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Sample records for antitumor antibiotic c-1027

  1. Draft genome sequence of Streptomyces globisporus C-1027, which produces an antitumor antibiotic consisting of a nine-membered enediyne with a chromoprotein.

    Science.gov (United States)

    Wang, Lifei; Wang, Songmei; He, Qing; Yu, Tengfei; Li, Qinglian; Hong, Bin

    2012-08-01

    Streptomyces globisporus C-1027 is the producer of antitumor antibiotic C-1027, a nine-membered enediyne-containing compound. Here we present a draft genome sequence of S. globisporus C-1027 containing the intact biosynthetic gene cluster for this antibiotic. The genome also carries numerous sets of genes for the biosynthesis of diverse secondary metabolites. PMID:22815456

  2. Characterization of the SgcF epoxide hydrolase supporting an (R)-vicinal diol intermediate for enediyne antitumor antibiotic C-1027 biosynthesis.

    Science.gov (United States)

    Lin, Shuangjun; Horsman, Geoffrey P; Chen, Yihua; Li, Wenli; Shen, Ben

    2009-11-18

    C-1027 is a chromoprotein antitumor antibiotic consisting of an apoprotein and the C-1027 chromophore. The C-1027 chromophore possesses four distinct structural moieties-an enediyne core, a deoxy aminosugar, a benzoxazolinate, and an (S)-3-chloro-5-hydroxy-beta-tyrosine-the latter two of which are proposed to be appended to the enediyne core via a convergent biosynthetic strategy. Here we report the in vitro characterization of SgcF, an epoxide hydrolase from the C-1027 biosynthetic gene cluster that catalyzes regio- and stereospecific hydrolysis of styrene oxide, serving as an enediyne core epoxide intermediate mimic, to form a vicinal diol. Abolishment of C-1027 production in the DeltasgcF mutant strain Streptomyces globisporus SB1010 unambiguously establishes that sgcF plays an indispensable role in C-1027 biosynthesis. SgcF efficiently hydrolyzes (S)-styrene oxide, displaying an apparent K(m) of 0.6 +/- 0.1 mM and k(cat) of 48 +/- 1 min(-1), via attack at the alpha-position to exclusively generate the (R)-phenyl vicinal diol, consistent with the stereochemistry of the C-1027 chromophore. These findings support the role of SgcF in the proposed convergent pathway for C-1027 biosynthesis, unveiling an (R)-vicinal diol as a key intermediate. Interestingly, SgcF can also hydrolyze (R)-styrene oxide to afford preferentially the (R)-phenyl vicinal diol via attack at the beta-position, albeit with significantly reduced efficiency (apparent K(m) of 2.0 +/- 0.4 mM and k(cat) = 4.3 +/- 0.3 min(-1)). Although the latter activity unlikely contributes to C-1027 biosynthesis in vivo, such enantioconvergence arising from complementary regioselective hydrolysis of a racemic substrate could be exploited to engineer epoxide hydrolases with improved regio- and/or enantiospecificity. PMID:19856960

  3. The Structure of L-Tyrosine 2,3-Aminomutase frmo the C-1027 Enediyne Antitumor Antibiotic Biosynthetic Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Christianson,C.; Montavon, T.; Van Lanen, S.; Shen, B.; Bruner, S.

    2007-01-01

    The SgcC4 L-tyrosine 2,3-aminomutase (SgTAM) catalyzes the formation of (S)-{beta}-tyrosine in the biosynthetic pathway of the enediyne antitumor antibiotic C-1027. SgTAM is homologous to the histidine ammonia lyase family of enzymes whose activity is dependent on the methylideneimidazole-5-one (MIO) cofactor. Unlike the lyase enzymes, SgTAM catalyzes additional chemical transformations resulting in an overall stereospecific 1,2-amino shift in the substrate L-tyrosine to generate (S)-{beta}-tyrosine. Previously, we provided kinetic, spectroscopic, and mutagenesis data supporting the presence of MIO in the active site of SgTAM [Christenson, S. D.; Wu, W.; Spies, A.; Shen, B.; and Toney, M. D. (2003) Biochemistry 42, 12708-12718]. Here we report the first X-ray crystal structure of an MIO-containing aminomutase, SgTAM, and confirm the structural homology of SgTAM to ammonia lyases. Comparison of the structure of SgTAM to the L-tyrosine ammonia lyase from Rhodobacter sphaeroides provides insight into the structural basis for aminomutase activity. The results show that SgTAM has a closed active site well suited to retain ammonia and minimize the formation of lyase elimination products. The amino acid determinants for substrate recognition and catalysis can be predicted from the structure, setting the framework for detailed mechanistic investigations.

  4. The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne antitumor antibiotic biosynthetic pathway.

    Science.gov (United States)

    Christianson, Carl V; Montavon, Timothy J; Van Lanen, Steven G; Shen, Ben; Bruner, Steven D

    2007-06-19

    The SgcC4 l-tyrosine 2,3-aminomutase (SgTAM) catalyzes the formation of (S)-beta-tyrosine in the biosynthetic pathway of the enediyne antitumor antibiotic C-1027. SgTAM is homologous to the histidine ammonia lyase family of enzymes whose activity is dependent on the methylideneimidazole-5-one (MIO) cofactor. Unlike the lyase enzymes, SgTAM catalyzes additional chemical transformations resulting in an overall stereospecific 1,2-amino shift in the substrate l-tyrosine to generate (S)-beta-tyrosine. Previously, we provided kinetic, spectroscopic, and mutagenesis data supporting the presence of MIO in the active site of SgTAM [Christenson, S. D.; Wu, W.; Spies, A.; Shen, B.; and Toney, M. D. (2003) Biochemistry 42, 12708-12718]. Here we report the first X-ray crystal structure of an MIO-containing aminomutase, SgTAM, and confirm the structural homology of SgTAM to ammonia lyases. Comparison of the structure of SgTAM to the l-tyrosine ammonia lyase from Rhodobacter sphaeroides provides insight into the structural basis for aminomutase activity. The results show that SgTAM has a closed active site well suited to retain ammonia and minimize the formation of lyase elimination products. The amino acid determinants for substrate recognition and catalysis can be predicted from the structure, setting the framework for detailed mechanistic investigations. PMID:17516659

  5. Regiospecific chlorination of (S)-beta-tyrosyl-S-carrier protein catalyzed by SgcC3 in the biosynthesis of the enediyne antitumor antibiotic C-1027.

    Science.gov (United States)

    Lin, Shuangjun; Van Lanen, Steven G; Shen, Ben

    2007-10-17

    C-1027 is a potent antitumor antibiotic composed of an apo-protein and a reactive enediyne chromophore. The chromophore consists of four different chemical subunits including an (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine moiety, the biosynthesis of which from l-alpha-tyrosine is catalyzed by six proteins, SgcC, SgcC1, SgcC2, SgcC3, SgcC4, and SgcC5. Biochemical characterization of SgcC3 unveiled the following: (i) SgcC3 is a flavin adenine dinucleotide (FAD)-dependent halogenase; (ii) SgcC3 acts only on the SgcC2 peptidyl carrier protein-tethered substrates; (iii) SgcC3-catalyzed halogenation requires O2 and reduced FAD and either the C-1027 pathway-specific flavin reductase SgcE6 or E. coli flavin reductase (Fre) can support the SgcC3 activity; (iv) SgcC3 also efficiently catalyzes bromination but not fluorination or iodination; (v) SgcC3 can utilize both (S)- and (R)-beta-tyrosyl-S-SgcC2 but not 3-hydroxy-beta-tyrosyl-S-SgcC2 as a substrate. These results establish that SgcC3 catalyzes the third enzymatic transformation during the biosynthesis of the (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine moiety of C-1027 from l-alpha-tyrosine. SgcC3 now represents the second biochemically characterized flavin-dependent halogenase that acts on a carrier protein-tethered substrate. These findings will facilitate the engineering of new C-1027 analogs by combinatorial biosynthesis methods. PMID:17887753

  6. Improvement of the enediyne antitumor antibiotic C-1027 production by manipulating its biosynthetic pathway regulation in Streptomyces globisporus.

    Science.gov (United States)

    Chen, Yihua; Yin, Min; Horsman, Geoff P; Shen, Ben

    2011-03-25

    The production of C-1027 in Streptomyces globisporus was previously increased 2- to 3-fold by manipulating three pathway-specific activators, SgcR1, SgcR2, and SgcR3. In this study, we have further characterized two putative C-1027 regulatory genes, sgcE1 and sgcR, by in vivo inactivation. The HxlR family DNA-binding protein SgcE1 was not essential for C-1027 biosynthesis, since inactivation of sgcE1 showed no effect on C-1027 production. In contrast, the proposed repressive role of the sgcR gene was confirmed by a 3-fold increase in C-1027 production in the ΔsgcR mutant S. globisporus SB1022 strain relative to the wild-type strain. Considering SgcR shows no significant similarity to any protein of known function, it may be representative of a new family of regulatory proteins. Finally, overexpression of the previously characterized activator sgcR1 in S. globisporus SB1022 increased the C-1027 yield to 37.5 ± 7.7 mg/L, which is about 7-fold higher than the wild-type strain. PMID:21250756

  7. Substrate specificity of the adenylation enzyme SgcC1 involved in the biosynthesis of the enediyne antitumor antibiotic C-1027.

    Science.gov (United States)

    Van Lanen, Steven G; Lin, Shuangjun; Dorrestein, Pieter C; Kelleher, Neil L; Shen, Ben

    2006-10-01

    C-1027 is an enediyne antitumor antibiotic composed of a chromophore with four distinct chemical moieties, including an (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine moiety that is derived from l-alpha-tyrosine. SgcC4, a novel aminomutase requiring no added co-factor that catalyzes the formation of the first intermediate (S)-beta-tyrosine and subsequently SgcC1 homologous to adenylation domains of nonribosomal peptide synthetases, was identified as specific for the SgcC4 product and did not recognize any alpha-amino acids. To definitively establish the substrate for SgcC1, a full kinetic characterization of the enzyme was performed using amino acid-dependent ATP-[(32)P]PP(i) exchange assay to monitor amino acid activation and electrospray ionization-Fourier transform mass spectroscopy to follow the loading of the activated beta-amino acid substrate to the peptidyl carrier protein SgcC2. The data establish (S)-beta-tyrosine as the preferred substrate, although SgcC1 shows promiscuous activity toward aromatic beta-amino acids such as beta-phenylalanine, 3-chloro-beta-tyrosine, and 3-hydroxy-beta-tyrosine, but all were <50-fold efficient. A putative active site mutant P571A adjacent to the invariant aspartic acid residue of all alpha-amino acid-specific adenylation domains known to date was prepared as a preliminary attempt to probe the substrate specificity of SgcC1; however the mutation resulted in a loss of activity with all substrates except (S)-beta-tyrosine, which was 142-fold less efficient relative to the wild-type enzyme. In total, SgcC1 is now confirmed to catalyze the second step in the biosynthesis of the (S)-3-chloro-4,5-dihydroxy-beta-phenylalanine moiety of C-1027, presenting downstream enzymes with an (S)-beta-tyrosyl-S-SgcC2 thioester substrate, and represents the first beta-amino acid-specific adenylation enzyme characterized biochemically. PMID:16887797

  8. Characterization of the two-component, FAD-dependent monooxygenase SgcC that requires carrier protein-tethered substrates for the biosynthesis of the enediyne antitumor antibiotic C-1027.

    Science.gov (United States)

    Lin, Shuangjun; Van Lanen, Steven G; Shen, Ben

    2008-05-21

    C-1027 is a potent antitumor antibiotic composed of an apoprotein (CagA) and a reactive enediyne chromophore. The chromophore has four distinct chemical moieties, including an ( S)-3-chloro-5-hydroxy-beta-tyrosine moiety, the biosynthesis of which from l-alpha-tyrosine requires five proteins: SgcC, SgcC1, SgcC2, SgcC3, and SgcC4; a sixth protein, SgcC5, catalyzes the incorporation of this beta-amino acid moiety into C-1027. Biochemical characterization of SgcC has now revealed that (i) SgcC is a two-component, flavin adenine dinucleotide (FAD)-dependent monooxygenase, (ii) SgcC is only active with SgcC2 (peptidyl carrier protein)-tethered substrates, (iii) SgcC-catalyzed hydroxylation requires O 2 and FADH 2, the latter supplied by the C-1027 pathway-specific flavin reductase SgcE6 or Escherichia coli flavin reductase Fre, and (iv) SgcC efficiently catalyzes regioselective hydroxylation of 3-substituted beta-tyrosyl-S-SgcC2 analogues, including the chloro-, bromo-, iodo-, fluoro-, and methyl-substituted analogues, but does not accept 3-hydroxy-beta-tyrosyl-S-SgcC2 as a substrate. Together with the in vitro data for SgcC4, SgcC1, and SgcC3, the results establish that SgcC catalyzes the hydroxylation of ( S)-3-chloro-beta-tyrosyl-S-SgcC2 as the final step in the biosynthesis of the ( S)-3-chloro-5-hydroxy-beta-tyrosine moiety prior to incorporation into C-1027. SgcC now represents the first biochemically characterized two-component, FAD-dependent monooxygenase that acts on a carrier-protein-tethered aromatic substrate. PMID:18426211

  9. Complete genome sequence of Streptomyces globisporus C-1027, the producer of an enediyne antibiotic lidamycin.

    Science.gov (United States)

    Li, Xingxing; Lei, Xuan; Zhang, Cong; Jiang, Zhibo; Shi, Yuanyuan; Wang, Songmei; Wang, Lifei; Hong, Bin

    2016-03-20

    Streptomyces globisporus C-1027 produces a nine-membered enediyne antitumor antibiotic lidamycin. Here we report the complete genome sequence of S. globisporus C-1027, which consists of a 7,608,611bp linear chromosome, a 167,754bp linear plasmid SGLP1 and a 7,234bp circular plasmid pSGL1. The biosynthetic gene cluster for lidamycin was located in the linear plasmid SGLP1. Genome analysis also revealed a number of genes related to biosynthesis of diverse secondary metabolites. The genome sequence of C-1027 will enable us to disclose biosynthetic pathways of these secondary metabolites and discover new natural products with potential applications notably in human health. PMID:26853480

  10. Disruption of cagA, the apoprotein gene of chromoprotein antibiotic C-1027, eliminates holo-antibiotic production, but not the cytotoxic chromophore.

    Science.gov (United States)

    Cui, Zhihui; Wang, Lifei; Wang, Songmei; Li, Guangwei; Hong, Bin

    2009-11-01

    C-1027 is a chromoprotein of the nine-membered enediyne antitumour antibiotic family, comprising apoprotein to stabilize and transport the enediyne chromophore. The disruption of apoprotein gene cagA within the C-1027 biosynthetic gene cluster abolished C-1027 holo-antibiotic production detected by an antibacterial assay, as well as the expression of the apoprotein and C-1027 chromophore extracted following protein precipitation of the culture supernatant. Complementation of the cagA-disrupted mutant AKO with the intact cagA gene restored C-1027 production, suggesting that cagA is indispensable for holo-antibiotic production. Overexpression of cagA in the wild-type strain resulted in a significant increase in C-1027 production as expected. Surprisingly, electrospray ionization (ESI)-MS and ESI-MS/MS analyses suggested that the AKO mutant still produced the C-1027 enediyne chromophore [m/z=844 (M+H)(+)] and its aromatized product [m/z=846 (M+H)(+)]. Consistent with this, the results from gene expression analysis using real-time reverse transcriptase-PCR showed that transcripts of the positive regulator sgcR3 and the structural genes sgcA1, sgcC4, sgcD6 and sgcE were readily detected in the AKO mutant as well as in the wild-type and the complementation strain. These results provided, for the first time, evidence suggesting that the apoprotein of C-1027 is not essential in the self-resistance mechanism for the enediyne chromophore. PMID:19845765

  11. A predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of 9-membered enediyne antitumor antibiotics

    OpenAIRE

    Horsman, Geoffrey P.; Lechner, Anna; Ohnishi, Yasuo; Moore, Bradley S.; Shen, Ben

    2013-01-01

    Nine-membered enediyne antitumor antibiotics C-1027, neocarzinostatin (NCS), and kedarcidin (KED) possess enediyne cores to which activity-modulating peripheral moieties are attached via (R)- or (S)-vicinal diols. We have previously shown that this stereochemical difference arises from hydrolysis of epoxide precursors by epoxide hydrolases (EHs) with different regioselectivities – the “inverting” EH, such as SgcF, hydrolyzes an (S)-epoxide substrate to yield an (R)-diol in C-1027 biosynthesis...

  12. Biosynthesis of enediyne antitumor antibiotics.

    Science.gov (United States)

    Van Lanen, Steven G; Shen, Ben

    2008-01-01

    The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been cloned and sequenced, providing the foundation to understand natures' means to biosynthesize such complex, exotic molecules. Presented here is a review of the current progress in delineating the biosynthesis of the enediynes with an emphasis on the model enediyne, C-1027. PMID:18397168

  13. A free-standing condensation enzyme catalyzing ester bond formation in C-1027 biosynthesis.

    Science.gov (United States)

    Lin, Shuangjun; Van Lanen, Steven G; Shen, Ben

    2009-03-17

    Nonribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of many biologically active peptides and typically are modular, with each extension module minimally consisting of a condensation, an adenylation, and a peptidyl carrier protein domain responsible for incorporation of an amino acid into the growing peptide chain. C-1027 is a chromoprotein antitumor antibiotic whose enediyne chromophore consists of an enediyne core, a deoxy aminosugar, a benzoxazolinate, and a beta-amino acid moiety. Bioinformatics analysis suggested that the activation and incorporation of the beta-amino acid moiety into C-1027 follows an NRPS mechanism whereby biosynthetic intermediates are tethered to the peptidyl carrier protein SgcC2. Here, we report the biochemical characterization of SgcC5, an NRPS condensation enzyme that catalyzes ester bond formation between the SgcC2-tethered (S)-3-chloro-5-hydroxy-beta-tyrosine and (R)-1-phenyl-1,2-ethanediol, a mimic of the enediyne core. SgcC5 uses (S)-3-chloro-5-hydroxy-beta-tyrosyl-SgcC2 as the donor substrate and exhibits regiospecificity for the C-2 hydroxyl group of the enediyne core mimic as the acceptor substrate. Remarkably, SgcC5 is also capable of catalyzing amide bond formation, albeit with significantly reduced efficiency, between (S)-3-chloro-5-hydroxy-beta-tyrosyl-(S)-SgcC2 and (R)-2-amino-1-phenyl-1-ethanol, an alternative enediyne core mimic bearing an amine at its C-2 position. Thus, SgcC5 is capable of catalyzing both ester and amide bond formation, providing an evolutionary link between amide- and ester-forming condensation enzymes. PMID:19246381

  14. Biosynthesis of Enediyne Antitumor Antibiotics

    OpenAIRE

    Van Lanen, Steven G.; Shen, Ben

    2008-01-01

    The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been...

  15. Predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of nine-membered enediyne antitumor antibiotics.

    Science.gov (United States)

    Horsman, Geoffrey P; Lechner, Anna; Ohnishi, Yasuo; Moore, Bradley S; Shen, Ben

    2013-08-01

    Nine-membered enediyne antitumor antibiotics C-1027, neocarzinostatin (NCS), and kedarcidin (KED) possess enediyne cores to which activity-modulating peripheral moieties are attached via (R)- or (S)-vicinal diols. We have previously shown that this stereochemical difference arises from hydrolysis of epoxide precursors by epoxide hydrolases (EHs) with different regioselectivities. The inverting EHs, such as SgcF, hydrolyze an (S)-epoxide substrate to yield an (R)-diol in C-1027 biosynthesis, whereas the retaining EHs, such as NcsF2 and KedF, hydrolyze an (S)-epoxide substrate to yield an (S)-diol in NCS and KED biosynthesis. We now report the characterization of a series of EH mutants and provide a predictive model for EH regioselectivity in the biosynthesis of the nine-membered enediyne antitumor antibiotics. A W236Y mutation in SgcF increased the retaining activity toward (S)-styrene oxide by 3-fold, and a W236Y/Q237M double mutation in SgcF, mimicking NcsF2 and KedF, resulted in a 20-fold increase in the retaining activity. To test the predictive utility of these mutations, two putative enediyne biosynthesis-associated EHs were identified by genome mining and confirmed as inverting enzymes, SpoF from Salinospora tropica CNB-440 and SgrF (SGR_625) from Streptomyces griseus IFO 13350. Finally, phylogenetic analysis of EHs revealed a familial classification according to inverting versus retaining activity. Taken together, these results provide a predictive model for vicinal diol stereochemistry in enediyne biosynthesis and set the stage for further elucidating the origins of EH regioselectivity. PMID:23844627

  16. A predictive model for epoxide hydrolase-generated stereochemistry in the biosynthesis of 9-membered enediyne antitumor antibiotics

    Science.gov (United States)

    Horsman, Geoffrey P.; Lechner, Anna; Ohnishi, Yasuo; Moore, Bradley S.; Shen, Ben

    2013-01-01

    Nine-membered enediyne antitumor antibiotics C-1027, neocarzinostatin (NCS), and kedarcidin (KED) possess enediyne cores to which activity-modulating peripheral moieties are attached via (R)- or (S)-vicinal diols. We have previously shown that this stereochemical difference arises from hydrolysis of epoxide precursors by epoxide hydrolases (EHs) with different regioselectivities – the “inverting” EH, such as SgcF, hydrolyzes an (S)-epoxide substrate to yield an (R)-diol in C-1027 biosynthesis, while the “retaining” EHs, such as NcsF2 and KedF, hydrolyze an (S)-epoxide substrate to yield an (S)-diol in NCS and KED biosynthesis. We now report the characterization of a series of EH mutants and provide a predictive model for EH regioselectivity in the biosynthesis of the 9-membered enediyne antitumor antibiotics. A W236Y mutation in SgcF increased the retaining activity towards (S)-styrene oxide 3-fold, and a W236Y/Q237M double mutation in SgcF, mimicking NcsF2 and KedF, resulted in a 20-fold increase in the retaining activity. To test the predictive utility of these mutations, two putative enediyne biosynthesis-associated EHs were identified by genome mining and confirmed as inverting enzymes – SpoF from Salinospora tropica CNB-440 and SgrF (SGR_625) from Streptomyces griseus IFO 13350. Finally, phylogenetic analysis of EHs revealed a familial classification according to inverting versus retaining activity. Taken together, these results provide a predictive model for the vicinal diol stereochemistry in enediyne biosynthesis and set the stage for further elucidating the origins of EH regioselectivity. PMID:23844627

  17. Vicenistatin, a novel 20-membered macrocyclic lactam antitumor antibiotic.

    Science.gov (United States)

    Shindo, K; Kamishohara, M; Odagawa, A; Matsuoka, M; Kawai, H

    1993-07-01

    A new antitumor antibiotic vicenistatin was isolated from the culture broth of Streptomyces sp. HC34. The structure of vicenistatin was elucidated by NMR spectral analysis. Vicenistatin exhibited antitumor activity against human colon carcinoma Co-3 in the xenograft model. PMID:8360102

  18. Total Synthesis of the Antitumor Antibiotic Basidalin.

    Science.gov (United States)

    Acosta, Jaime A M; Muddala, Ramesh; Barbosa, Luiz C A; Boukouvalas, John

    2016-08-01

    The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-β-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal. PMID:27347696

  19. Esperamicins, a class of potent antitumor antibiotics: mechanism of action.

    OpenAIRE

    Long, B H; Golik, J; Forenza, S; Ward, B; Rehfuss, R; Dabrowiak, J C; Catino, J J; Musial, S T; Brookshire, K W; Doyle, T W

    1989-01-01

    The esperamicins represent a class of antitumor antibiotics characterized by an unusual chemical core structure and extremely potent cytotoxicity. The mechanism by which these drugs produce cytotoxicity was investigated and found to be related to the formation of single- and double-strand DNA breaks. Using five structurally related analogs, we defined a structure-activity relationship for cytotoxicity in various eukaryotic and DNA-repair-deficient prokaryotic cell lines, for DNA breakage in a...

  20. Pharmacology and therapeutic applications of enediyne antitumor antibiotics.

    Science.gov (United States)

    Shao, Rong-Guang

    2008-01-01

    The natural compounds that interfere with cellular DNA such as enediyne antitumor antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the enediyne antitumor agents that are approved for clinical use and undergoing pre-clinical or clinical evaluation are reviewed. Most enediyne compounds have shown potent activity against the proliferation of various cancer cells, including cells that display resistance to other chemotherapeutic drugs. Enediyne derivatives, such as an immunoconjugate composed of an enediyne compound and monoclonal antibody, reveal stronger activity and selectivity for human cancer cells. The mechanism underlying the anticancer activity of these enediyne antitumor agents may mainly lie in their generation of DNA double-strand breaks. Increasing evidence shows that the enediyne-induced DNA double-strand breaks can engage the activation of DNA damage response proteins, arresting cell cycle progression and eventually leading to apoptotic cell death. Continued investigation of the mechanisms of action and development of new enediyne derivatives and conjugates may provide more effective therapeutics for cancer treatments. PMID:20021423

  1. Pharmacokinetics of C-1027 in mice as determined by TCA-RA method

    Institute of Scientific and Technical Information of China (English)

    You-Ping Liu; Quan-Sheng Li; Yu-Rong Huang; Mao-Jin Zhou; Chang-Xiao Liu

    2005-01-01

    AIM: To validate a radioactivity assay, the TCA-RA method,for the measurement of C-1027 in serum and to evaluate its application in determination of pharmacokinetics of C-1027 in mice.METHODS: 125I-C-1027 was prepared by the Iodogen method and separated by HPLC. The radioactivity assay was established and used to determine 125I-C-1027 in mice at doses of 10, 50 and 100 μg/kg after precipitation with20% trichloroacetic acid (TCA-RA method). Severalpharmacokinetic parameters were determined after intravenous injection of 125I-C-1027 to mice.RESULTS: After intravenous injection of 125I-C-1027 to mice,at doses of 10, 50 and 100 μg/kg; the apparent distribution volumes (Vd) were 0.26, 0.31 and 0.33 L/kg; the biological half-lives (T1/2) were 3.10, 3.40 and 3.90 h; the areas under curve (AUC) were 18.41, 103.69 and 202.74 ng/h/mL; the elimination rate constants (K) were 1.04, 1.26 and 0.58/h;and the total body clearance (Cl) were 0.54, 0.48 and0.49 L/kg/h, respectively.CONCLUSION: TCA-RA is a sensitive, reliable and suitable method for the determination of 125I-C-1027 in mouse serum.

  2. Comparative Analysis of the Biosynthetic Gene Clusters and Pathways for Three Structurally Related Antitumor Antibiotics Bleomycin, Tallysomycin and Zorbamycin†

    OpenAIRE

    Galm, Ute; Wendt-Pienkowski, Evelyn; Wang, Liyan; Huang, Sheng-Xiong; Unsin, Claudia; Tao, Meifeng; Coughlin, Jane M.; Shen, Ben

    2011-01-01

    The biosynthetic gene clusters for the glycopeptide antitumor antibiotics bleomycin (BLM), tallysomycin (TLM), and zorbamycin (ZBM) have been recently cloned and characterized from Streptomyces verticillus ATCC15003, Streptoalloteichus hindustanus E465-94 ATCC31158, and Streptomyces flavoviridis ATCC21892, respectively. The striking similarities and differences among the biosynthetic gene clusters for the three structurally related glycopeptide antitumor antibiotics prompted us to compare and...

  3. Sweet antibiotics – the role of glycosidic residues in antibiotic and antitumor activity and their randomization

    Czech Academy of Sciences Publication Activity Database

    Křen, Vladimír; Řezanka, Tomáš

    2008-01-01

    Roč. 32, č. 5 (2008), s. 858-889. ISSN 0168-6445 R&D Projects: GA MŠk(CZ) LC06010; GA AV ČR IAA400200503 Institutional research plan: CEZ:AV0Z50200510 Keywords : glycosides * sweet antibiotic s * aglycone Subject RIV: CE - Biochemistry Impact factor: 7.963, year: 2008

  4. Microencapsulation of anti-tumor, antibiotic and thrombolytic drugs in microgravity

    Science.gov (United States)

    Morrison, Dennis R.; Mosier, Benjamin; Cassanto, John

    1994-01-01

    Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.

  5. A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis.

    Science.gov (United States)

    Zhang, Jian; Van Lanen, Steven G; Ju, Jianhua; Liu, Wen; Dorrestein, Pieter C; Li, Wenli; Kelleher, Neil L; Shen, Ben

    2008-02-01

    The enediynes, unified by their unique molecular architecture and mode of action, represent some of the most potent anticancer drugs ever discovered. The biosynthesis of the enediyne core has been predicted to be initiated by a polyketide synthase (PKS) that is distinct from all known PKSs. Characterization of the enediyne PKS involved in C-1027 (SgcE) and neocarzinostatin (NcsE) biosynthesis has now revealed that (i) the PKSs contain a central acyl carrier protein domain and C-terminal phosphopantetheinyl transferase domain; (ii) the PKSs are functional in heterologous hosts, and coexpression with an enediyne thioesterase gene produces the first isolable compound, 1,3,5,7,9,11,13-pentadecaheptaene, in enediyne core biosynthesis; and (iii) the findings for SgcE and NcsE are likely shared among all nine-membered enediynes, thereby supporting a common mechanism to initiate enediyne biosynthesis. PMID:18223152

  6. Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. I. Taxonomy of the producing strain, fermentation, isolation and biological properties.

    Science.gov (United States)

    Nakagawa, M; Hsu, Y H; Hirota, A; Shima, S; Nakayama, M

    1989-02-01

    A new diterpene antitumor antibiotic, myrocin C, has been isolated from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The antibiotic was effective against Gram-positive bacteria, fungi and yeasts, and prolonged the life span of mice bearing Ehrlich ascites carcinoma. PMID:2494145

  7. QSAR-Assisted Virtual Screening of Lead-Like Molecules from Marine and Microbial Natural Sources for Antitumor and Antibiotic Drug Discovery

    Directory of Open Access Journals (Sweden)

    Florbela Pereira

    2015-03-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Florbela Pereira

    2014-01-01

    Full Text Available 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.

  9. Antibiotics

    Science.gov (United States)

    Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...

  10. Antitumor, antibiotic and antileishmanial properties of the Pyranonaphthoquinone Psychorubrin from Mitracarpus frigidus

    Directory of Open Access Journals (Sweden)

    Rodrigo L. Fabri

    2012-12-01

    Full Text Available The bioactivity guided fractionation of the dichloromethane extract of Mitracarpus frigidus afforded the pyranonaphthoquinone psychorubrin. This compound, hitherto unknown in the genus Mitracarpus, had its biological activity evaluated against one panel of bacteria and two fungi, three tumor cell lines (HL60, Jurkat and MCF-7 and four Leishmania species. Its identity was confirmed unambiguously by ¹H, 13C, ¹H-COSY, IR and UV-Vis spectroscopy and mass spectrometry. Psychorubrin displayed a very promising antitumor with IC50 of 4.5, 5.6 and 1.1 µM for HL60, Jurkat and MCF-7 cell lines, respectively. Antimicrobial activity, mainly against Cryptococcus neoformans (MIC of 87.3 µM was observed. A pronounced antileishmanial potential was also verified with IC50 varying from 1.7 to 2.7 µM for the Leishmania species tested. This is the first report of the presence of pyranonapthoquinones in the Mitracarpus genus, which may serve as a chemotaxonomical marker.O fracionamento biomonitorado do extrato diclorometânico de Mitracarpus frigidus forneceu a piranonaftoquinona psicorubrina. Essa substância, até então desconhecida no gênero Mitracarpus, teve sua atividade biológica avaliada contra várias bactérias e dois fungos, três linhagens de células tumorais (HL60, Jurkat e MCF-7 e quatro espécies de Leishmania. Sua estrutura foi confirmada por meio de ¹H, 13C, ¹H-COSY, IR e UV-Vis e espectrometria de massas. Psicorubrina exibiu uma atividade antitumoral promissora com CI50 de 4,5, 5,6 e 1,1 µM para HL60, Jurkat e MCF-7, respectivamente. Atividade antimicrobiana, principalmente contra Cryptococcus neoformans (CIM de 87,3 µM, foi observada. Um pronunciado potencial leishmanicida também foi verificado com CI50 variando de 1,7 - 2,7 µM para as diferentes espécies de Leishmania testadas. Este é o primeiro relato da presença de piranonaftoquinonas no gênero Mitracarpus, que poderão ser úteis como marcadores quimiotaxonômicos.

  11. A QSAR approach for virtual screening of lead-like molecules en route to antitumor and antibiotic drugs from marine and microbial natural products

    Directory of Open Access Journals (Sweden)

    Florbela Pereira

    2014-05-01

    Figure 1. The unreported 15 lead antibiotic MNPs and MbNPs from AntiMarin database, using the best Rfs antibiotic model with a probability of being antibiotic greater than or equal to 0.8. Figure 2. The selected 4 lead antitumor MNPs and MbNPs from the AntiMarin database, using the best Rfs antitumor model with a probability of being antitumor greater than or equal to 0.8. The present work corroborates by one side the results of our previous work6 and enables the presentation of a new set of possible lead like bioactive compounds. Additionally, it is shown the usefulness of quantum-chemical descriptors in the discrimination of biological active and inactive compounds. The use of the εHOMO quantum-chemical descriptor in the discrimination of large scale data sets of lead-like or drug-like compounds has never been reported. This approach results in the reduction, in great extent, of the number of compounds used in real screens, and it reinforces the results of our previous work. Furthermore, besides the virtual screening, the computational methods can be very useful to build appropriate databases, allowing for effective shortcuts of NP extracts dereplication procedures, which will certainly result in increasing the efficiency of drug discovery.

  12. Antibiotics.

    Science.gov (United States)

    Hariprasad, Seenu M; Mieler, William F

    2016-01-01

    The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However, since the completion of the EVS, numerous unresolved issues remain. The use of oral antibiotics has important implications for the ophthalmologist, particularly in the prophylaxis and/or management of postoperative, posttraumatic, or bleb-associated bacterial endophthalmitis. One can reasonably conclude that significant intraocular penetration of an antibiotic after oral administration may be a property unique to the newer-generation fluoroquinolones. Prophylactic use of mupirocin nasal ointment resulted in significant reduction of conjunctival flora with or without preoperative topical 5% povidone-iodine preparation. Ocular fungal infections have traditionally been very difficult to treat due to limited therapeutic options both systemically and intravitreally. Because of its broad spectrum of coverage, low MIC90 levels for the organisms of concern, good tolerability, and excellent bioavailability, voriconazole through various routes of administration may be useful to the ophthalmologist in the primary treatment of or as an adjunct to the current management of ocular fungal infections. PMID:26501865

  13. Regiospecific O-Methylation of Naphthoic Acids Catalyzed by NcsB1, an O-Methyltransferase Involved in the Biosynthesis of the Enediyne Antitumor Antibiotic Neocarzinostatin*S⃞

    OpenAIRE

    Luo, Yinggang; Lin, Shuangjun; Zhang, Jian; Cooke, Heather A.; Bruner, Steven D.; Shen, Ben

    2008-01-01

    Neocarzinostatin, a clinical anticancer drug, is the archetypal member of the chromoprotein family of enediyne antitumor antibiotics that are composed of a nonprotein chromophore and an apoprotein. The neocarzinostatin chromophore consists of a nine-membered enediyne core, a deoxyaminosugar, and a naphthoic acid moiety. We have previously cloned and sequenced the neocarzinostatin biosynthetic gene cluster and proposed that the biosynthesis of the naphthoic acid moiety and its incorporation in...

  14. Molecular Basis of Substrate Promiscuity for the SAM-Dependent O-Methyltransferase NcsB1, Involved in the Biosynthesis of the Enediyne Antitumor Antibiotic Neocarzinostatin

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, H.; Guenther, E; Luo, Y; Shen, B; Bruner, S

    2009-01-01

    The small molecule component of chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide, and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway [Luo, Y., Lin, S., Zhang, J., Cooke, H. A., Bruner, S. D., and Shen, B. (2008) J. Biol. Chem. 283, 14694-14702]. Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By cocrystallizing the enzyme with various combinations of the cofactor and substrate analogues, details of the active site structure have been established. Changes in subdomain orientation were observed via comparison of structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding of the substrate. In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization.

  15. Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.

    Science.gov (United States)

    Cooke, Heather A; Guenther, Elizabeth L; Luo, Yinggang; Shen, Ben; Bruner, Steven D

    2009-10-13

    The small molecule component of chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide, and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway [Luo, Y., Lin, S., Zhang, J., Cooke, H. A., Bruner, S. D., and Shen, B. (2008) J. Biol. Chem. 283, 14694-14702]. Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By cocrystallizing the enzyme with various combinations of the cofactor and substrate analogues, details of the active site structure have been established. Changes in subdomain orientation were observed via comparison of structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding of the substrate. In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization. PMID:19702337

  16. Structural, conformational, and theoretical binding studies of antitumor antibiotic porfiromycin (N-methylmitomycin C), a covalent binder of DNA, by X-ray, NMR, and molecular mechanics.

    Science.gov (United States)

    Arora, S K; Cox, M B; Arjunan, P

    1990-11-01

    X-ray, NMR, and molecular mechanics studies on antitumor antibiotic porfiromycin (C16H20N4O5), a covalent binder of DNA, have been carried out to study the structure, conformation, and theoretical interactions with DNA. The crystal structure was solved by direct methods and refined to an R value of 0.052. The configurations at C(9), C(9a), C(1), and C(2) are S, R, S, and S, except for the orientation of the aziridine ring and (carbamoyloxy)methyl side chain. The five-membered ring attached to the aziridine ring adopts an envelope conformation. The solution conformation is similar to that observed in the solid state except for the (carbamoyloxy)methyl side chain. Monovalent and cross-linked models of the drug bound to DNA have been energetically refined by using molecular mechanics. The results indicate that, in the case of monocovalent binding, the drug clearly prefers a d(CpG) sequence rather than a d(GpC) sequence. In the case of the cross-linked model there is no clear-cut preference of d(CpG) over d(GpC), indicating that the binding preference of the drug may be kinetic rather than thermodynamic. PMID:2231597

  17. Cloning and sequencing of the kedarcidin biosynthetic gene cluster from Streptoalloteichus sp. ATCC 53650 revealing new insights into biosynthesis of the enediyne family of antitumor antibiotics.

    Science.gov (United States)

    Lohman, Jeremy R; Huang, Sheng-Xiong; Horsman, Geoffrey P; Dilfer, Paul E; Huang, Tingting; Chen, Yihua; Wendt-Pienkowski, Evelyn; Shen, Ben

    2013-03-01

    Enediyne natural product biosynthesis is characterized by a convergence of multiple pathways, generating unique peripheral moieties that are appended onto the distinctive enediyne core. Kedarcidin (KED) possesses two unique peripheral moieties, a (R)-2-aza-3-chloro-β-tyrosine and an iso-propoxy-bearing 2-naphthonate moiety, as well as two deoxysugars. The appendage pattern of these peripheral moieties to the enediyne core in KED differs from the other enediynes studied to date with respect to stereochemical configuration. To investigate the biosynthesis of these moieties and expand our understanding of enediyne core formation, the biosynthetic gene cluster for KED was cloned from Streptoalloteichus sp. ATCC 53650 and sequenced. Bioinformatics analysis of the ked cluster revealed the presence of the conserved genes encoding for enediyne core biosynthesis, type I and type II polyketide synthase loci likely responsible for 2-aza-l-tyrosine and 3,6,8-trihydroxy-2-naphthonate formation, and enzymes known for deoxysugar biosynthesis. Genes homologous to those responsible for the biosynthesis, activation, and coupling of the l-tyrosine-derived moieties from C-1027 and maduropeptin and of the naphthonate moiety from neocarzinostatin are present in the ked cluster, supporting 2-aza-l-tyrosine and 3,6,8-trihydroxy-2-naphthoic acid as precursors, respectively, for the (R)-2-aza-3-chloro-β-tyrosine and the 2-naphthonate moieties in KED biosynthesis. PMID:23360970

  18. Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.

    Science.gov (United States)

    Luo, Yinggang; Lin, Shuangjun; Zhang, Jian; Cooke, Heather A; Bruner, Steven D; Shen, Ben

    2008-05-23

    Neocarzinostatin, a clinical anticancer drug, is the archetypal member of the chromoprotein family of enediyne antitumor antibiotics that are composed of a nonprotein chromophore and an apoprotein. The neocarzinostatin chromophore consists of a nine-membered enediyne core, a deoxyaminosugar, and a naphthoic acid moiety. We have previously cloned and sequenced the neocarzinostatin biosynthetic gene cluster and proposed that the biosynthesis of the naphthoic acid moiety and its incorporation into the neocarzinostatin chromophore are catalyzed by five enzymes NcsB, NcsB1, NcsB2, NcsB3, and NcsB4. Here we report the biochemical characterization of NcsB1, unveiling that: (i) NcsB1 is an S-adenosyl-L-methionine-dependent O-methyltransferase; (ii) NcsB1 catalyzes regiospecific methylation at the 7-hydroxy group of its native substrate, 2,7-dihydroxy-5-methyl-1-naphthoic acid; (iii) NcsB1 also recognizes other dihydroxynaphthoic acids as substrates and catalyzes regiospecific O-methylation; and (iv) the carboxylate and its ortho-hydroxy groups of the substrate appear to be crucial for NcsB1 substrate recognition and binding, and O-methylation takes place only at the free hydroxy group of these dihydroxynaphthoic acids. These findings establish that NcsB1 catalyzes the third step in the biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore and further support the early proposal for the biosynthesis of the naphthoic acid and its incorporation into the neocarzinostatin chromophore with free naphthoic acids serving as intermediates. NcsB1 represents another opportunity that can now be exploited to produce novel neocarzinostatin analogs by engineering neocarzinostatin biosynthesis or applying directed biosynthesis strategies. PMID:18387946

  19. Antibiotics Quiz

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  20. Antibiotic Resistance

    Science.gov (United States)

    Antibiotics are medicines that fight bacterial infections. Used properly, they can save lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able to resist the effects of an antibiotic. Using antibiotics can lead to resistance. ...

  1. Natural glycoconjugates with antitumor activity.

    Science.gov (United States)

    La Ferla, Barbara; Airoldi, Cristina; Zona, Cristiano; Orsato, Alexandre; Cardona, Francisco; Merlo, Silvia; Sironi, Erika; D'Orazio, Giuseppe; Nicotra, Francesco

    2011-03-01

    Cancer is one of the major causes of death worldwide. As a consequence, many different therapeutic approaches, including the use of glycosides as anticancer agents, have been developed. Various glycosylated natural products exhibit high activity against a variety of microbes and human tumors. In this review we classify glycosides according to the nature of their aglycone (non-saccharidic) part. Among them, we describe anthracyclines, aureolic acids, enediyne antibiotics, macrolide and glycopeptides presenting different strengths and mechanisms of action against human cancers. In some cases, the glycosidic residue is crucial for their activity, such as in anthracycline, aureolic acid and enediyne antibiotics; in other cases, Nature has exploited glycosylation to improve solubility or pharmacokinetic properties, as in the glycopeptides. In this review we focus our attention on natural glycoconjugates with anticancer properties. The structure of several of the carbohydrate moieties found in these conjugates and their role are described. The structure–activity relationship of some of these compounds, together with the structural features of their interaction with the biological targets, are also reported. Taken together, all this information is useful for the design of new potential anti-tumor drugs. PMID:21120227

  2. Forgotten antibiotics

    DEFF Research Database (Denmark)

    Pulcini, Céline; Bush, Karen; Craig, William A;

    2012-01-01

    disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were...... available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better...

  3. Antibiotic Resistance

    Science.gov (United States)

    ... Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products For Consumers Home For Consumers Consumer Information by Audience For Women Antibiotic Resistance Share Tweet Linkedin Pin it More ...

  4. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources of...... antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I...... to rationally design drug combinations that limit the evolution of antibiotic resistance due to counteracting evolutionary trajectories. My results highlight that an in-depth knowledge about the genetic responses to the individual antimicrobial compounds enables the prediction of responses to drug...

  5. Antitumor compounds from marine actinomycetes.

    OpenAIRE

    Salas, José A.; Carmen Méndez; Carlos Olano

    2009-01-01

    Chemotherapy is one of the main treatments used to combat cancer. A great number of antitumor compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinomycetes are the producers of a large number of natural products with different biological activities, including antitumor properties. These antitumor compounds belong to several structural classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides, macrolides, non-ribosomal pept...

  6. Cytokines and antitumor immunity.

    Science.gov (United States)

    Müller, Ludmila; Pawelec, Graham

    2003-06-01

    Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation ("danger") signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy. PMID:12779349

  7. Beyond Antibiotics?

    Directory of Open Access Journals (Sweden)

    LE Nicolle

    2006-01-01

    Full Text Available The AMMI Canada meeting in March 2006 hosted a symposium exploring the potential alternatives to antibiotics for the prevention and treatment of infection. Four papers summarizing talks from that session are published in this issue of the Journal (1-4. These reviews address the scientific underpinnings for a number of proposed concepts, and summarize the current status of clinical use. The approaches - probiotics, bacteriophage therapy, and manipulation of innate immunity - are all intriguing but are still removed from immediate practical applications.

  8. Facts about Antibiotic Resistance

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  9. Antibiotic / Antimicrobial Resistance Glossary

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  10. Antitumor Immunity and Dietary Compounds

    Directory of Open Access Journals (Sweden)

    Annalise R. Smith

    2013-12-01

    Full Text Available The mechanisms by which natural dietary compounds exert their antitumor effects have been the focus of a large number of research efforts in recent years. Induction of apoptosis by inhibition of cell proliferative pathways is one of the common means of cell death employed by these dietary compounds. However, agents that can activate an antitumor immune response in addition to a chemotherapeutic effect may be useful adjuvants or alternative therapies for the treatment of cancer. The focus of this review is to highlight representative dietary compounds, namely Withania somnifera, Panax ginseng, curcumin and resveratrol with special emphasis on their antitumor immune mechanism of action. Each of these dietary compounds and their sources has a history of safe human use as food or in herbal medicine traditions, potentially making them ideal therapeutics. Here we report the recent advances in the cellular immune mechanisms utilized by these compounds to induce antitumor immunity. Taken together, these findings provide a new perspective for exploiting novel dietary compounds as chemoimmunotherapeutic anti-cancer agents.

  11. Ribonucleases and their antitumor activity

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Josef

    2001-01-01

    Roč. 129, č. 3 (2001), s. 175-191. ISSN 1532-0456 R&D Projects: GA ČR GA523/01/0114; GA AV ČR KSK5052113 Keywords : angiogenin * antitumor * ribonuclease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.930, year: 2001

  12. Strengthening Control of Antibiotics

    Institute of Scientific and Technical Information of China (English)

    EthelLu

    2005-01-01

    IT is a well-known fact that buy-ng guns is much easier than purchasing antibiotics in the United States. In China, however, the situation is different. According to a recent WHO survey,about 80 percent of Chinese inpatients take antibiotic medicines, and 58 percent of them are prescribed multifunctional antibiotics,

  13. Know When Antibiotics Work

    Centers for Disease Control (CDC) Podcasts

    2015-04-15

    This podcast provides a brief background about antibiotics and quick tips to help prevent antibiotic resistance.  Created: 4/15/2015 by Division of Bacterial Diseases (DBD), National Center for Immunization and Respiratory Disease (NCIRD), Get Smart: Know When Antibiotics Work Program.   Date Released: 4/16/2015.

  14. Antibiotic resistant in microorganisms

    Science.gov (United States)

    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 ...

  15. Frontline antibiotic therapy.

    Science.gov (United States)

    MacGowan, Alasdair; Albur, Maha

    2013-06-01

    The need to use front-line antibiotics wisely has never been greater. Antibiotic resistance and multi-drug resistant infection, driven by antibiotic use, remain major public health and professional concerns. To overcome these infection problems, use of older antibiotics active against multi drug-resistant pathogens is increasing - for example, colistin, fosfomycin, pivmecillinam, pristinamycin, temocillin and oral tetracyclines. The number of new antibacterials reaching clinical practice has reduced significantly in the last 20 years, most being focused on therapy of Gram-positive infection - eg linezolid, daptomycin, telavancin and ceftaroline. Recent guidance on antibiotic stewardship in NHS trusts in England is likely to provide a backdrop to antibiotic use in hospitals in the next 5 years. PMID:23760700

  16. High Antibiotic Consumption

    DEFF Research Database (Denmark)

    Malo, Sara; José Rabanaque, María; Feja, Cristina;

    2014-01-01

    a high proportion of antibiotics not recommended as first choice in primary health care. In conclusion, heavy antibiotic users consisted mainly of children and old adults. Inappropriate overuse of antibiotics (high quantity, high frequency, and inappropriate antibiotic choice) leads to a substantial...... individuals with highest consumption) were responsible for 21% of the total DDD consumed and received ≥6 packages per year. Elderly adults (≥60 years) and small children (0-9 years) were those exposed to the highest volume of antibiotics and with the most frequent exposure, respectively. Heavy users received...... risk of the emergence and spread of resistant bacteria, and interventions to reduce overuse of antibiotics should therefore primarily be targeted children and elderly people....

  17. Structural organization of C60 fullerene, doxorubicin, and their complex in physiological solution as promising antitumor agents

    International Nuclear Information System (INIS)

    Specific features of structural self-organization of C60 fullerene (1 nm size range), antitumor antibiotic doxorubicin (Dox) and their complex in physiological solution (0.9 % NaCl) have been investigated by means of atomic-force microscopy, dynamic light scattering, and small-angle X-ray scattering. Significant ordering of the mixed system, C60 + Dox, was observed, suggesting the complexation between these drugs, and giving insight into the mechanism of enhancement of Dox antitumor effect on simultaneous administration with C60 fullerene

  18. Structural organization of C{sub 60} fullerene, doxorubicin, and their complex in physiological solution as promising antitumor agents

    Energy Technology Data Exchange (ETDEWEB)

    Prylutskyy, Yu. I. [Taras Shevchenko National University of Kyiv (Ukraine); Evstigneev, M. P., E-mail: max-evstigneev@mail.ru [Belgorod State University, Department of Biology and Chemistry (Russian Federation); Cherepanov, V. V. [Institute of Physics of NAS of Ukraine (Ukraine); Kyzyma, O. A.; Bulavin, L. A.; Davidenko, N. A. [Taras Shevchenko National University of Kyiv (Ukraine); Scharff, P. [Ilmenau University of Technology (Germany)

    2015-01-15

    Specific features of structural self-organization of C{sub 60} fullerene (1 nm size range), antitumor antibiotic doxorubicin (Dox) and their complex in physiological solution (0.9 % NaCl) have been investigated by means of atomic-force microscopy, dynamic light scattering, and small-angle X-ray scattering. Significant ordering of the mixed system, C{sub 60} + Dox, was observed, suggesting the complexation between these drugs, and giving insight into the mechanism of enhancement of Dox antitumor effect on simultaneous administration with C{sub 60} fullerene.

  19. Understanding Antibiotic Resistance

    OpenAIRE

    Goulart-Touma, Christiane

    2014-01-01

    The evolution of antibiotic resistance among bacteria threatens our continued ability to treat infectious diseases. The need for sustainable strategies to cure bacterial infections has never been greater. So far, all attempts to restore susceptibility after resistance arises have been unsuccessful, including restrictions on prescribing antibiotics (Andersson DI et al.2011) and antibiotic cycling (Andersson DI et al. 2005, Bergstrom CT et al. 2004). Part of the problem may be that those effor...

  20. Antibiotics: Miracle Drugs

    Centers for Disease Control (CDC) Podcasts

    2015-04-16

    The overuse of antibiotics has led to the development of resistance among bacteria, making antibiotics ineffective in treating certain conditions. This podcast discusses the importance of talking to your healthcare professional about whether or not antibiotics will be beneficial if you’ve been diagnosed with an infectious disease.  Created: 4/16/2015 by Division of Bacterial Diseases (DBD), National Center for Immunization and Respiratory Disease (NCIRD), Get Smart: Know When Antibiotics Work Program.   Date Released: 4/16/2015.

  1. Structure of polysaccharide antibiotics

    International Nuclear Information System (INIS)

    Study of the structure of antibiotics having two or several sugars in their molecule. One may distinguish: the polysaccharide antibiotics themselves, made up of two or several sugars either with or without nitrogen, such as streptomycin, neomycins, paromomycine, kanamycin, chalcomycin; the hetero-polysaccharide antibiotics made up of one saccharide part linked to an aglycone of various type through a glucoside: macrolide, pigment, pyrimidine purine. Amongst these latter are: erythromycin, magnamycin, spiramycin, oleandomycin, cinerubin and amicetin. The sugars can either play a direct role in biochemical reactions or act as a dissolving agent, as far as the anti-microbe power of these antibiotics is concerned. (author)

  2. ANTITUMOR EFFECTS OF MONOCLONAL ANTIBODY FAB′ FRAGMENT CONTAINING IMMUNOCONJUGATES

    Institute of Scientific and Technical Information of China (English)

    刘小云; 甄永苏

    2002-01-01

    Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DTT),while Fab′ fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by β mercaptoethanol.The conjugation between Fab′ fragment and pingyangmycin (PYM),an antitumor antibiotic,was mediated by dextran T 40.Immunoreactivity of Fab′ PYM conjugates with cancer cells was determined by ELISA,and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay.Antitumor effects of the Fab′ PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. Results.The molecular weight of Fab′ fragment was approximately 53 kD,while the average molecular weight of Fab′ PYM conjugate was 170 kD.The Fab′ PYM conjugates showed immunoreactivity with antigen relevant cancer cells and selective cytotoxicity against target cells.Administered intravenously,Fab′ PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. Conclusion.Fab′ PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth,suggesting its therapeutic potential in cancer treatment.

  3. The future of antibiotics.

    Science.gov (United States)

    Spellberg, Brad

    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

  4. Immunomodulatory actions of antibiotics

    Directory of Open Access Journals (Sweden)

    Minić Svetlana

    2009-01-01

    Full Text Available Introduction. Antimicrob drugs and immune system interaction has been studied since the pioneer works of Metchnikoff. After the introduction of antibiotics in clinical practice this area has attracted little attention of investigators, because of the lack of standards. This is the reason that the studying of the influence of antibiotics on immune system is still at its beginning. Aim: To point out the immunomodulatory action of some antibiotics on certain components of immune system. Methods and results. The literaure findings show that antibiotics exspress immunomodulatory action on some components of immune system such as fagocytes (polymorphonucleary, macrophages, monocytes, cytokines, immunoglobulines, and on cellular immunity. The principles of antibiotics action on phagocyte are the inhibition of chemotaxis and oxidants production. Macrolides applied for a short time enchance the phagocytic functions while their long use leads to immunosupression. Some cephalosporines and rifampicin in therapeutic doses inhibit the oxydative metabolism of macrophages. Tetracyclines, clindamycines, chloramphenicol and tobramycin inhibit the synthesis of superoxyd anione. The action of some antibiotics on cytokine and specific antibodies is also important. Cellular immunity can be affected as well. After administration of certain antibiotics it takes 1-2 weeks to reestablish normal cellular immunity, and for other even more. Conclusion. There is still no clear standing on real effects of antibiotics on the immune system. Clinicians should search for more information from this new-old field of investigation in order to give more adequate therapy to patients.

  5. ANTITUMOR EFFECT OF SNAKE VENOMS

    Directory of Open Access Journals (Sweden)

    R. J. DA SILVA

    1996-01-01

    Full Text Available The search for biological antitumor agents has been pursued for over half a century. Snake venom has been shown to possess a wide spectrum of biological activities. The objectives of the present review are to evaluate the existing controversies on this subject published in a number of papers and to propose probable explanations for the phenomena observed. We reported our results obtained in a study, in which we evaluated the action of the venoms of Crotalus durissus terrificus and Bothrops jararaca on Ehrlich ascites tumor cells. We noticed an important antitumor effect, mainly with Bothrops jararaca venom, as well as an increase in the functional activity of macrophages. We also observed an increase in the number of mononuclear and polymorphonuclear cells with Bothrops jararaca venom. Considering these findings, we postulate that both Bothrops jararaca and Crotalus durissus terrificus venoms can act directly on tumor cells. In addition, we propose an indirect mechanism, based on the stimulation of the inflammatory response, to inhibit tumor growth and to promote its rejection.

  6. Antitumoral activity of marine organism

    International Nuclear Information System (INIS)

    The study of the natural products from marine organism constitute a relatively recent scientific researcher field with high potentialities tanking in consideration that the oceans cover the three of the four parts of the earth. Poryphera and Bryozoans have been the Phylum more studied owning to the vulnerability, their soft body, their habitat on rocks, their slow movement and bright colors, for these reason these organisms are able to produce chemical substances as defense methods against depredators. Same mechanism is exhibit by the seaweeds with the production of secondary metabolites . In the present communication are exposed the main results obtained on the world a Cuba until the present in the looking for of substances with antitumor action from marine organism

  7. Targeting Antibiotic Resistance.

    Science.gov (United States)

    Chellat, Mathieu F; Raguž, Luka; Riedl, Rainer

    2016-06-01

    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

  8. Antibiotics for uncomplicated diverticulitis

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel M; Wille-Jørgensen, Peer

    2012-01-01

    Diverticulitis is an inflammatory complication to the very common condition diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics with reference to the microbiology, extrapolation from trials on complicated intra-abdominal infections and clinical experience....

  9. Antibiotic induced meningitis.

    OpenAIRE

    1994-01-01

    Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion ...

  10. Antibiotic Precautions in Athletes

    OpenAIRE

    Fayock, Kristopher; Voltz, Matthew; Sandella, Bradley; Close, Jeremy; Lunser, Matthew; Okon, Joshua

    2014-01-01

    Context: Antibiotics are the mainstay of treatment for bacterial infections in patients of all ages. Athletes who maximally train are at risk for illness and various infections. Routinely used antibiotics have been linked to tendon injuries, cardiac arrhythmias, diarrhea, photosensitivity, cartilage issues, and decreased performance. Evidence Acquisition: Relevant articles published from 1989 to 2012 obtained through searching MEDLINE and OVID. Also, the Food and Drug Administration website w...

  11. [Analysis of antibiotic usage].

    Science.gov (United States)

    Balpataki, R; Balogh, J; Zelkó, R; Vincze, Z

    2001-01-01

    Economic analysis is founded on the assumption that resources are limited and that should be used in a way that maximizes the benefits gained. Pharmacoeconomics extends these assumptions to drug treatment. Therefore, a full pharmacoeconomic analysis must consider two or more alternative treatments and should be founded on measurement of incremental cost, incremental efficacy, and the value of successful outcome. Antibiotic policy based only on administrative restrictions is failed, instead of it disease formularies and infectologist consultation system are needed. Equally important are various programmes that encourage the cost-conscious use of the antibiotics chosen. Some of the methods evaluated in the literature include: streamlining from combination therapy to a single agent, early switching from parenteral to oral therapy, initiating treatment with oral agents, administering parenteral antibiotic at home from outset of therapy, and antibiotic streamlining programmes that are partnered with infectious disease physicians. The solution is the rational and adequate use of antibiotics, based on the modern theory and practice of antibiotic policy and infection control, that cannot be carried out without the activities of experts in this field. PMID:11769090

  12. Phenotypic Resistance to Antibiotics

    Directory of Open Access Journals (Sweden)

    Jose L. Martinez

    2013-04-01

    Full Text Available The development of antibiotic resistance is usually associated with genetic changes, either to the acquisition of resistance genes, or to mutations in elements relevant for the activity of the antibiotic. However, in some situations resistance can be achieved without any genetic alteration; this is called phenotypic resistance. Non-inherited resistance is associated to specific processes such as growth in biofilms, a stationary growth phase or persistence. These situations might occur during infection but they are not usually considered in classical susceptibility tests at the clinical microbiology laboratories. Recent work has also shown that the susceptibility to antibiotics is highly dependent on the bacterial metabolism and that global metabolic regulators can modulate this phenotype. This modulation includes situations in which bacteria can be more resistant or more susceptible to antibiotics. Understanding these processes will thus help in establishing novel therapeutic approaches based on the actual susceptibility shown by bacteria during infection, which might differ from that determined in the laboratory. In this review, we discuss different examples of phenotypic resistance and the mechanisms that regulate the crosstalk between bacterial metabolism and the susceptibility to antibiotics. Finally, information on strategies currently under development for diminishing the phenotypic resistance to antibiotics of bacterial pathogens is presented.

  13. [Prophylactic antibiotics in neurosurgery].

    Science.gov (United States)

    Iacob, G; Iacob, Simona; Cojocaru, Inimioara

    2007-01-01

    Because of a low risk of infection (around 2-3%), prophylactic use of antibiotics in neurosurgery is a controversial issue. Some neurosurgeons consider that there are strong arguments against the use of antimicrobials (promotion of antibiotic-resistant strains of bacteria, superinfection and adverse drug reactions) and meticulous aseptic techniques could be more usefully than prophylactic antibiotics. On the other hand, despite of being rare, the consequences of a neurosurgical infection can be dramatic and may result in a rapid death, caused by meningitis, cerebritis, abscess formation or sepsis. Clinical studies emphasized that the most important factors influencing the choice of antibiotic prophylaxis in neurosurgery is the patient's immune status, virulence of the pathogens and the type of surgery ("clean contaminated"--procedure that crosses the cranial sinuses, "clean non-implant"--procedure that does not cross the cranial sinuses, CSF shunt surgery, skull fracture). Prophylaxis has become the standard of care for contaminated and clean-contaminated surgery, also for surgery involving insertion of artificial devices. The antibiotic (first/second generation of cephalosporins or vancomycin in allergic patients) should recover only the cutaneous possibly contaminating flora (S. aureus, S. epidermidis) and should be administrated 30' before the surgical incision, intravenously in a single dose. Most studies pointed that identification of the risk factors for infections, correct asepsis and minimal prophylactic antibiotic regimen, help neurosurgeons to improve patient care and to decrease mortality without selecting resistant bacteria. PMID:18293694

  14. Strategies to Minimize Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Sang Hee Lee

    2013-09-01

    Full Text Available 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.

  15. Ecological antibiotic policy.

    Science.gov (United States)

    Høiby, N

    2000-09-01

    Development of resistance to antibiotics is a major problem worldwide. The normal oropharyngeal flora, the intestinal flora and the skin flora play important roles in this development. Within a few days after the onset of antibiotic therapy, resistant Escherichia coli, Haemophilus influenzae and Staphylococcus epidermidis can be detected in the normal flora of volunteers or patients. Horizontal spread of the resistance genes to other species, e.g. Salmonella spp., Staphylococcus aureus and Streptococcus pneumoniae, occurs by conjugation or transformation. An ecologically sound antibiotic policy favours the use of antibiotics with little or no impact on the normal flora. Prodrug antibiotics which are not active against the bacteria in the mouth and the intestine (before absorption) and which are not excreted to a significant degree via the intestine, saliva or skin are therefore preferred. Prodrugs such as pivampicillin, bacampicillin, pivmecillinam and cefuroxime axetil are favourable from an ecological point of view. Experience from Scandinavia supports this, since resistance to mecillinam after 20 years of use is low (about 5%) and stable. PMID:11051626

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

    Directory of Open Access Journals (Sweden)

    Saswati eSengupta

    2013-03-01

    Full Text Available 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 subinhibitory concentrations acting as signalling molecules supporting 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 behaviour 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 genes that confer resistance to antibiotics in

  17. Antitumor effects of electrochemical treatment

    Institute of Scientific and Technical Information of China (English)

    Héctor Manuel Camué Ciria; Maraelys Morales González; Lisset Ortíz Zamora; Luis Enrique Bergues Cabrales; Gustavo Victoriano Sierra González; Luciana Oliveira de Oliveira; Rodrigo Zanella

    2013-01-01

    Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas.This treatment is noted for its great effectiveness,minimal invasiveness and local effect.Several studies have been conducted worldwide to evaluate the antitumoral effect of this therapy.In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained.By this reason,researchers have suggested various mechanisms to explain how direct electric current destroys tumor cells.Although,it is generally accepted this treatment induces electrolysis,electroosmosis and electroporation in tumoral tissues.However,action mechanism of this alternative modality on the tumor tissue is not well understood.Although the principle of Electrochemical treatment is simple,a standardized method is not yet available.The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process.The present work analyzes the latest and most important research done on the electrochemical treatment of tumors.We conclude with our point of view about the destruction mechanism features of this alternative therapy.Also,we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy.In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done.Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.

  18. [Antibiotical prophylaxy in gynecology].

    Science.gov (United States)

    Záhumenský, J; Menzlová, E; Zmrhal, J; Kučera, E

    2013-08-01

    Gynecological surgery is considered to be clear with possible contamination by gram-positive cocci from the skin, gram-negatives from the perineum or groins or polymicrobial biocenosis from vagina, depending on the surgical approach. Antibiotical prophylaxy enforces the natural mechanisms of immunity and helps to exclude present infection. There were presented many studies comparing useful effect of prophylaxis in gynecological surgery. The benefits of antibiotical prophylaxy before IUD insertion, before the cervical surgery and before hysteroscopies were not verified. On the other hand the prophylaxy of vaginal surgery including vaginal hysterectomy decreases the number of postoperative febrile complications. The positive influence of prophylaxis before the simple laparoscopy and laparoscopy without bowel injury or the opening of the vagina was not evidently verified. In abdominal hysterectomy the antibiotical prophylaxy decreases the incidence of postoperative complications significantly. The administration of 2 g of cefazolin can be recommended. In procedures taking more than 3 hours the repeated administration of cefazolin is suitable. New urogynecological procedures, using mesh implants, were not sufficiently evaluated as for postoperative infections and the posible antibiotical effect. The presence of implant in possibly non sterile area should be considered as high risc of postoperative complications. PMID:24040985

  19. Antibiotics in interventional radiology

    International Nuclear Information System (INIS)

    The range and number of interventional procedures is rapidly increasing each year. A major complication associated with many procedures is infection, which can result in serious adverse outcomes for the patient. Consequently, antibiotics are amongst the most common pharmaceuticals used by the interventionist, particularly for non-vascular procedures, yet almost no randomized controlled trial data exist to inform our decision when formulating appropriate antibiotic prophylaxis regimens. The purpose of this review is to provide an update on the utilization of antibiotics for common interventional radiology procedures, focusing on timing and duration of antibiotic prophylaxis. - Highlights: • Prophylaxis when necessary should be given immediately prior to the procedure for optimum effect. • Where possible single agents with a narrow spectrum of activity should be used. • Account should be taken of the clinical circumstances of the patient, including surgical history. • Continuous review of agents is necessary, ideally with input from the local microbiology department. • The importance of maximum sterile precautions cannot be overstated

  20. Polylactide-polyglycolide antibiotic implants.

    Science.gov (United States)

    Garvin, Kevin; Feschuk, Connie

    2005-08-01

    Surgeons continually struggle to reduce orthopaedic infections, but no current treatment offers minimum side effects with maximum effectiveness. Antibiotics mixed in plaster of paris have been successful in treating large bony defects in patients with chronic osteomyelitis, and have the advantage of being well tolerated and absorbed by the body. Antibiotics impregnated in polymethylmethacrylate (PMMA) have offered local antibiotic delivery with some success. However, the effect of the antibiotic on the bone cement, the inconsistent elution of the antibiotic, and the need to remove the PMMA implant drives the need for a better system of antibiotic delivery. Polymers or copolymers of antibiotic-impregnated polylactic acid, polyglycolic acid or polyparadioxanone may provide an absorbable system for localized antibiotic delivery. Similar biodegradable systems used to treat small bone fractures have been successful with minimal side effects. In vitro studies have shown promising results of antibiotic elution from bioabsorbable microspheres and beads. Animal in vivo tests have shown that antibiotic impregnated polymers can successfully treat induced osteomyelitis in rabbits and dogs. These studies have provided consistent reproducible results, and now it is time to plan human trials to assess the efficacy of antibiotic microspheres implanted in infected bone and to plan in vivo and in vitro animal testing to investigate the feasibility of antibiotic-polymer-coated components. PMID:16056034

  1. Primary Screeningof Substanceswith Potential Antitumor Activity

    OpenAIRE

    А.Kh. Khasenova; Sh.Zh.Daurenbekova

    2015-01-01

    A primary screening of antitumor substances was carried out among strains of actinomycetes isolated from the samples of natural substrates of arid zones in the Ile-Balkhash region. Antitumor properties of actinomycetes against Staphylococcus aureus209Р(S. aureus 209P) and its mutants UF-2 and UF-3 were studied using the agar block technique. The diameter of growth inhibition zone was measured after incubation of the test microorganisms at a temperature of 37 °C for 24 hours. 16...

  2. Environmental pollution by antibiotics and by antibiotic resistance determinants

    International Nuclear Information System (INIS)

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  3. Doxycycline potentiates antitumor effect of cyclophosphamide in mice

    International Nuclear Information System (INIS)

    Cyclophosphamide (CPA) is a widely used chemotherapeutic drug in neoplasias. It is a DNA and protein alkylating agent that has a broad spectrum of activity against variety of neoplasms including breast cancer. The therapeutic effectiveness of CPA is limited by the high-dose hematopoietic, renal, and cardiac toxicity that accompanies the systemic distribution of liver-derived activated drug metabolites. The present study examines the potential of combining well-tolerated antibiotic doxycycline (DOX) with CPA and understanding the mechanism of cell killing. Interestingly, we found that DOX significantly enhances the tumor regression activity of CPA on xenograft mice model bearing MCF-7 cells. DOX also potentiates MCF-7 cell killing by CPA in vitro. In presence of DOX (3 μg/ml), the IC50 value of CPA decreased significantly from 10 to 2.5 mM. Additional analyses indicate that the tumor suppressor p53 and p53-regulated proapoptotic Bax were upregulated in vivo and in vitro following CPA treatment in combination with DOX, suggesting that upregulation of p53 may contribute to the enhancement of antitumor effect of CPA by DOX. Furthermore, downregulation of antiapoptotic Bcl-2 was observed in animals treated with CPA and CPA plus DOX when compared to untreated or DOX-treated groups. Our results raise the possibility that this combination chemotherapeutic regimen may lead to additional improvements in treatment of breast cancer

  4. Pneumococcal resistance to antibiotics.

    OpenAIRE

    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 pneumo...

  5. Antibiotics in dental practice

    OpenAIRE

    2007-01-01

    The oral cavity and it surrounding tissue are habitats for many bacteria. Therefore a rationale for the use of antibacterial agents rises. During my time as a dental student, me often meet conditions were antibiotics are pointed out as the treatment of chose, as indicated or not recommended. According to Norwegian drug regulations (Tørisen 2007) dentists have: The right to requisition necessary medical agents in connection with dental treatment and prevention and treatment of diseases in the...

  6. DNA Modifications by Novel Antitumor Platinum Drugs

    Czech Academy of Sciences Publication Activity Database

    Brabec, Viktor

    Kiev : National Taras Shevchenko University, 2001, s. SC-L3. [NATO Advanced Research Workshop Autumn School: Frontiers in Molecular-Scale Science and Technology of Fullerene, Nanotube, Nanosilicon and Biopolymer (DNA, Protein) Multifunctional Nanosystems. Kiev (UA), 09.09.2001-12.09.2001] Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA * antitumor * platinum drugs Subject RIV: BO - Biophysics

  7. Hypoxia-targeting antitumor prodrugs and photosensitizers

    International Nuclear Information System (INIS)

    Tumor hypoxia has been identified as a key subject for tumor therapy, since hypoxic tumor cells show resistance to treatment of tumor tissues by radiotherapy, chemotherapy and phototherapy. For improvement of tumor radiotherapy, we have proposed a series of radiation-activated prodrugs that could selectively release antitumor agent 5-fluorouracil or 5-fluorodeoxyuridine under hypoxic conditions. Recently, we attempted to develop two families of novel hypoxia-targeting antitumor agents, considering that tumor-hypoxic environment is favorable to biological and photochemical reductions. The first family of prodrugs was derived from camptothecin as a potent topoisomerase I inhibitor and several bioreductive motifs. These prodrugs could be activated by NADPH-cytochrome P450 reductase or DT-diaphorase to release free camptothecin, and thereby showed hypoxia-selective cytotoxictiy towards tumor cells. These prodrugs were also applicable to the real-time monitoring of activation and antitumor effect by fluorometry. Furthermore, the camptothecin-bioreductive motif conjugates was confirmed to show an oxygen-independent DAN photocleaving activity, which could overcome a drawback of back electron transfer occurring in the photosensitized one-electron oxidation of DNA. Thus, these camptothecin derivatives could be useful to both chemotherapy and phototherapy for hypoxic tumor cells. The second family of prodrugs harnessed UV light for cancer therapy, incorporating the antitumor agent 5-fluorourcil and the photolabile 2-nitrobenzyl chromophores. The attachment of a tumor-homing cyclic peptide CNGRC was also employed to construct the prototype of tumor-targeting photoactiaved antitumor prodrug. These novel prodrugs released high yield of 5-fluorourcil upon UV irradiation at λex=365 nm, while being quite stable in the dark. The photoactivation mechanism was also clarified by means of nanosecond laser flash photolysis. (authors)

  8. Optimizing Antibiotic Use in Nursing Homes Through Antibiotic Stewardship.

    Science.gov (United States)

    Sloane, Philip D; Huslage, Kirk; Kistler, Christine E; Zimmerman, Sheryl

    2016-01-01

    Antibiotic stewardship is becoming a requirement for nursing homes. Programs should be interdisciplinary and multifaceted; should have support from nursing home administrators; and should aim to promote antibiotics only when needed, not just in case. Recommended components include use of evidence-based guidelines; ongoing monitoring of antibiotic prescriptions, cultures, and study results; monitoring of health outcomes; use of nursing home-specific antibiograms; regular reporting and feedback to medical providers and nurses; and education of residents and families. PMID:27621341

  9. Antibiotic prevention of postcataract endophthalmitis

    DEFF Research Database (Denmark)

    Kessel, Line; Flesner, Per; Andresen, Jens;

    2015-01-01

    Endophthalmitis is one of the most feared complications after cataract surgery. The aim of this systematic review was to evaluate the effect of intracameral and topical antibiotics on the prevention of endophthalmitis after cataract surgery. A systematic literature review in the MEDLINE, CINAHL......, Cochrane Library and EMBASE databases revealed one randomized trial and 17 observational studies concerning the prophylactic effect of intracameral antibiotic administration on the rate of endophthalmitis after cataract surgery. The effect of topical antibiotics on endophthalmitis rate was reported by one...... with the use of intracameral antibiotic administration of cefazolin, cefuroxime and moxifloxacin, whereas no effect was found with the use of topical antibiotics or intracameral vancomycin. Endophthalmitis occurred on average in one of 2855 surgeries when intracameral antibiotics were used compared to...

  10. Antibiotics in otorhinolaryngology practice

    Directory of Open Access Journals (Sweden)

    Stefan-Mikić Sandra

    2002-01-01

    Full Text Available Introduction This study investigated utilization of antibacterial agents at the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman and at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, in the period February - March 2001. Material and methods All antibacterial agents were classified as group J, regarding Anatomic-Therapeutic-Chemical Classification. Data on drug utilization were presented in Defined Daily Doses (DDD. Patients who were under observation were all treated with antibiotics. Results In regard to prescribed treatment in the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman, most outpatients were treated with macrolide antibiotics - in 26.21%; combination of penicillin and beta-lactamase inhibitors in 20.83% and pyranosides in 16.12%. At the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, macrolides and lincosamines were most frequently used - in 20.46%; cephalosporins in 19.87% and penicillins susceptible to beta-lactamase in 18.85%. It is extremely positive and in agreement with current pharmacotherapeutic principles that in both institutions peroral ampicillins have not been prescribed. Aminoglycosides have been prescribed in less than 1% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman, whereas they were much more frequently prescribed at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad - in 11.25%. Although there is a positive postantibiotic effect in regard to these antibiotics and it is recommended to use them once a day, in both examined institutions aminoglycosides were given twice a day. In regard to bacterial identification it was done in 80.76% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad - Liman, while in the Ear, Nose and Throat Clinic of the Clinical Center

  11. Antibiotics and oral contraceptives.

    Science.gov (United States)

    Rubin, D F

    1981-04-01

    Dermatologists often prescribe oral tetracycline for the control of acne, primarily, and to a much lesser extent, for the treatment of cutaneous infections. A number of the patients taking tetracycline are also taking birth control pills. A recent article in the British Medical Journal (1980;1:293) indicates that this combination can lead to a failure of the (OC) oral contraceptive. Such failure had been associated with ampicillin as well. It is believed that the mechanism for this was the disturbance in normal gut flora, with consequent effects on bacterial hydrolysis of steroid conjugates. This would interrupt the enterohepatic circulation of contraceptive steroids, resulting in a less than normal concentration of circulating steroids. It was recommended that women taking low-dose OCs take extra precautions against pregnancy during any cycle in which antibiotics are given. In regard to our care of and responsibilities to our patients, and in an era when malpractice suits for all types of reasons are more common, it certainly behooves dermatologists to recognize and be concerned about this potential consequence of prescribing oral antibiotics. PMID:7212735

  12. Antitumor Activities of Metal Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Maria Pilar Vinardell

    2015-06-01

    Full Text Available Nanoparticles have received much attention recently due to their use in cancer therapy. Studies have shown that different metal oxide nanoparticles induce cytotoxicity in cancer cells, but not in normal cells. In some cases, such anticancer activity has been demonstrated to hold for the nanoparticle alone or in combination with different therapies, such as photocatalytic therapy or some anticancer drugs. Zinc oxide nanoparticles have been shown to have this activity alone or when loaded with an anticancer drug, such as doxorubicin. Other nanoparticles that show cytotoxic effects on cancer cells include cobalt oxide, iron oxide and copper oxide. The antitumor mechanism could work through the generation of reactive oxygen species or apoptosis and necrosis, among other possibilities. Here, we review the most significant antitumor results obtained with different metal oxide nanoparticles.

  13. First synthesis of antitumoral dasyscyphin B

    OpenAIRE

    Akhaouzan, Ali; Fern??ndez, Antonio; Mansour, Ahmed I.; ??lvarez, Esteban; Haid??ur, Ali; ??lvarez-Manzaneda, Ram??n; Chahboun, Rachid; ??lvarez-Manzaneda, Enrique

    2013-01-01

    The first synthesis of dasyscyphin B, an antitumoral metabolite obtained from the ascomycete Dasyscyphus niveus, has been achieved starting from commercial abietic acid. The key steps of the synthetic sequence are the diastereoselective ??-methylation of a ketoaldehyde, followed by an intramolecular aldol condensation and the further Diels???Alder cycloaddition of a dienol ester. The procedure reported will allow the synthesis of related metabolites functionalized in the A ring.

  14. The antitumor activity of the fungicide ciclopirox

    OpenAIRE

    Zhou, Hongyu; Shen, Tao; Luo, Yan; Liu, Lei; Chen, Wenxing; Xu, Baoshan; Han, Xiuzhen; Pang, Jia; Rivera, Chantal A; Huang, Shile

    2010-01-01

    Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results indicate that CPX inhibited cell proliferation and induced apoptosis in human rhabdomyosarcoma (Rh30), breast carcinoma (MDA-MB231), and colon adenocarcinoma (HT-29) cells in a co...

  15. Impact of antitumor therapy on nutrition

    International Nuclear Information System (INIS)

    The treatment of the cancer patient by surgery, chemotherapy or radiation therapy can impose significant nutritional disabilities on the host. The nutritional disabilities seen in the tumor-bearing host from antitumor therapy are produced by factors which either limit oral intake or cause malabsorption of nutrients. The host malnutrition caused as a consequence of surgery, chemotherapy or radiation therapy assumes even more importance when one realizes that many cancer patients are already debilitated from their disease

  16. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    OpenAIRE

    Cesar Echeverria; Juan Francisco Santibañez; Oscar Donoso-Tauda; Escobar, Carlos A.; Rodrigo Ramirez-Tagle

    2009-01-01

    Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in Hep...

  17. Antitumor action of bovine seminal ribonuclease

    International Nuclear Information System (INIS)

    Unlike the bovine pancreatic ribonuclease (RNase A), bovine seminal ribonuclease (BS RNase) displays various biological activities; including antitumor activity, immunosuppressivity, spermatogenicity and embryo-toxicity. To learn more about its antitumor effect we tested BS RNase on the growth of 16 cell lines derived from patients with various hematological malignancies. The cells of lymphoid origin were generally more susceptible to BS RNase, administered in the range of concentrations from 2 to 100 μg/ml, than the myeloid ones. RNase A used at the same concentrations did not exert any inhibitory effect. The inhibitory effect of BS RNase persisted in cultured cells three times wash in complete medium and cell re-cultivation in fresh medium free of BS RNase. Four cell lines were very little sensitive (KG-1 and U-937) or resistant (JOK and NAMALWA) to BS RNase regardless of their origin. The in vivo antitumor effect of BS RNase was tested on human prostate carcinoma transplanted to athymic nude mice. The daily dose of BS RNase (0.25 mg/20 g) was administered for three weeks except weekends (15 doses) by three different ways (intraperitoneally - i.p., subcutaneously - s.c. and intratumorally - i.t.). Whereas i.p. administration was ineffective, s.c. administration significantly reduced size of the tumors and i.t. administration abolished half of the tumors in treated mice. The average of treated mice decreased during the experiment by 10-15%. (author)

  18. [Antibiotic stability in magistral collyria].

    Science.gov (United States)

    Tihărău, A; Voiculescu, E; Vancea, S; Teodorescu, A; Cherecheş, S

    1990-01-01

    The paper presents the results of a study on physicochemical and and microbiological stability of collyria with such antibiotics as: Kanamicin, Oxacilin, Colistin, Erythromycin and Rifampicin. The authors insist on the necessity of preparing the ophthalmic solution with the antibiotics studies, with solvent for eye drops as provided for by RF IX and keeping at +4 degrees C, at dark. PMID:2101048

  19. Antibiotic Prophylaxis in Pediatric Dentistry

    OpenAIRE

    Davydova N.V.; Suyetenkov D.Ye.; Firsova I.V.; Oleynikova N.M.

    2011-01-01

    Identify options for the indications for antibiotic prophylaxis in children's dental reception. The analysis of publications shows that the basis of current trends prevention of postoperative wound infection in pediatric surgery should be measures aimed at eliminating or reducing the influence of risk factors, as well as the use of antibiotic prophylaxis

  20. Antibiotic Prophylaxis in Pediatric Dentistry

    Directory of Open Access Journals (Sweden)

    Davydova N.V.

    2011-03-01

    Full Text Available Identify options for the indications for antibiotic prophylaxis in children's dental reception. The analysis of publications shows that the basis of current trends prevention of postoperative wound infection in pediatric surgery should be measures aimed at eliminating or reducing the influence of risk factors, as well as the use of antibiotic prophylaxis

  1. The Antibiotic Resistance Problem Revisited

    Science.gov (United States)

    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…

  2. Gramicidin A: A New Mission for an Old Antibiotic

    Directory of Open Access Journals (Sweden)

    Justin M David

    2015-01-01

    Full Text Available Gramicidin A (GA is a channel-forming ionophore that renders biological membranes permeable to specific cations which disrupts cellular ionic homeostasis.  It is a well-known antibiotic, however it’s potential as a therapeutic agent for cancer has not been widely evaluated.  In two recently published studies, we showed that GA treatment is toxic to cell lines and tumor xenografts derived from renal cell carcinoma (RCC, a devastating disease that is highly resistant to conventional therapy.  GA was found to possess the qualities of both a cytotoxic drug and a targeted angiogenesis inhibitor, and this combination significantly compromised RCC growth in vitro and in vivo.  In this review, we summarize our recent research on GA, discuss the possible mechanisms whereby it exerts its anti-tumor effects, and share our perspectives on the future opportunities and challenges to the use of GA as a new anticancer agent.

  3. The Prehistory of Antibiotic Resistance.

    Science.gov (United States)

    Perry, Julie; Waglechner, Nicholas; Wright, Gerard

    2016-01-01

    Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. PMID:27252395

  4. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  5. Antibiotics for acute maxillary sinusitis

    DEFF Research Database (Denmark)

    Ahovuo-Saloranta, Anneli; Borisenko, Oleg V; Kovanen, Niina;

    2008-01-01

    antibiotics from different classes for acute maxillary sinusitis in adults. We included trials with clinically diagnosed acute sinusitis, whether or not confirmed by radiography or bacterial culture. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened search results, extracted......BACKGROUND: Expert opinions vary on the appropriate role of antibiotics for sinusitis, one of the most commonly diagnosed conditions among adults in ambulatory care. OBJECTIVES: We examined whether antibiotics are effective in treating acute sinusitis, and if so, which antibiotic classes are the...... most effective. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2007, Issue 3); MEDLINE (1950 to May 2007) and EMBASE (1974 to June 2007). SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing antibiotics with placebo or...

  6. Antibiotic Resistance of Shigella Species in Iran

    OpenAIRE

    A.Mehr-Movahed; J. Nikkhah

    1987-01-01

    Antibiotic resistance in Shigella species has been showing a rising trend all over the world. This study was performed to discover the state of antibiotic resistance of Shigella species with regards to six common antibiotics in use in Iran.

  7. Antitumor activity of polyacrylates of noble metals in experiment

    OpenAIRE

    Larisa A. Ostrovskaya; David B. Korman; Natalia V. Bluhterova; Margarita M. Fomina; Valentina A. Rikova; Claudia A. Abzaeva; Larisa V. Zhilitskaya; Nina O. Yarosh

    2014-01-01

    The aim of this research has been the study of the antitumor activity of polymetalacrylate derivatives containing in their structure noble metals. Metallic derivatives of polyacrylic acid were not previously tested as antitumor agents.The antitumor activity of polyacrylates, containing argentum (argacryl), aurum (auracryl) and platinum (platacryl) against experimental models of murine solid tumors (Lewis lung carcinoma and Acatol adenocarcinoma) as well as acute toxicity have been studied. It...

  8. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

    Directory of Open Access Journals (Sweden)

    Roderick I. Mackie

    2013-07-01

    Full Text Available Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

  9. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

    KAUST Repository

    Hong, Pei-Ying

    2013-07-31

    Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water.

  10. An NGR-integrated and enediyne-energized apoprotein shows CD13-targeting antitumor activity.

    Science.gov (United States)

    Zheng, Yan-Bo; Shang, Bo-Yang; Li, Yi; Zhen, Yong-Su

    2013-03-01

    Targeting and inhibiting angiogenesis is a promising strategy for treatment of cancer. NGR peptide motif is a tumor-homing peptide, which could bind with CD13 expressed on tumor blood vessels. Lidamycin is a highly potent antitumor antibiotic, which is composed of an apoprotein (LDP) and an active enediyne chromophore (AE). Here, an NGR-integrated and enediyne-energized apoprotein composed of cyclic NGR peptide and lidamycin was developed by a two-step procedure. Firstly, we prepared the fusion protein composed of NGR peptide and LDP by recombinant DNA technology. Then, AE was reloaded to the fusion protein to get NGR-LDP-AE. Our experiments showed that NGR-LDP could bind to CD13-expressing HT-1080 cells, whereas the recombinant LDP (rLDP) showed weak binding. NGR-LDP-AE exerted highly potent cytotoxicity to cultured tumor cells in vitro. In vivo antitumor activity was evaluated in murine hepatoma 22 (H22) model and human fibrosarcoma HT-1080 model. At the tolerable dose, NGR-LDP-AE and lidamycin inhibited H22 tumor growth by 94.8 and 66.9%, and the median survival time of the mice was 62 and 37 days, respectively. In the HT-1080 model, NGR-LDP-AE inhibited tumor growth by 88.6%, which was statistically different from that of lidamycin (74.5%). Immunohistochemical study showed that NGR-LDP could bind to tumor blood vessels. Conclusively, these results demonstrate that fusion of LDP with CNGRC peptide delivers AE to tumor blood vessels and improves its antitumor activity. PMID:23206754

  11. Antitumor Immunity Induced after α Irradiation

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Gorin

    2014-04-01

    Full Text Available Radioimmunotherapy (RIT is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses β-emitting radioisotopes, but recently, a growing interest has emerged for the clinical development of α particles. α emitters are ideal for killing isolated or small clusters of tumor cells, thanks to their specific characteristics (high linear energy transfer and short path in the tissue, and their effect is less dependent on dose rate, tissue oxygenation, or cell cycle status than γ and X rays. Several studies have been performed to describe α emitter radiobiology and cell death mechanisms induced after α irradiation. But so far, no investigation has been undertaken to analyze the impact of α particles on the immune system, when several studies have shown that external irradiation, using γ and X rays, can foster an antitumor immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 (213Bi irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective antitumor response that is mediated by tumor-specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that 213Bi-treated MC-38 cells release “danger signals” and activate dendritic cells. Our results demonstrate that α irradiation can stimulate adaptive immunity, elicits an efficient antitumor protection, and therefore is an immunogenic cell death inducer, which provides an attractive complement to its direct cytolytic effect on tumor cells.

  12. Systemic antibiotic therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Anoop Kapoor

    2012-01-01

    Full Text Available Systemic antibiotics in conjunction with scaling and root planing (SRP, can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy.

  13. Antibiotics as CECs: An Overview of the Hazards Posed by Antibiotics and Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Geoffrey Ivan Scott

    2016-04-01

    Full Text Available ABSTRACTMonitoring programs have traditionally monitored legacy contaminants but are shifting focus to Contaminants of Emerging Concern (CECs. CECs present many challenges for monitoring and assessment, because measurement methods don't always exist nor have toxicological studies been fully conducted to place results in proper context. Also some CECs affect metabolic pathways to produce adverse outcomes that are not assessed through traditional toxicological evaluations. Antibiotics are CECs that pose significant environmental risks including development of both toxic effects at high doses and antibiotic resistance at doses well below the Minimum Inhibitory Concentration (MIC which kill bacteria and have been found in nearly half of all sites monitored in the US. Antimicrobial resistance has generally been attributed to the use of antibiotics in medicine for humans and livestock as well as aquaculture operations. The objective of this study was to assess the extent and magnitude of antibiotics in the environment and estimate their potential hazards in the environment. Antibiotics concentrations were measured in a number of monitoring studies which included Waste Water Treatment Plants (WWTP effluent, surface waters, sediments and biota. A number of studies reported levels of Antibiotic Resistant Microbes (ARM in surface waters and some studies found specific ARM genes (e.g. the blaM-1 gene in E. coli which may pose additional environmental risk. High levels of this gene were found to survive WWTP disinfection and accumulated in sediment at levels 100-1000 times higher than in the sewerage effluent, posing potential risks for gene transfer to other bacteria.in aquatic and marine ecosystems. Antibiotic risk assessment approaches were developed based on the use of MICs and MIC Ratios [High (Antibiotic Resistant/Low (Antibiotic Sensitive MIC] for each antibiotic indicating the range of bacterial adaptability to each antibiotic to help define the No

  14. Antitumor activity of the immunomodulatory lead Cumaside.

    Science.gov (United States)

    Aminin, D L; Chaykina, E L; Agafonova, I G; Avilov, S A; Kalinin, V I; Stonik, V A

    2010-06-01

    A new immunomodulatory lead Cumaside that is a complex of monosulfated triterpene glycosides from the sea cucumber Cucumaria japonica and cholesterol possesses significantly less cytotoxic activity against sea urchin embryos and Ehrlich carcinoma cells than the corresponding glycosides. Nevertheless Cumaside has an antitumor activity against different forms of experimental mouse Ehrlich carcinoma in vivo both independently and in combination with cytostatics. The highest effect occurs at a treatment once a day for 7 days before the tumor inoculation followed by Cumaside treatment once a day for 7 days. Prophylactic treatment with Cumaside and subsequent therapeutic application of 5-fluorouracil suppressed the tumor growth by 43%. PMID:20227525

  15. PARP1 Inhibitors: antitumor drug design

    OpenAIRE

    MALYUCHENKO N.V.; Kotova, E. Yu.; Kulaeva, O. I.; Kirpichnikov, M P; STUDITSKIY V.M.

    2015-01-01

    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1–2 million molecules per cell) serving as a “sensor” for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PA...

  16. PARP1 INHIBITORS: ANTITUMOR DRUG DESIGN

    OpenAIRE

    MALYUCHENKO N.V.; KOTOVA E. YU.; Kulaeva, O. I.; Kirpichnikov, M P; STUDITSKIY V.M.

    2015-01-01

    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1-2 million molecules per cell) serving as a “sensor” for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PA...

  17. Prophylactic antibiotics versus post- operative antibiotics in herniorraphy

    Directory of Open Access Journals (Sweden)

    Abedulla Khan Kayamkani

    2015-07-01

    Full Text Available Postoperative surgical site infections are a major source of illness.  Infection results in longer hospital stay and higher costs.  Uses of preoperative antibiotics have been standardized and are being used routinely in most clinical surgeries and include controversial areas like breast surgery and herniorraphy. Objective of the study is to find out the benefit of prophylactic use of antibiotics in the management of herniorraphy.This project was carried out in a multispeciality tertiary care teaching hospital from 1st-30th April in 2002. Group 1 patients were treated prophylactically half an hour before surgery with single dose of I.V. antibiotics (injection.  Ampicillin 1gm + injection.  Gentamicin 80mg. Group 2 patients were treated post surgery with capsule. Ampicillin 500mg 4 times a day for 7 days and injection. Gentamicin twice a day for first 4 days. In case of group 1 patients only one out of 20 patients (5% was infected.  Whereas in-group 2 patients 5 out of 20 patients (25% were infected. The cost of prophylactic antibiotic treatment was Rs. 25.56 per patient.  The postoperative antibiotic treatment cost was Rs. 220.4 per patient.  That means postoperative treatment is around 8.62 times costlier than prophylactic treatment.             From this study it is evident that prophylactic (preoperative treatment is better than postoperative treatment with antibiotics.

  18. Mission Critical: Preventing Antibiotic Resistance

    Science.gov (United States)

    ... Remember antibiotics have side effects. Prevent infections by practicing good hand hygiene and getting recommended vaccines. View ... program that includes, at a minimum, this checklist : Leadership commitment: Dedicate necessary human, financial, and IT resources. ...

  19. Antibiotic resistance of bacterial biofilms

    DEFF Research Database (Denmark)

    Hoiby, N.; Bjarnsholt, T.; Givskov, M.;

    2010-01-01

    A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis...... to antibiotics. Biofilm growth is associated with an increased level of mutations as well as with quorum-sensing-regulated mechanisms. Conventional resistance mechanisms such as chromosomal beta-lactamase, upregulated efflux pumps and mutations in antibiotic target molecules in bacteria also contribute...... to the survival of biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy. A promising strategy may be the use of enzymes that can dissolve the biofilm matrix (e.g. DNase and alginate lyase) as well as quorum...

  20. Antibiotic associated diarrhoea: Infectious causes

    OpenAIRE

    Ayyagari A; Agarwal J; Garg A

    2003-01-01

    Nearly 25% of antibiotic associated diarrhoeas (AAD) is caused by Clostridium difficile, making it the commonest identified and treatable pathogen. Other pathogens implicated infrequently include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp. and Salmonella spp. Most mild cases of AAD are due to non-infectious causes which include reduced break down of primary bile acids and decrease metabolism of carbohydrates, allergic or toxic effects of antibiotic ...

  1. Systemic antibiotic therapy in periodontics

    OpenAIRE

    Anoop Kapoor; Ranjan Malhotra; Vishakha Grover; Deepak Grover

    2012-01-01

    Systemic antibiotics in conjunction with scaling and root planing (SRP), can offer an additional benefit over SRP alone in the treatment of periodontitis, in terms of clinical attachment loss (CAL) and pocket depth change, and reduced risk of additional CAL loss. However, antibiotics are not innocuous drugs. Their use should be justified on the basis of a clearly established need and should not be substituted for adequate local treatment. The aim of this review is to discuss the rationale, pr...

  2. Antibiotic resistance in wild birds

    OpenAIRE

    Bonnedahl, Jonas; Järhult, Josef D.

    2014-01-01

    Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further...

  3. Genome Mining for antibiotics biosynthesis pathways with antiSMASH 3

    DEFF Research Database (Denmark)

    Weber, Tilmann; Kim, Hyun Uk; Blin, Kai;

    2014-01-01

    Microorganisms are the most important source of natural products with antimicrobial or antitumor activity. These natural products are the main source for anti-­‐infectives; 80% of antibiotics currently in medical use are derived from this class of compounds. In the past, functional screenings......://antismash.secondarymetabolites.org). antiSMASH3 currently is the most comprehensive automated genome mining platform for natural product biosynthetic pathways. It automatically screens genomic data of bacteria and fungi for the presence of 24 different types of secondary metabolite biosynthetic pathways. For different classes of secondary...

  4. Smart Mesoporous Nanomaterials for Antitumor Therapy

    Directory of Open Access Journals (Sweden)

    Marina Martínez-Carmona

    2015-11-01

    Full Text Available The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc. or external (temperature, light, magnetic field, etc. stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.

  5. The antitumor activity of the fungicide ciclopirox.

    Science.gov (United States)

    Zhou, Hongyu; Shen, Tao; Luo, Yan; Liu, Lei; Chen, Wenxing; Xu, Baoshan; Han, Xiuzhen; Pang, Jia; Rivera, Chantal A; Huang, Shile

    2010-11-15

    Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here, we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results indicate that CPX inhibited cell proliferation and induced apoptosis in human rhabdomyosarcoma (Rh30), breast carcinoma (MDA-MB231) and colon adenocarcinoma (HT-29) cells in a concentration-dependent manner. By cell cycle analysis, CPX induced accumulation of cells in G(1)/G(0) phase of the cell cycle. Concurrently, CPX downregulated cellular protein expression of cyclins (A, B1, D1 and E) and cyclin-dependent kinases (CDK2 and CDK4) and upregulated expression of the CDK inhibitor p21(Cip1), leading to hypophosphorylation of retinoblastoma protein. CPX also downregulated protein expression of Bcl-xL and survivin and enhanced cleavages of Bcl-2. Z-VAD-FMK, a pan-caspase inhibitor, partially prevented CPX-induced cell death, suggesting that CPX-induced apoptosis of cancer cells is mediated at least in part through caspase-dependent mechanism. The results indicate that CPX is a potential antitumor agent. PMID:20225320

  6. [Self-medication with antibiotics in Poland

    NARCIS (Netherlands)

    Olczak, A.; Grzesiowski, P.; Hryniewicz, W.; Haaijer-Ruskamp, F.M.

    2006-01-01

    Antibiotic resistance, the important public health threat, depends on antibiotic overuse/misuse. Self-medication with antibiotics is of serious medical concern. The aim of the study, as a part of SAR project (Self-medication with antibiotic in Europe) was to survey the incidence of this phenomenon.

  7. Expedient antibiotics production: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bienkowski, P.R.; Byers, C.H.; Lee, D.D.

    1988-05-01

    The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented. This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.

  8. Macrolide antibiotics and the airway: antibiotic or non-antibiotic effects?

    LENUS (Irish Health Repository)

    Murphy, D M

    2010-03-01

    The macrolides are a class of antibiotics widely prescribed in infectious disease. More recently, there has been considerable interest in potential indications for these agents, in addition to their simple antibacterial indications, in a number of lung pathophysiologies.

  9. Antibiotic use in Lithuania, 2003 - 2008

    OpenAIRE

    Beržanskytė, Aušra

    2009-01-01

    Antimicrobial resistance is mainly caused by inappropriate and abundant use of antibiotics. To enlighten the most relevant problematic areas in antibiotic use, where the decisions should be made, the different levels were analysed in this study: the self-medication with antibiotics of the population, ambulatory and also hospital antibiotic use. The results showed that wrong perception about antibiotics is characteristic to Lithuanian population, as there is lack of privity, while traditions o...

  10. Antibiotics: Use and misuse in pediatric dentistry

    Directory of Open Access Journals (Sweden)

    F C Peedikayil

    2011-01-01

    Full Text Available Antibiotics are commonly used in dentistry for prophylactic as well as for therapeutic purposes. Most often antibiotics are used in unwarranted situations, which may give rise to resistant bacterial strains. Dentists want to make their patients well and to prevent unpleasant complications. These desires, coupled with the belief that many oral problems are infectious, stimulate the prescribing of antibiotics. Good knowledge about the indications of antibiotics is the need of the hour in prescribing antibiotics for dental conditions.

  11. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    Science.gov (United States)

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  12. Background antibiotic resistance patterns in antibiotic-free pastured poultry production

    Science.gov (United States)

    Antibiotic resistance (AR) is a significant public health issue, and agroecosystems are often viewed as major environmental sources of antibiotic resistant foodborne pathogens. While the use of antibiotics in agroecosystems can potentially increase AR, appropriate background resistance levels in th...

  13. Onconase: A ribonuclease with antitumor activity

    Directory of Open Access Journals (Sweden)

    Małgorzata Zwolińska

    2010-02-01

    Full Text Available Onconase (ranpirnase is a homologous protein obtained from [i]Rana pipiens [/i]frog eggs. The activity of onconase, and particularly its antitumor effect, is strictly connected with ribonuclease (RN-ase activity. Onconase induces cell death through the decomposition of inner cellular RNA, inhibition of protein synthesis, and inhibition of cell growth and proliferation and it also specifically triggers tumor cell apoptosis. A very important mechanisms of its cytotoxicity is also its antioxidant activity. The results of preclinical trials demonstrated a high activity of onconase against tumor cells, also those resistant to cytostatics. Moreover, onconase showed synergic activity with other commonly used anticancer drugs. Several clinical trials were performed on patients suffering from kidney, breast, and pancreatic cancers. Most recently a phase III study of onconase in patients with mesothelioma was completed. There are also ongoing phase I and II clinical trials with non-small-cell lung cancer (NSCLC.

  14. Antibiotic allergy in cystic fibrosis.

    Science.gov (United States)

    Parmar, J S; Nasser, S

    2005-06-01

    Allergic reactions to antibiotics are more common in cystic fibrosis (CF) than in the general population. This in part is due to the improving survival in adults with CF and the increased use of high dose intravenous antibiotics. While some are immediate anaphylaxis type (IgE mediated) reactions, the majority are late onset and may have non-specific features such as rash and fever. Piperacillin has consistently been found to have the highest rate of reported reactions (30-50%). There is a low risk of cross reactions between penicillins and other non-beta-lactam classes of antibiotics in penicillin skin prick positive patients. Carbapenems should only be used with extreme caution in patients with positive skin prick tests to penicillin. However, aztreonam can be used safely in patients who are penicillin allergic with positive skin prick reactions. The aminoglycosides are a relatively uncommon cause of allergic reactions, but patients who react to one member of the family may cross react with other aminoglycosides. Desensitisation relies on the incremental introduction of small quantities of the allergen and has been used for penicillins, ceftazidime, tobramycin and ciprofloxacin and must be repeated before each course. Personalized cards should be regularly updated for patients who develop allergic reactions. Written instructions on the emergency treatment of allergic reactions should be provided to patients self-administering intravenous antibiotics at home. Further research is required to identify risk factors and predictors for antibiotic allergy. PMID:15923254

  15. Fungal Biotransformation of Tetracycline Antibiotics.

    Science.gov (United States)

    Shang, Zhuo; Salim, Angela A; Khalil, Zeinab; Bernhardt, Paul V; Capon, Robert J

    2016-08-01

    The commercial antibiotics tetracycline (3), minocycline (4), chlortetracycline (5), oxytetracycline (6), and doxycycline (7) were biotransformed by a marine-derived fungus Paecilomyces sp. to yield seco-cyclines A-H (9-14, 18 and 19) and hemi-cyclines A-E (20-24). Structures were assigned by detailed spectroscopic analysis, and in the case of 10 X-ray crystallography. Parallel mechanisms account for substrate-product specificity, where 3-5 yield seco-cyclines and 6 and 7 yield hemi-cyclines. The susceptibility of 3-7 to fungal biotransformation is indicative of an unexpected potential for tetracycline "degradation" (i.e., antibiotic resistance) in fungal genomes. Significantly, the fungal-derived tetracycline-like viridicatumtoxins are resistant to fungal biotransformation, providing chemical insights that could inform the development of new tetracycline antibiotics resistant to enzymatic degradation. PMID:27419475

  16. Antibiotics and the resistant microbiome

    DEFF Research Database (Denmark)

    Sommer, Morten; Dantas, Gautam

    2011-01-01

    . Less appreciated are the concomitant changes in the human microbiome in response to these assaults and their contribution to clinical resistance problems. Studies have shown that pervasive changes to the human microbiota result from antibiotic treatment and that resistant strains can persist for years....... Additionally, culture-independent functional characterization of the resistance genes from the microbiome has demonstrated a close evolutionary relationship between resistance genes in the microbiome and in pathogens. Application of these techniques and novel cultivation methods are expected to significantly...... expand our understanding of the interplay between antibiotics and the microbiome....

  17. Antibiotic allergy in cystic fibrosis

    OpenAIRE

    Parmar, J.; Nasser, S.

    2005-01-01

    Allergic reactions to antibiotics are more common in cystic fibrosis (CF) than in the general population. This in part is due to the improving survival in adults with CF and the increased use of high dose intravenous antibiotics. While some are immediate anaphylaxis type (IgE mediated) reactions, the majority are late onset and may have non-specific features such as rash and fever. Piperacillin has consistently been found to have the highest rate of reported reactions (30–50%). There is a low...

  18. Experimental chemotherapy-induced skin necrosis in swine. Mechanistic studies of anthracycline antibiotic toxicity and protection with a radical dimer compound.

    OpenAIRE

    Averbuch, S D; M. Boldt; Gaudiano, G; Stern, J B; Koch, T H; Bachur, N. R.

    1988-01-01

    The reactivity of antitumor anthracycline and mitomycin C antibiotics with the oxomorpholinyl radical dimers, bi(3,5,5-trimethyl-2-oxomorpholin-3-yl) (TM3) and bi(3,5-dimethyl-5-hydroxymethyl-2-oxomorpholin-3-yl) (DHM3), was studied in vitro. The oxomorpholinyl radical reduced daunorubicin to a quinone methide intermediate that reacted with solvent to form 7-deoxydaunorubicinone. The solvolysis reaction followed first order kinetics, and the reactivity rate constants (k2) measured for seven a...

  19. Probiotic approach to prevent antibiotic resistance.

    Science.gov (United States)

    Ouwehand, Arthur C; Forssten, Sofia; Hibberd, Ashley A; Lyra, Anna; Stahl, Buffy

    2016-06-01

    Probiotics are live microorganisms, mainly belonging to the genera Lactobacillus and Bifidobacterium, although also strain of other species are commercialized, that have a beneficial effect on the host. From the perspective of antibiotic use, probiotics have been observed to reduce the risk of certain infectious disease such as certain types of diarrhea and respiratory tract infection. This may be accompanied with a reduced need of antibiotics for secondary infections. Antibiotics tend to be effective against most common diseases, but increasingly resistance is being observed among pathogens. Probiotics are specifically selected to not contribute to the spread of antibiotic resistance and not carry transferable antibiotic resistance. Concomitant use of probiotics with antibiotics has been observed to reduce the incidence, duration and/or severity of antibiotic-associated diarrhea. This contributes to better adherence to the antibiotic prescription and thereby reduces the evolution of resistance. To what extent probiotics directly reduce the spread of antibiotic resistance is still much under investigation; but maintaining a balanced microbiota during antibiotic use may certainly provide opportunities for reducing the spread of resistances. Key messages Probiotics may reduce the risk for certain infectious diseases and thereby reduce the need for antibiotics. Probiotics may reduce the risk for antibiotic-associated diarrhea Probiotics do not contribute to the spread of antibiotic resistance and may even reduce it. PMID:27092975

  20. Synthesis of Olaparib Derivatives and Their Antitumor Activities

    Institute of Scientific and Technical Information of China (English)

    LOU Xi-yu; YANG Xuan; DING Yi-li; WANG Jian-jun; YAN Qing-yan; HUANG Xian-gui; GUO Yang-hui

    2013-01-01

    A series of Olaparib derivatives was synthesized,and their structures were confirmed by 1H NMR,MS and elemental analysis.Their antitumor activities on breast cancer susceptbility gene 1/2(BRCA1/2)-deficient cancer cell lines including HCC1937,Capan-1 and MDA-MB-436 were evaluated.The antitumor activity of compound Olaparib-1 was better than the positive control Olaparib in BRCAl-deficient cell line HCC1937.

  1. Synthesis and Antitumor Activities In Vitro of Solanesylpiperazinotriamine

    Institute of Scientific and Technical Information of China (English)

    Chao Pie WANG; Jian Hong WANG; Ying GAN; Zhi Yong CHEN; Gang Jun DU; Jin ZHAO

    2006-01-01

    A series of novel antitumor agents-the solanesylpiperazinotriamine derivatives were designed and synthesized, their structures were confirmed by IR, 1H-NMR, MS, and element analysis. The preliminary tests showed that at low micromolar concentrations these compounds exhibited obvious toxicity on tumor cells in vitro, and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations they also evidently enhanced the curative effect of vincristine.

  2. Use of Antibiotics in Children

    DEFF Research Database (Denmark)

    Pottegård, Anton; Broe, Anne; Aabenhus, Rune;

    2015-01-01

    Background: We aimed to describe the use of systemic antibiotics among children in Denmark. Methods: National data on drug use in Denmark were extracted from the Danish National Prescription Database. We used prescription data for all children in Denmark aged 0 to 11 years from January 1, 2000 to...

  3. ANTIBIOTIC THERAPY FOR ENT INFECTIONS

    Directory of Open Access Journals (Sweden)

    A. B. Turovsky

    2014-07-01

    Full Text Available The paper outlines basic principles of and new approaches to antibiotic therapy for ENT and upper respiratory tract infections, from point of view of the authors, on the basis of the data available in Russian and foreign literature.

  4. Antibiotics and the burn patient.

    Science.gov (United States)

    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. PMID:20510518

  5. Do We Need New Antibiotics?

    Czech Academy of Sciences Publication Activity Database

    Spížek, Jaroslav; Novotná, Jitka; Janata, Jiří

    Seoul : COEX Convention and Exhibition Center , 2009. s. 218-218. [Annual World Congress of Industrial Biotechnology 2009 /2./. 05.04.2009-07.04.2009, Seoul] R&D Projects: GA AV ČR IAA500200810 Institutional research plan: CEZ:AV0Z50200510 Keywords : antibiotics Subject RIV: EE - Microbiology, Virology

  6. Antibiotic associated diarrhoea: Infectious causes

    Directory of Open Access Journals (Sweden)

    Ayyagari A

    2003-01-01

    Full Text Available Nearly 25% of antibiotic associated diarrhoeas (AAD is caused by Clostridium difficile, making it the commonest identified and treatable pathogen. Other pathogens implicated infrequently include Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp. and Salmonella spp. Most mild cases of AAD are due to non-infectious causes which include reduced break down of primary bile acids and decrease metabolism of carbohydrates, allergic or toxic effects of antibiotic on intestinal mucosa and pharmacological effect on gut motility. The antibiotics most frequently associated with C. difficile associated diarrhoea are clindamycin, cephalosporin, ampicillin and amoxicillin. Clinical presentation may vary from mild diarrhoea to severe colitis and pseudomembranous colitis associated with high morbidity and mortality. The most sensitive and specific diagnostic test for C. difficile infection is tissue culture assay for cytotoxicity of toxin B. Commercial ELISA kits are available. Though less sensitive, they are easy to perform and are rapid. Withdrawal of precipitating antibiotic is all that is needed for control of mild to moderate cases. For severe cases of AAD, oral metronidazole is the first line of treatment, and oral vancomycin is the second choice. Probiotics have been used for recurrent cases.

  7. Antibiotic resistance pattern in uropathogens

    OpenAIRE

    Gupta V; Yadav A; Joshi R

    2002-01-01

    Uropathogenic strains from inpatient and outpatient departments were studied from April 1997 to March 1999 for their susceptibility profiles. The various isolates were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii and Enterococcus faecalis. Antibiotic susceptibility pattern of these isolates revealed that for outpatients, first generation cephalosporins, nitrofurantoin, norfloxacin/ciprofloxacin were effective for treatment of urina...

  8. A study of antibiotic prescribing

    DEFF Research Database (Denmark)

    Jaruseviciene, L.; Radzeviciene-Jurgute, R.; Jurgutis, A.; Lazarus, J.V.; Ovhed, I.; Strandberg, E.L.; Bjerrum, L.

    2012-01-01

    clinically or pharmacologically. Methods. 22 Lithuanian and 29 Russian GPs participated in five focus group discussions. Thematic analysis was used to analyse the data. Results. We identified four main thematic categories: patients' faith in antibiotics as medication for upper respiratory tract infections...

  9. Antibiotics, Formula Feeding Might Change Baby's 'Microbiome'

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_159392.html Antibiotics, Formula Feeding Might Change Baby's 'Microbiome' C-section birth ... microbiomes" are altered by cesarean births, antibiotics and formula feeding. "The microbiome is really important in how ...

  10. Antibiotic 'Report Card' Drills Guidelines into Dentists

    Science.gov (United States)

    ... 160702.html Antibiotic 'Report Card' Drills Guidelines Into Dentists Seeing their prescription rates leads some to change ... 30, 2016 TUESDAY, Aug. 30, 2016 (HealthDay News) -- Dentists are less likely to prescribe antibiotics for patients ...

  11. FDA Bolsters Warnings about Class of Antibiotics

    Science.gov (United States)

    ... html FDA Bolsters Warnings About Class of Antibiotics Fluoroquinolones such as Cipro, Levaquin should be reserved for ... label warnings on a class of antibiotics called fluoroquinolones because the drugs can lead to disabling side ...

  12. Danger of Antibiotic Overuse (For Parents)

    Science.gov (United States)

    ... don’t work against them. This is called bacterial resistance or antibiotic resistance. Treating these resistant bacteria requires ... child gets sick? To minimize the risk of bacterial resistance, keep these tips in mind: Take antibiotics only ...

  13. Antibiotic and Antimicrobial Resistance: Threat Report 2013

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Antibiotic Resistance Threats in the United States, 2013 Recommend on Facebook Tweet Share Compartir This report, Antibiotic resistance threats in the United States, 2013 gives a first- ...

  14. Antibiotics: Use and misuse in pediatric dentistry

    OpenAIRE

    F C Peedikayil

    2011-01-01

    Antibiotics are commonly used in dentistry for prophylactic as well as for therapeutic purposes. Most often antibiotics are used in unwarranted situations, which may give rise to resistant bacterial strains. Dentists want to make their patients well and to prevent unpleasant complications. These desires, coupled with the belief that many oral problems are infectious, stimulate the prescribing of antibiotics. Good knowledge about the indications of antibiotics is the need of the hour in prescr...

  15. Squalamine: an aminosterol antibiotic from the shark.

    OpenAIRE

    Moore, K.S.; Wehrli, S; Roder, H; Rogers, M.; Forrest, J N; McCrimmon, D; Zasloff, M.

    1993-01-01

    In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias. This water-soluble antibiotic, which we have named squalamine, exhibits potent bact...

  16. Antibiotic Resistance of Shigella Species in Iran

    Directory of Open Access Journals (Sweden)

    A.Mehr-Movahed

    1987-07-01

    Full Text Available Antibiotic resistance in Shigella species has been showing a rising trend all over the world. This study was performed to discover the state of antibiotic resistance of Shigella species with regards to six common antibiotics in use in Iran.

  17. Advanced nanocarriers for an antitumor peptide

    International Nuclear Information System (INIS)

    In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules

  18. Advanced nanocarriers for an antitumor peptide

    Energy Technology Data Exchange (ETDEWEB)

    Pippa, Natassa [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Pispas, Stergios [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute (Greece); Demetzos, Costas, E-mail: demetzos@pharm.uoa.gr [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Sivolapenko, Gregory [University of Patras, Laboratory of Pharmacokinetics, Department of Pharmacy (Greece)

    2013-11-15

    In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules.

  19. Antitumor activity of chemical modified natural compounds

    Directory of Open Access Journals (Sweden)

    Marilda Meirelles de Oliveira

    1991-01-01

    Full Text Available Search of new activity substances starting from chemotherapeutic agents, continously appears in international literature. Perhaps this search has been done more frequently in the field of anti-tumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of supercomputers and emergence of computer net systems, willopen new avenues to rational drug design" (Portoghese, P. S. J. Med. Chem. 1989, 32, 1. Unknown pharmacological active compounds synthetized by plants can be found even without this eletronic devices, as tradicional medicine has pointed out in many contries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplasic drugs will be examined, particularly those done by Brazilian researches.

  20. Excretion of Antibiotic Resistance Genes by Dairy Calves Fed Milk Replacers with Varying Doses of Antibiotics

    OpenAIRE

    Thames, Callie H; Pruden, Amy; James, Robert E.; Ray, Partha P.; Knowlton, Katharine F.

    2012-01-01

    Elevated levels of antibiotic resistance genes (ARGs) in soil and water have been linked to livestock farms and in some cases feed antibiotics may select for antibiotic resistant gut microbiota. The purpose of this study was to examine the establishment of ARGs in the feces of calves receiving milk replacer containing no antibiotics versus subtherapeutic or therapeutic doses of tetracycline and neomycin. The effect of antibiotics on calf health was also of interest. Twenty-eight male and fema...

  1. Surface modeling of soil antibiotics.

    Science.gov (United States)

    Shi, Wen-jiao; Yue, Tian-xiang; Du, Zheng-ping; Wang, Zong; Li, Xue-wen

    2016-02-01

    Large numbers of livestock and poultry feces are continuously applied into soils in intensive vegetable cultivation areas, and then some veterinary antibiotics are persistent existed in soils and cause health risk. For the spatial heterogeneity of antibiotic residues, developing a suitable technique to interpolate soil antibiotic residues is still a challenge. In this study, we developed an effective interpolator, high accuracy surface modeling (HASM) combined vegetable types, to predict the spatial patterns of soil antibiotics, using 100 surface soil samples collected from an intensive vegetable cultivation area located in east of China, and the fluoroquinolones (FQs), including ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX), were analyzed as the target antibiotics. The results show that vegetable type is an effective factor to be combined to improve the interpolator performance. HASM achieves less mean absolute errors (MAEs) and root mean square errors (RMSEs) for total FQs (NFX+CFX+EFX), NFX, CFX and EFX than kriging with external drift (KED), stratified kriging (StK), ordinary kriging (OK) and inverse distance weighting (IDW). The MAE of HASM for FQs is 55.1 μg/kg, and the MAEs of KED, StK, OK and IDW are 99.0 μg/kg, 102.8 μg/kg, 106.3 μg/kg and 108.7 μg/kg, respectively. Further, RMSE simulated by HASM for FQs (CFX, EFX and NFX) are 106.2 μg/kg (88.6 μg/kg, 20.4 μg/kg and 39.2 μg/kg), and less 30% (27%, 22% and 36%), 33% (27%, 27% and 43%), 38% (34%, 23% and 41%) and 42% (32%, 35% and 51%) than the ones by KED, StK, OK and IDW, respectively. HASM also provides better maps with more details and more consistent maximum and minimum values of soil antibiotics compared with the measured data. The better performance can be concluded that HASM takes the vegetable type information as global approximate information, and takes local sampling data as its optimum control constraints. PMID:26613514

  2. A new member of the 4-methylideneimidazole-5-one–containing aminomutase family from the enediyne kedarcidin biosynthetic pathway

    Science.gov (United States)

    Huang, Sheng-Xiong; Lohman, Jeremy R.; Huang, Tingting; Shen, Ben

    2013-01-01

    4-Methylideneimidazole-5-one (MIO)-containing aminomutases catalyze the conversion of l-α-amino acids to β-amino acids with either an (R) or an (S) configuration. l-Phenylalanine and l-tyrosine are the only two natural substrates identified to date. The enediyne chromophore of the chromoprotein antitumor antibiotic kedarcidin (KED) harbors an (R)-2-aza-3-chloro-β-tyrosine moiety reminiscent of the (S)-3-chloro-5-hydroxy-β-tyrosine moiety of the C-1027 enediyne chromophore, the biosynthesis of which uncovered the first known MIO-containing aminomutase, SgcC4. Comparative analysis of the KED and C-1027 biosynthetic gene clusters inspired the proposal for (R)-2-aza-3-chloro-β-tyrosine biosynthesis starting from 2-aza-l-tyrosine, featuring KedY4 as a putative MIO-containing aminomutase. Here we report the biochemical characterization of KedY4, confirming its proposed role in KED biosynthesis. KedY4 is an MIO-containing aminomutase that stereospecifically catalyzes the conversion of 2-aza-l-tyrosine to (R)-2-aza-β-tyrosine, exhibiting no detectable activity toward 2-aza-l-phenylalanine or l-tyrosine as an alternative substrate. In contrast, SgcC4, which stereospecifically catalyzes the conversion of l-tyrosine to (S)-β-tyrosine in C-1027 biosynthesis, exhibits minimal activity with 2-aza-l-tyrosine as an alternative substrate but generating (S)-2-aza-β-tyrosine, a product with the opposite stereochemistry of KedY4. This report of KedY4 broadens the scope of known substrates for the MIO-containing aminomutase family, and comparative studies of KedY4 and SgcC4 provide an outstanding opportunity to examine how MIO-containing aminomutases control substrate specificity and product enantioselectivity. PMID:23633564

  3. Use of antibiotics in plant agriculture.

    Science.gov (United States)

    Stockwell, V O; Duffy, B

    2012-04-01

    Antibiotics are essential for control of bacterial diseases of plants, especially fire blight of pear and apple and bacterial spot of peach. Streptomycin is used in several countries; the use of oxytetracycline, oxolinic acid and gentamicin is limited to only a few countries. Springtime antibiotic sprays suppress pathogen growth on flowers and leaf surfaces before infection; after infection, antibiotics are ineffective. Antibiotics are applied when disease risk is high, and consequently the majority of orchards are not treated annually. In 2009 in the United States, 16,465 kg (active ingredient) was applied to orchards, which is 0.12% of the total antibiotics used in animal agriculture. Antibiotics are active on plants for less than a week, and significant residues have not been found on harvested fruit. Antibiotics have been indispensable for crop protection in the United States for more than 50 years without reports of adverse effects on human health or persistent impacts on the environment. PMID:22849276

  4. Uncialamycin, a new enediyne antibiotic.

    Science.gov (United States)

    Davies, Julian; Wang, Hao; Taylor, Terry; Warabi, Kaoru; Huang, Xin-Hui; Andersen, Raymond J

    2005-11-10

    [structure: see text] Laboratory cultures of an undescribed streptomycete obtained from the surface of a British Columbia lichen produce uncialamycin (1), a new enediyne antibiotic. The structure of uncialamycin (1) has been elucidated by analysis of spectroscopic data. Uncialamycin (1) exhibits potent in vitro antibacterial activity against gram-positive and gram-negative human pathogens, including Burkholderia cepacia, a major cause of morbidity and mortality in patients with cystic fibrosis. PMID:16268546

  5. Minocycline: far beyond an antibiotic

    OpenAIRE

    Garrido-Mesa, N; Zarzuelo, A; Gálvez, J

    2013-01-01

    Minocycline is a second-generation, semi-synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram-positive and gram-negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti-microbial activity, including anti-inflammatory and anti-apoptotic acti...

  6. Bacterial infections: antibiotics and decontamination.

    Science.gov (United States)

    Gould, Dinah

    Infectious disease is caused by bacteria, viruses, fungi, protozoa and micro-organisms including the mycoplasmas, rickettsiae and chlamydiae. Most of the infections commonly encountered in the UK are caused either by bacteria or viruses. This article describes bacterial structure and function to explain how antibiotics work and the processes of decontamination such as cleaning, disinfection and sterilisation, which are important in infection control. PMID:15224613

  7. Crotalus durissus terrificus venom as a source of antitumoral agents

    Directory of Open Access Journals (Sweden)

    MA Soares

    2010-01-01

    Full Text Available The basic knowledge on neoplasms is increasing quickly; however, few advances have been achieved in clinical therapy against tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients' survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and characterize the antitumoral effect of Crotalus durissus terrificus venom (CV and its polypeptide, crotoxin, on benign and malignant tumors, respectively, pituitary adenoma and glioblastoma. The results demonstrated that CV possess a powerful antitumoral effect on benign (pituitary adenoma and malignant (glioblastoma multiforme tumors with IC50 values of 0.96 ± 0.11 µg/mL and 2.15 ± 0.2 µg/mL, respectively. This antitumoral effect is cell-cycle-specific and dependent on extracellular calcium, an important factor for crotoxin phospholipase A2 activity. The CV antitumoral effect can be ascribed, at least partially, to the polypeptide crotoxin that also induced brain tumor cell death. In spite of the known CV nephrotoxicity and neurotoxicity, acute treatment with its antitumoral dose established in vitro was not found to be toxic to the analyzed animals. These results indicate the biotechnological potential of CV as a source of pharmaceutical templates for cancer therapy.

  8. Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases.

    Science.gov (United States)

    Zhong, Gen-Shen; Wu, Min-Na; Guo, Xiao-Fang; Zhang, Sheng-Hua; Miao, Qing-Fang; Zhen, Yong-Su

    2012-10-01

    Gelatinases play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. Lidamycin is an enediyne antitumor antibiotic with potent cytotoxicity. We previously reported that a tandem scFv format (dFv-LDP-AE) showed enhanced binding ability with gelatinases compared with the scFv-lidamycin conjugate (Fv-LDP-AE). In this study, the antitumor activities of dFv-LDP-AE on hepatocellular carcinoma (HCC) were evaluated in vitro and in vivo. By SDS-PAGE analysis, it was found that partial fusion protein dFv-LDP existed as dimer; the results of ELISA and immunofluorescence demonstrated that the fusion protein dFv-LDP could efficiently bind to hepatoma cells in vitro. The apparent arrest of cell cycle at G2/M phase and induction of apoptosis at nanomole levels indicated that the dFv-LDP-AE was very potent against HCC. In in vivo experiments, dFv-LDP-AE shown enhanced cytotoxic effects compared to those of LDM. Administration at mouse tolerable dosage level, the inhibition rate of tumor growth was 89.5% of dFv-LDP-AE vs. 73.6% of LDM on transplantable H22 in mice (Penediyne-energized fusion protein dFv-LDP-AE showed potential application as a new agent for therapeutic appications in HCC. PMID:22797730

  9. Antibiotics as CECs: An Overview of the Hazards Posed by Antibiotics and Antibiotic Resistance

    OpenAIRE

    Geoffrey Ivan Scott; Porter, Dwayne E.; R. Sean Norman; C. Hart Scott; Miguel Ignacio Uyaguari-Diaz; Keith eMaruya; Steve B. Weisberg; Fulton, Michael H.; Ed F. Wirth; Janet eMooore; Pennington , Paul L.; Daniel eSchlenk; Cobb, George P.; Denslow, Nancy D.

    2016-01-01

    ABSTRACTMonitoring programs have traditionally monitored legacy contaminants but are shifting focus to Contaminants of Emerging Concern (CECs). CECs present many challenges for monitoring and assessment, because measurement methods don't always exist nor have toxicological studies been fully conducted to place results in proper context. Also some CECs affect metabolic pathways to produce adverse outcomes that are not assessed through traditional toxicological evaluations. Antibiotics are CEC...

  10. Antitumor activity of polyacrylates of noble metals in experiment

    Directory of Open Access Journals (Sweden)

    Larisa A. Ostrovskaya

    2014-08-01

    Full Text Available The aim of this research has been the study of the antitumor activity of polymetalacrylate derivatives containing in their structure noble metals. Metallic derivatives of polyacrylic acid were not previously tested as antitumor agents.The antitumor activity of polyacrylates, containing argentum (argacryl, aurum (auracryl and platinum (platacryl against experimental models of murine solid tumors (Lewis lung carcinoma and Acatol adenocarcinoma as well as acute toxicity have been studied. It is found that the polyacrylates of noble metals are able to inhibit tumor growth up to 50-90% in comparison with the control. Auracryl induced the inhibition of the Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90% in comparison with the control, results recommending it for further advanced preclinical studies.

  11. Synthesis and antitumor activity of novel 10-amino acids ester homocamptothecin analogues

    Institute of Scientific and Technical Information of China (English)

    Liang You; Wan Nian Zhang; Zhen Yuan Miao; Wei Guo; Xiao Ying Che; Wen Ya Wang; Chun Quan Sheng; Jiang Zhong Yao; Ting Zhou

    2008-01-01

    Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method.The results showed that some of the compound had higher antitumor activity than iritecan.

  12. Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy.

    Science.gov (United States)

    Lee, Sie Huey; Teo, Jeanette; Heng, Desmond; Ng, Wai Kiong; Zhao, Yanli; Tan, Reginald B H

    2016-04-01

    Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness. This work therefore seeks to identify and tailor-make useful combination regimens (that are potentially rotatable and synergistic) as attractive alternative strategies to address the rising rates of drug resistance. Three potentially rotatable ternary dry powder inhaler constructs (each involving colistin and 2 other different-classed antibiotics chosen from rifampicin, meropenem, and tigecycline) were identified (with distinct complementary killing mechanisms), coformulated via spray drying, evaluated on their aerosol performance using a Next-Generation Impactor and tested for their efficacies against a number of MDR pathogens. The powder particles were of respirable size (d50, 3.1 ± 0.3 μm-3.4 ± 0.1 μm) and predominantly crumpled in morphology. When dispersed via a model dry powder inhaler (Aerolizer(®)) at 60 L/min, the powders showed concomitant in vitro deposition with fine particle fractions of ∼53%-70%. All formulations were successfully tested in the laboratory to be highly effective against the MDR pathogens. In addition, a favorable synergistic interaction was detected across all 3 formulations when tested against MDR Pseudomonas aeruginosa. PMID:27019964

  13. Response to "Antibiotic Use and Resistance"

    DEFF Research Database (Denmark)

    Malo, Sara; Rabanaque, María José; Feja, Christina; Lallana, María Jesús; Aguilar, Isabel; Bjerrum, Lars

    2014-01-01

    As mentioned, antibiotic consumption in heavy users, especially in children, is really striking. Certainly, our results revealed an antibiotic use in this age group higher than published in previous studies, and in line with different reports repeatedly presenting the high antibiotic consumption...... existing in Spain compared with other European countries (1). Determinants involved in antibiotic prescribing are numerous and varied. It is true that therapeutic failures lead to repeated courses of antibiotic treatment. However, it is not probably the only reason. Frequent and high consumption of...... antibiotics, as observed in heavy users, could also be due to factors related to the GP, patient and parents' expectations or the influence exerted by the pharmaceutical industry (2). This article is protected by copyright. All rights reserved....

  14. Factors Affecting the Cost Effectiveness of Antibiotics

    Directory of Open Access Journals (Sweden)

    Steven Simoens

    2011-01-01

    Full Text Available In an era of spiraling health care costs and limited resources, policy makers and health care payers are concerned about the cost effectiveness of antibiotics. The aim of this study is to draw on published economic evaluations with a view to identify and illustrate the factors affecting the cost effectiveness of antibiotic treatment of bacterial infections. The findings indicate that the cost effectiveness of antibiotics is influenced by factors relating to the characteristics and the use of antibiotics (i.e., diagnosis, comparative costs and comparative effectiveness, resistance, patient compliance with treatment, and treatment failure and by external factors (i.e., funding source, clinical pharmacy interventions, and guideline implementation interventions. Physicians need to take into account these factors when prescribing an antibiotic and assess whether a specific antibiotic treatment adds sufficient value to justify its costs.

  15. Naphthyridinomycin, a DNA-reactive antibiotic.

    OpenAIRE

    Zmijewski, M J; Miller-Hatch, K; Goebel, M.

    1982-01-01

    Naphthyridinomycin is a novel quinone antibiotic that is produced in liquid shake cultures by Streptomyces lusitanus. Fermentation studies have shown that this antibiotic is produced maximally after 96 h of cell growth. L-[methyl-3H]methionine efficiently labels naphthyridinomycin when it is added to a fermentation mixture 24 h before culture is harvested. Unlabeled and radioactively labeled naphthyridinomycin were used to determine the mechanism of action of this unique antibiotic. Naphthyri...

  16. Antibiotics for the Treatment of Hepatic Encephalopathy

    OpenAIRE

    Patidar, Kavish R.; Bajaj, Jasmohan S.

    2013-01-01

    The treatment of hepatic encephalopathy (HE) is complex and therapeutic regimens vary according to the acuity of presentation and the goals of therapy. Most treatments for HE rely on manipulating the intestinal milieu and therefore antibiotics that act on the gut form a key treatment strategy. Prominent antibiotics studied in HE are neomycin, metronidazole, vancomycin and rifaximin. For the management of the acute episode, all antibiotics have been tested. However the limited numbers studied,...

  17. DETECTION OF ANTIBIOTIC RESIDUES IN RAW MILK

    Directory of Open Access Journals (Sweden)

    G. Karim

    1978-06-01

    Full Text Available Milk and milk products containing antibiotics especially penicillin may present a health hazard to individuals who are super sensitized to penicillin. A total of 620 samples of raw milk which were delivered to Tehran pasteurization plant were examined. 294 samples were antibiotic-negative and 326 samples showed to contain antibiotic. Considering the results obtained, certain recommendations were made to prevent public health hazards and economic losses.

  18. Superbugs and antibiotics in the newborn

    OpenAIRE

    Alessandro Borghesi; Mauro Stronati

    2015-01-01

    Antibiotic resistance has become an urgent and global issue, with 700,000 deaths attributable to multidrug-resistance occurring each year worldwide. The overuse of antibiotics, both in animal industry and in clinical settings, and the generated selective pressure, are the main factors implicated in the emergence of resistant strains. The Centers for Disease Control and Prevention (CDC) have pointed out that more than half of hospital patients receive an antibiotic during their stay, and nearl...

  19. Antibiotic Resistance in Childhood with Pneumococcal Infection

    OpenAIRE

    Ali Gunes

    2013-01-01

    Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with me...

  20. Antitumor Properties of Modified Detonation Nanodiamonds and Sorbed Doxorubicin on the Model of Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Medvedeva, N N; Zhukov, E L; Inzhevatkin, E V; Bezzabotnov, V E

    2016-01-01

    We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds. PMID:26742746

  1. Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells

    OpenAIRE

    QIAO, ZHIXIN; He, Min; HE, MU; Li, Weijing; WANG, XUANLIN; Wang, Yanbing; KUAI, QIYUAN; Li, Changlan; REN, SUPING; Yu, Qun

    2016-01-01

    Pancreatic cancer is a fatal human malignancy associated with an exceptionally poor prognosis. Novel therapeutic strategies are urgently required to treat this disease. In addition to immunosuppressive activity, triptolide possesses strong antitumor activity and synergistically enhances the antitumor activities of conventional chemotherapeutic drugs in preclinical models of pancreatic cancer. The present study investigated the antitumor effects of triptolide in pancreatic cancer cells, either...

  2. Antibiotic research and development: business as usual?

    Science.gov (United States)

    Harbarth, S; Theuretzbacher, U; Hackett, J

    2015-01-01

    The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is that it is scientifically challenging to discover new antibiotics that are active against the antibiotic-resistant bacteria of current clinical concern. However, the main hurdle is diminishing economic incentives. Increased global calls to minimize the overuse of antibiotics, the cost of meeting regulatory requirements and the low prices of currently marketed antibiotics are strong deterrents to antibacterial drug development programmes. New economic models that create incentives for the discovery of new antibiotics and yet reconcile these incentives with responsible antibiotic use are long overdue. DRIVE-AB is a €9.4 million public-private consortium, funded by the EU Innovative Medicines Initiative, that aims to define a standard for the responsible use of antibiotics and to develop, test and recommend new economic models to incentivize investment in producing new anti-infective agents. PMID:25673635

  3. Deliberations on the impact of antibiotic contamination on dissemination of antibiotic resistance genes in aquatic environments

    OpenAIRE

    Berglund, Björn

    2014-01-01

    The great success of antibiotics in treating bacterial infectious diseases has been hampered by the increasing prevalence of antibiotic resistant bacteria. Not only does antibiotic resistance threaten to increase the difficulty in treating bacterial infectious diseases, but it could also make medical procedures such as routine surgery and organ transplantations very dangerous to perform. Traditionally, antibiotic resistance has been regarded as a strictly clinical problem and studies of the p...

  4. Antibiotic Resistance in Wastewater : Methicillin-resistant Staphylococcus aureus (MRSA)and antibiotic resistance genes

    OpenAIRE

    Börjesson, Stefan

    2009-01-01

    A large part of the antibiotics consumed ends up in wastewater, and in the wastewater the antibiotics may exert selective pressure for or maintain resistance among microorganisms. Antibiotic resistant bacteria and genes encoding antibiotic resistance are commonly detected in wastewater, often at higher rates and concentrations compared to surface water. Wastewater can also provide favourable conditions for the growth of a diverse bacterial community, which constitutes a basis for the selectio...

  5. [Health economics and antibiotic therapy].

    Science.gov (United States)

    Leclercq, P; Bigdéli, M

    1995-01-01

    In the field of antibiotic therapy, particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications. Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions. After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation. An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria. The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations. If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician. PMID:7481251

  6. Molecular modelling of betalactamic antibiotic

    Directory of Open Access Journals (Sweden)

    Elso Manuel Cruz Cruz

    2010-02-01

    Full Text Available Background: The antibacterial properties of a compound are the result of its molecular structure. To establish the structural and electronic characteristics makes possible to understand the mechanisms of its action and becomes paramount for the rational design new drugs. Objective: To model some of the molecular properties of betalactamic antibiotics and inhibitors of the betalactamases and to relate them with their pharmacological actions. Method: The molecular structures were optimized with PM3• semiempiric calculus. The structure of the betalactamic ring in the different compounds was compared. The molecular properties were calculated according to the Density Functional Theory at a B3LYP/6-31G(d level. The density of the atomic charges and the frontier orbitals were analyzed. Results There are variations in the calculated properties that make possible to define two groups of compounds: one for the monobactams and the inhibitors of the betalactamases, with less planarity in the ring and less reactivity and another one with the penicillins, cephalosporins and carbapenems, planer, more structurally stable and reactive. Conclusions: The modelled molecular properties of the betalactamic antibiotics and inhibitors of the betalactamases show agreement with its pharmacological action.

  7. Antitumor effect of magnetite nanoparticles in cat mammary adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sincai, Mariana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania)]. E-mail: msincai@yahoo.com; Ganga, Diana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania); Ganga, Marius [Private Veterinary Practice, Timisoara (Romania); Argherie, Diana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania); Bica, Doina [Laboratory of Magnetic Fluids, Center for Fundamental and Advanced Technical Research, Romanian Academy-Timisoara Branch (Romania)

    2005-05-15

    The antitumor effect of a magnetic fluid was studied after direct inoculation into cat mammary tumors. An external magnetic field was used to retain the nanoparticles in the tumor tissue. After 2 month, the mammary tumor regressed very much in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process.

  8. Antitumor effect of magnetite nanoparticles in cat mammary adenocarcinoma

    International Nuclear Information System (INIS)

    The antitumor effect of a magnetic fluid was studied after direct inoculation into cat mammary tumors. An external magnetic field was used to retain the nanoparticles in the tumor tissue. After 2 month, the mammary tumor regressed very much in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process

  9. Encapsulation of antitumor drug methotrexate in liposome vesicles

    International Nuclear Information System (INIS)

    Liposome vesicles containing antitumor drug methotrexate (MTX) were prepared. MTX was labelled by the tritium ion beam method. After purification by TLC, the specific radioactivity of 3H-MTX was 1.19 GBq/mmol with radiochemical purity orver 95%. Under various forming conditions of liposome vesicles, the efficiency of encapsulation was 21-53%

  10. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  11. Jacalin-Activated Macrophages Exhibit an Antitumor Phenotype

    Science.gov (United States)

    Danella Polli, Cláudia; Pereira Ruas, Luciana; Chain Veronez, Luciana; Herrero Geraldino, Thais; Rossetto de Morais, Fabiana; Roque-Barreira, Maria Cristina; Pereira-da-Silva, Gabriela

    2016-01-01

    Tumor-associated macrophages (TAMs) have an ambiguous and complex role in the carcinogenic process, since these cells can be polarized into different phenotypes (proinflammatory, antitumor cells or anti-inflammatory, protumor cells) by the tumor microenvironment. Given that the interactions between tumor cells and TAMs involve several players, a better understanding of the function and regulation of TAMs is crucial to interfere with their differentiation in attempts to skew TAM polarization into cells with a proinflammatory antitumor phenotype. In this study, we investigated the modulation of macrophage tumoricidal activities by the lectin jacalin. Jacalin bound to macrophage surface and induced the expression and/or release of mainly proinflammatory cytokines via NF-κB signaling, as well as increased iNOS mRNA expression, suggesting that the lectin polarizes macrophages toward the antitumor phenotype. Therefore, tumoricidal activities of jacalin-stimulated macrophages were evaluated. High rates of tumor cell (human colon, HT-29, and breast, MCF-7, cells) apoptosis were observed upon incubation with supernatants from jacalin-stimulated macrophages. Taken together, these results indicate that jacalin, by exerting a proinflammatory activity, can direct macrophages to an antitumor phenotype. Deep knowledge of the regulation of TAM functions is essential for the development of innovative anticancer strategies. PMID:27119077

  12. Superbugs and antibiotics in the newborn

    Directory of Open Access Journals (Sweden)

    Alessandro Borghesi

    2015-10-01

    Full Text Available Antibiotic resistance has become an urgent and global issue, with 700,000 deaths attributable to multidrug-resistance occurring each year worldwide. The overuse of antibiotics, both in animal industry and in clinical settings, and the generated selective pressure, are the main factors implicated in the emergence of resistant strains. The Centers for Disease Control and Prevention (CDC have pointed out that more than half of hospital patients receive an antibiotic during their stay, and nearly a third receive a broad-spectrum antibiotic. In neonatal units, previous antibiotic exposure to third-generation cephalosporin and carbapenem were identified as independent risk factors for infection caused by multi-drug resistant strains. While resistant ‘superbugs’ emerge, the arsenal to fight these microorganisms is progressively shrinking, as the number of newly discovered antibiotics approved by the Food and Drug administration each year is dropping. In face of global spread of antibiotic resistance and of the limited development of new drugs, policies and rules are under study by agencies (CDC, World Health Organization and governments, in order to: i facilitate and foster the discovery of new antibiotic compounds; ii develop new, alternative therapies able to potentiate or modulate the host immune response or to abrogate the resistance and virulence factors in the microorganisms; and iii prevent the emergence of resistance through antibiotic stewardship programs, educational programs, and reduction of antibiotic use in livestock; the field of neonatal medicine will need its own, newborn-tailored, antibiotic stewardship programs to be implemented in the NICUs. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai

  13. Optimizing antibiotic selection in treating COPD exacerbations

    Directory of Open Access Journals (Sweden)

    Attiya Siddiqi

    2008-03-01

    Full Text Available Attiya Siddiqi, Sanjay SethiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Veterans Affairs Western New York Health Care System and University of Buffalo, State University of New York, Buffalo, New York, USAAbstract: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.Keywords: COPD, exacerbation, bronchitis, antibiotics

  14. Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 1: Antibiotic Prescribing Patterns, Sources of Antibiotic Exposure, Antibiotic Consumption and Emergence of Antibiotic Resistance, Impact of Alterations in Antibiotic Prescribing, and Clinical Sequelae of Antibiotic Use.

    Science.gov (United States)

    Del Rosso, James Q; Webster, Guy F; Rosen, Ted; Thiboutot, Diane; Leyden, James J; Gallo, Richard; Walker, Clay; Zhanel, George; Eichenfield, Lawrence

    2016-04-01

    Oral and topical antibiotics are commonly prescribed in dermatologie practice, often for noninfectious disorders, such as acne vulgaris and rosacea. Concerns related to antibiotic exposure from both medical and nonmedical sources require that clinicians consider in each case why and how antibiotics are being used and to make appropriate adjustments to limit antibiotic exposure whenever possible. This first article of a three-part series discusses prescribing patterns in dermatology, provides an overview of sources of antibiotic exposure, reviews the relative correlations between the magnitude of antibiotic consumption and emergence of antibiotic resistance patterns, evaluates the impact of alterations in antibiotic prescribing, and discusses the potential relevance and clinical sequelae of antibiotic use, with emphasis on how antibiotics are used in dermatology. PMID:27462384

  15. Antitumor activity of fermented noni exudates and its fractions.

    Science.gov (United States)

    Li, Jinhua; Chang, Leng-Chee; Wall, Marisa; Wong, D K W; Yu, Xianzhong; Wei, Yanzhang

    2013-01-01

    Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.p.) injection of fermented noni exudates (fNE) were previously found to induce significant tumor rejection in a S180 mouse sarcoma tumor model, while natural killer (NK) cells were demonstrated to be markedly involved in fNE-induced antitumor activity. In this study, fNE was partitioned into three fractions and their antitumor effects were examined using i.p. injection or as water supplement. The in vivo animal study results showed that when delivered by i.p. injection, n-butanol fraction of fNE (BuOH) effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions resisted tumor cells. The tumor-resistant mice effectively rejected more and higher doses of tumor challenge, indicating that the immune system was activated. The findings confirm those of an earlier study showing fNE to have anti-tumor activity and demonstrating that the n-butanol fraction of fNE contains active antitumor components, to be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention. PMID:24649140

  16. Topical and oral antibiotics for acne vulgaris.

    Science.gov (United States)

    Del Rosso, James Q

    2016-06-01

    Antibiotics, both oral and topical, have been an integral component of the management of acne vulgaris (AV) for approximately 6 decades. Originally thought to be effective for AV due to their ability to inhibit proliferation of Propionibacterium acnes, it is now believed that at least some antibiotics also exert anti-inflammatory effects that provide additional therapeutic benefit. To add, an increase in strains of P acnes and other exposed bacteria that are less sensitive to antibiotics used to treat AV have emerged, with resistance directly correlated geographically with the magnitude of antibiotic use. Although antibiotics still remain part of the therapeutic armamentarium for AV treatment, current recommendations support the following when used to treat AV: 1) monotherapy use should be avoided; 2) use benzoyl peroxide concomitantly to reduce emergence of resistant P acnes strains; 3) oral antibiotics should be used in combination with a topical regimen for moderate-to-severe inflammatory AV; and 4) use oral antibiotics over a limited duration to achieve control of inflammatory AV with an exit plan in place to discontinue their use as soon as possible. When selecting an oral antibiotic to treat AV, potential adverse effects are important to consider. PMID:27416309

  17. [Modification of antibiotic resistance in microbial symbiosis].

    Science.gov (United States)

    Aznabaeva, L M; Usviatsov, B Ia; Bukharin, O V

    2010-01-01

    In antibiotic therapy it is necessary to use drugs active against the pathogen in its association with the host normal microflora. The aim of the study was to investigate modification of antibiotic resistance under conditions of the pathogen association with the representatives of the host normal microflora and to develop the microbiological criteria for determining effectiveness of antibacterials. Modification of microbial antibiotic resistance was investigated in 408 associations. Various changes in the antibiotic resistance of the strains were revealed: synergism, antagonism and indifference. On the basis of the results it was concluded that in the choice of the antibiotic active against Staphylococcus aureus and Streptococcus pyogenes the preference should be given to oxacillin, gentamicin and levomycetin, since the resistance of the pathogens to these antibiotics under the association conditions did not increase, which could contribute to their destruction, whereas the resistance of the normoflora increased or did not change, which was important for its retention in the biocenosis. The data on changeability of the antibiotic resistance of the microbial strains under the association conditions made it possible to develop microbiological criteria for determining effectiveness of antibiotics in the treatment of inflammatory diseases of microbial etiology (RF Patent No. 2231554). PMID:21033469

  18. Antibiotics: Pharmacists Can Make the Difference

    Centers for Disease Control (CDC) Podcasts

    2015-04-16

    In this podcast, a pharmacist counsels a frustrated father about appropriate antibiotic use and symptomatic relief options for his son's cold.  Created: 4/16/2015 by Division of Bacterial Diseases (DBD), National Center for Immunization and Respiratory Disease (NCIRD), Get Smart: Know When Antibiotics Work Program.   Date Released: 4/16/2015.

  19. Mining metagenomic datasets for antibiotic resistance genes

    Science.gov (United States)

    Antibiotics are medicines that are used to kill, slow down, or prevent the growth of susceptible bacteria. They became widely used in the mid 20th century for controlling disease in humans, animals, and plants, and for a variety of industrial purposes. Antibiotic resistance is a broad term. There ...

  20. Antibiotic resistance: a physicist’s view

    Science.gov (United States)

    Allen, Rosalind; Waclaw, Bartłomiej

    2016-08-01

    The problem of antibiotic resistance poses challenges across many disciplines. One such challenge is to understand the fundamental science of how antibiotics work, and how resistance to them can emerge. This is an area where physicists can make important contributions. Here, we highlight cases where this is already happening, and suggest directions for further physics involvement in antimicrobial research.

  1. Antibiotic tolerance and resistance in biofilms

    DEFF Research Database (Denmark)

    Ciofu, Oana; Tolker-Nielsen, Tim

    One of the most important features of microbial biofilms is their tolerance to antimicrobial agents and components of the host immune system. The difficulty of treating biofilm infections with antibiotics is a major clinical problem. Although antibiotics may decrease the number of bacteria in...

  2. Snort Sniffle Sneeze: No Antibiotics Please

    Centers for Disease Control (CDC) Podcasts

    2009-09-29

    Antibiotics aren't always the answer for sneezes or sore throats. This podcast discusses ways to feel better without antibiotics.  Created: 9/29/2009 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/29/2009.

  3. Antibiotic RX in Hospitals: Proceed with Caution

    Centers for Disease Control (CDC) Podcasts

    2014-03-04

    This podcast is based on the March 2014 CDC Vital Signs report. Antibiotics save lives, but poor prescribing practices can put patients at risk for health problems. Learn how to protect patients by protecting antibiotics.  Created: 3/4/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 3/4/2014.

  4. Analysis of antibiotic consumption in burn patients.

    Science.gov (United States)

    Soleymanzadeh-Moghadam, Somayeh; Azimi, Leila; Amani, Laleh; Rastegar Lari, Aida; Alinejad, Faranak; Rastegar Lari, Abdolaziz

    2015-01-01

    Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used. The results indicated that P. aeruginosa is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR) microorganisms, but it can also decrease the cost of treatment. PMID:26124986

  5. Analysis of antibiotic consumption in burn patients

    Directory of Open Access Journals (Sweden)

    Soleymanzadeh-Moghadam, Somayeh

    2015-06-01

    Full Text Available Infection control is very important in burn care units, because burn wound infection is one of the main causes of morbidity and mortality among burn patients. Thus, the appropriate prescription of antibiotics can be helpful, but unreasonable prescription can have detrimental consequences, including greater expenses to patients and community alike. The aim of this study was to determine the effect of antibiotic therapy on the emergence of antibiotic-resistant bacteria. 525 strains of and were isolated from 335 hospitalized burn patients. Antibiotic susceptibility tests were performed after identification the strains. The records of patients were audited to find the antibiotic used.The results indicated that is the most prevalent Gram-negative bacteria. Further, it showed a relation between abuse of antibiotics and emergence of antibiotic resistance. Control of resistance to antibiotics by appropriate prescription practices not only facilitates prevention of infection caused by multi-drug resistant (MDR microorganisms, but it can also decrease the cost of treatment.

  6. Antibiotic prophylaxis in clean general surgery

    International Nuclear Information System (INIS)

    To find out the incidence of surgical site infection in clean general surgery cases operated without prophylactic antibiotics. One hundred and twenty-four clean surgical cases operated without antibiotic prophylaxis between July 2003 and December 2004, were studied and these were compared with similar number of cases who received antibiotics. The data was collected and analyzed using software SPSS (version 10.0). Chi-square and student-t test were used to analyze the association between antibiotics and wound infection. The most frequent operation was repair of various hernias, 69.3% in group A and 75% in group B. More operations were carried out between 21-30 years, 38.7% in group A and 41.9% in group B. Surgical site infection occurred in one patient (0.8%) in each group. Chi-square test (0.636) applied to group A and B showed no association of infection and administration/ no administration of antibiotics (p > 0.25). The t-test applied on group A and B (t=0) also showed no significant difference between administration of antibiotics/ no-antibiotics and infection (p > 0.25). The use of prophylactic antibiotic in clean, non implant and elective cases is unnecessary. (author)

  7. Antibiotic research and development: business as usual?

    NARCIS (Netherlands)

    Harbarth, S.; Theuretzbacher, U.; Hackett, J.; Hulscher, M.

    2015-01-01

    The global burden of antibiotic resistance is tremendous and, without new anti-infective strategies, will continue to increase in the coming decades. Despite the growing need for new antibiotics, few pharmaceutical companies today retain active antibacterial drug discovery programmes. One reason is

  8. Doxorubicine and antibiotics influence on dynamics of population development of Staphylococcus aureus and Escherichia coli

    Directory of Open Access Journals (Sweden)

    O.G. Shapoval

    2010-03-01

    Full Text Available Infectious complications in oncologic patients often occur as a result of antitumor therapy that demands the prescription of antimicrobic preparations. one of the main infectious agents in oncology is Staphylococci and Escherichia coli. The aim of this work is to study doxorubicine and ceftriaxon influence on dynamics of population development of strains of Staphylococcus aureus, doxorubicine and amikacine - on dynamics of population development of strains of Escherichia coli. Five strains of each type (one-standard and four-clinical cultivated in meatpeptone broth, which contains non-inhibitory concentrations of experimental preparations. in any period of time after the sowing the measurement of optical density of growing cultures has been carried out. it has been determined, that doxorubicine in non-inhibitory concentrations increases overwhelming effect of these antibiotics on dynamics of population development of experimental strains

  9. The 'liaisons dangereuses' between iron and antibiotics.

    Science.gov (United States)

    Ezraty, Benjamin; Barras, Frédéric

    2016-05-01

    The decline in the rate of new antibiotic discovery is of growing concern, and new antibacterial strategies must now be explored. This review brings together research in two fields (metals in biology and antibiotics) in the hope that collaboration between scientists working in these two areas will lead to major advances in understanding and the development of new approaches to tackling microbial pathogens. Metals have been used as antiseptics for centuries. In this review, we focus on iron, an essential trace element that can nevertheless be toxic to bacteria. We review the many situations in which iron and antibiotics have combinatorial effects when used together. Understanding the molecular relationships between iron and antibiotics, from pure chemistry to gene reprogramming via biochemical competition, is important not only to increase basic knowledge, but also for the development of treatments against pathogens, with a view to optimizing antibiotic efficacy. PMID:26945776

  10. Prophylactic antibiotics in transurethral prostatectomy

    DEFF Research Database (Denmark)

    Qvist, N; Christiansen, H.M.; Ehlers, D

    1984-01-01

    The study included 88 patients with sterile urine prior to transurethral prostatectomy. Forty-five received a preoperative dose of 2 g of cefotaxime (Claforan) and the remaining 43 were given 10 ml of 0.9% NaCl. The two groups did not differ in frequency of postoperative urinary infection (greate...... of infection and the few side effects of the infections that did occur, prophylactic treatment with an antibiotic is not indicated for transurethral prostatectomy in patients with sterile urine.......The study included 88 patients with sterile urine prior to transurethral prostatectomy. Forty-five received a preoperative dose of 2 g of cefotaxime (Claforan) and the remaining 43 were given 10 ml of 0.9% NaCl. The two groups did not differ in frequency of postoperative urinary infection (greater...

  11. Antibiotic resistance pattern in uropathogens

    Directory of Open Access Journals (Sweden)

    Gupta V

    2002-01-01

    Full Text Available Uropathogenic strains from inpatient and outpatient departments were studied from April 1997 to March 1999 for their susceptibility profiles. The various isolates were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii and Enterococcus faecalis. Antibiotic susceptibility pattern of these isolates revealed that for outpatients, first generation cephalosporins, nitrofurantoin, norfloxacin/ciprofloxacin were effective for treatment of urinary tract infection but for inpatients, parenteral therapy with newer aminoglycosides and third generation cephalosporins need to be advocated as the organisms for nosocomial UTI exhibit a high degree of drug resistance. Trimethoprim and sulphamethoxazole combination was not found to be effective for the treatment of urinary tract infections as all the uropathogens from inpatients and outpatients showed high degree of resistance to co-trimoxazole. Culture and sensitivity of the isolates from urine samples should be done as a routine before advocating the therapy.

  12. Antibiotics in Animal Feed Contribute to Drug-Resistant Germs

    Science.gov (United States)

    ... medlineplus/news/fullstory_158316.html Antibiotics in Animal Feed Contribute to Drug-Resistant Germs: Study Individual farm ... HealthDay News) -- Use of antibiotics in farm animal feed is helping drive the worldwide increase in antibiotic- ...

  13. Enabling factors for antibiotic prescribing for upper respiratory tract infections

    DEFF Research Database (Denmark)

    Jaruseviciene, Lina; Radzeviciene Jurgute, Ruta; Bjerrum, Lars;

    2013-01-01

    necessity for political leadership to encourage clinically grounded antibiotic use; over-the-counter sale of antibiotics; designation of antibiotics as reimbursable medications; supervision by external oversight institutions; lack of guidelines for the treatment of upper respiratory tract infections; and...

  14. Identification of Antibiotic Use Pattern as an Effort to Control Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Ivan S. Pradipta

    2012-03-01

    Full Text Available The objective of this study is to determine quantity and pattern of antibiotic use in hospitalized patients at one of Bandung’s private hospital that can give benefit in control of antibiotic resistance and procurement planning of antibiotic. Data of antibiotic consumption were obtained from hospital pharmacy department on February–September 2011. Data were processed using the ATC/DDD and DU90% method. There were 390,98 DDD/100 bed days and 381,34 DDD/100 bed days total of an-tbiotic use in 2009 and 2010. Thirty nine antibiotic were consumed in 2009 within 11 kind of antibiotics in DU90% segment (ceftriaxone, amoxicillin, cefotaxime, ciprofloxacin, levofloxacin, metronidazole, cefixime, doxycycline, thiamphenicol, cefodoxime, cefalexin and 44 antibiotic were consumed in 2010 within 18 kind of antibiotics in DU90% segment (ceftriaxone, ciprofloxacin, amoxicillin, cefixime, levofloxacin, cefadroxil, cefotaxime, metronidazole, thiamphenicol, doxycycline, clindamycin, chloramphenicol, amikacin, sulbactam, gentamycin, streptomycin, cefoperazone, canamycin. There were decline of antibiotic use that followed decline number of bed days/year in 2009–2010, but in both antibiotic kind and quantity of DU90% antibiotic group were increased.

  15. Abiotic degradation of antibiotic ionophores

    International Nuclear Information System (INIS)

    Hydrolytic and photolytic degradation were investigated for the ionophore antibiotics lasalocid, monensin, salinomycin, and narasin. The hydrolysis study was carried out by dissolving the ionophores in solutions of pH 4, 7, and 9, followed by incubation at three temperatures of 6, 22, and 28 °C for maximum 34 days. Using LC–MS/MS for chemical analysis, lasalocid was not found to hydrolyse in any of the tested environments. Monensin, salinomycin, and narasin were all stable in neutral or alkaline solution but hydrolysed in the solution with a pH of 4. Half-lives at 25 °C were calculated to be 13, 0.6, and 0.7 days for monensin, salinomycin, and narasin, respectively. Absorbance spectra from each compound indicated that only lasalocid is degraded by photolysis (half-life below 1 h) due to an absorbance maximum around 303 nm, and monensin, salinomycin, and narasin are resistant to direct photolysis because they absorb light of environmentally irrelevant wavelengths. -- Highlights: •Constants for calculation of hydrolysis rates are estimated. •At 25 °C and a pH of 4, monensin hydrolyses with a half-life (t1/2) of 13 days. •Salinomycin and narasin hydrolyse with t1/2 of half a day at 25 °C and a pH of 4. •Lasalocid does not hydrolyse, but is likely to be susceptible to direct photolysis. •Monensin, salinomycin and narasin are not susceptible to direct photolysis. -- Antibiotic ionophores were found to undergo either hydrolysis in acidic environments (monensin, salinomycin, and narasin) or photolysis (lasalocid)

  16. Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline.

    Science.gov (United States)

    Brogan, David M; Mossialos, Elias

    2016-02-01

    Over the past decade, there has been a growing recognition of the increasing growth of antibiotic resistant bacteria and a relative decline in the production of novel antibacterial therapies. The combination of these two forces poses a potentially grave threat to global health, in both developed and developing countries. Current market forces do not provide appropriate incentives to stimulate new antibiotic development, thus we propose a new incentive mechanism: the Options Market for Antibiotics. This mechanism, modelled on the principle of financial call options, allows payers to buy the right, in early stages of development, to purchase antibiotics at a discounted price if and when they ever make it to market approval. This paper demonstrates the effect of such a model on the expected Net Present Value of a typical antibacterial project. As part of an integrated strategy to confront the impending antibiotic crisis, the Options Market for Antibiotics may effectively stimulate corporate and public investment into antibiotic research and development. PMID:26808335

  17. Antibiotics and antibiotic-resistant bacteria in waters associated with a hospital in Ujjain, India

    Directory of Open Access Journals (Sweden)

    Marothi Yogyata

    2010-07-01

    Full Text Available Abstract Background Concerns have been raised about the public health implications of the presence of antibiotic residues in the aquatic environment and their effect on the development of bacterial resistance. While there is information on antibiotic residue levels in hospital effluent from some other countries, information on antibiotic residue levels in effluent from Indian hospitals is not available. Also, concurrent studies on antibiotic prescription quantity in a hospital and antibiotic residue levels and resistant bacteria in the effluent of the same hospital are few. Therefore, we quantified antibiotic residues in waters associated with a hospital in India and assessed their association, if any, with quantities of antibiotic prescribed in the hospital and the susceptibility of Escherichia coli found in the hospital effluent. Methods This cross-sectional study was conducted in a teaching hospital outside the city of Ujjain in India. Seven antibiotics - amoxicillin, ceftriaxone, amikacin, ofloxacin, ciprofloxacin, norfloxacin and levofloxacin - were selected. Prescribed quantities were obtained from hospital records. The samples of the hospital associated water were analysed for the above mentioned antibiotics using well developed and validated liquid chromatography/tandem mass spectrometry technique after selectively isolating the analytes from the matrix using solid phase extraction. Escherichia coli isolates from these waters were tested for antibiotic susceptibility, by standard Kirby Bauer disc diffusion method using Clinical and Laboratory Standard Institute breakpoints. Results Ciprofloxacin was the highest prescribed antibiotic in the hospital and its residue levels in the hospital wastewater were also the highest. In samples of the municipal water supply and the groundwater, no antibiotics were detected. There was a positive correlation between the quantity of antibiotics prescribed in the hospital and antibiotic residue levels in

  18. Get Smart: Know When Antibiotics Work - Sinus Infection (Sinusitis)

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  19. Get Smart: Know When Antibiotics Work - Influenza (Flu)

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  20. Get Smart: Know When Antibiotics Work - Ear Infections

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  1. Get Smart: Know When Antibiotics Work - Urinary Tract Infection

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  2. Get Smart: Know When Antibiotics Work - Sore Throat

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  3. Get Smart: Know When Antibiotics Work - Symptom Relief

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  4. Get Smart: Know When Antibiotics Work - What You Can Do

    Science.gov (United States)

    ... Recommendations Pediatric Treatment Recommendations Inpatient Healthcare Professionals Community Pharmacists Continuing Education & Curriculum Opportunities Weighing in on Antibiotic Resistance Improving Prescribing Outpatient Antibiotic Stewardship Interventions That Work Systematic Reviews ...

  5. "Practical knowledge" and perceptions of antibiotics and antibiotic resistance among drugsellers in Tanzanian private drugstores

    Directory of Open Access Journals (Sweden)

    Tomson Göran

    2010-09-01

    Full Text Available Abstract Background Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Methods Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Results Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85% said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic

  6. [Antibiotic resistance of bacteria to 6 antibiotics in secondary effluents of municipal wastewater treatment plants].

    Science.gov (United States)

    Lu, Sun-Qin; Li, Yi; Huang, Jing-Jing; Wei, Bin; Hu, Hong-Ying

    2011-11-01

    Prevalence of antibiotic-resistant bacteria in wastewater effluents is concerned as an emerging contaminant. To estimate antibiotic resistance in secondary effluents of municipal wastewater treatment plants, antibiotic tolerance of heterotrophic bacteria, proportion of antibiotic-resistant bacteria and hemi-inhibitory concentrations of six antibiotics (penicillin, ampicillin, cefalexin, chloramphenicol, tetracycline and rifampicin) were determined at two wastewater treatment plants (WWTPs) in Beijing. The results showed that proportions of ampicillin-resistant bacteria in WWTP-G and chloramphenicol-resistant bacteria in WWTP-Q were highest to 59% and 44%, respectively. The concentrations of ampicillin-resistant bacteria in the effluents of WWTP-G and WWTP-Q were as high as 4.0 x 10(3) CFU x mL(-1) and 3.5 x 10(4) CFU x mL(-1), respectively; the concentrations of chloramphenicol-resistant bacteria were 4.9 x 10(2) CFU x mL(-1) and 4.6 x 10(4) CFU x mL(-1), respectively. The data also indicated that the hemi-inhibitory concentrations of heterotrophic bacteria to 6 antibiotics were much higher than common concentrations of antibiotics in sewages, which suggested that antibiotic-resistant bacteria could exist over a long period in the effluents with low concentrations of antibiotics. Antibiotic-resistant bacteria could be a potential microbial risk during sewage effluent reuse or emission into environmental waters. PMID:22295644

  7. Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics

    Directory of Open Access Journals (Sweden)

    Björn Berglund

    2015-09-01

    Full Text Available Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs. Horizontal gene transfer (HGT events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment.

  8. Fungal treatment for the removal of antibiotics and antibiotic resistance genes in veterinary hospital wastewater.

    Science.gov (United States)

    Lucas, D; Badia-Fabregat, M; Vicent, T; Caminal, G; Rodríguez-Mozaz, S; Balcázar, J L; Barceló, D

    2016-06-01

    The emergence and spread of antibiotic resistance represents one of the most important public health concerns and has been linked to the widespread use of antibiotics in veterinary and human medicine. The overall elimination of antibiotics in conventional wastewater treatment plants is quite low; therefore, residual amounts of these compounds are continuously discharged to receiving surface waters, which may promote the emergence of antibiotic resistance. In this study, the ability of a fungal treatment as an alternative wastewater treatment for the elimination of forty-seven antibiotics belonging to seven different groups (β-lactams, fluoroquinolones, macrolides, metronidazoles, sulfonamides, tetracyclines, and trimethoprim) was evaluated. 77% of antibiotics were removed after the fungal treatment, which is higher than removal obtained in conventional treatment plants. Moreover, the effect of fungal treatment on the removal of some antibiotic resistance genes (ARGs) was evaluated. The fungal treatment was also efficient in removing ARGs, such as ermB (resistance to macrolides), tetW (resistance to tetracyclines), blaTEM (resistance to β-lactams), sulI (resistance to sulfonamides) and qnrS (reduced susceptibility to fluoroquinolones). However, it was not possible to establish a clear link between concentrations of antibiotics and corresponding ARGs in wastewater, which leads to the conclusion that there are other factors that should be taken into consideration besides the antibiotic concentrations that reach aquatic ecosystems in order to explain the emergence and spread of antibiotic resistance. PMID:26991378

  9. Antibiotic sensitivity profiles determined with an Escherichia coli gene knockout collection: generating an antibiotic bar code.

    Science.gov (United States)

    Liu, Anne; Tran, Lillian; Becket, Elinne; Lee, Kim; Chinn, Laney; Park, Eunice; Tran, Katherine; Miller, Jeffrey H

    2010-04-01

    We have defined a sensitivity profile for 22 antibiotics by extending previous work testing the entire KEIO collection of close to 4,000 single-gene knockouts in Escherichia coli for increased susceptibility to 1 of 14 different antibiotics (ciprofloxacin, rifampin [rifampicin], vancomycin, ampicillin, sulfamethoxazole, gentamicin, metronidazole, streptomycin, fusidic acid, tetracycline, chloramphenicol, nitrofurantoin, erythromycin, and triclosan). We screened one or more subinhibitory concentrations of each antibiotic, generating more than 80,000 data points and allowing a reduction of the entire collection to a set of 283 strains that display significantly increased sensitivity to at least one of the antibiotics. We used this reduced set of strains to determine a profile for eight additional antibiotics (spectinomycin, cephradine, aztreonem, colistin, neomycin, enoxacin, tobramycin, and cefoxitin). The profiles for the 22 antibiotics represent a growing catalog of sensitivity fingerprints that can be separated into two components, multidrug-resistant mutants and those mutants that confer relatively specific sensitivity to the antibiotic or type of antibiotic tested. The latter group can be represented by a set of 20 to 60 strains that can be used for the rapid typing of antibiotics by generating a virtual bar code readout of the specific sensitivities. Taken together, these data reveal the complexity of intrinsic resistance and provide additional targets for the design of codrugs (or combinations of drugs) that potentiate existing antibiotics. PMID:20065048

  10. Separation, antitumor activities, and encapsulation of polypeptide from Chlorella pyrenoidosa.

    Science.gov (United States)

    Wang, Xiaoqin; Zhang, Xuewu

    2013-01-01

    Chlorella pyrenoidosa is a unicellular green algae and has been a popular foodstuff worldwide. However, no reports on the antitumor peptides from such a microalgae are available in the literature. In this study, using low-temperature high-pressure extraction, enzymatic hydrolysis, ion exchange, and gel filtration chromatography, we separated a polypeptide that exhibited inhibitory activity on human liver cancer HepG2 cells, and named the polypeptide CPAP (C. pyrenoidosa antitumor polypeptide). Furthermore, the micro- and nanoencapsulation of CPAP were investigated by using two methods: complex coacervation and ionotropic gelation. The in vitro release tests revealed that CPAP was well preserved against gastric enzymatic degradation after micro/nanoencapsulation and the slowly controlled release in the intestine could be potentially achieved. These results suggest that CPAP may be a useful ingredient in food, nutraceutical, and pharmaceutical applications. PMID:23606619

  11. Synthesis of lapachol analogues with possible antitumoral activity

    International Nuclear Information System (INIS)

    The lapachol is presented as a hydroxynaphthoquinone and, like many naphthoquinones, has had diverse biological activity, such as antiparasitic, antimicrobial, antifungal and anticancer even. The lateral alkyl chain has been an important factor in the activity of the 2-hydroxy-l,4-naphthoquinone. The synthesis of analogous compounds to lapachol is presented, by alkylating C3 of 2-hydroxy-l,4-naphthoquinone (lawsone) by tertiary carbocations, secondary and benzilic. Several methodologies of synthesis were used to achieve products formed, the reactions have presented yields moderate to good. The derivatives were characterized by spectroscopic methods (UV, IR, 1H-NMR, 13C-NMR), mass spectrometry and high-resolution melting points. Antitumor activity tests were performed in three cell lines, the results obtained have showed that some of the synthesized compounds, can become seeded in future research for the evaluation of the antitumor activity of other analogues lapachol. (author)

  12. [Research progress on anti-tumor effect of Huaier].

    Science.gov (United States)

    Yang, Ai-lin; Hu, Zhong-dong; Tu, Peng-fei

    2015-12-01

    Huaier (Trametes robiniophila) has been widely used as an adjuvant drug for cancer treatment in China. The anti-cancer effect of Huaier extract has been confirmed in liver cancer, lung cancer, breast cancer, ovarian cancer, gastric cancer, and so on. The main mechanisms by which Huaier exerts an anti-neoplastic effect include inhibition of the growth and proliferation of cancer cells, induction of apoptosis of cancer cells, suppression of angiogenesis, inhibition of the invasion and migration of cancer cells, regulation of oncogenes and tumor suppressor genes expression, improving immunity, and reversal of drug resistance in cancer cells. In order to provide references for further study and clinical application on anti-tumor effect of Huaier, the latest research progress on anti-tumor effect of Huaier in recent years is summarized in this paper. PMID:27245026

  13. Broad spectrum antibiotic compounds and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Koglin, Alexander; Strieker, Matthias

    2016-07-05

    The discovery of a non-ribosomal peptide synthetase (NRPS) gene cluster in the genome of Clostridium thermocellum that produces a secondary metabolite that is assembled outside of the host membrane is described. Also described is the identification of homologous NRPS gene clusters from several additional microorganisms. The secondary metabolites produced by the NRPS gene clusters exhibit broad spectrum antibiotic activity. Thus, antibiotic compounds produced by the NRPS gene clusters, and analogs thereof, their use for inhibiting bacterial growth, and methods of making the antibiotic compounds are described.

  14. Crotalus durissus terrificus venom as a source of antitumoral agents

    OpenAIRE

    MA Soares; PB Pujatti; CL Fortes-Dias; Antonelli, L.; RG Santos

    2010-01-01

    The basic knowledge on neoplasms is increasing quickly; however, few advances have been achieved in clinical therapy against tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients' survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and characterize the antitumoral effect of Crotalus durissus terrificus venom (CV) and its polypep...

  15. Tumor necrosis factor-alpha antitumor and immunomodulatory effects

    OpenAIRE

    Scheringa, Marcel

    1991-01-01

    textabstractIn the first part of this thesis we examined the possibilities of using the cytokine tumor necrosis factor-alpha (TNFcx) for the latter aproach. Although multiple studies have been performed regarding the antitumor action of TNFcx, it is still not clear whether TNFcx has sufficient potential to be used as immunotherapeutic agent in vivo. In this part of this thesis an answer to this important question is given Whereas cancer immunotherapy might benefit from immunostimulation with ...

  16. Antitumor Activity of Monoterpenes Found in Essential Oils

    OpenAIRE

    2014-01-01

    Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action ...

  17. Synthesis and antitumor activity of novel podophyllotoxin derivatives

    Institute of Scientific and Technical Information of China (English)

    Ming Zhao; Min Feng; Shu Fang Bai; Yuan Zhang; Wen Chao Bi; Hong Chen

    2009-01-01

    In order to find compounds with superior bioactivity and overcoming multidrug resistance, a novel series of 4β-N-substituted podophyllotoxin derivatives were synthesized and evaluated as potential antitumor agents. Seven novel podophyllotoxin derivatives were synthesized by linking 4β-amino-4-deoxypodophyllotoxin with alcohols through maleic acid and tested against K562 and K562/A02 using MTT assay in vitro.

  18. Antitumor mechanisms of metformin: Signaling, metabolism, immunity and beyond

    Directory of Open Access Journals (Sweden)

    Ismael Samudio

    2010-08-01

    Full Text Available Metformin is a synthetic biguanide first described in the 1920´s as a side product of the synthesis of N,N-dimethylguanidine. Like otherrelated biguanides, metformin displays antihyperglycemic properties, and has become the most widely prescribed oral antidiabetic medicinearound the world. Intriguing recent evidence suggests that metformin has chemopreventive and direct antitumor properties, and severalongoing clinical studies around the world are using this agent alone or in combination with chemotherapeutic schemes to determineprospectively its safety and efficacy in the treatment of human cancer. Notably, immune activating effects of metformin have recently beendescribed, and may support a notion put forth in the 1950s that this agent possessed antiviral and antimalarial effects. However, how theseeffects may contribute to its observed antitumor effects in retrospective studies has not been discussed. Mechanistically, metformin has beenshown to activate liver kinase B1 (LKB1 and its downstream target AMP-activated kinase (AMPK. The activation of AMPK has beenproposed to mediate metformin´s glucose lowering effect, although recent evidence suggests that this agent can inhibit electron transport inhepatocyte mitochondria resulting in AMPK-independent inhibition of hepatic gluconeogenesis. Likewise, albeit activation of AMPK andthe resulting inhibition of the mammalian target of rapamycin (mTOR signaling have been suggested to mediate the antitumor effects ofmetformin, AMPK-independent growth inhibitory properties of this agent in tumor cells have also been described. Here we present a briefreview of the signaling, metabolic, and immune effects of metformin and discuss how their interplay may orchestrate the antitumor effectsof this agent. In addition, we provide the rationale for a compassionate use study of metformin in combination with metronomic chemotherapy.

  19. Anti-tumor Action and Clinical Application of Proteasome Inhibitor

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yong-ming; YU Mei-xia; LONG Hui; HUANG Shi-ang

    2008-01-01

    Ubiquitin-proteasome pathway mediates the degradation of cell protein,and cell cycle,gene translation and expression,antigen presentation and inflammatory development.Proteasome inhibitor Call inhibit growth and proliferation of tumor cell,induce apoptosis and reverse multipledrug resistance of tumor cell,increase the sensitivity of other chemomerapeutic drugs and radiotherapy,and is a novel class of potent anti-tumor agents.

  20. Snake venoms components with antitumor activity in murine melanoma cells

    International Nuclear Information System (INIS)

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  1. Functional and mechanistic analysis of telomerase: An antitumor drug target.

    Science.gov (United States)

    Chen, Yinnan; Zhang, Yanmin

    2016-07-01

    The current research on anticancer drugs focuses on exploiting particular traits or hallmarks unique to cancer cells. Telomerase, a special reverse transcriptase, has been recognized as a common factor in most tumor cells, and in turn a distinctive characteristic with respect to non-malignant cells. This feature has made telomerase a preferred target for anticancer drug development and cancer therapy. This review aims to analyze the pharmacological function and mechanism and role of telomerase in oncogenesis; to provide fundamental knowledge for research on the structure, function, and working mechanism of telomerase; to expound the role that telomerase plays in the initiation and development of tumor and its relationship with tumor cell growth, proliferation, apoptosis, and related pathway molecules; and to display potential targets of antitumor drug for inhibiting the expression, reconstitution, and trafficking of the enzyme. We therefore summarize recent advances in potential telomerase inhibitors for antitumor including natural products, synthetic small molecules, peptides and proteins, which indicate that optimizing the delivery method and drug combination could be of help in a combinatorial drug treatment for tumor. More extensive understanding of the structure, biogenesis, and mechanism of telomerase will provide invaluable information for increasing the efficiency of rational antitumor drug design. PMID:27118336

  2. Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives.

    Science.gov (United States)

    Gaziano, Roberta; Moroni, Gabriella; Buè, Cristina; Miele, Martino Tony; Sinibaldi-Vallebona, Paola; Pica, Francesca

    2016-01-15

    Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice. PMID:26798435

  3. Antitumor effects of the benzophenanthridine alkaloidsanguinarine: Evidence and perspectives

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Historically, natural products have represented a significantsource of anticancer agents, with plant-deriveddrugs becoming increasingly explored. In particular,sanguinarine is a benzophenanthridine alkaloid obtainedfrom the root of Sanguinaria canadensis , and from otherpoppy Fumaria species, with recognized anti-microbial,anti-oxidant and anti-inflammatory properties. Recently,increasing evidence that sanguinarine exibits anticancerpotential through its capability of inducing apoptosisand/or antiproliferative effects on tumor cells, has beenproved. Moreover, its antitumor seems to be due notonly to its pro-apoptotic and inhibitory effects on tumorgrowth, but also to its antiangiogenic and anti-invasiveproperties. Although the precise mechanisms underlyingthe antitumor activity of this compound remain notfully understood, in this review we will focus on themost recent findings about the cellular and molecularpathways affected by sanguinarine, together withthe rationale of its potential application in clinic. Thecomplex of data currently available suggest the potentialapplication of sanguinarine as an adjuvant in the therapyof cancer, but further pre-clinical studies are neededbefore such an antitumor strategy can be effectivelytranslated in the clinical practice.

  4. Jungle Honey Enhances Immune Function and Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Miki Fukuda

    2011-01-01

    Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.

  5. Antitumor efficacy of vaccinia virus-modified tumor cell vaccine

    International Nuclear Information System (INIS)

    The antitumor efficacies of vaccinia virus-modified tumor cell vaccines were examined in murine syngeneic MH134 and X5563 tumor cells. UV-inactivated vaccinia virus was inoculated i.p. into C3H/HeN mice that had received whole body X-irradiation at 150 rads. After 3 weeks, the vaccines were administered i.p. 3 times at weekly intervals. One week after the last injection, mice were challenged i.p. with various doses of syngeneic MH134 or X5563 viable tumor cells. Four methods were used for preparing tumor cell vaccines: X-ray irradiation; fixation with paraformaldehyde for 1 h or 3 months; and purification of the membrane fraction. All four vaccines were effective, but the former two vaccines were the most effective. A mixture of the membrane fraction of untreated tumor cells and UV-inactivated vaccinia virus also had an antitumor effect. These results indicate that vaccine with the complete cell structure is the most effective. The membrane fraction of UV-inactivated vaccinia virus-absorbed tumor cells was also effective. UV-inactivated vaccinia virus can react with not only intact tumor cells but also the purified membrane fraction of tumor cells and augment antitumor activity

  6. Effects of antibiotic treatment of nonlactating dairy cows on antibiotic resistance patterns of bovine mastitis pathogens.

    OpenAIRE

    Berghash, S R; Davidson, J. N.; Armstrong, J. C.; Dunny, G M

    1983-01-01

    Antibiotic resistance patterns of the major groups of bovine mastitis pathogens (Streptococcus agalactiae, other streptococci, Staphylococcus aureus, and Staphylococcus epidermidis) were examined by determining the minimum inhibitory concentration (MIC) of 13 different antibiotics against bacterial isolates from dairy cattle. The bacterial strains were obtained from milk samples from each cow in 21 New York state dairy herd surveys. In 12 herd surveys (high antibiotic-use group), all 365 cows...

  7. Metagenomic exploration of antibiotic resistance in soil.

    Science.gov (United States)

    Monier, Jean-Michel; Demanèche, Sandrine; Delmont, Tom O; Mathieu, Alban; Vogel, Timothy M; Simonet, Pascal

    2011-06-01

    The ongoing development of metagenomic approaches is providing the means to explore antibiotic resistance in nature and address questions that could not be answered previously with conventional culture-based strategies. The number of available environmental metagenomic sequence datasets is rapidly expanding and henceforth offer the ability to gain a more comprehensive understanding of antibiotic resistance at the global scale. Although there is now evidence that the environment constitutes a vast reservoir of antibiotic resistance gene determinants (ARGDs) and that the majority of ARGDs acquired by human pathogens may have an environmental origin, a better understanding of their diversity, prevalence and ecological significance may help predict the emergence and spreading of newly acquired resistances. Recent applications of metagenomic approaches to the study of ARGDs in natural environments such as soil should help overcome challenges concerning expanding antibiotic resistances. PMID:21601510

  8. Race against time to develop new antibiotics

    OpenAIRE

    2011-01-01

    The second part of a series of three news features on antimicrobial resistance looks at how the antibiotics pipeline is drying up while resistance to existing drugs is increasing. Theresa Braine reports.

  9. What Can Be Done about Antibiotic Resistance?

    Science.gov (United States)

    ... WHO issued its Global Strategy for Containment of Antimicrobial Resistance , a document aimed at policy-makers that urges ... of existing antibiotics by modifying them so the bacterial enzymes that cause resistance cannot attack them. Alternately, "decoy" molecules can be ...

  10. Do antibiotics decrease effectiveness of oral contraceptives?

    Science.gov (United States)

    Cottet, C

    1996-09-01

    The number of accidental pregnancies occurring in oral contraceptive (OC) users who are concurrently taking certain antibiotics and antifungal agents exceeds the 1% failure rate associated with OCs, suggesting some form of drug interaction. Two mechanisms of action have been proposed to explain this phenomenon. First, drugs such as rifampin and griseofulvin induce liver enzymes that break down the estrogen and progestin contained in OCs, reducing plasma hormone levels. Second, changes in the intestinal bacterial flora induced by penicillin and tetracycline may reduce the gut's absorption of hormones, also compromising efficacy. Since rifampin and griseofulvin are the medications most frequently implicated in accidental pregnancies in OC users, the induction of liver enzymes is the more probable, potent cause of failure. Although the risk of pregnancy due to OC-antibiotic interactions is extremely small, OC users prescribed antibiotics should be warned to use condoms or spermicides until the antibiotics are discontinued. PMID:9006212

  11. Antibiotics May Blunt Breast-Feeding's Benefits

    Science.gov (United States)

    ... fighting infection because of the immunity offered in mother's milk," said Dr. William Muinos, a pediatric gastroenterologist at Nicklaus Children's Hospital in Miami. Antibiotics kill the bacteria in the gut, he said. "If ...

  12. Too Many People Still Take Unneeded Antibiotics

    Science.gov (United States)

    ... of short-term respiratory conditions, such as colds, bronchitis, sore throats, and sinus and ear infections, the researchers reported. "About half of antibiotic prescriptions for acute respiratory conditions were unnecessary," Fleming-Dutra said. In ...

  13. Get Smart: Know When Antibiotics Work

    Centers for Disease Control (CDC) Podcasts

    2008-09-10

    This podcast answers questions from the public about appropriate antibiotic use.  Created: 9/10/2008 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/15/2008.

  14. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

    Petersen, Michael Mørk; Hettwer, Werner H; Grum-Schwensen, Tomas

    2015-01-01

    conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. RESULTS: We screened 96 patients and enrolled 60 participants......-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. METHODS: We performed a pilot international multi-centre RCT. We used central randomisation to......% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. CONCLUSIONS: It is feasible to conduct a definitive multi-centre RCT of...

  15. Controlling antibiotic resistance in the ICU

    NARCIS (Netherlands)

    Derde, L.P.G.

    2013-01-01

    Patients admitted to intensive care units (ICUs) are frequently colonized with (antibiotic-resistant) bacteria, which may lead to healthcare associated infections. Antimicrobial-resistant bacteria (AMRB), such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (V

  16. Priorities for antibiotic resistance surveillance in Europe

    DEFF Research Database (Denmark)

    Fluit, A. C.; van der Bruggen, J. T.; Aarestrup, Frank Møller; Verhoef, J.; Jansen, W. T. M.

    2006-01-01

    Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitud......Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be...... various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during...... development of antibiotic resistance....

  17. Intravenous to oral antibiotic switch therapy.

    Science.gov (United States)

    Cunha, Burke A.

    2001-05-01

    I.v.-to-p.o. switch therapy has become the mainstay of antibiotic therapy for the majority of patients. I.v.-to-p.o. switch therapy is inappropriate for critically ill patients who require i.v. antibiotic therapy and should not be considered in patients who have the inability to absorb drugs. These exceptions constitute a very small percentage of hospitalized patients for which i.v.-to-p.o. switch therapy is ideal. I.v.-to-p.o. switch therapy is best achieved with antibiotics that have high bioavailability that result in the same blood and tissue concentrations of antibiotic as their intravenous counterpart and have few gastrointestinal side effects. Antibiotics ideal for i.v.-to-p.o. switch programs include chloramphenicol, clindamycin, metronidazole, TMP-SMX, fluconazole, itraconazole, voriconazole, doxycycline, minocycline, levofloxacin, gatifloxacin, moxifloxacin and linezolid. Antibiotics that may be used in i.v.-to-p.o. switch programs that have lower bioavailability but are effective include beta-lactams and macrolides. For antibiotics with no oral formulation, e.g., carbapenems, equivalent coverage must be provided with an oral antibiotic from an unrelated class. Excluding gastrointestinal malabsorptive disorders, disease state is not a determinant of suitability for i.v.-to-p.o. switch programs. I.v.-to-p.o. switch programs should be used in patients with any infectious disease disorder for which there is effective oral therapy and is not limited to certain infectious diseases. Oral absorption of antibiotics is near normal in all but the most critically ill patients. Therefore, even in sick, hospitalized individuals, p.o. therapy is appropriate. I.v-to-p.o. switch therapy has several important advantages including decreasing drug cost (i.v. vs. p.o.), decreasing length of stay permitting earlier discharge and optimal reimbursement and decreasing or eliminating i.v. line phlebitis and sepsis with its cost implications. Clinicians should consider all

  18. Antibiotics Cure Anthrax in Animal Models▿

    OpenAIRE

    Weiss, Shay; Kobiler, David; Levy, Haim; Pass, Avi; Ophir, Yakir; Rothschild, Nili; Tal, Arnon; Schlomovitz, Josef; Altboum, Zeev

    2011-01-01

    Respiratory anthrax, in the absence of early antibiotic treatment, is a fatal disease. This study aimed to test the efficiency of antibiotic therapy in curing infected animals and those sick with anthrax. Postexposure prophylaxis (24 h postinfection [p.i.]) of guinea pigs infected intranasally with Bacillus anthracis Vollum spores with doxycycline, ofloxacin, imipenem, and gentamicin conferred protection. However, upon termination of treatment, the animals died from respiratory anthrax. Combi...

  19. DNA-Aptamers Binding Aminoglycoside Antibiotics

    OpenAIRE

    Nadia Nikolaus; Beate Strehlitz

    2014-01-01

    Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminog...

  20. Intensive Care Unit Infections and Antibiotic Use

    OpenAIRE

    Ayşegül Yeşilkaya; Hande Arslan

    2011-01-01

    Burn wound infections is the leading cause of morbidity and mortality in burn trauma patients. Although burn wound is sterile at the beginning, because of risk factors such as prolonged hospital stay, immunesuppression and burn affecting large body surface area, colonisation firstly with Staphylococcus aureus and then Pseudomonas aeruginosa will occur later. Delay in wound closure and treatment with broad-spectrum antibiotic will result wound colonisation with antibiotic-resistant bacteria. T...

  1. Cooperative Electrostatic Polymer-Antibiotic Nanoplexes

    OpenAIRE

    Vadala, Timothy Patrick

    2010-01-01

    Many pathogenic bacteria can enter phagocytic cells and replicate in them, and these intracellular bacteria are difficult to treat because the recommended antibiotics do not transport into the cells efficiently. Examples include food-borne bacteria such as Salmonella and Listeria as well as more toxic bacteria such as Brucella and the Mycobacteria that lead to tuberculosis. Current treatments utilize aminoglycoside antibiotics that are polar and positively charged and such drugs do not ente...

  2. Multiple antibiotic resistance in Stenotrophomonas maltophilia.

    OpenAIRE

    Alonso, A.; Martínez, J L

    1997-01-01

    A cryptic multidrug resistance (MDR) system in Stenotrophomonas maltophilia, the expression of which is selectable by tetracycline, is described. Tetracycline resistance was the consequence of active efflux of the antibiotic, and it was associated with resistance to quinolones and chloramphenicol, but not to aminoglycosides or beta-lactam antibiotics. MDR is linked to the expression of an outer membrane protein (OMP54) both in a model system and in multidrug-resistant clinical isolates.

  3. Antibiotics promote aggregation within aquatic bacterial communities

    OpenAIRE

    Corno, Gianluca; Coci, Manuela; Giardina, Marco; Plechuk, Sonia; Campanile, Floriana; Stefani, Stefania

    2014-01-01

    The release of antibiotics (AB) into the environment poses several threats for human health due to potential development of AB-resistant natural bacteria. Even though the use of low-dose antibiotics has been promoted in health care and farming, significant amounts of AB are observed in aquatic environments. Knowledge on the impact of AB on natural bacterial communities is missing both in terms of spread and evolution of resistance mechanisms, and of modifications of community composition and ...

  4. Antibiotics promote aggregation within aquatic bacterial communities

    OpenAIRE

    ManuelaCoci; MarcoGiardina

    2014-01-01

    The release of antibiotics (AB) into the environment poses several threats for human health due to potential development of ABresistant natural bacteria. Even though the use of low-dose antibiotics has been promoted in health care and farming, significant amounts of AB are observed in aquatic environments. Knowledge on the impact of AB on natural bacterial communities is missing both in terms of spread and evolution of resistance mechanisms, and of modifications of community composition and p...

  5. Modulation of RNA function by aminoglycoside antibiotics.

    OpenAIRE

    Schroeder, R; Waldsich, C; Wank, H

    2000-01-01

    One of the most important families of antibiotics are the aminoglycosides, including drugs such as neomycin B, paromomycin, gentamicin and streptomycin. With the discovery of the catalytic potential of RNA, these antibiotics became very popular due to their RNA-binding capacity. They serve for the analysis of RNA function as well as for the study of RNA as a potential therapeutic target. Improvements in RNA structure determination recently provided first insights into the decoding site of the...

  6. Update on the Management of Antibiotic Allergy

    OpenAIRE

    Thong, Bernard Yu-Hor

    2010-01-01

    Drug allergy to antibiotics may occur in the form of immediate or non-immediate (delayed) hypersensitivity reactions. Immediate reactions are usually IgE-mediated whereas non-immediate hypersensitivity reactions are usually non-IgE or T-cell mediated. The clinical manifestations of antibiotic allergy may be cutaneous, organ-specific (e.g., blood dyscracias, hepatitis, interstitial nephritis), systemic (e.g., anaphylaxis, drug induced hypersensitivity syndrome) or various combinations of these...

  7. Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria.

    Science.gov (United States)

    Bennett, P M

    2008-03-01

    Bacteria have existed on Earth for three billion years or so and have become adept at protecting themselves against toxic chemicals. Antibiotics have been in clinical use for a little more than 6 decades. That antibiotic resistance is now a major clinical problem all over the world attests to the success and speed of bacterial adaptation. Mechanisms of antibiotic resistance in bacteria are varied and include target protection, target substitution, antibiotic detoxification and block of intracellular antibiotic accumulation. Acquisition of genes needed to elaborate the various mechanisms is greatly aided by a variety of promiscuous gene transfer systems, such as bacterial conjugative plasmids, transposable elements and integron systems, that move genes from one DNA system to another and from one bacterial cell to another, not necessarily one related to the gene donor. Bacterial plasmids serve as the scaffold on which are assembled arrays of antibiotic resistance genes, by transposition (transposable elements and ISCR mediated transposition) and site-specific recombination mechanisms (integron gene cassettes).The evidence suggests that antibiotic resistance genes in human bacterial pathogens originate from a multitude of bacterial sources, indicating that the genomes of all bacteria can be considered as a single global gene pool into which most, if not all, bacteria can dip for genes necessary for survival. In terms of antibiotic resistance, plasmids serve a central role, as the vehicles for resistance gene capture and their subsequent dissemination. These various aspects of bacterial resistance to antibiotics will be explored in this presentation. PMID:18193080

  8. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

    Science.gov (United States)

    Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

    2011-11-01

    The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria. PMID:22029522

  9. Identification of Antibiotic Use Pattern as an Effort to Control Antibiotic Resistance

    OpenAIRE

    Ivan S. Pradipta; Ellin Febrina; Muhammad H. Ridwan; Rani Ratnawati

    2012-01-01

    The objective of this study is to determine quantity and pattern of antibiotic use in hospitalized patients at one of Bandung’s private hospital that can give benefit in control of antibiotic resistance and procurement planning of antibiotic. Data of antibiotic consumption were obtained from hospital pharmacy department on February–September 2011. Data were processed using the ATC/DDD and DU90% method. There were 390,98 DDD/100 bed days and 381,34 DDD/100 bed days total of an-tbiotic use i...

  10. Multiple strategies to activate gold nanoparticles as antibiotics

    Science.gov (United States)

    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.

  11. Transfer of antibiotic resistant bacteria from animals to man

    DEFF Research Database (Denmark)

    Wegener, Henrik Caspar; Aarestrup, Frank Møller; Gerner-Smidt, P.; Bager, Flemming

    Antibiotic resistance develops in zoonotic bacteria in response to antibiotics used in food animals. A close association exists between the amounts of antibiotics used and the levels of resistance observed. The classes of antibiotics routinely used for treatment of human infections are also used ...

  12. Reducing Parental Demand for Antibiotics by Promoting Communication Skills

    Science.gov (United States)

    Alder, Stephen C.; Trunnell, Eric P.; White, George L., Jr.; Lyon, Joseph L.; Reading, James P.; Samore, Matthew H.; Magill, Michael K.

    2005-01-01

    Antibiotic-resistant strains of bacteria are continuing to emerge as high rates of antibiotic use persist. Children are among the highest users of antibiotics, with parents influencing physician decision-making regarding antibiotic prescription. An intervention based on Social Cognitive Theory (SCT) to reduce parents' expectations for antibiotics…

  13. Patterns of antibiotic use in the community in Denmark

    NARCIS (Netherlands)

    Muscat, Mark; Monnet, Dominique L.; Klemmensen, Thomas; Grigoryan, Larissa; Jensen, Maria Hummelshoj; Andersen, Morten; Haaijer-Ruskamp, Flora M.

    2006-01-01

    A cross-sectional descriptive population survey was conducted in 2003 to examine epidemiological characteristics of antibiotic use in the community in Denmark and particularly in the area of self-medication with antibiotics. Self-medication with antibiotics was rare in Denmark. 97% of antibiotics us

  14. Necessity of Antibiotics following Simple Exodontia.

    Science.gov (United States)

    Yousuf, Waqas; Khan, Moiz; Mehdi, Hasan; Mateen, Sana

    2016-01-01

    Introduction. The aim of our study is to assess the need for postoperative antibiotics following simple exodontia and determine its role in minimizing patient discomfort and postoperative complications. Material and Methods. All the patients undergoing simple extractions were grouped into two categories: Group 1, patients receiving antibiotics, and Group 2, patients receiving no antibiotics. Patients were recalled on the sixth day to assess postoperative complications. On recall, patients were evaluated for signs of persistent inflammation and signs of dry socket. Presence of persistent inflammation and/or suppuration on the 6th day was considered as wound infection. Results. A total of 146 patients were included in this study. Out of the total sample, 134 (91.8%) presented with no postoperative complications and 12 (8.2%) had postoperative complications, out of which 11 (7.5%) patients presented with dry socket (alveolar osteitis), 5 (3.4%) in the antibiotic group and 6 (4.1%) in the nonantibiotic group. Only 1 patient (0.7%) was reported with infection of the extraction socket in the nonantibiotic group, whereas no case of infection was found in the antibiotic group. Conclusion. Antibiotics are not required after simple extractions in patients who are not medically comprised nor do they have any role in preventing postoperative complications. PMID:27110426

  15. ADJUNCTIVE USE OF ANTIBIOTICS IN PERIODONTAL THERAPY

    Directory of Open Access Journals (Sweden)

    Ece Barça

    2015-10-01

    Full Text Available Periodontal diseases are infectious diseases with a mixed microbial aetiology and marked inflammatory response leading to destruction of underlying tissue. Periodontal therapy aims to eliminate pathogens associated with the disease and attain periodontal health. Periodontitis is generally treated by nonsurgical mechanical debridement and regular periodontal maintenance care. Periodontal surgery may be indicated for some patients to improve access to the root surface; however, mechanical debridement alone may not be helpful in all cases. In such cases, adjunctive systemic antibiotic therapy remains the treatment of choice. It can reach microorganisms at the base of the deep periodontal pockets and furcation areas via serum, and also affects organisms residing within gingival epithelium and connective tissue. This review aims to provide an update on clinical issues regarding when and how to prescribe systemic antibiotics in periodontal therapy. The points discussed are the mode of antibiotic action, susceptible periodontal pathogens, antibiotic dosage, antibiotic use in treatment of periodontal disease, and mechanism of bacterial resistance to each antibiotic.

  16. DNA-Aptamers Binding Aminoglycoside Antibiotics

    Directory of Open Access Journals (Sweden)

    Nadia Nikolaus

    2014-02-01

    Full Text Available Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

  17. Squalamine: an aminosterol antibiotic from the shark.

    Science.gov (United States)

    Moore, K S; Wehrli, S; Roder, H; Rogers, M; Forrest, J N; McCrimmon, D; Zasloff, M

    1993-02-15

    In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias. This water-soluble antibiotic, which we have named squalamine, exhibits potent bactericidal activity against both Gram-negative and Gram-positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. The chemical structure of the antibiotic 3 beta-N-1-(N-[3-(4-aminobutyl)]- 1,3-diaminopropane)-7 alpha,24 zeta-dihydroxy-5 alpha-cholestane 24-sulfate has been determined by fast atom bombardment mass spectroscopy and NMR. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with spermidine. The discovery of squalamine in the shark implicates a steroid as a potential host-defense agent in vertebrates and provides insights into the chemical design of a family of broad-spectrum antibiotics. PMID:8433993

  18. Mycobacterium abscessus: a new antibiotic nightmare.

    Science.gov (United States)

    Nessar, Rachid; Cambau, Emmanuelle; Reyrat, Jean Marc; Murray, Alan; Gicquel, Brigitte

    2012-04-01

    The intrinsic and acquired resistance of Mycobacterium abscessus to commonly used antibiotics limits the chemotherapeutic options for infections caused by these mycobacteria. Intrinsic resistance is attributed to a combination of the permeability barrier of the complex multilayer cell envelope, drug export systems, antibiotic targets with low affinity and enzymes that neutralize antibiotics in the cytoplasm. To date, acquired resistance has only been observed for aminoglycosides and macrolides, which is conferred by mutations affecting the genes encoding the antibiotic targets (rrs and rrl, respectively). Here we summarize previous and recent findings on the resistance of M. abscessus to antibiotics in light of what has been discovered for other mycobacteria. Since we can now distinguish three groups of strains belonging to M. abscessus (M. abscessus sensu stricto, Mycobacterium massiliense and Mycobacterium bolletii), studies on antibiotic susceptibility and resistance should be considered according to this new classification. This review raises the profile of this important pathogen and highlights the work needed to decipher the molecular events responsible for its extensive chemotherapeutic resistance. PMID:22290346

  19. SELF MEDICATION PATTERN AMONG DENTISTS WITH ANTIBIOTICS

    Directory of Open Access Journals (Sweden)

    Shubha

    2013-11-01

    Full Text Available Self medication with antibiotics has become a common practice among people, and more so among those with medical background. Dentists are one group who have kno wledge and accessibility to antibiotics. Hence this study was aimed at knowing the prevalence of self medication with antibiotics among dentists reasons for not visiting the physician. RESULT: Prevalence rate of self medication among dentist was 78.18%. Mo st common cause for self medication were common cold, tooth ache and sore throat. Most common antibiotic used was azithromycin next to ampicillin. Most common reason for not visiting doctor was that participants were themselves a doctor. CONCLUSION: Though dentists have knowledge about antibiotics, knowledge on appropriate usage of antibiotics is poor. This may have a bad impact on practice. Hence they have to overcome the ego and take proper advice from physician which may help the community in curbing ant ibiotic resistance The only limitation of the study was small sample size as dentists from only two colleges were considered. There is a need for study in large number of population.

  20. From antiseptics to antibiotics – and back?

    Directory of Open Access Journals (Sweden)

    Assadian, Ojan

    2007-09-01

    Full Text Available There is no straight line to trace the trajectory of antiseptics; rather, this has been manifested more as a fluctuating line, a backwards and forwards movement, seen in the wake of major discoveries but of colossal mistakes too. While today no one would allow their prophylactic policies to be guided by miasma or contagia, there continues to be some uncertainly about how to manage anti-infectives effectively even today. When in 1941 the first human being was successfully treated with penicillin, interest in antiseptics gradually waned. From that time onwards, everything was treated with antibiotics, unleashing a race for the discovery of novel antibiotics, as witnessed decades earlier in the case of antiseptics. The significance of antiseptics declined to such an extent that among physicians they were associated merely with cleaning agents or sanitary disinfection. Today, at the beginning of the 21st century we know that the euphoria generated by antibiotics was just another station along the pathway of discoveries. Bacterial infections and new, hitherto unknown infectious diseases continue to play a major role. Several viral infections continue to be refractory to successful treatment and bacterial antibiotic resistance has become a problem worldwide. The most effective countermeasures no longer entail only the development of new antibiotics but above all responsible management of antibiotics and strict observance of infection control measures in the hospital setting. Set against that background, interest in antiseptics has been rekindled. In that spirit we can look eagerly forward over the coming years to further developments in antisepsis.

  1. Antibiotic prescribing policy and Clostridium difficile diarrhoea.

    LENUS (Irish Health Repository)

    O'Connor, K A

    2012-02-03

    BACKGROUND: Broad-spectrum antibiotics, particularly intravenous cephalosporins, are associated with Clostridium difficile diarrhoea. Diarrhoea due to C. difficile is a growing problem in hospitals, especially among elderly patients. AIM: To establish whether changing an antibiotic policy with the aim of reducing the use of injectable cephalosporins leads to a reduction in the incidence of C. difficile diarrhoea in elderly patients. DESIGN: Retrospective analysis. METHODS: A group of patients who were subject to the new antibiotic policy from the period following July 2000, were compared with patients who were admitted prior to July 2000 and were not subject to the new policy. Infections, antibiotic prescriptions and mortality rates were determined from case notes, and C. difficle diarrhoea rates from microbiological data. RESULTS: Intravenous cephalosporin use fell from 210 to 28 defined daily doses (p < 0.001) following the change in antibiotic policy, with a corresponding increase in piperacillin-tazobactam (p < 0.001) and moxifloxacin (p < 0.001) use. The new policy led to a significant reduction in C. difficile diarrhoea cases. The relative risk of developing C. difficile infection with the old policy compared to the new policy was 3.24 (95%CI 1.07-9.84, p = 0.03). DISCUSSION: The antibiotic policy was successfully introduced into an elderly care service. It reduced both intravenous cephalosporin use and C. difficile diarrhoea.

  2. A cell penetrating peptide-integrated and enediyne-energized fusion protein shows potent antitumor activity.

    Science.gov (United States)

    Ru, Qin; Shang, Bo-Yang; Miao, Qing-Fang; Li, Liang; Wu, Shu-Ying; Gao, Rui-Juan; Zhen, Yong-Su

    2012-11-20

    Arginine-rich peptides belong to a subclass of cell penetrating peptides that are taken up by living cells and can be detected freely diffusing inside the cytoplasm and nucleoplasm. This phenomenon has been attributed to either an endocytotic mode of uptake and a subsequent release from vesicles or a direct membrane penetration. Lidamycin is an antitumor antibiotic, which consists of an active enediyne chromophore (AE) and a noncovalently bound apoprotein (LDP). In the present study, a fusion protein (Arg)(9)-LDP composed of cell penetrating peptide (Arg)(9) and LDP was prepared by DNA recombination, and the enediyne-energized fusion protein (Arg)(9)-LDP-AE was prepared by molecular reconstitution. The data in fixed cells demonstrated that (Arg)(9)-LDP could rapidly enter cells, and the results based on fluorescence activated cell sorting indicated that the major route for (Arg)(9)-mediated cellular uptake of protein molecules was endocytosis. (Arg)(9)-LDP-AE demonstrated more potent cytotoxicity against different carcinoma cell lines than lidamycin in vitro. In the mouse hepatoma 22 model, (Arg)(9)-LDP-AE (0.3mg/kg) suppressed the tumor growth by 89.2%, whereas lidamycin (0.05 mg/kg) by 74.6%. Furthermore, in the glioma U87 xenograft model in nude mice, (Arg)(9)-LDP-AE at 0.2mg/kg suppressed tumor growth by 88.8%, compared with that of lidamycin by 62.9% at 0.05 mg/kg. No obvious toxic effects were observed in all groups during treatments. The results showed that energized fusion protein (Arg)(9)-LDP-AE was more effective than lidamycin and would be a promising candidate for glioma therapy. In addition, this approach to manufacturing fusion proteins might serve as a technology platform for the development of new cell penetrating peptides-based drugs. PMID:22982402

  3. A study on recent tendency of anti-tumor herbal acupuncture

    OpenAIRE

    Yoo Hwa-Seung; Lee Yong-Yeon; Cho Jung-Hyo; Lee Yeon-Weol; Son Chang-Gue; Cho Chong-Kwan; Hwang Kyu-Jeong

    2001-01-01

    Objectives: The purpose of this study is to develop and activate anti-tumor herbal acupuncture for cancer patients in South Korea. Methods: We investigated some literatures on anti-tumor herbal acupuncture which is used in South Korea and China, and made diagrams. Results: The results are summarized as follows. Anti-tumor herbal acupuncture is one of the traditional oriental medical method which is effective for cancer patients. In domestic studies, most of herb materials are belong to ...

  4. A Recent Study of Anti-tumor Herbal Acupuncture in Korea

    OpenAIRE

    Hwa-Seung Yoo; Sun-hwi Bang; Chong-Kwan Cho

    2006-01-01

    Objectives : This systematic review summarizes the existing evidence on anti-tumor herbal acupuncture in South Korea. Methods : Literature searches were conducted in four databases. All studies of anti-tumor herbal acupuncture which has been published in South Korea until May, 2006 were included. Data were extracted according to pre-defined criteria by two independent reviewers. Results : We found 73 papers related to anti-tumor herbal acupuncture in South Korea. Seventy of seventy-thre...

  5. Detection of residues antibiotics in food using a microbiological method

    International Nuclear Information System (INIS)

    Antibiotics are effective therapeutic agents because of their property of selective bacterial toxicity which helps controlling infections. Animals, just like humans, can be treated with antibiotics. This use of antibiotics can lead to the development of resistance. Resistant strains may cause severe infections in humans and animals. In addition, antibiotic residues might represent a problem for human health. Our objective is to develop a microbiological method for the detection of antibiotic residues in poultry(muscle, liver,...). For this purpose, antibiotic sensitive bacteria and selective agar media were used. An inhibition growth zone surrounds each of the food samples containing antibiotic residues after a prescribed incubation time. (Author). 23 refs

  6. Magnetic separation of antibiotics by electrochemical magnetic seeding

    International Nuclear Information System (INIS)

    Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

  7. Emergence and dissemination of antibiotic resistance: a global problem.

    Science.gov (United States)

    Choudhury, R; Panda, S; Singh, D V

    2012-01-01

    Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure. PMID:23183460

  8. Magnetic separation of antibiotics by electrochemical magnetic seeding

    Energy Technology Data Exchange (ETDEWEB)

    Ihara, I; Toyoda, K [Department of Agricultural Engineering and Socio Economics, Kobe University, Nada, Kobe 657-8501 (Japan); Beneragama, N; Umetsu, K [Department of Animal Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan)], E-mail: ihara@port.kobe-u.ac.jp

    2009-03-01

    Magnetic separation of several classes of antibiotics was investigated using electrochemical magnetic seeding. Electrocoagulation with a sacrificial anode followed by addition of magnetite particles was applied for the magnetic seeding of antibiotics. With electrochemical magnetic seeding using an iron anode, tetracycline antibiotics (oxytetracycline, chlortetracycline, doxycycline and tetracycline) and cephalosporin antibiotic (cefdinir) were rapidly removed from synthetic wastewater by magnetic separation using a neodymium magnet. Iron and aluminium anodes were suitable for magnetic seeding of the antibiotics. The results indicated that the ability of antibiotics to form strong complex with iron and aluminium allowed the higher removal by magnetic separation. This method would be appropriate for rapid treatment of antibiotics in wastewater.

  9. Interaction between antitumor drug and silver nanoparticles:combined fluorscence and surface enhanced Raman scattering study

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Hong Wang; Zhuyuan Wang; Xuebin Tan; Chunyuan Song; Ruohu Zhang; Jin Li; Yiping Cui

    2009-01-01

    Optical methods and MTT method are used to characterize the antiproliferation effect of antitumor drug 9-aminoacridine (9AA) with and without silver nanoparticles.Intracellular surface enhanced Raman scat tering (SERS) spectra and fluorescent spectra of 9AA indicate the form of 9AA adsorbed on the surface of silver nanoparticles.Although both silver nanoparticles and antitumor drug can inhibit the growth of Hela cells,silver nanoparticles can slow down the antiproliferation effect on Hela cells at low concentration of antitumor drugs.Our experimental results suggest that silver nanoparticles may serve as slow-release drug carriers,which is important in antitumor drug delivery.

  10. Fate of Antibiotics and Antibiotic Resistance during Digestion and Composting: A Review.

    Science.gov (United States)

    Youngquist, Caitlin P; Mitchell, Shannon M; Cogger, Craig G

    2016-03-01

    Antibiotics and antibiotic-resistant bacteria (ARB) enter the environment through municipal and agricultural waste streams and pose a potential risk to human and livestock health through either direct exposure to antibiotic-resistant pathogens or selective pressure on the soil microbial community. This review summarizes current literature on the fate of antibiotics, ARB, and antibiotic resistance genes (ARGs) during anaerobic digestion and composting of manure and wastewater residuals. Studies have shown that removal of antibiotics varies widely during mesophilic anaerobic digestion, even within the same class of antibiotics. Research on ARB shows a wide range of removal under mesophilic conditions, with nearly complete removal under thermophilic conditions. Research on 16 antibiotics in 11 different studies using both bench-scale and farm-scale composting systems demonstrates that composting significantly reduces levels of extractable antibiotics in livestock manure in nearly all cases. Calculated half-lives ranged from 0.9 to 16 d for most antibiotics. There is more limited evidence that levels of ARB are also reduced by composting. Studies of the fate of ARGs show mixed evidence for removal during both mesophilic and thermophilic anaerobic digestion and during thermophilic composting. Antibiotic resistance genes are DNA structures, so they may persist until the DNA structure is degraded, yet the bacterium may have been rendered nonviable long before the DNA is completely degraded. Additional research would be of value to determine optimum anaerobic digestion and composting conditions for removal of ARB and to increase understanding of the fate of ARGs during anaerobic digestion and composting. PMID:27065401

  11. Thiols screened by the neocarzinostatin protein for preserving or detoxifying its bound enediyne antibiotic.

    Science.gov (United States)

    Chi, Hung-Wen; Huang, Chun-Chi; Chin, Der-Hang

    2012-05-14

    Neocarzinostatin is an antibiotic chromoprotein produced by Streptomyces carzinostaticus. Its enediyne-containing chromophore exhibits high DNA cleavage activity and belongs to one of the most potent categories of antitumor agents. The labile chromophore is readily inactivated by environmental thiols including the most abundant glutathione. How the microorganism preserves the secreted antibiotic and at the same time is immune to its toxicity are of interest. Site-directed mutagenesis studies of the neocarzinostatin protein have shown that residues D33 and D99 play primary and secondary roles, respectively, in preserving neocarzinostatin from acidic glutathione whereas D79 and other residues around the opening of the binding cleft have an insignificant effect. Biothiol analyses revealed that cells of S. carzinostaticus produced no glutathione, but instead neutral mycothiol, which is known to serve functions analogous to glutathione. Mycothiol was the only neutral-charged thiol produced by the organism; all other identified biothiols carried at least partial negative charges. When the bacteria were cultured under conditions that stimulated the biosynthesis of neocarzinostatin, the yield of mycothiol increased significantly, which suggests mycothiol-dependent cellular detoxification. Treating neocarzinostatin samples with the cell extract that retained active sulfhydryls led to efficient drug inactivation, which indicates that mycothiol is allowed to approach the protein-bound chromophore. The anionic side-chains of D33 and D99 in the neocarzinostatin protein played two critical roles in a single thiol-screening operation: Preserving the antibiotic for defense and survival by rejecting the ubiquitous glutathione through charge-charge repulsion in the outer-cell environment and detoxifying the toxin in the inner-cell body for self-resistance by accepting the cell-produced neutral mycothiol. PMID:22473745

  12. Preoperative Antibiotics and Mortality in the Elderly

    Science.gov (United States)

    Silber, Jeffrey H.; Rosenbaum, Paul R.; Trudeau, Martha E.; Chen, Wei; Zhang, Xuemei; Lorch, Scott A.; Kelz, Rachel Rapaport; Mosher, Rachel E.; Even-Shoshan, Orit

    2005-01-01

    Objective and Background: It is generally thought that the use of preoperative antibiotics reduces the risk of postoperative infection, yet few studies have described the association between preoperative antibiotics and the risk of dying. The objective of this study was to determine whether preoperative antibiotics are associated with a reduced risk of death. Methods: We performed a multivariate matched, population-based, case-control study of death following surgery on 1362 Pennsylvania Medicare patients between 65 and 85 years of age undergoing general and orthopedic surgery. Cases (681 deaths within 60 days from hospital admission) were randomly selected throughout Pennsylvania using claims from 1995 and 1996. Models were developed to scan Medicare claims, looking for controls who did not die and who were the closest matches to the previously selected cases based on preoperative characteristics. Cases and their controls were identified, and charts were abstracted to define antibiotic use and obtain baseline severity adjustment data. Results: For general surgery, the odds of dying within 60 days were less than half in those treated with preoperative antibiotics within 2 hours of incision as compared with those without such treatment: (odds ratio = 0.44; 95% confidence interval, 0.32–0.60), P < 0.0001). For orthopedic surgery, no significant mortality reduction was observed (OR = 0.85; 95% confidence interval, 0.54–1.32; P < 0.464). Interpretation: Preoperative antibiotics are associated with a substantially lower 60-day mortality rate in elderly patients undergoing general surgery. In patients who appear to be comparable, the risk of death was half as large among those who received preoperative antibiotics. PMID:15973108

  13. Antibiotic treatment affects intestinal permeability and gut microbial composition in Wistar rats dependent on antibiotic class

    DEFF Research Database (Denmark)

    Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera; Linninge, Caroline; Ahrne, Siv; Højberg, Ole; Licht, Tine Rask; Bahl, Martin Iain

    potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (n=12 per group) were dosed by oral gavage with either amoxicillin...

  14. Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture.

    Science.gov (United States)

    Chuah, Li-Oon; Effarizah, M E; Goni, Abatcha Mustapha; Rusul, Gulam

    2016-06-01

    Catfish is one of the most cultivated species worldwide. Antibiotics are usually used in catfish farming as therapeutic and prophylactic agents. In the USA, only oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and florfenicol are approved by the Food Drug Administration for specific fish species (e.g., catfish and salmonids) and their specific diseases. Misuse of antibiotics as prophylactic agents in disease prevention, however, is common and contributes in the development of antibiotic resistance. Various studies had reported on antibiotic residues and/or resistance in farmed species, feral fish, water column, sediments, and, in a lesser content, among farm workers. Ninety percent of the world aquaculture production is carried out in developing countries, which lack regulations and enforcement on the use of antibiotics. Hence, efforts are needed to promote the development and enforcement of such a regulatory structure. Alternatives to antibiotics such as antibacterial vaccines, bacteriophages and their lysins, and probiotics have been applied to curtail the increasing emergence of antibiotic-resistant bacteria due to the imprudent application of antibiotics in aquaculture. PMID:27038482

  15. Characterization of Antibiotics and Antibiotic Resistance Genes on an Ecological Farm System

    Directory of Open Access Journals (Sweden)

    Songhe Zhang

    2015-01-01

    Full Text Available There is a growing concern worldwide about the prevalence of antibiotics and antibiotic resistance genes (ARGs on the farm. In this study, we investigated the distribution of seven antibiotics and ten ARGs in fresh and dried pig feces, in biogas slurry, and in grape-planting soil from an ecological farm. Antibiotics including sulfamethazine, norfloxacin, ofloxacin, tetracycline, oxytetracycline, and chlortetracycline were detected in these samples (except for sulfamethoxazole in dried feces. In general, antibiotics levels in samples were in the sequence: biogas slurry > fresh feces > soil or dried feces. Results of ecological risk assessments revealed that among the seven antibiotics chlortetracycline showed the highest ecological risk. Among the ten ARGs, sulI and tetO were the most prevalent on this ecological farm. There were positive correlations between certain ARGs and the corresponding antibiotics on this ecological farm. Therefore, continuous monitoring of antibiotics and their corresponding ARGs should be conducted in the agroecosystem near the concentrated animal farming operation systems.

  16. Nouws antibiotics test: Validation of a post-screening method for antibiotic residues in kidney

    NARCIS (Netherlands)

    Pikkemaat, M.G.; Oostra-van Dijk, S.; Schouten, J.; Rapallini, M.; Kortenhoeven, L.; Egmond, van H.J.

    2009-01-01

    Anticipating the rise in ‘suspect’ samples caused by the introduction of a more sensitive screening test for the presence of antibiotic residues in slaughter animals, an additional microbial post-screening method was developed. The test comprises four antibiotic group specific test plates, optimized

  17. RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance.

    Science.gov (United States)

    Alam, Md Kausar; Alhhazmi, Areej; DeCoteau, John F; Luo, Yu; Geyer, C Ronald

    2016-03-17

    Antibiotic resistance arises from the maintenance of resistance mutations or genes acquired from the acquisition of adaptive de novo mutations or the transfer of resistance genes. Antibiotic resistance is acquired in response to antibiotic therapy by activating SOS-mediated DNA repair and mutagenesis and horizontal gene transfer pathways. Initiation of the SOS pathway promotes activation of RecA, inactivation of LexA repressor, and induction of SOS genes. Here, we have identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response. These inhibitors potentiate the activity of bactericidal antibiotics, including members of the quinolone, β-lactam, and aminoglycoside families in both Gram-negative and Gram-positive bacteria. They reduce the ability of bacteria to acquire antibiotic resistance mutations and to transfer mobile genetic elements conferring resistance. This study highlights the advantage of including RecA inhibitors in bactericidal antibiotic therapies and provides a new strategy for prolonging antibiotic shelf life. PMID:26991103

  18. Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class

    DEFF Research Database (Denmark)

    Tulstrup, Monica Vera-Lise; Christensen, Ellen Gerd; Carvalho, Vera;

    2015-01-01

    , potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage...

  19. Fate and transport of veterinary antibiotics, antibiotic-resistant bacteria, and antibiotic resistance gene from fields receiving poultry manure during storm events

    Science.gov (United States)

    Antimicrobials are used in production agriculture to treat disease and promote animal growth, but the presence of antibiotics in the environment raises concern about widespread antibiotic resistance. This study documents the occurrence and transport of tylosin, tetracycline, enterococci resistant to...

  20. A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yuan-Wu Chen

    Full Text Available Oral squamous cell carcinoma (OSCC is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

  1. Antibiotic resistance - the interplay between antibiotic use in animals and human beings

    DEFF Research Database (Denmark)

    Singer, R.S.; Finch, R.; Wegener, Henrik Caspar;

    2003-01-01

    levels in people has also come under scrutiny. Antimicrobials are used therapeutically and prophylactically in animals. More controversially, antimicrobials are also used as growth promoters to improve the ability of the animal to convert feed into body mass. Some argue that the impact of use...... meant the problem of antibiotic resistance is fast escalating into a global health crisis. There is no doubt that misuse of these drugs in human beings has contributed to the increasing rates of resistance, but recently the use of antibiotics in food animals and its consequent effect on resistance...... of antibiotics in animals-whether therapeutic or as growth promoters-pales by comparison with human use, and that efforts should be concentrated on the misuse of antibiotics in people. Others warn of the dangers of unregulated and unnecessary use of antibiotics, especially growth promoters in animal husbandry...

  2. Synergistic Antitumor Efficacy of Oncolytic Adenovirus Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Yue-min; QIAN Qi-jun; SONG San-tai; JIANG Ze-fei; ZHANG Qi; QU Yi-mei; SU Chang-qing; ZHAO Chuan-hua; LI Zhi-qiang; GE Fei-jiao

    2007-01-01

    Objective: Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods: We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results: In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion: We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.

  3. Glycosylated antitumor ether lipids: activity and mechanism of action.

    Science.gov (United States)

    Arthur, Gilbert; Bittman, Robert

    2014-05-01

    Glycosylated antitumor ether lipids (GAELs) are distinguished from the alkyllysophospholipids or alkylphosphocholines classes of antitumor ether lipids (AEL) by the presence of a sugar moiety. Non-phosphorus GAELs, the subject of this review, have a sugar moiety in place of the phosphobase found in alkyllysophospholipids. Analogues of non-phosphorus GAELs with glucose, maltose, arabinose, or disaccharide moieties have been synthesized. Non-phosphorus GAELs with monosaccharides have cytotoxic and antiproliferative effects against cancer cells derived from a wide range of tissues, including drug resistant cell lines. The most active compound of this group to date is 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (11), which displays in vitro activity similar to or greater than that of ET-18-OCH3, the AEL "gold" standard. While the detailed molecular mechanism of action of non-phosphorus GAELs is not known, the data indicate that non-phosphorus GAELs are taken up by endocytosis and incorporated into early endosomes. The presence of non-phosphorus GAELs perturbs the maturation of the endocytic vesicles, resulting in the formation of large acidic vacuoles. Cell death appears to be the result of the release of cathepsins from the vacuoles into the cytosol and subsequent activation of a death pathway that is independent of the mitochondria and independent of apoptosis. The ability of these GAELs to kill cells via an apoptosis-independent mechanism makes them prime candidates for development of effective compounds against chemo-resistant tumors and cancer stem cells. The disaccharide-linked GAELs do not have cytotoxic activity but rather inhibit cancer cell motility due to the ability of the compounds to block specific calcium-activated potassium channels in cells. The antitumor activities displayed by these experimental compounds augurs well for their eventual development into clinically useful agents for cancer treatment. PMID:24628233

  4. BIOSYNTHESIS AND PROPERTIES OF ANTIBIOTIC BATUMIN

    Directory of Open Access Journals (Sweden)

    V. V. Klochko

    2014-12-01

    Full Text Available Biosynthesis of antistaphylococcal antibiotic batumin under periodic conditions of Pseudomonas batumici growth has been studied. Antibiotic synthesis in fermenter occurred across the culture growth and achieved its maximal value after 50–55 hours. The active oxygen utilization by the producing strain was observed during 20–55 hours of fermentation with maximum after 40–45 hours. Antibiotic yield was 175–180 mg/l and depended on intensity of aeration. contrast to «freshly isolated» antibiotic after fermentation the long-term kept batumin has shown two identical by molecular mass peaks according to the chromato-mass spectrometric analysis. Taking into account of batumin molecule structure the conclusion has been made that the most probable isomerization type is keto-enolic tautomerism. At the same time batumin is diastereoisomer of kalimantacin A which has the same chemical structure. The optic rotation angle is [α]d25 = +56.3° for kalimantacin and [α]d25 = –13.5° for batumin. The simultaneous P. batumici growth and antibiotic biosynthesis and the ability of this molecule to optical isomerisation and keto-enolic forms formation allow us to suppose that batumin plays a certain role in metabolism of the producing strain.

  5. Utilisation of antibiotic therapy in community practice.

    LENUS (Irish Health Repository)

    McGowan, B

    2008-10-01

    The aim of the study was to identify outpatient antibiotic consumption between Jan 2000 and Dec 2005 through analysis of the HSE-Primary Care Reimbursement Services (PCRS) database as part of the Surveillance of Antimicrobial Resistance in Ireland (SARI) project. Total antibiotic consumption on the PCRS scheme between January 2000 and December 2005 expressed in Defined Daily Dose per 1000 PCRS inhabitants per day increased by 26%. The penicillin group represents the highest consumption accounting for approximately 50% of the total outpatient antibiotic use. Total DIDs for this group increased by 25% between 2000 and 2005. Co-amoxiclav and amoxicillin account for 80% of the total consumption of this group of anti-infectives. With the exception of aminoglycosides and sulfonamides which demonstrated a decrease in DID consumption of 47% and 8% respectively, all other groups of anti-infectives had an increase in DID consumption of greater than 25% during the study period. Antibiotic prescribing data is a valuable tool for assessing public health strategies aiming to optimise antibiotic prescribing.

  6. Antibiotic resistance: are we all doomed?

    Science.gov (United States)

    Collignon, P

    2015-11-01

    Antibiotic resistance is a growing and worrying problem associated with increased deaths and suffering for people. Overall, there are only two factors that drive antimicrobial resistance, and both can be controlled. These factors are the volumes of antimicrobials used and the spread of resistant micro-organisms and/or the genes encoding for resistance. The One Health concept is important if we want to understand better and control antimicrobial resistance. There are many things we can do to better control antimicrobial resistance. We need to prevent infections. We need to have better surveillance with good data on usage patterns and resistance patterns available across all sectors, both human and agriculture, locally and internationally. We need to act on these results when we see either inappropriate usage or resistance levels rising in bacteria that are of concern for people. We need to ensure that food and water sources do not spread multi-resistant micro-organisms or resistance genes. We need better approaches to restrict successfully what and how antibiotics are used in people. We need to restrict the use of 'critically important' antibiotics in food animals and the entry of these drugs into the environment. We need to ensure that 'One Health' concept is not just a buzz word but implemented. We need to look at all sectors and control not only antibiotic use but also the spread and development of antibiotic resistant bacteria - both locally and internationally. PMID:26563691

  7. Antibiotic Prescription Practices Among Children with Influenza.

    Science.gov (United States)

    Nitsch-Osuch, A; Gyrczuk, E; Wardyn, A; Życinska, K; Brydak, L

    2016-01-01

    The important factor in the development of resistance to antibiotics is their overuse, especially for viral respiratory infections. The aim of the study was to find out the frequency of the antibiotic therapy administrated to children with influenza. A total of 114 children younger than 59 months seeking care for the acute respiratory tract infection was enrolled into the study. The patients had influenza-like symptoms: fever > 38 °C, cough, and sore throat of less than 4 days duration. Nasal and pharyngeal swabs were tested for influenza A and B virus with a real-time PCR. Thirty six cases of influenza were diagnosed: 34 of influenza A (H3N2) and 2 of influenza B. The rate of influenza infection was 32 % in the study group. The antibiotic therapy was ordered for 58 % patients with influenza. Antibiotics were given less frequently in the outpatient setting (33 %) compared with the hospitalized patients (93 %) (p clavulanic acid, cefuroxime, and amoxicillin. None of the patients received oseltamivir. Antibiotics were overused, while antivirals were underused among children with influenza. To improve health care quality, more efforts in the diagnosis of influenza and the appropriate use of antimicrobials and antivirals are required. PMID:26801146

  8. Antibiotics in development targeting protein synthesis.

    Science.gov (United States)

    Sutcliffe, Joyce A

    2011-12-01

    The resolution of antibiotic-ribosomal subunit complexes and antibacterial-protein complexes at the atomic level has provided new insights into modifications of clinically relevant antimicrobials and provided new classes that target the protein cellular apparatus. New chemistry platforms that use fragment-based drug design or allow novel modifications in known structural classes are being used to design new antibiotics that overcome known resistance mechanisms and extend spectrum and potency by circumventing ubiquitous efflux pumps. This review provides details on seven antibiotics in development for treatment of moderate-to-severe community-acquired bacterial pneumonia and/or acute bacterial skin and skin structure infections: solithromycin, cethromycin, omadacycline, CEM-102, GSK1322322, radezolid, and tedizolid. Two antibiotics of the oxazolidinone class, PF-02341272 and AZD5847, are being developed as antituberculosis agents. Only three antibiotics that target the protein cellular machinery, TP-434, GSK2251052, and plazomicin, have a spectrum that encompasses multidrug-resistant Gram-negative pathogens. These compounds provide hope for treating key pathogens that cause serious disease in both the community and the hospital. PMID:22191530

  9. NMR studies on antitumor drug candidates, berberine and berberrubine

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Young Wook; Jung, Jin Won; Kang, Mi Ran; Chung, In Kwon; Lee, Weon Tae [Yonsei Univ., Seoul (Korea, Republic of)

    2002-03-01

    Berberine and berberrubine, which display antitumor activity, have also demonstrated distinct enzyme-poisoning activities by stabilizing topoisomerase II-DNA cleavable complexes. The protoberberine berberrubine differs in chemical structure with berberine at only one position, however, it shows a prominent activity different from berberine. Solution structures of berberine and berberrubine determined by NMR spectroscopy are similar, however, the minor structural rearrangement has been observed near 19 methoxy or hydroxyl group. We suggest that the DNA cleavage activities of topoisomerase II poisons could be correlated with both chemical environments and minor structural change together with hydrophobicity of interacting side chains of drugs with DNA molecules.

  10. [Polyacrylates of noble metals as potential antitumor drugs].

    Science.gov (United States)

    Ostrovskaia, L A; Voronkov, M G; Korman, D B; Bliukhterova, N V; Fomina, M M; Rykova, V A; Abzaeva, K A; Zhilitskaia, L V

    2014-01-01

    The antitumor activity of polyacrylates of the noble metals containing argentum (argacryl), aurum (auracryl) and platinum (platacryl) has been studied using experimental murine solid tumor models (Lewis lung carcinoma and Acatol adenocarcinoma). It has been found that polyacrylates of the noble metals are capable of inhibiting tumor development by 50-90% compared to control. Auracryl that inhibites the growth of Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90%, respectively, compared to control is the most efficient among the tested compounds and can be recommended for the further profound preclinical studies. PMID:25707247

  11. Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives.

    Science.gov (United States)

    El-Nassan, Hala Bakr

    2015-04-01

    The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC50 value of 7.24 nM/mL. PMID:24899376

  12. THEORETICAL STUDY OF PODOPHYLLOTOXIN AND QUINOLONE ANALOGUES AS ANTITUMOR DRUGS

    Institute of Scientific and Technical Information of China (English)

    何峰; 戴颖仪; 朱孝峰; 黄爱东; 张翎; 颜少平; 刘宗潮

    2002-01-01

    Objective: To study the active sites of podophyllotoxin derivatives. Methods: Some podophyllotoxin derivatives were analyzed by quantum and mechanics method. Results: Some information was given according to the calculation results about HOMO and LUMO electron density. The C-4 position is the position for effective modification. The B ring and E ring are important active centers. Conclusion: The hole of positive charge in B ring easily combines with an acceptor within the molecular. Some quinolones with similar electronic construction to podophyllotoxin may have antitumor activity.

  13. Tumor Regulatory T Cells Potently Abrogate Antitumor Immunity1

    OpenAIRE

    Liu, Zuqiang; Kim, Jin H.; Falo, Louis D.; You, Zhaoyang

    2009-01-01

    Treg from mice bearing a breast tumor were elevated (tumor Treg). In vitro, whereas tumor Treg ability to inhibit tumor-primed CD4+ T cell activity is comparable to Treg from naïve mice (naïve Treg), only tumor Treg suppress naïve CD8+ T cell activation and DC function. Neither tumor Treg nor naïve Treg can suppress antitumor immunity at the effector phase of the immune response induced by adoptively-transferred tumor-primed CD4+ T cells. This is consistent with the observation that, in this ...

  14. Patents, antibiotics, and autarky in Spain.

    Science.gov (United States)

    Romero De Pablos, Ana

    2014-01-01

    Patents on antibiotics were introduced in Spain in 1949. Preliminary research reveals diversification in the types of antibiotics: patents relating to penicillin were followed by those relating to streptomycin, erythromycin and tetracycline. There was also diversification in the firms that applied for patents: while Merck & Co. Incorporated and Schenley Industries Inc. were the main partners with Spanish antibiotics manufacturers in the late 1940s, this industrial space also included many others, such as Eli Lilly & Company, Abbott Laboratories, Chas. Pfizer & Co. Incorporated, and American Cyanamid Company in the mid-1970s. The introduction of these drugs in Spain adds new elements to a re-evaluation of the autarkic politics of the early years of the Franco dictatorship. PMID:26054209

  15. Tolerance of staphylococci to bactericidal antibiotics.

    Science.gov (United States)

    Vaudaux, Pierre; Lew, Daniel P

    2006-05-01

    Antibiotic therapy for deep-seated staphylococcal infections, especially when they are associated with artificial devices used for orthopedic surgery is often associated with failure. Standard anti-staphylococcal bactericidal antibiotics, such as semi-synthetic penicillins, cephalosporins, or glycopeptides, are effective when given prophylactically in clinical conditions or experimental trials of implant-related infections. However, the efficacy of all anti-staphylococcal agents is seriously diminished on already established implant-related deep-seated infections, which then frequently require surgical implant removal to obtain a cure. The failure of antibiotic therapy to cure established staphylococcal foreign-body infections may arise in part from a broad-spectrum phenotypic tolerance expressed in vivo to different classes of antimicrobial agents. The molecular and physiological mechanisms of this in vivo tolerance remain poorly understood. PMID:16651066

  16. Antibiotics for the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Ogrendik M

    2013-12-01

    Full Text Available Mesut OgrendikDivision Physical Therapy and Rheumatology, Nazilli State Hospital, Nazilli, TurkeyAbstract: Antibiotic treatment for rheumatoid arthritis (RA commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment.Keywords: oral bacteria, treatment, disease-modifying antirheumatic drugs, periodontitis

  17. Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2015-01-01

    Conclusions: Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors. This mHSP/P vaccine exerted greater antitumor effects than did HSP70, HSP60, or tumor lysates alone.

  18. Synthesis and in vitro antitumor activity of new butenolide-containing dithiocarbamates.

    Science.gov (United States)

    Wang, Xiao-Juan; Xu, Hai-Wei; Guo, Lin-Lin; Zheng, Jia-Xin; Xu, Bo; Guo, Xiao; Zheng, Chen-Xin; Liu, Hong-Min

    2011-05-15

    Three series of butenolide-containing dithiocarbamates were designed and synthesized. Their anti-tumor activity in vitro was evaluated. Among them compound I-14 exhibited broad spectrum anti-cancer activity against five human cancer cell lines with IC(50) dithiocarbamate side chains on the C-3 position of butenolide was crucial for anti-tumor activity. PMID:21486694

  19. Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection

    Science.gov (United States)

    Surawicz, Christina M.

    Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.

  20. Efforts to slacken antibiotic resistance: Labeling meat products from animals raised without antibiotics in the United States.

    Science.gov (United States)

    Centner, Terence J

    2016-09-01

    As bacteria and diseases spread due to climatic change, greater amounts of antibiotics will be used thereby exacerbating the problem of antibiotic resistance. To help slacken the development of resistant bacteria, the medical community is attempting to reduce unnecessary and excessive usage of antibiotics. One of the targets is the use of antibiotics for enhancing animal growth and promoting feed efficiency in the production of food animals. While governments can adopt regulations prohibiting nontherapeutic uses of antibiotics in food animals and strategies to reduce antibiotic usage, another idea is to publicize when antibiotics are used in food animal production by allowing labeled meat products. This paper builds upon existing labeling and marketing efforts in the United States to show how a government can develop a verified antibiotic-free labeling program that would allow consumers to purchase meat products from animals that had never received antibiotics. PMID:27236477

  1. Antibiotics, probiotics and prebiotics in IBD.

    Science.gov (United States)

    Bernstein, Charles N

    2014-01-01

    The dysbiosis theory of inflammatory bowel disease (IBD) posits that there is an alteration in the gut microbiome as an important underpinning of disease etiology. It stands to reason then, that administering agents that could impact on the balance of microbes on the gut could be impactful on the course of IBD. Herein is a review of the controlled trials undertaken to assess the use of antibiotics that would kill or suppress potentially injurious microbes, probiotics that would overpopulate the gut with potentially beneficial microbes or prebiotics that provide a metabolic substrate that enhances the growth of potentially beneficial microbes. With regard to antibiotics, the best data are for the use of nitroimadoles postoperatively in Crohn's disease (CD) to prevent disease recurrence. Otherwise, the data are limited with the regard to any lasting benefit of antibiotics sustaining remission in either CD or ulcerative colitis (UC). A recent meta-analysis concluded that antibiotics are superior to placebo at inducing remission in CD or UC, although the meta-analysis grouped a variety of antibiotics with different spectra of activity. Despite the absence of robust clinical trial data, antibiotics are widely used to treat perineal fistulizing CD and acute and chronic pouchitis. Probiotics have not been shown to have a beneficial role in CD. However, Escherichia coli Nissle 1917 has comparable effects to low doses of mesalamine in maintaining remission in UC. VSL#3, a combination of 8 microbes, has been shown to have an effect in inducing remission in UC and preventing pouchitis. Prebiotics have yet to be shown to have an effect in any form of IBD, but to date controlled trials have been small. The use of antibiotics should be balanced against the risks they pose. Even probiotics may pose some risk and should not be assumed to be innocuous especially when ingested by persons with a compromised epithelial barrier. Prebiotics may not be harmful but may cause

  2. Antibiotic residues in milk from Moldavia, Romania

    OpenAIRE

    Gheorghe Solcan; Ovidiu Popescu; Andrei C. Grădinaru

    2011-01-01

    The present paper is a study based on the determination of antibiotic residues in milk samplescollected from farms in the NE Romania (Moldavia). Contamination seasonality and the correlations withSCC and TBC values were investigated. Out of 2785 total milk samples, 124 were positive (+) (4.45%)and 130 samples were uncertain (±) (4.67%). The presence of antibiotics was confirmed in 109 positive(+) samples (87.9%) and 24 uncertain (±) samples (18.46%), the difference being false-positivereactio...

  3. Effects of probiotics and antibiotics on biofilms

    OpenAIRE

    Pradeep, B.; Pandey, P K; S. Ayyappan

    2003-01-01

    Experiments were conducted to study the effects of probiotics and antibiotics on 3-months old biofilms formed on three different substrates, namely glass, granite and fiberglass reinforced plastic. The variations in heterotrophic bacterial populations associated with biofilms were monitored for a period of one month after one-time application of the probiotic Biogreen (Gee Key Marine Pvt. Ltd, Chennai) at 0.2 mg lˉ¹ and the antibiotic tetracycline at 1.0 mg lˉ¹. The variations in heterotrophi...

  4. Triple antibiotic paste in root canal therapy

    Directory of Open Access Journals (Sweden)

    Rangasamy Vijayaraghavan

    2012-01-01

    Full Text Available The success of the endodontic treatment depends on the microbial suppression in the root canal and periapical region. Endodontic instrumentation alone cannot achieve a sterile condition. With the advent of non-instrumentation endodontic treatment and lesion sterilization and tissue repair, local application of antibiotics has been investigated. Triple antibiotic paste (TAP containing metronidazole, ciprofloxacin, and minocycline has been reported to be a successful regimen in controlling the root canal pathogen and in managing non-vital young permanent tooth. This paper reviews the existing literature on biocompatibility, efficiency, drawbacks of TAP in endodontic therapy and pulp revascularization.

  5. How to Fight Back Against Antibiotic Resistance

    DEFF Research Database (Denmark)

    Dantas, Gautam; Sommer, Morten

    2014-01-01

    Mapping the exchange of genes between pathogens and nonpathogens offers new ways to understand and manage the spread of drug-resistant strains. In reality, the development of new antibiotics is only part of the solution, as pathogens will inevitably develop resistance to even the most promising new...... compounds. To save the era of antibiotics, scientists must figure out what it is about bacterial pathogens that makes resistance inevitable. Although most studies on drug resistance have focused on disease causing pathogens, recent efforts have shifted attention to the resistomes of nonpathogenic bacteria...

  6. Antitumor activity of levan polysaccharides from selected microorganisms.

    Science.gov (United States)

    Yoo, Sang-Ho; Yoon, Eun Ju; Cha, Jaeho; Lee, Hyeon Gyu

    2004-04-01

    Levans were isolated from the cultures of Gluconoacetobacter xylinus (G-levan; Mw = 40,000), Microbacterium laevaniformans (M; Mw = 710,000), Rahnella aquatilis (R; Mw = 380,000), and Zymomonas mobilis (Z; Mw = 570,000). The levans were composed mainly of fructose residues when analyzed by TLC and HPLC, and their main backbones were beta-(2,6)-linkages with beta-(2,1)-branches by GC-MS and NMR. In the in vitro antitumor activity test of the levans against eight different tumor cell lines, relatively stronger activity was observed from the SNU-1 and HepG2. The M- (52.54-62.05%) and R-levan (52.15-58.58%) showed the significantly high activity against SNU-1, while M-levan showed the highest (49.93-61.82%) activity against HepG2. During the in vivo analysis of inhibitory activity of the levans against Sarcoma-180 growth, M-, R- and Z-levans showed strong antitumor activity (average 66%) but G-levan (42%) had significantly lower activity. PMID:15178007

  7. Antitumor activity of C-phycocyanin from Arthronema africanum (Cyanophyceae

    Directory of Open Access Journals (Sweden)

    Elena Gardeva

    2014-10-01

    Full Text Available Pure C-phycocyanin (C-PC was isolated from Arthronema africanumto evaluate its potential antitumor effects in vivo and in vitro. Experimental myeloid Graffi tumor in hamsters was used as a model. The cell proliferation assay showed that C-PC treatment, at concentration of 100 µg mL-1 for 24 h, significantly inhibited the growth of Graffi tumor cells (51.4% viability. Agarose gel electrophoresis of the genomic DNA of treated cells displayed time-and concentration-dependent fragmentation pattern, typical for apoptosis. Apoptotic process was related to the increase in cellular manganese and copper/zinc superoxide dismutases and glutathione reductase activities, coupled with a low catalase activity. In vivo C-PC administration (5.0 mg kg-1 body weight suppressed the tumor transplantability and growth, while the mean survival time of the tumor-bearing hamsters was increased. The results revealed promising antitumor activities of A. africanum C-PC and suggested the potential of this natural biliprotein pigment for future pharmacological and medical applications. The study provided new data on the mechanism of the C-PC induced apoptosis in which the imbalance of antioxidant enzymes that favoured hydrogen peroxide accumulation might play a leading role.

  8. Antitumor effect of sonodynamically activated pyrrolidine tris-acid fullerene

    Science.gov (United States)

    Iwase, Yumiko; Nishi, Koji; Fujimori, Junya; Fukai, Toshio; Yumita, Nagahiko; Ikeda, Toshihiko; Chen, Fu-shin; Momose, Yasunori; Umemura, Shin-ichiro

    2016-07-01

    In this study, the sonodynamically induced antitumor effect of pyrrolidine tris-acid fullerene (PTF) was investigated. Sonodynamically induced antitumor effects of PTF by focused ultrasound were investigated using isolated sarcoma-180 cells and mice bearing ectopically-implanted colon 26 carcinoma. Cell damage induced by ultrasonic exposure was enhanced by 5-fold in the presence of 80 µM PTF. The combined treatment of ultrasound and PTF suppressed the growth of the implanted colon 26 carcinoma. Ultrasonically induced 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (4oxoTEMPO) production in the presence and absence of PTF was assessed, and it was shown that 80 µM PTF enhanced 4oxoTEMPO production as measured by ESR spectroscopy. Histidine, a reactive oxygen scavenger, significantly reduced cell damage and 4oxoTEMPO generation caused by ultrasonic exposure in the presence of PTF. These results suggest that singlet oxygen is likely to be involved in the ultrasonically induced cell damage enhanced by PTF.

  9. Replicase-based plasmid DNA shows anti-tumor activity

    Directory of Open Access Journals (Sweden)

    Weiss Richard

    2011-03-01

    Full Text Available Abstract Background Double stranded RNA (dsRNA has multiple anti-tumor mechanisms. Over the past several decades, there have been numerous attempts to utilize synthetic dsRNA to control tumor growth in animal models and clinical trials. Recently, it became clear that intracellular dsRNA is more effective than extracellular dsRNA on promoting apoptosis and orchestrating adaptive immune responses. To overcome the difficulty in delivering a large dose of synthetic dsRNA into tumors, we propose to deliver a RNA replicase-based plasmid DNA, hypothesizing that the dsRNA generated by the replicase-based plasmid in tumor cells will inhibit tumor growth. Methods The anti-tumor activity of a plasmid (pSIN-β that encodes the sindbis RNA replicase genes (nsp1-4 was evaluated in mice with model tumors (TC-1 lung cancer cells or B16 melanoma cells and compared to a traditional pCMV-β plasmid. Results In cell culture, transfection of tumor cells with pSIN-β generated dsRNA. In mice with model tumors, pSIN-β more effectively delayed tumor growth than pCMV-β, and in some cases, eradicated the tumors. Conclusion RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth.

  10. Replicase-based plasmid DNA shows anti-tumor activity

    International Nuclear Information System (INIS)

    Double stranded RNA (dsRNA) has multiple anti-tumor mechanisms. Over the past several decades, there have been numerous attempts to utilize synthetic dsRNA to control tumor growth in animal models and clinical trials. Recently, it became clear that intracellular dsRNA is more effective than extracellular dsRNA on promoting apoptosis and orchestrating adaptive immune responses. To overcome the difficulty in delivering a large dose of synthetic dsRNA into tumors, we propose to deliver a RNA replicase-based plasmid DNA, hypothesizing that the dsRNA generated by the replicase-based plasmid in tumor cells will inhibit tumor growth. The anti-tumor activity of a plasmid (pSIN-β) that encodes the sindbis RNA replicase genes (nsp1-4) was evaluated in mice with model tumors (TC-1 lung cancer cells or B16 melanoma cells) and compared to a traditional pCMV-β plasmid. In cell culture, transfection of tumor cells with pSIN-β generated dsRNA. In mice with model tumors, pSIN-β more effectively delayed tumor growth than pCMV-β, and in some cases, eradicated the tumors. RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth

  11. Electroporation: A New Approach Enhancing Antitumor Effects of Cytoxan

    Institute of Scientific and Technical Information of China (English)

    Yang Kong(杨孔); Yue Bisong; Wang Zishu; Zou Fangdong; Zhao Ermi; Wang Baoyi; Zhang Hong

    2003-01-01

    Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (Eps) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. In vitro, with scan electromicroscope (SEM) and Trypan blue staining examination, the best parameter of Eps of electroporation is studied by the S-180 cells exposed to EP with various voltages, pulses , capacitance. The best parameter of EP of electroporation is 600V/cm, 6 pulses, 10 μF. In the in vivo study, ECT is studied with the Cytoxan (CTX) injected directly into the tumor followed immediately by a local EP at the tumor site. Four parameters, which include the tumor inhibitory ratio, the curing ratio and the vas capillare of tumor, the tumor's histopathological characteristics are determined and compared among the ECT group, the control group, the EP-only group and the drug-only group. The results indicate that the antitumor effect of CTX is significantly enhanced by electroporation.

  12. Use of antibiotic agents in a large teaching hospital. The impact of Antibiotic Guidelines.

    Science.gov (United States)

    Harvey, K; Stewart, R; Hemming, M; Moulds, R

    1983-09-01

    Three surveys of antibiotic use have been conducted at The Royal Melbourne Hospital. The first was conducted in 1978, before the introduction of the booklet, Antibiotic Guidelines; the second was conducted eight months after, and the most recent, four years after, its distribution. In 1978, 30% of 563 patients surveyed were receiving antibiotic therapy; this proportion declined to 28% of 967 patients studied in 1982. At the beginning of 1978, 52% of all treatments audited were judged appropriate when compared with those recommended in the Guidelines; this proportion rose to 72% in the second survey and was maintained at 70% in 1982. Certain inappropriate prescribing patterns persisted, such as the use of amoxycillin for the treatment of primary pneumonia, surgical antibiotic prophylaxis which was started too late, and the failure to simplify therapy when the results of microbiological investigations became available. Antibiotic guidelines facilitate the auditing of antibiotic usage and aid rational prescribing. Nevertheless, additional measures appear necessary if specific patterns of misuse of antibiotic agents are to be corrected. PMID:6678384

  13. Sensitivity of antibiotic resistant and antibiotic susceptible Escherichia coli, Enterococcus and Staphylococcus strains against ozone.

    Science.gov (United States)

    Heß, Stefanie; Gallert, Claudia

    2015-12-01

    Tolerance of antibiotic susceptible and antibiotic resistant Escherichia coli, Enterococcus and Staphylococcus strains from clinical and wastewater samples against ozone was tested to investigate if ozone, a strong oxidant applied for advanced wastewater treatment, will affect the release of antibiotic resistant bacteria into the aquatic environment. For this purpose, the resistance pattern against antibiotics of the mentioned isolates and their survival after exposure to 4 mg/L ozone was determined. Antibiotic resistance (AR) of the isolates was not correlating with higher tolerance against ozone. Except for ampicillin resistant E. coli strains, which showed a trend towards increased resistance, E. coli strains that were also resistant against cotrimoxazol, ciprofloxacin or a combination of the three antibiotics were similarly or less resistant against ozone than antibiotic sensitive strains. Pigment-producing Enterococcus casseliflavus and Staphylococcus aureus seemed to be more resistant against ozone than non-pigmented species of these genera. Furthermore, aggregation or biofilm formation apparently protected bacteria in subsurface layers from inactivation by ozone. The relatively large variance of tolerance against ozone may indicate that resistance to ozone inactivation most probably depends on several factors, where AR, if at all, does not play a major role. PMID:26608763

  14. [Primary research on anti-tumor activity of panaxadiol fatty acid esters].

    Science.gov (United States)

    Zhang, Chun-Hong; Zhang, Lian-Xue; Li, Xiang-Gao; Gao, Yu-Gang; Liu, Ya-Jing

    2006-11-01

    For making use of Ginseng resources and finding new anti-tumor drugs, the anti-tumor activity of three kinds of new panaxadiol fatty acid ester derivates: 3beta-acetoxy panaxadiol (I), 3beta-palmitic acid aceloxy panaxadiol (II), 3beta-octadecanoic acid aceloxy panaxadiol (Ill) and panaxaiol were compared through the method of cell stain and counting. Tumor cell was Vero cell line. Positive control was 5-FU. Blank was RPM11640 culture medium. Negative control was RPM11640 culture medium and the solvent for subjected drugs. The result showed that compound I had the strongest anti-tumor activity, second was panaxadiol, II and III had the same and the weakest antitumor activity. Furthermore, the anti-tumor activities of panaxadiol fatty acid ester derivates showed positive correlation with subjects' concentrations, but no relationship with molecular weight of fatty acid. PMID:17228662

  15. Relationships between antibiotics and antibiotic resistance gene levels in municipal solid waste leachates in Shanghai, China.

    Science.gov (United States)

    Wu, Dong; Huang, Zhiting; Yang, Kai; Graham, David; Xie, Bing

    2015-04-01

    Many studies have quantified antibiotics and antibiotic resistance gene (ARG) levels in soils, surface waters, and waste treatment plants (WTPs). However, similar work on municipal solid waste (MSW) landfill leachates is limited, which is concerning because antibiotics disposal is often in the MSW stream. Here we quantified 20 sulfonamide (SA), quinolone (FQ), tetracycline (TC), macrolide (ML), and chloramphenicol (CP) antibiotics, and six ARGs (sul1, sul2, tetQ, tetM, ermB, and mefA) in MSW leachates from two Shanghai transfer stations (TS; sites Hulin (HL) and Xupu (XP)) and one landfill reservoir (LR) in April and July 2014. Antibiotic levels were higher in TS than LR leachates (985 ± 1965 ng/L vs 345 ± 932 ng/L, n = 40), which was because of very high levels in the HL leachates (averaging at 1676 ± 5175 ng/L, n = 40). The mean MLs (3561 ± 8377 ng/L, n = 12), FQs (975 ± 1608 ng/L, n = 24), and SAs (402 ± 704 ng/L, n = 42) classes of antibiotics were highest across all samples. ARGs were detected in all leachate samples with normalized sul2 and ermB levels being especially elevated (-1.37 ± 1.2 and -1.76 ± 1.6 log (copies/16S-rDNA), respectively). However, ARG abundances did not correlate with detected antibiotic levels, except for tetW and tetQ with TC levels (r = 0.88 and 0.81, respectively). In contrast, most measured ARGs did significantly correlate with heavy metal levels (p < 0.05), especially with Cd and Cr. This study shows high levels of ARGs and antibiotics can prevail in MSW leachates and landfills may be an underappreciated as a source of antibiotics and ARGs to the environment. PMID:25760223

  16. Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.

    Science.gov (United States)

    Yap, Polly Soo Xi; Lim, Swee Hua Erin; Hu, Cai Ping; Yiap, Beow Chin

    2013-06-15

    In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC≤0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance. PMID:23537749

  17. REDUCTION OF ANTIBIOTIC RESISTANCE IN BACTERIA: A REVIEW

    Directory of Open Access Journals (Sweden)

    Suresh Jaiswal et al.

    2012-03-01

    Full Text Available Drug resistant bacteria have been posing a major challenge to the effective control of bacterial infections for quite some time. One of the main causes of antibiotics drug resistance is antibiotic overuse, abuse, and in some cases, misuse, due to incorrect diagnosis. Bacterial antibiotic resistance is a significant issues faced by various industries, including the food and agricultural industries, the medical and veterinary profession and others. The potential for transfer of antibiotics resistance, or of potentially lethal antibiotic resistant bacteria, for example from a food animal to human consumer, is of particular concern. A method of controlling development and spread of antibiotic-resistant bacteria include changes in antibiotic usage and pattern of usage of different antibiotics. However, the ability of bacteria to adapt to antibiotic usage and to acquire resistance to existing and new antibiotics usage overcomes such conventional measures, and requires the continued development of alternative means of control of antibiotic resistance bacteria. Alternative means for overcoming the tendency of bacteria to acquire resistance to antibiotic control measures have taken various forms. This article explains one method evaluated for control, that is reducing or removing antibiotic resistance is so called “curing” of antibiotic resistance. Antibiotic resistance is formed in the chromosomal elements. Thus elimination of such drug-resistance plasmids results in loss of antibiotics resistance by the bacterial cell. “Curing” of a microorganism refers to the ability of the organism to spontaneously lose a resistance plasmid under the effect of particular compounds and environmental conditions, thus recovering the antibiotic sensitive state.

  18. Emerging antibiotic resistance in bacteria with special reference to India

    Indian Academy of Sciences (India)

    D Raghunath

    2008-11-01

    The antibiotic era started in the 1940s and changed the profile of infectious diseases and human demography. The burgeoning classes and numbers promised much and elimination of this major cause of human (and animal) morbidity appeared possible. Bacterial antibiotic resistance which was observed soon after antibiotic introduction has been studied extensively. Diverse mechanisms have been demonstrated and the genetic basis elucidated. The resilience of the prokaryote ecosystems to antibiotic stress has been realized. The paper presents these subjects briefly to afford an overview. The epidemiology of antibiotic resistance is dealt with and community practices in different countries are described. The role of high antibiotic usage environments is indicated. The implication of the wide use of antibiotics in animals has been pointed out. Steadily increasing antibiotic resistance and decreasing numbers of newer antibiotics appear to point to a post-antibiotic period during which treatment of infections would become increasingly difficult. This article attempts to review the global antimicrobial resistance scene and juxtaposes it to the Indian experience. The prevalence in India of antibiotic resistance among major groups of pathogens is described. The factors that determine the prevalent high antibiotic resistance rates have been highlighted. The future research activity to ensure continued utility of antibiotics in the control of infections has been indicated.

  19. Cloning, sequencing, and functional analysis of the biosynthetic gene cluster of macrolactam antibiotic vicenistatin in Streptomyces halstedii.

    Science.gov (United States)

    Ogasawara, Yasushi; Katayama, Kinya; Minami, Atsushi; Otsuka, Miyuki; Eguchi, Tadashi; Kakinuma, Katsumi

    2004-01-01

    Vicenistatin, an antitumor antibiotic isolated from Streptomyces halstedii, is a unique 20-membered macrocyclic lactam with a novel aminosugar vicenisamine. The vicenistatin biosynthetic gene cluster (vin) spanning approximately 64 kbp was cloned and sequenced. The cluster contains putative genes for the aglycon biosynthesis including four modular polyketide synthases (PKSs), glutamate mutase, acyl CoA-ligase, and AMP-ligase. Also found in the cluster are genes of NDP-hexose 4,6-dehydratase and aminotransferase for vicenisamine biosynthesis. For the functional confirmation of the cluster, a putative glycosyltransferase gene product, VinC, was heterologously expressed, and the vicenisamine transfer reaction to the aglycon was chemically proved. A unique feature of the vicenistatin PKS is that the loading module contains only an acyl carrier protein domain, in contrast to other known PKS-loading modules containing certain activation domains. Activation of the starter acyl group by separate polypeptides is postulated as well. PMID:15112997

  20. Lipid bilayer-assisted release of an enediyne antibiotic from neocarzinostatin chromoprotein.

    Science.gov (United States)

    Hariharan, Parameswaran; Sudhahar, Christopher Gunasekaran; Chou, Shan-Ho; Chin, Der-Hang

    2010-09-01

    The nine-membered enediyne class has drawn extensive interest because of extremely high antitumor potency and intricate interactions with its carrier protein. While the drug-induced DNA cleavage reactions have been mostly elucidated, the critical release-transport process of the labile enediyne molecule in cellular environment remained obscure. Using neocarzinostatin chromoprotein as a model, we demonstrated a lipid bilayer-assisted release mechanism. The in vitro enediyne release rate under aqueous conditions was found to be too slow to account for its efficient DNA cleavage action. Via the presence of lipid bilayers, chaotropic agents, or organic solvents, we found the release was substantially enhanced. The increased rate was linearly dependent on the lipid bilayer concentration and the dielectric value of the binary organic solvent mixtures. While lipid bilayers provided a low surrounding dielectricity to assist in drug release, there were no major conformational changes in the apo and holo forms of the carrier protein. In addition, the lifespan of the released enediyne chromophore was markedly extended through partitioning of the chromophore in the hydrophobic bilayer phase, and the lipid bilayer-stabilized enediyne chromophore significantly enhanced DNA cleavage in vitro. Collectively, we depicted how a lipid bilayer membrane efficiently enhanced dissociation of the enediyne chromophore through a hydrophobic sensing release mechanism and then acted as a protector of the released enediyne molecule until its delivery to the target DNA. The proposed membrane-assisted antibiotic release-transport model might signify a new dimension to our understanding of the modus operandi of the antitumor enediyne drugs. PMID:20712297

  1. 4-methylideneimidazole-5-one-containing aminomutases in enediyne biosynthesis.

    Science.gov (United States)

    Lohman, Jeremy R; Shen, Ben

    2012-01-01

    Many natural products contain unusual aromatic β-amino acids or moieties derived therefrom. The biosynthesis of these β-amino acids was first elucidated during a biosynthetic study of the enediyne antitumor antibiotic C-1027, when an enzyme, SgcC4, was discovered to convert L-tyrosine to (S)-β-tyrosine. SgcC4 is similar in sequence and structure to 4-methylideneimidazole-5-one (MIO)-containing ammonia lyases. Whereas the ammonia lyases use the electrophilic power of the MIO group to catalyze the release of ammonia from aromatic amino acids to generate α,β-unsaturated carboxylic acids as final products, SgcC4 retains the α,β-unsaturated carboxylic acid and amine as intermediates and reappends the amino group to the β-carbon, affording a β-amino acid as the final product. The study of SgcC4 led to the subsequent discovery of other MIO-containing aminomutases with altered substrate specificity and product stereochemistry, including MdpC4 from the biosynthetic pathway of the enediyne antitumor antibiotic maduropeptin. This chapter describes protocols for the enzymatic and structural characterization of these MIO-containing aminomutases as exemplified by SgcC4 and MdpC4. These protocols are applicable to the study of other aminomutases. PMID:23034235

  2. Antibiotic Resistance in Children with Bloody Diarrhea

    Directory of Open Access Journals (Sweden)

    Hamedi Abdolkarim

    2009-05-01

    Full Text Available Shigellosis is an important public health problem, especially in developing countries. Antibiotic treatment of bacterial dysentery, aimed at resolving diarrhea or reducing its duration is especially indicated whenever malnutrition is present. First-line drugs include ampicillin and trimethoprim sulfamethoxazole(TMP-SMX; however multidrug-resistance has occurred and careful antibiotic selection must be considered in prescribing .When epidemiologic data indicate a rise in resistancy, fluoroquinolones may be used in adults and oral third-generation cephalosporins and nalidixic acid in children. All children (n=2400 with acute diarrhea who were admitted to the Pediatric department of Dr.sheykh Hospital Mashhad, Iran from March 2004 to March 2005 were selected and their stool culture were obtained, then positive cultures (312 cases,13% were evaluated by antibiogram. This study showed that in heavily populated areas of IRAN like Mashhad, 97% shigella strain isolated from children with bloody diarrhea were sensitive to nalidixic acid, ciprofloxacin and cefixime and rarely susceptible to ampicillin and cotrimoxazole. There is increasing resistance of Shigella to most of the antibiotics in use, and for this reason, careful selection of antibiotics must use considered in each area. Development and use of new drugs are expensive and have severe limitations in the third world. Simple prophylactic alternatives are therefore, required, such as awareness of hygienic child care practices and early promotion of breast feeding. For treatment of shigellosis in infants Ceftriaxon, and in children Nalidixic Acid is recommended.

  3. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

    Touw, D J; Brimicombe, R W; Hodson, M E; Heijerman, H G; Bakker, W

    1995-01-01

    Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis. However, its contribution to the improvement of lung function, infection and quality of life is not well-established. All articles published from 1965 until the present time concerning the inhalation of antibi

  4. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Szkudlarek-Mikho, Maria; Saunders, Rudel A. [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States); Yap, Sook Fan [Faculty of Medicine and Health Sciences, Department of Pre-Clinical Sciences, University of Tunku Abdul Rahman (Malaysia); Ngeow, Yun Fong [Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603 (Malaysia); Chin, Khew-Voon, E-mail: khew-voon.chin@utoledo.edu [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)

    2012-11-30

    Highlights: Black-Right-Pointing-Pointer Salinomycin inhibits preadipocyte differentiation into adipocytes. Black-Right-Pointing-Pointer Salinomycin inhibits transcriptional regulation of adipogenesis. Black-Right-Pointing-Pointer Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor {gamma}. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  5. New antibiotic agents for bloodstream infections.

    Science.gov (United States)

    Vergidis, Paschalis I; Falagas, Matthew E

    2008-11-01

    Infections due to multidrug-resistant pathogens have shown a dramatic worldwide increase in prevalence. Bloodstream infections (BSIs) represent an important cause of morbidity and mortality in hospitalised patients. Research in the field led to the introduction of several novel antibiotic agents in the fight against bacterial pathogens. New antibiotics used against Gram-positive bacteria, mainly meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci, include daptomycin, linezolid, quinupristin/dalfopristin and semisynthetic lipoglycopeptides. Among the Gram-negative bacteria, extended-spectrum beta-lactamase-producing Enterobacteriaceae as well as highly resistant Pseudomonas and Acinetobacter isolates are of particular concern. Doripenem is a recently approved carbapenem. Polymyxins are reconsidered as valuable therapeutic options for Gram-negative infections. Tigecycline, a glycylcycline, and ceftobiprole, a novel cephalosporin under investigation, have activity both against Gram-positive and Gram-negative organisms. In addition to the above agents, alternative treatment approaches that require further investigation have also been introduced into clinical practice. These include antibiotic lock therapy and continuous intravenous administration of antibiotics. In this article, we review the above treatment options for BSIs based on current clinical evidence. Comparative trials specifically focusing on patients with bacteraemia were generally not performed; however, a proportion of patients from the reported studies did have bacteraemia. PMID:18723329

  6. Aminoglycoside antibiotics and autism: a speculative hypothesis

    Directory of Open Access Journals (Sweden)

    Manev Hari

    2001-10-01

    Full Text Available Abstract Background Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. Presentation We hypothesize that aminoglycoside antibiotics could a trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. Testing Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children and the onset of autism symptoms (hypothesis "a", or between amino glycoside use and improvement of these symptoms (hypothesis "b". Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". Implications It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism.

  7. Quality milk and tests for antibiotic residues.

    Science.gov (United States)

    Sischo, W M

    1996-06-01

    One goal of total quality management is to prevent the occurrence of antibiotics in raw milk shipped from the farm. An effective approach to meet this goal is the implementation of HACCP (Hazard Analysis Critical Control Point) procedures, which are part of the Milk and Dairy Beef Quality Assurance Program for antibiotic avoidance. The program defines 10 critical control points, including screening tests for preventing antibiotic residues. Although milk from individual cows clearly should be tested to ensure that antibiotic-free milk is leaving the farm, it is not clear whether any existing tests can be reliably used on milk samples from individual cows, or even on samples from bulk tanks. The FDA acceptance procedures have not required that bulk milk tests undergo a population evaluation; these tests have not been objectively evaluated for individual cows. Of more concern, detection limits differ among tests, sometimes approaching zero. Despite the intent of the Pasteurized Milk Ordinance, milk acceptability definitions vary between states. In addition, the predictive value of test results has not been integrated into the regulatory process. Although largely ignored by the regulatory agencies, these issues cannot be ignored by the dairy industry. Ultimately, the milk testing program should become a component of the quality process that is centered on the farm and that measures the success of the industry in producing high quality milk rather than being a regulatory program that searches for a flawed product. PMID:8827472

  8. Methodology in improving antibiotic implementation policies.

    Science.gov (United States)

    Özgenç, Onur

    2016-06-26

    The basic requirements of antibiotic prescribing are components of methodology; knowledge, logical reasoning, and analysis. Antimicrobial drugs are valuable but limited resources, different from other drugs and they are among the most commonly prescribed drugs all over the world. They are the only drugs which do not intentionally affect the patient. They affect the pathogens which invade the host. The emergence and spread of antibiotic-resistant pathogens are accelerated by heavy antibiotic usage. The effective antimicrobial stewardship and infection control program have been shown to limit the emergence of antimicrobial-resistant bacteria. In this respect, education for antibiotic prescribing could be designed by going through the steps of scientific methodology. A defined leadership and a coordinated multidisciplinary approach are necessary for optimizing the indication, selection, dosing, route of administration, and duration of antimicrobial therapy. In scenarios, knowledge is also as important as experience for critical decision making as is designated. In this setting, the prevalence and resistance mechanisms of antimicrobials, and their interactions with other drugs need to be observed. In this respect, infectious disease service should play an important role in improving antimicrobial use by giving advice on the appropriate use of antimicrobial agents, and implementing evidence-based guidelines. PMID:27376019

  9. Polyene antibiotic that inhibits membrane transport proteins.

    Science.gov (United States)

    te Welscher, Yvonne Maria; van Leeuwen, Martin Richard; de Kruijff, Ben; Dijksterhuis, Jan; Breukink, Eefjan

    2012-07-10

    The limited therapeutic arsenal and the increase in reports of fungal resistance to multiple antifungal agents have made fungal infections a major therapeutic challenge. The polyene antibiotics are the only group of antifungal antibiotics that directly target the plasma membrane via a specific interaction with the main fungal sterol, ergosterol, often resulting in membrane permeabilization. In contrast to other polyene antibiotics that form pores in the membrane, the mode of action of natamycin has remained obscure but is not related to membrane permeabilization. Here, we demonstrate that natamycin inhibits growth of yeasts and fungi via the immediate inhibition of amino acid and glucose transport across the plasma membrane. This is attributable to ergosterol-specific and reversible inhibition of membrane transport proteins. It is proposed that ergosterol-dependent inhibition of membrane proteins is a general mode of action of all the polyene antibiotics, of which some have been shown additionally to permeabilize the plasma membrane. Our results imply that sterol-protein interactions are fundamentally important for protein function even for those proteins that are not known to reside in sterol-rich domains. PMID:22733749

  10. A Review of Antibiotic Use in Pregnancy.

    Science.gov (United States)

    Bookstaver, P Brandon; Bland, Christopher M; Griffin, Brooke; Stover, Kayla R; Eiland, Lea S; McLaughlin, Milena

    2015-11-01

    During pregnancy, untreated sexually transmitted or urinary tract infections are associated with significant morbidity, including low birth weight, preterm birth, and spontaneous abortion. Approximately one in four women will be prescribed an antibiotic during pregnancy, accounting for nearly 80% of prescription medications in pregnant women. Antibiotic exposures during pregnancy have been associated with both short-term (e.g., congenital abnormalities) and long-term effects (e.g., changes in gut microbiome, asthma, atopic dermatitis) in the newborn. However, it is estimated that only 10% of medications have sufficient data related to safe and effective use in pregnancy. Antibiotics such as beta-lactams, vancomycin, nitrofurantoin, metronidazole, clindamycin, and fosfomycin are generally considered safe and effective in pregnancy. Fluoroquinolones and tetracyclines are generally avoided in pregnancy. Physiologic changes in pregnancy lead to an increase in glomerular filtration rate, increase in total body volume, and enhanced cardiac output. These changes may lead to pharmacokinetic alterations in antibiotics that require dose adjustment or careful monitoring and assessment. PMID:26598097

  11. Colistin : Revival of an Old Polymyxin Antibiotic

    NARCIS (Netherlands)

    Dijkmans, Anneke C.; Wilms, Erik B.; Kamerling, Ingrid M. C.; Birkhoff, Willem; Ortiz-Zacarias, Natalia V.; van Nieuwkoop, Cees; Verbrugh, Henri A.; Touw, Daan J.

    2015-01-01

    Colistin (polymyxin E) is a positively charged deca-peptide antibiotic that disrupts the integrity of the outer membrane of the cell wall of gram-negative bacteria by binding to the lipid A moiety of lipopolysaccharides, resulting in cell death. The endotoxic activity of lipopolysaccharides is simul

  12. The antibiotic resistance in cave environments

    Czech Academy of Sciences Publication Activity Database

    Elhottová, Dana; Petrásek, Jiří; Jirout, Jiří; Chroňáková, Alica; Kyselková, Martina; Volná, Lucie

    Košice : Pavol Jozef Šafárik University in Košice, 2012. s. 41-42. [International Conference on Subterranean Biology /21./. 02.09.2012-07.09.2012, Košice] Institutional support: RVO:60077344 Keywords : antibiotic resistance * cave environments Subject RIV: EH - Ecology, Behaviour

  13. Physics and the Production of Antibiotics: 2

    Science.gov (United States)

    Fairbrother, Robert; Riddle, Wendy; Fairbrother, Neil

    2006-01-01

    In an article in the preceding issue we discussed the design and construction of fermenters in which antibiotics are cultured. For industrial purposes these fermenters can range in size up to 500 m[cube]. They have to be sterilized, filled with sterile culture medium and the culture itself and supplied with oxygen continuously. In some cases they…

  14. Modulation of RNA function by aminoglycoside antibiotics.

    Science.gov (United States)

    Schroeder, R; Waldsich, C; Wank, H

    2000-01-01

    One of the most important families of antibiotics are the aminoglycosides, including drugs such as neomycin B, paromomycin, gentamicin and streptomycin. With the discovery of the catalytic potential of RNA, these antibiotics became very popular due to their RNA-binding capacity. They serve for the analysis of RNA function as well as for the study of RNA as a potential therapeutic target. Improvements in RNA structure determination recently provided first insights into the decoding site of the ribosome at high resolution and how aminoglycosides might induce misreading of the genetic code. In addition to inhibiting prokaryotic translation, aminoglycosides inhibit several catalytic RNAs such as self-splicing group I introns, RNase P and small ribozymes in vitro. Furthermore, these antibiotics interfere with human immunodeficiency virus (HIV) replication by disrupting essential RNA-protein contacts. Most exciting is the potential of many RNA-binding antibiotics to stimulate RNA activities, conceiving small-molecule partners for the hypothesis of an ancient RNA world. SELEX (systematic evolution of ligands by exponential enrichment) has been used in this evolutionary game leading to small synthetic RNAs, whose NMR structures gave valuable information on how aminoglycosides interact with RNA, which could possibly be used in applied science. PMID:10619838

  15. Salinomycin, a polyether ionophoric antibiotic, inhibits adipogenesis

    International Nuclear Information System (INIS)

    Highlights: ► Salinomycin inhibits preadipocyte differentiation into adipocytes. ► Salinomycin inhibits transcriptional regulation of adipogenesis. ► Pharmacological effects of salinomycin suggest toxicity in cancer therapy. -- Abstract: The polyether ionophoric antibiotics including monensin, salinomycin, and narasin, are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming. Their effects on human health, however, are not fully understood. Recent studies showed that salinomycin is a cancer stem cell inhibitor. Since poultry consumption has risen sharply in the last three decades, we asked whether the consumption of meat tainted with growth promoting antibiotics might have effects on adipose cells. We showed in this report that the ionophoric antibiotics inhibit the differentiation of preadipocytes into adipocytes. The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ. These results suggest that the ionophoric antibiotics can be exploited as novel anti-obesity therapeutics and as pharmacological probes for the study of adipose biology. Further, the pharmacological effects of salinomycin could be a harbinger of its toxicity on the adipose tissue and other susceptible target cells in cancer therapy.

  16. Antibiotics for acute otitis media in children

    NARCIS (Netherlands)

    Venekamp, Roderick P.; Sanders, Sharon L.; Glasziou, Paul P.; Del Mar, Chris B.; Rovers, Maroeska M.

    2015-01-01

    BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Antibiotic use for AOM varies from 56% in the Netherlands to 95% in the USA, Canada and Australia. This is an update of a Cochrane review first published in The Cochrane Library in Issue 1, 1997 a

  17. Distribution of multiple antibiotic resistant Vibrio spp across Palk Bay

    Digital Repository Service at National Institute of Oceanography (India)

    Sneha, K.G.; Anas, A.; Jayalakshmy, K.V.; Jasmin, C.; VipinDas, P.V.; Pai, S.S.; Pappu, S.; Nair, M.; Muraleedharan, K.R.; Sudheesh, K.; Nair, S.

    Presence of multiple antibiotic resistant microorganisms in marine systems is increasingly a focus of concern as they pose potential health risk to humans and animals. The present study reports the distribution, diversity, antibiotic resistance...

  18. Antibiotic-Resistant Bacteria Detected in Sewage Spill

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_160031.html Antibiotic-Resistant Bacteria Detected in Sewage Spill 'People need to be ... News) -- Sewer line breaks can release antibiotic-resistant bacteria that pose a public health threat, a new ...

  19. Mild Appendicitis Complication Rates Similar for Surgery, Antibiotics

    Science.gov (United States)

    ... nih.gov/medlineplus/news/fullstory_157975.html Mild Appendicitis Complication Rates Similar for Surgery, Antibiotics Decision not ... News) -- Antibiotics can be used to treat mild appendicitis, but the condition returns in some patients who ...

  20. Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

    DEFF Research Database (Denmark)

    Wollenberger, Leah; Halling-Sørensen, B.; Kusk, Kresten Ole

    2000-01-01

    The acute and chronic toxicity of nine antibiotics used both therapeutically and as growth promoters in intensive farming was investigated on the freshwater crustacean Daphnia magna. The effect of the antibiotics metronidazole (M), olaquindox (OL), oxolinic acid (OA), oxytetracycline (OTC...

  1. Oral Antibiotics in Acne Vulgaris: Therapeutic Response Over 5 Years

    OpenAIRE

    2010-01-01

    Introduction: Antibiotic resistant P. acnes have influenced acne therapy worldwide resulting in increased use of topical and systemic retinoids. Judicious use of oral antibiotic is important for effective therapeutic outcome.

  2. Antibiotic Resistance Threats in the U.S.

    Science.gov (United States)

    ... What's this? Submit Button Past Emails CDC Features Antibiotic Resistance Threats in the US Recommend on Facebook Tweet Share Compartir Antibiotics are powerful tools for fighting illness and disease, ...

  3. Antibiotic Resistance Common in Kids' Urinary Tract Infections

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_157809.html Antibiotic Resistance Common in Kids' Urinary Tract Infections Researchers ... coli bacteria are now failing to respond to antibiotic treatment, a new review warns. The culprit, according ...

  4. Cooperative Antibiotic Resistance in a Multi-Drug Environment

    Science.gov (United States)

    Yurtsev, Eugene; Dai, Lei; Gore, Jeff

    2013-03-01

    The emergence of antibiotic resistance in bacteria is a significant health concern. A frequent mechanism of antibiotic resistance involves the production of an enzyme which inactivates the antibiotic. By inactivating the antibiotic, resistant cells can ``share'' their resistance with other cells in the bacterial population, suggesting that it may be possible to observe cooperation between strains that inactivate different antibiotics. Here, we experimentally track the population dynamics of two E. coli strains in the presence of two different antibiotics. We find that together the strains are able to grow in antibiotic concentrations that inhibit growth of either of the strains individually. We observe that even when there is stable coexistence between the two strains, the population size of each strain can undergo large oscillations. We expect that our results will provide insight into the evolution of antibiotic resistance and the evolutionary origin of phenotypic diversity and cooperative behaviors.

  5. Antibiotic Residues - A Global Health Hazard

    Directory of Open Access Journals (Sweden)

    Nisha A.R.

    Full Text Available Use of Antibiotic that might result in deposition of residues in meat, milk and eggs must not be permitted in food intended for human consumption. If use of antibiotics is necessary as in prevention and treatment of animal diseases, a withholding period must be observed until the residues are negligible or no longer detected. The use of antibiotics to bring about improved performance in growth and feed efficiency, to synchronize or control of reproductive cycle and breeding performance also often lead to harmful residual effects. Concern over antibiotic residues in food of animal origin occurs in two times; one which produces potential threat to direct toxicity in human, second is whether the low levels of antibiotic exposure would result in alteration of microflora, cause disease and the possible development of resistant strains which cause failure of antibiotic therapy in clinical situations. A withdrawal period is established to safeguard human from exposure of antibiotic added food. The withdrawal time is the time required for the residue of toxicological concern to reach safe concentration as defined by tolerance. It is the interval from the time an animal is removed from medication until permitted time of slaughter. Heavy responsibility is placed on the veterinarian and livestock producer to observe the period for a withdrawal of a drug prior to slaughter to assure that illegal concentration of drug residue in meat, milk and egg do not occur. Use of food additives may improve feed efficiency 17% in beef cattle, 10% in lambs, 15% in poultry and 15% in swine. But their indiscriminate use will produce toxicity in consumers. WHO and FAO establish tolerances for a drug, pesticide or other chemical in the relevant tissues of food producing animals. The tolerance is the tissue concentration below, which a marker residue for the drug or chemical must fall in the target tissue before that animal edible tissues are considered safe for human

  6. Control of fluxes towards antibiotics and the role of primary metabolism in production of antibiotics

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Eliasson Lantz, Anna; Nielsen, Jacob

    2004-01-01

    Yield improvements in antibiotic-producing strains have classically been obtained through random mutagenesis and screening. An attractive alternative to this strategy is the rational design of producer strains via metabolic engineering, an approach that offers the possibility to increase yields...... metabolic network. Here we describe and discuss available methods for identification of these steps, both in antibiotic biosynthesis pathways and in the primary metabolism, which serves as the supplier of precursors and cofactors for the secondary metabolism. Finally, the importance of precursor and...... cofactor supply from primary metabolism in the biosynthesis of different types of antibiotics is discussed and recent developments in metabolic engineering towards increased product yields in antibiotic producing strains are reviewed....

  7. Antibiotic resistance - the interplay between antibiotic use in animals and human beings

    DEFF Research Database (Denmark)

    Singer, R.S.; Finch, R.; Wegener, Henrik Caspar; Bywater, R.; Walters, J.; Lipsitch, M.

    2003-01-01

    meant the problem of antibiotic resistance is fast escalating into a global health crisis. There is no doubt that misuse of these drugs in human beings has contributed to the increasing rates of resistance, but recently the use of antibiotics in food animals and its consequent effect on resistance....... There is a growing concern over the transmission of resistant bacteria via the food chain. Many questions will be difficult to resolve, such as how do you distinguish the fraction of resistance in human beings that originated from animals? If we wait to see evidence that a significant amount of...... antibiotic resistance really does come through the food chain, will it be too late for action? In this forum, we present different perspectives from both human and animal medicine, to better understand the complexity of the problem of antibiotic resistance and examine the challenges that lie ahead....

  8. Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein.

    Science.gov (United States)

    Moghadam, Ali; Niazi, Ali; Afsharifar, Alireza; Taghavi, Seyed Mohsen

    2016-01-01

    In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP) with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents. PMID:27459300

  9. Excretion of antibiotic resistance genes by dairy calves fed milk replacers with varying doses of antibiotics

    Directory of Open Access Journals (Sweden)

    Callie H. Thames

    2012-04-01

    Full Text Available Elevated levels of antibiotic resistance genes (ARGs in soil and water have been linked to livestock farms and in some cases feed antibiotics may select for antibiotic resistant gut microbiota. The purpose of this study was to examine the establishment of ARGs in the feces of calves receiving milk replacer containing no antibiotics versus subtherapeutic or therapeutic doses of tetracycline and neomycin. The effect of antibiotics on calf health was also of interest. Twenty-eight male and female dairy calves were assigned to one of the three antibiotic treatment groups at birth and fecal samples were collected at weeks 6, 7 (prior to weaning, and 12 (5 weeks after weaning. ARGs corresponding to the tetracycline (tetC, tetG, tetO, tetW, and tetX, macrolide (ermB, ermF, and sulfonamide (sul1, sul2 classes of antibiotics along with the class I integron gene, intI1, were monitored by quantitative polymerase chain reaction as potential indicators of direct selection, co-selection, or horizontal gene transfer of ARGs. Surprisingly, there was no significant effect of antibiotic treatment on the absolute abundance (gene copies/ g wet manure of any of the ARGs except ermF, which was lower in the antibiotic-treated calf manure, presumably because a significant portion of host bacterial cells carrying ermF were not resistant to tetracycline or neomycin. However, relative abundance (gene copies normalized to 16S rRNA genes of tetO was higher in calves fed the highest dose of antibiotic than in the other treatments. All genes, except tetC and intI1, were detectable in feces from 6 weeks onwards, and tetW and tetG significantly increased (P<0.10, even in control calves. Overall, the results provide new insight into the colonization of calf gut flora with ARGs in the early weeks. Although feed antibiotics exerted little effect on the ARGs monitored in this study, the fact that they also provided no health benefit suggests that the greater than conventional

  10. Gene-Drug Interactions and the Evolution of Antibiotic Resistance

    OpenAIRE

    Palmer, Adam Christopher

    2012-01-01

    The evolution of antibiotic resistance is shaped by interactions between genes, the chemical environment, and an antibiotic's mechanism of action. This thesis explores these interactions with experiments, theory, and analysis, seeking a mechanistic understanding of how different interactions between genes and drugs can enhance or constrain the evolution of antibiotic resistance. Chapter 1 investigates the effects of the chemical decay of an antibiotic. Tetracycline resistant and sensitive bac...

  11. Trends in antibiotic use among outpatients in New Delhi, India

    Directory of Open Access Journals (Sweden)

    Holloway Kathleen

    2011-04-01

    Full Text Available Abstract Background The overall volume of antibiotic consumption in the community is one of the foremost causes of antimicrobial resistance. There is much ad-hoc information about the inappropriate consumption of antibiotics, over-the-counter availability, and inadequate dosage but there is very little actual evidence of community practices. Methods This study surveyed antibiotic use in the community (December 2007-November 2008 using the established methodology of patient exit interviews at three types of facilities: 20 private retail pharmacies, 10 public sector facilities, and 20 private clinics to obtain a complete picture of community antibiotic use over a year. The Anatomical Therapeutic Chemical (ATC classification and the Defined Daily Dose (DDD measurement units were assigned to the data. Antibiotic use was measured as DDD/1000 patients visiting the facility and also as percent of patients receiving an antibiotic. Results During the data collection period, 17995, 9205, and 5922 patients visiting private retail pharmacies, public facilities and private clinics, respectively, were included in our study. 39% of the patients attending private retail pharmacies and public facilities and 43% of patients visiting private clinics were prescribed at least one antibiotic. Consumption patterns of antibiotics were similar at private retail pharmacies and private clinics where fluoroquinolones, cephalosporins, and extended spectrum penicillins were the three most commonly prescribed groups of antibiotics. At public facilities, there was a more even use of all the major antibiotic groups including penicillins, fluoroquinolones, macrolides, cephalosporins, tetracyclines, and cotrimoxazole. Newer members from each class of antibiotics were prescribed. Not much seasonal variation was seen although slightly higher consumption of some antibiotics in winter and slightly higher consumption of fluoroquinolones during the rainy season were observed

  12. Prevalence and Predictors of Antibiotic Administration during Pregnancy and Birth

    DEFF Research Database (Denmark)

    Stokholm, Jakob; Schjørring, Susanne; Pedersen, Louise;

    2013-01-01

    Antibiotic treatment during pregnancy and birth is very common. In this study, we describe the estimated prevalence of antibiotic administration during pregnancy and birth in the COPSAC2010 pregnancy cohort, and analyze dependence on social and lifestyle-related factors.......Antibiotic treatment during pregnancy and birth is very common. In this study, we describe the estimated prevalence of antibiotic administration during pregnancy and birth in the COPSAC2010 pregnancy cohort, and analyze dependence on social and lifestyle-related factors....

  13. Isolated cell behavior drives the evolution of antibiotic resistance

    OpenAIRE

    Artemova, Tatiana; Gerardin, Ylaine; Dudley, Carmel; Vega, Nicole M.; Gore, Jeff

    2015-01-01

    Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the collective inactivation of antibiotic by the bacterial population can cause the measured MIC to depend strongly on the initial cell density. In cases where this inoculum effect is strong, the rela...

  14. Functional metagenomics for the investigation of antibiotic resistance

    OpenAIRE

    Mullany, Peter

    2014-01-01

    Antibiotic resistance is a major threat to human health and well-being. To effectively combat this problem we need to understand the range of different resistance genes that allow bacteria to resist antibiotics. To do this the whole microbiota needs to be investigated. As most bacteria cannot be cultivated in the laboratory, the reservoir of antibiotic resistance genes in the non-cultivatable majority remains relatively unexplored. Currently the only way to study antibiotic resistance in thes...

  15. Assessment of Bacterial Antibiotic Resistance Transfer in the Gut

    OpenAIRE

    Susanne Schjørring; Krogfelt, Karen A.

    2011-01-01

    We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract. During the last decades, the emergence of antibiotic resistant strains and treatment failures of bacterial infections have increased the public awareness of antibiotic usage. The use of broad spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the emergence of multiresistant bacteria, which results in a vicious circle of treatments and emergence of new antibiotic res...

  16. Widespread antibiotic resistance of diarrheagenic Escherichia coli and Shigella species

    OpenAIRE

    Azam Fatahi Sadeghabadi; Ali Ajami; Reza Fadaei; Masoud Zandieh; Elham Heidari; Mahmoud Sadeghi; Behrooz Ataei; Shervin Ghaffari Hoseini

    2014-01-01

    Background: Antibiotic resistance of enteric pathogens particularly Shigella species, is a critical world-wide problem and monitoring their resistant pattern is essential, because the choice of antibiotics is absolutely dependent on regional antibiotic susceptibility patterns. During summer 2013, an unusual increase in number of diarrheal diseases was noticed in Isfahan, a central province of Iran. Therefore, the antibiotic resistance of diarrheagenic Escherichia coli and Shigella species iso...

  17. Antibiotic trials for coronary heart disease.

    Science.gov (United States)

    Anderson, Jeffrey L; Muhlestein, Joseph B

    2004-01-01

    The possibility has been raised in recent years that infection might contribute as an inflammatory stimulus to chronic "noninfectious" degenerative diseases. Within the past decade, serious attention has been given to the possibility of bacterial vectors as causal factors of atherosclerosis. To date, the greatest amount of information has related to the intracellular organism Chlamydia pneumoniae. This interest has been stimulated by the frequent finding of bacterial antigens and, occasionally, recoverable organisms, within human atherosclerotic plaque. Indirect evidence for and against the benefit of anti-Chlamydia antibiotic agents comes from epidemiologic studies. Given the potential for confounding in observational studies, prospective, randomized intervention trials are required. These antibiotic trials have generated enthusiastic expectations for proving (or disproving) the infectious-disease hypothesis of atherosclerosis and establishing new therapies. However, these expectations have been tempered by important limitations and uncertainties. Negative outcomes can be explained not only by an incorrect hypothesis but also by inadequate study size or design or by an ineffective antibiotic regimen. In contrast, if studies are positive, the hypothesis still is not entirely proved, because a nonspecific anti-inflammatory effect or an anti-infective action against other organisms might be operative. The clinical trial data to date have not provided adequate support for the clinical use of antibiotics in primary or secondary prevention of coronary heart disease. New and innovative experimental approaches, in addition to traditionally designed antibiotic trials, should be welcome in our attempts to gain adequate insight into the role of infection in atherosclerosis and its therapy. PMID:15061624

  18. Intensive Care Unit Infections and Antibiotic Use

    Directory of Open Access Journals (Sweden)

    Ayşegül Yeşilkaya

    2011-07-01

    Full Text Available Burn wound infections is the leading cause of morbidity and mortality in burn trauma patients. Although burn wound is sterile at the beginning, because of risk factors such as prolonged hospital stay, immunesuppression and burn affecting large body surface area, colonisation firstly with Staphylococcus aureus and then Pseudomonas aeruginosa will occur later. Delay in wound closure and treatment with broad-spectrum antibiotic will result wound colonisation with antibiotic-resistant bacteria. To control colonization and to prevent burn wound infection topical antimicrobial dressings are used. The criteria used for the diagnosis of sepsis and wound infections are different in burn victims. Surface swabs from burn wounds must be cultured for the early assestment of infection. Although histopathological examination and quantitative culture of wound tissue biopsy has been known as the gold standard for the verification of invasive burn wound infection, many burn centers cannot do histopathological examination. When the traditional treatment modalities such as debridement of necrotic tissue, cleaning of wound and topical antimicrobial dressing application fails in the management of burn patient, cultures must be taken from possible foci of infection for the early diagnosis. After specimen collection, empirical bactericidal systemic antibiotic treatment should be started promptly. Inappropriate utilization of antibiotics may cause selection of resistant bacteria in the flora of the patient and of the burn unit which facilitates an infection or an outbreak at the end. Infection control in the burn unit includes surveillance cultures, cohort patient care staff, standard isolation precautions, strict hand hygiene compliance and appropariate antibiotic utilization. (Journal of the Turkish Society Intensive Care 2011; 9 Suppl: 55-61

  19. The Shared Antibiotic Resistome of Soil Bacteria and Human Pathogens

    DEFF Research Database (Denmark)

    Forsberg, Kevin J.; Reyes, Alejandro; Wang, Bin;

    2012-01-01

    From Farm to Clinic?Soil organisms have long been assumed to be an important source of antibiotic resistance genes, in part because of antibiotic-treated livestock and in part because of the natural ecology of antibiotic production in the soil. Forsberg et al. (p. 1107) developed a metagenomic pr...

  20. Outpatient antibiotic prescriptions from 1992 to 2001 in The Netherlands

    NARCIS (Netherlands)

    Kuyvenhoven, MM; van Balen, FAM; Verheij, TJM

    2003-01-01

    Objectives: Although Dutch outpatient antibiotic prescription rates are low compared with other European countries, continuing to scrutinize trends in outpatient antibiotic use is important in order to identify possible increases in antibiotic use or inappropriate increases in the use of particular

  1. Get Smart: Know When Antibiotics Work - What Everyone Should Know

    Science.gov (United States)

    ... age. It’s important to only take antibiotics for bacterial infections since they can put you or your child at risk for harmful side effects and antibiotic-resistant infections. Top of Page Related Links Antibiotic/Antimicrobial Resistance Get Smart for Healthcare Get Smart: Know When ...

  2. In-feed antibiotic effects on the swine intestinal microbiome

    Science.gov (United States)

    Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 years. The impact of such antibiotic use on the treatment of human diseases is hotly debated. Based on metagenomic and qPCR analysis, we show that antibiotic resis...

  3. Evaluation of antibiotic use in a Lebanese hospital

    OpenAIRE

    Ibrahim, Mohamad

    2016-01-01

    Antimicrobial resistance is a significant global health problem. Misuse of antibiotics is associated with antimicrobial resistance which presents clinicians with treatment challenges and increases the complexity of the decision making process related to the selection of appropriate antibiotic therapy. Antibiotic resistant organisms can often lead to nosocomial infections (NIs) and undoubtedly causes patient harm and increases healthcare costs. According to the National Insti...

  4. Pharmacy students’ knowledge and attitudes about antibiotics in Kosovo

    Science.gov (United States)

    Fejza, Albina; Kryeziu, Zeqir; Kadrija, Kushtrim; Musa, Malbora

    2016-01-01

    Objective: The main objective of this study was to assess the knowledge and attitude among Pharmacy students of the University of Prishtina in regards to the antibiotics. Methods: 144 pharmacy students at the University of Prishtina were recruited in this study to complete a self-administered questionnaire. The total number of questions in this questionnaire was eight (8), covering two (2) major themes: self-report of the current and past antibiotic use and behavior; and anticipated prescription behavior of antibiotics upon graduation. The data was statistically analyzed through using SPSS for Windows. Descriptive analysis was employed, and the results were expressed in frequency and percentages. Results: The results showcased a good knowledge of antibiotic among students. The most common answer of students’ knowledge about antibiotics was good or moderate (82 %), while 63.2% of the subjects used antibiotics by self-decision, most of them (45 %) for sore throat. Upon graduation, 56.9 % of the students will not sell antibiotics without prescription and 85.4% think that module for rational use of antibiotics is very necessary to be inside the pharmacy syllabus. Conclusion: The study showed good and moderate knowledge of pharmacy students regarding the antibiotics. Half of them use antibiotics by self-decision but the majority of them stated that they will not serve the antibiotics without medical prescription. Specific modules and training for proper antibiotic use should be implemented within the Pharmacy program in The Faculty of Medicine. PMID:27011780

  5. Identifying targets for quality improvement in hospital antibiotic prescribing

    NARCIS (Netherlands)

    Spreuwel, P.C. van; Blok, H.; Langelaar, M.F.; Kullberg, B.J.; Mouton, J.W.; Natsch, S.S.

    2015-01-01

    OBJECTIVES: To audit antibiotic use in a university hospital and to identify targets for quality improvement in a setting with low antibiotic use and resistance rates. METHODOLOGY: A point-prevalence survey (PPS), using a patient-based audit tool for antibiotic use, was executed in the Radboud Unive

  6. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false First aid antibiotic active ingredients. 333.110... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any...

  7. Oral antibiotics for perforated appendicitis is not recommended

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Rosenberg, Jacob; Alamili, Mahdi

    2010-01-01

    In the majority of surgical departments in Denmark, the postoperative treatment for acute perforated appendicitis comprises three days of intravenous antibiotics. Recently, it has been proposed that such antibiotic regimen should be replaced by orally administered antibiotics. The aim of this paper...

  8. COMPARISON OF SINGLE DOSE PROPHYLACTIC ANTIBIOTICS VERSUS FIVE DAYS ANTIBIOTIC IN CESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Zeel

    2014-03-01

    Full Text Available AIMS AND OBJECTIVES: To compare if single dose antibiotic is as effective as multiple doses in prevention of post-operative infection in caesarean section. To compare the cost effectiveness of drugs in both the groups. MATERIAL AND METHOD: This prospective randomized controlled study was carried out to evaluate the effectiveness of single dose antibiotic versus multiple doses in caesarean section. The study population consisted of 600 patients that were randomly allocated to single or multiple dose groups. All potentially infected cases were excluded from this study. All patients received inj Cefotaxime IV half hour before surgery. In addition the multiple dose group received antibiotics for five days post-operatively. Each patient in the study was observed till discharge for presence of any morbidity like endometritis, urinary tract infections, and wound infections. STATISTICAL ANALYSISIS: Fischer exact test, unpaired t test used for analysis. RESULTS: There was no statistically significance in the rate of infections in both the groups. The rate of febrile morbidity, endometritis, urinary tract infection and wound infections were statistically not significant. However the difference in cost of antibiotic in both the groups was significant. CONCLUSIONS: Single dose antibiotics are effective as multiple doses in prevention of post-operative infections in caesarean sections Careful periodic surveillance of antibiotic prophylaxis is necessary to detect the emergence of drug resistant strains of bacteria in our institution because it caters to the needs of local population.

  9. Antibiotic concentration and antibiotic-resistant bacteria in two shallow urban lakes after stormwater event.

    Science.gov (United States)

    Zhang, Songhe; Pang, Si; Wang, PeiFang; Wang, Chao; Han, Nini; Liu, Bin; Han, Bing; Li, Yi; Anim-Larbi, Kwaku

    2016-05-01

    Stormwater runoff is generally characterized as non-point source pollution. In the present study, antibiotic concentration and antibiotic susceptibilities of cultivable heterotrophic bacteria were investigated in two small shallow urban lakes before and after strong storm event. Several antibiotics, lactose-fermenting bacteria and cultivable heterotrophic bacteria concentrations increased in surface water and/or surface sediment of two small urban lakes (Lake Xuanwu and Wulongtan) after strong storm event. In general, the frequencies of bacteria showing resistance to nine antibiotics increased after storm event. Based on the 16S rRNA genes of 50 randomly selected isolates from each water sample of two lakes, Aeromonas and Bacillus were dominant genera in samples from two lakes, while genera Proteus and Lysinibacillus were the third abundant genera in Lake Xuanwu and Wulongtu, respectively. Presences of nine antibiotic resistance genes (ARGs) in the 100 isolates were detected and most of these isolates harbored at least two ARGs with different functions. The detection frequency of ARGs in Gram-negative isolates was higher than that in Gram-positive isolates. The most prevalent integron in 100 isolates was int(II) (n = 28), followed by int(I) (n = 17) and int(III) (n = 17). Our results indicate that strong storm events potentially contribute to the transfer of ARGs and antibiotic-resistant bacteria from land-sewer system to the urban Lakes. PMID:26865482

  10. Monitoring Antibiotic Residues and Corresponding Antibiotic Resistance Genes in an Agroecosystem

    Directory of Open Access Journals (Sweden)

    Yasser M. Awad

    2015-01-01

    Full Text Available Antibiotic resistance genes (ARGs have been commonly reported due to the overuse worldwide of antibiotics. Antibiotic overuse disturbs the environment and threatens public human health. The objective of this study was to measure the residual concentrations of veterinary antibiotics in the tetracycline group (TCs, including tetracycline (TC and chlortetracycline (CTC, as well as those in the sulfonamide group (SAs, including sulfamethazine (SMT, sulfamethoxazole (SMX, and sulfathiazole (STZ. We also isolated the corresponding ARGs in the agroecosystem. Four sediment samples and two rice paddy soil samples were collected from sites near a swine composting facility along the Naerincheon River in Hongcheon, Korea. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS was employed with a solid-phase extraction method to measure the concentration of each antibiotic. ARGs were identified by the qualitative polymerase chain-reaction using synthetic primers. SAs and their corresponding ARGs were highly detected in sediment samples whereas TCs were not detected except for sediments sample #1. ARGs for TCs and SAs were detected in rice paddy soils, while ARGs for TCs were only found in sediment #2 and #4. Continuous monitoring of antibiotic residue and its comprehensive impact on the environment is needed to ensure environmental health.

  11. Inappropriate antibiotic prescribing and demand for antibiotics in patients with upper respiratory tract infections is hardly different in female versus male patients as seen in primary care

    DEFF Research Database (Denmark)

    Bagger, Kathrine; Nielsen, Anni Brit Sternhagen; Siersma, Volkert;

    2015-01-01

    Background: Unnecessary prescribing of antibiotics is a major public health concern. General practitioners (GPs) prescribe most antibiotics, often for upper respiratory tract infections (URTIs), and have in general been shown to prescribe antibiotics more often to women. No studies have examined...... unnecessary antibiotics demonstrated a demand for antibiotics, but no gender difference was found in this group. Conclusion: This study indicated a high rate of unnecessary antibiotic prescribing for URTIs in general practice, but overall found no gender differences in receiving unnecessary antibiotic...

  12. Finding New Tricks for Old Drugs: Tumoricidal Activity of Non-Traditional Antitumor Drugs.

    Science.gov (United States)

    Zhang, Fangrong; Li, Min; Wang, Junling; Liang, Xi; Su, Yujie; Wang, Wei

    2016-06-01

    Chemotherapy, a traditional method, plays an important role in tumor therapy. Currently, common clinical antitumor drugs have several defects like poor efficacy, side effects, etc. Furthermore, developing new antitumor drugs takes a long time and requires many resources. Recent studies have found that oldies are newbies for the oncologist, such as flavonoid, metformin, aspirin, etc. These non-traditional antitumor drugs (NTADs) are widely used in management of non-cancer diseases, which gained FDA approval for treatment of patients. Increasingly, studies about antitumor action of NTADs have attracted many researchers' interests. A giant amount of studies showed a decrease in cancer incidence in NTAD-treated patients. Several reports outlined a direct inhibitory effect of NTADs on cancer cell growth and antitumoral actions. This review summarized the research progress on antitumor effects of ten NTADs. Retrospective and meta-analyses of trials also showed that these NTADs had preventive effects against cancer in vitro and in vivo. These drugs represent a promising option for cancer treatment, which have clear benefits including clinical safety, obvious curative effect, and saving medical and health resources. Judged from previous reports, future studies will yield valuable data about the profitable effects of these drugs. With a better understanding of its mechanisms of antitumor activity, NTADs may become available for combination with chemotherapy or targeted therapy in clinic. PMID:27032934

  13. Antitumor effects of radioiodinated antisense oligonucleotide mediated by VIP receptor

    International Nuclear Information System (INIS)

    Purpose: we had constructed a targeting delivery system based on intestinal peptide (VIP) for antisense oligonucleotide (ASON) transfer into VIP receptor-positive cells in previous study. The aims of present studies are to observe the antitumor effect of VIP-131I-ASON in HT29 human colon adenocarcinoma xenografts. Methods: A 15-met phosphorothioate ASON, which was complementary to the translation start region of the C-myc oncogene mRNA, was labeled with 131I and the labelled compound was linked to the VIP bound covalently 'to a polylysine chain so as to deliver oligonucleotide into tumor cells. Distribution experiments for evaluating the radiolabeled antisense complexe uptake in tumor tissue were performed in BALB/c nude mice bearing with HT29 tumor xenografts. Nude mice beating HT29 tumor xenografts were adminstered VIP-131I-ASON (3.7,7.4 MBq) or 131I-ASON (3.7 MBq), 131I labeled control sense and nosense DNA (3.7 MBq), or saline. Antitumor effects were assessed using endpoints of tumor growth delay. C-myc-encoded protein expression of tumor was measured by immunocytohistochemical staining. Results: Distribution experiment performed with athymic mice bearing human colon tumor xenografts revealed maximal accumulation of conjugated ASON in the tumor tissue 2 h after administration and significantly higher than that in nude mice injected unconjngated ASON [(5.89±1.03)%ID/g and(1.56±0.31)%ID/g, respectively; t=7.7954 P<0.001]. The radioratio of tumor to muscle was peaked 4h after administration. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing their growth rate 7-fold compare with that in saline-treated mice(tumor growth delay, 25.4±0.89 day). The antitumor effects of unconjugated 131I-ASON were much less profound than VIP-131I-ASON (tumor growth delay, 3.2±1.3 and 25.4±0.89 day, respectively; q=51.4126 P<0.01). Sense, nosense control ON with VIP carder caused no therapeutic effect. There was no progressive weight loss or

  14. Gene Therapy of Cancer: Induction of Anti-Tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    ChengQian; JesusPrieto

    2004-01-01

    Many malignancies lack satisfactory treatment and new therapeutic options are urgently needed. Gene therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the tissues. Different gene therapy strategies against cancers have been developed. A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene therapy. Among these strategies, induction of anti-tumor immunity is the most promising approach. Gene therapy with cytokines has reached unprecedented success in preclinical models of cancer. Synergistic rather than additive effects have been demonstrated by combination of gene transfer of cytokines/chemokines, costimulatory molecules or adoptive cell therapy. Recent progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy, a procedure which may have a notorious impact in the management of cancers lacking effective treatment. Cellular & Molecular Immunology. 2004;1(2):105-111.

  15. Telomerase:a novel target of antitumor agents

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Telomerase activity was found to be high in various human cancers, but absent in most normal tissues. Its expression pattern made it a novel target for antitumor agents. Several strategies against telomerase were presented in this review. Targeting the telomerase RNA component by oligonucleotide/ribozyme was considered to be one of the most hopeful approaches. Some progresses were made in this area, such as the use of PANs and 2- 5A antisense compounds. The relationships among telomerase activity and cell differentiation, signal transduction, oncogene, tumor suppressor gene as well as cell cycle modulation also provided a series of valuable ideas in designing anti-telomerase drugs for cancer therapy. In conclusion, although there is still a long way in understanding the mechanism and regulation of telomerase, the advance of studies on telomerase has allowed the development of numerous strategies for the treatment of cancer.

  16. Synthesis and antitumor activity of natural compound aloe emodin derivatives.

    Science.gov (United States)

    Thimmegowda, Naraganahalli R; Park, Chanmi; Shwetha, Bettaswamigowda; Sakchaisri, Krisada; Liu, Kangdong; Hwang, Joonsung; Lee, Sangku; Jeong, Sook J; Soung, Nak K; Jang, Jae H; Ryoo, In-Ja; Ahn, Jong S; Erikson, Raymond L; Kim, Bo Y

    2015-05-01

    In this study, we have synthesized novel water soluble derivatives of natural compound aloe emodin 4(a-j) by coupling with various amino acid esters and substituted aromatic amines, in an attempt to improve the anticancer activity and to explore the structure-activity relationships. The structures of the compounds were determined by (1) H NMR and mass spectroscopy. Cell growth inhibition assays revealed that the aloe emodin derivatives 4d, 4f, and 4i effectively decreased the growth of HepG2 (human liver cancer cells) and NCI-H460 (human lung cancer cells) and some of the derivatives exhibited comparable antitumor activity against HeLa (Human epithelial carcinoma cells) and PC3 (prostate cancer cells) cell lines compared to that of the parent aloe emodin at low micromolar concentrations. PMID:25323822

  17. Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

    Directory of Open Access Journals (Sweden)

    Claudia Palena

    2010-01-01

    Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

  18. A mathematical model of the dynamics of antitumor laser immunotherapy

    Science.gov (United States)

    Dawkins, Bryan A.; Laverty, Sean M.

    2014-02-01

    We use a mathematical model to describe and predict the population dynamics of tumor cells, immune cells, and other immune components in a host undergoing laser immunotherapy treatment against metastatic cancer. We incorporate key elements of the treatment into the model: a function describing the laser-induced primary tumor cell death and parameters capturing the role and strength of the primary immunoadjuvant, glycated chitosan. We focus on identifying conditions that ensure a successful treatment. In particular, we study the patient response (i.e., anti-tumor immune dynamics and treatment outcome) in two different but related mathematical models as we vary quantitative features of the immune system (supply, proliferation, death, and interaction rates). We compare immune dynamics of a `baseline' immune model against an `augmented' model (with additional cell types and antibodies) and in both, we find that using strong immunoadjuvants, like glycated chitosan, that enhance dendritic cell activity yields more promising patient outcomes.

  19. Study on the Interaction between Antitumor Drug Daunomycin and DNA

    Institute of Scientific and Technical Information of China (English)

    CHENG Gui-Fang; ZHAO Jie; TU Yong-Hua; HE Pin-Gang; FANG Yu-Zhi

    2005-01-01

    A detection of anthracycline antitumor drug daunomycin (DNR) reacting with DNA in simulate metabolism in vitro has been made. It was found that DNR could react with DNA to form DNR-DNA adducts. The adduct compositions of DNR with fish sperm DNA and thermally denaturated DNA were determined. The equilibrium association constant K of DNR with fish sperm DNA is 1.98 × 105 L/mol and that of DNR with denaturated DNA is 2.29 × 104 L/mol. Semiquinone free radicals, metabolic products of DNR, can destroy both fish sperm DNA and its thermally denaturated DNA. It is verified by hyperchromic effect increase observed in UV spectrum and AFM experiments. The mechanism of DNA degradation has also been investigated. Results obtained allow one to explain the reason of side effect of anthracycline drug and give the way to depress, which were of clinical significance.

  20. Antitumor effect of metformin in esophageal cancer: in vitro study.

    Science.gov (United States)

    Kobayashi, Mitsuyoshi; Kato, Kiyohito; Iwama, Hisakazu; Fujihara, Shintaro; Nishiyama, Noriko; Mimura, Shima; Toyota, Yuka; Nomura, Takako; Nomura, Kei; Tani, Joji; Miyoshi, Hisaaki; Kobara, Hideki; Mori, Hirohito; Murao, Koji; Masaki, Tsutomu

    2013-02-01

    Recent studies suggest that metformin, which is a member of the biguanide family and commonly used as an oral anti-hyperglycemic agent, may reduce cancer risk and improve prognosis of numerous types of cancer. However, the mechanisms underlying the antitumor effect of metformin on esophageal cancer remain unknown. The goal of the present study was to evaluate the effects of metformin on the proliferation of human ESCC in vitro, and to study changes in the expression profile of microRNAs (miRNAs), since miRNAs have previously been associated with the antitumor effects of metformin in other human cancers. The human ESCC cell lines T.T, KYSE30 and KYSE70 were used to study the effects of metformin on human ESCC in vitro. In addition, we used miRNA array tips to explore the differences between miRNAs in KYSE30 cells with and without metformin treatment. Metformin inhibited the proliferation of T.T, KYSE30 and KYSE70 cells in vitro. Metformin blocked the cell cycle in G0/G1 in vitro. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, as well as decreases in cyclin-dependent kinase (Cdk)4, Cdk6 and phosphorylated retinoblastoma protein (Rb). In addition, the expression of miRNAs was markedly altered with the treatment of metformin in vitro. Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6. PMID:23229592

  1. Deprivation of human natural killer cells and antitumor immune response

    Directory of Open Access Journals (Sweden)

    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: Cell-based immunotherapy has been given increased attention as a treatment for cancer. Human natural killer (NK cells are resident lymphocyte populations. They exhibit potent antitumor activity without human leukocyte antigen matching and without prior antigen exposure. They also are a promising tool for immunotherapy of solid and hematologic cancers. However, most cancer patients do not have enough NK cells to induce an effective antitumor immune response. This demonstrates a need for a source of NK cells that can supplement the endogenous cell population. Material and methods: In this study, we derived induced pluripotent stem cells (iPSCs from peripheral blood T-lymphocytes using Sendai virus vectors. Results: Generated iPSCs exhibited monoclonal T cell receptors (TCR rearrangement in their genome, a hallmark of mature terminally differentiated T cells. These iPSCs were differentiated into NK cells using a two-stage coculture system: iPSCs into hematopoietic CD34+ cells with feeder cells M210-B4 (ATCC, USA and CD34+ cells into mature NK cells with AFT024 cells (ATCC, USA. Our results showed that iPSC-derived NK cells expressed CD56, CD16, NKp 44 and NKp 46, possessed high cytotoxic activity  and produced high level of interferon-γ. Conclusion: Based on our data, derivation of NK cells from induced pluripotent stem cells should be considered in the treatment of oncologic diseases.This would allow for the development of cell therapy for cancer using immunologically compatible NK cells derived from iPSCs. This may contribute to a more efficient treatment of oncologic diseases in addition to traditional cancer treatment.

  2. Radiation protection and antitumor effects in Hatakeshimeji (Lyophyllum decastes sing)

    International Nuclear Information System (INIS)

    The effect on an anti-tumor is admitted in the lyophyllum decastes sing extraction thing, and it has the action mechanism cleared to depend on the immunity action. The existence of the synergistic effect in effect on an anti-tumor radiation irradiation, an individual with the medication of lyophyllum decastes sing and effect on combination and the effect on protection of the leukocyte decrease by the radiation was examined by this research. After about 2x106 inoculated sarcoma 180 on the ICR mice, a lyophyllum decastes sing extraction thing gave 100mg/kg for 2 weeks in endoceliac at the every other day. After that, the radiation irradiation of 2 Gy was done three times, and it went to the sutra time target the number of the leukocytes, the lymph node ball some prizes of measurement. And, weight and tumor size were measured after the cancer cell inoculation two weeks. The decrease of the clear tumor size was recognized by the group that only a cancer cell was inoculated by the radiation independent irradiation group, lyophyllum decastes sing and the radiation combination group though tumor size increased as it passed. It faced by the group that only a cancer cell was inoculated after the irradiation 15 days though it died the precedent, and a half existed by lyophyllum decastes sing and the radiation combination group. And, the numbers of the leukocytes, the number of the lymphocyte were on the increase regardless of the existence of the radiation irradiation by the medication of lyophyllum decastes sing. It thinks with the thing that the effect is shown for the effect on immunity recovery in the radiotherapy and the prevention of a side effect of the radiation from this result. Showing the effect for not only effect on prevention of the cancer and effect on healing but also the effect on immunity recovery in the radiotherapy, the prevention of a side effect by taking lyophyllum decastes sing is considered

  3. The Anti-Oxidant and Antitumor Properties of Plant Polysaccharides.

    Science.gov (United States)

    Jiao, Rui; Liu, Yingxia; Gao, Hao; Xiao, Jia; So, Kwok Fai

    2016-01-01

    Oxidative stress has been increasingly recognized as a major contributing factor in a variety of human diseases, from inflammation to cancer. Although certain parts of signaling pathways are still under investigation, detailed molecular mechanisms for the induction of diseases have been elucidated, especially the link between excessive oxygen reactive species (ROS) damage and tumorigenesis. Emerging evidence suggests anti-oxidant therapy can play a key role in treating those diseases. Among potential drug resources, plant polysaccharides are natural anti-oxidant constituents important for human health because of their long history in ethnopharmacology, wide availability and few side effects upon consumption. Plant polysaccharides have been shown to possess anti-oxidant, anti-inflammation, cell viability promotion, immune-regulation and antitumor functions in a number of disease models, both in laboratory studies and in the clinic. In this paper, we reviewed the research progress of signaling pathways involved in the initiation and progression of oxidative stress- and cancer-related diseases in humans. The natural sources, structural properties and biological actions of several common plant polysaccharides, including Lycium barbarum, Ginseng, Zizyphus Jujuba, Astragalus lentiginosus, and Ginkgo biloba are discussed in detail, with emphasis on their signaling pathways. All of the mentioned common plant polysaccharides have great potential to treat oxidative stress and cancinogenic disorders in cell models, animal disease models and clinical cases. ROS-centered pathways (e.g. mitochondrial autophagy, MAPK and JNK) and transcription factor-related pathways (e.g. NF-[Formula: see text]B and HIF) are frequently utilized by these polysaccharides with or without the further involvement of inflammatory and death receptor pathways. Some of the polysaccharides may also influence tumorigenic pathways, such as Wnt and p53 to play their anti-tumor roles. In addition, current

  4. Antibiotics in Canadian poultry productions and anticipated alternatives

    Directory of Open Access Journals (Sweden)

    Moussa Sory Diarra

    2014-06-01

    Full Text Available 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 in feed (growth promoters 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 spread within microbial communities. In Canada, poultry production involves more than 2,600 regulated chicken producers. There are several antibiotics approved as feed additives available for poultry farmers. Feed recipes and mixtures greatly vary 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 sporadic 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

  5. Antibiotics in Canadian poultry productions and anticipated alternatives.

    Science.gov (United States)

    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

  6. Fate and transport of antibiotic residues and antibiotic resistance genetic determinants during manure storage, treatment, and land application

    Science.gov (United States)

    Antibiotics are used in swine production for therapeutic treatment of disease and at sub-therapeutic levels for growth promotion and improvement of feed efficiency. It is estimated that ca.75% of antibiotics are not absorbed by animals and are excreted in waste. Antibiotic resistance selection occur...

  7. Determination of Antibiotic Resistance and Synergistic Effect of Multiple Antibiotics on Helicobacter Pylori Isolated from the Stomach Ulcer Biopsy Specimens

    Directory of Open Access Journals (Sweden)

    Habibi Nava, F. (MSc

    2014-06-01

    Full Text Available Background and Objective: Resistance of Helicobacter Pylori (H. pylori to antibiotics is the main cause of relapse into Helcobacterial infections. With the use of several antibiotics that have synergistic effect, we can inhibit this antibiotic resistance. Thus, we aimed at determining resistance patterns and assessing the synergy of combining multiple antibiotics on H. pylori. Material and Methods: Biopsy specimens were taken from 100 patients with gastric ulcer referred to Imam Reza hospital in Amol, north of Iran. After isolation and identification of H. Pylori, antibiogram was performed with different antibiotic disks containing one antibiotic, a combination of two antibiotics (metronidazole + clarithromycin and three antibiotics (metronidazole + Claritromycin + Ciprofloxacin. Results: In this study, H. pylori were isolated from 53 (53% biopsy specimens. Of these, 49 (5.92% were resistant to metronidazole, 14 (26% to amoxicillin, 10 (19% to clarithromycin, 7 (13% to tetracycline, 13 (5/24% to furazolidone and 7 (13% to ciprofloxacin. In survey of synergistic effect, an increase in inhibition zone diameter around of combined disks was seen up to 5mm compared to the most effective antibiotic. Conclusion: The inhibition zone diameter of discs containing two and three antibiotics was large, in comparison with one antibiotic. Key words: H. Pylori; Antibiotic Resistance; Synergy Effect

  8. An Investigation on a Novel Anti-tumor Fusion Peptide of FSH33-53-IIKK

    Science.gov (United States)

    Yang, Runlin; Liu, Ping; Pan, Donghui; zhang, Pengjun; Bai, Zhicheng; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Yan, Yongjun; Liu, Xingdang; Yang, Min

    2016-01-01

    A novel fusion peptide FSH33-53-IIKK was designed and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor toxicity. In vitro and in vivo study showed the anti-tumor activity of FSH33-53-IIKK was enhanced compared to that of IIKK only. FSH33-53-IIKK could inhibit the growth of tumor via apoptosis and autophagy pathways. In summary, combining the tumor marker-target peptide and anti-tumor peptide together may be an efficient way to search for better anti-tumor candidates. PMID:27313792

  9. Oral antibiotics for perforated appendicitis is not recommended

    DEFF Research Database (Denmark)

    Alamili, Mahdi; Gögenur, Ismail; Rosenberg, Jacob

    2010-01-01

    In the majority of surgical departments in Denmark, the postoperative treatment for acute perforated appendicitis comprises three days of intravenous antibiotics. Recently, it has been proposed that such antibiotic regimen should be replaced by orally administered antibiotics. The aim of this paper...... was to give an overview of studies on acute perforated appendicitis with postoperative oral antibiotics. Five studies were found in a database search covering the 1966-2009 period. There is no evidence to support a conversion of the postoperative antibiotic regimen from intravenous to oral...... administration in patients with acute perforated appendicitis....

  10. Bacteriocins: exploring alternatives to antibiotics in mastitis treatment

    Directory of Open Access Journals (Sweden)

    Reneé Pieterse

    2010-10-01

    Full Text Available Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease.

  11. Influence of Antibiotics Added in Milk over Yogurth Quality

    Directory of Open Access Journals (Sweden)

    Cornelia Vintila

    2010-10-01

    Full Text Available Large spectrum antibiotics used in different cow diseases leads to their release in milk altering its proprieties during processing. Knowing the inhibitory effect of antibiotics upon lactic bacteria development and multiplying we followed the effect of gentamycin, a large spectrum antibiotic added in different doses in milk used for yogurth processing. In our research, besides the effect of antibiotica we followed also the influence of milk fat content upon milk clotting time, while antibiotics added in milk incease the clotting time of yogurth. Clotting density deceases proportional with the dosis of antibiotics added to milk.

  12. Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action

    Directory of Open Access Journals (Sweden)

    Carlet Jean

    2012-02-01

    Full Text Available Abstract Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action". Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs.

  13. Lipid II as a target for antibiotics.

    Science.gov (United States)

    Breukink, Eefjan; de Kruijff, Ben

    2006-04-01

    Lipid II is a membrane-anchored cell-wall precursor that is essential for bacterial cell-wall biosynthesis. The effectiveness of targeting Lipid II as an antibacterial strategy is highlighted by the fact that it is the target for at least four different classes of antibiotic, including the clinically important glycopeptide antibiotic vancomycin. However, the growing problem of bacterial resistance to many current drugs, including vancomycin, has led to increasing interest in the therapeutic potential of other classes of compound that target Lipid II. Here, we review progress in understanding of the antibacterial activities of these compounds, which include lantibiotics, mannopeptimycins and ramoplanin, and consider factors that will be important in exploiting their potential as new treatments for bacterial infections. PMID:16531990

  14. Rapid diagnostics and appropriate antibiotic use.

    Science.gov (United States)

    Rice, Louis B

    2011-05-01

    Most antibiotics are prescribed by physicians lacking postgraduate training in infectious diseases. As such, prescribing physicians have varying levels of interest and sophistication in thinking about how to use molecular and microbiological data to inform therapeutic choices. Strategies designed to modify physician antimicrobial-prescribing practices must therefore choose simplicity over complexity and must acknowledge our fundamental ignorance of many of the specifics of antibiotic-microorganism interactions. They must also acknowledge the critical nature of bacterial illnesses in hospitalized patients and the importance of delivering effective antimicrobial therapy early in the illness. "Back-end" strategies that evaluate therapy at defined intervals will be more readily accepted than strategies limiting physician choices early in the illness. It is therefore critical that we develop rapid and reliable microbiological assays, evidence-based recommendations on appropriate durations of therapy, and accurate surrogate markers of infection resolution. PMID:21460296

  15. Antibiotic Prescription in Danish General Practice

    DEFF Research Database (Denmark)

    Sydenham, Rikke Vognbjerg; Plejdrup Hansen, Malene; Pedersen, Line Bjørnskov;

    2016-01-01

    explore how the GPs prescription behaviour is influenced by selected factors. Antibiotics are essential when treating potentially lethal infections. An increasing development of resistant bacteria is considered one of the primary threats to public health. The majority of antibiotics (90%) are prescribed...... selected factors (microbiological diagnostics, point-of-care tests, patients’ expectations) in the management of infectious diseases. 3. Results This PhD project is scheduled to be carried out in 2016-2019. The hypotheses and anticipated perspectives will be discussed at the conference. 4. Conclusions The...... project will contribute to existing knowledge with information on the diagnostic approaches to infections in general practice. The results will create a base for targeted interventions aiming to optimize diagnostic approaches to infectious diseases benefitting the individual patient and society as a whole....

  16. Nonmedical Uses of Antibiotics: Time to Restrict Their Use?

    Directory of Open Access Journals (Sweden)

    Richard William Meek

    2015-10-01

    Full Text Available The global crisis of antibiotic resistance has reached a point where, if action is not taken, human medicine will enter a postantibiotic world and simple injuries could once again be life threatening. New antibiotics are needed urgently, but better use of existing agents is just as important. More appropriate use of antibiotics in medicine is vital, but the extensive use of antibiotics outside medical settings is often overlooked. Antibiotics are commonly used in animal husbandry, bee-keeping, fish farming and other forms of aquaculture, ethanol production, horticulture, antifouling paints, food preservation, and domestically. This provides multiple opportunities for the selection and spread of antibiotic-resistant bacteria. Given the current crisis, it is vital that the nonmedical use of antibiotics is critically examined and that any nonessential use halted.

  17. Nonmedical Uses of Antibiotics: Time to Restrict Their Use?

    Science.gov (United States)

    Meek, Richard William; Vyas, Hrushi; Piddock, Laura Jane Violet

    2015-10-01

    The global crisis of antibiotic resistance has reached a point where, if action is not taken, human medicine will enter a postantibiotic world and simple injuries could once again be life threatening. New antibiotics are needed urgently, but better use of existing agents is just as important. More appropriate use of antibiotics in medicine is vital, but the extensive use of antibiotics outside medical settings is often overlooked. Antibiotics are commonly used in animal husbandry, bee-keeping, fish farming and other forms of aquaculture, ethanol production, horticulture, antifouling paints, food preservation, and domestically. This provides multiple opportunities for the selection and spread of antibiotic-resistant bacteria. Given the current crisis, it is vital that the nonmedical use of antibiotics is critically examined and that any nonessential use halted. PMID:26444324

  18. Antibiotic misuse in the community--a contributor to resistance?

    LENUS (Irish Health Repository)

    Carey, B

    2012-02-03

    The problem of antibiotic resistance is associated with the indiscriminate usage of antibiotics. Efforts have been directed at encouraging the rational use of these drugs to reduce the volume of antibiotic consumption and decrease resistance rates. There is evidence to suggest that the misuse of antibiotics by patients may also contribute to the problem. We describe a survey of a random selection of patients attending a General Practitioners\\' surgery over a six week period in an effort to estimate the level of non-compliance to antibiotic therapy in the community. The results suggest that there may be a significant level of antibiotic misuse prevalent in the local community. We discuss these results and present evidence in the literature suggesting how antibiotic misuse may affect resistance in the community. The factors affecting patient compliance to therapy are outlined along with suggested measures to improve compliance among patients.

  19. Emergence and dissemination of antibiotic resistance: A global problem

    Directory of Open Access Journals (Sweden)

    R Choudhury

    2012-01-01

    Full Text Available Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure.

  20. Microbiological End-Point Determination of Antibiotics

    OpenAIRE

    Rumney, C. J.; Coutts, J. T.; Smith, J. S.; Rowland, I R

    2011-01-01

    There is currently some concern regarding the possibility that consumption, by humans, of small quantities of veterinary antibiotics, present as residues in meat, might adversely alter the indigenous gut microflora. This study aimed to assess the potential effect on the human gut microflora of exposure to low levels of tilmicosin and spiramycin. Four groups of 4 human-flora-associated rats were dosed for 5 days with either water, tilmicosin (400 or 120 µg/kg/day) or spiramycin (500...

  1. Antibiotic residues in milk from Moldavia, Romania

    Directory of Open Access Journals (Sweden)

    Gheorghe Solcan

    2011-11-01

    Full Text Available The present paper is a study based on the determination of antibiotic residues in milk samplescollected from farms in the NE Romania (Moldavia. Contamination seasonality and the correlations withSCC and TBC values were investigated. Out of 2785 total milk samples, 124 were positive (+ (4.45%and 130 samples were uncertain (± (4.67%. The presence of antibiotics was confirmed in 109 positive(+ samples (87.9% and 24 uncertain (± samples (18.46%, the difference being false-positivereactions. Betalactams were identified in 27.90% of the samples, at an average concentration of 26.65μg/kg. Gentamicin/neomycin were identified in 25% of samples, at an average concentration of 198.68μg gentamicin/kg and 2048.53 μg neomycin/kg. Tetracyclines were identified in 24.42% of the samples,at an average concentration of 271.43 μg/kg. Gentamicin/streptomycin were identified in 15.11% of thesamples, at an average concentrations of 198.68 μg gentamicin/kg and 280.61 μg streptomycin/kg. Themacrolides were identified in 7.56% of the samples, at an average concentration of 97.87 μg tylosin/kg.The antibiotic contamination of milk was low in January (CSi= 0.51 and July (CSi = 0.59, and increasedin April (CSi = 1.77 and May (CSi = 1.43. The milk contamination with antibiotics was associated withincreased SCC and TBC values.

  2. Pharmacokinetic interactions of the macrolide antibiotics.

    Science.gov (United States)

    Ludden, T M

    1985-01-01

    The macrolide antibiotics erythromycin and triacetyloleandomycin (troleandomycin) are prescribed for many types of infections. As such they are often added to other preexisting drug therapy. Thus, there are frequent opportunities for the interaction of these antibiotics with other drugs. Both erythromycin and triacetyloleandomycin appear to have the potential to inhibit drug metabolism in the liver and also drug metabolism by micro-organisms in the gut, either through their antibiotic effect or through complex formation and inactivation of microsomal drug oxidising enzymes. Of the two agents, triacetyloleandomycin appears to be the more potent inhibitor of microsomal drug metabolism. Published studies indicate that triacetyloleandomycin can significantly decrease the metabolism of methylprednisolone, theophylline and carbamazepine. Its ability to cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in patients on oral contraceptives may also be related to its inhibitory effect on drug metabolism. Erythromycin appears to be a much weaker inhibitor of drug metabolism. There are numerous reports describing apparent interactions of erythromycin with theophylline and a lesser number of reports dealing with carbamazepine, warfarin methylprednisolone and digoxin. There are sufficient data to suggest that erythromycin can, in some individuals, inhibit the elimination of methylprednisolone, theophylline, carbamazepine and warfarin. The mean change in drug clearance is about 20 to 25% in most cases, with some patients having a much larger change than others. Like tetracycline, erythromycin also appears to have the potential for increasing the bioavailability of digoxin in patients who excrete high amounts of reduced digoxin metabolites, apparently through destruction of the gut flora that form these compounds. Concurrent administration of triacetyloleandomycin with drugs whose metabolism is known to be affected or that could potentially be affected

  3. The Local Treatment of Burns With Antibiotics

    OpenAIRE

    Napoli, B.; D’Arpa, N.; Masellis, A.; Masellis, M.

    2005-01-01

    After presenting an analysis of the principal antiseptics used for the local treatment of burns, highlighting their toxicity and the limitations of their antibacterial effectiveness, we describe the therapeutic protocol used in our burns centre (where antibacterial treatment consists exclusively of antibiotics for both local and systemic use). We review the data regarding actual and predicted mortality, and mortality due to septicaemia during the years 2000-2003.

  4. Cardiac dysrhythmia resulting from antibiotic abuse

    OpenAIRE

    Basil Nwaneri Okeahialam

    2015-01-01

    Antibiotics are commonly used to combat infections and could be used in treating some connective diseases. They are not without side effects especially when used without regard to age, gender, diseases and their severity, comorbidity, and idiosyncrasies. This is more likely to occur when dispensed by unqualified persons to selves or others. Consequences of inappropriate use include various morbidities and in some instances death. This is a report of a middle-aged man with several risk factors...

  5. Photodynamic inactivation of antibiotic-resistant pathogens

    International Nuclear Information System (INIS)

    Nowadays methicillin-resistant strain Staphylococcus aureus (MRSA) is one of the most widespread multiresistant bacteria. Photodynamic inactivation (PDI) of microorganisms by photosensitizers (PS) may be an effective and alternative therapeutic option against antibiotic resistant bacteria. The effectiveness of new PS cationic porphyrin Zn-TBut4PyP was tested on two strains of S. aureus (MRSA and methicillin-sensitive S. aureus). It is shown that Zn-TBut4PyP has high photodynamic activity against both strains

  6. Antibiotic resistance of lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Bulajić Snežana

    2008-01-01

    Full Text Available Knowledge on the antibiotic resistance of lactic acid bacteria is still limited, possibly because of the large numbers of genera and species encountered in this group, as well as variances in their resistance spectra. The EFSA considers antibiotic resistances, especially transferable resistances, an important decision criterion for determining a strain's QPS status. There are no approved standards for the phenotypic or genotypic evaluation of antibiotic resistances in food isolates. Also, the choice of media is problematic, as well as the specification of MIC breakpoint values as a result of the large species variation and the possible resulting variation in MIC values between species and genera. The current investigations in this field showed that we might end up with a range of different species- or genus-specific breakpoint values that may further increase the current complexity. Another problem associated with safety determinations of starter strains is that once a resistance phenotype and an associated resistance determinant have been identified, it becomes difficult to show that this determinant is not transferable, especially if the resistance gene is not located on a plasmid and no standard protocols for showing genetic transfer are available. Encountering those problems, the QPS system should allow leeway for the interpretations of results, especially when these relate to the methodology for resistance phenotype determinations, determinations of MIC breakpoints for certain genera, species, or strains, the nondeterminability of a genetic basis of a resistance phenotype and the transferability of resistance genes.

  7. [Antibiotic-associated diarrhea in clinical practice].

    Science.gov (United States)

    Luzina, E V; Lareva, N V

    2013-01-01

    Antibiotic-associated diarrhea (AAD) is considered to mean at least 3 shapeless stool episodes within 2 or more consecutive days when using antibacterial agents. Due to the fact that antibiotics are used most commonly to treat many diseases, AAD is one of the topical problems for different clinical specialists. There has recently been increased interest in this condition due to its higher morbidity and mortality rates and the emergence of novel treatment-resistant virulent strains of Clostridium difficile 027 and 078/126. The paper discusses the possible risk of developing AAD depending on the class of the antibiotic used, as well as the mechanisms of its development. Infectious diarrhea most frequently results from bacterial overgrowth due to that the obligate intestinal microflora is suppressed by antibacterial drugs. C. difficile, Clostridium perfringers, Staphylococcus aureus, Salmonella spp., Klebsiella oxytoca, and Candida spp. are etiological factors in the development of this diarrhea. The severest intestinal lesions include pseudomembranous colitis (PMC) caused by C. difficile. The clinical and endoscopic picture and methods for the diagnosis and treatment of PMC are described. Therapy for this menacing condition is traditionally based on the use of metronidazole and vancomycin. In 2011, the US Food and Drug Administration approved the new drug fidaxomycin whose superiority over vancomycin has been demonstrated by a recurrence criterion. The paper discusses in detail other treatment options, including the use of probiotics. PMID:23653946

  8. Selective condensation of DNA by aminoglycoside antibiotics.

    Science.gov (United States)

    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. PMID:26646261

  9. Antibiotic Resistance in Childhood with Pneumococcal Infection

    Directory of Open Access Journals (Sweden)

    Ali Gunes

    2013-10-01

    Full Text Available Aim: Resistance to antibiotics is better. Between should not be in capitals. Antibiotics resistant has been increasing in pneumococci that cause serious diseases such as pneumonia, meningitis in recent years. The resistance rates vary between geographic regions. In this study, we aimed to determine antibiotic resistance rates in pneumococcal infections in our region. Material and Method: This study included 31 pneumococcal strains isolated from blood, CSF and urine samples of patients with meningitis, sepsis and urinary tract infections who admitted Dicle University Medicine School Children Clinic and Diyarbakir Pediatric Hospital Between December 2004-April 2007. Reproducing clinical specimens with alpha-hemolysis, optochin-sensitive, bile soluble and gram-positive diplococci morphology was defined as S. pneumoniae. The antimicrobial susceptibilities of strains were measured by the E-test method. MIC values of penicillin against pneumococci was accepted as <0.06 mg / ml value of the sensitive, 0.12-1μg/ml mid-level resistance, ≥ 2 mg / ml value of the high-level resistance. Results: It was found 16% mid-level penicillin resistance and 3.2% high-level penicillin resistance by E-test method. 80.7% of Strains were percent of the penicillin-sensitive. Seftiriakson resistance was found as 3.2%. there was not Vancomycin resistance. Discussion: We think penicillin therapy is enough effective for pneumococcal infections except serious conditions such as meningitis and sepsis. Also we think it should be supported by multicenter studies.

  10. Antibiotic Susceptibility of Potentially Probiotic Vaginal Lactobacilli

    Directory of Open Access Journals (Sweden)

    María Elena Nader-Macías

    2006-09-01

    Full Text Available Objective. To study the antimicrobial susceptibility of six vaginal probiotic lactobacilli. Methods. The disc diffusion method in Müeller Hinton, LAPTg and MRS agars by the NCCLS (National Committee for Clinical Laboratory Standards procedure was performed. Due to the absence of a Lactobacillus reference strains, the results were compared to those of Staphylococcus aureus ATCC29213. Minimal Inhibitory Concentration (MIC with 21 different antibiotics in LAPTg agar and broth was also determined. Results. LAPTg and MRS agars are suitable media to study antimicrobial susceptibility of lactobacilli. However, the NCCLS procedure needs to be standardized for this genus. The MICs have shown that all Lactobacillus strains grew at concentrations above 10 μg/mL of chloramphenicol, aztreonam, norfloxacin, ciprofloxacin, ceftazidime, ceftriaxone, streptomycin and kanamycin. Four lactobacilli were sensitive to 1 μg/mL vancomycin and all of them were resistant to 1000 μg/mL of metronidazole. Sensitivity to other antibiotics depended on each particular strain. Conclusions. The NCCLS method needs to be standardized in an appropriate medium to determine the antimicrobial susceptibility of Lactobacillus. Vaginal probiotic lactobacilli do not display uniform susceptibility to antibiotics. Resistance to high concentrations of metronidazole suggests that lactobacilli could be simultaneously used with a bacterial vaginosis treatment to restore the vaginal normal flora.

  11. Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms

    Institute of Scientific and Technical Information of China (English)

    Zhi-bin LIN; Hui-na ZHANG

    2004-01-01

    Ganoderma lucidum (G lucidum) is a medicinal fungus with a variety of biological activities. It has long been used as a folk remedy for promotion of health and longevity in China and other oriental countries. The most attractive character of this kind of medicinal fungus is its immunomodulatory and anti-tumor activities. Large numbers of studies have shown that G lucidum modulate many components of the immune system such as the antigen-presenting cells, NK cells, T and B lymphocytes. The water extract and the polysaccharides fraction of G lucidum exhibited significant anti-tumor effect in several tumor-bearing animals mainly through its immunoenhancing activity. Recent studies also showed that the alcohol extract or the triterpene fraction of G lucidum possessed antitumor effect, which seemed to be related to the cytotoxic activity against tumor cells directly. Preliminary study indicated that antiangiogenic effect may be involved antitumor activity of G lucidum.

  12. Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents†

    OpenAIRE

    Kuo, Reen-Yen; Qian, Keduo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2009-01-01

    This article reviews the antitumor and anti-HIV activities of naturally occurring triterpenoids, including the lupane, ursane, oleanane, lanostane, dammarane, and miscellaneous scaffolds. Structure–activity relationships of selected natural compounds and their synthetic derivatives are also discussed.

  13. Synthesis and Antitumor Activity of C-2/C-10 Modified Analogues of Docetaxel

    Institute of Scientific and Technical Information of China (English)

    Wei Shuo FANG; Hong Yan LIU; Qi Cheng FANG

    2005-01-01

    Four 10-propionyl docetaxel analogues (11a-d) with 2α-amido substituents were prepared, and their antitumor activity against three solid tumor cell lines and their drug-resistant counterparts were determined.

  14. A review about the development of fucoidan in antitumor activity: Progress and challenges.

    Science.gov (United States)

    Wu, Lei; Sun, Jing; Su, Xitong; Yu, Qiuli; Yu, Qiuyang; Zhang, Peng

    2016-12-10

    Fucoidan is composed of l-fucose, sulfate groups and one or more small proportions of d-xylose, d-mannose, d-galactose, l-rhamnose, arabinose, glucose, d-glucuronic acid and acetyl groups in different kinds of brown seaweeds. Many reports have demonstrated that fucoidan has antitumor activities on various cancers. However, until now, few reviews have discussed the antitumor activity of fucoidan and few reports have summarized detailed molecular mechanisms of its actions and antitumor challenges of fucoidan specially. In this review, the antitumor signaling pathway mechanisms related to fucoidan are elucidated as much detail as possible. Besides, the factors affecting the anticancer effects of fucoidan, the structural characteristics of fucoidan with anticancer activities and the challenges for the further development of fucoidan are also summarized and evaluated. The existing similar and different conclusions are summarized in an attempt to provide guidelines to help further research, and finally contribute to go into market as chemotherapeumtics. PMID:27577901

  15. 5α-reductase inhibitors, antiviral and anti-tumor activities of some steroidal cyanopyridinone derivatives.

    Science.gov (United States)

    Al-Mohizea, Abdullah M; Al-Omar, Mohamed A; Abdalla, Mohamed M; Amr, Abdel-Galil E

    2012-01-01

    We herein report the 5α-reductase inhibitors, antiviral and anti-tumor activities of some synthesized heterocyclic cyanopyridone and cyanothiopyridone derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds, except 3b, were interestingly less toxic than the reference drug (Prednisolone(®)). Seventeen heterocyclic derivatives containing a cyanopyridone or cyanothiopyridone rings fused to a steroidal moiety were synthesized and screened for their 5α-reductase inhibitors, antiviral and anti-tumor activities comparable to that of Anastrozole, Bicalutamide, Efavirenz, Capravirine, Ribavirin, Oseltamivir and Amantadine as the reference drugs. Some of the compounds exhibited better 5α-reductase inhibitors, antiviral and anti-tumor activities than the reference drugs. The detailed 5α-reductase inhibitors, antiviral and anti-tumor activities of the synthesized compounds were reported. PMID:22057085

  16. Antibiotic-releasing porous polymethylmethacrylate/gelatin/antibiotic constructs for craniofacial tissue engineering.

    Science.gov (United States)

    Shi, Meng; Kretlow, James D; Spicer, Patrick P; Tabata, Yasuhiko; Demian, Nagi; Wong, Mark E; Kasper, F Kurtis; Mikos, Antonios G

    2011-05-30

    An antibiotic-releasing porous polymethylmethacrylate (PMMA) construct was developed to maintain the bony space and prime the wound site in the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite craniofacial tissue defects. Porous PMMA constructs incorporating gelatin microparticles (GMPs) were fabricated by the sequential assembly of GMPs, the antibiotic colistin, and a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid. PMMA/gelatin/antibiotic constructs with varying gelatin incorporation and drug content were investigated to elucidate the relationship between material composition and construct properties (porosity and drug release kinetics). The porosity of PMMA/gelatin/antibiotic constructs ranged between 7.6±1.8% and 38.4±1.4% depending on the amount of gelatin incorporated and the drug solution added for gelatin swelling. The constructs released colistin over 10 or 14 days with an average release rate per day above 10 μg/ml. The porosity and in vitro colistin release kinetics of PMMA/gelatin/antibiotic constructs were tuned by varying the material composition and fabrication parameters. This study demonstrates the potential of gelatin-incorporating PMMA constructs as a functional space maintainer for both promoting tissue healing/coverage and addressing local infections, enabling better long-term success of the definitive regenerated tissue construct. PMID:21295086

  17. Targeting antibiotics to households for trachoma control.

    Directory of Open Access Journals (Sweden)

    Isobel M Blake

    Full Text Available BACKGROUND: Mass drug administration (MDA is part of the current trachoma control strategy, but it can be costly and results in many uninfected individuals receiving treatment. Here we explore whether alternative, targeted approaches are effective antibiotic-sparing strategies. METHODOLOGY/PRINCIPAL FINDINGS: We analysed data on the prevalence of ocular infection with Chlamydia trachomatis and of active trachoma disease among 4,436 individuals from two communities in The Gambia (West Africa and two communities in Tanzania (East Africa. An age- and household-structured mathematical model of transmission was fitted to these data using maximum likelihood. The presence of active inflammatory disease as a marker of infection in a household was, in general, significantly more sensitive (between 79% [95%CI: 60%-92%] and 86% [71%-95%] across the four communities than as a marker of infection in an individual (24% [16%-33%]-66% [56%-76%]. Model simulations, under the best fit models for each community, showed that targeting treatment to households has the potential to be as effective as and significantly more cost-effective than mass treatment when antibiotics are not donated. The cost (2007US$ per incident infection averted ranged from 1.5 to 3.1 for MDA, from 1.0 to 1.7 for household-targeted treatment assuming equivalent coverage, and from 0.4 to 1.7 if household visits increased treatment coverage to 100% in selected households. Assuming antibiotics were donated, MDA was predicted to be more cost-effective unless opportunity costs incurred by individuals collecting antibiotics were included or household visits improved treatment uptake. Limiting MDA to children was not as effective in reducing infection as the other aforementioned distribution strategies. CONCLUSIONS/SIGNIFICANCE: Our model suggests that targeting antibiotics to households with active trachoma has the potential to be a cost-effective trachoma control measure, but further work is

  18. Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

    OpenAIRE

    Svetla Angelova; Zlatina Gospodinova; Maria Krasteva; Georgi Antov; Valentin Lozanov; Tsanko Markov; Stefan Bozhanov; Elena Georgieva; Vanio Mitev

    2013-01-01

    Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction o...

  19. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents–A drug repurposing strategy

    OpenAIRE

    Chia-Hsien Wu; Li-Yuan Bai; Ming-Hsui Tsai; Po-Chen Chu; Chang-Fang Chiu; Michael Yuanchien Chen; Shih-Jiuan Chiu; Jo-Hua Chiang; Jing-Ru Weng

    2016-01-01

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the pa...

  20. Efficient microwave irradiation enhanced stereoselective synthesis and antitumor activity of indolylchalcones and their pyrazoline analogs

    Indian Academy of Sciences (India)

    Magdy A H Zahran; Hanan F Salama; Yasmin G Abdin; Amira M Gamal-Eldeen

    2010-07-01

    2-Aryl-1-indole-3-carbaldehyde derivatives underwent Claisen-Schmidt condensation with acetophenone derivatives under microwave irradiation condition compared with the conventional heating to afford excellent yields of trans substituted indolylchalcones which subjected to condensation reaction with phenylhydrazine to afford their indolylpyrazoline analogs. The antitumor activity of the synthesized compounds was examined and evaluated against human hepatocellular carcinoma cell line (Hep-G2) as well as the half maximal inhibitory concentration (IC50). Most of them showed high potent antitumor activity.

  1. Myeloid-Derived Suppressor Cells and anti-tumor T cells: a complex relationship

    OpenAIRE

    Monu, Ngozi R.; Frey, Alan B.

    2012-01-01

    Myeloid-Derived Suppressor Cells (MDSC) are immature myeloid cells that are potent inhibitors of immune cell function and which accumulate under conditions of inflammation, especially cancer. MDSC are suggested to promote the growth of cancer by both enhancement of tumor angiogenesis and metastasis and also inhibition of antitumor immune responses. The presence of deficient and/or defective antitumor adaptive and innate immune responses, coincident with accumulation of MDSC in lymphoid organs...

  2. Medicinal Plants Used as Antitumor Agents in Brazil: An Ethnobotanical Approach

    OpenAIRE

    Joabe Gomes de Melo; Ariane Gaspar Santos; Elba Lúcia Cavalcanti de Amorim; Silene Carneiro do Nascimento; Ulysses Paulino de Albuquerque

    2011-01-01

    In this study, we describe the medicinal plants that have been reported to be antitumor agents and that have been used in ethnobotanic research in Brazil to answer the following questions: what is the abundance of plants reported to be antitumor in Brazil? Have the plant species used for tumor treatment in traditional Brazilian medicine been sufficiently examined scientifically? Our analysis included papers published between 1980 and 2008. A total of 84 medicinal plant species were reported t...

  3. The antitumor effect of locoregional magnetic cobalt ferrite in dog mammary adenocarcinoma

    International Nuclear Information System (INIS)

    The endocytosis of nanosized magnetic particles by tumor cells led to numerous tests to establish the use of this phenomenon in antitumor therapy. The direct antitumor effect of a biocompatible cobalt-ferrite-based magnetic fluid directly inoculated in bitch mammary tumors was studied. A direct correlation between tumor cell lysis and cobalt ferrite was established in tumors. Massive endocytosis of magnetic particles was observed 1 h after the contact of magnetic fluid with tumor cells

  4. In Search of the E. coli Compounds that Change the Antibiotic Production Pattern of Streptomyces coelicolor During Inter-species Interaction.

    Science.gov (United States)

    Mavituna, Ferda; Luti, Khalid Jaber Kadhum; Gu, Lixing

    2016-08-01

    The aim of this work was to investigate the interaction between E.coli and Streptomyces coelicolor A3 (2) for the increased production of undecylprodigiosin and identify the E. coli actives mediating this inter-species interaction. The antibiotics of interest were the red-pigmented undecylprodigiosin and blue-pigmented actinorhodin. Pure cultures of S. coelicolor in a defined medium produced higher concentrations of actinorhodin compared to those of undecylprodigiosin. The latter however, is more important due to its immunosuppressive and antitumor properties. As a strategy to increase undecylprodigiosin production, we added separately, live cells and heat-killed cells of E. coli C600, and the cell-free supernatant of E. coli culture to S. coelicolor cultures in shake flasks. The interaction with live cells of E. coli altered the antibiotic production pattern and undecylprodigiosin production was enhanced by 3.5-fold compared to the pure cultures of S. coelicolor and actinorhodin decreased by 15-fold. The heat-killed cells of E. coli however, had no effect on antibiotic production. In all cases, growth and glucose consumption of S. coelicolor remained almost the same as those observed in the pure culture indicating that the changes in antibiotic production were not due to nutritional stress. Results with cell-free supernatant of E. coli culture indicated that the interaction between S. coelicolor and E. coli was mediated via diffusible molecule(s). Using a set of extraction procedures and agar-well diffusion bioassays, we isolated and preliminarily identified a class of compounds. For the preliminary verification, we added the compound which was the common chemical structural moiety in this class of compounds to the pure S. coelicolor cultures. We observed similar effects on antibiotic production as with the live E. coli cells and their supernatant indicating that this class of compounds secreted by E. coli indeed could act as actives during interspecies

  5. A new model for ligand release. Role of side chain in gating the enediyne antibiotic.

    Science.gov (United States)

    Hariharan, Parameswaran; Liang, Wenchuan; Chou, Shan-Ho; Chin, Der-Hang

    2006-06-01

    Antitumor antibiotic chromoproteins such as neocarzinostatin involve a labile toxin that is tightly bound by a protective protein with very high affinity but must also be freed to exert its function. Contrary to the prevalent concept of ligand release, we established that toxin release from neocarzinostatin requires no major backbone conformational changes. We report, herein, that subtle changes in the side chains of specific amino acid residues are adequate to gate the release of chromophore. A recombinant wild type aponeocarzinostatin and its variants mutated around the opening of the chromophore binding cleft are employed to identify specific side chains likely to affect chromophore release. Preliminary, biophysical characterization of mutant apoproteins by circular dichroism and thermal denaturation indicate that the fundamental structural characteristics of wild type protein are conserved in these mutants. The chromophore reconstitution studies further show that all mutants are able to bind chromophore efficiently with similar complex structures. NMR studies on 15N-labeled mutants also suggest the intactness of binding pocket structure. Kinetic studies of chromophore release monitored by time course fluorescence and quantitative high pressure liquid chromatography analyses show that the ligand release rate is significantly enhanced only in Phe78 mutants. The extent of DNA cleavage in vitro corresponds well to the rate of chromophore release. The results provide the first clear-cut indication of how toxin release can be controlled by a specific side chain of a carrier protein. PMID:16567802

  6. Public Beliefs about Antibiotics, Infection and Resistance: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Helen Madden

    2013-11-01

    Full Text Available We aimed to gain an in-depth understanding of public views and ways of talking about antibiotics. Four focus groups were held with members of the public. In addition, 39 households were recruited and interviews, diaries of medicine taking, diaries of any contact with medication were used to explore understanding and use of medication. Discussions related to antibiotics were identified and analyzed. Participants in this study were worried about adverse effects of antibiotics, particularly for recurrent infections. Some were concerned that antibiotics upset the body’s “balance”, and many used strategies to try to prevent and treat infections without antibiotics. They rarely used military metaphors about infection (e.g., describing bacteria as invading armies but instead spoke of clearing infections. They had little understanding of the concept of antibiotic resistance but they thought that over-using antibiotics was unwise because it would reduce their future effectiveness. Previous studies tend to focus on problems such as lack of knowledge, or belief in the curative powers of antibiotics for viral illness, and neglect the concerns that people have about antibiotics, and the fact that many people try to avoid them. We suggest that these concerns about antibiotics form a resource for educating patients, for health promotion and social marketing strategies.

  7. Use of antibiotics by primary care doctors in Hong Kong

    Directory of Open Access Journals (Sweden)

    Lam Tai

    2009-05-01

    Full Text Available Abstract Objectives To determine the use of antibiotics by primary care doctors. Methods General practitioners in Hong Kong were invited to fill in a short questionnaire on every patient with infection that they had seen on the first full working day once every three months for four consecutive quarters starting from December 2005. Results Forty six primary care doctors took part and a total of 3096 completed questionnaires were returned. The top three diagnoses were upper respiratory tract infection (46.7%, gastrointestinal infection (8.2% and pharyngitis (7.1%. Thirty percent of patient encounters with infections were prescribed antibiotics but only 5.2% of patient encounters with upper respiratory tract infection (URTI were prescribed antibiotics. Amino-penicillins were the most commonly used antibiotics while beta-lactam/beta-lactamase inhibitor combinations (BLBLIs were the second most commonly used antibiotics and they accounted for 16.5% and 14.0% of all antibiotics used respectively. Of all patients or their carers, those who demanded or wished for antibiotics were far more likely to be prescribed antibiotics (Pearson chi-square test, p Conclusion The antibiotic prescribing patterns of primary care doctors in Hong Kong are broadly similar to primary care doctors in other developed countries but a relatively low rate of antibiotics is used for URTI.

  8. Stimulation of granulocytic cell iodination by pine cone antitumor substances

    International Nuclear Information System (INIS)

    Antitumor substances (Fractions VI and VII) prepared from the NaOH extract of pine cone significantly stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood adherent mononuclear cells, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells. In contrast, these fractions did not significantly increase the iodination of nonadherent mononuclear cells, red blood cells, other human leukemic cell lines (U-937, THP-1, K-562), human diploid fibroblast (UT20Lu), or mouse cell lines (L-929, J774.1). Iodination of HL-60 cells, which were induced to differentiate by treatment with either retinoic acid or tumor necrosis factor, were stimulated less than untreated cells. The stimulation of iodination of both PMN and HL-60 cells required the continuous presence of these fractions and was almost completely abolished by the presence of myeloperoxidase inhibitors. The stimulation activity of these fractions was generally higher than that of various other immunopotentiators. Possible mechanisms of extract stimulation of myeloperoxidase-containing cell iodination are discussed

  9. Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya [BWH-HST Center for Biomedical Engineering, Harvard Medical School, 65 Landsdowne street, Cambridge, MA 02139 (United States); Amarasiriwardena, Chitra J; Lupoli, Nicola, E-mail: ssengupta2@partners.org [Channing Laboratory, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, 65 Landsdowne street, Cambridge, MA 02139 (United States)

    2011-07-01

    The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC{sub 50} = 0.77 {+-} 0.11 {mu}M comparable to that of free cisplatin (IC{sub 50} = 0.44 {+-} 0.09 {mu}M). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.

  10. Antitumor constituents from the leaves of Carya cathayensis.

    Science.gov (United States)

    Cao, Xu-Dong; Ding, Zhi-Shan; Jiang, Fu-Sheng; Ding, Xing-Hong; Chen, Jian-Zhen; Chen, Su-Hong; Lv, Gui-Yuan

    2012-01-01

    This study aimed to find cytotoxic chemical constituents from Carya cathayensis leaves (LCC) by using various chromatographic procedures. Identification of the chemical constituents was carried out by various spectroscopic techniques and classical chemical methods. The cytotoxic activity of the constituents was assayed on HeLa and HepG2 cell lines by staining with 3-(4,5-dimethylthiahiazol-2-y1)-2,5-di-phenytetrazolium bromide (MTT). Six flavanoids, namely (1) pinostrobin, (2) pinostrobin chalcone, (3) wogonin, (4) cardamonin, (5) alpinetin and (6) tectochrysin were identified from this species. Compounds 2-6 were isolated from this kind of plant for the first time. MTT results showed that wogonin has a moderate cytotoxic activity with IC(50) values of 17.03 ± 2.41 and 44.23 ± 3.87 µM against HeLa and HepG2 cell lines, respectively. According to the correlation of primary the structure and activity, 8-methoxy substituent in these flavones may be a major factor of the antitumor activity. PMID:22007794

  11. GMCSF-armed vaccinia virus induces an antitumor immune response.

    Science.gov (United States)

    Parviainen, Suvi; Ahonen, Marko; Diaconu, Iulia; Kipar, Anja; Siurala, Mikko; Vähä-Koskela, Markus; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli

    2015-03-01

    Oncolytic Western Reserve strain vaccinia virus selective for epidermal growth factor receptor pathway mutations and tumor-associated hypermetabolism was armed with human granulocyte-macrophage colony-stimulating factor (GMCSF) and a tdTomato fluorophore. As the assessment of immunological responses to human transgenes is challenging in the most commonly used animal models, we used immunocompetent Syrian golden hamsters, known to be sensitive to human GMCSF and semipermissive to vaccinia virus. Efficacy was initially tested in vitro on various human and hamster cell lines and oncolytic potency of transgene-carrying viruses was similar to unarmed virus. The hGMCSF-encoding virus was able to completely eradicate subcutaneous pancreatic tumors in hamsters, and to fully protect the animals from subsequent rechallenge with the same tumor. Induction of specific antitumor immunity was also shown by ex vivo co-culture experiments with hamster splenocytes. In addition, histological examination revealed increased infiltration of neutrophils and macrophages in GMCSF-virus-treated tumors. These findings help clarify the mechanism of action of GMCSF-armed vaccinia viruses undergoing clinical trials. PMID:25042001

  12. Epidemiological Interpretation of Studies Examining the Effect of Antibiotic Usage on Resistance

    OpenAIRE

    Schechner, V.; Temkin, E.; Harbarth, S.; Carmeli, Y; Schwaber, M. J.

    2013-01-01

    Bacterial resistance to antibiotics is a growing clinical problem and public health threat. Antibiotic use is a known risk factor for the emergence of antibiotic resistance, but demonstrating the causal link between antibiotic use and resistance is challenging. This review describes different study designs for assessing the association between antibiotic use and resistance and discusses strengths and limitations of each. Approaches to measuring antibiotic use and antibiotic resistance are pre...

  13. Antibiotic Sensitivity Profiles Determined with an Escherichia coli Gene Knockout Collection: Generating an Antibiotic Bar Code ▿ †

    Science.gov (United States)

    Liu, Anne; Tran, Lillian; Becket, Elinne; Lee, Kim; Chinn, Laney; Park, Eunice; Tran, Katherine; Miller, Jeffrey H.

    2010-01-01

    We have defined a sensitivity profile for 22 antibiotics by extending previous work testing the entire KEIO collection of close to 4,000 single-gene knockouts in Escherichia coli for increased susceptibility to 1 of 14 different antibiotics (ciprofloxacin, rifampin [rifampicin], vancomycin, ampicillin, sulfamethoxazole, gentamicin, metronidazole, streptomycin, fusidic acid, tetracycline, chloramphenicol, nitrofurantoin, erythromycin, and triclosan). We screened one or more subinhibitory concentrations of each antibiotic, generating more than 80,000 data points and allowing a reduction of the entire collection to a set of 283 strains that display significantly increased sensitivity to at least one of the antibiotics. We used this reduced set of strains to determine a profile for eight additional antibiotics (spectinomycin, cephradine, aztreonem, colistin, neomycin, enoxacin, tobramycin, and cefoxitin). The profiles for the 22 antibiotics represent a growing catalog of sensitivity fingerprints that can be separated into two components, multidrug-resistant mutants and those mutants that confer relatively specific sensitivity to the antibiotic or type of antibiotic tested. The latter group can be represented by a set of 20 to 60 strains that can be used for the rapid typing of antibiotics by generating a virtual bar code readout of the specific sensitivities. Taken together, these data reveal the complexity of intrinsic resistance and provide additional targets for the design of codrugs (or combinations of drugs) that potentiate existing antibiotics. PMID:20065048

  14. Antibiotics in acute necrotizing pancreatitis --- perspective of a developing country

    International Nuclear Information System (INIS)

    Prophylactic antibiotics in acute necrotizing pancreatitis is controversial. The mortality of acute necrotizing pancreatitis is 8-25% in the western world. In view of the limited resources available for managing the complications of infected pancreatitis in developing countries, the use of prophylactic antibiotics may be recommended in selected cases. Various antibiotics show good penetration into the pancreatic tissue; imipenem and quinolones have better penetration. Clinical trials on the use of prophylactic antibiotics in necrotizing pancreatitis have been reviewed. Prophylactic antibiotics have been considered if greater than 30% pancreatic necrosis as documented by CT scan. Imipenem can be given for a duration of 10 to 14 days if no systemic complications are present. In a developing country where the cost of managing complications of pancreatitis can be a limiting factor for patients, the use of prophylactic antibiotics early on in the disease in selected cases can be beneficial. (author)

  15. The ionising radiation effect on reactivation of antibiotics

    International Nuclear Information System (INIS)

    The effect of gamma-radiation on the molecular structure of antibiotics was studied with a view to extending their useful life beyond the current expiration period. The following antibiotics were examined: penicillin, bicillin-3,5, streptomycine, and ampioxe. The samples were irradiated by Co-60 gamma-radiation from a research irradiator. Doses of 0.1, 1, 5, 7, and 10 Gy were applied. The processes were elucidated using the classical method of 2-divisible serial dilutions and IR-spectroscopy. All the measurements were carried out at 300 K. The IR-spectra revealed that the chemical structure of new and old antibiotics is identical; the change in the antibiotic activity is generally a result of deformation of the molecule or change in its conformation; the reactivation process returns the molecule to its previous state and the activity of antibiotic after reactivation meets established standards. Hence, this method can be used for the reactivation of expired antibiotics

  16. OCULAR INFECTIONS: RATIONAL APPROACH TO ANTIBIOTIC THERAPY

    Directory of Open Access Journals (Sweden)

    Mulla Summaiya A

    2012-02-01

    Full Text Available Background: Isolation of common pathogens involved in ocular infection and their in-vitro susceptibility to commonly used ocular antibiotics, as well as the trends in antibiotic resistance developed by these pathogens were investigated. Material/Methods: All patients with suspected bacterial ocular infections presenting between march 2010 and feb 2011 were examined under slit lamp microscope and samples were collected by using aseptic techniques. All samples were processed for direct microscopy, culture and identification by standard methods. Susceptibility testing was done by Kirby-Bauer method as per CLSI guideline. Results: Out of 116 patients with ocular infections 130 samples were collected, from which 38 different organisms were isolated. Gram-positive cocci 21 (55%, gram-negative cocco-bacilli 5(31% and gram-negative bacilli 12 (32% were isolated. Coagulase negative Staphylococci (37% and Pseudomonas species (21% were the most commonly-isolated. Gatifloxacin has highest efficacy (89% against all isolates. Majority of gram positive cocci were susceptible to vancomycin, gatifloxacin, cefazolin, gram negative cocco-bacilli to amikacin, tobramycin, fluoroquinolone and gram negative bacilli to gatifloxacin. Conclusion: Majority of ocular infection is caused by gram positive organisms which were susceptible to vancomycin followed by gram negative organisms susceptible to amikacin, fluoroquinolone, gram negative cocco-bacilli to amikacin and tobramycin, and gatifloxacin effective against both type of organisms. The information provided in this article help the clinician in formulating rationale-based empirical antibiotic treatment of bacterial ocular infections. [National J of Med Res 2012; 2(1.000: 22-24

  17. Cardiac dysrhythmia resulting from antibiotic abuse

    Directory of Open Access Journals (Sweden)

    Basil Nwaneri Okeahialam

    2015-01-01

    Full Text Available Antibiotics are commonly used to combat infections and could be used in treating some connective diseases. They are not without side effects especially when used without regard to age, gender, diseases and their severity, comorbidity, and idiosyncrasies. This is more likely to occur when dispensed by unqualified persons to selves or others. Consequences of inappropriate use include various morbidities and in some instances death. This is a report of a middle-aged man with several risk factors for cardiovascular disease, who on the side had chronic osteomyelitis. Wound swab grew organisms sensitive to levofloxacin, and he had the drug prescribed to him by the attending orthopedic surgeon. With reduction in discharge to the point that he no longer bound his foot in bandage, he went on using the drug beyond the duration of prescription without reverting to his orthopedic surgeon until he developed sudden onset palpitation and shortness of breath. With this was an unusual tachyarrhythmia which defied initial measures. This prompted further review of his drug history when he admitted to taking levofloxacin for up to 3 months. Suspecting it to be the culprit, he was advised to discontinue it. With this, his symptoms started to abate, alongside gradual improvement in electrocardiograms till eventual normalization. This report is made to highlight the possibility that some antibiotics have the propensity to induce arrhythmias that can be very serious especially in cardiovascular disease-burdened patients. Such patients then go into heart failure and it becomes difficult to tell which came first, the arrhythmia or the heart failure. Resolving the order of onset assists in proper management. As a result, it is being recommended that patients with unexplained arrhythmias with or without heart failure should have their drug histories evaluated. Uncontrolled prescription and use of antibiotics should also be discouraged.

  18. Antibiotics promote aggregation within aquatic bacterial communities.

    Science.gov (United States)

    Corno, Gianluca; Coci, Manuela; Giardina, Marco; Plechuk, Sonia; Campanile, Floriana; Stefani, Stefania

    2014-01-01

    The release of antibiotics (AB) into the environment poses several threats for human health due to potential development of AB-resistant natural bacteria. Even though the use of low-dose antibiotics has been promoted in health care and farming, significant amounts of AB are observed in aquatic environments. Knowledge on the impact of AB on natural bacterial communities is missing both in terms of spread and evolution of resistance mechanisms, and of modifications of community composition and productivity. New approaches are required to study the response of microbial communities rather than individual resistance genes. In this study a chemostat-based experiment with 4 coexisting bacterial strains has been performed to mimicking the response of a freshwater bacterial community to the presence of antibiotics in low and high doses. Bacterial abundance rapidly decreased by 75% in the presence of AB, independently of their concentration, and remained constant until the end of the experiment. The bacterial community was mainly dominated by Aeromonas hydrophila and Brevundimonas intermedia while the other two strains, Micrococcus luteus and Rhodococcus sp. never exceed 10%. Interestingly, the bacterial strains, which were isolated at the end of the experiment, were not AB-resistant, while reassembled communities composed of the 4 strains, isolated from treatments under AB stress, significantly raised their performance (growth rate, abundance) in the presence of AB compared to the communities reassembled with strains isolated from the treatment without AB. By investigating the phenotypic adaptations of the communities subjected to the different treatments, we found that the presence of AB significantly increased co-aggregation by 5-6 fold. These results represent the first observation of co-aggregation as a successful strategy of AB resistance based on phenotype in aquatic bacterial communities, and can represent a fundamental step in the understanding of the effects of AB

  19. Cystic fibrosis, intravenous antibiotics, and home therapy.

    Science.gov (United States)

    Hammond, L J; Caldwell, S; Campbell, P W

    1991-01-01

    The survival rate of patients with cystic fibrosis has improved considerably in the last 20 years. Although not all of the factors accounting for this change are understood, aggressive nutritional management and treatment of pulmonary exacerbations certainly play a role. Home intravenous (IV) antibiotic delivery for pulmonary exacerbation has proved to be as effective as hospital treatment and offers significant advantages to the patient and family. This article examines the microbiology of pulmonary infections in patients with cystic fibrosis, as well as antimicrobial therapy, methods of IV administration, home IV therapy, and the nurse practitioner's role in this home program in the future. PMID:1990112

  20. Platform for a Technological Leap in Antibiotics.

    Science.gov (United States)

    Heinzelmann, Elsbeth

    2015-01-01

    NTN Swiss Biotech™ brings together the Swiss Biotech Association SBA, which is involved in regulatory, financial and legal issues, and biotechnet Switzerland, which is active in translational R&D, to provide a technology base for joint projects. Biotechnet aims to push promising domains by creating topic-oriented platforms that enable academia and industry to work together to produce R&D results of major importance to society and the economy. The first activity initiated by biotechnet is the Antibiotics Platform that has now been launched. PMID:26842338

  1. Chemical modification of antifungal polyene macrolide antibiotics

    International Nuclear Information System (INIS)

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  2. The global problem of antibiotic resistance.

    Science.gov (United States)

    Gootz, Thomas D

    2010-01-01

    Amid the recent attention justly focused on the potential problem of microbial sources for weapons of bioterrorism, it is also apparent that human pathogens frequently isolated from infections in patients from community and hospital sources have been growing more resistant to commonly used antibiotics. Much of the growth of multiple-drug-resistant (MDR) bacterial pathogens can be contributed to the overuse of broad-spectrum antimicrobial products. However, an equally troubling and often overlooked component of the problem involves the elegant ways in which pathogenic bacteria continually evolve complex genetic systems for acquiring and regulating an endless array of antibiotic-resistance mechanisms. Efforts to develop new antimicrobials have over the past two decades been woefully behind the rapid evolution of resistance genes developing among both gram-positive and gram-negative pathogens. Several new agents that are best suited for use in the hospital environment have been developed to combat staphylococci resistant to beta-lactam antimicrobials following acquisition of the mecA gene. However, the dramatic spread in the US of the now common community strain of Staphylococcus aureus USA300 has shifted the therapeutic need for new antibiotics useful against MRSA to the community. As the pharmaceutical industry focused on discovering new agents for use against MRSA, hospitals in many parts of the world have seen the emergence of gram-negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae that are clinically resistant to almost all available antimicrobials. Such MDR isolates usually contain multiple-resistance determinants, including loss of outer membrane porins via gene inactivation by chromosomally encoded insertion sequences, up-regulation of inate efflux pumps, as well as acquisition of drug-inactivating enzymes whose genes are encoded on self-transmissible plasmids, integrons, and complex transposable elements

  3. Resistance to last-resort antibiotics in natural environments

    OpenAIRE

    Tacão, Marta Cristina Oliveira Martins

    2014-01-01

    Last-resort antibiotics are the final line of action for treating serious infections caused by multiresistant strains. Over the years the prevalence of resistant bacteria has been increasing. Natural environments are reservoirs of antibiotic resistance, highly influenced by human-driven activities. The importance of aquatic systems on the evolution of antibiotic resistance is highlighted from the assumption that clinically-relevant resistance genes have originated in strains ...

  4. Influence of Antibiotics Added in Milk over Yogurth Quality

    OpenAIRE

    Cornelia Vintila; Adela Marcu; Teodor Vintila; Daniela Roxana Vintilă; Adrian Marcu

    2010-01-01

    Large spectrum antibiotics used in different cow diseases leads to their release in milk altering its proprieties during processing. Knowing the inhibitory effect of antibiotics upon lactic bacteria development and multiplying we followed the effect of gentamycin, a large spectrum antibiotic added in different doses in milk used for yogurth processing. In our research, besides the effect of antibiotica we followed also the influence of milk fat content upon milk clotting time, while antibioti...

  5. The importance of antibiotic residues presence detection in milk

    OpenAIRE

    Dubravka Samaržija; Neven Antunac

    2002-01-01

    Antibiotic residues are the most present inhibitory substances in milkhaving undesirable effect on human health, technological characteristics and the quality of milk and dairy products. In order to protect consumer's health and to ensure high quality milk production, European Union (EU) regulation 2377/90 sets a maximum permitted levels for antibiotic residues in milk. Although the presence of antibiotic residues in milk can be due to animal diseases treatment, and in the case of milking ani...

  6. Rifaximin for maintenance therapy in antibiotic-dependent pouchitis

    OpenAIRE

    Lopez A Rocio; Remzi Feza H; Shen Bo; Queener Elaine

    2008-01-01

    Abstract Background Pouchitis is the most common long-term complication of in patients with restorative proctocolectomy and ileal pouch-anal anastomosis. Patients often develop antibiotic-dependent form of pouchitis requiring long-term antibiotic therapy for remission maintenance. Rifaximin, an oral, non-systemic, broad-spectrum antibiotic with a favorable safety profile, may be a promising candidate agent for maintenance therapy. This historical cohort open-label study investigated the effic...

  7. Antibiotic Adjuvants: Diverse Strategies for Controlling Drug-Resistant Pathogens

    OpenAIRE

    Gill, Erin E.; Franco, Octavio L.; Robert E. W. Hancock

    2014-01-01

    The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance ...

  8. Some aspects of genetic control of antibiotic biosynthesis in Streptomyces

    OpenAIRE

    М. P. Teplitskaya; I. E. Sokolova

    2005-01-01

    These work contain a review of basic hypotheses and experimental information in relation to the problem of antibiotic synthesis regulation by the bacteria of the Streptomyces family. Data on cluster organization of antibiotics biosynthesis genes in these microorganisms were generalized. The examples of the positive and negative specific control of antibiotic production genes were resulted. Except for it, proofs that confirm participation of a few genes of more high level in the process of ini...

  9. Comparison of Common Antibiotic Therapies for Haemophilus Pleuropneumonia in Pigs

    OpenAIRE

    Willson, Philip J.; Osborne, A. Dudley

    1985-01-01

    Three experiments were done to evaluate some antibiotic therapies that are used commonly to treat pigs infected with Haemophilus pleuropneumoniae. Haemophilus-free piglets, 12 weeks of age, were challenged in a chamber with an aerosol of H. pleuropneumoniae serotype 1 and were medicated with antibiotics at various times before or after challenge. Antibiotic formulations which are commonly used to treat pneumonia in swine were used. They were chloramphenicol, penicillin, and a long-acting form...

  10. Bordetella avium Antibiotic Resistance, Novel Enrichment Culture, and Antigenic Characterization

    OpenAIRE

    Beach, Nathan M; Thompson, Seth; Mutnick, Rachel; Brown, Lisa; Kettig, Gina; Puffenbarger, Robyn; Miyamoto, David; Temple, Louise

    2012-01-01

    Bordetella avium continues to be an economic issue in the turkey industry as the causative agent of bordetellosis, which often leads to serious secondary infections. This study presents a broad characterization of the antibiotic resistance patterns in this diverse collection of B. avium strains collected over the past thirty years. In addition, the plasmid basis for the antibiotic resistance was characterized. The antibiotic resistance pattern allowed the development of a novel enrichment cul...

  11. Isolation of lytic phages for clinical antibiotic resistant Pseudomonas aeruginosa

    OpenAIRE

    Pires, Diana; Sillankorva, Sanna; Faustino, A.; Azeredo, Joana

    2009-01-01

    Pseudomonas aeruginosa is a relevant opportunist pathogen involved in noso-comial infections. P. aeruginosa uses an arsenal of virulence factors to cause serious infections and one of the most worrying characteristics of this bacte-rium is its low antibiotic susceptibility. The low susceptibility to antibiotics can be attributed to a concerted action of multidrug efflux pumps with chromo-somally-encoded antibiotic resistance genes and the low permeability of the bacterial cellular envelopes. ...

  12. Antibiotic Susceptibilities of Acinetobacter Baumanii Strains Isolated from Clinical Samples

    OpenAIRE

    Harun Aðca

    2013-01-01

         Aim :  In this study it was aimed to investigate the antibiotic susceptibilities of Acinetobacter baumanii strains isolated from various clinical samples sent to Tavsanli State Hospital Microbiology Laboratory retrospectively. Material and Method: All of the cultures were examined for the agent and antibiotic susceptibilities. For the identification of bacteria, various chemical tests and BBL Crystal E/NF (Beckton Dickinson, ABD) system was used. Antibiotic susce...

  13. Prescription of antibiotics and awareness of antibiotic costs by paediatricians in two hospitals in Greece.

    Science.gov (United States)

    Maltezou, Helena C; Mougkou, Katerina; Iosifidis, Elias; Katerelos, Panos; Roilides, Emmanuel; Theodoridou, Maria

    2014-02-01

    Our aim was to study the antibiotic prescription practices and the knowledge about antibiotic costs, brand and generic drugs of paediatricians working in two hospitals in Greece. The 2007 national guidelines were used as the gold standard for antibiotic prescription. A total of 126 paediatricians participated in the study (50.4% response rate). The mean compliance rate with the guidelines was 50.1% (range per infection: 10.6-84.7%). The mean scores of knowledge about antibiotic costs and about brand name and generic drugs were 35.6 and 60.3%, respectively. Linear regression analysis found a significant association between the mean compliance rate with the national guidelines and the paediatricians' age (mean compliance rates were 49.1, 53.0, and 43.0% in the ≤ 30, 31-40, and > 40 years age-groups, respectively; P  =  0.003). In conclusion, five years after the first national guidelines were issued in Greece only half of the paediatricians working in hospitals comply fully with them. PMID:24410189

  14. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption

    DEFF Research Database (Denmark)

    Megraud, Francis; Coenen, Samuel; Versporten, Ann;

    2013-01-01

    in different countries. DESIGN: Primary antibiotic resistance rates of H pylori were determined from April 2008 to June 2009 in 18 European countries. Data on yearly and cumulative use over several years of systemic antibacterial agents in ambulatory care for the period 2001-8 were expressed in Defined Daily...

  15. Characterization of Renibacterium salmoninarum with reduced susceptibility to macrolide antibiotics by a standardized antibiotic susceptibility test.

    Science.gov (United States)

    Rhodes, Linda D; Nguyen, Oanh T; Deinhard, Rebecca K; White, Teresa M; Harrell, Lee W; Roberts, Marilyn C

    2008-08-01

    Three cohorts of juvenile and subadult Chinook salmon Oncorhynchus tshawytscha received multiple treatments with macrolide antibiotics for bacterial kidney disease (BKD) during rearing in a captive broodstock program. A total of 77 mortalities among the cohorts were screened for Renibacterium salmoninarum, the etiologic agent of BKD, by agar culture from kidney, and isolates from 7 fish were suitable for growth testing in the presence of macrolide antibiotics. The minimum inhibitory concentration (MIC) of erythromycin and azithromycin was determined by a modification of the standardized broth assay using defined medium. The American Type Culture Collection (ATCC) type strain 33209 exhibited a MIC of 0.008 microg m(-1) to either erythromycin or azithromycin. Isolates from 3 fish displayed MICs identical to the MICs for the ATCC type strain 33209. In contrast, isolates from 4 fish exhibited higher MICs, ranging between 0.125 and 0.250 microg ml(-1) for erythromycin and between 0.016 and 0.031 microg ml(-1) for azithromycin. Sequence analysis of the mutational hotspots for macrolide resistance in the 23S rDNA gene and the open reading frames of ribosomal proteins L4 and L22 found identical sequences among all isolates, indicating that the phenotype was not due to mutations associated with the drug-binding site of 23S rRNA. These results are the first report of R. salmoninarum with reduced susceptibility to macrolide antibiotics isolated from fish receiving multiple antibiotic treatments. PMID:18814542

  16. Protective role of E. coli outer membrane vesicles against antibiotics.

    Science.gov (United States)

    Kulkarni, Heramb M; Nagaraj, R; Jagannadham, Medicharla V

    2015-12-01

    The outer membrane vesicles (OMVs) from bacteria are known to posses both defensive and protective functions and thus participate in community related functions. In the present study, outer membrane vesicles have been shown to protect the producer bacterium and two other bacterial species from the growth inhibitory effects of some antibiotics. The OMVs isolated from E. coli MG1655 protected the bacteria against membrane-active antibiotics colistin, melittin. The OMVs of E. coli MG1655 could also protect P. aeruginosa NCTC6751 and A. radiodioresistens MMC5 against these membrane-active antibiotics. However, OMVs could not protect any of these bacteria against the other antibiotics ciprofloxacin, streptomycin and trimethoprim. Hence, OMVs appears to protect the bacterial community against membrane-active antibiotics and not other antibiotics, which have different mechanism of actions. The OMVs of E. coli MG1655 sequester the antibiotic colistin, whereas their protein components degrade the antimicrobial peptide melittin. Proteomic analysis of OMVs revealed the presence of proteases and peptidases which appear to be involved in this process. Thus, the protection of bacteria by OMVs against antibiotics is situation dependent and the mechanism differs for different situations. These studies suggest that OMVs of bacteria form a common defense for the bacterial community against specific antibiotics. PMID:26640046

  17. Antibiotic Susceptibility of Commensal Bacteria from Human Milk.

    Science.gov (United States)

    Chen, Po-Wen; Tseng, Shu-Ying; Huang, Mao-Sheng

    2016-02-01

    Recent studies have focused on foodborne or commensal bacteria as vehicles of antibiotic resistance. However, the antibiotic resistance of milk bacteria from healthy donors is still vague in Taiwan. For this purpose, human milk samples were obtained from randomly recruited 19 healthy women between 3 and 360 days post-partum. Antibiotic susceptibility profile of bacteria from milk samples was determined. About 20 bacterial species were isolated from milk samples including Staphylococcus (6 species), Streptococcus (4 species), Enterococcus (2 species), Lactobacillus (1 species), and bacteria belonging to other genera (7 species). Some opportunistic or potentially pathogenic bacteria including Kluyvera ascorbata, Klebsiella oxytoca, Klebsiella pneumoniae, Acinetobacter baumannii, Actinomyces bovis, and Staphylococcus aureus were also isolated. Intriguingly, Staphylococcus isolates (22 strains) were resistant to 2–8 of 8 antibiotics, while Streptococcus isolates (3 strains) were resistant to 3–7 of 9 antibiotics, and members of the genus Enterococcus (5 strains) were resistant to 3–8 of 9 antibiotics. Notably, Staphylococcus lugdunensis, S. aureus, Streptococcus parasanguinis, Streptococcus pneumonia, and Enterococcus faecalis were resistant to vancomycin, which is considered as the last-resort antibiotic. Therefore, this study shows that most bacterial strains in human milk demonstrate mild to strong antibiotic resistance. Whether commensal bacteria in milk could serve as vehicles of antibiotic resistance should be further investigated. PMID:26494365

  18. Characterization of antibiotic-resistant bacteria in rendered animal products.

    Science.gov (United States)

    Hofacre, C L; White, D G; Maurer, J J; Morales, C; Lobsinger, C; Hudson, C

    2001-01-01

    Antibiotics are used in food animal production to treat diseases and also to improve performance. Antibiotics are not used on all farms, and antibiotic resistance is occasionally found on farms that do not use antibiotics. Rendered animal protein products are often included in poultry feeds and could potentially serve as a source of antibiotic-resistant bacteria. One hundred sixty-five rendered animal protein products from cattle, poultry, and fish were aseptically collected from poultry feed mills. Fifty-five percent of the poultry meal samples had detectable levels of gram-negative bacteria ranging from 40 to 10,440 colony-forming units/g of sample. Poultry meal and meat and bone meal had the greatest number of samples with bacteria resistant to five or more antibiotics. A high percentage of feed samples (85%) contained bacteria resistant to amoxicillin, ampicillin, clavulanic acid, or cephalothin, whereas few samples contained bacteria resistant to ciprofloxacin, kanamycin, or trimethoprim/sulfamethoxazole. Acinetobacter calcoaceticus, Citrobacter freundii, and Enterobacter cloacae were the most commonly isolated antibiotic-resistant bacteria. Isolation for Salmonella was also performed, with 14% of the meat and bone meal samples containing Salmonella sp. Only one of the meat and bone meal isolates, Salmonella livingstone, was resistant to five or more antibiotics. Many of the antibiotic-resistant bacteria contained integrons, genetic elements that mediate multiple drug resistance. PMID:11785899

  19. Antibiotic resistance in food lactic acid bacteria--a review.

    Science.gov (United States)

    Mathur, Shalini; Singh, Rameshwar

    2005-12-15

    Antibiotics are a major tool utilized by the health care industry to fight bacterial infections; however, bacteria are highly adaptable creatures and are capable of developing resistance to antibiotics. Consequently, decades of antibiotic use, or rather misuse, have resulted in bacterial resistance to many modern antibiotics. This antibiotic resistance can cause significant danger and suffering for many people with common bacterial infections, those once easily treated with antibiotics. For several decades studies on selection and dissemination of antibiotic resistance have focused mainly on clinically relevant species. However, recently many investigators have speculated that commensal bacteria including lactic acid bacteria (LAB) may act as reservoirs of antibiotic resistance genes similar to those found in human pathogens. The main threat associated with these bacteria is that they can transfer resistance genes to pathogenic bacteria. Genes conferring resistance to tetracycline, erythromycin and vancomycin have been detected and characterized in Lactococcus lactis, Enterococci and, recently, in Lactobacillus species isolated from fermented meat and milk products. A number of initiatives have been recently launched by various organizations across the globe to address the biosafety concerns of starter cultures and probiotic microorganisms. The studies can lead to better understanding of the role played by the dairy starter microorganisms in horizontal transfer of antibiotic resistance genes to intestinal microorganisms and food-associated pathogenic bacteria. PMID:16289406

  20. Adaptive Landscapes of Resistance Genes Change as Antibiotic Concentrations Change.

    Science.gov (United States)

    Mira, Portia M; Meza, Juan C; Nandipati, Anna; Barlow, Miriam

    2015-10-01

    Most studies on the evolution of antibiotic resistance are focused on selection for resistance at lethal antibiotic concentrations, which has allowed the detection of mutant strains that show strong phenotypic traits. However, solely focusing on lethal concentrations of antibiotics narrowly limits our perspective of antibiotic resistance evolution. New high-resolution competition assays have shown that resistant bacteria are selected at relatively low concentrations of antibiotics. This finding is important because sublethal concentrations of antibiotics are found widely in patients undergoing antibiotic therapies, and in nonmedical conditions such as wastewater treatment plants, and food and water used in agriculture and farming. To understand the impacts of sublethal concentrations on selection, we measured 30 adaptive landscapes for a set of TEM β-lactamases containing all combinations of the four amino acid substitutions that exist in TEM-50 for 15 β-lactam antibiotics at multiple concentrations. We found that there are many evolutionary pathways within this collection of landscapes that lead to nearly every TEM-genotype that we studied. While it is known that the pathways change depending on the type of β-lactam, this study demonstrates that the landscapes including fitness optima also change dramatically as the concentrations of antibiotics change. Based on these results we conclude that the presence of multiple concentrations of β-lactams in an environment result in many different adaptive landscapes through which pathways to nearly every genotype are available. Ultimately this may increase the diversity of genotypes in microbial populations. PMID:26113371

  1. Antibiotic use during pregnancy alters the commensal vaginal microbiota

    DEFF Research Database (Denmark)

    Stokholm, J.; Schjørring, S.; Eskildsen, Carl Emil Aae;

    2014-01-01

    Antibiotics may induce alterations in the commensal microbiota of the birth canal in pregnant women. Therefore, we studied the effect of antibiotic administration during pregnancy on commensal vaginal bacterial colonization at gestational week 36. Six hundred and sixty-eight pregnant women from the...... significant changes in vaginal Streptococcus agalactiae (group B streptoccocus) or Staphylococcus aureus colonization following antibiotic treatment in pregnancy. Antibiotic administration during pregnancy leads to alterations in the vaginal microbiological ecology prior to birth, with potential morbidity......, and long-term effects on the early microbial colonization of the neonate....

  2. Mitomycin antibiotic reductive potential and related pharmacological activities.

    Science.gov (United States)

    Pan, S S; Gonzalez, H

    1990-06-01

    Relationships of reductive potential, kinetics of enzymatic reduction, augmented oxygen consumption, and cytotoxicity were determined for seven clinically relevant mitomycin antibiotics. Potentials for one-electron reduction were obtained by cyclic voltammetry analysis in dimethyl sulfoxide with 0.1 M tetraethyl-ammonium perchlorate. These potentials were -0.55 V for N7-acetylmitomycin C, -0.61 V for mitomycin A, -0.75 V for N7-(p-hydroxyphenyl)mitomycin C, -0.79 V for N7-(dimethylamino-methylene)mitomycin C, -0.81 V for N7-(2-(4-nitrophenyldithio)-ethyl)-mitomycin C, -0.81 V for mitomycin C, and -0.89 V for porfiromycin. All seven antibiotics were reduced by xanthine oxidase and NADPH-cytochrome P450 reductase, but the rate of reduction varied for each antibiotic and each enzyme. The less negative the reductive potential of an antibiotic, the more easily that antibiotic was reduced enzymatically. These seven mitomycin antibiotics also augmented oxygen consumption by rat liver microsomes. As with their reduction by xanthine oxidase and NADPH-cytochrome P450 reductase, the less negative the reductive potential of an antibiotic, the more it augmented oxygen consumption. Cytotoxicity of each antibiotic was assessed by defining the IC50 against HCT 116 human colon carcinoma cells. A relationship between the reductive potential of these antibiotics and their cytotoxicity against HCT 116 cells was also observed. PMID:2113607

  3. Over-the-counter suboptimal dispensing of antibiotics in Uganda

    Directory of Open Access Journals (Sweden)

    Mukonzo JK

    2013-08-01

    Full Text Available Jackson K Mukonzo,1,2 Proscovia M Namuwenge,1 Gildo Okure,3 Benjamin Mwesige,1 Olivia K Namusisi,4 David Mukanga4 1Center for Operational Research Africa, Kampala, Uganda; 2Department of Pharmacology and Therapeutics, 3School of Public Health, Makerere University, Kampala, Uganda; 4African Field Epidemiologist Network, Kampala, Uganda Background: Overuse and misuse of antibiotics is a serious global problem. While resistance to older antibiotics is increasing, development of newer molecules has stalled. Resistance to the existing antibiotics that is largely driven by their high-volume use is a global public health problem. Uganda is one of the countries where prescription-only drugs, including antibiotics, can be obtained over the counter. We determined the rate of antibiotic dispensing and use in Uganda. Methods: The study utilized a descriptive cross-sectional study design to determine the number of antibiotic "prescribed" daily doses per 1,000 clients. Data were collected from one health center II, eight general/district hospitals, one national referral hospital, and 62 registered community pharmacies. From each study site, data were collected for five consecutive days over the months of November 2011 to January 2012. Results: The overall antibiotic issue rate was 43.2%. Amoxicillin, metronidazole, ciprofloxacin, sulfamethoxazole–trimethoprim, cloxacillin, and ampicillin, belonging to the WHO anatomical therapeutic chemical classifications of penicillin with extended spectra, imidazole derivatives, fluoroquinolones, and sulfonamide–trimethoprim combinations, constituted 70% of the issued antibiotics. About 41% of antibiotics were issued over the counter. At community pharmacies, where 30% of antibiotic dispensing occurred, the number of prescribed daily doses/1,000 antibiotic clients was 4,169 compared to 6,220, 7,350 and 7,500 at general/district hospitals, the national referral hospital, and the health center, respectively. Conclusion

  4. Antibiotics as a selective driver for conjugation dynamics.

    Science.gov (United States)

    Lopatkin, Allison J; Huang, Shuqiang; Smith, Robert P; Srimani, Jaydeep K; Sysoeva, Tatyana A; Bewick, Sharon; Karig, David K; You, Lingchong

    2016-01-01

    It is generally assumed that antibiotics can promote horizontal gene transfer. However, because of a variety of confounding factors that complicate the interpretation of previous studies, the mechanisms by which antibiotics modulate horizontal gene transfer remain poorly understood. In particular, it is unclear whether antibiotics directly regulate the efficiency of horizontal gene transfer, serve as a selection force to modulate population dynamics after such gene transfer has occurred, or both. Here, we address this question by quantifying conjugation dynamics in the presence and absence of antibiotic-mediated selection. Surprisingly, we find that sublethal concentrations of antibiotics from the most widely used classes do not significantly increase the conjugation efficiency. Instead, our modelling and experimental results demonstrate that conjugation dynamics are dictated by antibiotic-mediated selection, which can both promote and suppress conjugation dynamics. Our findings suggest that the contribution of antibiotics to the promotion of horizontal gene transfer may have been overestimated. These findings have implications for designing effective antibiotic treatment protocols and for assessing the risks of antibiotic use. PMID:27572835

  5. Supramolecular Antibiotic Switches: A Potential Strategy for Combating Drug Resistance.

    Science.gov (United States)

    Bai, Haotian; Lv, Fengting; Liu, Libing; Wang, Shu

    2016-08-01

    Bacterial infectious disease is a serious public health concern throughout the world. Pathogen drug resistance, arising from both rational use and abuse/misuse of germicides, complicates the situation. Aside from developing novel antibiotics and antimicrobial agents, molecular approaches have become another significant method to overcome the problem of pathogen drug resistance. Established supramolecular systems, the antibiotic properties of which can be switched "on" and "off" through host-guest interactions, show great potential in combating issues regarding antibiotic resistance in the long term, as indicated by several recent studies. In this Concept, recently developed strategies for antibacterial regulation are summarized and further directions for research into antibiotic switches are proposed. PMID:27312106

  6. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic.

    Science.gov (United States)

    Kaur, Dardi Charan; Chate, Sadhana Sanjay

    2015-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Staphylococcus aureus demonstrates a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin, until the most recent, linezolid and daptomycin. Methicillin resistant S. aureus (MRSA) has become endemic today in hospitals worldwide. Resistance to the newer antimicrobial-agents - linezolid, vancomycin, teicoplanin, and daptomycin are been reported and also the fear of pandrug-resistance. This study was carried out to know the antimicrobial resistant pattern of MRSA to newer antibiotic, to know any isolates are extensively-drug resistant (XDR)/pandrug resistant (PDR), inducible macrolide-lincosamide streptogramin B (iMLSB), and mupirocin resistance. Thirty-six MRSA isolates resistant to the routinely tested antibiotic were further tested for list of antibiotic by a group of international experts. Isolates were tested for iMLSB and mupirocin resistance by the disk diffusion method. Of 385 MRSA, 36 (9.35%) isolates of MRSA were resistant to the routinely tested antibiotic. Among these 36 MRSA isolates, none of our isolates were XDR/PDR or showed resistant to anti-MRSA cephalosporins (ceftaroline), phosphonic acids, glycopeptides, glycylcyclines, and fucidanes. Lower resistance was seen in oxazolidinones (2.78%), streptogramins (5.56%), lipopeptide (5.56%). Thirty-four (94.44%) isolates showed constitutive MLSB (cMLSB) resistance and two (5.56%) iMLSB phenotypes. High- and low-level mupirocin resistance were seen in 13 (36.11%) and six (16.67%), respectively. In our study, none of our isolates were XDR or PDR. No resistance was observed to ceftaroline, telavancin, teicoplanin, and vancomycin; but the presence of linezolid resistance (1, 2.28%) and daptomycin resistance (2, 5

  7. Antibiotic contamination and occurrence of antibiotic-resistant bacteria in aquatic environments of northern Vietnam.

    Science.gov (United States)

    Hoa, Phan Thi Phuong; Managaki, Satoshi; Nakada, Norihide; Takada, Hideshige; Shimizu, Akiko; Anh, Duong Hong; Viet, Pham Hung; Suzuki, Satoru

    2011-07-01

    The ubiquitous application and release of antibiotics to the environment can result in bacterial antibiotic resistance, which in turn can be a serious risk to humans and other animals. Southeast Asian countries commonly apply an integrated recycling farm system called VAC (Vegetable, Aquaculture and Caged animal). In the VAC environment, antibiotics are released from animal and human origins, which would cause antibiotic-resistant bacteria (ARB). This study evaluated occurrence of ARB in the VAC environment in northern Vietnam, with quantitative analysis of antibiotic pollution. We found that sulfonamides were commonly detected at all sites. In dry season, while sulfamethazine was a major contaminant in pig farm pond (475-6662 ng/l) and less common in city canal and aquaculture sites, sulfamethoxazole was a major one in city canal (612-4330 ng/l). Erythromycin (154-2246 ng/l) and clarithromycin (2.8-778 ng/ml) were the common macrolides in city canal, but very low concentrations in pig farm pond and aquaculture sites. High frequencies of sulfamethoxazole-resistant bacteria (2.14-94.44%) were found whereas the occurrence rates of erythromycin-resistant bacteria were lower (Aeromonas were the major genera. Twenty three of 25 genera contained sul genes. This study showed specific contamination patterns in city and VAC environments and concluded that ARB occurred not only within contaminated sites but also those less contaminated. Various species can obtain resistance in VAC environment, which would be reservoir of drug resistance genes. Occurrence of ARB is suggested to relate with rainfall condition and horizontal gene transfer in diverse microbial community. PMID:21669325

  8. Fate of antibiotic resistant cultivable heterotrophic bacteria and antibiotic resistance genes in wastewater treatment processes.

    Science.gov (United States)

    Zhang, Songhe; Han, Bing; Gu, Ju; Wang, Chao; Wang, Peifang; Ma, Yanyan; Cao, Jiashun; He, Zhenli

    2015-09-01

    Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants of environmental concern. Heterotrophic bacteria in activated sludge have an important role in wastewater treatment plants (WWTPs). However, the fate of cultivable heterotrophic ARB and ARGs in WWPTs process remains unclear. In the present study, we investigated the antibiotic-resistant phenotypes of cultivable heterotrophic bacteria from influent and effluent water of three WWTPs and analysed thirteen ARGs in ARB and in activated sludge from anoxic, anaerobic and aerobic compartments. From each influent or effluent sample of the three plants, 200 isolates were randomly tested for susceptibility to 12 antibiotics. In these samples, between 5% and 64% isolates showed resistance to >9 antibiotics and the proportion of >9-drug-resistant bacteria was lower in isolates from effluent than from influent. Eighteen genera were identified in 188 isolates from influent (n=94) and effluent (n=94) of one WWTP. Six genera (Aeromonas, Bacillus, Lysinibacillus, Microbacterium, Providencia, and Staphylococcus) were detected in both influent and effluent samples. Gram-negative and -positive isolates dominated in influent and effluent, respectively. The 13 tetracycline-, sulphonamide-, streptomycin- and β-lactam-resistance genes were detected at a higher frequency in ARB from influent than from effluent, except for sulA and CTX-M, while in general, the abundances of ARGs in activated sludge from two of the three plants were higher in aerobic compartments than in anoxic ones, indicating abundant ARGs exit in the excess sledges and/or in uncultivable bacteria. These findings may be useful for elucidating the effect of WWTP on ARB and ARGs. PMID:25950407

  9. The synthesis of a novel octapeptidolipid antibiotic

    International Nuclear Information System (INIS)

    The bacillomycins comprise a group of antifungal polypeptide antibiotic compounds closely related in terms of their physico-chemical properties, amino acid and β-amino fatty acid compositions. Iturin A, which belongs to the bacillomycins, consists of seven amino acids. Attempts to produce a β-NC15 fatty acid in acceptable yield proved unsuccessful and was later discarded in favour of the preparation of a β-NC14 fatty acid. The different experimental procedures used and results obtained when preparing both fatty acids are detailed. The method developed in preparing the β-NC14 fatty acid affords a new general synthetic route for the production of β-amino fatty acids in good yield. The strategy considered in selecting which amino acid to commence the peptide synthesis with, the use in the Merrifield procedure of N-protected amino acids, coupling reagents, deprotecting and cleaving agents, and the HPLC purification procedures used for the linear and cyclic octapeptides, are all described. The 1H-NMR spectrum of the synthetic cyclic compound compared favourably with the spectrum of natural iturin A and these results are also presented. This dissertation presents the total synthesis of a novel octapeptidolipid antifungal antibiotic (iturin A analogue), utilising the Merrifield solid phase procedure. The biological activity of the synthesised and purified linear and cyclic iturin A analogues were compared with that of bacillomycin S. The test for biological activity and results obtained are described and illustrated with photographic plates

  10. [Expert systems and antibiotic sensitivity test].

    Science.gov (United States)

    Flandrois, J; Carret, G

    1991-01-01

    Artificial intelligence is a part of computer science that deals with programs mimicking intelligence of man. Artificial intelligence is now used to check the quality of the determination of antibiotics susceptibility of bacteria. This application is useful because antibiotic susceptibility is subject to biological and technical variation that have to be detected. Three types of reasoning are used either by the biologist or by expert systems: low level quality checking dealing with individual results, microbiological interpretation of the whole set of results and medical interpretation of the results. The use of artificial intelligence in these fields is sustained by the structured nature of the knowledge. Two type of expert systems are already of routine use, either based on production rules (ATB plus EXPERT, bioMerieux, La Balme-les-Grottes, France and SIR, 12A, Montpellier, France), or on object-oriented representation of the knowledge (EXPRIM from our laboratory). The main problem is, as usually in artificial intelligence applications, to transfer human expertise into an adapted knowledge base. The advantage of experts systems over man are their reproducibility of answer and their availability. PMID:2064087

  11. Prevalence of Antibiotic-Resistant Bacteria on Rectal Swabs and Factors Affecting Resistance to Antibiotics in Patients Undergoing Prostate Biopsy

    OpenAIRE

    Kim, Jong Beom; Jung, Seung Il; Hwang, Eu Chang; Kwon, Dong Deuk

    2014-01-01

    Purpose The prevalence of antibiotic-resistant bacteria on rectal swabs in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy and the factors affecting resistance to antibiotics were evaluated. Materials and Methods Two hundred twenty-three men who underwent TRUS-guided prostate biopsy from November 2011 to December 2012 were retrospectively evaluated. Rectal swabs were cultured on MacConkey agar to identify antibiotic-resistant bacteria in rectal flora before TRUS-guide...

  12. Acetylated starch nanocrystals: Preparation and antitumor drug delivery study.

    Science.gov (United States)

    Xiao, Huaxi; Yang, Tao; Lin, Qinlu; Liu, Gao-Qiang; Zhang, Lin; Yu, Fengxiang; Chen, Yuejiao

    2016-08-01

    In this study, we developed a new nanoparticulate system for acetylated starch nanocrystals (ASN) using broken rice. ASN with different degrees of substitution (DS) of 0.04, 0.08 and 0.14 were prepared using acetic anhydride as acetylating agent through reaction with starch nanocrystals (SN). The resulting ASN were investigated for the capability to load and release doxorubicin hydrochloride (DOX), and the antitumor activities of DOX-loaded SN and DOX-loaded ASN were evaluated as potential drug delivery systems for cancer therapy. Cellular uptake and cytotoxicity of nanocrystals and the DOX-loaded nanocrystals were investigated using fluorescence microscopy and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. Compared with acetylated starches (AS) and native starches (NS), ASN with DS 0.14 loaded up to 6.07% of DOX with a higher loading efficiency of 91.1% and had steadier drug-release rates. Toxicity analysis using the rat hepatocytes model suggested that ASN was biocompatible and could be used for drug delivery. Furthermore, ASN were taken up by cancer cells in vitro and significantly enhanced the cytotoxicity of DOX against HeLa human cervical carcinoma cells. The IC50 value of DOX-loaded ASN-DS 0.14 was 3.8μg/mL for 24h of treatment, which was significantly lower than that of free DOX (21μg/mL). These results indicate that the prepared ASN using broken rice is a promising vehicle for the controlled delivery of DOX for cancer therapy. PMID:27156696

  13. Antitumoral Effect of L. inermis in Mice with EAC

    Directory of Open Access Journals (Sweden)

    Mehmet Ozaslan

    2009-01-01

    Full Text Available In recent years, prophylactic usage of natural products and tendency to resort to alternative medicine has increased rapidly. Henna (Lawsonia sp. has been used not only cosmetically but also medicinally in Turkish population. Among the studies of henna’s antifungal, anti-microbial, tuberculostatic and antitumoral effects come on the science. In this study, we planned to research the effect of Lawsonia inermis that is an oxidant agent against development of cancer, by constituting peritonitis carcinomatous with Ehrlich ascites cells. The animals were divided to three groups and Lawsonia inermis extract and tap water were given to mice for 5 days. After 5 days, all of animals were decapitated by cervical dislocation and their liver tissues were sampled to measure reduced glutathione (GSH level. Mean Survival Time (MST and Average Survival Time (AST were calculated; peritoneal liquid pH was measured; Ehrlich Ascites Carcinoma (EAC cells were counted with hemocytometer. At the result, the longest life period was detected on the group which was given 10 mg/kg/day Lawsonia inermis. In group 2 and 3 which were given Lawsonia inermis following to forming Ehrlich ascites carcinoma, total number of cancer cell decreased. The scaled pH levels belonging to group 2 and 3 changed into alkaline compared to that of group1 (pH = 6.2. Glutathione levels of liver tissue were determined to decrease in group 2 and 3 in comparison with group1. In conclusion, Lawsonia inermis may lead cells to apoptosis related to deficiency in detoxification of intracellular radicals.

  14. Herceptin-geldanamycin immunoconjugates: pharmacokinetics, biodistribution, and enhanced antitumor activity.

    Science.gov (United States)

    Mandler, Raya; Kobayashi, Hisataka; Hinson, Ella R; Brechbiel, Martin W; Waldmann, Thomas A

    2004-02-15

    The efficacy of monoclonal antibodies (mAbs) as single agents in targeted cancer therapy has proven to be limited. Arming mAbs with a potent toxic drug could enhance their activity. Here we report that conjugating geldanamycin (GA) to the anti-HER2 mAb Herceptin improved the activity of Herceptin. The IC(50)s of the immunoconjugate H-GA were 10-200-fold lower than that of Herceptin in antiproliferative assays, depending on the cell line. The H-GA mode of action involved HER2 degradation, which was partially lactacystin sensitive and thus proteasome dependent. The linkage between GA and Herceptin remained stable in the circulation, as suggested by the pharmacokinetics of Herceptin and conjugated GA, which were almost identical and significantly different from that of free GA. Tumor uptake of Herceptin and H-GA were similar (52 +/- 7 and 43 +/- 7% of the initial injected dose per gram tissue, respectively; P = 0.077), indicating no apparent damage attributable to conjugation. Therapy experiments in xenograft-bearing mice consisted of weekly i.p. doses, 4 mg/kg for 4 months. H-GA showed a greater antitumor effect than Herceptin because it induced tumor regression in 69% of the recipients compared with 7% by Herceptin alone. Median survival time was 145 days as opposed to 78 days, and 31% of the recipients remained tumor free 2 months after therapy was terminated versus 0% in the Herceptin group. Enhancement of Herceptin activity could be of significant clinical value. In addition, the chemical linkage and the considerations in therapeutic regimen described here could be applied to other immunoconjugates for targeted therapy of a broad spectrum of cancers. PMID:14973048

  15. The Comparison of Procalcitonin Guidance Administer Antibiotics with Empiric Antibiotic Therapy in Critically Ill Patients Admitted in Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Atabak Najafi

    2015-10-01

    Full Text Available The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU with systemic inflammatory response syndrome (SIRS.  A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30 and patients who undergoing antibiotic empiric therapy as control group (n=30. Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03. Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88. Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01. However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23.  Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups.

  16. Antibiotic use during pregnancy alters the commensal vaginal microbiota.

    Science.gov (United States)

    Stokholm, J; Schjørring, S; Eskildsen, C E; Pedersen, L; Bischoff, A L; Følsgaard, N; Carson, C G; Chawes, B L K; Bønnelykke, K; Mølgaard, A; Jacobsson, B; Krogfelt, K A; Bisgaard, H

    2014-07-01

    Antibiotics may induce alterations in the commensal microbiota of the birth canal in pregnant women. Therefore, we studied the effect of antibiotic administration during pregnancy on commensal vaginal bacterial colonization at gestational week 36. Six hundred and sixty-eight pregnant women from the novel unselected Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010 ) pregnancy cohort participated in this analysis. Detailed information on oral antibiotic prescriptions during pregnancy filled at the pharmacy was obtained and verified prospectively. Vaginal samples were obtained at pregnancy week 36 and cultured for bacteria. Women who received oral antibiotics during any pregnancy trimester had an increased rate of colonization by Staphylococcus species in the vaginal samples as compared with samples obtained from women without any antibiotic treatment during pregnancy (adjusted OR 1.63, 95% CI 1.06-2.52, p 0.028). Oral antibiotic administration in the third trimester were also associated with increased colonization by Staphylococcus species (adjusted OR 1.98, 95% CI 1.04-3.76, p 0.037). These bacteriological changes were associated with urinary tract infection antibiotics. Women treated in the third trimester of pregnancy were more often colonized by Escherichia coli than women without antibiotic treatment in the third trimester (adjusted OR 1.91, 95% CI 1.04-3.52, p 0.038). This change was associated with respiratory tract infection (RTI) antibiotics. We did not observe any significant changes in vaginal Streptococcus agalactiae (group B streptoccocus) or Staphylococcus aureus colonization following antibiotic treatment in pregnancy. Antibiotic administration during pregnancy leads to alterations in the vaginal microbiological ecology prior to birth, with potential morbidity, and long-term effects on the early microbial colonization of the neonate. PMID:24118384

  17. A study on recent tendency of anti-tumor herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Yoo Hwa-Seung

    2001-12-01

    Full Text Available Objectives: The purpose of this study is to develop and activate anti-tumor herbal acupuncture for cancer patients in South Korea. Methods: We investigated some literatures on anti-tumor herbal acupuncture which is used in South Korea and China, and made diagrams. Results: The results are summarized as follows. Anti-tumor herbal acupuncture is one of the traditional oriental medical method which is effective for cancer patients. In domestic studies, most of herb materials are belong to action of cooling&detoxification(25.0% and strengthening body resistance(46.4% which are proved to have effects of anti-tumor, immune activation and preventing tumor. In China, point injection therapy are used for improving symptoms of cancer patients and healing tumor. Also herbal intravenous injection is used for combination of chinese traditional and western cancer therapy and treating cancer patients variously. Conclusions: From the above results, it is expected that anti-tumor herbal acupuncture is useful to improve clinical symptoms and quality of life(QOL of cancer patients. Also we must develop new progressive methods of point injection and herbal intravenous injection for treating cancer patients, and advance clinical studies and trials.

  18. ANTITUMOR EFFECT OF SARCNU IN A 06-METHYLGUANINE-DNA METHYLTRANSFERASE POSITIVE HUMAN GLIOMA XENOGRAFT MODEL

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-methylguanine-DNA methyltransferase (MGMT) positive tumors in vivo. Methods: MGMT positive human glioma cell line SF-767 xenografts in nude mice were treated with SarCNU. The antitumor efficacy of SarCNU was compared with the results of 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment with or without 06-benzylguanine (06-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 06-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (p<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than 06-BG plus BCNU treatment (F=51.7, p=0.00036). Conclusion: Since SarCNU enters cells via extraneuronal monoamine transporter (EMT), the enhanced antitumor activity of SarCNU in this MGMT positive human tumor xenograft model may be due to the presence of EMT in SF-767.SarCNU may be used as an alternative treatment for MGMT positive tumors, specifically for tumors expressing EMT.

  19. Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells.

    Science.gov (United States)

    Butler, Marcus O; Friedlander, Philip; Milstein, Matthew I; Mooney, Mary M; Metzler, Genita; Murray, Andrew P; Tanaka, Makito; Berezovskaya, Alla; Imataki, Osamu; Drury, Linda; Brennan, Lisa; Flavin, Marisa; Neuberg, Donna; Stevenson, Kristen; Lawrence, Donald; Hodi, F Stephen; Velazquez, Elsa F; Jaklitsch, Michael T; Russell, Sara E; Mihm, Martin; Nadler, Lee M; Hirano, Naoto

    2011-04-27

    Although advanced-stage melanoma patients have a median survival of less than a year, adoptive T cell therapy can induce durable clinical responses in some patients. Successful adoptive T cell therapy to treat cancer requires engraftment of antitumor T lymphocytes that not only retain specificity and function in vivo but also display an intrinsic capacity to survive. To date, adoptively transferred antitumor CD8(+) T lymphocytes (CTLs) have had limited life spans unless the host has been manipulated. To generate CTLs that have an intrinsic capacity to persist in vivo, we developed a human artificial antigen-presenting cell system that can educate antitumor CTLs to acquire both a central memory and an effector memory phenotype as well as the capacity to survive in culture for prolonged periods of time. We examined whether antitumor CTLs generated using this system could function and persist in patients. We showed that MART1-specific CTLs, educated and expanded using our artificial antigen-presenting cell system, could survive for prolonged periods in advanced-stage melanoma patients without previous conditioning or cytokine treatment. Moreover, these CTLs trafficked to the tumor, mediated biological and clinical responses, and established antitumor immunologic memory. Therefore, this approach may broaden the availability of adoptive cell therapy to patients both alone and in combination with other therapeutic modalities. PMID:21525398

  20. Experimental research on effects of a new Traditional Chinese medicine on antitumor metastases

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective: To study the efficacy and mechanism of AT-1 a new compound (an aqueous agent extracted from a Traditional Chinese herb with antiplatelet efficacy) on antitumor metastases in mice. Methods: AT-1,a compound extracted from a Traditional Chinese herb, was prepared by our lab. C57BL/6 female mice, which were transplanted H22 liver cancer cells, received the agent. The tumor nodules, the pulmonary metastasis rate and tumor cell proliferation activity were tested. The tumor cells were exposed to different concentrations of AT-1, and then the condition of the tumor proliferations were tested. Results: High and middle dosages of AT-1 inhibited both the lymphatic and blood systemic tumor pulmonary metastases significantly, but had no effect on inhibition of the tumor cell proliferation in vitro. Conclusion:The major antitumor actions of AT-1 may be on antitumor metastases, and the compounnd may be a new candidate for antitumor metastases agent. More study of the mechanism and action of AT1 on antitumor metastases and the actions are still being done deeply.