamines. The lipopolyamines bind and neutralize LPS in in vitro experiments as well as in animal models of endotoxicity, and thus present novel and exciting leads for rational, structure-based development of LPS-sequestering agents of potential clinical value. Copyright © 2001 John Wiley & Sons, Ltd. [source]


    The Role of Prion Peptide Structure and Aggregation in Toxicity and Membrane Binding

    JOURNAL OF NEUROCHEMISTRY, Issue 6 2000
    Dawn L. Rymer
    Abstract: Prion diseases are neurodegenerative disorders associatedwith a conformational change in the normal cellular isoform of the prionprotein, PrPC, to an abnormal scrapie isoform, PrPSC.Unlike the ,-helical PrPC, the protease-resistant core ofPrPSC is predominantly ,-sheet and possesses a tendency topolymerize into amyloid fibrils. We performed experiments with two synthetichuman prion peptides, PrP(106-126) and PrP(127-147), to determine how peptidestructure affects neurotoxicity and protein-membrane interactions. Peptidesolutions possessing ,-sheet and amyloid structures were neurotoxic toPC12 cells in vitro and bound with measurable affinities to cholesterol-richphospholipid membranes at ambient conditions, but peptide solutions lackingstable ,-sheet structures and amyloid content were nontoxic and possessedless than one tenth of the binding affinities of the amyloid-containingpeptides. Regardless of structure, the peptide binding affinities tocholesterol-depleted membranes were greatly reduced. These results suggestthat the ,-sheet and amyloid structures of the prion peptides give riseto their toxicity and membrane binding affinities and that membrane bindingaffinity, especially in cholesterol-rich environments, may be related totoxicity. Our results may have significance in understanding the role of thefibrillogenic cerebral deposits associated with some of the prion diseases inneurodegeneration and may have implications for other amyloidoses. [source]


    Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitonin

    JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2004
    Rakhi B. Shah
    Abstract The usefulness of enzyme inhibitors and absorption enhancers with least mucosal cell cytotoxicity was evaluated on Caco-2 cell monolayers. The temporal cytotoxicity of several protease inhibitors at 500 ,g/mL (e.g., turkey and chicken ovomucoids, aprotinin, and Protease Inhibitor Cocktail) and absorption enhancers [e.g., cholate (3%), glycocholate (3%), glycosursodeoxycholate (3%), ethylenediaminetetraacetic acid (EDTA, 0.1%), hydroxypropyl-,-cyclodextrin (HP-,-CD, 5%), hydroxypropyl-,-cylcodextrin (HP-,-CD, 5%), ,-cylcodextrin (,-CD, 5%), tetradecyl-,- D -maltoside (0.25%), octylglucoside (0.25%), citric acid (10%), glycyrrhetinic acid (0.34 mM), and Tween-80® (0.1%)] was measured by monitoring their effect on Caco-2 cell viability. Cell viability was measured by mannitol permeability measurements, transepithelial electrical resistance (TEER) measurements, DNA-propidium iodide staining assay, and WST-1 assay (tetrazolium salt based assay). Sodium dodecyl sulfate (0.1%), a potent surfactant, was used as a positive control. Chicken and turkey ovomucoids were nontoxic to cells as evaluated by all the methods used. Aprotinin decreased the TEER, whereas plasma membrane damage was seen with Protease Inhibitor Cocktail after a 24-h period. With respect to the absorption enhancers, the toxicity increased directly as a result of an increase in the time of incubation. The enhancers EDTA and HP-,-CD can be used safely for a short period of time, whereas glycosursodeoxycholate, glycyrrhetinic acid, octylglucoside, HP-,-CD, and ,-CD can be used for a longer period. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 1070,1082, 2004 [source]


    Therapeutic potential of melatonin in traumatic central nervous system injury

    JOURNAL OF PINEAL RESEARCH, Issue 2 2009
    Supriti Samantaray
    Abstract:, A vast literature extolling the benefits of melatonin has accumulated during the past four decades. Melatonin was previously considered of importance to seasonal reproduction and circadian rhythmicity. Currently, it appears to be a versatile anti-oxidative and anti-nitrosative agent, a molecule with immunomodulatory actions and profound oncostatic activity, and also to play a role as a potent neuroprotectant. Nowadays, melatonin is sold as a dietary supplement with differential availability as an over-the-counter aid in different countries. There is a widespread agreement that melatonin is nontoxic and safe considering its frequent, long-term usage by humans at both physiological and pharmacological doses with no reported side effects. Endeavors toward a designated drug status for melatonin may be enormously rewarding in clinics for treatment of several forms of neurotrauma where effective pharmacological intervention has not yet been attained. This mini review consolidates the data regarding the efficacy of melatonin as an unique neuroprotective agent in traumatic central nervous system (CNS) injuries. Well-documented actions of melatonin in combating traumatic CNS damage are compiled from various clinical and experimental studies. Research on traumatic brain injury and ischemia/reperfusion are briefly outlined here as they have been recently reviewed elsewhere, whereas the studies on different animal models of the experimental spinal cord injury have been extensively covered in this mini review for the first time. [source]


    Ambient-temperature copper-catalyzed atom transfer radical polymerization of methacrylates in ethylene glycol solvents

    JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 8 2005
    Solomon M. Kimani
    Abstract The use of ethylene glycol solvents in the room-temperature atom transfer radical polymerization (ATRP) of various hydrophobic and hydrophilic methacrylates is demonstrated. Unlike many of the very polar solvents described in the literature for room-temperature ATRP, these solvents have good solvency for a wide range of polymers and monomers and are cheap and relatively nontoxic. Ethylene glycols with one hydroxyl and one methoxy group, such as tri(ethylene glycol) monomethyl ether (TEGMME), provide optimal results. The polymerization of methyl methacrylate in TEGMME with CuBr/N,N,N,N,,N,-pentamethyldiethylenetriamine as the catalyst requires the addition of CuCl2 at the beginning of the reaction to produce well-controlled polymerizations. This leads to polymers with predictable molecular weights and relatively narrow polydispersities. Polymerization in solvents that are fully methoxy-capped terminate prematurely because of catalyst precipitation. The electrochemical behavior of copper complexes in selected solvents is examined to determine why these solvents provide good rates at room temperature. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1588,1598, 2005 [source]


    Biodegradable polymers with variable architectures via ring-expansion polymerization

    JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 19 2004
    Hans R. Kricheldorf
    Abstract Kinetically controlled ring-expansion polymerizations (REPs) are defined syntheses generating cyclic oligomers and polymers without linear intermediates and without equilibration reactions. This review reports syntheses of cyclic metal alkoxides and their use as initiators for REPs of lactones, cyclic diesters, and cyclocarbonates. In addition to homopolyesters, telechelic oligoesters or polyesters, random copolyesters, and A,B,A triblock copolymers can be prepared by these REPs. The in situ combination of REPs with condensation (mostly acylation) reactions allows a broad variation of end groups. The in situ combination of REPs with polycondensation enables various chain-extension reactions, including the syntheses of multiblock copolymers. With spirocyclic initiators, four-armed stars with functional end groups may be prepared. The in situ combination of REPs with condensation reactions of trifunctional or multifunctional reagents makes a broad variety of networks accessible. The average segment lengths may be controlled via the monomer/initiator ratios of the REP. All materials produced via the aforementioned REP processes are biodegradable and nontoxic, and this allows for biomedical and pharmaceutical applications. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4723,4742, 2004 [source]


    Poly(vinyl chloride) on the way from the 19th century to the 21st century

    JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 3 2004
    D. Braun
    Abstract Despite all the technical and economic problems and the public discussions on the environmental dangers and hazards of chlorine chemistry, poly(vinyl chloride) (PVC) is the second most produced plastic (with a worldwide capacity of about 31 million tons), placing after polyolefins and before styrene polymers. Presently, PVC production worldwide is growing at a rate of more than 4% per year. The application of PVC was first described in a patent in 1913, but only after 1930 did a sustained interest in PVC arise in several industrial laboratories. The most remarkable milestones in PVC history and their importance to the development of macromolecular chemistry are briefly described, and some present PVC research and industrial applications, with respect to polymerization, stabilization, bulk property modification, and chemical and material recycling of PVC waste, are discussed. Some actual selected topics include the emulsion polymerization of vinyl chloride with polymeric surfactants and controlled free-radical polymerization with nitroxyls, whereas ionic and metal organic initiators have not found any technical applications. Chemical reactions offer many possibilities for the modification of PVC, but they have been not used on a technical scale yet. Much work has been done on stabilization with nontoxic or metal-free systems. The bulk properties of PVC can be influenced by impact modification through the addition of graft copolymers or by blending with other polymers. Also presented are some problems and recent developments in PVC recycling. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 578,586, 2004 [source]


    Reduction of Ethanol-Derived Acetaldehyde Induced Motivational Properties by l -Cysteine

    ALCOHOLISM, Issue 1 2009
    Alessandra T. Peana
    Background:, Experimental evidences suggest that acetaldehyde (ACD) contributes to the positive motivational properties of ethanol (EtOH) as assessed by the place conditioning paradigm; indeed, we found that by reducing ACD production and/or by using ACD-sequestrating agents, EtOH is deprived from its motivational properties. Thiol products, such as the amino acid cysteine, are known to be effective ACD-sequestering agents. Cysteine is able to covalently bind ACD thereby forming a stable, nontoxic 2-methyl-thiazolidine-4-carboxylic acid compound. Thus, we treated rats with l -cysteine before intragastric administration of EtOH or ACD. Methods:, Male Wistar rats were pretreated intraperitoneally with saline or l -cysteine (10, 20, or 30 mg/kg), before intragastric administration of saline, EtOH (1 g/kg), or ACD (20 mg/kg). The specificity of l -cysteine effect was addressed using morphine-induced conditioned place preference (cpp) (2.5 mg/kg, i.p.). Results:,l -cysteine dose-dependently prevented both EtOH and ACD-induced cpp but did not interfere with morphine-induced cpp, suggesting that l -cysteine specifically modulates the motivational properties of EtOH. Conclusion:, The present results further underscore the role of EtOH-derived ACD in EtOH-induced motivational properties. l -cysteine, by binding EtOH-derived ACD, would deprive it of its rewarding properties and reduce its abuse liability. [source]


    Optical probing and imaging of live cells using SERS labels

    JOURNAL OF RAMAN SPECTROSCOPY, Issue 1 2009
    Janina Kneipp
    Abstract During surface-enhanced Raman scattering (SERS), molecules exhibit a significant increase in their Raman signals when attached, or in very close vicinity, to gold or silver nanostructures. This effect is exploited as the basis of a new class of optical labels. Here we demonstrate robust and sensitive SERS labels as probes for imaging live cells. These hybrid labels consist of gold nanoparticles with Rose Bengal or Crystal Violet attached as reporter molecules. These new labels are stable and nontoxic, do not suffer from photobleaching, and can be excited at any excitation wavelength, even in the near infrared. SERS labels can be detected and imaged through the specific Raman signatures of the reporters. In addition, surface-enhanced Raman spectroscopy in the local optical fields of the gold nanoparticles also provides sensitive information on the immediate molecular environment of the label in the cell and allows imaging of the native constituents of the cell. This is demonstrated by images based on a characteristic Raman line of the reporter as well as by displaying lipids based on the SERS signal of the CH deformation/bending modes at ,1470 cm,1. Copyright © 2008 John Wiley & Sons, Ltd. [source]


    Mesostructured Silica for Optical Functionality, Nanomachines, and Drug Delivery

    JOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 2009
    Yaroslav Klichko
    Silica thin films and nanoparticles prepared using sol,gel chemistry are derivatized with active molecules to generate new functional materials. The mild conditions associated with sol,gel processing allow for the incorporation of a range of dopants including organic or inorganic dyes, biomolecules, surfactants, and molecular machines. Silica nanoparticles embedded with inorganic nanocrystals, and films containing living cells have also been synthesized. Silica templated with surfactants to create mesostructure contains physically and chemically different regions that can be selectively derivatized using defined techniques to create dynamic materials. Using two different techniques, donor,acceptor pairs can be doped into separated regions simultaneously and photo-induced electron transfer between the molecules can be measured. Mesoporous silica materials are also useful supports for molecular machines. Machines including snap-tops and nanoimpellers that are designed to control the release of guest molecules trapped within the pores are described. Mesoporous silica nanoparticles are promising materials for drug delivery and other biomedical applications because they are nontoxic and can be taken up by living cells. Through appropriate design and synthesis, multifunctional mesoporous silica nanoparticles for sophisticated bio-applications are created. [source]


    A Novel Micellar PEGylated Hyperbranched Polyester as a Prospective Drug Delivery System for Paclitaxel

    MACROMOLECULAR BIOSCIENCE, Issue 9 2008
    Christina Kontoyianni
    Abstract A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aqueous solutions of BH40-PEG of 10, 30, 60, and 90 mg,·,mL,1, respectively. More than 50% of the drug is released at a steady rate and release is almost complete within 10 h. The toxicity of BH40-PEG was assessed in vitro with A549 human lung carcinoma cells and found to be nontoxic for 3 h incubation up to a 1.75 mg,·,mL,1 concentration while LD50 was 3.5 mg,·,mL,1. Finally, it was efficiently internalized in cells, primarily in the absence of foetal bovine serum, while confocal microscopy revealed the preferential localization of the compound in cell nuclei. [source]


    Novel Types of Carborane-Carrier Hyaluronan Derivatives via "Click Chemistry",

    MACROMOLECULAR BIOSCIENCE, Issue 7 2008
    Chiara Di Meo
    Abstract Two new HA derivatives bearing carborane rings were synthesized by click chemistry. The optimal conditions were assessed for the preparation of biocompatible boron carriers, potentially suitable for application in BNCT and capable of targeting the CD44 antigen. The new polymeric samples were characterized by means of NMR-spectroscopy techniques that gave degrees of 17 and 8% for HAAACB and HapACB, respectively. Both HAAACB and HApACB turned out to be nontoxic for colorectal, ovarian and bladder tumor cell lines, to disclose a specific interaction with the CD44 antigen as the native hyaluronan moiety, and to deliver boron-atom concentrations largely sufficient for BNCT therapy when accumulated in cancer cells. [source]


    Reactivity to sodium tetrachloropalladate (Na2[PdCl4]) compared to PdCl2 and NiCl2 in lymphocyte proliferation tests

    ALLERGY, Issue 8 2009
    J. Muris
    Background:, For patch testing, replacement of the commonly used palladium dichloride (PdCl2) by sodium tetrachloropalladate (Na2[PdCl4]) was recently demonstrated to improve test accuracy and show a significant correlation with nickel (Ni), supporting the concept of cross-reactivity between Pd and Ni. A promising alternative to metal allergy patch testing is the in vitro lymphocyte proliferation test (LTT). Objectives:, The aim of this study was to test whether Na2[PdCl4] is also more sensitive for diagnosing Pd allergy with a standardized LTT. Patients/methods:, After determining optimal nontoxic and nonmitogenic concentrations for Na2[PdCl4], blood samples from 105 patients with clinical suspicion of metal allergy were tested with an LTT called memory lymphocyte immuno stimulation assay for Na2[PdCl4], PdCl2 and NiCl2. Reaction profiles were analysed for concordant positive reactions. Results:, Using the conventional cut-off of stimulation index , 3, 74.3% showed a positive reaction to NiCl2, 15.2% to PdCl2 and 28.6% to Na2[PdCl4]. All positive results to PdCl2 were covered by Na2[PdCl4]. From the 30 positive reactions to Na2[PdCl4], 26 (87%) were concordant for NiCl2 reactivity. Conclusion:, In LTT, the use of Na2[PdCl4] results in more positive reactions in Pd allergy testing which are in concordance with positive reactions to PdCl2 and NiCl2. [source]