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Sample records for antibiotic molecules bypassing

  1. High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance.

    PubMed

    Wambaugh, Morgan A; Shakya, Viplendra P S; Lewis, Adam J; Mulvey, Matthew A; Brown, Jessica C S

    2017-06-01

    Antibiotic-resistant infections kill approximately 23,000 people and cost $20,000,000,000 each year in the United States alone despite the widespread use of small-molecule antimicrobial combination therapy. Antibiotic combinations typically have an additive effect: the efficacy of the combination matches the sum of the efficacies of each antibiotic when used alone. Small molecules can also act synergistically when the efficacy of the combination is greater than the additive efficacy. However, synergistic combinations are rare and have been historically difficult to identify. High-throughput identification of synergistic pairs is limited by the scale of potential combinations: a modest collection of 1,000 small molecules involves 1 million pairwise combinations. Here, we describe a high-throughput method for rapid identification of synergistic small-molecule pairs, the overlap2 method (O2M). O2M extracts patterns from chemical-genetic datasets, which are created when a collection of mutants is grown in the presence of hundreds of different small molecules, producing a precise set of phenotypes induced by each small molecule across the mutant set. The identification of mutants that show the same phenotype when treated with known synergistic molecules allows us to pinpoint additional molecule combinations that also act synergistically. As a proof of concept, we focus on combinations with the antibiotics trimethoprim and sulfamethizole, which had been standard treatment against urinary tract infections until widespread resistance decreased efficacy. Using O2M, we screened a library of 2,000 small molecules and identified several that synergize with the antibiotic trimethoprim and/or sulfamethizole. The most potent of these synergistic interactions is with the antiviral drug azidothymidine (AZT). We then demonstrate that understanding the molecular mechanism underlying small-molecule synergistic interactions allows the rational design of additional combinations that

  2. 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).

  3. Bypass of genetic constraints during mutator evolution to antibiotic resistance.

    PubMed

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2015-04-07

    Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a β-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness.

  4. In silico screening for antibiotic escort molecules to overcome efflux.

    PubMed

    Rahman, Sheikh S; Simovic, Ivana; Gibbons, Simon; Zloh, Mire

    2011-11-01

    Resistance to antibiotics is a growing problem worldwide and occurs in part due to the overexpression of efflux pumps responsible for the removal of antibiotics from bacterial cells. The current study examines complex formation between efflux pump substrates and escort molecules as a criterion for an in silico screening method for molecules that are able to potentiate antibiotic activities. Initially, the SUPERDRUG database was queried to select molecules that were similar to known multidrug resistance (MDR) modulators. Molecular interaction fields generated by GRID and the docking module GLUE were used to calculate the interaction energies between the selected molecules and the antibiotic norfloxacin. Ten compounds forming the most stable complexes with favourable changes to the norfloxacin molecular properties were tested for their potentiation ability by efflux pump modulation assays. Encouragingly, two molecules were proven to act as efflux pump modulators, and hence provide evidence that complex formation between a substrate and a drug can be used for in silico screening for novel escort molecules.

  5. Antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery.

    PubMed

    Poeran, Jashvant; Mazumdar, Madhu; Rasul, Rehana; Meyer, Joanne; Sacks, Henry S; Koll, Brian S; Wallach, Frances R; Moskowitz, Alan; Gelijns, Annetine C

    2016-02-01

    Antibiotic use, particularly type and duration, is a crucial modifiable risk factor for Clostridium difficile. Cardiac surgery is of particular interest because prophylactic antibiotics are recommended for 48 hours or less (vs ≤24 hours for noncardiac surgery), with increasing vancomycin use. We aimed to study associations between antibiotic prophylaxis (duration/vancomycin use) and C difficile among patients undergoing coronary artery bypass grafting. We extracted data on coronary artery bypass grafting procedures from the national Premier Perspective claims database (2006-2013, n = 154,200, 233 hospitals). Multilevel multivariable logistic regressions measured associations between (1) duration (<2 days, "standard" vs ≥2 days, "extended") and (2) type of antibiotic used ("cephalosporin," "cephalosporin + vancomycin," "vancomycin") and C difficile as outcome. Overall C difficile prevalence was 0.21% (n = 329). Most patients (59.7%) received a cephalosporin only; in 33.1% vancomycin was added, whereas 7.2% received vancomycin only. Extended prophylaxis was used in 20.9%. In adjusted analyses, extended prophylaxis (vs standard) was associated with significantly increased C difficile risk (odds ratio, 1.43; confidence interval, 1.07-1.92), whereas no significant associations existed for vancomycin use as adjuvant or primary prophylactic compared with the use of cephalosporins (odds ratio, 1.21; confidence interval, 0.92-1.60, and odds ratio, 1.39; confidence interval, 0.94-2.05, respectively). Substantial inter-hospital variation exists in the percentage of extended antibiotic prophylaxis (interquartile range, 2.5-35.7), use of adjuvant vancomycin (interquartile range, 4.2-61.1), and vancomycin alone (interquartile range, 2.3-10.4). Although extended use of antibiotic prophylaxis was associated with increased C difficile risk after coronary artery bypass grafting, vancomycin use was not. The observed hospital variation in antibiotic prophylaxis

  6. Review of Antibiotic and Non-Antibiotic Properties of Beta-lactam Molecules.

    PubMed

    Ochoa-Aguilar, Abraham; Ventura-Martinez, Rosa; Sotomayor-Sobrino, Marco Antonio; Gómez, Claudia; Morales-Espinoza, María del Rosario

    2016-01-01

    Beta-lactam molecules are a family of drugs commonly used for their antibiotic properties; however, recent research has shown that several members of this group present a large number of other effects such as neuroprotective, antioxidant, analgesic or immunomodulatory capabilities. These properties have been used in both preclinical and clinical studies in different diseases such as hypoxic neuronal damage or acute and chronic pain. The present work briefly reviews the antibiotic effect of these molecules, and will then focus specially on the non-antibiotic effects of three beta-lactam subfamilies: penicillins, cephalosporins and beta lactamase inhibitors, each of which have different molecular structure and pharmacokinetics and therefore have several potential clinical applications. A thorough search of bibliographic databases for peer-reviewed research was performed including only classic experiments or high quality reviews for the antibiotic mechanisms of beta-lactam molecules and only experimental research papers where included when the non-antibiotic properties of these molecules were searched. Only published articles from indexed journals were included. Quality of retrieved papers was assessed using standard tools. The characteristics of screened papers were described and findings of included studies were contextualized to either a mechanistic or a clinical framework. Seventy-eight papers were included in the review; the majority (56) were relative to the non-antibiotic properties of beta-lactam molecules. The non-antibiotic effects reviewed were divided accordingly to the amount of information available for each one. Twelve papers outlined the epileptogenic effects induced by beta-lactam molecules administration; these included both clinical and basic research as well as probable mechanistic explanations. Eighteen papers described a potential neuroprotective effect, mostly in basic in vitro and in vivo experiments. Analgesic properties where identified in

  7. Dosing antibiotic prophylaxis during cardiopulmonary bypass-a higher level of complexity? A structured review.

    PubMed

    Paruk, Fathima; Sime, Fekade B; Lipman, Jeffrey; Roberts, Jason A

    2017-04-01

    In highly invasive procedures such as open heart surgery, the risk of post-operative infection is particularly high due to exposure of the surgical field to multiple foreign devices. Adequate antibiotic prophylaxis is an essential intervention to minimise post-operative morbidity and mortality. However, there is a lack of clear understanding on the adequacy of traditional prophylactic dosing regimens, which are rarely supported by data. The aim of this structured review is to describe the relevant pharmacokinetic/pharmacodynamic (PK/PD) considerations for optimal antibiotic prophylaxis for major cardiac surgery including cardiopulmonary bypass (CPB). A structured review of the relevant published literature was performed and 45 relevant studies describing antibiotic pharmacokinetics in patients receiving extracorporeal CPB as part of major cardiac surgery were identified. Some of the studies suggested marked PK alterations in the peri-operative period with increases in volume of distribution (Vd) by up to 58% and altered drug clearances of up to 20%. Mechanisms proposed as causing the PK changes included haemodilution, hypothermia, retention of the antibiotic within the extracorporeal circuit, altered physiology related to a systemic inflammatory response, and maldistribution of blood flow. Of note, some studies reported no or minimal impact of the CPB procedure on antibiotic pharmacokinetics. Given the inconsistent data, ongoing research should focus on clarifying the influence of CPB procedure and related clinical covariates on the pharmacokinetics of different antibiotics during cardiac surgery. Traditional prophylactic dosing regimens may need to be re-assessed to ensure sufficient drug exposures that will minimise the risk of surgical site infections. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  8. Neutrophil adhesion molecule expression during cardiopulmonary bypass: a comparative study of roller and centrifugal pumps.

    PubMed

    Macey, M G; McCarthy, D A; Trivedi, U R; Venn, G E; Chambers, D J; Brown, K A

    1997-09-01

    The purpose of this study was to determine whether adhesion molecules and markers of cell activation were preferentially increased on blood neutrophils during cardiopulmonary bypass (CPB) and whether such effects were influenced by the use of a roller pump or a centrifugal pump. Forty-six patients undergoing open heart surgery were randomly allocated into either the roller or centrifugal groups. Blood (1 ml volumes) was removed from arterial and venous lines immediately before and 1 h after the start of bypass. Whole blood samples were immunolabelled and flow cytometry used to measure the distribution and expression of the adhesion molecules CD11b, CD18, CD62L on neutrophils, monocytes and lymphocytes, in addition to CD64 on neutrophils and monocytes, and CD14 on monocytes. The expression of CD11b was significantly enhanced on neutrophils in arterial and venous samples from both the roller pump (mean 84% and 100% increase, respectively; p < 0.001) and centrifugal pump (mean 74% and 73% increase, respectively; p < 0.001) groups. Neutrophil L-selectin expression increased to a small but significant extent in arterial and venous samples from the centrifugal pump group (mean 16% increase; p < 0.001) and in venous samples from the roller pump group (mean 10% increase; p < 0.01). Neither the percentage of neutrophils bearing CD11b/CD18, CD62L and CD64, nor the expression of adhesion molecules on lymphocytes and monocytes were modified by 1 h of bypass. These results suggest that patients subjected to CPB with roller or centrifugal pumps are equally at risk to neutrophil activation that could lead to increased interaction of these cells with blood vessel walls.

  9. Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic.

    PubMed

    Kottur, Jithesh; Sharma, Amit; Gore, Kiran R; Narayanan, Naveen; Samanta, Biswajit; Pradeepkumar, Pushpangadan I; Nair, Deepak T

    2015-01-06

    The reduction in the efficacy of therapeutic antibiotics represents a global problem of increasing intensity and concern. Nitrofuran antibiotics act primarily through the formation of covalent adducts at the N(2) atom of the deoxyguanosine nucleotide in genomic DNA. These adducts inhibit replicative DNA polymerases (dPols), leading to the death of the prokaryote. N(2)-furfuryl-deoxyguanosine (fdG) represents a stable structural analog of the nitrofuran-induced adducts. Unlike other known dPols, DNA polymerase IV (PolIV) from E. coli can bypass the fdG adduct accurately with high catalytic efficiency. This property of PolIV is central to its role in reducing the sensitivity of E. coli toward nitrofuran antibiotics such as nitrofurazone (NFZ). We present the mechanism used by PolIV to bypass NFZ-induced adducts and thus improve viability of E. coli in the presence of NFZ. Our results can be used to develop specific inhibitors of PolIV that may potentiate the activity of nitrofuran antibiotics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa.

    PubMed

    Guo, Qiaoyun; Wei, Yu; Xia, Bin; Jin, Yongxin; Liu, Chang; Pan, Xiaolei; Shi, Jing; Zhu, Feng; Li, Jinlong; Qian, Lei; Liu, Xinqi; Cheng, Zhihui; Jin, Shouguang; Lin, Jianping; Wu, Weihui

    2016-01-11

    The rising antibiotic resistance of bacteria imposes a severe threat on human health. Inhibition of bacterial virulence is an alternative approach to develop new antimicrobials. Molecules targeting antibiotic resistant enzymes have been used in combination with cognate antibiotics. It might be ideal that a molecule can simultaneously suppress virulence factors and antibiotic resistance. Here we combined genetic and computer-aided inhibitor screening to search for such molecules against the bacterial pathogen Pseudomonas aeruginosa. To identify target proteins that control both virulence and antibiotic resistance, we screened for mutants with defective cytotoxicity and biofilm formation from 93 transposon insertion mutants previously reported with increased antibiotic susceptibility. A pyrD mutant displayed defects in cytotoxicity, biofilm formation, quorum sensing and virulence in an acute mouse pneumonia model. Next, we employed a computer-aided screening to identify potential inhibitors of the PyrD protein, a dihydroorotate dehydrogenase (DHODase) involved in pyrimidine biosynthesis. One of the predicted inhibitors was able to suppress the enzymatic activity of PyrD as well as bacterial cytotoxicity, biofilm formation and antibiotic resistance. A single administration of the compound reduced the bacterial colonization in the acute mouse pneumonia model. Therefore, we have developed a strategy to identify novel treatment targets and antimicrobial molecules.

  11. Identification of a small molecule that simultaneously suppresses virulence and antibiotic resistance of Pseudomonas aeruginosa

    PubMed Central

    Guo, Qiaoyun; Wei, Yu; Xia, Bin; Jin, Yongxin; Liu, Chang; Pan, Xiaolei; Shi, Jing; Zhu, Feng; Li, Jinlong; Qian, Lei; Liu, Xinqi; Cheng, Zhihui; Jin, Shouguang; Lin, Jianping; Wu, Weihui

    2016-01-01

    The rising antibiotic resistance of bacteria imposes a severe threat on human health. Inhibition of bacterial virulence is an alternative approach to develop new antimicrobials. Molecules targeting antibiotic resistant enzymes have been used in combination with cognate antibiotics. It might be ideal that a molecule can simultaneously suppress virulence factors and antibiotic resistance. Here we combined genetic and computer-aided inhibitor screening to search for such molecules against the bacterial pathogen Pseudomonas aeruginosa. To identify target proteins that control both virulence and antibiotic resistance, we screened for mutants with defective cytotoxicity and biofilm formation from 93 transposon insertion mutants previously reported with increased antibiotic susceptibility. A pyrD mutant displayed defects in cytotoxicity, biofilm formation, quorum sensing and virulence in an acute mouse pneumonia model. Next, we employed a computer-aided screening to identify potential inhibitors of the PyrD protein, a dihydroorotate dehydrogenase (DHODase) involved in pyrimidine biosynthesis. One of the predicted inhibitors was able to suppress the enzymatic activity of PyrD as well as bacterial cytotoxicity, biofilm formation and antibiotic resistance. A single administration of the compound reduced the bacterial colonization in the acute mouse pneumonia model. Therefore, we have developed a strategy to identify novel treatment targets and antimicrobial molecules. PMID:26751736

  12. Bypassing kinase activity of the tomato Pto resistance protein with small molecule ligands.

    PubMed

    Salomon, Dor; Bonshtien, Arale; Mayrose, Maya; Zhang, Chao; Shokat, Kevan M; Sessa, Guido

    2009-05-29

    The tomato (Solanum lycopersicum) protein kinase Pto confers resistance to Pseudomonas syringae pv. tomato bacteria expressing the AvrPto and AvrPtoB effector proteins. Pto specifically recognizes both effectors by direct physical interactions triggering activation of immune responses. Here, we used a chemical-genetic approach to sensitize Pto to analogs of PP1, an ATP-competitive small molecule inhibitor. By using PP1 analogs in combination with the sensitized Pto (Pto(as)), we examined the role of Pto kinase activity in effector recognition and signal transduction. Strikingly, while PP1 analogs efficiently inhibited kinase activity of Pto(as) in vitro, they enhanced interactions of Pto(as) with AvrPto and AvrPtoB in a yeast two-hybrid system. In addition, in the presence of PP1 analogs, Pto(as) bypassed mutations either at an autophosphorylation site critical for the Pto-AvrPto interaction or at catalytically essential residues and interacted with both effectors. Moreover, in the presence of the PP1 analog 3MB-PP1, a kinase-deficient form of Pto(as) triggered an AvrPto-dependent hypersensitive response in planta. These findings suggest that, rather than phosphorylation per se, a conformational change likely triggered by autophosphorylation in Pto and mimicked by ligand binding in Pto(as) is a prerequisite for recognition of bacterial effectors. Following recognition, kinase activity appears to be dispensable for Pto signaling in planta. The chemical-genetic strategy applied here to develop specific small molecule inhibitors of Pto represents an invaluable tool for the study of biological functions of other plant protein kinases in vivo.

  13. Designed to penetrate: Time-resolved interaction of single antibiotic molecules with bacterial pores

    NASA Astrophysics Data System (ADS)

    Nestorovich, Ekaterina M.; Danelon, Christophe; Winterhalter, Mathias; Bezrukov, Sergey M.

    2002-07-01

    Membrane permeability barriers are among the factors contributing to the intrinsic resistance of bacteria to antibiotics. We have been able to resolve single ampicillin molecules moving through a channel of the general bacterial porin, OmpF (outer membrane protein F), believed to be the principal pathway for the -lactam antibiotics. With ion channel reconstitution and high-resolution conductance recording, we find that ampicillin and several other efficient penicillins and cephalosporins strongly interact with the residues of the constriction zone of the OmpF channel. Therefore, we hypothesize that, in analogy to substrate-specific channels that evolved to bind certain metabolite molecules, antibiotics have "evolved" to be channel-specific. Molecular modeling suggests that the charge distribution of the ampicillin molecule complements the charge distribution at the narrowest part of the bacterial porin. Interaction of these charges creates a region of attraction inside the channel that facilitates drug translocation through the constriction zone and results in higher permeability rates.

  14. Improving the representation of peptide-like inhibitor and antibiotic molecules in the Protein Data Bank.

    PubMed

    Dutta, Shuchismita; Dimitropoulos, Dimitris; Feng, Zukang; Persikova, Irina; Sen, Sanchayita; Shao, Chenghua; Westbrook, John; Young, Jasmine; Zhuravleva, Marina A; Kleywegt, Gerard J; Berman, Helen M

    2014-06-01

    With the accumulation of a large number and variety of molecules in the Protein Data Bank (PDB) comes the need on occasion to review and improve their representation. The Worldwide PDB (wwPDB) partners have periodically updated various aspects of structural data representation to improve the integrity and consistency of the archive. The remediation effort described here was focused on improving the representation of peptide-like inhibitor and antibiotic molecules so that they can be easily identified and analyzed. Peptide-like inhibitors or antibiotics were identified in over 1000 PDB entries, systematically reviewed and represented either as peptides with polymer sequence or as single components. For the majority of the single-component molecules, their peptide-like composition was captured in a new representation, called the subcomponent sequence. A novel concept called "group" was developed for representing complex peptide-like antibiotics and inhibitors that are composed of multiple polymer and nonpolymer components. In addition, a reference dictionary was developed with detailed information about these peptide-like molecules to aid in their annotation, identification and analysis. Based on the experience gained in this remediation, guidelines, procedures, and tools were developed to annotate new depositions containing peptide-like inhibitors and antibiotics accurately and consistently. © 2013 The Authors Biopolymers Published by Wiley Periodicals, Inc.

  15. [Relationship between ion channel properties and the structure of the lactone ring of polyene antibiotic molecules].

    PubMed

    Borisova, M P; Ermishkin, L N; Sil'bershteĭn, A Ia; Kasumov, Kh M; Potseluev, V M

    1978-01-01

    Properties of ionic channels created by amphoterecin B, nystatine and mycoheptin in phospholipid--cholesterol bilayer have been compared. Ionic conductivity and selectivity of channels as well as the frequency of transitions between an open state and a closed one depend on lacton ring structure. Appearance of one more carbonyl group in mycoheptin molecule leads to a decrease of channel anion permeability. Any pair of these antibiotics being added into different aqueous solutions create combined channels. These data confirm hypothesis that polyene antibiotics create channels of two half-pores formed in different monolayers of the membrane.

  16. Antibiotics

    MedlinePlus

    ... there. Antibiotics do not fight infections caused by viruses, such as Colds Flu Most coughs and bronchitis Sore throats, unless caused by strep If a virus is making you sick, taking antibiotics may do ...

  17. A novel protocol for antibiotic prophylaxis based on preoperative kidney function in patients undergoing open heart surgery under cardiopulmonary bypass.

    PubMed

    Odaka, Mizuho; Minakata, Kenji; Toyokuni, Hideaki; Yamazaki, Kazuhiro; Yonezawa, Atsushi; Sakata, Ryuzo; Matsubara, Kazuo

    2015-08-01

    This study aimed to develop and assess the effectiveness of a protocol for antibiotic prophylaxis based on preoperative kidney function in patients undergoing open heart surgery. We established a protocol for antibiotic prophylaxis based on preoperative kidney function in patients undergoing open heart surgery. This novel protocol was assessed by comparing patients undergoing open heart surgery before (control group; n = 30) and after its implementation (protocol group; n = 31) at Kyoto University Hospital between July 2012 and January 2013. Surgical site infections (SSIs) were observed in 4 control group patients (13.3 %), whereas no SSIs were observed in the protocol group patients (P < 0.05). The total duration of antibiotic use decreased significantly from 80.7 ± 17.6 h (mean ± SD) in the control group to 55.5 ± 14.9 h in the protocol group (P < 0.05). Similarly, introduction of the protocol significantly decreased the total antibiotic dose used in the perioperative period (P < 0.05). Furthermore, antibiotic regimens were changed under suspicion of infection in 5 of 30 control group patients, whereas none of the protocol group patients required this additional change in the antibiotic regimen (P < 0.05). Our novel antibiotic prophylaxis protocol based on preoperative kidney function effectively prevents SSIs in patients undergoing open heart surgery.

  18. Synergy among antibacterial peptides and between peptides and small-molecule antibiotics.

    PubMed

    Cassone, Marco; Otvos, Laszlo

    2010-06-01

    Antimicrobial peptides are key components of native immunity. Unlike most common small-molecule antibiotics, antimicrobial peptides have been refined by evolution to work synergistically within the host environment. The mechanisms of synergy are complex and specific, and it is only now that they are beginning to be understood. Thus, antimicrobial peptides are top candidates to broaden our limited therapeutic arsenal, and are very well suited to be used in synergic combinations with currently available antibiotics. In order for this promising strategy to become a reality, however, some key steps in basic and translational research need to be improved. These include the standardization and critical evaluation of testing and quantification methods, the characterization of the molecular mechanism of action, the study of indirect antibacterial activity such as immune-response modulation, and several other aspects that will be presented and discussed, with a focus primarily on antibacterial therapy. There will be a special focus on advances and innovations that might significantly improve the future perspectives of antimicrobial peptides from a therapeutic point-of-view.

  19. Physical methods to quantify small antibiotic molecules uptake into Gram-negative bacteria.

    PubMed

    Winterhalter, Mathias; Ceccarelli, Matteo

    2015-09-01

    The development of antibiotics against Gram-negative bacteria is a challenge: any active compound must cross the outer cell envelope composed of a hydrophilic highly charged lipopolysaccharide layer followed by a tight hydrophobic layer containing water filled gates called porins to reach the hydrophilic periplasmic space and depending on the target with the further need to cross the hydrophobic inner membrane. In addition to a possible rapid enzymatic deactivation efflux pumps shuffle compounds back outside. The resulting low permeability of cell envelope requires high dose and leads therefore to toxicity problems. Despite its relevance the permeability barrier in Gram-negative bacteria is not well understood partially caused by the lack of appropriate direct assays. Here we give a brief introduction on current available techniques to quantify passive diffusion of small hydrophilic molecules into Gram-negative bacteria.

  20. Towards Development of Small Molecule Lipid II Inhibitors as Novel Antibiotics

    PubMed Central

    Chauhan, Jamal; Cardinale, Steven; Fang, Lei; Huang, Jing; Kwasny, Steven M.; Pennington, M. Ross; Basi, Kelly; diTargiani, Robert; Capacio, Benedict R.; MacKerell, Alexander D.; Opperman, Timothy J.; Fletcher, Steven; de Leeuw, Erik P. H.

    2016-01-01

    Recently we described a novel di-benzene-pyrylium-indolene (BAS00127538) inhibitor of Lipid II. BAS00127538 (1-Methyl-2,4-diphenyl-6-((1E,3E)-3-(1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)pyryl-1-ium) tetrafluoroborate is the first small molecule Lipid II inhibitor and is structurally distinct from natural agents that bind Lipid II, such as vancomycin. Here, we describe the synthesis and biological evaluation of 50 new analogs of BAS00127538 designed to explore the structure-activity relationships of the scaffold. The results of this study indicate an activity map of the scaffold, identifying regions that are critical to cytotoxicity, Lipid II binding and range of anti-bacterial action. One compound, 6jc48-1, showed significantly enhanced drug-like properties compared to BAS00127538. 6jc48-1 has reduced cytotoxicity, while retaining specific Lipid II binding and activity against Enterococcus spp. in vitro and in vivo. Further, this compound showed a markedly improved pharmacokinetic profile with a half-life of over 13 hours upon intravenous and oral administration and was stable in plasma. These results suggest that scaffolds like that of 6jc48-1 can be developed into small molecule antibiotic drugs that target Lipid II. PMID:27776124

  1. Probing the Mechanism of LAL-32, a Gold Nanoparticle-Based Antibiotic Discovered through Small Molecule Variable Ligand Display.

    PubMed

    Byrne-Nash, Rose; Lucero, Danielle M; Osbaugh, Niki A; Melander, Roberta J; Melander, Christian; Feldheim, Daniel L

    2017-07-19

    The unrelenting rise of antimicrobial-resistant bacteria has necessitated the search for novel antibiotic solutions. Herein we describe further mechanistic studies on a 2.0-nm-diameter gold nanoparticle-based antibiotic (designated LAL-32). This antibiotic exhibits bactericidal activity against the Gram-negative bacterium Escherichia coli at 1.0 μM, a concentration significantly lower than several clinically available antibiotics (such as ampicillin and gentamicin), and acute treatment with LAL-32 does not give rise to spontaneous resistant mutants. LAL-32 treatment inhibits cellular division, daughter cell separation, and twin-arginine translocation (Tat) pathway dependent shuttling of proteins to the periplasm. Furthermore, we have found that the cedA gene imparts increased resistance to LAL-32, and shown that an E. coli cedA transposon mutant exhibits increased susceptibility to LAL-32. Taken together, these studies further implicate cell division pathways as the target for this nanoparticle-based antibiotic and demonstrate that there may be inherently higher barriers for resistance evolution against nanoscale antibiotics in comparison to their small molecule counterparts.

  2. N-Heterocyclic molecule-capped gold nanoparticles as effective antibiotics against multi-drug resistant bacteria

    NASA Astrophysics Data System (ADS)

    Feng, Yan; Chen, Wenwen; Jia, Yuexiao; Tian, Yue; Zhao, Yuyun; Long, Fei; Rui, Yukui; Jiang, Xingyu

    2016-07-01

    We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N-heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs.We demonstrate that N-heterocyclic molecule-capped gold nanoparticles (Au NPs) have broad-spectrum antibacterial activity. Optimized antibacterial activity can be achieved by using different initial molar ratios (1 : 1 and 10 : 1) of N-heterocyclic prodrugs and the precursor of Au NPs (HAuCl4). This work opens up new avenues for antibiotics based on Au NPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03317b

  3. Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo.

    PubMed

    Hein, E; Munthe-Fog, L; Thiara, A S; Fiane, A E; Mollnes, T E; Garred, P

    2015-02-01

    The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands, including biomaterials in vitro, and low ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3-mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, ficolin-1 and -3. In the Bioline® group the ficolin-2 levels decreased significantly after initiation of surgery (P < 0.0001) and remained reduced throughout the sampling period. This was not seen for Phisio®-coated circuits. Ficolin-3-mediated complement activation potential was reduced significantly in both groups after start of operation (P < 0.0001), whereas soluble C3a and TCC in the samples were increased (P < 0.0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures. © 2014 British Society for Immunology.

  4. Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens

    PubMed Central

    2014-01-01

    Background Extensive use of antibiotics has fostered the emergence of superbugs that are resistant to multidrugs, which becomes a great healthcare and public concern. Previous studies showed that quorum sensing signal DSF (diffusible signal factor) not only modulates bacterial antibiotic resistance through intraspecies signaling, but also affects bacterial antibiotic tolerance through interspecies communication. These findings motivate us to exploit the possibility of using DSF and its structurally related molecules as adjuvants to influence antibiotic susceptibility of bacterial pathogens. Results In this study, we have demonstrated that DSF signal and its structurally related molecules could be used to induce bacterial antibiotic susceptibility. Exogenous addition of DSF signal (cis-11-methyl-2-dodecenoic acid) and its structural analogues could significantly increase the antibiotic susceptibility of Bacillus cereus, possibly through reducing drug-resistant activity, biofilm formation and bacterial fitness. The synergistic effect of DSF and its structurally related molecules with antibiotics on B. cereus is dosage-dependent. Combination of DSF with gentamicin showed an obviously synergistic effect on B. cereus pathogenicity in an in vitro model. We also found that DSF could increase the antibiotic susceptibility of other bacterial species, including Bacillus thuringiensis, Staphylococcus aureus, Mycobacterium smegmatis, Neisseria subflava and Pseudomonas aeruginosa. Conclusion The results indicate a promising potential of using DSF and its structurally related molecules as novel adjuvants to conventional antibiotics for treatment of infectious diseases caused by bacterial pathogens. PMID:24575808

  5. Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens.

    PubMed

    Deng, Yinyue; Lim, Amy; Lee, Jasmine; Chen, Shaohua; An, Shuwen; Dong, Yi-Hu; Zhang, Lian-Hui

    2014-02-27

    Extensive use of antibiotics has fostered the emergence of superbugs that are resistant to multidrugs, which becomes a great healthcare and public concern. Previous studies showed that quorum sensing signal DSF (diffusible signal factor) not only modulates bacterial antibiotic resistance through intraspecies signaling, but also affects bacterial antibiotic tolerance through interspecies communication. These findings motivate us to exploit the possibility of using DSF and its structurally related molecules as adjuvants to influence antibiotic susceptibility of bacterial pathogens. In this study, we have demonstrated that DSF signal and its structurally related molecules could be used to induce bacterial antibiotic susceptibility. Exogenous addition of DSF signal (cis-11-methyl-2-dodecenoic acid) and its structural analogues could significantly increase the antibiotic susceptibility of Bacillus cereus, possibly through reducing drug-resistant activity, biofilm formation and bacterial fitness. The synergistic effect of DSF and its structurally related molecules with antibiotics on B. cereus is dosage-dependent. Combination of DSF with gentamicin showed an obviously synergistic effect on B. cereus pathogenicity in an in vitro model. We also found that DSF could increase the antibiotic susceptibility of other bacterial species, including Bacillus thuringiensis, Staphylococcus aureus, Mycobacterium smegmatis, Neisseria subflava and Pseudomonas aeruginosa. The results indicate a promising potential of using DSF and its structurally related molecules as novel adjuvants to conventional antibiotics for treatment of infectious diseases caused by bacterial pathogens.

  6. A novel antibiotic-delivery system by using ovotransferrin as targeting molecule.

    PubMed

    Ibrahim, Hisham R; Tatsumoto, Sayuri; Ono, Hajime; Van Immerseel, Filip; Raspoet, Ruth; Miyata, Takeshi

    2015-01-23

    Synthetic antibiotics and antimicrobial agents, such as sulfonamide and triclosan (TCS), have provided new avenues in the treatment of bacterial infections, as they target lethal intracellular pathways. Sulfonamide antibiotics block synthesis of folic acid by inhibiting dihydrofolate reductase (DHFR) while TCS block fatty acid synthesis through inhibition of enoyl-ACP reductase (FabI). They are water-insoluble agents and high doses are toxic, limiting their therapeutic efficiency. In this study, an antibiotic drug-targeting strategy based on utilizing ovotransferrin (OTf) as a carrier to allow specific targeting of the drug to microbial or mammalian cells via the transferrin receptor (TfR) is explored, with potential to alleviate insolubility and toxicity problems. Complexation, through non-covalent interaction, with OTf turned sulfa antibiotics or TCS into completely soluble in aqueous solution. OTf complexes showed superior bactericidal activity against several bacterial strains compared to the activity of free agents. Strikingly, a multi-drug resistant Salmonella strain become susceptible to antibiotics-OTf complexes while a tolC-knockout mutant strain become susceptible to OTf and more sensitive to the complexes. The antibiotic bound to OTf was, thus exported through the multi-drug efflux pump TolC in Salmonella wild-type strain. Further, antibiotics-OTf complexes were able to efficiently kill intracellular pathogens after infecting human colon carcinoma cells (HCT-116). The results demonstrate, for the first time, that the TfR mediated endocytosis of OTf can be utilized to specifically target drugs directly to pathogens or intracellularly infected cells and highlights the potency of the antibiotic-OTf complex for the treatment of infectious diseases.

  7. Antibiotic Resistance and Regulation of the Gram-Negative Bacterial Outer Membrane Barrier by Host Innate Immune Molecules

    PubMed Central

    2016-01-01

    ABSTRACT The Gram-negative outer membrane is an important barrier that provides protection against toxic compounds, which include antibiotics and host innate immune molecules such as cationic antimicrobial peptides. Recently, significant research progress has been made in understanding the biogenesis, regulation, and functioning of the outer membrane, including a recent paper from the laboratory of Dr. Brett Finlay at the University of British Columbia (J. van der Heijden et al., mBio 7:e01238-16, 2016, http://dx.doi.org/10.1128/mBio.01541-16). These investigators demonstrate that toxic oxygen radicals, such as those found in host tissues, regulate outer membrane permeability by altering the outer membrane porin protein channels to regulate the influx of oxygen radicals as well as β-lactam antibiotics. This commentary provides context about this interesting paper and discusses the prospects of utilizing increased knowledge of outer membrane biology to develop new antibiotics for antibiotic-resistant Gram-negative bacteria. PMID:27677793

  8. Inhibition of cell surface expression of endothelial adhesion molecules by ursolic acid prevents intimal hyperplasia of venous bypass grafts in rats

    PubMed Central

    Zeller, Iris; Wiedemann, Dominik; Schwaiger, Stefan; Stelzmüller, Marlies; Kreutmayer, Simone; Leberfing, Oliver; Stuppner, Hermann; Bernhard, David

    2012-01-01

    OBJECTIVES Despite rapid progress in surgical techniques, there is still a significant lack of surgery-supportive pharmacological treatments. The aim of this study was to test the hypothesis that ursolic acid (UA) may prevent intimal hyperplasia of venous bypass grafts. METHODS The hypothesis was tested by means of primary cell isolation and culture followed by real-time polymerase chain reaction, western blotting, fluorescence microscopy and fluorescence-activated cell sorting analyses, as well as an in vivo rat model for intimal hyperplasia of venous bypass grafts and immunohistochemistry and histochemistry. RESULTS The local application of UA significantly inhibited intimal hyperplasia in vivo (intimal thickness control: 25 μm, UA group: 18 μM–8 weeks after surgery). The UA treatment of grafts significantly resulted in reduced endothelial vascular cell adhesion molecule-1 (VCAM-1) expression, reduced infiltration of the grafts vessel wall by CD45-positive cells and increased smooth muscle cell (SMC) death. In in vitro condition, it could be shown that UA inhibits VCAM-1 expression downstream of NFκB and is likely to interfere with VCAM-1 protein synthesis in endothelial cells. Quantification of cell death in vascular smooth muscle cells treated with UA indicated that UA is a potent inducer of SMC apoptosis. CONCLUSIONS Our results suggest that UA-mediated inhibition of endothelial VCAM-1 expression reduces the infiltration of venous bypass grafts by CD45-positive cells and inhibits intimal hyperplasia. Apoptosis induction in SMCs may be another method in which UA reduces intimal thickening. UA may constitute a surgery-supportive pharmacon that reduces intimal hyperplasia of vein grafts. PMID:22551965

  9. Simple molecular model for the binding of antibiotic molecules to bacterial ion channels

    NASA Astrophysics Data System (ADS)

    Mafé, Salvador; Ramírez, Patricio; Alcaraz, Antonio

    2003-10-01

    A molecular model aimed at explaining recent experimental data by Nestorovich et al. [Proc. Natl. Acad. Sci. USA 99, 9789 (2002)] on the interaction of ampicillin molecules with the constriction zone in a channel of the general bacterial porin, OmpF (outer membrane protein F), is presented. The model extends T. L. Hill's theory for intermolecular interactions in a pair of binding sites [J. Am. Chem. Soc. 78, 3330 (1956)] by incorporating two binding ions and two pairs of interacting sites. The results provide new physical insights on the role of the complementary pattern of the charge distributions in the ampicillin molecule and the narrowest part of the channel pore. Charge matching of interacting sites facilitates drug binding. The dependence of the number of ampicillin binding events per second with the solution pH and salt concentration is explained qualitatively using a reduced number of fundamental concepts.

  10. Assessing Specific Oligonucleotides and Small Molecule Antibiotics for the Ability to Inhibit the CRD-BP-CD44 RNA Interaction

    PubMed Central

    Thomsen, Dana; Lee, Chow H.

    2014-01-01

    Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3′UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862–3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862–3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions. PMID:24622399

  11. Assessing specific oligonucleotides and small molecule antibiotics for the ability to inhibit the CRD-BP-CD44 RNA interaction.

    PubMed

    King, Dustin T; Barnes, Mark; Thomsen, Dana; Lee, Chow H

    2014-01-01

    Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3'UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862-3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862-3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions.

  12. A chemoinformatics approach to the discovery of lead-like molecules from marine and microbial sources en route to antitumor and antibiotic drugs.

    PubMed

    Pereira, Florbela; Latino, Diogo A R S; Gaudêncio, Susana P

    2014-01-27

    The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure-Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened-57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature.

  13. A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs

    PubMed Central

    Pereira, Florbela; Latino, Diogo A. R. S.; Gaudêncio, Susana P.

    2014-01-01

    The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature. PMID:24473174

  14. Heart bypass surgery

    MedlinePlus

    Off-pump coronary artery bypass; OPCAB; Beating heart surgery; Bypass surgery - heart; CABG; Coronary artery bypass graft; Coronary artery bypass surgery; Coronary bypass surgery; Coronary artery disease - CABG; CAD - CABG; Angina - ...

  15. A novel STK1-targeted small-molecule as an "antibiotic resistance breaker" against multidrug-resistant Staphylococcus aureus.

    PubMed

    Kant, Sashi; Asthana, Shailendra; Missiakas, Dominique; Pancholi, Vijay

    2017-07-11

    Ser/Thr protein kinase (STK1) plays a critical role in cell wall biosynthesis of and drug resistance in methicillin-resistant Staphylococcus aureus (MRSA). MRSA strains lacking STK1 become susceptible to failing cephalosporins, such as Ceftriaxone and Cefotaxime. STK1, despite being nonessential protein for MRSA survival, it can serve as an important therapeutic agent for combination therapy. Here, we report a novel small molecule quinazoline compound, Inh2-B1, which specifically inhibits STK1 activity by directly binding to its ATP-binding catalytic domain. Functional analyses encompassing in vitro growth inhibition of MRSA, and in vivo protection studies in mice against the lethal MRSA challenge indicated that at high concentration neither Inh2-B1 nor Ceftriaxone or Cefotaxime alone was able to inhibit the growth of bacteria or protect the challenged mice. However, the growth of MRSA was inhibited, and a significant protection in mice against the bacterial challenge was observed at a micromolar concentration of Ceftriaxone or Cefotaxime in the presence of Inh2-B1. Cell-dependent minimal to no toxicity of Inh2-B1, and its abilities to down-regulate cell wall hydrolase genes and disrupt the biofilm formation of MRSA clearly indicated that Inh2-B1 serves as a therapeutically important "antibiotic-resistance-breaker," which enhances the bactericidal activity of Ceftriaxone/Cefotaxime against highly pathogenic MRSA infection.

  16. [1H NMR analysis of the complex formation of aromatic molecules of antibiotic and vitamin in aqueous solution: heteroassociation of actinomycin D and flavin mononucleotide].

    PubMed

    Veselkov, A N; Evstigneev, M P; Rozvadovskaia, A O; Mukhina, Iu V; Rybakova, K A

    2005-01-01

    The molecular mechanism of the combined action of antibiotic and vitamin was studied by NMR spectroscopy. The heteroassociation of the antitumor antibiotic actinomycin D and flavin mononucleotide was investigated as a function of concentration and temperature by 500 MHz 1H NMR spectroscopy. The equilibrium association constant, the thermodynamic parameters (deltaH, deltaS) of heteroassociation of actinomycin D with flavin mononucleotide, and the limiting values of proton chemical shifts in the heterocomplex were determined from the concentration and temperature dependences of proton chemical shifts of molecules. The most favorable structure of the 1:1 actinomycin D-flavin mononucleotide heteroassociation complex was determined using both the molecular mechanics methods (X-PLOR software) and the limiting values of proton chemical shifts of the molecules. In the calculated structure, the planes of the chromophores of actinomycin D and flavin mononucleotide molecules in the 1:1 heterocomplex are parallel and separated from each other by a distance of about 0.34 nm. At the same time, there is a probability of formation of intermolecular hydrogen bonds in the calculated structure of 1:1 actinomycin D-flavin mononucleotide complex. The analysis of the results obtained suggests that aromatic molecules of vitamins, e.g., flavin mononucleotide, can form energetically favorable heterocomplexes with aromatic antitumor antibiotics in aqueous solution, modulating thereby the efficacy of their medical and biological action.

  17. [Study on the molecule epidemiological between resistances of 7 genes interrelated 4 antibiotic to isolated Streptococcus pneumoniae in children].

    PubMed

    Ding, Yun-fang; Mi, Zu-huang; Zhang, Jian-hua; Tao, Yun-zhen; Qin, Ling

    2005-06-01

    To investigate the molecule epidemic for 7 genes interrelated penicillin, erythromycin, tetracycline, vancomycin resistance of isolated Streptococcus pneumoniae (SP) in children at Suzhou area. (1) Thirty-one pneumococcal isolates were collected from respiratory tract secretions of children with respiratory diseases from Nov 2002 to Apr 2003 at the Children's Hospital of Suzhou University (reference strain ATCC49619). (2) Penicillin susceptibility was determined by E-test, while erythromycin, tetracycline, vancomycin were determined by K-B disk. (3) The detecting of pbp2B, ermA/B, mefA, tetM, vanA, vanB genes by PCR, Sequencing pbp2B genes, Contrasting pbp2B DNA sequences among pneumococcal isolates and SP R6 [penicillin sensitive (www.ncbi.nlm.gov/nucleotide, NC-003098)]. Of thirty-one isolates studied, the results were shown as follows; (1) Penicillin sensibility 38.7% (n = 12), penicillin resistance 61.3% (n = 19), pbp2B mutation 64.5% (n = 20); (2) Erythromycin sensibility 9.7% (n = 3), erythromycin resistance 90.3% (n = 28), ermA/B 71% (n = 22), mefA 32.1% (n = 10), ermA/B + mefA 87.1% (n = 27); (3) Tetracycline sensibility 9.7% (n = 3), tetracycline resistance 90.3% (n = 28), tetM 90.3% (n = 28); (4) Vancomycin sensibility 100% (n = 31), vanA, vanB all 0%. Among pneumococcal isolates at our area, penicillin, erythromycin, tetracycline resistance were high, vancomycin was sensitive. Detecting 7 genes interrelated penicillin, erythromycin, tetracycline, vancomycin resistance expressed genotypies for antibiotic resistances in pneumococcal isolates.

  18. Novel anti-infective molecule from innate immune cells as an antibiotic-alternative to control infections caused by Apicomplexa

    USDA-ARS?s Scientific Manuscript database

    With increasing needs for the global animal industry to address the regulatory restrictions on the use of antibiotic growth promoters (AGPs) in animal production, there is much interest to find alternatives to AGPs. To develop alternatives to antibiotics against the major poultry parasitic disease, ...

  19. Coronary Artery Bypass Grafting

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Coronary Artery Bypass Grafting? Coronary artery bypass grafting (CABG) is ... bypass multiple coronary arteries during one surgery. Coronary Artery Bypass Grafting Figure A shows the location of ...

  20. Bifunctional quorum-quenching and antibiotic-acylase MacQ forms a 170-kDa capsule-shaped molecule containing spacer polypeptides.

    PubMed

    Yasutake, Yoshiaki; Kusada, Hiroyuki; Ebuchi, Teppei; Hanada, Satoshi; Kamagata, Yoichi; Tamura, Tomohiro; Kimura, Nobutada

    2017-08-21

    Understanding the molecular mechanisms of bacterial antibiotic resistance will help prepare against further emergence of multi-drug resistant strains. MacQ is an enzyme responsible for the multi-drug resistance of Acidovorax sp. strain MR-S7. MacQ has acylase activity against both N-acylhomoserine lactones (AHLs), a class of signalling compounds involved in quorum sensing, and β-lactam antibiotics. Thus, MacQ is crucial as a quencher of quorum sensing as well as in conferring antibiotic resistance in Acidovorax. Here, we report the X-ray structures of MacQ in ligand-free and reaction product complexes. MacQ forms a 170-kDa capsule-shaped molecule via face-to-face interaction with two heterodimers consisting of an α-chain and a β-chain, generated by the self-cleaving activity of a precursor polypeptide. The electron density of the spacer polypeptide in the hollow of the molecule revealed the close orientation of the peptide-bond atoms of Val20SP-Gly21SP to the active-site, implying a role of the residues in substrate binding. In mutational analyses, uncleaved MacQ retained degradation activity against both AHLs and penicillin G. These results provide novel insights into the mechanism of self-cleaving maturation and enzymatic function of N-terminal nucleophile hydrolases.

  1. Gastric bypass surgery - discharge

    MedlinePlus

    Bariatric surgery - gastric bypass - discharge; Roux-en-Y gastric bypass - discharge; Gastric bypass - Roux-en-Y - discharge; Obesity ... Gloy VL, Briel M, Bhatt DL, et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic ...

  2. Supramolecular Nanofibers Self-assembled from Cationic Small Molecules Derived from Repurposed Poly(ethylene teraphthalate) for Antibiotic Delivery.

    PubMed

    Liu, Shaoqiong; Fukushima, Kazuki; Venkataraman, Shrinivas; Hedrick, James L; Yang, Yi Yan

    2017-09-30

    Low molecular weight cationic compounds were synthesized from re-purposed poly(ethylene teraphthalate) (PET) and used to self-assemble into high aspect ratio supramolecular nanofibers for encapsulation and delivery of anionic antibiotics. The antibiotic piperacillin/tazobactam (PT) was successfully loaded into the nanofibers through ionic interaction between anionic PT and the cationic nanofibers without loss of the nanofiber features. These PT-loaded nanofibers demonstrated high loading efficiency and sustained delivery for PT. The antimicrobial activity of PT-loaded nanofibers remained potent towards both Gram-positive and Gram-negative bacteria. Importantly, in a P. aeruginosa-infected mouse skin wound model, the treatment with the PT-loaded nanofibers was more effective than free PT for wound healing as evidenced by the significantly lower P. aeruginosa counts at the wound sites and histological analysis. This strategy can be applied to deliver a variety of anionic antibiotics for improved treatment efficacy of various infections. Copyright © 2017. Published by Elsevier Inc.

  3. Antibiotic resistance in Mycobacterium tuberculosis: peroxidase intermediate bypass causes poor isoniazid activation by the S315G mutant of M. tuberculosis catalase-peroxidase (KatG).

    PubMed

    Suarez, Javier; Ranguelova, Kalina; Schelvis, Johannes P M; Magliozzo, Richard S

    2009-06-12

    KatG (catalase-peroxidase) in Mycobacterium tuberculosis is responsible for activation of isoniazid (INH), a pro-drug used to treat tuberculosis infections. Resistance to INH is a global health problem most often associated with mutations in the katG gene. The origin of INH resistance caused by the KatG[S315G] mutant enzyme is examined here. Overexpressed KatG[S315G] was characterized by optical, EPR, and resonance Raman spectroscopy and by studies of the INH activation mechanism in vitro. Catalase activity and peroxidase activity with artificial substrates were moderately reduced (50 and 35%, respectively), whereas the rates of formation of oxyferryl heme:porphyrin pi-cation radical and the decay of heme intermediates were approximately 2-fold faster in KatG[S315G] compared with WT enzyme. The INH binding affinity for the resting enzyme was unchanged, whereas INH activation, measured by the rate of formation of an acyl-nicotinamide adenine dinucleotide adduct considered to be a bactericidal molecule, was reduced by 30% compared with WT KatG. INH resistance is suggested to arise from a redirection of catalytic intermediates into nonproductive reactions that interfere with oxidation of INH. In the resting mutant enzyme, a rapid evolution of 5-c heme to 6-c species occurred in contrast with the behavior of WT KatG and KatG[S315T] and consistent with greater flexibility at the heme edge in the absence of the hydroxyl of residue 315. Insights into the effects of mutations at residue 315 on enzyme structure, peroxidation kinetics, and specific interactions with INH are presented.

  4. Threading the Needle: Small-Molecule Targeting of a Xenobiotic Receptor to Ablate Escherichia coli Polysaccharide Capsule Expression Without Altering Antibiotic Resistance.

    PubMed

    Arshad, Mehreen; Goller, Carlos C; Pilla, Danielle; Schoenen, Frank J; Seed, Patrick C

    2016-04-15

    Uropathogenic Escherichia coli (UPEC), a leading cause of urinary tract and invasive infections worldwide, is rapidly acquiring multidrug resistance, hastening the need for selective new anti-infective agents. Here we demonstrate the molecular target of DU011, our previously discovered potent, nontoxic, small-molecule inhibitor of UPEC polysaccharide capsule biogenesis and virulence. Real-time polymerase chain reaction analysis and a target-overexpression drug-suppressor screen were used to localize the putative inhibitor target. A thermal shift assay quantified interactions between the target protein and the inhibitor, and a novel DNase protection assay measured chemical inhibition of protein-DNA interactions. Virulence of a regulatory target mutant was assessed in a murine sepsis model. MprA, a MarR family transcriptional repressor, was identified as the putative target of the DU011 inhibitor. Thermal shift measurements indicated the formation of a stable DU011-MprA complex, and DU011 abrogated MprA binding to its DNA promoter site. Knockout of mprA had effects similar to that of DU011 treatment of wild-type bacteria: a loss of encapsulation and complete attenuation in a murine sepsis model, without any negative change in antibiotic resistance. MprA regulates UPEC polysaccharide encapsulation, is essential for UPEC virulence, and can be targeted without inducing antibiotic resistance. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  5. [THE ROLE OF (p)ppGpp MOLECULES IN FORMATION OF "STRICT RESPONSE" IN BACTERIA AND BIOSYNTHESIS OF ANTIBIOTICS AND MORPHOLOGICAL DIFFERENTIATION IN ACTINOMYCETES].

    PubMed

    Klymyshin, D; Stephanyshyn, O; Fedorenko, V

    2016-01-01

    Strict response is a pleiotropic physiological response of cells caused by lack of aminoacetylated tRNAs. Experimentally, this response occurs due to the lack of amino acids in the environment and the limitation of tRNA aminoacylation even in the presence of the corresponding amino acids in the cell. Many features of this response indicate its dependence on the accumulation of ppGpp molecules. There is a correlation between the growth rate of actinomycetes and biosynthesis of their secondary metabolites. Introduction of additional relA gene copies of ppGpp synthetase can affect the production of antibiotics in streptomycetes. The article presents the authors' own experimental data, dedicated to the influence of heterologous relA gene expression in Streptomyces nogalater cells.

  6. MHC class I molecules with Superenhanced CD8 binding properties bypass the requirement for cognate TCR recognition and nonspecifically activate CTLs.

    PubMed

    Wooldridge, Linda; Clement, Mathew; Lissina, Anna; Edwards, Emily S J; Ladell, Kristin; Ekeruche, Julia; Hewitt, Rachel E; Laugel, Bruno; Gostick, Emma; Cole, David K; Debets, Reno; Berrevoets, Cor; Miles, John J; Burrows, Scott R; Price, David A; Sewell, Andrew K

    2010-04-01

    CD8(+) CTLs are essential for effective immune defense against intracellular microbes and neoplasia. CTLs recognize short peptide fragments presented in association with MHC class I (MHCI) molecules on the surface of infected or dysregulated cells. Ag recognition involves the binding of both TCR and CD8 coreceptor to a single ligand (peptide MHCI [pMHCI]). The TCR/pMHCI interaction confers Ag specificity, whereas the pMHCI/CD8 interaction mediates enhanced sensitivity to Ag. Striking biophysical differences exist between the TCR/pMHCI and pMHCI/CD8 interactions; indeed, the pMHCI/CD8 interaction can be >100-fold weaker than the cognate TCR/pMHCI interaction. In this study, we show that increasing the strength of the pMHCI/CD8 interaction by approximately 15-fold results in nonspecific, cognate Ag-independent pMHCI tetramer binding at the cell surface. Furthermore, pMHCI molecules with superenhanced affinity for CD8 activate CTLs in the absence of a specific TCR/pMHCI interaction to elicit a full range of effector functions, including cytokine/chemokine release, degranulation and proliferation. Thus, the low solution binding affinity of the pMHCI/CD8 interaction is essential for the maintenance of CTL Ag specificity.

  7. Peripheral artery bypass - leg

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/007394.htm Peripheral artery bypass - leg To use the sharing features on this page, please enable JavaScript. Peripheral artery bypass is surgery to reroute the blood supply ...

  8. Change in gut microbiota is correlated with alterations in the surface molecule expression of monocytes after Roux-en-Y gastric bypass surgery in obese type 2 diabetic patients

    PubMed Central

    Chen, Hui; Qian, Lei; Lv, Qiangsheng; Yu, Jianxiu; Wu, Wei; Qian, Haixin

    2017-01-01

    Objectives: Persistent low-grade chronic inflammation is common in type 2 diabetes (T2D) and obesity. To date, the underlying molecular mechanism is not well understood. In this study, we aimed to investigate gut microbiota and the expression of monocyte surface molecules in obese T2D subjects who underwent Roux-en-Y gastric bypass (RYGB) surgery. Methods: Twenty-four T2D patients were enrolled. Gut microbiota was assessed by measuring bacterial DNA. The phenotypes and biological functions of monocytes, and the expression of monocyte surface molecules were examined by flow cytometry. Results: RYGB led to significant alterations in the phenotypes of monocytes. Moreover, the ability of monocyte migration was significantly decreased after RYGB (P<0.05), which was consistent with reduced Chemokine-receptors CCR2 expression of CD14+CD16+ monocytes (P<0.05) and CX3CR1 expression of the three monocytes subsets (P<0.05). RYGB also resulted in a shift of gut microbiota in the obese T2D patients. Spearman’s rank correlation coefficient showed a link between gut microbiota and monocyte subsets where the increased Bacteroidetes was negatively correlated with the variation of CD14dimCD16+ monocyte percentage (r=-0.477, P<0.05). Furthermore, the decreased counts of Escherichia were positively correlated with the variation of TNF-α secretion (r=0.442, P<0.05) and TLR4 (r=0.425, P<0.05) expression onCD14+CD16+ monocytes. Conclusions: This study, for the first time, demonstrated a link between the changes in gut microbiota and alterations in both phenotypes and functions of monocytes after RYGB, which may contribute significantly to the low-grade chronic inflammation in obese T2D patients. PMID:28386350

  9. Change in gut microbiota is correlated with alterations in the surface molecule expression of monocytes after Roux-en-Y gastric bypass surgery in obese type 2 diabetic patients.

    PubMed

    Chen, Hui; Qian, Lei; Lv, Qiangsheng; Yu, Jianxiu; Wu, Wei; Qian, Haixin

    2017-01-01

    Objectives: Persistent low-grade chronic inflammation is common in type 2 diabetes (T2D) and obesity. To date, the underlying molecular mechanism is not well understood. In this study, we aimed to investigate gut microbiota and the expression of monocyte surface molecules in obese T2D subjects who underwent Roux-en-Y gastric bypass (RYGB) surgery. Methods: Twenty-four T2D patients were enrolled. Gut microbiota was assessed by measuring bacterial DNA. The phenotypes and biological functions of monocytes, and the expression of monocyte surface molecules were examined by flow cytometry. Results: RYGB led to significant alterations in the phenotypes of monocytes. Moreover, the ability of monocyte migration was significantly decreased after RYGB (P<0.05), which was consistent with reduced Chemokine-receptors CCR2 expression of CD14(+)CD16(+) monocytes (P<0.05) and CX3CR1 expression of the three monocytes subsets (P<0.05). RYGB also resulted in a shift of gut microbiota in the obese T2D patients. Spearman's rank correlation coefficient showed a link between gut microbiota and monocyte subsets where the increased Bacteroidetes was negatively correlated with the variation of CD14(dim)CD16(+) monocyte percentage (r=-0.477, P<0.05). Furthermore, the decreased counts of Escherichia were positively correlated with the variation of TNF-α secretion (r=0.442, P<0.05) and TLR4 (r=0.425, P<0.05) expression onCD14(+)CD16(+) monocytes. Conclusions: This study, for the first time, demonstrated a link between the changes in gut microbiota and alterations in both phenotypes and functions of monocytes after RYGB, which may contribute significantly to the low-grade chronic inflammation in obese T2D patients.

  10. [Kinetics of ceftazidime in prophylactic administration during cardiopulmonary bypass].

    PubMed

    Lonský, V; Dominik, J; Lonská, V; Hejzlar, M; Mand'ák, J; Pozlerová, E; Marsíková, M; Snítilová, M; Kubícek, J

    1999-01-01

    Serum ceftazidime levels were followed in 21 patients in which routine coronary bypass surgery with cardiopulmonary bypass was performed. Each patient received one gram of ceftazidime intravenously with anesthesia induction. Antibiotic concentrations were estimated using the microbiologic assay diffusion plate method. The average operation time was 220 +/- 41 minutes (range 130-310). The start of cardiopulmonary bypass was 86 +/- 21 minutes and the full flow time was 104 +/- 21 minutes after starting of ceftazidime application. It can be stated that the decline of ceftazidime serum levels after starting of cardiopulmonary bypass was faster in comparison with standard serum curves of this antibiotic. The concentrations of ceftazidime at the end of some operations were under the supposed minimal inhibitory concentrations for some microorganisms possibly implicated. No infection was recorded.

  11. Antibiotics in the environment.

    PubMed

    Larsson, D G Joakim

    2014-05-01

    Molecules with antibiotic properties, produced by various microbes, have been around long before mankind recognized their usefulness in preventing and treating bacterial infections. Bacteria have therefore been exposed to selection pressures from antibiotics for very long times, however, generally only on a micro-scale within the immediate vicinity of the antibiotic-producing organisms. In the twentieth century we began mass-producing antibiotics, mainly synthetic derivatives of naturally produced antibiotic molecules, but also a few entirely synthetic compounds. As a consequence, entire bacterial communities became exposed to unprecedented antibiotic selection pressures, which in turn led to the rapid resistance development we are facing today among many pathogens. We are, rightly, concerned about the direct selection pressures of antibiotics on the microbial communities that reside in or on our bodies. However, other environments, outside of our bodies, may also be exposed to antibiotics through different routes, most often unintentionally. There are concerns that increased selection pressures from antibiotics in the environment can contribute to the recruitment of resistance factors from the environmental resistome to human pathogens. This paper attempts to 1) provide a brief overview of environmental exposure routes of antibiotics, 2) provide some thoughts about our current knowledge of the associated risks for humans as well as ecosystems, and 3) indicate management options to reduce risks.

  12. Antibiotics Quiz

    MedlinePlus

    ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary For ... Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Core Elements of Outpatient Antibiotic Stewardship ...

  13. Coronary–Coronary Bypass

    PubMed Central

    Erdil, Nevzat; Ates, Sanser; Demirkilic, Ufuk; Tatar, Harun; Sag, Cemal

    2002-01-01

    There is increased risk of systemic embolism during cardiopulmonary bypass in patients with a severely atherosclerotic ascending aorta. We report a coronary–coronary bypass in a 74-year-old man with a porcelain aorta. He underwent a proximal right coronary–distal right coronary artery bypass with a saphenous vein graft, combined with a pedicled arterial graft (left internal mammary artery) to the left anterior descending artery, in the presence of a beating heart without cardiopulmonary bypass. The patient survived without evidence of perioperative myocardial infarction or cerebrovascular accident. One year later, follow-up angiography showed graft patency with good distal runoff. Coronary–coronary bypass on a beating heart without cardiopulmonary bypass can be performed safely in a patient with porcelain aorta. (Tex Heart Inst J 2002;29:54–5) PMID:11995853

  14. The double life of antibiotics.

    PubMed

    Yap, Mee-Ngan F

    2013-01-01

    Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response.

  15. Heart bypass surgery

    MedlinePlus Videos and Cool Tools

    Heart bypass surgery begins with an incision made in the chest, with the breastbone cut exposing the heart. Next, a portion of the saphenous vein is ... used to bypass the blocked arteries in the heart. The venous graft is sewn to the aorta ...

  16. Molecular mechanisms of antibiotic resistance.

    PubMed

    Wright, Gerard D

    2011-04-14

    Over the past decade, resistance to antibiotics has emerged as a crisis of global proportion. Microbes resistant to many and even all clinically approved antibiotics are increasingly common and easily spread across continents. At the same time there are fewer new antibiotic drugs coming to market. We are reaching a point where we are no longer able to confidently treat a growing number of bacterial infections. The molecular mechanisms of drug resistance provide the essential knowledge on new drug development and clinical use. These mechanisms include enzyme catalyzed antibiotic modifications, bypass of antibiotic targets and active efflux of drugs from the cell. Understanding the chemical rationale and underpinnings of resistance is an essential component of our response to this clinical challenge.

  17. Evolving medicinal chemistry strategies in antibiotic discovery.

    PubMed

    Pawlowski, Andrew C; Johnson, Jarrod W; Wright, Gerard D

    2016-12-01

    Chemical modification of synthetic or natural product antibiotic scaffolds to expand potency and spectrum and to bypass mechanisms of resistance has dominated antibiotic drug discovery and proven immensely successful. However, the inexorable evolution of drug resistance coupled with a drought in innovation in antibiotic discovery contribute to a dearth of new drugs entering to market. Better understanding of the physicochemical properties of antibiotic chemical space is required to inform new antibiotic discovery. Innovations such as the development of antibiotic adjuvants to preserve efficacy of existing drugs together with expanding antibiotic chemical diversity through synthetic biology or new techniques to mine antibiotic producing organisms, are required to bridge the growing gap between the need for new drugs and their discovery.

  18. Gastric Bypass Surgery

    MedlinePlus

    ... much you can eat or by reducing the absorption of nutrients, or both. Gastric bypass and other ... you can eat at one sitting and reducing absorption of nutrients. The surgeon cuts across the top ...

  19. Gastric bypass surgery

    MedlinePlus

    ... your legs to help prevent blood clots from forming. You will receive shots of medicine to prevent ... diversion with duodenal switch Dumping syndrome References Buchwald H. Laparoscopic Roux-en-Y gastric bypass. In: Buchwald ...

  20. Seizures Following Cardiopulmonary Bypass

    PubMed Central

    Brouwer, Monique E.; McMeniman, William J.

    2016-01-01

    Abstract: Seizures following cardiopulmonary bypass are an immediate and alarming indication that a neurologic event has occurred. A case report of a 67-year-old man undergoing aortic valve surgery who unexpectedly experiences seizures following cardiopulmonary bypass is outlined. Possible contributing factors including atheromatous disease in the aorta, low cerebral perfusion pressures, an open-chamber procedure, and the use of tranexamic acid are identified. PMID:27729707

  1. QSAR-assisted virtual screening of lead-like molecules from marine and microbial natural sources for antitumor and antibiotic drug discovery.

    PubMed

    Pereira, Florbela; Latino, Diogo A R S; Gaudêncio, Susana P

    2015-03-17

    A Quantitative Structure-Activity Relationship (QSAR) approach for classification was used for the prediction of compounds as active/inactive relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1746 compounds from PubChem with empirical CDK descriptors and semi-empirical quantum-chemical descriptors. A data set of 183 active pharmaceutical ingredients was additionally used for the external validation of the best models. The best classification models for antibiotic and antitumor activities were used to screen a data set of marine and microbial natural products from the AntiMarin database-25 and four lead compounds for antibiotic and antitumor drug design were proposed, respectively. The present work enables the presentation of a new set of possible lead like bioactive compounds and corroborates the results of our previous investigations. By other side it is shown the usefulness of quantum-chemical descriptors in the discrimination of biologically active and inactive compounds. None of the compounds suggested by our approach have assigned non-antibiotic and non-antitumor activities in the AntiMarin database and almost all were lately reported as being active in the literature.

  2. The multifaceted roles of antibiotics and antibiotic resistance in nature

    PubMed Central

    Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

    2013-01-01

    Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host–parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics

  3. Bypass Flow Study

    SciTech Connect

    Richard Schultz

    2011-09-01

    The purpose of the fluid dynamics experiments in the MIR (Matched Index of-Refraction) flow system at Idaho National Laboratory (INL) is to develop benchmark databases for the assessment of Computational Fluid Dynamics (CFD) solutions of the momentum equations, scalar mixing, and turbulence models for the flow ratios between coolant channels and bypass gaps in the interstitial regions of typical prismatic standard fuel element (SFE) or upper reflector block geometries of typical Modular High-temperature Gas-cooled Reactors (MHTGR) in the limiting case of negligible buoyancy and constant fluid properties. The experiments use Particle Image Velocimetry (PIV) to measure the velocity fields that will populate the bypass flow study database.

  4. Antibiotic Agents

    MedlinePlus

    ... Work Contact Us ABOUT THE ISSUE What is Antibiotic Resistance? General Background Science of Resistance Glossary References POLICY ... for Adaptation Genetics and Drug Resistance Reservoirs of Antibiotic Resistance Project (ROAR) INTERNATIONAL CHAPTERS APUA Chapter Network Africa ...

  5. History of Antibiotics Research.

    PubMed

    Mohr, Kathrin I

    2016-01-01

    . Whenever a new antibiotic reached the market it did not take long until scientists observed the first resistant germs. Since the marketing of the first antibiotic there is a neck-on-neck race between scientists who discover natural or develop semisynthetic and synthetic bioactive molecules and bacteria, which have developed resistance mechanisms. The emphasis of this chapter is to give an overview of the history of antibiotics research. The situation within the pre-antibiotic era as well as in the early antibiotic era will be described until the Golden Age of Antibiotics will conclude this time travel. The most important antibiotic classes, information about their discovery, activity spectrum, mode of action, resistance mechanisms, and current application will be presented.

  6. Superior Vena Cava Bypass

    PubMed Central

    Trainini, Jorge Carlos; Auricchio, Renato; Del Bagno, Horacio Augusto; Federico, Vicente; Acrich, Mario Willie; Osorio, Julio Nestor

    1983-01-01

    A case of superior vena cava obstruction due to carcinoma of unknown origin is reported. A superior vena cava bypass with polytetrafluoroethylene was performed by suturing the prosthesis to the left innominate vein and the right atrium, respectively. Long-term satisfactory results were achieved. Images PMID:15227139

  7. [Antibiotic Stewardship].

    PubMed

    Lanckohr, Christian; Ellger, Björn

    2016-02-01

    The adequate management of infections is an important task in critical care medicine which has an effect on patient outcome. As a result, the prevalence of antiinfective therapy is high in intensive care units. In the face of an unsettling development of worldwide microbial resistance, an optimization and reduction of antiinfective therapy is necessary. Antibiotic stewardship tries to improve antiinfective therapy with an interdisciplinary approach. One overall objective of antibiotic stewardship is the reduction of resistance induction in order to preserve the therapeutic efficiency of antibiotics. Intensive care units are important fields of action for antibiotic stewardship interventions. This article reviews available evidence and some practical aspects for antibiotic stewardship.

  8. Antibiotics from microbes: converging to kill.

    PubMed

    Fischbach, Michael A

    2009-10-01

    As genetically encoded small molecules, antibiotics are phenotypes that have resulted from mutation and natural selection. Advances in genetics, biochemistry, and bioinformatics have connected hundreds of antibiotics to the gene clusters that encode them, allowing these molecules to be analyzed using the tools of evolutionary biology. This review surveys examples of convergent evolution from microbially produced antibiotics, including the convergence of distinct gene clusters on similar phenotypes and the merger of distinct gene clusters into a single functional unit. Examining antibiotics through an evolutionary lens highlights the versatility of biosynthetic pathways, reveals lessons for combating antibiotic resistance, and provides an entry point for studying the natural roles of these natural products.

  9. Antibiotics in late clinical development.

    PubMed

    Fernandes, Prabhavathi; Martens, Evan

    2017-06-01

    Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Direct identification of antibiotic resistance genes on single plasmid molecules using CRISPR/Cas9 in combination with optical DNA mapping

    PubMed Central

    Müller, Vilhelm; Rajer, Fredrika; Frykholm, Karolin; Nyberg, Lena K.; Quaderi, Saair; Fritzsche, Joachim; Kristiansson, Erik; Ambjörnsson, Tobias; Sandegren, Linus; Westerlund, Fredrik

    2016-01-01

    Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping of single plasmids in nanofluidic channels, which provides detailed information about the plasmids present in a bacterial isolate. In a single experiment, we obtain the number of different plasmids in the sample, the size of each plasmid, an optical barcode that can be used to identify and trace the plasmid of interest and information about which plasmid that carries a specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with a guide-RNA (gRNA) complementary to the gene of interest that linearizes the circular plasmids at a specific location that is identified using the optical DNA maps. We demonstrate the principle on clinically relevant extended spectrum beta-lactamase (ESBL) producing isolates. We discuss how the gRNA sequence can be varied to obtain the desired information. The gRNA can either be very specific to identify a homogeneous group of genes or general to detect several groups of genes at the same time. Finally, we demonstrate an example where we use a combination of two gRNA sequences to identify carbapenemase-encoding genes in two previously not characterized clinical bacterial samples. PMID:27905467

  11. Direct identification of antibiotic resistance genes on single plasmid molecules using CRISPR/Cas9 in combination with optical DNA mapping.

    PubMed

    Müller, Vilhelm; Rajer, Fredrika; Frykholm, Karolin; Nyberg, Lena K; Quaderi, Saair; Fritzsche, Joachim; Kristiansson, Erik; Ambjörnsson, Tobias; Sandegren, Linus; Westerlund, Fredrik

    2016-12-01

    Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping of single plasmids in nanofluidic channels, which provides detailed information about the plasmids present in a bacterial isolate. In a single experiment, we obtain the number of different plasmids in the sample, the size of each plasmid, an optical barcode that can be used to identify and trace the plasmid of interest and information about which plasmid that carries a specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with a guide-RNA (gRNA) complementary to the gene of interest that linearizes the circular plasmids at a specific location that is identified using the optical DNA maps. We demonstrate the principle on clinically relevant extended spectrum beta-lactamase (ESBL) producing isolates. We discuss how the gRNA sequence can be varied to obtain the desired information. The gRNA can either be very specific to identify a homogeneous group of genes or general to detect several groups of genes at the same time. Finally, we demonstrate an example where we use a combination of two gRNA sequences to identify carbapenemase-encoding genes in two previously not characterized clinical bacterial samples.

  12. Direct identification of antibiotic resistance genes on single plasmid molecules using CRISPR/Cas9 in combination with optical DNA mapping

    NASA Astrophysics Data System (ADS)

    Müller, Vilhelm; Rajer, Fredrika; Frykholm, Karolin; Nyberg, Lena K.; Quaderi, Saair; Fritzsche, Joachim; Kristiansson, Erik; Ambjörnsson, Tobias; Sandegren, Linus; Westerlund, Fredrik

    2016-12-01

    Bacterial plasmids are extensively involved in the rapid global spread of antibiotic resistance. We here present an assay, based on optical DNA mapping of single plasmids in nanofluidic channels, which provides detailed information about the plasmids present in a bacterial isolate. In a single experiment, we obtain the number of different plasmids in the sample, the size of each plasmid, an optical barcode that can be used to identify and trace the plasmid of interest and information about which plasmid that carries a specific resistance gene. Gene identification is done using CRISPR/Cas9 loaded with a guide-RNA (gRNA) complementary to the gene of interest that linearizes the circular plasmids at a specific location that is identified using the optical DNA maps. We demonstrate the principle on clinically relevant extended spectrum beta-lactamase (ESBL) producing isolates. We discuss how the gRNA sequence can be varied to obtain the desired information. The gRNA can either be very specific to identify a homogeneous group of genes or general to detect several groups of genes at the same time. Finally, we demonstrate an example where we use a combination of two gRNA sequences to identify carbapenemase-encoding genes in two previously not characterized clinical bacterial samples.

  13. Access to the bypassed stomach after gastric bypass.

    PubMed

    Fobi, M A; Chicola, K; Lee, H

    1998-06-01

    The gastric bypass (GBP) Operation is progressively being widely used to treat severe obesity. One problem with this operation is that it leaves the bypassed segment of the gastrointestinal tract not readily available for either mechanical, radiological or endoscopic evaluation. We have addressed this problem by putting a gastrostomy tube in the bypassed stomach at the time of the GBP. A radio-opaque marker placed around the gastrostomy site enables easy radiological localization of and thus easy percutaneous access to the bypassed stomach. The surgical technique is presented.

  14. Seal Bypass Systems (Invited)

    NASA Astrophysics Data System (ADS)

    Cartwright, J. A.

    2009-12-01

    Joe Cartwright 3DLab, School of Earth, Ocean and Planetary Sciences, Cardiff University, Main Building, Park Place, Cardiff CF10 3YE, Wales, UK (cartwrightja@cf.ac.uk) A conceptual model for the analysis of the sealing potential of caprock sequences is summarised here based on the recognition that many high quality seals are breached episodically or semi-permanently by a range of geological structures that act as seal by-pass systems (SBS). We formally define SBS as seismically resolvable geological features embedded within sealing sequences that promote cross-stratal fluid migration and allow fluids to bypass the pore network. We advance the concept that if such bypass systems exist within a given sealing sequence sequence, then predictions of sealing capacity based exclusively on rock physical properties such as capillary entry pressure/hydraulic conductivity will be largely negated by the capacity of the bypass system to breach the grain and pore network. This model is based largely on observations of sealing sequences using 3D seismic data, in which there is direct evidence of highly focused vertical or sub-vertical fluid flow from subsurface reservoirs up through the sealing sequence with leakage internally at higher levels or to the surface as seeps or pockmarks. We classify SBS into three main classes based on seismic interpretational criteria: (1) fault related, (2) intrusion-related, and (3) pipe-related. Examples are presented of each class of SBS in a relevant context of a particular sealing sequence, and where seismic evidence of hydrocarbon leakage allows the role of the bypass features to be evaluated. These include mud volcano conduits, sandstone intrusions, normal and thrust faults, blowout pipes and igneous intrusions. We show how each class exhibits different modes of behaviour with potential for different scaling relationships between flux and dimensions, and different short and long-term impacts on seal behaviour. We conclude with an analysis of

  15. Multiple strategies to activate gold nanoparticles as antibiotics

    NASA Astrophysics Data System (ADS)

    Zhao, Yuyun; Jiang, Xingyu

    2013-08-01

    Widespread antibiotic resistance calls for new strategies. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. This paper reviews the progress in activating gold nanoparticles with nonantibiotic or antibiotic molecules to combat bacterial resistance, analyzes the gap between experimental achievements and real clinical application, and suggests some potential directions in developing antibacterial nanodrugs.

  16. Antibiotic Resistance

    MedlinePlus

    ... are even stronger. Bacteria and Viruses Questions about Antibiotic Resistance Bacteria and Viruses Bacteria and viruses are the two ... even help us to digest food. But other bacteria cause bad diseases like TB and lyme disease. Questions about Antibiotic Resistance Does this affect me? If you have a ...

  17. Antibiotic Safety

    MedlinePlus

    ... very important to know that antibiotics cannot kill virus germs but can kill bacteria germs. Viral infections should not be treated with antibiotics. Some examples of viral illnesses include: • Common cold—stuffy nose, sore throat, sneezing, cough, headache • Influenza ( ...

  18. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

    PubMed

    Vafai, Scott B; Mevers, Emily; Higgins, Kathleen W; Fomina, Yevgenia; Zhang, Jianming; Mandinova, Anna; Newman, David; Shaw, Stanley Y; Clardy, Jon; Mootha, Vamsi K

    2016-01-01

    Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology.

  19. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors

    PubMed Central

    Mevers, Emily; Higgins, Kathleen W.; Fomina, Yevgenia; Zhang, Jianming; Mandinova, Anna; Newman, David; Shaw, Stanley Y.; Clardy, Jon; Mootha, Vamsi K.

    2016-01-01

    Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as “complex I bypass.” In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology. PMID:27622560

  20. Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli.

    PubMed

    Sahlberg Bang, Charlotte; Demirel, Isak; Kruse, Robert; Persson, Katarina

    2017-01-01

    Treatment of urinary tract infections is today a challenge due to the increasing prevalence of multidrug-resistant ESBL-producing uropathogenic Escherichia coli (UPEC). There is an urgent need for new treatment strategies for multidrug-resistant UPEC and preferably with targets that have low potential for development of resistance. Carbon monoxide-releasing molecules (CORMs) are novel and potent antibacterial agents. The present study examines the transcriptomic targets of CORM-2 in a multidrug-resistant ESBL-producing UPEC isolate in response to a single exposure to CORM-2 and after repeated exposure to CORM-2. The bacterial viability and minimal inhibitory concentration (MIC) were also examined after repeated exposure to CORM-2. Microarray analysis revealed that a wide range of processes were affected by CORM-2, including a general trend of down-regulation in energy metabolism and biosynthesis pathways and up-regulation of the SOS response and DNA repair. Several genes involved in virulence (ibpB), antibiotic resistance (marAB, mdtABC) and biofilm formation (bhsA, yfgF) were up-regulated, while some genes involved in virulence (kpsC, fepCEG, entABE), antibiotic resistance (evgA) and biofilm formation (artIP) were down-regulated. Repeated exposure to CORM-2 did not alter the gene expression patterns, the growth inhibitory response to CORM-2 or the MIC values for CORM-2, cefotaxime, ciprofloxacin and trimethoprim. This study identifies several enriched gene ontologies, modified pathways and single genes that are targeted by CORM-2 in a multidrug-resistant UPEC isolate. Repeated exposure to CORM-2 did not change the gene expression patterns or fold changes and the susceptibility to CORM-2 remained after repeated exposure.

  1. Bypass surgery for lower extremity limb salvage: vein bypass.

    PubMed

    El-Sayed, Hosam F

    2012-01-01

    Bypass surgery for limb salvage in cases of chronic limb ischemia is a well-established treatment modality. Use of an autogenous vein provides the best conduit for infrainguinal arterial bypass procedures, particularly for bypass to the infrapopliteal arteries. In this article, we discuss infrainguinal vein bypass surgery including indications, perioperative care, and long-term follow up. We also discuss the outcomes of the procedure with regard to patient survival and limb salvage. The autogenous vein continues to be the best available conduit with the highest patency rate and the best treatment option. Compared to all other revascularization options for infrainguinal disease, the vein bypass has the best limb salvage and long-term survival in patients appropriately selected for the procedure.

  2. New approaches to antibiotic discovery.

    PubMed

    Kealey, C; Creaven, C A; Murphy, C D; Brady, C B

    2017-03-08

    New antibiotics are urgently required by human medicine as pathogens emerge with developed resistance to almost all antibiotic classes. Pioneering approaches, methodologies and technologies have facilitated a new era in antimicrobial discovery. Innovative culturing techniques such as iChip and co-culturing methods which use 'helper' strains to produce bioactive molecules have had notable success. Exploiting antibiotic resistance to identify antibacterial producers performed in tandem with diagnostic PCR based identification approaches has identified novel candidates. Employing powerful metagenomic mining and metabolomic tools has identified the antibiotic'ome, highlighting new antibiotics from underexplored environments and silent gene clusters enabling researchers to mine for scaffolds with both a novel mechanism of action and also few clinically established resistance determinants. Modern biotechnological approaches are delivering but will require support from government initiatives together with changes in regulation to pave the way for valuable, efficacious, highly targeted, pathogen specific antimicrobial therapies.

  3. Heart bypass surgery incision (image)

    MedlinePlus

    ... the left part of the chest between the ribs. This incision is much less traumatic than the traditional heart bypass surgery incision which separates the breast bone. Minimally invasive heart bypass surgery allows the patient less pain and a faster recovery.

  4. Spiritual Bypass: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Glosoff, Harriet L.; Hammond, Cheree

    2010-01-01

    The phenomenon of spiritual bypass has received limited attention in the transpersonal psychology and counseling literature and has not been subjected to empirical inquiry. This study examines the phenomenon of spiritual bypass by considering how spirituality, mindfulness, alexithymia (emotional restrictiveness), and narcissism work together to…

  5. Spiritual Bypass: A Preliminary Investigation

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Glosoff, Harriet L.; Hammond, Cheree

    2010-01-01

    The phenomenon of spiritual bypass has received limited attention in the transpersonal psychology and counseling literature and has not been subjected to empirical inquiry. This study examines the phenomenon of spiritual bypass by considering how spirituality, mindfulness, alexithymia (emotional restrictiveness), and narcissism work together to…

  6. Medium bypass turbofan engine

    SciTech Connect

    Williams, S.B.; Jones, J.F.; Dorer, D.K.

    1986-07-08

    A gas turbine engine of the turbofan type is described which consists of: A. a generally tubular axially extending housing assembly defining a radially outer annular bypass duct extending from the inlet end of the housing assembly to the exhaust end thereof; B. an annular burner positioned within the housing assembly radially inwardly of the bypass duct and concentric to the central axis of the housing assembly; C. a low pressure spool assembly including a first shaft journaled on the central axis of the housing assembly, a fan on the first shaft disposed proximate the inlet end of the housing assembly, and a low pressure turbine on the first shaft disposed proximate the exhaust end of the housing assembly; and D. a high pressure spool assembly including a hollow second shaft telescopically received over the first shaft, a high pressure compressor on the second shaft positioned between the fan and the burner, a high pressure turbine on the second shaft positioned between the burner and the low pressure turbine, and an annular rotary slinger on the second shaft positioned between the high pressure compressor and the high pressure turbine and arranged to sling fuel radially outwardly into the burner.

  7. Passive bypass valve assembly

    SciTech Connect

    Siedlecki, W.F. Jr.

    1992-05-19

    This patent describes a bypass valve assembly for controlling fluid flow in a gas turbine engine. It comprises an annular frame including an outer casing, an inner casing spaced from the outer casing to define a channel for channeling fluid flow and the outer casing including an annular opening therein; a plurality of circumferentially juxtaposed bypass valve doors disposed in the annular opening, each of the valve doors having an inner surface for facing the fluid flowable in the channel, an outer surface, a first end pivotally connected to the frame, and a second end, the doors being positionable in a first position generally parallel to the outer casing, and in a second position inclined relative to the outer casing, the fluid flow flowable against the door inner surface being effective for generating a fluid force on the door; and means for automatically positioning the doors in first and second positions in response to differential pressure across the door, the positioning means providing a torque on the doors for moving the door from the first to the second positions and including torque adjustment means for reducing the torque for at least a portion of travel of the doors from the second to the first positions.

  8. [Antibiotic stewardship].

    PubMed

    Kerwat, Klaus; Wulf, Hinnerk

    2014-09-01

    Resistance against antibiotics is continuously increasing throughout the world and has become a very serious problem. For just this reason "Antibiotic Stewardship Programs" have been developed. These programs are intended to lead to a sustained improvement in the situation and to assure a rational practice for the prescription of anti-infective agents in medical facilities. The aim is to prescribe the correct antibiotic therapy to the right patient at the most appropriate point in time. An AWMF S3 guideline on this topic published by the German Society for Infectiology (S3-Leitlinie StrategienzurSicherungrationalerAntibiotika-AnwendungimKrankenhaus.AWMF-Registernummer 092/001 - S3 Guideline on Strategies for the Rational Use of Antibiotics in Hospitals. AWMF - Registry Number 092/001) has been available since the end of 2013. An essential aspect therein is the expert interdisciplinary cooperation of a team comprising a clinically experienced infectiologist, a hospital pharmacist and a consultant for microbiology.

  9. Bypass diode integration

    NASA Technical Reports Server (NTRS)

    Shepard, N. F., Jr.

    1981-01-01

    Protective bypass diodes and mounting configurations which are applicable for use with photovoltaic modules having power dissipation requirements in the 5 to 50 watt range were investigated. Using PN silicon and Schottky diode characterization data on packaged diodes and diode chips, typical diodes were selected as representative for each range of current carrying capacity, an appropriate heat dissipating mounting concept along with its environmental enclosure was defined, and a thermal analysis relating junction temperature as a function of power dissipation was performed. In addition, the heat dissipating mounting device dimensions were varied to determine the effect on junction temperature. The results of the analysis are presented as a set of curves indicating junction temperature as a function of power dissipation for each diode package.

  10. Cardiopulmonary Bypass Without Heparin.

    PubMed

    Rehfeldt, Kent H; Barbara, David W

    2016-03-01

    Due to familiarity, short half-life, ease of monitoring, and the availability of a reversal agent, heparin remains the anticoagulant of choice for cardiac operations requiring cardiopulmonary bypass (CPB). However, occasionally patients require CPB but should not receive heparin, most often because of acute or subacute heparin-induced thrombocytopenia (HIT). In these cases, if it is not feasible to wait for the disappearance of HIT antibodies, an alternative anticoagulant must be selected. A number of non-heparin anticoagulant options have been explored. However, current recommendations suggest the use of a direct thrombin inhibitor such as bivalirudin. This review describes the use of heparin alternatives for the conduct of CPB with a focus on the direct thrombin inhibitors.

  11. Major histocompatibility complex class I molecules with super-enhanced CD8 binding properties bypass the requirement for cognate TCR recognition and non-specifically activate cytotoxic T lymphocytes1

    PubMed Central

    Wooldridge, Linda; Clement, Matthew; Lissina, Anna; Edwards, Emily S. J.; Ladell, Kristin; Ekeruche, Julia; Hewitt, Rachel E.; Laugel, Bruno; Gostick, Emma; Cole, David K.; Debets, Reno; Berrevoets, Cor; Miles, John J.; Burrows, Scott R.; Price, David A.; Sewell, Andrew K.

    2010-01-01

    CD8+ cytotoxic T lymphocytes (CTL) are essential for effective immune defence against intracellular microbes and neoplasia. CTL recognize short peptide fragments presented in association with major histocompatibility complex class I (MHCI) molecules on the surface of infected or dysregulated cells. Antigen recognition involves the binding of both T cell receptor (TCR) and CD8 co-receptor to a single ligand (pMHCI). The TCR/pMHCI interaction confers antigen specificity, whereas the pMHCI/CD8 interaction mediates enhanced sensitivity to antigen. Striking biophysical differences exist between the TCR/pMHCI and pMHCI/CD8 interactions; indeed, the pMHCI/CD8 interaction can be >100-fold weaker than the cognate TCR/pMHCI interaction. Here, we show that increasing the strength of the pMHCI/CD8 interaction by ~15-fold results in non-specific, cognate antigen-independent pMHCI tetramer binding at the cell surface. Furthermore, pMHCI molecules with super-enhanced affinity for CD8 activate CTL in the absence of a specific TCR/pMHCI interaction to elicit a full range of effector functions, including cytokine/chemokine release, degranulation and proliferation. Thus, the low solution binding affinity of the pMHCI/CD8 interaction is essential for the maintenance of CTL antigen specificity. PMID:20190139

  12. Photovoltaic module bypass diode encapsulation

    NASA Technical Reports Server (NTRS)

    Shepard, N. J., Jr.

    1983-01-01

    The design and processing techniques necessary to incorporate bypass diodes within the module encapsulant are presented. The Semicon PN junction diode cells were selected. Diode junction to heat spreader thermal resistance measurements, performed on a variety of mounted diode chip types and sizes, have yielded values which are consistently below 1 deg C per watt, but show some instability when thermally cycled over the temperature range from -40 to 150 deg C. Three representative experimental modules, each incorporating integral bypass diode/heat spreader assemblies of various sizes, were designed. Thermal testing of these modules enabled the formulation of a recommended heat spreader plate sizing relationship. The production cost of three encapsulated bypass diode/heat spreader assemblies were compared with similarly rated externally mounted packaged diodes. It is concluded that, when proper designed and installed, these bypass diode devices will improve the overall reliability of a terrestrial array over a 20 year design lifetime.

  13. Genomic tools to profile antibiotic mode of action.

    PubMed

    Cardona, Silvia T; Selin, Carrie; Gislason, April S

    2015-01-01

    The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and development of novel antibacterial therapies. Some of the root causes that have hampered current antibiotic drug development are the lack of understanding of the mode of action (MOA) of novel antibiotic molecules and the poor characterization of the bacterial physiological response to antibiotics that ultimately causes resistance. Here, we review how bacterial genetic tools can be applied at the genomic level with the goal of profiling resistance to antibiotics and elucidating antibiotic MOAs. Specifically, we highlight how chemical genomic detection of the MOA of novel antibiotic molecules and antibiotic profiling by next-generation sequencing are leveraging basic antibiotic research to unprecedented levels with great opportunities for knowledge translation.

  14. Designing Safer and Greener Antibiotics

    PubMed Central

    Jordan, Andrew; Gathergood, Nicholas

    2013-01-01

    Since the production of the first pharmaceutically active molecules at the beginning of the 1900s, drug molecules and their metabolites have been observed in the environment in significant concentrations. In this review, the persistence of antibiotics in the environment and their associated effects on ecosystems, bacterial resistance and health effects will be examined. Solutions to these problems will also be discussed, including the pharmaceutical industries input, green chemistry, computer modeling and representative ionic liquid research. PMID:27029311

  15. Cerebral oxygenation during cardiopulmonary bypass

    PubMed Central

    Wardle, S; Yoxall, C; Weindling, A

    1998-01-01

    Cerebral fractional oxygen extraction (FOE) was monitored in 30 children, using near infrared spectroscopy during cardiopulmonary bypass, to investigate the effect of hypothermia and circulatory arrest. One group of children (n = 15) underwent profound hypothermia with total circulatory arrest (n = 8) or continuous flow (n =7). Another group (n = 15), of whom only one had circulatory arrest, underwent mild (n = 6) or moderate (n = 9) hypothermia.
 The mean FOE (SD) before bypass was 0.35 (0.12) and this correlated negatively with the preoperative arterial oxygen content (r=−0.58). Between the stage of cooling on bypass and cold bypass there was a reduction in FOE in all groups. Between cold bypass and rewarming there was an increase in FOE only in the groups with continuous flow. In the circulatory arrest group, the FOE remained low during rewarming and was significantly lower than that of the continuous flow group. No patients died and none had neurological abnormalities postoperatively.
 Apparent changes in oxidised cytochrome oxidase concentration were also monitored using near infrared spectroscopy. There was a fall in cytochrome aa3 on starting cardiopulmonary bypass, but there were no significant differences in the changes in cytochrome aa3 between any stage in any of the patient groups.
 Using this non-invasive technique, cooling was shown to reduce cerebral FOE. During rewarming on bypass there was an increase in cerebral FOE only in patients who had had continuous flow bypass. In contrast, the cerebral FOE in those with circulatory arrest remained constant after arrest and during the duration of the study. This may have implications for the timing of hypoxic brain injury.

 PMID:9534672

  16. Multiscale Models of Antibiotic Probiotics

    PubMed Central

    Kaznessis, Yiannis N.

    2014-01-01

    The discovery of antibiotics is one of the most important advances in the history of humankind. For eighty years human life expectancy and standards of living improved greatly thanks to antibiotics. But bacteria have been fighting back, developing resistance to our most potent molecules. New, alternative strategies must be explored as antibiotic therapies become obsolete because of bacterial resistance. Mathematical models and simulations guide the development of complex technologies, such as aircrafts, bridges, communication systems and transportation systems. Herein, models are discussed that guide the development of new antibiotic technologies. These models span multiple molecular and cellular scales, and facilitate the development of a technology that addresses a significant societal challenge. We argue that simulations can be a creative source of knowledge. PMID:25313349

  17. The Double Life of Antibiotics

    PubMed Central

    Yap, Mee-Ngan F.

    2013-01-01

    Antibiotic resistance is a persistent health care problem worldwide. Evidence for the negative consequences of subtherapeutic feeding in livestock production has been mounting while the antibiotic pipeline is drying up. In recent years, there has been a paradigm shift in our perception of antibiotics. Apart from its roles in self-defense, antibiotics also serve as inter-microbial signaling molecules, regulators of gene expression, microbial food sources, and as mediators of host immune response. “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily under-dose himself and by exposing his microbes to nonlethal quantities of the drug make them resistant.”~Alexander Fleming PMID:24003650

  18. Antibiotics that target protein synthesis.

    PubMed

    McCoy, Lisa S; Xie, Yun; Tor, Yitzhak

    2011-01-01

    The key role of the bacterial ribosome makes it an important target for antibacterial agents. Indeed, a large number of clinically useful antibiotics target this complex translational ribonucleoprotein machinery. The majority of these compounds, mostly of natural origin, bind to one of the three key ribosomal sites: the decoding (or A-site) on the 30S, the peptidyl transferase center (PTC) on the 50S, and the peptide exit tunnel on the 50S. Antibiotics that bind the A-site, such as the aminoglycosides, interfere with codon recognition and translocation. Peptide bond formation is inhibited when small molecules like oxazolidinones bind at the PTC. Finally, macrolides tend to block the growth of the amino acid chain at the peptide exit tunnel. In this article, the major classes of antibiotics that target the bacterial ribosome are discussed and classified according to their respective target. Notably, most antibiotics solely interact with the RNA components of the bacterial ribosome. The surge seen in the appearance of resistant bacteria has not been met by a parallel development of effective and broad-spectrum new antibiotics, as evident by the introduction of only two novel classes of antibiotics, the oxazolidinones and lipopeptides, in the past decades. Nevertheless, this significant health threat has revitalized the search for new antibacterial agents and novel targets. High resolution structural data of many ribosome-bound antibiotics provide unprecedented insight into their molecular contacts and mode of action and inspire the design and synthesis of new candidate drugs that target this fascinating molecular machine.

  19. Bypass rewiring and robustness of complex networks

    NASA Astrophysics Data System (ADS)

    Park, Junsang; Hahn, Sang Geun

    2016-08-01

    A concept of bypass rewiring is introduced, and random bypass rewiring is analytically and numerically investigated with simulations. Our results show that bypass rewiring makes networks robust against removal of nodes including random failures and attacks. In particular, random bypass rewiring connects all nodes except the removed nodes on an even degree infinite network and makes the percolation threshold 0 for arbitrary occupation probabilities. In our example, the even degree network is more robust than the original network with random bypass rewiring, while the original network is more robust than the even degree networks without random bypass. We propose a greedy bypass rewiring algorithm which guarantees the maximum size of the largest component at each step, assuming which node will be removed next is unknown. The simulation result shows that the greedy bypass rewiring algorithm improves the robustness of the autonomous system of the Internet under attacks more than random bypass rewiring.

  20. The expression of antibiotic resistance genes in antibiotic-producing bacteria.

    PubMed

    Mak, Stefanie; Xu, Ye; Nodwell, Justin R

    2014-08-01

    Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance. © 2014 John Wiley & Sons Ltd.

  1. Antibiotics From Microbes: Converging To Kill

    PubMed Central

    Fischbach, Michael A.

    2011-01-01

    Summary As genetically encoded small molecules, antibiotics are phenotypes that have resulted from mutation and natural selection. Advances in genetics, biochemistry, and bioinformatics have connected hundreds of antibiotics to the gene clusters that encode them, allowing these molecules to be analyzed using the tools of evolutionary biology. This review surveys examples of convergent evolution from microbially produced antibiotics, including the convergence of distinct gene clusters on similar phenotypes and the merger of distinct gene clusters into a single functional unit. Examining antibiotics through an evolutionary lens highlights the versatility of biosynthetic pathways, reveals lessons for combating antibiotic resistance, and provides an entry point for studying the natural roles of these natural products. PMID:19695947

  2. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance.

  3. Carotid bypass for carotid occlusion.

    PubMed

    Hage, Ziad A; Behbahani, Mandana; Amin-Hanjani, Sepideh; Charbel, Fady T

    2015-07-01

    The 2-year risk of ipsilateral ischemic stroke following internal carotid artery occlusion (ICAO) in a patient undergoing maximal medical therapy is 5-8% per year. While medical therapy may reduce the risk of stroke, it does not completely eliminate it. Since the 1985 extracranial-intracranial (EC-IC) bypass study, additional trials have been conducted to further investigate the usefulness of EC-IC bypass surgery in more selected patients with cerebral ischemia and impaired hemodynamic reserve. These important studies will be briefly reviewed in this article, as well as a discussion regarding the utility of bypass surgery for ICAO in current clinical practice. In addition, a short discussion regarding the pathophysiology of carotid occlusion will be presented. We will also highlight our own institutional patient selection criteria based on the latest methods for hemodynamic assessment, as well as our intraoperative flow assisted surgical techniques (FAST), and post-operative patient follow-up.

  4. Microbiological effects of sublethal levels of antibiotics.

    PubMed

    Andersson, Dan I; Hughes, Diarmaid

    2014-07-01

    The widespread use of antibiotics results in the generation of antibiotic concentration gradients in humans, livestock and the environment. Thus, bacteria are frequently exposed to non-lethal (that is, subinhibitory) concentrations of drugs, and recent evidence suggests that this is likely to have an important role in the evolution of antibiotic resistance. In this Review, we discuss the ecology of antibiotics and the ability of subinhibitory concentrations to select for bacterial resistance. We also consider the effects of low-level drug exposure on bacterial physiology, including the generation of genetic and phenotypic variability, as well as the ability of antibiotics to function as signalling molecules. Together, these effects accelerate the emergence and spread of antibiotic-resistant bacteria among humans and animals.

  5. Coronary Artery Disease: Angioplasty or Bypass Surgery?

    MedlinePlus

    Coronary artery disease: Angioplasty or bypass surgery? I'm getting a cardiac catheterization. If blockages are found, ... angioplasty or bypass surgery? Answers from Rekha Mankad, M.D. During cardiac catheterization, your doctor will examine ...

  6. Secondary and College LD Bypass Strategies.

    ERIC Educational Resources Information Center

    Mosby, Robert J.

    1981-01-01

    The author describes the Developmental By-Pass (DBP) Instructional technology for teaching secondary and college learning disabled (LD) students by allowing students to bypass ordering and organizational deficits. (SB)

  7. Types of Coronary Artery Bypass Grafting

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Coronary Artery Bypass Grafting There are several types of coronary ... for you based on your needs. Traditional Coronary Artery Bypass Grafting Traditional CABG is used when at ...

  8. Psychological Effects of Intestinal Bypass Surgery.

    ERIC Educational Resources Information Center

    Wampler, Richard S.; And Others

    1980-01-01

    Preoperative and postoperative intestinal bypass patients were evaluated. Results suggest that postoperative bypass patients have improved psychological health and an increased sense of freedom and well-being but may need assistance in improving self-concepts. (Author)

  9. Technology Solutions Case Study: Preventing Thermal Bypass

    SciTech Connect

    none,

    2012-10-01

    This project highlights the importance of continuous air barriers in full alignment with insulation to prevent thermal bypasses and achieve high energy performance, and recommends use of ENERGY STAR's Thermal Bypass Inspection Checklist.

  10. 30 CFR 77.302 - Bypass stacks.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....302 Bypass stacks. Thermal dryer systems shall include a bypass stack, relief stack or individual discharge stack provided with automatic venting which will permit gases from the dryer heating unit to bypass the heating chamber and vent to the outside atmosphere during any shutdown operation. ...

  11. 30 CFR 77.302 - Bypass stacks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....302 Bypass stacks. Thermal dryer systems shall include a bypass stack, relief stack or individual discharge stack provided with automatic venting which will permit gases from the dryer heating unit to bypass the heating chamber and vent to the outside atmosphere during any shutdown operation. ...

  12. Antibiotic Capture by Bacterial Lipocalins Uncovers an Extracellular Mechanism of Intrinsic Antibiotic Resistance.

    PubMed

    El-Halfawy, Omar M; Klett, Javier; Ingram, Rebecca J; Loutet, Slade A; Murphy, Michael E P; Martín-Santamaría, Sonsoles; Valvano, Miguel A

    2017-03-14

    The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins.IMPORTANCE Current research on antibiotic action and resistance focuses on targeting essential functions within bacterial cells. We discovered a previously unrecognized mode of general bacterial antibiotic resistance operating in the extracellular space, which depends on bacterial protein molecules called lipocalins. These molecules are highly conserved in most bacteria and have the ability to capture different classes of antibiotics outside bacterial cells. We also discovered that liposoluble vitamins, such as vitamin E, overcome in vitro and in vivo antibiotic resistance mediated by bacterial lipocalins, providing an unexpected new alternative to combat resistance by using this vitamin or its derivatives as antibiotic adjuvants.

  13. Interventions in Infrainguinal Bypass Grafts

    SciTech Connect

    Mueller-Huelsbeck, S. Order, B.-M.; Jahnke, T.

    2006-02-15

    The interventional radiologist plays an important role in the detection and prevention of infrainguinal bypass failure. Early detection and evaluation of flow-limiting lesions effectively preserve graft (venous bypass and polyester or expanded polytetrafluoroethylene bypass) patency by identifying stenoses before occlusion occurs. Delay in treatment of the at-risk graft may result in graft failure and a reduced chance of successful revascularization. For this reason, surveillance protocols form an important part of follow-up after infrainguinal bypass surgery. As well as having an understanding of the application of imaging techniques including ultrasound, MR angiography, CT angiography and digital subtraction angiography, the interventional radiologist should have detailed knowledge of the minimally invasive therapeutic options. Percutaneous transluminal angioplasty (PTA), or alternatively cutting balloon angioplasty, is the interventional treatment of choice in prevention of graft failure and occlusion. Further alternatives include metallic stent placement, fibrinolysis, and mechanical thrombectomy. Primary assisted patency rates following PTA can be up to 65% at 5 years. When the endovascular approach is unsuccessful, these therapeutic options are complemented by surgical procedures including vein patch revision, jump grafting, or placement of a new graft.

  14. Heart bypass surgery - minimally invasive

    MedlinePlus

    ... MIDCAB; Robot-assisted coronary artery bypass; RACAB; Keyhole heart surgery; CAD - MIDCAB; Coronary artery disease - MIDCAB ... To perform this surgery: The heart surgeon will make a 3- to 5-inch (8 to 13 centimeters) surgical cut in the left part of your chest ...

  15. Hybrid antibiotics - clinical progress and novel designs.

    PubMed

    Parkes, Alastair L; Yule, Ian A

    2016-07-01

    There is a growing need for new antibacterial agents, but success in development of antibiotics in recent years has been limited. This has led researchers to investigate novel approaches to finding compounds that are effective against multi-drug resistant bacteria, and that delay onset of resistance. One such strategy has been to link antibiotics to produce hybrids designed to overcome resistance mechanisms. The concept of dual-acting hybrid antibiotics was introduced and reviewed in this journal in 2010. In the present review the authors sought to discover how clinical candidates described had progressed, and to examine how the field has developed. In three sections the authors cover the clinical progress of hybrid antibiotics, novel agents produced from hybridisation of two or more small-molecule antibiotics, and novel agents produced from hybridisation of antibiotics with small-molecules that have complementary activity. Many key questions regarding dual-acting hybrid antibiotics remain to be answered, and the proposed benefits of this approach are yet to be demonstrated. While Cadazolid in particular continues to progress in the clinic, suggesting that there is promise in hybridisation through covalent linkage, it may be that properties other than antibacterial activity are key when choosing a partner molecule.

  16. Direction of aminoacylated transfer RNAs into antibiotic synthesis and peptidoglycan-mediated antibiotic resistance.

    PubMed

    Shepherd, Jennifer; Ibba, Michael

    2013-09-17

    Prokaryotic aminoacylated-transfer RNAs often need to be efficiently segregated between translation and other cellular biosynthetic pathways. Many clinically relevant bacteria, including Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa direct some aminoacylated-tRNA species into peptidoglycan biosynthesis and/or membrane phospholipid modification. Subsequent indirect peptidoglycan cross-linkage or change in membrane permeability is often a prerequisite for high-level antibiotic resistance. In Streptomycetes, aminoacylated-tRNA species are used for antibiotic synthesis as well as antibiotic resistance. The direction of coding aminoacylated-tRNA molecules away from translation and into antibiotic resistance and synthesis pathways are discussed in this review.

  17. Intestinal perforation caused by insertion of a nasogastric tube late after gastric bypass.

    PubMed

    Van Dinter, Thomas G; John, Lijo; Guileyardo, Joseph M; John S, Fordtran

    2013-01-01

    A 57-year-old woman, who had undergone Roux-en-Y gastric bypass surgery 9 years earlier, was admitted to the intensive care unit because of pneumonia. Despite antibiotic therapy, she died 40 days later, apparently because of sepsis and organ failure related to the pneumonia. However, the patient's family requested an autopsy, which revealed that her death was due to perforation of the Roux limb of her gastric bypass, which had resulted in severe peritonitis. The perforation was caused by a nasogastric tube inserted for enteral nutrition. We discuss ways nasogastric tubes might be inserted more safely after gastric bypass, the response of Baylor University Medical Center at Dallas to this complication, and the role of autopsy in improving the quality of hospital care.

  18. Intestinal perforation caused by insertion of a nasogastric tube late after gastric bypass

    PubMed Central

    Van Dinter, Thomas G.; John, Lijo; Guileyardo, Joseph M.; John S., Fordtran

    2013-01-01

    A 57-year-old woman, who had undergone Roux-en-Y gastric bypass surgery 9 years earlier, was admitted to the intensive care unit because of pneumonia. Despite antibiotic therapy, she died 40 days later, apparently because of sepsis and organ failure related to the pneumonia. However, the patient's family requested an autopsy, which revealed that her death was due to perforation of the Roux limb of her gastric bypass, which had resulted in severe peritonitis. The perforation was caused by a nasogastric tube inserted for enteral nutrition. We discuss ways nasogastric tubes might be inserted more safely after gastric bypass, the response of Baylor University Medical Center at Dallas to this complication, and the role of autopsy in improving the quality of hospital care. PMID:23382601

  19. Hybrid Endovascular Solutions for Supra-Aortic Vessels Extra-Anatomic Bypass Infection.

    PubMed

    Fadda, Gian Franco; Marino, Mario; Kasemi, Holta; Di Angelo, Costantino Luca; Ronchey, Sonia; Serrao, Eugenia; Orrico, Matteo; Mangialardi, Nicola

    2015-11-01

    The use of extra-anatomic bypasses for the hybrid repair of thoracic aortic pathologies should consider the risk of vascular graft infection. Graft infections at cervical level are extremely rare and are associated with high mortality and morbidity rates. We report 2 cases of infected extra-anatomic bypasses for supra-aortic vessels debranching treated with a hybrid approach: re-extra-anatomical bypass with the Viabahn Open Revascularization Technique (VORTEC) in the first patient and the EndoVAC approach in the second case. Endovascular techniques may offer bail-out solutions in a hybrid fashion to treat vascular graft infection in patients considered unfeasible for the conventional surgical repair, associated with appropriate antibiotic therapy.

  20. Mini cardiopulmonary bypass: Anesthetic considerations

    PubMed Central

    Alsatli, Raed A.

    2012-01-01

    This review article is going to elaborate on the description, components, and advantages of mini-cardiopulmonary bypass (mini-CPB), with special reference to the anesthetic management and fast track anesthesia with mini-CPB. There are several clinical advantages of mini-CPB like, reduced inflammatory reaction to the pump, reduced need for allogenic blood transfusion and lower incidence of postoperative neurological complications. There are certainly important points that have to be considered by anesthesiologists to avoid sever perturbation in the cardiac output and blood pressure during mini-CPB. Fast-track anesthesia provides advantages regarding fast postoperative recovery from anesthesia, and reduction of postoperative ventilation time. Mini bypass offers a sound alternative to conventional CPB, and has definite advantages. It has its limitations, but even with that it has a definite place in the current practice of cardiac surgery. PMID:25885494

  1. Antibiotic-bonded PTFE vascular grafts: the effect of silver antibiotic on bioactivity following implantation.

    PubMed

    Kinney, E V; Bandyk, D F; Seabrook, G A; Kelly, H M; Towne, J B

    1991-05-01

    Use of an infection-resistant vascular prosthesis has appeal for grafting in sites of potential contamination or to replace graft segments involved in low-grade infections caused by coagulase-negative staphylococci (CNS). In this study, antibiotic retention on polytetrafluoroethylene (PTFE) grafts prepared using three antibiotic-bonding methods was compared following implantation into the arterial circulation. Ciprofloxacin or silver-ciprofloxacin was bonded to PTFE surfaces by surfactant-mediated or direct bonding methods. Antibiotic-bonded grafts of each type (n = 8) or control grafts (n = 2) were used to replace the carotid or femoral arteries of 10 dogs. Duplicate grafts segments (0.5 x 0.5 cm) were explanted at various time intervals ranging from 1 hr to 14 days later and imprinted onto culture plates of Klebsiella pneumonia. Antibiotic retention (micrograms/ml) was determined by measuring zones of inhibition and correlated with known disc concentrations of ciprofloxacin. Antibacterial bioactivity of grafts bonded with silver-antibiotic complexes was superior (P less than 0.02) to bonding of antibiotic alone at 3 and 24 hr following implantation. Ciprofloxacin retention in excess of the minimum bactericidal concentration (0.5 microgram/ml) of Staphylococcus epidermidis was demonstrated on all silver-antibiotic-bonded grafts after 14 days of implantation. At 7 and 14 days following implantation, the bioactivity of all antibiotic-bonded grafts exceeded 0.125 micrograms/ml of ciprofloxacin, the minimum inhibitory concentration of S. epidermidis. Bonding of silver-ciprofloxacin on PTFE grafts provided an effective source of local antibiotic release at levels which may be useful for bypass grafting in contaminated wounds or for in situ replacement of grafts infected by CNS.

  2. Biosynthesis of Tetrahydroisoquinoline Antibiotics.

    PubMed

    Tang, Gong-Li; Tang, Man-Cheng; Song, Li-Qiang; Zhang, Yue

    2016-01-01

    The tetrahydroisoquinoline (THIQ) alkaloids are naturally occurring antibiotics isolated from a variety of microorganisms and marine invertebrates. This family of natural products exhibit broad spectrum antimicrobial and strong antitumor activities, and the potency of clinical application has been validated by the marketing of ecteinascidin 743 (ET-743) as anticancer drug. In the past 20 years, the biosynthetic gene cluster of six THIQ antibiotics has been characterized including saframycin Mx1 from Myxococcus xanthus, safracin-B from Pseudomonas fluorescens, saframycin A, naphthyridinomycin, and quinocarcin from Streptomyces, as well as ET-743 from Ecteinascidia turbinata. This review gives a brief summary of the current status in understanding the molecular logic for the biosynthesis of these natural products, which provides new insights on the biosynthetic machinery involved in the nonribosomal peptide synthetase system. The proposal of the THIQ biosynthetic pathway not only shows nature's route to generate such complex molecules, but also set the stage to develop a different process for production of ET-743 by synthetic biology.

  3. Evolution of antibiotic resistance without antibiotic exposure.

    PubMed

    Knöppel, Anna; Näsvall, Joakim; Andersson, Dan I

    2017-09-11

    Antibiotic use is the main driver in the emergence of antibiotic resistance. Another unexplored possibility is that resistance evolves coincidentally in response to other selective pressures. We show that selection in the absence of antibiotics can co-select for decreased susceptibility to several antibiotics. Thus, genetic adaptation of bacteria to natural environments may drive resistance evolution by generating a pool of resistance mutations that selection could act on to enrich resistant mutants when antibiotic exposure occurs. Copyright © 2017 Knöppel et al.

  4. Bacteriocins - a viable alternative to antibiotics?

    PubMed

    Cotter, Paul D; Ross, R Paul; Hill, Colin

    2013-02-01

    Solutions are urgently required for the growing number of infections caused by antibiotic-resistant bacteria. Bacteriocins, which are antimicrobial peptides produced by certain bacteria, might warrant serious consideration as alternatives to traditional antibiotics. These molecules exhibit significant potency against other bacteria (including antibiotic-resistant strains), are stable and can have narrow or broad activity spectra. Bacteriocins can even be produced in situ in the gut by probiotic bacteria to combat intestinal infections. Although the application of specific bacteriocins might be curtailed by the development of resistance, an understanding of the mechanisms by which such resistance could emerge will enable researchers to develop strategies to minimize this potential problem.

  5. Fourier transform infrared and Raman spectroscopy studies on magnetite/Ag/antibiotic nanocomposites

    NASA Astrophysics Data System (ADS)

    Ivashchenko, Olena; Jurga-Stopa, Justyna; Coy, Emerson; Peplinska, Barbara; Pietralik, Zuzanna; Jurga, Stefan

    2016-02-01

    This article presents a study on the detection of antibiotics in magnetite/Ag/antibiotic nanocomposites using Fourier transform infrared (FTIR) and Raman spectroscopy. Antibiotics with different spectra of antimicrobial activities, including rifampicin, doxycycline, cefotaxime, and ceftriaxone, were studied. Mechanical mixtures of antibiotics and magnetite/Ag nanocomposites, as well as antibiotics and magnetite nanopowder, were investigated in order to identify the origin of FTIR bands. FTIR spectroscopy was found to be an appropriate technique for this task. The spectra of the magnetite/Ag/antibiotic nanocomposites exhibited very weak (for doxycycline, cefotaxime, and ceftriaxone) or even no (for rifampicin) antibiotic bands. This FTIR "invisibility" of antibiotics is ascribed to their adsorbed state. FTIR and Raman measurements show altered Csbnd O, Cdbnd O, and Csbnd S bonds, indicating adsorption of the antibiotic molecules on the magnetite/Ag nanocomposite structure. In addition, a potential mechanism through which antibiotic molecules interact with magnetite/Ag nanoparticle surfaces is proposed.

  6. Abdominal Pain following Gastric Bypass: Suspects & Solutions

    PubMed Central

    Greenstein, Alexander J.; O’Rourke, Robert W.

    2010-01-01

    Introduction Gastric bypass remains the mainstay of surgical therapy for obesity. Abdominal pain after gastric bypass is common, and accounts for up to half of all postoperative complaints and emergency room visits. This manuscript reviews the most important causes of abdominal pain specific to gastric bypass and discusses management considerations. Data Sources The current surgical literature was reviewed using PubMed, with a focus on abdominal pain after gastric bypass and the known pathologies that underlie its pathogenesis. Conclusions The differential diagnosis for abdominal pain after gastric bypass is large and includes benign and life-threatening entities. Its diverse causes require a broad evaluation that should be directed by history and clinical presentation. In the absence of a clear diagnosis, the threshold for surgical exploration in patients with abdominal pain after gastric bypass should be low. PMID:21333269

  7. Ramjet bypass duct and preburner configuration

    NASA Technical Reports Server (NTRS)

    Orlando, Robert J. (Inventor)

    1994-01-01

    A combined turbofan and ramjet aircraft engine includes a forward bypass duct which allows the engine to operate more efficiently during the turbofan mode of operation. By mounting a ramjet preburner in the forward duct and isolating this duct from the turbofan bypass air, a transition from turbofan operation to ramjet operation can take place at lower flight Mach numbers without incurring pressure losses or blockage in the turbofan bypass air.

  8. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria.

    PubMed

    Uppu, Divakara S S M; Konai, Mohini M; Sarkar, Paramita; Samaddar, Sandip; Fensterseifer, Isabel C M; Farias-Junior, Celio; Krishnamoorthy, Paramanandam; Shome, Bibek R; Franco, Octávio L; Haldar, Jayanta

    2017-01-01

    Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.

  9. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria

    PubMed Central

    Uppu, Divakara S. S. M.; Konai, Mohini M.; Sarkar, Paramita; Samaddar, Sandip; Fensterseifer, Isabel C. M.; Farias-Junior, Celio; Krishnamoorthy, Paramanandam; Shome, Bibek R.; Franco, Octávio L.

    2017-01-01

    Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections. PMID:28837596

  10. Antibiotic therapy of aortic graft infection: treatment and prevention recommendations.

    PubMed

    Hodgkiss-Harlow, Kelley D; Bandyk, Dennis F

    2011-12-01

    Surgical site infection (SSI) after aortic intervention, an uncommon but serious vascular condition, requires patient-specific antibiotic therapy. Effective treatment and prevention requires the vascular surgeon to be cognizant of changing SSI microbiology, advances in antibiotic delivery, and patient characteristics. The majority of aortic graft infections are caused by Gram-positive bacteria, with methicillin-resistant Staphylococcus aureus now the prevalent pathogen. Nasal carriage of methicillin-sensitive or methicillin-resistant S aureus strains, diabetes mellitus, recent hospitalization, a failed arterial reconstruction, and the presence of a groin incision are important SSI risk factors. Overall, the aortic SSI rate is higher than predicted by the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance risk category system; ranging from 5% after open or endovascular aortic interventions to as high as 10% to 15% after aortofemoral bypass or uni-aortoiliac grafting with femorofemoral bypass. Perioperative measures to reduce S aureus nares and skin colonization, administration of antibiotic prophylaxis, meticulous wound closure/care, and therapy directed to optimize patient host defense regulation mechanisms (eg, temperature, oxygenation, blood sugar) can minimize SSI occurrence. Antibiotic therapy for aortic graft infection should utilize bactericidal drugs that penetrate bacteria biofilms and can be delivered to the surgical site both parenterally and locally in the form of antibiotic-impregnated beads or prosthetic grafts.

  11. Inelastic insights for molecular tunneling pathways: bypassing the terminal groups.

    PubMed

    Troisi, Alessandro; Ratner, Mark A

    2007-05-21

    As an example of the use of inelastic transport to deduce structure in molecular transport junctions, we compute the orientation dependence of the Inelastic Electron Tunneling (IET) spectrum of the 1-pentane monothiolate. We find that upon increasing the tilting angle of the molecule with respect to the normal to the electrode the spectrum changes as the intensity of some vibrations is enhanced. These differences occur because for higher tilting angles the tunneling path that bypasses the terminal group grows in importance. IETS can therefore be used to establish the molecular orientation in junctions terminating with alkyl chains and to investigate experimentally the relative importance of the available tunneling paths.

  12. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass coronary pressure gauge... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure... the coronary arteries. (b) Classification. Class II (performance standards). ...

  13. History of cardiopulmonary bypass (CPB).

    PubMed

    Hessel, Eugene A

    2015-06-01

    The development of cardiopulmonary bypass (CPB), thereby permitting open-heart surgery, is one of the most important advances in medicine in the 20th century. Many currently practicing cardiac anesthesiologists, cardiac surgeons, and perfusionists are unaware of how recently it came into use (60 years) and how much the practice of CPB has changed during its short existence. In this paper, the development of CPB and the many changes and progress that has taken place over this brief period of time, making it a remarkably safe endeavor, are reviewed. The many as yet unresolved questions are also identified, which sets the stage for the other papers in this issue of this journal.

  14. Antibiotics and the burn patient.

    PubMed

    Ravat, François; Le-Floch, Ronan; Vinsonneau, Christophe; Ainaud, Pierre; Bertin-Maghit, Marc; Carsin, Hervé; Perro, Gérard

    2011-02-01

    Infection is a major problem in burn care and especially when it is due to bacteria with hospital-acquired multi-resistance to antibiotics. Moreover, when these bacteria are Gram-negative organisms, the most effective molecules are 20 years old and there is little hope of any new product available even in the distant future. Therefore, it is obvious that currently available antibiotics should not be misused. With this aim in mind, the following review was conducted by a group of experts from the French Society for Burn Injuries (SFETB). It examined key points addressing the management of antibiotics for burn patients: when to use or not, time of onset, bactericidia, combination, adaptation, de-escalation, treatment duration and regimen based on pharmacokinetic and pharmacodynamic characteristics of these compounds. The authors also considered antibioprophylaxis and some other key points such as: infection diagnosis criteria, bacterial inoculae and local treatment. French guidelines for the use of antibiotics in burn patients have been designed up from this work.

  15. Proteome studies of bacterial antibiotic resistance mechanisms.

    PubMed

    Vranakis, Iosif; Goniotakis, Ioannis; Psaroulaki, Anna; Sandalakis, Vassilios; Tselentis, Yannis; Gevaert, Kris; Tsiotis, Georgios

    2014-01-31

    Ever since antibiotics were used to help humanity battle infectious diseases, microorganisms straight away fought back. Antibiotic resistance mechanisms indeed provide microbes with possibilities to by-pass and survive the action of antibiotic drugs. Several methods have been employed to identify these microbial resistance mechanisms in an ongoing effort to reduce the steadily increasing number of treatment failures due to multi-drug-resistant microbes. Proteomics has evolved to an important tool for this area of research. Following rapid advances in whole genome sequencing, proteomic technologies have been widely used to investigate microbial gene expression. This review highlights the contribution of proteomics in identifying microbial drug resistance mechanisms. It summarizes different proteomic studies on bacteria resistant to different antibiotic drugs. The review further includes an overview of the methodologies used, as well as lists key proteins identified, thus providing the reader not only a summary of research already done, but also directions for future research. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.

  16. Biotechnology of polyketides: New breath of life for the novel antibiotic genetic pathways discovery through metagenomics

    PubMed Central

    Gomes, Elisângela Soares; Schuch, Viviane; de Macedo Lemos, Eliana Gertrudes

    2013-01-01

    The discovery of secondary metabolites produced by microorganisms (e.g., penicillin in 1928) and the beginning of their industrial application (1940) opened new doors to what has been the main medication source for the treatment of infectious diseases and tumors. In fact, approximately 80 years after the discovery of the first antibiotic compound, and despite all of the warnings about the failure of the “goose that laid the golden egg,” the potential of this wealth is still inexorable: simply adjust the focus from “micro” to “nano”, that means changing the look from microorganisms to nanograms of DNA. Then, the search for new drugs, driven by genetic engineering combined with metagenomic strategies, shows us a way to bypass the barriers imposed by methodologies limited to isolation and culturing. However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens. Although the first advances in genetic engineering date back to 1990, there is still a lack of high-throughput methods to speed up the screening of new genes and design new molecules by recombination of pathways. In addition, it is necessary an increase in the variety of heterologous hosts and improvements throughout the full drug discovery pipeline. Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways. In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms. PMID:24688489

  17. Biotechnology of polyketides: new breath of life for the novel antibiotic genetic pathways discovery through metagenomics.

    PubMed

    Gomes, Elisângela Soares; Schuch, Viviane; de Macedo Lemos, Eliana Gertrudes

    2013-12-01

    The discovery of secondary metabolites produced by microorganisms (e.g., penicillin in 1928) and the beginning of their industrial application (1940) opened new doors to what has been the main medication source for the treatment of infectious diseases and tumors. In fact, approximately 80 years after the discovery of the first antibiotic compound, and despite all of the warnings about the failure of the "goose that laid the golden egg," the potential of this wealth is still inexorable: simply adjust the focus from "micro" to "nano", that means changing the look from microorganisms to nanograms of DNA. Then, the search for new drugs, driven by genetic engineering combined with metagenomic strategies, shows us a way to bypass the barriers imposed by methodologies limited to isolation and culturing. However, we are far from solving the problem of supplying new molecules that are effective against the plasticity of multi- or pan-drug-resistant pathogens. Although the first advances in genetic engineering date back to 1990, there is still a lack of high-throughput methods to speed up the screening of new genes and design new molecules by recombination of pathways. In addition, it is necessary an increase in the variety of heterologous hosts and improvements throughout the full drug discovery pipeline. Among numerous studies focused on this subject, those on polyketide antibiotics stand out for the large technical-scientific efforts that established novel solutions for the transfer/engineering of major metabolic pathways using transposons and other episomes, overcoming one of the main methodological constraints for the heterologous expression of major pathways. In silico prediction analysis of three-dimensional enzymatic structures and advances in sequencing technologies have expanded access to the metabolic potential of microorganisms.

  18. Ultra High Bypass Integrated System Test

    NASA Image and Video Library

    2015-09-14

    NASA’s Environmentally Responsible Aviation Project, in collaboration with the Federal Aviation Administration (FAA) and Pratt & Whitney, completed testing of an Ultra High Bypass Ratio Turbofan Model in the 9’ x 15’ Low Speed Wind Tunnel at NASA Glenn Research Center. The fan model is representative of the next generation of efficient and quiet Ultra High Bypass Ratio Turbofan Engine designs.

  19. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Bypass. 403.17 Section 403.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRE-TREAT-MENT REGULATIONS FOR EXIST-ING AND NEW SOURCES OF POLLUTION § 403.17 Bypass....

  20. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Definitions. (1) Bypass means the intentional diversion of wastestreams from any portion of an Industrial User... applicable Pretreatment Standards or Requirements. An Industrial User may allow any bypass to occur which... paragraphs (c) and (d) of this section. (c) Notice. (1) If an Industrial User knows in advance of the...

  1. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Bypass. 403.17 Section 403.17 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRE-TREAT-MENT REGULATIONS FOR EXIST-ING AND NEW SOURCES OF POLLUTION § 403.17 Bypass....

  2. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... bypass, such as the use of auxiliary treatment facilities, retention of untreated wastes, or maintenance... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRETREATMENT REGULATIONS FOR EXISTING AND NEW SOURCES OF POLLUTION § 403.17 Bypass. (a...

  3. 40 CFR 403.17 - Bypass.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... bypass, such as the use of auxiliary treatment facilities, retention of untreated wastes, or maintenance... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GENERAL PRETREATMENT REGULATIONS FOR EXISTING AND NEW SOURCES OF POLLUTION § 403.17 Bypass. (a...

  4. Engineering persister-specific antibiotics with synergistic antimicrobial functions.

    PubMed

    Schmidt, Nathan W; Deshayes, Stephanie; Hawker, Sinead; Blacker, Alyssa; Kasko, Andrea M; Wong, Gerard C L

    2014-09-23

    Most antibiotics target growth processes and are ineffective against persister bacterial cells, which tolerate antibiotics due to their reduced metabolic activity. These persisters act as a genetic reservoir for resistant mutants and constitute a root cause of antibiotic resistance, a worldwide problem in human health. We re-engineer antibiotics specifically for persisters using tobramycin, an aminoglycoside antibiotic that targets bacterial ribosomes but is ineffective against persisters with low metabolic and cellular transport activity. By giving tobramycin the ability to induce nanoscopic negative Gaussian membrane curvature via addition of 12 amino acids, we transform tobramycin itself into a transporter sequence. The resulting molecule spontaneously permeates membranes, retains the high antibiotic activity of aminoglycosides, kills E. coli and S. aureus persisters 4-6 logs better than tobramycin, but remains noncytotoxic to eukaryotes. These results suggest a promising paradigm to renovate traditional antibiotics.

  5. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex, E [Brookfield, IL; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL; Diaz, Rocio [Chicago, IL; Vukovic, Lela [Westchester, IL

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  6. Bypass Surgery in Limb Salvage: Polytetrafluoroethylene Prosthetic Bypass

    PubMed Central

    Naoum, Joseph J.; Arbid, Elias J.

    2012-01-01

    Polytetrafluoroethylene (PTFE) grafts have proven to be an adequate alternative conduit for peripheral bypass operations. Whether or not one uses PTFE depends on several factors: surgeon preference, individual patient circumstances, or when autologous greater saphenous vein is not available or adequate. These conventional grafts have evolved and undergone modification. The intraluminal surface has been coated with carbon or bonded with heparin. The structure of grafts has been modified with the creation of a hood or cuff, with the incorporation of a stent-graft segment for a sutureless anastomosis, or the fusion of PTFE with an outer polyester layer to minimize suture hole bleeding. This evolution intends to limit graft thrombogenicity, ameliorate the formation of intimal hyperplasia, decrease complications, and improve overall graft patency. PMID:23342188

  7. The antibiotics in the chemical space.

    PubMed

    Gualtieri, Maxime; Banéres-Roquet, Françoise; Villain-Guillot, Philippe; Pugnière, Martine; Leonetti, Jean-Paul

    2009-01-01

    Ensuring the availability of new antibiotics to eradicate resistant pathogens is a critical issue, but very few new antibacterials have been recently commercialized. In an effort to rationalize their discovery process, the industry has utilized chemical library and high-throughput approaches already applied in other therapeutical areas to generate new antibiotics. This strategy has turned out to be poorly adapted to the reality of antibacterial discovery. Commercial chemical libraries contain molecules with specific molecular properties, and unfortunately systemic antibacterials are more hydrophilic and have more complex structures. These factors are critical, since hydrophobic antibiotics are generally inactive in the presence of serum. Here, we review how the skewed distribution of systemic antibiotics in chemical space influences the discovery process.

  8. Combating Antibiotic Resistance

    MedlinePlus

    ... For Consumers Home For Consumers Consumer Updates Combating Antibiotic Resistance Share Tweet Linkedin Pin it More sharing options ... however, have contributed to a phenomenon known as antibiotic resistance. This resistance develops when potentially harmful bacteria change ...

  9. Antibiotic-Associated Diarrhea

    MedlinePlus

    ... treatment. C. difficile infection C. difficile is a toxin-producing bacteria that causes antibiotic-associated colitis, which ... doctor feels they're necessary. Antibiotics can treat bacterial infections, but they won't help viral infections, ...

  10. Neuropsychological changes after cardiopulmonary bypass for coronary artery bypass grafting.

    PubMed

    Wimmer-Greinecker, G; Matheis, G; Brieden, M; Dietrich, M; Oremek, G; Westphal, K; Winkelmann, B R; Moritz, A

    1998-08-01

    An alarming incidence (1% to 83%) of neuropsychological dysfunction has been reported after operations using cardiopulmonary bypass (CPB). The present clinical study re-evaluates these complications with current CPB technology in a strictly selected low-risk group of coronary artery bypass (CABG) patients. 76 CABG patients, without history of stroke or internal carotid artery stenosis, were examined before, 5 days after, and 2 months after surgery. A neuropsychological test battery was employed according to the "Statement of Consensus on Assessment of Neurobehavioral Outcomes after Cardiac Surgery". Tests include the Block Design Test (problem-solving strategies, recognition and analysis of forms), the Trail Making Test (cognitive achievement at speed), and the Digit Span Test (short-term memory and memory of figures). Both postoperative test scores were not significantly decreased as compared to preoperative values. In contrast, neuron specific enolase (NSE) and S100 b protein, biochemical markers of cerebral injury, increased markedly during and immediately after surgery (NSE preop.: 7.07 +/- 2.40 ng/ml, 1 h postop.: 13.64 +/- 4.50 ng/ml, p < 0.001; S100 b preop.: 0.04 +/- 0.07 ng/ml, after crossclamp: 0.90 +/- 0.69 ng/ml, p < 0.001). One patient displayed postoperative transitional syndrome, another patient suffered from transitory paresis and hypesthesia of the left arm, which disappeared during hospital stay. Biochemical markers demonstrate significant postoperative cerebral injury during and immediately after CPB. However, CPB for CABG does not lead to marked impairment of neuropsychological scores, and clinically relevant neurological findings were observed in one patient only.

  11. Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

    PubMed Central

    Liu, Gang; Chandra, Govind; Niu, Guoqing

    2013-01-01

    SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

  12. Molecular regulation of antibiotic biosynthesis in streptomyces.

    PubMed

    Liu, Gang; Chater, Keith F; Chandra, Govind; Niu, Guoqing; Tan, Huarong

    2013-03-01

    Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes.

  13. Combined endovascular and surgical treatment of infected carotid-carotid bypass graft.

    PubMed

    Younis, George; Reul, George J; Krajcer, Zvonimir

    2006-10-01

    To present a complex case involving an infected carotid-carotid bypass graft that was successfully treated with a stent-graft and subsequent surgical removal of the infected graft. A 75-year-old woman presented with persistent purulent drainage of an infected and exposed carotid-carotid prosthetic bypass graft. Wound cultures revealed methicillin-resistant Staphylococcus aureus. She was treated with appropriate intravenous antibiotic therapy without improvement in wound drainage. Because of her comorbid conditions, a decision was made to pursue endovascular revascularization of her left and right common carotid arteries (CCA), with subsequent surgical removal of the infected prosthetic graft. The patient underwent balloon angioplasty; a 7x18-mm Omnilink stent was deployed in the innominate artery and a 7x18-mm Herculink stent in the ostial left CCA. During the same procedure, the carotid-carotid bypass graft was excluded with deployment of an 8x50-mm Viabahn stent-graft in the right CCA. Several days later, the infected and now thrombosed carotid-carotid bypass graft was surgically removed, and an area of adjacent muscle was used to patch the previously excluded connection of the bypass from the right CCA. A saphenous vein patch was used to repair the defect in the left CCA. Her postoperative course was uneventful. At 1 year, the clinical and duplex examinations revealed satisfactory wound healing and patent left and right CCAs. This case indicates that a combined endovascular and surgical approach may be a safe and effective option in the treatment of carotid-carotid bypass graft infection.

  14. Finding alternatives to antibiotics

    USDA-ARS?s Scientific Manuscript database

    The spread of antibiotic-resistant pathogens requires new treatments. The availability of new antibiotics has severely declined, and so alternatives to antibiotics need to be considered in both animal agriculture and human medicine. Products for disease prevention are different than products for d...

  15. Antibiotic resistant in microorganisms

    USDA-ARS?s Scientific Manuscript database

    Antimicrobial agents are necessary for use in veterinary medicine including the production of food producing animals. Antibiotic use is indicated for the treatment of bacterial target organisms and/or disease for which the antibiotic was developed. However, an unintended consequence of antibiotic ...

  16. Capacity analysis of a bypass of roundabouts

    NASA Astrophysics Data System (ADS)

    Sedlačik, Ivan; Slabý, Petr

    2017-09-01

    The capacity of the roads network mainly depends on the capacity of its nodal points - intersections. A connecting branch or a bypass is a lane or lanes inserted between two adjacent branches of a roundabout, providing redirection of vehicles, that would otherwise burden a circular lane. A bypass effect to the capacity of roundabouts, but also other types of level intersections, is undeniable. A connecting branch increases the total capacity of an intersection that takes a part of vehicles performing a manoeuver of the first right turn completely out of an intersection area. Redirecting vehicles reduces delay times at intersections and reduces queues at the entrance to an intersection. Bypasses improve the quality of transport. Limiting for the capacity of bypasses is the point of disconnection from the entrance into the roundabout and the connection point into the exit from the roundabout. Central parts of the bypasses have minimal effects on the capacity. The length of a bypass has to match with the maximum length of a queue of waiting vehicles at a given intensity level. The article deals with analysis of the bypass capacity at the roundabouts.

  17. Gastric bypass reversal: a 7-year experience.

    PubMed

    Pernar, Luise I M; Kim, Julie J; Shikora, Scott A

    After gastric bypass, some patients develop conditions that ultimately require reversal of the bypass. There are currently few publications on the topic to guide clinicians. To describe the indications, techniques, and outcomes for gastric bypass reversal. Two academic medical centers. We conducted a retrospective chart review of all patients who underwent gastric bypass reversal at our institutions between 2008 and 2015. Information regarding the original operation, the indications for reversal, procedures performed, and the postoperative outcomes were collected and analyzed. Nineteen patients underwent gastric bypass reversal. All but 4 reversal operations were performed laparoscopically. The indications for reversal were malnutrition or excessive weight loss (6 patients); chronic nausea, vomiting, and abdominal pain (5); neuroglycopenia (4); massive small bowel loss due to internal hernia (3); and need for surveillance gastric endoscopy (1). In the perioperative period, 4 patients had a complication that required intervention. Five patients required additional delayed procedures. One patient was lost to follow-up. The remaining patients' mean follow-up was 22±18 months. Symptoms that prompted reversal of the gastric bypass resolved in the majority of patients. However, 1 patient's hypoglycemia did not resolve and 2 continued to have diarrhea. Six patients were weaned off of total parenteral nutrition. Laparoscopic gastric bypass reversal is feasible and well tolerated. The procedure can be employed to treat a variety of conditions that may occur after gastric bypass and the majority of patients benefit, with resolution of symptoms. In a carefully selected patient population, gastric bypass reversal should be considered if conservative approaches to adverse conditions fail. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  18. Gastric bypass reduces fat intake and preference.

    PubMed

    le Roux, Carel W; Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R; Spector, Alan C; Olbers, Torsten; Lutz, Thomas A

    2011-10-01

    Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation.

  19. Gastric bypass reduces fat intake and preference

    PubMed Central

    Bueter, Marco; Theis, Nadine; Werling, Malin; Ashrafian, Hutan; Löwenstein, Christian; Athanasiou, Thanos; Bloom, Stephen R.; Spector, Alan C.; Olbers, Torsten; Lutz, Thomas A.

    2011-01-01

    Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation. PMID:21734019

  20. Systemic antibiotics in periodontics.

    PubMed

    Slots, Jørgen

    2004-11-01

    This position paper addresses the role of systemic antibiotics in the treatment of periodontal disease. Topical antibiotic therapy is not discussed here. The paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. The document consists of three sections: 1) concept of antibiotic periodontal therapy; 2) efficacy of antibiotic periodontal therapy; and 3) practical aspects of antibiotic periodontal therapy. The conclusions drawn in this paper represent the position of the American Academy of Periodontology and are intended for the information of the dental profession.

  1. Bearing-bypass material system test

    NASA Astrophysics Data System (ADS)

    Crew, John H., Jr.

    1988-01-01

    A material specimen containing a central hole is bolted between two bearing guide plates. An applied load control exerts an applied load, either tension or compression, to one end of the specimen and a bypass load control applies a bypass load to the other end of the specimen. Both load controls have their control inputs supplied by a single input signal generator. The difference between the applied load and the bypass load is transmitted through the bolt and plate to the bearing load cells.

  2. 21 CFR 870.4380 - Cardiopulmonary bypass pump speed control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass pump speed control. 870... Cardiopulmonary bypass pump speed control. (a) Identification. A cardiopulmonary bypass pump speed control is a... control the speed of blood pumps used in cardiopulmonary bypass surgery. (b) Classification. Class...

  3. 21 CFR 870.4380 - Cardiopulmonary bypass pump speed control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass pump speed control. 870... Cardiopulmonary bypass pump speed control. (a) Identification. A cardiopulmonary bypass pump speed control is a... control the speed of blood pumps used in cardiopulmonary bypass surgery. (b) Classification. Class...

  4. 21 CFR 870.4380 - Cardiopulmonary bypass pump speed control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass pump speed control. 870... Cardiopulmonary bypass pump speed control. (a) Identification. A cardiopulmonary bypass pump speed control is a... control the speed of blood pumps used in cardiopulmonary bypass surgery. (b) Classification. Class...

  5. 21 CFR 870.4380 - Cardiopulmonary bypass pump speed control.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass pump speed control. 870... Cardiopulmonary bypass pump speed control. (a) Identification. A cardiopulmonary bypass pump speed control is a... control the speed of blood pumps used in cardiopulmonary bypass surgery. (b) Classification. Class...

  6. 30 CFR 56.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overtravel by-pass switches. 56.19018 Section... Hoisting Hoists § 56.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall...

  7. 30 CFR 57.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Overtravel by-pass switches. 57.19018 Section... Hoisting Hoists § 57.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall...

  8. 21 CFR 870.4380 - Cardiopulmonary bypass pump speed control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pump speed control. 870... Cardiopulmonary bypass pump speed control. (a) Identification. A cardiopulmonary bypass pump speed control is a... control the speed of blood pumps used in cardiopulmonary bypass surgery. (b) Classification. Class...

  9. 30 CFR 57.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Overtravel by-pass switches. 57.19018 Section... Hoisting Hoists § 57.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  10. 30 CFR 57.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Overtravel by-pass switches. 57.19018 Section... Hoisting Hoists § 57.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  11. 30 CFR 56.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Overtravel by-pass switches. 56.19018 Section... Hoisting Hoists § 56.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  12. 30 CFR 56.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Overtravel by-pass switches. 56.19018 Section... Hoisting Hoists § 56.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  13. 30 CFR 57.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Overtravel by-pass switches. 57.19018 Section... Hoisting Hoists § 57.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  14. 30 CFR 57.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Overtravel by-pass switches. 57.19018 Section... Hoisting Hoists § 57.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  15. 30 CFR 56.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Overtravel by-pass switches. 56.19018 Section... Hoisting Hoists § 56.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  16. 30 CFR 56.19018 - Overtravel by-pass switches.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Overtravel by-pass switches. 56.19018 Section... Hoisting Hoists § 56.19018 Overtravel by-pass switches. When an overtravel by-pass switch is installed, the... switch is held in the closed position by the hoistman. The overtravel by-pass switch shall return...

  17. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass coronary pressure gauge... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood...

  18. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass coronary pressure gauge...

  19. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass coronary pressure gauge...

  20. 21 CFR 870.4310 - Cardiopulmonary bypass coronary pressure gauge.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Cardiopulmonary bypass coronary pressure gauge. (a) Identification. A cardiopulmonary bypass coronary pressure gauge is a device used in cardiopulmonary bypass surgery to measure the pressure of the blood perfusing... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass coronary pressure gauge...

  1. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the bypass...

  2. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the bypass...

  3. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the bypass...

  4. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the bypass...

  5. 21 CFR 870.4400 - Cardiopulmonary bypass blood reservoir.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass blood reservoir. 870.4400... bypass blood reservoir. (a) Identification. A cardiopulmonary bypass blood reservoir is a device used in conjunction with short-term extracorporeal circulation devices to hold a reserve supply of blood in the bypass...

  6. Tensions in Antibiotic Prescribing

    PubMed Central

    Metlay, Joshua P; Shea, Judy A; Crossette, Linda B; Asch, David A

    2002-01-01

    BACKGROUND To reduce the prevalence of antibiotic-resistant bacteria in the community, physicians must optimize their use of antibiotics. However, optimal use from the perspective of the community (reserving newer agents for future use) is not always consistent with optimal use from the perspective of the individual patient (prescribing newer, broader agents). OBJECTIVES To identify preferred patterns of antibiotic prescribing for patients with community-acquired pneumonia (CAP), measure explicit attitudes toward antibiotics and antibiotic resistance, and determine the relationship between these prescribing patterns and attitudes. DESIGN Cross-sectional anonymous mail survey. PARTICIPANTS National random sample of 400 generalist physicians (general internal medicine and family practice) and 429 infectious diseases specialists. MEASUREMENTS Rank ordering of antibiotic preferences for a hypothetical outpatient with CAP and reasons for antibiotic selection. Endorsement of attitudes regarding antibiotic prescribing decisions and resistance. RESULTS Both generalists and infectious diseases specialists were more likely to prefer newer, broader drugs for the treatment of CAP compared to older agents still recommended by national guidelines. Physicians rated the issue of contributing to antibiotic resistance lowest among 7 determinants of their choices. CONCLUSIONS Despite national guidelines and increasing public awareness, the public health concern of contributing to the problem of antibiotic resistance does not exert a strong impact on physician prescribing decisions for CAP. Future efforts to optimize antibiotic prescribing decisions will need to consider options for increasing the impact of public health issues on the patient-oriented decisions of individual physicians. PMID:11841523

  7. Antibiotic resistance in Chlamydiae.

    PubMed

    Sandoz, Kelsi M; Rockey, Daniel D

    2010-09-01

    There are few documented reports of antibiotic resistance in Chlamydia and no examples of natural and stable antibiotic resistance in strains collected from humans. While there are several reports of clinical isolates exhibiting resistance to antibiotics, these strains either lost their resistance phenotype in vitro, or lost viability altogether. Differences in procedures for chlamydial culture in the laboratory, low recovery rates of clinical isolates and the unknown significance of heterotypic resistance observed in culture may interfere with the recognition and interpretation of antibiotic resistance. Although antibiotic resistance has not emerged in chlamydiae pathogenic to humans, several lines of evidence suggest they are capable of expressing significant resistant phenotypes. The adept ability of chlamydiae to evolve to antibiotic resistance in vitro is demonstrated by contemporary examples of mutagenesis, recombination and genetic transformation. The isolation of tetracycline-resistant Chlamydia suis strains from pigs also emphasizes their adaptive ability to acquire antibiotic resistance genes when exposed to significant selective pressure.

  8. Interstellar molecules

    NASA Technical Reports Server (NTRS)

    Townes, C. H.

    1976-01-01

    Progress in the discovery and study of interstellar molecules is summarized. The 36 molecular species thus far identified in interstellar space are listed in several groups which include simple hydrides, oxides, and sulfides, various derivatives of ammonia, molecules involving linear carbon chains, cyanides, and molecules related in structure to formaldehyde, alcohols, or ethers. Several free radicals are described, the discovery of molecules in external galaxies is discussed, and possible mechanisms for molecular formation are noted. Methods for examining relative isotopic abundances by measuring molecules in interstellar clouds are outlined, mechanisms for the excitation of interstellar molecules are reviewed, and values are presented for the C-12/C-13 abundance ratio in a number of interstellar clouds. The detection of interstellar masers is discussed along with pumping mechanisms and masing transitions in H2CO, CH, OH, and SiO. The nature of dense interstellar clouds is examined in terms of several simple and complex cloud models, with emphasis on multiple condensation models.

  9. Antibiotics in Canadian poultry productions and anticipated alternatives

    PubMed Central

    Diarra, Moussa S.; Malouin, François

    2014-01-01

    The use of antibiotics in food-producing animals has significantly increased animal health by lowering mortality and the incidence of diseases. Antibiotics also have largely contributed to increase productivity of farms. However, antibiotic usage in general and relevance of non-therapeutic antibiotics (growth promoters) in feed need to be reevaluated especially because bacterial pathogens of humans and animals have developed and shared a variety of antibiotic resistance mechanisms that can easily be spread within microbial communities. In Canada, poultry production involves more than 2600 regulated chicken producers who have access to several antibiotics approved as feed additives for poultry. Feed recipes and mixtures vary greatly geographically and from one farm to another, making links between use of a specific antibiotic feed additive and production yields or selection of specific antibiotic-resistant bacteria difficult to establish. Many on-farm studies have revealed the widespread presence of antibiotic-resistant bacteria in broiler chickens. While some reports linked the presence of antibiotic-resistant organisms to the use of feed supplemented with antibiotics, no recent studies could clearly demonstrate the benefit of antimicrobial growth promoters on performance and production yields. With modern biosecurity and hygienic practices, there is a genuine concern that intensive utilization of antibiotics or use of antimicrobial growth promoters in feed might no longer be useful. Public pressure and concerns about food and environmental safety (antibiotic residues, antibiotic-resistant pathogens) have driven researchers to actively look for alternatives to antibiotics. Some of the alternatives include pre- and probiotics, organic acids and essential oils. We will describe here the properties of some bioactive molecules, like those found in cranberry, which have shown interesting polyvalent antibacterial and immuno-stimulatory activities. PMID:24987390

  10. Antibiotics in Canadian poultry productions and anticipated alternatives.

    PubMed

    Diarra, Moussa S; Malouin, François

    2014-01-01

    The use of antibiotics in food-producing animals has significantly increased animal health by lowering mortality and the incidence of diseases. Antibiotics also have largely contributed to increase productivity of farms. However, antibiotic usage in general and relevance of non-therapeutic antibiotics (growth promoters) in feed need to be reevaluated especially because bacterial pathogens of humans and animals have developed and shared a variety of antibiotic resistance mechanisms that can easily be spread within microbial communities. In Canada, poultry production involves more than 2600 regulated chicken producers who have access to several antibiotics approved as feed additives for poultry. Feed recipes and mixtures vary greatly geographically and from one farm to another, making links between use of a specific antibiotic feed additive and production yields or selection of specific antibiotic-resistant bacteria difficult to establish. Many on-farm studies have revealed the widespread presence of antibiotic-resistant bacteria in broiler chickens. While some reports linked the presence of antibiotic-resistant organisms to the use of feed supplemented with antibiotics, no recent studies could clearly demonstrate the benefit of antimicrobial growth promoters on performance and production yields. With modern biosecurity and hygienic practices, there is a genuine concern that intensive utilization of antibiotics or use of antimicrobial growth promoters in feed might no longer be useful. Public pressure and concerns about food and environmental safety (antibiotic residues, antibiotic-resistant pathogens) have driven researchers to actively look for alternatives to antibiotics. Some of the alternatives include pre- and probiotics, organic acids and essential oils. We will describe here the properties of some bioactive molecules, like those found in cranberry, which have shown interesting polyvalent antibacterial and immuno-stimulatory activities.

  11. Frataxin-bypassing Isu1: characterization of the bypass activity in cells and mitochondria.

    PubMed

    Yoon, Heeyong; Knight, Simon A B; Pandey, Alok; Pain, Jayashree; Zhang, Yan; Pain, Debkumar; Dancis, Andrew

    2014-04-01

    Frataxin is a conserved mitochondrial protein, and deficiency underlies the neurodegenerative disease Friedreich's ataxia. Frataxin interacts with the core machinery for Fe-S cluster assembly in mitochondria. Recently we reported that in frataxin-deleted yeast strains, a spontaneously occurring mutation in one of two genes encoding redundant Isu scaffold proteins, bypassed the mutant phenotypes. In the present study we created strains expressing a single scaffold protein, either Isu1 or the bypass mutant M107I Isu1. Our results show that in the frataxin-deletion strain expressing the bypass mutant Isu1, cell growth, Fe-S cluster protein activities, haem proteins and iron homoeostasis were restored to normal or close to normal. The bypass effects were not mediated by changes in Isu1 expression level. The persulfide-forming activity of the cysteine desulfurase was diminished in the frataxin deletion (∆yfh1 ISU1) and was improved by expression of the bypass Isu1 (∆yfh1 M107I ISU1). The addition of purified bypass M107I Isu1 protein to a ∆yfh1 lysate conferred similar enhancement of cysteine desulfurase as did frataxin, suggesting that this effect contributed to the bypass mechanism. Fe-S cluster-forming activity in isolated mitochondria was stimulated by the bypass Isu1, albeit at a lower rate. The rescuing effects of the bypass Isu1 point to ways that the core defects in Friedreich's ataxia mitochondria can be restored.

  12. Exhaust gas bypass valve control for thermoelectric generator

    SciTech Connect

    Reynolds, Michael G; Yang, Jihui; Meisner, Greogry P.; Stabler, Francis R.; De Bock, Hendrik Pieter Jacobus; Anderson, Todd Alan

    2012-09-04

    A method of controlling engine exhaust flow through at least one of an exhaust bypass and a thermoelectric device via a bypass valve is provided. The method includes: determining a mass flow of exhaust exiting an engine; determining a desired exhaust pressure based on the mass flow of exhaust; comparing the desired exhaust pressure to a determined exhaust pressure; and determining a bypass valve control value based on the comparing, wherein the bypass valve control value is used to control the bypass valve.

  13. Gastric infarction following gastric bypass surgery.

    PubMed

    Do, Patrick H; Kang, Young S; Cahill, Peter

    2016-04-01

    Gastric infarction is an extremely rare occurrence owing to the stomach's extensive vascular supply. We report an unusual case of gastric infarction following gastric bypass surgery. We describe the imaging findings and discuss possible causes of this condition.

  14. Heart bypass surgery - minimally invasive - discharge

    MedlinePlus

    ... thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest . 2012;141(2 ... bypass surgery - minimally invasive Heart failure - overview High blood cholesterol ...

  15. Ribosomal Antibiotics: Contemporary Challenges

    PubMed Central

    Auerbach-Nevo, Tamar; Baram, David; Bashan, Anat; Belousoff, Matthew; Breiner, Elinor; Davidovich, Chen; Cimicata, Giuseppe; Eyal, Zohar; Halfon, Yehuda; Krupkin, Miri; Matzov, Donna; Metz, Markus; Rufayda, Mruwat; Peretz, Moshe; Pick, Ophir; Pyetan, Erez; Rozenberg, Haim; Shalev-Benami, Moran; Wekselman, Itai; Zarivach, Raz; Zimmerman, Ella; Assis, Nofar; Bloch, Joel; Israeli, Hadar; Kalaora, Rinat; Lim, Lisha; Sade-Falk, Ofir; Shapira, Tal; Taha-Salaime, Leena; Tang, Hua; Yonath, Ada

    2016-01-01

    Most ribosomal antibiotics obstruct distinct ribosomal functions. In selected cases, in addition to paralyzing vital ribosomal tasks, some ribosomal antibiotics are involved in cellular regulation. Owing to the global rapid increase in the appearance of multi-drug resistance in pathogenic bacterial strains, and to the extremely slow progress in developing new antibiotics worldwide, it seems that, in addition to the traditional attempts at improving current antibiotics and the intensive screening for additional natural compounds, this field should undergo substantial conceptual revision. Here, we highlight several contemporary issues, including challenging the common preference of broad-range antibiotics; the marginal attention to alterations in the microbiome population resulting from antibiotics usage, and the insufficient awareness of ecological and environmental aspects of antibiotics usage. We also highlight recent advances in the identification of species-specific structural motifs that may be exploited for the design and the creation of novel, environmental friendly, degradable, antibiotic types, with a better distinction between pathogens and useful bacterial species in the microbiome. Thus, these studies are leading towards the design of “pathogen-specific antibiotics,” in contrast to the current preference of broad range antibiotics, partially because it requires significant efforts in speeding up the discovery of the unique species motifs as well as the clinical pathogen identification. PMID:27367739

  16. Bypass diode for a solar cell

    DOEpatents

    Rim, Seung Bum [Palo Alto, CA; Kim, Taeseok [San Jose, CA; Smith, David D [Campbell, CA; Cousins, Peter J [Menlo Park, CA

    2012-03-13

    Bypass diodes for solar cells are described. In one embodiment, a bypass diode for a solar cell includes a substrate of the solar cell. A first conductive region is disposed above the substrate, the first conductive region of a first conductivity type. A second conductive region is disposed on the first conductive region, the second conductive region of a second conductivity type opposite the first conductivity type.

  17. Prophylactic digitalization for coronary artery bypass surgery.

    PubMed

    Johnson, L W; Dickstein, R A; Fruehan, C T; Kane, P; Potts, J L; Smulyan, H; Webb, W R; Eich, R H

    1976-05-01

    One hundred and twenty patients undergoing aortocoronary bypass procedures were randomly placed into control and digitalized groups. All were initially in normal sinus rhythm and without evidence of congestive heart failure. Supraventricular arrhythmias occurred in 17 of 66 controls and in only three of 54 digitalized patients (P less than 0.01). There was no evidence of digitals toxicity. Based on this evidence we recommend prophylactic digitalization for patients having aortocoronary bypass operations.

  18. The Dalles Dam juvenile bypass electrical systems

    SciTech Connect

    Bannister, B.D.; Luck, B.

    1995-12-31

    The Corps of Engineers is in the process of providing a juvenile fish bypass system at The Dalles Lock and Dam project on the lower Columbia River. This system is intended to preserve and enhance the dwindling stocks of wild anadromous fish. The impact of the proposed facilities on the electrical systems and on plant operations are developed along with descriptions of the special bypass features including the incorporation of provisions for a future small hydropower generator.

  19. Monsanto may bypass NIH in microbe test.

    PubMed

    Sun, Marjorie

    1985-01-11

    The Monsanto Company is planning to ask the Environmental Protection Agency for clearance to field test a genetically engineered microbial pesticide, bypassing the traditional approval process of the National Institutes of Health. Although only federally funded institutions are required to obtain NIH approval for genetic engineering tests, Monsanto is the first company to bypass the NIH regulatory process, which has become mired in a lawsuit brought by Jeremy Rifkin.

  20. MHD Energy Bypass Scramjet Engine

    NASA Technical Reports Server (NTRS)

    Mehta, Unmeel B.; Bogdanoff, David W.; Park, Chul; Arnold, Jim (Technical Monitor)

    2001-01-01

    Revolutionary rather than evolutionary changes in propulsion systems are most likely to decrease cost of space transportation and to provide a global range capability. Hypersonic air-breathing propulsion is a revolutionary propulsion system. The performance of scramjet engines can be improved by the AJAX energy management concept. A magneto-hydro-dynamics (MHD) generator controls the flow and extracts flow energy in the engine inlet and a MHD accelerator downstream of the combustor accelerates the nozzle flow. A progress report toward developing the MHD technology is presented herein. Recent theoretical efforts are reviewed and ongoing experimental efforts are discussed. The latter efforts also include an ongoing collaboration between NASA, the US Air Force Research Laboratory, US industry, and Russian scientific organizations. Two of the critical technologies, the ionization of the air and the MHD accelerator, are briefly discussed. Examples of limiting the combustor entrance Mach number to a low supersonic value with a MHD energy bypass scheme are presented, demonstrating an improvement in scramjet performance. The results for a simplified design of an aerospace plane show that the specific impulse of the MHD-bypass system is better than the non-MHD system and typical rocket over a narrow region of flight speeds and design parameters. Equilibrium ionization and non-equilibrium ionization are discussed. The thermodynamic condition of air at the entrance of the engine inlet determines the method of ionization. The required external power for non-equilibrium ionization is computed. There have been many experiments in which electrical power generation has successfully been achieved by magneto-hydrodynamic (MHD) means. However, relatively few experiments have been made to date for the reverse case of achieving gas acceleration by the MHD means. An experiment in a shock tunnel is described in which MHD acceleration is investigated experimentally. MHD has several

  1. Thrust reverser for high bypass turbofan engine

    SciTech Connect

    Matta, R.K.; Bhutiani, P.K.

    1990-05-08

    This patent describes a thrust reverser for a gas turbine engine of the type which includes an outer wall spaced from the center body of a core engine to define a bypass duct therebetween. The thrust reverser comprising: circumferentially displaced blocker doors, each of the doors being movable between a normal position generally aligned with the outer wall and a thrust reversing position extending transversely of the bypass duct for blocking the exhaust of air through the bypass duct and directing the air through an opening in the outer wall for thrust reversal; each of the blocker doors being of lightweight construction and including a pit in the inner surface thereof in the normal position; means for covering the pit during normal flow of air through the bypass duct to reduce the pressure drop in the bypass duct and to reduce noise. The covering means including a pit cover hingedly mounted at one end thereof on the blocker door and means of biasing the pit cover away from the blocker door to a position providing smooth flow of air through the bypass duct during normal operation.

  2. Cardiopulmonary bypass: Evidence or experience based?

    PubMed

    Bartels, Claus; Gerdes, Anja; Babin-Ebell, Jörg; Beyersdorf, Friedhelm; Boeken, Udo; Doenst, Torsten; Feindt, Peter; Heiermann, Michael; Schlensak, Christian; Sievers, Hans-Hinrich

    2002-07-01

    Evidence-based medicine is emerging as a new paradigm for medical practice. The purpose of this study was to evaluate the amount and quality of scientific evidence supporting principles that are currently applied for cardiopulmonary bypass performance. A survey of all German departments of cardiac surgery regarding cardiopulmonary bypass performance disclosed major differences. Consequently, for 48 major principles of cardiopulmonary bypass performance, relevant Medical Subject Headings were identified, and a literature search of the Medline database was performed. Two sequentially applied sets of inclusion-exclusion criteria were selected to assess the best available evidence. Thirty-three thousand articles relating to the subject were identified. Among these, 1500 fulfilled the first set of inclusion criteria: meta-analysis of (randomized) controlled clinical trials and in vitro and animal studies. Rigorous methodological criteria were then applied to further select remaining publications. Ultimately, 225 articles referring to major cardiopulmonary bypass principles were identified as providing the best available evidence. These were graded according to their methodological rigor (susceptibility to bias). The scientific evidence on the investigated cardiopulmonary bypass principles did not prove to be of a high enough level to allow general recommendations to be made. The scientific data concerning the effectiveness and safety of key principles of cardiopulmonary bypass are insufficient in both amount and quality of scientific evidence to serve as a basis for practical, evidence-based guidelines.

  3. Discovery and preclinical development of new antibiotics.

    PubMed

    Hughes, Diarmaid; Karlén, Anders

    2014-05-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted.

  4. [Rational use of antibiotics].

    PubMed

    Walger, P

    2016-06-01

    International and national campaigns draw attention worldwide to the rational use of the available antibiotics. This has been stimulated by the high prevalence rates of drug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), a threatening spread of development of resistance in Gram-negative rod-shaped bacteria and the selection of Clostridium difficile with a simultaneous clear reduction in the development of new antibiotics. The implementation of antibiotic stewardship programs aims to maintain their effectiveness by a rational use of the available antibiotics. The essential target of therapy with antibiotics is successful treatment of individual patients with bacterial infections. The optimal clinical treatment results can only be achieved when the toxicity, selection of pathogens and development of resistance are minimized. This article presents the principles of a rational antibiotic therapy.

  5. Antibiotics and Breastfeeding.

    PubMed

    de Sá Del Fiol, Fernando; Barberato-Filho, Silvio; de Cássia Bergamaschi, Cristiane; Lopes, Luciane Cruz; Gauthier, Timothy P

    2016-01-01

    During the breastfeeding period, bacterial infections can occur in the nursing mother, requiring the use of antibiotics. A lack of accurate information may lead health care professionals and mothers to suspend breastfeeding, which may be unnecessary. This article provides information on the main antibiotics that are appropriate for clinical use and the interference of these antibiotics with the infant to support medical decisions regarding the discontinuation of breastfeeding. We aim to provide information on the pharmacokinetic factors that interfere with the passage of antibiotics into breast milk and the toxicological implications of absorption by the infant. Publications related to the 20 most frequently employed antibiotics and their transfer into breast milk were evaluated. The results demonstrate that most antibiotics in clinical use are considered suitable during breastfeeding; however, the pharmacokinetic profile of each drug must be observed to ensure the resolution of the maternal infection and the safety of the infant.

  6. Platforms for antibiotic discovery.

    PubMed

    Lewis, Kim

    2013-05-01

    The spread of resistant bacteria, leading to untreatable infections, is a major public health threat but the pace of antibiotic discovery to combat these pathogens has slowed down. Most antibiotics were originally isolated by screening soil-derived actinomycetes during the golden era of antibiotic discovery in the 1940s to 1960s. However, diminishing returns from this discovery platform led to its collapse, and efforts to create a new platform based on target-focused screening of large libraries of synthetic compounds failed, in part owing to the lack of penetration of such compounds through the bacterial envelope. This article considers strategies to re-establish viable platforms for antibiotic discovery. These include investigating untapped natural product sources such as uncultured bacteria, establishing rules of compound penetration to enable the development of synthetic antibiotics, developing species-specific antibiotics and identifying prodrugs that have the potential to eradicate dormant persisters, which are often responsible for hard-to-treat infections.

  7. Biotic acts of antibiotics

    PubMed Central

    Aminov, Rustam I.

    2013-01-01

    Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic – in particular mammalian – cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and β-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed. PMID:23966991

  8. Metagenomic small molecule discovery methods

    PubMed Central

    Charlop-Powers, Zachary; Milshteyn, Aleksandr; Brady, Sean F.

    2014-01-01

    Metagenomic approaches to natural product discovery provide the means of harvesting bioactive small molecules synthesized by environmental bacteria without the requirement of first culturing these organisms. Advances in sequencing technologies and general metagenomic methods are beginning to provide the tools necessary to unlock the unexplored biosynthetic potential encoded by the genomes of uncultured environmental bacteria. Here, we highlight recent advances in sequence- and functional- based metagenomic approaches that promise to facilitate antibiotic discovery from diverse environmental microbiomes. PMID:25000402

  9. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  10. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  11. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  12. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  13. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  14. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  15. Brain microvascular function during cardiopulmonary bypass

    SciTech Connect

    Sorensen, H.R.; Husum, B.; Waaben, J.; Andersen, K.; Andersen, L.I.; Gefke, K.; Kaarsen, A.L.; Gjedde, A.

    1987-11-01

    Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.

  16. Changing trends in emergency coronary bypass surgery.

    PubMed

    Maganti, Manjula; Brister, Stephanie J; Yau, Terrence M; Collins, Susan; Badiwala, Mitesh; Rao, Vivek

    2011-10-01

    Patients undergoing emergency coronary artery bypass grafting represent a unique and high-risk population that remains challenging for cardiac surgeons. We examined the changing trends in patients undergoing emergency bypass grafting over the past 20 years. We conducted a retrospective review of our database between 1990 and 2009 and patients were divided into 2 groups based on year of operation: 1990-1999, n = 393; 2000-2009, n = 184. The primary outcomes of interest for this study are operative mortality and incidence of low cardiac output syndrome. The percentage of patients undergoing emergency coronary bypass grafting has decreased from 2.7% to 1.7% over time. The percentage of patients with dyslipidemia, hypertension, triple vessel disease, peripheral vascular disease, and left main disease increased over time (P < .05). Operative mortality remained at 8.1% in both year groups. Preoperative hypertension, congestive heart failure, left ventricular ejection fraction less than 20%, and previous cardiac surgery independently predicted operative mortality by logistic regression analysis. Low cardiac output syndrome developed in 25% of the patient population undergoing emergency bypass grafting. The independent predictors of low cardiac output syndrome were small body surface area, congestive heart failure, shock, myocardial infarction, earlier decade (1990-1999) and increased age. Despite a changing preoperative risk profile, the operative mortality of emergency coronary artery bypass grafting has remained stable over the years. However, mortality remains significantly above the observed mortality in elective bypass grafting. Continued improvements in the management of heart failure and the care of the elderly will likely result in reduced risks of emergency coronary artery bypass grafting. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  17. Sugar-Grafted Cyclodextrin Nanocarrier as a "Trojan Horse" for Potentiating Antibiotic Activity.

    PubMed

    Li, Min; Neoh, Koon Gee; Xu, Liqun; Yuan, Liang; Leong, David Tai; Kang, En-Tang; Chua, Kim Lee; Hsu, Li Yang

    2016-05-01

    The use of "Trojan Horse" nanocarriers for antibiotics to enhance the activity of antibiotics against susceptible and resistant bacteria is investigated. Antibiotic carriers (CD-MAN and CD-GLU) are prepared from β-cyclodextrin grafted with sugar molecules (D-mannose and D-glucose, respectively) via azide-alkyne click reaction. The sugar molecules serve as a chemoattractant enticing the bacteria to take in higher amounts of the antibiotic, resulting in rapid killing of the bacteria. Three types of hydrophobic antibiotics, erythromycin, rifampicin and ciprofloxacin, are used as model drugs and loaded into the carriers. The minimum inhibitory concentration of the antibiotics in the CD-MAN-antibiotic and CD-GLU-antibiotic complexes for Gram-negative Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii strains, and a number of Gram-positive Staphylococcus aureus strains, including the methicillin-resistant strains (MRSA), are reduced by a factor ranging from 3 to >100. The CD-MAN-antibiotic complex is also able to prolong the stability of the loaded antibiotic and inhibit development of intrinsic antibiotic resistance in the bacteria. These non-cytotoxic sugar-modfied nanocarriers can potentiate the activity of existing antibiotics, especially against multidrug-resistant bacteria, which is highly advantageous in view of the paucity of new antibiotics in the pipeline.

  18. "Orpheus" cardiopulmonary bypass simulation system.

    PubMed

    Morris, Richard W; Pybus, David A

    2007-12-01

    In this paper we describe a high-fidelity perfusion simulation system intended for use in the training and continuing education of perfusionists. The system comprises a hydraulic simulator, an electronic interface unit and a controlling computer with associated real-time computer models. It is designed for use within an actual operating theatre, or within a specialized simulation facility. The hydraulic simulator can be positioned on an operating table and physically connected to the circuit of the institutional heart-lung machine. The institutional monitoring system is used to display the arterial and central venous pressures, the ECG and the nasopharyngeal temperature using appropriate connections. The simulator is able to reproduce the full spectrum of normal and abnormal events that may present during the course of cardiopulmonary bypass. The system incorporates a sophisticated blood gas model that accurately predicts the behavior of a modern, hollow-fiber oxygenator. Output from this model is displayed in the manner of an in-line blood gas electrode and is updated every 500 msecs. The perfusionist is able to administer a wide variety of drugs during a simulation session including: vasoconstrictors (metaraminol, epinephrine and phenylephrine), a vasodilator (sodium nitroprusside), chronotropes (epinephrine and atropine), an inotrope (epinephrine) and modifiers of coagulation (heparin and protamine). Each drug has a pharmacokinetic profile based on a three-compartment model plus an effect compartment. The simulation system has potential roles in the skill training of perfusionists, the development of crisis management protocols, the certification and accreditation of perfusionists and the evaluation of new perfusion equipment and/or techniques.

  19. tRNAs as Antibiotic Targets

    PubMed Central

    Chopra, Shaileja; Reader, John

    2014-01-01

    Transfer RNAs (tRNAs) are central players in the protein translation machinery and as such are prominent targets for a large number of natural and synthetic antibiotics. This review focuses on the role of tRNAs in bacterial antibiosis. We will discuss examples of antibiotics that target multiple stages in tRNA biology from tRNA biogenesis and modification, mature tRNAs, aminoacylation of tRNA as well as prevention of proper tRNA function by small molecules binding to the ribosome. Finally, the role of deacylated tRNAs in the bacterial “stringent response” mechanism that can lead to bacteria displaying antibiotic persistence phenotypes will be discussed. PMID:25547494

  20. [Management of prosthetic graft infection after lower limb arterial bypasses].

    PubMed

    Li, Qing-le; Zhang, Xiao-Ming; Zhang, Xue-Min; Shen, Chen-Yang; Fang, Jie; Jiang, Jing-Jun; Jiao, Yang; Zhao, Jun-Lai; Zhang, Tao

    2010-07-01

    To summarize the experience in management of prosthetic graft infection (PGI) after lower limb arterial bypasses and investigate optimal measures for prevention and treatment. Records of 15 cases of PGI between January 2004 and December 2009 were retrospectively analyzed, including 14 male and 1 female with the average age of 64.8 years (ranged from 40 to 84 years). PGI occurred from 5 d to 59 months (average 6.4 months) after the last reconstructive procedures with symptoms as follow: nonhealing wound with vascular graft exposure in 8 cases, persistent sinus related to vascular graft with purulent secretion in 5 cases and without secretion in 1 case, and ill-incorporated graft with peri-graft fluid in 1 case. Broad-spectrum antibiotics were administrated in all PGI cases. Surgical treatments included local debridement and drainage in 4 cases (one death from postoperative acute myocardial infarction), local debridement and skin flap rotation in one case, complete removal of the occluded infected grafts in 8 cases including major amputation in 3 cases, removal of patent infected graft and extra-anatomic bypass with silver-bonded Dacron vascular graft in 1 case, and partial removal of patent infected graft without reconstruction in 1 case with a re-canalized stent-graft. Limb salvage was achieved in 9 cases, and 4 cases received major amputation. One case was failed to follow-up and one died of postoperative acute myocardial infarction. Initially 13 patients were followed and 2 died during follow-up (because of colon carcinoma and intracranial hemorrhage respectively). Eleven patients were followed for 1 to 70 months (average 22.3 months) including 8 cases with limb salvage and 3 with major amputation. Accumulative mortality rate, amputation rate, and graft occlusion rate were 20% (3/15), 26.7% (4/15), and 53.3% (8/15) respectively. PGI after lower limb arterial bypasses is a devastating complication with high risk of graft occlusion and amputation. Removal of the

  1. The future of antibiotics.

    PubMed

    Spellberg, Brad

    2014-06-27

    Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on 'push' incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed.

  2. Replacement for antibiotics: Lysozyme

    USDA-ARS?s Scientific Manuscript database

    Antibiotics have been fed at subtherapeutic levels to swine as growth promoters for more than 60 years, and the majority of swine produced in the U.S. receive antibiotics in their feed at some point in their production cycle. These compounds benefit the producers by minimizing production losses by ...

  3. Antibiotic-Resistant Bacteria.

    ERIC Educational Resources Information Center

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

    A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

  4. [Antibiotics: present and future].

    PubMed

    Bérdy, János

    2013-04-14

    The author discuss the up to date interpretation of the concept of antibiotics and antibiotic research, as well as the present role of various natural, semisynthetic and synthetic antibiotic compounds in various areas of the human therapy. The origin and the total number of all antibiotics and applied antibiotics in the practice, as well as the bioactive microbial metabolites (antibiotics) in other therapeutical, non-antibiotic fields (including agriculture) are also reviewed. The author discusses main problems, such as increasing (poly)resistance, virulence of pathogens and the non-scientific factors (such as a decline of research efforts and their sociological, economic, financial and regulatory reasons). A short summary of the history of Hungarian antibiotic research is also provided. The author briefly discusses the prospects in the future and the general advantages of the natural products over synthetic compounds. It is concluded that new approaches for the investigation of the unlimited possibilities of the living world are necessary. The discovery of new types or simply neglected (micro)organisms and their biosynthetic capabilities, the introduction of new biotechnological and genetic methods (genomics, metagenom, genome mining) are absolutely required in the future.

  5. The future of antibiotics

    PubMed Central

    2014-01-01

    Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

  6. Economics of antibiotic administration.

    PubMed

    Sommers, Ben D

    2003-03-01

    This article examines several elements of antibiotic administration that make it worthy of policy analysis, including microbial resistance, contagion, competing brand and generic drugs, and formulary restrictions by insurers and hospitals. These topics are explored using two concepts from health economics, cost-effectiveness and externalities, revealing theoretical and empirical evidence that society may not be using antibiotics as efficiently as it could.

  7. Setamycin, a new antibiotic.

    PubMed

    Omura, S; Otoguro, K; Nishikiori, T; Oiwa, R; Iwai, Y

    1981-10-01

    A new antibiotic, setamycin, was extracted from the mycelia of a rare actinomycete strain KM-6054. The antibiotic, the molecular formula of which was found to be C42H61NO12 (tentative), is a yellow powder showing activity against some fungi, trichomonads and weakly against Gram-positive bacteria.

  8. [Side effects of antibiotics].

    PubMed

    Hoigné, R

    1975-03-01

    The clinically severe and newer forms of antibiotic side effects are reviewed. The study covers the following antibiotics: penicillins, cephalosporins, aminoglycosides and polymyxins, tetracyclines, chloramphenicol and thiamphenicol, macrolides and lincomycin, rifamycins and sulfonamides. Special reference is made to (1) hematologic side effects, and (2) general evaluation of drug reactions. The relationship between reaction time and clinical symptoms is of particular practical significance.

  9. Antibiotic-Resistant Bacteria.

    ERIC Educational Resources Information Center

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

    A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

  10. Internal Maxillary Bypass for Complex Pediatric Aneurysms.

    PubMed

    Wang, Long; Lu, Shuaibin; Qian, Hai; Shi, Xiang'en

    2017-07-01

    Complex pediatric aneurysms (PAs) are an unusual clinicopathologic entity. Data regarding the use of a bypass procedure to treat complex PAs are limited. Internal maxillary artery-to-middle cerebral artery bypass with radial artery graft was used to isolate PAs. Bypass patency and aneurysm stability were evaluated using intraoperative Doppler ultrasound, indocyanine green videoangiography, and postoperative angiography. Modified Rankin Scale was used to assess neurologic function. Over a 5-year period, 7 pediatric patients (≤18 years old) were included in our analysis. Mean age of patients was 14.4 years (range, 12-18 years), and mean size of PAs was 23.6 mm (range, 9-37 mm). All cases manifested with complex characteristics. Proximal artery occlusion was performed in 3 cases, complete excision following aneurysmal distal internal maxillary artery bypass was performed in 2 cases, and combined proximal artery occlusion and aneurysm excision was performed in the 2 remaining cases. Mean intraoperative blood flow was 61.6 mL/minute (range, 40.0-90.8 mL/minute). Graft patency rate was 100% during postoperative recovery and at the last follow-up examination (mean, 20 months; range, 7-45 months). All patients had excellent outcomes except for 1 patient who died of multiple-organ failure. Internal maxillary artery bypass is an essential technique for treatment of selected cases of complex PAs. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Antibiotics: a new hope.

    PubMed

    Wright, Gerard D

    2012-01-27

    Antibiotic resistance is one of the most significant challenges to the health care sector in the 21st century. A myriad of resistance mechanisms have emerged over the past decades and are widely disseminated worldwide through bacterial populations. At the same time there have been ever fewer new antibiotics brought to market, and the pharmaceutical industry increasingly sees antibiotics as a poor investment. Paradoxically, we are in a Golden Age of understanding how antibiotics work and where resistance comes from. This knowledge is fueling a renaissance of interest and innovation in antibiotic discovery, synthesis, and mechanism that is poised to inform drug discovery to address pressing clinical needs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. [Mechanisms of antibiotic resistance].

    PubMed

    Mühlemann, K

    2002-01-01

    Antibiotics interfere with structural and regulatory elements of bacterial cells leading to growth arrest or cell death. Bacteria have evolved a variety of strategies to overcome the effects of antibiotics. Examples are enzymatic destruction, alteration of the target, efflux and permeability changes. Resistance towards the same substance can be mediated by several mechanisms. Efflux pumps can probably act as mediators of higher resistance development. Alteration of common targets can lead to cross-resistance against several classes of antibiotics. Genetic events, such as point mutations, transfer of plasmids and gen regulation, can mediate a rapid emergence of resistance. Therefore, substances like rifampicin should be only used in combination with other drugs. Accumulation of resistance genes under common regulatory control in integrons induces co-resistance against substances of different specificity. Detailed knowledge of resistance mechanisms, their evolution and dynamics is important for a rational use of antibiotics and other strategies against antibiotic resistance.

  13. [Antibiotics and gait disorders].

    PubMed

    Gomez-Porro, P; Vinagre-Aragon, A; Zabala-Goiburu, J A

    2016-12-01

    The neurological toxicity of many antibiotics has been reported in a number of articles and clinical notes. In this review antibiotics are classified according to the physiopathogenic mechanism that can give rise to a gait disorder, taking both clinical and experimental data into account. An exhaustive search was conducted in Google Scholar and PubMed with the aim of finding reviews, articles and clinical cases dealing with gait disorders secondary to different antibiotics. The different antibiotics were separated according to the physiopathogenic mechanism that could cause them to trigger a gait disorder. They were classified into antibiotics capable of producing cerebellar ataxia, vestibular ataxia, sensitive ataxia or an extrapyramidal gait disorder. The main aim was to group all the drugs that can give rise to a gait disorder, in order to facilitate the clinical suspicion and, consequently, the management of patients.

  14. Experimental Investigation of By-pass Transition

    NASA Astrophysics Data System (ADS)

    Sengupta, Tapan; Lim, T. T.; Chattopadhyay, Manojit

    2000-11-01

    By-pass transition, a phenomenon often encountered in nature and engineering devices, is a complex flow instability caused by moving disturbances over bodies. To date this phenomenon is not fully explained. In the present research a controlled experiment is performed to show that the violent breakdown during by-pass transition is dominated by a two-dimensional mechanism and the resultant broadband energy spectrum of the corresponding turbulent flow is excited at the receptivity stage itself by the primary instability. The experiment is conducted in a water tunnel using dye visualisation technique, and the by-pass transition is created by controlled motion of captive vortices. In the presentation, apart from showing video images of the phenomenon, the similarity of the observed events with secondary instability and fully developed turbulent flows will be discussed.

  15. Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride

    SciTech Connect

    Harvey, R.A.; Alcid, D.V.; Greco, R.S.

    1982-09-01

    Polytetrafluoroethylene (PTFE) treated with the cationic surfactant, triodecylmethylammonium chloride (TDMAC), binds /sup 14/C-penicillin (1.5 to 2 mg antibiotic/cm graft), whereas untreated PTFE or PTFE treated with anionic detergents shows little binding of antibiotic. TDMAC-treated PTFE concomitantly binds penicillin and heparin, generating a surface that potentially can resist both infection and thrombosis. The retention of these biologically active molecules is not due to passive entrapment in the PTFE but reflects an ionic interaction between the anionic ligands and surface-bound TDMAC. Penicillin bound to PTFE is not removed by exhaustive washing in aqueous buffers but is slowly released in the presence of plasma or when the PTFE is placed in a muscle pouch in the rat. Muscle tissue adjacent to the treated PTFE shows elevated levels of antibiotic following implantation. PTFE treated with TDMAC and placed in a muscle pouch binds /sup 14/C-penicillin when it is locally irrigated with antibiotic or when penicillin is administered intravenously. Thus, the TDMAC surface treated either in vitro or in vivo with penicillin provides an effective in situ source for the timed release of antibiotic.

  16. Actinomycetes: still a source of novel antibiotics.

    PubMed

    Genilloud, Olga

    2017-08-18

    Covering: 2006 to 2017Actinomycetes have been, for decades, one of the most important sources for the discovery of new antibiotics with an important number of drugs and analogs successfully introduced in the market and still used today in clinical practice. The intensive antibacterial discovery effort that generated the large number of highly potent broad-spectrum antibiotics, has seen a dramatic decline in the large pharma industry in the last two decades resulting in a lack of new classes of antibiotics with novel mechanisms of action reaching the clinic. Whereas the decline in the number of new chemical scaffolds and the rediscovery problem of old known molecules has become a hurdle for industrial natural products discovery programs, new actinomycetes compounds and leads have continued to be discovered and developed to the preclinical stages. Actinomycetes are still one of the most important sources of chemical diversity and a reservoir to mine for novel structures that is requiring the integration of diverse disciplines. These can range from novel strategies to isolate species previously not cultivated, innovative whole cell screening approaches and on-site analytical detection and dereplication tools for novel compounds, to in silico biosynthetic predictions from whole gene sequences and novel engineered heterologous expression, that have inspired the isolation of new NPs and shown their potential application in the discovery of novel antibiotics. This review will address the discovery of antibiotics from actinomycetes from two different perspectives including: (1) an update of the most important antibiotics that have only reached the clinical development in the recent years despite their early discovery, and (2) an overview of the most recent classes of antibiotics described from 2006 to 2017 in the framework of the different strategies employed to untap novel compounds previously overlooked with traditional approaches.

  17. [Simplified laparoscopic gastric bypass. Initial experience].

    PubMed

    Hernández-Miguelena, Luis; Maldonado-Vázquez, Angélica; Cortes-Romano, Pablo; Ríos-Cruz, Daniel; Marín-Domínguez, Raúl; Castillo-González, Armando

    2014-01-01

    Antecedentes: la cirugía de la obesidad comprende diversos procedimientos gastrointestinales. El bypass gástrico en Y de Roux es el prototipo de los procedimientos mixtos y el más practicado en el mundo en sus diversas variedades. Una técnica similar y novedosa es la adoptada por Cardoso-Ramos y Galvao denominada "bypass simplificado" que rápidamente se aceptó por la mayor facilidad y resultados muy parecidos a la técnica convencional. Objetivo: describir los resultados a un año del bypass gástrico simplificado para el tratamiento de la obesidad mórbida. Material y métodos: estudio retrospectivo y descriptivo de todos los pacientes a quienes se realizó bypass gástrico de enero de 2008 a julio de 2012, en la clínica de obesidad de un hospital privado de la Ciudad de México. Resultados: se estudiaron 90 pacientes con diagnóstico de obesidad mórbida, con límites de edad de 18 y 65 años, operados para bypass gástrico simplificado. En 10% de los pacientes hubo complicaciones, las más frecuentes fueron: hemorragia y hernia interna. Durante el periodo de estudio la mortalidad fue de 0%. La pérdida de peso promedio a los 12 meses fue de 72.7%. Conclusión: el bypass gástrico simplificado laparoscópico es una cirugía segura, con buenos resultados a mediano plazo, y con una pérdida del exceso de peso adecuada en 71% de los casos.

  18. Modeling Sediment Bypassing around Rocky Headlands

    NASA Astrophysics Data System (ADS)

    George, D. A.; Largier, J. L.; Pasternack, G. B.; Erikson, L. H.; Storlazzi, C. D.; Barnard, P.

    2016-12-01

    Sediment bypassing rocky headlands remains understudied despite the importance of characterizing littoral processes and sediment budgets for erosion abatement, climate change adaptation, and beach management. This study was developed to identify controlling factors on and the mechanisms supporting sediment bypassing. Sediment flux around four idealized rocky headlands was investigated using the hydrodynamic model Delft3D and spectral wave model SWAN. The experimental design involved 120 simulations to explore the influence of headland morphology, substrate composition, sediment grain size, and oceanographic forcing. Headlands represented sizes and shapes found in natural settings, grain sizes ranged from fine to medium sand, and substrates from sandy beds to offshore bedrock reefs. The oceanography included a constructed representative tide, an alongshore background current, and four wave conditions derived from observational records in the eastern Pacific Ocean. A bypassing ratio was developed for alongshore flux between upstream and downstream cross-shore transects to determine the degree of blockage by a headland. Results showed that northwesterly oblique large waves (Hs = 7 m, Tp = 16 s) generated the most flux around headlands, whereas directly incident waves blocked flux across a headland apex. The headland shape heavily influenced the sediment fate by changing the relative angle between the shoreline and the incident waves. The bypassing ratio characterized each headland's capacity to allow alongshore flux under different wave conditions. All headlands may allow flux, although larger ones block sediment more effectively, promoting their ability to be littoral cell boundaries compared to smaller headlands. The controlling factors on sediment bypassing were determined to be wave angle, shape and size of the headland, and sediment grain size. This novel numerical modeling study advances headland modeling from the generic realm to broadly applicable classes of

  19. Battery Cell By-Pass Circuit

    NASA Technical Reports Server (NTRS)

    Evers, Jeffrey (Inventor); Gelger, Ronald V. (Inventor)

    2001-01-01

    The invention is a circuit and method of limiting the charging current voltage from a power supply net work applied to an individual cell of a plurality of cells making up a battery being charged in series. It is particularly designed for use with batteries that can be damaged by overcharging, such as Lithium-ion type batteries. In detail. the method includes the following steps: 1) sensing the actual voltage level of the individual cell; 2) comparing the actual voltage level of the individual cell with a reference value and providing an error signal representative thereof; and 3) by-passing the charging current around individual cell necessary to keep the individual cell voltage level generally equal a specific voltage level while continuing to charge the remaining cells. Preferably this is accomplished by by-passing the charging current around the individual cell if said actual voltage level is above the specific voltage level and allowing the charging current to the individual cell if the actual voltage level is equal or less than the specific voltage level. In the step of bypassing the charging current, the by-passed current is transferred at a proper voltage level to the power supply. The by-pass circuit a voltage comparison circuit is used to compare the actual voltage level of the individual cell with a reference value and to provide an error signal representative thereof. A third circuit, designed to be responsive to the error signal, is provided for maintaining the individual cell voltage level generally equal to the specific voltage level. Circuitry is provided in the third circuit for bypassing charging current around the individual cell if the actual voltage level is above the specific voltage level and transfers the excess charging current to the power supply net work. The circuitry also allows charging of the individual cell if the actual voltage level is equal or less than the specific voltage level.

  20. [The threat of antibiotic resistance: origin, impact and public health perspectives].

    PubMed

    Struelens, M J; Denis, O; Rodriguez-Villalobos, H; Hallin, M

    2007-09-01

    Bacterial resistance to antibiotics is as old as the living planet, i.e. over 3 billion years ago when bacterial life emerged together with its biological warfare weapons, the antibiotics. Bacteria can readily develop a diverse array of antibiotic resistance mechanisms, including selection of mutants which produce modified low-affinity drug targets, exhibit reduced drug permeability or increased drug efflux. Another pathway is through acquisition of mobile genetic determinants of drug inactivating enzymes, target protection or bypass mechanisms. Antibiotic resistance has accelerated and spread across the community of human and animal bacteria following massive use of antibiotics for over half-a century in human and veterinary medicine and agriculture. Today, the increasing prevalence of resistance among many bacterial pathogens is no longer counter-balanced by the launching of innovative and active antibiotics. This imbalanced "arms race" undermines the escalating use of broad-spectrum antibiotics and increases the risk of therapeutic failure, drug side effets and excess costs of care. The accumulation of antibiotic resistance genes and their epidemic dissemination is fuelled by the selective pressure associated with excess and inappropriate use of antibiotics combined with insufficient infection prevention and control measures. Confronting this threat effectively requires new strategies to be implemented globally, nationally, and locally across all healthcare and agricultural sectors.

  1. Snake Venom: Any Clue for Antibiotics and CAM?

    PubMed Central

    2005-01-01

    Lately several naturally occurring peptides presenting antimicrobial activity have been described in the literature. However, snake venoms, which are an enormous source of peptides, have not been fully explored for searching such molecules. The aim of this work is to review the basis of antimicrobial mechanisms revealing snake venom as a feasible source for searching an antibiotic prototype. Therefore, it includes (i) a description of the constituents of the snake venoms involved in their main biological effects during the envenomation process; (ii) examples of snake venom molecules of commercial use; (iii) mechanisms of action of known antibiotics; and (iv) how the microorganisms can be resistant to antibiotics. This review also shows that snake venoms are not totally unexplored sources for antibiotics and complementary and alternative medicine (CAM). PMID:15841277

  2. Coronary Artery Bypass Surgery: MedlinePlus Health Topic

    MedlinePlus

    ... and Blood Institute Start Here Coronary Artery Bypass (Texas Heart Institute) Also in Spanish Coronary Artery Bypass ... and Blood Institute) Specifics Limited-Access Heart Surgery (Texas Heart Institute) Also in Spanish Types of Coronary ...

  3. Polymorphous ventricular tachycardia following cardiopulmonary bypass.

    PubMed Central

    Thompson, L. D.; Cohen, A. J.; Bellasis, R. M.

    1996-01-01

    A 62-year-old African-American man who underwent coronary artery bypass surgery was found to have repetitive ventricular tachycardia of the "Torsade des pointes" type. The arrhythmia was resistant to bretylium, lidocaine, and pacing, but was controlled by intravenous magnesium sulfate. The recurrent attacks were abolished by a bolus of 1 g magnesium sulfate and controlled using a 1 mg/minute drip for 12 hours. This case shows the effectiveness of intravenous magnesium in controlling Torsade des pointes in postoperative coronary bypass patients. PMID:8583493

  4. Biosensors, antibiotics and food.

    PubMed

    Virolainen, Nina; Karp, Matti

    2014-01-01

    Antibiotics are medicine's leading asset for fighting microbial infection, which is one of the leading causes of death worldwide. However, the misuse of antibiotics has led to the rapid spread of antibiotic resistance among bacteria and the development of multiple resistant pathogens. Therefore, antibiotics are rapidly losing their antimicrobial value. The use of antibiotics in food production animals is strictly controlled by the European Union (EU). Veterinary use is regulated to prevent the spread of resistance. EU legislation establishes maximum residue limits for veterinary medicinal products in foodstuffs of animal origin and enforces the establishment and execution of national monitoring plans. Among samples selected for monitoring, suspected noncompliant samples are screened and then subjected to confirmatory analysis to establish the identity and concentration of the contaminant. Screening methods for antibiotic residues are typically based on microbiological growth inhibition, whereas physico-chemical methods are used for confirmatory analysis. This chapter discusses biosensors, especially whole-cell based biosensors, as emerging screening methods for antibiotic residues. Whole-cell biosensors can offer highly sensitive and specific detection of residues. Applications demonstrating quantitative analysis and specific analyte identification further improve their potential as screening methods.

  5. Solving the Antibiotic Crisis.

    PubMed

    Wright, Gerard D

    2015-02-13

    Antibiotics are essential for both treating and preventing infectious diseases. Paradoxically, despite their importance as pillars of modern medicine, we are in danger of losing antibiotics because of the evolution and dissemination of resistance mechanisms throughout all pathogenic microbes. This fact, coupled with an inability to bring new drugs to market at a pace that matches resistance, has resulted in a crisis of global proportion. Solving this crisis requires the actions of many stakeholders, but chemists, chemical biologists, and microbiologists must drive the scientific innovation that is required to maintain our antibiotic arsenal. This innovation requires (1) a deep understanding of the evolution and reservoirs of resistance; (2) full knowledge of the molecular mechanisms of antibiotic action and resistance; (3) the discovery of chemical and genetic probes of antibiotic action and resistance; (4) the integration of systems biology into antibiotic discovery; and (5) the discovery of new antimicrobial chemical matter. Addressing these pressing scientific gaps will ensure that we can meet the antibiotic crisis with creativity and purpose.

  6. Selective condensation of DNA by aminoglycoside antibiotics.

    PubMed

    Kopaczynska, M; Schulz, A; Fraczkowska, K; Kraszewski, S; Podbielska, H; Fuhrhop, J H

    2016-05-01

    The condensing effect of aminoglycoside antibiotics on the structure of double-stranded DNA was examined. The selective condensation of DNA by small molecules is an interesting approach in biotechnology. Here, we present the interaction between calf thymus DNA and three types of antibiotic molecules: tobramycin, kanamycin, and neomycin. Several techniques were applied to study this effect. Atomic force microscopy, transmission electron microscopy images, and nuclear magnetic resonance spectra showed that the interaction of tobramycin with double-stranded DNA caused the rod, toroid, and sphere formation and very strong condensation of DNA strands, which was not observed in the case of other aminoglycosides used in the experiment. Studies on the mechanisms by which small molecules interact with DNA are important in understanding their functioning in cells, in designing new and efficient drugs, or in minimizing their adverse side effects. Specific interactions between tobramycin and DNA double helix was modeled using molecular dynamics simulations. Simulation study shows the aminoglycoside specificity to bend DNA double helix, shedding light on the origins of toroid formation. This phenomenon may lighten the ototoxicity or nephrotoxicity issues, but also other adverse reactions of aminoglycoside antibiotics in the human body.

  7. Variable volume combustor with an air bypass system

    DOEpatents

    Johnson, Thomas Edward; Ziminsky, Willy Steve; Ostebee, Heath Michael; Keener, Christopher Paul

    2017-02-07

    The present application provides a combustor for use with flow of fuel and a flow of air in a gas turbine engine. The combustor may include a number of micro-mixer fuel nozzles positioned within a liner and an air bypass system position about the liner. The air bypass system variably allows a bypass portion of the flow of air to bypass the micro-mixer fuel nozzles.

  8. Sampling the antibiotic resistome.

    PubMed

    D'Costa, Vanessa M; McGrann, Katherine M; Hughes, Donald W; Wright, Gerard D

    2006-01-20

    Microbial resistance to antibiotics currently spans all known classes of natural and synthetic compounds. It has not only hindered our treatment of infections but also dramatically reshaped drug discovery, yet its origins have not been systematically studied. Soil-dwelling bacteria produce and encounter a myriad of antibiotics, evolving corresponding sensing and evading strategies. They are a reservoir of resistance determinants that can be mobilized into the microbial community. Study of this reservoir could provide an early warning system for future clinically relevant antibiotic resistance mechanisms.

  9. Opportunities for Synthetic Biology in Antibiotics: Expanding Glycopeptide Chemical Diversity

    PubMed Central

    2012-01-01

    Synthetic biology offers a new path for the exploitation and improvement of natural products to address the growing crisis in antibiotic resistance. All antibiotics in clinical use are facing eventual obsolesce as a result of the evolution and dissemination of resistance mechanisms, yet there are few new drug leads forthcoming from the pharmaceutical sector. Natural products of microbial origin have proven over the past 70 years to be the wellspring of antimicrobial drugs. Harnessing synthetic biology thinking and strategies can provide new molecules and expand chemical diversity of known antibiotic scaffolds to provide much needed new drug leads. The glycopeptide antibiotics offer paradigmatic scaffolds suitable for such an approach. We review these strategies here using the glycopeptides as an example and demonstrate how synthetic biology can expand antibiotic chemical diversity to help address the growing resistance crisis. PMID:23654249

  10. Opportunities for synthetic biology in antibiotics: expanding glycopeptide chemical diversity.

    PubMed

    Thaker, Maulik N; Wright, Gerard D

    2015-03-20

    Synthetic biology offers a new path for the exploitation and improvement of natural products to address the growing crisis in antibiotic resistance. All antibiotics in clinical use are facing eventual obsolesce as a result of the evolution and dissemination of resistance mechanisms, yet there are few new drug leads forthcoming from the pharmaceutical sector. Natural products of microbial origin have proven over the past 70 years to be the wellspring of antimicrobial drugs. Harnessing synthetic biology thinking and strategies can provide new molecules and expand chemical diversity of known antibiotic scaffolds to provide much needed new drug leads. The glycopeptide antibiotics offer paradigmatic scaffolds suitable for such an approach. We review these strategies here using the glycopeptides as an example and demonstrate how synthetic biology can expand antibiotic chemical diversity to help address the growing resistance crisis.

  11. Clinical experimentation with aerosol antibiotics: current and future methods of administration.

    PubMed

    Zarogoulidis, Paul; Kioumis, Ioannis; Porpodis, Konstantinos; Spyratos, Dionysios; Tsakiridis, Kosmas; Huang, Haidong; Li, Qiang; Turner, J Francis; Browning, Robert; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Konstantinos

    2013-01-01

    Currently almost all antibiotics are administered by the intravenous route. Since several systems and situations require more efficient methods of administration, investigation and experimentation in drug design has produced local treatment modalities. Administration of antibiotics in aerosol form is one of the treatment methods of increasing interest. As the field of drug nanotechnology grows, new molecules have been produced and combined with aerosol production systems. In the current review, we discuss the efficiency of aerosol antibiotic studies along with aerosol production systems. The different parts of the aerosol antibiotic methodology are presented. Additionally, information regarding the drug molecules used is presented and future applications of this method are discussed.

  12. Clinical experimentation with aerosol antibiotics: current and future methods of administration

    PubMed Central

    Zarogoulidis, Paul; Kioumis, Ioannis; Porpodis, Konstantinos; Spyratos, Dionysios; Tsakiridis, Kosmas; Huang, Haidong; Li, Qiang; Turner, J Francis; Browning, Robert; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Konstantinos

    2013-01-01

    Currently almost all antibiotics are administered by the intravenous route. Since several systems and situations require more efficient methods of administration, investigation and experimentation in drug design has produced local treatment modalities. Administration of antibiotics in aerosol form is one of the treatment methods of increasing interest. As the field of drug nanotechnology grows, new molecules have been produced and combined with aerosol production systems. In the current review, we discuss the efficiency of aerosol antibiotic studies along with aerosol production systems. The different parts of the aerosol antibiotic methodology are presented. Additionally, information regarding the drug molecules used is presented and future applications of this method are discussed. PMID:24115836

  13. Chloroquinolines block antibiotic efflux pumps in antibiotic-resistant Enterobacter aerogenes isolates.

    PubMed

    Ghisalberti, Didier; Mahamoud, Abdallah; Chevalier, Jacqueline; Baitiche, Milad; Martino, Michèle; Pagès, Jean-Marie; Barbe, Jacques

    2006-06-01

    Efflux mechanisms protect bacterial cells by pumping out toxic compounds and actively contribute to bacterial multidrug resistance. Agents inhibiting efflux pumps are of interest for the control of multidrug-resistant bacterial infections. Herein we report the effects of new chloroquinoline derivatives that render resistant Enterobacter aerogenes isolates noticeably more susceptible to structurally unrelated antibiotics. In addition, some of these chloroquinolines increase the intracellular concentration of chloramphenicol. Some of the molecules tested in this work are able to inhibit the main efflux pump (AcrAB-TolC), which is involved in E. aerogenes antibiotic resistance.

  14. The role of antibiotics and antibiotic resistance in nature.

    PubMed

    Aminov, Rustam I

    2009-12-01

    Investigations of antibiotic resistance from an environmental prospective shed new light on a problem that was traditionally confined to a subset of clinically relevant antibiotic-resistant bacterial pathogens. It is clear that the environmental microbiota, even in apparently antibiotic-free environments, possess an enormous number and diversity of antibiotic resistance genes, some of which are very similar to the genes circulating in pathogenic microbiota. It is difficult to explain the role of antibiotics and antibiotic resistance in natural environments from an anthropocentric point of view, which is focused on clinical aspects such as the efficiency of antibiotics in clearing infections and pathogens that are resistant to antibiotic treatment. A broader overview of the role of antibiotics and antibiotic resistance in nature from the evolutionary and ecological prospective suggests that antibiotics have evolved as another way of intra- and inter-domain communication in various ecosystems. This signalling by non-clinical concentrations of antibiotics in the environment results in adaptive phenotypic and genotypic responses of microbiota and other members of the community. Understanding the complex picture of evolution and ecology of antibiotics and antibiotic resistance may help to understand the processes leading to the emergence and dissemination of antibiotic resistance and also help to control it, at least in relation to the newer antibiotics now entering clinical practice.

  15. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  16. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  17. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  18. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  19. Bypass apparatus and method for series connected energy storage devices

    DOEpatents

    Rouillard, Jean; Comte, Christophe; Daigle, Dominik

    2000-01-01

    A bypass apparatus and method for series connected energy storage devices. Each of the energy storage devices coupled to a common series connection has an associated bypass unit connected thereto in parallel. A current bypass unit includes a sensor which is coupled in parallel with an associated energy storage device or cell and senses an energy parameter indicative of an energy state of the cell, such as cell voltage. A bypass switch is coupled in parallel with the energy storage cell and operable between a non-activated state and an activated state. The bypass switch, when in the non-activated state, is substantially non-conductive with respect to current passing through the energy storage cell and, when in the activated state, provides a bypass current path for passing current to the series connection so as to bypass the associated cell. A controller controls activation of the bypass switch in response to the voltage of the cell deviating from a pre-established voltage setpoint. The controller may be included within the bypass unit or be disposed on a control platform external to the bypass unit. The bypass switch may, when activated, establish a permanent or a temporary bypass current path.

  20. 21 CFR 870.4390 - Cardiopulmonary bypass pump tubing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pump tubing. 870.4390... bypass pump tubing. (a) Identification. A cardiopulmonary bypass pump tubing is polymeric tubing which is used in the blood pump head and which is cyclically compressed by the pump to cause the blood to...

  1. 20 CFR 631.18 - Federal by-pass authority.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Federal by-pass authority. 631.18 Section 631... Procedures § 631.18 Federal by-pass authority. (a) In the event that a State fails to submit a biennial State... Secretary's intent to exercise by-pass authority and an opportunity to request and to receive a hearing...

  2. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow. The...

  3. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow. The...

  4. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow. The...

  5. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow. The...

  6. 21 CFR 870.4320 - Cardiopulmonary bypass pulsatile flow generator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass pulsatile flow generator... Cardiopulmonary bypass pulsatile flow generator. (a) Identification. A cardiopulmonary bypass pulsatile flow generator is an electrically and pneumatically operated device used to create pulsatile blood flow. The...

  7. 46 CFR 56.20-20 - Valve bypasses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Valve bypasses. 56.20-20 Section 56.20-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Valves § 56.20-20 Valve bypasses. (a) Sizes of bypasses shall be in accordance with MSS SP-45...

  8. 21 CFR 870.4430 - Cardiopulmonary bypass intracardiac suction control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass intracardiac suction....4430 Cardiopulmonary bypass intracardiac suction control. (a) Identification. A cardiopulmonary bypass intracardiac suction control is a device which provides the vacuum and control for a cardiotomy return sucker...

  9. 46 CFR 56.20-20 - Valve bypasses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Valve bypasses. 56.20-20 Section 56.20-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Valves § 56.20-20 Valve bypasses. (a) Sizes of bypasses shall be in accordance with MSS SP-45...

  10. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger. (b...

  11. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger. (b...

  12. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger. (b...

  13. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass temperature controller. 870... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller is a device used to control the temperature of the fluid entering and leaving a heat exchanger. (b...

  14. 21 CFR 870.4250 - Cardiopulmonary bypass temperature controller.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass temperature controller. 870.4250 Section 870.4250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Cardiopulmonary bypass temperature controller. (a) Identification. A cardiopulmonary bypass temperature controller...

  15. Fighting antibiotic resistance in the intensive care unit using antibiotics.

    PubMed

    Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

    2015-01-01

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

  16. Charge-transfer chromatographic study of the interaction of antibiotics with sodium dodecylsulfate.

    PubMed

    Forgács, E; Csethati, T

    1997-06-01

    The interaction of 29 antibiotics with the anionic surfactant sodium dodecylsulfate (SDS) was studied by charge-transfer reversed-phase chromatography carried out on impregnated silica layers using water-methanol mixtures as eluents. The hydrophobicity of antibiotics and the relative strength of SDS-antibiotic interaction was calculated separately for each antibiotic-SDS pair. SDS interacted with 17 antibiotics where the antibiotic-SDS complex was either more hydrophilic or more hydrophobic than the uncomplexed molecule. The relative strength of interaction depended considerably on the molecular structure of the antibiotics. No significant linear correlation was found between the hydrophobicity parameters of antibiotics and their capacity to interact with SDS. Stepwise regression analysis proved that the inductive effect of substituents, their electron-withdrawing power and proton-acceptor capacity exert a significance influence on the strength of interaction.

  17. Antibiotic production by actinomycetes: the Janus faces of regulation.

    PubMed

    Cundliffe, Eric

    2006-07-01

    This manuscript reviews some of the common regulatory mechanisms that control antibiotic production in actinomycetes. These ubiquitous bacteria, collectively responsible for the earthy smell of soil, are prolific producers of antibiotics and other secondary metabolites. The content of this review is biased towards the author's current research interests, concerning the action of regulatory gene products that control transcription of antibiotic-biosynthetic genes and the associated involvement of low molecular weight signalling molecules of the gamma-butyrolactone family. As a result, much fertile ground remains unturned particularly in the area of environmental monitoring and responses of actinomycetes to stimuli so perceived. Reviews casting a broader net are cited in the text.

  18. Natural and engineered biosynthesis of nucleoside antibiotics in Actinomycetes.

    PubMed

    Chen, Wenqing; Qi, Jianzhao; Wu, Pan; Wan, Dan; Liu, Jin; Feng, Xuan; Deng, Zixin

    2016-03-01

    Nucleoside antibiotics constitute an important family of microbial natural products bearing diverse bioactivities and unusual structural features. Their biosynthetic logics are unique with involvement of complex multi-enzymatic reactions leading to the intricate molecules from simple building blocks. Understanding how nature builds this family of antibiotics in post-genomic era sets the stage for rational enhancement of their production, and also paves the way for targeted persuasion of the cell factories to make artificial designer nucleoside drugs and leads via synthetic biology approaches. In this review, we discuss the recent progress and perspectives on the natural and engineered biosynthesis of nucleoside antibiotics.

  19. Glycopeptide antibiotic biosynthesis.

    PubMed

    Yim, Grace; Thaker, Maulik N; Koteva, Kalinka; Wright, Gerard

    2014-01-01

    Glycopeptides such as vancomycin, teicoplanin and telavancin are essential for treating infections caused by Gram-positive bacteria. Unfortunately, the dwindled pipeline of new antibiotics into the market and the emergence of glycopeptide-resistant enterococci and other resistant bacteria are increasingly making effective antibiotic treatment difficult. We have now learned a great deal about how bacteria produce antibiotics. This information can be exploited to develop the next generation of antimicrobials. The biosynthesis of glycopeptides via nonribosomal peptide assembly and unusual amino acid synthesis, crosslinking and tailoring enzymes gives rise to intricate chemical structures that target the bacterial cell wall. This review seeks to describe recent advances in our understanding of both biosynthesis and resistance of these important antibiotics.

  20. Targeting Antibiotic Resistance

    PubMed Central

    Chellat, Mathieu F.; Raguž, Luka

    2016-01-01

    Abstract Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens. PMID:27000559

  1. Resistance-resistant antibiotics.

    PubMed

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms.

  2. [Antibiotics in primary care].

    PubMed

    Steciwko, Andrzej; Lubieniecka, Małgorzata; Muszyńska, Agnieszka

    2011-05-01

    Discovered in the forties of the twentieth century antimicrobial agents have changed the world. Currently, due to their overuse, we are threatened by the increasing resistance of bacteria to antibiotics, and soon we may face a threat of inability to fight these pathogens. For that reason, the world, European and national organizations introduce antibiotics protection programs. In Poland since 2004, the National Program of Protection of Antibiotics is being held. The concept of rational antibiotic therapy is associated not only with the appropriate choice of therapy or antimicrobial dosage but also with a reduction in costs associated with a refund of medicines. Antibiotics are prescribed mostly by primary care physicians (GP), and about one fifth of visits to family doctor's office ends with prescribing antimicrobial drug. These trends are probably related to both the difficulty in applying the differential diagnosis of viral and bacterial infection in a primary care doctor's office, as well as patient's conviction about the effectiveness of antibiotic therapy in viral infections. However, although patients often want to influence the therapeutic decisions and ask their doctor for prescribing antimicrobial drug, the right conversation with a doctor alone is the critical component in satisfaction with medical care. Many countries have established standards to clarify the indications for use of antibiotics and thereby reduce their consumption. The next step is to monitor the prescribing and use of these drugs and to assess the rise of drug resistance in the area. In Poland, the recommendations regarding outpatient respiratory tract infections treatment were published and usage of antimicrobial agents monitoring has begun. However, lack of publications covering a broad analysis of antibiotic therapy and drug resistance on Polish territory is still a problem. Modem medicine has yet another tool in the fight against bacteria--they are bacteriophages. Phage therapy is

  3. Planetary science: Bypassing the habitable zone

    NASA Astrophysics Data System (ADS)

    Ingersoll, Andrew P.

    2017-08-01

    In our own solar system, Venus is too hot, Mars is too cold and Earth is just right. Simulations show that making an icy planet habitable is not as simple as melting its ice: many icy bodies swing from too cold to too hot, bypassing just right.

  4. Delirium in Children After Cardiac Bypass Surgery.

    PubMed

    Patel, Anita K; Biagas, Katherine V; Clarke, Eunice C; Gerber, Linda M; Mauer, Elizabeth; Silver, Gabrielle; Chai, Paul; Corda, Rozelle; Traube, Chani

    2017-02-01

    To describe the incidence of delirium in pediatric patients after cardiac bypass surgery and explore associated risk factors and effect of delirium on in-hospital outcomes. Prospective observational single-center study. Fourteen-bed pediatric cardiothoracic ICU. One hundred ninety-four consecutive admissions following cardiac bypass surgery, 1 day to 21 years old. Subjects were screened for delirium daily using the Cornell Assessment of Pediatric Delirium. Incidence of delirium in this sample was 49%. Delirium most often lasted 1-2 days and developed within the first 1-3 days after surgery. Age less than 2 years, developmental delay, higher Risk Adjustment for Congenital Heart Surgery 1 score, cyanotic disease, and albumin less than three were all independently associated with development of delirium in a multivariable model (all p < 0.03). Delirium was an independent predictor of prolonged ICU length of stay, with patients who were ever delirious having a 60% increase in ICU days compared with patients who were never delirious (p < 0.01). In our institution, delirium is a frequent problem in children after cardiac bypass surgery, with identifiable risk factors. Our study suggests that cardiac bypass surgery significantly increases children's susceptibility to delirium. This highlights the need for heightened, targeted delirium screening in all pediatric cardiothoracic ICUs to potentially improve outcomes in this vulnerable patient population.

  5. Educational Programs for By-Passed Populations.

    ERIC Educational Resources Information Center

    Morgan, Don A., Ed.

    The objective of the symposium from which this document resulted was to give visibility to some worthwhile programs for mobile and "by-passed" populations, in order to allow those in attendance at the symposium and those exposed to the published proceedings to capitalize on what has been learned through these programs. The conference report points…

  6. Sexual Adjustment following Coronary Bypass Surgery.

    ERIC Educational Resources Information Center

    Thurer, Shari

    1981-01-01

    Sexual adjustment of 19 individuals was measured before and four months after their coronary bypass surgery. Test variables were subject to an analysis of variance. Patients showed significant improvement in physical condition. Sexual adjustment, however, did not improve, as measured by the Structured and Scaled Interview to Measure Maladjustment.…

  7. Antibiotic Resistance in Acne Treatment.

    PubMed

    Adler, Brandon L; Kornmehl, Heather; Armstrong, April W

    2017-08-01

    What is the evidence for antibiotic resistance in acne, and how does resistance affect treatment? Use of topical and systemic antibiotics for acne is associated with formation of resistance in Propionibacterium acnes and other bacteria, with clinical consequences. Guidelines recommend resistance reduction strategies including avoidance of antibiotic monotherapy, combination treatment with topical modalities, and limiting the duration of oral antibiotic use.

  8. [The history of antibiotics].

    PubMed

    Yazdankhah, Siamak; Lassen, Jørgen; Midtvedt, Tore; Solberg, Claus Ola

    2013-12-10

    The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases.

  9. Antibiotic prophylaxis in surgery.

    PubMed

    Lewis, R T

    1981-11-01

    This review examines the principles and practice of antibiotic prophylaxis in surgery. Such prophylaxis is required to decrease the frequency of postoperative infection in most patients with clean-contaminated and contaminated wounds, to prevent infrequent but devastating infection of prostheses in cardiovascular and orthopedic surgery and to prevent endocarditis in noncardiac surgery in patients who have valvular heart disease. Prophylaxis should begin before operation; it is usually unnecessary afterwards. The antibiotic may be given topically or parenterally. The latter is more certain, but oral prophylaxis in bowel surgery may offer additional protection by reducing colonic flora, and topical wound and peritoneal antibiotics may be augment protective antibiotic levels at those sites. Antibiotics, such as the cephalosporin cefazolin (but not cephalothin), which penetrate blood and tissues rapidly and for prolonged periods, afford excellent prophylaxis at most sites. But for prophylaxis in colonic surgery, antibiotics directed against Bacteroides fragilis may be superior, and to prevent endocarditis in noncardiac surgery, vancomycin or a combination of penicillin and an aminoglycoside is best.

  10. Cefazolin and linezolid penetration into sternal cancellous bone during coronary artery bypass grafting.

    PubMed

    Andreas, Martin; Zeitlinger, Markus; Wisser, Wilfried; Jaeger, Walter; Maier-Salamon, Alexandra; Thalhammer, Florian; Kocher, Alfred; Hiesmayr, Joerg-Michael; Laufer, Guenther; Hutschala, Doris

    2015-11-01

    Deep sternal wound infection is a severe complication after cardiac surgery. Insufficient antibiotic target site concentrations may account for variable success of perioperative prophylaxis. Therefore, we measured perioperative penetration of cefazolin and of linezolid into sternal cancellous bone after sternotomy in coronary artery bypass grafting (CABG) patients by in vivo microdialysis. Nine patients underwent CABG using a skeletonized left internal mammary artery. Standard antibiotic prophylaxis consisted of 4 g cefazolin prior to skin incision and additional 2 g during skin closure. In addition, 600 mg of linezolid were administered prior to skin incision and after 12 h for study purposes. Two microdialysis probes were inserted into the sternal cancellous bone (left and right side) after sternotomy. First mean peak cefazolin and linezolid plasma concentrations were 273 ± 92 µg/ml and 22.1 ± 8.9 µg/ml, respectively. Mean peak concentrations of antibiotics in sternal cancellous bone on the left and right sternal side were 112 ± 59 µg/ml and 159 ± 118 µg/ml for cefazolin and 10.9 ± 4.0 µg/ml and 12.6 ± 6.1 µg/ml for linezolid, respectively. Cefazolin exceeded the required tissue concentrations for relevant pathogens by far, but linezolid did not gain effective tissue concentrations in all patients for some relevant pathogens. Mammary artery harvesting had no significant effect on antibiotic tissue penetration. Direct measurement of antibiotic concentration in sternal cancellous bone with in vivo microdialysis is technically demanding but safe and feasible. We could demonstrate sufficient antibiotic coverage with our standard cefazolin-dosing regimen in the sternal cancellous bone during cardiac surgery. Mammary artery harvesting had no clinically relevant effect on tissue penetration. Linezolid concentrations were not sufficient for some relevant pathogens. © The Author 2014. Published by Oxford University Press on behalf of the European Association

  11. Strategies to Minimize Antibiotic Resistance

    PubMed Central

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-01-01

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

  12. Strategies to minimize antibiotic resistance.

    PubMed

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-09-12

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.

  13. Bypass surgery for chronic lower limb ischaemia.

    PubMed

    Antoniou, George A; Georgiadis, George S; Antoniou, Stavros A; Makar, Ragai R; Smout, Jonathan D; Torella, Francesco

    2017-04-03

    Bypass surgery is one of the mainstay treatments for patients with critical lower limb ischaemia (CLI). This is the second update of the review first published in 2000. To assess the effects of bypass surgery in patients with chronic lower limb ischaemia. For this update, the Cochrane Vascular Group searched its trials register (last searched October 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (last searched Issue 9, 2016). We selected randomised controlled trials of bypass surgery versus control or any other treatment. The primary outcome parameters were defined as early postoperative non-thrombotic complications, procedural mortality, clinical improvement, amputation, primary patency, and mortality within follow-up. For the update, two review authors extracted data and assessed trial quality. We analysed data using odds ratio (OR) and 95% confidence intervals (CIs). We applied fixed-effect or random-effects models. We selected 11 trials reporting a total of 1486 participants. Six trials compared bypass surgery with percutaneous transluminal angioplasty (PTA), and one each with remote endarterectomy, thromboendarterectomy, thrombolysis, exercise, and spinal cord stimulation. The quality of the evidence for the most important outcomes of bypass surgery versus PTA was high except for clinical improvement and primary patency. We judged the quality of evidence for clinical improvement to be low, due to heterogeneity between the studies and the fact that this was a subjective outcome assessment and, therefore, at risk of detection bias. We judged the quality of evidence for primary patency to be moderate due heterogeneity between the studies. For the remaining comparisons, the evidence was limited. For several outcomes, the CIs were wide.Comparing bypass surgery with PTA revealed a possible increase in early postinterventional non-thrombotic complications (OR 1.29, 95% CI 0.96 to 1.73; six studies; 1015 participants

  14. Discovery and preclinical development of new antibiotics

    PubMed Central

    Karlén, Anders

    2014-01-01

    Antibiotics are the medical wonder of our age, but an increasing frequency of resistance among key pathogens is rendering them less effective. If this trend continues the consequences for cancer patients, organ transplant patients, and indeed the general community could be disastrous. The problem is complex, involving abuse and overuse of antibiotics (selecting for an increasing frequency of resistant bacteria), together with a lack of investment in discovery and development (resulting in an almost dry drug development pipeline). Remedial approaches to the problem should include taking measures to reduce the selective pressures for resistance development, and taking measures to incentivize renewed investment in antibiotic discovery and development. Bringing new antibiotics to the clinic is critical because this is currently the only realistic therapy that can ensure the level of infection control required for many medical procedures. Here we outline the complex process involved in taking a potential novel antibiotic from the initial discovery of a hit molecule, through lead and candidate drug development, up to its entry into phase I clinical trials. The stringent criteria that a successful drug must meet, balancing high efficacy in vivo against a broad spectrum of pathogens, with minimal liabilities against human targets, explain why even with sufficient investment this process is prone to a high failure rate. This emphasizes the need to create a well-funded antibiotic discovery and development pipeline that can sustain the continuous delivery of novel candidate drugs into clinical trials, to ensure the maintenance of the advanced medical procedures we currently take for granted. PMID:24646082

  15. Adjuvant strategies for potentiation of antibiotics to overcome antimicrobial resistance.

    PubMed

    Pieren, Michel; Tigges, Marcel

    2012-10-01

    Alarming facts about the occurrence and spreading of multiple antibiotic resistant bacteria have caught the attention of global surveillance authorities and public media. The demand for novel effective antimicrobial drugs is high and on the rise while, at the same time, the supply of fresh 'magic bullets' is drying up. This review summarizes examples of recent strategies for development of adjunctive antibiotic therapies that overcome microbial resistance and thus rejuvenate the existing arsenal of drugs. Recent studies have demonstrated the potential of compounds that inhibit the action of the repressor protein implicated in ethionamide resistance, thus stimulating activation of the drug and thereby restoring the activity of the antibiotic for treatment of Mycobacterium tuberculosis. Such specific interference with regulators or signal transduction mechanisms involved in antibiotic resistance or virulence provides a new toolbox for novel combinations of antimicrobial drugs with adjuvant molecules lacking intrinsic antibiotic activity. In addition to the development of new antibiotics and vaccination initiatives this strategy of restoring or potentiating the activity of existing antibiotics may help to postpone the day when antibiotics are no longer generally efficacious.

  16. Global Transcriptome and Physiological Responses of Acinetobacter oleivorans DR1 Exposed to Distinct Classes of Antibiotics

    PubMed Central

    Heo, Aram; Jang, Hyun-Jin; Sung, Jung-Suk; Park, Woojun

    2014-01-01

    The effects of antibiotics on environment-originated nonpathogenic Acinetobacter species have been poorly explored. To understand the antibiotic-resistance mechanisms that function in nonpathogenic Acinetobacter species, we used an RNA-sequencing (RNA-seq) technique to perform global gene-expression profiling of soil-borne Acinetobacter oleivorans DR1 after exposing the bacteria to 4 classes of antibiotics (ampicillin, Amp; kanamycin, Km; tetracycline, Tc; norfloxacin, Nor). Interestingly, the well-known two global regulators, the soxR and the rpoE genes are present among 41 commonly upregulated genes under all 4 antibiotic-treatment conditions. We speculate that these common genes are essential for antibiotic resistance in DR1. Treatment with the 4 antibiotics produced diverse physiological and phenotypic changes. Km treatment induced the most dramatic phenotypic changes. Examination of mutation frequency and DNA-repair capability demonstrated the induction of the SOS response in Acinetobacter especially under Nor treatment. Based on the RNA-seq analysis, the glyoxylate-bypass genes of the citrate cycle were specifically upregulated under Amp treatment. We also identified newly recognized non-coding small RNAs of the DR1 strain, which were also confirmed by Northern blot analysis. These results reveal that treatment with antibiotics of distinct classes differentially affected the gene expression and physiology of DR1 cells. This study expands our understanding of the molecular mechanisms of antibiotic-stress response of environment-originated bacteria and provides a basis for future investigations. PMID:25330344

  17. Global transcriptome and physiological responses of Acinetobacter oleivorans DR1 exposed to distinct classes of antibiotics.

    PubMed

    Heo, Aram; Jang, Hyun-Jin; Sung, Jung-Suk; Park, Woojun

    2014-01-01

    The effects of antibiotics on environment-originated nonpathogenic Acinetobacter species have been poorly explored. To understand the antibiotic-resistance mechanisms that function in nonpathogenic Acinetobacter species, we used an RNA-sequencing (RNA-seq) technique to perform global gene-expression profiling of soil-borne Acinetobacter oleivorans DR1 after exposing the bacteria to 4 classes of antibiotics (ampicillin, Amp; kanamycin, Km; tetracycline, Tc; norfloxacin, Nor). Interestingly, the well-known two global regulators, the soxR and the rpoE genes are present among 41 commonly upregulated genes under all 4 antibiotic-treatment conditions. We speculate that these common genes are essential for antibiotic resistance in DR1. Treatment with the 4 antibiotics produced diverse physiological and phenotypic changes. Km treatment induced the most dramatic phenotypic changes. Examination of mutation frequency and DNA-repair capability demonstrated the induction of the SOS response in Acinetobacter especially under Nor treatment. Based on the RNA-seq analysis, the glyoxylate-bypass genes of the citrate cycle were specifically upregulated under Amp treatment. We also identified newly recognized non-coding small RNAs of the DR1 strain, which were also confirmed by Northern blot analysis. These results reveal that treatment with antibiotics of distinct classes differentially affected the gene expression and physiology of DR1 cells. This study expands our understanding of the molecular mechanisms of antibiotic-stress response of environment-originated bacteria and provides a basis for future investigations.

  18. Quinolones: from antibiotics to autoinducers

    PubMed Central

    Heeb, Stephan; Fletcher, Matthew P; Chhabra, Siri Ram; Diggle, Stephen P; Williams, Paul; Cámara, Miguel

    2011-01-01

    Since quinine was first isolated, animals, plants and microorganisms producing a wide variety of quinolone compounds have been discovered, several of which possess medicinally interesting properties ranging from antiallergenic and anticancer to antimicrobial activities. Over the years, these have served in the development of many synthetic drugs, including the successful fluoroquinolone antibiotics. Pseudomonas aeruginosa and related bacteria produce a number of 2-alkyl-4(1H)-quinolones, some of which exhibit antimicrobial activity. However, quinolones such as the Pseudomonas quinolone signal and 2-heptyl-4-hydroxyquinoline act as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. Here, we review selectively this extensive family of bicyclic compounds, from natural and synthetic antimicrobials to signalling molecules, with a special emphasis on the biology of P. aeruginosa. In particular, we review their nomenclature and biochemistry, their multiple properties as membrane-interacting compounds, inhibitors of the cytochrome bc1 complex and iron chelators, as well as the regulation of their biosynthesis and their integration into the intricate quorum-sensing regulatory networks governing virulence and secondary metabolite gene expression. PMID:20738404

  19. Quinolones: from antibiotics to autoinducers.

    PubMed

    Heeb, Stephan; Fletcher, Matthew P; Chhabra, Siri Ram; Diggle, Stephen P; Williams, Paul; Cámara, Miguel

    2011-03-01

    Since quinine was first isolated, animals, plants and microorganisms producing a wide variety of quinolone compounds have been discovered, several of which possess medicinally interesting properties ranging from antiallergenic and anticancer to antimicrobial activities. Over the years, these have served in the development of many synthetic drugs, including the successful fluoroquinolone antibiotics. Pseudomonas aeruginosa and related bacteria produce a number of 2-alkyl-4(1H)-quinolones, some of which exhibit antimicrobial activity. However, quinolones such as the Pseudomonas quinolone signal and 2-heptyl-4-hydroxyquinoline act as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. Here, we review selectively this extensive family of bicyclic compounds, from natural and synthetic antimicrobials to signalling molecules, with a special emphasis on the biology of P. aeruginosa. In particular, we review their nomenclature and biochemistry, their multiple properties as membrane-interacting compounds, inhibitors of the cytochrome bc(1) complex and iron chelators, as well as the regulation of their biosynthesis and their integration into the intricate quorum-sensing regulatory networks governing virulence and secondary metabolite gene expression.

  20. Antibiotics for acute bronchitis.

    PubMed

    Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

    2017-06-19

    The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and to assess adverse effects of antibiotic therapy for people with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2016, Issue 11 (accessed 13 January 2017), MEDLINE (1966 to January week 1, 2017), Embase (1974 to 13 January 2017), and LILACS (1982 to 13 January 2017). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 5 April 2017. Randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in people without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. We did not identify any new trials for inclusion in this 2017 update. We included 17 trials with 5099 participants in the primary analysis. The quality of trials was generally good. At follow-up there was no difference in participants described as being clinically improved between the antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15). Participants given antibiotics were less likely to have a cough (4 studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) 6) and a night cough (4 studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7). Participants given antibiotics had a shorter mean cough duration (7 studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated participants were more likely to be improved according to clinician's global assessment (6 studies

  1. Antibiotics after rattlesnake envenomation.

    PubMed

    LoVecchio, Frank; Klemens, Jane; Welch, Sharon; Rodriguez, Ron

    2002-11-01

    To record the outcome, with regard to infection rate, of patients with rattlesnake bites (RSBs) who do not receive prophylactic antibiotics, a prospective observational study was performed of patients with RSBs treated at our institution during a consecutive 18-month period. The inclusion criteria were RSBs <24 h old and completion of follow-up (telephone call, mail reply, medical toxicologist, or private physician examination) 7-10 days following envenomation. Fifty-six consecutive patients (Median age: 32.8 years [range 4-67 years]) were enrolled. One patient was excluded because of presentation 38 h after envenomation and two patients failed to complete the required follow-up. One patient received a dose of antibiotics before transfer. Antibiotics were discontinued upon arrival. Of the total 56 RSB patients, 34 (61%) RSBs involved the upper extremity and 22 (39%) involved the lower extremity. Six patients (11%) applied ice and two (4%) used a tourniquet before evaluation. The mean arrival time was 2.7 h (Range <1-24 h). Forty-three patients (81%) received antivenin. Fifty-three patients (100%) had extremity swelling and 38 patients (72%) had tender proximal lymph nodes. Of the 53 patients who completed the study, 3 (6%) received antibiotics from their primary care physicians at 7-10 day follow-up, with no cases (0%) of documented infection. Prophylactic antibiotics are not indicated in patients with rattlesnake bites.

  2. Synthetic biology era: Improving antibiotic's world.

    PubMed

    Guzmán-Trampe, Silvia; Ceapa, Corina D; Manzo-Ruiz, Monserrat; Sánchez, Sergio

    2017-01-31

    The emergence of antibiotic-resistant pathogen microorganisms is problematic in the context of the current spectrum of available medication. The poor specificity and the high toxicity of some available molecules have made imperative the search for new strategies to improve the specificity and to pursue the discovery of novel compounds with increased bioactivity. Using living cells as platforms, synthetic biology has counteracted this problem by offering novel pathways to create synthetic systems with improved and desired functions. Among many other biotechnological approaches, the advances in synthetic biology have made it possible to design and construct novel biological systems in order to look for new drugs with increased bioactivity. Advancements have also been made in the redesigning of RNA and DNA molecules in order to engineer antibiotic clusters for antibiotic overexpression. As for the production of these antibacterial compounds, yeasts and filamentous fungi as well as gene therapy are utilized to enhance protein solubility. Specific delivery is achieved by creating chimeras using plant genes into bacterial hosts. Some of these synthetic systems are currently in clinical trials, proving the proficiency of synthetic biology in terms of both pharmacological activities as well as an increase in the biosafety of treatments. It is possible that we may just be seeing the tip of the iceberg, and synthetic biology applications will overpass expectations beyond our present knowledge.

  3. The surgical technique of the Fobi-Pouch operation for obesity (the transected silastic vertical gastric bypass).

    PubMed

    Fobi, M A; Lee, H

    1998-06-01

    The Fobi-Pouch operation (FPO) for obesity is the product of clinical trials, more than 15 years of personal clinical experience and information gathered from publications, scientific meetings, and personal communications with other bariatric surgeons. The essence of the operation is the small vertical pouch (< 25 ml), an externally supported stoma, the interposed Roux-en-Y limb, the gastrostomy and the bypassed stomach marker to facilitate percutaneous transabdominal access to the bypassed segment. Patients undergoing this operation are usually given bowel prep the day before the operation, admitted the morning of the operation and started on subcutaneous heparin, prophylactic antibiotic and hydration. Antithrombotic sequential compression devices are regularly used. The hospital stay is usually 4 days. Our results and those of other surgeons who have used this modification substantiate the rationale for the modifications entailed in the FPO. Our longer-term experience and results are being compiled for publication.

  4. Antibiotics for acute bronchitis.

    PubMed

    Smith, Susan M; Fahey, Tom; Smucny, John; Becker, Lorne A

    2014-03-01

    The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care. To assess the effects of antibiotics in improving outcomes and assess adverse effects of antibiotic therapy for patients with a clinical diagnosis of acute bronchitis. We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January week 1, 2014), EMBASE (1974 to January 2014) and LILACS (1982 to January 2014). Randomised controlled trials (RCTs) comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in patients without underlying pulmonary disease. At least two review authors extracted data and assessed trial quality. Seventeen trials with 3936 participants were included in the primary analysis. The quality of trials was generally good. There was limited evidence to support the use of antibiotics in acute bronchitis. At follow-up, there was no difference in participants described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15; number needed to treat for an additional beneficial outcome (NNTB) 22. Participants given antibiotics were less likely to have a cough (four studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; NNTB 6); have a night cough (four studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7) and a shorter mean cough duration (seven studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated patients were more likely to be unimproved according to clinician's global assessment (six studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 25); have an abnormal lung exam (five studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB

  5. Tetracycline Antibiotics and Resistance.

    PubMed

    Grossman, Trudy H

    2016-04-01

    Tetracyclines possess many properties considered ideal for antibiotic drugs, including activity against Gram-positive and -negative pathogens, proven clinical safety, acceptable tolerability, and the availability of intravenous (IV) and oral formulations for most members of the class. As with all antibiotic classes, the antimicrobial activities of tetracyclines are subject to both class-specific and intrinsic antibiotic-resistance mechanisms. Since the discovery of the first tetracyclines more than 60 years ago, ongoing optimization of the core scaffold has produced tetracyclines in clinical use and development that are capable of thwarting many of these resistance mechanisms. New chemistry approaches have enabled the creation of synthetic derivatives with improved in vitro potency and in vivo efficacy, ensuring that the full potential of the class can be explored for use against current and emerging multidrug-resistant (MDR) pathogens, including carbapenem-resistant Enterobacteriaceae, MDR Acinetobacter species, and Pseudomonas aeruginosa. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  6. The Golden bypass landslide, Golden, Colorado

    USGS Publications Warehouse

    Highland, L.M.; Brown, W. M.

    1993-01-01

    Slope instability along a new highway bypass in Golden, Colorado, became a major concern in 1993. Rains and snowmelt accelerated movement of a landslide that had begun to develop before the bypass was opened to traffic in July of 1991. The downslope movement of earth materials increased significantly in 1993. During the first few months of the year, the landslide pushed onto the west shoulder of the road and crumpled the pavement beneath the south-bound lane. As we prepare this article (September, 1993), the slide continues to encroach onto the highway, posing a persistent problem despite repeated efforts to slow or stop its movement. As this article will show, permanent solutions to landslide problems of this kind are difficult to obtain. 

  7. Coronary artery bypass surgery in elderly people

    PubMed Central

    Natarajan, Arun; Samadian, Samad; Clark, Stephen

    2007-01-01

    An increasing number of elderly individuals are now undergoing coronary artery bypass surgery. Elderly patients, compared with patients of a younger age group, present for surgery with a greater burden of risk factors and reduced functional levels. Short‐term outcomes are hence poorer in them. But symptom relief occurs in most survivors and is accompanied by excellent rates of long‐term survival and a good quality of life. Therefore, an individualised risk–benefit profile must be carefully constructed by clinicians, taking into account several different factors and not just age alone. This review summarises the current concepts of coronary artery bypass surgery from the perspective of the very old. PMID:17344568

  8. Bypass surgery in limb salvage: inflow procedures.

    PubMed

    Bismuth, Jean; Duran, Cassidy

    2013-04-01

    Proper management of lower-extremity inflow vessel disease is critical to the success of distal interventions. Aortobifemoral bypass is the most effective means of treating aortoiliac disease, but this invasive procedure is not always ideal for a patient population that often has diffuse vascular disease and multiple comorbidities. Technologic advances and increasing experience have fundamentally altered the management algorithm for lower-extremity vascular lesions, and endovascular options have become the first-line therapy for Trans-Atlantic Inter-Society Guidelines (TASC) class A and B lesions. In fact, an endovascular first approach is being endorsed even for highly complex TASC C and even TASC D lesions. Other alternatives include minimally invasive (laparoscopic or robotic) options or extra-anatomic bypass procedures. Inadequate outflow can compromise any inflow procedure, but inflow treatment failures are the crux of all limb salvage in patients with lower-extremity vascular disease.

  9. Early rehabilitative treatment in aortocoronary bypass surgery.

    PubMed

    Petrucci, Lucia; Ramella, Francesca C; Ricotti, Susanna; Carlisi, Ettore; Di Natali, Giuseppe; Messina, Sara; Pavese, Chiara; Nicolardi, Salvatore; D'Armini, Andrea M; Dalla Toffola, Elena

    2013-01-01

    The objective of this retrospective study is to analyze functional recovery and response to rehabilitation treatment during the immediate postoperative phase of aortocoronary bypass (ACB) surgery. We studied 319 patients, who had undergone ACB surgery and who needed post-acute rehabilitation. All patients presented post-operative respiratory dysfunction, 300 cases presented inability in position changes and needed neuromotor exercises in addition to chest physiotherapy. Rehabilitation treatment began at a mean number of 1.79 +/-1.37 days after surgery and continued for 5.78 +/- 3.59 days. At the discharge, at mean 5.47 +/- 2.25 days after surgery, most of patients (65.61%) walked independently. Our study described a protocol of early rehabilitative treatment that appeared to be suitable in promoting patients'functional recovery after aortocoronary bypass surgery.

  10. Altered coronary microvascular serotonin receptor expression after coronary artery bypass grafting utilizing cardiopulmonary bypass

    PubMed Central

    Robich, Michael P.; Araujo, Eugenio G.; Feng, Jun; Osipov, Robert M.; Clements, Richard T.; Bianchi, Cesario; Sellke, Frank W.

    2009-01-01

    Objectives Evaluate the role of serotonin receptors 1B and 2A, thromboxane synthase and receptor and phospholipases A2 and C in response to cardiopulmonary bypass in patients. Methods Atrial tissue was harvested from patients before and after cardiopulmonary bypass with cardioplegia (n=13). Coronary microvessels were assessed for vasoactive response to serotonin with and without inhibitors of 5-HT1B and 5-HT2A receceptors, phospholipase A2 and C. Expression of 5-HT1B and 5-HT2A mRNA was determined by RT-PCR. Expression of 5-HT1B, 5-HT2A, Thromboxane A2 receptor and synthase protein was determined by immunoblotting and immunohistochemistry. Results Exposure of microvessels to serotonin elicited a 7.3 ± 2% relaxation response pre-bypass, changing to a strong contraction response of -19.2 ± 2% after bypass (p<0.001). Addition of either a specific 5-HT1B antagonist or inhibitor of PLA2 resulted in a significant decrease in the contractile response to -8.6 ±1% (p<0.001) and 2.8 ± 3% (p= 0.001), respectively. 5-HT1B receptor mRNA expression increased 1.82 ± 0.34 fold after bypass (p=0.044), while 5-HT2A mRNA expression did not change. 5-HT1B receptor, but not 5-HT2A, protein expression increased after bypass by 1.35 ± 0.7 fold (p=0.0413). Neither thromboxane synthase nor thromboxane receptor expression changed after bypass. Immunohistochemistry demonstrated 5-HT1B receptor increased mainly in the arterial smooth muscle. There was no appreciable difference in arterial expression of either thromboxane synthase or receptor. Conclusion These data indicate that 5-HT-induced vascular dysfunction after cardiopulmonary bypass with cardioplegia may be mediated by increased expression of 5-HT1B receptor and subsequent PLA2 activation in myocardial coronary smooth muscle. Mini Abstract The expression of 5-HT1B receptor protein and mRNA were increased in the atrial myocardium after cardioplegia and cardiopulmonary bypass (CP-CPB). Serotonin elicited a strong contraction

  11. Antibiotic prophylaxis in otolaryngologic surgery

    PubMed Central

    Ottoline, Ana Carolina Xavier; Tomita, Shiro; Marques, Marise da Penha Costa; Felix, Felippe; Ferraiolo, Priscila Novaes; Laurindo, Roberta Silveira Santos

    2013-01-01

    Summary Aim: Antibiotic prophylaxis aims to prevent infection of surgical sites before contamination or infection occurs. Prolonged antibiotic prophylaxis does not enhance the prevention of surgical infection and is associated with higher rates of antibiotic-resistant microorganisms. This review of the literature concerning antibiotic prophylaxis, with an emphasis on otolaryngologic surgery, aims to develop a guide for the use of antibiotic prophylaxis in otolaryngologic surgery in order to reduce the numbers of complications stemming from the indiscriminate use of antibiotics. PMID:25991999

  12. Lessons learned from gastric bypass operations in rats.

    PubMed

    Seyfried, Florian; le Roux, Carel W; Bueter, Marco

    2011-01-01

    Numerous studies using gastric bypass rat models have been recently conducted to uncover underlying physiological mechanisms of Roux-en-Y gastric bypass. Reflecting on lessons learned from gastric bypass rat models may thus aid the development of gastric bypass models in mice and other species. This review aims to discuss technical and experimental details of published gastric bypass rat models to understand advantages and limitations of this experimental tool. The review is based on PubMed literature using the search terms 'animal model', 'rodent model', 'bariatric surgery', 'gastric bypass', and 'Roux-en-Y gastric bypass'. All studies published up until February 2011 were included. 32 studies describing 15 different rat gastric bypass models were included. Description of surgical technique differs in terms of pouch size, limb lengths, preservation of the vagal nerve, and mortality rate. Surgery was carried out exclusively in male rats of different strains and ages. Pre- and postoperative diets also varied significantly. Technical and experimental variations in published gastric bypass rat models complicate comparison and identification of potential physiological mechanisms involved in gastric bypass. In summary, there is no clear evidence that any of these models is superior, but there is an emerging need for standardization of the procedure to achieve consistent and comparable data. Copyright © 2011 S. Karger AG, Basel.

  13. Human cytokine responses to coronary artery bypass grafting with and without cardiopulmonary bypass.

    PubMed

    Strüber, M; Cremer, J T; Gohrbandt, B; Hagl, C; Jankowski, M; Völker, B; Rückoldt, H; Martin, M; Haverich, A

    1999-10-01

    Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response. This has been attributed to cytokine release caused by extracorporeal circulation and myocardial ischemia. This study compares the inflammatory response after CABG with cardiopulmonary bypass and after minimally invasive direct coronary artery bypass grafting (MIDCABG) without cardiopulmonary bypass. Cytokine release and complement activation (interleukin-6 and interleukin-8, soluble tumor necrosis factor receptors 1 and 2, complement factor C3a, and C1 esterase inhibitor) were determined in 24 patients before and after CABG or MIDCABG. The maximum body temperature, chest drainage, and fluid balance were recorded for 24 hours after operation. Release of interleukin-6, interleukin-8, and tumor necrosis factor receptors 1 and 2 was significantly higher (p < or = 0.005) in the CABG group than the MIDCABG group just after operation. After 24 hours, a significant increase in interleukin-6 was also found in the MIDCABG group (p = 0.001) compared with preoperative value. Body temperature and fluid balance were significantly higher after CABG (p < or = 0.001). Minimally invasive direct coronary artery bypass grafting represents a less traumatizing technique of surgical revascularization. The reduction in the inflammatory response may be advantageous for patients with a high degree of comorbidity.

  14. Effects of Cardiopulmonary Bypass on Hemostasis

    DTIC Science & Technology

    2007-11-02

    agents as possible alternatives to heparin anticoagulation during CPB. Some of the agents mat have been found to be promising in these studies...67-76. 22Q. Terrell MR, Walenga JM, Koza MJ, et al. Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass. AnnThorac Surg...procedures, systemic anticoagulation with 3mg/kg of heparin prior to the institution of CPB elicits a modest but significant prolongation of the

  15. Aircraft High Bypass Fan Engine Performance

    DTIC Science & Technology

    1994-03-01

    in component efficiencies, combustor design, development of high temperature alloys , and the development of the high bypass fan. The biggest advance...Partially Modified 29.3:1 1.58:1 9.0:1 2900 7029 0.6213 P/M 107 Partially Modified 29.3:1 1.53:1 9.0:1 2700 6660 0.606 F/M 103 Fully Modified 29.3:1 1.53:1

  16. Control of Bypass Transition for Textile Surface

    NASA Astrophysics Data System (ADS)

    Kikuchi, Satoshi; Shimoji, Masayuki; Watanabe, Hideo; Kohama, Yasuaki

    The present research deals with turbulent friction reduction for bypass transition on a flat plate with a textile surface. Unique boundary layers such as those found in swimsuits, sail wings, or skiwear, where certain boundary layer trip structure-like folded edges or masts of a sailboat exist, contain limited turbulence level in the boundary layer even under laminar conditions. A turbulent transition delay in such boundary layers is observed for textile surfaces.

  17. Histoplasma infection of aortofemoral bypass graft.

    PubMed

    Patel, Nishit; Bronze, Michael S

    2014-05-01

    Histoplasma infection of vascular grafts is extremely rare. To our knowledge, there are only 4 cases reported with Histoplasma capsulatum infection of the aortic graft. All had previous disseminated histoplasmosis and atherosclerotic peripheral vascular disease. They were treated surgically with explantation of the infected graft and reimplantation of new graft in extra-anatomic uninfected site. The authors present a new case of H capsulatum infection of aortofemoral bypass graft, but unlike the other cases, this case was managed without surgical intervention.

  18. Tackling antibiotic resistance

    PubMed Central

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.

    2014-01-01

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

  19. Predicting antibiotic resistance.

    PubMed

    Martínez, José L; Baquero, Fernando; Andersson, Dan I

    2007-12-01

    The treatment of bacterial infections is increasingly complicated because microorganisms can develop resistance to antimicrobial agents. This article discusses the information that is required to predict when antibiotic resistance is likely to emerge in a bacterial population. Indeed, the development of the conceptual and methodological tools required for this type of prediction represents an important goal for microbiological research. To this end, we propose the establishment of methodological guidelines that will allow researchers to predict the emergence of resistance to a new antibiotic before its clinical introduction.

  20. Antibiotics in Animal Products

    NASA Astrophysics Data System (ADS)

    Falcão, Amílcar C.

    The administration of antibiotics to animals to prevent or treat diseases led us to be concerned about the impact of these antibiotics on human health. In fact, animal products could be a potential vehicle to transfer drugs to humans. Using appropri ated mathematical and statistical models, one can predict the kinetic profile of drugs and their metabolites and, consequently, develop preventive procedures regarding drug transmission (i.e., determination of appropriate withdrawal periods). Nevertheless, in the present chapter the mathematical and statistical concepts for data interpretation are strictly given to allow understanding of some basic pharma-cokinetic principles and to illustrate the determination of withdrawal periods

  1. Antibiotics and preterm labor.

    PubMed

    Mertz, H L; Ernest, J M

    2001-08-01

    Prematurity is a profound obstetric problem and to date no effective treatment or prevention strategies have been found. Many animal and clinical data exist to link infection and preterm labor, yet clinical trials examining the effect of antibiotic treatment in patients with patterns labor and intact membranes have been conflicting and disappointing. Beyond treatment to reduce neonatal group B streptococcal infection, sexually transmitted infections, symptomatic bacterial vaginosis, and bacteriuria, no clinical data exist at this time to support the routine use of antibiotics in patients with preterm labor and intact membranes.

  2. New classes of antibiotics.

    PubMed

    Moir, Donald T; Opperman, Timothy J; Butler, Michelle M; Bowlin, Terry L

    2012-10-01

    Several novel chemical classes of antibiotics are currently in human clinical studies. While most are narrow spectrum agents that inhibit unexploited targets, the susceptible pathogens are clinically important, including staphylococci, pseudomonads, and mycobacteria. Given the paucity of antibacterial agents consisting of novel chemical scaffolds that act on established targets, these new antibacterial scaffolds, which are active against new targets, represent an important advance in the battle against antibiotic resistance. Indeed, most of these compounds are unlikely to be subject to existing compound-based or target-based resistance mechanisms.

  3. Synthesis of Antibiotics.

    PubMed

    Kalesse, Markus; Böhm, Andreas; Kipper, Andi; Wandelt, Vanessa

    The synthesis of β-lactams, tetracyclines, and erythromycins as three of the major families of antibiotics will be described herein. We will describe why these antibiotics were the ultimate synthetic targets in the past and how modern synthetic organic chemistry has evolved to address these challenges with new, improved strategies and methods. An additional aspect we would like to highlight here is the fact that these first syntheses had to be particularly creative as most of the modern synthetic methods were not available at that time, or were developed in the course of these syntheses.

  4. Discovery research: the scientific challenge of finding new antibiotics.

    PubMed

    Livermore, David M

    2011-09-01

    The dwindling supply of new antibiotics largely reflects regulatory and commercial challenges, but also a failure of discovery. In the 1990s the pharmaceutical industry abandoned its classical ways of seeking antibiotics and instead adopted a strategy that combined genomics with high-throughput screening of existing compound libraries. Too much emphasis was placed on identifying targets and molecules that bound to them, and too little emphasis was placed on the ability of these molecules to permeate bacteria, evade efflux and avoid mutational resistance; moreover, the compound libraries were systematically biased against antibiotics. The sorry result is that no antibiotic found by this strategy has yet entered clinical use and many major pharmaceutical companies have abandoned antibiotic discovery. Although a raft of start-up companies-variously financed by venture capital, charity or public money--are now finding new antibiotic compounds (some of them very promising in vitro or in early trials), their development through Phase III depends on financial commitments from large pharmaceutical companies, where the discouraging regulatory environment and the poor likely return on investment remain paramount issues.

  5. Antibiotics and antibiotic resistance in agroecosystems: State of the science

    USDA-ARS?s Scientific Manuscript database

    We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly su...

  6. Percutaneous venovenous bypass in orthotopic liver transplantation.

    PubMed

    Washburn, W K; Lewis, W D; Jenkins, R L

    1995-11-01

    Since January 1994, we have used percutaneous placement of both the subclavian and femoral cannulae to establish access for venovenous bypass during orthotopic liver transplantation. Percutaneous subclavian and femoral cannulae were used in 36 patients of which 5 had portal decompression by placement of a cannula in inferior mesenteric vein percutaneously through the abdominal wall. Intraoperative placement of the subclavian cannula is facilitated by placing a subclavian central venous line before the abdominal incision. One patient underwent exploration for femoral vein bleeding early in our experience. Another patient sustained hypotension as a result of a kinked subclavian cannula. In 4 patients, early in this experience, we had difficulty placing the subclavian cannula and resorted to axillary vein cut-down. There were no episodes of deep venous thrombosis detected by routine postoperative duplex ultrasonography. Minimum and maximum flow rates were significantly better (P < .01), with percutaneously placed cannulae in comparison to a control group of patients who underwent transplantation in whom we used the standard venous cut-down approach with a #7 Gott shunt (2.14 and 3.17 L/min v 1.65 and 2.41 L/min, respectively). Percutaneous placement of cannulae for venovenous bypass during liver transplantation is quick, safe, and effective. We would advocate this technique as an alternative approach for patients in whom bypass is deemed necessary.

  7. Aortic surgery using total miniaturized cardiopulmonary bypass.

    PubMed

    Issitt, Richard W; Mulholland, John W; Oliver, Martin D; Yarham, Gemma J; Borra, Philippa J; Morrison, Paul; Dimarakis, Ioannis; Anderson, Jon R

    2008-08-01

    Few centers have attempted aortic surgery using miniaturized cardiopulmonary bypass (MCPB) systems due to concerns of air handling. The extra corporeal circuit optimized (ECCO) total MCPB system uses a venous air removal device and a parallel soft-shell reservoir that allows for venting of the heart. At our institution, total MCPB is used for all coronary artery bypass graft patients. Our objective was to assess the suitability of the ECCO total MCPB system during aortic surgery. Fifty consecutive and unselected aortic procedures using the ECCO system were undertaken. Surgical feasibility, air removal ability, and blood transfusion requirements were audited to determine the efficacy of this technique. The bypass time was 81.6 +/- 28.0 minutes and the ischemic time was 56.7 +/- 18.9 minutes. Total MCPB handled 1,910 +/- 404 mL of vented blood with 96 venous air removal device activations noted. The blood product transfusion rate was 12%, which was below the surgical transfusion rate for our unit. There were no complications. Aortic surgery can be undertaken safely and effectively using the ECCO total MCPB system.

  8. Vein harvesting and techniques for infrainguinal bypass.

    PubMed

    Albäck, Anders; Saarinen, Eva; Venermo, Maarit

    2016-04-01

    In order to achieve good long term results after bypass surgery, alongside with good inflow and outflow arteries, the bypass graft material also has an important role. The best patency and limb salvage rates are achieved with autologous vein. If great saphenous vein is not available, acceptable long-term results can be achieved with arm veins and lesser saphenous vein. The quality and size of the vein are important. A small-caliber vein, increased wall thickness, postphlebitic changes and varicosities are associated with a risk of early failure. Preoperative vein mapping with ultrasound reduces readmissions and postoperative surgical site infections. During the mapping, the vein to be used and its main tributaries are marked with a permanent marker pen. To reduce wound complication rates we recommend bridged incisions in vein harvesting. Endoscopic vein harvesting seems to have no benefit compared to open techniques in lower limb bypasses, and has been associated with higher risk of primary patency loss at one year. With deep tunneling of the graft the problems caused by wound infection can be avoided.

  9. 78 FR 46594 - Prospective Grant of Start-up Exclusive License: Topical Antibiotic With Immune Stimulating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-01

    ... Antibiotic With Immune Stimulating Oligodeoxynucleotide Molecules To Speed Wound Healing; and Use of CpG... to Speed Wound Healing'' and US application 12/205,756 (E-328-2001/1-US-01) filed September 2008 and... oligodeoxynucleotides (ODNs) to accelerate wound healing. The E-294- 2011/0, technology relates to an antibiotic...

  10. Horizontal gene transfer and antibiotic resistance plasmids in multi-drug resistant Salmonella enterica serovars

    USDA-ARS?s Scientific Manuscript database

    Antibiotic resistant foodborne pathogens pose serious public health concerns and increase the burden of disease treatment. Antibiotic resistance genes can reside on the bacterial chromosome or on other self-replicating DNA molecules such as plasmids. The resistance genes/DNA can be transferred int...

  11. A new strategy to fight antimicrobial resistance: the revival of old antibiotics

    PubMed Central

    Cassir, Nadim; Rolain, Jean-Marc; Brouqui, Philippe

    2014-01-01

    The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is limiting the options for effective antibiotic therapy. Moreover, this alarming spread of antimicrobial resistance has not been paralleled by the development of novel antimicrobials. Resistance to the scarce new antibiotics is also emerging. In this context, the rational use of older antibiotics could represent an alternative to the treatment of MDR bacterial pathogens. It would help to optimize the armamentarium of antibiotics in the way to preserve new antibiotics and avoid the prescription of molecules known to favor the spread of resistance (i.e., quinolones). Furthermore, in a global economical perspective, this could represent a useful public health orientation knowing that several of these cheapest “forgotten” antibiotics are not available in many countries. We will review here the successful treatment of MDR bacterial infections with the use of old antibiotics and discuss their place in current practice. PMID:25368610

  12. The MAR1 transporter is an opportunistic entry point for antibiotics.

    PubMed

    Conte, Sarah S; Lloyd, Alan M

    2010-01-01

    The vast quantities of antibiotics used in modern agriculture contaminate the environment and threaten human health. Recent studies have shown that crop plants grown in soil fertilized with manure from antibiotic-treated animals can accumulate antibiotic within the plant body, thus making them an additional antibiotic exposure route for consumers. Until recently, mechanisms of antibiotic entry and subcellular partitioning within plant cells were virtually unknown. We have uncovered and characterized a transporter gene in Arabidopsis thaliana, MAR1, which appears to control antibiotic entry into the chloroplast. Antibiotic resistance via MAR1 is specific to the aminoglycoside class, and is conferred by loss-of-function mutations, which is rather unusual, since most transporter-based antibiotic resistance is conferred by overexpression or gain-of-function mutations in efflux pumps with poor substrate specificity. Since MAR1 overexpression lines exhibit various iron starvation phenotypes, we propose that MAR1 transports an iron chelation molecule that is mimicked specifically by aminoglycoside antibiotics, and this facilitates their entry into the chloroplast. Knowledge about MAR1 enhances our understanding of how antibiotics might enter the plant cell, which may aid in the production of crop plants that are incapable of antibiotic accumulation, as well as further the development of new plant-based antibiotic resistance markers.

  13. Antibiotics and Resistance: Glossary

    MedlinePlus

    ... bacteria are stained dark purple. Cell walls of gram-negative bacteria are more permeable - they do not retain much of the dye, and so their cell walls do not show much stain. Growth promoters A class of substances, usually antibiotics, ...

  14. Resistance-Resistant Antibiotics

    PubMed Central

    Oldfield, Eric; Feng, Xinxin

    2014-01-01

    New antibiotics are needed because as drug resistance is increasing, the introduction of new antibiotics is decreasing. Here, we discuss six possible approaches to develop ‘resistance-resistant’ antibiotics. First, multi-target inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy due to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, re-purposing existing drugs can lead to combinations of multi-target therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and in some cases suggest that sensitivity to existing antibiotics may be restored, in otherwise drug resistant organisms. PMID:25458541

  15. Mechanisms of Antibiotic Resistance

    PubMed Central

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

  16. Ruling out antibiotics.

    PubMed

    Griffiths, Matt

    2017-06-14

    Most upper respiratory tract infections are viral. As antibiotics are only effective if the infection is caused by bacteria, they are not recommended in most cases. However, prescribing for respiratory tract infections in primary care is not an exact science, and deciding whether an infection is viral or bacterial is often down to individual clinicians.

  17. Sources of novel antibiotics--aside the common roads.

    PubMed

    Donadio, Stefano; Maffioli, Sonia; Monciardini, Paolo; Sosio, Margherita; Jabes, Daniela

    2010-12-01

    Microbial pathogens are becoming increasingly resistant to available treatments, and new antibiotics are badly needed, but the pipeline of compounds under development is scarce. Furthermore, the majority of antibiotics under development are improved derivatives of marketed compounds, which are at best only partially effective against prevailing resistance mechanisms. In contrast, antibiotics endowed with new mechanisms of action are expected to be highly effective against multi-drug resistant pathogens. In this review, examples are provided of new antibiotics classes in late discovery or clinical development, arising from three different avenues: (1) compounds discovered and never brought to market by large pharmaceutical companies; (2) old compounds reanalyzed and rejuvinated with today's tools; and (3) newly discovered molecules. For each compound, we will briefly describe original discovery, mechanism of action, any known resistance, antimicrobial profile, and current status of development.

  18. Antibiotics and specialized metabolites from the human microbiota.

    PubMed

    Mousa, Walaa K; Athar, Bilal; Merwin, Nishanth J; Magarvey, Nathan A

    2017-10-11

    Covering: 2000 to 2017Decades of research on human microbiota have revealed much of their taxonomic diversity and established their direct link to health and disease. However, the breadth of bioactive natural products secreted by our microbial partners remains unknown. Of particular interest are antibiotics produced by our microbiota to ward off invasive pathogens. Members of the human microbiota exclusively produce evolved small molecules with selective antimicrobial activity against human pathogens. Herein, we expand upon the current knowledge concerning antibiotics derived from human microbiota and their distribution across body sites. We analyze, using our in-house chem-bioinformatic tools and natural products database, the encoded antibiotic potential of the human microbiome. This compilation of information may create a foundation for the continued exploration of this intriguing resource of chemical diversity and expose challenges and future perspectives to accelerate the discovery rate of small molecules from the human microbiota.

  19. Antibiotics, Pediatric Dysbiosis, and Disease

    PubMed Central

    Vangay, Pajau; Ward, Tonya; Gerber, Jeffrey S.; Knights, Dan

    2017-01-01

    Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome’s responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy. PMID:25974298

  20. Antibiotic-Resistant Gonorrhea (ARG)

    MedlinePlus

    ... please visit this page: About CDC.gov . Gonorrhea Antibiotic Resistance Basic Information Laboratory Information Resources & References Combating the ... Page Surveillance Trends and Treatment Challenges Laboratory Issues Antibiotic resistance (AR) is the ability of bacteria to resist ...

  1. Bacterial cheating limits antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

    2012-02-01

    The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

  2. Antibiotics, pediatric dysbiosis, and disease.

    PubMed

    Vangay, Pajau; Ward, Tonya; Gerber, Jeffrey S; Knights, Dan

    2015-05-13

    Antibiotics are by far the most common medications prescribed for children. Recent epidemiological data suggests an association between early antibiotic use and disease phenotypes in adulthood. Antibiotic use during infancy induces imbalances in gut microbiota, called dysbiosis. The gut microbiome's responses to antibiotics and its potential link to disease development are especially complex to study in the changing infant gut. Here, we synthesize current knowledge linking antibiotics, dysbiosis, and disease and propose a framework for studying antibiotic-related dysbiosis in children. We recommend future studies into the microbiome-mediated effects of antibiotics focused on four types of dysbiosis: loss of keystone taxa, loss of diversity, shifts in metabolic capacity, and blooms of pathogens. Establishment of a large and diverse baseline cohort to define healthy infant microbiome development is essential to advancing diagnosis, interpretation, and eventual treatment of pediatric dysbiosis. This approach will also help provide evidence-based recommendations for antibiotic usage in infancy.

  3. Antibiotics and Pregnancy: What's Safe?

    MedlinePlus

    Healthy Lifestyle Pregnancy week by week Is it safe to take antibiotics during pregnancy? Answers from Roger W. Harms, M. ... 2014 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/expert-answers/antibiotics-and-pregnancy/ ...

  4. Structure aided design of chimeric antibiotics.

    PubMed

    Karoli, Tomislav; Mamidyala, Sreeman K; Zuegg, Johannes; Fry, Scott R; Tee, Ernest H L; Bradford, Tanya A; Madala, Praveen K; Huang, Johnny X; Ramu, Soumya; Butler, Mark S; Cooper, Matthew A

    2012-04-01

    The rise of antibiotic resistance is of great clinical concern. One approach to reducing the development of resistance is to co-administer two or more antibiotics with different modes of action. However, it can be difficult to control the distribution and pharmacokinetics of two drugs to ensure both concentrations remain within the range of therapeutic efficacy whilst avoiding adverse effects. Hybrid drugs, where two drugs are linked together with a flexible linker, have been explored, but the resultant large, flexible molecules can have poor bioavailability. We have developed a chimeric approach using click chemistry where the pharmacophores of two drugs are overlapped into a single smaller, more drug-like molecule. Design and selection of compounds were assisted by in silico structural docking. We prepared a series of compounds that include candidates showing activity against the targets of both trimethoprim; dihydrofolate reductase, and ciprofloxacin; DNA gyrase and topoisomerase IV. The resultant triazole containing molecules show modest, but broad spectrum activities against drug sensitive and resistant Gram-negative and Gram-positive bacteria, with no observable cytotoxicity.

  5. Hypopotassemia following open heart surgery by cardio-pulmonary bypass.

    PubMed

    Abe, T; Nagata, Y; Yoshioka, K; Iyomasa, Y

    1977-01-01

    1. In this study where potassium concentration of perfusate of heart-lung machine was made high and no potassium was given until two hours after by-pass, the fall of plasma potassium level due to heart-lung bypass occurred in two stages, namely one hour of complete bypass and two hours after the end of bypass. 2. Regarding to the decrease of these plasma potassium level, increase of potassium excretion into urine and the movement of potassium from extracellular fluid into cells are presumed to be causes. Their genesis was discussed. 3. To prevent hypopotassemia following bypass, it is recommended to add KCl in the perfusate of heart-lung machine and to give intravenous drip of KCl immediately after bypass.

  6. Mind Molecules

    PubMed Central

    Snyder, Solomon H.

    2011-01-01

    Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius “Julie” Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the “high” that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes. PMID:21543333

  7. Supercomputer Simulations Help Develop New Approach to Fight Antibiotic Resistance

    ScienceCinema

    Zgurskaya, Helen; Smith, Jeremy

    2016-11-23

    ORNL leveraged powerful supercomputing to support research led by University of Oklahoma scientists to identify chemicals that seek out and disrupt bacterial proteins called efflux pumps, known to be a major cause of antibiotic resistance. By running simulations on Titan, the team selected molecules most likely to target and potentially disable the assembly of efflux pumps found in E. coli bacteria cells.

  8. Supercomputer Simulations Help Develop New Approach to Fight Antibiotic Resistance

    SciTech Connect

    Zgurskaya, Helen; Smith, Jeremy

    2016-11-17

    ORNL leveraged powerful supercomputing to support research led by University of Oklahoma scientists to identify chemicals that seek out and disrupt bacterial proteins called efflux pumps, known to be a major cause of antibiotic resistance. By running simulations on Titan, the team selected molecules most likely to target and potentially disable the assembly of efflux pumps found in E. coli bacteria cells.

  9. Investigating the Antibiotic Resistance Problem.

    ERIC Educational Resources Information Center

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

    Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

  10. Antibiotic Prophylaxis in Orbital Fractures

    PubMed Central

    Reiss, Benjamin; Rajjoub, Lamise; Mansour, Tamer; Chen, Tony; Mumtaz, Aisha

    2017-01-01

    Purpose: To determine whether prophylactic antibiotic use in patients with orbital fracture prevent orbital infection. Design: Retrospective cohort study. Participants: All patients diagnosed with orbital fracture between January 1, 2008 and March 1, 2014 at The George Washington University Hospital and Clinics. Main Outcome Measures: Development of orbital infection. Results: One hundred seventy-two patients with orbital fracture met our inclusion and exclusion criteria. No orbital infections were documented. Twenty subjects (12%) received no prophylactic antibiotic, and two (1%) received only one dose of antibiotics pre-operatively for surgery. For primary antibiotic, 136 subjects (79%) received oral antibiotics, and 14 (8%) received intravenous (IV) antibiotics (excluding cefazolin). Cephalexin and amoxicillin-clavulanate were the most prescribed oral antibiotics that are equally effective. Five-to-seven day courses of antibiotics had no increased infections compared to ten-to-fourteen day courses. Calculated boundaries for effectiveness of prophylactic antibiotics ranged from a Number Needed to Treat (NNT) of 75 to a Number Needed to Harm (NNH) of 198. Conclusion: Antibiotics for prevention of orbital infection in patients with orbital fractures have become widely used. Coordination between trauma teams and specialists is needed to prevent patient overmedication and antibiotic resistance. Should antibiotics be used, shorter courses and avoidance of broad spectrum agents are recommended. Additional studies are needed. PMID:28400887

  11. Investigating the Antibiotic Resistance Problem.

    ERIC Educational Resources Information Center

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

    Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

  12. Danger of Antibiotic Overuse (For Parents)

    MedlinePlus

    ... 1- to 2-Year-Old The Danger of Antibiotic Overuse KidsHealth > For Parents > The Danger of Antibiotic ... by not reaching for the prescription pad. How Antibiotics Work Antibiotics, first used in the 1940s, are ...

  13. Heat exchanger bypass system for an absorption refrigeration system

    DOEpatents

    Reimann, Robert C.

    1984-01-01

    A heat exchanger bypass system for an absorption refrigeration system is disclosed. The bypass system operates to pass strong solution from the generator around the heat exchanger to the absorber of the absorption refrigeration system when strong solution builds up in the generator above a selected level indicative of solidification of strong solution in the heat exchanger or other such blockage. The bypass system includes a bypass line with a gooseneck located in the generator for controlling flow of strong solution into the bypass line and for preventing refrigerant vapor in the generator from entering the bypass line during normal operation of the refrigeration system. Also, the bypass line includes a trap section filled with liquid for providing a barrier to maintain the normal pressure difference between the generator and the absorber even when the gooseneck of the bypass line is exposed to refrigerant vapor in the generator. Strong solution, which may accumulate in the trap section of the bypass line, is diluted, to prevent solidification, by supplying weak solution to the trap section from a purge system for the absorption refrigeration system.

  14. Use of Robotics During Laparoscopic Gastric Bypass for Morbid Obesity

    PubMed Central

    Artuso, Dominick; Grossi, Robert

    2005-01-01

    To evaluate the theoretical increased precision offered by utilization of the robotic instrument, we attempted to determine whether incorporation of its use into traditional laparoscopic gastric bypass would duplicate or improve the success of the operation without increasing complications. The Roux-en-Y gastric bypass is the most commonly performed procedure for morbid obesity in the United States. We performed 120 gastric bypass procedures with traditional laparoscopy during a 30-month period. We began introducing the da Vinci Robotic Surgical System into our laparoscopic gastric bypass procedure and evaluated its effectiveness. PMID:16121869

  15. Jejunioleal Bypass Procedures in Morbid Obesity: Preoperative Psychological Findings

    ERIC Educational Resources Information Center

    Webb, Warren W.; And Others

    1976-01-01

    Seventy patients who averaged 155 percent overweight and requested jejunioleal bypass surgery as a treatment intervention for morbid obesity were studied preoperatively for prominent psychological characteristics. (Author)

  16. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.

  17. Selection of antibiotic resistance at very low antibiotic concentrations

    PubMed Central

    2014-01-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed. PMID:24694026

  18. Selection of antibiotic resistance at very low antibiotic concentrations.

    PubMed

    Sandegren, Linus

    2014-05-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  19. Antibiotic alternatives: the substitution of antibiotics in animal husbandry?

    PubMed Central

    Cheng, Guyue; Hao, Haihong; Xie, Shuyu; Wang, Xu; Dai, Menghong; Huang, Lingli; Yuan, Zonghui

    2014-01-01

    It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment. PMID:24860564

  20. Bacterial gasotransmitters: an innate defense against antibiotics.

    PubMed

    Luhachack, Lyly; Nudler, Evgeny

    2014-10-01

    In recent decades, there has been growing interest in the field of gasotransmitters, endogenous gaseous signaling molecules (NO, H2S, and CO), as regulators of a multitude of biochemical pathways and physiological processes. Most of the concerted effort has been on eukaryotic gasotransmitters until the subsequent discovery of bacterial counterparts. While the fundamental aspects of bacterial gasotransmitters remain undefined and necessitate further research, we will discuss a known specific role they play in defense against antibiotics. Considering the current dilemma of multidrug-resistant bacteria we consider it particularly prudent to exploring novel targets and approaches, of which the bacterial gasotransmitters, nitric oxide and hydrogen sulfide represent.

  1. Isotope effects, dynamic matching, and solvent dynamics in a Wittig reaction. Betaines as bypassed intermediates.

    PubMed

    Chen, Zhuo; Nieves-Quinones, Yexenia; Waas, Jack R; Singleton, Daniel A

    2014-09-24

    The mechanism of the Wittig reaction of anisaldehyde with a stabilized ylide was studied by a combination of (13)C kinetic isotope effects, conventional calculations, and molecular dynamics calculations in a cluster of 53 THF molecules. The isotope effects support a cycloaddition mechanism involving two sequential transition states associated with separate C-C and P-O bond formations. However, the betaine structure in between the two transition states is bypassed as an equilibrated intermediate in most trajectories. The role of the dynamics of solvent equilibration in the nature of mechanistic intermediates is discussed.

  2. Isotope Effects, Dynamic Matching, and Solvent Dynamics in a Wittig Reaction. Betaines as Bypassed Intermediates

    PubMed Central

    2015-01-01

    The mechanism of the Wittig reaction of anisaldehyde with a stabilized ylide was studied by a combination of 13C kinetic isotope effects, conventional calculations, and molecular dynamics calculations in a cluster of 53 THF molecules. The isotope effects support a cycloaddition mechanism involving two sequential transition states associated with separate C–C and P–O bond formations. However, the betaine structure in between the two transition states is bypassed as an equilibrated intermediate in most trajectories. The role of the dynamics of solvent equilibration in the nature of mechanistic intermediates is discussed. PMID:25208686

  3. Generic antibiotics in Japan.

    PubMed

    Fujimura, Shigeru; Watanabe, Akira

    2012-08-01

    Generic drugs have been used extensively in many developed countries, although their use in Japan has been limited. Generic drugs reduce drug expenses and thereby national medical expenditure. Because generic drugs provide advantages for both public administration and consumers, it is expected that they will be more widely used in the future. However, the diffusion rate of generic drugs in Japan is quite low compared with that of other developed countries. An investigation on generic drugs conducted by the Ministry of Health, Labour and Welfare in Japan revealed that 17.2 % of doctors and 37.2 % of patients had not used generic drugs. The major reasons for this low use rate included distrust of off-patent products and lower drug price margin compared with the brand name drug. The generic drugs available in the market include external drugs such as wet packs, antihypertensive agents, analgesics, anticancer drugs, and antibiotics. Among them, antibiotics are frequently used in cases of acute infectious diseases. When the treatment of these infections is delayed, the infection might be aggravated rapidly. The pharmacokinetics-pharmacodynamics (PK-PD) theory has been adopted in recent chemotherapy, and in many cases, the most appropriate dosage and administration of antibiotics are determined for individual patients considering renal function; high-dosage antibiotics are used preferably for a short duration. Therefore, a highly detailed antimicrobial agent is necessary. However, some of the generic antibiotics have less antibacterial potency or solubility than the brand name products. We showed that the potency of the generic products of vancomycin and teicoplanin is lower than that of the branded drugs by 14.6 % and 17.3 %, respectively. Furthermore, we confirmed that a generic meropenem drug for injection required about 82 s to solubilize in saline, whereas the brand product required only about 21 s. It was thought that the cause may be the difference in size of bulk

  4. Molecular mechanisms of antibiotic resistance.

    PubMed

    Blair, Jessica M A; Webber, Mark A; Baylay, Alison J; Ogbolu, David O; Piddock, Laura J V

    2015-01-01

    Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.

  5. Biosynthetic Genes for the Tetrodecamycin Antibiotics

    PubMed Central

    Gverzdys, Tomas

    2016-01-01

    ABSTRACT We recently described 13-deoxytetrodecamycin, a new member of the tetrodecamycin family of antibiotics. A defining feature of these molecules is the presence of a five-membered lactone called a tetronate ring. By sequencing the genome of a producer strain, Streptomyces sp. strain WAC04657, and searching for a gene previously implicated in tetronate ring formation, we identified the biosynthetic genes responsible for producing 13-deoxytetrodecamycin (the ted genes). Using the ted cluster in WAC04657 as a reference, we found related clusters in three other organisms: Streptomyces atroolivaceus ATCC 19725, Streptomyces globisporus NRRL B-2293, and Streptomyces sp. strain LaPpAH-202. Comparing the four clusters allowed us to identify the cluster boundaries. Genetic manipulation of the cluster confirmed the involvement of the ted genes in 13-deoxytetrodecamycin biosynthesis and revealed several additional molecules produced through the ted biosynthetic pathway, including tetrodecamycin, dihydrotetrodecamycin, and another, W5.9, a novel molecule. Comparison of the bioactivities of these four molecules suggests that they may act through the covalent modification of their target(s). IMPORTANCE The tetrodecamycins are a distinct subgroup of the tetronate family of secondary metabolites. Little is known about their biosynthesis or mechanisms of action, making them an attractive subject for investigation. In this paper we present the biosynthetic gene cluster for 13-deoxytetrodecamycin in Streptomyces sp. strain WAC04657. We identify related clusters in several other organisms and show that they produce related molecules. PMID:27137499

  6. [Repeat bypass surgery for intracranial hemorrhage 30 years after indirect bypass for moyamoya disease].

    PubMed

    Hori, Satoshi; Kashiwazaki, Daina; Akioka, Naoki; Hamada, Hideo; Kuwayama, Naoya; Kuroda, Satoshi

    2014-04-01

    A 39-year-old man had been diagnosed with moyamoya disease and underwent a bilateral encephalo-duro-arterio-synangiosis(EDAS)intervention at the age of 9 years. During the 30 years after his bilateral EDAS, he experienced no cerebrovascular events. However, at age 39, he suddenly presented with mild consciousness disturbance and vomiting and was transferred to a local hospital. Brain CT showed an intracerebral hemorrhage associated with ventricular hematoma. He was referred to our hospital for further investigation and treatment. Cerebral angiography showed faint collaterals through the site of the bilateral EDAS and development of basal moyamoya vessels. SPECT showed decreased cerebral blood flow(CBF)and cerebrovascular reactivity(CVR)in the right frontal lobe. We diagnosed him with delayed cerebral hemorrhage due to delayed rupturing of fragile moyamoya vessels after indirect bypass. The patient underwent a repeat bypass surgery(STA-MCA anastomosis and encephalo-duro-myo-arterio-pericranial synangiosis;EDMAPS)on the right side. He showed improvement in cerebral hemodynamics after surgery, and has since remained free from cerebrovascular events. Hemorrhagic events occurring a very long time after indirect bypass surgery in pediatric-onset moyamoya disease are rare. In such cases, a lifelong follow-up strategy may be necessary. Repeat bypass surgery may be a powerful tool to prevent such hemorrhagic events.

  7. Preoperative graft assessment in aortocoronary bypass surgery

    PubMed Central

    Tinica, Grigore; Vartic, Cristina Luca; Mocanu, Veronica; Baran, Dana; Butcovan, Doina

    2016-01-01

    Coronary artery bypass graft (CABG) is a surgical procedure able to improve the blood supply to the myocardium. In the present study, the distal segments of grafts taken from the internal thoracic artery (ITA), radial artery (RA) and saphenous vein (SV) for use in aortocoronary bypass surgery were examined. The morphologies of the grafts were investigated in order to draw conclusions concerning their patency and viability. In addition, clinical and laboratory risk factors considered to be significant predictors of lesion severity in graft vessels used in CABGs were investigated. In total, 54 distal graft segments of ITAs, RAs and SVs from 20 men and 6 women aged between 42 and 78 years, were evaluated. Histological analyses were used to visualize graft lesions. Morphometrically, the intimal thickness index (ITI) and luminal narrowing were assessed as an indication of graft patency. The histological changes observed in the graft vessel walls included the presence of distinct atheromatous plaques (fatty streaks in 2 cases) or thickening of the intima (20 cases) and media (17 cases). Morphometric analysis showed that the mean ITI of the vessel conduits was 0.37 in the SVs, 0.95 in the RAs, and 1.66 in the ITAs. No patient had >50% conduit stenosis. By assessing the association between risk factors and graft lesions, it was found that all the patients showed risk factors for atherosclerosis, such as age (61.54%), arterial hypertension (65.38%), hyperlipidemia (65.38%), smoking (34.61%), diabetes mellitus (38.46%) and obesity (15.38%). The presence of pre-existing lesions in bypass grafts may contribute to a reduction in their viability, particularly in the case of venous grafts. Further long-term follow-ups are mandatory to evaluate the consequences of such lesions upon the patency of the grafts. PMID:27446279

  8. Embolic Activity During In Vivo Cardiopulmonary Bypass

    PubMed Central

    DeFoe, Gordon R.; Dame, Norman A.; Farrell, Mark S.; Ross, Cathy S.; Langner, Craig W.; Likosky, Donald S.

    2014-01-01

    Abstract: Neurologic injury after cardiac surgery is principally associated with emboli. Although much work has focused on surgical sources of emboli, less attention has been focused on emboli associated with the heart–lung machine. We tested whether emboli are associated with discrete processes during cardiopulmonary bypass (CPB). One hundred patients undergoing cardiothoracic surgery were enrolled between April 2008 and May 2011 at a single medical center. During each surgical procedure, emboli were counted in three CPB locations: the venous side (Channel 1), before the arterial line filter (Channel 2), and after the arterial line filter (Channel 3). We used prespecified event markers to identify perfusionist interventions. Identical circuits were used on all patients. Of the 100 patients enrolled, 62 underwent isolated coronary artery bypass grafting (CABG), 17 underwent isolated valve operations, and 21 underwent CABG plus valve. Median counts across Channels 1, 2, and 3 were 69,853, 3,017, and 1,251, respectively. The greatest contributor to emboli in Channels 1, 2, and 3, respectively, were achieving the calculated CPB flow, opening of the electronic arterial line clamp, and introducing a hemofilter. The circuit technology was efficient in reducing total emboli counts from Channels 1–2 irrespective of the size of the emboli. Nearly 71% of all emboli 30–100 mm in size were removed from the circuit between Channels 2 and 3. No significant association was found between emboli counts and S100B release. Emboli occur frequently during CPB and are predominantly associated with the initiation of bypass, operation of the electronic arterial line clamp, and the initiation of a hemofilter. Continued work to reduce the occurrence of emboli is warranted. PMID:25208432

  9. Femoropopliteal bypass for claudication: vein vs. PTFE.

    PubMed

    Allen, B T; Reilly, J M; Rubin, B G; Thompson, R W; Anderson, C B; Flye, M W; Sicard, G A

    1996-03-01

    The vascular graft of choice for femoropopliteal bypass in patients with intolerable claudication is controversial. We retrospectively reviewed our experience with 239 patients suffering from claudication secondary to superficial femoral artery obstruction. Femoropopliteal reconstruction was performed with saphenous vein to the below-knee popliteal artery in 66 patients (BK-vein). Polytetrafluoroethylene (PTFE) was used in 128 patients as a bypass graft to the above-knee popliteal artery (AK-PTFE) and 45 patients had a PTFE graft to the below-knee popliteal artery (BK-PTFE). All patients were enrolled in a postoperative graft surveillance program with graft revision when appropriate. There was one perioperative death (0.4%). Primary patency at 5 years for AK-PTFE, BK-PTFE, and BK-vein was 58.0%, and 60.3%, respectively, and was not significantly different among the graft groups. Graft revision for failed/failing grafts resulted in 5-year secondary patency rates of 79.2% (AK-PTFE), 73.3% (BK-PTFE), and 74.4% (BK-vein). These secondary patency rates were not statistically different. Eventual conversion to a vein graft in patients initially treated with PTFE maximized patency in the femoropopliteal segment with 5-year patency rates of 84.6% and 93.0% for the AK-PTFE and BK-PTFE graft groups, respectively. Major leg amputation was necessary during the entire course of the study in eight (3.3%) patients. We conclude that long-term patency rates for femoropopliteal bypass in patients with intolerable claudication are similar for PTFE and autologous saphenous vein grafts.

  10. Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance.

    PubMed

    Blair, Jessica M A; Richmond, Grace E; Piddock, Laura J V

    2014-01-01

    Gram-negative bacteria express a plethora of efflux pumps that are capable of transporting structurally varied molecules, including antibiotics, out of the bacterial cell. This efflux lowers the intracellular antibiotic concentration, allowing bacteria to survive at higher antibiotic concentrations. Overexpression of some efflux pumps can cause clinically relevant levels of antibiotic resistance in Gram-negative pathogens. This review discusses the role of efflux in resistance of clinical isolates of Gram-negative bacteria, the regulatory mechanisms that control efflux pump expression, the recent advances in our understanding of efflux pump structure and how inhibition of efflux is a promising future strategy for tackling multidrug resistance in Gram-negative pathogens.

  11. Bypassing the Kohn-Sham equations with machine learning.

    PubMed

    Brockherde, Felix; Vogt, Leslie; Li, Li; Tuckerman, Mark E; Burke, Kieron; Müller, Klaus-Robert

    2017-10-11

    Last year, at least 30,000 scientific papers used the Kohn-Sham scheme of density functional theory to solve electronic structure problems in a wide variety of scientific fields. Machine learning holds the promise of learning the energy functional via examples, bypassing the need to solve the Kohn-Sham equations. This should yield substantial savings in computer time, allowing larger systems and/or longer time-scales to be tackled, but attempts to machine-learn this functional have been limited by the need to find its derivative. The present work overcomes this difficulty by directly learning the density-potential and energy-density maps for test systems and various molecules. We perform the first molecular dynamics simulation with a machine-learned density functional on malonaldehyde and are able to capture the intramolecular proton transfer process. Learning density models now allows the construction of accurate density functionals for realistic molecular systems.Machine learning allows electronic structure calculations to access larger system sizes and, in dynamical simulations, longer time scales. Here, the authors perform such a simulation using a machine-learned density functional that avoids direct solution of the Kohn-Sham equations.

  12. Antibiotic use and microbiome function.

    PubMed

    Ferrer, Manuel; Méndez-García, Celia; Rojo, David; Barbas, Coral; Moya, Andrés

    2017-06-15

    Our microbiome should be understood as one of the most complex components of the human body. The use of β-lactam antibiotics is one of the microbiome covariates that influence its composition. The extent to which our microbiota changes after an antibiotic intervention depends not only on the chemical nature of the antibiotic or cocktail of antibiotics used to treat specific infections, but also on the type of administration, duration and dose, as well as the level of resistance that each microbiota develops. We have begun to appreciate that not all bacteria within our microbiota are vulnerable or reactive to different antibiotic interventions, and that their influence on both microbial composition and metabolism may differ. Antibiotics are being used worldwide on a huge scale and the prescription of antibiotics is continuing to rise; however, their effects on our microbiota have been reported for only a limited number of them. This article presents a critical review of the antibiotics or antibiotic cocktails whose use in humans has been linked to changes in the composition of our microbial communities, with a particular focus on the gut, oral, respiratory, skin and vaginal microbiota, and on their molecular agents (genes, proteins and metabolites). We review the state of the art as of June 2016, and cover a total of circa 68 different antibiotics. The data herein are the first to compile information about the bacteria, fungi, archaea and viruses most influenced by the main antibiotic treatments prescribed nowadays. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Flow characteristics in narrowed coronary bypass graft

    NASA Astrophysics Data System (ADS)

    Bernad, S. I.; Bosioc, A.; Bernad, E. S.; Petre, I.; Totorean, A. F.

    2016-06-01

    Tortuous saphenous vein graft (SVG) hemodynamics was investigated using computational fluid dynamics (CFD) techniques. Computed tomography (CT) technology is used for non-invasive bypass graft assessment 7 days after surgery. CT investigation shown two regions with severe shape remodelling first is an elbow type contortion and second is a severe curvature with tortuous area reduction. In conclusion, the helical flow induced by vessel torsion may stabilize the blood flow in the distal part of the SVG, reducing the flow disturbance and suppressing the flow separation, but in the distal end of the graft, promote the inflammatory processes in the vessels.

  14. Bypass diode for a solar cell

    DOEpatents

    Rim, Seung Bum; Kim, Taeseok; Smith, David D; Cousins, Peter J

    2013-11-12

    Methods of fabricating bypass diodes for solar cells are described. In once embodiment, a method includes forming a first conductive region of a first conductivity type above a substrate of a solar cell. A second conductive region of a second conductivity type is formed on the first conductive region. In another embodiment, a method includes forming a first conductive region of a first conductivity type above a substrate of a solar cell. A second conductive region of a second conductivity type is formed within, and surrounded by, an uppermost portion of the first conductive region but is not formed in a lowermost portion of the first conductive region.

  15. Flow characteristics in narrowed coronary bypass graft

    SciTech Connect

    Bernad, S. I.; Bosioc, A.; Totorean, A. F.; Bernad, E. S.; Petre, I.

    2016-06-08

    Tortuous saphenous vein graft (SVG) hemodynamics was investigated using computational fluid dynamics (CFD) techniques. Computed tomography (CT) technology is used for non-invasive bypass graft assessment 7 days after surgery. CT investigation shown two regions with severe shape remodelling first is an elbow type contortion and second is a severe curvature with tortuous area reduction. In conclusion, the helical flow induced by vessel torsion may stabilize the blood flow in the distal part of the SVG, reducing the flow disturbance and suppressing the flow separation, but in the distal end of the graft, promote the inflammatory processes in the vessels.

  16. Conduits for Coronary Bypass: Vein Grafts

    PubMed Central

    Farkas, Emily A

    2012-01-01

    The saphenous vein has been the principal conduit for coronary bypass grafting from the beginning, circa 1970. This report briefly traces this history and concomitantly presents one surgeons experience and personal views on use of the vein graft. As such it is not exhaustive but meant to be practical with a modest number of references. The focus is that of providing guidance and perspective which may be at variance with that of others and recognizing that there may be many ways to accomplish the task at hand. Hopefully the surgeon in training/early career may find this instructive on the journey to surgical maturity. PMID:23130300

  17. Reviving old antibiotics.

    PubMed

    Theuretzbacher, Ursula; Van Bambeke, Françoise; Cantón, Rafael; Giske, Christian G; Mouton, Johan W; Nation, Roger L; Paul, Mical; Turnidge, John D; Kahlmeter, Gunnar

    2015-08-01

    In the face of increasing antimicrobial resistance and the paucity of new antimicrobial agents it has become clear that new antimicrobial strategies are urgently needed. One of these is to revisit old antibiotics to ensure that they are used correctly and to their full potential, as well as to determine whether one or several of them can help alleviate the pressure on more recent agents. Strategies are urgently needed to 're-develop' these drugs using modern standards, integrating new knowledge into regulatory frameworks and communicating the knowledge from the research bench to the bedside. Without a systematic approach to re-developing these old drugs and rigorously testing them according to today's standards, there is a significant risk of doing harm to patients and further increasing multidrug resistance. This paper describes factors to be considered and outlines steps and actions needed to re-develop old antibiotics so that they can be used effectively for the treatment of infections.

  18. Antibiotic drug discovery.

    PubMed

    Wohlleben, Wolfgang; Mast, Yvonne; Stegmann, Evi; Ziemert, Nadine

    2016-09-01

    Due to the threat posed by the increase of highly resistant pathogenic bacteria, there is an urgent need for new antibiotics; all the more so since in the last 20 years, the approval for new antibacterial agents had decreased. The field of natural product discovery has undergone a tremendous development over the past few years. This has been the consequence of several new and revolutionizing drug discovery and development techniques, which is initiating a 'New Age of Antibiotic Discovery'. In this review, we concentrate on the most significant discovery approaches during the last and present years and comment on the challenges facing the community in the coming years. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  19. Antibiotics and oral contraceptives.

    PubMed

    DeRossi, Scott S; Hersh, Elliot V

    2002-10-01

    With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3%. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution

  20. Antibiotics in microbial coculture.

    PubMed

    Ueda, Kenji; Beppu, Teruhiko

    2017-04-01

    Today, the frequency of discovery of new antibiotics in microbial culture is significantly decreasing. The evidence from whole-genome surveys suggests that many genes involved in the synthesis of unknown metabolites do exist but are not expressed under conventional cultivation conditions. Therefore, it is urgently necessary to study the conditions that make otherwise silent genes active in microbes. Here we overview the knowledge on the antibiotic production promoted by cocultivation of multiple microbial strains. Accumulating evidence indicates that cocultivation can be an effective way to stimulate the production of substances that are not formed during pure cultivation. Characterization of the promotive factors produced by stimulator strains is expected to give clues to the development of effective cultivation conditions for drug discovery.

  1. [Resistance to antibiotics].

    PubMed

    Sánchez, Jesús Silva

    2006-01-01

    Bacterial resistance to antibiotics is a major public health problem around the world causing high rates of morbi-mortality and economic problems in hospital settings. Major bacterial causing nosocomial infections are: extended-spectrum beta-lactameses (ESBL) producing enterobacteria, methicillin resistance Staphylococcus aureus, coagulase negative Staphylococcus, metallo fl-lactamases (MBL) producing Pseudomonas aeruginosa, Streptococcus pneumoniae, Enterococcus spp, Acinetobacter baumani. This last bacteria is not very often isolated in hospital settings yet, but it is multi-resistance pathogen causing high mortality. Helicobacter pylori, which is not a nosocomial pathogen but is associated to gastric diseases (from gastritis to gastric cancer). Infections prevention, to obtain an accuracy diagnostic and effective treatment, use antibiotic wisely and pathogen dissemination prevention (hand washing), are important steps to control the bacterial resistance.

  2. Pneumococcal resistance to antibiotics.

    PubMed Central

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  3. Surveillance of antibiotic resistance

    PubMed Central

    Johnson, Alan P.

    2015-01-01

    Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439

  4. D-Lactic acidosis after jejunoileal bypass: identification of organic anions by nuclear magnetic resonance spectroscopy.

    PubMed

    Traube, M; Bock, J L; Boyer, J L

    1983-02-01

    A 40-year-old man with jejunoileal bypass developed a syndrome of bizarre behavior, slurred speech, ataxic gait, and inappropriate affect, associated with a metabolic acidosis characterized by an increase in the anion gap. Serum L-lactate level was normal, but high-resolution proton nuclear magnetic resonance spectrums of the patient's serum showed a high concentration of lactate. A diagnosis of D-lactic acidosis was confirmed by a specific enzymatic assay for D-lactate. The D-lactic acidosis was cleared using antibiotic therapy, suggesting that D-lactate is produced from fermentation of ingested carbohydrate by colonic bacteria. Nuclear magnetic resonance spectroscopy is a rapid screening test for identifying organic acids in patients with unexplained acidosis. Neuropsychiatric symptoms in patients with short bowel syndrome may be associated with D-lactic acidosis.

  5. Clinical evolution of mediastinitis in patients undergoing adjuvant hyperbaric oxygen therapy after coronary artery bypass surgery

    PubMed Central

    do Egito, Julyana Galvão Tabosa; Abboud, Cely Saad; de Oliveira, Aline Pâmela Vieira; Máximo, Carlos Alberto Gonçalves; Montenegro, Carolina Moreira; Amato, Vivian Lerner; Bammann, Roberto; Farsky, Pedro Silvio

    2013-01-01

    ABSTRACT Objective: To evaluate the use of hyperbaric oxygen therapy as an adjunctive treatment in mediastinitis after coronary artery bypass surgery. Methods: This is a retrospective descriptive study, performed between October 2010 and February 2012. Hyperbaric oxygen therapy was indicated in difficult clinical management cases despite antibiotic therapy. Results: We identified 18 patients with mediastinitis during the study period. Thirty three microorganisms were isolated, and polymicrobial infection was present in 11 cases. Enterobacteriaceae were the most prevalent pathogens and six were multi-resistant agents. There was only 1 hospital death, 7 months after the oxygen therapy caused by sepsis, unrelated to hyperbaric oxygen therapy. This treatment was well-tolerated. Conclusion: The initial data showed favorable clinical outcomes. PMID:24136762

  6. The effect of adult and pediatric cardiopulmonary bypass on pharmacokinetic and pharmacodynamic parameters.

    PubMed

    van Saet, Annewil; de Wildt, Saskia N; Knibbe, Catherijne A J; Bogers, A D J J C; Stolker, Robert J; Tibboel, Dick

    2013-11-01

    Cardiopulmonary bypass (CPB) is known to have important effects on the disposition of drugs, which in turn may have important implications for the efficacy and toxicity of drug therapy. These effects constantly change throughout CPB and some continue to exert influence after the patient has been successfully weaned. In children, developmental and disease specific changes in drug disposition and effect also need to be taken into account when studying the effects of CPB. This review will provide an extensive overview of the current literature concerning the mechanisms behind the effects CPB has on pharmacokinetic and pharmacodynamic parameters. Also the effects of CPB on individual anesthetic drugs and sedatives, opioids, neuromuscular blocking agents, antibiotics and miscellaneous medications will be reviewed. Special attention will be paid to the pediatric population.

  7. Putrescine reduces antibiotic-induced oxidative stress as a mechanism of modulation of antibiotic resistance in Burkholderia cenocepacia.

    PubMed

    El-Halfawy, Omar M; Valvano, Miguel A

    2014-07-01

    Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic-resistant bacterium Burkholderia cenocepacia protects less-resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sublethal concentrations of PmB and other bactericidal antibiotics induces reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS, such as superoxide ion and hydrogen peroxide, was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild-type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sublethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine-synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study reveals BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections.

  8. Perioperative Use of Erythromycin Reduces Cognitive Decline After Coronary Artery Bypass Grafting Surgery: A Pilot Study.

    PubMed

    Thomaidou, Evanthia; Argiriadou, Helena; Vretzakis, Georgios; Megari, Kalliopi; Taskos, Nikolaos; Chatzigeorgiou, Georgios; Anastasiadis, Kyriakos

    Adverse neurologic outcome can be a debilitating complication after cardiac surgery. The aim of this study was to investigate the potential neuroprotective action of erythromycin, a well known antibiotic agent, regarding postoperative cognitive decline in patients undergoing cardiac surgery. Forty patients scheduled for elective coronary artery bypass grafting surgery were prospectively randomly assigned in 2 groups: the erythromycin group (n = 19) who received erythromycin at a dose of 25 mg/kg before and after surgery and the control group (n = 21) who did not receive it. All patients were monitored with near-infrared spectroscopy during the operation. Interleukin (IL) 1 and IL-6 as inflammatory markers and tau protein as a marker of brain injury were measured before and after surgery. Neurocognitive assessment was performed before surgery, on the day of discharge, and at 3 months postoperatively. Both groups were comparable in terms of demographic and clinical data. Patients who took erythromycin presented with significantly better cognitive performance before discharge and 3 months after surgery. No significant differences between the 2 groups referring to IL-1 and IL-6 values were detected. Tau serum values were lower in the erythromycin group after surgery. Erythromycin administration attenuates cerebral damage and postoperative cognitive decline after coronary artery bypass grafting surgery. The study was retrospectively registered at ClinicalTrials.gov (NCT01274754). Study start day: November 2008.

  9. 20 CFR 631.38 - State by-pass authority.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false State by-pass authority. 631.38 Section 631.38 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROGRAMS UNDER TITLE III OF THE JOB TRAINING PARTNERSHIP ACT State Administration § 631.38 State by-pass authority....

  10. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed...

  11. 20 CFR 631.38 - State by-pass authority.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false State by-pass authority. 631.38 Section 631.38 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROGRAMS UNDER TITLE III OF THE JOB TRAINING PARTNERSHIP ACT State Administration § 631.38 State by-pass authority. (a...

  12. 20 CFR 631.38 - State by-pass authority.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false State by-pass authority. 631.38 Section 631.38 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROGRAMS UNDER TITLE III OF THE JOB TRAINING PARTNERSHIP ACT State Administration § 631.38 State by-pass authority. (a...

  13. Bearing-Bypass Loading On Bolted Composite Joints

    NASA Technical Reports Server (NTRS)

    Crews, John H.; Naik, Rajiv-Vikas A.

    1989-01-01

    Unexpected interaction between effects of bypass and bearing loads reported. Combined experimental and analytical study described in NASA technical memorandum conducted to investigate effects of simultaneous bearing and bypass loading on graphite/epoxy laminate. Results important in emerging technology of composites for use in wide range of applications. Includes applications in aircraft, boats, and automobiles, in which bolted connections to composites increasingly important.

  14. Reverse bias protected solar array with integrated bypass battery

    NASA Technical Reports Server (NTRS)

    Landis, Geoffrey A (Inventor)

    2012-01-01

    A method for protecting the photovoltaic cells in a photovoltaic (PV) array from reverse bias damage by utilizing a rechargeable battery for bypassing current from a shaded photovoltaic cell or group of cells, avoiding the need for a bypass diode. Further, the method mitigates the voltage degradation of a PV array caused by shaded cells.

  15. At 1050 Gallery, Block 65, view of coaster gate bypass ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    At 1050 Gallery, Block 65, view of coaster gate bypass valve (for turbine-generator unit G-10, this bypass-valve unit manufactured by Western Koppers Co., Fort Wayne, Ind., 1938), looking southeast. - Columbia Basin Project, Grand Coulee Dam & Franklin D. Roosevelt Lake, Across Columbia River, Southeast of Town of Grand Coulee, Grand Coulee, Grant County, WA

  16. The in situ saphenous vein bypass graft: radiologic aspects.

    PubMed

    Schwarz, W; Nozick, J; Richmand, D; Rodgers, B; Simpson, A; Argila, C; Honickman, S

    1986-03-01

    The use of the in situ saphenous vein for bypassing arterial occlusions in the lower extremities appears to have a higher patency rate than other bypass procedures but presents unique technical problems, such as lysing valves and occluding venous tributaries. Forty-four patients undergoing in situ bypasses had preoperative arteriograms. Special attention was paid to the small runoff vessels around the ankle, which are not suitable for reversed bypass procedures but may be adequate for in situ bypasses. Eight patients also had preoperative saphenous venograms, which revealed surgically important abnormalities in six cases. Postoperative arteriograms obtained within 2 weeks in 10 patients and within 2-12 months in 15 patients revealed persistent arteriovenous fistulas in four patients, stenoses in nine, occlusions in five, and progressive disease in the nonbypassed arteries in five patients. Early recognition of these problems led to 11 surgical repairs; nine repairs used the interventional radiologic procedures of balloon angioplasty, transcatheter embolization, and catheter thrombolysis. In this group of 44 patients, five patients died with patent bypasses and three patients required amputation despite functioning bypasses. Only four amputations were attributed to bypass failure. This low figure may be due to the close cooperation of the vascular surgeons and the vascular radiologists in dealing with these complicated cases.

  17. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed under...

  18. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed under...

  19. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed under...

  20. 46 CFR 154.550 - Excess flow valve: Bypass.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Excess flow valve: Bypass. 154.550 Section 154.550 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES SAFETY... and Process Piping Systems § 154.550 Excess flow valve: Bypass. If the excess flow valve allowed under...

  1. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiopulmonary bypass cardiotomy return sucker. 870.4420 Section 870.4420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  2. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cardiopulmonary bypass cardiotomy return sucker. 870.4420 Section 870.4420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  3. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cardiopulmonary bypass cardiotomy return sucker. 870.4420 Section 870.4420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  4. 21 CFR 870.4420 - Cardiopulmonary bypass cardiotomy return sucker.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cardiopulmonary bypass cardiotomy return sucker. 870.4420 Section 870.4420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... from the chest or heart during cardiopulmonary bypass surgery. (b) Classification. Class...

  5. 20 CFR 631.18 - Federal by-pass authority.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Federal by-pass authority. 631.18 Section 631.18 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROGRAMS UNDER... Secretary's intent to exercise by-pass authority and an opportunity to request and to receive a hearing...

  6. 20 CFR 631.18 - Federal by-pass authority.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Federal by-pass authority. 631.18 Section 631.18 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROGRAMS UNDER... Secretary's intent to exercise by-pass authority and an opportunity to request and to receive a hearing...

  7. [Cardiac rehabilitation after coronary artery bypass surgery].

    PubMed

    Dayan, Victor; Ricca, Roberto

    2014-01-01

    Ischemic heart disease is the leading cause of death worldwide with an increase in the incidence in younger populations. Today revascularization strategies are capable of alleviating acute ischemia and/or chronic ischemia. These can be performed percutaneously or through surgery. Even if we improve myocardial perfusion by these methods, the main determinant in maintaining patency of coronary arteries and bypass is a correctly instituted secondary prevention. This is the main focus of cardiac rehabilitation proposals. Although much has been published about the role of cardiac rehabilitation after percutaneous revascularization, there is little work able to synthesize the current state of cardiac rehabilitation in patients undergoing coronary artery bypass surgery. The aim of this paper is to review the effect of rehabilitation in the return to work, survival, functional capacity, depression and anxiety, as well as compare centralized vs. home rehabilitation in this patient population. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  8. Previous gastric bypass surgery complicating total thyroidectomy.

    PubMed

    Alfonso, Bianca; Jacobson, Adam S; Alon, Eran E; Via, Michael A

    2015-03-01

    Hypocalcemia is a well-known complication of total thyroidectomy. Patients who have previously undergone gastric bypass surgery may be at increased risk of hypocalcemia due to gastrointestinal malabsorption, secondary hyperparathyroidism, and an underlying vitamin D deficiency. We present the case of a 58-year-old woman who underwent a total thyroidectomy for the follicular variant of papillary thyroid carcinoma. Her history included Roux-en-Y gastric bypass surgery. Following the thyroid surgery, she developed postoperative hypocalcemia that required large doses of oral calcium carbonate (7.5 g/day), oral calcitriol (up to 4 μg/day), intravenous calcium gluconate (2.0 g/day), calcium citrate (2.0 g/day), and ergocalciferol (50,000 IU/day). Her serum calcium levels remained normal on this regimen after hospital discharge despite persistent hypoparathyroidism. Bariatric surgery patients who undergo thyroid surgery require aggressive supplementation to maintain normal serum calcium levels. Preoperative supplementation with calcium and vitamin D is strongly recommended.

  9. Conduit options in coronary artery bypass surgery.

    PubMed

    Canver, C C

    1995-10-01

    The choice of graft conduit is crucial to the success of coronary artery bypass grafting (CABG) because the patency of a coronary conduit is closely associated with an uneventful postoperative course and a better long-term patient survival. The standard conduits used for CABG are the greater saphenous vein (GSV) and the internal thoracic artery (ITA). An excellent substitute conduit for coronary bypass operations that can be taken "off the shelf" is certainly the dream of every practicing cardiac surgeon. However, virtually every synthetic and biologic alternative to arterial conduits or autologous fresh saphenous vein has proved disappointing. Fortunately, patients with absolutely no autologous conduit alternatives are uncommon. Circumstances exist, however, that often necessitate the use of alternative conduits such as young hyperlipemic patients, absent or unsuitable autologous ITAs and GSV as a result of previous myocardial revascularization, peripheral arterial reconstruction, and varicose vein ligation procedures. This review provides an update on the clinical work done with all coronary conduits available for myocardial surgical revascularization.

  10. Jet noise from ultrahigh bypass turbofan engines

    NASA Astrophysics Data System (ADS)

    Posey, Joe W.; Norum, Thomas D.; Brown, Martha C.; Bhat, Thonse R. S.

    2002-05-01

    Modern commercial jet transport aircraft are powered by turbofan engines. Thrust from a turbofan engine is derived in part from the exhaust of a ducted fan, which may or may not be mixed with the core exhaust before exiting the nacelle. The historical trend has been toward ever higher bypass ratios (BPRs). The BPR is the ratio of air mass passing through the fan to that going through the core. The higher BPR engines can be more efficient and quieter. In general, a higher BPR results in lower average exhaust velocities and less jet noise. In order to address a scarcity of noise data for BPRs greater than 6, an extensive database collection effort was undertaken using the Jet Engine Simulator in NASA Langley's Low Speed Aeroacoustic Wind Tunnel. Forward flight simulations of Mach 0.1, 0.2, and 0.28 were used with BPRs of 5, 8, 11, and 14. Data was taken over the entire operating line of the simulated engines along with parametric deviations to provide a complete set of sensitivity measurements. The results will be used to develop an empirical jet noise prediction capability for ultrahigh bypass engines.

  11. The impact of perioperative atelectasis on antibiotic penetration into lung tissue: an in vivo microdialysis study.

    PubMed

    Hutschala, Doris; Kinstner, Christian; Skhirtladze, Keso; Mayer-Helm, Bernhard-Xaver; Zeitlinger, Markus; Wisser, Wilfried; Müller, Markus; Tschernko, Edda

    2008-10-01

    Postoperative pneumonia is a potentially devastating complication associated with high mortality in intensive care unit (ICU)-patients. One of the major predisposing factors is the perioperative occurrence of atelectatic formations in non-dependent lung areas. Perioperative ventilation/perfusion mismatch due to atelectasis may influence antibiotic distribution to lung tissue, hence increasing the risk of postoperative pneumonia. We evaluated whether differences in ventilation/perfusion mismatch can influence antibiotic distribution into lung tissue by means of in vivo microdialysis, comparing patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) (atelectasis model), with patients operated with the off-pump coronary artery bypass grafting (OPCAB)-technique. We compared five patients operated with CPB (CPB-group) and five patients undergoing CABG with OPCAB-technique (OPCAB-group). Levofloxacin (500 mg) was administered intravenously, after surgery, in the ICU. Time versus concentration profiles of levofloxacin in lung tissue and plasma were measured at regular time-intervals. In the OPCAB-group, the median of the maximum concentration of levofloxacin in lung tissue (4.1 microg ml(-1) +/- 7, range 3.7-11.8 microg ml(-1)) was significantly higher compared with the CPB-group (2.5 microg ml(-1) +/- 0.3, range 2.0-2.9 microg ml(-1)) (P = 0.046). Median levofloxacin tissue/plasma area under the concentration curve (AUC) ratio in lung tissue was 0.3 +/- 0.2 (range 0.1-0.7) in the CPB-group versus 0.7 +/- 1.6 (range 0.4-0.8) in the OPCAB-group (P = 0.015). Data indicate that postoperative interstitial antibiotic concentration is influenced by perioperative atelectasis formation. Our findings suggest the re-evaluation of clinical dosing schemas of antibiotic therapy in a variety of diseases associated with atelectasis formation.

  12. Cardiopulmonary bypass: development of John Gibbon's heart-lung machine

    PubMed Central

    Passaroni, Andréia Cristina; Silva, Marcos Augusto de Moraes; Yoshida, Winston Bonetti

    2015-01-01

    Objective To provide a brief review of the development of cardiopulmonary bypass. Methods A review of the literature on the development of extracorporeal circulation techniques, their essential role in cardiovascular surgery, and the complications associated with their use, including hemolysis and inflammation. Results The advancement of extracorporeal circulation techniques has played an essential role in minimizing the complications of cardiopulmonary bypass, which can range from various degrees of tissue injury to multiple organ dysfunction syndrome. Investigators have long researched the ways in which cardiopulmonary bypass may insult the human body. Potential solutions arose and laid the groundwork for development of safer postoperative care strategies. Conclusion Steady progress has been made in cardiopulmonary bypass in the decades since it was first conceived of by Gibbon. Despite the constant evolution of cardiopulmonary bypass techniques and attempts to minimize their complications, it is still essential that clinicians respect the particularities of each patient's physiological function. PMID:26107456

  13. Rationalizing antibiotic use to limit antibiotic resistance in India.

    PubMed

    Ganguly, Nirmal K; Arora, N K; Chandy, Sujith J; Fairoze, Mohamed Nadeem; Gill, J P S; Gupta, Usha; Hossain, Shah; Joglekar, Sadhna; Joshi, P C; Kakkar, Manish; Kotwani, Anita; Rattan, Ashok; Sudarshan, H; Thomas, Kurien; Wattal, Chand; Easton, Alice; Laxminarayan, Ramanan

    2011-09-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics.

  14. Suppression of antibiotic resistance acquisition by combined use of antibiotics.

    PubMed

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

    2015-10-01

    We analyzed the effect of combinatorial use of antibiotics with a trade-off relationship of resistance, i.e., resistance acquisition to one drug causes susceptibility to the other drug, and vice versa, on the evolution of antibiotic resistance. We demonstrated that this combinatorial use of antibiotics significantly suppressed the acquisition of resistance. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  15. Rationalizing antibiotic use to limit antibiotic resistance in India+

    PubMed Central

    2011-01-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

  16. Antibiotics as intermicrobial signaling agents instead of weapons

    PubMed Central

    Linares, J. F.; Gustafsson, I.; Baquero, F.; Martinez, J. L.

    2006-01-01

    It has been widely assumed that the ecological function of antibiotics in nature is fighting against competitors. This made them a good example of the Darwinian struggle-for-life in the microbial world. Based on this idea, it also has been believed that antibiotics, even at subinhibitory concentrations, reduce virulence of bacterial pathogens. Herein, using a combination of genomic and functional assays, we demonstrate that specific antibiotics (namely tobramycin, tetracycline, and norfloxacin) at subinhibitory concentrations trigger expression of determinants influencing the virulence of the major opportunistic bacterial pathogen Pseudomonas aeruginosa. All three antibiotics induce biofilm formation; tobramycin increases bacterial motility, and tetracycline triggers expression of P. aeruginosa type III secretion system and consequently bacterial cytotoxicity. Besides their relevance in the infection process, those determinants are relevant for the ecological behavior of this bacterial species in natural, nonclinical environments, either by favoring colonization of surfaces (biofilm, motility) or for fighting against eukaryotic predators (cytotoxicity). Our results support the notion that antibiotics are not only bacterial weapons for fighting competitors but also signaling molecules that may regulate the homeostasis of microbial communities. At low concentrations, they can even be beneficial for the behavior of susceptible bacteria in natural environments. This is a complete change on our vision on the ecological function of antibiotics with clear implications both for the treatment of infectious diseases and for the understanding of the microbial relationships in the biosphere. PMID:17148599

  17. Small intestinal bacterial overgrowth and thiamine deficiency after Roux-en-Y gastric bypass surgery in obese patients.

    PubMed

    Lakhani, Shilen V; Shah, Hiral N; Alexander, Kenneth; Finelli, Frederick C; Kirkpatrick, John R; Koch, Timothy R

    2008-05-01

    It has been proposed that thiamine deficiency after gastric bypass surgery in obese patients results from prolonged nausea and emesis. We hypothesized that thiamine deficiency is induced by altered gut ecology. This report includes 2 retrospective studies of obese patients who underwent Roux-en-Y gastric bypass surgery at our institution from 1999 to 2005. In the first study, 80 patients (52 women and 28 men) had measurement of whole-blood thiamine diphosphate level and serum folate level. In these 80 patients, 39 (49%) had thiamine diphosphate levels less than the lower limit of the reference range, and 28 (72%) of the 39 had folate levels higher than the upper limit of the reference range, an indicator of small intestinal bacterial overgrowth. In 41 patients with normal thiamine levels, only 14 (34%) had folate levels higher than the upper limit of the reference range (chi(2) test, P < .01). In the second study, 21 patients (17 women and 4 men) had thiamine diphosphate levels less than the lower limit of the reference range and abnormal glucose-hydrogen breath tests, consistent with small intestinal bacterial overgrowth. Fifteen patients received oral thiamine supplements, but repeated thiamine levels remained low in all 15. Nine of these patients then received oral antibiotic therapy; repeated thiamine levels were found to be normal in all 9 patients. These results support the hypothesis that small intestinal bacterial overgrowth results from altered gut ecology and induces thiamine deficiency after gastric bypass surgery in obese patients.

  18. 75 FR 71145 - San Joaquin River Restoration Program: Reach 4B, Eastside Bypass, and Mariposa Bypass Channel and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... bypasses and maintain the current flood operations and conveyance capacity of the system. Additionally, the Proposed Action may result in an opportunity for improvements to the existing flood system. These..., and the Mariposa Bypass. The planning and environmental review for the Proposed Action is...

  19. Inhibition of photosynthesis by a fluoroquinolone antibiotic.

    PubMed

    Aristilde, Ludmilla; Melis, Anastasios; Sposito, Garrison

    2010-02-15

    Recent microcosm studies have revealed that fluoroquinolone (FQ) antibiotics can have ecotoxicological impacts on photosynthetic organisms, but little is known about the mechanisms of toxicity. We employed a combination of modeling and experimental techniques to explore how FQs may have these unintended secondary toxic effects. Structure-activity analysis revealed that the quinolone ring and secondary amino group typically present in FQ antibiotics may mediate their action as quinone site inhibitors in photosystem II (PS-II), a key enzyme in photosynthetic electron transport. Follow-up molecular simulations involving nalidixic acid (Naldx), a nonfluorinated quinolone with a demonstrated adverse impact on photosynthesis, and ciprofloxacin (Cipro), the most commonly used FQ antibiotic, showed that both may interfere stereochemically with the catalytic activity of reaction center II (RC-II), the pheophytin-quinone-type center present in PS-II. Naldx can occupy the same binding site as the secondary quinone acceptor (Q(B)) in RC-II and interact with amino acid residues required for the enzymatic reduction of Q(B). Cipro binds in a somewhat different manner, suggesting a different mechanism of interference. Fluorescence induction kinetics, a common method of screening for PS-II inhibition, recorded for photoexcited thylakoid membranes isolated from Cipro-exposed spinach chloroplasts, indicated that Cipro interferes with the transfer of energy from excited antenna chlorophyll molecules to the reaction center in RC-II ([Cipro] >or= 5 microM in vitro and >or=10 microM in vivo) and thus delays the kinetics of photoreduction of the primary quinone acceptor (Q(A); [Cipro] >or= 0.6 microM in vitro). Spinach plants exposed to Cipro exhibited severe growth inhibition characterized by a decrease in both the synthesis of leaves and growth of the roots ([Cipro] >or= 0.5 microM in vivo). Our results thus demonstrate that Cipro and related FQ antibiotics may interfere with

  20. Comparison of inflammatory response following coronary revascularization with or without cardiopulmonary bypass

    PubMed Central

    Gasz, Balázs; Benkö, László; Jancsó, Gábor; Lantos, János; Szántó, Zalán; Alotti, Nasri; Röth, Erzsébet

    2004-01-01

    BACKGROUND: It is well known that conventional coronary revascularization is associated with a pronounced systemic inflammatory response due to the application of cardiopulmonary bypass (CPB). OBJECTIVE: To compare the effects of coronary artery bypass grafting (CABG) with (on-pump) or without (off-pump) extra-corporeal circulation observing certain inflammatory response parameters. METHODS: Twenty patients undergoing CABG with (CPB group: 10 patients) or without (off-pump coronary artery bypass grafting [OPCAB] group: 10 patients) CPB were enrolled in this prospective, randomized study. Blood samples were collected three times during the operation and on postoperative days 1, 2, 3 and 7. The plasma level of proinflammatory cytokine tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay method following stimulation, and the expression of adhesion molecules (CD11, CD18) of leukocytes were determined by flow cytometry. Furthermore, white blood cell (WBC) and neutrophil count were carried out. RESULTS: The WBC and neutrophil counts rose markedly in both groups following the operation and remained at this increased level during the observation period. There was a significant difference in WBC and neutrophil counts between the two groups of patients on postoperative day 7. A significant difference in the level of TNF-alpha was found between the two groups on postoperative day 2 (P<0.05). An intense increase was observed with CPB, which significantly exceeded the values of the OPCAB group without extracorporeal circulation in the early postoperative period. The CD11a and CD18 expression of leukocytes decreased during the operation and on postoperative day 1; thereafter, it increased markedly. There was a significant difference in adhesion molecule expression between the two groups on postoperative day 2. CONCLUSION: The investigation revealed that inflammatory response reactions following extracorporeal circulation could be reduced

  1. Antibiotic use in plant agriculture.

    PubMed

    McManus, Patricia S; Stockwell, Virginia O; Sundin, George W; Jones, Alan L

    2002-01-01

    Antibiotics have been used since the 1950s to control certain bacterial diseases of high-value fruit, vegetable, and ornamental plants. Today, the antibiotics most commonly used on plants are oxytetracycline and streptomycin. In the USA, antibiotics applied to plants account for less than 0.5% of total antibiotic use. Resistance of plant pathogens to oxytetracycline is rare, but the emergence of streptomycin-resistant strains of Erwinia amylovora, Pseudomonas spp., and Xanthomonas campestris has impeded the control of several important diseases. A fraction of streptomycin-resistance genes in plant-associated bacteria are similar to those found in bacteria isolated from humans, animals, and soil, and are associated with transfer-proficient elements. However, the most common vehicles of streptomycin-resistance genes in human and plant pathogens are genetically distinct. Nonetheless, the role of antibiotic use on plants in the antibiotic-resistance crisis in human medicine is the subject of debate.

  2. [Antibiotic therapy: impact and resistance].

    PubMed

    Weiler, S; Corti, N

    2014-04-01

    Many achievements in modern medicine, such as in transplantation medicine, cancer therapy, surgery, and intensive care medicine would have been impossible without effective treatment of bacterial infections. Antibiotic resistance is on the rise; the reasons for this are complex and vary greatly. Knowledge about the impact of antibiotics and mechanisms of antibiotic resistance, which are the cornerstones of calculated and targeted antibiotic therapy, is imperative. This review describes the pharmacodynamics of relevant antibiotics in emergency and intensive care medicine. Commonly resistant bacteria with clinical relevance and the respective mechanisms of resistance are highlighted. Furthermore, the use of antiinfectives for reserve treatment of severe infections is discussed. Understanding the mechanisms of resistance and effects of antibiotics are fundamental for efficient and successful treatment of bacterial infections and for the reduction of resistant species.

  3. Antibiotics from predatory bacteria

    PubMed Central

    Korp, Juliane; Vela Gurovic, María S

    2016-01-01

    Summary Bacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism. PMID:27340451

  4. Antibiotics from predatory bacteria.

    PubMed

    Korp, Juliane; Vela Gurovic, María S; Nett, Markus

    2016-01-01

    Bacteria, which prey on other microorganisms, are commonly found in the environment. While some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. Anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. Consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. Here, we will present the results from recent chemical investigations of this bacterial group, compare the biosynthetic potential with that of non-predatory bacteria and discuss the link between predation and secondary metabolism.

  5. Endless Resistance. Endless Antibiotics?

    PubMed Central

    Fisher, Jed F.; Mobashery, Shahriar

    2016-01-01

    The practice of medicine was profoundly transformed by the introduction of the antibiotics (compounds isolated from Nature) and the antibacterials (compounds prepared by synthesis) for the control of bacterial infection. As a result of the extraordinary success of these compounds over decades of time, a timeless biological activity for these compounds has been presumed. This presumption is no longer. The inexorable acquisition of resistance mechanisms by bacteria is retransforming medical practice. Credible answers to this dilemma are far better recognized than they are being implemented. In this perspective we examine (and in key respects, reiterate) the chemical and biological strategies being used to address the challenge of bacterial resistance. PMID:27746889

  6. Antibiotic consumption and antibiotic stewardship in Swedish hospitals.

    PubMed

    Hanberger, Håkan; Skoog, Gunilla; Ternhag, Anders; Giske, Christian G

    2014-05-01

    The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumonia-data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels.

  7. Antibiotic consumption and antibiotic stewardship in Swedish hospitals

    PubMed Central

    Skoog, Gunilla; Ternhag, Anders; Giske, Christian G.

    2014-01-01

    Background The aim of this paper was to describe and analyze the effect of antibiotic policy changes on antibiotic consumption in Swedish hospitals and to review antibiotic stewardship in Swedish hospitals. Results The main findings were: 1) Antibiotic consumption has significantly increased in Swedish hospitals over the last decade. The consumption of cephalosporins has decreased, whereas that of most other drugs including piperacillin-tazobactam, carbapenems, and penicillinase-sensitive and -resistant penicillins has increased and replaced cephalosporins. 2) Invasive infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae have increased, but the proportion of pathogens resistant to third-generation cephalosporins causing invasive infections is still very low in a European and international perspective. Furthermore, the following gaps in knowledge were identified: 1) lack of national, regional, and local data on the incidence of antibiotic resistance among bacteria causing hospital-acquired infections e.g. bloodstream infections and hospital-acquired pneumonia—data on which standard treatment guidelines should be based; 2) lack of data on the incidence of Clostridium difficile infections and the effect of change of antibiotic policies on the incidence of C. difficile infections and infections caused by antibiotic-resistant pathogens; and 3) lack of prospective surveillance programs regarding appropriate antibiotic treatment, including selection of optimal antimicrobial drug regimens, dosage, duration of therapy, and adverse ecological effects such as increases in C. difficile infections and emergence of antibiotic-resistant pathogens. Conclusions Evidence-based actions to improve antibiotic use and to slow down the problem of antibiotic resistance need to be strengthened. The effect of such actions should be analyzed, and standard treatment guidelines should be continuously updated at national, regional, and local levels. PMID:24724823

  8. [Antibiotics: drug and food interactions].

    PubMed

    Hodel, M; Genné, D

    2009-10-07

    Antibiotics are widely prescribed in medical practice. Many of them induce or are subject to interactions that may diminish their anti-infectious efficiency or elicit toxic effects. Food intake can influence the effectiveness of an antibiotic. Certain antibiotics can lower the effectiveness of oral contraception. Oral anticoagulation can be influenced to a great extent by antibiotics and controls are necessary. Interactions are also possible via enzymatic induction or inhibition of cytochromes. The use of an interaction list with substrates of cytochromes enables to anticipate. Every new prescription should consider a possible drug or food interaction.

  9. [Usage of antibiotics in hospitals].

    PubMed

    Ternák, G; Almási, I

    1996-12-29

    The authors publish the results of a survey conducted among hospital records of patients discharged from eight inpatient's institutes between 1-31st of January 1995 to gather information on the indications and usage of antibiotics. The institutes were selected from different part of the country to represent the hospital structure as much as possible. Data from the 13,719 documents were recorded and analysed by computer program. It was found that 27.6% of the patients (3749 cases) received antibiotic treatment. 407 different diagnosis and 365 different surgical procedures (as profilaxis) were considered as indications of antibiotic treatment (total: 4450 indications for 5849 antibiotic treatment). The largest group of patients receiving antibiotics was of antibiotic profilaxis (24.56%, 1093 cases), followed by lower respiratory tract infections (19.89%, 849 cases), uroinfections (10.53%, 469 cases) and upper respiratory tract infections. Relatively large group of patients belonged to those who had fever or subfebrility without known reason (7.35%, 327 cases) and to those who did not have any proof in their document indicating the reasons of antibiotic treatment (6.4%, 285 cases). We can not consider the antibiotic indications well founded in those groups of patients (every sixth or every fifth cases). The most frequently used antibiotics were of [2-nd] generation cefalosporins. The rate of nosocomial infections were found as 6.78% average. The results are demonstrated on diagrams and table.

  10. [Bacterial resistance and antibiotic prescription: a survey of hospital physician perception, attitude, and knowledge].

    PubMed

    Naqvi, A; Pulcini, C

    2010-11-01

    The authors' goal was to assess physicians' perception of antibiotic prescribing practice and of bacterial resistance. We questioned 503 interns and senior physicians in the Nice University Hospital. Three hundred and twenty-two out of five hundred and three (64 %) physicians answered the questionnaire. Antibiotic resistance was perceived as a national problem by 98 % of physicians, but only 74 % rated the problem as important in their own daily practice. Fifty-nine percent of interns and 34 % of senior physicians respectively had received some training on antibiotic prescribing in the past 12 months. Only 33 % of physicians knew the exact prevalence of MRSA in their hospital. Senior physicians were more confident than interns when prescribing an antibiotic. The three issues they were the less confident with were: indications of antibiotic combinations, reassessment, and duration of antibiotic treatment. They were aware that antibiotic overuse, prescription of broad-spectrum molecules, or subtherapeutic doses of antibiotics were the three major causes of antibiotic resistance. They believed that the most useful measures to improve antibiotic prescription were: availability of guidelines, specific courses, readily accessible advice from an infectious diseases specialist, and audit plus feedback. The collected data provides useful information for the implementation of strategies to optimize adherence to good antimicrobial stewardship. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  11. Transient Diabetes Insipidus Following Cardiopulmonary Bypass.

    PubMed

    Ekim, Meral; Ekim, Hasan; Yilmaz, Yunus Keser; Bolat, Ali

    2015-04-01

    Diabetes insipidus (DI) results from inadequate output of Antidiuretic Hormone (ADH) from the pituitary gland (central DI) or the inability of the kidney tubules to respond to ADH (nephrogenic DI). ADH is an octapeptide produced in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior lobe of the pituitary gland. Cardiopulmonary Bypass (CPB) has been shown to cause a six-fold increased circulating ADH levels 12 hours after surgery. However, in some cases, ADH release may be transiently suppressed due to cardioplegia (cardiac standstill) or CPB leading to DI. We present the postoperative course of a 60-year-old man who developed transient DI after CPB. He was successfully treated by applying nasal desmopressin therapy. Relevant biochemical parameters should be monitored closely in patients who produce excessive urine after open heart surgery.

  12. Outcomes of coronary artery bypass graft surgery

    PubMed Central

    Hawkes, Anna Louise; Nowak, Madeleine; Bidstrup, Benjamin; Speare, Richard

    2006-01-01

    This review article summarizes the major studies that have investigated the outcomes of coronary artery bypass graft surgery (CABG). The article includes a review of the literature in the areas of: history of CABG; indications for CABG; and measurement of quality of life following CABG, including prolongation of life, physical functioning (ie, relief from angina and dyspnea, physical activity, as well as complications of surgery and re-hospitalization), psychological functioning, and social functioning. Overall, the literature demonstrates that the outcomes of CABG have historically been measured in terms of mortality and morbidity; however, it has now been well recognized that adjustment to CABG is a multidimensional phenomenon that is not fully explained by medical factors. Therefore, in addition to studying mortality and morbidity outcomes following CABG, many recent studies have identified that it is important to investigate various physical, psychological, and social variables that have a significant impact on post-operative adjustment to CABG. PMID:17323602

  13. Factor V Leiden and Cardiopulmonary Bypass.

    PubMed

    Uppal, Victor; Rosin, Mark; Marcoux, Jo-Anne; Olson, Marnie; Bezaire, Jennifer; Dalshaug, Gregory

    2015-12-01

    We present a case of a patient with factor V Leiden with an antithrombin III activity of 67% who received a successful aortic valve replacement supported by cardiopulmonary bypass (CPB). A safe level of anticoagulation was achieved by monitoring activated clotting time (ACT) and heparin concentration ensuring adequate anticoagulation throughout the procedure. Results from ACT, heparin dose response, heparin protamine titration, and thrombelastography are given. Factor V Leiden patients can be safely anti-coagulated using heparin for CPB procedures when monitored with ACT, heparin protamine titration, and thrombelastography. Postoperative chest tube losses were 360 mL, less than half our institutional average. Anticoagulation for the pre-and post-operative phase is also discussed.

  14. [Nutritional follow-up after gastric bypass].

    PubMed

    Gasteyger, C; Giusti, V

    2006-03-29

    Roux-en-Y gastric bypass has become one of the main bariatric procedures. This surgical operation shows excellent results in weight evolution and quality of life and allows a decrease of mortality. However, it leads, relatively often, to nutritional deficiencies which need an effective post-operative follow-up. This follow-up includes not only medical and dietetic encounters but also regular blood analyses made every 3 months during the first post-operative year, every 6 months the second year, then each year. The most frequent deficiencies are those in vitamin B12, iron and folic acid. The secondary hyperparathyroidism characterized by an increase of PTH associated to a low vitamin D and a normal calcium, is quite frequent.

  15. Angiographic assessment of biografts for femoropopliteal bypass.

    PubMed

    Boontje, A H

    1986-01-01

    A series of 257 femoropopliteal bypass procedures with a Biograft is analysed. The cumulative patency rate after 6 years is 64% for the whole series. This corresponds with a cumulative patency rate of 74% for AK cases and 44% for BK cases. Follow-up angiography to assess the morphology of the Biografts, was performed after 1 year and after 3-5 years. Angiography after 1 year (N = 126) showed few alterations: tortuosity in 3%, segmentation or wrinkling in 3%, slight diffuse dilatation in 4% and local stenosis in 2%. Angiography after 3-5 years (N = 82) revealed interesting changes. Besides tortuosity in 6% and segmentation in 29%, there were anastomotic aneurysms in 2%. Changes in the diameter of the body of the graft were remarkable and occurred in 46%. Diffuse regular or irregular dilatation, local ectasia or stenosis was found. Clinical implications are discussed.

  16. Biventricular bypass: alternative to univentricular bypass and total artificial heart-bridge.

    PubMed

    Chilaya, S M; Khodeli, N G

    1991-10-01

    Left ventricular and biventricular bypasses (LVBs, BVBs) were performed in 102 experiments in sheep, goats, and donkeys. Biventricular bypass was performed in the assisted circulation mode or in the paracorporeal artificial heart bridge (PCAHB) mode when the natural heart fibrillates. During implantation of artificial ventricles instead of a heart-lung bypass, counterpulsation was used. Several types of connective conduits were developed and tested in experiments. The conduits included bifurcational connective pipes that permit "intake" of blood into artificial ventricles from atria and ventricles of the natural heart simultaneously and consequently provide effective blood flow through shunts not depending on the state of the natural heart (acute cardiac weakness or asystole). Monitoring gas content (PO2, PCO2, and pH) in the myocardium of both ventricles suggested development of right ventricular failure under conditions of LVB before hemodynamic changes occurred and confirmed the preferability of BVB over other methods of assisted circulation, as it is most effective and capable of normalizing short-term cardiac disturbances in the course of the 1st 2 days. Survival time of experimental animals (2-3 days for dogs, 5-12 days for sheep, goats, and donkeys) is sufficient to overcome acute cardiac insufficiency. This suggests that BVB in the assisted circulation mode or PCAHB mode can serve as a bridge for cardiac transplantation for the time of search for the available organ.

  17. Comparison of neutrophil:lymphocyte ratios following coronary artery bypass surgery with or without cardiopulmonary bypass.

    PubMed

    Aldemir, Mustafa; Baki, Elif Doğan; Adali, Fahri; Çarşanba, Görkem; Tecer, Evren; Taş, Hanife Uzel

    2015-01-01

    Coronary artery bypass graft (CABG) surgery may induce postoperative systemic changes in leukocyte counts, including leukocytosis, neutrophilia or lymphopenia. This retrospective clinical study investigated whether off-pump coronary artery bypass (OPCAB) surgery working on the beating heart without extracorporeal circulation could favourably affect leukocyte counts, including neutrophil-tolymphocyte (N:L) ratio, after CABG. In this study, 30 patients who underwent isolated CABG with cardiopulmonary bypass (CPB), and another 30 patients who underwent the same operation without CPB between May 2010 and May 2013, were screened from the computerised database of our hospital. Pre-operative, and first and fifth postoperative day differential counts of leukocytes with the N:L ratio of peripheral blood were obtained. A significant increase in total leukocyte and neutrophil counts and N:L ratio, and a decrease in lymphocyte counts were observed at all time points after surgery in both groups. N:L ratio was significantly higher in the CPB group compared with the OPCAB group on the first postoperative day (20.73 ± 13.85 vs 10.19 ± 4.55, p < 0.001), but this difference disappeared on the fifth postoperative day. CPB results in transient but significant changes in leukocyte counts in the peripheral blood stream in terms of N:L ratio compared with the off-pump technique of CABG.

  18. Comparison of neutrophil:lymphocyte ratios following coronary artery bypass surgery with or without cardiopulmonary bypass

    PubMed Central

    Aldemir, Mustafa; Adalı, Fahri; Çarşanba, Görkem; Tecer, Evren; Bakı, Elif Doğan; Taş, Hanife Uzel

    2015-01-01

    Objective Coronary artery bypass graft (CABG) surgery may induce postoperative systemic changes in leukocyte counts, including leukocytosis, neutrophilia or lymphopenia. This retrospective clinical study investigated whether offpump coronary artery bypass (OPCAB) surgery working on the beating heart without extracorporeal circulation could favourably affect leukocyte counts, including neutrophil-tolymphocyte (N:L) ratio, after CABG. Methods In this study, 30 patients who underwent isolated CABG with cardiopulmonary bypass (CPB), and another 30 patients who underwent the same operation without CPB between May 2010 and May 2013, were screened from the computerised database of our hospital. Pre-operative, and first and fifth postoperative day differential counts of leukocytes with the N:L ratio of peripheral blood were obtained. Results A significant increase in total leukocyte and neutrophil counts and N:L ratio, and a decrease in lymphocyte counts were observed at all time points after surgery in both groups. N:L ratio was significantly higher in the CPB group compared with the OPCAB group on the first postoperative day (20.73 ± 13.85 vs 10.19 ± 4.55, p < 0.001), but this difference disappeared on the fifth postoperative day. Conclusion CPB results in transient but significant changes in leukocyte counts in the peripheral blood stream in terms of N:L ratio compared with the off-pump technique of CABG. PMID:25903477

  19. Laparoscopic Conversion of One Anastomosis Gastric Bypass to a Standard Roux-en-Y Gastric Bypass.

    PubMed

    Amor, Imed Ben; Petrucciani, Niccolo; Kassir, Radwan; Al Munifi, Abdullah; Piche, Thierry; Debs, Tarek; Gugenheim, Jean

    2017-05-01

    One anastomosis gastric bypass (OAGB) demonstrated results similar to traditional Roux-en-Y procedures [1-3], in terms of weight loss and resolution of obesity-related comorbidities. The main controversy regarding OAGB is the concern for an association between biliary alkaline gastritis and esophageal or gastric cancer raised by some studies [4]. We present the case of a 51-year-old woman with a BMI of 41 kg/m2 who underwent a laparoscopic OAGB in 2014. One year later, she consulted for recurrent heartburns. An upper GI endoscopy showed pouchitis and bile reflux in the esophagus. Medical treatment of gastroesophageal reflux disease was ineffective. We decided to convert the OAGB to a Roux-en-Y gastric bypass (RYGB). In this video, we show how to revise an OAGB to treat chronic bile reflux, by converting the procedure to a standard RYGB. The intervention starts by restoring the normal anatomy of the small bowel, with the resection of the gastrojejunal anastomosis, which was located at 250-cm du Treitz's ligament. Then, the gastric pouch is created. A standard Roux-en-Y gastric bypass is performed. The resection of the gastrojejunal anastomosis allows fashioning the Roux-en-Y limb with the classical measures. This technique allows a conversion to a standard RYGB and is effective in treating the biliary reflux.

  20. Antibiotic production in space

    NASA Astrophysics Data System (ADS)

    Klaus, David; Brown, Robert; Cierpik, Kim

    1998-01-01

    A wide variety of previous experiments have indicated that the space flight environment has a positive influence on the proliferation of microorganisms. Based on this premise, it was hypothesized that the production of secondary metabolites (specifically antibiotics) would also be increased as a consequence of the enhanced growth. Pilot studies performed onboard two shuttle missions to date have indicated that microbial antibiotic production was significantly increased in space grown colonies relative to comparable, matched ground controls. The practical application of these preliminary findings is being investigated. The empirical data are being analyzed in an attempt to establish specific gravity-dependent cause and effect relationships. An analytical model is being developed to further establish how physical principles might give rise to the various physiological responses observed to be altered in space. The envisioned commercial applications stemming from the unique knowledge of how gravity affects natural processes range from developing methods for increasing terrestrial pharmaceutic production efficiency to, ultimately perhaps, the design of economically feasible, space-borne fermentation and bioprocessing platforms.

  1. Diagnostic tools for post-gastric bypass hypoglycaemia.

    PubMed

    Emous, M; Ubels, F L; van Beek, A P

    2015-10-01

    In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature. © 2015 World Obesity.

  2. The reliability of bypass diodes in PV modules

    NASA Astrophysics Data System (ADS)

    Dhere, Neelkanth G.; Shiradkar, Narendra; Schneller, Eric; Gade, Vivek

    2013-09-01

    The operating conditions of bypass diodes in PV modules deployed in the field are considerably harsher than the conditions at which the diode manufacturers test the diodes. This has a potential to significantly reduce the operating life of bypass diodes and has raised concerns about the safety and reliability of PV modules as a whole. The study of modes and mechanisms of the failures encountered in bypass diodes used in PV modules can provide important information which would be useful to predict the module lifetime. This paper presents the review of the failure modes and mechanisms observed in bypass diodes and current work related to reliability testing of bypass diodes. The International PV Module Quality Assurance Task Force has recommended following four potential areas of research to understand the reliability issues of bypass diodes: Electrostatic Discharge, reverse bias thermal runaway testing, forward bias overheating and transition testing of forward bias to reverse bias. As a joint collaborative effort between Florida Solar Energy Center and Solar and Environmental Test Laboratory at Jabil Inc., laboratory testing of bypass diodes on the guidelines provided by the International PV Module Quality Assurance Task Force has been initiated. Preliminary results from this work are presented in this paper.

  3. Alongshore sediment bypassing as a control on river mouth morphodynamics

    NASA Astrophysics Data System (ADS)

    Nienhuis, Jaap H.; Ashton, Andrew D.; Nardin, William; Fagherazzi, Sergio; Giosan, Liviu

    2016-04-01

    River mouths, shoreline locations where fluvial and coastal sediments are partitioned via erosion, trapping, and redistribution, are responsible for the ultimate sedimentary architecture of deltas and, because of their dynamic nature, also pose great management and engineering challenges. To investigate the interaction between fluvial and littoral processes at wave-dominated river mouths, we modeled their morphologic evolution using the coupled hydrodynamic and morphodynamic model Delft3D-SWAN. Model experiments replicate alongshore migration of river mouths, river mouth spit development, and eventual spit breaching, suggesting that these are emergent phenomena that can develop even under constant fluvial and wave conditions. Furthermore, we find that sediment bypassing of a river mouth develops though feedbacks between waves and river mouth morphology, resulting in either continuous bypassing pathways or episodic bar bypassing pathways. Model results demonstrate that waves refracting into the river mouth bar create a zone of low alongshore sediment transport updrift of the river mouth, which reduces sediment bypassing. Sediment bypassing, in turn, controls the river mouth migration rate and the size of the river mouth spit. As a result, an intermediate amount of river discharge maximizes river mouth migration. The fraction of alongshore sediment bypassing can be predicted from the balance between the jet and the wave momentum flux. Quantitative comparisons show a match between our modeled predictions of river mouth bypassing and migration rates observed in natural settings.

  4. CFD Analysis of Core Bypass Phenomena

    SciTech Connect

    Richard W. Johnson; Hiroyuki Sato; Richard R. Schultz

    2010-03-01

    The U.S. Department of Energy is exploring the potential for the VHTR which will be either of a prismatic or a pebble-bed type. One important design consideration for the reactor core of a prismatic VHTR is coolant bypass flow which occurs in the interstitial regions between fuel blocks. Such gaps are an inherent presence in the reactor core because of tolerances in manufacturing the blocks and the inexact nature of their installation. Furthermore, the geometry of the graphite blocks changes over the lifetime of the reactor because of thermal expansion and irradiation damage. The existence of the gaps induces a flow bias in the fuel blocks and results in unexpected increase of maximum fuel temperature. Traditionally, simplified methods such as flow network calculations employing experimental correlations are used to estimate flow and temperature distributions in the core design. However, the distribution of temperature in the fuel pins and graphite blocks as well as coolant outlet temperatures are strongly coupled with the local heat generation rate within fuel blocks which is not uniformly distributed in the core. Hence, it is crucial to establish mechanistic based methods which can be applied to the reactor core thermal hydraulic design and safety analysis. Computational Fluid Dynamics (CFD) codes, which have a capability of local physics based simulation, are widely used in various industrial fields. This study investigates core bypass flow phenomena with the assistance of commercial CFD codes and establishes a baseline for evaluation methods. A one-twelfth sector of the hexagonal block surface is modeled and extruded down to whole core length of 10.704m. The computational domain is divided vertically with an upper reflector, a fuel section and a lower reflector. Each side of the sector grid can be set as a symmetry boundary

  5. CFD Analysis of Core Bypass Phenomena

    SciTech Connect

    Richard W. Johnson; Hiroyuki Sato; Richard R. Schultz

    2009-11-01

    The U.S. Department of Energy is exploring the potential for the VHTR which will be either of a prismatic or a pebble-bed type. One important design consideration for the reactor core of a prismatic VHTR is coolant bypass flow which occurs in the interstitial regions between fuel blocks. Such gaps are an inherent presence in the reactor core because of tolerances in manufacturing the blocks and the inexact nature of their installation. Furthermore, the geometry of the graphite blocks changes over the lifetime of the reactor because of thermal expansion and irradiation damage. The existence of the gaps induces a flow bias in the fuel blocks and results in unexpected increase of maximum fuel temperature. Traditionally, simplified methods such as flow network calculations employing experimental correlations are used to estimate flow and temperature distributions in the core design. However, the distribution of temperature in the fuel pins and graphite blocks as well as coolant outlet temperatures are strongly coupled with the local heat generation rate within fuel blocks which is not uniformly distributed in the core. Hence, it is crucial to establish mechanistic based methods which can be applied to the reactor core thermal hydraulic design and safety analysis. Computational Fluid Dynamics (CFD) codes, which have a capability of local physics based simulation, are widely used in various industrial fields. This study investigates core bypass flow phenomena with the assistance of commercial CFD codes and establishes a baseline for evaluation methods. A one-twelfth sector of the hexagonal block surface is modeled and extruded down to whole core length of 10.704m. The computational domain is divided vertically with an upper reflector, a fuel section and a lower reflector. Each side of the one-twelfth grid can be set as a symmetry boundary

  6. Miniaturized cardiopulmonary bypass: the Hammersmith technique

    PubMed Central

    2013-01-01

    Background Conventional Cardiopulmonary Bypass (cCPB) is a trigger of systemic inflammatory reactions, hemodilution, coagulopathy, and organ failure. Miniaturised Cardiopulmonary Bypass (mCPB) has the potential to reduce these deleterious effects. Here, we describe our standardised ‘Hammersmith’ mCPB technique, used in all types of adult cardiac operations including major aortic surgery. Methods The use of mCPB remains limited by the diversity of technologies which range from extremely complex, micro systems to ones very similar to cCPB. Our approach is designed around the principle of balancing the benefits of miniaturisation; reducing foreign surface area while maintaining patient safety. Results From January 2010 to March 2011, a single surgeon performed 184 consecutive operations (Euro score Logistic 8.4+/-9.9): 61 aortic valve replacements, 78 CABGs, 25 aortic valve replacement and CABG and 17 other procedures (major aortic surgery, re-do operations or double/triple valve replacements). Our clinical experience suggests that: i. Venous drainage is optimally maintained using kinetic energy. ii. Venous collapse pressure depends on the patient’s anatomy and cannula size, but most importantly on the negative pressure generated by venous drainage. iii. The patient-prime interaction is optimised with antegrade and retrograde autologous priming, which mixes the blood and prime away from the tissues and results in a reduced oncotic destabilization. iv. mCPB is a safe and reproducible technique Conclusion The Hammersmith mCPB is a “next generation” system which uses standard commercially available components. It aims to maintain safety margin and the benefit of miniaturised system whilst reducing the human factor demands. PMID:23731623

  7. Antibiotic drug advertising in medical journals.

    PubMed

    Gilad, Jacob; Moran, Lia; Schlaeffer, Francisc; Borer, Abraham

    2005-01-01

    Advertising is a leading strategy for drug promotion. We analysed 779 advertisements in 24 medical journals, 25% of which featured antibiotics. Antibiotic advertisements showed differences compared to those of other drugs. None addressed the issue of antibiotic resistance. Efforts to prevent antibiotic resistance should take antibiotic advertising into consideration.

  8. The Staphylococcus aureus FASII bypass escape route from FASII inhibitors.

    PubMed

    Morvan, Claire; Halpern, David; Kénanian, Gérald; Pathania, Amit; Anba-Mondoloni, Jamila; Lamberet, Gilles; Gruss, Alexandra; Gloux, Karine

    2017-10-01

    Antimicrobials targeting the fatty acid synthesis (FASII) pathway are being developed as alternative treatments for bacterial infections. Emergence of resistance to FASII inhibitors was mainly considered as a consequence of mutations in the FASII target genes. However, an alternative and efficient anti-FASII resistance strategy, called here FASII bypass, was uncovered. Bacteria that bypass FASII incorporate exogenous fatty acids in membrane lipids, and thus dispense with the need for FASII. This strategy is used by numerous Gram-positive low GC % bacteria, including streptococci, enterococci, and staphylococci. Some bacteria repress FASII genes once fatty acids are available, and "constitutively" shift to FASII bypass. Others, such as the major pathogen Staphylococcus aureus, can undergo high frequency mutations that favor FASII bypass. This capacity is particularly relevant during infection, as the host supplies the fatty acids needed for bacteria to bypass FASII and thus become resistant to FASII inhibitors. Screenings for anti-FASII resistance in the presence of exogenous fatty acids confirmed that FASII bypass confers anti-FASII resistance among clinical and veterinary isolates. Polymorphisms in S. aureus FASII initiation enzymes favor FASII bypass, possibly by increasing availability of acyl-carrier protein, a required intermediate. Here we review FASII bypass and consequences in light of proposed uses of anti-FASII to treat infections, with a focus on FASII bypass in S. aureus. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  9. Monitoring microemboli during cardiopulmonary bypass with the EDAC quantifier.

    PubMed

    Lynch, John E; Wells, Christopher; Akers, Tom; Frantz, Paul; Garrett, Donna; Scott, M Lance; Williamson, Lisa; Agnew, Barbara; Lynch, John K

    2010-09-01

    Gaseous emboli may be introduced into the bypass circuit both from the surgical field and during perfusionist interventions. While circuits provide good protection against massive air embolism, they do not remove gaseous microemboli (GME) from the bypass circuit. The purpose of this preliminary study is to assess the incidence of GME during bypass surgery and determine if increased GME counts were associated with specific events during bypass surgery. In 30 cases divided between 15 coronary artery bypass grafts and 15 valve repairs, GME were counted and sizedt the three locations on the bypass circuit using the EDAC" Quantifier (Luna Innovations, Roanoke, VA). A mean of 45,276 GME were detected after the arterial line filter during these 30 cases, with significantly more detected (p = .04) post filter during valve cases (mean = 72,137 +/- 22,113) than coronary artery bypass graft cases (mean = 18,416 +/- 7831). GME detected post filter were significantly correlated in time with counts detected in the venous line (p < .001). Specific events associated with high counts included the initiation of cardiopulmonary bypass, heart manipulations, insertion and removal of clamps, and the administration of drugs. Global factors associated with increased counts post filter included higher venous line counts and higher post reservoir/bubble trap counts. The mean number of microemboli detected during bypass surgery was much higher than reported in other studies of emboli incidence, most likely due to the increased sensitivity of the EDAC Quantifier compared to other detection modalities. The results furthermore suggest the need for further study of the clinical significance of these microemboli and what practices may be used to reduce GME incidence. Increased in vitro testing of the air handling capability of different circuit designs, along with more clinical studies assessing best clinical practices for reducing GME activity, is recommended.

  10. Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics.

    PubMed

    González-Bello, Concepción

    2017-09-15

    Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  11. Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

    PubMed

    Beardmore, Robert Eric; Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

    2017-04-01

    Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as "antibiotic cycling" and "antibiotic mixing." However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to "cycle" between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic. : antibiotic cycling, antibiotic mixing, optimal control, stochastic models.

  12. Effect of cardiopulmonary bypass on gastrointestinal perfusion and function.

    PubMed

    Gaer, J A; Shaw, A D; Wild, R; Swift, R I; Munsch, C M; Smith, P L; Taylor, K M

    1994-02-01

    Gastric mucosal tonometry was used to determine the adequacy of gastrointestinal perfusion in 10 patients undergoing elective myocardial revascularization. Patients were prospectively randomized to receive either pulsatile or nonpulsatile flow during cardiopulmonary bypass. All patients showed a reduction in gastric mucosal perfusion during bypass, manifested by a reduction in the gastric mucosal pH, which occurred independently of variations in the arterial pH. In the group of patients receiving nonpulsatile flow, this reduction was significantly greater (p < 0.05). Cardiopulmonary bypass using nonpulsatile flow is associated with the development of a gastric mucosal acidosis, which may have implications for the development of postoperative complications.

  13. Coronary artery bypass grafting in an achondroplastic dwarf.

    PubMed

    Balaguer, J M; Perry, D; Crowley, J; Moran, J M

    1995-01-01

    To our knowledge, coronary bypass for complications of coronary artery disease in achondroplasia has not previously been described. Achondroplasia, in and of itself, is not a contraindication to coronary bypass. Although the anatomic reserve of saphenous vein is less in achondroplastic dwarfs than in people of normal stature, that vessel and the internal mammary artery can be harvested in routine fashion. A 60-year-old woman with several risk factors for coronary artery disease underwent successful bypass surgery, which included the use of both a saphenous vein and the left internal mammary artery.

  14. [Bypass spanning the knee joint with synthetic prosthesis].

    PubMed

    Müller-Wiefel, H

    1989-01-01

    Synthetic tubes are the second choice for below-knee bypass materials. The ring-reinforced thin-walled Goretex-PTFE graft is an approved material which was tested in a multicenter study. The primary 3 years patency for below-knee femoral-popliteal bypass was 64%, for crural bypass 39%. A total of 195 grafts have been implanted. Long-term patency depends very much on the run-off conditions (81% in good and 43% in bad cases). The over-all limb salvage rate was 80% after 3 years.

  15. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management.

    PubMed

    Sardana, Kabir; Gupta, Tanvi; Garg, Vijay K; Ghunawat, Sneha

    2015-07-01

    Antibiotic resistance in cutaneous Propionobacterium is a global problem. As a general rule, resistance levels are high to macrolides, trimethoprim/sulfamethoxazole and clindamycin, while tetracyclines and levofloxacin have low resistance potential. Newer preparations like doxycycline MR and doxycycline 20 mg are subantimicrobial and may not lead to resistance. Sampling techniques are crucial to determine resistance. Genomic evaluation using 16S ribosomal RNA gene sequencing can be useful in diagnosing mutations and mapping phylotypes of Propionobacterium acnes. Resistance may lead to slow response and relapses. Apart from benzoyl peroxide, azelaic acid, topical dapsone, oral zinc and retinoids, novel molecules with little resistance potential include octadecenedioic acid, phytosphingosine, lauric acid, retapamulin, resveratrol, T-3912 and NB-003. The use of oral retinoids and non-antibiotics like zinc can prevent resistance and help reduce the dependence on antibiotics.

  16. Antibiotics and Bacterial Resistance in the 21st Century

    PubMed Central

    Fair, Richard J; Tor, Yitzhak

    2014-01-01

    Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed. PMID:25232278

  17. Nanoformulated antibiotics: the next step for pathogenic bacteria control.

    PubMed

    Saúde, Amanda Caroline Marques; Cherobim, Mariana Dornelles; Amaral, André Corrêa; Dias, Simoní Campos; Franco, Octávio Luiz

    2013-01-01

    The resistance of infectious bacteria to current antibiotics is a worldwide problem. Previous studies have demonstrated the efficacy of nanostructured molecules against pathogens as an innovative methodology for the development of novel drugs. Currently, 95% of properties limited pharmacies applicability such as low solubility, short half-life in the circulatory system, toxicity associated to controlled release and immunogenicity. Furthermore, nanobiotechnology provides a different perspective for modifying these properties and allows innovative drug development. In this context, this review aims to describe different methods, polymers, and drugs used to obtain and analyze nanostructures associated with antibiotics as an unconventional and innovative tool for bacterial control. Biotechnology provides a different perspective for modifying drug properties and allows innovative drug development. This review describes nanostructures in association with antibiotics as an unconventional and innovative tool for bacterial control.

  18. 34 CFR 300.192 - Notice of intent to implement a by-pass.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Notice of intent to implement a by-pass. 300.192... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.192 Notice of intent to implement a by-pass. (a) Before taking any final action to implement a by-pass,...

  19. 34 CFR 300.198 - Continuation of a by-pass.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Continuation of a by-pass. 300.198 Section 300.198... CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.198 Continuation of a by-pass. The Secretary continues a by-pass until the Secretary determines that the SEA, LEA or...

  20. 34 CFR 300.191 - Provisions for services under a by-pass.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Provisions for services under a by-pass. 300.191 Section... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.191 Provisions for services under a by-pass. (a) Before implementing a by-pass, the Secretary consults with...

  1. 34 CFR 300.198 - Continuation of a by-pass.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 34 Education 2 2014-07-01 2013-07-01 true Continuation of a by-pass. 300.198 Section 300.198... CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.198 Continuation of a by-pass. The Secretary continues a by-pass until the Secretary determines that the SEA, LEA or...

  2. 34 CFR 300.191 - Provisions for services under a by-pass.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false Provisions for services under a by-pass. 300.191... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.191 Provisions for services under a by-pass. (a) Before implementing a by-pass, the Secretary consults with...

  3. 34 CFR 300.191 - Provisions for services under a by-pass.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 34 Education 2 2013-07-01 2013-07-01 false Provisions for services under a by-pass. 300.191... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.191 Provisions for services under a by-pass. (a) Before implementing a by-pass, the Secretary consults with...

  4. 34 CFR 300.198 - Continuation of a by-pass.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 2 2012-07-01 2012-07-01 false Continuation of a by-pass. 300.198 Section 300.198... CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.198 Continuation of a by-pass. The Secretary continues a by-pass until the Secretary determines that the SEA, LEA or...

  5. 34 CFR 300.198 - Continuation of a by-pass.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true Continuation of a by-pass. 300.198 Section 300.198... CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.198 Continuation of a by-pass. The Secretary continues a by-pass until the Secretary determines that the SEA, LEA or...

  6. 34 CFR 300.191 - Provisions for services under a by-pass.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true Provisions for services under a by-pass. 300.191 Section... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.191 Provisions for services under a by-pass. (a) Before implementing a by-pass, the Secretary consults with...

  7. Beating heart versus conventional cardiopulmonary bypass: the octopus experience: a randomized comparison of 281 patients undergoing coronary artery bypass surgery with or without cardiopulmonary bypass.

    PubMed

    van Dijk, Diederik; Diephuis, Jan C; Nierich, Arno P; Keizer, Annemieke M A; Kalkman, Cor J

    2006-06-01

    In the Octopus Study, 281 coronary artery bypass surgery patients were randomized to surgery with or without cardiopulmonary bypass. The primary objective was to compare cognitive outcome between off-pump and on-pump coronary artery bypass surgery. Before and after surgery, psychologists administered a battery of 10 neuropsychological tests to the patients. Cognitive decline was defined as a decrease in an individual's performance of at least 20% from baseline, in at least 20% of the main variables. According to this definition, cognitive decline was present in 21% in the off-pump group and 29% in the on-pump group, 3 months after the procedure (P = .15). At 12 months, cognitive decline was present in 31% in the off-pump group and 34% in the on-pump group (P = .69). These results indicated that patients undergoing coronary artery bypass surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months. The same definition of cognitive decline was also applied to 112 volunteers not undergoing surgery. The definition labeled 28% of the control subjects as suffering from cognitive decline, 3 months after their first assessment. This suggests that the natural fluctuations in performance during repeated neuropsychological testing should be included in the statistical analysis of cognitive decline. Using an alternative definition of cognitive decline that takes these natural fluctuations in performance into account, the proportions of coronary artery bypass surgery patients displaying cognitive decline were substantially lower. This indicates that the incidence of cognitive decline after coronary artery bypass surgery has been overestimated.

  8. Linitis Plastica of the bypassed stomach 7 years after Roux-en-Y gastric bypass. A Case Report.

    PubMed

    Haenen, Filip Wn; Gys, Ben; Moreels, Tom; Michielsen, Maartje; Gys, Tobie; Lafullarde, Thierry

    2016-06-03

    Laparoscopic Roux-en-Y gastric bypass (RYGB) is currently the preferred surgical procedure to treat morbid obesity. It has proven its effects on excess weight loss and its positive effect on comorbidities. One of the main issues, however, is the postoperative evaluation of the bypassed gastric remnant. In literature, cancer of the excluded stomach after RYGB is rare. We describe the case of a 52-year-old woman with gastric linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass, diagnosed by means of laparoscopy and Single-Balloon enteroscopy, and it's clinical importance. Linitis plastica of the excluded stomach after RYGB is a very rare entity. This case report shows the importance of long-term postoperative follow-up, and the importance of Single-Balloon enteroscopy for visualization of the bypassed stomach remnant, when other investigations remain without results. This case report is only the second report of a linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass.

  9. Effects of coronary artery bypass grafting on cellular immunity with or without cardiopulmonary bypass: changes in lymphocytes subsets.

    PubMed

    Akbas, Haluk; Erdal, A Cenk; Demiralp, Emel; Alp, Mete

    2002-12-01

    Cell-mediated immunity responses decrease after all kinds of surgical procedures. Either anesthesia or surgical trauma plays an important role in this effect. Identification of functional lymphocyte subsets, by using appropriate monoclonal antibodies and analysis of flow cytometry data, appears to provide an accurate measurement of cellular immune competence. We found a significant decrease in the total number of T helper/inducer cells (p<0.035), B cells (p<0.043) and natural killer cells (NK) (p<0.018) but in contrast, increase in NK cell activity (p<0.012) in the peripheral arterial blood of ten patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (group 1) immediately after surgery and postoperative day 1 (POD1). On the other hand, there was no significant change of these parameters occurred in the peripheral arterial blood of ten patients (group 2) who were undergoing coronary artery bypass grafting without cardiopulmonary bypass. Therefore, we conclude that coronary artery bypass grafting (CABG) with cardiopulmonary bypass induce a greater decrease in immunologic response than CABG without cardiopulmonary bypass (off pump) operations. Nevertheless, off pump CABG operations do not induce a greater decrease in immunologic response than other surgical operations.

  10. Biotherapeutics as alternatives to antibiotics

    USDA-ARS?s Scientific Manuscript database

    Increasing pressure to limit antibiotic use in agriculture is heightening the need for alternative methods to reduce the adverse effects of clinical and subclinical disease on livestock performance that are currently managed by in-feed antibiotic usage. Immunomodulators have long been sought as such...

  11. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  12. Antibiotic use in livestock production

    USDA-ARS?s Scientific Manuscript database

    Antibiotic usage is a useful and commonly implemented practice in livestock and production agriculture that has progressively gained attention in recent years from consumers of animal products due to concerns about human and environmental health. Sub-therapeutic usage of antibiotics has led to a con...

  13. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  14. Single-Molecule Studies of Telomeres and Telomerase.

    PubMed

    Parks, Joseph W; Stone, Michael D

    2017-05-22

    Telomeres are specialized chromatin structures that protect chromosome ends from dangerous processing events. In most tissues, telomeres shorten with each round of cell division, placing a finite limit on cell growth. In rapidly dividing cells, including the majority of human cancers, cells bypass this growth limit through telomerase-catalyzed maintenance of telomere length. The dynamic properties of telomeres and telomerase render them difficult to study using ensemble biochemical and structural techniques. This review describes single-molecule approaches to studying how individual components of telomeres and telomerase contribute to function. Single-molecule methods provide a window into the complex nature of telomeres and telomerase by permitting researchers to directly visualize and manipulate the individual protein, DNA, and RNA molecules required for telomere function. The work reviewed in this article highlights how single-molecule techniques have been utilized to investigate the function of telomeres and telomerase.

  15. An experimental study of the electrical activity of the bypassed stomach in the Roux-en-Y gastric bypass.

    PubMed

    Ferraz, Alvaro Antônio Bandeira; Leão, Cristiano Souza; Campos, Josemberg Marins; Coelho, Antônio Roberto Barros; Zilbestein, Bruno; Ferraz, Edmundo Machado

    2007-01-01

    Surgical options for morbid obesity are diverse, and the Roux-en-Y gastric bypass, initially described by Fobi has gained popularity. Knowledge about the physiology of the bypassed stomach is limited because this newly produced segment of the stomach is inaccessible to endoscopic or contrast radiological studies. To evaluate the myoelectric activity of the bypassed stomach and its reply to the feeding. An experimental protocol was conducted to evaluate postoperative gastric bypassed motility in dogs submitted to the Roux-en-Y gastric bypass procedure. Two groups of five animals were studied on postoperative fasting and after a standard meal, recording electrical response and control activity. Both control and Roux-en-Y gastric bypass operated study group had a pair of electrodes placed on three points of the remaining stomach: fundus, body and antrum. Data registration was performed after complete ileus resolution, and analysed with DATA Q Inst. series 200. The results achieved on the conditions of this study suggest that: 1. the remaining stomach maintain the same pattern of motility; 2. there is a reduced fasting electromyography activity following the Roux-en-Y gastric bypass procedure; 3. significantly reduced fasting electric control activity when compared both groups, and a markedly reduced fasting response electric activity and; 4. the electric response to the feeding kept the same standard of the stomach, however in a statistically reduced way. The electrical activity of the bypassed stomach of Roux-en-Y gastric bypass procedure kept the same pattern but in a statistically reduced number of contraction.

  16. Antibiotics, microbiota, and immune defense

    PubMed Central

    Ubeda, Carles; Pamer, Eric G.

    2012-01-01

    The gastrointestinal tract microbiota contributes to the development and differentiation of the mammalian immune system. The composition of the microbiota affects immune responses and affects susceptibility to infection by intestinal pathogens and development of allergic and inflammatory bowel diseases. Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities and decreases host resistance to antibiotic-resistant microbes. Here, we review recent advances that begin to define the interactions between complex intestinal microbial populations and the mammalian immune system and how this relation is perturbed by antibiotic administration. We further discuss how antibiotic-induced disruption of the microbiota and immune homeostasis can lead to disease and we review strategies to restore immune defenses during antibiotic administration. PMID:22677185

  17. Antibiotic prophylaxis in otolaryngologic surgery.

    PubMed

    Obeso, Sergio; Rodrigo, Juan P; Sánchez, Rafael; López, Fernando; Díaz, Juan P; Suárez, Carlos

    2010-01-01

    Since the beginning of the 80s, numerous clinical trials have shown a significant reduction in the incidence of infections in clean-contaminated upper respiratory tract surgery, due to perioperative use of antibiotics; however, there is no consensus about the best antibiotic protocol. Moreover, there are no universally accepted guidelines about flap reconstructive procedures. In otological and rhinological surgery, tonsillectomy, cochlear implant and laryngo-pharyngeal laser surgery, the use of antibiotics frequently depends on institutional or personal preferences rather than the evidence available. We reviewed clinical trials on different otorhinolaryngological procedures, assessing choice of antibiotic, length of treatment and administration route. There are no clinical trials for laryngo-pharyngeal laser surgery. Nor are there clinical trials on implant cochlear surgery or neurosurgical clean-contaminated procedures, but in these circumstances, antibiotic prophylaxis is recommended.

  18. Antibiotic and Antimicrobial Resistance: Threat Report 2013

    MedlinePlus

    ... with Antibiotic-Resistant Bacteria [page 18] Assessment of Domestic Antibiotic-Resistant Threats [page 20] Running Out of ... Preventing the Spread of Resistance [page 32] CDC's Work to Prevent Infections and Antibiotic Resistance in Healthcare ...

  19. [Enteropathogens and antibiotics].

    PubMed

    González-Torralba, Ana; García-Esteban, Coral; Alós, Juan-Ignacio

    2015-08-12

    Infectious gastroenteritis remains a public health problem. The most severe cases are of bacterial origin. In Spain, Campylobacter and Salmonella are the most prevalent bacterial genus, while Yersinia and Shigella are much less frequent. Most cases are usually self-limiting and antibiotic therapy is not generally indicated, unless patients have risk factors for severe infection and shigellosis. Ciprofloxacin, third generation cephalosporins, azithromycin, ampicillin, cotrimoxazole and doxycycline are the most recommended drugs. The susceptibility pattern of the different bacteria determines the choice of the most appropriate treatment. The aim of this review is to analyse the current situation, developments, and evolution of resistance and multidrug resistance in these 4 enteric pathogens. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  20. Apicoaortic Valve Conduit for a Patient with Aortic Valve Stenosis and Patent Coronary Bypass Grafts Using Cardiopulmonary Bypass

    PubMed Central

    Shackelford, Anthony G.; Relle, Margaret A.; Lombardi, Sarah A.

    2015-01-01

    Abstract: In adults over 65 years of age, aortic valve stenosis has been found to be present in 2–9% within this group. Furthermore, aortic valve replacements in patients whom have had a previous coronary artery bypass grafting surgery have a mortality rate as high as 18%. A non-conventional effective surgical approach of bypassing the aortic valve by inserting an apicoaortic valve conduit (AVC) connecting the left ventricular apex to the descending thoracic aorta has been previously documented. We describe the case of a successful implantation of an AVC in a 64-year-old Caucasian male using cardiopulmonary bypass. PMID:26834287

  1. Apicoaortic Valve Conduit for a Patient with Aortic Valve Stenosis and Patent Coronary Bypass Grafts Using Cardiopulmonary Bypass.

    PubMed

    Shackelford, Anthony G; Relle, Margaret A; Lombardi, Sarah A

    2015-12-01

    In adults over 65 years of age, aortic valve stenosis has been found to be present in 2-9% within this group. Furthermore, aortic valve replacements in patients whom have had a previous coronary artery bypass grafting surgery have a mortality rate as high as 18%. A non-conventional effective surgical approach of bypassing the aortic valve by inserting an apicoaortic valve conduit (AVC) connecting the left ventricular apex to the descending thoracic aorta has been previously documented. We describe the case of a successful implantation of an AVC in a 64-year-old Caucasian male using cardiopulmonary bypass.

  2. [Epidemiological overview of antibiotic resistance in France and worldwide].

    PubMed

    Arlet, Guillaume

    2012-09-01

    Antibiotic resistance appeared early after the introduction of these molecules in therapeutic. But, this resistance has long been confined to care facilities. Twenty years ago, resistance emerged in community with the methicillin resistance in Staphylococcus aureus and also with the reduced susceptibility to penicillin in pneumococci, which are good examples. Fortunately, for these two species, in France, the situation appears to be controlled. The most worrying now is the emergence of resistance to major antimicrobial agents in Escherichia coli both in community and in hospitals. The third-generation cephalosporins and the fluoroquinolones are concerned. This situation is currently not well controlled here and worldwide. The only recourse remaining carbapenems, antibiotics reserved for hospital use. Unfortunately, new mechanisms of resistance to these molecules are emerging.

  3. Symbiosis-inspired approaches to antibiotic discovery.

    PubMed

    Adnani, Navid; Rajski, Scott R; Bugni, Tim S

    2017-07-06

    Covering: 2010 up to 2017Life on Earth is characterized by a remarkable abundance of symbiotic and highly refined relationships among life forms. Defined as any kind of close, long-term association between two organisms, symbioses can be mutualistic, commensalistic or parasitic. Historically speaking, selective pressures have shaped symbioses in which one organism (typically a bacterium or fungus) generates bioactive small molecules that impact the host (and possibly other symbionts); the symbiosis is driven fundamentally by the genetic machineries available to the small molecule producer. The human microbiome is now integral to the most recent chapter in animal-microbe symbiosis studies and plant-microbe symbioses have significantly advanced our understanding of natural products biosynthesis; this also is the case for studies of fungal-microbe symbioses. However, much less is known about microbe-microbe systems involving interspecies interactions. Microbe-derived small molecules (i.e. antibiotics and quorum sensing molecules, etc.) have been shown to regulate transcription in microbes within the same environmental niche, suggesting interspecies interactions whereas, intraspecies interactions, such as those that exploit autoinducing small molecules, also modulate gene expression based on environmental cues. We, and others, contend that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized. Particularly intriguing is the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Notably, many of the studies summarized here result from advances in "omics" technologies and highlight how symbioses have given rise to new anti-bacterial and antifungal natural products now being discovered.

  4. 1. PLENUM INTERIOR, SHOWING HEATING COILS AND BYPASS Hot ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. PLENUM INTERIOR, SHOWING HEATING COILS AND BY-PASS - Hot Springs National Park, Bathhouse Row, Fordyce Bathhouse: Mechanical & Piping Systems, State Highway 7, 1 mile north of U.S. Highway 70, Hot Springs, Garland County, AR

  5. Oil Bypass Filter Technology Performance Evaluation - January 2003 Quarterly Report

    SciTech Connect

    Laurence R. Zirker; James E. Francfort

    2003-01-01

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  6. Oil Bypass Filter Technology Performance Evaluation - First Quarterly Report

    SciTech Connect

    Zirker, L.R.; Francfort, J.E.

    2003-01-31

    This report details the initial activities to evaluate the performance of the oil bypass filter technology being tested by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass systems from the puraDYN Corporation. Each bus averages about 60,000 miles a year. The evaluation includes an oil analysis regime to monitor the presence of necessary additives in the oil and to detect undesirable contaminants. Very preliminary economic analysis suggests that the oil bypass system can reduce life-cycle costs. As the evaluation continues and oil avoidance costs are quantified, it is estimated that the bypass system economics may prove increasingly favorable, given the anticipated savings in operational costs and in reduced use of oil and waste oil avoidance.

  7. 14. DRAGLINE BEGINNING CONSTRUCTION OF THE BYPASS CHANNEL CONNECTING THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. DRAGLINE BEGINNING CONSTRUCTION OF THE BY-PASS CHANNEL CONNECTING THE DIVERSION GATE ALONG THE OUTLET CHANNEL WITH THE ORIGINAL CHANNEL OF THE SOURIS RIVER - Upper Souris National Wildlife Refuge, Dam 83, Souris River Basin, Foxholm, Surrey (England), ND

  8. [Preliminary study of colloid osmotic pressure for cardiopulmonary bypass].

    PubMed

    Wang, D; Xiang, L; Luo, J

    1996-12-01

    The ideal colloid osmotic pressure is beneficial to decrease the fluid accumulated in the pulmonary and other tissue during cardiopulmonary bypass. Schupbach reported the proper colloidosmotic pressure for cardiopulmonary bypass was 2.1 kPa (16 mmHg). Colloid osmotic pressures of blood and priming fluid during cardiopulmonary bypass were measured in 28 patients with heart disease by using colloid osmotic pressure detection apparatus. The value of colloid osmotic pressure suitable for the designed standard was apparently different among the Gelofusine group and other groups. P value was 0.005. Priming fluid for cardiopulmonary bypass needs to satisfy the quality and the quantity of colloid osmotic pressure. Using Albumin isn't economical. Whole blood and plazma are not suitable for increasing colloid osmotic pressure. Hydroxyethyl starch or Gelofusine is best choice in priming to get designed standard of colloid osmotic pressure. The ratio of hydroxyethyl starch or Gelofusine in priming fluid should beyond 1/2.

  9. Spasm in Arterial Grafts in Coronary Artery Bypass Grafting Surgery.

    PubMed

    He, Guo-Wei; Taggart, David P

    2016-03-01

    Spasm of arterial grafts in coronary artery bypass grafting surgery is still a clinical problem, and refractory spasm can occasionally be lethal. Perioperative spasm in bypass grafts and coronary arteries has been reported in 0.43% of all coronary artery bypass grafting surgery, but this may be an underestimate. Spasm can develop not only in the internal mammary artery but more frequently in the right gastroepiploic and radial artery. The mechanism of spasm can involve many pathways, particularly those involving regulation of the intracellular calcium concentration. Endothelial dysfunction also plays a role in spasm. Depending on the clinical scenario, the possibility of spasm during and after coronary artery bypass grafting should be confirmed by angiography. If present, immediate intraluminal injection of vasodilators is often effective, although other procedures such as an intraaortic balloon pump or extracorporeal membrane oxygenation may also become necessary to salvage the patient. Prevention of spasm involves many considerations, and the principles are discussed in this review article.

  10. What to Expect After Coronary Artery Bypass Grafting

    MedlinePlus

    ... What To Expect After Coronary Artery Bypass Grafting Recovery in the Hospital After surgery, you'll typically ... for 3 to 5 days before going home. Recovery at Home Your doctor will give you specific ...

  11. [Psychoprophylaxis in patients after coronary artery bypass graft operations].

    PubMed

    Rymaszewska, Joanna; Chładzińska-Kiejna, Sylwia; Górna, Renata; Kustrzycki, Wojciech

    2004-05-01

    The paper presented problems of quality of life and psychosocial functioning of patients following coronary artery bypass grafting operations. Possibilities of psychoprophylactic effects towards these patients and its efficacy were described.

  12. Protection of semiconductor converters for controlled bypass reactors

    SciTech Connect

    Dolgopolov, A. G.; Akhmetzhanov, N. G.; Karmanov, V. F.

    2010-05-15

    Possible ways of protecting thyristor converters in systems for magnetizing 110 - 500 kV controlled bypass reactors during switching and automatic reclosing are examined based on experience with the development of equipment, line tests, and mathematical modelling.

  13. Subarachnoid-subarachnoid bypass for spinal adhesive arachnoiditis.

    PubMed

    Tachibana, Toshiya; Moriyama, Tokuhide; Maruo, Keishi; Inoue, Shinichi; Arizumi, Fumihiro; Yoshiya, Shinichi

    2014-11-01

    The authors report a case of adhesive arachnoiditis (AA) and arachnoid cyst successfully treated by subarachnoid to subarachnoid bypass (S-S bypass). Arachnoid cysts or syringes sometimes compress the spinal cord and cause compressive myelopathy that requires surgical treatment. However, surgical treatment for AA is challenging. A 57-year-old woman developed leg pain and gait disturbance. A dorsal arachnoid cyst compressed the spinal cord at T7-9, the spinal cord was swollen, and a small syrinx was present at T9-10. An S-S bypass was performed from T6-7 to T11-12. The patient's gait disturbance resolved immediately after surgery. Two years later, a small arachnoid cyst developed. However, there was no neurological deterioration. The myelopathy associated with thoracic spinal AA, subarachnoid cyst, and syrinx improved after S-S bypass.

  14. What to Expect during Coronary Artery Bypass Grafting

    MedlinePlus

    ... support from an anesthesiologist, perfusionist (heart-lung bypass machine specialist), other surgeons, and nurses. There are several ... The tube will connect to a ventilator (a machine that supports breathing). The surgeon will make an ...

  15. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  16. Roux-en-Y Gastric Bypass Operation in Rats

    PubMed Central

    Bueter, Marco; Abegg, Kathrin; Seyfried, Florian; Lutz, Thomas A.; le Roux, Carel W.

    2012-01-01

    Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality benefit is bariatric surgery1,2. Consequently, there has been a steady rise in the number of bariatric operations done worldwide in recent years with the Roux-en-Y gastric bypass (gastric bypass) being the most commonly performed operation3. Against this background, it is important to understand the physiological mechanisms by which gastric bypass induces and maintains body weight loss. These mechanisms are yet not fully understood, but may include reduced hunger and increased satiation4,5, increased energy expenditure6,7, altered preference for food high in fat and sugar8,9, altered salt and water handling of the kidney10 as well as alterations in gut microbiota11. Such changes seen after gastric bypass may at least partly stem from how the surgery alters the hormonal milieu because gastric bypass increases the postprandial release of peptide-YY (PYY) and glucagon-like-peptide-1 (GLP-1), hormones that are released by the gut in the presence of nutrients and that reduce eating12. During the last two decades numerous studies using rats have been carried out to further investigate physiological changes after gastric bypass. The gastric bypass rat model has proven to be a valuable experimental tool not least as it closely mimics the time profile and magnitude of human weight loss, but also allows researchers to control and manipulate critical anatomic and physiologic factors including the use of appropriate controls. Consequently, there is a wide array of rat gastric bypass models available in the literature reviewed elsewhere in more detail 13-15. The description of the exact surgical technique of these models varies widely and differs e.g. in terms of pouch size, limb lengths, and the preservation of the vagal nerve. If reported, mortality rates seem to range from 0 to 35%15. Furthermore, surgery has been carried out

  17. Roux-en-Y gastric bypass operation in rats.

    PubMed

    Bueter, Marco; Abegg, Kathrin; Seyfried, Florian; Lutz, Thomas A; le Roux, Carel W

    2012-06-11

    Currently, the most effective therapy for the treatment of morbid obesity to induce significant and maintained body weight loss with a proven mortality benefit is bariatric surgery. Consequently, there has been a steady rise in the number of bariatric operations done worldwide in recent years with the Roux-en-Y gastric bypass (gastric bypass) being the most commonly performed operation. Against this background, it is important to understand the physiological mechanisms by which gastric bypass induces and maintains body weight loss. These mechanisms are yet not fully understood, but may include reduced hunger and increased satiation, increased energy expenditure, altered preference for food high in fat and sugar, altered salt and water handling of the kidney as well as alterations in gut microbiota. Such changes seen after gastric bypass may at least partly stem from how the surgery alters the hormonal milieu because gastric bypass increases the postprandial release of peptide-YY (PYY) and glucagon-like-peptide-1 (GLP-1), hormones that are released by the gut in the presence of nutrients and that reduce eating. During the last two decades numerous studies using rats have been carried out to further investigate physiological changes after gastric bypass. The gastric bypass rat model has proven to be a valuable experimental tool not least as it closely mimics the time profile and magnitude of human weight loss, but also allows researchers to control and manipulate critical anatomic and physiologic factors including the use of appropriate controls. Consequently, there is a wide array of rat gastric bypass models available in the literature reviewed elsewhere in more detail. The description of the exact surgical technique of these models varies widely and differs e.g. in terms of pouch size, limb lengths, and the preservation of the vagal nerve. If reported, mortality rates seem to range from 0 to 35%. Furthermore, surgery has been carried out almost exclusively in male

  18. Antibiotic Resistance: MedlinePlus Health Topic

    MedlinePlus

    ... and Tests Susceptibility Testing (American Association for Clinical Chemistry) Prevention and Risk Factors Antibiotic Resistance (Food and Drug Administration) Antibiotic Resistance Threats in the ...

  19. Hypoparathyroidism after total thyroidectomy in patients with previous gastric bypass.

    PubMed

    Droeser, Raoul A; Ottosson, Johan; Muth, Andreas; Hultin, Hella; Lindwall-Åhlander, Karin; Bergenfelz, Anders; Almquist, Martin

    2017-03-01

    Case reports suggest that patients with previous gastric bypass have an increased risk of severe hypocalcemia after total thyroidectomy, but there are no population-based studies. The prevalence of gastric bypass before thyroidectomy and the risk of hypocalcemia after thyroidectomy in patients with previous gastric bypass were investigated. By cross-linking The Scandinavian Quality Registry for Thyroid, Parathyroid and Adrenal Surgery with the Scandinavian Obesity Surgery Registry patients operated with total thyroidectomy without concurrent or previous surgery for hyperparathyroidism were identified and grouped according to previous gastric bypass. The risk of treatment with intravenous calcium during hospital stay, and with oral calcium and vitamin D at 6 weeks and 6 months postoperatively was calculated by using multiple logistic regression in the overall cohort and in a 1:1 nested case-control analysis. We identified 6115 patients treated with total thyroidectomy. Out of these, 25 (0.4 %) had undergone previous gastric bypass surgery. In logistic regression, previous gastric bypass was not associated with treatment with i.v. calcium (OR 2.05, 95 % CI 0.48-8.74), or calcium and/or vitamin D at 6 weeks (1.14 (0.39-3.35), 1.31 (0.39-4.42)) or 6 months after total thyroidectomy (1.71 (0.40-7.32), 2.28 (0.53-9.75)). In the nested case-control analysis, rates of treatment for hypocalcemia were similar in patients with and without previous gastric bypass. Previous gastric bypass surgery was infrequent in patients undergoing total thyroidectomy and was not associated with an increased risk of postoperative hypocalcemia.

  20. Off-pump coronary artery bypass: techniques, pitfalls, and results.

    PubMed

    Hoff, Steven J

    2009-01-01

    In an attempt to advance the surgical treatment of coronary artery disease, surgeons sought a way to offer the proven benefits of coronary revascularization and avoid the side effects of cardiopulmonary bypass by performing revascularization in the beating heart (off-pump coronary artery bypass). This review will describe the development and refinement of the technique, pitfalls to its widespread adoption, and an up-to-date assessment of current results.