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Sample records for restrained antimicrobial arylamide

  1. De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers

    PubMed Central

    Choi, Sungwook; Isaacs, Andre; Clements, Dylan; Liu, Dahui; Kim, Hyemin; Scott, Richard W.; Winkler, Jeffrey D.; DeGrado, William F.

    2009-01-01

    The emergence of drug-resistant bacteria has compromised the use of many conventional antibiotics, leading to heightened interest in a variety of antimicrobial peptides. Although these peptides have attractive potential as antibiotics, their size, stability, tissue distribution, and toxicity have hampered attempts to harness these capabilities. To address such issues, we have developed small (molecular mass <1,000 Da) arylamide foldamers that mimic antimicrobial peptides. Hydrogen-bonded restraints in the arylamide template rigidify the conformation via hydrogen bond formation and increase activity toward Staphylococcus aureus and Escherichia coli. The designed foldamers are highly active against S. aureus in an animal model. These results demonstrate the application of foldamer templates as therapeutics. PMID:19359494

  2. Antibacterial Mechanism of Action of Arylamide Foldamers ▿ †

    PubMed Central

    Mensa, Bruk; Kim, Yong Ho; Choi, Sungwook; Scott, Richard; Caputo, Gregory A.; DeGrado, William F.

    2011-01-01

    Small arylamide foldamers designed to mimic the amphiphilic nature of antimicrobial peptides (AMPs) have shown potent bactericidal activity against both Gram-negative and Gram-positive strains without many of the drawbacks of natural AMPs. These foldamers were shown to cause large changes in the permeability of the outer membrane of Escherichia coli. They cause more limited permeabilization of the inner membrane which reaches critical levels corresponding with the time required to bring about bacterial cell death. Transcriptional profiling of E. coli treated with sublethal concentrations of the arylamides showed induction of genes related to membrane and oxidative stresses, with some overlap with the effects observed for polymyxin B. Protein secretion into the periplasm and the outer membrane is also compromised, possibly contributing to the lethality of the arylamide compounds. The induction of membrane stress response regulons such as rcs coupled with morphological changes at the membrane observed by electron microscopy suggests that the activity of the arylamides at the membrane represents a significant contribution to their mechanism of action. PMID:21844313

  3. Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

    PubMed Central

    More, Satish S; Chaitanya, T Krishna; Kumar, Yadla Sateesh; Meruva, Suresh Babu; Rao, L Vaikunta

    2013-01-01

    Summary A highly efficient synthesis of enantiomerically pure (S) and (R)-isomers of N-(2,3-dihydroxypropyl)arylamides has been developed with good overall yields in a two step process. The key step involves the ring opening of the chiral epoxide with a nitrogen heterocyclic carbene (NHC) and further rearrangement to chiral N-(2,3-dihydroxypropyl)arylamides in high yields and enantioselectivity. During the reaction, no erosion in chiral purity was observed. PMID:24204425

  4. Modeling of Arylamide Helix Mimetics in the p53 Peptide Binding Site of hDM2 Suggests Parallel and Anti-Parallel Conformations Are Both Stable

    PubMed Central

    Fuller, Jonathan C.; Jackson, Richard M.; Edwards, Thomas A.; Wilson, Andrew J.; Shirts, Michael R.

    2012-01-01

    The design of novel α-helix mimetic inhibitors of protein-protein interactions is of interest to pharmaceuticals and chemical genetics researchers as these inhibitors provide a chemical scaffold presenting side chains in the same geometry as an α-helix. This conformational arrangement allows the design of high affinity inhibitors mimicking known peptide sequences binding specific protein substrates. We show that GAFF and AutoDock potentials do not properly capture the conformational preferences of α-helix mimetics based on arylamide oligomers and identify alternate parameters matching solution NMR data and suitable for molecular dynamics simulation of arylamide compounds. Results from both docking and molecular dynamics simulations are consistent with the arylamides binding in the p53 peptide binding pocket. Simulations of arylamides in the p53 binding pocket of hDM2 are consistent with binding, exhibiting similar structural dynamics in the pocket as simulations of known hDM2 binders Nutlin-2 and a benzodiazepinedione compound. Arylamide conformations converge towards the same region of the binding pocket on the 20 ns time scale, and most, though not all dihedrals in the binding pocket are well sampled on this timescale. We show that there are two putative classes of binding modes for arylamide compounds supported equally by the modeling evidence. In the first, the arylamide compound lies parallel to the observed p53 helix. In the second class, not previously identified or proposed, the arylamide compound lies anti-parallel to the p53 helix. PMID:22916232

  5. Intramolecular hydrogen bonds: ab initio Car Parrinello simulations of arylamide torsions

    NASA Astrophysics Data System (ADS)

    Doerksen, Robert J.; Chen, Bin; Klein, Michael L.

    2003-10-01

    Gas-phase, room temperature Car-Parrinello molecular dynamics simulations using the HCTH density functional are reported for the arylamides acetanilide ( 1) and ortho-methylthioacetanilide ( 2). The simulations show that in 1, rotation around the ring-amide bond is relatively unrestricted. By contrast, in 2 the methylthio side chain encourages the amide to be directed with N-H pointing toward S, not to flip by 360°, and furthermore to remain close to coplanar with the benzene ring. Because of an intramolecular N-H⋯S hydrogen bond, the N-H stretch frequency of 2 is red-shifted by ˜78 cm -1 compared to that of 1.

  6. Motion restraining device

    NASA Technical Reports Server (NTRS)

    Ford, A. G. (Inventor)

    1977-01-01

    A motion-restraining device for dissipating at a controlled rate the force of a moving body is discussed. The device is characterized by a drive shaft adapted to be driven in rotation by a moving body connected to a tape wound about a reel mounted on the drive shaft, and an elongated pitman link having one end pivotally connected to the crankshaft and the opposite end thereof connected with the mass through an energy dissipating linkage. A shuttle is disposed within a slot and guided by rectilinear motion between a pair of spaced impact surfaces. Reaction forces applied at impact of the shuttle with the impact surfaces include oppositely projected force components angularly related to the direction of the applied impact forces.

  7. Involuntary memories and restrained eating.

    PubMed

    Ball, Christopher T

    2015-05-01

    Most involuntary memories are elicited by external cues (e.g., smells, sounds) that have unique associations with specific memories (Berntsen's cue-retrieval hypothesis), but involuntary memories can sometimes be elicited by weak, even imperceptible, cues that raise the activation level of an already primed memory (Berntsen's motivation-priming hypothesis) to also reach conscious awareness during times of low attentional focus. The current study examined the effects of a motivation bias (restrained eating) on the involuntary memories recorded in daily diaries for seven days by 56 female participants. A large proportion of the involuntary memories were elicited by food-related cues and occurred in food-related contexts. A significant correlation was found between the participants' scores on a restrained eating scale and the percentage of involuntary memories involving cooking and eating content. These results parallel previous research involving voluntary memory retrievals during restrained eating.

  8. Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides.

    PubMed

    Aboraia, Ahmed S; Yee, Sook Wah; Gomaa, Mohamed Sayed; Shah, Nikhil; Robotham, Anna C; Makowski, Bart; Prosser, David; Brancale, Andrea; Jones, Glenville; Simons, Claire

    2010-07-15

    A series of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides were prepared, using an efficient three- to five-step synthesis, and evaluated for their inhibitory activity against human cytochrome P450C24A1 (CYP24A1) hydroxylase. Inhibition ranged from IC50 0.3-72 microM compared with the standard ketoconazole IC50 0.52 microM, with the styryl derivative (11c) displaying enhanced activity (IC50=0.3 microM) compared with the standard, providing a useful preliminary lead for drug development.

  9. Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties.

    PubMed

    Gamal El-Din, Mahmoud M; El-Gamal, Mohammed I; Abdel-Maksoud, Mohammed S; Yoo, Kyung Ho; Oh, Chang-Hyun

    2016-08-25

    A novel series of 1,3,4-triarylpyrazole derivatives possessing terminal arylamide or arylurea terminal moieties has been designed and synthesized. Their in vitro antiproliferative activities were investigated against a panel of 58 cell lines of nine different cancer types at the NCI, USA. The urea analogues 2b, 2c, and 2f as well as the amide derivatives 3e and 3f exerted the highest mean % inhibition values over the 58 cell line panel at 10 μM, and thus were further tested in 5-dose testing mode to determine their GI50, TGI, and LC50 values. The above mentioned compounds have shown stronger antiproliferative activities in terms of potency and efficacy upon comparing their results with Sorafenib as a reference compound. Among them, compounds 2c and 2f possessing 3,4-dichlorophenylurea terminal moiety showed the highest mean %inhibition value of about 99.85 and 104.15% respectively over the 58-cell line panel at 10 μM concentration. Also compounds 2b, 3e, and 3f exhibited mean % inhibition over 80% at 10 μM concentration. The GI50 value of compound 3e over K-562 cancer cell line was 0.75 μM. Accordingly, compound 2f was screened over seven kinases at a single-dose concentration of 10 μM to profile its kinase inhibitory activity. Interestingly, the compound showed highly inhibitory activities (90.44% and 87.71%) against BRAF (V600E) and RAF1 kinases, respectively. Its IC50 value against BRAF (V600E) was 0.77 μM. Compounds 2b, 2c, 2f, 3e, and 3f exerted high selectivity towards cancer cell lines than L132 normal lung cells. PMID:27155467

  10. Successful restrained eating and trait impulsiveness.

    PubMed

    van Koningsbruggen, Guido M; Stroebe, Wolfgang; Aarts, Henk

    2013-01-01

    Restrained eaters with high scores on the Perceived Self-Regulatory Success in Dieting Scale (PSRS) are more successful than low scorers in regulating their food intake. According to the theory of temptation-elicited goal activation (Fishbach, Friedman, & Kruglanski, 2003), they have become successful because, due to earlier repeated instances of successful self-control, they formed an associative link between temptations and thoughts of dieting. It is unclear, however, why they should have been more successful in earlier attempts at self-control than their unsuccessful counterparts. We examined whether trait impulsiveness plays a role by investigating the associations between dietary restraint, trait impulsiveness, and PSRS. Results showed that the interaction between dietary restraint and impulsiveness predicted dieting success: A lower level of impulsiveness was associated with greater dieting success among restrained eaters. These results suggest that restrained eaters who are less impulsive are more likely to become successful restrained eaters as identified with the PSRS.

  11. Apparatus for restraining and transporting dies

    DOEpatents

    Allison, James W.; LaBarre, Timothy L.

    1994-01-01

    Apparatus for restraining and transporting dies in punch press operations is provided. A floatation platen for supporting a die on the platen's upper surface has a plurality of recessed gas exhaust ports on the platen's lower surface. A source of pressurized gas delivers gas to a platen manifold, for delivery to orifices located in the gas exhaust ports. The flow of gas is controlled by a first valve adjacent the gas source and a second valve adjacent the manifold, with the second valve being used to control the gas flow during movement of the die. In this fashion, a die may be moved on a cushion of air from one workstation to a selected second workstation. A moveable hydraulically operated restraining fixture is also provided, for clamping the die in position during the compacting phase, and for releasing the die after completion of the compacting phase by releasing the hydraulic pressure on the restraining fixture. When pressure in the hydraulic cylinders on the restraining fixture is reversed, the restraining fixture will retract so that there is no contact between the die and the restraining fixture, thereby allowing the die to be removed from a first workstation and moved to a second selected workstation.

  12. A simple validated RP-HPLC bioanalytical method for the quantitative determination of a novel valproic acid arylamide derivative in rat hepatic microsomes.

    PubMed

    Silva-Trujillo, Arianna; Correa-Basurto, José; Romero-Castro, Aurelio; Albores, Arnulfo; Mendieta-Wejebe, Jessica Elena

    2015-04-01

    A simple and specific bioanalytical method based on reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with ultraviolet detection was developed and validated for the determination of a novel valproic acid arylamide, N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) in rat hepatic microsomes (a subcellular fraction containing phase I enzymes, especially cytochrome P450). The chromatographic separation was achieved using a reversed-phase Zorbax SB-C18 column and a mobile phase of acetic acid in water (0.2% v/v) and acetonitrile (40:60 v/v) with a flow rate of 0.5 mL/min. The calibration curve was linear over the range of 882-7060 ng/mL (r(2)  = 0.9987), and the lower limit of quantification and the lower limit of determination were found to be 882 and 127.99 ng/mL, respectively. The method was validated with excellent sensitivity, and intra-day accuracy and precision varied from 93.79 to 93.12%, and from 2.12 to 4.36%, respectively. The inter-day accuracy and precision ranged from 93.29 to 97.30% and from 0.68 to 3.60%, respectively. The recovery of HO-AAVPA was measured between 91.36 and 97.98%. The assay was successfully applied to the analysis of kinetic metabolism and pharmacokinetic parameters in vitro by a substrate depletion approach.

  13. Restrained point-charge models for disaccharides.

    PubMed

    Sigfridsson, Emma; Ryde, Ulf; Bush, Bruce L

    2002-02-01

    Various methods for deriving atomic partial charges from the quantum chemical electrostatic potential and moments have been tested for the sucrose molecule. We show that if no further information is used, the charges on some carbon atoms become large and charge patterns involving these atoms are badly determined and poorly transferable. Adding lone-pairs on the ether oxygen atoms or dividing the molecule into smaller fragments did not cure the instabilities. We develop a method, CHELP-BOW0, that restrains charges toward zero with different weights for different atoms. These harmonic restraints preserve the linear form of the least-squares equations, which are solved in a single step using singular-value decomposition. CHELP-BOW0 improves the chemical transferability of the charges compared to unrestrained methods, and slightly improves their conformational transferability. It introduces a modest degradation of the fit compared to unrestrained CHELP-BOW (mean average deviation of the potential 0.00016 vs. 0.00010 a.u.). A second new method, CHELP-BOWC, avoids the need for restraints by including several conformations in the fit, weighting each according to its estimated energy in solution. CHELP-BOWC charges are more transferable than CHELP-BOW or CHELP-BOW0 charges to conformations not included in the training set. Restraints to zero charge do not further improve transferability of the CHELP-BOWC charges. We, therefore, recommend CHELP-BOW charges for rigid molecules and CHELP-BOWC charges for flexible molecules. PMID:11908498

  14. Role of the Conformational Rigidity in the Design of Biomimetic Antimicrobial Compounds

    SciTech Connect

    Ivankin, Andrey; Livne, Liran; Mor, Amram; Caputo, Gregory A.; DeGrado, William F.; Meron, Mati; Lin, Binhua; Gidalevitz, David

    2011-08-16

    A link between structural flexibility of biomimetic antimicrobials and their ability to penetrate into the hydrophobic core and disrupt the integrity of bacterial lipid model membranes has been established using liquid surface X-ray scattering techniques. Results indicate that the modes of interaction of flexible and conformationally restrained antimicrobials with the bacterial membranes are different.

  15. A restraining system for rhesus monkeys used in space research.

    PubMed

    Florence, G; Riondet, L; Malecki, H; Blanquie, J P; Martin, F; Viso, M; Milhaud, C L

    1995-02-01

    A new chronic restraining system has been designed specifically for male rhesus monkeys (8-13 kg) housed in weightlessness for scientific purposes. The restraining system consists of a coat (jacket and skirt) and a chair. The system separates the thorax from the lower part of the body, and allows large movements of the upper part of the body. The macaque can feed and groom itself, and can also sleep in close-to-normal position. PMID:8613974

  16. Color-dependent learning in restrained Africanized honey bees.

    PubMed

    Jernigan, C M; Roubik, D W; Wcislo, W T; Riveros, A J

    2014-02-01

    Associative color learning has been demonstrated to be very poor using restrained European honey bees unless the antennae are amputated. Consequently, our understanding of proximate mechanisms in visual information processing is handicapped. Here we test learning performance of Africanized honey bees under restrained conditions with visual and olfactory stimulation using the proboscis extension response (PER) protocol. Restrained individuals were trained to learn an association between a color stimulus and a sugar-water reward. We evaluated performance for 'absolute' learning (learned association between a stimulus and a reward) and 'discriminant' learning (discrimination between two stimuli). Restrained Africanized honey bees (AHBs) readily learned the association of color stimulus for both blue and green LED stimuli in absolute and discriminatory learning tasks within seven presentations, but not with violet as the rewarded color. Additionally, 24-h memory improved considerably during the discrimination task, compared with absolute association (15-55%). We found that antennal amputation was unnecessary and reduced performance in AHBs. Thus color learning can now be studied using the PER protocol with intact AHBs. This finding opens the way towards investigating visual and multimodal learning with application of neural techniques commonly used in restrained honey bees.

  17. Antimicrobials Treatment

    NASA Astrophysics Data System (ADS)

    Drosinos, Eleftherios H.; Skandamis, Panagiotis N.; Mataragas, Marios

    The use of antimicrobials is a common practice for preservation of foods. Incorporation, in a food recipe, of chemical antimicrobials towards inhibition of spoilage and pathogenic micro-organisms results in the compositional modification of food. This treatment is nowadays undesirable for the consumer, who likes natural products. Scientific community reflecting consumers demand for natural antimicrobials has made efforts to investigate the possibility to use natural antimicrobials such us bacteriocins and essential oils of plant origin to inhibit microbial growth.

  18. Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans.

    PubMed

    Hua, J; Yamarthy, R; Felsenstein, S; Scott, R W; Markowitz, K; Diamond, G

    2010-12-01

    Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans but numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (with molecular weight < 1000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-minimum inhibitory concentration levels did not lead to resistant Candida, in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.

  19. Activity of Antimicrobial Peptide Mimetics in the Oral Cavity: I. Activity Against Biofilms of Candida albicans

    PubMed Central

    Hua, Jianyuan; Yamarthy, Radha; Felsenstein, Shaina; Scott, Richard W.; Markowitz, Kenneth; Diamond, Gill

    2010-01-01

    Summary Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans, however numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (MW <1,000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-MIC levels did not lead to resistant Candida in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies. PMID:21040515

  20. Antimicrobial peptides

    PubMed Central

    2014-01-01

    With increasing antibiotics resistance, there is an urgent need for novel infection therapeutics. Since antimicrobial peptides provide opportunities for this, identification and optimization of such peptides have attracted much interest during recent years. Here, a brief overview of antimicrobial peptides is provided, with focus placed on how selected hydrophobic modifications of antimicrobial peptides can be employed to combat also more demanding pathogens, including multi-resistant strains, without conferring unacceptable toxicity. PMID:24758244

  1. Ulcers in restrained rats: Study of protective substances

    NASA Technical Reports Server (NTRS)

    Buche, L.; Gallaire, D.

    1980-01-01

    The genesis of ulcers in restrained rats is discussed through an investigation of the relationship between the protective effects of nervous system effectual substances examined vis-a-vis ulcers in restrained rats and their elective or secondary pharmacologic effects. The substances used were capable of either peripheral parasympatholytic, sympatholytic, ganglioplegic, spasmolytic effects or central, hypnotic, tranquilizing, neuroleptic, analgesic effects. The regular and considerable protection observed with parasympatholytics (atropine sulfate, benzylonium bromide, dihexyverine, J.L. 1344) and a ganglioplegic (pentamethonium) is a function of their anticholinergic properties. It is of less importance with dibenamine, a sympatholytic action on the adrenergic receptors. Among the central depressive substances tested (hypnotics, tranquilizers, neuroleptics, analgesic), phenobarbital at a nonhypnotic dose, and dextromoramide at a nonanalgesic dose, show antiulcerous effects, which are found with chlorpromazine only at cataleptogenic doses.

  2. Are Temporary Restraining Orders More Likely to Be Issued When Applications Mention Firearms?

    ERIC Educational Resources Information Center

    Vittes, Katherine A.; Sorenson, Susan B.

    2006-01-01

    Restraining orders, an important legal intervention for victims of domestic violence, have broad potential for injury prevention. Using data from one of the busiest restraining order clinics in the nation, the authors examined 1,354 applicants' descriptions of abuse. Most (89.2%) applicants were issued a restraining order. A total of 16.0% of…

  3. Injury causation scenarios in belt-restrained nearside child occupants.

    PubMed

    Maltese, Matthew R; Locey, Caitlin M; Jermakian, Jessica S; Nance, Michael L; Arbogast, Kristy B

    2007-10-01

    Successful development of side impact safety systems for rear row child occupants requires an understanding of injury causation and mitigation. However, data to guide the design of such safety systems for seat belt-restrained occupants is limited to injury risk assessments. Thus, we sought to elucidate Injury Causation Scenarios (ICS's) in children restrained by seat belts in nearside impacts. Included in the study were 4 to 15 year old children, involved in a side impact, seated on the nearside in the rear rows, restrained by a seat belt alone (no booster seats or side airbags) and who received an AIS 2+ injury. A Contact Point Map summarized the vehicle components that contribute to the injuries. The majority of head and face contacts points were found horizontally within the rear half of the window, and vertically from the window sill to the center of the window, and were a result of contact with both interior structures and structures on the crash partner. The most prevalent intracranial injuries included cerebral contusions, diffuse axonal injury (DAI), and subdural or subarachnoid hematoma/hemorrhage. The most common cause of torso and abdominal injury was contact with the side interior structure, and injuries included spleen lacerations or ruptures, liver lacerations and contusions, lung contusions, rib fractures, and clavicle fractures. Protuberances on the door interior, such as the armrest, were the most common source of abdominal injury in this dataset. These data provide important guidance for the development of rear row safety systems for belt-restrained children with no side airbags in nearside crashes. PMID:18278602

  4. Dieting and restrained eating as prospective predictors of weight gain.

    PubMed

    Lowe, Michael R; Doshi, Sapna D; Katterman, Shawn N; Feig, Emily H

    2013-09-02

    Research in normal weight individuals paradoxically suggests that measures of attempted eating restriction might represent robust predictors of weight gain. This review examined the extent to which measures of dieting (e.g., self-reported weight loss dieting in the past year) and dietary restraint (e.g., the Cognitive Restraint scale from the Three-Factor Eating Questionnaire) have prospectively predicted weight change. We located and reviewed 25 prospective studies containing 40 relevant comparisons. Studies were limited to those in which participants were non-obese (with a mean BMI between 18.5 and 30) and averaged at least 12 years old. Neither measure predicted future weight loss. Fifteen of the 20 comparisons (75%) that examined measures of dieting significantly predicted future weight gain whereas only 1 of 20 (5%) that examined restrained eating measures did so. Two plausible explanations for these findings are that: (1) dieters and restrained eaters do not differ in terms of an underlying proneness toward weight gain, but restrained eating represents a more effective means of preventing it; and (2) normal weight individuals who diet do so because they are resisting a powerful predisposition toward weight gain which dieting ultimately fails to prevent. Recent dieting in non-obese individuals may be a valuable proxy of susceptibility to weight gain. This easily assessed characteristic could identify individuals for whom obesity prevention interventions would be particularly appropriate.

  5. Antimicrobial Polymer

    DOEpatents

    McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

    2004-09-28

    A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The polymeric composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from metals, metal alloys, metal salts, metal complexes and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one example embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl; and the metallic antimicrobial agent is selected from chelated silver ions, silver metal, chelated copper ions, copper metal, chelated zinc ions, zinc metal and mixtures thereof.

  6. Antimicrobial Resistance

    MedlinePlus

    ... antibiotic are known as methicillin-resistant S. aureus or MRSA. Antibiotics and other antimicrobial drugs first became widely ... factors for infection are known as community-associated MRSA (CA-MRSA). Recently, several cases overseas and in ...

  7. Geomorpho-tectonic evolution of the Jamaican restraining bend

    NASA Astrophysics Data System (ADS)

    Domínguez-González, Leomaris; Andreani, Louis; Stanek, Klaus P.; Gloaguen, Richard

    2015-01-01

    This work applies recent advances in tectonic geomorphology in order to understand the geomorphic evolution of the Jamaican restraining bend located along the Caribbean-Gonâve-North American plate boundary. We propose a classification of landscapes according to their erosional stages. The approach is mainly based on the combination of two DEM-based geomorphic indices: the hypsometric integral which highlights elevated surfaces, and the surface roughness which increases when the relief is incised by the drainage network. River longitudinal profiles were also analyzed as the drainage network responds quickly to base-level change triggered by external forcing such as tectonics. Anomalies in river profiles (knickpoints and convex segments) were mapped using stream length-gradient (SL) and normalized steepness (ksn) indices. The results provide new insights for understanding the complex evolution of the Jamaican restraining bend. Three main morphotectonic regions were identified in Jamaica: (1) the Blue Mountain-Wagwater unit located at the eastern tip of the island, (2) the Jamaican highlands plateau which covers most of the northern and central areas and (3) the tilted block province located along the southern part of Jamaica. Each region has a specific morphological signature which marks a different stage in the Late Miocene to present evolution of the Jamaican restraining bend. The evolution of the bend is mainly associated with the western propagation of major E-trending strike-slip faults and NW-trending thrusts. In the western and central parts of Jamaica the present-day motion between the Caribbean plate and the Gonâve microplate is broadly distributed along several structures, while in the easternmost part of the island this motion seems to be almost completely accommodated along the Blue Mountain range and the Plantain-Garden Fault.

  8. Transverse Vibrations of Double Bellows Expansion Joint Restrained Against Rotation

    SciTech Connect

    Kameswara, Rao C.; Radhakrishna, M.

    2002-07-01

    The paper presents the results of investigation of transverse vibrations of double bellows expansion joint restrained against rotation on either end. A theoretical model is developed based on the Bernoulli-Euler beam theory and includes added mass of the fluid flowing inside the pipe-bellow-pipe assembly. Neglecting effect of shear, an exact frequency equation is derived for the transverse vibrations of double bellows expansion joint including the effects of end elastic restraints against rotation. Numerical results are presented for an example bellow showing the effects of variation of elastic restraints and internal pressure on the first two modes of vibration. (authors)

  9. Thermal Behavior of Cylindrical Buckling Restrained Braces at Elevated Temperatures

    PubMed Central

    Talebi, Elnaz; Tahir, Mahmood Md.; Yasreen, Airil

    2014-01-01

    The primary focus of this investigation was to analyze sequentially coupled nonlinear thermal stress, using a three-dimensional model. It was meant to shed light on the behavior of Buckling Restraint Brace (BRB) elements with circular cross section, at elevated temperature. Such bracing systems were comprised of a cylindrical steel core encased in a strong concrete-filled steel hollow casing. A debonding agent was rubbed on the core's surface to avoid shear stress transition to the restraining system. The numerical model was verified by the analytical solutions developed by the other researchers. Performance of BRB system under seismic loading at ambient temperature has been well documented. However, its performance in case of fire has yet to be explored. This study showed that the failure of brace may be attributed to material strength reduction and high compressive forces, both due to temperature rise. Furthermore, limiting temperatures in the linear behavior of steel casing and concrete in BRB element for both numerical and analytical simulations were about 196°C and 225°C, respectively. Finally it is concluded that the performance of BRB at elevated temperatures was the same as that seen at room temperature; that is, the steel core yields prior to the restraining system. PMID:24526915

  10. Taurine and proliferation of lymphocytes in physically restrained rats

    PubMed Central

    2010-01-01

    Background Taurine is present in lymphocytes and seems to modulate certain immune cell functions. Among the effects of taurine on these cells are protection against antioxidants and regulation of inflammatory aspects of the immune response. Stress affects antigen presentation, traffic and proliferation of leukocytes, as well as antibody and cytokine secretion. The purposes of this study were to explore the possible direct effects of taurine concentrations on lymphoproliferation and interleukins levels in control and in physical restrained rats. Methods Lymphocytes of male Sprague-Dawley rats, stressed by physical restrain and controls (5 h per day for 5 days) were isolated from blood by Histopaque (1077 g/l) and differential adhesion to plastic, and then cultured (72 h) in the presence of different concentrations of taurine (0.5 – 50 mM), β-alanine (0.5 – 50 mM), or both, without or with the T cells mitogen, concanavalin A. Plasma and lymphocytes levels of pro-inflammatory interleukin-1β and anti-inflammatory interleukin-10 were respectively measured by Pierce Endogen rat ELISA Kits. Taurine in plasma and in lymphocytes were determined by HPLC. Results Lymphoproliferation of resting cells significantly decreased in the presence of 3 and 6 mM taurine and increased up to control level at 12 mM taurine. In concanavalin A-activated lymphocytes, the effect of taurine was greater. β-alanine increased lymphoproliferation in a bell shaped dose-dependent manner and decreased it in activated lymphocytes but in a lower magnitude. In combination, β-alanine impaired the effect of taurine at 3 and 6 mM. After restriction, no change in lymphoproliferation was observed at different concentrations of the amino acids without or with concanavalin A, although pro-inflammatory interleukin and taurine in plasma and in lymphocytes significantly increased. Conclusions Taurine affects lymphoproliferation in control rats, following a dose-dependent manner, an effect that might

  11. Unilateral buckling of elastically restrained rectangular mild steel plates

    NASA Astrophysics Data System (ADS)

    Smith, S. T.; Bradford, M. A.; Oehlers, D. J.

    This paper considers the elastic unilateral buckling of rectangular mild steel plates that are restrained elastically and subjected to bending and axial actions. A variational formulation of the Ritz method using linear combinations of harmonic functions for the buckling deformations is used to establish an eigenproblem to determine the plate local buckling coefficients. The motivation for the study is the retrofit of reinforced concrete beams by gluing and then bolting steel plates to the sides of the beam. Such plates, when acting compositely with the concrete beam, are subjected to predominantly bending and axial actions which may cause unilateral local buckling. Whereas the bolts provide complete restraint against buckling at discrete points, the glue may also inhibit local buckling between these nodal points since it acts as a continuous elastic restraint. The influence of the glue stiffness, support conditions and plate proportions on the unilateral buckling of such plates are assessed.

  12. Protein structure refinement with adaptively restrained homologous replicas.

    PubMed

    Della Corte, Dennis; Wildberg, André; Schröder, Gunnar F

    2016-09-01

    A novel protein refinement protocol is presented which utilizes molecular dynamics (MD) simulations of an ensemble of adaptively restrained homologous replicas. This approach adds evolutionary information to the force field and reduces random conformational fluctuations by coupling of several replicas. It is shown that this protocol refines the majority of models from the CASP11 refinement category and that larger conformational changes of the starting structure are possible than with current state of the art methods. The performance of this protocol in the CASP11 experiment is discussed. We found that the quality of the refined model is correlated with the structural variance of the coupled replicas, which therefore provides a good estimator of model quality. Furthermore, some remarkable refinement results are discussed in detail. Proteins 2016; 84(Suppl 1):302-313. © 2015 Wiley Periodicals, Inc. PMID:26441154

  13. Dynamic modelling of mechanical systems with opposing restrained preloaded stiffnesses

    NASA Astrophysics Data System (ADS)

    Rogers, R. J.; Garland, P.; Oliver, M.

    2004-07-01

    Preloaded springs are used in many mechanical systems such as suspension systems and linkages, as well as household items such as clothing clasps. Usually, the preload has no effect on small amplitude dynamic responses which occur about the mean preloaded position. However if the system has opposing preloaded elastic elements, where unloading is limited by restraints such as central rods which preserve the preload, then the preload has a dramatic effect on a system's dynamic response. When such a system is set into free oscillation, the period of motion steadily decreases as the amplitude diminishes. Until now the authors have not seen this behavior described elsewhere. The present work is motivated by the modelling of joysticks which are used to actuate hydraulic systems in a wide variety of mobile construction and forestry equipment. Their use for long periods of time may lead to repetitive strain injuries in an operator's upper limbs, neck and back. In order to assess the total force required to move a joystick, the stiffness, damping and inertia characteristics must be determined. A mathematical model for joystick dynamics is presented and the effect of restrained spring preloads on the changing period of free vibration is explained. In addition, procedures to estimate the non-symmetric non-linear damping from experimental data are described. By simulating the dynamic response in MATLAB TM, the damping is fine-tuned by comparing the joystick's simulated free oscillation response with its experimental response. Finally, the torque waveform required to perform a simple joystick motion is estimated. The methods developed in this paper could be applied to any lumped-parameter mechanical system where there are opposing restrained preloaded elastic elements.

  14. Altered regional homogeneity and efficient response inhibition in restrained eaters.

    PubMed

    Dong, D; Lei, X; Jackson, T; Wang, Y; Su, Y; Chen, H

    2014-04-25

    Restrained eaters (REs) characterized by less efficient response inhibition are at risk for future onset of binge eating and bulimic pathology. Previous imaging studies investigating REs have been based on task-related functional magnetic resonance imaging (fMRI) and little is known about resting-state neural activity underlying restrained eating. To illuminate this issue, we investigated resting-state fMRI differences between REs (n=22) and unrestrained eaters (UREs) (n=30) using regional homogeneity (ReHo) analysis, which measures the temporal synchronization of spontaneous fluctuations. Samples were equated on body mass index (BMI) and caloric deprivation levels (i.e., 14±2.1h since last evening meal) before undergoing fMRI. Correlation analyses were performed between the ReHo index of identified regions and response inhibition based on stop-signal reaction time (SSRT) within each sample. Compared with UREs, REs showed more ReHo in brain regions associated with food reward (i.e., orbitofrontal cortex (OFC), dorsal-lateral prefrontal cortex (dlPFC)), attention (i.e., lingual gyrus, cuneus, inferior parietal lobule) and somatosensory functioning (i.e., paracentral lobule, anterior insula). In addition, ReHo values for the left dlPFC and left anterior insula, respectively, were negatively and positively correlated with SSRT among REs but not UREs. In concert with previous studies, these results suggest altered local synchronization may help to explain why dieting to maintain or lose weight often fails or increases risk for binge eating among REs. PMID:24513387

  15. Body Dissatisfaction Mediates the Relationship between Self-Esteem and Restrained Eating in Female Undergraduates

    ERIC Educational Resources Information Center

    Gianini, Loren M.; Smith, Jane Ellen

    2008-01-01

    The purpose of the current study was to examine the eating behavior, self-esteem, and social anxiety of restrained and non-restrained eaters exposed to an interpersonal stressor. Sixty female undergraduate students completed questionnaires and took part in a stressor and taste test. Results indicated that self-esteem was not predictive of eating…

  16. Are temporary restraining orders more likely to be issued when applications mention firearms?

    PubMed

    Vittes, Katherine A; Sorenson, Susan B

    2006-06-01

    Restraining orders, an important legal intervention for victims of domestic violence, have broad potential for injury prevention. Using data from one of the busiest restraining order clinics in the nation, the authors examined 1,354 applicants' descriptions of abuse. Most (89.2%) applicants were issued a restraining order. A total of 16.0% of applicants mentioned a firearm in their descriptions of abuse; doing so was not associated with restraining order issuance. About 1 in 20 applicants, even if issued a restraining order, would not be protected by the federal firearm purchase and possession prohibitions because they had not lived with or had a child with the defendant. However, the proportion of these individuals who report threatened or actual use of firearms against them is similar to that of other applicants. Federal and, when relevant, state law should be modified to include these persons.

  17. Restrained eating: an experimental disentanglement of the disinhibiting variables of perceived calories and food type.

    PubMed

    Knight, L J; Boland, F J

    1989-11-01

    The influence of food type on the restrained eating pattern was examined. In Study 1, subjects rated the degree to which each of 149 foods were dietary permissable or dietary forbidden. The number of avoided foods correlated positively with restraint score. Study 2 compared Herman and Mack's (1975) 1- and 2-milk shake preloads to two nonforbidden preloads of equivalent calories. Food type, and not perceived calories, was found to be the element of the preload required to cause disinhibition among restrained eaters, both within the experiment and outside the experimental setting. Study 3 examined the effects of anticipated consumption (varying food type and calories) on the restrained eating pattern. Only restrained eaters anticipating a forbidden food (whether high or low in calories) were disinhibited. The restrained literature was reconsidered in light of the forbidden food hypothesis.

  18. Antimicrobial Peptides

    PubMed Central

    Bahar, Ali Adem; Ren, Dacheng

    2013-01-01

    The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs), a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes) and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics). PMID:24287494

  19. Antimicrobial peptides.

    PubMed

    Bahar, Ali Adem; Ren, Dacheng

    2013-11-28

    The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill "superbugs" emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs), a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes) and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics).

  20. Animation of Antimicrobial Resistance

    MedlinePlus

    ... 08 Animation of Antimicrobial Resistance (text version) Arabic Translation - Animation of Antimicrobial Resistance (WMV - 19.2MB) Chinese Translation - Animation of Antimicrobial Resistance (WMV - 19.2MB) French ...

  1. Buckling and modal analysis of rotationally restrained orthotropic plates

    NASA Astrophysics Data System (ADS)

    Villarreal, Enrique; Abajo, Daniel

    2015-10-01

    This paper describes a theoretical approach for the static buckling, eigenfrequency and vibration buckling analysis of typical orthotropic plates used in aeronautical constructions. The plates are constrained with any combination of simply-supported and rotationally restrained edges, and are subjected to biaxial compressive loads. The derivation of closed-form solutions is discussed, and the results are presented in the form of design charts, where the effect of the restraint stiffness is highlighted. The proposed design charts allow a more accurate initial sizing of typical aerospace structural components, like stiffened panels, where both static and dynamic buckling loads are fundamental for the final design. As compared to classical solutions based on simply-supported and clamped edges, the modeling of the edge constraint as an elastic restraint provides a more refined description of the real stringer-stiffened panel. The results demonstrate that, in contrast to the commonly adopted simply-supported boundary condition, a reduction of the design conservativeness can be achieved if the stiffness of the restraint is accounted for. A novel set of results relative to the vibration buckling is derived, illustrating that the dynamic buckling tends to increase for load frequencies higher than the first natural frequency.

  2. Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division.

    PubMed

    Adachi, Yoshihiro; Itoh, Kie; Yamada, Tatsuya; Cerveny, Kara L; Suzuki, Takamichi L; Macdonald, Patrick; Frohman, Michael A; Ramachandran, Rajesh; Iijima, Miho; Sesaki, Hiromi

    2016-09-15

    Mitochondria divide to control their size, distribution, turnover, and function. Dynamin-related protein 1 (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the head group and acyl chains of phospholipids. Drp1 recognizes the head group of phosphatidic acid (PA) and two saturated acyl chains of another phospholipid by penetrating into the hydrophobic core of the membrane. The dual phospholipid interactions restrain Drp1 via inhibition of oligomerization-stimulated GTP hydrolysis that promotes membrane constriction. Moreover, a PA-producing phospholipase, MitoPLD, binds Drp1, creating a PA-rich microenvironment in the vicinity of a division apparatus. Thus, PA controls the activation of Drp1 after the formation of the division apparatus. PMID:27635761

  3. Seismic Energy Demand of Buckling-Restrained Braced Frames

    SciTech Connect

    Choi, Hyunhoon; Kim, Jinkoo

    2008-07-08

    In this study seismic analyses of steel structures were carried out to examine the effect of ground motion characteristics and structural properties on energy demands using 60 earthquake ground motions recorded in different soil conditions, and the results were compared with those of previous works. Analysis results show that ductility ratios and the site conditions have significant influence on input energy. The ratio of hysteretic to input energy is considerably influenced by the ductility ratio and the strong motion duration. It is also observed that as the predominant periods of the input energy spectra are significantly larger than those of acceleration response spectra used in the strength design, the strength demand on a structure designed based on energy should be checked especially in short period structures. For that reason framed structures with buckling-restrained-braces (BRBs) were designed in such a way that all the input energy was dissipated by the hysteretic energy of the BRBs, and the results were compared with those designed by conventional strength-based design procedure.

  4. Quantum mechanics/molecular mechanics restrained electrostatic potential fitting.

    PubMed

    Burger, Steven K; Schofield, Jeremy; Ayers, Paul W

    2013-12-01

    We present a quantum mechanics/molecular mechanics (QM/MM) method to evaluate the partial charges of amino acid residues for use in MM potentials based on their protein environment. For each residue of interest, the nearby residues are included in the QM system while the rest of the protein is treated at the MM level of theory. After a short structural optimization, the partial charges of the central residue are fit to the electrostatic potential using the restrained electrostatic potential (RESP) method. The resulting charges and electrostatic potential account for the individual environment of the residue, although they lack the transferable nature of library partial charges. To evaluate the quality of the QM/MM RESP charges, thermodynamic integration is used to measure the pKa shift of the aspartic acid residues in three different proteins, turkey egg lysozyme, beta-cryptogein, and Thioredoxin. Compared to the AMBER ff99SB library values, the QM/MM RESP charges show better agreement between the calculated and experimental pK(a) values for almost all of the residues considered.

  5. PIPKIγ targets to the centrosome and restrains centriole duplication.

    PubMed

    Xu, Qingwen; Zhang, Yuxia; Xiong, Xunhao; Huang, Yan; Salisbury, Jeffery L; Hu, Jinghua; Ling, Kun

    2014-03-15

    Centriole biogenesis depends on the polo-like kinase (PLK4) and a small group of structural proteins. The spatiotemporal regulation of these proteins at pre-existing centrioles is essential to ensure that centriole duplication occurs once per cell cycle. Here, we report that phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C, hereafter referred to as PIPKIγ) plays an important role in centriole fidelity. PIPKIγ localized in a ring-like pattern in the intermediate pericentriolar materials around the proximal end of the centriole in G1, S and G2 phases, but not in M phase. This localization was dependent upon an association with centrosomal protein of 152 KDa (CEP152). Without detaining cells in S or M phase, the depletion of PIPKIγ led to centriole amplification in a manner that was dependent upon PLK4 and spindle assembly abnormal protein 6 homolog (SAS6). The expression of exogenous PIPKIγ reduced centriole amplification that occurred as a result of endogenous PIPKIγ depletion, hydroxyurea treatment or PLK4 overexpression, suggesting that PIPKIγ is likely to function at the PLK4 level to restrain centriole duplication. Importantly, we found that PIPKIγ bound to the cryptic polo-box domain of PLK4 and that this binding reduced the kinase activity of PLK4. Together, our findings suggest that PIPKIγ is a novel negative regulator of centriole duplication, which acts by modulating the homeostasis of PLK4 activity.

  6. Coincident Phosphatidic Acid Interaction Restrains Drp1 in Mitochondrial Division.

    PubMed

    Adachi, Yoshihiro; Itoh, Kie; Yamada, Tatsuya; Cerveny, Kara L; Suzuki, Takamichi L; Macdonald, Patrick; Frohman, Michael A; Ramachandran, Rajesh; Iijima, Miho; Sesaki, Hiromi

    2016-09-15

    Mitochondria divide to control their size, distribution, turnover, and function. Dynamin-related protein 1 (Drp1) is a critical mechanochemical GTPase that drives constriction during mitochondrial division. It is generally believed that mitochondrial division is regulated during recruitment of Drp1 to mitochondria and its oligomerization into a division apparatus. Here, we report an unforeseen mechanism that regulates mitochondrial division by coincident interactions of Drp1 with the head group and acyl chains of phospholipids. Drp1 recognizes the head group of phosphatidic acid (PA) and two saturated acyl chains of another phospholipid by penetrating into the hydrophobic core of the membrane. The dual phospholipid interactions restrain Drp1 via inhibition of oligomerization-stimulated GTP hydrolysis that promotes membrane constriction. Moreover, a PA-producing phospholipase, MitoPLD, binds Drp1, creating a PA-rich microenvironment in the vicinity of a division apparatus. Thus, PA controls the activation of Drp1 after the formation of the division apparatus.

  7. Folate Deficiency Could Restrain Decidual Angiogenesis in Pregnant Mice

    PubMed Central

    Li, Yanli; Gao, Rufei; Liu, Xueqing; Chen, Xuemei; Liao, Xinggui; Geng, Yanqing; Ding, Yubin; Wang, Yingxiong; He, Junlin

    2015-01-01

    The mechanism of birth defects induced by folate deficiency was focused on mainly in fetal development. Little is known about the effect of folate deficiency on the maternal uterus, especially on decidual angiogenesis after implantation which establishes vessel networks to support embryo development. The aim of this study was to investigate the effects of folate deficiency on decidual angiogenesis. Serum folate levels were measured by electrochemiluminescence. The status of decidual angiogenesis was examined by cluster designation 34 (CD34) immunohistochemistry and the expression of angiogenic factors, including vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF), and VEGF receptor 2 (VEGFR2) were also tested. Serum levels of homocysteine (Hcy), follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2) were detected by Enzyme-linked immunosorbent assay. The folate-deficient mice had a lower folate level and a higher Hcy level. Folate deficiency restrained decidual angiogenesis with significant abnormalities in vascular density and the enlargement and elongation of the vascular sinus. It also showed a reduction in the expressions of VEGFA, VEGFR2, and PLGF. In addition, the serum levels of P4, E2, LH, and PRL were reduced in folate-deficient mice, and the expression of progesterone receptor (PR) and estrogen receptor α (ERα) were abnormal. These results indicated that folate deficiency could impaire decidual angiogenesis and it may be related to the vasculotoxic properties of Hcy and the imbalance of the reproductive hormone. PMID:26247969

  8. 29 CFR 101.37 - Application for temporary relief or restraining orders.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROCEDURES Procedure Under Section 10 (j) and (l) of the Act § 101.37 Application for temporary relief or restraining orders. Whenever it is deemed advisable to seek temporary injunctive relief under section 10(j)...

  9. 29 CFR 101.37 - Application for temporary relief or restraining orders.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROCEDURES Procedure Under Section 10 (j) and (l) of the Act § 101.37 Application for temporary relief or restraining orders. Whenever it is deemed advisable to seek temporary injunctive relief under section 10(j)...

  10. Food Antimicrobials Nanocarriers

    PubMed Central

    Blanco-Padilla, Adriana; Soto, Karen M.; Hernández Iturriaga, Montserrat

    2014-01-01

    Natural food antimicrobials are bioactive compounds that inhibit the growth of microorganisms involved in food spoilage or food-borne illness. However, stability issues result in degradation and loss of antimicrobial activity. Nanoencapsulation allows protection of antimicrobial food agents from unfavorable environmental conditions and incompatibilities. Encapsulation of food antimicrobials control delivery increasing the concentration of the antimicrobials in specific areas and the improvement of passive cellular absorption mechanisms resulted in higher antimicrobial activity. This paper reviews the present state of the art of the nanostructures used as food antimicrobial carriers including nanoemulsions, nanoliposomes, nanoparticles, and nanofibers. PMID:24995363

  11. De Novo Design of Antimicrobial Polymers, Foldamers, and Small Molecules: From Discovery to Practical Applications

    PubMed Central

    Tew, Gregory N.; Scott, Richard W.; Klein, Michael L.; DeGrado, William F.

    2009-01-01

    Conspectus Antimicrobial peptides (AMPs) provide protection against a variety of pathogenic bacteria and are, therefore, an important part of the innate immune system. Over the last decade, there has been considerable interest in developing AMPs as intravenously administered antibiotics. However, despite extensive efforts in the pharmaceutical and biotechnology industry, it has proven difficult to achieve this goal. While researchers have solved some relatively simple problems such as susceptibility to proteolysis, more severe problems have included the expense of the materials, toxicity, limited efficacy, and limited tissue distribution. In this Account, we describe our efforts to design and synthesize “foldamers”-- short sequence-specific oligomers based on arylamide and β-amino acid backbones, which fold into well-defined secondary structures-- that could act as antimicrobial agents. We reasoned that small “foldamers” would be less expensive to produce than peptides, and might have better tissue distribution. It should be easier to fine-tune the structures and activities of these molecules to minimize toxicity. Because the activities of many AMPs depends primarily on their overall physicochemical properties rather than the fine details of their precise amino acid sequences, we have designed and synthesized very small “coarse-grained” molecules, which are far simpler than naturally produced AMPs. The molecular design of these foldamers epitomizes the positively charged amphiphilic structures believed to be responsible for the activity of AMPs. The designed oligomers show greater activity than the parent peptides. They have also provided leads for novel small molecule therapeutics that show excellent potency in animal models for multi-drug resistant bacterial infections. In addition, such molecules can serve as relatively simple experimental systems for investigations aimed at understanding the mechanism of action for this class of antimicrobial

  12. Restraining Loose Equipment Aboard the International Space Station: The Payload Equipment Restraint System

    NASA Technical Reports Server (NTRS)

    Smith Kenneth A.; Reynolds, David W.

    2003-01-01

    As the International Space Station (ISS) grows, so do the supplies and equipment needed to support its daily operations. Each day many items must be unstowed and moved to various worksites so that they are readily available to the crew. Due to the lack of gravity, these items ,may become loose and float away if not restrained. The Payload Equipment Restraint System (PERS) was developed to meet the new and unique challenge of restraining loose equipment aboard the ISS.

  13. Antimicrobial peptides.

    PubMed

    Zhang, Ling-Juan; Gallo, Richard L

    2016-01-11

    Antimicrobial peptides and proteins (AMPs) are a diverse class of naturally occurring molecules that are produced as a first line of defense by all multicellular organisms. These proteins can have broad activity to directly kill bacteria, yeasts, fungi, viruses and even cancer cells. Insects and plants primarily deploy AMPs as an antibiotic to protect against potential pathogenic microbes, but microbes also produce AMPs to defend their environmental niche. In higher eukaryotic organisms, AMPs can also be referred to as 'host defense peptides', emphasizing their additional immunomodulatory activities. These activities are diverse, specific to the type of AMP, and include a variety of cytokine and growth factor-like effects that are relevant to normal immune homeostasis. In some instances, the inappropriate expression of AMPs can also induce autoimmune diseases, thus further highlighting the importance of understanding these molecules and their complex activities. This Primer will provide an update of our current understanding of AMPs. PMID:26766224

  14. The control dilemma in eating behavior: influence of temptation cues in restrained versus unrestrained eaters.

    PubMed

    Peláez-Fernández, María Angeles; Extremera, Natalio

    2011-11-01

    The present research explored the effects of pre-exposure to temptation primes and dieting primes on food intake, goal accessibility and explicit automatic evaluations of food-enjoyment and dieting goals among restrained and unrestrained eaters. Participants (n= 166) were randomly assigned to three conditions: food-cue, dieting, or control, in which they were exposed to incidental presentation of gourmet, fashion or geographic magazines, respectively. Words related to the goals of dieting and/or food- enjoyment were presented in a computer decision task following the incidental presentation of gourmet, dieting, and geographic magazine photographs. The computer task and the presentation of food were counterbalanced. Participants' food intake was assessed in a taste-rating task. Restrained eaters ate more than did unrestrained eaters across the three conditions. Restrained eaters who were exposed to food cues ate more than did restrained eaters in the control condition and they evaluated the goal of dieting more negatively compared to restrained eaters in the other two conditions. These findings were inconsistent with 'Counteractive Self-Control Theory' but consistent with previous studies on the effects of food-cue exposure in restrained eaters.

  15. Antimicrobial Drugs in Fighting against Antimicrobial Resistance

    PubMed Central

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i.e., mutation and horizontal gene transfer of resistance determinants), the community level resistance (i.e., bilofilms and persisters) is also an issue causing antimicrobial therapy difficulties. Therefore, anti-resistance and antibiofilm strategies have currently become research hotspot to combat antimicrobial resistance. Although metallic nanoparticles can both kill bacteria and inhibit biofilm formation, the toxicity is still a big challenge for their clinical applications. In conclusion, rational use of the existing antimicrobials and combinational use of new strategies fighting against antimicrobial resistance are powerful warranties to preserve potent antimicrobial drugs for both humans and animals. PMID:27092125

  16. Antimicrobial Drugs in Fighting against Antimicrobial Resistance.

    PubMed

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i.e., mutation and horizontal gene transfer of resistance determinants), the community level resistance (i.e., bilofilms and persisters) is also an issue causing antimicrobial therapy difficulties. Therefore, anti-resistance and antibiofilm strategies have currently become research hotspot to combat antimicrobial resistance. Although metallic nanoparticles can both kill bacteria and inhibit biofilm formation, the toxicity is still a big challenge for their clinical applications. In conclusion, rational use of the existing antimicrobials and combinational use of new strategies fighting against antimicrobial resistance are powerful warranties to preserve potent antimicrobial drugs for both humans and animals. PMID:27092125

  17. Studies on effect of stress preconditioning in restrain stress-induced behavioral alterations.

    PubMed

    Kaur, Rajneet; Jaggi, Amteshwar Singh; Singh, Nirmal

    2010-02-01

    Stress preconditioning has been documented to confer on gastroprotective effects on stress-induced gastric ulcerations. However, the effects of prior exposure of stress preconditioning episodes on stress-induced behavioral changes have not been explored yet. Therefore the present study was designed to investigate the ameliorative effects of stress preconditioning in immobilization stress-induced behavioral alterations in rats. The rats were subjected to restrain stress by placing in restrainer (5.5 cm in diameter and 18 cm in length) for 3.5 h. Stress preconditioning was induced by subjecting the rats to two cycles of restraint and restrain-free periods of 15 min each. Furthermore, a similar type of stress preconditioning was induced using different time cycles of 30 and 45 min. The extent and severity of the stress-induced behavioral alterations were assessed using different behavioral tests such as hole-board test, social interaction test, open field test, and actophotometer. Restrain stress resulted in decrease in locomotor activity, frequency of head dips and rearing in hole board, line crossing and rearing in open field, and decreased following and increased avoidance in social interaction test. Stress preconditioning with two cycles of 15, 30 or 45 min respectively, did not attenuate stress-induced behavioral changes to any extent. It may be concluded that stress preconditioning does not seem to confer any protective effect in modulating restrain stress-induced behavioral alterations.

  18. Antimicrobial Treatments and Efficacy

    EPA Science Inventory

    To limit exposure to indoor biological contamination a risk-management approach which employs various antimicrobial treatments can effectively control contaminants and reduce exposure. Antimicrobial treatment of biological contaminants, especially mold in buildings, it is often n...

  19. Disarming batterers through restraining orders: the promise and the reality in California.

    PubMed

    Seave, Paul L

    2006-06-01

    Laws that prohibit persons under a domestic violence restraining order from purchasing or possessing a firearm are a primary way to keep guns out of the hands of batterers. In July 2005, the California Attorney General's Task Force on the Local Criminal Justice Response to Domestic Violence issued a report called Keeping the Promise: Victim Safety and Batterer Accountability. The report focused, in part, on the extent to which California's domestic violence restraining order system succeeds in disarming batterers. Restraining orders are the principal means by which the criminal justice system can accomplish this objective. The Task Force found that criminal justice agencies and the courts performed poorly in this area. The report strongly recommended that a more strategic, collaborative use of laws already on the books could significantly improve performance, without much additional expense. What follows is a summary of those finding and recommendations. PMID:16679495

  20. PARTIAL RESTRAINING FORCE INTRODUCTION METHOD FOR DESIGNING CONSTRUCTION COUNTERMESURE ON ΔB METHOD

    NASA Astrophysics Data System (ADS)

    Nishiyama, Taku; Imanishi, Hajime; Chiba, Noriyuki; Ito, Takao

    Landslide or slope failure is a three-dimensional movement phenomenon, thus a three-dimensional treatment makes it easier to understand stability. The ΔB method (simplified three-dimensional slope stability analysis method) is based on the limit equilibrium method and equals to an approximate three-dimensional slope stability analysis that extends two-dimensional cross-section stability analysis results to assess stability. This analysis can be conducted using conventional spreadsheets or two-dimensional slope stability computational software. This paper describes the concept of the partial restraining force in-troduction method for designing construction countermeasures using the distribution of the restraining force found along survey lines, which is based on the distribution of survey line safety factors derived from the above-stated analysis. This paper also presents the transverse distributive method of restraining force used for planning ground stabilizing on the basis of the example analysis.

  1. Structure of the antimicrobial peptide tachystatin A.

    PubMed

    Fujitani, Naoki; Kawabata, Shun-ichiro; Osaki, Tsukasa; Kumaki, Yasuhiro; Demura, Makoto; Nitta, Katsutoshi; Kawano, Keiichi

    2002-06-28

    The solution structure of antimicrobial peptide tachystatin A from the Japanese horseshoe crab (Tachypleus tridentatus) was determined by two-dimensional nuclear magnetic resonance measurements and distance-restrained simulated annealing calculations. The correct pairs of disulfide bonds were also confirmed in this study. The obtained structure has a cysteine-stabilized triple-stranded beta-sheet as a dominant secondary structure and shows an amphiphilic folding observed in many membrane-interactive peptides. Interestingly, tachystatin A shares structural similarities with the calcium channel antagonist omega-agatoxin IVA isolated from spider toxin and mammalian defensins, and we predicted that omega-agatoxin IVA also have the antifungal activity. These structural comparisons and functional correspondences suggest that tachystatin A and omega-agatoxin IVA may exert the antimicrobial activity in a manner similar to defensins, and we have confirmed such activity using fungal culture assays. Furthermore, tachystatin A is a chitin-binding peptide, and omega-agatoxin IVA also showed chitin-binding activities in this study. Tachystatin A and omega-agatoxin IVA showed no structural homology with well known chitin-binding motifs, suggesting that their structures belong to a novel family of chitin-binding peptides. Comparison of their structures with those of cellulose-binding proteins indicated that Phe(9) of tachystatin A might be an essential residue for binding to chitin.

  2. Disarming Batterers through Restraining Orders: The Promise and the Reality in California

    ERIC Educational Resources Information Center

    Seave, Paul L.

    2006-01-01

    Laws that prohibit persons under a domestic violence restraining order from purchasing or possessing a firearm are a primary way to keep guns out of the hands of batterers. In July 2005, the California Attorney General's Task Force on the Local Criminal Justice Response to Domestic Violence issued a report called Keeping the Promise: Victim Safety…

  3. Neural correlates of restrained eaters' high susceptibility to food cues: An fMRI study.

    PubMed

    Wang, Yu; Dong, Debo; Todd, Jackson; Du, Jie; Yang, Zhou; Lu, Hui; Chen, Hong

    2016-09-19

    Many studies have reported that specific susceptibility to food cues plays an important role in disordered eating behavior. However, whether restraint status modulates the neural bases of attentional bias to different types of food cues remains unknown. Thus, functional magnetic resonance imaging (fMRI) was conducted in individuals (12 restraint eaters, 12 unrestraint eaters) exposed to high/low-energy food and neutral images while performing a two-choice oddball task. The results indicated that restrained eaters responded more quickly to high-energy food images than to neutral and low-energy food images. More notably, compared with unrestrained eaters, restrained eaters showed faster reaction times, hyper-activation in a much wider array of reward (e.g., insula/orbitofrontal cortex), attention (superior frontal gyrus) and visual processing (e.g., superior temporal gyrus) regions, and hypo-activation in cognitive control areas (e.g., anterior cingulate) in response to high-energy food cues. Furthermore, among restrained eaters, the longest reaction times were found for low-energy food images, and activation of the attention and visual-related cortex (e.g., superior parietal gyrus) in the low-neutral contrast condition was significantly stronger than in unrestrained eaters. These findings contribute to our understanding of susceptibility to food cues: in addition to the special sensitivity (attentional bias) to high-energy food images, restrained eaters may also be more sensitive (allocate more attentional resources) to low-energy food images. These potential neural bases of restrained eaters may help clarify why dieting to lose or maintain weight is so often unsuccessful. PMID:27524674

  4. Antimicrobials in beekeeping.

    PubMed

    Reybroeck, Wim; Daeseleire, Els; De Brabander, Hubert F; Herman, Lieve

    2012-07-01

    The bee diseases American and European foulbrood and nosemosis can be treated with anti-infectious agents. However, in the EU and the USA the use of these agents in beekeeping is strictly regulated due to the lack of tolerance (e.g. Maximum Residue Limit) for residues of antibiotics and chemotherapeutics in honey. This article reviews the literature dealing with antimicrobials of interest in apiculture, stability of these antimicrobials in honey, and disposition of the antimicrobials in honeybee hives.

  5. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... Antimicrobial (Drug) Resistance Antibiotic-Resistant Mycobacterium tuberculosis (TB) Methicillin-Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococci (VRE) Multidrug-Resistant Neisseria ...

  6. Reworking of structural inheritance at strike-slip restraining-bends: templates from sandbox analogue models

    NASA Astrophysics Data System (ADS)

    Nestola, Yago; Storti, Fabrizio; Cavozzi, Cristian; Magistroni, Corrado; Meda, Marco; Piero Righetti, Fabrizio

    2016-04-01

    Structural inheritance plays a fundamental role during crustal deformation because pre-existing fault and shear zones typically provide weakness zone suitable to fail again when affected by a new regional stress field. Re-activation of structural inheritance is expected to unavoidably increase the complexity of structural architectures, whose geometric and kinematic patterns can significantly deviate from what expected in newly deformed crustal sectors. Availability of templates from analogue models can provide a very effective tool to help unraveling such a structural complexity. For this purpose, we simulated the reworking of a set of basement hosted pre-existing fault zones at strike-slip restraining fault bends. In the models, the mechanical stratigraphy consists of a basement, made of a mixture of dry kaolin and sand to slightly increase cohesion, and a sedimentary cover made by pure dry sand. Inherited fault zones are confined to the basement and coated by a thin veneer of silicone putty. In the experimental programme, the geometry of the left-lateral restraining bend is maintained the same, with a bending angle of 30° of the restraining fault segment. The strike of the inherited fault zones, measured counterclockwise with respect to that of the master strike-slip fault zone outside the restraining bend, was 0°, 30°, and 60° in different experiments, respectively. An end member experiment without inheritance was also run for comparison. Our experimental results show that the angle that the inherited fault zones make with the restraining bend plays a fundamental role in governing the deformation pattern. When structural inheritance is near parallel to the master strike-slip fault zone, synthetic shears form and severely compartmentalize the transpressional pop-up anticline growing on top of the restraining bend. Fault-bounded blocks undergo sinistral escape during transpression. On the other hand, when structural inheritance makes a high angle to the

  7. Antimicrobial Peptides in 2014

    PubMed Central

    Wang, Guangshun; Mishra, Biswajit; Lau, Kyle; Lushnikova, Tamara; Golla, Radha; Wang, Xiuqing

    2015-01-01

    This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms. PMID:25806720

  8. The danger signal S100B integrates pathogen- and danger-sensing pathways to restrain inflammation.

    PubMed

    Sorci, Guglielmo; Giovannini, Gloria; Riuzzi, Francesca; Bonifazi, Pierluigi; Zelante, Teresa; Zagarella, Silvia; Bistoni, Francesco; Donato, Rosario; Romani, Luigina

    2011-03-01

    Humans inhale hundreds of Aspergillus conidia without adverse consequences. Powerful protective mechanisms may ensure prompt control of the pathogen and inflammation. Here we reveal a previously unknown mechanism by which the danger molecule S100B integrates pathogen- and danger-sensing pathways to restrain inflammation. Upon forming complexes with TLR2 ligands, S100B inhibited TLR2 via RAGE, through a paracrine epithelial cells/neutrophil circuit that restrained pathogen-induced inflammation. However, upon binding to nucleic acids, S100B activated intracellular TLRs eventually resolve danger-induced inflammation via transcriptional inhibition of S100B. Thus, the spatiotemporal regulation of TLRs and RAGE by S100B provides evidence for an evolving braking circuit in infection whereby an endogenous danger protects against pathogen-induced inflammation and a pathogen-sensing mechanism resolves danger-induced inflammation.

  9. Impact response of restrained PMHS in frontal sled tests: skeletal deformation patterns under seat belt loading.

    PubMed

    Shaw, Greg; Parent, Dan; Purtsezov, Sergey; Lessley, David; Crandall, Jeff; Kent, Richard; Guillemot, Herve; Ridella, Stephen A; Takhounts, Erik; Martin, Peter

    2009-11-01

    This study evaluated the response of restrained post-mortem human subjects (PMHS) in 40 km/h frontal sled tests. Eight male PMHS were restrained on a rigid planar seat by a custom 3-point shoulder and lap belt. A video motion tracking system measured three-dimensional trajectories of multiple skeletal sites on the torso allowing quantification of ribcage deformation. Anterior and superior displacement of the lower ribcage may have contributed to sternal fractures occurring early in the event, at displacement levels below those typically considered injurious, suggesting that fracture risk is not fully described by traditional definitions of chest deformation. The methodology presented here produced novel kinematic data that will be useful in developing biofidelic human models. Additional analysis of the data produced by the reported tests as well as additional tests with a variety of loading conditions are required to fully characterize torso response including ribcage fracture tolerance.

  10. Investigation on frictional characteristics and drawbead restraining force of steel with/without coating

    NASA Astrophysics Data System (ADS)

    Chen, Lianfeng; Zheng, Tianran; Chen, Qing; Zhang, Jun

    2013-12-01

    Advanced high strength steels (AHSS) are used more and more in automotive industry for increasing crashworthiness and weight reduction. Improving metal flow and reduce friction are important to forming the part and decrease part reject rates of AHSS. The present study focused on friction characteristics and drawbead restraining force of Dual Phase (DP) steels with or without coating, such as DP980, DP780, DP590, DP780+Z, DP780+ZF, DP590+Z, using experimental approach. The effect of material properties, temperature, sliding velocity, surface roughness, dry and lubricant on friction behavior of DP steels is investigated. The contrast of DP steels with mild IF steel is carried out. The restraining force draw through different radius of drawbead is evaluated. This study is benefit to the set up of technique parameters during sheet metal forming simulation.

  11. Selective attention to food and body shape words in dieters and restrained nondieters.

    PubMed

    Green, M W; Rogers, P J

    1993-12-01

    The current study investigated the presence of an attentional bias towards the processing of body shape and food-related material amongst noneating disordered women. Subjects carried out a computer-based Stroop color-naming task in which they had to name the colors of food-related words, body shape-related words, and two sets of matched neutral words. Significant color-naming disruptions of both food and body shape-related material were found for highly restrained eaters, irrespective of whether they were currently dieting. There were no reliable differences in color-naming times found for low to medium restrained eaters. Procedural differences probably account for the failure of previous studies to reveal such effects in nonclinical groups. PMID:8293036

  12. Experimental and numerical study of restraining force development in inclined draw beads

    NASA Astrophysics Data System (ADS)

    Raghavan, K. S.; Narainen, R.; Smith, L. M.

    2013-12-01

    Inclined (angled) draw bead geometries are becoming increasingly common as body styling requirements necessitate external panel shapes with considerable curvature. The restraining force that develops as material undergoes bending and frictional contact varies with bead geometry, material strength level and ambient lubrication conditions. In this study, an FEA based parametric approach is used to model the effects of material strength, friction condition, and binder angle on draw bead restraining force (DBRF). A finite element draw bead simulation was calibrated to experimental data for a 250 MPa electro-galvanized bake-hardenable specimen. The experimental data is used to confirm that the DBRF vs. binder angle curve roughly follows a concave shaped second order function with a maximum somewhere in the positive binder angle domain.

  13. Alternative Antimicrobial Approach: Nano-Antimicrobial Materials

    PubMed Central

    Beyth, Nurit; Houri-Haddad, Yael; Domb, Avi; Khan, Wahid; Hazan, Ronen

    2015-01-01

    Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail. PMID:25861355

  14. Absolute Binding Free Energy Calculations Using Molecular Dynamics Simulations with Restraining Potentials

    PubMed Central

    Wang, Jiyao; Deng, Yuqing; Roux, Benoît

    2006-01-01

    The absolute (standard) binding free energy of eight FK506-related ligands to FKBP12 is calculated using free energy perturbation molecular dynamics (FEP/MD) simulations with explicit solvent. A number of features are implemented to improve the accuracy and enhance the convergence of the calculations. First, the absolute binding free energy is decomposed into sequential steps during which the ligand-surrounding interactions as well as various biasing potentials restraining the translation, orientation, and conformation of the ligand are turned “on” and “off.” Second, sampling of the ligand conformation is enforced by a restraining potential based on the root mean-square deviation relative to the bound state conformation. The effect of all the restraining potentials is rigorously unbiased, and it is shown explicitly that the final results are independent of all artificial restraints. Third, the repulsive and dispersive free energy contribution arising from the Lennard-Jones interactions of the ligand with its surrounding (protein and solvent) is calculated using the Weeks-Chandler-Andersen separation. This separation also improves convergence of the FEP/MD calculations. Fourth, to decrease the computational cost, only a small number of atoms in the vicinity of the binding site are simulated explicitly, while all the influence of the remaining atoms is incorporated implicitly using the generalized solvent boundary potential (GSBP) method. With GSBP, the size of the simulated FKBP12/ligand systems is significantly reduced, from ∼25,000 to 2500. The computations are very efficient and the statistical error is small (∼1 kcal/mol). The calculated binding free energies are generally in good agreement with available experimental data and previous calculations (within ∼2 kcal/mol). The present results indicate that a strategy based on FEP/MD simulations of a reduced GSBP atomic model sampled with conformational, translational, and orientational restraining

  15. Effects of restrained eating behaviour on insulin sensitivity in normal-weight individuals.

    PubMed

    Martins, C; Morgan, L M; Robertson, M D

    2009-03-23

    Restrained eating behaviour has been linked to abnormalities in metabolic and endocrine functions. However, the impact of restraint on fasting insulin and glucose plasma levels and insulin sensitivity remains controversial. Moreover, the few postprandial studies to date are limited by an inappropriate sampling time frame and a low "net" energy and carbohydrate load. The aims of this study are to assess the role of dietary restraint on fasting and postprandial plasma levels of insulin, glucose, triacylglycerol (TAG) and non esterified fatty acids (NEFA) in healthy volunteers with a normal and stable body weight and to determine whether the effect of restraint on the plasma levels of the previous hormones/metabolites is load dependent. Normal-weight participants (21 women and 12 men) were classified as restrained/unrestrained based on the restraint scale of the Three Factor Eating Questionnaire-18R and Dutch Eating Behaviour Questionnaire. The impact of restraint on the plasma levels of different hormones/metabolites was measured, in response to a 500 kcal and 1000 kcal breakfast, using a randomised crossover design. Restraint was associated with lower fasting insulin plasma levels (P<0.05) and a lower insulin (P<0.015) and glucose (P<0.05) plasma levels in the postprandial state, but did not impact on TAG or NEFA. Moreover, restrained eaters showed a better fasting (P<0.05) and postprandial insulin sensitivity (P<0.01). Restrained eating behaviour has, therefore, a significant impact on both fasting and postprandial glucose metabolism, being associated with increased insulin sensitivity. These findings suggest the need for adjusting for restraint level in studies where glucose metabolism is a major outcome.

  16. Vibration Analysis of Orthotropic Mindlin Plates with Edges Elastically Restrained against Rotation

    NASA Astrophysics Data System (ADS)

    Chung, J. H.; Chung, T. Y.; Kim, K. C.

    1993-05-01

    The free vibration analysis of the orthotropic Mindlin plates with edges elastically restrained against rotation has been accomplished using the Rayleigh-Ritz method. Polynomials with properties corresponding to those of the Timoshenko beam functions are introduced as trial functions in the spatial representation of the deflection and rotations of cross sections in two directions of the plates. The results obtained by using polynomials are nearly the same as the Timoshenko beam functions results, but were obtained with considerably less numerical efforts.

  17. Peak and end effects on remembered enjoyment of eating in low and high restrained eaters.

    PubMed

    Robinson, Eric; Blissett, Jackie; Higgs, Suzanne

    2011-08-01

    Memory is likely to be important in food choice because many food likes and dislikes are learnt. Evidence suggests that the final few moments of an experience ('end effect') and the most intense moments of an experience ('peak effect') have a disproportionately large influence on hedonic memories. In Study 1 we examined whether the end effect bias is applicable to remembered enjoyment of a food and whether this holds true for restrained and unrestrained eaters. One hundred and four participants ate the same yoghurt but half the participants experienced a pleasant end and half a bland end (control condition). Although both the 'pleasant ending' and control group had a similar online enjoyment of the yoghurt, unrestrained eaters who experienced a pleasant end remembered it to have been significantly more enjoyable than those in the control condition. No end effect was observed for restrained eaters. In Study 2 we examined predictors of remembered enjoyment of a multi-item meal. Forty-six participants consumed and rated 5 buffet style food items as part of a lunch time meal. For unrestrained eaters, remembered enjoyment of the meal was only predicted by 'peak' online enjoyment of the most liked item. Participant's enjoyment of the first, last and least liked items did not predict remembered enjoyment. For restrained eaters, remembered enjoyment was not predicted by any of the four predictor variables. These results suggest that for unrestrained eaters key moments in eating experiences have disproportionately large influence on remembered enjoyment of eating.

  18. Peak and end effects on remembered enjoyment of eating in low and high restrained eaters.

    PubMed

    Robinson, Eric; Blissett, Jackie; Higgs, Suzanne

    2011-08-01

    Memory is likely to be important in food choice because many food likes and dislikes are learnt. Evidence suggests that the final few moments of an experience ('end effect') and the most intense moments of an experience ('peak effect') have a disproportionately large influence on hedonic memories. In Study 1 we examined whether the end effect bias is applicable to remembered enjoyment of a food and whether this holds true for restrained and unrestrained eaters. One hundred and four participants ate the same yoghurt but half the participants experienced a pleasant end and half a bland end (control condition). Although both the 'pleasant ending' and control group had a similar online enjoyment of the yoghurt, unrestrained eaters who experienced a pleasant end remembered it to have been significantly more enjoyable than those in the control condition. No end effect was observed for restrained eaters. In Study 2 we examined predictors of remembered enjoyment of a multi-item meal. Forty-six participants consumed and rated 5 buffet style food items as part of a lunch time meal. For unrestrained eaters, remembered enjoyment of the meal was only predicted by 'peak' online enjoyment of the most liked item. Participant's enjoyment of the first, last and least liked items did not predict remembered enjoyment. For restrained eaters, remembered enjoyment was not predicted by any of the four predictor variables. These results suggest that for unrestrained eaters key moments in eating experiences have disproportionately large influence on remembered enjoyment of eating. PMID:21570432

  19. 3-D Coupled FE Analysis and Experimental Validation of Restrained Welding to Control Angular Distortion

    NASA Astrophysics Data System (ADS)

    Damale, A. V.; Nandurkar, K. N.

    2012-10-01

    Welding induced distortion is one of the critical defects in the welded structures. Angular distortion is most pronounced which badly affects the welded structures. Non-uniform heating during welding develops this angular distortion. Various methods are available to control/minimize the welding distortions. One of the methods available to control this distortion is restraining, in which clamping pressure is applied on the deforming edges of the plates. In the present study, a 3-dimensional coupled transient thermal analysis is done for simulating the restraining phenomenon of welding. The developed transient thermal heat source was used to simulate the arc welding phenomenon. The element birth and death technique was used for simulating filler material deposition. Thermal model was verified by comparing the macrograph of Finite Element Analysis (FEA) model and the weld and verification of structural model was done by comparing the measured and predicted angular distortions. Experimental and Finite Element (FE) analysis is done for both conventional welding and welding under restraining pressure. Transient thermal and non-linear structural analyses were carried out in order to predict angular distortions. The Finite Element Method analysis and experimental verification is done for manual metal arc welding process.

  20. Experimental Tests of a Real Building Seismically Retrofitted by Special Buckling-Restrained Braces

    SciTech Connect

    D'Aniello, Mario; Della Corte, Gaetano; Mazzolani, Federico M.

    2008-07-08

    Buckling Restrained Braces (BRBs), differently from conventional braces, do not exhibit appreciable difference between the tensile and compression capacity and no strength degradation of brace capacity under compressive and cyclic loading. Since lateral and local buckling behaviour modes are restrained, large inelastic capacities are attainable. Hence, BRBs may represent an efficient and reliable solution for reducing the seismic vulnerability of buildings. Results of experimental tests on the response of a real two-story reinforced concrete (RC) building equipped with BRBs are presented and discussed. The considered BRBs are a special 'only-steel' version of the more common 'unbonded braces'. In particular, two different BRBs have been tested. Both of them are detachable 'only-steel' devices, consisting in a rectangular steel plate and a restraining steel sleeve. The latter is composed by two omega shapes which are bolted together. The main characteristic of the braces consists in the possibility to hide them within the space between the facing and the backing of masonry infill walls commonly used for RC buildings.

  1. Positive fantasies or negative contrasts: the effect of media body ideals on restrained eaters' mood, weight satisfaction, and food intake.

    PubMed

    Boyce, Jessica A; Kuijer, Roeline G; Gleaves, David H

    2013-09-01

    Although viewing media body ideals promotes body dissatisfaction and problematic eating among women (e.g., extreme restraint/overeating), some argue that women only report such negative effects because they think that they are meant to (i.e., demand characteristics). Because restrained eaters are trying to lose weight, they might be vulnerable to such media exposure. However, because of demand characteristics, evidence is mixed. Therefore, we minimized demand characteristics and explored whether media body ideals would trigger restrained eaters to report negative (negative mood, weight dissatisfaction) or positive (positive mood, weight satisfaction) effects. We also hypothesized that this change (negative or positive) would encourage food intake. Restrained and unrestrained eaters (n=107) memorized media or control images. Restrained eaters exposed to media images reported decreased weight satisfaction and increased negative mood, but their food intake was not significantly affected. Perhaps paying advertent attention to the images caused goal-related negative affect, which triggered restraint.

  2. Antimicrobial Peptides in Reptiles

    PubMed Central

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  3. Fast Disinfecting Antimicrobial Surfaces

    PubMed Central

    Madkour, Ahmad E.; Dabkowski, Jeffery M.; Nüsslein, Klaus; Tew, Gregory N.

    2013-01-01

    Silicon wafers and glass surfaces were functionalized with facially amphiphilic antimicrobial copolymers using the “grafting from” technique. Surface initiated atom transfer radical polymerization (ATRP) was used to grow poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces. Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S. aureus and E. coli 100% in less than 5 min. The molecular weight and grafting density of the polymer were controlled by varying the polymerization time and initiator surface density. Antimicrobial studies showed that the killing efficiency of these surfaces was independent of polymer layer thickness or grafting density within the range of surfaces studied. PMID:19177651

  4. Pharmacogenomics of antimicrobial agents.

    PubMed

    Aung, Ar Kar; Haas, David W; Hulgan, Todd; Phillips, Elizabeth J

    2014-01-01

    Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use.

  5. Pharmacogenomics of antimicrobial agents

    PubMed Central

    Aung, Ar Kar; Haas, David W; Hulgan, Todd; Phillips, Elizabeth J

    2015-01-01

    Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use. PMID:25495412

  6. Novel antimicrobial textiles

    NASA Astrophysics Data System (ADS)

    Cho, Unchin

    2003-10-01

    Many microorganisms can survive, and perhaps proliferate on textiles, generating adverse effects such as: disease transmission, odor generation, pH changes, staining, discoloration and loss of performance. These adverse effects may threaten users' health, deteriorate textile properties and degrade service quality. It may, therefore, be desirable to incorporate antimicrobials on textiles for controlling the growth of microorganisms. This dissertation focuses on the development of antimicrobial fibers and fabrics by integration of antimicrobials with these textiles. The applications of hydantoin-based halamines were mainly investigated in the research. The typical process is that hydantoin containing compounds are grafted onto textiles and transformed to halamine by chlorination. Hydantoin-based halamines are usually chloramines that release chlorine (Cl+) via cleavage of the -NCl functional group which attacks and kills microbes. The antimicrobial behavior is rechargeable many times by rinsing the fiber or fabric with chlorine-containing solution. Some quaternary ammonium type antimicrobials were also investigated in this research. The choice of integrating techniques is dependant on both the textile and antimicrobial compounds. In this dissertation, the nine approaches were studied for incorporating antimicrobial with various textiles: (1) co-extrusion of fibers with halamine precursor additive; (2) grafting of the quaternary ammonium compounds onto ethylene-co-acrylic acid fiber for creating quaternary ammonium type antimicrobial fiber; (3) entrapment of the additives in thermally bonded bicomponent nonwoven fabrics; (4) attaching antimicrobial additives to surfaces with latex adhesive coating; (5) grafting of antimicrobial compounds onto rubber latex via UV exposure; (6) reaction of halamine with needle-punched melamine formaldehyde nonwoven fabric and laminates; (7) coating melamine resin onto tent fabrics and laminates; (8) synthesis of super absorbent polymer

  7. Antimicrobial compounds in tears.

    PubMed

    McDermott, Alison M

    2013-12-01

    The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here.

  8. Antimicrobial Compounds in Tears

    PubMed Central

    McDermott, Alison M.

    2013-01-01

    The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here. PMID:23880529

  9. Antimicrobial resistance in livestock.

    PubMed

    Catry, B; Laevens, H; Devriese, L A; Opsomer, G; De Kruif, A

    2003-04-01

    Antimicrobial resistance may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs. Related problems are now arising in human medicine, such as the appearance of multi-resistant food-borne pathogens. Product characteristics, dose, treatment interval and duration of treatment influence the selection pressure for antimicrobial drug resistance. There are theoretical, experimental and clinical indications that the emergence of de novo resistance in a pathogenic population can be prevented by minimizing the time that suboptimal drug levels are present in the infected tissue compartment. Until recently, attention has been focused on target pathogens. However, it should be kept in mind that when antimicrobial drugs are used in an individual, resistance selection mainly affects the normal body flora. In the long term, this is at least equally important as resistance selection in the target pathogens, as the horizontal transfer of resistance genes converts almost all pathogenic bacteria into potential recipients for antimicrobial resistance. Other factors contributing to the epidemiology of antimicrobial resistance are the localization and size of the microbial population, and the age, immunity and contact intensity of the host. In livestock, dynamic herd-related resistance patterns have been observed in different animal species.

  10. Denali in a box: analog experiments modeled after a natural setting provide insight on gentle restraining bend deformation

    NASA Astrophysics Data System (ADS)

    Fendick, Anne; Bemis, Sean; Toeneboehn, Kevin; Cooke, Michele; Benowitz, Jeff

    2016-04-01

    Despite restraining bends along strike-slip faults creating zones of focused uplift, the relative contributions from parameters such as fault geometry and scale, obliquity, rheological contrasts, and deformation rates are not well-constrained. Similarities between simple analog models (conducted with homogenous materials) and natural restraining bend systems (typically associated with heterogeneous crust) suggest that there are first-order controls on restraining bend deformation that operate independent of heterogeneity in the upper crust. To investigate these controls we examine the Mount McKinley restraining bend (MMRB) of the Denali fault system in south-central Alaska. The MMRB is associated with an ~18 degree bend in the Denali fault and exhibits strongly asymmetric topography and rock uplift. The viscous relaxation time and the ratio of crustal thickness to the restraining bend stepover distance are scaled within the analog model to that of the MMRB. We compare uplift patterns, localization of deformation, formation of new faults, and displacement fields for the model set up and the natural bend to understand the influence of different variables on the overall system to determine what controls the deformation. As shown in previous analog model studies, asymmetric topography characteristically forms with restraining bend angles of <20°. In our model, a continuous, through-going fault within the restraining bend accompanies a narrow zone of deformation on one side of the bend and a broader zone of deformation the opposite side. However, the active thrust faults of the MMRB are purely dip-slip, whereas the thrust faults formed in the model appear to be oblique-slip. The geometry and slip rates of active faults in the MMRB, as well as preliminary thermochronometric data, suggest that the restraining bend itself is migrating relative to previously deformed deposits. Conventional understanding of restraining bends is that fixed bends produce the highest

  11. Ca2+ signaling in arterioles and small arteries of conscious, restrained, optical biosensor mice

    PubMed Central

    Fairfax, Seth T.; Mauban, Joseph R. H.; Hao, Scarlett; Rizzo, Mark A.; Zhang, Jin; Wier, W. Gil

    2014-01-01

    Two-photon fluorescence microscopy and conscious, restrained optical biosensor mice were used to study smooth muscle Ca2+ signaling in ear arterioles. Conscious mice were used in order to preserve normal mean arterial blood pressure (MAP) and sympathetic nerve activity (SNA). ExMLCK mice, which express a genetically-encoded smooth muscle-specific FRET-based Ca2+ indicator, were equipped with blood pressure telemetry and immobilized for imaging. MAP was 101 ± 4 mmHg in conscious restrained mice, similar to the freely mobile state (107 ± 3 mmHg). Oscillatory vasomotion or irregular contractions were observed in most arterioles (71%), with the greatest oscillatory frequency observed at 0.25 s−1. In a typical arteriole with an average diameter of ~35 μm, oscillatory vasomotion of a 5–6 μm magnitude was accompanied by nearly uniform [Ca2+] oscillations from ~0.1 to 0.5 μM, with maximum [Ca2+] occurring immediately before the rapid decrease in diameter. Very rapid, spatially uniform “Ca2+ flashes” were also observed but not asynchronous propagating Ca2+ waves. In contrast, vasomotion and dynamic Ca2+ signals were rarely observed in ear arterioles of anesthetized exMLCK biosensor mice. Hexamethonium (30 μg/g BW, i.p.) caused a fall in MAP to 74 ± 4 mmHg, arteriolar vasodilation, and abolition of vasomotion and synchronous Ca2+ transients. Summary: MAP and heart rate (HR) were normal during high-resolution Ca2+ imaging of conscious, restrained mice. SNA induced continuous vasomotion and irregular vasoconstrictions via spatially uniform Ca2+ signaling within the arterial wall. FRET-based biosensor mice and two-photon imaging provided the first measurements of [Ca2+] in vascular smooth muscle cells in arterioles of conscious animals. PMID:25339912

  12. Column strength of tubes elastically restrained against rotation at the ends

    NASA Technical Reports Server (NTRS)

    Osgood, William R

    1938-01-01

    Report presents the results of a study made of the effects of known end restraint on commercially available round and streamline tubing of chromium-molybdenum steel, duralumin, stainless steel, and heat-treated chromium-molybdenum steel; and a more accurate method than any previously available, but still a practical method, was developed for designing compression members in riveted or welded structures, particularly aircraft. Two hundred specimens were tested as short, medium-length, and long columns with freely supported ends or elastically restrained ends. Tensile and compressive tests were made on each piece of original tubing from which column specimens were cut.

  13. Neotectonics of Hispaniola - Plate motion, sedimentation, and seismicity at a restraining bend

    NASA Technical Reports Server (NTRS)

    Mann, P.; Matumoto, T.; Burke, K.

    1984-01-01

    The question as to the extent to which earthquake mechanisms define plate motion is addressed in view of the pattern of Neogene faulting, volcanism, and sedimentation in Hispaniola. The structure of two fault systems that approximately define the northern and southern coasts of the island suggest an east-west trend in relative plate motion, which is consistent with previous findings. The intervening area consists of en echelon mountain ranges thrust up at the restraining bend from the early Miocene. A Pleistocene volcanic province within this area is interpreted as defining a diffuse extensional fault termination of the southern strike-slip fault zone.

  14. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

    PubMed

    Awasthi, Saurabh; Saraswathi, N T

    2016-06-01

    Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation. PMID:26893056

  15. Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function.

    PubMed

    Awasthi, Saurabh; Saraswathi, N T

    2016-06-01

    Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation.

  16. DisVis: quantifying and visualizing accessible interaction space of distance-restrained biomolecular complexes

    PubMed Central

    van Zundert, G.C.P.; Bonvin, A.M.J.J.

    2015-01-01

    Summary: We present DisVis, a Python package and command line tool to calculate the reduced accessible interaction space of distance-restrained binary protein complexes, allowing for direct visualization and quantification of the information content of the distance restraints. The approach is general and can also be used as a knowledge-based distance energy term in FFT-based docking directly during the sampling stage. Availability and implementation: The source code with documentation is freely available from https://github.com/haddocking/disvis. Contact: a.m.j.j.bonvin@uu.nl Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26026169

  17. Safeguarding the integrity of science communication by restraining 'rational cheating' in peer review.

    PubMed

    Barroga, Edward F

    2014-11-01

    Peer review is the pillar of the integrity of science communication. It is often beset with flaws as well as accusations of unreliability and lack of predictive validity. 'Rational cheating' by reviewers is a threat to the validity of peer review. It may diminish the value of good papers by unfavourable appraisals of the reviewers whose own works have lower scientific merits. This article analyzes the mechanics and defects of peer review and focuses on rational cheating in peer review, its implications, and options to restrain it.

  18. The relation of hedonic hunger and restrained eating to lateralized frontal activation.

    PubMed

    Winter, S R; Feig, E H; Kounios, J; Erickson, B; Berkowitz, S; Lowe, M R

    2016-09-01

    Asymmetrical alpha activation in the prefrontal cortex (frontal asymmetry) in electroencephalography (EEG) has been related to eating behavior. Prior studies linked dietary restraint with right frontal asymmetry [1] and disinhibition with left frontal asymmetry [2]. The current study simultaneously assessed restrained eating and hedonic hunger (drive for food reward in the absence of hunger) in relation to frontal asymmetry. Resting-state EEG and measures of restrained eating (Revised Restraint Scale; RRS) and hedonic hunger (Power of Food Scale; PFS) were assessed in 61 non-obese adults. Individually, hedonic hunger predicted left asymmetry. However, PFS and RRS were correlated (r=0.48, p<0.05) and there was a significant interaction between PFS and RRS on frontal asymmetry, p<0.01. Results indicated that those high in hedonic hunger exhibited left asymmetry irrespective of RRS scores; among those low in PFS, only those high in RRS showed right asymmetry. Results were consistent with literature linking avoidant behaviors (restraint) with right-frontal asymmetry and approach behaviors (binge eating) with left-frontal asymmetry. It appears that a strong drive toward palatable foods predominates at a neural level even when restraint is high. Findings suggest that lateralized frontal activity is an indicator of motivation both to consume and to avoid consuming highly palatable foods.

  19. Collision-avoidance behaviors of minimally restrained flying locusts to looming stimuli

    PubMed Central

    Chan, R. WM.; Gabbiani, F.

    2013-01-01

    SUMMARY Visually guided collision avoidance is of paramount importance in flight, for instance to allow escape from potential predators. Yet, little is known about the types of collision-avoidance behaviors that may be generated by flying animals in response to an impending visual threat. We studied the behavior of minimally restrained locusts flying in a wind tunnel as they were subjected to looming stimuli presented to the side of the animal, simulating the approach of an object on a collision course. Using high-speed movie recordings, we observed a wide variety of collision-avoidance behaviors including climbs and dives away from – but also towards – the stimulus. In a more restrained setting, we were able to relate kinematic parameters of the flapping wings with yaw changes in the trajectory of the animal. Asymmetric wing flapping was most strongly correlated with changes in yaw, but we also observed a substantial effect of wing deformations. Additionally, the effect of wing deformations on yaw was relatively independent of that of wing asymmetries. Thus, flying locusts exhibit a rich range of collision-avoidance behaviors that depend on several distinct aerodynamic characteristics of wing flapping flight. PMID:23364572

  20. Mathematical modeling and full-scale shaking table tests for multi-curve buckling restrained braces

    NASA Astrophysics Data System (ADS)

    Tsai, C. S.; Lin, Yungchang; Chen, Wenshin; Su, H. C.

    2009-09-01

    Buckling restrained braces (BRBs) have been widely applied in seismic mitigation since they were introduced in the 1970s. However, traditional BRBs have several disadvantages caused by using a steel tube to envelope the mortar to prevent the core plate from buckling, such as: complex interfaces between the materials used, uncertain precision, and time consumption during the manufacturing processes. In this study, a new device called the multi-curve buckling restrained brace (MC-BRB) is proposed to overcome these disadvantages. The new device consists of a core plate with multiple neck portions assembled to form multiple energy dissipation segments, and the enlarged segment, lateral support elements and constraining elements to prevent the BRB from buckling. The enlarged segment located in the middle of the core plate can be welded to the lateral support and constraining elements to increase buckling resistance and to prevent them from sliding during earthquakes. Component tests and a series of shaking table tests on a full-scale steel structure equipped with MC-BRBs were carried out to investigate the behavior and capability of this new BRB design for seismic mitigation. The experimental results illustrate that the MC-BRB possesses a stable mechanical behavior under cyclic loadings and provides good protection to structures during earthquakes. Also, a mathematical model has been developed to simulate the mechanical characteristics of BRBs.

  1. Influence of Nutrition Claims on Appetite Sensations according to Sex, Weight Status, and Restrained Eating

    PubMed Central

    Doucet, Éric; Pomerleau, Sonia

    2016-01-01

    Nutrition claims may help people to adopt healthier eating habits, but little is known about the potential cognitive effects of such claims on appetite sensations. The main purpose of this study was to evaluate the impact of nutrition claims and individual factors on perceived appetite sensations. According to a three (“healthy” versus “diet” (i.e., satiating) versus “hedonic”) by two (restrained or not restrained) by two (normal-weight or overweight/obese) by two (men versus women) factorial design, 164 males and 188 females aged 18–65 were invited to taste an oatmeal-raisin snack in a blinded and ad libitum context. Visual analog scales (150 mm) were used to evaluate appetite sensations before and over 1 h after consumption period. BMI and Restraint Scale were used to categorize participants according to their weight and restraint status. No main condition effect was observed for any of the four appetite sensations. However, subgroups analysis revealed significant differences among specific subgroups. A main effect of sex was also observed for all appetite sensations with men reporting higher levels of desire to eat, hunger and prospective food consumption, and lower levels of fullness than women. These findings highlight the importance of considering individual characteristics in interaction when studying appetite sensations. PMID:27725885

  2. Head excursion of restrained human volunteers and hybrid III dummies in steady state rollover tests.

    PubMed

    Moffatt, Edward; Hare, Barry; Hughes, Raymond; Lewis, Lance; Iiyama, Hiroshi; Curzon, Anne; Cooper, Eddie

    2003-01-01

    Seatbelts provide substantial benefits in rollover crashes, yet occupants still receive head and neck injuries from contacting the vehicle roof interior when the roof exterior strikes the ground. Prior research has evaluated rollover restraint performance utilizing anthropomorphic test devices (dummies), but little dynamic testing has been done with human volunteers to learn how they move during rollovers. In this study, the vertical excursion of the head of restrained dummies and human subjects was measured in a vehicle being rotated about its longitudinal roll axis at roll rates from 180-to-360 deg/sec and under static inversion conditions. The vehicle's restraint design was the commonly used 3-point seatbelt with continuous loop webbing and a sliding latch plate. This paper presents an analysis of the observed occupant motion and provides a comparison of dummy and human motion under similar test conditions. Thirty-five tests (eighteen static and seventeen dynamic) were completed using two different sizes of dummies and human subjects in both near and far-side roll directions. The research indicates that far-side rollovers cause the restrained test subjects to have greater head excursion than near-side rollovers, and that static inversion testing underestimates head excursion for far-side occupants. Human vertical head excursion of up to 200 mm was found at a roll rate of 220 deg/sec. Humans exhibit greater variability in head excursion in comparison to dummies. Transfer of seatbelt webbing through the latch plate did not correlate directly with differences in head excursion.

  3. Cilengitide restrains the osteoclast-like bone resorbing activity of myeloma plasma cells.

    PubMed

    Tucci, Marco; Stucci, Stefania; Felici, Claudia; Cafforio, Paola; Resta, Leonardo; Rossi, Roberta; Silvestris, Franco

    2016-04-01

    Cilengitide (CLG) is an inhibitor of both αv β3 and αv β5 integrins, with a defined anti-tumour effect in glioblastoma. Pre-clinical studies demonstrate its ability to restrain the bone resorbing property of metastatic osteotropic tumours and we have previously shown that the disablement of αv β3 in multiple myeloma (MM) plasma cells results in exhaustion of their in vitro osteoclast (OC)-like activity on bone substrate. Here, we investigated the effect of CLG on this functional property of MM cells. Both αv β3 and αv β5 were measured on primary marrow MM cells from 19 patients, and the effect of CLG on proliferation, apoptosis and adhesion was investigated in parallel with MM cell lines and OCs from healthy donors. In addition, the effect of CLG on the capability of malignant plasma cells to produce erosive lacunae on calcium phosphate was explored in relation to the activation of intracellular kinases of molecular pathways of both integrins. Ultrastructural microscopy was used to evaluate the morphological changes in MM cells due to the effect of CLG on cell adhesion. The data from our study demonstrate that CLG restrains the bone resorbing function of MM cells by disabling their adhesion properties. Further investigations in pre-clinical studies of osteotropic tumours are warranted.

  4. Neurofeedback reduces overeating episodes in female restrained eaters: a randomized controlled pilot-study.

    PubMed

    Schmidt, Jennifer; Martin, Alexandra

    2015-12-01

    Overeating episodes, despite of intentions to control weight, are a common problem among women. Recurring episodes of overeating and dietary failure have been reported to result in higher Body Mass Indexes and to induce severe distress even in non-clinical groups. Based on findings from physiological research on eating behavior and craving, as well as previous biofeedback studies, we derived a cue exposure based EEG neurofeedback protocol to target overeating episodes. The treatment was evaluated in a randomized controlled trial, comparing a neurofeedback group (NFG; n = 14) with a waiting list control group (WLG; n = 13) in a sub-clinical sample of female restrained eaters. At post-treatment, the number of weekly overeating episodes and subsequent distress were significantly reduced in the NFG compared to the WLG (p < .01; r > .50). In a 3 month follow-up, effects in the NFG remained stable. As secondary outcomes, perceived dieting success was enhanced after the treatment. At follow-up, additional beneficial effects on trait food craving were observed. Altogether, we found preliminary evidence for the cue exposure neurofeedback against overeating episodes in female restrained eaters, although specific effects and underlying mechanisms still have to be explored in future research.

  5. The effects of emotion regulation on the desire to overeat in restrained eaters.

    PubMed

    Svaldi, Jennifer; Tuschen-Caffier, Brunna; Lackner, Helmut K; Zimmermann, Sabine; Naumann, Eva

    2012-10-01

    The aim of the present study was to test whether emotion regulation (ER) strategies are underlying processes in the link between negative emotions and the desire to overeat (DTE) in high restrained eaters (HR). Forty-eight female HR and 46 female low restrained eaters (LR) watched three sadness inducing film clips. Thereby, participants were randomly assigned to and trained in one of three conditions while watching the first two clips: to suppress upcoming emotions, to accept upcoming emotions or to reappraise the situation. After that, they participated in an experiment in which the learned ER strategy was implemented while watching the third sadness inducing film clip. DTE and sadness were assessed prior to and at the end of each clip. Additionally, physiological measures of the sympathetic and parasympathetic branch were obtained. In the HR group emotion acceptance and suppression lead to a significant increase of the DTE from baseline to post-film, while there was no change in DTE in the reappraisal condition. However, psychophysiological measures were not moderated by ER strategies. The results are discussed in terms of the limited resource model.

  6. Buckling Behavior of Long Anisotropic Plates Subjected to Elastically Restrained Thermal Expansion

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2002-01-01

    An approach for synthesizing buckling results for, and behavior of, thin balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and elastically restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexurally anisotropic plates that are subjected to combined mechanical loads and is based on useful nondimensional parameters. In addition, stiffness-weighted laminate thermal-expansion parameters and compliance coefficients are derived that are used to determine critical temperatures in terms of physically intuitive mechanical-buckling coefficients. The effects of membrane orthotropy and membrane anisotropy are included in the general formulation. Many results are presented for some common laminates that are intended to facilitate a structural designer's transition to the use of generic buckling design curves. Several curves that illustrate the fundamental parameters used in the analysis are presented, for nine contemporary material systems, that provide physical insight into the buckling response in addition to providing useful design data. Examples are presented that demonstrate the use of generic design curves. The analysis approach and generic results indicate the effects and characteristics of elastically restrained laminate thermal expansion or contraction, membrane orthotropy and anisotropy, and flexural orthotropy and anisotropy in a very general and unifying manner.

  7. A thermal active restrained shrinkage ring test to study the early age concrete behaviour of massive structures

    SciTech Connect

    Briffaut, M.; Benboudjema, F.; Nahas, G.

    2011-01-15

    In massive concrete structures, cracking may occur during hardening, especially if autogenous and thermal strains are restrained. The concrete permeability due to this cracking may rise significantly and thus increase leakage (in tank, nuclear containment...) and reduce the durability. The restrained shrinkage ring test is used to study the early age concrete behaviour (delayed strains evolution and cracking). This test shows, at 20 {sup o}C and without drying, for a concrete mix which is representative of a French nuclear power plant containment vessel (w/c ratio equal to 0.57), that the amplitude of autogenous shrinkage (about 40 {mu}m/m for the studied concrete mix) is not high enough to cause cracking. Indeed, in this configuration, thermal shrinkage is not significant, whereas this is a major concern for massive structures. Therefore, an active test has been developed to study cracking due to restrained thermal shrinkage. This test is an evolution of the classical restrained shrinkage ring test. It allows to take into account both autogenous and thermal shrinkages. Its principle is to create the thermal strain effects by increasing the temperature of the brass ring (by a fluid circulation) in order to expand it. With this test, the early age cracking due to restrained shrinkage, the influence of reinforcement and construction joints have been experimentally studied. It shows that, as expected, reinforcement leads to an increase of the number of cracks but a decrease of crack widths. Moreover, cracking occurs preferentially at the construction joint.

  8. Make up your mind about food: A healthy mindset attenuates attention for high-calorie food in restrained eaters.

    PubMed

    Werthmann, Jessica; Jansen, Anita; Roefs, Anne

    2016-10-01

    Attention bias for food could be a cognitive pathway to overeating in obesity and restrained eating. Yet, empirical evidence for individual differences (e.g., in restrained eating and body mass index) in attention bias for food is mixed. We tested experimentally if temporarily induced health versus palatability mindsets influenced attention bias for food, and whether restrained eating moderated this relation. After manipulating mindset (health vs. palatability) experimentally, food-related attention bias was measured by eye-movements (EM) and response latencies (RL) during a visual probe task depicting high-calorie food and non-food. Restrained eating was assessed afterwards. A significant interaction of mindset and restrained eating on RL bias emerged, β = 0.36, t(58) = 2.05, p = 0.045: A health mindset - as compared to a palatability mindset - attenuated attention bias for high-caloric food only in participants with higher eating restraint. No effects were observed on EM biases. The current results demonstrate that state differences in health versus palatability mindsets can cause attenuated attention bias for high-calorie food cues in participants with higher eating restraint. Our findings add to emerging evidence that state differences in mindsets can bias attention for food, above the influence of trait differences.

  9. Make up your mind about food: A healthy mindset attenuates attention for high-calorie food in restrained eaters.

    PubMed

    Werthmann, Jessica; Jansen, Anita; Roefs, Anne

    2016-10-01

    Attention bias for food could be a cognitive pathway to overeating in obesity and restrained eating. Yet, empirical evidence for individual differences (e.g., in restrained eating and body mass index) in attention bias for food is mixed. We tested experimentally if temporarily induced health versus palatability mindsets influenced attention bias for food, and whether restrained eating moderated this relation. After manipulating mindset (health vs. palatability) experimentally, food-related attention bias was measured by eye-movements (EM) and response latencies (RL) during a visual probe task depicting high-calorie food and non-food. Restrained eating was assessed afterwards. A significant interaction of mindset and restrained eating on RL bias emerged, β = 0.36, t(58) = 2.05, p = 0.045: A health mindset - as compared to a palatability mindset - attenuated attention bias for high-caloric food only in participants with higher eating restraint. No effects were observed on EM biases. The current results demonstrate that state differences in health versus palatability mindsets can cause attenuated attention bias for high-calorie food cues in participants with higher eating restraint. Our findings add to emerging evidence that state differences in mindsets can bias attention for food, above the influence of trait differences. PMID:27174250

  10. The tempting effect of forbidden foods. High calorie content evokes conflicting implicit and explicit evaluations in restrained eaters.

    PubMed

    Hoefling, Atilla; Strack, Fritz

    2008-11-01

    In this study, restrained and unrestrained eaters' immediate evaluations of high calorie content and low calorie content were measured, both when being deprived of food and when satiated. As an indirect measure, the Extrinsic Affective Simon Task (EAST) [De Houwer, J. (2003). The Extrinsic Affective Simon Task. Experimental Psychology, 50, 77-85.] was used. Explicit attitudes towards high calorie content and low calorie content were also assessed. Food deprivation was found to boost the value of food for all subjects on an impulsive level of information processing. More importantly, it was also found that restrained eaters exhibit a dissociative pattern of positive implicit and negative explicit attitudes towards high calorie content, but not towards low calorie content. Furthermore, restrained eaters evaluated high calorie content more negative than unrestrained eaters on an explicit level, but more positive on an implicit level. Results from this study are twofold. First, they suggest that conflicting evaluative reactions from two systems of information processing may play a central role in the restrained eater's dilemma. Second, individual differences between restrained and unrestrained eaters' attitudes towards high calorie content should further be investigated.

  11. General principles of antimicrobial therapy.

    PubMed

    Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

    2011-02-01

    Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.

  12. General principles of antimicrobial therapy.

    PubMed

    Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

    2011-02-01

    Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community. PMID:21282489

  13. [Growth promoting antimicrobials].

    PubMed

    Hoogkamp-Korstanje, J A

    1999-06-19

    The committee 'Growth promoting antimicrobials' of the Health Council of the Netherlands in 1998 advised immediate prohibition of all growth promoting antimicrobials related to human drugs and decrease of use of other growth promoting antimicrobials during the next three years in Europe. It is clear that frequent use of antibiotics is associated with development of resistance by selection in animals (and man), but it is not proven that this is an explanation of resistance in the human community. We know only little about the mechanisms and conditions of transfer of bacteria to man. Other questions raised are: what about the resulting possible increase of therapeutic application of antibiotics in animals, how to handle the increase of dung, nitrogen and phosphate in the environment and how farmers can survive with a decrease in income, sometimes by as much as 50%? Although many will feel sympathy for the report and its recommendations, implementing them will be difficult and possibly premature. PMID:10416481

  14. Antimicrobial Peptides from Fish

    PubMed Central

    Masso-Silva, Jorge A.; Diamond, Gill

    2014-01-01

    Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

  15. Antimicrobial Graft Copolymer Gels.

    PubMed

    Harvey, Amanda C; Madsen, Jeppe; Douglas, C W Ian; MacNeil, Sheila; Armes, Steven P

    2016-08-01

    In view of the growing worldwide rise in microbial resistance, there is considerable interest in designing new antimicrobial copolymers. The aim of the current study was to investigate the relationship between antimicrobial activity and copolymer composition/architecture to gain a better understanding of their mechanism of action. Specifically, the antibacterial activity of several copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and 2-hydroxypropyl methacrylate (HPMA) toward Staphylococcus aureus was examined. Both block and graft copolymers were synthesized using either atom transfer radical polymerization or reversible addition-fragmentation chain transfer polymerization and characterized via (1)H NMR, gel permeation chromatography, rheology, and surface tensiometry. Antimicrobial activity was assessed using a range of well-known assays, including direct contact, live/dead staining, and the release of lactate dehydrogenase (LDH), while transmission electron microscopy was used to study the morphology of the bacteria before and after the addition of various copolymers. As expected, PMPC homopolymer was biocompatible but possessed no discernible antimicrobial activity. PMPC-based graft copolymers comprising PHPMA side chains (i.e. PMPC-g-PHPMA) significantly reduced both bacterial growth and viability. In contrast, a PMPC-PHPMA diblock copolymer comprising a PMPC stabilizer block and a hydrophobic core-forming PHPMA block did not exhibit any antimicrobial activity, although it did form a biocompatible worm gel. Surface tensiometry studies and LDH release assays suggest that the PMPC-g-PHPMA graft copolymer exhibits surfactant-like activity. Thus, the observed antimicrobial activity is likely to be the result of the weakly hydrophobic PHPMA chains penetrating (and hence rupturing) the bacterial membrane. PMID:27409712

  16. A comparative study of pi-arene-bridged lanthanum arylamide and aryloxide dimers. Solution behavior, exchange mechanisms, and X-ray crystal structures of La2(NH-2,6-iPr2C6H3)6, La(NH-2,6-iPr2C6H3)3(THF)3, and La(NH-2,6-iPr2C6H3)3(py)2.

    PubMed

    Giesbrecht, Garth R; Gordon, John C; Clark, David L; Hay, P Jeffrey; Scott, Brian L; Tait, C Drew

    2004-05-26

    Reaction of 3 equiv of 2,6-diisopropylaniline with La[N(SiMe(3))(2)](3) produces the dimeric species La(2)(NHAr)(6) (1). X-ray crystallography reveals a centrosymmetric structure, where the dimeric unit is bridged by intermolecular eta(6)-arene interactions of a unique arylamide ligand attached to an adjacent metal center. Exposure of 1 to THF results in formation of the monomeric tris-THF adduct La(NHAr)(3)(THF)(3) (2), which was shown by X-ray crystallography to maintain a fac-octahedral structure in the solid state. (1)H NMR spectroscopy illustrates that the binding of THF to 1 to form 2 is reversible and removal of THF under vacuum regenerates dimeric 1. Addition of pyridine to 1 yields the monomeric bis-pyridine adduct La(NHAr)(3)(py)(2) (3), which exhibits a distorted trigonal-bipyramidal La metal center. Solution (1)H NMR, IR, and Raman spectroscopy indicate that the pi-arene-bridged dimeric structure of 1 is maintained in solution. Variable-temperature (1)H NMR spectroscopic investigations of 1 are consistent with a monomer-dimer equilibrium at elevated temperature. In contrast, variable-temperature (1)H NMR spectroscopic investigations of the aryloxide analogue La(2)(OAr)(6) (4) show that the bridging and terminal aryloxide groups exchange by a mechanism in which the dimeric nature of the compound is retained. Density functional theory (DFT) calculations were carried out on model compounds La(2)(OC(6)H(5))(6), La(2)(NHC(6)H(5))(6), and (C(6)H(5)R)La(XC(6)H(5))(3), where X = O or NH and R = H, OH, or NH(2). The formation of eta(6)-arene interactions is energetically favored over monomeric LaX(3) (X = OPh or NHPh) with the aryloxide pi-arene interaction being stronger than the arylamide pi-arene interaction. Calculation of vibrational frequencies reveals the origin of the observed IR spectral behavior of both La(2)(OC(6)H(5))(6) and La(2)(NHC(6)H(5))(6), with the higher energy nu(C=C) stretch due to terminal ligands and the lower energy stretch associated

  17. A regulatory focus perspective on eating behavior: how prevention and promotion focus relates to emotional, external, and restrained eating.

    PubMed

    Pfattheicher, Stefan; Sassenrath, Claudia

    2014-01-01

    By applying regulatory focus theory (RFT) to the context of eating behavior, the present research examines the relations between individual differences in the two motivational orientations as conceptualized in RFT, that is, prevention-focused and promotion-focused self-regulation and emotional, external, and restrained eating. Building on a representative study conducted in the Netherlands (N = 4,230), it is documented that individual differences in prevention focus are positively related to emotional eating whereas negligible associations are found in regards to external and restrained eating. Individual differences in promotion focus are positively related to external eating whereas negligible associations are found in regards to emotional and restrained eating. In relating RFT to different eating styles we were able to document significant relations of basic self-regulatory orientations with regard to essential daily behavior associated with health and well-being. The implications for changing eating styles are discussed.

  18. The effect of brand and caloric information on flavor perception and food consumption in restrained and unrestrained eaters.

    PubMed

    Cavanagh, Kevin V; Kruja, Blina; Forestell, Catherine A

    2014-11-01

    The goal of the current study was to determine whether provision of brand and caloric information affects sensory perception and consumption of a food in restrained (n=84) and unrestrained eaters (n=104). Using a between-subjects 2 × 2 × 3 design, female restrained and unrestrained eaters were asked to taste and rate a cookie that was labeled with a brand associated with healthful eating (Kashi(®)) or one associated with unhealthful eating (Nabisco(®)). Additionally, some participants were presented with a nutrition label alongside the brand name indicating that one serving contained 130 calories (Low-Calorie Condition), or 260 calories (High-Calorie Condition). The remaining participants were not shown a nutrition label (No Label Condition). Results indicated that those in the No Label or the High-Calorie Condition perceived the healthful branded cookie to have a better flavor than those who received the unhealthful branded cookie regardless of their restraint status. However, restrained eaters in the No Label Condition consumed more of the healthful than the unhealthful branded cookie, whereas those in the Low-Calorie Condition consumed more of the unhealthful than the healthful branded cookie. In contrast, unrestrained eaters ate more of the healthful branded cookie regardless of the caloric information provided. Thus, although restrained and unrestrained eaters' perceptions are similarly affected by branding and caloric information, brands and caloric information interact to affect restrained eaters' consumption. This study reveals that labeling foods as low calorie may create a halo effect which may lead to over-consumption of these foods in restrained eaters.

  19. The effect of brand and caloric information on flavor perception and food consumption in restrained and unrestrained eaters.

    PubMed

    Cavanagh, Kevin V; Kruja, Blina; Forestell, Catherine A

    2014-11-01

    The goal of the current study was to determine whether provision of brand and caloric information affects sensory perception and consumption of a food in restrained (n=84) and unrestrained eaters (n=104). Using a between-subjects 2 × 2 × 3 design, female restrained and unrestrained eaters were asked to taste and rate a cookie that was labeled with a brand associated with healthful eating (Kashi(®)) or one associated with unhealthful eating (Nabisco(®)). Additionally, some participants were presented with a nutrition label alongside the brand name indicating that one serving contained 130 calories (Low-Calorie Condition), or 260 calories (High-Calorie Condition). The remaining participants were not shown a nutrition label (No Label Condition). Results indicated that those in the No Label or the High-Calorie Condition perceived the healthful branded cookie to have a better flavor than those who received the unhealthful branded cookie regardless of their restraint status. However, restrained eaters in the No Label Condition consumed more of the healthful than the unhealthful branded cookie, whereas those in the Low-Calorie Condition consumed more of the unhealthful than the healthful branded cookie. In contrast, unrestrained eaters ate more of the healthful branded cookie regardless of the caloric information provided. Thus, although restrained and unrestrained eaters' perceptions are similarly affected by branding and caloric information, brands and caloric information interact to affect restrained eaters' consumption. This study reveals that labeling foods as low calorie may create a halo effect which may lead to over-consumption of these foods in restrained eaters. PMID:24979333

  20. Removing guns from batterers: findings from a pilot survey of domestic violence restraining order recipients in California.

    PubMed

    Vittes, Katherine A; Webster, Daniel W; Frattaroli, Shannon; Claire, Barbara E; Wintemute, Garen J

    2013-05-01

    Persons under certain domestic violence restraining orders in California are required to surrender any firearms in their possession within 24 hours of service. The California Department of Justice funded a pilot program in which Sheriff's Offices in two counties developed a system for better enforcing the firearm surrender requirement. As part of a larger process evaluation, 17 restraining order recipients were interviewed about their experiences with and feelings about the removal of firearms from their abusers. Most women surveyed wanted firearms removed and felt safer as a result of their removal. Implications of the findings are discussed.

  1. Gun Violence Restraining Orders: Alternative or Adjunct to Mental Health-Based Restrictions on Firearms?

    PubMed

    Frattaroli, Shannon; McGinty, Emma E; Barnhorst, Amy; Greenberg, Sheldon

    2015-06-01

    The gun violence restraining order (GVRO) is a new tool for preventing gun violence. Unlike traditional approaches to prohibiting gun purchase and possession, which rely on a high threshold (adjudication by criminal justice or mental health systems) before intervening, the GVRO allows family members and intimate partners who observe a relative's dangerous behavior and believe it may be a precursor to violence to request a GVRO through the civil justice system. Once issued by the court, a GVRO authorizes law enforcement to remove any guns in the respondent's possession and prohibits the respondent from purchasing new guns. In September 2014, California's governor signed AB1014 into law, making California the first U.S. state to enact a GVRO law. This article describes the GVRO and the rationale behind the concept, considers case examples to assess the potential impact of the GVRO as a strategy for preventing gun violence, and reviews the content of the California law. PMID:25990840

  2. Non-restrained measurement of Young's modulus for soft tissue using a photoacoustic technique

    NASA Astrophysics Data System (ADS)

    Wadamori, Naoki

    2014-09-01

    A miniaturized sensor was developed to determine the Young's modulus of tumors based on photoacoustic spectroscopy. The sensor had a chamber height of 5.3 mm and diameter of 5.8 mm; thus, this device is smaller than conventional endoscopes, the outer diameters of which are typically about 10 mm. A non-restrained methodology for determining the Young's modulus of tumors was proposed based on the resonance frequency of the photoacoustic signal. The proposed approach was applied to silicone rubbers with six different Young's moduli (30, 64, 123, 224, 396, and 574 kPa) and showed good resolution (±2 kPa) and high reproducibility. These results show that the photoacoustic technique can be applied to mechanically characterize soft tissue by diagnostic endoscopy.

  3. Gun Violence Restraining Orders: Alternative or Adjunct to Mental Health-Based Restrictions on Firearms?

    PubMed

    Frattaroli, Shannon; McGinty, Emma E; Barnhorst, Amy; Greenberg, Sheldon

    2015-06-01

    The gun violence restraining order (GVRO) is a new tool for preventing gun violence. Unlike traditional approaches to prohibiting gun purchase and possession, which rely on a high threshold (adjudication by criminal justice or mental health systems) before intervening, the GVRO allows family members and intimate partners who observe a relative's dangerous behavior and believe it may be a precursor to violence to request a GVRO through the civil justice system. Once issued by the court, a GVRO authorizes law enforcement to remove any guns in the respondent's possession and prohibits the respondent from purchasing new guns. In September 2014, California's governor signed AB1014 into law, making California the first U.S. state to enact a GVRO law. This article describes the GVRO and the rationale behind the concept, considers case examples to assess the potential impact of the GVRO as a strategy for preventing gun violence, and reviews the content of the California law.

  4. Buckling Behavior of Long Anisotropic Plates Subjected to Elastically Restrained Thermal Expansion and Contraction

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2004-01-01

    An approach for synthesizing buckling results for thin balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and elastically restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexural anisotropic plates that are subjected to combined mechanical loads. In addition, stiffness-weighted laminate thermal-expansion parameters and compliance coefficients are derived that are used to determine critical temperatures in terms of physically intuitive mechanical-buckling coefficients. Many results are presented for some common laminates that are intended to facilitate a structural designer s transition to the use of the generic buckling design curves. Several curves that illustrate the fundamental parameters used in the analysis are presented, for nine contemporary material systems, that provide physical insight into the buckling response in addition to providing useful design data. Examples are presented that demonstrate the use of the generic design curves.

  5. Restraining order for dendritic cells: all quiet on the fetal front.

    PubMed

    Chakraborty, Rana; Pulendran, Bali

    2009-07-01

    The paradoxical ability to launch effective immunity against pathogens while avoiding the horror autotoxicus of autoimmunity is one of the most remarkable features of the mammalian immune system. This assumes a particular evolutionary significance at the maternal/fetal interface, where avoidance of immune reactivity to the fetus is vital to the propagation of the species itself. Several mechanisms of suppressing maternal immunity against the fetus have been described. The article by Collins et al. in this issue of the JCI describes a novel mechanism of avoiding immune surveillance in which the migratory capacity of dendritic cells at the maternal/fetal interface is restrained (see the related article beginning on page 2062). PMID:19603541

  6. Antimicrobial properties of honey.

    PubMed

    Israili, Zafar H

    2014-01-01

    Honey has been widely accepted as food and medicine by all generations, traditions, and civilizations, both ancient and modern. For at least 2700 years, honey has been used by humans to treat a variety of ailments through topical application, but only recently have the antiseptic and antimicrobial properties of honey been discovered. Honey has been reported to be effective in a number of human pathologies. Clinical studies have demonstrated that application of honey to severely infected cutaneous wounds rapidly clears infection from the wound and improves tissue healing. A large number of in vitro and limited clinical studies have confirmed the broad-spectrum antimicrobial (antibacterial, antifungal, antiviral, and antimycobacterial) properties of honey, which may be attributed to the acidity (low pH), osmotic effect, high sugar concentration, presence of bacteriostatic and bactericidal factors (hydrogen peroxide, antioxidants, lysozyme, polyphenols, phenolic acids, flavonoids, methylglyoxal, and bee peptides), and increase in cytokine release, and to immune modulating and anti-inflammatory properties of honey; the antimicrobial action involves several mechanisms. Despite a large amount of data confirming the antimicrobial activity of honey, there are no studies that support the systemic use of honey as an antibacterial agent. PMID:23782759

  7. Strontium ranelate inhibits titanium-particle-induced osteolysis by restraining inflammatory osteoclastogenesis in vivo.

    PubMed

    Liu, Xing; Zhu, Shijun; Cui, Jingfu; Shao, Hongguo; Zhang, Wen; Yang, Huilin; Xu, Yaozeng; Geng, Dechun; Yu, Long

    2014-11-01

    Wear-particle-induced osteolysis is considered to be the main reason for revision after arthroplasty. Although the exact mechanism remains unclear, inflammatory osteoclastogenesis plays an important role in this process. Strontium ranelate (SR) was found to have a therapeutic effect on osteoporosis in postmenopausal women. Based on prior studies, the present authors hypothesized that SR prevents wear-particle-induced osteolysis through restraining inflammatory osteoclastogenesis. The present study used 80 male C57BL/J6 mice to test this hypothesis in a murine osteolysis model. All experimental animals were randomly divided into four groups: a control group; a SR group; a titanium group; and a titanium+SR group. Once titanium particles had been implanted in mice, the mice were administered SR (900 mg kg(-1) day(-1)) by gavage for 14 days. After 14 days, the calvaria were collected for micro-computed tomography (μCT), histological and molecular analysis. The results of μCT and histomorphometric analysis demonstrated that SR markedly inhibited bone resorption and the generation of tartrate-resistant acid-phosphatase-positive cells in vivo, compared with titanium-stimulated calvaria. Reverse transcription polymerase chain reaction and ELISAs showed that SR stimulated the mRNA and protein expression of osteoprotegerin, and inhibited gene and protein expression of receptor activators of nuclear factor-kappa B ligand in titanium-particle-charged calvaria. In addition, SR obviously reduced the secretion of tumor necrosis factor-α and interleukin-1β in the calvaria of the titanium group. It was concluded that SR inhibits titanium-induced osteolysis by restraining inflammatory osteoclastogenesis, and that it could be developed as a new drug to prevent and treat aseptic loosening. PMID:25078426

  8. Head Excursion of Restrained Human Volunteers and Hybrid III Dummies in Steady State Rollover Tests

    PubMed Central

    Moffatt, Edward; Hare, Barry; Hughes, Raymond; Lewis, Lance; Iiyama, Hiroshi; Curzon, Anne; Cooper, Eddie

    2003-01-01

    Seatbelts provide substantial benefits in rollover crashes, yet occupants still receive head and neck injuries from contacting the vehicle roof interior when the roof exterior strikes the ground. Prior research has evaluated rollover restraint performance utilizing anthropomorphic test devices (dummies), but little dynamic testing has been done with human volunteers to learn how they move during rollovers. In this study, the vertical excursion of the head of restrained dummies and human subjects was measured in a vehicle being rotated about its longitudinal roll axis at roll rates from 180-to-360 deg/sec and under static inversion conditions. The vehicle’s restraint design was the commonly used 3-point seatbelt with continuous loop webbing and a sliding latch plate. This paper presents an analysis of the observed occupant motion and provides a comparison of dummy and human motion under similar test conditions. Thirty-five tests (eighteen static and seventeen dynamic) were completed using two different sizes of dummies and human subjects in both near and far-side roll directions. The research indicates that far-side rollovers cause the restrained test subjects to have greater head excursion than near-side rollovers, and that static inversion testing underestimates head excursion for far-side occupants. Human vertical head excursion of up to 200 mm was found at a roll rate of 220 deg/sec. Humans exhibit greater variability in head excursion in comparison to dummies. Transfer of seatbelt webbing through the latch plate did not correlate directly with differences in head excursion. PMID:12941241

  9. Differences in Thoracic Injury Causation Patterns Between Seat Belt Restrained Children and Adults

    PubMed Central

    Arbogast, Kristy B.; Locey, Caitlin M.; Zonfrillo, Mark R.

    2012-01-01

    The objective of this research was to delineate age-based differences in specific thoracic injury diagnoses for seat belt restrained rear seat occupants and describe the associated injury causation in order to provide insight into how the load of the seat belt is transferred to occupants of various sizes. Using data from the Crash Investigation Research and Engineering Network (CIREN), 20 cases of rear seated, lap and shoulder belt restrained occupants with AIS2+ thoracic injuries in frontal crashes were reviewed. Seven were children and adolescents age 8–15 years, 5 were 16–24 years, 3 were 25–54 years, and 5 were 55+ years. Six of the seven 8–15 year olds sustained injuries to the lung in the form of pulmonary contusion or pneumothorax. Only three of the seven sustained a skeletal (sternum or rib) fracture; only one of these three involved multiple ribs bilaterally. In contrast, four of the five 16–24 year olds sustained at least one rib fracture - often multiple and bilateral. The adult cohort (25+ years) was involved in predominantly more minor crashes; however they all sustained complex rib fractures – seven of the eight involved multiple ribs, four of the eight were also bilateral. Belt compression – either from the shoulder belt or the lap belt – was identified as the primary cause of the thoracic injuries. Often, there was clear evidence of the location of belt loading from AIS 1 chest contusions or abrasions. These findings have implications for age-based thoracic injury criteria suggesting that that different metrics may be needed for different age groups. PMID:23169131

  10. Differences in thoracic injury causation patterns between seat belt restrained children and adults.

    PubMed

    Arbogast, Kristy B; Locey, Caitlin M; Zonfrillo, Mark R

    2012-01-01

    The objective of this research was to delineate age-based differences in specific thoracic injury diagnoses for seat belt restrained rear seat occupants and describe the associated injury causation in order to provide insight into how the load of the seat belt is transferred to occupants of various sizes. Using data from the Crash Investigation Research and Engineering Network (CIREN), 20 cases of rear seated, lap and shoulder belt restrained occupants with AIS2+ thoracic injuries in frontal crashes were reviewed. Seven were children and adolescents age 8-15 years, 5 were 16-24 years, 3 were 25-54 years, and 5 were 55+ years. Six of the seven 8-15 year olds sustained injuries to the lung in the form of pulmonary contusion or pneumothorax. Only three of the seven sustained a skeletal (sternum or rib) fracture; only one of these three involved multiple ribs bilaterally. In contrast, four of the five 16-24 year olds sustained at least one rib fracture - often multiple and bilateral. The adult cohort (25+ years) was involved in predominantly more minor crashes; however they all sustained complex rib fractures - seven of the eight involved multiple ribs, four of the eight were also bilateral. Belt compression - either from the shoulder belt or the lap belt - was identified as the primary cause of the thoracic injuries. Often, there was clear evidence of the location of belt loading from AIS 1 chest contusions or abrasions. These findings have implications for age-based thoracic injury criteria suggesting that that different metrics may be needed for different age groups.

  11. Solution structure of the octamer motif in immunoglobulin genes via restrained molecular dynamics calculations.

    PubMed

    Weisz, K; Shafer, R H; Egan, W; James, T L

    1994-01-11

    The solution structure of the DNA decamer d(CATTTGCATC)-d(GATGCAAATG), comprising the octamer motif of immunoglobulin genes, is determined by restrained molecular dynamics (rMD) simulations. The restraint data set includes interproton distances and torsion angles for the deoxyribose sugar ring which were previously obtained by a complete relaxation matrix analysis of the two-dimensional nuclear Overhauser enhancement (2D NOE) intensities and by the quantitative simulation of cross-peaks in double-quantum-filtered correlated (2QF-COSY) spectra. The influence of torsion angles and the number of experimental distance restraints on the structural refinement has been systematically examined. Omitting part of the experimental NOE-derived distances results in reduced restraint violations and lower R factors but impairs structural convergence in the rMD refinement. Eight separate restrained molecular dynamics simulations were carried out for 20 ps each, starting from either energy-minimized A- or B-DNA. Mutual atomic root-mean-square (rms) differences among the refined structures are well below 1 A and comparable to the rms fluctuations of the atoms about their average position, indicating convergence to essentially identical structures. The average refined structure was subjected to an additional 100 ps of rMD simulations and analyzed in terms of average torsion angles and helical parameters. The B-type duplex exhibits clear sequence-dependent variations in its geometry with a narrow minor groove at the T3.A3 tract and a large positive roll at the subsequent TG.CA step. This is accompanied by a noticeable bend of the global helix axis into the major groove. There is also evidence of significant flexibility of the sugar-phosphate backbone with rapid interconversion among different conformers.

  12. Triclosan antimicrobial polymers

    PubMed Central

    Petersen, Richard C.

    2016-01-01

    Triclosan antimicrobial molecular fluctuating energies of nonbonding electron pairs for the oxygen atom by ether bond rotations are reviewed with conformational computational chemistry analyses. Subsequent understanding of triclosan alternating ether bond rotations is able to help explain several material properties in Polymer Science. Unique bond rotation entanglements between triclosan and the polymer chains increase both the mechanical properties of polymer toughness and strength that are enhanced even better through secondary bonding relationships. Further, polymer blend compatibilization is considered due to similar molecular relationships and polarities. With compatibilization of triclosan in polymers a more uniform stability for nonpolar triclosan in the polymer solid state is retained by the antimicrobial for extremely low release with minimum solubility into aqueous solution. As a result, triclosan is projected for long extended lifetimes as an antimicrobial polymer additive. Further, triclosan rapid alternating ether bond rotations disrupt secondary bonding between chain monomers in the resin state to reduce viscosity and enhance polymer blending. Thus, triclosan is considered for a polymer additive with multiple properties to be an antimicrobial with additional benefits as a nonpolar toughening agent and a hydrophobic wetting agent. The triclosan material relationships with alternating ether bond rotations are described through a complete different form of medium by comparisons with known antimicrobial properties that upset bacterial cell membranes through rapid fluctuating mechanomolecular energies. Also, triclosan bond entanglements with secondary bonding can produce structural defects in weak bacterial lipid membranes requiring pliability that can then interfere with cell division. Regarding applications with polymers, triclosan can be incorporated by mixing into a resin system before cure, melt mixed with thermoplastic polymers that set on cooling

  13. Starch-based Antimicrobial Films Incorporated with Lauric Acid and Chitosan

    NASA Astrophysics Data System (ADS)

    Salleh, E.; Muhamad, I. I.

    2010-03-01

    Antimicrobial (AM) packaging is one of the most promising active packaging systems. Starch-based film is considered an economical material for antimicrobial packaging. This study aimed at the development of food packaging based on wheat starch incorporated with lauric acid and chitosan as antimicrobial agents. The purpose is to restrain or inhibit the growth of spoilage and/or pathogenic microorganisms that are contaminating foods. The antimicrobial effect was tested on B. substilis and E. coli. Inhibition of bacterial growth was examined using two methods, i.e. zone of inhibition test on solid media and liquid culture test (optical density measurements). The control and AM films (incorporated with chitosan and lauric acid) were produced by casting method. From the observations, AM films exhibited inhibitory zones. Interestingly, a wide clear zone on solid media was observed for B. substilis growth inhibition whereas inhibition for E. coli was not as effective as B. substilis. From the liquid culture test, the AM films clearly demonstrated a better inhibition against B. substilis than E. coli.

  14. 49 CFR 393.108 - How is the working load limit of a tiedown, or the load restraining value of a friction mat...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... load restraining value of a friction mat, determined? 393.108 Section 393.108 Transportation Other... load restraining value of a friction mat, determined? (a) The working load limit (WLL) of a tiedown... load limits. (g) Friction mats which are not marked or rated by the manufacturer shall be considered...

  15. 49 CFR 393.108 - How is the working load limit of a tiedown, or the load restraining value of a friction mat...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... load restraining value of a friction mat, determined? 393.108 Section 393.108 Transportation Other... load restraining value of a friction mat, determined? (a) The working load limit (WLL) of a tiedown... load limits. (g) Friction mats which are not marked or rated by the manufacturer shall be considered...

  16. 49 CFR 393.108 - How is the working load limit of a tiedown, or the load restraining value of a friction mat...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... load restraining value of a friction mat, determined? 393.108 Section 393.108 Transportation Other... load restraining value of a friction mat, determined? (a) The working load limit (WLL) of a tiedown... load limits. (g) Friction mats which are not marked or rated by the manufacturer shall be considered...

  17. 49 CFR 393.108 - How is the working load limit of a tiedown, or the load restraining value of a friction mat...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... load restraining value of a friction mat, determined? 393.108 Section 393.108 Transportation Other... load restraining value of a friction mat, determined? (a) The working load limit (WLL) of a tiedown... load limits. (g) Friction mats which are not marked or rated by the manufacturer shall be considered...

  18. 49 CFR 393.108 - How is the working load limit of a tiedown, or the load restraining value of a friction mat...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... load restraining value of a friction mat, determined? 393.108 Section 393.108 Transportation Other... load restraining value of a friction mat, determined? (a) The working load limit (WLL) of a tiedown... load limits. (g) Friction mats which are not marked or rated by the manufacturer shall be considered...

  19. Can we prevent antimicrobial resistance by using antimicrobials better?

    PubMed

    Soothill, Germander; Hu, Yanmin; Coates, Anthony

    2013-06-10

    Since their development over 60 years ago, antimicrobials have become an integral part of healthcare practice worldwide. Recently, this has been put in jeopardy by the emergence of widespread antimicrobial resistance, which is one of the major problems facing modern medicine. In the past, the development of new antimicrobials kept us one step ahead of the problem of resistance, but only three new classes of antimicrobials have reached the market in the last thirty years. A time is therefore approaching when we may not have effective treatment against bacterial infections, particularly for those that are caused by Gram-negative organisms. An important strategy to reduce the development of antimicrobial resistance is to use antimicrobials more appropriately, in ways that will prevent resistance. This involves a consideration of the pharmacokinetic and pharmacodynamics properties of antimicrobials, the possible use of combinations, and more appropriate choice of antimicrobials, which may include rapid diagnostic testing and antimicrobial cycling. Examples given in this review include Mycobacterium tuberculosis, Gram-negative and Gram-positive organisms. We shall summarise the current evidence for these strategies and outline areas for future development.

  20. Motor Vehicle Crash–Related Injury Causation Scenarios for Spinal Injuries in Restrained Children and Adolescents

    PubMed Central

    ZONFRILLO, MARK R.; LOCEY, CAITLIN M.; SCARFONE, STEVEN R.; ARBOGAST, KRISTY B.

    2016-01-01

    Objective Motor vehicle crash (MVC)-related spinal injuries result in significant morbidity and mortality in children. The objective was to identify MVC-related injury causation scenarios for spinal injuries in restrained children. Methods This was a case series of occupants in MVCs from the Crash Injury Research and Engineering Network (CIREN) data set. Occupants aged 0–17 years old with at least one Abbreviated Injury Scale (AIS) 2+ severity spinal injury in vehicles model year 1990+ that did not experience a rollover were included. Unrestrained occupants, those not using the shoulder portion of the belt restraint, and those with child restraint gross misuse were excluded. Occupants with preexisting comorbidities contributing to spinal injury and occupants with limited injury information were also excluded. A multidisciplinary team retrospectively reviewed each case to determine injury causation scenarios (ICSs). Crash conditions, occupant and restraint characteristics, and injuries were qualitatively summarized. Results Fifty-nine cases met the study inclusion criteria and 17 were excluded. The 42 occupants included sustained 97 distinct AIS 2+ spinal injuries (27 cervical, 22 thoracic, and 48 lumbar; 80 AIS-2, 15 AIS-3, 1 AIS-5, and 1 AIS-6), with fracture as the most common injury type (80%). Spinal-injured occupants were most frequently in passenger cars (64%), and crash direction was most often frontal (62%). Mean delta-V was 51.3 km/h ± 19.4 km/h. The average occupant age was 12.4 ± 5.3 years old, and 48% were 16- to 17-year-olds. Thirty-six percent were right front passengers and 26% were drivers. Most occupants were lap and shoulder belt restrained (88%). Non-spinal AIS 2+ injuries included those of the lower extremity and pelvis (n = 56), head (n = 43), abdomen (n = 39), and thorax (n = 36). Spinal injury causation was typically due to flexion or lateral bending over the lap and or shoulder belt or child restraint harness, compression by occupant

  1. Antimicrobial Resistance in Agriculture

    PubMed Central

    Thanner, Sophie; Drissner, David

    2016-01-01

    ABSTRACT In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans. PMID:27094336

  2. Substandard/Counterfeit Antimicrobial Drugs

    PubMed Central

    Kelesidis, Theodoros

    2015-01-01

    SUMMARY Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue. PMID:25788516

  3. Substandard/counterfeit antimicrobial drugs.

    PubMed

    Kelesidis, Theodoros; Falagas, Matthew E

    2015-04-01

    Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue. PMID:25788516

  4. [Neruda and antimicrobial resistance].

    PubMed

    Cotera, Alejandro

    2011-07-01

    Antimicrobial resistance has been a problem in medicine, since their incorporation to clinical practice. Numerous papers have been written on the subject. The analysis of two poems by Pablo Neruda "How much does a man live" and "Larynx", included in the volume "Estravagario" and published for the first time in 1957 and 1958, give us an incredible revelation about the concept of resistance. In these poems aureomycin, the first antimicrobial of the family of tetracyclines, was included as a poetic figure and the therapeutic action of antimicrobials was described. "Never so much bugs died I tons of them fell I but the few that remained olive I manifested their perversity". These writings incorporated novel concepts, even for physicians of that time and described the closeness of death that a patient may perceive during the course of a given disease. The capacity of Pablo Neruda to extract the essence of situations and to anticipate to conditions that only years later became clinically relevant problems, is noteworthy. PMID:22051837

  5. [Neruda and antimicrobial resistance].

    PubMed

    Cotera, Alejandro

    2011-07-01

    Antimicrobial resistance has been a problem in medicine, since their incorporation to clinical practice. Numerous papers have been written on the subject. The analysis of two poems by Pablo Neruda "How much does a man live" and "Larynx", included in the volume "Estravagario" and published for the first time in 1957 and 1958, give us an incredible revelation about the concept of resistance. In these poems aureomycin, the first antimicrobial of the family of tetracyclines, was included as a poetic figure and the therapeutic action of antimicrobials was described. "Never so much bugs died I tons of them fell I but the few that remained olive I manifested their perversity". These writings incorporated novel concepts, even for physicians of that time and described the closeness of death that a patient may perceive during the course of a given disease. The capacity of Pablo Neruda to extract the essence of situations and to anticipate to conditions that only years later became clinically relevant problems, is noteworthy.

  6. Assessment of Prone Positioning of Restrained, Seated Crewmembers in a Post Landing Stable 2 Orion Configuration

    NASA Technical Reports Server (NTRS)

    Barr, Yael; Fogarty, Jennifer

    2010-01-01

    During the Orion landing and recovery subsystem design review, June 2009, it was noted that the human system and various vehicle systems, the environmental control and life support (ECLSS) and guidance, navigation and control (GN&C) systems for example, are negatively affected by Orion assuming a stable 2 (upside down; Figure A) configuration post landing. The stable 2 configuration is predicted to occur about 50% of the time based on Apollo landing data and modeling of the current capsule. The stable 2 configuration will be countered by an active up-righting system (crew module up-righting system; CMUS). Post landing balloons will deploy and inflate causing the vehicle to assume or maintain the stable 1 (up-right; Figure B) configuration. During the design review it was proposed that the up-righting system could be capable of righting the vehicle within 60 seconds. However, this time limit posed a series of constraints on the design which made it less robust than desired. The landing and recovery subsystem team requested an analysis of Orion vehicle systems as well as the human system with regard to the effect of stable 2 in order to determine if an up-righting response time greater than 60 seconds could be tolerated. The following report focuses on the assessment of the human system in the posture assumed when Orion is in the stable 2 configuration. Stable 2 will place suited, seated, and restrained crewmembers in a prone (facedown), head-up position for a period of time dependent on the functionality of the up-righting systems, ability of the crew to release themselves from the seat and restraints, and/or time to arrival of rescue forces. Given that the Orion seat and restraint system design is not complete and therefore, not available for evaluation, Space Medicine assessed how long a healthy but deconditioned crewmember could stay in this prone, restrained position and the physiological consequences of this posture by researching terrestrial analogs and

  7. Strategies to Combat Antimicrobial Resistance

    PubMed Central

    Uchil, Rajesh R; Kohli, Gurdeep Singh; Katekhaye, Vijay M

    2014-01-01

    The global burden of antimicrobial resistance is rising and is associated with increased morbidity and mortality in clinical and community setting. Spread of antibiotic resistance to different environmental niches and development of superbugs have further complicated the effective control strategies. International, national and local approaches have been advised for control and prevention of antimicrobial resistance. Rational use of antimicrobials, regulation on over-the-counter availability of antibiotics, improving hand hygiene and improving infection prevention and control are the major recommended approaches. Thorough understanding of resistance mechanism and innovation in new drugs and vaccines is the need. A multidisciplinary, collaborative, regulatory approach is demanded for combating antimicrobial resistance. PMID:25177596

  8. A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation.

    PubMed

    Atianand, Maninjay K; Hu, Wenqian; Satpathy, Ansuman T; Shen, Ying; Ricci, Emiliano P; Alvarez-Dominguez, Juan R; Bhatta, Ankit; Schattgen, Stefan A; McGowan, Jason D; Blin, Juliana; Braun, Joerg E; Gandhi, Pallavi; Moore, Melissa J; Chang, Howard Y; Lodish, Harvey F; Caffrey, Daniel R; Fitzgerald, Katherine A

    2016-06-16

    Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS localizes at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3' end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses, highlighting the importance of lincRNAs in the immune system.

  9. Klar ensures thermal robustness of oskar localization by restraining RNP motility

    PubMed Central

    Gaspar, Imre; Yu, Yanxun V.; Cotton, Sean L.; Kim, Dae-Hwan

    2014-01-01

    Communication usually applies feedback loop–based filters and amplifiers to ensure undistorted delivery of messages. Such an amplifier acts during Drosophila melanogaster midoogenesis, when oskar messenger ribonucleic acid (mRNA) anchoring depends on its own locally translated protein product. We find that the motor regulator Klar β mediates a gain-control process that prevents saturation-based distortions in this positive feedback loop. We demonstrate that, like oskar mRNA, Klar β localizes to the posterior pole of oocytes in a kinesin-1–dependent manner. By live imaging and semiquantitative fluorescent in situ hybridization, we show that Klar β restrains oskar ribonucleoprotein motility and decreases the posterior-ward translocation of oskar mRNA, thereby adapting the rate of oskar delivery to the output of the anchoring machinery. This negative regulatory effect of Klar is particularly important for overriding temperature-induced changes in motility. We conclude that by preventing defects in oskar anchoring, this mechanism contributes to the developmental robustness of a poikilothermic organism living in a variable temperature environment. PMID:25049271

  10. Proline oxidase–adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation

    PubMed Central

    Lettieri Barbato, D; Aquilano, K; Baldelli, S; Cannata, S M; Bernardini, S; Rotilio, G; Ciriolo, M R

    2014-01-01

    The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-α, peroxisome proliferator-activated receptor-γ coactivator-1α), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders. PMID:24096872

  11. Executive control resources and snack food consumption in the presence of restraining versus facilitating cues.

    PubMed

    Hall, Peter A; Lowe, Cassandra; Vincent, Corita

    2014-08-01

    Prior studies have documented a negative relationship between strength of executive control resources (ECRs) and frequency of snack food consumption. However, little is known about what effect environmental cues (restraining versus facilitating) have on the engagement of such control resources. We presented 88 healthy adults with standardized tests of ECRs followed by a bogus taste test for three appetitive snack foods. Participants were randomly assigned to receive instructions to eat the bare minimum to make their ratings ("restraint condition"), eat as much as they like ("facilitation condition") or no special instructions. We surreptitiously measured the weight of food consumed during the taste test. Findings revealed a main effect of treatment condition, such that those in the restraint condition ate significantly less than those in either of the other conditions; however, this main effect was qualified by an ECR by treatment condition interaction. Specifically, those in the facilitation condition showed a strong negative association between ECR strength and amount of food consumed, whereas those in the restraint and control conditions did not. Findings suggest that the effect of ECR strength on consumption of snack food varies substantially by the characteristics of contextual cues.

  12. Spontaneous regional brain activity links restrained eating to later weight gain among young women.

    PubMed

    Dong, Debo; Jackson, Todd; Wang, Yulin; Chen, Hong

    2015-07-01

    Theory and prospective studies have linked restrained eating (RE) to risk for future weight gain and the onset of obesity, but little is known about resting state neural activity that may underlie this association. To address this gap, resting fMRI was used to test the extent to which spontaneous neural activity in regions associated with inhibitory control and food reward account for potential relations between baseline RE levels and changes in body weight among dieters over a one-year interval. Spontaneous regional activity patterns corresponding to RE were assessed among 50 young women using regional homogeneity (ReHo) analysis, which measured temporal synchronization of spontaneous fluctuations within a food deprivation condition. Analyses indicated higher baseline RE scores predicted more weight gain at a one-year follow-up. Furthermore, food-deprived dieting women with high dietary restraint scores exhibited more spontaneous local activity in brain regions associated with the expectation and valuation for food reward [i.e., orbitofrontal cortex (OFC)/ventromedial prefrontal cortex (VMPFC)] and reduced spontaneous local activity in inhibitory control regions [i.e., bilateral dorsal-lateral prefrontal cortex (DLPFC)] at baseline. Notably, the association between baseline RE and follow-up weight gain was mediated by decreased local synchronization of the right DLPFC in particular and, to a lesser degree, increased local synchronization of the right VMPFC. In conjunction with previous research, these findings highlight possible neural mechanisms underlying the relation between RE and risk for weight gain. PMID:26004091

  13. DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination

    PubMed Central

    Zamudio, Natasha; Barau, Joan; Teissandier, Aurélie; Walter, Marius; Borsos, Maté; Servant, Nicolas; Bourc'his, Déborah

    2015-01-01

    DNA methylation is essential for protecting the mammalian germline against transposons. When DNA methylation-based transposon control is defective, meiotic chromosome pairing is consistently impaired during spermatogenesis: How and why meiosis is vulnerable to transposon activity is unknown. Using two DNA methylation-deficient backgrounds, the Dnmt3L and Miwi2 mutant mice, we reveal that DNA methylation is largely dispensable for silencing transposons before meiosis onset. After this, it becomes crucial to back up to a developmentally programmed H3K9me2 loss. Massive retrotransposition does not occur following transposon derepression, but the meiotic chromatin landscape is profoundly affected. Indeed, H3K4me3 marks gained over transcriptionally active transposons correlate with formation of SPO11-dependent double-strand breaks and recruitment of the DMC1 repair enzyme in Dnmt3L−/− meiotic cells, whereas these features are normally exclusive to meiotic recombination hot spots. Here, we demonstrate that DNA methylation restrains transposons from adopting chromatin characteristics amenable to meiotic recombination, which we propose prevents the occurrence of erratic chromosomal events. PMID:26109049

  14. Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10.

    PubMed

    Xie, Luokun; Choudhury, Gourav Roy; Winters, Ali; Yang, Shao-Hua; Jin, Kunlin

    2015-01-01

    Forkhead box P3 (Foxp3)(+) regulatory T (Treg) cells maintain the immune tolerance and prevent inflammatory responses in the periphery. However, the presence of Treg cells in the CNS under steady state has not been studied. Here, for the first time, we show a substantial TCRαβ (+) CD4(+) Foxp3(+) T-cell population (cerebral Treg cells) in the rat cerebrum, constituting more than 15% of the cerebral CD4(+) T-cell compartment. Cerebral Treg cells showed an activated/memory phenotype and expressed many Treg-cell signature genes at higher levels than peripheral Treg cells. Consistent with their activated/memory phenotype, cerebral Treg cells robustly restrained the LPS-induced inflammatory responses of brain microglia/macrophages, suggesting a role in maintaining the cerebral homeostasis by inhibiting the neuroinflammation. In addition, brain astrocytes were the helper cells that sustained Foxp3 expression in Treg cells through IL-2/STAT5 signaling, showing that the interaction between astrocytes and Treg cells contributes to the maintenance of Treg-cell identity in the brain. Taken together, our work represents the first study to characterize the phenotypic and functional features of Treg cells in the rat cerebrum. Our data have provided a novel insight for the contribution of Treg cells to the immunosurveillance and immunomodulation in the cerebrum under steady state.

  15. Spontaneous regional brain activity links restrained eating to later weight gain among young women.

    PubMed

    Dong, Debo; Jackson, Todd; Wang, Yulin; Chen, Hong

    2015-07-01

    Theory and prospective studies have linked restrained eating (RE) to risk for future weight gain and the onset of obesity, but little is known about resting state neural activity that may underlie this association. To address this gap, resting fMRI was used to test the extent to which spontaneous neural activity in regions associated with inhibitory control and food reward account for potential relations between baseline RE levels and changes in body weight among dieters over a one-year interval. Spontaneous regional activity patterns corresponding to RE were assessed among 50 young women using regional homogeneity (ReHo) analysis, which measured temporal synchronization of spontaneous fluctuations within a food deprivation condition. Analyses indicated higher baseline RE scores predicted more weight gain at a one-year follow-up. Furthermore, food-deprived dieting women with high dietary restraint scores exhibited more spontaneous local activity in brain regions associated with the expectation and valuation for food reward [i.e., orbitofrontal cortex (OFC)/ventromedial prefrontal cortex (VMPFC)] and reduced spontaneous local activity in inhibitory control regions [i.e., bilateral dorsal-lateral prefrontal cortex (DLPFC)] at baseline. Notably, the association between baseline RE and follow-up weight gain was mediated by decreased local synchronization of the right DLPFC in particular and, to a lesser degree, increased local synchronization of the right VMPFC. In conjunction with previous research, these findings highlight possible neural mechanisms underlying the relation between RE and risk for weight gain.

  16. CD200 restrains macrophage attack on oligodendrocyte precursors via toll-like receptor 4 downregulation.

    PubMed

    Hayakawa, Kazuhide; Pham, Loc-Duyen D; Seo, Ji Hae; Miyamoto, Nobukazu; Maki, Takakuni; Terasaki, Yasukazu; Sakadžić, Sava; Boas, David; van Leyen, Klaus; Waeber, Christian; Kim, Kyu-Won; Arai, Ken; Lo, Eng H

    2016-04-01

    There are numerous barriers to white matter repair after central nervous system injury and the underlying mechanisms remain to be fully understood. In this study, we propose the hypothesis that inflammatory macrophages in damaged white matter attack oligodendrocyte precursor cells via toll-like receptor 4 signaling thus interfering with this endogenous progenitor recovery mechanism. Primary cell culture experiments demonstrate that peritoneal macrophages can attack and digest oligodendrocyte precursor cells via toll-like receptor 4 signaling, and this phagocytosis of oligodendrocyte precursor cells can be inhibited by using CD200-Fc to downregulate toll-like receptor 4. In an in vivo model of white matter ischemia induced by endothelin-1, treatment with CD200-Fc suppressed toll-like receptor 4 expression in peripherally circulating macrophages, thus restraining macrophage phagocytosis of oligodendrocyte precursor cells and leading to improved myelination. Taken together, these findings suggest that deleterious macrophage effects may occur after white matter ischemia, whereby macrophages attack oligodendrocyte precursor cells and interfere with endogenous recovery responses. Targeting this pathway with CD200 may offer a novel therapeutic approach to amplify endogenous oligodendrocyte precursor cell-mediated repair of white matter damage in mammalian brain.

  17. Occurring mechanism and restraining method research of numerical noise signal in penetration simulation

    NASA Astrophysics Data System (ADS)

    Wang, Chen; Wang, Yabin

    2016-08-01

    In hard target penetration simulation, the existing researches of the convergence of results are mainly concentrating in the corresponding relationship between penetration depth and mesh scales. However, the influence of the mesh difference on the penetration resistance and acceleration signals are seldom refer to. This paper presents the occurring mechanism and restraining method of numerical noise signal in penetration simulation. First, the concept of the noise signal izs proposed. By taking a 3D penetration simulation as example, the influence of the noise signal on the penetration resistance in different mesh scales and impact velocity is studied. To ensure the convergence of the computational results, the grid scale of the target is encrypted to 1:1:8. In addition, modern spectrum analysis method is introduced to further analyze the penetration resistance signal. The research results presented is useful to improve the computational accuracy of high speed projectile penetration simulation, and provide important reference for carrying out structural design and optimization of fuze system.

  18. β2-Syntrophin Is a Cdk5 Substrate That Restrains the Motility of Insulin Secretory Granules

    PubMed Central

    Schubert, Sandra; Knoch, Klaus-Peter; Ouwendijk, Joke; Mohammed, Shabaz; Bodrov, Yury; Jäger, Melanie; Altkrüger, Anke; Wegbrod, Carolin; Adams, Marvin E.; Kim, Yong; Froehner, Stanley C.; Jensen, Ole N.; Kalaidzidis, Yannis; Solimena, Michele

    2010-01-01

    The molecular basis for the interaction of insulin granules with the cortical cytoskeleton of pancreatic β-cells remains unknown. We have proposed that binding of the granule protein ICA512 to the PDZ domain of β2-syntrophin anchors granules to actin filaments and that the phosphorylation/dephosphorylation of β2-syntrophin regulates this association. Here we tested this hypothesis by analyzing INS-1 cells expressing GFP-β2-syntrophin through the combined use of biochemical approaches, imaging studies by confocal and total internal reflection fluorescence microscopy as well as electron microscopy. Our results support the notion that β2-syntrophin restrains the mobility of cortical granules in insulinoma INS-1 cells, thereby reducing insulin secretion and increasing insulin stores in resting cells, while increasing insulin release upon stimulation. Using mass spectrometry, in vitro phosphorylation assays and β2-syntrophin phosphomutants we found that phosphorylation of β2-syntrophin on S75 near the PDZ domain decreases its binding to ICA512 and correlates with increased granule motility, while phosphorylation of S90 has opposite effects. We further show that Cdk5, which regulates insulin secretion, phosphorylates S75. These findings provide mechanistic insight into how stimulation displaces insulin granules from cortical actin, thus promoting their motility and exocytosis. PMID:20886068

  19. Effects of chewing gum on short-term appetite regulation in moderately restrained eaters.

    PubMed

    Hetherington, Marion M; Regan, Martin F

    2011-10-01

    Orosensory stimulation is an important contributing factor to the development of satiation. Providing orosensory stimulation with few calories may satisfy appetite and help to suppress cravings for high energy snacks. This may be a useful strategy for those motivated to lose or maintain weight. The present study tested the hypothesis that chewing sweetened gum will reduce subjective appetite and subsequent snack intake in moderately restrained eaters. Within-subjects, repeated measures study, sixty healthy participants (53 women; body mass index, in kg/m(2): 26.2±4.5) came to the laboratory 4 times for a standard lunch. Immediately after this meal, participants rated hunger, appetite and cravings for sweet and salty snacks every hour until they returned to the laboratory 3 h later for snack. On two occasions during this 3 h period participants chewed gum for at least 15 min at hourly intervals (45 min) and on two occasions no gum was chewed. On two occasions salty snacks were offered and on two occasions sweet snacks were provided. A small but significant reduction in snack intake was observed, chewing gum reduced weight of snack consumed by 10% compared to no gum (p<0.05). Overall, chewing gum for at least 45 min significantly suppressed rated hunger, appetite and cravings for snacks and promoted fullness (p<0.05). This study demonstrated some benefit of chewing gum which could be of utility to those seeking an aid to appetite control. PMID:21718732

  20. Brain activation in restrained and unrestrained eaters: an fMRI study.

    PubMed

    Coletta, Maria; Platek, Steven; Mohamed, Feroze B; van Steenburgh, J Jason; Green, Deborah; Lowe, Michael R

    2009-08-01

    Restraint theory has been used to model the process that produces binge eating. However, there is no satisfactory explanation for the tendency of restrained eaters (REs) to engage in counterregulatory eating, an ostensible analogue of binge eating. Using functional magnetic resonance imaging (fMRI), the authors investigated brain activation of normal weight REs (N = 9) and unrestrained eaters (UREs; N = 10) when fasted and fed and viewing pictures of highly and moderately palatable foods and neutral objects. When fasted and viewing highly palatable foods, UREs showed widespread bilateral activation in areas associated with hunger and motivation, whereas REs showed activation only in the cerebellum, an area previously implicated in low-level processing of appetitive stimuli. When fed and viewing high palatability foods, UREs showed activation in areas related to satiation and memory, whereas REs showed activation in areas implicated in desire, expectation of reward, and goal-defined behavior. These findings parallel those from behavioral research. The authors propose that the counterintuitive findings from preload studies and the present study are due to the fact that REs are less hungry than UREs when fasted and find palatable food more appealing than UREs when fed.

  1. A Novel Restraining Device for Small Animal Imaging Exams: Validation in Rabbits

    PubMed Central

    Barbosa, Carlos Henrique; Carvalho, Antonio Carlos; de Souza, Sérgio; Machado, Fernanda; Guedes, Fábio; Monteiro, André; Schanaider, Alberto

    2015-01-01

    Objective. To develop, validate, and patent a Restraining Device for Small Animal Imaging Exams (RDSAIE) that allows exams to be comfortably conducted without risks to animals and professionals. Methods. A RDSAIE with a mobile cover and shelf was built with transparent acrylic material. A total of six anesthetized rabbits were used to perform the following imaging exams of the skull: Cone Beam Computed Tomography, Magnetic Resonance Imaging, and Scintigraphy. Results. The device showed great functionality and full visibility of the animal behavior, which remained fully stabilized and immobilized in either the horizontal or vertical position without the need for a person to remain in the test room to assist them. The procedures were performed without difficulty, and images of good resolution and without artifacts were obtained. Conclusion. The RDSAIE is comfortable, safe, efficient, and ergonomic. It allows the easy placement of animals in different body positions, including the vertical, the maintenance of postural stability, and full visibility. It may be constructed for animals heavier than 4 kg and it is adaptable for translational studies in anima nobile. PMID:26114109

  2. E3 Ubiquitin Ligase RLIM Negatively Regulates c-Myc Transcriptional Activity and Restrains Cell Proliferation

    PubMed Central

    Wang, Lan; Cai, Hao; Zhu, Jingjing; Yu, Long

    2016-01-01

    RNF12/RLIM is a RING domain-containing E3 ubiquitin ligase whose function has only begun to be elucidated recently. Although RLIM was reported to play important roles in some biological processes such as imprinted X-chromosome inactivation and regulation of TGF-β pathway etc., other functions of RLIM are largely unknown. Here, we identified RLIM as a novel E3 ubiquitin ligase for c-Myc, one of the most frequently deregulated oncoproteins in human cancers. RLIM associates with c-Myc in vivo and in vitro independently of the E3 ligase activity of RLIM. Moreover, RLIM promotes the polyubiquitination of c-Myc protein independently of Ser62 and Thr58 phosphorylation of c-Myc. However, RLIM-mediated ubiquitination does not affect c-Myc stability. Instead, RLIM inhibits the transcriptional activity of c-Myc through which RLIM restrains cell proliferation. Our results suggest that RLIM may function as a tumor suppressor by controlling the activity of c-Myc oncoprotein. PMID:27684546

  3. Ischemia Reperfusion Unveils Impaired Capacity of Older Adults to Restrain Oxidative Insult

    PubMed Central

    Davies, Sean S.; Traustadóttir, Tinna; Stock, Anthoney A.; Ye, Fei; Shyr, Yu; Harman, S. Mitchell; Roberts, L. Jackson

    2009-01-01

    Age independently predicts poor outcome in a variety of medical settings including sepsis, trauma, severe burns, and surgery. Since these conditions are associated with oxidative stress, we hypothesized that the capacity to constrain oxidative insult diminishes with age, leading to more extensive oxidative damage during trauma. To test this hypothesis, we used supra-systolic inflation of an arm blood pressure cuff to safely induce localized forearm ischemia/reperfusion (I/R) and quantified plasma F2-isoprostane (IsoP) levels in serial blood samples. Prior to I/R, IsoP levels were similar in young (20-33 yrs) and older adults (62-81 yrs). After I/R challenge, the magnitude and duration of increased IsoP levels was significantly greater in older adults. Because aging is associated with declining levels of sex hormones that contribute to regulation of antioxidant enzyme expression, we then examined the response to I/R in older women receiving hormone replacement therapy, and found these women did not manifest the amplified IsoP response found in untreated older women. These finding demonstrate that aging impairs the ability to restrain oxidative damage after an acute insult, which may contribute to the increased vulnerability of older adults to traumatic conditions, and establishes a useful method to identify effective interventions to ameliorate this deficiency. PMID:19596063

  4. Buckling Behavior of Long Anisotropic Plates Subjected to Fully Restrained Thermal Expansion

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2003-01-01

    An approach for synthesizing buckling results and behavior for thin, balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and which are fully-restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexurally anisotropic plates that are subjected to combined mechanical loads and is based on useful nondimensional parameters. In addition, stiffness-weighted laminate thermal-expansion parameters are derived and used to determine critical temperature changes in terms of physically intuitive mechanical buckling coefficients. The effects of membrane orthotropy and anisotropy are included. Many results are presented for some common laminates that are intended to facilitate a structural designer's transition to the use of the generic buckling design curves that are presented in the paper. Several generic buckling design curves are presented that provide physical insight into buckling response and provide useful design data. Examples are presented that demonstrate the use of generic design curves. The analysis approach and generic results indicate the effects and characteristics of laminate thermal expansion, membrane orthotropy and anisotropy, and flexural orthotropy and anisotropy in a very general, unifying manner.

  5. Buckling Behavior of Long Anisotropic Plates Subjected to Fully Restrained Thermal Expansion

    NASA Technical Reports Server (NTRS)

    Nemeth, Michael P.

    2001-01-01

    An approach for synthesizing buckling results and behavior for thin balanced and unbalanced symmetric laminates that are subjected to uniform heating or cooling and fully restrained against thermal expansion or contraction is presented. This approach uses a nondimensional analysis for infinitely long, flexurally anisotropic plates that are subjected to combined mechanical loads and is based on useful nondimensional parameters. In addition, stiffness-weighted laminate thermal-expansion parameters are derived that are used to determine critical temperatures in terms of physically intuitive mechanical buckling coefficients, and the effects of membrane orthotropy and membrane anisotropy are included. Many results are presented for some common laminates that are intended to facilitate a structural designer's transition to the use of the generic buckling design curves that are presented in the paper. Several generic buckling design curves are presented that provide physical insight into the buckling response in addition to providing useful design data. Examples are presented that demonstrate the use of the generic design curves. The analysis approach and generic results indicate the effects and characteristics of laminate thermal expansion, membrane orthotropy and anisotropy, and flexural orthotropy and anisotropy in a very general and unifying manner.

  6. Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function.

    PubMed

    Messner, Simon; Schuermann, David; Altmeyer, Matthias; Kassner, Ingrid; Schmidt, Darja; Schär, Primo; Müller, Stefan; Hottiger, Michael O

    2009-11-01

    Poly(ADP-ribose) polymerase 1 (PARP1) is a chromatin-associated nuclear protein and functions as a molecular stress sensor. At the cellular level, PARP1 has been implicated in a wide range of processes, such as maintenance of genome stability, cell death, and transcription. PARP1 functions as a transcriptional coactivator of nuclear factor kappaB (NF-kappaB) and hypoxia inducible factor 1 (HIF1). In proteomic studies, PARP1 was found to be modified by small ubiquitin-like modifiers (SUMOs). Here, we characterize PARP1 as a substrate for modification by SUMO1 and SUMO3, both in vitro and in vivo. PARP1 is sumoylated at the single lysine residue K486 within its automodification domain. Interestingly, modification of PARP1 with SUMO does not affect its ADP-ribosylation activity but completely abrogates p300-mediated acetylation of PARP1, revealing an intriguing crosstalk of sumoylation and acetylation on PARP1. Genetic complementation of PARP1-depleted cells with wild-type and sumoylation-deficient PARP1 revealed that SUMO modification of PARP1 restrains its transcriptional coactivator function and subsequently reduces gene expression of distinct PARP1-regulated target genes.

  7. Is beauty in the eye of the beholder? Effects of weight and shape on attractiveness ratings of female line drawings by restrained and nonrestrained eaters.

    PubMed

    Forestell, Catherine A; Humphrey, Tara M; Stewart, Sherry H

    2004-05-01

    This study tested the differences between restrained and nonrestrained eaters' attractiveness perceptions of female line drawings, of their own figures, and the ideal female figure. Female line drawings varied systematically in body weight and in waist and hip circumference. Forty-six female undergraduate students, 23 nonrestrainers and 23 restrainers, rated stimuli in attractiveness, identified the figure which best represented their own body type (PAF), and the ideal body figure (IF) according to the Restraint Scale [RS; Herman, C. P., & Polivy, J. (1980). Restrained eating. In: A. Stunkard (Ed.), Obesity (pp. 208-225). Philadelphia, PA: Saunders]. Restrainers did not generally differ from nonrestrainers in attractiveness ratings or in their choice of IF. However, differences between IF and PAF were larger in restrainers than in nonrestrainers because restrainers chose PAFs with larger hips than nonrestrainers did. This difference between the restraint groups was independent of between-group differences in hip size. This discrepancy between IF and PAF may contribute to the restrainers' motivation to diet. PMID:15093780

  8. Engineering Antimicrobials Refractory to Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant superbugs are a persistent problem in modern health care, demonstrating the need for a new class of antimicrobials that can address this concern. Triple-acting peptidoglycan hydrolase fusions are a novel class of antimicrobials which have qualities well suited to avoiding resis...

  9. Antimicrobial stewardship: philosophy versus practice.

    PubMed

    Dodds Ashley, Elizabeth S; Kaye, Keith S; DePestel, Daryl D; Hermsen, Elizabeth D

    2014-10-15

    To promote the judicious use of antimicrobials and preserve their usefulness in the setting of growing resistance, a number of policy-making bodies and professional societies have advocated the development of antimicrobial stewardship programs. Although these programs have been implemented at many institutions in the United States, their impact has been difficult to measure. Current recommendations advocate the use of both outcome and process measures as metrics for antimicrobial stewardship. Although patient outcome metrics have the greatest impact on the quality of care, the literature shows that antimicrobial use and costs are the indicators measured most frequently by institutions to justify the effectiveness of antimicrobial stewardship programs. The measurement of more meaningful outcomes has been constrained by difficulties inherent to these measures, lack of funding and resources, and inadequate study designs. Antimicrobial stewardship can be made more credible by refocusing the antimicrobial review process to target specific disease states, reassessing the usefulness of current metrics, and integrating antimicrobial stewardship program initiatives into institutional quality and safety efforts.

  10. How to fight antimicrobial resistance.

    PubMed

    Foucault, Cédric; Brouqui, Philippe

    2007-03-01

    Antimicrobial misuse results in the development of resistance and superbugs. Over recent decades, resistance has been increasing despite continuing efforts to control it, resulting in increased mortality and cost. Many authorities have proposed local, regional and national guidelines to fight against this phenomenon, and the usefulness of these programmes has been evaluated. Multifaceted intervention seems to be the most efficient method to control antimicrobial resistance. Monitoring of bacterial resistance and antibiotic use is essential, and the methodology has now been homogenized. The implementation of guidelines and infection control measures does not control antimicrobial resistance and needs to be reinforced by associated measures. Educational programmes and rotation policies have not been evaluated sufficiently in the literature. Combination antimicrobial therapy is inefficient in controlling antimicrobial resistance.

  11. Restraining the motion of a ligand for modulating the structural phase transition in two isomorphic polar coordination polymers.

    PubMed

    Wang, Bao-Ying; Xu, Wei-Jian; Xue, Wei; Lin, Rui-Biao; Du, Zi-Yi; Zhou, Dong-Dong; Zhang, Wei-Xiong; Chen, Xiao-Ming

    2014-06-28

    A structural phase transition induced by ligand motion was found in a new polar coordination polymer: [Cu(NCS)2(4-APy)2]n (4-APy = 4-aminopyridine). Restraining such motion in an isomorphic compound [Cu(NCS)2(4-MeAPy)2]n (4-MeAPy = 4-methylaminopyridine) results in distinct phase transition behaviour. These findings provide a new clue for modulating phase transition behaviour in known materials.

  12. Boundary beam characteristics orthonormal polynomials in energy approach for vibration of symmetric laminates. II - Elastically restrained boundaries

    NASA Astrophysics Data System (ADS)

    Hung, K. C.; Lim, M. K.; Liew, K. M.

    This paper presents an eigenvalue formulation for the vibration analysis of symmetrically laminated rectangular plates subjected to translational and rotational restraints at the edges. The Rayleigh-Ritz method, along with the deflection functions assumed in sets of orthogonally generated polynomials, is used to perform the analysis. The total strain energy of the elastically restrained rectangular plate is the sum of the bending strain energy and elastic strain energy of translational and rotational restraints. This resulting strain energy combined with the kinetic energy of the plate formed the total energy functional which is minimized to obtain the governing eigenvalue equation of the elastically restrained symmetrically laminated rectangular plate. In this paper, several examples of elastically restrained laminated plates with different fiber orientation angles and stacking sequences have been solved to demonstrate the accuracy and efficiency of the present method. The combined effects of laminate stacking sequences, fiber orientation angle and translational and rotational stiffnesses of the elastic edges on the vibrational response have been carefully examined.

  13. The adaptive immune system restrains Alzheimer's disease pathogenesis by modulating microglial function.

    PubMed

    Marsh, Samuel E; Abud, Edsel M; Lakatos, Anita; Karimzadeh, Alborz; Yeung, Stephen T; Davtyan, Hayk; Fote, Gianna M; Lau, Lydia; Weinger, Jason G; Lane, Thomas E; Inlay, Matthew A; Poon, Wayne W; Blurton-Jones, Mathew

    2016-03-01

    The innate immune system is strongly implicated in the pathogenesis of Alzheimer's disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting "Rag-5xfAD" mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive-innate immunity cross talk and accelerated disease progression. PMID:26884167

  14. [Metal ions restrain the elimination of 4-tert-octylphenol by delta-MnO2].

    PubMed

    Li, Fei-Li; Mou, Hua-Qian

    2013-06-01

    The effect of metal ions on elimination of 4-t-OP by synthetic delta-MnO2 suspension at pH 4.0 was studied. Experiments indicated that the removal of 4-t-OP by delta-MnO2 achieved 100% at reaction time of 150 min. However, the removal of 4-t-OP by delta-MnO2 was restrained when metal ions were added, and the higher concentration of metal ion was, the stronger the inhibition produced. Additionally, there were apparent differences among the inhibitory effect of the tested metal ions. Firstly, Pb2+ and Mn2+ had the strongest effect at pH 4.0, followed by the transition metal ions, then the alkaline earth ions, while the alkali metal ions had little influence on the removal of 4-t-OP by delta-MnO2. Also comparing the adsorption results of metal ions by delta-MnO2, Pb2+ showed the greatest attraction with delta-MnO2, and among the other metal ions, transition metal ions were adsorbed a little more strongly on delta-MnO2 than alkaline earth metal ions. Consequences showed that the inhibitory effects of metal ions were due to their occupying reactive sites on delta-MnO2 surface, which competed with 4-t-OP. Moreover, the dissimilar suppressions were contributed by the different adsorption capacities, surface structure change of MnO2 and the difference of free metal ion percentage in solution as well as metal ions radii.

  15. Adaptation to stress induced by restraining rats and mice in nose-only inhalation holders.

    PubMed

    Narciso, Sandy P; Nadziejko, Elizabeth; Chen, Lung Chi; Gordon, Terry; Nadziejko, Christine

    2003-09-15

    There are limited data on the efficacy of procedures for adapting rodents to restraint in nose-only holders. We examined: (1) What effect does restraint in nose-only holders have on heart rate and body temperature? (2) Does a gradual increase in the duration of restraint facilitate adaptation? (3) How long does it take for rodents to become fully adapted to nose-only holders? (4) Do rats and mice respond and adapt similarly to restraint in nose only holders? Heart rate and body temperature were monitored as measures of stress using electrocardiograph (ECG) transmitters in male C57Bl/6J mice and Sprague-Dawley rats. In naive animals during the first hour of restraint, heart rate increased by 58 beats per minute (BPM) (18.6%) in rats and by 174 BPM (32.3%) in mice as compared to cage controls. Temperature increased by 2 degrees C in mice and was unchanged in rats compared to cage controls. Heart rate and temperature values remained within normal physiologic values during restraint. In rats, the response to restraint in nose-only holders was the same after 4 days regardless of whether the duration of restraint was increased gradually to 4 h/day or kept constant at 4 h/day. In mice, the group that was gradually adapted had a statistically significant higher heart rate and temperature after 4 days than the fixed-duration adapted group. Rats and mice restrained for 4 h/day every day showed a gradual decrease in heart rate and temperature over time. Full adaptation to restraint required 14 days of fixed-duration daily restraint.

  16. Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments

    PubMed Central

    Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M.; Schulten, Klaus; Roux, Benoît

    2015-01-01

    The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with

  17. Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

    PubMed

    Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

    2015-10-01

    The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with

  18. The adaptive immune system restrains Alzheimer's disease pathogenesis by modulating microglial function.

    PubMed

    Marsh, Samuel E; Abud, Edsel M; Lakatos, Anita; Karimzadeh, Alborz; Yeung, Stephen T; Davtyan, Hayk; Fote, Gianna M; Lau, Lydia; Weinger, Jason G; Lane, Thomas E; Inlay, Matthew A; Poon, Wayne W; Blurton-Jones, Mathew

    2016-03-01

    The innate immune system is strongly implicated in the pathogenesis of Alzheimer's disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting "Rag-5xfAD" mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive-innate immunity cross talk and accelerated disease progression.

  19. Cyclooxygenase-derived vasoconstriction restrains hypoxia-mediated cerebral vasodilation in young adults with metabolic syndrome

    PubMed Central

    Harrell, John W.

    2013-01-01

    Poor cerebrovascular function in metabolic syndrome (MetSyn) likely contributes to elevated risk of cerebrovascular disease in this growing clinical population. Younger MetSyn adults without clinical evidence of cerebrovascular disease exhibit preserved hypercapnic vasodilation yet markedly impaired hypoxic vasodilation, but the mechanisms behind reduced hypoxic vasodilation are unknown. Based on data from rats, we tested the hypothesis that younger adults with MetSyn exhibit reduced cerebral hypoxic vasodilation due to loss of vasodilating prostaglandins. Middle cerebral artery velocity (MCAv) was measured with transcranial Doppler ultrasound in adults with MetSyn (n = 13, 33 ± 3 yr) and healthy controls (n = 15, 31 ± 2 yr). Isocapnic hypoxia was induced by titrating inspired oxygen to lower arterial saturation to 90% and 80% for 5 min each. Separately, hypercapnia was induced by increasing end-tidal CO2 10 mmHg above baseline levels. Cyclooxygenase inhibition (100 mg indomethacin) was conducted in a randomized double-blind, placebo controlled design. MCAv was normalized for group differences in blood pressure (healthy: 89 ± 2 mmHg vs. MetSyn: 102 ± 2 mmHg) as cerebrovascular conductance index (CVCi), and used to assess cerebral vasodilation. Hypoxia increased CVCi in both groups; however, vasodilation was ∼55% lower in MetSyn at SpO2 = 80% (P < 0.05). Indomethacin tended to decrease hypoxic vasodilation in healthy controls, and unexpectedly increased dilation in MetSyn (P < 0.05). In contrast to hypoxia, hypercapnia-mediated vasodilation was similar between groups, as was the decrease in vasodilation with indomethacin. These data indicate increased production of vasoconstrictor prostaglandins restrains hypoxic cerebral vasodilation in MetSyn, preventing them from responding appropriately to this important physiological stressor. PMID:24213610

  20. Structural refinement of membrane proteins by restrained molecular dynamics and solvent accessibility data.

    PubMed

    Sompornpisut, Pornthep; Roux, Benoît; Perozo, Eduardo

    2008-12-01

    We present an approach for incorporating solvent accessibility data from electron paramagnetic resonance experiments in the structural refinement of membrane proteins through restrained molecular dynamics simulations. The restraints have been parameterized from oxygen (PiO(2)) and nickel-ethylenediaminediacetic acid (PiNiEdda) collision frequencies, as indicators of lipid or aqueous exposed spin-label sites. These are enforced through interactions between a pseudoatom representation of the covalently attached Nitroxide spin-label and virtual "solvent" particles corresponding to O(2) and NiEdda in the surrounding environment. Interactions were computed using an empirical potential function, where the parameters have been optimized to account for the different accessibilities of the spin-label pseudoatoms to the surrounding environment. This approach, "pseudoatom-driven solvent accessibility refinement", was validated by refolding distorted conformations of the Streptomyces lividans potassium channel (KcsA), corresponding to a range of 2-30 A root mean-square deviations away from the native structure. Molecular dynamics simulations based on up to 58 electron paramagnetic resonance restraints derived from spin-label mutants were able to converge toward the native structure within 1-3 A root mean-square deviations with minimal computational cost. The use of energy-based ranking and structure similarity clustering as selection criteria helped in the convergence and identification of correctly folded structures from a large number of simulations. This approach can be applied to a variety of integral membrane protein systems, regardless of oligomeric state, and should be particularly useful in calculating conformational changes from a known reference crystal structure. PMID:18676641

  1. Antimicrobial resistance in Canada

    PubMed Central

    Conly, John

    2002-01-01

    Antibiotic resistance has increased rapidly during the last decade, creating a serious threat to the treatment of infectious diseases. Canada is no exception to this worldwide phenomenon. Data from the Canadian Nosocomial Infection Surveillance Program have revealed that the incidence of methicillin-resistant Staphylococcus aureus, as a proportion of S. aureus isolates, increased from 1% in 1995 to 8% by the end of 2000, and vancomycin-resistant enterococcus has been documented in all 10 provinces since the first reported outbreak in 1995. The prevalence of nonsusceptible Streptococcus pneumoniae in Canada in 2000 was found to be 12%. Human antimicrobial prescriptions, adjusted for differences in the population, declined 11% based on the total number of prescriptions dispensed between 1995 and 2000. There was also a 21% decrease in β-lactam prescriptions during this same period. These data suggest that systematic efforts to reduce unnecessary prescribing of antimicrobials to outpatients in Canada, beginning after a national consensus conference in 1997, may be having an impact. There is, however, still a need for continued concerted efforts on a national, provincial and regional level to quell the rising tide of antibiotic resistance. PMID:12406948

  2. The Relationship between Antimicrobial Use and Antimicrobial Resistance in Europe

    PubMed Central

    Cars, Otto; Buchholz, Udo; Mölstad, Sigvard; Goettsch, Wim; Veldhuijzen, Irene K.; Kool, Jacob L.; Sprenger, Marc J.W.; Degener, John E.

    2002-01-01

    In Europe, antimicrobial resistance has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS). We examined the relationship between penicillin nonsusceptibility of invasive isolates of Streptococcus pneumoniae (an indicator organism) and antibiotic sales. Information was collected on 1998-99 resistance data for invasive isolates of S. pneumoniae to penicillin, based on surveillance data from EARSS and on outpatient sales during 1997 for beta-lactam antibiotics and macrolides. Our results show that in Europe antimicrobial resistance is correlated with use of beta-lactam antibiotics and macrolides. PMID:11927025

  3. Lipopolysaccharide neutralization by antimicrobial peptides: a gambit in the innate host defense strategy.

    PubMed

    Pulido, David; Nogués, M Victòria; Boix, Ester; Torrent, Marc

    2012-01-01

    Antimicrobial peptides (AMPs) are nowadays understood as broad multifunctional tools of the innate immune system to fight microbial infections. In addition to its direct antimicrobial action, AMPs can modulate the host immune response by promoting or restraining the recruitment of cells and chemicals to the infection focus. Binding of AMPs to lipopolysaccharide is a critical step for both their antimicrobial action and their immunomodulatory properties. On the one hand, removal of Gram-negative bacteria by AMPs can be an effective strategy to prevent a worsened inflammatory response that may lead to septic shock. On the other hand, by neutralizing circulating endotoxins, AMPs can successfully reduce nitric oxide and tumor necrosis factor-α production, hence preventing severe tissue damage. Furthermore, AMPs can also interfere with the Toll-like receptor 4 recognition system, suppressing cytokine production and contributing to modulate the inflammatory response. Here, we review the immune system strategies devised by AMPs to avoid an exacerbated inflammatory response and thus prevent a fatal end to the host.

  4. [Antimicrobial susceptibility in Chile 2012].

    PubMed

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  5. Novel Formulations for Antimicrobial Peptides

    PubMed Central

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  6. Antimicrobial properties of hemoglobin.

    PubMed

    Sheshadri, Preethi; Abraham, Jayanthi

    2012-12-01

    Hemoglobin consists of a heme containing component and a globin unit. It exists as a tetramer with 2 α subunits and 2 β subunits in adults and with 2 α subunits and 2 γ chains in infants. On proteolytic cleavage, hemoglobin breaks down to produce many biologically active compounds, among which are hemocidins, those which exhibit antimicrobial property. The generation of these peptides does not depend on the blood group, Rhesus factor, age and sex of the healthy donors. The microbicidal activity has been observed against a variety of gram positive and Gram-negative bacteria, and against filamentous fungi, yeast and even certain parasites. The discovery of hemocidins opens a new field for research into the details of the peptides acting as second line of defence in boosting the innate immune system of the organisms.

  7. Interferon-Gamma Receptor Signaling Plays an Important Role in Restraining Murine Ovarian Tumor Progression

    PubMed Central

    Bian, Guanglin; Leigh, Nicholas D.; Du, Wei; Zhang, Lei; Li, Li; Cao, Xuefang

    2016-01-01

    Immune cell-derived cytotoxic pathways have been implicated in antitumor immune responses. The goal of this study is to characterize how these cytotoxic pathways influence ovarian cancer development. We have utilized the TgMISIIR-TAg transgenic mouse model which expresses the transforming SV40 TAg in the ovary, leading to spontaneous development of ovarian tumors that closely mimic human epithelial ovarian cancer. To test how perforin (Prf1), granzyme B (GzmB) and interferon-gamma (IFNg) impact tumor occurrence and progression, we bred the TgMISIIR-TAg transgene into Prf1−/−, GzmB−/−, and IFNgR1−/− mice. The transgenic females developed peritoneal tumors at 9–15 weeks and succumbed at 184 ± 37 days of age with 100% penetrance (n=41). Knockout of these cytotoxic genes does not affect tumor occurrence. However, loss of function in the IFNg signaling pathway significantly expedited tumor progression with all of the IFNg R1−/− TgMISIIR-TAg females succumbing to tumor outgrowth at 167 ± 27 days of age (p=0.0074, n=24). In contrast, loss of function of Prf1 or GzmB did not significantly impact tumor progression and host survival. Since tumor cells in the IFNg R1−/− TgMISIIR-TAg mice are IFNg R1 deficient, we used the implantable MOSEC (mouse ovarian surface epithelial cell) tumor line to validate that IFNg R signaling in host immune cells but not in tumor cells impacts tumor progression. Indeed, when the IFNg -responsive MOSEC cells were inoculated, IFNg R1−/− mice exhibited significantly higher tumor burden compared to WT mice. Furthermore, a MOSEC-splenocyte co-culture system confirmed that IFNg R1−/− immune cells were less effective than WT immune cells in controlling MOSEC tumor growth in vitro. Together, these results indicate that the IFNg R signaling pathway plays an important role in restraining murine ovarian tumor progression.

  8. HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating intestinal epithelial cell differentiation.

    PubMed

    Turgeon, Naomie; Blais, Mylène; Gagné, Julie-Moore; Tardif, Véronique; Boudreau, François; Perreault, Nathalie; Asselin, Claude

    2013-01-01

    , epithelial HDAC1 and HDAC2 restrain the intestinal inflammatory response, by regulating intestinal epithelial cell proliferation and differentiation.

  9. Force Measurement Using Non-Restrained Models In A Shock Tunnel

    NASA Astrophysics Data System (ADS)

    Tanno, Hideyuki; Sato, Kazuo; Komuro, Tomoyuki; Takahashi, Massahiro; Itoh, Katsuhiro; Fujita, Kazuhisa; Laurence, Stuart; Hannemann, Klaus

    2011-05-01

    A novel force measurement technique has been developed at the impulsive facility HIEST, in which the test model is completely non-restrained for the duration of the test, so it experiences free-flight conditions for a period on the order of milliseconds. This technique was demonstrated with a three-component aerodynamic force measurement with a blunted cone of total length 318 mm and a total mass of 22 kg. At the beginning of the wind tunnel test, the blunted cone test model was suspended from electromagnets fixed on the test-section ceiling. The model was released when a triggering signal arrived from the tunnel start signal. The model then fell so that it met the hypersonic test flow just as it arrived in the test section, and made a soft landing on a model catcher with four hydraulic shock absorbers. A miniature model-onboard data-logger, which was a key technology for this technique, was also developed in order to store the measured data. The data-logger was designed to be small enough to be instrumented in test models, with an overall size of 50 mm x 70 mm x 50 mm, including batteries. Since the logger was designed to measure force and pressure, it includes six piezoelectric amplifiers and four piezoresistive amplifiers, as well as high-speed analog-digital converters, which digitize the measured data with 16-bit resolution. The logger’s sampling rate and sample size are 500 kHz and 200 ms, respectively. The logger waits for a trigger signal (accelerometer output) and then starts to take measurements. The trigger threshold and pre-trigger delay time can be adjusted arbitrarily. Measured data is stored to static memory for transfer to a PC via a USB interface after a wind tunnel test. To demonstrate the entire measurement system, wind tunnel experiments were conducted in HIEST. In the present wind tunnel test campaign, records of pressure and axial force were obtained under conditions of H0 = 4 MJ/kg, P0 = 14 MPa. This demonstrated that the system worked

  10. HDAC1 and HDAC2 Restrain the Intestinal Inflammatory Response by Regulating Intestinal Epithelial Cell Differentiation

    PubMed Central

    Turgeon, Naomie; Blais, Mylène; Gagné, Julie-Moore; Tardif, Véronique; Boudreau, François; Perreault, Nathalie; Asselin, Claude

    2013-01-01

    , epithelial HDAC1 and HDAC2 restrain the intestinal inflammatory response, by regulating intestinal epithelial cell proliferation and differentiation. PMID:24040068

  11. Antimicrobial seafood packaging: a review.

    PubMed

    Singh, Suman; Ho Lee, Myung; Park, Lnsik; Shin, Yangjai; Lee, Youn Suk

    2016-06-01

    Microorganisms are the major cause of spoilage in most seafood products; however, only few microbes, called the specific spoilage organisms (SSOs), contribute to the offensive off-flavors associated with seafood spoilage. In food, microbial degradation manifests itself as spoilage, or changes in the sensory properties of a food product, rendering it unsuitable for human consumption. The use of antimicrobial substances can control the general microflora as well as specific microorganisms related to spoilage to provide products with higher safety and better quality. Many antimicrobial compounds have been evaluated in film structures for use in seafood, especially organic acids and their salts, enzymes, bacteriocins; some studies have considered inorganic compounds such as AgSiO2, zinc oxide, silver zeolite, and titanium oxide. The characteristics of some organic antimicrobial packaging systems for seafood and their antimicrobial efficiency in film structures are reviewed in this article. PMID:27478206

  12. Antimicrobials for bacterial bioterrorism agents.

    PubMed

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  13. Economic impact of antimicrobial resistance.

    PubMed Central

    McGowan, J. E.

    2001-01-01

    One reason antimicrobial-drug resistance is of concern is its economic impact on physicians, patients, health-care administrators, pharmaceutical producers, and the public. Measurement of cost and economic impact of programs to minimize antimicrobial-drug resistance is imprecise and incomplete. Studies to describe and evaluate the problem will have to employ new methods and be of large scale to produce information that is broadly applicable. PMID:11294725

  14. Associations between Restrained Eating and the Size and Frequency of Overall Intake, Meal, Snack and Drink Occasions in the UK Adult National Diet and Nutrition Survey

    PubMed Central

    Olea López, Ana Lorena; Johnson, Laura

    2016-01-01

    Obesity is a global public health priority. Restrained eating is related to obesity and total energy intake but associations with the eating patterns are unclear. We examined the associations of restrained eating with the size and frequency of intake occasions among 1213 British adult (19–64 y) participants in a cross-sectional analysis of the UK National Diet and Nutrition Survey 2000. The Dutch Eating Behaviour Questionnaire assessed restrained eating. Overall intake occasions were all energy consumed in a 60 min period. A food-based classification separated intake occasions into meals, snacks, or drinks from seven-day weighed food diaries. Average daily frequency and size (kcal) of overall intake, meal, snack and drink occasions were calculated and associations with restrained eating were modelled using multiple linear regression including under-reporting of energy intake, age, gender, BMI, emotional eating, external eating and physical activity as covariates. Restrained eating was very weakly positively correlated with overall intake (r = 0.08, p<0.05) and meal frequency (r = 0.10, p<0.05) but not snack or drink frequency (r = 0.02 and -0.02 respectively). Adjusted regressions showed a one-point change in restrained eating was associated with 0.07 (95% CI 0.03, 0.11) more meal occasions/day and 0.13 (95% CI 0.01, 0.25) extra overall intake occasions/day. Overall intake occasion size was weakly negatively correlated with restrained eating regardless of type (r = -0.16 to -0.20, all p<0.0001). Adjusted regressions showed each one-point increase in restrained eating was associated with lower-energy meals (-15 kcal 95% CI -5.9, -24.2) and drinks (-4 kcal 95%CI -0.1, -8), but not snacks or overall intake occasions. Among a national sample of UK adults, greater restrained eating was associated with smaller and slightly more frequent eating, suggesting that restrained eaters restrict their energy intake by reducing meal/drink size rather than skipping snacks. PMID

  15. Associations between Restrained Eating and the Size and Frequency of Overall Intake, Meal, Snack and Drink Occasions in the UK Adult National Diet and Nutrition Survey.

    PubMed

    Olea López, Ana Lorena; Johnson, Laura

    2016-01-01

    Obesity is a global public health priority. Restrained eating is related to obesity and total energy intake but associations with the eating patterns are unclear. We examined the associations of restrained eating with the size and frequency of intake occasions among 1213 British adult (19-64 y) participants in a cross-sectional analysis of the UK National Diet and Nutrition Survey 2000. The Dutch Eating Behaviour Questionnaire assessed restrained eating. Overall intake occasions were all energy consumed in a 60 min period. A food-based classification separated intake occasions into meals, snacks, or drinks from seven-day weighed food diaries. Average daily frequency and size (kcal) of overall intake, meal, snack and drink occasions were calculated and associations with restrained eating were modelled using multiple linear regression including under-reporting of energy intake, age, gender, BMI, emotional eating, external eating and physical activity as covariates. Restrained eating was very weakly positively correlated with overall intake (r = 0.08, p<0.05) and meal frequency (r = 0.10, p<0.05) but not snack or drink frequency (r = 0.02 and -0.02 respectively). Adjusted regressions showed a one-point change in restrained eating was associated with 0.07 (95% CI 0.03, 0.11) more meal occasions/day and 0.13 (95% CI 0.01, 0.25) extra overall intake occasions/day. Overall intake occasion size was weakly negatively correlated with restrained eating regardless of type (r = -0.16 to -0.20, all p<0.0001). Adjusted regressions showed each one-point increase in restrained eating was associated with lower-energy meals (-15 kcal 95% CI -5.9, -24.2) and drinks (-4 kcal 95%CI -0.1, -8), but not snacks or overall intake occasions. Among a national sample of UK adults, greater restrained eating was associated with smaller and slightly more frequent eating, suggesting that restrained eaters restrict their energy intake by reducing meal/drink size rather than skipping snacks. PMID

  16. Associations between Restrained Eating and the Size and Frequency of Overall Intake, Meal, Snack and Drink Occasions in the UK Adult National Diet and Nutrition Survey.

    PubMed

    Olea López, Ana Lorena; Johnson, Laura

    2016-01-01

    Obesity is a global public health priority. Restrained eating is related to obesity and total energy intake but associations with the eating patterns are unclear. We examined the associations of restrained eating with the size and frequency of intake occasions among 1213 British adult (19-64 y) participants in a cross-sectional analysis of the UK National Diet and Nutrition Survey 2000. The Dutch Eating Behaviour Questionnaire assessed restrained eating. Overall intake occasions were all energy consumed in a 60 min period. A food-based classification separated intake occasions into meals, snacks, or drinks from seven-day weighed food diaries. Average daily frequency and size (kcal) of overall intake, meal, snack and drink occasions were calculated and associations with restrained eating were modelled using multiple linear regression including under-reporting of energy intake, age, gender, BMI, emotional eating, external eating and physical activity as covariates. Restrained eating was very weakly positively correlated with overall intake (r = 0.08, p<0.05) and meal frequency (r = 0.10, p<0.05) but not snack or drink frequency (r = 0.02 and -0.02 respectively). Adjusted regressions showed a one-point change in restrained eating was associated with 0.07 (95% CI 0.03, 0.11) more meal occasions/day and 0.13 (95% CI 0.01, 0.25) extra overall intake occasions/day. Overall intake occasion size was weakly negatively correlated with restrained eating regardless of type (r = -0.16 to -0.20, all p<0.0001). Adjusted regressions showed each one-point increase in restrained eating was associated with lower-energy meals (-15 kcal 95% CI -5.9, -24.2) and drinks (-4 kcal 95%CI -0.1, -8), but not snacks or overall intake occasions. Among a national sample of UK adults, greater restrained eating was associated with smaller and slightly more frequent eating, suggesting that restrained eaters restrict their energy intake by reducing meal/drink size rather than skipping snacks.

  17. Response, thermal regulatory threshold and thermal breakdown threshold of restrained RF-exposed mice at 905 MHz

    NASA Astrophysics Data System (ADS)

    Ebert, S.; Eom, S. J.; Schuderer, J.; Apostel, U.; Tillmann, T.; Dasenbrock, C.; Kuster, N.

    2005-11-01

    The objective of this study was the determination of the thermal regulatory and the thermal breakdown thresholds for in-tube restrained B6C3F1 and NMRI mice exposed to radiofrequency electromagnetic fields at 905 MHz. Different levels of the whole-body averaged specific absorption rate (SAR = 0, 2, 5, 7.2, 10, 12.6 and 20 W kg-1) have been applied to the mice inside the 'Ferris Wheel' exposure setup at 22 ± 2 °C and 30-70% humidity. The thermal responses were assessed by measurement of the rectal temperature prior, during and after the 2 h exposure session. For B6C3F1 mice, the thermal response was examined for three different weight groups (20 g, 24 g, 29 g), both genders and for pregnant mice. Additionally, NMRI mice with a weight of 36 g were investigated for an interstrain comparison. The thermal regulatory threshold of in-tube restrained mice was found at SAR levels between 2 W kg-1 and 5 W kg-1, whereas the breakdown of regulation was determined at 10.1 ± 4.0 W kg-1(K = 2) for B6C3F1 mice and 7.7 ± 1.6 W kg-1(K = 2) for NMRI mice. Based on a simplified power balance equation, the thresholds show a clear dependence upon the metabolic rate and weight. NMRI mice were more sensitive to thermal stress and respond at lower SAR values with regulation and breakdown. The presented data suggest that the thermal breakdown for in-tube restrained mice, whole-body exposed to radiofrequency fields, may occur at SAR levels of 6 W kg-1(K = 2) at laboratory conditions.

  18. Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: challenges and checklists.

    PubMed

    Gilchrist, M; Seaton, R A

    2015-04-01

    Outpatient parenteral antimicrobial therapy (OPAT) has become, for many countries, an established form of healthcare delivery. At the same time, there have been calls to ensure the prudent use of the existing antimicrobial armamentarium. For OPAT, this presents a dilemma. On one hand, stewardship principles look for the most effective agent with minimal collateral effects. In OPAT, whilst the aims of the service are similar, convenience of dosing to optimize early hospital discharge or admission avoidance may take precedence over an agent's spectrum of activity. This brief article aims to highlight the importance and explore the challenges of antimicrobial stewardship in the context of OPAT. Within the UK, the safe and effective use of antimicrobials is modelled around the IDSA/Society for Healthcare Epidemiology of America stewardship practice guidelines with local customization where appropriate. Current UK stewardship practice principles were compared with published good practice recommendations for OPAT to identify how OPAT could support the broader antimicrobial stewardship agenda. It is essential that antimicrobial stewardship teams should understand the challenges faced in the non-inpatient setting and the potential benefits/lower risks associated with avoided admission or shortened hospital stay in this population. Within its limitations, OPAT should practise stewardship principles, including optimization of intravenous to oral switch and the reporting of outcomes, healthcare-associated infections and re-admission rates. OPAT should report to the antimicrobial stewardship team. Ideally the OPAT team should be formally represented within the stewardship framework. A checklist has been proposed to aid OPAT services in ensuring they meet their stewardship agenda.

  19. Functional similarity between E6 proteins of cutaneous human papillomaviruses and the adenovirus E1A tumor-restraining module.

    PubMed

    Kuppuswamy, Mohan; Subramanian, T; Kostas-Polston, Elizabeth; Vijayalingam, S; Zhao, Ling-jun; Varvares, Mark; Chinnadurai, G

    2013-07-01

    The adenovirus E1A C-terminal region restrains oncogenic transformation through interaction with three distinct cellular protein complexes that include the DYRK1A/1B/HAN11 complex. The E6 proteins of beta-human papillomaviruses (beta-HPVs) also interact with the DYRK1/HAN11 complex. A variant of HPV5 E6 frequently found in epidermodysplasia verruciformis skin lesions interacted less efficiently with DYRK1A/HAN11. The E6 variant and E7 of HPV5 efficiently coimmortalized primary epithelial cells, suggesting that naturally arising variants may contribute potential oncogenic activities of beta-HPV E6 proteins. PMID:23637414

  20. Peptides and Peptidomimetics for Antimicrobial Drug Design

    PubMed Central

    Mojsoska, Biljana; Jenssen, Håvard

    2015-01-01

    The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics. PMID:26184232

  1. Editorial of the Special Issue Antimicrobial Polymers

    PubMed Central

    Piozzi, Antonella; Francolini, Iolanda

    2013-01-01

    The special issue “Antimicrobial Polymers” includes research and review papers concerning the recent advances on preparation of antimicrobial polymers and their relevance to industrial settings and biomedical field. Antimicrobial polymers have recently emerged as promising candidates to fight microbial contamination onto surfaces thanks to their interesting properties. In this special issue, the main strategies pursued for developing antimicrobial polymers, including polymer impregnation with antimicrobial agents or synthesis of polymers bearing antimicrobial moieties, were discussed. The future application of these polymers either in industrial or healthcare settings could result in an extremely positive impact not only at the economic level but also for the improvement of quality of life. PMID:24005863

  2. Hospital antimicrobial stewardship in the nonuniversity setting.

    PubMed

    Trivedi, Kavita K; Kuper, Kristi

    2014-06-01

    Inappropriate antimicrobial use and antimicrobial resistance persist across the healthcare continuum. Antimicrobial stewardship guidelines assist healthcare institutions in establishing antimicrobial stewardship programs but rely on infectious diseases expertise and leadership, which are not available in all settings. Despite this, many institutions have found ways to use available resources to perform stewardship activities, with improvements in antimicrobial use and reductions in resistance and cost. This article highlights success stories in nonuniversity hospital settings and proposes antimicrobial stewardship strategies that may be more feasible in settings with limited infectious diseases expertise, information technology, or financial resources.

  3. Focusing on media body ideal images triggers food intake among restrained eaters: a test of restraint theory and the elaboration likelihood model.

    PubMed

    Boyce, Jessica A; Kuijer, Roeline G

    2014-04-01

    Although research consistently shows that images of thin women in the media (media body ideals) affect women negatively (e.g., increased weight dissatisfaction and food intake), this effect is less clear among restrained eaters. The majority of experiments demonstrate that restrained eaters - identified with the Restraint Scale - consume more food than do other participants after viewing media body ideal images; whereas a minority of experiments suggest that such images trigger restrained eaters' dietary restraint. Weight satisfaction and mood results are just as variable. One reason for these inconsistent results might be that different methods of image exposure (e.g., slideshow vs. film) afford varying levels of attention. Therefore, we manipulated attention levels and measured participants' weight satisfaction and food intake. We based our hypotheses on the elaboration likelihood model and on restraint theory. We hypothesised that advertent (i.e., processing the images via central routes of persuasion) and inadvertent (i.e., processing the images via peripheral routes of persuasion) exposure would trigger differing degrees of weight dissatisfaction and dietary disinhibition among restrained eaters (cf. restraint theory). Participants (N = 174) were assigned to one of four conditions: advertent or inadvertent exposure to media or control images. The dependent variables were measured in a supposedly unrelated study. Although restrained eaters' weight satisfaction was not significantly affected by either media exposure condition, advertent (but not inadvertent) media exposure triggered restrained eaters' eating. These results suggest that teaching restrained eaters how to pay less attention to media body ideal images might be an effective strategy in media-literary interventions.

  4. Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance.

    PubMed

    Maddox, T W; Clegg, P D; Williams, N J; Pinchbeck, G L

    2015-11-01

    Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin-resistant Staphylococcus aureus has been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin-resistant Staphylococcus aureus strains either to be predominantly of types associated with horses or of sequence type ST398. Antimicrobial-resistant Escherichia coli (including multidrug-resistant and extended spectrum β-lactamase-producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci, Salmonella, Acinetobacter and Pseudomonas species. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.

  5. Antimicrobial action of sanguinarine.

    PubMed

    Godowski, K C

    1989-01-01

    Sanguinarine is a benzophenanthridine alkaloid derived from rhizomes of Sanguinaria canadensis L. (bloodroot). It is a cationic molecule which converts from an iminium ion form at pH less than 6 to an alkanolamine form at pH greater than 7. Sanguinaria extract is composed of sanguinarine and five other closely related alkaloids. The safety profile of both sanguinarine and sanguinaria extract provide a broad margin for their safe use in oral health products. Sanguinarine has broad antimicrobial activity as well as antiinflammatory properties. In vitro studies indicate that the anti-plaque action of sanguinaria is due to its ability to inhibit bacterial adherence to newly formed pellicle, its retention in plaque being 10-100 times its saliva concentration, and due to its antimicrobic properties. The MIC of sanguinarine ranges from 1 to 32 micrograms/mL for most species of plaque bacteria. Long term use of sanguinaria-containing toothpaste and oral rinse products does not predispose users to detrimental shifts in oral flora. Electron microscopic studies of bacteria exposed to sanguinarine demonstrate that bacteria aggregate and become morphologically irregular. Sanguinarine-containing slow release polymer systems are currently being developed for use in periodontitis treatment applications.

  6. Antimicrobial Peptides from Plants.

    PubMed

    Tam, James P; Wang, Shujing; Wong, Ka H; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  7. Antimicrobial Peptides from Plants

    PubMed Central

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  8. Purification of antimicrobial peptide from Antarctic Krill ( Euphausia superba) and its function mechanism

    NASA Astrophysics Data System (ADS)

    Zhao, Ling; Yin, Bangzhong; Liu, Qi; Cao, Rong

    2013-09-01

    The preliminary purification and antimicrobial mechanism of antimicrobial peptide from Antarctic Krill were studied in this paper. The results showed that the molecular weight range of antimicrobial polypeptide (CMCC-1) obtained by cation exchange chromatography was between 245-709D as detected by molecular sieve chromatography, and the minimum inhibition concentration (MIC) of CMCC-1 against Staphylococcus aureus was 5.0 mg mL-1. The antimicrobial mechanism of CMCC-1 was studied with S. aureus as indicator bacterium. Compared with control group, the results of the experimental group in which S. aureus was treated with CMCC-1 were as follows: 1) CMCC-1 could inhibit cell division at logarithmic phase. 2) The protein and reducing sugar content, and the conductivity of culture medium increased, and the activity of alkaline phosphatase and β-galactosidase could be detected in the culture medium. 3) Observation under scanning electron microscope revealed that somatic morphology became irregular, and then somatic surface became coarse. The cell became much smaller, and most somatic cells gathered. The boundary between cells became dim and finally fused as a whole. 4) Observation under transmission electron microscope showed that the surface of S. aureus became rough and the reproducing ability was restrained. The cell wall became thin and the cytoplasm shrunk. Substances inside cell leaked out, which caused cells death. 5) SDS-PAGE analysis showed that some bands disappeared, and the residual bands became vague. 6) The genomic DNA electrophoresis results showed that the genomic DNA bands of S. aureus were not degraded but the brightness significantly reduced. Thus, it is supposed that CMCC-1 could destroy the cell wall and membrane of S. aureu, increase the cell membrane permeability and the leaking-out of intracellular substances, and thus cause the death of S. aureu.

  9. Myosin-Va restrains the trafficking of Na+/K+-ATPase-containing vesicles in alveolar epithelial cells

    PubMed Central

    Lecuona, Emilia; Minin, Alexander; Trejo, Humberto E.; Chen, Jiwang; Comellas, Alejandro P.; Sun, Haiying; Grillo, Doris; Nekrasova, Oxana E.; Welch, Lynn C.; Szleifer, Igal; Gelfand, Vladimir I.; Sznajder, Jacob I.

    2009-01-01

    Summary Stimulation of Na+/K+-ATPase activity in alveolar epithelial cells by cAMP involves its recruitment from intracellular compartments to the plasma membrane. Here, we studied the role of the actin molecular motor myosin-V in this process. We provide evidence that, in alveolar epithelial cells, cAMP promotes Na+/K+-ATPase recruitment to the plasma membrane by increasing the average speed of Na+/K+-ATPase-containing vesicles moving to the cell periphery. We found that three isoforms of myosin-V are expressed in alveolar epithelial cells; however, only myosin-Va and Vc colocalized with the Na+/K+-ATPase in intracellular membrane fractions. Overexpression of dominant-negative myosin-Va or knockdown with specific shRNA increased the average speed and distance traveled by the Na+/K+-ATPase-containing vesicles, as well as the Na+/K+-ATPase activity and protein abundance at the plasma membrane to similar levels as those observed with cAMP stimulation. These data show that myosin-Va has a role in restraining Na+/K+-ATPase-containing vesicles within intracellular pools and that this restrain is released after stimulation by cAMP allowing the recruitment of the Na+/K+-ATPase to the plasma membrane and thus increased activity. PMID:19808891

  10. Assessment of buckling-restrained braced frame reliability using an experimental limit-state model and stochastic dynamic analysis

    NASA Astrophysics Data System (ADS)

    Andrews, Blake M.; Song, Junho; Fahnestock, Larry A.

    2009-09-01

    Buckling-restrained braces (BRBs) have recently become popular in the United States for use as primary members of seismic lateral-force-resisting systems. A BRB is a steel brace that does not buckle in compression but instead yields in both tension and compression. Although design guidelines for BRB applications have been developed, systematic procedures for assessing performance and quantifying reliability are still needed. This paper presents an analytical framework for assessing buckling-restrained braced frame (BRBF) reliability when subjected to seismic loads. This framework efficiently quantifies the risk of BRB failure due to low-cycle fatigue fracture of the BRB core. The procedure includes a series of components that: (1) quantify BRB demand in terms of BRB core deformation histories generated through stochastic dynamic analyses; (2) quantify the limit-state of a BRB in terms of its remaining cumulative plastic ductility capacity based on an experimental database; and (3) evaluate the probability of BRB failure, given the quantified demand and capacity, through structural reliability analyses. Parametric studies were conducted to investigate the effects of the seismic load, and characteristics of the BRB and BRBF on the probability of brace failure. In addition, fragility curves (i.e., conditional probabilities of brace failure given ground shaking intensity parameters) were created by the proposed framework. While the framework presented in this paper is applied to the assessment of BRBFs, the modular nature of the framework components allows for application to other structural components and systems.

  11. Structural Dynamics and Conformational Equilibria of SERCA Regulatory Proteins in Membranes by Solid-State NMR Restrained Simulations

    PubMed Central

    De Simone, Alfonso; Mote, Kaustubh R.; Veglia, Gianluigi

    2014-01-01

    Solid-state NMR spectroscopy is emerging as a powerful approach to determine structure, topology, and conformational dynamics of membrane proteins at the atomic level. Conformational dynamics are often inferred and quantified from the motional averaging of the NMR parameters. However, the nature of these motions is difficult to envision based only on spectroscopic data. Here, we utilized restrained molecular dynamics simulations to probe the structural dynamics, topology and conformational transitions of regulatory membrane proteins of the calcium ATPase SERCA, namely sarcolipin and phospholamban, in explicit lipid bilayers. Specifically, we employed oriented solid-state NMR data, such as dipolar couplings and chemical shift anisotropy measured in lipid bicelles, to refine the conformational ensemble of these proteins in lipid membranes. The samplings accurately reproduced the orientations of transmembrane helices and showed a significant degree of convergence with all of the NMR parameters. Unlike the unrestrained simulations, the resulting sarcolipin structures are in agreement with distances and angles for hydrogen bonds in ideal helices. In the case of phospholamban, the restrained ensemble sampled the conformational interconversion between T (helical) and R (unfolded) states for the cytoplasmic region that could not be observed using standard structural refinements with the same experimental data set. This study underscores the importance of implementing NMR data in molecular dynamics protocols to better describe the conformational landscapes of membrane proteins embedded in realistic lipid membranes. PMID:24940774

  12. Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation.

    PubMed

    Mishra, Vikas; Shuai, Bing; Kodali, Maheedhar; Shetty, Geetha A; Hattiangady, Bharathi; Rao, Xiaolan; Shetty, Ashok K

    2015-12-07

    Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy.

  13. Identifying Armed Respondents to Domestic Violence Restraining Orders and Recovering Their Firearms: Process Evaluation of an Initiative in California

    PubMed Central

    Frattaroli, Shannon; Claire, Barbara E.; Vittes, Katherine A.; Webster, Daniel W.

    2014-01-01

    Objectives. We evaluated a law enforcement initiative to screen respondents to domestic violence restraining orders for firearm ownership or possession and recover their firearms. Methods. The initiative was implemented in San Mateo and Butte counties in California from 2007 through 2010. We used descriptive methods to evaluate the screening process and recovery effort in each county, relying on records for individual cases. Results. Screening relied on an archive of firearm transactions, court records, and petitioner interviews; no single source was adequate. Screening linked 525 respondents (17.7%) in San Mateo County to firearms; 405 firearms were recovered from 119 (22.7%) of them. In Butte County, 88 (31.1%) respondents were linked to firearms; 260 firearms were recovered from 45 (51.1%) of them. Nonrecovery occurred most often when orders were never served or respondents denied having firearms. There were no reports of serious violence or injury. Conclusions. Recovering firearms from persons subject to domestic violence restraining orders is possible. We have identified design and implementation changes that may improve the screening process and the yield from recovery efforts. Larger implementation trials are needed. PMID:24328660

  14. Antimicrobial resistance in Scandinavia after ban of antimicrobial growth promoters.

    PubMed

    Bengtsson, Björn; Wierup, Martin

    2006-01-01

    The banned use of antimicrobial growth promoters resulted in a considerably decreased use of antimicrobials in food animal production in Sweden (65%), Denmark (47%), Norway (40%) and Finland (27%). The current prevalence of antimicrobial resistance in animal bacterial populations is also considerably lower than in some other countries in the EU. In the swine production, no or limited effect was found in the finisher production (>25 to 30 kg). Temporary negative effects occurred during the post weaning period (7-30 kg). In Denmark, the cost of production from birth to slaughter per pig produced increased by approximately 1.0 euro with a high variability between pig producers. In the broiler production the termination had no significant negative effect on animal health and welfare or on production economy. PMID:17127526

  15. Antimicrobial Resistance Mechanisms among Campylobacter

    PubMed Central

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  16. Antimicrobial implications of vitamin D

    PubMed Central

    Youssef, Dima A; Miller, Christopher WT; El-Abbassi, Adel M; Cutchins, Della C; Cutchins, Coleman; Grant, William B

    2011-01-01

    Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections. PMID:22259647

  17. Antimicrobial activities of squalamine mimics.

    PubMed

    Kikuchi, K; Bernard, E M; Sadownik, A; Regen, S L; Armstrong, D

    1997-07-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and fungi. Some had little or no hemolytic activity. The hydrophobicity of the sterol backbone and the length and the cationic charge of the side chains appeared to be critical determinants of activity. One of the squalamine mimics, SM-7, was bactericidal against Escherichia coli, Pseudomonas aeruginosa, and S. aureus; its activity was decreased by divalent or monovalent cations and by bovine serum albumin. Subinhibitory concentrations of SM-7 markedly enhanced the antimicrobial activity of rifampin against gram-negative rods. These results suggest that the compounds may disrupt an outer membrane of gram-negative rods. Squalamine mimics are a new class of broad-spectrum antimicrobial agents. The antagonism of their activity by serum and albumin and their hemolytic properties may limit their use as systemic agents. The squalamine mimics, because of their potencies, broad spectra of antimicrobial activity, and potential for systemic toxicity, appear to be good candidates for development as topical antimicrobial agents. PMID:9210661

  18. ACVIM consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance.

    PubMed

    Weese, J S; Giguère, S; Guardabassi, L; Morley, P S; Papich, M; Ricciuto, D R; Sykes, J E

    2015-01-01

    The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.

  19. Antimicrobial susceptibility of Mycoplasma hyorhinis.

    PubMed

    Wu, C C; Shryock, T R; Lin, T L; Faderan, M; Veenhuizen, M F

    2000-09-15

    A broth microdilution technique was used to determine the antimicrobial susceptibility of 15 field isolates of Mycoplasma hyorhinis to 10 antimicrobial agents, representative of different classes, and contrasting newer agents to existing ones. For the macrolides, the MIC(90) for tylosin and tilmicosin was 1 and 4 microg/ml, respectively, but was > or = 16 microg/ml for erythromycin. Tetracycline, lincomycin and enrofloxacin each had an MIC(90) of 2 microg/ml. The mycoplasma had similar levels of susceptibility to the aminoglycoside and aminocyclictol classes exhibiting an MIC(90) of 4 microg/ml for gentamicin and 2 microg/ml for spectinomycin. The isolates exhibited high MICs to trimethoprim/sulfamethoxazole with an MIC(90) > or = 16/304 microg/ml. In summary, M. hyorhinis isolates from the US had low MICs against a variety of antimicrobials tested, with the exception of erythromycin and trimethoprim/sulfamethoxazole. PMID:10925038

  20. Synthetic biology of antimicrobial discovery.

    PubMed

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

  1. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  2. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  3. Uses of antimicrobial genes from microbial genome

    DOEpatents

    Sorek, Rotem; Rubin, Edward M.

    2013-08-20

    We describe a method for mining microbial genomes to discover antimicrobial genes and proteins having broad spectrum of activity. Also described are antimicrobial genes and their expression products from various microbial genomes that were found using this method. The products of such genes can be used as antimicrobial agents or as tools for molecular biology.

  4. "Restrained eating" vs "trying to lose weight": how are they associated with body weight and tendency to overeat among postmenopausal women?

    PubMed

    Rideout, Candice A; Barr, Susan I

    2009-05-01

    In an effort to control body weight, many women diet or adopt a restrained approach to eating. Although common, dieting and dietary restraint remain poorly understood. Clarification of their association with health-related factors, such as body weight and overeating, is required. In this study, we explored how dieting and dietary restraint were associated with body mass index (BMI; calculated as kg/m2) and disinhibition (tendency to overeat) in a sample of 1,071 postmenopausal women aged 45 to 75 years. In a survey of dietary attitudes and body image, we asked about current dieting status and measured restrained eating and disinhibition. Self-reported height and weight were used to calculate BMI, which was confirmed in a subset. Participants were classified by dieting status (yes/no) and level of dietary restraint (high/low by median split).We examined the independent effects of dieting and restrained eating on BMI and disinhibition. More than half of the sample (53%) reported current dieting. Dieting and dietary restraint showed opposite associations with BMI. Among dieters, BMI was 4.1 higher (95% confidence interval: 3.6 to 4.6) than among nondieters. In contrast, BMI of restrained eaters was 1.0 lower (95% confidence interval: -1.6 to -0.5) than unrestrained eaters. Dieters had higher scores for disinhibition, but disinhibition scores of restrained eaters did not differ from those of unrestrained eaters. Our results suggest that dieting and dietary restraint are not equivalent. Finding that dietary restraint is associated with lower BMI (when considered independently of dieting) suggests that restrained eating, rather than dieting, may contribute to successful weight management.

  5. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  6. Antimicrobial drugs for treating cholera

    PubMed Central

    Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

    2014-01-01

    Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. Objectives To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Selection criteria Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Data collection and analysis Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Main results Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43

  7. Small amplitude, transverse vibrations of circular plates with an eccentric rectangular perforation elastically restrained against rotation and translation on both edges

    NASA Astrophysics Data System (ADS)

    Laura, P. A. A.; Avalos, D. R.

    2008-05-01

    The Rayleigh-Ritz variational method is applied to the determination of the first four frequency coefficients for small amplitude, transverse vibrations of circular plates with an eccentric, rectangular perforation that is elastically restrained against rotation and translation on both edges. Coordinate functions are used which identically satisfy the boundary conditions at the outer circular edge, while the restraining boundary conditions at the inner edge of the cutout are dealt with directly through the energetic terms in the functional expressions. The procedure seems to show very good numerical stability and convergence properties. As an added bonus, the method allows for increased flexibility in dealing with boundary conditions at the edge of the cutout.

  8. Comparative study of choleretic agents in anesthetized rats as well as in restrained and and unrestrained rats, with or without compensation for biliary loss

    NASA Technical Reports Server (NTRS)

    Labrid, C.; Dureng, G.; Tachon, J.; Duchene-Marullaz, P.

    1980-01-01

    Tests were conducted on Wistar rats by using 3 control choleretic agents: 1-phenyl-1-hydroxy n-pentane, dehydrocholic acid, and phenyl-dimethylacetic acid. The effects of these agents were compared in different experimental conditions. The comparative study of choleretic agents in anesthetized rats, in restrained and unrestrained rats, with or without compensation for biliary loss by the biliary secretion of restrained or unrestrained rats does not show, in systematic pharmecodynamic investigations, an obvious superiority over the methods based on the simple technique.

  9. How antimicrobial peptides disrupt lipid bilayers?

    NASA Astrophysics Data System (ADS)

    Sengupta, Durba

    2011-03-01

    The molecular basis for the activity of cyclic and linear antimicrobial peptides is analysed. We performed multi-scale molecular dynamics simulations and biophysical measurements to probe the interaction of antimicrobial peptides with model membranes. Two linear antimicrobial peptides, magainin and melittin and a cyclic one, BPC194 have been studied. We test different models to determine the generic and specific forces that lead to bilayer disruption. We probe whether interfacial stress or local membrane perturbation is more likely to lead to the porated state. We further analyse the reasons that determine specificity and increase of activity in antimicrobial peptides. The results provide detailed insight in the mode of action of antimicrobial peptides.

  10. Restrained and External-Emotional Eating Patterns in Young Overweight Children–Results of the Ulm Birth Cohort Study

    PubMed Central

    Brandt, Stephanie; Moss, Anja; Weck, Melanie; Florath, Ines; Wabitsch, Martin; Hebebrand, Johannes; Schimmelmann, Benno G.; Christiansen, Hanna

    2014-01-01

    Childhood obesity is one of the greatest public health challenges in Western countries. Abnormal eating behavior is thought to be a developmental trajectory to obesity. The Eating Pattern Inventory for Children (EPI-C) has not been used for children as young as eight years, and possible associations with body weight have not yet been established. Five hundred and twenty-one children of the Ulm Birth Cohort Study (UBCS; age eight) filled out the EPI-C and BMI was assessed. Adequacy of the scales was tested with confirmatory factor analysis and a MANOVA and cluster analysis established associations between eating patterns and BMI. The factor structure of the EPI-C was confirmed (GFI = .968) and abnormal eating behavior was associated with overweight (χ2(8) = 79.29, p<.001). The EPI-C is a valid assessment tool in this young age group. Overweight children consciously restrain their eating. PMID:25141134

  11. An alternative discourse of productive aging: A self-restrained approach in older Chinese people in Hong Kong.

    PubMed

    Luo, Minxia; Chui, Ernest Wing-Tak

    2016-08-01

    While Western discourses regarding productive aging emphasize individuals' contributions to economic productivity, the Confucian cultural heritage of the Chinese community may provide an alternative perspective. This qualitative study explores interpretations of what constitutes productive aging, based on a series of in-depth interviews with older Chinese people in Hong Kong. It shows that some of these individuals adopted a passive and indirect interpretation of productive aging, distinct from that found in Western countries. The Confucianism-based, collectivist, normative order underpinning Hong Kong society disposed these older people to adopting a self-restrained attitude with the aim of avoiding becoming a burden to others, especially family members. Such a tendency toward self-restraint or avoidance also encompassed a compromise between ideals and reality, with the older people opting to compromise their expectations of the younger generation as a whole, their adult children in particular, in terms of respect and reciprocity.

  12. Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice

    PubMed Central

    González-Sánchez, Carlos; Fraile, Juan-Carlos; Pérez-Turiel, Javier; Damm, Ellen; Schneider, Jochen G.; Zimmermann, Heiko; Schmitt, Daniel; Ihmig, Frank R.

    2016-01-01

    Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC) sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram). First experimental results are shown. PMID:27399713

  13. An alternative discourse of productive aging: A self-restrained approach in older Chinese people in Hong Kong.

    PubMed

    Luo, Minxia; Chui, Ernest Wing-Tak

    2016-08-01

    While Western discourses regarding productive aging emphasize individuals' contributions to economic productivity, the Confucian cultural heritage of the Chinese community may provide an alternative perspective. This qualitative study explores interpretations of what constitutes productive aging, based on a series of in-depth interviews with older Chinese people in Hong Kong. It shows that some of these individuals adopted a passive and indirect interpretation of productive aging, distinct from that found in Western countries. The Confucianism-based, collectivist, normative order underpinning Hong Kong society disposed these older people to adopting a self-restrained attitude with the aim of avoiding becoming a burden to others, especially family members. Such a tendency toward self-restraint or avoidance also encompassed a compromise between ideals and reality, with the older people opting to compromise their expectations of the younger generation as a whole, their adult children in particular, in terms of respect and reciprocity. PMID:27531450

  14. Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice.

    PubMed

    González-Sánchez, Carlos; Fraile, Juan-Carlos; Pérez-Turiel, Javier; Damm, Ellen; Schneider, Jochen G; Zimmermann, Heiko; Schmitt, Daniel; Ihmig, Frank R

    2016-01-01

    Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC) sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram). First experimental results are shown. PMID:27399713

  15. Helical Antimicrobial Sulfono- {gamma} -AApeptides

    SciTech Connect

    Li, Yaqiong; Wu, Haifan; Teng, Peng; Bai, Ge; Lin, Xiaoyang; Zuo, Xiaobing; Cao, Chuanhai; Cai, Jianfeng

    2015-06-11

    Host-defense peptides (HDPs) such as magainin 2 have emerged as potential therapeutic agents combating antibiotic resistance. Inspired by their structures and mechanism of action, herein we report the fi rst example of antimicrobial helical sulfono- γ - AApeptide foldamers. The lead molecule displays broad-spectrum and potent antimicrobial activity against multi-drug-resistant Gram- positive and Gram-negative bacterial pathogens. Time-kill studies and fl uorescence microscopy suggest that sulfono- γ -AApeptides eradicate bacteria by taking a mode of action analogous to that of HDPs. Clear structure - function relationships exist in the studied sequences. Longer sequences, presumably adopting more-de fi ned helical structures, are more potent than shorter ones. Interestingly, the sequence with less helical propensity in solution could be more selective than the stronger helix-forming sequences. Moreover, this class of antimicrobial agents are resistant to proteolytic degradation. These results may lead to the development of a new class of antimicrobial foldamers combating emerging antibiotic-resistant pathogens.

  16. Antimicrobial activity of Pseudognaphalium moritzianum.

    PubMed

    Rangel, D; Garcia, I; Velasco, J; Buitrago, D; Velazco, E

    2002-12-01

    The antimicrobial activity of ethanol, acetone and aqueous extracts of the aerial parts of Pseudognaphalium moritzianum was evaluated. Ethanol and acetone extracts showed activity against Staphlococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. The aqueous extract was active against S. aureus and P. aeruginosa.

  17. Antimicrobial resistance: a global response.

    PubMed Central

    Smith, Richard D.; Coast, Joanna

    2002-01-01

    Resistance to antimicrobial therapies reduces the effectiveness of these drugs, leading to increased morbidity, mortality, and health care expenditure. Because globalization increases the vulnerability of any country to diseases occurring in other countries, resistance presents a major threat to global public health, and no country acting on its own can adequately protect the health of its population against it. International collective action is therefore essential. Nevertheless, responsibility for health remains predominantly national. Consequently, there is a potentially significant disparity between the problems and solutions related to antimicrobial resistance and the institutions and mechanisms that are available to deal with them. This paper considers the capacity of national and international institutions and mechanisms to generate a collective response to antimicrobial resistance. Strategies for containing resistance are outlined, with particular reference to globally coordinated activities of countries. The adequacy of national and international responses to resistance is assessed, and the actions that international bodies could take to solve difficulties associated with present responses are highlighted. Approaches are suggested for securing international collective action for the containment of antimicrobial resistance. PMID:11953791

  18. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity. PMID:24918540

  19. Molecular Detection of Antimicrobial Resistance

    PubMed Central

    Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

    2001-01-01

    The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

  20. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  1. Antimicrobial Polymers with Metal Nanoparticles

    PubMed Central

    Palza, Humberto

    2015-01-01

    Metals, such as copper and silver, can be extremely toxic to bacteria at exceptionally low concentrations. Because of this biocidal activity, metals have been widely used as antimicrobial agents in a multitude of applications related with agriculture, healthcare, and the industry in general. Unlike other antimicrobial agents, metals are stable under conditions currently found in the industry allowing their use as additives. Today these metal based additives are found as: particles, ions absorbed/exchanged in different carriers, salts, hybrid structures, etc. One recent route to further extend the antimicrobial applications of these metals is by their incorporation as nanoparticles into polymer matrices. These polymer/metal nanocomposites can be prepared by several routes such as in situ synthesis of the nanoparticle within a hydrogel or direct addition of the metal nanofiller into a thermoplastic matrix. The objective of the present review is to show examples of polymer/metal composites designed to have antimicrobial activities, with a special focus on copper and silver metal nanoparticles and their mechanisms. PMID:25607734

  2. Antimicrobial activity of quaternized heteroxylans.

    PubMed

    Ebringerová, A; Belicová, A; Ebringer, L

    1994-11-01

    A series of quaternized D-xylan polysaccharides, differing in the structural features of their macromolecular backbone, were tested for antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Saccharomyces cerevisiae. Activity was comparable with that of the cationic surfactant, cetyltrimethylammonium bromide, and depended on the degree of quaternization and the structural backbone of the derivatives.

  3. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-06-10

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity.

  4. Antimicrobial activity of Securidaca longipedunculata.

    PubMed

    Ajali, U; Chukwurah, B K C

    2004-11-01

    The folk herbal uses of Securidaca longipedunculata in the treatment of diarrhea, boils, gonorrhea, and cough prompted phytochemical analyses and antimicrobial activity screening of extracts of the root. Some flavonoids isolated showed activity against many micro-organisms. These flavonoids were isolated using chromatographic methods. PMID:15636189

  5. The in Vitro Immune-Modulating Properties of a Sweat Gland-Derived Antimicrobial Peptide Dermcidin.

    PubMed

    Wang, Echo; Qiang, Xiaoling; Li, Jianhua; Zhu, Shu; Wang, Ping

    2016-01-01

    The epidermal barriers of the skin serve as the first layer of defense by limiting the access of many pathogens to the blood circulation. In addition, human skin also contains sweat glands that can secrete a wide array of antimicrobial peptides to restrain the growth of various microbes. In the case of microbial infection, macrophages and monocytes constitute the first line of defense by producing a wide array of proinflammatory cytokines and chemokines. This process is triggered either by pathogen-associated molecular pattern molecules (such as bacterial endotoxin) or damage-associated molecular pattern molecules (such as HMGB1). In light of our findings that a sweat gland-derived antimicrobial peptide, dermcidin, affected both pathogen-associated molecular pattern and damage-associated molecular pattern-induced cytokines/chemokines by macrophages/monocytes, we propose that dermcidin may play an important role in the regulation of the innate immune responses to infection and injury. Future investigations are warranted to further test this understudied hypothesis in both preclinical and clinical settings.

  6. Combating Antimicrobial Resistance in Foodborne Microorganisms.

    PubMed

    Lai, Edward P C; Iqbal, Zafar; Avis, Tyler J

    2016-02-01

    This review addresses an important public health hazard affecting food safety. Antimicrobial agents are used in foods to reduce or eliminate microorganisms that cause disease. Many traditional organic compounds, novel synthetic organic agents, natural products, peptides, and proteins have been extensively studied for their effectiveness as antimicrobial agents against foodborne Campylobacter spp., Escherichia coli, Listeria spp. and Salmonella. However, antimicrobial resistance can develop in microorganisms, enhancing their ability to withstand the inhibiting or killing action of antimicrobial agents. Knowledge gaps still exist with regard to the actual chemical and microbiological mechanisms that must be identified to facilitate the search for new antimicrobial agents. Technical implementation of antimicrobial active packing films and coatings against target microorganisms must also be improved for extended product shelf life. Recent advances in antimicrobial susceptibility testing can provide researchers with new momentum to pursue their quest for a resistance panacea.

  7. Access to effective antimicrobials: a worldwide challenge.

    PubMed

    Laxminarayan, Ramanan; Matsoso, Precious; Pant, Suraj; Brower, Charles; Røttingen, John-Arne; Klugman, Keith; Davies, Sally

    2016-01-01

    Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.

  8. Access to effective antimicrobials: a worldwide challenge.

    PubMed

    Laxminarayan, Ramanan; Matsoso, Precious; Pant, Suraj; Brower, Charles; Røttingen, John-Arne; Klugman, Keith; Davies, Sally

    2016-01-01

    Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics. PMID:26603918

  9. Antimicrobial activity of trout hepcidin.

    PubMed

    Alvarez, Claudio A; Guzmán, Fanny; Cárdenas, Constanza; Marshall, Sergio H; Mercado, Luis

    2014-11-01

    Hepcidin is an antimicrobial peptide and a hormone produced mostly the liver. It is a cysteine-rich peptide with a highly conserved β-sheet structure. Recently, we described the hepcidin expression in liver of rainbow trout and its inducibility by iron overloading and lipopolysaccharide (LPS). Thus, in this work, we focused in analyzing the importance of the peptide conformation associated to its oxidative state in the antimicrobial activity. This peptide showed a α-helix conformation in reduced state and the characteristic β-sheet conformation in the oxidized state. Antimicrobial activity assays showed that the oxidized peptide is more effective than the reduced peptide against Escherichia coli and the important salmon fish pathogen Piscirickettsia salmonis. In addition, confocal analysis of P. salmonis culture exposed to trout hepcidin coupled with rhodamine revealed the intracellular location of this peptide and Sytox permeation assay showed that membrane disruption is not the mechanism of its antimicrobial action. Moreover, a conserved ATCUN motif was detected in the N-terminus of this peptide. This sequence has been described as a small metal-binding site that has been implicated in DNA cleavage. In this work we proved that this peptide is able to induce DNA hydrolysis in the presence of ascorbate and CuCl2. When the same experiments were carried out using a variant with truncated N-terminus no DNA hydrolysis was observed. Our results suggest that correct folding of hepcidin is required for its antimicrobial activity and most likely the metal-binding site (ATCUN motif) present in its N-terminus is involved in the oxidative damage to macromolecules. PMID:24794583

  10. Antimicrobial Stewardship and Urinary Tract Infections

    PubMed Central

    Abbo, Lilian M.; Hooton, Thomas M.

    2014-01-01

    Urinary tract infections are the most common bacterial infections encountered in ambulatory and long-term care settings in the United States. Urine samples are the largest single category of specimens received by most microbiology laboratories and many such cultures are collected from patients who have no or questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed inappropriately in such patients. Antimicrobial use, whether appropriate or inappropriate, is associated with the selection for antimicrobial-resistant organisms colonizing or infecting the urinary tract. Infections caused by antimicrobial-resistant organisms are associated with higher rates of treatment failures, prolonged hospitalizations, increased costs and mortality. Antimicrobial stewardship consists of avoidance of antimicrobials when appropriate and, when antimicrobials are indicated, use of strategies to optimize the selection, dosing, route of administration, duration and timing of antimicrobial therapy to maximize clinical cure while limiting the unintended consequences of antimicrobial use, including toxicity and selection of resistant microorganisms. This article reviews successful antimicrobial stewardship strategies in the diagnosis and treatment of urinary tract infections. PMID:27025743

  11. IL-10 inhibits while calcitriol reestablishes placental antimicrobial peptides gene expression.

    PubMed

    Olmos-Ortiz, Andrea; Noyola-Martínez, Nancy; Barrera, David; Zaga-Clavellina, Verónica; Avila, Euclides; Halhali, Ali; Biruete, Benjamín; Larrea, Fernando; Díaz, Lorenza

    2015-04-01

    IL-10 and calcitriol help to achieve a successful pregnancy by suppressing active maternal immunity; however, these factors exert opposite effects upon microbial infections. In the skin and immune cells, IL-10 downregulates β-defensins while calcitriol induces cathelicidin gene expression in various tissues including placenta. Though, the regulation of human placental β-defensins by IL-10 and calcitriol has not been studied. Therefore, we explored the regulation of these antimicrobial peptides expression in cultured placental cells by calcitriol and IL-10 alone and combined. Real time PCR showed that calcitriol stimulated, while IL-10 inhibited, β-defensins and cathelicidin gene expression (P<0.05). In coincubations studies, calcitriol was able to maintain antimicrobial peptides gene expression above control values, overriding IL-10 inhibitory effects. Calcitriol downregulated endogenous IL-10 secretion. Interestingly, calcitriol and TNF-α cooperatively enhanced β-defensins, while TNF-α reduced basal and calcitriol-stimulated cathelicidin gene expression. In summary, calcitriol and IL-10 exerted opposite effects on antimicrobial peptides expression in the human placenta, suggesting that unbalanced production of IL-10 and calcitriol could be deleterious to innate immune responses during gestation. Our results suggest that calcitriol enhancement of placental defenses involves two mechanisms: (1) downregulation of IL-10 secretion and (2) direct upregulation of β-defensins and cathelicidin gene expression. Considering that IL-10 and calcitriol differentially regulate the innate immune response in the placenta, in the case of an infection, calcitriol might restrict IL-10 permissive actions towards microbial invasion while restrains inflammation, allowing for pregnancy to continue in quiescence. These results strongly advice maternal vitamin D sufficiency during pregnancy.

  12. Antimicrobial peptides in the brain.

    PubMed

    Su, Yanhua; Zhang, Kai; Schluesener, Hermann J

    2010-10-01

    Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune system of many species. The brain is an immunologically privileged organ but can produce a robust immune response against pathogens and cell debris, promoting rapid and efficient clearance. AMPs may be critically involved in the innate immune system of the brain. Though the mechanisms of AMPs' action in the brain still need further elucidation, many studies have shown that AMPs are multifunctional molecules in the brain. In addition to antimicrobial action, they take part in congenital and adaptive immune reactions (immunoregulation), function as signaling molecules in tissue repair, inflammation and other important processes through different mechanisms, and they might, in addition, become diagnostic markers of brain disease.

  13. Antimicrobial resistance of mastitis pathogens.

    PubMed

    Oliver, Stephen P; Murinda, Shelton E

    2012-07-01

    Antibiotics are used extensively in the dairy industry to combat disease and to improve animal performance. Antibiotics such as penicillin, cephalosporin, streptomycin, and tetracycline are used for the treatment and prevention of diseases affecting dairy cows caused by a variety of gram-positive and gram-negative bacteria. Antibiotics are often administrated routinely to entire herds to prevent mastitis during the dry period. An increase in the incidence of disease in a herd generally results in increased use of antimicrobials, which in turn increases the potential for antibiotic residues in milk and the potential for increased bacterial resistance to antimicrobials. Continued use of antibiotics in the treatment and prevention of diseases of dairy cows will continue to be scrutinized. It is clear that strategies employing the prudent use of antimicrobials are needed. This clearly illustrates the importance of effective herd disease prevention and control programs. Based on studies published to date, scientific evidence does not support widespread, emerging resistance among mastitis pathogens to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in dairy cows can contribute to increased antimicrobial resistance. While antimicrobial resistance does occur, we are of the opinion that the advantages of using antibiotics for the treatment of mastitis far outweigh the disadvantages. The clinical consequences of antimicrobial resistance of dairy pathogens affecting humans appear small. Antimicrobial resistance among dairy pathogens, particularly those found in milk, is likely not a human health concern as long as the milk is pasteurized. However, there are an increasing number of people who choose to consume raw milk. Transmission of an antimicrobial-resistant mastitis pathogen and/or foodborne pathogen to humans could occur

  14. Antimicrobial resistance in Saudi Arabia

    PubMed Central

    Zowawi, Hosam M.

    2016-01-01

    Antimicrobial resistance (AMR) is increasingly being highlighted as an urgent public and animal health issue worldwide. This issue is well demonstrated in bacteria that are resistant to last-line antibiotics, suggesting a future with untreatable infections. International agencies have suggested combating strategies against AMR. Saudi Arabia has several challenges that can stimulate the emergence and spread of multidrug-resistant bacteria. Tackling these challenges need efforts from multiple sectors to successfully control the spread and emergence of AMR in the country. Actions should include active surveillance to monitor the emergence and spread of AMR. Infection prevention and control precautions should also be optimized to limit further spread. Raising awareness is essential to limit inappropriate antibiotics use, and the antibiotic stewardship programs in hospital settings, outpatients, and community pharmacies, should regulate the ongoing use of antimicrobials. PMID:27570847

  15. Bacteriophage endolysins as novel antimicrobials

    PubMed Central

    Schmelcher, Mathias; Donovan, David M; Loessner, Martin J

    2013-01-01

    Endolysins are enzymes used by bacteriophages at the end of their replication cycle to degrade the peptidoglycan of the bacterial host from within, resulting in cell lysis and release of progeny virions. Due to the absence of an outer membrane in the Gram-positive bacterial cell wall, endolysins can access the peptidoglycan and destroy these organisms when applied externally, making them interesting antimicrobial candidates, particularly in light of increasing bacterial drug resistance. This article reviews the modular structure of these enzymes, in which cell wall binding and catalytic functions are separated, as well as their mechanism of action, lytic activity and potential as antimicrobials. It particularly focuses on molecular engineering as a means of optimizing endolysins for specific applications, highlights new developments that may render these proteins active against Gram-negative and intracellular pathogens and summarizes the most recent applications of endolysins in the fields of medicine, food safety, agriculture and biotechnology. PMID:23030422

  16. Antimicrobial Peptides from Marine Proteobacteria

    PubMed Central

    Desriac, Florie; Jégou, Camille; Balnois, Eric; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

    2013-01-01

    After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs. PMID:24084784

  17. Cholic acid derivatives: novel antimicrobials.

    PubMed

    Savage, P B; Li, C

    2000-02-01

    Mimics of squalamine and polymyxin B (PMB) have been prepared from cholic acid in hope of finding new antimicrobial agents. The squalamine mimics include the polyamine and sulphate functionalities found in the parent antibiotic, however, the positions relative to the steroid nucleus have been exchanged. The PMB mimics include the conservation of functionality among the polymyxin family of antibiotics, the primary amine groups and a hydrophobic chain. Although the squalamine and PMB mimics are morphologically dissimilar, they display similar activities. Both are simple to prepare and demonstrate broad spectrum antimicrobial activity against Gram-negative and Gram-positive organisms. Specific examples may be inactive alone, yet effectively permeabilise the outer membranes of Gram-negative bacteria rendering them sensitive to hydrophobic antibiotics. Problems associated with some of the squalamine and PMB mimics stem from their haemolytic activity and interactions with serum proteins, however, examples exist without these side effects which can sensitise Gram-negative bacteria to hydrophobic antibiotics. PMID:11060676

  18. Antimicrobials & cholera: are we stranded?

    PubMed

    Ghosh, Amit; Ramamurthy, T

    2011-02-01

    Antimicrobial resistance poses a major threat in the treatment of infectious diseases. Though significant progress in the management of diarrhoeal diseases has been achieved by improved hygiene, development of new antimicrobials and vaccines, the burden remains the same, especially in children below 5 yr of age. In the case of cholera, though oral rehydration treatment is the mainstay, antimicrobial therapy is mandatory at times to reduce the volume of stool and shorten the duration of the disease. Though for many pathogens, antimicrobial resistance emerged soon after the introduction of antibiotics, Vibrio cholerae remained sensitive to most of the antibiotics for quite a long period. However, the scenario changed over the years and today, V. cholerae strains isolated world over are resistant to multiple antibiotics. A myriad number of mechanisms underlie this phenomenon. These include production of extended-spectrum beta-lactamases, enhanced multi-drug efflux pump activity, plasmid-mediated quinolone and fluoroquinolone resistance, and chromosomal mutations. Horizontal transfer of resistance determinants with mobile genetic elements like integrons and the integrating conjugative elements (ICEs), SXTs help in the dissemination of drug resistance. Though all strains isolated are not resistant to all antibiotics and we are not as yet "stranded", expanding spectrum of drug resistance is a definite cause for concern. Pipelines of discovery of new antibiotics are drying up as major pharmaceutical companies are losing interest in investing money in this endeavour, mainly due to the short shelf-life of the antibiotics and also due to the fast emergence of drug resistance. To address this issue, attempts are now being made to discover drugs which are pathogen specific and target their "virulence mechanisms". It is expected that development of resistance against such antibiotics would take much longer. This review briefly focuses on all these issues.

  19. Benchmarking antimicrobial drug use in hospitals.

    PubMed

    Ibrahim, Omar M; Polk, Ron E

    2012-04-01

    Measuring and monitoring antibiotic use in hospitals is believed to be an important component of the strategies available to antimicrobial stewardship programs to address acquired antimicrobial resistance. Recent efforts to organize large numbers of hospitals into networks allow for interhospital comparisons of a variety of healthcare processes and outcomes, a process often called 'benchmarking'. For comparisons of antimicrobial use to be valid, usage figures must be risk-adjusted to account for differences in patient mix and hospital characteristics. The purpose of this review is to describe recent methods to benchmark antimicrobial drug use and to critically assess the potential advantages and the remaining challenges. While many methodological challenges remain, and the clinical outcomes resulting from benchmarking programs have yet to be determined, recent developments suggest that benchmarking antimicrobial drug use will become an important component of antimicrobial stewardship program activities.

  20. Antimicrobial hydrogels for the treatment of infection

    PubMed Central

    Veiga, Ana Salomé; Schneider, Joel P.

    2014-01-01

    The increasing prevalence of microbial infections, especially those associated with impaired wound healing and biomedical implant failure has spurred the development of new materials having antimicrobial activity. Hydrogels are a class of highly hydrated material finding use in diverse medical applications such as drug delivery, tissue engineering, as wound fillers and as implant coatings, to name a few. The biocompatible nature of many gels make them a convenient starting platform to develop selectively active antimicrobial materials. Hydrogels with antimicrobial properties can be obtained through the encapsulation or covalent immobilization of known antimicrobial agents, or the material itself can be designed to possess inherent antimicrobial activity. In this review we present an overview of antimicrobial hydrogels that have recently been developed and when possible provide a discussion relevant to their mechanism of action. PMID:24122459

  1. Antimicrobial hydrogels for the treatment of infection.

    PubMed

    Veiga, Ana Salomé; Schneider, Joel P

    2013-11-01

    The increasing prevalence of microbial infections, especially those associated with impaired wound healing and biomedical implant failure has spurred the development of new materials having antimicrobial activity. Hydrogels are a class of highly hydrated material finding use in diverse medical applications such as drug delivery, tissue engineering, as wound fillers, and as implant coatings, to name a few. The biocompatible nature of many gels make them a convenient starting platform to develop selectively active antimicrobial materials. Hydrogels with antimicrobial properties can be obtained through the encapsulation or covalent immobilization of known antimicrobial agents, or the material itself can be designed to possess inherent antimicrobial activity. In this review we present an overview of antimicrobial hydrogels that have recently been developed and when possible provide a discussion relevant to their mechanism of action.

  2. Use of antimicrobial agents in aquaculture.

    PubMed

    Park, Y H; Hwang, S Y; Hong, M K; Kwon, K H

    2012-04-01

    The aquaculture industry has grown dramatically, and plays an important role in the world's food supply chain. Antimicrobial resistance in bacteria associated with food animals receives much attention, and drug use in aquaculture is also an important issue. There are many differences between aquatic and terrestrial management systems, such as the methods used for administration of drugs. Unique problems are related to the application of drugs in aquatic environments. Residual drugs in fish products can affect people who consume them, and antimicrobials released into aquatic environments can select for resistant bacteria. Moreover, these antimicrobial-resistant bacteria, or their resistance genes, can be transferred to humans. To decrease the risks associated with the use of antimicrobials, various regulations have been developed. In addition, it is necessary to prevent bacterial diseases in aquatic animals by vaccination, to improve culture systems, and to monitor the amount of antimicrobial drugs used and the prevalence of antimicrobial-resistant bacteria.

  3. Collagen-like antimicrobial peptides.

    PubMed

    Masuda, Ryo; Kudo, Masakazu; Dazai, Yui; Mima, Takehiko; Koide, Takaki

    2016-11-01

    Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016. PMID:27271210

  4. Plant Products as Antimicrobial Agents

    PubMed Central

    Cowan, Marjorie Murphy

    1999-01-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations. PMID:10515903

  5. Antimicrobial Properties of Amyloid Peptides

    PubMed Central

    Kagan, Bruce L.; Jang, Hyunbum; Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh; Nussinov, Ruth

    2011-01-01

    More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-β structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape β-strand-turn-β-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids are not only toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function. PMID:22081976

  6. Insect inducible antimicrobial peptides and their applications.

    PubMed

    Ezzati-Tabrizi, Reyhaneh; Farrokhi, Naser; Talaei-Hassanloui, Reza; Alavi, Seyed Mehdi; Hosseininaveh, Vahid

    2013-12-01

    Antimicrobial peptides (AMPs) are found as important components of the innate immune system (host defense) of all invertebrates. These peptides can be constitutively expressed or induced in response to microbial infections. Indeed, they vary in their amino acid sequences, potency and antimicrobial activity spectra. The smaller AMPs act greatly by disrupting the structure or function of microbial cell membranes. Here, the insect innate immune system with emphasis on inducible antimicrobial peptide properties against microbial invaders has been discussed.

  7. Correlations between Income Inequality and Antimicrobial Resistance

    PubMed Central

    Kirby, Andrew; Herbert, Annie

    2013-01-01

    Objectives The aim of this study is to investigate if correlations exist between income inequality and antimicrobial resistance. This study’s hypothesis is that income inequality at the national level is positively correlated with antimicrobial resistance within developed countries. Data collection and analysis Income inequality data were obtained from the Standardized World Income Inequality Database. Antimicrobial resistance data were obtained from the European antimicrobial Resistance Surveillance Network and outpatient antimicrobial consumption data, measured by Defined daily Doses per 1000 inhabitants per day, from the European Surveillance of antimicrobial Consumption group. Spearman’s correlation coefficient (r) defined strengths of correlations of: > 0.8 as strong, > 0.5 as moderate and > 0.2 as weak. Confidence intervals and p values were defined for all r values. Correlations were calculated for the time period 2003-10, for 15 European countries. Results Income inequality and antimicrobial resistance correlations which were moderate or strong, with 95% confidence intervals > 0, included the following. Enterococcus faecalis resistance to aminopenicillins, vancomycin and high level gentamicin was moderately associated with income inequality (r= ≥0.54 for all three antimicrobials). Escherichia coli resistance to aminoglycosides, aminopenicillins, third generation cephalosporins and fluoroquinolones was moderately-strongly associated with income inequality (r= ≥0.7 for all four antimicrobials). Klebsiella pneumoniae resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones was moderately associated with income inequality (r= ≥0.5 for all three antimicrobials). Staphylococcus aureus methicillin resistance and income inequality were strongly associated (r=0.87). Conclusion As income inequality increases in European countries so do the rates of antimicrobial resistance for bacteria including E. faecalis, E. coli, K. pneumoniae

  8. Antimicrobial technology in orthopedic and spinal implants

    PubMed Central

    Eltorai, Adam EM; Haglin, Jack; Perera, Sudheesha; Brea, Bielinsky A; Ruttiman, Roy; Garcia, Dioscaris R; Born, Christopher T; Daniels, Alan H

    2016-01-01

    Infections can hinder orthopedic implant function and retention. Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion. Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems, material science, immunology, and polymer chemistry are in development and early clinical use. This review outlines orthopedic implant antimicrobial technology, its current applications and supporting evidence, and clinically promising future directions. PMID:27335811

  9. Antimicrobial polymer films for food packaging

    NASA Astrophysics Data System (ADS)

    Concilio, S.; Piotto, S.; Sessa, L.; Iannelli, P.; Porta, A.; Calabrese, E. C.; Galdi, M. R.; Incarnato, L.

    2012-07-01

    New antimicrobial polymeric systems were realized introducing new antimicrobial azo compounds in PP and LDPE matrices. The polymeric materials containing different percentage of azo compounds were mold-casted and the obtained film were tested in vitro against Gram+ and Gram- bacteria and fungi. These results hold promise for the fabrication of bacteria-resistant polymer films by means of simple melt processing with antimicrobial azo-dyes.

  10. Outpatient parenteral antimicrobial therapy in pediatrics: an opportunity to expand antimicrobial stewardship.

    PubMed

    Knackstedt, Elizabeth D; Stockmann, Chris; Davis, Carly R; Thorell, Emily A; Pavia, Andrew T; Hersh, Adam L

    2015-02-01

    We reviewed patient discharges with outpatient parenteral antimicrobial therapy (OPAT) to determine whether outpatient parenteral antimicrobial therapy was modifiable or unnecessary at a large tertiary care children's hospital. At least one modification definitely or possibly would have been recommended for 78% of episodes. For more than 40% of episodes, outpatient parenteral antimicrobial therapy was potentially not indicated. PMID:25633007

  11. Promoting antimicrobial stewardship: using video tools for junior doctors' induction.

    PubMed

    Hadjiphilippou, Savvas; Odogwu, Sarah-Elizabeth; Jeyaratnam, Dakshika

    2014-02-01

    Antimicrobial prescribing is linked to key issues in infection control and patient safety. This article presents a novel video tool for junior doctors promoting antimicrobial stewardship, and thus safe antimicrobial prescribing, through improved awareness of local information technology systems.

  12. Antimicrobial use and resistance in animals.

    PubMed

    McEwen, Scott A; Fedorka-Cray, Paula J

    2002-06-01

    Food animals in the United States are often exposed to antimicrobials to treat and prevent infectious disease or to promote growth. Many of these antimicrobials are identical to or closely resemble drugs used in humans. Precise figures for the quantity of antimicrobials used in animals are not publicly available in the United States, and estimates vary widely. Antimicrobial resistance has emerged in zoonotic enteropathogens (e.g., Salmonella spp., Campylobacter spp.), commensal bacteria (e.g., Escherichia coli, enterococci), and bacterial pathogens of animals (e.g., Pasteurella, Actinobacillus spp.), but the prevalence of resistance varies. Antimicrobial resistance emerges from the use of antimicrobials in animals and the subsequent transfer of resistance genes and bacteria among animals and animal products and the environment. To slow the development of resistance, some countries have restricted antimicrobial use in feed, and some groups advocate similar measures in the United States. Alternatives to growth-promoting and prophylactic uses of antimicrobials in agriculture include improved management practices, wider use of vaccines, and introduction of probiotics. Monitoring programs, prudent use guidelines, and educational campaigns provide approaches to minimize the further development of antimicrobial resistance. PMID:11988879

  13. The Potential of Antimicrobial Peptides as Biocides

    PubMed Central

    Laverty, Garry; Gorman, Sean P.; Gilmore, Brendan F.

    2011-01-01

    Antimicrobial peptides constitute a diverse class of naturally occurring antimicrobial molecules which have activity against a wide range of pathogenic microorganisms. Antimicrobial peptides are exciting leads in the development of novel biocidal agents at a time when classical antibiotics are under intense pressure from emerging resistance, and the global industry in antibiotic research and development stagnates. This review will examine the potential of antimicrobial peptides, both natural and synthetic, as novel biocidal agents in the battle against multi-drug resistant pathogen infections. PMID:22072905

  14. [Pattern of antimicrobial susceptibility of enterococci strains].

    PubMed

    Hoyos, A; Gutiérrez, J; Piédrola, G

    1995-04-01

    Enterococci resistance to antimicrobials has increased lately. We studied the susceptibility to 12 antimicrobials of 150 enterococci strains coming from hospitalized and outpatients, using the agar dilution method. Teicoplanin, followed by imipenem and amoxicilin-clavulanic acid had the lower minimal inhibitory concentrations. No strains of E faecalis was resistant to ampicillin, whereas 14% of E faecium had minimal inhibitory concentrations over 8 micrograms/ml. The high minimal inhibitory concentrations of cefpirome (64 micrograms/ml) renders this antimicrobial useless in the treatment of enterococcal infections. Betalactamase production and resistance to glucopeptides were not detected. Antimicrobial susceptibility of strains coming for hospitalized or outpatients were similar.

  15. Antimicrobial Resistance: Is the World UNprepared?

    PubMed

    2016-09-01

    Long Blurb: On September 21st 2016 the United Nations General Assembly convenes in New York, United States to tackle a looming and seemingly inevitable global challenge with the potential to threaten the health and wellbeing of all people: antimicrobial resistance. In an Editorial, the PLOS Medicine Editors reflect on the challenge of coordinating the response to antimicrobial resistance in order to ensure the viability of current antimicrobials and the development of new therapies against resistant pathogens. Short Blurb: In this month's Editorial, the PLOS Medicine Editors reflect on the upcoming United Nations General Assembly meeting which convenes to discuss the global challenge of antimicrobial resistance. PMID:27618631

  16. Presence of antimicrobial resistance and antimicrobial use in sows are risk factors for antimicrobial resistance in their offspring.

    PubMed

    Callens, Bénédicte; Faes, Christel; Maes, Dominiek; Catry, Boudewijn; Boyen, Filip; Francoys, Delphine; de Jong, Ellen; Haesebrouck, Freddy; Dewulf, Jeroen

    2015-02-01

    This study investigated whether antimicrobial-resistant Escherichia coli in apparently healthy sows and antimicrobial administration to sows and piglets influenced antimicrobial resistance in fecal commensal E. coli from piglets. Sixty sows from three herds and three of their piglets were sampled at several time points. Antimicrobial usage data during parturition and farrowing were collected. Clinical resistance was determined for two isolates per sampling time point for sows and piglets using disk diffusion. Only 27.4% of E. coli isolates from newborn piglets showed no resistance. Resistance to one or two antimicrobial classes equaled 41.2% and 46.8% in isolates from sows and piglets, respectively, for the overall farrowing period. Multiresistance to at least four classes was found as frequently in sows (15.6%) as in piglets (15.2%). Antimicrobial resistance in piglets was influenced by antimicrobial use in sows and piglets and by the sow resistance level (p≤0.05). Using aminopenicillins and third-generation cephalosporins in piglets affected resistance levels in piglets (odds ratios [OR] >1; p≤0.05). Using enrofloxacin in piglets increased the odds for enrofloxacin resistance in piglets (OR=26.78; p≤0.0001) and sows at weaning (OR=4.04; p≤0.05). For sows, antimicrobial exposure to lincomycin-spectinomycin around parturition increased the resistance to ampicillin, streptomycin, trimethoprim-sulfadiazine in sows (OR=21.33, OR=142.74, OR=18.03; p≤0.05) and additionally to enrofloxacin in piglets (OR=7.50; p≤0.05). This study demonstrates that antimicrobial use in sows and piglets is a risk factor for antimicrobial resistance in the respective animals. Moreover, resistance determinants in E. coli from piglets are selected by using antimicrobials in their dam around parturition.

  17. Antimicrobial drugs for treating cholera

    PubMed Central

    Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

    2014-01-01

    Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. Objectives To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Selection criteria Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Data collection and analysis Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Main results Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43

  18. The contribution of nasal receptors to the cardiac response to diving in restrained and unrestrained redhead ducks (Aythya americana).

    PubMed

    Furilla, R A; Jones, D R

    1986-03-01

    In restrained redhead ducks, forced submergence caused heart rate to fall from 100 +/- 3 beats min-1 (mean +/- S.E.M., N = 12) to a stable underwater rate of 35 +/- 4 beats min-1 (N = 12) within 5 s after submergence. Bradycardia was unaffected by breathing oxygen before a dive, but was virtually eliminated by local anaesthesia of the narial region. In contrast, in a dabbling duck (Anas platyrhynchos) bradycardia in short dives was eliminated by breathing oxygen before a dive. In unrestrained diving, on a man-made pond, heart rate in redheads diving voluntarily (y) was related to pre-dive heart rate (x) by the equation y = 76 + 0.29 +/- 0.05x +/- 17 (r2 = 0.71). Chasing, to induce submergence, had variable effects on this relationship. Local anaesthesia of the narial region inhibited voluntary diving but heart rates in chase-induced dives after nasal blockade were significantly higher, by 10-30%, than those obtained from untreated ducks in chase-induced dives. Breathing oxygen before voluntary dives had no apparent effect on heart rate after 2-5 s submergence. Voluntary head submersion by dabbling ducks caused no change in heart rate. We conclude that nasal receptors make only a minor contribution to cardiac responses in unrestrained dives, compared with forced dives, in diving ducks. Furthermore, these results show that little can be learned about cardiac responses in free diving ducks from studies of forced dives in dabblers or divers. PMID:3958677

  19. A method to restrain the charging effect on an insulating substrate in high energy electron beam lithography

    NASA Astrophysics Data System (ADS)

    Mingyan, Yu; Shirui, Zhao; Yupeng, Jing; Yunbo, Shi; Baoqin, Chen

    2014-12-01

    Pattern distortions caused by the charging effect should be reduced while using the electron beam lithography process on an insulating substrate. We have developed a novel process by using the SX AR-PC 5000/90.1 solution as a spin-coated conductive layer, to help to fabricate nanoscale patterns of poly-methyl-methacrylate polymer resist on glass for phased array device application. This method can restrain the influence of the charging effect on the insulating substrate effectively. Experimental results show that the novel process can solve the problems of the distortion of resist patterns and electron beam main field stitching error, thus ensuring the accuracy of the stitching and overlay of the electron beam lithography system. The main characteristic of the novel process is that it is compatible to the multi-layer semiconductor process inside a clean room, and is a green process, quite simple, fast, and low cost. It can also provide a broad scope in the device development on insulating the substrate, such as high density biochips, flexible electronics and liquid crystal display screens.

  20. Manganese-containing cellulose nanocomposites: the restrain effect of cellulose treated with NaOH/urea aqueous solutions.

    PubMed

    Ma, Ming-Guo; Deng, Fu; Yao, Ke

    2014-10-13

    In this article, the manganese-containing cellulose nanocomposites were obtained using microcrystalline cellulose and Mn(CH3COO)2 · 4H2O in the NaOH/urea aqueous solutions by a efficient microwave-assisted method. The effects of the heating time and Mn(CH3COO)2 · 4H2O concentration on the cellulose nanocomposites were investigated. It was found that the microcrystalline cellulose pretreated with NaOH/urea aqueous solutions played an important role in the phase, shape, and thermal stability of manganese-containing cellulose nanocomposites. Well-crystalline phases of manganese oxides were not observed in the manganese-containing cellulose nanocomposites. Furthermore, well-crystalline phases of manganese oxides were not also observed by thermal treatment of the manganese-containing cellulose nanocomposites at 600 °C for 3h. These results could be attributed to the restrain effect of cellulose treated with NaOH/urea aqueous solutions. It was supposed the possible mechanism during the phase transformation of cellulose nanocomposites.

  1. Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

    SciTech Connect

    Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.; Shyamala, G.; Moses, Harold L.; Barcellos-Hoff, Mary Helen

    2005-03-03

    Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha} co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.

  2. Vibro-acoustic analysis of a rectangular cavity bounded by a flexible panel with elastically restrained edges.

    PubMed

    Du, Jing T; Li, Wen L; Xu, Hong A; Liu, Zhi G

    2012-04-01

    A coupled system consisting of an acoustic cavity and an elastic panel is a classical problem in structural acoustics and is typically analyzed using modal approaches based on in vacuo structural modes and the rigidly walled acoustic modes which are pre-determined based on separate component models. Such modeling techniques, however, tend to suffer the following drawbacks or limitations: (a) a panel is only subjected to ideal boundary conditions such as the simply supported, (b) the coupling between the cavity and panel is considered weak, and (c) the particle velocity cannot be correctly predicted from the pressure gradient on the contacting interface, to name a few. Motivated by removing these restrictions, this paper presents a general method for the vibro-acoustic analysis of a three-dimensional (3D) acoustic cavity bounded by a flexible panel with general elastically restrained boundary conditions. The displacement of the plate and the sound pressure in the cavity are constructed in the forms of standard two-dimensional and 3D Fourier cosine series supplemented by several terms introduced to ensure and accelerate the convergence of the series expansions. The unknown expansions coefficients are treated as the generalized coordinates and determined using the Rayleigh-Ritz procedure based on the energy expressions for the coupled structural acoustic system. The accuracy and effectiveness of the proposed method are demonstrated through numerical examples and comparisons with the results available in the literature.

  3. Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function.

    PubMed

    Matott, Michael P; Ruyle, Brian C; Hasser, Eileen M; Kline, David D

    2016-03-01

    The nucleus tractus solitarii (nTS) is the initial central termination site for visceral afferents and is important for modulation and integration of multiple reflexes including cardiorespiratory reflexes. Glutamate is the primary excitatory neurotransmitter in the nTS and is removed from the extracellular milieu by excitatory amino acid transporters (EAATs). The goal of this study was to elucidate the role of EAATs in the nTS on basal synaptic and neuronal function and cardiorespiratory regulation. The majority of glutamate clearance in the central nervous system is believed to be mediated by astrocytic EAAT 1 and 2. We confirmed the presence of EAAT 1 and 2 within the nTS and their colocalization with astrocytic markers. EAAT blockade withdl-threo-β-benzyloxyaspartic acid (TBOA) produced a concentration-related depolarization, increased spontaneous excitatory postsynaptic current (EPSC) frequency, and enhanced action potential discharge in nTS neurons. Solitary tract-evoked EPSCs were significantly reduced by EAAT blockade. Microinjection of TBOA into the nTS of anesthetized rats induced apneic, sympathoinhibitory, depressor, and bradycardic responses. These effects mimicked the response to microinjection of exogenous glutamate, and glutamate responses were enhanced by EAAT blockade. Together these data indicate that EAATs tonically restrain nTS excitability to modulate cardiorespiratory function.

  4. The Rho-GTPase Rnd1 Suppresses Mammary Tumorigenesis and EMT by Restraining Ras-MAPK signaling

    PubMed Central

    Okada, Tomoyo; Sinha, Surajit; Esposito, Ilaria; Schiavon, Gaia; López-Lago, Miguel A.; Su, Wenjing; Pratilas, Christine A.; Abele, Cristina; Hernandez, Jonathan M.; Ohara, Masahiro; Okada, Morihito; Viale, Agnes; Heguy, Adriana; Socci, Nicholas D.; Sapino, Anna; Seshan, Venkatraman E.; Long, Stephen; Inghirami, Giorgio; Rosen, Neal; Giancotti, Filippo G.

    2015-01-01

    SUMMARY We identified the Rho-GTPase Rnd1 as a candidate metastasis suppressor through bioinformatics analysis and showed that its depletion disrupt epithelial adhesion and polarity, induced Epithelial-to-Mesenchymal Transition (EMT), and cooperated with deregulated expression of c-Myc or loss of p53 to cause neoplastic conversion. Mechanistic studies revealed that Rnd1 suppresses Ras signalling by activating the GAP domain of Plexin B1, which inhibits Rap1. Rap1 inhibition in turn led to derepression of p120-RasGAP, which was able to inhibit Ras. Inactivation of Rnd1 in mammary epithelial cells induced highly undifferentiated and invasive tumors in mice. Conversely, Rnd1 expression inhibited spontaneous and experimental lung colonization in mouse models of metastasis. Genomic studies indicated that gene deletion in combination with epigenetic silencing or, more rarely, point mutation inactivates RND1 in human breast cancer. These results reveal a previously unappreciated mechanism through which Rnd1 restrains activation of Ras-MAPK signaling and breast tumor initiation and progression. PMID:25531777

  5. Catalytic stimulation by restrained active-site floppiness--the case of high density lipoprotein-bound serum paraoxonase-1.

    PubMed

    Ben-David, Moshe; Sussman, Joel L; Maxwell, Christopher I; Szeler, Klaudia; Kamerlin, Shina C L; Tawfik, Dan S

    2015-03-27

    Despite the abundance of membrane-associated enzymes, the mechanism by which membrane binding stabilizes these enzymes and stimulates their catalysis remains largely unknown. Serum paraoxonase-1 (PON1) is a lipophilic lactonase whose stability and enzymatic activity are dramatically stimulated when associated with high-density lipoprotein (HDL) particles. Our mutational and structural analyses, combined with empirical valence bond simulations, reveal a network of hydrogen bonds that connect HDL binding residues with Asn168--a key catalytic residue residing >15Å from the HDL contacting interface. This network ensures precise alignment of N168, which, in turn, ligates PON1's catalytic calcium and aligns the lactone substrate for catalysis. HDL binding restrains the overall motion of the active site and particularly of N168, thus reducing the catalytic activation energy barrier. We demonstrate herein that disturbance of this network, even at its most far-reaching periphery, undermines PON1's activity. Membrane binding thus immobilizes long-range interactions via second- and third-shell residues that reduce the active site's floppiness and pre-organize the catalytic residues. Although this network is critical for efficient catalysis, as demonstrated here, unraveling these long-rage interaction networks is challenging, let alone their implementation in artificial enzyme design.

  6. Holding and restraining children for clinical procedures within an acute care setting: an ethical consideration of the evidence.

    PubMed

    Bray, Lucy; Snodin, Jill; Carter, Bernie

    2015-06-01

    This critical reflection on the ethical concerns of current practice is underpinned by a systematic synthesis of current evidence focusing on why and how children are held or restrained for clinical procedures within acute care and the experiences of those present when a child is held against their wishes. Empirical evidence from a range of clinical settings internationally demonstrates that frequently children are held for procedures to be completed; younger children and those requiring procedures perceived as urgent are more likely to be held. Parents and health professionals express how holding children for procedures can cause feelings of moral distress expressed as uncertainty, guilt and upset and that this act breaches the trusting and protective relationship established with children. Despite this, children's rights and alternatives to holding are not always respected or explored. Children's experiences and perceptions are absent from current literature. Children and young people have a moral right to have their voice and protests heard and respected and for these to inform judgements of their best interests and the actions of health professionals. Without robust evidence, debate and recognition that children are frequently held against their wishes in clinical practice for procedures which may not be urgent, children's rights will continue to be compromised. PMID:25053126

  7. Restrain of bone growth by estrogen-mimetic peptide-1 (EMP-1): a micro-computed tomographic study.

    PubMed

    Kasher, Roni; Bajayo, Alon; Gabet, Yankel; Nevo, Nava; Fridkin, Mati; Katchalski-Katzir, Ephraim; Kohen, Fortune; Bab, Itai

    2009-06-01

    Estrogen has a key role in the regulation of skeletal growth and maintenance of bone mass. Recently, we developed peptides having estrogen-like activity as potential estrogen-based new drugs. The aim of the present study was to evaluate the influence of long-term administration of the most efficacious of these peptides, the hexapeptide EMP-1 (VSWFFE), on bone mass and development. EMP-1 was injected daily to ovariectomized (OVX) and intact young, sexually mature female mice for 10 weeks. Whole femora, including the cartilaginous growth plates were analyzed by micro-computed tomography (microCT). We found that peptide EMP-1 restrains bone growth in OVX mice: it inhibited dramatically bone longitudinal growth (40%), and decreased femoral diaphyseal diameter. Peptide EMP-1 had no effect on bone growth in normal mice, and did not influence the OVX-induced bone loss. We then developed a new microCT methodology to evaluate uncalcified and calcified growth plate parameters. In the OVX mice, peptide EMP-1 reduced volume and thickness of the uncalcified growth plate, a possible cause for the inhibition of bone longitudinal growth. Peptide EMP-1 may be used as a lead compound for the development of drugs to treat acromegalic patients.

  8. Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance.

    PubMed

    Holman, Devin B; Chénier, Martin R

    2015-11-01

    Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gut microbiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gut microbiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gut microbiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gut microbiota and on antimicrobial resistance determinants in the gut microbiota. PMID:26414105

  9. Antimicrobial peptides: premises and promises.

    PubMed

    Reddy, K V R; Yedery, R D; Aranha, C

    2004-12-01

    Antimicrobial peptides (AMPs) are an important component of the natural defences of most living organisms against invading pathogens. These are relatively small (< 10kDa), cationic and amphipathic peptides of variable length, sequence and structure. During the past two decades several AMPs have been isolated from a wide variety of animals, both vertebrates and invertebrates, and plants as well as from bacteria and fungi. Most of these peptides are obtained from different sources like macrophages, neutrophils, epithelial cells, haemocytes, fat body, reproductive tract, etc. These peptides exhibit broad-spectrum activity against a wide range of microorganisms including Gram-positive and Gram-negative bacteria, protozoa, yeast, fungi and viruses. A few peptides have also been found to be cytotoxic to sperm and tumour cells. AMPs are classified based on the three dimensional structural studies carried out with the help of NMR. The peptides are broadly classified into five major groups namely (a) peptides that form alpha-helical structures, (b) peptides rich in cysteine residues, (c) peptides that form beta-sheet, (d) peptides rich in regular amino acids namely histatin, arginine and proline and (e) peptides composed of rare and modified amino acids. Most of these peptides are believed to act by disrupting the plasma membrane leading to the lysis of the cell. AMPs have been found to be excellent candidates for developing novel antimicrobial agents and a few of these peptides show antimicrobial activity against pathogens causing sexually transmitted infection (STI), including HIV/HSV. Peptides, namely magainin and nisin have been shown to demonstrate contraceptive properties in vitro and in vivo. A few peptides have already entered clinical trials for the treatment of impetigo, diabetic foot ulcers and gastric helicobacter infections. In this review, we discuss the source, structures and mode of action with special reference to therapeutic considerations of various AMPs

  10. Antimicrobial edible films and coatings.

    PubMed

    Cagri, Arzu; Ustunol, Zeynep; Ryser, Elliot T

    2004-04-01

    Increasing consumer demand for microbiologically safer foods, greater convenience, smaller packages, and longer product shelf life is forcing the industry to develop new food-processing, cooking, handling, and packaging strategies. Nonfluid ready-to-eat foods are frequently exposed to postprocess surface contamination, leading to a reduction in shelf life. The food industry has at its disposal a wide range of nonedible polypropylene- and polyethylene-based packaging materials and various biodegradable protein- and polysaccharide-based edible films that can potentially serve as packaging materials. Research on the use of edible films as packaging materials continues because of the potential for these films to enhance food quality, food safety, and product shelf life. Besides acting as a barrier against mass diffusion (moisture, gases, and volatiles), edible films can serve as carriers for a wide range of food additives, including flavoring agents, antioxidants, vitamins, and colorants. When antimicrobial agents such as benzoic acid, sorbic acid, propionic acid, lactic acid, nisin, and lysozyme have been incorporated into edible films, such films retarded surface growth of bacteria, yeasts, and molds on a wide range of products, including meats and cheeses. Various antimicrobial edible films have been developed to minimize growth of spoilage and pathogenic microorganisms, including Listeria monocytogenes, which may contaminate the surface of cooked ready-to-eat foods after processing. Here, we review the various types of protein-based (wheat gluten, collagen, corn zein, soy, casein, and whey protein), polysaccharide-based (cellulose, chitosan, alginate, starch, pectin, and dextrin), and lipid-based (waxes, acylglycerols, and fatty acids) edible films and a wide range of antimicrobial agents that have been or could potentially be incorporated into such films during manufacture to enhance the safety and shelf life of ready-to-eat foods.

  11. Antimicrobial and biofilm inhibiting diketopiperazines.

    PubMed

    de Carvalho, M P; Abraham, W-R

    2012-01-01

    Diketopiperazines are the smallest cyclic peptides known. 90% of Gram-negative bacteria produce diketopiperazines and they have also been isolated from Gram-positive bacteria, fungi and higher organisms. Biosynthesis of cyclodipeptides can be achieved by dedicated nonribosomal peptide synthetases or by a novel type of synthetases named cyclopeptide synthases. Since the first report in 1924 a large number of bioactive diketopiperazines was discovered spanning activities as antitumor, antiviral, antifungal, antibacterial, antiprion, antihyperglycemic or glycosidase inhibitor agents. As infections are of increasing concern for human health and resistances against existing antibiotics are growing this review focuses on the antimicrobial activities of diketopiperazines. The antibiotic bicyclomycin is a diketopiperazine and structure activity studies revealed the unique nature of this compound which was finally developed for clinical applications. The antimicrobial activities of a number of other diketopiperazines along with structure activity relationships are discussed. Here a special focus is on the activity-toxicity problem of many compounds setting tight limitations to their application as drugs. Not only these classical antimicrobial activities but also proposed action in modulating bacterial communication as a new target to control biofilms will be evaluated. Pathogens organized in biofilms are difficult to eradicate because of the increase of their tolerance for antibiotics for several orders. Diketopiperazines were reported to modulate LuxR-mediated quorum-sensing systems of bacteria, and they are considered to influence cell-cell signaling offering alternative ways of biofilm control by interfering with microbial communication. Concluding the review we will finally discuss the potential of diketopiperazines in the clinic to erase biofilm infections.

  12. TESTING ANTIMICROBIAL EFFICACY ON POROUS MATERIALS

    EPA Science Inventory

    The efficacy of antimicrobial treatments to eliminate or control biological growth in the indoor environment can easily be tested on nonporous surfaces. However, the testing of antimicrobial efficacy on porous surfaces, such as those found in the indoor environment [i.e., gypsum ...

  13. Legal issues associated with antimicrobial drug resistance.

    PubMed Central

    Fidler, D. P.

    1998-01-01

    An effective public health strategy against the development of antimicrobial drug resistance needs to be informed by legal as well as scientific analysis. This article describes some legal issues arising from current efforts against antimicrobial resistance and underscores the interdependence between law and public health in these efforts. PMID:9621187

  14. Antimicrobial Constituents from Allium hookeri Root.

    PubMed

    Kima, Jung-Eun; Seo, Ji-Hye; Bae, Min-Suk; Bae, Chun-Sik; Yoo, Jin-Cheol; Bang, Mi-Ae; Cho, Seung-Sik; Park, Dae-Hun

    2016-02-01

    In this study, we partially purified the ethyl acetate soluble fraction of the ethanol extract of the root of Allum hookeri. We identified seven compounds, benzoic acid, tetradecanoic acid, hexadecanoic acid, ferulic acid, cinnamic acid, octadecanoic acid and hexanedioic acid, that have antimicrobial activity using GC-MS, and evaluated the antimicrobial susceptibility and MIC (minimum inhibitory concentration) against multidrug-resistant bacteria.

  15. Antimicrobial resistance issues in beef production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance threats to human health as identified have been recognized as a critical global public health concern. Linkage of some threats to beef production is discussed. The relevance to beef production of recent government actions will be examined. Prominent antimicrobial resistance ...

  16. Antimicrobial food packaging: potential and pitfalls

    PubMed Central

    Malhotra, Bhanu; Keshwani, Anu; Kharkwal, Harsha

    2015-01-01

    Nowadays food preservation, quality maintenance, and safety are major growing concerns of the food industry. It is evident that over time consumers’ demand for natural and safe food products with stringent regulations to prevent food-borne infectious diseases. Antimicrobial packaging which is thought to be a subset of active packaging and controlled release packaging is one such promising technology which effectively impregnates the antimicrobial into the food packaging film material and subsequently delivers it over the stipulated period of time to kill the pathogenic microorganisms affecting food products thereby increasing the shelf life to severe folds. This paper presents a picture of the recent research on antimicrobial agents that are aimed at enhancing and improving food quality and safety by reduction of pathogen growth and extension of shelf life, in a form of a comprehensive review. Examination of the available antimicrobial packaging technologies is also presented along with their significant impact on food safety. This article entails various antimicrobial agents for commercial applications, as well as the difference between the use of antimicrobials under laboratory scale and real time applications. Development of resistance amongst microorganisms is considered as a future implication of antimicrobials with an aim to come up with actual efficacies in extension of shelf life as well as reduction in bacterial growth through the upcoming and promising use of antimicrobials in food packaging for the forthcoming research down the line. PMID:26136740

  17. Cationic Antimicrobial Polymers and Their Assemblies

    PubMed Central

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2013-01-01

    Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

  18. Synthesis and antimicrobial activity of squalamine analogue.

    PubMed

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

  19. Antimicrobial Resistance in the Environment.

    PubMed

    Williams, Maggie R; Stedtfeld, Robert D; Guo, Xueping; Hashsham, Syed A

    2016-10-01

    This review summarizes important publications from 2015 pertaining to the occurrence of antimicrobial resistance (AMR) in the environment. Emphasis is placed on sources of antibiotic resistance in the aquatic environment including wastewater treatment plants, hospitals, and agriculture, treatment and mitigation techniques, and surveillance and analysis methodologies for characterizing abundance data. As such, this review is organized into the following sections: i) occurrence of AMR in the environment, including surface waters, aquaculture, and wastewater ii) treatment technologies, and iii) technologies for rapid surveillance of AMR, iv) transmission between matrices, v) databases and analysis methods, and vi) gaps in AMR understanding. PMID:27620115

  20. [Antimicrobial sensitive of Morganella morganii].

    PubMed

    Zalas-Wiecek, Patrycja; Michalska, Anna; Sielska, Barbara; Gospodarek, Eugenia

    2011-01-01

    The aim of this study was the evaluation of the antimicrobial sensitive of Morganella morganii rods isolated from clinical samples. This study included 50 of M. morganii strains isolated in the Clinical Microbiology Department of dr. A. Jurasz University Hospital in 2008-2009. All of strains were sensitive to carbapenems (imipenem, meropenem, ertapenem, doripenem) and piperacillin/tazobactam and most of them to beta-lactam antibiotics, aminoglycosides and fluorochinolons. Resistance to tetracyclines demonstrated 38,0% strains and to doxycycline - 40,0%. One out of 6 strains isolated from urine samples were sensitive to nitrofurantoin. Extended Spectrum Beta-Lactamases were produced by 5 (10,0%) strains.

  1. Outcomes of custody and visitation petitions when fathers are restrained by protection orders: the case of the New York family courts.

    PubMed

    Rosen, Leora N; O'Sullivan, Chris S

    2005-08-01

    A random sample of custody and visitation petitions filed in New York City Family Courts in 1995 was used to examine outcomes of mothers' Order of Protection (OP) Petitions in relation to parents' custody and visitation petitions. Fathers restrained by OPs were more likely to secure visitation orders (64%) than not. In contrast, 80.8% of fathers' custody petitions were dismissed when they were restrained by OPs. Fathers' custody petitions were most likely to be ordered when mothers' OP petitions were withdrawn. Mothers were most likely to secure custody when their OP petitions were ordered or withdrawn. Courts rarely denied petitions. Those that did not result in court orders were either withdrawn by the petitioner or dismissed by the court (most likely because of failure of the petitioner to appear in court). This pattern has negative implications for battered women who may be vulnerable to pressure or threats from abusive ex-partners.

  2. Antimicrobial peptides important in innate immunity.

    PubMed

    Cederlund, Andreas; Gudmundsson, Gudmundur H; Agerberth, Birgitta

    2011-10-01

    Antimicrobial peptides are present in all walks of life, from plants to animals, and they are considered to be endogenous antibiotics. In general, antimicrobial peptides are determinants of the composition of the microbiota and they function to fend off microbes and prevent infections. Antimicrobial peptides eliminate micro-organisms through disruption of their cell membranes. Their importance in human immunity, and in health as well as disease, has only recently been appreciated. The present review provides an introduction to the field of antimicrobial peptides in general and discusses two of the major classes of mammalian antimicrobial peptides: the defensins and the cathelicidins. The review focuses on their structures, their main modes of action and their regulation.

  3. Methods of Antimicrobial Coating of Diverse Materials

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of coating diverse substrate materials with antimicrobial agents have been developed. Originally intended to reduce health risks to astronauts posed by pathogenic microorganisms that can grow on surfaces in spacecraft, these methods could also be used on Earth for example, to ensure sterility of surgical inserts and other medical equipment. The methods involve, generally, chemical preparation of substrate surfaces to enable attachment of antimicrobial molecules to the substrate surfaces via covalent bonds. Substrate materials that have been treated successfully include aluminum, glass, a corrosion-resistant nickel alloy, stainless steel, titanium, and poly(tetrafluoroethylene). Antimicrobial agents that have been successfully immobilized include antibiotics, enzymes, bacteriocins, bactericides, and fungicides. A variety of linkage chem istries were employed. Activity of antimicrobial coatings against gram-positive bacteria, gram-negative bacteria, and fungi was demonstrated. Results of investigations indicate that the most suitable combination of antimicrobial agent, substrate, and coating method depends upon the intended application.

  4. Epidemiology of antimicrobial resistance in bloodstream infections.

    PubMed

    Akova, Murat

    2016-04-01

    Antimicrobial resistance in bacterial pathogens is a worldwide challenge leading high morbidity and mortality in clinical settings. Multidrug resistant patterns in gram-positive and -negative bacteria have resulted in difficult-to-treat or even untreatable infections with conventional antimicrobials. Since the early identification of causative microorganisms and their antimicrobial susceptibility patterns in patients with bacteremia and other serious infections is lacking in many healthcare institutions, broad spectrum antibiotics are liberally and mostly unnecessarily used. Such practice has, in turn, caused dramatic increases in emerging resistance and when coupled with poor practice of infection control, resistant bacteria can easily be disseminated to the other patients and the environment. Thus, availability of updated epidemiological data on antimicrobial resistance in frequently encountered bacterial pathogens will be useful not only for deciding on empirical treatment strategies, but also devising an effective antimicrobial stewardship program in hospitals. PMID:26984779

  5. Application of natural antimicrobials for food preservation.

    PubMed

    Tiwari, Brijesh K; Valdramidis, Vasilis P; O'Donnell, Colm P; Muthukumarappan, Kasiviswanathan; Bourke, Paula; Cullen, P J

    2009-07-22

    In this review, antimicrobials from a range of plant, animal, and microbial sources are reviewed along with their potential applications in food systems. Chemical and biochemical antimicrobial compounds derived from these natural sources and their activity against a range of pathogenic and spoilage microorganisms pertinent to food, together with their effects on food organoleptic properties, are outlined. Factors influencing the antimicrobial activity of such agents are discussed including extraction methods, molecular weight, and agent origin. These issues are considered in conjunction with the latest developments in the quantification of the minimum inhibitory (and noninhibitory) concentration of antimicrobials and/or their components. Natural antimicrobials can be used alone or in combination with other novel preservation technologies to facilitate the replacement of traditional approaches. Research priorities and future trends focusing on the impact of product formulation, intrinsic product parameters, and extrinsic storage parameters on the design of efficient food preservation systems are also presented. PMID:19548681

  6. To eat or not to eat red meat. A closer look at the relationship between restrained eating and vegetarianism in college females.

    PubMed

    Forestell, Catherine A; Spaeth, Andrea M; Kane, Stephanie A

    2012-02-01

    Previous research has suggested that vegetarianism may serve as a mask for restrained eating. The purpose of this study was to compare the dietary habits and lifestyle behaviors of vegetarians (n=55), pesco-vegetarians (n=28), semi-vegetarians (n=29), and flexitarians (n=37), to omnivores (n=91), who do not restrict animal products from their diets. A convenience sample of college-age females completed questionnaires about their eating habits, food choice motivations, and personality characteristics. Results indicated that while vegetarians and pesco-vegetarians were more open to new experiences and less food neophobic, they were not more restrained than omnivores. Rather semi-vegetarians; those who restricted only red meat from their diet, and flexitarians; those who occasionally eat red meat, were significantly more restrained than omnivores. Whereas food choices of semi-vegetarians and flexitarians were motivated by weight control, vegetarians and pesco-vegetarians' food choices were motivated by ethical concerns. By focusing specifically on semi-vegetarian and flexitarian subgroups, more effective approaches can be developed to ensure that their concerns about weight loss do not lead to unhealthful or disordered eating patterns.

  7. Worry or craving? A selective review of evidence for food-related attention biases in obese individuals, eating-disorder patients, restrained eaters and healthy samples.

    PubMed

    Werthmann, Jessica; Jansen, Anita; Roefs, Anne

    2015-05-01

    Living in an 'obesogenic' environment poses a serious challenge for weight maintenance. However, many people are able to maintain a healthy weight indicating that not everybody is equally susceptible to the temptations of this food environment. The way in which someone perceives and reacts to food cues, that is, cognitive processes, could underlie differences in susceptibility. An attention bias for food could be such a cognitive factor that contributes to overeating. However, an attention bias for food has also been implicated with restrained eating and eating-disorder symptomatology. The primary aim of the present review was to determine whether an attention bias for food is specifically related to obesity while also reviewing evidence for attention biases in eating-disorder patients, restrained eaters and healthy-weight individuals. Another aim was to systematically examine how selective attention for food relates (causally) to eating behaviour. Current empirical evidence on attention bias for food within obese samples, eating-disorder patients, and, even though to a lesser extent, in restrained eaters is contradictory. However, present experimental studies provide relatively consistent evidence that an attention bias for food contributes to subsequent food intake. This review highlights the need to distinguish not only between different (temporal) attention bias components, but also to take different motivations (craving v. worry) and their impact on attentional processing into account. Overall, the current state of research suggests that biased attention could be one important cognitive mechanism by which the food environment tempts us into overeating. PMID:25311212

  8. Inspiration or deflation? Feeling similar or dissimilar to slim and plus-size models affects self-evaluation of restrained eaters.

    PubMed

    Papies, Esther K; Nicolaije, Kim A H

    2012-01-01

    The present studies examined the effect of perceiving images of slim and plus-size models on restrained eaters' self-evaluation. While previous research has found that such images can lead to either inspiration or deflation, we argue that these inconsistencies can be explained by differences in perceived similarity with the presented model. The results of two studies (ns=52 and 99) confirmed this and revealed that restrained eaters with high (low) perceived similarity to the model showed more positive (negative) self-evaluations when they viewed a slim model, compared to a plus-size model. In addition, Study 2 showed that inducing in participants a similarities mindset led to more positive self-evaluations after viewing a slim compared to a plus-size model, but only among restrained eaters with a relatively high BMI. These results are discussed in the context of research on social comparison processes and with regard to interventions for protection against the possible detrimental effects of media images. PMID:21962524

  9. Worry or craving? A selective review of evidence for food-related attention biases in obese individuals, eating-disorder patients, restrained eaters and healthy samples.

    PubMed

    Werthmann, Jessica; Jansen, Anita; Roefs, Anne

    2015-05-01

    Living in an 'obesogenic' environment poses a serious challenge for weight maintenance. However, many people are able to maintain a healthy weight indicating that not everybody is equally susceptible to the temptations of this food environment. The way in which someone perceives and reacts to food cues, that is, cognitive processes, could underlie differences in susceptibility. An attention bias for food could be such a cognitive factor that contributes to overeating. However, an attention bias for food has also been implicated with restrained eating and eating-disorder symptomatology. The primary aim of the present review was to determine whether an attention bias for food is specifically related to obesity while also reviewing evidence for attention biases in eating-disorder patients, restrained eaters and healthy-weight individuals. Another aim was to systematically examine how selective attention for food relates (causally) to eating behaviour. Current empirical evidence on attention bias for food within obese samples, eating-disorder patients, and, even though to a lesser extent, in restrained eaters is contradictory. However, present experimental studies provide relatively consistent evidence that an attention bias for food contributes to subsequent food intake. This review highlights the need to distinguish not only between different (temporal) attention bias components, but also to take different motivations (craving v. worry) and their impact on attentional processing into account. Overall, the current state of research suggests that biased attention could be one important cognitive mechanism by which the food environment tempts us into overeating.

  10. E2F7 regulates transcription and maturation of multiple microRNAs to restrain cell proliferation

    PubMed Central

    Mitxelena, Jone; Apraiz, Aintzane; Vallejo-Rodríguez, Jon; Malumbres, Marcos; Zubiaga, Ana M.

    2016-01-01

    E2F transcription factors (E2F1-8) are known to coordinately regulate the expression of a plethora of target genes, including those coding for microRNAs (miRNAs), to control cell cycle progression. Recent work has described the atypical E2F factor E2F7 as a transcriptional repressor of cell cycle-related protein-coding genes. However, the contribution of E2F7 to miRNA gene expression during the cell cycle has not been defined. We have performed a genome-wide RNA sequencing analysis to identify E2F7-regulated miRNAs and show that E2F7 plays as a major role in the negative regulation of a set of miRNAs that promote cellular proliferation. We provide mechanistic evidence for an interplay between E2F7 and the canonical E2F factors E2F1-3 in the regulation of multiple miRNAs. We show that miR-25, -26a, -27b, -92a and -7 expression is controlled at the transcriptional level by the antagonistic activity of E2F7 and E2F1-3. By contrast, let-7 miRNA expression is controlled indirectly through a novel E2F/c-MYC/LIN28B axis, whereby E2F7 and E2F1-3 modulate c-MYC and LIN28B levels to impact let-7 miRNA processing and maturation. Taken together, our data uncover a new regulatory network involving transcriptional and post-transcriptional mechanisms controlled by E2F7 to restrain cell cycle progression through repression of proliferation-promoting miRNAs. PMID:26961310

  11. Analysis of the Efficiency of Fugitive Dust Restrain Methods on Bare Land of Da-an River

    NASA Astrophysics Data System (ADS)

    CHEN, H.

    2013-12-01

    Nowadays due to the increasing severity of season fugitive dust at estuary area, the public agencies of government gradually pay more attention to various refrain works. However, it is difficult to evaluate the efficiency of various refrain methods because of lacking of appropriate quantitative index. As a consequence, the only way to understand the fundamentals and efficiency of various refrain works at current stage is to implement the constructions directly on the bare land of riverbed and perform a series of field monitoring. In this study, incorporating with construction cost a FDRE (Fugitive Dust Restrain Efficiency) value was defined to evaluate the cost/refrain-efficiency of various refrain works. Moreover, two case histories of fugitive dust emission at the estuary of Da-An river during Ka-Maegi and Fung-Wong typhoons of 2008 were used for FDRE and cost/refrain-efficiency analyses. Firstly, numerical simulations of fugitive dust emission were performed for the estuary area of Da-An river to calculate the concentration of PM2.5 and PM10 with and without installation of fugitive dust refrain works and the corresponding FDRE values. Subsequently, considering the construction cost and FDRE value one can determine the FDRB values for various refrain works. Meanwhile, the simulations of fugitive dust concentrations were converted into PSI (Pollutant Standard Index) value to evaluate the air quality during fugitive dust emission at the estuary. According to the analyses, without considering the construction cost, the water curtain method (or sprinkling method) is capable of providing the highest FDRE value and best refrain effect to fugitive dust. On the contrary, the vein-type watering covering has the highest FDRB value and is the most economic method to fugitive dust refrain. Construction layout of vein-type water covering method on bare land of riverbed sites of FDRE monitoring stations (P1~P7) and PSI evaluating central point (Q1)

  12. A rapid release of corticosteroid-binding globulin from the liver restrains the glucocorticoid hormone response to acute stress.

    PubMed

    Qian, Xiaoxiao; Droste, Susanne K; Gutièrrez-Mecinas, María; Collins, Andrew; Kersanté, Flavie; Reul, Johannes M H M; Linthorst, Astrid C E

    2011-10-01

    A strict control of glucocorticoid hormone responses to stress is essential for health. In blood, glucocorticoid hormones are for the largest part bound to corticosteroid-binding globulin (CBG), and just a minor fraction of hormone is free. Only free glucocorticoid hormone is able to exert biological effects, but little is known about its regulation during stress. We found, using a dual-probe in vivo microdialysis method, that in rats, the forced-swim stress-induced rise in free corticosterone (its major glucocorticoid hormone) is strikingly similar in the blood and in target compartments such as the subcutaneous tissue and the brain. However, in all compartments, the free corticosterone response was delayed by 20-30 min as compared with the total corticosterone response in the blood. We discovered that CBG is the key player in this delay. Swim stress evoked a fast (within 5 min) and profound rise in CBG protein and binding capacity in the blood through a release of the protein from the liver. Thus, the increase in circulating CBG levels after stress restrains the rise in free corticosterone concentrations for approximately 20 min in the face of mounting total hormone levels in the circulation. The stress-induced increase in CBG seems to be specific for moderate and strong stressors. Both restraint stress and forced swimming caused an increase in circulating CBG, whereas its levels were not affected by mild novelty stress. Our data uncover a new, highly dynamic role for CBG in the regulation of glucocorticoid hormone physiology after acute stress.

  13. A non-human primate model of bipedal locomotion under restrained condition allowing gait studies and single unit brain recordings.

    PubMed

    Goetz, L; Piallat, B; Thibaudier, Y; Montigon, O; David, O; Chabardès, S

    2012-03-15

    For decades, several animal models of locomotion have allowed a better understanding of the basic physiological mechanisms of gait. However, unlike most of the mammals, the Order Primates is characterized by fundamental changes in locomotor behaviour. In particular, some primates use a specific pattern of locomotion and are able to naturally walk bipedally due possibly to a specific supra-spinal control of locomotion. These features must be taken into account when one considers to study the intrinsic properties of human gait. Thus, an experimental model of bipedal locomotion allowing precise and reproducible analysis of gait in non-human primate is still lacking. This study describes a non-human primate model of bipedal locomotion under restrained condition. We undertook a kinematic and biomechanic study in three Macaca fascicularis trained to walk bipedally on a treadmill. One of the primate was evaluated in complete head fixation. Gait visual analysis and electromyographic recordings provided pertinent description of the gait pattern. Step frequencies, step lengths, cycle and stance phase durations were correlated with Froude number (dimensionless velocity), whereas swing phase durations remained non-correlated. Gait patterns observed in our model were similar to those obtained in freely bipedal Macaca fuscata and to a lesser extend to Humans. Gait pattern was not modified by head fixation thereby allowing us to perform precise and repetitive micro electrode recordings of deep cerebral structures. Thus, the present model could provide a pertinent pre-clinical tool to study gait parameters and their neuronal control but also could be helpful to validate new therapeutics interventions. PMID:22155386

  14. 11β-Hydroxysteroid Dehydrogenase Type 1 Is Expressed in Neutrophils and Restrains an Inflammatory Response in Male Mice

    PubMed Central

    Coutinho, Agnes E.; Kipari, Tiina M. J.; Zhang, Zhenguang; Esteves, Cristina L.; Lucas, Christopher D.; Gilmour, James S.; Webster, Scott P.; Walker, Brian R.; Hughes, Jeremy; Savill, John S.; Seckl, Jonathan R.; Rossi, Adriano G.

    2016-01-01

    Endogenous glucocorticoid action within cells is enhanced by prereceptor metabolism by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts intrinsically inert cortisone and 11-dehydrocorticosterone into active cortisol and corticosterone, respectively. 11β-HSD1 is highly expressed in immune cells elicited to the mouse peritoneum during thioglycollate-induced peritonitis and is down-regulated as the inflammation resolves. During inflammation, 11β-HSD1-deficient mice show enhanced recruitment of inflammatory cells and delayed acquisition of macrophage phagocytic capacity. However, the key cells in which 11β-HSD1 exerts these effects remain unknown. Here we have identified neutrophils (CD11b+,Ly6G+,7/4+ cells) as the thioglycollate-recruited cells that most highly express 11β-HSD1 and show dynamic regulation of 11β-HSD1 in these cells during an inflammatory response. Flow cytometry showed high expression of 11β-HSD1 in peritoneal neutrophils early during inflammation, declining at later states. In contrast, expression in blood neutrophils continued to increase during inflammation. Ablation of monocytes/macrophages by treatment of CD11b-diphtheria-toxin receptor transgenic mice with diphtheria toxin prior to thioglycollate injection had no significant effect on 11β-HSD1 activity in peritoneal cells, consistent with neutrophils being the predominant 11β-HSD1 expressing cell type at this time. Similar to genetic deficiency in 11β-HSD1, acute inhibition of 11β-HSD1 activity during thioglycollate-induced peritonitis augmented inflammatory cell recruitment to the peritoneum. These data suggest that neutrophil 11β-HSD1 increases during inflammation to contribute to the restraining effect of glucocorticoids upon neutrophil-mediated inflammation. In human neutrophils, lipopolysaccharide activation increased 11β-HSD1 expression, suggesting the antiinflammatory effects of 11β-HSD1 in neutrophils may be conserved in humans. PMID:27145012

  15. A Simple and Accurate Method To Calculate Free Energy Profiles and Reaction Rates from Restrained Molecular Simulations of Diffusive Processes.

    PubMed

    Ovchinnikov, Victor; Nam, Kwangho; Karplus, Martin

    2016-08-25

    A method is developed to obtain simultaneously free energy profiles and diffusion constants from restrained molecular simulations in diffusive systems. The method is based on low-order expansions of the free energy and diffusivity as functions of the reaction coordinate. These expansions lead to simple analytical relationships between simulation statistics and model parameters. The method is tested on 1D and 2D model systems; its accuracy is found to be comparable to or better than that of the existing alternatives, which are briefly discussed. An important aspect of the method is that the free energy is constructed by integrating its derivatives, which can be computed without need for overlapping sampling windows. The implementation of the method in any molecular simulation program that supports external umbrella potentials (e.g., CHARMM) requires modification of only a few lines of code. As a demonstration of its applicability to realistic biomolecular systems, the method is applied to model the α-helix ↔ β-sheet transition in a 16-residue peptide in implicit solvent, with the reaction coordinate provided by the string method. Possible modifications of the method are briefly discussed; they include generalization to multidimensional reaction coordinates [in the spirit of the model of Ermak and McCammon (Ermak, D. L.; McCammon, J. A. J. Chem. Phys. 1978, 69, 1352-1360)], a higher-order expansion of the free energy surface, applicability in nonequilibrium systems, and a simple test for Markovianity. In view of the small overhead of the method relative to standard umbrella sampling, we suggest its routine application in the cases where umbrella potential simulations are appropriate.

  16. Vascular Smooth Muscle LRP6 Limits Arteriosclerotic Calcification in Diabetic LDLR-/- Mice by Restraining Noncanonical Wnt Signals

    PubMed Central

    Cheng, Su-Li; Ramachandran, Bindu; Behrmann, Abraham; Shao, Jian-Su; Mead, Megan; Smith, Carolyn; Krchma, Karen; Arredondo, Yoanna Bello; Kovacs, Attila; Kapoor, Kapil; Brill, Laurence M.; Perera, Ranjan; Williams, Bart O.; Towler, Dwight A.

    2015-01-01

    Rationale Wnt signaling regulates key aspects of diabetic vascular disease. Objective We generated SM22-Cre;LRP6(fl/fl);LDLR-/- mice to determine contributions of Wnt co-receptor LRP6 in the vascular smooth muscle lineage (VSM) of male LDLR-null mice, a background susceptible to diet (HFD) - induced diabetic arteriosclerosis. Methods and Results As compared to LRP6(fl/fl);LDLR-/- controls, SM22-Cre;LRP6(fl/fl);LDLR-/- (LRP6-VKO) siblings exhibited increased aortic calcification on HFD without changes in fasting glucose, lipids, or body composition. Pulse wave velocity (index of arterial stiffness) was also increased. Vascular calcification paralleled enhanced aortic osteochondrogenic programs and circulating osteopontin (OPN), a matricellular regulator of arteriosclerosis. Survey of ligands and Frizzled (Fzd) receptor profiles in LRP6-VKO revealed upregulation of canonical and noncanonical Wnts alongside Fzd10. Fzd10 stimulated noncanonical signaling and OPN promoter activity via an USF-activated cognate inhibited by LRP6. RNAi revealed that USF1 but not USF2 supports OPN expression in LRP6-VKO VSM, and immunoprecipitation confirmed increased USF1 association with OPN chromatin. ML141, an antagonist of cdc42/Rac1 noncanonical signaling, inhibited USF1 activation, osteochondrogenic programs, alkaline phosphatase, and VSM calcification. Mass spectrometry identified LRP6 binding to protein arginine methyltransferase (PRMT) - 1, and nuclear asymmetric dimethylarginine modification was increased with LRP6-VKO. RNAi demonstrated that PRMT1 inhibits OPN and TNAP while PRMT4 supports expression. USF1 complexes containing the H3R17Me2a signature of PRMT4 are increased with LRP6-VKO. Jmjd6, a demethylase downregulated with LRP6 deficiency, inhibits OPN and TNAP expression, USF1:H3R17Me2a complex formation and transactivation. Conclusions LRP6 restrains VSM noncanonical signals that promote osteochondrogenic differentiation, mediated in part via USF1- and arginine methylation

  17. Diurnal, seasonal, and sex patterns of heart rate in grip-restrained African giant rats (Cricetomys gambianus, Waterhouse)

    PubMed Central

    Dzenda, Tavershima; Ayo, Joseph O; Sinkalu, Victor O; Yaqub, Lukuman S

    2015-01-01

    This study was carried out to determine heart rate (HR) values, including diurnal, seasonal, and sex patterns, in the African giant rat (Cricetomys gambianus, Waterhouse). HR was measured using stethoscope in grip-restrained African giant rats of either sex (103 bucks and 98 does), live-trapped from a tropical Savannah, and caged individually in the laboratory during the harmattan (cold-dry), hot-dry, and rainy seasons over a 3-year period. The HR fluctuated between 90 and 210 beats per minute (bpm) throughout the study period. Diurnal changes in HR (mean ± SEM) during the hot-dry and rainy seasons were nonsignificant (P > 0.05), but the morning and afternoon values differed (P < 0.01) during the cold-dry season. The HR varied (P < 0.05) among seasons, with peak, nadir, and moderate values recorded during the cold-dry (165.8 ± 0.51 bpm), hot-dry (153.1 ± 0.74 bpm), and rainy (163.4 ± 0.70 bpm) seasons, respectively. Mean HR of bucks was lower than that of does during the cold-dry (P < 0.0001) and hot-dry (P < 0.01) seasons, but sex difference during the rainy season was insignificant (P > 0.05). Overall, mean HR was lower (P < 0.0001) in bucks (158.8 ± 0.53 bpm) than in does (164.8 ± 0.53 bpm). In conclusion, values of HR in African giant rats are shown for the first time. Season, sex, and daytime influenced the HR, and should be considered during clinical evaluations of the rats. PMID:26471756

  18. Antimicrobial outcomes in plasma medicine

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas P.; Stalder, Kenneth R.; Woloszko, Jean

    2015-03-01

    Plasma is referred to as the fourth state of matter and is frequently generated in the environment of a strong electric field. The result consists of highly reactive species--ions, electrons, reactive atoms and molecules, and UV radiation. Plasma Medicine unites a number of fields, including Physics, Plasma Chemistry, Cell Biology, Biochemistry, and Medicine. The treatment modality utilizes Cold Atmospheric Plasma (CAP), which is able to sterilize and treat microbes in a nonthermal manner. These gas-based plasma systems operate at close to room temperature and atmospheric pressure, making them very practical for a range of potential treatments and are highly portable for clinical use throughout the health care system. The hypothesis is that gas based plasma kills bacteria, fungus, and viruses but spares mammalian cells. This paper will review systematic work which shows examples of systems and performance in regards to antimicrobial effects and the sparing of mammalian cells. The mechanism of action will be discussed, as well as dosing for the treatment of microbial targets, including sterilization processes, another important healthcare need. In addition, commercial systems will be overviewed and compared, along with evidence-based, patient results. The range of treatments cover wound treatment and biofilms, as well as antimicrobial treatment, with little chance for resistance and tolerance, as in drug regimens. Current clinical studies include applications in dentistry, food treatment, cancer treatment, wound treatment for bacteria and biofilms, and systems to combat health care related infections.

  19. Antimicrobial Peptides: Versatile Biological Properties

    PubMed Central

    Pushpanathan, Muthuirulan; Rajendhran, Jeyaprakash

    2013-01-01

    Antimicrobial peptides are diverse group of biologically active molecules with multidimensional properties. In recent past, a wide variety of AMPs with diverse structures have been reported from different sources such as plants, animals, mammals, and microorganisms. The presence of unusual amino acids and structural motifs in AMPs confers unique structural properties to the peptide that attribute for their specific mode of action. The ability of these active AMPs to act as multifunctional effector molecules such as signalling molecule, immune modulators, mitogen, antitumor, and contraceptive agent makes it an interesting candidate to study every aspect of their structural and biological properties for prophylactic and therapeutic applications. In addition, easy cloning and recombinant expression of AMPs in heterologous plant host systems provided a pipeline for production of disease resistant transgenic plants. Besides these properties, AMPs were also used as drug delivery vectors to deliver cell impermeable drugs to cell interior. The present review focuses on the diversity and broad spectrum antimicrobial activity of AMPs along with its multidimensional properties that could be exploited for the application of these bioactive peptides as a potential and promising drug candidate in pharmaceutical industries. PMID:23935642

  20. Combination Effects of Antimicrobial Peptides

    PubMed Central

    Yu, Guozhi; Baeder, Desiree Y.; Regoes, Roland R.

    2016-01-01

    Antimicrobial peptides (AMPs) are ancient and conserved across the tree of life. Their efficacy over evolutionary time has been largely attributed to their mechanisms of killing. Yet, the understanding of their pharmacodynamics both in vivo and in vitro is very limited. This is, however, crucial for applications of AMPs as drugs and also informs the understanding of the action of AMPs in natural immune systems. Here, we selected six different AMPs from different organisms to test their individual and combined effects in vitro. We analyzed their pharmacodynamics based on the Hill function and evaluated the interaction of combinations of two and three AMPs. Interactions of AMPs in our study were mostly synergistic, and three-AMP combinations displayed stronger synergism than two-AMP combinations. This suggests synergism to be a common phenomenon in AMP interaction. Additionally, AMPs displayed a sharp increase in killing within a narrow dose range, contrasting with those of antibiotics. We suggest that our results could lead a way toward better evaluation of AMP application in practice and shed some light on the evolutionary consequences of antimicrobial peptide interactions within the immune system of organisms. PMID:26729502

  1. Antimicrobial use and antimicrobial resistance in nosocomial pathogens at a tertiary care hospital in Pune

    PubMed Central

    Nair, Velu; Sharma, Dinesh; Sahni, A.K.; Grover, Naveen; Shankar, S.; Jaiswal, S.S.; Dalal, S.S.; Basannar, D.R.; Phutane, Vivek S.; Kotwal, Atul; Gopal Rao, G.; Batura, Deepak; Venkatesh, M.D.; Sinha, Tapan; Kumar, Sushil; Joshi, D.P.

    2015-01-01

    Background Resistance to antimicrobial agents is emerging in wide variety of nosocomial and community acquired pathogens. Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance. This study was conducted to gain insight into the prevalent antimicrobial prescribing practices, and antimicrobial resistance pattern in nosocomial pathogens at a tertiary care hospital in Pune, India. Methods Series of one day cross sectional point prevalence surveys were carried out on four days between March and August 2014. All eligible in patients were included in the study. A structured data entry form was used to collect the data for each patient. Relevant samples were collected for microbiological examination from all the clinically identified hospital acquired infection cases. Results 41.73% of the eligible patients (95% CI: 39.52–43.97) had been prescribed at least one antimicrobial during their stay in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%). Majority of the organisms isolated from Hospital acquired infection (HAI cases) were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams. Conclusion There is need to have regular antimicrobial susceptibility surveillance and dissemination of this information to the clinicians. In addition, emphasis on the rational use of antimicrobials, antimicrobial rotation and strict adherence to the standard treatment guidelines is very essential. PMID:25859071

  2. Remote Antimicrobial Stewardship in Community Hospitals.

    PubMed

    Wood, Zachary H; Nicolsen, Nicole C; Allen, Nichole; Cook, Paul P

    2015-11-13

    Antimicrobial stewardship has become standard practice at university medical centers, but the practice is more difficult to implement in remote community hospitals that lack infectious diseases trained practitioners. Starting in 2011, six community hospitals within the Vidant Health system began an antimicrobial stewardship program utilizing pharmacists who reviewed charts remotely from Vidant Medical Center. Pharmacists made recommendations within the electronic medical record (EMR) to streamline, discontinue, or switch antimicrobial agents. Totals of charts reviewed, recommendations made, recommendations accepted, and categories of intervention were recorded. Linear regression was utilized to measure changes in antimicrobial use over time. For the four larger hospitals, recommendations for changes were made in an average of 45 charts per month per hospital and physician acceptance of the pharmacists' recommendations varied between 83% and 88%. There was no significant decrease in total antimicrobial use, but much of the use was outside of the stewardship program's review. Quinolone use decreased by more than 50% in two of the four larger hospitals. Remote antimicrobial stewardship utilizing an EMR is feasible in community hospitals and is generally received favorably by physicians. As more community hospitals adopt EMRs, there is an opportunity to expand antimicrobial stewardship beyond the academic medical center.

  3. Recent Advances in Antimicrobial Polymers: A Mini-Review

    PubMed Central

    Huang, Keng-Shiang; Yang, Chih-Hui; Huang, Shu-Ling; Chen, Cheng-You; Lu, Yuan-Yi; Lin, Yung-Sheng

    2016-01-01

    Human safety and well-being is threatened by microbes causing numerous infectious diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising antimicrobial strategy for fighting pathogens and have received considerable attention in both academic and industrial research. This mini-review presents the advances made in antimicrobial polymers since 2013. Antimicrobial mechanisms exhibiting either passive or active action and polymer material types containing bound or leaching antimicrobials are introduced. This article also addresses the applications of these antimicrobial polymers in the medical, food, and textile industries. PMID:27657043

  4. Danish Integrated Antimicrobial Resistance Monitoring and Research Program

    PubMed Central

    Heuer, Ole E.; Emborg, Hanne-Dorthe; Bagger-Skjøt, Line; Jensen, Vibeke F.; Rogues, Anne-Marie; Skov, Robert L.; Agersø, Yvonne; Brandt, Christian T.; Seyfarth, Anne Mette; Muller, Arno; Hovgaard, Karin; Ajufo, Justin; Bager, Flemming; Aarestrup, Frank M.; Frimodt-Møller, Niels; Wegener, Henrik C.; Monnet, Dominique L.

    2007-01-01

    Resistance to antimicrobial agents is an emerging problem worldwide. Awareness of the undesirable consequences of its widespread occurrence has led to the initiation of antimicrobial agent resistance monitoring programs in several countries. In 1995, Denmark was the first country to establish a systematic and continuous monitoring program of antimicrobial drug consumption and antimicrobial agent resistance in animals, food, and humans, the Danish Integrated Antimicrobial Resistance Monitoring and Research Program (DANMAP). Monitoring of antimicrobial drug resistance and a range of research activities related to DANMAP have contributed to restrictions or bans of use of several antimicrobial agents in food animals in Denmark and other European Union countries. PMID:18217544

  5. Human antimicrobial peptides and proteins.

    PubMed

    Wang, Guangshun

    2014-05-13

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between -3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat

  6. Human Antimicrobial Peptides and Proteins

    PubMed Central

    Wang, Guangshun

    2014-01-01

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to

  7. Antimicrobial Dose in Obese Patient

    PubMed Central

    Kassab, Sawsan; Syed Sulaiman, Syed Azhar; Abdul Aziz, Noorizan

    2007-01-01

    Introduction Obesity is a chronic disease that has become one of major public health issue in Malaysia because of its association with other disease states including cardiovascular disease and diabetes. Despite continuous efforts to educate the public about the health risks associated with obesity, prevalence of the disease continues to increase. Dosing of many medications are based on weight, limited data are available on how antimicrobial agents should be dosed in obesity. The aim of this case presentation is to discuss dose of antibiotic in obese patient. Case report: Patient: GMN, Malay, Female, 45 year old, 150kg, transferred from medical ward to ICU with problems of fever, orthopnea, sepsis secondary to nosocomial pneumonia. She was admitted to hospital a week ago for SOB on exertion, cyanosis, mildly dyspneic, somasthenia, bilateral ankle swelling. There was no fever, cough, chest pain, clubbing, flapping tremor. Her grand father has pre-morbid history of obesity, HPT, DM and asthma. She was non alcoholic, smoker, and not on diet control. The diagnosis Pickwickian syndrome was made. Patient was treated with IV Dopamine 11mcg/kg/min, IV Morphine 4mg/h. IV GTN 15mcg/min, IV Ca gluconate 10g/24h for 3/7, IV Zantac 50mg tds, IV Augmentin 1.2g tds, IV Lasix 40mg od, IV Plasil 10mg tds, S.c heparin 5000IU bd. patient become stable and moved to medical ward to continue her treatment. Discussion: The altered physiologic function seen in obese patients is a concern in patients receiving antimicrobial agents because therapeutic outcomes depend on achieving a minimum inhibitory concentration (MIC). The therapeutic effect of any drug can be altered when any of the 4 pharmacokinetic processes (absorption, distribution, metabolism, or elimination) are altered. Decreased blood flow rates and increased renal clearance in obese patients can affect drug distribution and elimination. Changes in serum protein levels can change the metabolism and distribution of drugs that are

  8. Ultrashort Antimicrobial Peptides with Antiendotoxin Properties

    PubMed Central

    Chih, Ya-Han; Lin, Yen-Shan; Yip, Bak-Sau; Wei, Hsiu-Ju; Chu, Hung-Lun; Yu, Hui-Yuan; Cheng, Hsi-Tsung

    2015-01-01

    Release of lipopolysaccharide (LPS) (endotoxin) from bacteria into the bloodstream may cause serious unwanted stimulation of the host immune system. Some but not all antimicrobial peptides can neutralize LPS-stimulated proinflammatory responses. Salt resistance and serum stability of short antimicrobial peptides can be boosted by adding β-naphthylalanine to their termini. Herein, significant antiendotoxin effects were observed in vitro and in vivo with the β-naphthylalanine end-tagged variants of the short antimicrobial peptides S1 and KWWK. PMID:26033727

  9. Comparative evaluation of antimicrobials for textile applications.

    PubMed

    Windler, Lena; Height, Murray; Nowack, Bernd

    2013-03-01

    Many antimicrobial technologies are available for textiles. They may be used in many different textile applications to prevent the growth of microorganisms. Due to the biological activity of the antimicrobial compounds, the assessment of the safety of these substances is an ongoing subject of research and regulatory scrutiny. This review aims to give an overview on the main compounds used today for antimicrobial textile functionalization. Based on an evaluation of scientific publications, market data as well as regulatory documents, the potential effects of antimicrobials on the environment and on human health were considered and also life cycle perspectives were taken into account. The characteristics of each compound were summarized according to technical, environmental and human health criteria. Triclosan, silane quaternary ammonium compounds, zinc pyrithione and silver-based compounds are the main antimicrobials used in textiles. The synthetic organic compounds dominate the antimicrobials market on a weight basis. On the technical side the application rates of the antimicrobials used to functionalize a textile product are an important parameter with treatments requiring lower dosage rates offering clear benefits in terms of less active substance required to achieve the functionality. The durability of the antimicrobial treatment has a strong influence on the potential for release and subsequent environmental effects. In terms of environmental criteria, all compounds were rated similarly in effective removal in wastewater treatment processes. The extent of published information about environmental behavior for each compound varies, limiting the possibility for an in-depth comparison of all textile-relevant parameters across the antimicrobials. Nevertheless the comparative evaluation showed that each antimicrobial technology has specific risks and benefits that should be taken into account in evaluating the suitability of different antimicrobial products. The

  10. Antimicrobial activity of Gentiana lutea L. extracts.

    PubMed

    Savikin, Katarina; Menković, Nebojsa; Zdunić, Gordana; Stević, Tatjana; Radanović, Dragoja; Janković, Teodora

    2009-01-01

    Methanolic extracts of flowers and leaves of Gentiana lutea L., together with the isolated compounds mangiferin, isogentisin and gentiopicrin, were used to investigate the antimicrobial activity of the plant. A variety of Gram-positive and Gram-negative bacteria as well as the yeast Candida albicans has been included in this study. Both extracts and isolated compounds showed antimicrobial activity with MIC values ranging from 0.12-0.31 mg/ml. Our study indicated that the synergistic activity of the pure compounds may be responsible for the good antimicrobial effect of the extracts. Quantification of the secondary metabolites was performed using HPLC.

  11. Naturally occurring antimicrobials for minimally processed foods.

    PubMed

    Davidson, P Michael; Critzer, Faith J; Taylor, T Matthew

    2013-01-01

    Natural antimicrobials are gaining increased interest from researchers and food manufacturers alike seeking to discover label-friendly alternatives to the widely implemented synthetic compounds. Naturally occurring antimicrobials can be applied directly to food to protect food quality, extend food shelf life by inhibiting or inactivating spoilage microorganisms, and improve food safety by inhibiting or inactivating food-borne pathogens. There are a great number of natural antimicrobials derived from animal, plant, and microbial sources. This manuscript reviews their efficacy against spoilage and pathogenic organisms, their methods of evaluation, and their application in various foods as well as the development of novel delivery systems and incorporation with other hurdles.

  12. [Antimicrobial peptide in dentisty. Literature review].

    PubMed

    Sato, F Simain; Rompen, E; Heinen, E

    2009-12-01

    The use of antimicrobial substances has contributed to the development of multiple antimicrobial resistances (1), challenging the pharmaceutical industry to develop with new, innovative, and effective molecules. Discovered around 1980, molecules called natural antimicrobial peptides (AMPs) appear to hold great potential for the treatment of infections. These cationic peptides are able to stop the bacterial development and to control infections. The purpose of this review is to help improve the understanding of the way AMPs operate in the context of the development of new cures against viruses, bacteria, and mushrooms found in the human body in general and in the oral cavity in particular. PMID:20143750

  13. Comparative evaluation of antimicrobials for textile applications.

    PubMed

    Windler, Lena; Height, Murray; Nowack, Bernd

    2013-03-01

    Many antimicrobial technologies are available for textiles. They may be used in many different textile applications to prevent the growth of microorganisms. Due to the biological activity of the antimicrobial compounds, the assessment of the safety of these substances is an ongoing subject of research and regulatory scrutiny. This review aims to give an overview on the main compounds used today for antimicrobial textile functionalization. Based on an evaluation of scientific publications, market data as well as regulatory documents, the potential effects of antimicrobials on the environment and on human health were considered and also life cycle perspectives were taken into account. The characteristics of each compound were summarized according to technical, environmental and human health criteria. Triclosan, silane quaternary ammonium compounds, zinc pyrithione and silver-based compounds are the main antimicrobials used in textiles. The synthetic organic compounds dominate the antimicrobials market on a weight basis. On the technical side the application rates of the antimicrobials used to functionalize a textile product are an important parameter with treatments requiring lower dosage rates offering clear benefits in terms of less active substance required to achieve the functionality. The durability of the antimicrobial treatment has a strong influence on the potential for release and subsequent environmental effects. In terms of environmental criteria, all compounds were rated similarly in effective removal in wastewater treatment processes. The extent of published information about environmental behavior for each compound varies, limiting the possibility for an in-depth comparison of all textile-relevant parameters across the antimicrobials. Nevertheless the comparative evaluation showed that each antimicrobial technology has specific risks and benefits that should be taken into account in evaluating the suitability of different antimicrobial products. The

  14. The role of public health in antimicrobial stewardship in healthcare.

    PubMed

    Trivedi, Kavita K; Pollack, Loria A

    2014-10-15

    Education, surveillance, and promotion of antimicrobial stewardship align with the goals of public health to prevent disease, promote health, and prolong life. Many US federal and state public health organizations are already engaged in antimicrobial stewardship activities. Healthcare providers are encouraged to work with public health officials on appropriate local antimicrobial stewardship strategies to attain the common goal of reducing antimicrobial resistance and preserving antimicrobials for future generations.

  15. Antimicrobial photodynamic therapy: An overview

    PubMed Central

    Rajesh, S.; Koshi, Elizabeth; Philip, Koshi; Mohan, Aparna

    2011-01-01

    Inflammatory periodontal disease caused by dental plaque is characterized by the clinical signs of inflammation and loss of periodontal tissue support. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. But the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. The possibility of development of resistance to antibiotics by the target organism has led to the development of a new antimicrobial concept with fewer complications. Photodynamic therapy (PDT) involves the use of low power lasers with appropriate wavelength to kill micro organisms treated with a photosensitizer drug. PDT could be a useful adjunct to mechanical as well as antibiotics in eliminating periopathogenic bacteria. PMID:22368354

  16. Antimicrobial peptides of multicellular organisms

    NASA Astrophysics Data System (ADS)

    Zasloff, Michael

    2002-01-01

    Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

  17. Antimicrobial activities of Barringtonia acutangula.

    PubMed

    Rahman, M Mukhlesur; Polfreman, David; MacGeachan, Jodie; Gray, Alexander I

    2005-06-01

    Crude extracts and VLC fractions from the stem bark of Barringtonia acutangula (L.) Gaertn (Fam. Lecythidaceae) were screened for their antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria and two fungi using a microdilution titre assay. Among the crude extracts, petroleum ether extract showed good activity against all test organisms. The VLC fraction PE 16 was found to be very effective against Bacillus subtilis (MIC=25 microg/ml) and Aspergillus niger (MIC=12.5 microg/ml). The activities were compared to standard antibiotics-kanamycin and fluconazole. The major compound from PE16 was identified as 12, 20(29)-lupadien-3-ol by NMR spectroscopy. PMID:16114086

  18. Antimicrobial dihydroisocoumarins from Crassocephalum biafrae.

    PubMed

    Tabopda, Turibio K; Fotso, Gislain W; Ngoupayo, Joseph; Mitaine-Offer, Anne-Claire; Ngadjui, Bonaventure T; Lacaille-Dubois, Marie-Aleth

    2009-09-01

    Bioassay-guided fractionation of the CHCl (3)-soluble extract of the stem bark of Crassocephalum biafrae (Asteraceae) resulted in the isolation of three new dihydroisocoumarins, named biafraecoumarins A ( 1), B ( 2), and C ( 3); two known triterpenes ( 4 and 5); and a known ceramide ( 6). The structures of the new compounds were established as 7-but-15-enyl-6,8-dihydroxy-3( R)-penta-9,11-dienylisochroman-1-one ( 1), 7-butyl-6,8-dihydroxy-3( R)-penta-9,11-dienylisochroman-1-one ( 2), and 7-butyl-6,8-dihydroxy-3( R)-pent-10-enylisochroman-1-one ( 3) using spectroscopic data. Compounds 1- 3 exhibit low to significant antimicrobial activities against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Pseudomonas picketti, Trichphyton longifusus, Aspergillus flavus, Microsporum canis, Fusarium solani, Candida albicans, and Candida glabrata. PMID:19350487

  19. Antimicrobial Peptides in Human Sepsis

    PubMed Central

    Martin, Lukas; van Meegern, Anne; Doemming, Sabine; Schuerholz, Tobias

    2015-01-01

    Nearly 100 years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1–3 and human beta-defensins (HBDs) 1–3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1–3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1–3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1–11 (hLF 1–11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections

  20. Experimental determination of optimal root-mean-square deviations of macromolecular bond lengths and angles from their restrained ideal values.

    PubMed

    Tickle, Ian J

    2007-12-01

    A number of inconsistencies are apparent in the recent research paper by Jaskolski et al. [(2007), Acta Cryst. D63, 611-620] concerning their recommendations for the values of the magnitude and resolution-dependence of the root-mean-square deviations (RMSDs) of bond lengths and angles from their restrained ideal values in macromolecular refinement, as well as their suggestions for the use of variable standard uncertainties dependent on atomic displacement parameters (ADPs) and occupancies. Whilst many of the comments and suggestions in the paper regarding updates for the ideal geometry values proposed by Engh and Huber are entirely reasonable and supported by the experimental evidence, the recommendations concerning the optimal values of RMSDs appear to be in conflict with previous experimental and theoretical work in this area [Tickle et al. (1998), Acta Cryst. D54, 243-252] and indeed appear to be based on a misunderstanding of the distinction between RMSD and standard uncertainty (SU). In contrast, it is proposed here that the optimal values of all desired weighting parameters, in particular the weighting parameters for the ADP differences and for the diffraction terms, be estimated by the purely objective procedure of maximizing the experiment-based log(free likelihood). In principle, this allows all weighting parameters that are not known accurately a priori to be scaled globally, relative to those that are known accurately, for an optimal refinement. The RMS Z score (RMSZ) is recommended as a more satisfactory statistic than the RMSD to assess the extent to which the geometry deviates from the ideal values and a theoretical rationale for the results obtained is presented in which the optimal RMSZ is identified as the calculated versus true Z-score correlation coefficient, the latter being a monotonic function of the resolution cutoff of the data. Regarding the proposal to use variable standard uncertainties, it is suggested that any departure from the current

  1. Mechanical Analysis of an SM 2 Blk IV restrained firing within a concentric canister launcher test unit

    SciTech Connect

    Kassner, M C; Kennedy, T C; Puttapitukporn, T; Rosen, R S

    1999-03-01

    The Office of Naval Research (ONR) and PMS512 have undertaken a program to develop a new Vertical Launching System (VLS) for future generation ships, such as the DD-21 Destroyer. The Naval Sea Systems Command Combat Weapons Program (NAVSEA 05K) and Naval Surface Warfare Center Dahlgren Division (NSWCDD) are working jointly with industry and universities to develop one such launcher design, the Concentric Canister Launcher (CCL). The basic CCL design consists of a tube made of two concentric cylinders; one end is open, the other is sealed with a hemispherical end cap. During firing, the missile exhaust gas is turned 180 degrees by the hemispherical end cap and flows through the annular space between inner and outer cylinders. Depending on the missile utilized and the particular service environment of the CCL, maximum temperatures within the cylinder material have been calculated to exceed 2000 F. In an earlier study [1], the authors determined the high temperature mechanical properties of several candidate alloys being considered for fabrication of the CCL. This study [1] found that, of these candidate materials, titanium alloys exhibit higher yield stresses than that of 316L stainless steel at temperatures up to about 1000 F; above 1500 F, the yield stress of 316L stainless steel is comparable to those of the titanium alloys. The 316L stainless steel was found to strain harden (increase its flow stress with increasing strain) at temperatures up to about 1800 F. The ability of the 316L stainless steel to strain harden at high temperatures may provide an added margin of safety for engineering design of the CCL. The objective of the current study was to perform a computer simulation of the structural response of a CCL during a restrained firing, one in which a SM-2 Blk IV missile would fail to exit the canister. A finite element model of the inner cylinder, outer cylinder, end rings (mounting brackets), and lateral restraints in the uptake was constructed. An elastic

  2. Making a Case for Pediatric Antimicrobial Stewardship Programs.

    PubMed

    Magsarili, Heather K; Girotto, Jennifer E; Bennett, Nicholas J; Nicolau, David P

    2015-11-01

    Although antimicrobials are commonly used in children, it is important to remember that they can have a profound impact on this unique patient population. Inadvertent consequences of antiinfective use in children include antimicrobial resistance, infection caused by Clostridium difficile, increased risk of obesity, and adverse drug events. In addition, compared with adults, children have different dosing requirements, antimicrobial formulation needs, pharmacokinetics, and antimicrobial susceptibility profiles. Therefore, pediatric-specific antimicrobial stewardship efforts are needed to promote appropriate use of antimicrobials in children. The primary purposes of this review article are to provide a rationale behind pediatric-focused antimicrobial stewardship and to describe currently available evidence regarding the initiatives of pediatric antimicrobial stewardship programs (ASPs). A literature search of the Medline database was performed (from inception through March 2015). The studies included in this review focus on antimicrobial stewardship interventions in inpatient pediatric settings. Ten inpatient studies involving pediatric-focused antimicrobial stewardship interventions were identified from the published literature. Four studies used the core strategy of prospective audit with feedback; two used prior approval. The remaining four used supplemental antimicrobial stewardship strategies (guidelines, clinical pathways, and computerized decision support tools). In general, the interventions resulted in decreased antimicrobial use, reduced antimicrobial costs, and fewer prescribing errors. Children have unique medical needs related to antimicrobials and deserve focused ASP efforts. The literature regarding pediatric antimicrobial stewardship interventions is limited, but published interventions may serve as paradigms for developing pediatric ASPs as demonstrated by the general success of these interventions.

  3. Antimicrobial silver: an unprecedented anion effect.

    PubMed

    Swathy, J R; Sankar, M Udhaya; Chaudhary, Amrita; Aigal, Sahaja; Anshup; Pradeep, T

    2014-01-01

    Silver is an indispensable metal but its use has to be minimised for sustainable growth. Much of the silver lost during use is unrecoverable; an example being its use as an antimicrobial agent, a property known since ages. While developing methods to create an affordable drinking water purifier especially for the developing world, we discovered that 50 parts per billion (ppb) of Ag(+) released continuously from silver nanoparticles confined in nanoscale cages is enough to cause antimicrobial activity in conditions of normal water. Here we show that the antibacterial and antiviral activities of Ag(+) can be enhanced ~1,000 fold, selectively, in presence of carbonate ions whose concentration was maintained below the drinking water norms. The protective layers of the organisms were affected during the carbonate-assisted antimicrobial activity. It is estimated that ~1,300 tons of silver can be saved annually using this new way to enhance its antimicrobial activity. PMID:25418185

  4. Membrane disruption mechanism of antimicrobial peptides

    NASA Astrophysics Data System (ADS)

    Lee, Ka Yee

    2012-04-01

    Largely distributed among living organisms, antimicrobial peptides are a class of small (<100 residues) host defense peptides that induce selective membrane lytic activity against microbial pathogens. The permeabilizing behavior of these diverse peptides has been commonly attributed to the formation of pores, and such pore formation has been categorized as barrel-stave, toroidal, or carpet-like. With the continuing discovery of new peptide species, many are uncharacterized and the exact mechanism is unknown. Through the use of atomic force microscopy, the disruption of supported lipid bilayer patches by protegrin-1 is concentration-dependent. The intercalation of antimicrobial peptide into the bilayer results in structures beyond that of pore formation, but with the formation of worm-like micelles at high peptide concentration. Our results suggest that antimicrobial peptide acts to lower the interfacial energy of the bilayer in a way similar to detergents. Antimicrobial peptides with structural differences, magainin-1 and aurein 1.1, exhibit a mechanistic commonality.

  5. Antimicrobial-Coated Granules for Disinfecting Water

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

  6. Antimicrobial dispensing by Ontario dairy veterinarians

    PubMed Central

    Léger, David F.; Newby, Nathalie C.; Reid-Smith, Richard; Anderson, Neil; Pearl, David L.; Lissemore, Kerry D.; Kelton, David F.

    2015-01-01

    This questionnaire-based cross-sectional study was designed to capture the demographics of dairy practitioners in Ontario and to describe aspects of antimicrobial dispensing on-farm and over-the-counter by these veterinarians. The information collected revealed that the prescription status of a drug and the level of veterinary-client-patient relationship were important elements of dispensing policies. Over-the-counter dispensing records were incomplete, while only a small proportion of on-farm dispensing records contained pertinent information and directions as required by the Veterinarians Act. While respondents recognized that antimicrobial use in dairy herds could lead to resistance in cattle, few indicated that this was a significant public health issue. Veterinarians can play a key role in antimicrobial stewardship, part of which is the provision of complete written dispensing instructions to producers for antimicrobial use in dairy cattle. PMID:26130834

  7. Towards Self-regenerating Antimicrobial Polymer Surfaces

    PubMed Central

    Dorner, Franziska; Boschert, David; Schneider, Alexandra; Hartleb, Wibke; Al-Ahmad, Ali; Lienkamp, Karen

    2016-01-01

    Regeneration of functional polymer surfaces after damage or contamination is an unresolved scientific challenge, and also of practical importance. In this proof-of-concept study, we present a method to regenerate a functional surface property using a polymer multi-layer architecture. This is exemplified using antimicrobially active surfaces. The idea is to shed the top layer of the polymer layer stack, like a reptile shedding its skin. The proof-of-concept stack consists of two antimicrobial layers and a degradable interlayer. Shedding of the top layer is enabled by degrading that interlayer. The shedding process was analyzed by quantitative fluorescence microscopy, ellipsometry, and FTIR spectroscopy. Antimicrobial assays revealed that the functionality of the emerging antimicrobial layer was fully retained after shedding. PMID:27489747

  8. Antimicrobial dispensing by Ontario dairy veterinarians.

    PubMed

    Léger, David F; Newby, Nathalie C; Reid-Smith, Richard; Anderson, Neil; Pearl, David L; Lissemore, Kerry D; Kelton, David F

    2015-07-01

    This questionnaire-based cross-sectional study was designed to capture the demographics of dairy practitioners in Ontario and to describe aspects of antimicrobial dispensing on-farm and over-the-counter by these veterinarians. The information collected revealed that the prescription status of a drug and the level of veterinary-client-patient relationship were important elements of dispensing policies. Over-the-counter dispensing records were incomplete, while only a small proportion of on-farm dispensing records contained pertinent information and directions as required by the Veterinarians Act. While respondents recognized that antimicrobial use in dairy herds could lead to resistance in cattle, few indicated that this was a significant public health issue. Veterinarians can play a key role in antimicrobial stewardship, part of which is the provision of complete written dispensing instructions to producers for antimicrobial use in dairy cattle. PMID:26130834

  9. Antimicrobial silver: An unprecedented anion effect

    PubMed Central

    Swathy, J. R.; Sankar, M. Udhaya; Chaudhary, Amrita; Aigal, Sahaja; Anshup; Pradeep, T.

    2014-01-01

    Silver is an indispensable metal but its use has to be minimised for sustainable growth. Much of the silver lost during use is unrecoverable; an example being its use as an antimicrobial agent, a property known since ages. While developing methods to create an affordable drinking water purifier especially for the developing world, we discovered that 50 parts per billion (ppb) of Ag+ released continuously from silver nanoparticles confined in nanoscale cages is enough to cause antimicrobial activity in conditions of normal water. Here we show that the antibacterial and antiviral activities of Ag+ can be enhanced ~1,000 fold, selectively, in presence of carbonate ions whose concentration was maintained below the drinking water norms. The protective layers of the organisms were affected during the carbonate-assisted antimicrobial activity. It is estimated that ~1,300 tons of silver can be saved annually using this new way to enhance its antimicrobial activity. PMID:25418185

  10. Statistical metamodeling for revealing synergistic antimicrobial interactions.

    PubMed

    Chen, Hsiang Chia; Chen, Chia Hsiang; Gau, Vincent; Zhang, Donna D; Liao, Joseph C; Wang, Fei-Yue; Wong, Pak Kin

    2010-01-01

    Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future. PMID:21124958

  11. Statistical Metamodeling for Revealing Synergistic Antimicrobial Interactions

    PubMed Central

    Chen, Chia Hsiang; Gau, Vincent; Zhang, Donna D.; Liao, Joseph C.; Wang, Fei-Yue; Wong, Pak Kin

    2010-01-01

    Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future. PMID:21124958

  12. Antimicrobial defense and persistent infection in insects.

    PubMed

    Haine, Eleanor R; Moret, Yannick; Siva-Jothy, Michael T; Rolff, Jens

    2008-11-21

    During 400 million years of existence, insects have rarely succumbed to the evolution of microbial resistance against their potent antimicrobial immune defenses. We found that microbial clearance after infection is extremely fast and that induced antimicrobial activity starts to increase only when most of the bacteria (99.5%) have been removed. Our experiments showed that those bacteria that survived exposure to the insect's constitutive immune response were subsequently more resistant to it. These results imply that induced antimicrobial compounds function primarily to protect the insect against the bacteria that persist within their body, rather than to clear microbial infections. These findings suggest that understanding of the management of antimicrobial peptides in natural systems might inform medical treatment strategies that avoid the risk of drug resistance. PMID:19023083

  13. Antimicrobial activity of borate-buffered solutions.

    PubMed Central

    Houlsby, R D; Ghajar, M; Chavez, G O

    1986-01-01

    A minimal salts medium adjusted to physiological pH and osmolality was buffered with either 0.3% phosphate or 1.2% borate and evaluated for antimicrobial activity. The borate-buffered medium, either with or without a carbon source, exhibited significant antimicrobial activity against 15 Pseudomonas strains, 12 strains of enteric bacteria, and 7 strains of staphylococci. The borate-buffered system appears suitable for use as a generic vehicle for ophthalmic pharmaceutical agents. PMID:3729341

  14. The interpretation of antimicrobial susceptibility patterns.

    PubMed Central

    Martin, S W; Meek, A H

    1981-01-01

    The results of a computer model designed to demonstrate the effect of antimicrobial exposure (therapy) on the likelihood of isolating putative pathogens and on the proportion of successfully isolated organisms resistant to specific antimicrobials are presented. The results indicate that the observed percentage resistant is not a reliable indicator of the actual percentage resistant in the source population. Data from the Bruce County Beef Project in 1979-80 are used to verify some of the assumptions used in the model. PMID:7196279

  15. Antimicrobial prophylaxis in caesarean section delivery

    PubMed Central

    Liu, Ronghua; Lin, Lin; Wang, Dujuan

    2016-01-01

    Antimicrobial prophylaxis is used routinely for pre-, intra- and post-operative caesarean section. One of the most important risk factors for postpartum infection is caesarean delivery. Caesarean section shows a higher incidence of infection than vaginal delivery. It is complicated by surgical site infections, endometritis or urinary tract infection. The aim of the present study was to assess the usage of antimicrobials in women undergoing caesarean section at a Tertiary Care Hospital. A prospective study was conducted in 100 women during the period of February 2013 to August 2013 in the inpatient Department of Gynaecology and Obstetrics. Data collected included the age of the patient, gravidity, and type of caesarean section, which was analyzed for the nature and number of antimicrobials prescribed, duration of treatment, polypharmacy, fixed-dose combinations, generic/brand names used and failure of prophylaxis. Antimicrobial prophylaxis was administered to the patients. The most commonly prescribed antimicrobial was a combination of ceftriaxone and sulbactam. Of 100 patients, 87% were aged 20–35 years. The highest proportion of patients were primigravida 72%. Elective procedure was carried out in 38%, the remaining were emergency C-section in whom intra- and post-operative antimicrobial prophylaxis was given for a duration of 7 days. In total, 27% of patients were reported with infection even after the antimicrobial prophylaxis. In conclusion, pre-operative prophylaxis was given in the early rupture of membranes. Fixed-dose combinations were preferred. Incidence of infection even after antimicrobial prophylaxis was reported due to pre-existing infection, debilitating disease or prolonged rupture of membranes. Patients with recurrent infection were shifted to amoxicillin and clavulinic acid combination. Drugs were prescribed only by brand names which is of concern. PMID:27446303

  16. Report: Antimicrobial activity of Kalanchoe laciniata.

    PubMed

    Manan, Maria; Hussain, Liaqat; Ijaz, Hira; Qadir, Muhammad Imran

    2016-07-01

    This study was conducted to identify antimicrobial potential of Kalanchoe laciniata. The plants were extracted with 30-70% aqueous-methanol and n-hexane. The antimicrobial activities were examined using agar well diffusion method against bacteria (Staphylococcus aureus, Escherichia coli) and fungi (Candidaalbicans). Results showed that E. coli were more sensitive than Staphylococcus aureus and Candida albicans. The largest zone of inhibition (52 mm) was recorded against E. coli with the n-hexane extract of Kalanchoe laciniata.

  17. Industrial food animal production, antimicrobial resistance, and human health.

    PubMed

    Silbergeld, Ellen K; Graham, Jay; Price, Lance B

    2008-01-01

    Antimicrobial resistance is a major public health crisis, eroding the discovery of antimicrobials and their application to clinical medicine. There is a general lack of knowledge of the importance of agricultural antimicrobial use as a factor in antimicrobial resistance even among experts in medicine and public health. This review focuses on agricultural antimicrobial drug use as a major driver of antimicrobial resistance worldwide for four reasons: It is the largest use of antimicrobials worldwide; much of the use of antimicrobials in agriculture results in subtherapeutic exposures of bacteria; drugs of every important clinical class are utilized in agriculture; and human populations are exposed to antimicrobial-resistant pathogens via consumption of animal products as well as through widespread release into the environment.

  18. Understanding the mechanisms and drivers of antimicrobial resistance.

    PubMed

    Holmes, Alison H; Moore, Luke S P; Sundsfjord, Arnfinn; Steinbakk, Martin; Regmi, Sadie; Karkey, Abhilasha; Guerin, Philippe J; Piddock, Laura J V

    2016-01-01

    To combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed. Emergence of antimicrobial resistance in microorganisms is a natural phenomenon, yet antimicrobial resistance selection has been driven by antimicrobial exposure in health care, agriculture, and the environment. Onward transmission is affected by standards of infection control, sanitation, access to clean water, access to assured quality antimicrobials and diagnostics, travel, and migration. Strategies to reduce antimicrobial resistance by removing antimicrobial selective pressure alone rely upon resistance imparting a fitness cost, an effect not always apparent. Minimising resistance should therefore be considered comprehensively, by resistance mechanism, microorganism, antimicrobial drug, host, and context; parallel to new drug discovery, broad ranging, multidisciplinary research is needed across these five levels, interlinked across the health-care, agriculture, and environment sectors. Intelligent, integrated approaches, mindful of potential unintended results, are needed to ensure sustained, worldwide access to effective antimicrobials. PMID:26603922

  19. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats

    PubMed Central

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H.; Desai, S.D.

    2016-01-01

    Introduction Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. Aim To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. Materials and Methods Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. Results Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. Conclusion Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels. PMID:27656428

  20. Quaternized Chitosan as an Antimicrobial Agent: Antimicrobial Activity, Mechanism of Action and Biomedical Applications in Orthopedics

    PubMed Central

    Tan, Honglue; Ma, Rui; Lin, Chucheng; Liu, Ziwei; Tang, Tingting

    2013-01-01

    Chitosan (CS) is a linear polysaccharide with good biodegradability, biocompatibility and antimicrobial activity, which makes it potentially useful for biomedical applications, including an antimicrobial agent either alone or blended with other polymers. However, the poor solubility of CS in most solvents at neutral or high pH substantially limits its use. Quaternary ammonium CS, which was prepared by introducing a quaternary ammonium group on a dissociative hydroxyl group or amino group of the CS, exhibited improved water solubility and stronger antibacterial activity relative to CS over an entire range of pH values; thus, this quaternary modification increases the potential biomedical applications of CS in the field of anti-infection. This review discusses the current findings on the antimicrobial properties of quaternized CS synthesized using different methods and the mechanisms of its antimicrobial actions. The potential antimicrobial applications in the orthopedic field and perspectives regarding future studies in this field are also considered. PMID:23325051

  1. Characterization of Novel Antimicrobial Peptoids

    PubMed Central

    Goodson, Bob; Ehrhardt, Anton; Ng, Simon; Nuss, John; Johnson, Kirk; Giedlin, Marty; Yamamoto, Ralph; Moos, Walter H.; Krebber, Anke; Ladner, Martha; Giacona, Mary Beth; Vitt, Charles; Winter, Jill

    1999-01-01

    Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 μg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity against Staphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. β-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model. PMID:10348765

  2. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    PubMed

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread.

  3. Derivation of Reliable Geometries in QM Calculations of DNA Structures: Explicit Solvent QM/MM and Restrained Implicit Solvent QM Optimizations of G-Quadruplexes.

    PubMed

    Gkionis, Konstantinos; Kruse, Holger; Šponer, Jiří

    2016-04-12

    Modern dispersion-corrected DFT methods have made it possible to perform reliable QM studies on complete nucleic acid (NA) building blocks having hundreds of atoms. Such calculations, although still limited to investigations of potential energy surfaces, enhance the portfolio of computational methods applicable to NAs and offer considerably more accurate intrinsic descriptions of NAs than standard MM. However, in practice such calculations are hampered by the use of implicit solvent environments and truncation of the systems. Conventional QM optimizations are spoiled by spurious intramolecular interactions and severe structural deformations. Here we compare two approaches designed to suppress such artifacts: partially restrained continuum solvent QM and explicit solvent QM/MM optimizations. We report geometry relaxations of a set of diverse double-quartet guanine quadruplex (GQ) DNA stems. Both methods provide neat structures without major artifacts. However, each one also has distinct weaknesses. In restrained optimizations, all errors in the target geometries (i.e., low-resolution X-ray and NMR structures) are transferred to the optimized geometries. In QM/MM, the initial solvent configuration causes some heterogeneity in the geometries. Nevertheless, both approaches represent a decisive step forward compared to conventional optimizations. We refine earlier computations that revealed sizable differences in the relative energies of GQ stems computed with AMBER MM and QM. We also explore the dependence of the QM/MM results on the applied computational protocol. PMID:26914292

  4. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    PubMed

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

  5. Derivation of Reliable Geometries in QM Calculations of DNA Structures: Explicit Solvent QM/MM and Restrained Implicit Solvent QM Optimizations of G-Quadruplexes.

    PubMed

    Gkionis, Konstantinos; Kruse, Holger; Šponer, Jiří

    2016-04-12

    Modern dispersion-corrected DFT methods have made it possible to perform reliable QM studies on complete nucleic acid (NA) building blocks having hundreds of atoms. Such calculations, although still limited to investigations of potential energy surfaces, enhance the portfolio of computational methods applicable to NAs and offer considerably more accurate intrinsic descriptions of NAs than standard MM. However, in practice such calculations are hampered by the use of implicit solvent environments and truncation of the systems. Conventional QM optimizations are spoiled by spurious intramolecular interactions and severe structural deformations. Here we compare two approaches designed to suppress such artifacts: partially restrained continuum solvent QM and explicit solvent QM/MM optimizations. We report geometry relaxations of a set of diverse double-quartet guanine quadruplex (GQ) DNA stems. Both methods provide neat structures without major artifacts. However, each one also has distinct weaknesses. In restrained optimizations, all errors in the target geometries (i.e., low-resolution X-ray and NMR structures) are transferred to the optimized geometries. In QM/MM, the initial solvent configuration causes some heterogeneity in the geometries. Nevertheless, both approaches represent a decisive step forward compared to conventional optimizations. We refine earlier computations that revealed sizable differences in the relative energies of GQ stems computed with AMBER MM and QM. We also explore the dependence of the QM/MM results on the applied computational protocol.

  6. Negative affect-induced food intake in non-dieting women is reward driven and associated with restrained-disinhibited eating subtype.

    PubMed

    Fay, Stephanie H; Finlayson, Graham

    2011-06-01

    In humans the presence of negative affect is thought to promote food intake, although widespread variability surrounds this issue. Susceptibility to negative affect-induced eating may depend on trait eating behaviours, notably 'emotional eating', 'restrained eating' and 'disinhibited eating', but the evidence is not consistent. In the present study, 30 non-obese, non-dieting women were given access to palatable food while in a state of negative or neutral affect, induced by a validated autobiographical recall technique. As predicted, food intake was higher in the presence of negative affect; however, this effect was moderated by the pattern of eating behaviour traits and enhanced wanting for the test food. Specifically, high restraint and high disinhibition in combination with higher scores on emotional eating and food wanting was able to predict negative-affect intake (adjusted R(2)=.61), suggesting that individuals who are both restrained and vulnerable to disinhibited eating are particularly susceptible to negative-affect food intake via stimulation of food wanting. Identification of traits that predispose individuals to overconsume and a more detailed understanding of the specific behaviours driving such overconsumption may help to optimise strategies to prevent weight gain.

  7. The Endogenous Cell-Fate Factor Dachshund restrains Prostate Epithelial Cell Migration via Repression of Cytokine Secretion via a CXCL Signaling Module

    PubMed Central

    Chen, Ke; Wu, Kongming; Jiao, Xuanmao; Wang, Liping; Ju, Xiaoming; Wang, Min; Di Sante, Gabriele; Xu, Shaohua; Wang, Qiong; Li, Kevin; Sun, Xin; Xu, Congwen; Li, Zhiping; Casimiro, Mathew C.; Ertel, Adam; Addya, Sankar; McCue, Peter; Lisanti, Michael P.; Wang, Chenguang; Davis, Richard J.; Mardon, Graeme; Pestell, Richard G.

    2015-01-01

    Prostate cancer (PCa) is the second leading form of cancer death in men. In a subset of PCa patients increased chemokine signaling IL-8 and IL-6 correlates with androgen therapy-resistant prostate cancer (CRPC). IL-8 and IL-6 are produced by prostate epithelial cells and promote PCa cell invasion, however the mechanisms restraining prostate epithelial cell cytokine secretion are poorly understood. Herein the cell-fate determinant factor DACH1 inhibited androgen therapy-resistant prostate cancer (CRPC) tumor growth in mice. Using Dach1fl/fl/Probasin-Cre bi-transgenic mice, we show IL-8 and IL-6 secretion was altered ~1000 fold by endogenous Dach1. Endogenous Dach1 is shown to serve as a key endogenous restraint to prostate epithelial cell growth and restrains migration via CXCL signaling. DACH1 inhibited expression, transcription and secretion of the CXCL genes (IL-8, IL-6) by binding to their promoter regulatory regions in chromatin. DACH1 is thus a newly defined determinant of benign and malignant prostate epithelium cellular growth, migration and cytokine abundance in vivo. PMID:25769723

  8. Enhanced isoprene biosynthesis in Saccharomyces cerevisiae by engineering of the native acetyl-CoA and mevalonic acid pathways with a push-pull-restrain strategy.

    PubMed

    Lv, Xiaomei; Xie, Wenping; Lu, Wenqiang; Guo, Fei; Gu, Jiali; Yu, Hongwei; Ye, Lidan

    2014-09-30

    To explore the capacity of isoprene production in Saccharomyces cerevisiae, a rational push-pull-restrain strategy was proposed to engineer the mevalonic acid (MVA) and acetyl-CoA pathways. The strategy can be decomposed into the up-regulation of precursor supply in the acetyl-CoA module and the MVA pathway (push-strategy), increase of the isoprene branch flux (pull-strategy), and down-regulation of the competing pathway (restrain-strategy). Furthermore, to reduce the production cost arising from galactose addition and meanwhile maintain the high expression of Gal promoters, the galactose regulatory network was modulated by Gal80p deletion. Finally, the engineered strain YXM10-ispS-ispS could accumulate up to 37 mg/L isoprene (about 782-fold increase compared to the parental strain) under aerobic conditions with glycerol-sucrose as carbon source. In this way, a new potential platform for isoprene production was established via metabolic engineering of the yeast native pathways.

  9. Antimicrobial cyclic peptides for plant disease control.

    PubMed

    Lee, Dong Wan; Kim, Beom Seok

    2015-03-01

    Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  10. Antimicrobial Cyclic Peptides for Plant Disease Control

    PubMed Central

    Lee, Dong Wan; Kim, Beom Seok

    2015-01-01

    Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources. PMID:25774105

  11. Evaluation of antimicrobial properties of cork.

    PubMed

    Gonçalves, Filipa; Correia, Patrícia; Silva, Susana P; Almeida-Aguiar, Cristina

    2016-02-01

    Cork presents a range of diverse and versatile properties making this material suitable for several and extremely diverse industrial applications. Despite the wide uses of cork, its antimicrobial properties and potential applications have deserved little attention from industry and the scientific community. Thus, the main purpose of this work was the evaluation of the antibacterial properties of cork, by comparison with commercially available antimicrobial materials (Ethylene-Vinyl Acetate copolymer and a currently used antimicrobial commercial additive (ACA)), following the previous development and optimization of a method for such antimicrobial assay. The AATCC 100-2004 standard method, a quantitative procedure developed for the assessment of antimicrobial properties in textile materials, was used as reference and optimized to assess cork antibacterial activity. Cork displayed high antibacterial activity against Staphylococcus aureus, with a bacterial reduction of almost 100% (96.93%) after 90 minutes of incubation, similar to the one obtained with ACA. A more reduced but time-constant antibacterial action was observed against Escherichia coli (36% reduction of the initial number of bacterial colonies). To complement this study, antibacterial activity was further evaluated for a water extract of cork and an MIC of 6 mg mL(-1) was obtained against the reference strain S. aureus.

  12. Health and economic impacts of antimicrobial resistance.

    PubMed

    Holmberg, S D; Solomon, S L; Blake, P A

    1987-01-01

    For comparison of the impacts of infections due to antimicrobial-resistant bacteria with those of infections due to antimicrobial-susceptible strains of the same bacteria, data were evaluated from 175 published and unpublished reports of investigations of nosocomial and community-acquired infections with selected bacteria. The evaluation of outcomes of hospital-acquired infections with resistant organisms was often confounded by risk factors also associated with poor outcomes. Nevertheless, for both nosocomial and community-acquired infections, the mortality, the likelihood of hospitalization, and the length of hospital stay were usually at least twice as great for patients infected with drug-resistant strains as for those infected with drug-susceptible strains of the same bacteria. Poor outcomes could be attributed both to the expected effects of ineffective antimicrobial therapy and to the unexpected occurrence of drug-resistant infections complicated by prior antimicrobial therapy for other medical problems. Although the adverse economic and health effects of drug-resistant bacterial infections can only be roughly quantified, it is concluded that antimicrobial resistance is an important health problem and an economic burden to society. PMID:3321356

  13. Protease Inhibitors from Plants with Antimicrobial Activity

    PubMed Central

    Kim, Jin-Young; Park, Seong-Cheol; Hwang, Indeok; Cheong, Hyeonsook; Nah, Jae-Woon; Hahm, Kyung-Soo; Park, Yoonkyung

    2009-01-01

    Antimicrobial proteins (peptides) are known to play important roles in the innate host defense mechanisms of most living organisms, including plants, insects, amphibians and mammals. They are also known to possess potent antibiotic activity against bacteria, fungi, and even certain viruses. Recently, the rapid emergence of microbial pathogens that are resistant to currently available antibiotics has triggered considerable interest in the isolation and investigation of the mode of action of antimicrobial proteins (peptides). Plants produce a variety of proteins (peptides) that are involved in the defense against pathogens and invading organisms, including ribosome-inactivating proteins, lectins, protease inhibitors and antifungal peptides (proteins). Specially, the protease inhibitors can inhibit aspartic, serine and cysteine proteinases. Increased levels of trypsin and chymotrypsin inhibitors correlated with the plants resistance to the pathogen. Usually, the purification of antimicrobial proteins (peptides) with protease inhibitor activity was accomplished by salt-extraction, ultrafiltration and C18 reverse phase chromatography, successfully. We discuss the relation between antimicrobial and anti-protease activity in this review. Protease inhibitors from plants potently inhibited the growth of a variety of pathogenic bacterial and fungal strains and are therefore excellent candidates for use as the lead compounds for the development of novel antimicrobial agents. PMID:19582234

  14. An institutional review of antimicrobial stewardship interventions.

    PubMed

    Cao, Henry; Phe, Kady; Laine, Gregory A; Russo, Hannah R; Putney, Kimberly S; Tam, Vincent H

    2016-09-01

    In order to combat increasing rates of bacterial resistance, many institutions have implemented antimicrobial stewardship programmes (ASPs) to improve antibiotic use. To ascertain the potential impact of our stewardship programme at Baylor St Luke's Medical Center (Houston, TX), antimicrobial-related interventions were analysed over a 4-year period. ASP recommendations related to antimicrobial therapy from 2009 to 2012 were retrieved from the hospital electronic database and were retrospectively reviewed. The number of interventions for each time period was adjusted to the hospital census data. The interventions were randomly assessed and categorised for clinical significance based on established institutional guidelines. In total, 14654 non-duplicate antimicrobial therapy interventions were retrieved, of which 11874 (81.0%) were audited for accuracy. Approximately 13 interventions were made per 1000 patient-days, but there were no significant patterns observed regarding the number of interventions performed from month to month (range 8-21). The most frequent types of interventions were related to inappropriate dosing (39.0%), antimicrobial selection (20.5%) and drug allergy (13.0%). Serious adverse drug events (ADEs) were potentially avoided in 20.7% of all interventions. Cumulative potential cost avoidance was more than US$6.5 million. In our institution, proper drug and dose selection were the major components of the ASP. Without focusing solely on reduction of drug acquisition costs, implementation of an ASP could still be cost effective by improving the quality of patient care and avoiding ADEs with serious consequences. PMID:27530844

  15. Antimicrobial Activity of Carbon-Based Nanoparticles

    PubMed Central

    Maleki Dizaj, Solmaz; Mennati, Afsaneh; Jafari, Samira; Khezri, Khadejeh; Adibkia, Khosro

    2015-01-01

    Due to the vast and inappropriate use of the antibiotics, microorganisms have begun to develop resistance to the commonly used antimicrobial agents. So therefore, development of the new and effective antimicrobial agents seems to be necessary. According to some recent reports, carbon-based nanomaterials such as fullerenes, carbon nanotubes (CNTs) (especially single-walled carbon nanotubes (SWCNTs)) and graphene oxide (GO) nanoparticles show potent antimicrobial properties. In present review, we have briefly summarized the antimicrobial activity of carbon-based nanoparticles together with their mechanism of action. Reviewed literature show that the size of carbon nanoparticles plays an important role in the inactivation of the microorganisms. As major mechanism, direct contact of microorganisms with carbon nanostructures seriously affects their cellular membrane integrity, metabolic processes and morphology. The antimicrobial activity of carbon-based nanostructures may interestingly be investigated in the near future owing to their high surface/volume ratio, large inner volume and other unique chemical and physical properties. In addition, application of functionalized carbon nanomaterials as carriers for the ordinary antibiotics possibly will decrease the associated resistance, enhance their bioavailability and provide their targeted delivery. PMID:25789215

  16. Development and construction of low-cracking high-performance concrete (LC-HPC) bridge decks: Free shrinkage tests, restrained ring tests, construction experience, and crack survey results

    NASA Astrophysics Data System (ADS)

    Yuan, Jiqiu

    2011-12-01

    The development, construction, and evaluation of low-cracking high-performance concrete (LC-HPC) bridge decks are described based on laboratory test results and experiences gained during the construction of 13 LC-HPC bridge decks in Kansas, along with another deck bid under the LC-HPC specifications but for which the owner did not enforce the specification. This study is divided into four parts covering (1) an evaluation of the free shrinkage properties of LC-HPC candidate mixtures, (2) an investigation of the relationship between the evaporable water content in the cement paste and the free shrinkage of concrete, (3) a study of the restrained shrinkage performance of concrete using restrained ring tests, and (4) a description of the construction and preliminary evaluation of LC-HPC and control bridge decks constructed in Kansas. The first portion of the study involves evaluating the effects of the duration of curing, fly ash, and a shrinkage reducing admixture (SRA) on the free-shrinkage characteristics of concrete mixtures. The results indicate that an increase of curing period reduces free shrinkage. With 7 days of curing, concretes containing fly ash as a partial replacement for cement exhibit higher free shrinkage than concretes with 100% portland cement. When the curing period is increased to 14, 28, and 56 days, the adverse effect of adding fly ash on free shrinkage is minimized and finally reversed. The addition of an SRA significantly reduces free shrinkage for both the 100% portland cement mixture and the mixture containing fly ash. The second portion of the study investigates the relationship between the evaporable water content in the cement paste and the free shrinkage of concrete. A linear relationship between free shrinkage and evaporable water content in the cement paste is observed. For a given mixture, specimens cured for a longer period contain less evaporable water and exhibit lower free shrinkage and less weight loss in the free shrinkage

  17. [Antimicrobial properties of antiseptic composite with prolonged action].

    PubMed

    Paliĭ, G K; Nazarchuk, A A; Paliĭ, D V; Nazarchuk, G G; Gonchar, O O; Sukhliak, V V; Trofimenko, Iu Iu; Zadereĭ, N V; Stukan, O K

    2013-01-01

    Antimicrobial properties of a composite based on decamethoxine and modified polysaccharides (carboxymethylamylum, oxyethyl-cellulose) were studied. The composite was shown to have high antimicrobial activity against grampositive and gramnegative bacteria under different conditions of the experiment.

  18. Point-of-prescription interventions to improve antimicrobial stewardship.

    PubMed

    Hamilton, Keith W; Gerber, Jeffrey S; Moehring, Rebekah; Anderson, Deverick J; Calderwood, Michael S; Han, Jennifer H; Mehta, Jimish M; Pollack, Lori A; Zaoutis, Theoklis; Srinivasan, Arjun; Camins, Bernard C; Schwartz, David N; Lautenbach, Ebbing

    2015-04-15

    Antimicrobial stewardship is pivotal to improving patient outcomes, reducing adverse events, decreasing healthcare costs, and preventing further emergence of antimicrobial resistance. In an era in which antimicrobial resistance is increasing, judicious antimicrobial use is the responsibility of every healthcare provider. Antimicrobial stewardship programs (ASPs) have made headway in improving antimicrobial prescribing using such "top-down" methods as formulary restriction and prospective audit with feedback; however, engagement of prescribers has not been fully explored. Strategies that include frontline prescribers and other unit-based healthcare providers have the potential to expand stewardship, both to augment existing centralized ASPs and to provide alternative approaches to perform stewardship at healthcare facilities with limited resources. This review discusses interventions focusing on antimicrobial prescribing at the point of prescription as well as a pilot project to engage unit-based healthcare providers in antimicrobial stewardship.

  19. Antimicrobial stewardship interventions: thinking inside and outside the box.

    PubMed

    Hamilton, Keith W; Fishman, Neil O

    2014-06-01

    At present, less than half of all acute health care facilities have antimicrobial stewardship programs. By targeting areas that are vulnerable to inappropriate antimicrobial use and by using novel strategies to increase the reach of stewardship interventions, providers can make antimicrobial stewardship a universal practice in all health care settings. This review discusses how stewardship can make large impacts in areas where it has traditionally been absent in facilities both with and without formal antimicrobial stewardship programs.

  20. Bacterial strategies of resistance to antimicrobial peptides.

    PubMed

    Joo, Hwang-Soo; Fu, Chih-Iung; Otto, Michael

    2016-05-26

    Antimicrobial peptides (AMPs) are a key component of the host's innate immune system, targeting invasive and colonizing bacteria. For successful survival and colonization of the host, bacteria have a series of mechanisms to interfere with AMP activity, and AMP resistance is intimately connected with the virulence potential of bacterial pathogens. In particular, because AMPs are considered as potential novel antimicrobial drugs, it is vital to understand bacterial AMP resistance mechanisms. This review gives a comparative overview of Gram-positive and Gram-negative bacterial strategies of resistance to various AMPs, such as repulsion or sequestration by bacterial surface structures, alteration of membrane charge or fluidity, degradation and removal by efflux pumps.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. PMID:27160595

  1. Antimicrobial peptides in innate immune responses.

    PubMed

    Sørensen, Ole E; Borregaard, Niels; Cole, Alexander M

    2008-01-01

    Antimicrobial peptides (AMPs) are ancient effector molecules in the innate immune response of eukaryotes. These peptides are important for the antimicrobial efficacy of phagocytes and for the innate immune response mounted by epithelia of humans and other mammals. AMPs are generated either by de novo synthesis or by proteolytic cleavage from antimicrobially inactive proproteins. Studies of human diseases and animal studies have given important clues to the in vivo role of AMPs. It is now evident that dysregulation of the generation of AMPs in innate immune responses plays a role in certain diseases like Crohn's disease and atopic dermatitis. AMPs are attractive candidates for development of novel antibiotics due to their in vivo activity profile and some peptides may serve as templates for further drug development.

  2. Two novel antimicrobial peptides from centipede venoms.

    PubMed

    Peng, Kanfu; Kong, Yi; Zhai, Lei; Wu, Xiongfei; Jia, Peng; Liu, Jingze; Yu, Haining

    2010-01-01

    Centipede venoms are complex mixtures of biochemically and pharmacologically active components such as peptides and proteins. Very few are known about their pharmacological actions. The present work reports the structural and functional characterization of two antimicrobial peptides (scolopin 1 and -2) identified from centipede venoms of Scolopendra subspinipes mutilans by Sephadex gel filtration and reverse-phase high-performance liquid chromatography (RP-HPLC). The amino acid sequences of scolopin 1 and -2 were FLPKMSTKLRVPYRRGTKDYH and GILKKFMLHRGTKVYKMRTLSKRSH determined by Edman degradation and matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Both scolopin 1 and -2 showed strong antimicrobial activities against tested microorganisms including Gram-positive/negative bacteria and fungi. They also showed moderate hemolytic activity against both human and rabbit red cells. This is the first report of antimicrobial peptides from centipedes.

  3. Bacterial strategies of resistance to antimicrobial peptides.

    PubMed

    Joo, Hwang-Soo; Fu, Chih-Iung; Otto, Michael

    2016-05-26

    Antimicrobial peptides (AMPs) are a key component of the host's innate immune system, targeting invasive and colonizing bacteria. For successful survival and colonization of the host, bacteria have a series of mechanisms to interfere with AMP activity, and AMP resistance is intimately connected with the virulence potential of bacterial pathogens. In particular, because AMPs are considered as potential novel antimicrobial drugs, it is vital to understand bacterial AMP resistance mechanisms. This review gives a comparative overview of Gram-positive and Gram-negative bacterial strategies of resistance to various AMPs, such as repulsion or sequestration by bacterial surface structures, alteration of membrane charge or fluidity, degradation and removal by efflux pumps.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

  4. DNA as a target for antimicrobials.

    PubMed

    Bolhuis, Albert; Aldrich-Wright, Janice R

    2014-08-01

    Resistance to antimicrobials is one of the biggest threats to our healthcare. However, in the last few decades very few truly novel antimicrobial compounds have been brought to market, creating the potential threat of a post-antibiotic era in which infections are very difficult to treat. Identification of novel compounds with antimicrobial activity is therefore paramount. Ideally, novel compounds should be designed that are active against targets that are not or barely used, as it is less likely that resistance already exists against such compounds. One example of an underexplored target in the treatment of infections is DNA. In this review we describe a number of DNA binding compounds and discuss potential opportunities and problems.

  5. Antimicrobials in dermatologic surgery: facts and controversies.

    PubMed

    Shurman, Daniel L; Benedetto, Anthony V

    2010-01-01

    The two main uses of antimicrobials in dermatologic surgery include prophylaxis for bacteremia and prevention of localized surgical skin infection (LSSI). Bacteremia can result in hematogenous surgical infections such as infective endocarditis and prosthetic joint infection. Comprehensive guidelines from the American Heart Society (AHA), American Dental Association (ADA), and the American Academy of Orthopedic Surgeons (AAOS) have significantly reduced the number of patients in which prophylaxis is indicated for hematogenous surgical infection. The use of antimicrobials for localized surgical skin infection in dermatology is controversial. Although the overall trend in the literature supports the decreased use of antimicrobials in dermatologic surgery as a whole, it is important to know which situations still warrant antibiotics. This contribution will address the updated guidelines of the AHA, ADA, and AAOS, evidence-based techniques to decrease localized surgical skin infections, and situations in which antibiotics should be considered during dermatologic surgery. PMID:20797510

  6. Initiatives and resources to promote antimicrobial stewardship.

    PubMed

    Paño-Pardo, José Ramón; Campos, José; Natera Kindelán, Clara; Ramos, Antonio

    2013-09-01

    The development of an antimicrobial stewardship program (ASP) requires institutional support. However, obtaining sufficient institutional support is often a complex task that requires convincing the hospital's managers of the benefits of these programs. Additionally, in the design and implementation of an ASP, antimicrobial stewardship (AS) leaders need tools for diverse purposes, such as measuring antimicrobial consumption, education and training and designing protocols. In this review we provide useful information for AS promoters to facilitate the task of designing and implementing an ASP. First, we summarize information about various institutions that promote AS and include evidence that supports the need for and benefits of these programs. Then, several campaigns promoting AS are described. Finally, online resources for professionals dealing with AS are briefly summarized.

  7. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens

    PubMed Central

    Santajit, Sirijan; Indrawattana, Nitaya

    2016-01-01

    The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens. PMID:27274985

  8. The Antimicrobial Activity of Porphyrin Attached Polymers

    NASA Astrophysics Data System (ADS)

    Thompson, Lesley

    2008-03-01

    We are interested in testing the antimicrobial activity of a porphyrin that is attached to a polymer. The porphyrin (5-(4-carboxyphenyl)-10,15,20-tris-(4-pryridyl)) was synthesized from methyl 4-formyl benzoate, 4-pyridinecarboxaldehyde, and pyrrole and attached to a copolymer of polystyrene/poly(vinyl benzyl chloride), which was synthesized by free radical polymerization. The antimicrobial activity of the polymer-attached porphyrin was then determined for gram-negative E. Coli grown to 0.80 OD. In this procedure, glass slides were coated with polymer-attached porphyrin via dip-coating, and the E. Coli bacteria were plated in Luria Broth media. The plates were subsequently exposed to light overnight before they were incubated as porphyrins act as photo-sensitizers when irradiated with light. The polymer-attached porphyrin did exhibit antimicrobial activity and parameters that affect its efficiency will be discussed.

  9. Antimicrobial peptides: successes, challenges and unanswered questions.

    PubMed

    Wimley, William C; Hristova, Kalina

    2011-01-01

    Multidrug antibiotic resistance is an increasingly serious public health problem worldwide. Thus, there is a significant and urgent need for the development of new classes of antibiotics that do not induce resistance. To develop such antimicrobial compounds, we must look toward agents with novel mechanisms of action. Membrane-permeabilizing antimicrobial peptides (AMPs) are good candidates because they act without high specificity toward a protein target, which reduces the likelihood of induced resistance. Understanding the mechanism of membrane permeabilization is crucial for the development of AMPs into useful antimicrobial agents. Various models, some phenomenological and others more quantitative or semimolecular, have been proposed to explain the action of AMPs. While these models explain many aspects of AMP action, none of the models captures all of the experimental observations, and significant questions remain unanswered. Here, we discuss the state of the field and pose some questions that, if answered, could speed the discovery of clinically useful peptide antibiotics.

  10. Antimicrobial peptides and plant disease control.

    PubMed

    Montesinos, Emilio

    2007-05-01

    Several diseases caused by viruses, bacteria and fungi affect plant crops, resulting in losses and decreasing the quality and safety of agricultural products. Plant disease control relies mainly on chemical pesticides that are currently subject to strong restrictions and regulatory requirements. Antimicrobial peptides are interesting compounds in plant health because there is a need for new products in plant protection that fit into the new regulations. Living organisms secrete a wide range of antimicrobial peptides produced through ribosomal (defensins and small bacteriocins) or non-ribosomal synthesis (peptaibols, cyclopeptides and pseudopeptides). Several antimicrobial peptides are the basis for the design of new synthetic analogues, have been expressed in transgenic plants to confer disease protection or are secreted by microorganisms that are active ingredients of commercial biopesticides.

  11. Antimicrobials in animal agriculture: parables and policy.

    PubMed

    Scott, H M; Midgley, G; Loneragan, G H

    2015-04-01

    In addition to the scientific, economic, regulatory and other policy factors that impact on antimicrobial decision-making in different jurisdictions around the world, there exist ethical, social and cultural bases for the contemporary use of these products in animal agriculture. Thus, the use of the word 'parable' to describe the contemporary moral stories that help to guide ethical antimicrobial use practices and broader policy decisions in animal agriculture is appropriate. Several of these stories reflect difficult decisions that arise from conflicting moral imperatives (i.e. both towards animal welfare and towards human health). Understanding the factors that combine to define the past and present paradigms of antimicrobial usage is crucial to mapping a path forward. There exist barriers, as well as opportunities, for advancing scenarios for reducing antimicrobial usage under a variety of voluntary, regulatory and legal policy frameworks. Any new approaches will ideally be structured to extend the use of present-day antimicrobials into the future, to provide novel alternatives for regulating any newly introduced antimicrobial products so as to maximize their useful life span and to ensure the optimal use of these products in animal agriculture to protect not only the health of animals and the interests of animal health/agriculture stakeholders, but also the human health and the interests of the public at large. A full range of policy approaches, which span the realm from strictly enforced regulations and laws to voluntary guidelines and compliance, should be explored with respect to their risks and benefits in a variety of worldwide settings and in full consideration of a range of stakeholder values.

  12. Using genomics to identify novel antimicrobials.

    PubMed

    Kim, W H; Lillehoj, H S; Gay, C G

    2016-04-01

    There is a critical need in animal agriculture to develop novel antimicrobials and alternative strategies that will help to reduce the use of antibiotics and address the challenges of antimicrobial resistance. High-throughput gene expression analysis is providing new tools that are enabling the discovery of host-derived antimicrobial peptides. Examples of gene-encoded natural antibiotics that have gained attention include antimicrobial peptides such as human granulysin and its multi-species homolog, namely NK-lysin, which provide a protective response against a broad range of microbes and are a principal component of innate immunity in vertebrates. Both granulysin and NK-lysin are localised in cytolytic granules in natural killer and cytotoxic T lymphocytes. Host-derived NK-lysins that were first described in mammals are also found in avian species, and they have been shown to have antimicrobial activities that could potentially be used to control important poultry pathogens. Morphological alterations observed following chicken NK-lysin binding to Eimeria sporozoites and Escherichia coli membranes indicate damage and disruption of cell membranes, suggesting that NK-lysin kills pathogenic protozoans and bacteria by direct interaction. Genotype analysis revealed that chicken NK-lysin peptides derived from certain alleles were more effective at killing pathogens than those derived from others, which could potentially affect susceptibility to diseases. Although the host-derived antimicrobial peptides described in this paper may not, by themselves, be able to replace the antibiotics currently used in animal production, their use as specific treatments based on their known mechanisms of action is showing promising results. PMID:27217171

  13. Using genomics to identify novel antimicrobials.

    PubMed

    Kim, W H; Lillehoj, H S; Gay, C G

    2016-04-01

    There is a critical need in animal agriculture to develop novel antimicrobials and alternative strategies that will help to reduce the use of antibiotics and address the challenges of antimicrobial resistance. High-throughput gene expression analysis is providing new tools that are enabling the discovery of host-derived antimicrobial peptides. Examples of gene-encoded natural antibiotics that have gained attention include antimicrobial peptides such as human granulysin and its multi-species homolog, namely NK-lysin, which provide a protective response against a broad range of microbes and are a principal component of innate immunity in vertebrates. Both granulysin and NK-lysin are localised in cytolytic granules in natural killer and cytotoxic T lymphocytes. Host-derived NK-lysins that were first described in mammals are also found in avian species, and they have been shown to have antimicrobial activities that could potentially be used to control important poultry pathogens. Morphological alterations observed following chicken NK-lysin binding to Eimeria sporozoites and Escherichia coli membranes indicate damage and disruption of cell membranes, suggesting that NK-lysin kills pathogenic protozoans and bacteria by direct interaction. Genotype analysis revealed that chicken NK-lysin peptides derived from certain alleles were more effective at killing pathogens than those derived from others, which could potentially affect susceptibility to diseases. Although the host-derived antimicrobial peptides described in this paper may not, by themselves, be able to replace the antibiotics currently used in animal production, their use as specific treatments based on their known mechanisms of action is showing promising results.

  14. 40 CFR 158.2201 - Antimicrobial use patterns.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... DATA REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2201 Antimicrobial use patterns. (a) Antimicrobial use patterns. The 12 general use patterns used in the data tables in this... patterns. It is to be used in conjunction with the data tables in this subpart to determine...

  15. 40 CFR 158.2201 - Antimicrobial use patterns.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... DATA REQUIREMENTS FOR PESTICIDES Antimicrobial Pesticide Data Requirements § 158.2201 Antimicrobial use patterns. (a) Antimicrobial use patterns. The 12 general use patterns used in the data tables in this... patterns. It is to be used in conjunction with the data tables in this subpart to determine...

  16. Antimicrobial use and stewardship programs among dialysis centers.

    PubMed

    D'Agata, Erika M C

    2013-01-01

    Antimicrobial exposure contributes to the emergence and spread of multidrug-resistant organisms. As rates of colonization and infection with these organisms are among the highest in the population of chronic hemodialysis patients and antimicrobial exposure among this patient population is extensive, it is imperative to prescribe antimicrobials judiciously. Thirty to forty percent of chronic hemodialysis patients receive at least one dose of antimicrobials in outpatient centers over a one-year period. Up to 30% of these antimicrobials are prescribed inappropriately, as per national guidelines. The predominant reasons include (i) failure to de-escalate to a more narrow-spectrum antimicrobial, (ii) criteria for infection, especially skin and soft tissue infections, are not met, and (iii) indications and duration for surgical prophylaxis for minor vascular-access-related procedures do not follow recommended guidelines. Vancomycin, third- or fourth-generation cephalosporins and cefazolin are the most common antimicrobials or antimicrobial classes prescribed inappropriately. Antimicrobial stewardship programs reduce both inappropriate antimicrobial exposure and associated costs. Effective strategies include (i) education, (ii) guidelines and clinical pathways, (iii) antimicrobial order forms, (iv) de-escalation therapy, and (v) prospective audit and feedback. Dialysis centers need to identify a team of individuals that will lead the antimicrobial stewardship program. Administrative and financial support for this team is essential. After implementation of the program, regular monitoring for compliance with strategies, and identifying factors that are preventing compliance are necessary. The efficacy of the program should also be evaluated at regular intervals through process and outcome measures. PMID:23600755

  17. SecA: a potential antimicrobial target

    PubMed Central

    Chaudhary, Arpana S; Chen, Weixuan; Jin, Jinshan; Tai, Phang C; Wang, Binghe

    2015-01-01

    There is a consensus in the medical profession of the pressing need for novel antimicrobial agents due to issues related to drug resistance. In practice, solutions to this problem to a large degree lie with the identification of new and vital targets in bacteria and subsequently designing their inhibitors. We consider SecA a very promising antimicrobial target. In this review, we compile and analyze information available on SecA to show that inhibition of SecA has a multitude of consequences. Furthermore, we discuss issues critical to the design and evaluation of SecA inhibitors. PMID:26062397

  18. Antimicrobial Action of Compounds from Marine Seaweed

    PubMed Central

    Pérez, María José; Falqué, Elena; Domínguez, Herminia

    2016-01-01

    Seaweed produces metabolites aiding in the protection against different environmental stresses. These compounds show antiviral, antiprotozoal, antifungal, and antibacterial properties. Macroalgae can be cultured in high volumes and would represent an attractive source of potential compounds useful for unconventional drugs able to control new diseases or multiresistant strains of pathogenic microorganisms. The substances isolated from green, brown and red algae showing potent antimicrobial activity belong to polysaccharides, fatty acids, phlorotannins, pigments, lectins, alkaloids, terpenoids and halogenated compounds. This review presents the major compounds found in macroalga showing antimicrobial activities and their most promising applications. PMID:27005637

  19. Strategies for targeted antimicrobial photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Verma, Sarika; Sallum, Ulysses; Zheng, Xiang; Hasan, Tayyaba

    2009-06-01

    The photophysics and mechanisms of cell killing by photodynamic therapy (PDT) have been extensively studied in recent years, and PDT has received regulatory approval for the treatment of a number of diseases worldwide. As the application of this treatment modality expands with regard to both anatomical sites and diseases, it is important to develop strategies for enhancing PDT outcomes. Our group has focused on developing targeting strategies to enhance PDT for both cancerous as well as anti-microbial applications. In this article, we will discuss photosensitizer modification and conjugation strategies for targeted antimicrobial photodynamic therapy.

  20. Boosting salt resistance of short antimicrobial peptides.

    PubMed

    Chu, Hung-Lun; Yu, Hui-Yuan; Yip, Bak-Sau; Chih, Ya-Han; Liang, Chong-Wen; Cheng, Hsi-Tsung; Cheng, Jya-Wei

    2013-08-01

    The efficacies of many antimicrobial peptides are greatly reduced under high salt concentrations, therefore limiting their use as pharmaceutical agents. Here, we describe a strategy to boost salt resistance and serum stability of short antimicrobial peptides by adding the nonnatural bulky amino acid β-naphthylalanine to their termini. The activities of the short salt-sensitive tryptophan-rich peptide S1 were diminished at high salt concentrations, whereas the activities of its β-naphthylalanine end-tagged variants were less affected.

  1. Antimicrobial Stewardship for the Infection Control Practitioner.

    PubMed

    Nagel, Jerod L; Kaye, Keith S; LaPlante, Kerry L; Pogue, Jason M

    2016-09-01

    Antibiotic misuse is a serious patient safety concern and a national public health priority. Years of indiscriminant antibiotic use has promoted selection for antibiotic resistant bacteria and Clostridium difficile This crisis has led to clinicians being faced with managing untreatable infections, often in the most vulnerable patient populations. This review summarizes the goals of antimicrobial stewardship programs, the essential members needed to initiate a program, various antimicrobial stewardship strategies, the role of the infection control practitioner in stewardship, barriers to its implementation and maintenance, approaches to measure the impact of a program, and the steps needed to initiate a program.

  2. Antimicrobial Stewardship for the Infection Control Practitioner.

    PubMed

    Nagel, Jerod L; Kaye, Keith S; LaPlante, Kerry L; Pogue, Jason M

    2016-09-01

    Antibiotic misuse is a serious patient safety concern and a national public health priority. Years of indiscriminant antibiotic use has promoted selection for antibiotic resistant bacteria and Clostridium difficile This crisis has led to clinicians being faced with managing untreatable infections, often in the most vulnerable patient populations. This review summarizes the goals of antimicrobial stewardship programs, the essential members needed to initiate a program, various antimicrobial stewardship strategies, the role of the infection control practitioner in stewardship, barriers to its implementation and maintenance, approaches to measure the impact of a program, and the steps needed to initiate a program. PMID:27515147

  3. Octenidine dihydrochloride: chemical characteristics and antimicrobial properties.

    PubMed

    Assadian, Ojan

    2016-03-01

    The empiric use of antibiotics is being restricted due to the spread of antimicrobial resistance. However, topical antiseptics are less likely to induce resistance, owing to their unspecific mode of action and the high concentrations in which they can be used. One such antiseptic, octenidine dihydrochloride (OCT), can be used either prophylactically or therapeutically on the skin, mucosa and wounds. Evidence to support its use comes from in-vitro, animal and clinical studies on its safety, tolerability and efficacy. This article summarises the physical, chemical and antimicrobial properties of OCT in the context of wound care.

  4. Platelets: at the nexus of antimicrobial defence.

    PubMed

    Yeaman, Michael R

    2014-06-01

    Platelets have traditionally been viewed as fragmentary mediators of coagulation. However, recent molecular and cellular evidence suggests that they have multiple roles in host defence against infection. From first-responders that detect pathogens and rapidly deploy host-defence peptides, to beacons that recruit and enhance leukocyte functions in the context of infection, to liaisons that facilitate the T cell-B cell crosstalk that is required in adaptive immunity, platelets represent a nexus at the intersection of haemostasis and antimicrobial host defence. In this Review, I consider recent insights into the antimicrobial roles of platelets, which are mediated both directly and indirectly to integrate innate and adaptive immune responses to pathogens.

  5. Antimicrobial hasubanalactam alkaloid from Stephania glabra.

    PubMed

    Semwal, Deepak Kumar; Rawat, Usha

    2009-03-01

    A novel hasubanalactam alkaloid, named glabradine, has been isolated from the tubers of Stephania glabra, together with three known quaternary protoberberine alkaloids, palmatine, dehydrocorydalmine and stepharanine. The structure of glabradine was assigned as 7-O-demethyl-N,O-dimethyloxostephinine, by means of rigorous spectroscopic analysis including 2 D NMR measurements. It was evaluated for antimicrobial activity against Staphylococcus aureus, S. mutans, Microsporum gypseum, M. canis and Trichophyton rubrum and displayed potent antimicrobial activity superior to those of novobiocin and erythromycin used as positive controls. PMID:19148860

  6. Antimicrobial food equipment coatings: applications and challenges.

    PubMed

    Bastarrachea, Luis J; Denis-Rohr, Anna; Goddard, Julie M

    2015-01-01

    Emerging technologies in antimicrobial coatings can help improve the quality and safety of our food supply. The goal of this review is to survey the major classes of antimicrobial agents explored for use in coatings and to describe the principles behind coating processes. Technologies from a range of fields, including biomedical and textiles research, as well as current applications in food contact materials, are addressed, and the technical hurdles that must be overcome to enable commercial adaptation to food processing equipment are critically evaluated.

  7. Perceptions of antimicrobial usage, antimicrobial resistance and policy measures to reduce antimicrobial usage in convenient samples of Belgian, French, German, Swedish and Swiss pig farmers.

    PubMed

    Visschers, V H M; Backhans, A; Collineau, L; Iten, D; Loesken, S; Postma, M; Belloc, C; Dewulf, J; Emanuelson, U; Beilage, E Grosse; Siegrist, M; Sjölund, M; Stärk, K D C

    2015-04-01

    We conducted a survey among convenient samples of pig farmers (N=281) in Belgium, France, Germany, Sweden and Switzerland. We identified some significant differences among the five investigated countries (independent variable) regarding farmers' antimicrobial usage compared to their own country and worries related to pig farming (dependent variables), but most of the differences were rather small. In general, farmers perceived their own antimicrobial usage to be lower than that of their peers in the same country and lower than or similar to that of farmers from other countries. This may be a consequence of our convenience sample, resulting in self-selection of highly motivated farmers. Farmers were significantly more worried about financial/legal issues than about antimicrobial resistance. They believed that a reduction in revenues for slaughter pigs treated with a large amount of antimicrobials would have the most impact on reduced antimicrobial usage in their country. Further, farmers who were more worried about antimicrobial resistance and who estimated their own antimicrobial usage as lower than their fellow countrymen, perceived more impact from policy measures on the reduction of antimicrobials. Our results indicated that the same policy measures can be applied to reduce antimicrobial usage in pig farming in all five countries. Moreover, it seems worthwhile to increase pig farmers' awareness of the threat of antimicrobial resistance and its relation to antimicrobial usage; not only because pig farmers appeared little worried about antimicrobial usage but also because it affected farmers' perception of policy measures to reduce antimicrobial usage. Our samples were not representative for the national pig farmer populations. Further research is therefore needed to examine to what extent our findings can be generalised to these populations and to farmers in other countries.

  8. The effect of pretensioning and age on torso rollout in restrained human volunteers in far-side lateral and oblique loading.

    PubMed

    Arbogast, Kristy B; Mathews, Emily A; Seacrist, Thomas; Maltese, Matthew R; Hammond, Rachel; Balasubramanian, Sriram; Kent, Richard W; Tanji, Hiromasa; St Lawrence, Schuyler; Higuchi, Kazuo

    2012-10-01

    Far-side side impact loading of a seat belt restrained occupant has been shown to lead to torso slip out of the shoulder belt. A pretensioned seat belt may provide an effective countermeasure to torso rollout; however the effectiveness may vary with age due to increased flexibility of the pediatric spine compared to adults. To explore this effect, low-speed lateral (90°) and oblique (60°) sled tests were conducted using male human volunteers (20 subjects: 9-14 years old, 10 subjects: 18-30 years old), in which the crash pulse safety envelope was defined from an amusement park bumper-car impact. Each subject was restrained by a lap and shoulder belt system equipped with an electromechanical motorized seat belt retractor (EMSR) and photo- reflective targets were attached to a tight-fitting headpiece or adhered to the skin overlying key skeletal landmarks. Each subject was randomly assigned to either the 60° or 90° direction and was exposed to 4 test conditions - arms up (with hands on their knees) with EMSR on, arms down (with hands low on the hips) with EMSR on, arms up with EMSR off, arms down with EMSR off. The effect of age and pretensioning on the following outcomes was quantified: 1) lateral and forward displacement of the torso, 2) torso rollout angle projected onto three orthogonal planes, and 3) resultant belt-sternal distance. The effect of pretensioning on torso containment within the shoulder belt was strong in both impact directions across all metrics evaluated. EMSR activation significantly reduced lateral displacement of the suprasternal notch (~100 mm, p<0.0001), coronal projection of the torso rollout angle (~15°, p<0.0001), and belt sternal distance when the arms were down (~50 mm, p<0.05). The benefit of pretensioning was achieved by early engagement of the torso by the shoulder belt. An added benefit of pretensioning was the ability to make similar the torso kinematics across a range of anthropometries as assessed within and across age groups

  9. The effect of pretensioning and age on torso rollout in restrained human volunteers in far-side lateral and oblique loading.

    PubMed

    Arbogast, Kristy B; Mathews, Emily A; Seacrist, Thomas; Maltese, Matthew R; Hammond, Rachel; Balasubramanian, Sriram; Kent, Richard W; Tanji, Hiromasa; St Lawrence, Schuyler; Higuchi, Kazuo

    2012-10-01

    Far-side side impact loading of a seat belt restrained occupant has been shown to lead to torso slip out of the shoulder belt. A pretensioned seat belt may provide an effective countermeasure to torso rollout; however the effectiveness may vary with age due to increased flexibility of the pediatric spine compared to adults. To explore this effect, low-speed lateral (90°) and oblique (60°) sled tests were conducted using male human volunteers (20 subjects: 9-14 years old, 10 subjects: 18-30 years old), in which the crash pulse safety envelope was defined from an amusement park bumper-car impact. Each subject was restrained by a lap and shoulder belt system equipped with an electromechanical motorized seat belt retractor (EMSR) and photo- reflective targets were attached to a tight-fitting headpiece or adhered to the skin overlying key skeletal landmarks. Each subject was randomly assigned to either the 60° or 90° direction and was exposed to 4 test conditions - arms up (with hands on their knees) with EMSR on, arms down (with hands low on the hips) with EMSR on, arms up with EMSR off, arms down with EMSR off. The effect of age and pretensioning on the following outcomes was quantified: 1) lateral and forward displacement of the torso, 2) torso rollout angle projected onto three orthogonal planes, and 3) resultant belt-sternal distance. The effect of pretensioning on torso containment within the shoulder belt was strong in both impact directions across all metrics evaluated. EMSR activation significantly reduced lateral displacement of the suprasternal notch (~100 mm, p<0.0001), coronal projection of the torso rollout angle (~15°, p<0.0001), and belt sternal distance when the arms were down (~50 mm, p<0.05). The benefit of pretensioning was achieved by early engagement of the torso by the shoulder belt. An added benefit of pretensioning was the ability to make similar the torso kinematics across a range of anthropometries as assessed within and across age groups

  10. Host immune modulation by antimicrobial drugs: current knowledge and implications for antimicrobial chemotherapy.

    PubMed

    Banche, Giuliana; Allizond, Valeria; Mandras, Narcisa; Tullio, Vivian; Cuffini, Anna Maria

    2014-10-01

    It is known that antimicrobial agents possess several, beneficial, secondary properties which complement their primary antimicrobial activity like the immunomodulatory capacity that enforces host defense mechanisms or reduces host inflammatory response. In this review the current state of our recent research about the interaction between some antimicrobial agents and the immune system as complex pyramid of redundant cellular factors, humoral effectors and mediators against various microbial pathogens, will be presented and compared with recent literature data. The nature of such interactions is diverse and depends on the drug, the host immunological status and the microorganism. A more complete understanding of the host immune modulation by antimicrobial drugs may guide the selection of appropriate regimens for given clinical situations.

  11. Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists.

    PubMed

    Gilchrist, Mark; Wade, Paul; Ashiru-Oredope, Diane; Howard, Philip; Sneddon, Jacqueline; Whitney, Laura; Wickens, Hayley

    2015-09-01

    Antimicrobial stewardship in the UK has evolved dramatically in the last 15 years. Factors driving this include initial central funding for specialist pharmacists and mandatory reductions in healthcare-associated infections (particularly Clostridium difficile infection). More recently, the introduction of national stewardship guidelines, and an increased focus on stewardship as part of the UK five-year antimicrobial resistance strategy, have accelerated and embedded developments. Antimicrobial pharmacists have been instrumental in effecting changes at an organizational and national level. This article describes the evolution of the antimicrobial pharmacist role, its impact, the progress toward the actions listed in the five-year resistance strategy, and novel emerging areas in stewardship in the UK.

  12. Antimicrobial Polymeric Materials with Quaternary Ammonium and Phosphonium Salts

    PubMed Central

    Xue, Yan; Xiao, Huining; Zhang, Yi

    2015-01-01

    Polymeric materials containing quaternary ammonium and/or phosphonium salts have been extensively studied and applied to a variety of antimicrobial-relevant areas. With various architectures, polymeric quaternary ammonium/phosphonium salts were prepared using different approaches, exhibiting different antimicrobial activities and potential applications. This review focuses on the state of the art of antimicrobial polymers with quaternary ammonium/phosphonium salts. In particular, it discusses the structure and synthesis method, mechanisms of antimicrobial action, and the comparison of antimicrobial performance between these two kinds of polymers. PMID:25667977

  13. Molecular target of synthetic antimicrobial oligomer in bacterial membranes

    NASA Astrophysics Data System (ADS)

    Yang, Lihua; Gordon, Vernita; Som, Abhigyan; Cronan, John; Tew, Gregory; Wong, Gerard

    2008-03-01

    Antimicrobial peptides comprises a key component of innate immunity for a wide range of multicellular organisms. It has been shown that natural antimicrobial peptides and their synthetic analogs have demonstrated broad-spectrum antimicrobial activity via permeating bacterial membranes selectively. Synthetic antimicrobials with tunable structure and toxicological profiles are ideal for investigations of selectivity mechanisms. We investigate interactions and self-assembly using a prototypical family of antimicrobials based on phenylene ethynylene. Results from synchrotron small angle x-ray scattering (SAXS) results and in vitro microbicidal assays on genetically modified `knock-out' bacteria will be presented.

  14. Late Holocene Paleo-Uplift Events at the Tapion Restraining Bend in Haiti: Implications for Earthquake Recurrence in the Vicinity of the 2010 Rupture Zone

    NASA Astrophysics Data System (ADS)

    Taylor, F. W.; Mann, P.; Briggs, R. W.; Prentice, C. S.; Jean, P.; Shen, C.; Chiang, H.; Jiang, X.

    2011-12-01

    The January 12, 2010, Mw 7.0 earthquake in Haiti was caused by slip on one or more blind thrust faults north of the plate-bounding, left-lateral, strike-slip Enriquillo-Plaintain Garden fault zone (EPGFZ). Thrusting lifted ~50 km of coastline with maximum coastal uplift of 0.64 m. Prior to the 2010 event, the EPGFZ likely ruptured during the 1751 or 1770 earthquakes with left-lateral surface offsets on the main trace of the fault that range from 1.3 to 3.3 m. We mapped and dated evidence of paleo-uplifts near the topographically prominent Tapion restraining bend, an apparent right-step along the main trace of the EPGFZ. We found fossil corals that provide evidence of uplift prior to 2010 at two sites located 6.4 km apart along the steep seaward side of Tapion Ridge, but no other evidence of paleo-uplift anywhere in the 2010 uplift zone. Near the east end of Tapion, growth-position coral at ~ 1m ALC (above living coral post-2010 uplift) gave a 230Th/234U age of 2138 ± 11 yr. 2010 uplift here was ~0.37 m, so that the net uplift from 2138 ± 11 yr until the 2010 earthquake was ~0.63 m. Near the western end of Tapion, emerged in situ coral heads giving ages of 4241 ± 13 and 4346 ± 14 yr are planed off at ~0.5 m ALC and capped by a pebble conglomerate, but we estimate that these corals had extended to ~1 m ALC prior to erosion. An emerged bioerosion notch centered at 0.46 m ALC and the planed tops of the coral heads at ~0.5 m correspond well to the 0.44 m ALC of coral that lived prior to the 2010 uplift at this site. A higher emerged bioerosion notch centered at ~0.93 m ALC corresponds well to the elevation of the nearby 4241 ± 13 and 4346 ± 14 yr corals at ~1.0 m ALC prior to being planed off to ~0.5 m. The dated corals and 0.93 m ALC notch indicate ~0.5 m net uplift from ~4241 ± 13 until the 2010 earthquake. Thus, fossil corals at two sites near Tapion are now at similar elevations, but their ages are significantly different and indicate two distinct uplift ages

  15. Topical Antimicrobials for Burn Wound Infections

    PubMed Central

    Dai, Tianhong; Huang, Ying-Ying; Sharma, Sulbha K.; Hashmi, Javad T.; Kurup, Divya B.; Hamblin, Michael R.

    2010-01-01

    Throughout most of history, serious burns occupying a large percentage of body surface area were an almost certain death sentence because of subsequent infection. A number of factors such as disruption of the skin barrier, ready availability of bacterial nutrients in the burn milieu, destruction of the vascular supply to the burned skin, and systemic disturbances lead to immunosuppression combined together to make burns particularly susceptible to infection. In the 20th century the introduction of antibiotic and antifungal drugs, the use of topical antimicrobials that could be applied to burns, and widespread adoption of early excision and grafting all helped to dramatically increase survival. However the relentless increase in microbial resistance to antibiotics and other antimicrobials has led to a renewed search for alternative approaches to prevent and combat burn infections. This review will cover patented strategies that have been issued or filed with regard to new topical agents, preparations, and methods of combating burn infections. Animal models that are used in preclinical studies are discussed. Various silver preparations (nanocrystalline and slow release) are the mainstay of many approaches but antimicrobial peptides, topical photodynamic therapy, chitosan preparations, new iodine delivery formulations, phage therapy and natural products such as honey and essential oils have all been tested. This active area of research will continue to provide new topical antimicrobials for burns that will battle against growing multi-drug resistance. PMID:20429870

  16. Antimicrobial Peptides in Innate Immunity against Mycobacteria.

    PubMed

    Shin, Dong-Min; Jo, Eun-Kyeong

    2011-10-01

    Antimicrobial peptides/proteins are ancient and naturallyoccurring antibiotics in innate immune responses in a variety of organisms. Additionally, these peptides have been recognized as important signaling molecules in regulation of both innate and adaptive immunity. During mycobacterial infection, antimicrobial peptides including cathelicidin, defensin, and hepcidin have antimicrobial activities against mycobacteria, making them promising candidates for future drug development. Additionally, antimicrobial peptides act as immunomodulators in infectious and inflammatory conditions. Multiple crucial functions of cathelicidins in antimycobacterial immune defense have been characterized not only in terms of direct killing of mycobacteria but also as innate immune regulators, i.e., in secretion of cytokines and chemokines, and mediating autophagy activation. Defensin families are also important during mycobacterial infection and contribute to antimycobacterial defense and inhibition of mycobacterial growth both in vitro and in vivo. Hepcidin, although its role in mycobacterial infection has not yet been characterized, exerts antimycobacterial effects in activated macrophages. The present review focuses on recent efforts to elucidate the roles of host defense peptides in innate immunity to mycobacteria.

  17. Antimicrobial peptides in echinoderm host defense.

    PubMed

    Li, Chun; Blencke, Hans-Matti; Haug, Tor; Stensvåg, Klara

    2015-03-01

    Antimicrobial peptides (AMPs) are important effector molecules in innate immunity. Here we briefly summarize characteristic traits of AMPs and their mechanisms of antimicrobial activity. Echinoderms live in a microbe-rich marine environment and are known to express a wide range of AMPs. We address two novel AMP families from coelomocytes of sea urchins: cysteine-rich AMPs (strongylocins) and heterodimeric AMPs (centrocins). These peptide families have conserved preprosequences, are present in both adults and pluteus stage larvae, have potent antimicrobial properties, and therefore appear to be important innate immune effectors. Strongylocins have a unique cysteine pattern compared to other cysteine-rich peptides, which suggests a novel AMP folding pattern. Centrocins and SdStrongylocin 2 contain brominated tryptophan residues in their native form. This review also includes AMPs isolated from other echinoderms, such as holothuroidins, fragments of beta-thymosin, and fragments of lectin (CEL-III). Echinoderm AMPs are crucial molecules for the understanding of echinoderm immunity, and their potent antimicrobial activity makes them potential precursors of novel drug leads.

  18. An Alternative Antimicrobial Commercial Egg Washing Procedure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Presently, commercial eggs are washed with water containing an alkali detergent at approximately pH 11 followed by a chlorine rinse. At this pH, it is likely that there is little, if any, free chlorine in the final rinse to act as an antimicrobial against pathogens like Salmonella. Using a chlorine ...

  19. [Application on food preservative of antimicrobial peptides].

    PubMed

    Zhao, Hongyan; Mu, Yu; Zhao, Baohua

    2009-07-01

    Antimicrobial peptides are an integral component of the innate immune system, it can counteract outer membrane pathogen such as bacteria, fungi, viruses, protozoan and so on. Owing to the sterilization and innocuity, it has the potential to be crude food preservative. In this paper the uses of antibacterial peptides in the food preservative were analyzed.

  20. An insect pupal cell with antimicrobial properties

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil-dwelling insects have developed various defense mechanisms to defend against pathogen infection. The pecan weevil, Curculio caryae, spends two to three years in the soil inside an earthen cell. We hypothesized that the cell may possess antimicrobial properties. In a laboratory study, we teste...

  1. Helical antimicrobial polypeptides with radial amphiphilicity

    PubMed Central

    Xiong, Menghua; Lee, Michelle W.; Mansbach, Rachael A.; Song, Ziyuan; Bao, Yan; Peek, Richard M.; Yao, Catherine; Chen, Lin-Feng; Ferguson, Andrew L.; Wong, Gerard C. L.; Cheng, Jianjun

    2015-01-01

    α-Helical antimicrobial peptides (AMPs) generally have facially amphiphilic structures that may lead to undesired peptide interactions with blood proteins and self-aggregation due to exposed hydrophobic surfaces. Here we report the design of a class of cationic, helical homo-polypeptide antimicrobials with a hydrophobic internal helical core and a charged exterior shell, possessing unprecedented radial amphiphilicity. The radially amphiphilic structure enables the polypeptide to bind effectively to the negatively charged bacterial surface and exhibit high antimicrobial activity against both gram-positive and gram-negative bacteria. Moreover, the shielding of the hydrophobic core by the charged exterior shell decreases nonspecific interactions with eukaryotic cells, as evidenced by low hemolytic activity, and protects the polypeptide backbone from proteolytic degradation. The radially amphiphilic polypeptides can also be used as effective adjuvants, allowing improved permeation of commercial antibiotics in bacteria and enhanced antimicrobial activity by one to two orders of magnitude. Designing AMPs bearing this unprecedented, unique radially amphiphilic structure represents an alternative direction of AMP development; radially amphiphilic polypeptides may become a general platform for developing AMPs to treat drug-resistant bacteria. PMID:26460016

  2. Iron trafficking as an antimicrobial target

    PubMed Central

    Frederick, Rosanne E.; Mayfield, Jeffery A.; DuBois, Jennifer L.

    2013-01-01

    Iron is essential for the survival of most organisms. Microbial iron acquisition depends on multiple, sometimes complex steps, many of which are not shared by higher eukaryotes. Depriving pathogenic microbes of iron is therefore a potential antimicrobial strategy. The following minireview briefly describes general elements in microbial iron uptake pathways and summarizes some of the current work aiming at their medicinal inhibition. PMID:19350396

  3. Bacterial resistance and topical antimicrobial wash products.

    PubMed

    Jones, R D

    1999-08-01

    Current scientific evidence has not shown that a link exists between the use of topical antimicrobial formulations and antiseptic or antibiotic resistance. As a result of the extensive history and varied use of antiseptic products and ingredients, any selective pressure for antibiotic resistance that may be occurring or may be uncovered in the future because of antiseptic use would be expected to be insignificant compared with the selective pressure because of antibiotic use. This review illustrates the effectiveness of topical antimicrobial wash products against antibiotic-resistant and antiseptic-resistant bacteria in use settings as well as the studies performed (antiseptic, deodorant, and oral care) demonstrating the lack of development of resistance in long-term clinical studies. Although these studies illustrate that the use of topical antimicrobial products have not been shown to play a role in the fluctuations of the specific composition or resistance of the skin flora, changes in skin flora have been shown to occur. Based on current knowledge, the benefit from use of topical antimicrobial wash products in combination with standard infection control and personal hygiene practices far outweighs the risk of increased antibiotic resistance.

  4. Using C. elegans for antimicrobial drug discovery

    PubMed Central

    Desalermos, Athanasios; Muhammed, Maged; Glavis-Bloom, Justin; Mylonakis, Eleftherios

    2011-01-01

    Introduction The number of microorganism strains with resistance to known antimicrobials is increasing. Therefore, there is a high demand for new, non-toxic and efficient antimicrobial agents. Research with the microscopic nematode Caenorhabditis elegans can address this high demand for the discovery of new antimicrobial compounds. In particular, C. elegans can be used as a model host for in vivo drug discovery through high-throughput screens of chemical libraries. Areas covered This review introduces the use of substitute model hosts and especially C. elegans in the study of microbial pathogenesis. The authors also highlight recently published literature on the role of C. elegans in drug discovery and outline its use as a promising host with unique advantages in the discovery of new antimicrobial drugs. Expert opinion C. elegans can be used, as a model host, to research many diseases, including fungal infections and Alzheimer’s disease. In addition, high-throughput techniques, for screening chemical libraries, can also be facilitated. Nevertheless, C. elegans and mammals have significant differences that both limit the use of the nematode in research and the degree by which results can be interpreted. That being said, the use of C. elegans in drug discovery still holds promise and the field continues to grow, with attempts to improve the methodology already underway. PMID:21686092

  5. Phytoaccumulation of antimicrobials by hydroponic Cucurbita pepo.

    PubMed

    Aryal, Niroj; Reinhold, Dawn

    2013-01-01

    Consumer use of antimicrobial-containing products continuously introduces triclocarban and triclosan into the environment. Triclocarban and triclosan adversely affect plants and animals and have the potential to affect human health. Research examined the phytoaccumulation of triclocarban and triclosan by pumpkin (Cucurbita pepo cultivar Howden) and zucchini (Cucurbita pepo cultivar Gold Rush) grown hydroponically. Pumpkin and zucchini were grown in nutrient solution spiked with 0.315 microg/mL triclocarban and 0.289 microg/mL triclosan for two months. Concentrations of triclocarban and triclosan in nutrient solutions were monitored weekly. At the end of the trial, roots and shoots were analyzed for triclocarban and triclosan. Research demonstrated that pumpkin and zucchini accumulated triclocarban and triclosan. Root accumulation factors were 1.78 and 0.64 and translocation factors were 0.001 and 0.082 for triclocarban and triclosan, respectively. The results of this experiment were compared with a previous soil column study that represented environmentally relevant exposure of antimicrobials from biosolids and had similar root mass. Plants were not as efficient in removing triclocarban and triclosan in hydroponic systems as in soil systems. Shoot concentrations of antimicrobials were the same or lower in hydroponic systems than in soil columns, indicating that hydroponic system does not overpredict the concentrations of antimicrobials.

  6. Antimicrobial packaging for fresh-cut fruits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fresh-cut fruits are minimally processed produce which are consumed directly at their fresh stage without any further kill step. Microbiological quality and safety are major challenges to fresh-cut fruits. Antimicrobial packaging is one of the innovative food packaging systems that is able to kill o...

  7. The antimicrobial activity of phenoxyethanol in vaccines.

    PubMed

    Lowe, I; Southern, J

    1994-02-01

    The activity of the antimicrobial preservatives, phenoxyethanol and thiomersal, were compared in diphtheria, tetanus and pertussis (adsorbed) vaccine. Both chemicals were equally effective in inactivating challenge doses of Gram-negative and Gram-positive micro-organisms, as well as a yeast.

  8. Antimicrobial functionalized genetically engineered spider silk

    PubMed Central

    Gomes, Sílvia; Leonor, Isabel B.; Mano, João F.; Reis, Rui L.; Kaplan, David L.

    2011-01-01

    Genetically engineered fusion proteins offer potential as multifunctional biomaterials for medical use. Fusion or chimeric proteins can be formed using recombinant DNA technology by combining nucleotide sequences encoding different peptides or proteins that are otherwise not found together in nature. In the present study, three new fusion proteins were designed, cloned and expressed and assessed for function, by combining the consensus sequence of dragline spider silk with three different antimicrobial peptides. The human antimicrobial peptides human neutrophil defensin 2 (HNP-2), human neutrophil defensins 4 (HNP-4) and hepcidin were fused to spider silk through bioengineering. The spider silk domain maintained its self-assembly features, a key aspect of these new polymeric protein biomaterials, allowing the formation of β-sheets to lock in structures via physical interactions without the need for chemical cross-linking. These new functional silk proteins were assessed for antimicrobial activity against Gram - Escherichia coli and Gram + Staphylococcus aureus and microbicidal activity was demonstrated. Dynamic light scattering was used to assess protein aggregation to clarify the antimicrobial patterns observed. Attenuated-total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and circular dichroism (CD) were used to assess the secondary structure of the new recombinant proteins. In vitro cell studies with a human osteosarcoma cell line (SaOs-2) demonstrated the compatibility of these new proteins with mammalian cells. PMID:21458065

  9. Antimicrobial resistance: One Health, one problem.

    PubMed

    Clark, Kathryn

    2014-11-29

    The roles that the medical and veterinary professions can play in tackling antimicrobial resistance were discussed at the BVA Congress at the London Vet Show last week. It was clear from the debate that, while action is already being taken, much more needs to be done by both professions in the UK and overseas. Kathryn Clark reports.

  10. Occurrence of antimicrobials and antimicrobial resistance genes in beef cattle storage ponds and swine treatment lagoons.

    PubMed

    Zhang, Yuping; Zhang, Chiqian; Parker, David B; Snow, Daniel D; Zhou, Zhi; Li, Xu

    2013-10-01

    Livestock manure treatment and storage structures are potential environmental sources of antimicrobials and antimicrobial resistance genes (ARGs). In this study, the occurrence of antimicrobials and ARGs was investigated in the water and the sludge compartments of beef cattle storage ponds and swine lagoons. Analysis was focused on two families of antimicrobials (sulfonamide and tetracycline) and the corresponding ARGs (sul1, sul2, tetO, tetQ and tetX). Results showed that the pseudo-partitioning coefficients of tetracyclines were higher than those of sulfonamides, suggesting different distributions of these two classes of antimicrobials between water and sludge. The ARGs tested were detected in nearly all ponds and lagoons, with the highest relative abundance in sul2 at 6.3×10(-1) copies per 16S rRNA gene. A positive correlation was observed between total sul genes and total sulfonamides in water while the correlation was negative in sludge. No significant correlation was found between total tet genes and total tetracyclines in either water or sludge, but significant correlations were observed for certain individual tet genes. Ammonia concentrations strongly correlated with all ARGs except tetX. This study provided quantitative information on the occurrence of antimicrobials and ARGs in the liquid and solid compartments of typical manure treatment and storage structures. PMID:23838056

  11. In vitro antimicrobial activity of propolis and synergism between propolis and antimicrobial drugs.

    PubMed

    Stepanović, Srdjan; Antić, Natasa; Dakić, Ivana; Svabić-Vlahović, Milena

    2003-01-01

    The aim of this study was to investigate antimicrobial properties of ethanolic extract of 13 propolis (EEP) samples from different regions of Serbia against 39 microorganisms (14 resistant or multiresistant to antibiotics), and to determine synergistic activity between antimicrobials and propolis. Antimicrobial activity of propolis samples was evaluated by agar diffusion and agar dilution method. The synergistic action of propolis with antimicrobial drugs was assayed by the disc diffusion method on agar containing subinhibitory concentrations of propolis. Obtained results indicate that EEP, irrespectively of microbial resistance to antibiotics, showed significant antimicrobial activities against Gram-positive bacteria (MIC 0.078%-1.25% of EEP) and yeasts (0.16%-1.25%), while Gram-negative bacteria were less susceptible (1.25%-->5%). Enterococcus faecalis was the most resistant Gram-positive bacterium, Salmonella spp. the most resistant Gram-negative bacteria, and Candida albicans the most resistant yeast. EEP showed synergism with selected antibiotics, and displayed ability to enhance the activities of antifungals. The shown antimicrobial potential of propolis alone or in combination with certain antibiotics and antifungals is of potential medical interest.

  12. Occurrence of antimicrobials and antimicrobial resistance genes in beef cattle storage ponds and swine treatment lagoons.

    PubMed

    Zhang, Yuping; Zhang, Chiqian; Parker, David B; Snow, Daniel D; Zhou, Zhi; Li, Xu

    2013-10-01

    Livestock manure treatment and storage structures are potential environmental sources of antimicrobials and antimicrobial resistance genes (ARGs). In this study, the occurrence of antimicrobials and ARGs was investigated in the water and the sludge compartments of beef cattle storage ponds and swine lagoons. Analysis was focused on two families of antimicrobials (sulfonamide and tetracycline) and the corresponding ARGs (sul1, sul2, tetO, tetQ and tetX). Results showed that the pseudo-partitioning coefficients of tetracyclines were higher than those of sulfonamides, suggesting different distributions of these two classes of antimicrobials between water and sludge. The ARGs tested were detected in nearly all ponds and lagoons, with the highest relative abundance in sul2 at 6.3×10(-1) copies per 16S rRNA gene. A positive correlation was observed between total sul genes and total sulfonamides in water while the correlation was negative in sludge. No significant correlation was found between total tet genes and total tetracyclines in either water or sludge, but significant correlations were observed for certain individual tet genes. Ammonia concentrations strongly correlated with all ARGs except tetX. This study provided quantitative information on the occurrence of antimicrobials and ARGs in the liquid and solid compartments of typical manure treatment and storage structures.

  13. Magnesium Based Materials and their Antimicrobial Activity

    NASA Astrophysics Data System (ADS)

    Robinson, Duane Allan

    The overall goals of this body of work were to characterize the antimicrobial properties of magnesium (Mg) metal and nano-magnesium oxide (nMgO) in vitro, to evaluate the in vitro cytotoxicity of Mg metal, and to incorporate MgO nanoparticles into a polymeric implant coating and evaluate its in vitro antimicrobial properties. In the course of this work it was found that Mg metal, Mg-mesh, and nMgO have in vitro antimicrobial properties that are similar to a bactericidal antibiotic. For Mg metal, the mechanism of this activity appears to be related to an increase in pH (i.e. a more alkaline environment) and not an increase in Mg2+. Given that Mg-mesh is a Mg metal powder, the assumption is that it has the same mechanism of activity as Mg metal. The mechanism of activity for nMgO remains to be elucidated and may be related to a combination of interaction of the nanoparticles with the bacteria and the alkaline pH. It was further demonstrated that supernatants from suspensions of Mg-mesh and nMgO had the same antimicrobial effect as was noted when the particles were used. The supernatant from Mg-mesh and nMgO was also noted to prevent biofilm formation for two Staphylococcus strains. Finally, poly-epsilon-caprolactone (PCL) composites of Mg-mesh (PCL+Mg-mesh) and nMgO (PCL+nMgO) were produced. Coatings applied to screws inhibited growth of Escherichia coli and Pseudomonas aeruginosa and in thin disc format inhibited the growth of Staphylococcus aureus in addition to the E. coli and P. aeruginosa. Pure Mg metal was noted to have some cytotoxic effect on murine fibroblast and osteoblast cell lines, although this effect needs to be characterized further. To address the need for an in vivo model for evaluating implant associated infections, a new closed fracture osteomyelitis model in the femur of the rat was developed. Magnesium, a readily available and inexpensive metal was shown to have antimicrobial properties that appear to be related to its corrosion products and

  14. [(11)C]Raclopride binding in the striatum of minimally restrained and free-walking awake mice in a positron emission tomography study.

    PubMed

    Takuwa, Hiroyuki; Maeda, Jun; Ikoma, Yoko; Tokunaga, Masaki; Wakizaka, Hidekatsu; Uchida, Shouko; Kanno, Iwao; Taniguchi, Junko; Ito, Hiroshi; Higuchi, Makoto

    2015-12-01

    Anesthesia and restraint stress have profound impacts on brain functions, including neural activity and cerebrovascular function, possibly influencing functional and neurochemical positron emission tomography (PET) imaging data. For circumventing this effect, we developed an experimental system enabling PET imaging of free-walking awake mice with minimal restraints by fixing the head to a holder. The applicability of this system was investigated by performing PET imaging of D2 dopamine receptors with [(11)C]raclopride under the following three different conditions: (1) free-walking awake state; (2) 1.5% isoflurane anesthesia; and (3) whole-body restraint without anesthesia. [(11)C]raclopride binding potential (BP(ND)) values under isoflurane anesthesia and restrained awake state were significantly lower than under free-walking awake state (P < 0.01). Heart rates in restrained awake mice were significantly higher than those in free-walking awake mice (P < 0.01), suggesting that free-walking awake state minimized restraint stress during the PET scan. [(11)C] raclopride-PET with methamphetamine (METH) injection was also performed in awake and anesthetized mice. METH-induced reduction of [(11)C]raclopride BP(ND) in anesthetized mice showed a trend to be less than that in free-walking awake mice, implying that pharmacological modulation of dopaminergic transmissions could be sensitively captured by PET imaging of free-walking awake mice. We concluded that our system is of utility as an in vivo assaying platform for studies of brain functions and neurotransmission elements in small animals, such as those modeling neuropsychiatric disorders.

  15. Three-dimensional structure of potato carboxypeptidase inhibitor in solution. A study using nuclear magnetic resonance, distance geometry, and restrained molecular dynamics

    SciTech Connect

    Clore, G.M.; Gronenborn, A.M.; Nilges, M.; Ryan, C.A.

    1987-12-01

    The solution conformation of potato carboxypeptidase inhibitor (CPI) has been investigated by /sup 1/H NMR spectroscopy. The spectrum is assigned in a sequential manner by using two-dimensional NMR techniques to identify through-bond and through-space (<5 A) connectivities. A set of 309 approximate interproton distance restraints is derived from the two-dimensional nuclear Overhauser enhancement spectra and used as the basis of a three-dimensional structure determination by a combination of metric matrix distance geometry and restrained molecular dynamics calculations. A total of 11 converged distance geometry structures were computed and refined by using restrained molecular dynamics. The average atomic root mean square (rms) difference between the final 11 structures and the mean structure obtained by averaging their coordinates is 1.4 +/- 0.3 A for residues 2-39 and 0.9 +/- 0.2 A for residues 5-37. The corresponding values for all atoms are 1.9 +/- 0.3 and 1.4 +/- 0.2 A, respectively. The computed structures are very close to the X-ray structure of CPI in its complex with carboxypeptidase, and the backbone atomic rms difference between the mean of the computed structures and the X-ray structure is only 1.2 A. Nevertheless, there are some real differences present which are evidenced by significant deviations between the experimental upper interproton distance limits and the corresponding interproton distances derived from the X-ray structure. These principally occur in two regions, residues 18-20 and residues 28-30, the latter comprising part of the region of secondary contact between CPI and carboxypeptidase in the X-ray structure.

  16. Quantum dots (QDs) restrain human cervical carcinoma HeLa cell proliferation through inhibition of the ROCK-c-Myc signaling.

    PubMed

    Chen, Liqun; Qu, Guangbo; Zhang, Changwen; Zhang, Shuping; He, Jiuyang; Sang, Nan; Liu, Sijin

    2013-03-01

    Cancers often cause significant morbidity and even death to patients. To date, conventional therapies, such as chemotherapy, radiation and surgery, are often limited; meanwhile, novel anticancer therapeutics are urgently needed to improve clinical treatments. Rapid application of nanotechnology and nanomaterials represents a promising vista for the development of anti-cancer therapeutics. However, how to integrate the novel properties of nanotechnology and nanomaterials into cancer treatment warrants close investigation. In the current study, we report a novel finding about the inhibitory effect of CdSe quantum dots (QDs) on Rho-associated kinase (ROCK) activity in cervical carcinoma HeLa cells associated with the attenuation of the ROCK-c-Myc signaling. We mechanistically demonstrated that QD-conducted ROCK inhibition greatly diminished c-Myc protein stability due to reduced phosphorylation, and also suppressed its activity in transcribing target genes (e.g. HSPC111). Thus, the treatment of QDs greatly restrained HeLa cell growth by inducing cell cycle arrest at G1 phase due to the reduced ability of c-Myc in driving cell proliferation. Additionally, since HSPC111, one of the c-Myc targets, is involved in regulating cell growth through ribosomal biogenesis and assembly, the downregulation of HSPC111 could also contribute to diminished proliferation in HeLa cells upon QD treatment. These results together suggested that inhibition of ROCK activity or ROCK-mediated c-Myc signaling in tumor cells upon QD treatment might represent a promising strategy to restrain tumor progression for human cervical carcinoma.

  17. Antimicrobial biocompatible bioscaffolds for orthopaedic implants.

    PubMed

    Qureshi, Ammar T; Terrell, Lekeith; Monroe, W Todd; Dasa, Vinod; Janes, Marlene E; Gimble, Jeffrey M; Hayes, Daniel J

    2014-05-01

    Nationally, nearly 1.5 million patients in the USA suffer from ailments requiring bone grafts and hip and other joint replacements. Infections following internal fixation in orthopaedic trauma can cause osteomyelitis in 22-66% of cases and, if uncontrolled, the mortality rate can be as high as 2%. We characterize a procedure for the synthesis of antimicrobial and biocompatible poly-l-lactic acid (PLLA) and poly-ethyleneglycol (PEG) bioscaffolds designed to degrade and absorb at a controlled rate. The bioscaffold architecture aims to provide a suitable substrate for the controlled release of silver nanoparticles (SNPs) to reduce bacterial growth and to aid the proliferation of human adipose-derived stem cells (hASCs) for tissue-engineering applications. The fabricated bioscaffolds were characterized by scanning transmission microscope (SEM) and it showed that the addition of tncreasing concentrations of SNPs results in the formation of dendritic porous channels perpendicular to the axis of precipitation. The antimicrobial properties of these porous bioscaffolds were tested according to a modified ISO 22196 standard across varying concentrations of biomass-mediated SNPs to determine an efficacious antimicrobial concentration. The bioscaffolds reduced the Staphylococcus aureus and Escherichia coli viable colony-forming units by 98.85% and 99.9%, respectively, at an antimicrobial SNPs concentration of 2000 ppm. Human ASCs were seeded on bioscaffolds and cultured in vitro for 20 days to study the effect of SNPs concentration on the viability of cells. SEM analysis and the metabolic activity-based fluorescent dye, AlamarBlue®, demonstrated the growth of cells on the efficacious antimicrobial bioscaffolds. The biocompatibility of in vitro leached silver, quantified by inductively coupled plasma optical emission spectroscopy (ICP-OES), proved non-cytotoxic when tested against hASCs, as evaluated by MTT assay.

  18. Quantifying antimicrobial resistance at veal calf farms.

    PubMed

    Bosman, Angela B; Wagenaar, Jaap A; Wagenaar, Jaap; Stegeman, Arjan; Vernooij, Hans; Mevius, Dik

    2012-01-01

    This study was performed to determine a sampling strategy to quantify the prevalence of antimicrobial resistance on veal calf farms, based on the variation in antimicrobial resistance within and between calves on five farms. Faecal samples from 50 healthy calves (10 calves/farm) were collected. From each individual sample and one pooled faecal sample per farm, 90 selected Escherichia coli isolates were tested for their resistance against 25 mg/L amoxicillin, 25 mg/L tetracycline, 0.5 mg/L cefotaxime, 0.125 mg/L ciprofloxacin and 8/152 mg/L trimethoprim/sulfamethoxazole (tmp/s) by replica plating. From each faecal sample another 10 selected E. coli isolates were tested for their resistance by broth microdilution as a reference. Logistic regression analysis was performed to compare the odds of testing an isolate resistant between both test methods (replica plating vs. broth microdilution) and to evaluate the effect of pooling faecal samples. Bootstrap analysis was used to investigate the precision of the estimated prevalence of resistance to each antimicrobial obtained by several simulated sampling strategies. Replica plating showed similar odds of E. coli isolates tested resistant compared to broth microdilution, except for ciprofloxacin (OR 0.29, p ≤ 0.05). Pooled samples showed in general lower odds of an isolate being resistant compared to individual samples, although these differences were not significant. Bootstrap analysis showed that within each antimicrobial the various compositions of a pooled sample provided consistent estimates for the mean proportion of resistant isolates. Sampling strategies should be based on the variation in resistance among isolates within faecal samples and between faecal samples, which may vary by antimicrobial. In our study, the optimal sampling strategy from the perspective of precision of the estimated levels of resistance and practicality consists of a pooled faecal sample from 20 individual animals, of which 90 isolates are

  19. Repurposing celecoxib as a topical antimicrobial agent

    PubMed Central

    Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N.

    2015-01-01

    There is an urgent need for new antibiotics and alternative strategies to combat multidrug-resistant bacterial pathogens, which are a growing clinical issue. Repurposing existing approved drugs with known pharmacology and toxicology is an alternative strategy to accelerate antimicrobial research and development. In this study, we show that celecoxib, a marketed inhibitor of cyclooxygenase-2, exhibits broad-spectrum antimicrobial activity against Gram-positive pathogens from a variety of genera, including Staphylococcus, Streptococcus, Listeria, Bacillus, and Mycobacterium, but not against Gram-negative pathogens. However, celecoxib is active against all of the Gram-negative bacteria tested, including strains of, Acinetobacter, and Pseudomonas, when their intrinsic resistance is artificially compromised by outer membrane permeabilizing agents such as colistin. The effect of celecoxib on incorporation of radioactive precursors into macromolecules in Staphylococcus aureus was examined. The primary antimicrobial mechanism of action of celecoxib was the dose-dependent inhibition of RNA, DNA, and protein synthesis. Further, we demonstrate the in vivo efficacy of celecoxib in a methicillin-resistant S. aureus (MRSA) infected Caenorhabditis elegans whole animal model. Topical application of celecoxib (1 and 2%) significantly reduced the mean bacterial count in a mouse model of MRSA skin infection. Further, celecoxib decreased the levels of all inflammatory cytokines tested, including tumor necrosis factor-α, interleukin-6, interleukin-1 beta, and monocyte chemo attractant protein-1 in wounds caused by MRSA infection. Celecoxib also exhibited synergy with many conventional antimicrobials when tested against four clinical isolates of S. aureus. Collectively, these results demonstrate that celecoxib alone, or in combination with traditional antimicrobials, has a potential to use as a topical drug for the treatment of bacterial skin infections. PMID:26284040

  20. Topical antimicrobials for burn infections - an update.

    PubMed

    Sevgi, Mert; Toklu, Ani; Vecchio, Daniela; Hamblin, Michael R

    2013-12-01

    The relentless rise in antibiotic resistance among pathogenic bacteria and fungi, coupled with the high susceptibility of burn wounds to infection, and the difficulty of systemically administered antibiotics to reach damaged tissue, taken together have made the development of novel topical antimicrobials for burn infections a fertile area of innovation for researchers and companies. We previously covered the existing patent literature in this area in 2010, but the notable progress made since then, has highlighted the need for an update to bring the reader up to date on recent developments. New patents in the areas of topically applied antibiotics and agents that can potentiate the action of existing antibiotics may extend their useful lifetime. Developments have also been made in biofilm-disrupting agents. Antimicrobial peptides are nature's way for many life forms to defend themselves against attack by pathogens. Silver has long been known to be a highly active antimicrobial but new inorganic metal derivatives based on bismuth, copper and gallium have emerged. Halogens such as chlorine and iodine can be delivered by novel technologies. A variety of topically applied antimicrobials include chitosan preparations, usnic acid, ceragenins and XF porphyrins. Natural product derived antimicrobials such as tannins and essential oils have also been studied. Novel techniques to deliver reactive oxygen species and nitric oxide in situ have been developed. Light-mediated techniques include photodynamic therapy, ultraviolet irradiation, blue light, low-level laser therapy and titania photocatalysis. Passive immunotherapy employs antibodies against pathogens and their virulence factors. Finally an interesting new area uses therapeutic microorganisms such as phages, probiotic bacteria and protozoa to combat infections.

  1. Ceragenin mediated selectivity of antimicrobial silver nanoparticles.

    PubMed

    Hoppens, Mark A; Sylvester, Christopher B; Qureshi, Ammar T; Scherr, Thomas; Czapski, Desiree R; Duran, Randolph S; Savage, Paul B; Hayes, Daniel

    2014-08-27

    The understanding that common broad-spectrum antimicrobials disrupt natural microbial flora important in acquiring nutrients and preventing infection has resulted in a paradigm shift favoring more selective antimicrobials. This work explores silver nanoparticles conjugated with ceragenin, or cationic antimicrobials (CSA-SNPs), as a potential Gram-positive selective antimicrobial. Herein, CSA-SNPs are characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential, and high-performance liquid chromatography-electrospray time-of-flight mass spectrometry (HPLC-ESI-TOF-MS). The antimicrobial properties are determined through minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) and time-kill studies. Spatial selectivity of the conjugate nanoparticle was evaluated using confocal imaging, MATLAB statistical analysis, and video monitored interactions between bacteria and CSA-SNPs via laser trapping techniques. Cytotoxicity was also determined by live/dead staining and flow cytometry. Average particle size, as determined through TEM analysis, and hydrodynamic diameter, as determined via DLS, are 63.5 ± 38.8 and 102.23 ± 2.3 nm, respectively. The zeta potential of the SNP before and after CSA attachment is -18.23 and -8.34 mV, respectively. MIC/MBC data suggest that CSA-SNPs are 8 times more effective against Staphylococcus aureus than SNPs alone. Furthermore, MATLAB analysis of confocal imaging found that 70% of CSA-SNPs are within 2 μm of S. aureus, whereas this percentage falls to below 40% with respect to Escherichia coli. These results are bolstered further by laser trapping experiments demonstrating selective adherence of CSA-SNPs conjugates with bacterial strains. Cytotoxicity studies of CSA-SNPs against 3T3 fibroblasts indicate 50% cell viability at 50 ppm.

  2. Understanding antimicrobial stewardship: Disease severity treatment thresholds and antimicrobial alternatives among organic and conventional calf producers.

    PubMed

    Habing, Greg; Djordjevic, Catherine; Schuenemann, Gustavo M; Lakritz, Jeff

    2016-08-01

    Reductions in livestock antimicrobial use (AMU) can be achieved through identification of effective antimicrobial alternatives as well as accurate and stringent identification of cases requiring antimicrobial therapy. Objective measurements of selectivity that incorporate appropriate case definitions are necessary to understand the need and potential for reductions in AMU through judicious use. The objective of this study was to measure selectivity using a novel disease severity treatment threshold for calf diarrhea, and identify predictors of more selective application of antimicrobials among conventional dairy producers. A second objective of this study was to describe the usage frequency and perceptions of efficacy of common antimicrobial alternatives among conventional and organic producers. The cross-sectional survey was mailed to Michigan and Ohio, USA dairy producers and contained questions on AMU attitudes, AMU practices, veterinary-written protocols, and antimicrobial alternatives. The treatment threshold, defined based on the case severity where the producer would normally apply antimicrobials, was identified with a series of descriptions with increasing severity, and ordinal multivariable logistic regression was used to determine the association between the treatment threshold and individual or herd characteristics. The response rate was 49% (727/1488). Overall, 42% of conventional producers reported any veterinary-written treatment protocol, and 27% (113/412) of conventional producers had a veterinary-written protocol for the treatment of diarrhea that included a case identification. The majority (58%, 253/437) of conventional producers, but a minority (7%) of organic producers disagreed that antibiotic use in agriculture led to resistant bacterial infections in people. Among conventional producers, the proportion of producers applying antimicrobials for therapy increased from 13% to 67% with increasing case severity. The treatment threshold was low

  3. Engaging hospitalists in antimicrobial stewardship: Lessons from a multihospital collaborative.

    PubMed

    Mack, Megan R; Rohde, Jeffrey M; Jacobsen, Diane; Barron, James R; Ko, Christin; Goonewardene, Michael; Rosenberg, David J; Srinivasan, Arjun; Flanders, Scott A

    2016-08-01

    Inappropriate antimicrobial use in hospitalized patients contributes to antimicrobial-resistant infections and complications. We sought to evaluate the impact, barriers, and facilitators of antimicrobial stewardship best practices in a diverse group of hospital medicine programs. This multihospital initiative included 1 community nonteaching hospital, 2 community teaching hospitals, and 2 academic medical centers participating in a collaborative with the Centers for Disease Control and Prevention and the Institute for Healthcare Improvement. We conducted multimodal physician education on best practices for antimicrobial use including: (1) enhanced antimicrobial documentation, (2) improved quality and accessibility of local clinical guidelines, and (3) a 72-hour antimicrobial "timeout." Implementation barriers included variability in physician practice styles, lack of awareness of stewardship importance, and overly broad interventions. Facilitators included engaging hospitalists, collecting real time data and providing performance feedback, and appropriately limiting the scope of interventions. In 2 hospitals, complete antimicrobial documentation in sampled medical records improved significantly (4% to 51% and 8% to 65%, P < 0.001 for each comparison). A total of 726 antimicrobial timeouts occurred at 4 hospitals, and 30% resulted in optimization or discontinuation of antimicrobials. With careful attention to key barriers and facilitators, hospitalists can successfully implement effective antimicrobial stewardship practices. Journal of Hospital Medicine 2016;11:576-580. © 2016 Society of Hospital Medicine. PMID:27130473

  4. [Antimicrobial activity exerted by sodium dichloroisocyanurate].

    PubMed

    D'Auria, F D; Simonetti, G; Strippoli, V

    1989-01-01

    Sodium dichloroisocyanurate is a chlorinated cleaner. It was used for swimming pool sanitation and for the sterilisation of linen. Not recently ago sodium dichloroisocyanurate has substituted hypochlorite for the sterilisation of infant feeding bottles and teats. Sodium dichloroisocyanurate is soluble in water; this condition causes the hydrolysis of sodium dichloroisocyanurate in hypochlorous acid, that is the active agent, isocyanurate and isocyanurate chlorine. These compounds form a chlorine protein that carry out microbicidal activity. In a toxicology study has been shown that no severe changes in the normal metabolic function occurred, furthermore sodium dichloroisocyanurate has not shown teratogenic effects at the concentration of 200 mg/kg. The antimicrobial activity of sodium dichloroisocyanurate was evaluated against Gram negative bacteria such as E. coli or Salmonella typhimurium and against some fungi. This study illustrates a rapid antimicrobial activity using concentrations. Our study concentrated on the antimicrobial activity of sodium dichloroisocyanurate in some experimental conditions. We tested 66 strains of fungi, 28 Gram positive bacteria and 29 Gram negative bacteria. We also evaluated the antimicrobial activity of sodium dichloroisocyanurate against protozoa such as Trichomonas vaginalis. The antimicrobial activity was evaluated in cultural conditions and non cultural conditions; in these experiments we observed similar action in both the commercial product and pure substance. In cultural conditions sodium dichloroisocyanurate shows a good activity against fungi and bacteria, moreover it can be observed that the serum didn't interfere with its activity. In a non cultural condition the Candida was killed rapidly by the sodium dichloroisocyanurate but this activity is influenced by the growth phase of the yeast. Against mycelial form such as Penicillium and Aspergillus the sodium dichloroisocyanurate needs a longer contact time than yeast form

  5. Antimicrobial resistance in Libya: 1970-2011.

    PubMed

    Ghenghesh, Khalifa Sifaw; Rahouma, Amal; Tawil, Khaled; Zorgani, Abdulaziz; Franka, Ezzedin

    2013-01-01

    Resistance to antimicrobial agents is a major health problem that affects the whole world. Providing information on the past state of antimicrobial resistance in Libya may assist the health authorities in addressing the problem more effectively in the future. Information was obtained mainly from Highwire Press (including PubMed) search for the period 1970-2011 using the terms 'antibiotic resistance in Libya', 'antimicrobial resistance in Libya', 'tuberculosis in Libya', and 'primary and acquired resistance in Libya' in title and abstract. From 1970 to 2011 little data was available on antimicrobial resistance in Libya due to lack of surveillance and few published studies. Available data shows high resistance rates for Salmonella species in the late 1970s and has remained high to the present day. High prevalence rates (54-68%) of methicillin-resistant Staphylococcus aureus (MRSA) were reported in the last decade among S. aureus from patients with burns and surgical wound infections. No reports were found of vancomycin-resistant S. aureus (VRSA) or vancomycin-intermediate-resistant S. aureus (VISA) using standard methods from Libya up to the end of 2011. Reported rates of primary (i.e. new cases) and acquired (i.e. retreatment cases) multidrug-resistant tuberculosis (MDR-TB) from the eastern region of Libya in 1971 were 16.6 and 33.3% and in 1976 were 8.6 and 14.7%, in western regions in 1984-1986 were 11 and 21.5% and in the whole country in 2011 were estimated at 3.4 and 29%, respectively. The problem of antibiotic resistance is very serious in Libya. The health authorities in particular and society in general should address this problem urgently. Establishing monitoring systems based on the routine testing of antimicrobial sensitivity and education of healthcare workers, pharmacists, and the community on the health risks associated with the problem and benefits of prudent use of antimicrobials are some steps that can be taken to tackle the problem in the future.

  6. A shrimp C-type lectin inhibits proliferation of the hemolymph microbiota by maintaining the expression of antimicrobial peptides.

    PubMed

    Wang, Xian-Wei; Xu, Ji-Dong; Zhao, Xiao-Fan; Vasta, Gerardo Raul; Wang, Jin-Xing

    2014-04-25

    Some aquatic invertebrates such as shrimp contain low albeit stable numbers of bacteria in the circulating hemolymph. The proliferation of this hemolymph microbiota in such a nutrient-rich environment is tightly controlled in healthy animals, but the mechanisms responsible had remained elusive. In the present study, we report a C-type lectin (MjHeCL) from the kuruma shrimp (Marsupenaeus japonicus) that participates in restraining the hemolymph microbiota. Although the expression of MjHeCL did not seem to be modulated by bacterial challenge, the down-regulation of its expression by RNA interference led to proliferation of the hemolymph microbiota, ultimately resulting in shrimp death. This phenotype was rescued by the injection of recombinant MjHeCL, which restored the healthy status of the knockdown shrimp. A mechanistic analysis revealed that MjHeCL inhibited bacterial proliferation by modulating the expression of antimicrobial peptides. The key function of MjHeCL in the shrimp immune homeostasis might be related to its broader recognition spectrum of the hemolymph microbiota components than other lectins. Our study demonstrates the role of MjHeCL in maintaining the healthy status of shrimp and provides new insight into the biological significance of C-type lectins, a diversified and abundant lectin family in invertebrate species.

  7. Solution structure and model membrane interactions of temporins-SH, antimicrobial peptides from amphibian skin. A NMR spectroscopy and differential scanning calorimetry study.

    PubMed

    Abbassi, Feten; Galanth, Cécile; Amiche, Mohamed; Saito, Kazuko; Piesse, Christophe; Zargarian, Loussiné; Hani, Khaled; Nicolas, Pierre; Lequin, Olivier; Ladram, Ali

    2008-10-01

    Temporin-SHa and temporin-SHc are 13 residue long antimicrobial peptides from frog skin that have similar sequences but differ markedly in their membrane-damaging properties. Temporin-SHa contains a single basic lysine residue and has a unique antimicrobial spectrum of action among temporins, being very potent against Gram-positive and Gram-negative bacteria, yeasts, fungi, and protozoa. Temporin-SHc, which contains a single basic histidine residue, is inactive against Gram-negative bacteria, has a reduced efficacy against Gram-positive bacteria, but is still active against yeasts and fungi. Temporin-SHb, with no basic residue, has no antimicrobial activity. The three-dimensional structures of the peptides bound to SDS micelles were analyzed by CD and NMR spectroscopy combined with restrained molecular dynamics calculations. The peptides adopt well-defined amphipathic alpha-helical structures extending from residue 3 to residue 12, when bound to SDS micelles. The structures are stabilized by extensive interactions between aliphatic and aromatic side chains on the nonpolar face. Relaxation enhancements caused by paramagnetic probes showed that the peptides adopt nearly parallel orientations to the micelle surface and do not deeply penetrate into the micelle. The interaction of the peptides with model membranes was investigated by differential scanning calorimetry on anionic and zwitterionic multilamellar vesicles and membrane-permeabilization assays on calcein-loaded large unilamellar vesicles. Calorimetric data indicated that both temporin-SHa and -SHc reside at the hydrocarbon core-water interface of the anionic lipid bilayer but interact with anionic bilayers in a very different manner. This suggests that the charge-induced activity of temporins-SH for bacterial cells is due to changes in the membrane-disturbing mechanism of the bound peptides. PMID:18795798

  8. Controversies in Antimicrobial Stewardship: Focus on New Rapid Diagnostic Technologies and Antimicrobials

    PubMed Central

    Wenzler, Eric; Wong, Jordan R.; Goff, Debra A.; Jankowski, Christopher A.; Bauer, Karri A.

    2016-01-01

    Antimicrobial stewardship programs (ASPs) are challenged with ensuring appropriate antimicrobial use while minimizing expenditures. ASPs have consistently demonstrated improved patient outcomes and significant cost reductions but are continually required to justify the costs of their existence and interventions due to the silo mentality often adopted by hospital administrators. As new technologies and antimicrobials emerge, ASPs are in a constant tug-of-war between providing optimal clinical outcomes and ensuring cost containment. Additionally, robust data on cost-effectiveness of new rapid diagnostic technologies and antimicrobials with subsequent ASP interventions to provide justification are lacking. As the implementation of an ASP will soon be mandatory for acute care hospitals in the United States, ASPs must find ways to justify novel interventions to align themselves with healthcare administrators. This review provides a framework for the justification of implementing a rapid diagnostic test or adding a new antimicrobial to formulary with ASP intervention, reviews approaches to demonstrating cost-effectiveness, and proposes methods for which ASPs may reduce healthcare expenditures via alternative tactics. PMID:27025521

  9. Controversies in Antimicrobial Stewardship: Focus on New Rapid Diagnostic Technologies and Antimicrobials.

    PubMed

    Wenzler, Eric; Wong, Jordan R; Goff, Debra A; Jankowski, Christopher A; Bauer, Karri A

    2016-01-01

    Antimicrobial stewardship programs (ASPs) are challenged with ensuring appropriate antimicrobial use while minimizing expenditures. ASPs have consistently demonstrated improved patient outcomes and significant cost reductions but are continually required to justify the costs of their existence and interventions due to the silo mentality often adopted by hospital administrators. As new technologies and antimicrobials emerge, ASPs are in a constant tug-of-war between providing optimal clinical outcomes and ensuring cost containment. Additionally, robust data on cost-effectiveness of new rapid diagnostic technologies and antimicrobials with subsequent ASP interventions to provide justification are lacking. As the implementation of an ASP will soon be mandatory for acute care hospitals in the United States, ASPs must find ways to justify novel interventions to align themselves with healthcare administrators. This review provides a framework for the justification of implementing a rapid diagnostic test or adding a new antimicrobial to formulary with ASP intervention, reviews approaches to demonstrating cost-effectiveness, and proposes methods for which ASPs may reduce healthcare expenditures via alternative tactics. PMID:27025521

  10. The Risk of Some Veterinary Antimicrobial Agents on Public Health Associated with Antimicrobial Resistance and their Molecular Basis

    PubMed Central

    Hao, Haihong; Sander, Pascal; Iqbal, Zahid; Wang, Yulian; Cheng, Guyue; Yuan, Zonghui

    2016-01-01

    The risk of antimicrobial agents used in food-producing animals on public health associated with antimicrobial resistance continues to be a current topic of discussion as related to animal and human public health. In the present review, resistance monitoring data, and risk assessment results of some important antimicrobial agents were cited to elucidate the possible association of antimicrobial use in food animals and antimicrobial resistance in humans. From the selected examples, it was apparent from reviewing the published scientific literature that the ban on use of some antimicrobial agents (e.g., avoparcin, fluoroquinolone, tetracyclines) did not change drug resistance patterns and did not mitigate the intended goal of minimizing antimicrobial resistance. The use of some antimicrobial agents (e.g., virginiamycin, macrolides, and cephalosporins) in food animals may have an impact on the antimicrobial resistance in humans, but it was largely depended on the pattern of drug usage in different geographical regions. The epidemiological characteristics of resistant bacteria were closely related to molecular mechanisms involved in the development, fitness, and transmission of antimicrobial resistance. PMID:27803693

  11. Therapeutic antimicrobial peptides may compromise natural immunity.

    PubMed

    Habets, Michelle G J L; Brockhurst, Michael A

    2012-06-23

    Antimicrobial peptides (AMPs) have been proposed as a promising new class of antimicrobials despite warnings that therapeutic use could drive the evolution of pathogens resistant to our own immunity peptides. Using experimental evolution, we demonstrate that Staphylococcus aureus rapidly evolved resistance to pexiganan, a drug-candidate for diabetic leg ulcer infections. Evolved resistance was costly in terms of impaired growth rate, but costs-of-resistance were completely ameliorated by compensatory adaptation. Crucially, we show that, in some populations, experimentally evolved resistance to pexiganan provided S. aureus with cross-resistance to human-neutrophil-defensin-1, a key component of the innate immune response to infection. This unintended consequence of therapeutic use could drastically undermine our innate immune system's ability to control and clear microbial infections. Our results therefore highlight grave potential risks of AMP therapies, with implications for their development.

  12. Controlling the oral biofilm with antimicrobials.

    PubMed

    Marsh, P D

    2010-06-01

    The aim of this article is to review the properties of compounds available for the control of dental plaque biofilms, and describe their mode of action. The mouth is colonised by a diverse but characteristic collection of micro-organisms, which confer benefit to host. Numerous antiplaque (e.g. surfactants, essential oils) and antimicrobial agents (e.g. bisbiguanides, metal ions, phenols, quaternary ammonium compounds, etc.) have been successfully formulated into toothpastes and mouthrinses to control plaque biofilms. At high concentrations, these agents can remove biofilm and/or kill disease-associated bacteria, while even at sub-lethal levels they can inhibit the expression of pathogenic traits. Successful antimicrobial agents are able to meet the apparently contradictory requirements of maintaining the oral biofilm at levels compatible with oral health but without disrupting the natural and beneficial properties of the resident oral microflora.

  13. Condensing Heat Exchanger with Hydrophilic Antimicrobial Coating

    NASA Technical Reports Server (NTRS)

    Thomas, Christopher M. (Inventor); Ma, Yonghui (Inventor)

    2014-01-01

    A multi-layer antimicrobial hydrophilic coating is applied to a substrate of anodized aluminum, although other materials may form the substrate. A silver layer is sputtered onto a thoroughly clean anodized surface of the aluminum to about 400 nm thickness. A layer of crosslinked, silicon-based macromolecular structure about 10 nm thickness overlies the silver layer, and the outermost surface of the layer of crosslinked, silicon-based macromolecular structure is hydroxide terminated to produce a hydrophilic surface with a water drop contact angle of less than 10.degree.. The coated substrate may be one of multiple fins in a condensing heat exchanger for use in the microgravity of space, which has narrow channels defined between angled fins such that the surface tension of condensed water moves water by capillary flow to a central location where it is pumped to storage. The antimicrobial coating prevents obstruction of the capillary passages.

  14. Scientific evidence and research in antimicrobial stewardship.

    PubMed

    Almirante, Benito; Garnacho-Montero, José; Pachón, Jerónimo; Pascual, Álvaro; Rodríguez-Baño, Jesús

    2013-09-01

    Evaluating the impact of antibiotic stewardship programs is challenging. There is evidence that they are effective in terms of reducing the consumption and cost of antibiotics, although establishing their impact on antimicrobial resistance (beyond restrictive policies in outbreaks caused by specific antimicrobial resistant organisms) and clinical outcomes is more difficult. Proper definitions of exposure and outcome variables, the use of advanced and appropriate statistical analyses and well-designed quasi-experimental studies would more accurately support the conclusions. Cluster randomized trials should be used whenever possible and appropriate, although the limitations of this approach should also be acknowledged. These issues are reviewed in this paper. We conclude that there are good research opportunities in the field of antibiotic stewardship.

  15. New antimicrobial molecules and new antibiotic strategies.

    PubMed

    Rodríguez de Castro, Felipe; Naranjo, Olga Rajas; Marco, Javier Aspa; Violán, Jordi Solé

    2009-04-01

    Drug options for treatment of infections are increasingly limited. The pharmaceutical industry has found it difficult to discover new antimicrobial agents, and only two novel classes of antibiotics, the oxazolidinones and the cyclic lipopeptides, have entered the market since the late 1960s. Few new agents have reached the market in the last decade with potential interest for community-acquired pneumonia (CAP) treatment, including linezolid (the first oxazolidinone in clinical use), new fluoroquinolones, cefditoren, ertapenem, and telithromycin. Agents currently in clinical development include other novel quinolones and ketolides, broad-spectrum cephalosporin derivatives, faropenem, several glycopeptides, and iclaprim. Other molecules are considered to be promising candidates for the future. In addition to the foregoing agents, alternative treatment approaches have also been introduced into clinical practice, which include the administration of the appropriate antimicrobials in a timely manner and the consideration of the pharmacokinetic-pharmacodynamic properties of the agent(s). PMID:19296416

  16. Antimicrobial activity of Aspilia latissima (Asteraceae).

    PubMed

    Souza, Jeana M E; Chang, Marilene R; Brito, Daniela Z; Farias, Katyuce S; Damasceno-Junior, Geraldo A; Turatti, Izabel C C; Lopes, Norberto P; Santos, Edson A; Carollo, Carlos A

    2015-01-01

    We evaluated the antimicrobial activity of Aspilia latissima - an abundant plant from the Brazilian Pantanal region - against Candida albicans, Candida parapsilosis, Candida krusei, Candida tropicalis, Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli and Staphylococcus aureus. The crude extracts and fractions showed activity in all tested microorganisms. The chloroform fraction of the leaves and roots showed the most antimicrobial activity against S. aureus, with an MIC of 500 μg/mL. This fraction was submitted to bioautographic assays to characterize the activity of the compounds. Two bands from the leaves (L-A and L-B) and three bands from the roots (R-C, R-D and R-E) were bioactive. Within the root-derived bands, the terpene derivatives stigmasterol, kaurenoic acid and kaura-9(11), 16-dien-18-oic acid were identified. Antibiotic activity of A. latissima is reported for the first time.

  17. Antimicrobial resistance: A public health challenge

    PubMed Central

    Jindal, A.K.; Pandya, Kapil; Khan, I.D.

    2015-01-01

    Antimicrobial resistance has become a global concern. Though an evolutionary phenomenon, it is promulgated by faulty human behaviours. It is a growing concern ever since first reported in 1940s. Today, a plethora of newer generation antimicrobials have become ineffective against previously susceptible organisms. This is a huge challenge for health care managers all across the globe, compounded by the “discovery void” in the field of development of new antibiotics. If proper steps are not taken presently, the lurking fear of reaching a therapeutic dead end will become a reality. This paper aims at describing the pandemic of AMR from a public health perspective and suggesting strategies to deal with it in an effective and collaborative manner. PMID:25859082

  18. Terpenes with antimicrobial activity from Cretan propolis.

    PubMed

    Popova, Milena P; Chinou, Ioanna B; Marekov, Ilko N; Bankova, Vassya S

    2009-07-01

    Five terpenes, the diterpenes: 14,15-dinor-13-oxo-8(17)-labden-19-oic acid and a mixture of labda-8(17),13E-dien-19-carboxy-15-yl oleate and palmitate as well as the triterpenes, 3,4-seco-cycloart-12-hydroxy-4(28),24-dien-3-oic acid and cycloart-3,7-dihydroxy-24-en-28-oic acid were isolated from Cretan propolis. Moreover, 18 known compounds were also isolated, seven of them for the first time as propolis components. All structures were established on the basis of spectroscopic analysis and chemical evidence. All isolated compounds were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria as well as against some human pathogenic fungi showing a broad spectrum of antimicrobial activity.

  19. Multifactorial aspects of antimicrobial activity of propolis.

    PubMed

    Scazzocchio, F; D'Auria, F D; Alessandrini, D; Pantanella, F

    2006-01-01

    We investigated the antibacterial activity of sub-inhibitory concentrations of ethanolic extract of propolis (EEP), and its effect on the antibacterial activity of some antibiotics. Some clinically isolated Gram-positive strains were used. Moreover, sub-inhibitory concentrations of EEP were used to value its action on some important virulence factors like lipase and coagulase enzymes, and on biofilm formation in Staphylococcus aureus. Our results indicated that EEP had a significant antimicrobial activity towards all tested clinical strains. Adding EEP to antibacterial tested drugs, it drastically increased the antimicrobial effect of ampicillin, gentamycin and streptomycin, moderately the one of chloramphenicol, ceftriaxon and vancomycin, while there was no effect with erithromycin. Moreover, our results pointed out an inhibitory action of EEP on lipase activity of 18 Staphylococcus spp. strains and an inhibitory effect on coagulase of 11 S. aureus tested strains. The same EEP concentrations showed a negative interaction with adhesion and consequent biofilm formation in S. aureus ATCC 6538P.

  20. Resistance in antimicrobial photodynamic inactivation of bacteria.

    PubMed

    Maisch, Tim

    2015-08-01

    Antibiotics have increasingly lost their impact to kill bacteria efficiently during the last 10 years. The emergence and dissemination of superbugs with resistance to multiple antibiotic classes have occurred among Gram-positive and Gram-negative strains including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter strains. These six superbugs can "escape" more or less any single kind of antibiotic treatment. That means bacteria are very good at developing resistance against antibiotics in a short time. One new approach is called photodynamic antimicrobial chemotherapy (PACT) which already has demonstrated an efficient antimicrobial efficacy among multi-resistant bacteria. Until now it has been questionable if bacteria can develop resistance against PACT. This perspective summarises the current knowledge about the susceptibility of bacteria towards oxidative stress and sheds some light on possible strategies of the development of photodynamic inactivation of bacteria (PACT)-induced oxidative stress resistance by bacteria.

  1. Design and Application of Antimicrobial Peptide Conjugates

    PubMed Central

    Reinhardt, Andre; Neundorf, Ines

    2016-01-01

    Antimicrobial peptides (AMPs) are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT) or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry. PMID:27187357

  2. Antimicrobial Peptides, Skin Infections and Atopic Dermatitis

    PubMed Central

    Hata, Tissa R.; Gallo, Richard L.

    2008-01-01

    The innate immune system evolved over 2 billion years ago to first recognize pathogens then eradicate them. Several distinct defects in this ancient but rapidly responsive element of human immune defense account for the increased incidence of skin infections in atopics. These defects include abnormalities in the physical barrier of the epidermis, alterations in microbial pattern recognition receptors such as toll receptors and NOD, and a diminished capacity to increase the expression of antimicrobial peptides during inflammation. Several antimicrobial peptides are affected including; cathelicidin, HBD-2, and HBD-3, which are lower in lesional skin of atopics compared to other inflammatory skin diseases, and dermcidin, which is decreased in sweat. Other defects in the immune defense barrier of atopics include a relative deficiency in plasmacytoid dendritic cells. In the future, understanding the cause of these defects may allow therapeutic intervention to reduce the incidence of infection in atopic individuals and potentially decrease the severity of this disorder. PMID:18620136

  3. Antimicrobial activity of Aspilia latissima (Asteraceae)

    PubMed Central

    Souza, Jeana M.E.; Chang, Marilene R.; Brito, Daniela Z.; Farias, Katyuce S.; Damasceno-Junior, Geraldo A.; Turatti, Izabel C.C.; Lopes, Norberto P.; Santos, Edson A.; Carollo, Carlos A.

    2015-01-01

    Abstract We evaluated the antimicrobial activity of Aspilia latissima - an abundant plant from the Brazilian Pantanal region - against Candida albicans, Candida parapsilosis, Candida krusei, Candida tropicalis, Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli and Staphylococcus aureus. The crude extracts and fractions showed activity in all tested microorganisms. The chloroform fraction of the leaves and roots showed the most antimicrobial activity against S. aureus, with an MIC of 500 μg/mL. This fraction was submitted to bioautographic assays to characterize the activity of the compounds. Two bands from the leaves (L-A and L-B) and three bands from the roots (R-C, R-D and R-E) were bioactive. Within the root-derived bands, the terpene derivatives stigmasterol, kaurenoic acid and kaura-9(11), 16-dien-18-oic acid were identified. Antibiotic activity of A. latissima is reported for the first time. PMID:26691468

  4. Antimicrobial resistance: A public health challenge.

    PubMed

    Jindal, A K; Pandya, Kapil; Khan, I D

    2015-04-01

    Antimicrobial resistance has become a global concern. Though an evolutionary phenomenon, it is promulgated by faulty human behaviours. It is a growing concern ever since first reported in 1940s. Today, a plethora of newer generation antimicrobials have become ineffective against previously susceptible organisms. This is a huge challenge for health care managers all across the globe, compounded by the "discovery void" in the field of development of new antibiotics. If proper steps are not taken presently, the lurking fear of reaching a therapeutic dead end will become a reality. This paper aims at describing the pandemic of AMR from a public health perspective and suggesting strategies to deal with it in an effective and collaborative manner. PMID:25859082

  5. Ag-Composites with Antimicrobial Properties

    NASA Astrophysics Data System (ADS)

    Zampino, D.; Ferreri, T.; Puglisi, C.; Mancuso, M.; Zaccone, R.; Scaffaro, R.

    2008-08-01

    Polymer composites with antimicrobial properties were prepared by mixing plasticised poly(vinyl chloride) (PVC) pellets with silver nanoparticles and silver zeolite in the amount of 8 wt% and 10 wt%, respectively. Thermal and mechanical properties of PVC composites were obtained by tensile and calorimetric (TGA and DSC) measurements. Rheological characterization was also performed by a parallel plates rheometer. The results indicate that the thermal and mechanical properties of PVC composites were not affected by the presence of both silver additives, with respect to the pure plasticised PVC. The antibacterial activity of PVC composites was examined on Escherichia coli and Staphylococcus epidermidis in Trypticase Soy Broth and in Trypticase Soy Agar for the direct inhibition. PVC composite with Ag-zeolite exhibited antibacterial activity against S. epidermidis and E. coli in culture broth and direct inhibition in agar plate (inhibition zone: 2-4 mm), for more than 7 days. PVC composites containing silver nanoparticles showed very low antimicrobial activity.

  6. Assessing the antimicrobial activities of Ocins.

    PubMed

    Choyam, Shilja; Lokesh, Dhanashree; Kempaiah, Bettadaiah Bheemakere; Kammara, Rajagopal

    2015-01-01

    The generation of a zone of inhibition on a solid substrate indicates the bioactivity of antimicrobial peptides such as bacteriocin and enterocin. The indicator strain plays a significant role in bacteriocin assays. Other characteristics of bacteriocins, such as their dispersal ability and the different zymogram components, also affect bacteriocin assays. However, universal well diffusion assays for antimicrobials, irrespective of their ability to diffuse (bacteriocin and enterocin), do not exist. The ability of different zymography components to generate non-specific activities have rarely been explored in the literature. The purpose of the present work was to evaluate the impact of major factors (diffusion and rate of diffusion) in a solid substrate bioassay, and to document the adverse effects of sodium dodecyl sulfate in zymograms used to estimate the approximate molecular weight of bacteriocins. PMID:26441952

  7. Assessment of the antimicrobial properties of maggots.

    PubMed

    Margolin, Leon; Gialanella, Philip

    2010-06-01

    Chronic bacterial colonisation or infection of wound is one of the major factors interfering proper wound healing, especially in diabetic foot ulcers. This study assesses the potential antimicrobial properties of maggots in vitro. This is a prospective randomised experimental study. Complete lysis of methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, vancomycin-resistant Enterococcus and Candida albicans cultures in the area of maggot application was observed 24 hours after application of live maggots in all culture plates and was confirmed by Gram staining. This lysis persisted for more than 5 days after the maggot application. Complete lysis of the bacterial or fungal cultures in the area of maggot application provides convincing evidence for the antimicrobial property of maggots. This effect has a significant implication in management of diabetic foot ulcers and vascular ulcers.

  8. Antimicrobial proteins: From old proteins, new tricks.

    PubMed

    Smith, Valerie J; Dyrynda, Elisabeth A

    2015-12-01

    This review describes the main types of antimicrobial peptides (AMPs) synthesised by crustaceans, primarily those identified in shrimp, crayfish, crab and lobster. It includes an overview of their range of microbicidal activities and the current landscape of our understanding of their gene expression patterns in different body tissues. It further summarises how their expression might change following various types of immune challenges. The review further considers proteins or protein fragments from crustaceans that have antimicrobial properties but are more usually associated with other biological functions, or are derived from such proteins. It discusses how these unconventional AMPs might be generated at, or delivered to, sites of infection and how they might contribute to crustacean host defence in vivo. It also highlights recent work that is starting to reveal the extent of multi-functionality displayed by some decapod AMPs, particularly their participation in other aspects of host protection. Examples of such activities include proteinase inhibition, phagocytosis, antiviral activity and haematopoiesis. PMID:26320628

  9. Assessing the antimicrobial activities of Ocins

    PubMed Central

    Choyam, Shilja; Lokesh, Dhanashree; Kempaiah, Bettadaiah Bheemakere; Kammara, Rajagopal

    2015-01-01

    The generation of a zone of inhibition on a solid substrate indicates the bioactivity of antimicrobial peptides such as bacteriocin and enterocin. The indicator strain plays a significant role in bacteriocin assays. Other characteristics of bacteriocins, such as their dispersal ability and the different zymogram components, also affect bacteriocin assays. However, universal well diffusion assays for antimicrobials, irrespective of their ability to diffuse (bacteriocin and enterocin), do not exist. The ability of different zymography components to generate non-specific activities have rarely been explored in the literature. The purpose of the present work was to evaluate the impact of major factors (diffusion and rate of diffusion) in a solid substrate bioassay, and to document the adverse effects of sodium dodecyl sulfate in zymograms used to estimate the approximate molecular weight of bacteriocins. PMID:26441952

  10. Antimicrobial activity of tannins from Terminalia citrina.

    PubMed

    Burapadaja, S; Bunchoo, A

    1995-08-01

    Isolation of the fruit CH3OH extract of Terminalia citrina yielded five known tannins identified as corilagin (1) (3), punicalagin (2) (4), 1,3,6-tri-O-galloyl-beta-D-glucopyranose (3) (5), chebulagic acid (4) (6), and 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (5) (7) by comparison of their physical and spectral data with those of authentic samples. These tannins were tested for antimicrobial action. PMID:7480186

  11. Antimicrobial Peptides Design by Evolutionary Multiobjective Optimization

    PubMed Central

    Maccari, Giuseppe; Di Luca, Mariagrazia; Nifosí, Riccardo; Cardarelli, Francesco; Signore, Giovanni; Boccardi, Claudia; Bifone, Angelo

    2013-01-01

    Antimicrobial peptides (AMPs) are an abundant and wide class of molecules produced by many tissues and cell types in a variety of mammals, plant and animal species. Linear alpha-helical antimicrobial peptides are among the most widespread membrane-disruptive AMPs in nature, representing a particularly successful structural arrangement in innate defense. Recently, AMPs have received increasing attention as potential therapeutic agents, owing to their broad activity spectrum and their reduced tendency to induce resistance. The introduction of non-natural amino acids will be a key requisite in order to contrast host resistance and increase compound's life. In this work, the possibility to design novel AMP sequences with non-natural amino acids was achieved through a flexible computational approach, based on chemophysical profiles of peptide sequences. Quantitative structure-activity relationship (QSAR) descriptors were employed to code each peptide and train two statistical models in order to account for structural and functional properties of alpha-helical amphipathic AMPs. These models were then used as fitness functions for a multi-objective evolutional algorithm, together with a set of constraints for the design of a series of candidate AMPs. Two ab-initio natural peptides were synthesized and experimentally validated for antimicrobial activity, together with a series of control peptides. Furthermore, a well-known Cecropin-Mellitin alpha helical antimicrobial hybrid (CM18) was optimized by shortening its amino acid sequence while maintaining its activity and a peptide with non-natural amino acids was designed and tested, demonstrating the higher activity achievable with artificial residues. PMID:24039565

  12. Antimicrobial prophylaxis in minor and major surgery.

    PubMed

    Bassetti, M; Righi, E; Astilean, A; Corcione, S; Petrolo, A; Farina, E C; De Rosa, F G

    2015-01-01

    Surgical site infections (SSIs) are a frequent cause of morbidity following surgical procedures. Gram-positive cocci, particularly staphylococci, cause many of these infections, although Gram-negative organisms are also frequently involved. The risk of developing a SSI is associated with a number of factors, including aspects of the operative procedure itself, such as wound classification, and patient-related variables, such as preexisting medical conditions. Antimicrobial prophylaxis (AP) plays an important role in reducing SSIs, especially if patient-related risk factors for SSIs are present. The main components of antimicrobial prophylaxis are: timing, selection of drugs and patients, duration and costs. Compliance with these generally accepted preventive principles may lead to overall decreases in the incidence of these infections. Ideally the administration of the prophylactic agent should start within 30 minutes from the surgical incision. The duration of the AP should not exceed 24 hours for the majority of surgical procedures. The shortest effective period of prophylactic antimicrobial administration is not known and studies have demonstrated that post-surgical antibiotic administration is unnecessary. Furthermore, there were no proven benefits in multiple dose regimens when compared to single-dose regimens. The choice of an appropriate prophylactic antimicrobial agent should be based primarily on efficacy and safety. Broad spectrum antibiotics should be avoided due to the risk of promoting bacterial resistance. Cephalosporins are the most commonly used antibiotics in surgical prophylaxis; specifically, cefazolin or cefuroxime are mainly used in the prophylaxis regimens for cardio-thoracic surgery, vascular surgery, hip or knee arthroplasty surgery, neurosurgical procedures and gynecologic and obstetric procedures. A review of the prophylactic regimens regarding the main surgical procedures is presented.

  13. Strategies for antimicrobial drug delivery to biofilm.

    PubMed

    Martin, Claire; Low, Wan Li; Gupta, Abhishek; Amin, Mohd Cairul Iqbal Mohd; Radecka, Iza; Britland, Stephen T; Raj, Prem; Kenward, Ken M A

    2015-01-01

    Biofilms are formed by the attachment of single or mixed microbial communities to a variety of biological and/or synthetic surfaces. Biofilm micro-organisms benefit from many advantages of the polymicrobial environment including increased resistance against antimicrobials and protection against the host organism's defence mechanisms. These benefits stem from a number of structural and physiological differences between planktonic and biofilm-resident microbes, but two main factors are the presence of extracellular polymeric substances (EPS) and quorum sensing communication. Once formed, biofilms begin to synthesise EPS, a complex viscous matrix composed of a variety of macromolecules including proteins, lipids and polysaccharides. In terms of drug delivery strategies, it is the EPS that presents the greatest barrier to diffusion for drug delivery systems and free antimicrobial agents alike. In addition to EPS synthesis, biofilm-based micro-organisms can also produce small, diffusible signalling molecules involved in cell density-dependent intercellular communication, or quorum sensing. Not only does quorum sensing allow microbes to detect critical cell density numbers, but it also permits co-ordinated behaviour within the biofilm, such as iron chelation and defensive antibiotic activities. Against this backdrop of microbial defence and cell density-specific communication, a variety of drug delivery systems have been developed to deliver antimicrobial agents and antibiotics to extracellular and/or intracellular targets, or more recently, to interfere with the specific mechanisms of quorum sensing. Successful delivery strategies have employed lipidic and polymeric-based formulations such as liposomes and cyclodextrins respectively, in addition to inorganic carriers e.g. metal nanoparticles. This review will examine a range of drug delivery systems and their application to biofilm delivery, as well as pharmaceutical formulations with innate antimicrobial properties

  14. Hypoxic radiosensitization by the antimicrobial methyl paraben

    SciTech Connect

    Jacobs, G.P.; Sade, N.

    1984-08-01

    The antimicrobial preservative, methyl paraben (methyl-4-hydroxybenzoate) sensitizes anoxic buffered suspensions of Staphylococcus aureus to gamma-radiation. The maximal response at an 0.5 mM concentration represents a 150 percent increase in response over that for deoxygenated suspensions without additive, and 80 percent of the response for aerated suspensions alone. Methyl paraben is not toxic to the test organism under the present test conditions.

  15. The antimicrobial efficiency of silver activated sorbents

    NASA Astrophysics Data System (ADS)

    Đolić, Maja B.; Rajaković-Ognjanović, Vladana N.; Štrbac, Svetlana B.; Rakočević, Zlatko Lj.; Veljović, Đorđe N.; Dimitrijević, Suzana I.; Rajaković, Ljubinka V.

    2015-12-01

    This study is focused on the surface modifications of the materials that are used for antimicrobial water treatment. Sorbents of different origin were activated by Ag+-ions. The selection of the most appropriate materials and the most effective activation agents was done according to the results of the sorption and desorption kinetic studies. Sorption capacities of selected sorbents: granulated activated carbon (GAC), zeolite (Z), and titanium dioxide (T), activated by Ag+-ions were following: 42.06, 13.51 and 17.53 mg/g, respectively. The antimicrobial activity of Ag/Z, Ag/GAC and Ag/T sorbents were tested against Gram-negative bacteria E. coli, Gram-positive bacteria S. aureus and yeast C. albicans. After 15 min of exposure period, the highest cell removal was obtained using Ag/Z against S. aureus and E. coli, 98.8 and 93.5%, respectively. Yeast cell inactivation was unsatisfactory for all three activated sorbents. The antimicrobial pathway of the activated sorbents has been examined by two separate tests - Ag+-ions desorbed from the activated surface to the aqueous phase and microbial cell removal caused by the Ag+-ions from the solid phase (activated surface sites). The results indicated that disinfection process significantly depended on the microbial-activated sites interactions on the modified surface. The chemical state of the activating agent had crucial impact to the inhibition rate. The characterization of the native and modified sorbents was performed by X-ray diffraction technique, X-ray photoelectron spectroscopy and scanning electron microscope. The concentration of adsorbed and released ions was determined by inductively coupled plasma optical emission spectroscopy and mass spectrometry. The antimicrobial efficiency of activated sorbents was related not only to the concentration of the activating agent, but moreover on the surface characteristics of the material, which affects the distribution and the accessibility of the activating agent.

  16. Antimicrobial activities of selected Cyathus species.

    PubMed

    Liu, Ya-Jun; Zhang, Ke-Qin

    2004-02-01

    Twelve selected Cyathus species were tested for their abilities to produce antimicrobial metabolites. Most of them were found to produce secondary exo-metabolites that could induce morphological abnormalities of rice pathogenic fungi Pyricularia oryzae. Some extracts from the cultivated liquid obviously inhibited human pathogenic fungi Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans. Activities against six human pathogenic bacteria were also obtained from some of these extracts. PMID:15119855

  17. Stability of antimicrobial agents in peritoneal dialysate.

    PubMed Central

    Sewell, D L; Golper, T A

    1982-01-01

    The stability of cephapirin, gentamicin, penicillin G, nafcillin, ticarcillin, and vancomycin was tested in peritoneal dialysate at 25 degrees C for 24 h. All of the antimicrobial agents were stable except penicillin G, which lost 25% of activity over 24 h (P less than 0.01). The once-daily preparation of drug-dialysate solution is feasible for the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis. PMID:7103451

  18. Development of chitosan-based antimicrobial leather coatings.

    PubMed

    Fernandes, Isabel P; Amaral, Joana S; Pinto, Vera; Ferreira, Maria José; Barreiro, Maria Filomena

    2013-10-15

    The development of antimicrobial coatings for footwear components is of great interest both from industry and consumer's point of view. In this work, antimicrobial leather materials were developed taking advantage of chitosan intrinsic antimicrobial activity and film forming capacity. Considering the specificities of the leather tanning industry, different coating technologies, namely drum, calender and spray, were tested, being the best results achieved with the drum. This last approach was further investigated to assess the effect of chitosan content, type of solubilizing acid, and impregnation time on the achieved antimicrobial capacity. Considering chitosan price (economic reasons) and the obtained results (antimicrobial activity and coating effectiveness, as inspected by SEM), the impregnation in the drum using a chitosan content of 1% (w/v) in a formic acid solution during 2h, is proposed as the best option for obtaining leather with antimicrobial capacity.

  19. Antimicrobial polymer nanostructures: synthetic route, mechanism of action and perspective.

    PubMed

    Song, Jooyoung; Jang, Jyongsik

    2014-01-01

    Protection against bacterial infections is an important research field in modern society. Antimicrobial polymers have received considerable attention as next-generation biocides because they represent an ecologically friendly approach that does not promote resistance. In the last decade, many authors have reported the development of nano-sized antimicrobial polymers with enhanced bactericidal performance by increasing the active-area of biocides. This review presents several suitable methods of synthesis of antimicrobial polymer nanomaterials with various shapes, including a nanosphere and fibrous and tubular structures. We also discuss the antimicrobial mechanisms of these polymers. In addition, antimicrobial polymer thin films, which can inhibit bacterial adhesion, are introduced briefly with examples. Our aim is to present synthetic routes and formation mechanisms of various antimicrobial polymer nanostructures.

  20. Antimicrobial activity of endophytic fungi isolated from Swietenia macrophylla leaves.

    PubMed

    Ibrahim, Darah; Lee, Chong Chai; Sheh-Hong, Lim

    2014-02-01

    The endophytic fungi isolated from leaves of Swietenia macrophylla of different ages were examined for antimicrobial activity. The agar plug diffusion assay was used for primary screening, followed by the disc diffusion method. A total of 461 filamentous endophytic fungi were isolated and cultured to examine their antimicrobial properties. In the primary screen, 315 isolates (68.3%) exhibited activity against at least one of the test pathogenic microorganisms. The percentage of isolates exhibiting antimicrobial activity increased with leaf age. Endophytic fungal assemblages, as well as those isolates exhibiting antimicrobial properties appeared to increase with leaf age. The main antimicrobial compounds were produced extracellularly by the endophytic fungi. The results suggest that healthy leaves at older stages of growth can be a potential source for the isolation of endophytic fungi with antimicrobial properties.

  1. Novel food packaging systems with natural antimicrobial agents.

    PubMed

    Irkin, Reyhan; Esmer, Ozlem Kizilirmak

    2015-10-01

    A new type of packaging that combines food packaging materials with antimicrobial substances to control microbial surface contamination of foods to enhance product microbial safety and to extend shelf-life is attracting interest in the packaging industry. Several antimicrobial compounds can be combined with different types of packaging materials. But in recent years, since consumer demand for natural food ingredients has increased because of safety and availability, these natural compounds are beginning to replace the chemical additives in foods and are perceived to be safer and claimed to alleviate safety concerns. Recent research studies are mainly focused on the application of natural antimicrobials in food packaging system. Biologically derived compounds like bacteriocins, phytochemicals, enzymes can be used in antimicrobial food packaging. The aim of this review is to give an overview of most important knowledge about application of natural antimicrobial packagings with model food systems and their antimicrobial effects on food products. PMID:26396358

  2. Towards an antimicrobial ‘microglove’

    PubMed Central

    Reilman, Ewoud; Hagting, Joke G.; Flipsen, Theo; Ulmer, Herb; van Dijl, Jan Maarten

    2015-01-01

    A large proportion of hospital-related infections are acquired and spread due to the direct contacts between patients and healthcare workers. Accordingly, proper infection prevention measures, and especially hand hygiene, are key to limit the spread of infections in nosocomial settings. However, healthcare workers frequently experience difficulties in complying strictly to hand disinfection protocols. This study was therefore aimed at the development of a hand rub with antimicrobial activity that forms a protective film on the hand, a so-called microglove, in order to enhance hand hygiene. For this purpose, various co-polymer formulations consisting of different ratios of Polyvinylpyrrolidone (PVP) and a branched C20 derivatized maleate (M20) in combination with the known biocide benzalkonium chloride (BKC) were tested for their combined film-forming and antimicrobial activities. The results of a series of novel contamination and transmission assays show that a formulation of 80% PVP and 20% M20 co-polymer with 0.9% BKC fulfils the elementary requirements for an antimicrobial microglove. PMID:26564815

  3. IN-VITRO ANTIMICROBIAL ACTIVITY OF BRONCHOSOL.

    PubMed

    Witkowska-Banaszczak, Ewa; Michalak, Anna; Kędzia, Anna

    2015-01-01

    Bronchosol is a traditional medicinal product in the form of syrup used in cough and impeded expectoration. The active ingredients that it contains include extracts from the herb of thyme, the root of primrose and thymol. It is recommended in disorders of the respiratory tract when expectoration is impeded and secretion of liquid mucus in bronchi is insufficient. Antimicrobial activity of the components of Bronchosol, especially thyme and thymol, has frequently been reported in the literature. To date, there have not been any studies to confirm such activity of Bronchosol, though. The results of our research are the first one to point to the great activity of Bronchosol against microorganisms causing infections of the respiratory tract. It has been demonstrated that this product displayed antimicrobial activity against reference strains as well as strains of anaerobic and aerobic bacteria and fungi isolated from patients. The confirmation of the antimicrobial activity of Bronchosol provides an explanation of its effectiveness in the therapy of the respiratory tract infections. PMID:26642688

  4. Classification of antimicrobial peptides with imbalanced datasets

    NASA Astrophysics Data System (ADS)

    Camacho, Francy L.; Torres, Rodrigo; Ramos Pollán, Raúl

    2015-12-01

    In the last years, pattern recognition has been applied to several fields for solving multiple problems in science and technology as for example in protein prediction. This methodology can be useful for prediction of activity of biological molecules, e.g. for determination of antimicrobial activity of synthetic and natural peptides. In this work, we evaluate the performance of different physico-chemical properties of peptides (descriptors groups) in the presence of imbalanced data sets, when facing the task of detecting whether a peptide has antimicrobial activity. We evaluate undersampling and class weighting techniques to deal with the class imbalance with different classification methods and descriptor groups. Our classification model showed an estimated precision of 96% showing that descriptors used to codify the amino acid sequences contain enough information to correlate the peptides sequences with their antimicrobial activity by means of learning machines. Moreover, we show how certain descriptor groups (pseudoaminoacid composition type I) work better with imbalanced datasets while others (dipeptide composition) work better with balanced ones.

  5. Antioxidant and antimicrobial activities of Withania frutescens.

    PubMed

    El Bouzidi, Laila; Larhsini, Mustapha; Markouk, Mohamed; Abbad, Abdelaziz; Hassani, Lahcen; Bekkouche, Khalid

    2011-10-01

    In the present study, we report for the first time the antioxidant and antimicrobial activities of Withania frutescens (L.) Pauquy roots and leaves. Total phenolic content was determined using the Folin-Ciocalteu method and antioxidant activity was evaluated by the DPPH free radical scavenging and reducing power methods. Antimicrobial activity tests were carried out against ten bacterial species involved in nosocomial infections and two opportunistic clinical yeast isolates. The ethyl acetate and n-butanol leaf fractions exhibited the highest DPPH radical scavenging activity with IC50 = 4.53 +/- 0.12 and 8.49 +/- 0.46 microg/mL, respectively. The n-butanol root fraction showed the greatest reducing power comparable with that of quercetin at 0.4 mg/mL. The dichloromethane leaf fraction exhibited the highest antibacterial activity against both Gram-positive and Gram-negative bacteria with MIC values ranging between 50 and 400 microg/mL, depending on the tested bacteria. However, none of the examined extracts exhibited anticandidal activity. The polyphenol and glycowithanolide constituents appeared to be responsible for the antioxidant capacity of W. frutescens, whereas the observed antimicrobial activity may be due to the presence of withanolides.

  6. Effectiveness of antimicrobial food packaging materials.

    PubMed

    Cooksey, K

    2005-10-01

    Antimicrobial additives have been used successfully for many years as direct food additives. The literature provides evidence that some of these additives may be effective as indirect food additives incorporated into food packaging materials. Antimicrobial food packaging is directed toward the reduction of surface contamination of processed, prepared foods such as sliced meats and Frankfurter sausages (hot dogs). The use of such packaging materials is not meant to be a substitute for good sanitation practices, but it should enhance the safety of food as an additional hurdle for the growth of pathogenic and/or spoilage microorganisms. Studies have focused on establishing methods for coating low-density polyethylene film or barrier films with methyl cellulose as a carrier for nisin. These films have significantly reduced the presence of Listeria monocytogenes in solutions and in vacuum packaged hot dogs. Other research has focused on the use of chitosan to inhibit L. monocytogenes and chlorine dioxide sachets for the reduction of Salmonella on modified atmosphere-packaged fresh chicken breasts. Overall, antimicrobial packaging shows promise as an effective method for the inhibition of certain bacteria in foods, but barriers to their commercial implementation continue to exist. PMID:16227182

  7. ANTIMICROBIAL ACTIVITY OF EXTRACTS FROM ECUADORIAN LICHENS.

    PubMed

    Matvieieva, N A; Pasichnyk, L A; Zhytkevych, N V; Jacinto, Pabón Garcés Galo; Pidgorskyi, V S

    2015-01-01

    Antimicrobial activity of the ethanolic, isopropanolic, acetone, DMSO and aqueous extracts of the two lichen species from Ecuadorian highland, Usnea sp. and Stereocaulon sp. were explored in vitro against bacteria Bacillus subtilis, Escherichia coli and Staphylococcus aureus by the disc-diffusion method. Also the minimal inhibitory concentration (MIC) was determined. The strongest antimicrobial activity was found in DMSO extract of Usnea sp. compared to antibacterial activity of ciprfloxacin and cefazolin antibiotics. The inhibition zone was 28 mm, 30 mm, 31mm (DMSO extract, ciprfloxacin and cefazolin respectively) in case of B. subtilis usage as the test bacteria. MIC value for Usnea sp. and Stereocaulon sp. DMSO extracts was 0.4 mg/ml. E. coli was resistant to all kinds of extracts. The S. aureus sensitivity to lichen DMSO extracts was comparable to sensitivity of these microorganisms to tetracycline and vancomycin. Thereby, most kinds of extracts (ethanol, isopropanol, hexane, DMSO and acetone solvents) from Ecuadorian lichens Usnea sp. and Stereocaulon sp. with the exception of aqueous Stereocaulon sp. extracts possessed antibacterial activity against B. subtilis. DMSO lichen extracts had also antimicrobial activity against S. aureus. At the same time the extracts studied didn't demonstrate antibacterial activity against the representatives of the most common and harmful phytopathogenic bacteria tested. Further investigations of Ecuadorian lichens especially study of plants collected from extremal highland biotops can be very important in study of possibility of treatment of numerous diseases caused by pathogenic microorganisms. PMID:26214895

  8. Resistance to Antimicrobial Peptides in Vibrios

    PubMed Central

    Destoumieux-Garzón, Delphine; Duperthuy, Marylise; Vanhove, Audrey Sophie; Schmitt, Paulina; Wai, Sun Nyunt

    2014-01-01

    Vibrios are associated with a broad diversity of hosts that produce antimicrobial peptides (AMPs) as part of their defense against microbial infections. In particular, vibrios colonize epithelia, which function as protective barriers and express AMPs as a first line of chemical defense against pathogens. Recent studies have shown they can also colonize phagocytes, key components of the animal immune system. Phagocytes infiltrate infected tissues and use AMPs to kill the phagocytosed microorganisms intracellularly, or deliver their antimicrobial content extracellularly to circumvent tissue infection. We review here the mechanisms by which vibrios have evolved the capacity to evade or resist the potent antimicrobial defenses of the immune cells or tissues they colonize. Among their strategies to resist killing by AMPs, primarily vibrios use membrane remodeling mechanisms. In particular, some highly resistant strains substitute hexaacylated Lipid A with a diglycine residue to reduce their negative surface charge, thereby lowering their electrostatic interactions with cationic AMPs. As a response to envelope stress, which can be induced by membrane-active agents including AMPs, vibrios also release outer membrane vesicles to create a protective membranous shield that traps extracellular AMPs and prevents interaction of the peptides with their own membranes. Finally, once AMPs have breached the bacterial membrane barriers, vibrios use RND efflux pumps, similar to those of other species, to transport AMPs out of their cytoplasmic space. PMID:27025756

  9. ANTIMICROBIAL ACTIVITY OF EXTRACTS FROM ECUADORIAN LICHENS.

    PubMed

    Matvieieva, N A; Pasichnyk, L A; Zhytkevych, N V; Jacinto, Pabón Garcés Galo; Pidgorskyi, V S

    2015-01-01

    Antimicrobial activity of the ethanolic, isopropanolic, acetone, DMSO and aqueous extracts of the two lichen species from Ecuadorian highland, Usnea sp. and Stereocaulon sp. were explored in vitro against bacteria Bacillus subtilis, Escherichia coli and Staphylococcus aureus by the disc-diffusion method. Also the minimal inhibitory concentration (MIC) was determined. The strongest antimicrobial activity was found in DMSO extract of Usnea sp. compared to antibacterial activity of ciprfloxacin and cefazolin antibiotics. The inhibition zone was 28 mm, 30 mm, 31mm (DMSO extract, ciprfloxacin and cefazolin respectively) in case of B. subtilis usage as the test bacteria. MIC value for Usnea sp. and Stereocaulon sp. DMSO extracts was 0.4 mg/ml. E. coli was resistant to all kinds of extracts. The S. aureus sensitivity to lichen DMSO extracts was comparable to sensitivity of these microorganisms to tetracycline and vancomycin. Thereby, most kinds of extracts (ethanol, isopropanol, hexane, DMSO and acetone solvents) from Ecuadorian lichens Usnea sp. and Stereocaulon sp. with the exception of aqueous Stereocaulon sp. extracts possessed antibacterial activity against B. subtilis. DMSO lichen extracts had also antimicrobial activity against S. aureus. At the same time the extracts studied didn't demonstrate antibacterial activity against the representatives of the most common and harmful phytopathogenic bacteria tested. Further investigations of Ecuadorian lichens especially study of plants collected from extremal highland biotops can be very important in study of possibility of treatment of numerous diseases caused by pathogenic microorganisms.

  10. Toxicology of antimicrobial nanoparticles for prosthetic devices.

    PubMed

    Nuñez-Anita, Rosa Elvira; Acosta-Torres, Laura Susana; Vilar-Pineda, Jorge; Martínez-Espinosa, Juan Carlos; de la Fuente-Hernández, Javier; Castaño, Víctor Manuel

    2014-01-01

    Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered health-related products. Nanoparticles with antifungal effects are of great interest in the formulation of microbicidal materials. Fungi are found as innocuous commensals and colonize various habitats in and on humans, especially the skin and mucosa. As growth on surfaces is a natural part of the Candida spp. lifestyle, one can expect that Candida organisms colonize prosthetic devices, such as dentures. Macromolecular systems, due to their properties, allow efficient use of these materials in various fields, including the creation of reinforced nanoparticle polymers with antimicrobial activity. This review briefly summarizes the results of studies conducted during the past decade and especially in the last few years focused on the toxicity of different antimicrobial polymers and factors influencing their activities, as well as the main applications of antimicrobial polymers in dentistry. The present study addresses aspects that are often overlooked in nanotoxicology studies, such as careful time-dependent characterization of agglomeration and ion release.

  11. Toxicology of antimicrobial nanoparticles for prosthetic devices

    PubMed Central

    Nuñez-Anita, Rosa Elvira; Acosta-Torres, Laura Susana; Vilar-Pineda, Jorge; Martínez-Espinosa, Juan Carlos; de la Fuente-Hernández, Javier; Castaño, Víctor Manuel

    2014-01-01

    Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered health-related products. Nanoparticles with antifungal effects are of great interest in the formulation of microbicidal materials. Fungi are found as innocuous commensals and colonize various habitats in and on humans, especially the skin and mucosa. As growth on surfaces is a natural part of the Candida spp. lifestyle, one can expect that Candida organisms colonize prosthetic devices, such as dentures. Macromolecular systems, due to their properties, allow efficient use of these materials in various fields, including the creation of reinforced nanoparticle polymers with antimicrobial activity. This review briefly summarizes the results of studies conducted during the past decade and especially in the last few years focused on the toxicity of different antimicrobial polymers and factors influencing their activities, as well as the main applications of antimicrobial polymers in dentistry. The present study addresses aspects that are often overlooked in nanotoxicology studies, such as careful time-dependent characterization of agglomeration and ion release. PMID:25187703

  12. IN-VITRO ANTIMICROBIAL ACTIVITY OF BRONCHOSOL.

    PubMed

    Witkowska-Banaszczak, Ewa; Michalak, Anna; Kędzia, Anna

    2015-01-01

    Bronchosol is a traditional medicinal product in the form of syrup used in cough and impeded expectoration. The active ingredients that it contains include extracts from the herb of thyme, the root of primrose and thymol. It is recommended in disorders of the respiratory tract when expectoration is impeded and secretion of liquid mucus in bronchi is insufficient. Antimicrobial activity of the components of Bronchosol, especially thyme and thymol, has frequently been reported in the literature. To date, there have not been any studies to confirm such activity of Bronchosol, though. The results of our research are the first one to point to the great activity of Bronchosol against microorganisms causing infections of the respiratory tract. It has been demonstrated that this product displayed antimicrobial activity against reference strains as well as strains of anaerobic and aerobic bacteria and fungi isolated from patients. The confirmation of the antimicrobial activity of Bronchosol provides an explanation of its effectiveness in the therapy of the respiratory tract infections.

  13. Kombucha fermentation and its antimicrobial activity.

    PubMed

    Sreeramulu, G; Zhu, Y; Knol, W

    2000-06-01

    Kombucha was prepared in a tea broth (0.5% w/v) supplemented with sucrose (10% w/v) by using a commercially available starter culture. The pH decreased steadily from 5 to 2.5 during the fermentation while the weight of the "tea fungus" and the OD of the tea broth increased through 4 days of the fermentation and remained fairly constant thereafter. The counts of acetic acid-producing bacteria and yeasts in the broth increased up to 4 days of fermentation and decreased afterward. The antimicrobial activity of Kombucha was investigated against a number of pathogenic microorganisms. Staphylococcus aureus, Shigella sonnei, Escherichia coli, Aeromonas hydrophila, Yersinia enterolitica, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus epidermis, Campylobacter jejuni, Salmonella enteritidis, Salmonella typhimurium, Bacillus cereus, Helicobacterpylori, and Listeria monocytogenes were found to be sensitive to Kombucha. According to the literature on Kombucha, acetic acid is considered to be responsible for the inhibitory effect toward a number of microbes tested, and this is also valid in the present study. However, in this study, Kombucha proved to exert antimicrobial activities against E. coli, Sh. sonnei, Sal. typhimurium, Sal. enteritidis, and Cm. jejuni, even at neutral pH and after thermal denaturation. This finding suggests the presence of antimicrobial compounds other than acetic acid and large proteins in Kombucha. PMID:10888589

  14. Topical antimicrobial toolkit for wound infection.

    PubMed

    Woo, Kevin Y; Alam, Tarik; Marin, Joseph

    2014-11-01

    Increased bacterial burden and formation of biofilm has been recognized as one of the key factors contributing to delayed wound healing. There is a toolbox of topical antimicrobial wound dressings that incorporate silver, iodine, polyhexamethylene biguanide, methylene blue/gentian violet, and honey. This article reviews a diverse range of evidence to discuss the advantages and disadvantage of topical antimicrobial dressings. Discussion will provide guidance on when and how to use topical antimicrobial dressings to achieve optimal outcomes and cost-effective wound care. Chronic wounds do not follow a predictable and expected healing trajectory, and they may persist for months or years due to underlying disease processes, recurrent injury, and comorbidities.1 With an aging population and increased prevalence of chronic diseases, the majority of wounds are refractory to healing, placing a significant burden on the health system and individual patients. Bacterial burden and biofilm have been recognized as key factors contributing to persistent inflammation, tissue destruction, delayed wound healing, and other serious complications (especially in individuals who are frail and immune-compromised).2 It has been demonstrated that when bacterial growth reaches a critical threshold of 105 bacteria per gram of tissue, bacterial toxins can cause tissue damage in the superficial wound compartment, delaying healing.2 In the literature, this phenomenon is referred to as critical colonization, increased bacterial burden, superficial infection, or localized infection. According to a recent review, over 50% of chronic wounds exhibit signs and symptoms that are consistent with localized infection.3.

  15. Insect Antimicrobial Peptides and Their Applications

    PubMed Central

    Yi, Hui-Yu; Chowdhury, Munmun; Huang, Ya-Dong; Yu, Xiao-Qiang

    2014-01-01

    Insects are one of the major sources of antimicrobial peptides/proteins (AMPs). Since observation of antimicrobial activity in the hemolymph of pupae from the giant silk moths Samia Cynthia and Hyalophora cecropia in 1974 and purification of first insect AMP (cecropin) from H. cecropia pupae in 1980, over 150 insect AMPs have been purified or identified. Most insect AMPs are small and cationic, and they show activities against bacteria and/or fungi, as well as some parasites and viruses. Insect AMPs can be classified into four families based on their structures or unique sequences: the α-helical peptides (cecropin and moricin), cysteine-rich peptides (insect defensin and drosomycin), proline-rich peptides (apidaecin, drosocin and lebocin), and glycine-rich peptides/proteins (attacin and gloverin). Among insect AMPs, defensins, cecropins, proline-rich peptides and attacins are common, while gloverins and moricins have been identified only in Lepidoptera. Most active AMPs are small peptides of 20–50 residues, which are generated from larger inactive precursor proteins or pro-proteins, but gloverins (~14 kDa) and attacins (~20 kDa) are large antimicrobial proteins. In this mini-review, we will discuss current knowledge and recent progress in several classes of insect AMPs, including insect defensins, cecropins, attacins, lebocins and other proline-rich peptides, gloverins, and moricins, with a focus on structural-functional relationships and their potential applications. PMID:24811407

  16. Screening of natural products for antimicrobial agents.

    PubMed

    Silver, L; Bostian, K

    1990-07-01

    Antimicrobial research is geared toward the discovery and development of novel chemical structures such as therapeutic antimicrobial agents. The continuing problem of development of resistance to existing antibacterial agents and the dearth of good antifungal agents motivates this effort toward innovation. Selection of possible new enzyme targets for antibiotic inhibition may be made on theoretical grounds, but it appears premature to select any single, previously unvalidated target for the intensive study required for rational drug design. Instead, a broad screen of chemical entities can be undertaken, dedicated to the discovery of novel antimicrobial inhibitors. A number of target areas are under investigation, including fungal mRNA splicing and bacterial DNA synthesis. A major part of the endeavor is in the historically productive area of natural product screening. To make the best use of natural product resources for the discovery of novel antibiotics, a balance is struct between screening for inhibitors of rationally chosen targets for which clinically useful inhibitors are not yet available, and screening more broadly to ensure that rare activities of unanticipated mode-of-action are not missed.

  17. Antimicrobial Cu-bearing stainless steel scaffolds.

    PubMed

    Wang, Qiang; Ren, Ling; Li, Xiaopeng; Zhang, Shuyuan; Sercombe, Timothy B; Yang, Ke

    2016-11-01

    Copper-bearing stainless steel scaffolds with two different structures (Body Centered Cubic and Gyroid labyrinth) at two solid fractions (25% and 40%) were fabricated from both 316L powder and a mixture of 316L and elemental Cu powder using selective laser melting, and relative 316L scaffolds were served as control group. After processing, the antimicrobial testing demonstrated that the 316L-Cu scaffolds presented excellent antimicrobial activity against Escherichia coli and Staphylococcus aureus, and the cell viability assay indicated that there was no cytotoxic effect of 316L-Cu scaffolds on rat marrow mesenchymal stem cells. As such, these have the potential to reduce implant-associated infections. The Cu was also found to homogeneously distribute within the microstructure by scanning electronic microcopy. The addition of Cu would not significantly affect its strength and stiffness compared to 316L scaffold, and the stiffness of all the scaffolds (3-20GPa) is similar to that of bone and much less than that of bulk stainless steel. Consequently, fabrication of such low stiffness porous structures, especially coupled with the addition of antimicrobial Cu, may provide a new direction for medical stainless steels. PMID:27524049

  18. Antimicrobial peptide resistance in Neisseria meningitidis.

    PubMed

    Tzeng, Yih-Ling; Stephens, David S

    2015-11-01

    Antimicrobial peptides (AMPs) play an important role as a host defense against microbial pathogens and are key components of the human innate immune response. Neisseria meningitidis frequently colonizes the human nasopharynx as a commensal but also is a worldwide cause of epidemic meningitis and rapidly fatal sepsis. In the human respiratory tract, the only known reservoir of N. meningitidis, meningococci are exposed to human endogenous AMPs. Thus, it is not surprising that meningococci have evolved effective mechanisms to confer intrinsic and high levels of resistance to the action of AMPs. This article reviews the current knowledge about AMP resistance mechanisms employed by N. meningitidis. Two major resistance mechanisms employed by meningococci are the constitutive modification of the lipid A head groups of lipooligosaccharides by phosphoethanolamine and the active efflux pump mediated excretion of AMPs. Other factors influencing AMP resistance, such as the major porin PorB, the pilin biogenesis apparatus, and capsular polysaccharides, have also been identified. Even with an inherently high intrinsic resistance, several AMP resistance determinants can be further induced upon exposure to AMPs. Many well-characterized AMP resistance mechanisms in other Gram-negative bacteria are not found in meningococci. Thus, N. meningitidis utilizes a limited but highly effective set of molecular mechanisms to mediate antimicrobial peptide resistance. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.

  19. Declines in Outpatient Antimicrobial Use in Canada (1995–2010)

    PubMed Central

    Finley, Rita; Glass-Kaastra, Shiona K.; Hutchinson, Jim; Patrick, David M.; Weiss, Karl; Conly, John

    2013-01-01

    Background With rising reports of antimicrobial resistance in outpatient communities, surveillance of antimicrobial use is imperative for supporting stewardship programs. The primary objective of this article is to assess the levels of antimicrobial use in Canada over time. Methods Canadian antimicrobial use data from 1995 to 2010 were acquired and assessed by four metrics: population-adjusted prescriptions, Defined Daily Doses, spending on antimicrobials (inflation-adjusted), and average Defined Daily Doses per prescription. Linear mixed models were built to assess significant differences among years and antimicrobial groups, and to account for repeated measurements over time. Measures were also compared to published reports from European countries. Results Temporal trends in antimicrobial use in Canada vary by metric and antimicrobial grouping. Overall reductions were seen for inflation-adjusted spending, population-adjusted prescription rates and Defined Daily Doses, and increases were observed for the average number of Defined Daily Doses per prescription. The population-adjusted prescription and Defined Daily Doses values for 2009 were comparable to those reported by many European countries, while the average Defined Daily Dose per prescription for Canada ranked high. A significant reduction in the use of broad spectrum penicillins occurred between 1995 and 2004, coupled with increases in macrolide and quinolone use, suggesting that replacement of antimicrobial drugs may occur as new products arrive on the market. Conclusions There have been modest decreases of antimicrobial use in Canada over the past 15 years. However, continued surveillance of antimicrobial use coupled with data detailing antimicrobial resistance within bacterial pathogens affecting human populations is critical for targeting interventions and maintaining the effectiveness of these products for future generations. PMID:24146863

  20. Antimicrobial resistance in Swiss laying hens, prevalence and risk factors.

    PubMed

    Harisberger, M; Gobeli, S; Hoop, R; Dewulf, J; Perreten, V; Regula, G

    2011-09-01

    Antimicrobial resistance is an emerging concern to public health, and food-producing animals are known to be a potential source for transmission of resistant bacteria to humans. As legislation of the European Union requires to ban conventional cages for the housing of laying hens on the one hand, and a high food safety standard for eggs on the other hand, further investigations about the occurrence of antimicrobial resistance in alternative housing types are required. In this study, we determined antimicrobial resistance in indicator bacteria from 396 cloacal swabs from 99 Swiss laying hen farms among four alternative housing types during a cross-sectional study. On each farm, four hens were sampled and exposure to potential risk factors was identified with a questionnaire. The minimal inhibitory concentration was determined using broth microdilution in Escherichia coli (n=371) for 18 antimicrobials and in Enterococcus faecalis (n=138) and Enterococcus faecium (n=153) for 16 antimicrobials. All antimicrobial classes recommended by the European Food Safety Authority for E. coli and enterococci were included in the resistance profile. Sixty per cent of the E. coli isolates were susceptible to all of the considered antimicrobials and 30% were resistant to at least two antimicrobials. In E. faecalis, 33% of the strains were susceptible to all tested antimicrobials and 40% were resistant to two or more antimicrobials, whereas in E. faecium these figures were 14% and 39% respectively. Risk factor analyses were carried out for bacteria species and antimicrobials with a prevalence of resistance between 15% and 85%. In these analyses, none of the considered housing and management factors showed a consistent association with the prevalence of resistance for more than two combinations of bacteria and antimicrobial. Therefore we conclude that the impact of the considered housing and management practices on the egg producing farms on resistance in laying hens is low. PMID