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Sample records for antitumor antibiotic c-1027

  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. Cloning, expression and characterization of gene sgcD involved in the biosynthesis of novel antitumor lidamycin

    Institute of Scientific and Technical Information of China (English)

    LI; Min; (李敏); LIU; Wen; (刘文); LI; Yuan; (李元)

    2003-01-01

    Lidamycin with high antitumor activity is a novel enediyne antitumor antibiotic producedby Streptomyces globisporus C1027. The 75 kb biosynthesis gene cluster of lidamycin containing 33 open reading frames has been cloned from S. globisporus C1027. In this paper,the function ofsgcD (ORF24) is investigated. Gene disruption experiment proved that sgcD is involved in lidamy-cin biosynthesis. With homologous comparing analysis, we deduce that sgcD codes aminomutasecatalyzing α-tyrosine to β-tyrosine which is one motif for lidamycin. To identify the function of en-zyme coded by sgcD, sgcD is cloned into vector pET30a for inducing expression and the activity ofexpression product is analyzed. The result showed that the expression product ofsgcD has theactivity of aminomutase. Aminomutase coded by sgcD is the first characterized enzyme involved inthe biosynthesis of enediyne antitumor antibiotics. Our research will be helpfulto clarifying thebiosynthesis mechanism of such kind of antibiotic and to producing new antitumorcompounds.

  3. Ecteinascidins. A review of the chemistry, biology and clinical utility of potent tetrahydroisoquinoline antitumor antibiotics.

    Science.gov (United States)

    Le, V H; Inai, M; Williams, R M; Kan, T

    2015-02-01

    The ecteinascidin family comprises a number of biologically active compounds, containing two to three tetrahydroisoquinoline subunits. Although isolated from marine tunicates, these compounds share a common pentacyclic core with several antimicrobial compounds found in terrestrial bacteria. Among the tetrahydroisoquinoline natural products, ecteinascidin 743 (Et-743) stands out as the most potent antitumor antibiotics that it is recently approved for treatment of a number of soft tissue sarcomas. In this article, we will review the backgrounds, the mechanism of action, the biosynthesis, and the synthetic studies of Et-743. Also, the development of Et-743 as an antitumor drug is discussed.

  4. UCH9, a new antitumor antibiotic produced by Streptomyces: I. Producing organism, fermentation, isolation and biological activities.

    Science.gov (United States)

    Ogawa, H; Yamashita, Y; Katahira, R; Chiba, S; Iwasaki, T; Ashizawa, T; Nakano, H

    1998-03-01

    We developed a microbial prescreen using Bacillus stearothermophilus NUB3620 and bacteriophage TP-68 to detect potential antitumor compounds acting on DNA or topoisomerases. During the course of screening microbial cultures for their antibacteriophage activities, we found that Streptomyces sp. isolated from a soil sample collected in Iwakuni city, Yamaguchi prefecture, Japan, produced a new antitumor antibiotic, UCH9. UCH9 was isolated from culture broth by a combination of EtOAc extraction and column chromatography. UCH9 has a new structure related to the antitumor antibiotic chromomycins. It exhibited antimicrobial activity against Gram-positive organisms. UCH9 also showed cytotoxic activity against HeLa S3 cells with an IC50 value of 13 nM and exhibited antitumor activity in vivo against mouse leukemia P388.

  5. 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.

  6. Acute local irritative effect of (2''R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic.

    Science.gov (United States)

    Tone, H; Kiyosaki, T; Cuthbert, J A; Carr, S M; Aitken, R

    1986-02-01

    (2"R)-4'-O-Tetrahydropyranyladriamycin hydrochloride (THP), a new antitumor antibiotic, was administered to rabbits at a concentration from 0.02 to 0.5% by instillation, or by intracutaneous, subcutaneous or intramuscular injection to study its local irritative effect. The irritative effect of THP increased with concentration. At a concentration of 0.5%, THP was irritant to the eye, skin and muscle but at a concentration of 0.1% practically no effect was observed. The effect was equal to or lower than that of doxorubicin. An instillation of 0.5% THP caused reversible irritation effect on the eye. Slight conjunctival responses (redness and chemoisis) were observed. Rinsing reduced the irritative effect. Intracutaneous injection of 0.1 ml of 0.5% THP caused well defined, moderate erythema, surface ulceration and dermal necrosis. Cutaneous muscle necrosis also occurred. At a concentration of 0.02%, dermal necrosis and inflammatory cell infiltration were observed. Erythema, as well as muscle necrosis and calcification with giant cell reaction and inflammatory cell infiltration were observed by an intramuscular injection at a concentration of 0.5%. Subcutaneous injection of 0.5% THP showed no irritative effect.

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

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    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

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

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    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.

  10. 力达霉素产生菌球孢链霉菌C-1027中atrA同源基因的克隆及分析%Cloning and Analyses of atrA Homologous Gene atrA-gl Involved in Lidamycin Producing Strain Streptomyces globisporus C-1027

    Institute of Scientific and Technical Information of China (English)

    李光伟; 王丽非; 王松梅; 洪斌

    2010-01-01

    目的:在天蓝色链霉菌Streptomyces coelicolor A3(2)中多效性调节因子AtrA(AtrA-c)可通过激活放线紫红素途径特异性的调节因子ActⅡ-ORF4的转录来控制放线紫红素的产生.在灰色链霉菌Sreptomyces griseus NBRCl3350和阿维链霉菌Streptomyces avermitilis MA-4680中也发现了AtrA-c编码基因(atrA-c)的同源基因,分别影响链霉素和阿维菌素的生物合成.为探索球孢链霉菌C-1027(Sreptomyces globisporus C-1027)中是否存在AtrA,克隆球孢链霉菌C-1027中atrA基因并进行生物信息学分析,为进一步确定其对力达霉素产生的调控作用及调控机制奠定基础.方法:采用在球孢链霉菌C-1027中异源表达AtrA-c,来确定AtrA-c对力达霉素产量的影响;通过southern blot分析来判断在球孢链霉菌C-1027基因组中是否有atrA-c同源基因;PCR扩增方法获得球孢链霉菌c-1027atrA基因(atrA-gl)并测序;通过多种生物信息学软件来分析atrA-gl及其与旁侧基因的组织结构、对已发现的AtrA蛋白进行同源性比对及亲缘关系分析.结果:在球孢链霉菌C-1027中异源表达天蓝色链霉菌AtrA-c蛋白,发现其对力达霉素的产量有影响.以atrA-c为探针,通过Southern blot分析显示球孢链霉菌C-1027基因组中存在atrA-c的同源基因.PCR扩增得到球孢链霉菌c-1027的atrA基因的全序列以及该基因上下游的旁侧序列(GenBank/EMBI/DDRJ登录号GU723707).通过对球孢链霉菌C-1027、天蓝色链霉菌A3(2)、灰色链霉菌NBRCl3350以及阿维链霉菌MA-4680 AtrA蛋白序列进行同源性分析发现,4种AtrA蛋白编码氨基酸序列一致性达到65%~87%,相似性高达70%~89%.并且,球孢链霉菌C-1027 atrA基因与相邻基因形成的组织结构与天蓝色链霉菌和灰色链霉菌完全一致.根据蛋白质同源性绘制进化树,发现球孢链霉菌AtrA蛋白与灰色链霉菌AtrA蛋白亲缘关系最近.结论:确定在球孢链霉菌C-1027中存在atrA同源基因

  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. Efficient synthesis and evaluation of bis-pyridinium/bis-quinolinium metallosalophens as antibiotic and antitumor candidates

    Science.gov (United States)

    Elshaarawy, Reda F. M.; Eldeen, Ibrahim M.; Hassan, Eman M.

    2017-01-01

    Inspired with the pharmacological diversity of salophens and in our endeavor to explore a new strategy which may conflict the invasion of drug resistance, we report herein efficient synthetic routes for the synthesis of new RO-salophen(Cl), pyridinium/quinolinium-based salophens (3a-e) and metallosalophens (4a-j). These new architectures have been structurally characterized by elemental and spectral analysis as well pharmacologically evaluated for their in vitro antimicrobial, against a common panel of pathogenic bacterial and fungal strains, and anticancer activities against human colon carcinoma (HCT-116) cell lines. Antimicrobial assay results revealed that all tested compounds exhibited moderate to superb broad-spectrum efficacy in comparison to the standard antibiotic with a preferential ability to perform as a fungicides than to act as bactericides. Noteworthy, VO(II)-salophens are more effective in reduction HCT-116 cell viability than Cu(II)-salophens. For example, VO(II)-salophen3 (4f) (IC50 = 2.13 μg/mL) was ca. 10-fold more efficient than Cu(II)-salophen3 (4e) (IC50 = 20.30 μg/mL).

  13. Glionitrin A, an antibiotic-antitumor metabolite derived from competitive interaction between abandoned mine microbes

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    Park, H.B.; Kown, H.C.; Lee, C.H.; Yang, H.O. [Korean Institute of Science & Technology KIST, Kangnung (Republic of Korea)

    2009-02-15

    The nutrient conditions present in abandoned coal mine drainages create an extreme environment where defensive and offensive microbial interactions could be critical for survival and fitness. Coculture of a mine drainage-derived Sphingomonas bacterial strain, KMK-001, and a mine drainage-derived Aspergillus fumigatus fungal strain, KMC-901, resulted in isolation of a new diketopiperazine disulfide, glionitrin A (1). Compound 1 was not detected in monoculture broths of KMK-001 or KMC-901. The structure of 1, a (3S,10aS) diketopiperazine disulfide containing a nitro aromatic ring, was based on analysis of MS, NMR, and circular dichroism spectra and confirmed by X-ray crystal data. Glionitrin A displayed significant antibiotic activity against a series of microbes including methicillin-resistant Staphylococcus aureus. An in vitro MTT cytotoxicity assay revealed that 1 had potent submicromolar cytotoxic activity against four human cancer cell lines: HCT-116, A549, AGS, and DU145. The results provide further evidence that microbial coculture can produce novel biologically relevant molecules.

  14. Antibiotics

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    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 ...

  15. Two Streptomyces species producing antibiotic, antitumor, and anti-inflammatory compounds are widespread among intertidal macroalgae and deep-sea coral reef invertebrates from the central Cantabrian Sea.

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    Braña, Alfredo F; Braña, Afredo F; Fiedler, Hans-Peter; Nava, Herminio; González, Verónica; Sarmiento-Vizcaíno, Aida; Molina, Axayacatl; Acuña, José L; García, Luis A; Blanco, Gloria

    2015-04-01

    Streptomycetes are widely distributed in the marine environment, although only a few studies on their associations to algae and coral ecosystems have been reported. Using a culture-dependent approach, we have isolated antibiotic-active Streptomyces species associated to diverse intertidal marine macroalgae (Phyllum Heterokontophyta, Rhodophyta, and Chlorophyta), from the central Cantabrian Sea. Two strains, with diverse antibiotic and cytotoxic activities, were found to inhabit these coastal environments, being widespread and persistent over a 3-year observation time frame. Based on 16S rRNA sequence analysis, the strains were identified as Streptomyces cyaneofuscatus M-27 and Streptomyces carnosus M-40. Similar isolates to these two strains were also associated to corals and other invertebrates from deep-sea coral reef ecosystem (Phyllum Cnidaria, Echinodermata, Arthropoda, Sipuncula, and Anelida) living up to 4.700-m depth in the submarine Avilés Canyon, thus revealing their barotolerant feature. These two strains were also found to colonize terrestrial lichens and have been repeatedly isolated from precipitations from tropospheric clouds. Compounds with antibiotic and cytotoxic activities produced by these strains were identified by high-performance liquid chromatography (HPLC) and database comparison. Antitumor compounds with antibacterial activities and members of the anthracycline family (daunomycin, cosmomycin B, galtamycin B), antifungals (maltophilins), anti-inflamatory molecules also with antituberculosis properties (lobophorins) were identified in this work. Many other compounds produced by the studied strains still remain unidentified, suggesting that Streptomyces associated to algae and coral ecosystems might represent an underexplored promising source for pharmaceutical drug discovery.

  16. BlmB and TlmB provide resistance to the bleomycin family of antitumor antibiotics by N-acetylating metal-free bleomycin, tallysomycin, phleomycin, and zorbamycin.

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    Coughlin, Jane M; Rudolf, Jeffrey D; Wendt-Pienkowski, Evelyn; Wang, Liyan; Unsin, Claudia; Galm, Ute; Yang, Dong; Tao, Meifeng; Shen, Ben

    2014-11-11

    The bleomycin (BLM) family of glycopeptide-derived antitumor antibiotics consists of BLMs, tallysomycins (TLMs), phleomycins (PLMs), and zorbamycin (ZBM). The self-resistant elements BlmB and TlmB, discovered from the BLM- and TLM-producing organisms Streptomyces verticillus ATCC15003 and Streptoalloteichus hindustanus E465-94 ATCC31158, respectively, are N-acetyltransferases that provide resistance to the producers by disrupting the metal-binding domain of the antibiotics required for activity. Although each member of the BLM family of antibiotics possesses a conserved metal-binding domain, the structural differences between each member, namely, the bithiazole moiety and C-terminal amine of BLMs, have been suggested to instill substrate specificity within BlmB. Here we report that BlmB and TlmB readily accept and acetylate BLMs, TLMs, PLMs, and ZBM in vitro but only in the metal-free forms. Kinetic analysis of BlmB and TlmB reveals there is no strong preference or rate enhancement for specific substrates, indicating that the structural differences between each member of the BLM family play a negligible role in substrate recognition, binding, or catalysis. Intriguingly, the zbm gene cluster from Streptomyces flavoviridis ATCC21892 does not contain an N-acetyltransferase, yet ZBM is readily acetylated by BlmB and TlmB. We subsequently established that S. flavoviridis lacks the homologue of BlmB and TlmB, and ZbmA, the ZBM-binding protein, alone is sufficient to provide ZBM resistance. We further confirmed that BlmB can indeed confer resistance to ZBM in vivo in S. flavoviridis, introduction of which into wild-type S. flavoviridis further increases the level of resistance.

  17. [Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the bone marrow function of rabbits. (1) Intravenous administration by a single bolus injection].

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    Tone, H; Kiyosaki, T; Shirai, M

    1986-02-01

    New Zealand White rabbits were treated with (2"R)-4'-O-tetrahydropyranyladriamycin-HCl (THP), a new antitumor antibiotic, by an intravenous bolus injection at a dose of 1, 2 or 4 mg/kg. The peripheral leucocyte counts decreased markedly at doses of 2 and 4 mg/kg 1 to 7 days after injection, and the lymphocytes and neutrophils were affected. The nucleated cell count decreased in the bone marrow. Especially 3 days after injection, remarkable reductions of erythroids and immatured myelocytes were observed, with a subsequent rise of the matured myelocytes ratio in bone marrow cell constituents. These changes resulted in a marked increase of M/E ratio. Doxorubicin also showed an inhibitory effect on the bone marrow function of rabbits but the effect was slightly lower than THP. These changes of bone marrow cells reverted 7 days after injection and the recovery of the reduced peripheral leucocyte was also observed 14 days after injection. Therefore, it can be concluded that THP showed suppressive but reversible effects on the bone marrow function of rabbits.

  18. [Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the bone marrow function of rabbits. (2) Repeated intravenous injections].

    Science.gov (United States)

    Tone, H; Kiyosaki, T; Shirai, M

    1986-02-01

    (2''R)-4'-O-Tetrahydropyranyladriamycin-HCl (THP), a new antitumor antibiotic, was intravenously injected to New Zealand White rabbits at a dose of 2.5 mg/kg every 2 weeks for 6 weeks (3 courses) or at a dose of 0.5 mg/kg/day daily for the first 5 days of a 2-week course for 6 weeks (3 courses). The total dose was 7.5 mg/kg in both dosing schedules. The peripheral leucocyte and erythrocyte counts decreased. The leucocyte count decreased to 57% of the initial count on Day 3 in the first course and then increased gradually. The decrease was smaller in the divided dosing schedule than the single dosing. The nucleated cells, especially immatured myelocytes and erythroids reduced remarkably. Subsequently the matured myelocyte ratio in bone marrow cell constituents increased and the M/E ratio increased. These changes were observed on Day 3 and reverted by Day 9 in each course. The divided dosing schedule resulted in a higher nadir. All the changes in the peripheral blood and the bone marrow reverted even after the 3 course-treatment.

  19. Actinolactomycin, a New 2-Oxonanonoidal Antitumor Antibiotic Produced by Streptomyces flavoretus 18522, and its Inhibitory Effect on the Proliferation of Human Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Bing HAN; Cheng Bin CUI; Bing CAI; Xiu Feng JI; Xin Sheng YAO

    2005-01-01

    Actinolactomycin 1, a new 2-oxonanonoidal antitumor antibiotic, was isolated from the fermentation broth of Streptomyces flavoretus 18522 through a bioassay-guided separation procedure. The structure of 1 was determined as 4,7-dihydroxy-3,9-dimethyl-2-oxonanone by the spectroscopic methods. Compound 1 inhibited the proliferation of A2780, K562, HCT-15, A549and HeLa cells with the IC50 values of 1.4 ± 0.4 μmol/L, 8.4 ± 4.7 μmol/L, 9.4 ± 2.2 μmol/L, 15.4± 5.6 μmol/L and 13.7 ± 2.0 μmol/L, respectively. Flow cytometric analysis indicated that 1could inhibit the cell cycle of tsFT210, A2780 and K562 cells mainly at the G0/G1 phase and could also induce apoptosis in K562 cells.

  20. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin.

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    Gewirtz, D A

    1999-04-01

    The mechanisms responsible for the antiproliferative and cytotoxic effects of the anthracycline antibiotics doxorubicin (Adriamycin) and daunorubicin (daunomycin) have been the subject of considerable controversy. This commentary addresses the potential role of DNA synthesis inhibition, free radical formation and lipid peroxidation, DNA binding and alkylation, DNA cross-linking, interference with DNA strand separation and helicase activity, direct membrane effects, and the initiation of DNA damage via the inhibition of topoisomerase II in the interaction of these drugs with the tumor cell. One premise underlying this analysis is that only studies utilizing drug concentrations that reflect the plasma levels in the patient after either bolus administration or continuous infusion are considered to reflect the basis for drug action in the clinic. The role of free radicals in anthracycline cardiotoxicity is also discussed.

  1. Examination of Potential Anti-Tumor Activity of N-Thiolated b-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors

    Science.gov (United States)

    2006-08-01

    190- PMAPA ’has be ihown to have growth-suppressive effects in a broad range ocancersŖ()’. o ,njtance Nepomuceno et al.’ ave shown thai PA is capable... antibiotico . Lavori dell’Istituto d’Igiene di Cagliari, 1-11 (1948) 7. Burton, H.S. and E.P. Abraham: Isolation of antibiotics from a species of...delivered by antibody.Iirected catalysis. ioconjugate Chem 6, 40-446 (1995) 63. Satchi-Fainaro, R., H. Hailu, I.W. av !•• C. § merforl and R. uncanz [DEP 1

  2. Expression, Crystallization and Preliminary X-ray Diffraction Analyses of Med-ORF10 in the Biosynthetic Pathway of an Antitumor Antibiotic Medermycin.

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    Liu, Yanli; Liu, Shasha; Yang, Tingting; Guo, Xiaoxia; Jiang, Yali; Zahid, Kashif Rafiq; Liu, Ke; Liu, Jinlin; Yang, Jihong; Zhao, Haobin; Yang, Yi; Li, Aiying; Qi, Chao

    2015-12-01

    Medermycin, as a prominent member of benzoisochromanequinones, possesses strong antitumor activity and is biosynthesized under the control of a 29-ORF-containing biosynthetic gene cluster. Most of ORFs in this gene cluster have not been characterized, including a small protein encoding gene med-ORF10, proposed to play a regulatory role in biosynthesis of medermycin in an unknown mode. In this study, we reported the expression, protein preparation, crystallization and preliminary X-ray diffraction analyses of Med-ORF10 of the wild type Streptomyces strain. Firstly, we cloned and overexpressed med-ORF10 in Escherichia coli and purified the protein with 98% purity and 3 mg/L yield. Then, we crystallized the protein at concentration of 20 mg/mL in condition 22% PEG 3350, 0.2 M magnesium formate and collected the data at 1.78 Å resolution. Finally, we detected the expression of Med-ORF10 in Streptomyces by western blotting. In conclusion, this study confirmed the expression of Med-ORF10 protein in the wild-type strain of Streptomyces AM-7161 and collected the X-ray diffraction data of Med-ORF10 crystal at 1.78 Å resolution. These studies provide evidences for the functional Med-ORF10 protein in Streptomyces strains and facilitate our further investigation.

  3. Purification and identification of a high active anti-tumor antibiotic calicheamicin%高效抗肿瘤抗生素卡里奇霉素的分离纯化与鉴定

    Institute of Scientific and Technical Information of China (English)

    陈华; 郑玲辉; 孟强; 王继栋

    2011-01-01

    Objective Calicheamicin is a high active antitumor antibiotic produced by Micromonospora echinospora. The strain 912-36-2 is a high-yielding mutant from original strain by NTC and microwave mutation. The aims of this study were to purify calicheamicin from culture broth of M. Echinospora 912-36-2. Methods The culture broth was extracted with the same volume of ethyl acetate. The organic extract was evaporated and the residues were added with hexane. The hexane insoluble was collected by filtration. The insoluble was extracted by ethyl acetate and the extract was precipitated by a mixture of diethyl ether and hexane. The crude calicheamicin was obtained after filtration. Then calicheamicin was further purified by silica gel chromatography and preparative HPLC. The calicheamicin homologues produced by M. Echinospora 912-36-2 were analyzed by LC-MS. Results The purified calicheamicin was obtained after the isolation steps. The compound was analyzed by LC-MS and was identified as calicheamicin γ11 with molecular weight of 1367Da. Conclusion The established purification steps were useful forfurther industrialization of this product.%目的 研究从一株棘孢小单孢菌高产突变株912-36-2(Micromonospora echinospora 912-36-2)的发酵液中分离纯化抗肿瘤抗生素卡里奇霉素(calicheamicin)的方法,并得到纯品.方法 发酵液通过有机溶剂萃取、硅胶分离、制备HPLC精制等方法分离纯化卡里奇霉素,并用LC-MS方法鉴定卡里奇霉素的各组分.结果从M.echinospora 912-36-2发酵液中分离出一个卡里奇霉素组分,LC-MS检测结果证明其分子量为1367Da,为目标活性组分γ11.结论通过建立卡里奇霉素的分离提取工艺,为该产品的产业化开发提供基础.

  4. Alloferon-1抗生肽串联重组表达及重组Alloferon-1体外抗肿瘤活性%Serial recombinant expression and anti-tumor activity in vitro of antibiotic peptide Alloferon-1

    Institute of Scientific and Technical Information of China (English)

    徐小寅; 严杰; 孙琦

    2011-01-01

    Objective: To generate a recombinant expression system of repeated serial antibiotic peptide Alloferon-1 DNA segment with trypsin digestion site and to determine its anti-tumor activity in vitro. Methods: A 14 repeated serial DNA segment of Alloferon-1 with a lysine residual at the C-end that acts as the trypsin digestion site was constructed. pET42a vector and E. Coli BL21DE3 were applied to generate the prokaryotic expression system of the repeated serial DNA segment of Alloferon-1. The yield of target recombinant product was measured by SDS-PAGE and Bio-Rad Gel image system. Ni-NTA affinity column, trypsin digestion and Sephadex G-50 column were used to purify 14 rAlloferon-1-K fusion protein and rAlloferon-1 -K monomer. By using the co-cultivation of BALB/c mouse splenocyte with K562, KB or SGC tumor cells and CCK-8 detection method, the effects of rAlloferon-1 -K, chemosynthetic Alloferon-1 (cAlloferon-1) and Alloferon-1-K ( cAlloferon-1-K) on the growth and proliferation of tumor cells were detected. Results: The prokaryotic expression system E. Coli BL21DE3pET42a-14 Allofron-1-k efficiently expressed 14 rAlloferon-1-K fusion protein under inducement of IPTG.and the yield of fusion protein was approximate 30% of the total bacterial proteins. 0.1 ~ 10 ng/ml rAlloferon-1-K remarkably increased the effect of mouse splenocytes to inhibit the growth and proliferation of K562, KB and SGC cells ( P 0. 05). Conclusion; A prokaryotic expression system of repeated serial Alloferon-1 DNA segment has been successfully constructed with high yield of rAlloferon-1-K, which maintains anti-tumor activity in vitro.%目的:构建含胰蛋白酶酶切位点的Alloferon-1抗生肽重复串联DNA片段及其原核表达系统,了解有赖氨酸尾重组Alloferon-1( rAlloferon-1)体外抗肿瘤活性.方法:根据Alloferon-1序列不合精氨酸和赖氨酸的特点,构建C端加有含胰蛋白酶酶切位点赖氨酸的14 x Alloferon-1抗生肽重复串联DNA片段.采用pET42a

  5. Antibiotic Resistance

    Science.gov (United States)

    ... lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... resistant to several common antibiotics. To help prevent antibiotic resistance Don't use antibiotics for viruses like colds ...

  6. Antibiotic Safety

    Science.gov (United States)

    ... are not effectively treated with an antibiotic • Viral gastroenteritis Bacterial infections should be treated with antibiotics. Some ... you antibiotics for a viral infection. Antibiotics kill bacteria, not viruses. • T ake all of your prescribed ...

  7. Antibiotics Quiz

    Science.gov (United States)

    ... on the Farm Get Smart About Antibiotics Week Antibiotics Quiz Recommend on Facebook Tweet Share Compartir Try ... right of the answer you think is correct. Antibiotic Quiz Widget Copy the code for this widget, ...

  8. Antibiotic Agents

    Science.gov (United States)

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  9. 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...

  10. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Hansen, Malene Plejdrup; Hoffmann, Tammy C; McCullough, Amanda R

    2015-01-01

    Numerous opportunities are available in primary care for alleviating the crisis of increasing antibiotic resistance. Preventing patients from developing an acute respiratory infection (ARI) will obviate any need for antibiotic use downstream. Hygiene measures such as physical barriers and hand...... wrong. Shared decision making might be a solution, as it enables clinician and patient to participate jointly in making a health decision, having discussed the options together with the evidence for their harms as well as benefits. Furthermore, GPs' diagnostic uncertainty - often leading...... will greatly improve the use of antibiotics for ARIs. However, used in concert, combinations are likely to enable clinicians and health care systems to implement the strategies that will reduce antimicrobial resistance in the future....

  11. 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 combinations...

  12. Aerosolized Antibiotics.

    Science.gov (United States)

    Restrepo, Marcos I; Keyt, Holly; Reyes, Luis F

    2015-06-01

    Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

  13. Effects of pirarubicin, an antitumor antibiotic, on the cardiovascular system.

    Science.gov (United States)

    Hirano, S; Agata, N; Hara, Y; Iguchi, H; Shirai, M; Tone, H; Urakawa, N

    1991-01-01

    In the present study we examined the effects of pirarubicin [(2"R)-4'-O-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39-3.13 mg/kg, i.v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5 x 10(-6)-1.5 x 10(-5) M, THP markedly relaxed a contraction induced by 10(-7) M norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02-0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5 x 10(-5)-1.5 x 10(-4) M), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10(-6)-5 x 10(-5) M), chlorpheniramine (3 x 10(-7)-3 x 10(-5) M), and tripelennamine (3 x 10(-7)-3 x 10(-5) M) but not by propranolol (10(-6) M), cimetidine (10(-5) M), diltiazem (10(-6) M), or ryanodine (10(-8) M). THP given i.v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.

  14. Antitumor Peptides from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Mi Sun

    2011-10-01

    Full Text Available The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.

  15. Antibiotic-Associated Diarrhea

    Science.gov (United States)

    Antibiotic-associated diarrhea Overview By Mayo Clinic Staff Antibiotic-associated diarrhea refers to passing loose, watery stools ... after taking medications used to treat bacterial infections (antibiotics). Most often, antibiotic-associated diarrhea is mild and ...

  16. Facts about Antibiotic Resistance

    Science.gov (United States)

    ... Cost References Español: Datos breves Facts about Antibiotic Resistance Antibiotic resistance is one of the world’s most pressing public ... antibiotic use is a key strategy to control antibiotic resistance. Antibiotic resistance in children and older adults are ...

  17. Antibiotic / Antimicrobial Resistance Glossary

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

  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. 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.

  20. 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,

  1. 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.

  2. Systemic antibiotics in periodontics.

    Science.gov (United States)

    Slots, Jørgen

    2004-11-01

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

  3. High Antibiotic Consumption

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 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 risk...

  4. Antibiotic resistance in Chlamydiae.

    Science.gov (United States)

    Sandoz, Kelsi M; Rockey, Daniel D

    2010-09-01

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

  5. Ribosomal Antibiotics: Contemporary Challenges

    Directory of Open Access Journals (Sweden)

    Tamar Auerbach-Nevo

    2016-06-01

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

  6. Antibiotics and Breastfeeding.

    Science.gov (United States)

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

    2016-01-01

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

  7. Resistance to antibiotics

    OpenAIRE

    1999-01-01

    The antibiotics represent the most important therapeutic arsenal in the fight against pathogen microorganisms. Even in the beginning of their use, there was registered bacterial resistance, phenomenon thatbecame an alarming subject in the last decades. There are some types of resistance to antibiotics that are influenced by many factors. The resistance term can be used as microbiological resistance and clinical resistance. The resistance to antibiotics can be a natural phenomenon or a gained ...

  8. 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.

  9. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Steiner, Ulrich; Kollerova, Silvia; Jouvet, Lionel

    2016-01-01

    Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... cultures, rather than the individual level. Here, we used individual level bacteria data to confirm previous studies in how fast cells switch into a persistence stage, but our results challenge the fundamental idea that persistence comes with major costs of reduced growth (cell elongation) and division due...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

  10. Garcinia xanthones as orally active antitumor agents.

    Science.gov (United States)

    Zhang, Xiaojin; Li, Xiang; Sun, Haopeng; Wang, Xiaojian; Zhao, Li; Gao, Yuan; Liu, Xiaorong; Zhang, Shenglie; Wang, Yanyan; Yang, Yingrui; Zeng, Su; Guo, Qinglong; You, Qidong

    2013-01-10

    Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D₇.₄, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.

  11. Handling Time-dependent Variables : Antibiotics and Antibiotic Resistance

    NARCIS (Netherlands)

    Munoz-Price, L. Silvia; Frencken, Jos F.; Tarima, Sergey; Bonten, Marc

    2016-01-01

    Elucidating quantitative associations between antibiotic exposure and antibiotic resistance development is important. In the absence of randomized trials, observational studies are the next best alternative to derive such estimates. Yet, as antibiotics are prescribed for varying time periods, antibi

  12. Replacement for antibiotics: Lysozyme

    Science.gov (United States)

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

  13. Antibiotic-Resistant Bacteria.

    Science.gov (United States)

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

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

  14. Metagenomics and antibiotics.

    Science.gov (United States)

    Garmendia, L; Hernandez, A; Sanchez, M B; Martinez, J L

    2012-07-01

    Most of the bacterial species that form part of the biosphere have never been cultivated. In this situation, a comprehensive study of bacterial communities requires the utilization of non-culture-based methods, which have been named metagenomics. In this paper we review the use of different metagenomic techniques for understanding the effect of antibiotics on microbial communities, to synthesize new antimicrobial compounds and to analyse the distribution of antibiotic resistance genes in different ecosystems. These techniques include functional metagenomics, which serves to find new antibiotics or new antibiotic resistance genes, and descriptive metagenomics, which serves to analyse changes in the composition of the microbiota and to track the presence and abundance of already known antibiotic resistance genes in different ecosystems.

  15. Antibiotic Resistance Questions and Answers

    Science.gov (United States)

    ... on the Farm Get Smart About Antibiotics Week Antibiotic Resistance Questions and Answers Language: English Español (Spanish) ... a los antibióticos Questions about Bacteria, Viruses, and Antibiotics Q: What are bacteria and viruses? A: Bacteria ...

  16. Antibiotic prophylaxis in otolaryngologic surgery

    Directory of Open Access Journals (Sweden)

    Ottoline, Ana Carolina Xavier

    2013-01-01

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

  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. Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

    NARCIS (Netherlands)

    Leibovici, Leonard; Paul, Mical; Garner, Paul; Sinclair, David J; Afshari, Arash; Pace, Nathan Leon; Cullum, Nicky; Williams, Hywel C; Smyth, Alan; Skoetz, Nicole; Del Mar, Chris; Schilder, Anne G M; Yahav, Dafna; Tovey, David

    2016-01-01

    Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This

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

    Science.gov (United States)

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

    2015-01-01

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

  20. 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....

  1. Resistance-resistant antibiotics.

    Science.gov (United States)

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

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

  2. 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...

  3. Antibiotics after rattlesnake envenomation.

    Science.gov (United States)

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

    2002-11-01

    To record the outcome, with regard to infection rate, of patients with rattlesnake bites (RSBs) who do not receive prophylactic antibiotics, a prospective observational study was performed of patients with RSBs treated at our institution during a consecutive 18-month period. The inclusion criteria were RSBs envenomation. Fifty-six consecutive patients (Median age: 32.8 years [range 4-67 years]) were enrolled. One patient was excluded because of presentation 38 h after envenomation and two patients failed to complete the required follow-up. One patient received a dose of antibiotics before transfer. Antibiotics were discontinued upon arrival. Of the total 56 RSB patients, 34 (61%) RSBs involved the upper extremity and 22 (39%) involved the lower extremity. Six patients (11%) applied ice and two (4%) used a tourniquet before evaluation. The mean arrival time was 2.7 h (Range antibiotics from their primary care physicians at 7-10 day follow-up, with no cases (0%) of documented infection. Prophylactic antibiotics are not indicated in patients with rattlesnake bites.

  4. 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

  5. Tetracycline Antibiotics and Resistance.

    Science.gov (United States)

    Grossman, Trudy H

    2016-04-01

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

  6. Overdosing on Antibiotics

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Du, a Beijing resident in her 60s, believes that an antibiotic is a panacea for the maladies of her now 6-year-old grand- daughter Guoguo. Du began to take care of her granddaugh- ter since the child was merely 2 months old, for the gid's parents were busy. She is comfortable with her caretaker duties except when the girl runs high fevers. Then, the anxious grandma will feed the girl antibiotics or take her to a private child clinic nearby for intravenous infusion.

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

    Science.gov (United States)

    This review article proposes a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal ...

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

    Science.gov (United States)

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

    2015-10-01

    We analyzed the effect of combinatorial use of antibiotics with a trade-off relationship of resistance, i.e., resistance acquisition to one drug causes susceptibility to the other drug, and vice versa, on the evolution of antibiotic resistance. We demonstrated that this combinatorial use of antibiotics significantly suppressed the acquisition of resistance.

  9. Antibiotic resistance in Salmonella

    NARCIS (Netherlands)

    Vo, A.T.T.

    2007-01-01

    Immediately after their introduction in the beginning of the fourties of the previous century, the agents used to combat infectious diseases caused by bacteria were regarded with suspicion, but not long thereafter antibiotics had the status of miracle drugs. For decades mankind has lived under the i

  10. Mission Critical: Preventing Antibiotic Resistance

    Science.gov (United States)

    ... Button Past Emails CDC Features Mission Critical: Preventing Antibiotic Resistance Recommend on Facebook Tweet Share Compartir Can you ... spp. So, what can we do to prevent antibiotic resistance in healthcare settings? Patients, healthcare providers, healthcare facility ...

  11. Antibiotic-Resistant Gonorrhea (ARG)

    Science.gov (United States)

    ... Twitter STD on Facebook Sexually Transmitted Diseases (STDs) Antibiotic-Resistant Gonorrhea Basic Information Recommend on Facebook Tweet ... Page Surveillance Trends and Treatment Challenges Laboratory Issues Antibiotic resistance (AR) is the ability of bacteria to ...

  12. Antibiotics and Pregnancy: What's Safe?

    Science.gov (United States)

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

  13. Antitumor Activities of Kushen: Literature Review

    Directory of Open Access Journals (Sweden)

    Mingyu Sun

    2012-01-01

    Full Text Available To discover and develop novel natural compounds with therapeutic selectivity or that can preferentially kill cancer cells without significant toxicity to normal cells is an important area in cancer chemotherapy. Kushen, the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As and kushen flavonoids (KS-Fs are well-characterized components in kushen. KS-As containing oxymatrine, matrine, and total alkaloids have been developed in China as anticancer drugs. More potent antitumor activities were identified in KS-Fs than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor agents.

  14. 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.

  15. The antitumor activity of the fungicide ciclopirox

    OpenAIRE

    Zhou, Hongyu; Shen, Tao; Luo, Yan; Lei LIU; 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...

  16. Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

    DEFF Research Database (Denmark)

    Leibovici, Leonard; Paul, Mical; Garner, Paul

    2016-01-01

    be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized......Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies...

  17. Antibiotic prevention of postcataract endophthalmitis

    DEFF Research Database (Denmark)

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

    2015-01-01

    of 485 surgeries when intracameral antibiotics were not used. The relative risk (95% CI) of endophthalmitis was reduced to 0.12 (0.08; 0.18) when intracameral antibiotics were used. The difference was highly significant (p therapy is the best choice for preventing...... endophthalmitis after cataract surgery. We did not find evidence to conclude that topical antibiotic therapy prevents endophthalmitis....

  18. Investigating the Antibiotic Resistance Problem.

    Science.gov (United States)

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

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

  19. When and How to Take Antibiotics

    Science.gov (United States)

    ... Contact Us General Background: When & How to take Antibiotics When should you take antibiotics? What is the proper dosage? How safe are antibiotics? How does a physician decide which antibiotic to ...

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

    Science.gov (United States)

    Sandegren, Linus

    2014-05-01

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

  1. Environmental pollution by antibiotics and by antibiotic resistance determinants

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Jose Luis, E-mail: jlmtnez@cnb.csic.e [Departamento de Biotecnologia Microbiana, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Darwin 3, Cantoblanco, 28049 Madrid, and CIBERESP (Spain)

    2009-11-15

    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.

  2. Advanced research on anti-tumor effects of amygdalin.

    Science.gov (United States)

    Song, Zuoqing; Xu, Xiaohong

    2014-08-01

    Malignant tumors are the major disease that cause serious damage to human health, and have been listed as the premier diseases which seriously threatened human health by World Health Organization (WHO). In recent years the development of antitumor drugs has been gradually transformed from cytotoxic drugs to improving the selectivity of drugs, overcoming multidrug resistance, development of new targeted drugs and low toxicity with high specificity drugs. Amygdalin is a natural product that owns antitumor activity, less side effects, widely sourced and relatively low priced. All these features make the amygdalin a promising antitumor drugs, if combined with conditional chemotherapy drugs, which can produce synergistic effect. In this paper, we summarized the pharmacological activity, toxicity and antitumor activity of amygdalin, mainly focused on the advanced research of amygdalin on its antitumor effects in recent years, providing new insights for the development of new anticancer drugs, new targets searching and natural antitumor mechanism investigations.

  3. Advanced research on anti-tumor effects of amygdalin

    Directory of Open Access Journals (Sweden)

    Zuoqing Song

    2014-01-01

    Full Text Available Malignant tumors are the major disease that cause serious damage to human health, and have been listed as the premier diseases which seriously threatened human health by World Health Organization (WHO. In recent years the development of antitumor drugs has been gradually transformed from cytotoxic drugs to improving the selectivity of drugs, overcoming multidrug resistance, development of new targeted drugs and low toxicity with high specificity drugs. Amygdalin is a natural product that owns antitumor activity, less side effects, widely sourced and relatively low priced. All these features make the amygdalin a promising antitumor drugs, if combined with conditional chemotherapy drugs, which can produce synergistic effect. In this paper, we summarized the pharmacological activity, toxicity and antitumor activity of amygdalin, mainly focused on the advanced research of amygdalin on its antitumor effects in recent years, providing new insights for the development of new anticancer drugs, new targets searching and natural antitumor mechanism investigations.

  4. Molecular mechanisms of antibiotic resistance.

    Science.gov (United States)

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

    2015-01-01

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

  5. Reviving old antibiotics.

    Science.gov (United States)

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

    2015-08-01

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

  6. Prescribing antibiotics in general practice:

    DEFF Research Database (Denmark)

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

    the GPs’ prescribing behaviour is influenced by selected factors. Method The study consists of a register-based study and a questionnaire study. The register-based study is based on data from the Register of Medicinal Product Statistics (prescribed antibiotics), Statistics Denmark (socio-demographic data......Objectives The majority of antibiotics are prescribed from general practice. The use of broad-spectrum antibiotics increases the risk of development of bacteria resistant to antibiotic treatment. In spite of guidelines aiming to minimize the use of broad-spectrum antibiotics we see an increase...... in the use of these agents. The overall aim of the project is to explore factors influencing the decision process and the prescribing behaviour of the GPs when prescribing antibiotics. We will study the impact of microbiological testing on the choice of antibiotic. Furthermore the project will explore how...

  7. [General pharmacology of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic].

    Science.gov (United States)

    Tone, H; Kiyosaki, T; Nishimori, T; Kobayashi, F; Nishimura, K; Morino, H; Tsuchiyama, M

    1986-02-01

    General pharmacology of (2"R)-4'-O-tetrahydropyranyladriamycin hydrochloride (THP) was studied in experimental animals. Intravenous administration of THP showed no significant effect on the respiratory and cardiovascular systems, such as blood pressure, heart rate, ECG and respiration in anesthetized rabbits and dogs. But in rats and cats, THP produced a transient decrease in blood pressure resulted from vasodilation. The hypotension was not inhibited by antihistaminics. Contraction of isolated guinea-pig atria was stimulated by THP at high concentrations (10(-4) g/ml). THP inhibited the spontaneous movement of isolated rabbit ileum and rat uterus (virgin and pregnant) at high concentrations (10(-4) g/ml). In some isolated guinea-pig ileum preparations, THP partially (6 approximately 36%) antagonized the contraction inducing by acetylcholine, histamine, serotonin and barium chloride. Urine volume and urinary excretion of electrolytes were increased by intravenous injection of 5.0 mg/kg THP. Vascular permeability was progressed when administered intracutaneously. Hemolytic effect was shown at high concentrations (10(-4) g/ml) but no effect on the coagulation was found. No significant effect of THP was observed on the general behavior and central nervous system, autonomic nervous and peripheral nervous systems. Also, THP had no significant effect on gastrointestinal propulsion in mice, the mucous membranes of the stomach and duodenum of rats, or gastric acid and bile secretion in rats.

  8. Addressing resistance to antibiotics in systematic reviews of antibiotic interventions.

    Science.gov (United States)

    Leibovici, Leonard; Paul, Mical; Garner, Paul; Sinclair, David J; Afshari, Arash; Pace, Nathan Leon; Cullum, Nicky; Williams, Hywel C; Smyth, Alan; Skoetz, Nicole; Del Mar, Chris; Schilder, Anne G M; Yahav, Dafna; Tovey, David

    2016-09-01

    Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews.

  9. 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.

  10. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    Science.gov (United States)

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

    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 HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series. PMID:19333443

  11. Benzoylphenylurea sulfur analogues with potent antitumor activity.

    Science.gov (United States)

    Hallur, Gurulingappa; Jimeno, Antonio; Dalrymple, Susan; Zhu, Tao; Jung, M Katherine; Hidalgo, Manuel; Isaacs, John T; Sukumar, Saraswati; Hamel, Ernest; Khan, Saeed R

    2006-04-06

    A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to 1 (NSC-639829), against cancer cell lines. 6n was more effective than 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM.

  12. Antibiotics for acute maxillary sinusitis

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...... or 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...... with a pooled RR of 0.74 (95% CI 0.65 to 0.84) at 7 to 15 days follow up. None of the antibiotic preparations was superior to each other. AUTHORS' CONCLUSIONS: Antibiotics have a small treatment effect in patients with uncomplicated acute sinusitis in a primary care setting with symptoms for more than seven...

  13. Antibiotics from predatory bacteria

    Directory of Open Access Journals (Sweden)

    Juliane Korp

    2016-03-01

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

  14. Role of vasoactive amines in the antitumor activity of endotoxin

    NARCIS (Netherlands)

    Hofhuis, F.M.A.; Bloksma, N.; Kuper, C.F.; Willers, J.M.N.

    1984-01-01

    To estimate a possible role of vasoamines in the antitumor action of endotoxin, effects of isoproterenol, serotonin and adrenaline on subcutaneosly transplanted murine Meth A sarcoma and the capacity of these agents to elicit antitumor factors were studied. Macroscopically all agents induced tumor n

  15. 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.

  16. PARP1 Inhibitors: antitumor drug design.

    Science.gov (United States)

    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 PARP1 expression and treatment-resistance of tumors are correlated. PARP1 inhibitors are promising antitumor agents, since they act as chemo- and radiosensitizers in the conventional therapy of malignant tumors. Furthermore, PARP1 inhibitors can be used as independent, effective drugs against tumors with broken DNA repair mechanisms. Currently, third-generation PARP1 inhibitors are being developed, many of which are undergoing Phase II clinical trials. In this review, we focus on the properties and features of the PARP1 inhibitors identified in preclinical and clinical trials. We also describe some problems associated with the application of PARP1 inhibitors. The possibility of developing new PARP1 inhibitors aimed at DNA binding and transcriptional activity rather than the catalytic domain of the protein is discussed.

  17. 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.

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

    NARCIS (Netherlands)

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

    2015-01-01

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to cl

  19. Antibiotics and antibiotic resistance: a bitter fight against evolution.

    Science.gov (United States)

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

    2013-08-01

    One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance.

  20. 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…

  1. 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....

  2. What Can Be Done about Antibiotic Resistance?

    Science.gov (United States)

    ... Us General Background: What can be done about Antibiotic Resistance? What can I do? Are antibacterial agents, such ... regulated? Is there any international action on the antibiotic resistance issue? Can the effectiveness of existing antibiotics be ...

  3. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    Directory of Open Access Journals (Sweden)

    Cesar Echeverria

    2009-01-01

    Full Text Available 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 HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series.

  4. 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.

  5. 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.

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

    Science.gov (United States)

    Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I

    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.

  7. 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.

  8. Antibiotic prescribing for acute bronchitis

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars

    2016-01-01

    INTRODUCTION: Acute bronchitis is a self-limiting infectious disease characterized by acute cough with or without sputum but without signs of pneumonia. About 90% of cases are caused by viruses. AREAS COVERED: Antibiotics for acute bronchitis have been associated with an approximately half...... discusses the reason for this antibiotic overprescription. Other therapies targeted to control symptoms have also demonstrated a marginal or no effect. EXPERT COMMENTARY: Clinicians should be aware of the marginal effectiveness of antibiotic therapy. Some strategies like the use of rapid tests, delayed...

  9. Systemic antibiotic therapy in periodontics.

    Science.gov (United States)

    Kapoor, Anoop; Malhotra, Ranjan; Grover, Vishakha; Grover, Deepak

    2012-09-01

    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, proper selection, dosage and duration for antibiotic therapy so as to optimize the usefulness of drug therapy.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. Progress of Research in Antitumor Mechanisms with Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    韩淑燕; 李萍萍

    2009-01-01

    The anti-tumor effects of Chinese herbal medicines and their prescription preparations attracted more and more attention at home and abroad.Thus,it is becoming a hot research topic to exploit the anti-tumor mechanisms of Chinese medicine,and some of them have been partly clarified with the improved research ability to date.In brief,the Chinese herbal medicines possess unique advantages on the treatment of tumors through their multiple actions on multiple targets.

  15. A study of antibiotic prescribing

    DEFF Research Database (Denmark)

    Jaruseviciene, L.; Radzeviciene-Jurgute, R.; Jurgutis, A.;

    2012-01-01

    Background. Globally, general practitioners (GPs) write more than 90% of all antibiotic prescriptions. This study examines the experiences of Lithuanian and Russian GPs in antibiotic prescription for upper respiratory tract infections, including their perceptions of when it is not indicated...... 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...... for upper respiratory tract infections. Conclusions. Understanding the nature of physician-patient interaction is critical to the effective pursuit of clinically grounded antibiotic use as this study undertaken in Lithuania and the Russian Federation has shown. Both physicians and patients must be targeted...

  16. Antibiotic resistance: An ethical challenge.

    Science.gov (United States)

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper.

  17. Antibiotics, the pill, and pregnancy.

    OpenAIRE

    Mastrantonio, M; Minhas, H; Gammon, A.

    1999-01-01

    OBJECTIVES: To establish if advice concerning risks of pregnancy when taking oral contraceptive pill and antibiotics is being offered. METHOD: A retrospective audit of notes of 100 female patients aged 15-39 who were prescribed antibiotics. RESULTS: Documentation of use of contraception was noted in 3% of patients. Advice concerning risks and further precautions was noted in this 3% but not in any other records. CONCLUSION: The audit identified a gap in documentation and/or clinical practice ...

  18. Prophylactic antibiotics in orthopaedic surgery.

    Science.gov (United States)

    Prokuski, Laura; Clyburn, Terry A; Evans, Richard P; Moucha, Calin S

    2011-01-01

    The use of prophylactic antibiotics in orthopaedic surgery has been proven effective in reducing surgical site infections after hip and knee arthroplasty, spine procedures, and open reduction and internal fixation of fractures. To maximize the beneficial effect of prophylactic antibiotics, while minimizing any adverse effects, the correct antimicrobial agent must be selected, the drug must be administered just before incision, and the duration of administration should not exceed 24 hours.

  19. 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.

  20. Antibiotic utilisation for hospitalised paediatric patients

    NARCIS (Netherlands)

    Luinge, K; Kimpen, JLL; van Houten, M.A.

    1998-01-01

    Antibiotics are among the most commonly prescribed drugs in paediatrics. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies a

  1. 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.

  2. [Biodegradable polyhydroxyalkanoates as carriers for antitumor agents].

    Science.gov (United States)

    Shishatskaia, E I; Zhemchugova, A V; Volova, T G

    2005-01-01

    The possible use of biodegradable polyethers of microbial origin (polyhydroxyalkanoates) as matrices for deposition of daunorubicin (rubomycin), an antitumor anthracycline, was studied. The tablet dosage form of various rubomycin load (from 1 to 60% w/w) was prepared by cold compaction under pressure. The in vitro kinetics of the rubomycin release from the polymer matrix was investigated. It was shown that the rubomycin release to the medium resulted from the drug solution and diffusion within various periods, from tens hours to several weeks and months depending on the load. When the rubomycin load was under 20% w/w the drug release was prolonged and directly proportional to the observation time. When the rubomycin concentration was under 5%, the drug release kinetics corresponded to the type of the zero order reaction with prolonged release without sharp efflux at the initial stage of the observation. The findings showed that the polyhydroxyalkanoates were applicable as matrices for deposition of rubomycin and preparation of drugs with prolonged action.

  3. 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.

  4. 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.

  5. Dielectrophoretic assay of bacterial resistance to antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Johari, Juliana [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Huebner, Yvonne [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Hull, Judith C [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Dale, Jeremy W [School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom); Hughes, Michael P [School of Engineering, University of Surrey, Guildford, Surrey, GU2 7XH, UK (United Kingdom)

    2003-07-21

    The dielectrophoretic collection spectra of antibiotic-sensitive and antibiotic-resistant strains of Staphylococcus epidermidis have been determined. These indicate that in the absence of antibiotic treatment there is a strong similarity between the dielectric properties of sensitive and resistant strains, and that there is a significant difference between the sensitive strains before and after treatment with the antibiotic streptomycin after 24 h exposure. This method offers possibilities for the assessment of bacterial resistance to antibiotics. (note)

  6. In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain.

    Science.gov (United States)

    Báez, Roxana; Lopes, Miriam T; Salas, Carlos E; Hernández, Martha

    2007-10-01

    Stem bromelain (EC 3.4.22.32) is a major cysteine proteinase, isolated from pineapple ( Ananas comosus) stem. Its main medicinal use is recognized as digestive, in vaccine formulation, antitumoral and skin debrider for the treatment of burns. To verify the identity of the principle in stem fractions responsible for the antitumoral effect, we isolated bromelain to probe its pharmacological effects. The isolated bromelain was obtained from stems of adult pineapple plants by buffered aqueous extraction and cationic chromatography. The homogeneity of bromelain was confirmed by reverse phase HPLC, SDS-PAGE and N-terminal sequencing. The in vivo antitumoral/antileukemic activity was evaluated using the following panel of tumor lines: P-388 leukemia, sarcoma (S-37), Ehrlich ascitic tumor (EAT), Lewis lung carcinoma (LLC), MB-F10 melanoma and ADC-755 mammary adenocarcinoma. Intraperitoneal administration of bromelain (1, 12.5, 25 mg/kg), began 24 h after tumor cell inoculation in experiments in which 5-fluorouracil (5-FU, 20 mg/kg) was used as positive control. The antitumoral activity was assessed by the survival increase (% survival index) following various treatments. With the exception of MB-F10 melanoma, all other tumor-bearing animals had a significantly increased survival index after bromelain treatment. The largest increase ( approximately 318 %) was attained in mice bearing EAT ascites and receiving 12.5 mg/kg of bromelain. This antitumoral effect was superior to that of 5-FU, whose survival index was approximately 263 %, relative to the untreated control. Bromelain significantly reduced the number of lung metastasis induced by LLC transplantation, as observed with 5-FU. The antitumoral activity of bromelain against S-37 and EAT, which are tumor models sensitive to immune system mediators, and the unchanged tumor progression in the metastatic model suggests that the antimetastatic action results from a mechanism independent of the primary antitumoral effect.

  7. 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...

  8. 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...

  9. Detection of antibiotic residues in poultry meat.

    Science.gov (United States)

    Sajid, Abdul; Kashif, Natasha; Kifayat, Nasira; Ahmad, Shabeer

    2016-09-01

    The antibiotic residues in poultry meat can pose certain hazards to human health among them are sensitivity to antibiotics, allergic reactions, mutation in cells, imbalance of intestinal micro biota and bacterial resistance to antibiotics. The purpose of the present paper was to detect antibiotic residue in poultry meat. During the present study a total of 80 poultry kidney and liver samples were collected and tested for detection of different antibiotic residues at different pH levels Eschericha coli at pH 6, 7 and Staphyloccocus aureus at pH 8 & 9. Out of 80 samples only 4 samples were positive for antibiotic residues. The highest concentrations of antibiotic residue found in these tissues were tetracycline (8%) followed by ampicilin (4%), streptomycine (2%) and aminoglycosides (1%) as compared to other antibiotics like sulfonamides, neomycine and gentamycine. It was concluded that these microorganism at these pH levels could be effectively used for detection of antibiotic residues in poultry meat.

  10. 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.

  11. Antibiotic drugs targeting bacterial RNAs

    Directory of Open Access Journals (Sweden)

    Weiling Hong

    2014-08-01

    Full Text Available RNAs have diverse structures that include bulges and internal loops able to form tertiary contacts or serve as ligand binding sites. The recent increase in structural and functional information related to RNAs has put them in the limelight as a drug target for small molecule therapy. In addition, the recognition of the marked difference between prokaryotic and eukaryotic rRNA has led to the development of antibiotics that specifically target bacterial rRNA, reduce protein translation and thereby inhibit bacterial growth. To facilitate the development of new antibiotics targeting RNA, we here review the literature concerning such antibiotics, mRNA, riboswitch and tRNA and the key methodologies used for their screening.

  12. Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.

    Science.gov (United States)

    Niu, Guoqing; Tan, Huarong

    2015-02-01

    The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics.

  13. Antibiotic Policies in the Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Nese Saltoglu

    2003-08-01

    Full Text Available The antimicrobial management of patients in the Intensive Care Units are complex. Antimicrobial resistance is an increasing problem. Effective strategies for the prevention of antimicrobial resistance in ICUs have focused on limiting the unnecessary use of antibiotics and increasing compliance with infection control practices. Antibiotic policies have been implemented to modify antibiotic use, including national or regional formulary manipulations, antibiotic restriction forms, care plans, antibiotic cycling and computer assigned antimicrobial therapy. Moreover, infectious diseases consultation is a simple way to limit antibiotic use in ICU units. To improve rational antimicrobial using a multidisiplinary approach is suggested. [Archives Medical Review Journal 2003; 12(4.000: 299-309

  14. 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....

  15. Antibiotic resistance of bacterial biofilms

    DEFF Research Database (Denmark)

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

    2010-01-01

    and other components of the body's defence system. The persistence of, for example, staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is caused by biofilm-growing mucoid strains...... 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...

  16. 四环素类药物的非抗菌作用机制与非抗感染临床应用%Non - antibiotic Mechanism and Non - antibiotic Use of Tetracyclines

    Institute of Scientific and Technical Information of China (English)

    余彦国; 张瑾

    2012-01-01

    Recent studies found that tetracyclines have non - antibiotic property, and tetracyclines will be more promising in the treatment of diseases in bone metabolism, antitumor, etc. This article reviews the non - antibiotic mechanism and non - antibiotic use of tetracyclines, mainly including matrix metalloproteinases, intervene the production of the cytokine, eactive oxygen radicals and treatment periodontitis, osteoarthritis, diabetes, osteoporosis, antitumor, pleural effusion and so on.%近年研究发现四环素类药物具有非抗菌性质,在治疗骨代谢疾病,抗肿瘤等方面很好的临床应用前景。本文主要综述了四环素类药物抑制基质金属蛋白酶、干预细胞因子的产生、抗氧自由基等的非抗菌作用机制,以及治疗牙周炎、骨关节炎、糖尿病、骨质疏松症、抗肿瘤、胸腔积液等的非抗菌临床应用。

  17. 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.

  18. New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer.

    Science.gov (United States)

    Wang, Sheng-Qi; Zhao, Bo-Xin; Liu, Yuan; Wang, Ya-Tian; Liang, Qian-Ying; Cai, Yun; Zhang, Yun-Qi; Yang, Jiang-Hong; Song, Zhi-Hua; Li, Guo-Feng

    2016-04-01

    Small cell lung cancer (SCLC) remains one of the most aggressive tumors with a poor prognosis. The clinical outcome of SCLC patients has reached its plateau with the existing standard treatment and thus new therapies are urgently required. Accumulating evidences have indicated that doxycycline, a commonly used antibiotic, has antitumor activity against several malignancies. However, whether doxycycline has antitumor activity in SCLC and its underlying mechanisms remain unclear. Our investigation demonstrated that doxycycline could significantly inhibit the proliferation and colony formulation of SCLC cells (pdoxycycline could induce remarkable apoptosis of H446 cells in a concentration-dependent manner. RT-PCR and western blot assays proved that apoptosis induction effect of doxycycline was achieved via inducing the expression of caspase-3 and bax, as well as attenuating the expression of survivin and bcl-2. Moreover, the wound healing assay and Transwell assay indicated that doxycycline could significantly suppress the migration and invasion of H446 cells in a concentration-dependent manner (pdoxycycline on the migration and invasion of H446 cells was achieved via decreasing the secretion of MMP-2, MMP-9 and VEGF, as well as increasing the secretion of TIMP-2. Taken together, doxycycline dose-dependently suppressed the proliferation, colony formulation, migration and invasion of SCLC cells, as well as induced apoptosis. These findings encourage further investigations on the potential of doxycycline as a candidate drug for the treatment of SCLC.

  19. Interactions between inflammatory mediators in expression of antitumor cytostatic activity of macrophages

    NARCIS (Netherlands)

    I.L. Bonta; S. Ben-Efraim

    1990-01-01

    markdownabstractAbstract Antitumor properties and participation in inflammatory events are important characteristics of activated macrophages. We show here that both antitumor cytostatic function of macrophages and participation of these cells at inflammatory sites are controlled by two main group

  20. 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.

  1. Probiotic approach to prevent antibiotic resistance.

    Science.gov (United States)

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

    2016-01-01

    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.

  2. Fractionated photothermal antitumor therapy with multidye nanoparticles

    Directory of Open Access Journals (Sweden)

    Gutwein LG

    2012-01-01

    Full Text Available Luke G Gutwein1, Amit K Singh2, Megan A Hahn2, Michael C Rule3, Jacquelyn A Knapik4, Brij M Moudgil2, Scott C Brown2, Stephen R Grobmyer11Division of Surgical Oncology, Department of Surgery, College of Medicine, 2Particle Engineering Research Center, 3Cell and Tissue Analysis Core, McKnight Brain Institute, 4Department of Pathology, University of Florida, Gainesville, FL, USAPurpose: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs for fractionated photothermal antitumor therapy.Methods: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice.Results: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026 in experimental tumor-bearing mice

  3. 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.

  4. Use of antibiotics in children

    DEFF Research Database (Denmark)

    Pottegård, Anton; Broe, A.; Aabenhus, R.

    2015-01-01

    -1. There was little evidence of heavy users. Conclusion: Prescribing rate of antibiotics to children in Denmark remained stable at a high level from 2000 to 2012. An increase in the use of broad-spectrum beta-lactam penicillin was noted, but otherwise the prescribing pattern adhered well to National guidelines...

  5. Antibiotic resistance in probiotic bacteria

    Directory of Open Access Journals (Sweden)

    Miguel eGueimonde

    2013-07-01

    Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The main probiotic bacteria are strains belonging to the genera Lactobacillus and Bifidobacterium, although other representatives, such as Bacillus or Escherichia coli strains, have also been used. Lactobacillus and Bifidobacterium are two common inhabitants of the human intestinal microbiota. Also, some species are used in food fermentation processes as starters, or as adjunct cultures in the food industry. With some exceptions, antibiotic resistance in these beneficial microbes does not constitute a safety concern in itself, when mutations or intrinsic resistance mechanisms are responsible for the resistance phenotype. In fact, some probiotic strains with intrinsic antibiotic resistance could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, are often detected in the typical probiotic genera, and constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue.

  6. Origins and evolution of antibiotic resistance.

    Science.gov (United States)

    Davies, Julian; Davies, Dorothy

    2010-09-01

    Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

  7. Antibiotic 'Report Card' Drills Guidelines into Dentists

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_160702.html Antibiotic 'Report Card' Drills Guidelines Into Dentists Seeing their ... HealthDay News) -- Dentists are less likely to prescribe antibiotics for patients after seeing a "report card" on ...

  8. Antibiotic Resistance in Human Chronic Periodontitis Microbiota

    NARCIS (Netherlands)

    Rams, Thomas E.; Degener, John E.; van Winkelhoff, Arie J.

    2014-01-01

    Background: Patients with chronic periodontitis (CP) may yield multiple species of putative periodontal bacterial pathogens that vary in their antibiotic drug susceptibility. This study determines the occurrence of in vitro antibiotic resistance among selected subgingival periodontal pathogens in pa

  9. The antibiotics relo in bacteria resistance

    OpenAIRE

    Santana, Vinicius Canato; CESUMAR

    2007-01-01

    The paper explains how antibiotics help us to combat bacteriosis, and also presents a brief historical report about the emergence of the antibiotic era with the discovery of penicillin. It introduces the problem of bacteria resistance, and brings the concept of antibiotics and its that produce these substance, and brings the concept of antibiotics and its main function. It questions about the self-defense of the organisms that produce these substances. relates the bacteria structures attacked...

  10. Acquired antibiotic resistance genes: an overview.

    OpenAIRE

    Hoek, Angela H.A.M. van; Dik eMevius; Beatriz eGuerra; Peter eMullany; Adam Paul Roberts; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance mechanisms with special attentions to the antibiotic resistance genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is paid to mobile genetic elements such as plasmids, transposons and integrons, which are associated with antibiotic resistance genes, and involved in the dispersal of anti...

  11. Squalamine: an aminosterol antibiotic from the shark.

    OpenAIRE

    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...

  12. The determinants of the antibiotic resistance process

    Directory of Open Access Journals (Sweden)

    Beatriz Espinosa Franco

    2009-04-01

    Full Text Available Beatriz Espinosa Franco1, Marina Altagracia Martínez2, Martha A Sánchez Rodríguez1, Albert I Wertheimer31Facultad de Estudios Superiores Zaragoza (UNAM, Mexico; 2Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico; 3Temple University, Philadelphia, Pennsylvania, USABackground: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community.Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem.Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded.Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance.Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals.Keywords: antibiotic drug resistance

  13. Shift in antibiotic prescribing patterns in relation to antibiotic expenditure in paediatrics

    NARCIS (Netherlands)

    Kimpen, JLL; van Houten, M.A.

    1998-01-01

    In paediatrics, antibiotics are among the most commonly prescribed drugs. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies

  14. Delivery of antibiotics with polymeric particles.

    Science.gov (United States)

    Xiong, Meng-Hua; Bao, Yan; Yang, Xian-Zhu; Zhu, Yan-Hua; Wang, Jun

    2014-11-30

    Despite the wide use of antibiotics, bacterial infection is still one of the leading causes of hospitalization and mortality. The clinical failure of antibiotic therapy is linked with low bioavailability, poor penetration to bacterial infection sites, and the side effects of antibiotics, as well as the antibiotic resistance properties of bacteria. Antibiotics encapsulated in nanoparticles or microparticles made up of a biodegradable polymer have shown great potential in replacing the administration of antibiotics in their "free" form. Polymeric particles provide protection to antibiotics against environmental deactivation and alter antibiotic pharmacokinetics and biodistribution. Polymeric particles can overcome tissue and cellular barriers and deliver antibiotics into very dense tissues and inaccessible target cells. Polymeric particles can be modified to target or respond to particular tissues, cells, and even bacteria, and thereby facilitate the selective concentration or release of the antibiotic at infection sites, respectively. Thus, the delivery of antibiotics with polymeric particles augments the level of the bioactive drug at the site of infection while reducing the dosage and the dosing frequency. The end results are improved therapeutic effects as well as decreased "pill burden" and drug side effects in patients. The main objective of this review is to analyze recent advances and current perspectives in the use of polymeric antibiotic delivery systems in the treatment of bacterial infection.

  15. Antibiotic susceptibility profiles of oral pathogens

    NARCIS (Netherlands)

    Veloo, A. C. M.; Seme, K.; Raangs, E.; Rurenga, P.; Singadji, Z.; Wekema-Mulder, G.; van Winkelhoff, A. J.

    2012-01-01

    Periodontitis is a bacterial disease that can be treated with systemic antibiotics. The aim of this study was to establish the antibiotic susceptibility profiles of five periodontal pathogens to six commonly used antibiotics in periodontics. A total of 247 periodontal bacterial isolates were tested

  16. Influence of population density on antibiotic resistance

    NARCIS (Netherlands)

    Bruinsma, N; Hutchinson, JM; van den Bogaard, AE; Giamarellou, H; Degener, J; Stobberingh, EE

    2003-01-01

    Antibiotic consumption and population density as a measure of crowding in the community were related to the prevalence of antibiotic resistance of three cities in three different countries: St Johns in Newfoundland (Canada), Athens in Greece and Groningen in The Netherlands. Antibiotic consumption w

  17. Response to "Antibiotic Use and Resistance"

    DEFF Research Database (Denmark)

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

    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 ...

  18. New business models for antibiotic innovation.

    Science.gov (United States)

    So, Anthony D; Shah, Tejen A

    2014-05-01

    The increase in antibiotic resistance and the dearth of novel antibiotics have become a growing concern among policy-makers. A combination of financial, scientific, and regulatory challenges poses barriers to antibiotic innovation. However, each of these three challenges provides an opportunity to develop pathways for new business models to bring novel antibiotics to market. Pull-incentives that pay for the outputs of research and development (R&D) and push-incentives that pay for the inputs of R&D can be used to increase innovation for antibiotics. Financial incentives might be structured to promote delinkage of a company's return on investment from revenues of antibiotics. This delinkage strategy might not only increase innovation, but also reinforce rational use of antibiotics. Regulatory approval, however, should not and need not compromise safety and efficacy standards to bring antibiotics with novel mechanisms of action to market. Instead regulatory agencies could encourage development of companion diagnostics, test antibiotic combinations in parallel, and pool and make transparent clinical trial data to lower R&D costs. A tax on non-human use of antibiotics might also create a disincentive for non-therapeutic use of these drugs. Finally, the new business model for antibiotic innovation should apply the 3Rs strategy for encouraging collaborative approaches to R&D in innovating novel antibiotics: sharing resources, risks, and rewards.

  19. How can we improve antibiotic prescribing in primary care?

    NARCIS (Netherlands)

    Dyar, Oliver J.; Beović, Bojana; Vlahović-Palčevski, Vera; Verheij, Theo; Pulcini, Céline

    2016-01-01

    Antibiotic stewardship is a necessity given the worldwide antimicrobial resistance crisis. Outpatient antibiotic use represents around 90% of total antibiotic use, with more than half of these prescriptions being either unnecessary or inappropriate. Efforts to improve antibiotic prescribing need to

  20. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

    Science.gov (United States)

    Brown, David

    2015-12-01

    Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation.

  1. 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

  2. An antitumor compound julibroside J28 from Albizia julibrissin.

    Science.gov (United States)

    Liang, Hong; Tong, Wen-yong; Zhao, Yu-ying; Cui, Jing-rong; Tu, Guang-zhong

    2005-10-15

    A new triterpenoid saponin, julibroside J(28) (1), was isolated from the stem bark of Albizia julibrissin Durazz (Leguminosae) by using chromatographic method. The structure of 1 was established by spectroscopic methods. 1 displayed significant antitumor activity in vitro against PC-3M-1E8, Bel-7402, and HeLa cancer cell lines at 10 microM assayed by SRB method.

  3. Synthesis and anti-tumor activity of alkenyl camptothecin esters

    Institute of Scientific and Technical Information of China (English)

    Zhi-song CAO; John MENDOZA; Albert DEJESUS; Beppino GIOVANELLA

    2005-01-01

    Aim: To study the degrees of influence of changing side ester chains at position C20 of camptothecin on the anti-tumor activity of the molecules. Methods: The esterification reaction of camptothecin 1 and 9-nitrocamptothecin 2 with crotonic anhydride in pyridine gave the corresponding esters 3 and 4, respectively. The acylation of 1 and 2 with cinnamoyl chloride gave products 7 and 8. Epoxidation reaction of 3 and 4 with m-chloroperoxybenzoic acid in benzene solvent gave the products 5 and 6. Esters 3, 4, and 5 were tested for anti-tumor activity against 14 human cancer cell lines. Results: Both in vitro and in vivo anti-tumor activity studies for these esters were conducted and the data demonstrated positive results, that is, these esters were active against the tested tumor lines. Conclusion: Alkenyl esters 3 and 4 showed strong anti-tumor activity in vitro against 14 different cancer cell lines. Ester 3 was active against human breast carcinoma in mice and the toxicity of the agent was not observed in mice during the treatment, implying that this agent is effective for treatment with low toxicity.

  4. 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.

  5. 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.

  6. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance

    OpenAIRE

    Nishant A. Dafale; Uttam P. Semwal; Rupak K. Rajput; Singh, G. N.

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Resistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the pote...

  7. Antibiotic resistance in cancer patients.

    Science.gov (United States)

    Gudiol, Carlota; Carratalà, Jordi

    2014-08-01

    Bacterial infection is one of the most frequent complications in cancer patients and hematopoietic stem cell transplant recipients. In recent years, the emergence of antimicrobial resistance has become a significant problem worldwide, and cancer patients are among those affected. Treatment of infections due to multidrug-resistant (MDR) bacteria represents a clinical challenge, especially in the case of Gram-negative bacilli, since the therapeutic options are often very limited. As the antibiotics active against MDR bacteria present several disadvantages (limited clinical experience, higher incidence of adverse effects, and less knowledge of the pharmacokinetics of the drug), a thorough acquaintance with the main characteristics of these drugs is mandatory in order to provide safe treatment to cancer patients with MDR bacterial infections. Nevertheless, the implementation of antibiotic stewardship programs and infection control measures is the cornerstone for controlling the development and spread of these MDR pathogens.

  8. [Action of antibiotics as signalling molecules].

    Science.gov (United States)

    Bulgakova, V G; Vinogradova, K A; Orlova, T I; Kozhevin, P A; Polin, A N

    2014-01-01

    It was thought that antibiotics should be produced by soil microorganisms to inhibit the growth of competitors in natural habitats. Yet it has been shown that antibiotics at subinhibitory concentrations may have a role as signalling molecules providing cell-to-cell communication in bacteria in the environment. Antibiotics modulate gene transcription and regulate gene expression in microbial populations. Subinhibitory concentrations of antibiotics may cause a number of phenotypic and genotypic changes in microorganisms. These transcription changes are dependent on the interaction of antibiotics with macromolecular receptors such as ribosome or RNA-polymerase. Antibiotic signalling and quorum-sensing system are important regulatory mechanisms in bacteria. It was demonstrated that antibiotics interfered with quorum-sensing system.

  9. Bacterial vaccines and antibiotic resistance

    OpenAIRE

    Henriques-Normark, Birgitta; Normark, Staffan

    2014-01-01

    Spread of antibiotic resistance is mediated by clonal lineages of bacteria that besides being resistant also possess other properties promoting their success. Some vaccines already in use, such as the pneumococcal conjugate vaccines, have had an effect on these successful clones, but at the same time have allowed for the expansion and resistance evolution of previously minor clones not covered by the vaccine. Since resistance frequently is horizontally transferred it will be difficult to gene...

  10. Antitumor effect of seaweeds. II. Fractionation and partial characterization of the polysaccharide with antitumor activity from Sargassum fulvellum.

    Science.gov (United States)

    Yamamoto, I; Nagumo, T; Fujihara, M; Takahashi, M; Ando, Y

    1977-06-01

    An almost purified antitumor polysaccharide fraction (SFPP) was obtained by fractional precipitation with ethanol from hot-water extract of Sargassum fulvellum. The fraction showed remarkable tumor-inhibiting effect against sarcoma-180 implanted subcutaneously in mice. The results of chemical and physical analyses suggested that the active substance may be either a sulphated peptidoglycuronoglycan or a sulphated glycuronoglycan.

  11. 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.

  12. Antitumor activity of two gelsemine metabolites in rat liver microsomes.

    Science.gov (United States)

    Zhao, Qing-Chun; Hua, Wei; Zhang, Lin; Guo, Tao; Zhao, Ming-Hong; Yan, Ming; Shi, Guo-Bing; Wu, Li-Jun

    2010-09-01

    Gelsemine is one of the major alkaloids from Gelsemium elegans Benth., which has been used as an antitumor remedy in clinic. In this paper, metabolism of gelsemine has been investigated in vitro in phenobarbital-treated rat liver microsomes. The metabolites of gelsemine were separated and evaluated using the flash silica gel column, preparative HPLC, using NMR and MS methods. According to the spectral data, two metabolites, M1 and M2, were identified as 4-N-demethylgelsemine and 21-oxogelsemine, respectively. By the MTT method in vitro, the antitumor activities between gelsemine and its metabolites were compared in the HepG2 and HeLa cell lines. Moreover, the main metabolic pathway was further proposed.

  13. Mucin-like peptides from Echinococcus granulosus induce antitumor activity.

    Science.gov (United States)

    Noya, Verónica; Bay, Sylvie; Festari, María Florencia; García, Enrique P; Rodriguez, Ernesto; Chiale, Carolina; Ganneau, Christelle; Baleux, Françoise; Astrada, Soledad; Bollati-Fogolín, Mariela; Osinaga, Eduardo; Freire, Teresa

    2013-09-01

    There is substantial evidence suggesting that certain parasites can have antitumor properties. We evaluated mucin peptides derived from the helminth Echinococcus granulosus (denominated Egmuc) as potential inducers of antitumor activity. We present data showing that Egmuc peptides were capable of inducing an increase of activated NK cells in the spleen of immunized mice, a fact that was correlated with the capacity of splenocytes to mediate killing of tumor cells. We demonstrated that Egmuc peptides enhance LPS-induced maturation of dendritic cells in vitro by increasing the production of IL-12p40p70 and IL-6 and that Egmuc-treated DCs may activate NK cells, as judged by an increased expression of CD69. This evidence may contribute to the design of tumor vaccines and open new horizons in the use of parasite-derived molecules in the fight against cancer.

  14. Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A2

    Directory of Open Access Journals (Sweden)

    Raoudha Zouari-Kessentini

    2013-01-01

    Full Text Available Phospholipases type A2 (PLA2s are the most abundant proteins found in Viperidae snake venom. They are quite fascinating from both a biological and structural point of view. Despite similarity in their structures and common catalytic properties, they exhibit a wide spectrum of pharmacological activities. Besides being hydrolases, secreted phospholipases A2 (sPLA2 are an important group of toxins, whose action at the molecular level is still a matter of debate. These proteins can display toxic effects by different mechanisms. In addition to neurotoxicity, myotoxicity, hemolytic activity, antibacterial, anticoagulant, and antiplatelet effects, some venom PLA2s show antitumor and antiangiogenic activities by mechanisms independent of their enzymatic activity. This paper aims to discuss original finding against anti-tumor and anti-angiogenic activities of sPLA2 isolated from Tunisian vipers: Cerastes cerastes and Macrovipera lebetina, representing new tools to target specific integrins, mainly, and integrins.

  15. Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents.

    Science.gov (United States)

    Liu, Jia-Jia; Zhao, Meng-Yue; Zhang, Xin; Zhao, Xin; Zhu, Hai-Liang

    2013-11-01

    Within the past years, many researches on the synthesis, structure-activity relationships (SAR), antitumor, antiinflammatory and anti-bacterial activities of the pyrazole derivatives have been reported. Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents because of their good inhibitory activity against BRAF(V600E), EGFR, telomerase, ROS Receptor Tyrosine Kinase and Aurora-A kinase. In addition, pyrazole derivatives also show good antiinflammatory and anti-bacterial activities. In this review, the bioactivities of the pyrazole derivatives mentioned above will be summarized in detail. We sincerely hope that increasing knowledge of the SAR and cellular processes underlying the bioactivity of pyrazole derivatives will be beneficial to the rational design of new generation of small molecule drugs.

  16. Insights into antibiotic resistance through metagenomic approaches.

    Science.gov (United States)

    Schmieder, Robert; Edwards, Robert

    2012-01-01

    The consequences of bacterial infections have been curtailed by the introduction of a wide range of antibiotics. However, infections continue to be a leading cause of mortality, in part due to the evolution and acquisition of antibiotic-resistance genes. Antibiotic misuse and overprescription have created a driving force influencing the selection of resistance. Despite the problem of antibiotic resistance in infectious bacteria, little is known about the diversity, distribution and origins of resistance genes, especially for the unculturable majority of environmental bacteria. Functional and sequence-based metagenomics have been used for the discovery of novel resistance determinants and the improved understanding of antibiotic-resistance mechanisms in clinical and natural environments. This review discusses recent findings and future challenges in the study of antibiotic resistance through metagenomic approaches.

  17. Antibiotic Prescription in Danish General Practice

    DEFF Research Database (Denmark)

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

    2016-01-01

    are increasing. 2. Method The study consists of a registry study and a questionnaire study. The registry study is based on data from the Register of Medicinal Product Statistics (prescribed antibiotics), Statistics Denmark (socio-demographic data) and the Danish Microbiology Database (performed MDM). The project......1. Background & Aim The overall aim of the project is to describe antibiotic consumption in Danish general practice with emphasis on specific types of antibiotics. The project will shed light on the impact of microbiological diagnostic methods (MDM) on the choice of antibiotic and the project...... will 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...

  18. New antibiotic therapies for acne and rosacea.

    Science.gov (United States)

    Mays, Rana Majd; Gordon, Rachel A; Wilson, Janice M; Silapunt, Sirunya

    2012-01-01

    Acne and rosacea compromise a substantial portion of the dermatology clinical practice. Over the past century, many treatment modalities have been introduced with antibiotics playing a major role. Today, both oral and topical antibiotics are used in the management of acne and rosacea, with several novel formulations and/or combination regimens recently introduced. The latest studies suggest anti-inflammatory actions to be the most likely mechanism of antibiotics in acne and rosacea, shifting the focus to subantimicrobial-dose oral antibiotics and/or topical antibiotic regimens as the preferred first-line agents. Here we will discuss the most recent oral and topical antibiotic therapies available for treatment of acne and rosacea, with special focus on efficacy data, indication, dosing, and mechanism of action.

  19. Antitumor Activity of Monoterpenes Found in Essential Oils

    Directory of Open Access Journals (Sweden)

    Marianna Vieira Sobral

    2014-01-01

    Full Text Available 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 for bioactive substances are presented.

  20. 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.

  1. Synthesis and antitumor activity of 9-methyl-10-hydroxycamptothecin

    Institute of Scientific and Technical Information of China (English)

    Sheng Wang; Yu Yan Li; Qi Dong You

    2008-01-01

    A novel camptothecin analogue, 9-methyl-10-hydroxycamptothecin (4), was unexpectedly synthesized from 10-hydroxycamptothecin in two steps. The key step included an efficient Mannich-type reaction. The overall yield was 47.2%. An ether analogue of 4, 9-methyl-10-benzylaminomethoxycamptothecin (5), was also prepared. These new camptothecin analogues were evaluated for in vitro cytotoxicity against four human cancer cell lines, and exhibited more potent antitumor activities than contrals camptothecin and topotecan against several cancer cells.

  2. 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.

  3. Three anti-tumor saponins from Albizia julibrissin.

    Science.gov (United States)

    Zheng, Lu; Zheng, Jian; Zhao, Yuying; Wang, Bin; Wu, Lijun; Liang, Hong

    2006-05-15

    Three new triterpenoid saponins, julibroside J(29) (1), julibroside J(30) (2), and julibroside J(31) (3), were isolated from the stem bark of Albizia julibrissin Durazz. (Leguminosae) by using chromatographic method. Their structures were established by spectroscopic methods. Compounds 1, 2, and 3 displayed significant anti-tumor activities in vitro against PC-3M-1E8, HeLa, and MDA-MB-435 cancer cell lines at 10microM assayed by SRB and MTT methods.

  4. Proteasome inhibitory activity of thiazole antibiotics

    OpenAIRE

    Pandit, Bulbul; Bhat, Uppoor; Andrei L Gartel

    2011-01-01

    Thiopeptides are sulfur containing highly modified macrocyclic antibiotics with a central pyridine/tetrapyridine/dehydropiperidine ring with up to three thiazole substituents on positions 2, 3 and 6. Thiazole antibiotics with central pyridine nucleus have a macrocyclic loop connecting thiazole rings at position 2 and 3 described as ring A. In addition antibiotics with central tetrahydropyridine nucleus have a quinaldic acid macrocycle also connected to thiazole on position 2 described as ring...

  5. Priorities for antibiotic resistance surveillance in Europe

    DEFF Research Database (Denmark)

    Fluit, A. C.; van der Bruggen, J. T.; Aarestrup, Frank Møller

    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...... to the 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...... of antibiotic resistance....

  6. 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.

  7. Separation and nanoencapsulation of antitumor polypeptide from Spirulina platensis.

    Science.gov (United States)

    Zhang, Bochao; Zhang, Xuewu

    2013-01-01

    Spirulina platensis is a multicellular edible blue-green alga with abundant proteins (∼ 60%). No report is available on the antitumor polypeptides from the whole proteins of S. platensis. In this study, for the first time, an antitumor polypeptide Y2 from trypsin digest of S. platensis proteins was obtained by using freeze-thawing plus ultrasonication extraction, hydrolysis with four enzymes (trypsin, alcalase, papain, and pepsin), and gel filtration chromatography. The results showed that the degree of hydrolysis can be ordered as: trypsin (38.5%) > alcalase (31.2%) > papain (27.8%) > pepsin (7.1%). For MCF-7 and HepG2 cells, at 250 µg/mL, the maximum inhibitory rate of Y2 was 97%, while standard drug 5-FU was 55 and 97%, respectively. Furthermore, the nanoencapsulation of Y2 with chitosan (CS) was also investigated. After nanoencapsulation, the maximum encapsulation efficiency and polypeptides contents are 49 and 15%, respectively; and the antitumor activity is basically not lost. These data demonstrated the potential of nanopolypeptides (Y2-CS) in food and pharmaceutical applications.

  8. Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

    Science.gov (United States)

    Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

    2015-02-01

    The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (PPiper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

  9. Synergistic antitumor efficiency of docetaxel and curcumin against lung cancer

    Institute of Scientific and Technical Information of China (English)

    Haitao Yin; Rui Guo; Yong Xu; Yulong Zheng; Zhibo Hou; Xinzheng Dai; Zhengdong Zhang; Donghui Zheng; Hua'e Xu

    2012-01-01

    Curcumin (Cum),the principal polyphenolic curcuminoid,obtained from the turmeric rhizome Curcuma longa,is recently reported to have potential antitumor effects in vitro and in vivo.Docetaxel (Doc) is considered as first-line chemotherapy for the treatment of non-small cell lung cancer.Here we report for the first time that Cum could synergistically enhance the in vitro and in vivo antitumor efficacy of Doc against lung cancer.In the current study,combination index (CI) is calculated in both in vitro and in vivo studies to determine the interaction between Cum and Doc.In the in vitro cytotoxicity test,media-effect analysis clearly indicated a synergistic interaction between Cum and Doc in certain concentrations.Moreover,in vivo evaluation further demonstrated the superior anticancer efficacy of Cum + Doc compared with Doc alone by intravenous delivery in an established A549 transplanted xenograft model.Results showed that Cum synergistically increased the efficacy of Doc immediately after 4 days of the initial treatment.Additionally,simultaneous administration of Cum and Doc showed little toxicity to normal tissues including bone marrow and liver at the therapeutic doses.Therefore,in vitro and in vivo evaluations demonstrated the satisfying synergistic antitumor efficacy of Cum and Doc against lung cancer and the introduction of Cum in traditional chemotherapy is a most promising way to counter the spread of nonsmall cell lung cancer.

  10. 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.

  11. Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds.

    Science.gov (United States)

    Chen, Ling; Zhang, Qiao-Yan; Jia, Min; Ming, Qian-Liang; Yue, Wei; Rahman, Khalid; Qin, Lu-Ping; Han, Ting

    2016-05-01

    Plant endophytic fungi have been recognized as an important and novel resource of natural bioactive products, especially in anticancer application. This review mainly deals with the research progress on the production of anticancer compounds by endophytic fungi between 1990 and 2013. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. All strains of endophytes producing antitumor chemicals were classified taxonomically and the genera of Pestalotiopsis and Aspergillus as well as the taxol producing endophytes were focused on. Classification of endophytic fungi producing antitumor compounds has received more attention from mycologists, and it can also lead to the discovery of novel compounds with antitumor activity due to phylogenetic relationships. In this review, the structures of the anticancer compounds isolated from the newly reported endophytes between 2010 and 2013 are discussed including strategies for the efficient production of the desired compounds. The purpose of this review is to provide new directions in endophytic fungi research including integrated information relating to its anticancer compounds.

  12. Antioxidant, antimutagenic, and antitumor effects of pine needles (Pinus densiflora).

    Science.gov (United States)

    Kwak, Chung Shil; Moon, Sung Chae; Lee, Mee Sook

    2006-01-01

    Pine needles (Pinus densiflora Siebold et Zuccarini) have long been used as a traditional health-promoting medicinal food in Korea. To investigate their potential anticancer effects, antioxidant, antimutagenic, and antitumor activities were assessed in vitro and/or in vivo. Pine needle ethanol extract (PNE) significantly inhibited Fe(2+)-induced lipid peroxidation and scavenged 1,1-diphenyl- 2-picrylhydrazyl radical in vitro. PNE markedly inhibited mutagenicity of 2-anthramine, 2-nitrofluorene, or sodium azide in Salmonella typhimurium TA98 or TA100 in Ames tests. PNE exposure effectively inhibited the growth of cancer cells (MCF-7, SNU-638, and HL-60) compared with normal cell (HDF) in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In in vivo antitumor studies, freeze-dried pine needle powder supplemented (5%, wt/wt) diet was fed to mice inoculated with Sarcoma-180 cells or rats treated with mammary carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA, 50 mg/kg body weight). Tumorigenesis was suppressed by pine needle supplementation in the two model systems. Moreover, blood urea nitrogen and aspartate aminotransferase levels were significantly lower in pine needle-supplemented rats in the DMBA-induced mammary tumor model. These results demonstrate that pine needles exhibit strong antioxidant, antimutagenic, and antiproliferative effects on cancer cells and also antitumor effects in vivo and point to their potential usefulness in cancer prevention.

  13. Characterization and antitumor activity of a polysaccharide from Sarcodia ceylonensis.

    Science.gov (United States)

    Fan, Yijun; Lin, Mengchuan; Luo, Aoshuang; Chun, Ze; Luo, Aoxue

    2014-07-25

    A water-soluble polysaccharide from Sarcodia ceylonensis was obtained by using the method of water-extraction and ethanol-precipitation. The polysaccharide was further purified by chromatography on AB-8 and ADS-7 columns, yielding a pure polysaccharide termed SCP-60. The molecular weight (Mw) of SCP-60 was calculated to be 50.0 kDa, based on the calibration curve obtained with a series of Dextran T standards. The results of FT-IR indicated that the polysaccharide contains the α-configuration of sugar units. GC-MS analysis revealed that SCP-60 was mainly composed of galactose and glucose. NMR spectroscopy revealed SCP-60 had the backbone consisting of → 6)-α-Manp-(1 →, α-D-Glcp-(1 →, → 6)-α-D-Glcp-(1 → and → 6)-α-Galp-(1 →. In order to evaluate the antitumor activity in vivo of the polysaccharide, a sarcoma 180 model was used. The results showed SCP-60 had strong antitumor ability, meanwhile, SCP-60 at a high dose (100 mg/kg) could significantly increase the thymic and splenic indices of S180 mice, and strongly promote the secretion of IL-2, TNF-α and IFN-γ, increase the SOD activities and reduce the concentrations of MDA in blood. Therefore the polysaccharide SCP-60 should be explored as a novel potential antitumor drug.

  14. In Vitro Antitumor Activity of Sesquiterpene Lactones from Lychnophora trichocarpha

    Directory of Open Access Journals (Sweden)

    D.A. Saúde-Guimarães

    2014-06-01

    Full Text Available The sesquiterpene lactones lychnopholide and eremantholide C were isolated from Lychnophora trichocarpha Spreng. (Asteraceae, which is a plant species native to the Brazilian Savannah or Cerrado and popularly known as arnica. Sesquiterpene lactones are known to present a variety of biological activities including antitumor activity. The present paper reports on the evaluation of the in vitro antitumor activity of lychnopholide and eremantholide C, in the National Cancer Institute, USA (NCI, USA, against a panel of 52 human tumor cell lines of major human tumors derived from nine cancer types. Lychnopholide disclosed significant activity against 30 cell lines of seven cancer types with IC100 (total growth concentration inhibition values between 0.41 µM and 2.82 µM. Eremantholide C showed significant activity against 30 cell lines of eight cancer types with IC100 values between 21.40 µM and 53.70 µM. Lychnopholide showed values of lethal concentration 50% (LC50 for 30 human tumor cell lines between 0.72 and 10.00 µM, whereas eremantholide C presented values of LC50 for 21 human tumor cell lines between 52.50 and 91.20 µM. Lychnopholide showed an interesting profile of antitumor activity. The α-methylene-γ-lactone present in the structure of lychnopholide, besides two α,β- unsaturated carbonyl groups, might be responsible for the better activity and higher cytotoxicity of this compound in relation to eremantholide C.

  15. Antibiotics and antibiotic resistance in agroecosystems: Cultural methods and gaps in knowledge

    Science.gov (United States)

    Varying cultural methodologies are used in assessment of antibiotic resistance in environmental samples. Culture based methods commonly involve isolation of target bacteria on general or selective media, and assessing growth in response to specific concentrations of antibiotics. Though time consumin...

  16. Bactericidal antibiotics induce programmed metabolic toxicity

    Directory of Open Access Journals (Sweden)

    Aislinn D. Rowan

    2016-03-01

    Full Text Available The misuse of antibiotics has led to the development and spread of antibiotic resistance in clinically important pathogens. These resistant infections are having a significant impact on treatment outcomes and contribute to approximately 25,000 deaths in the U.S. annually. If additional therapeutic options are not identified, the number of annual deaths is predicted to rise to 317,000 in North America and 10,000,000 worldwide by 2050. Identifying therapeutic methodologies that utilize our antibiotic arsenal more effectively is one potential way to extend the useful lifespan of our current antibiotics. Recent studies have indicated that modulating metabolic activity is one possible strategy that can impact the efficacy of antibiotic therapy. In this review, we will address recent advances in our knowledge about the impacts of bacterial metabolism on antibiotic effectiveness and the impacts of antibiotics on bacterial metabolism. We will particularly focus on two studies, Lobritz, et al. (PNAS, 112(27: 8173-8180 and Belenky et al. (Cell Reports, 13(5: 968–980 that together demonstrate that bactericidal antibiotics induce metabolic perturbations that are linked to and required for bactericidal antibiotic toxicity.

  17. Antibiotic treatments and microbes in the gut.

    Science.gov (United States)

    Macfarlane, Sandra

    2014-04-01

    Antibiotic therapies are important in combating disease-causing microorganisms and maintaining host health. It is widely accepted that exposure of the gut microbiota to antibiotics can lead to decreased susceptibility and the development of multi-drug-resistant disease-causing organisms, which can be a major clinical problem. It is also important to consider that antibiotics not only target pathogenic bacteria in the gut, but also can have damaging effects on the ecology of commensal species. This can reduce intrinsic colonization resistance and contribute to problems with antibiotic resistance, including lateral transfer of resistance genes. Our knowledge of the impact of antibiotic treatment on the ecology of the normal microbiota has been increased by recent advances in molecular methods and use of in vitro model systems to investigate the impact of antibiotics on the biodiversity of gut populations and the spread of antibiotic resistance. These highlight the need for more detailed structural and functional information on the long-term antibiotic-associated alterations in the gut microbiome, and spread of antibiotic resistance genes. This will be crucial for the development of strategies, such as targeted therapeutics, probiotics, prebiotics and synbiotics, to prevent perturbations in the gut microbiota, the restoration of beneficial species and improvements in host health.

  18. Large-Scale Transposition Mutagenesis of Streptomyces coelicolor Identifies Hundreds of Genes Influencing Antibiotic Biosynthesis.

    Science.gov (United States)

    Xu, Zhong; Wang, Yemin; Chater, Keith F; Ou, Hong-Yu; Xu, H Howard; Deng, Zixin; Tao, Meifeng

    2017-03-15

    Gram-positive Streptomyces bacteria produce thousands of bioactive secondary metabolites, including antibiotics. To systematically investigate genes affecting secondary metabolism, we developed a hyperactive transposase-based Tn5 transposition system and employed it to mutagenize the model species Streptomyces coelicolor, leading to the identification of 51,443 transposition insertions. These insertions were distributed randomly along the chromosome except for some preferred regions associated with relatively low GC content in the chromosomal core. The base composition of the insertion site and its flanking sequences compiled from the 51,443 insertions implied a 19-bp expanded target site surrounding the insertion site, with a slight nucleic acid base preference in some positions, suggesting a relative randomness of Tn5 transposition targeting in the high-GC Streptomyces genome. From the mutagenesis library, 724 mutants involving 365 genes had altered levels of production of the tripyrrole antibiotic undecylprodigiosin (RED), including 17 genes in the RED biosynthetic gene cluster. Genetic complementation revealed that most of the insertions (more than two-thirds) were responsible for the changed antibiotic production. Genes associated with branched-chain amino acid biosynthesis, DNA metabolism, and protein modification affected RED production, and genes involved in signaling, stress, and transcriptional regulation were overrepresented. Some insertions caused dramatic changes in RED production, identifying future targets for strain improvement.IMPORTANCE High-GC Gram-positive streptomycetes and related actinomycetes have provided more than 100 clinical drugs used as antibiotics, immunosuppressants, and antitumor drugs. Their genomes harbor biosynthetic genes for many more unknown compounds with potential as future drugs. Here we developed a useful genome-wide mutagenesis tool based on the transposon Tn5 for the study of secondary metabolism and its regulation

  19. 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...... the biological sources for novel drug candidates. For high-­‐throughput genome mining, sophisticated software is required, which allows the prediction of putative biosynthetic products based on genomic data. Here, we present the new version 3 of the software antiSMASH (http......://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...

  20. Effects of temperature and antibiotics on persistence of antibiotic-resistant bacteria and antibiotic resistance genes in poultry litter

    Science.gov (United States)

    The effect of low, residual concentrations of antibiotics in manure and other environmental matrices is not well understood. It has been hypothesized that antibiotic concentrations below clinical MIC (minimal inhibitory concentrations) are still capable of selecting for resistance. The objective of ...

  1. Helicobacter pylori Antibiotic Resistance: Trends Over Time

    Directory of Open Access Journals (Sweden)

    Raymond G Lahaie

    2000-01-01

    Full Text Available Resistance to antibiotics can be a major problem in the treatment of bacterial infections. As the use of antibiotics increases, bacterial resistance to these agents is rising and in many cases is responsible for the failure of treatment regimens. Although the treatment of Helicobacter pylori infection requires the use of more than one antibiotic to obtain adequate eradication rates, the efficacy of the currently used antibiotic combinations has been shown to be decreased by resistance to one of the antibiotics. The use of antibiotics in regimens for the treatment of H pylori is increasing in many countries, including Canada. This increase is both in the use of these antibiotics alone for the treatment of nongastrointestinal infections and in their use in association with proton pump inhibitors for the treatment of H pylori infection. In several European and Asian countries, where resistance to antibiotics is being monitored, it has been demonstrated that H pylori resistance to metronidazole and to clarithromycin increased throughout the 1990s. Thus far, the data available in Canada do not show increased resistance to either of these antibiotics. As for other antibiotics used in the treatment of H pylori infection, such as tetracycline and amoxicillin, the rate of resistance to these agents is still very low and does not constitute a significant problem. Because the efficacy of the regimens used in the treatment of H pylori infection is compromised by resistance to the antibiotics used, it is important that H pylori resistance rates in Canada and throughout the world continue to be monitored. Only with such reliable data can the most optimal regimens be recommended.

  2. Curative effect of HF10 on liver and peritoneal metastasis mediated by host antitumor immunity

    Science.gov (United States)

    Hotta, Yoshihiro; Kasuya, Hideki; Bustos, Itzel; Naoe, Yoshinori; Ichinose, Toru; Tanaka, Maki; Kodera, Yasuhiro

    2017-01-01

    Background HF10 is a highly attenuated type 1 herpes simplex virus (HSV) with proven effective oncolytic effect. Previous investigations have demonstrated that colon cancer mice model treated with HF10 not only had better survival but were also resistant to the reimplantation of the antitumor effect mediated by host antitumor immunity. Importantly, it has also been noted that in mice with antitumors implanted on both sides of the back, an injection of HF10 on only one side strongly restrains not only the injected antitumor but also the non-injected ones. Materials and methods MC26 colon cancer cells were injected subcutaneously into the back, spleen, and intraperitoneal region of metastasis model mice. Antitumor volume and survival rate were monitored. To measure cytotoxic T lymphocytes (CTL) cytotoxicity against MC26, lymphocytes were extracted from the spleens of the peritoneal metastasis model mice as well as from the thymus of the liver metastasis model mice. The expression of interferon gamma was examined by enzyme-linked immunospot assay. Samples from the liver metastasis model mice were subjected to polymerase chain reaction to quantify the level of HSV genomes. Results HF10 was injected only on the back antitumor; however, a antitumor-suppressor effect was observed against liver and peritoneal metastases. When HF10 genome was measured, we observed lower genome on liver metastases compared to back antitumor genome quantity. CTL activity against MC26 was also observed. These results indicate that local administration of HF10 exerts a curative effect on systemic disease, mediated by host antitumor immunity. Conclusion HF10 local administration stimulates antitumor immunity to recognize antitumor-specific antigen, which then improves systemic disease. Metastatic antitumors lysis, on the other hand, appears to be mediated by the host immune system, rather than by virus-mediated direct oncolysis. PMID:28331843

  3. 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.

  4. 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.

  5. Acquired antibiotic resistance genes:an overview

    NARCIS (Netherlands)

    Hoek, A.H. van; Mevius, D.; Guerra, B.; Mullany, P.; Robberts, A.P.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance,

  6. Acquired antibiotic resistance genes: an overview

    NARCIS (Netherlands)

    Hoek, van A.H.; Mevius, D.J.; Guerra, B.; Mullany, P.; Roberts, A.P.; Aarts, H.J.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance,

  7. 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.

  8. Interplay between gut microbiota and antibiotics

    NARCIS (Netherlands)

    Jesus Bello Gonzalez, de Teresita

    2016-01-01

    The human body is colonized by a vast number of microorganisms collectively defined as the microbiota. In the gut, the microbiota has important roles in health and disease, and can serve as a host of antibiotic resistance genes. Disturbances in the ecological balance, e.g. by antibiotics, can affect

  9. Optimising Antibiotic Usage to Treat Bacterial Infections

    Science.gov (United States)

    Paterson, Iona K.; Hoyle, Andy; Ochoa, Gabriela; Baker-Austin, Craig; Taylor, Nick G. H.

    2016-11-01

    The increase in antibiotic resistant bacteria poses a threat to the continued use of antibiotics to treat bacterial infections. The overuse and misuse of antibiotics has been identified as a significant driver in the emergence of resistance. Finding optimal treatment regimens is therefore critical in ensuring the prolonged effectiveness of these antibiotics. This study uses mathematical modelling to analyse the effect traditional treatment regimens have on the dynamics of a bacterial infection. Using a novel approach, a genetic algorithm, the study then identifies improved treatment regimens. Using a single antibiotic the genetic algorithm identifies regimens which minimise the amount of antibiotic used while maximising bacterial eradication. Although exact treatments are highly dependent on parameter values and initial bacterial load, a significant common trend is identified throughout the results. A treatment regimen consisting of a high initial dose followed by an extended tapering of doses is found to optimise the use of antibiotics. This consistently improves the success of eradicating infections, uses less antibiotic than traditional regimens and reduces the time to eradication. The use of genetic algorithms to optimise treatment regimens enables an extensive search of possible regimens, with previous regimens directing the search into regions of better performance.

  10. 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.

  11. Antibiotic information application offers nurses quick support

    NARCIS (Netherlands)

    Wentzel, Jobke; Drie-Pierik, Regine; Nijdam, Lars; Geesing, Jos; Sanderman, Robbert; Gemert-Pijnen, van Julia E.W.C.

    2016-01-01

    Background Nurses can be crucial contributors to antibiotic stewardship programs (ASPs), interventions aimed at improving antibiotic use, but nurse empowerment in ASPs adds to their job complexity. Nurses work in complex settings with high cognitive loads, which ask for easily accessible information

  12. Antibiotic information application offers nurses quick support

    NARCIS (Netherlands)

    Wentzel, Jobke; van Drie-Pierik, Regine; Nijdam, Lars; Geesing, Jos; Sanderman, Robbert; van Gemert-Pijnen, Julia E. W. C.

    2016-01-01

    Background: Nurses can be crucial contributors to antibiotic stewardship programs (ASPs), interventions aimed at improving antibiotic use, but nurse empowerment in ASPs adds to their job complexity. Nurses work in complex settings with high cognitive loads, which ask for easily accessible informatio

  13. Polyene antibiotic that inhibits membrane transport proteins

    NARCIS (Netherlands)

    Te Welscher, Y.M.; van Leeuwen, M.R.; de Kruijff, B.; Dijksterhuis, J.; Breukink, E.

    2012-01-01

    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 inter

  14. Repairing the broken market for antibiotic innovation.

    Science.gov (United States)

    Outterson, Kevin; Powers, John H; Daniel, Gregory W; McClellan, Mark B

    2015-02-01

    Multidrug-resistant bacterial diseases pose serious and growing threats to human health. While innovation is important to all areas of health research, it is uniquely important in antibiotics. Resistance destroys the fruit of prior research, making it necessary to constantly innovate to avoid falling back into a pre-antibiotic era. But investment is declining in antibiotics, driven by competition from older antibiotics, the cost and uncertainty of the development process, and limited reimbursement incentives. Good public health practices curb inappropriate antibiotic use, making return on investment challenging in payment systems based on sales volume. We assess the impact of recent initiatives to improve antibiotic innovation, reflecting experience with all sixty-seven new molecular entity antibiotics approved by the Food and Drug Administration since 1980. Our analysis incorporates data and insights derived from several multistakeholder initiatives under way involving governments and the private sector on both sides of the Atlantic. We propose three specific reforms that could revitalize innovations that protect public health, while promoting long-term sustainability: increased incentives for antibiotic research and development, surveillance, and stewardship; greater targeting of incentives to high-priority public health needs, including reimbursement that is delinked from volume of drug use; and enhanced global collaboration, including a global treaty.

  15. 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

  16. 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.

  17. 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.

  18. Genetic architecture of intrinsic antibiotic susceptibility.

    Directory of Open Access Journals (Sweden)

    Hany S Girgis

    Full Text Available BACKGROUND: Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired. METHODOLOGY/PRINCIPAL FINDINGS: To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance. CONCLUSIONS/SIGNIFICANCE: Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect.

  19. Antibiotic-Resistant Bacteria: There is Hope.

    Science.gov (United States)

    Offner, Susan

    1998-01-01

    Argues that reduction in the use of antibiotics would enable antibiotic-sensitive bacteria to flourish. Presents an activity designed to show students how a small, seemingly unimportant difference in doubling time can, over a period of time, make an enormous difference in population size. (DDR)

  20. 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.

  1. 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.

  2. Advances in pneumococcal antibiotic resistance.

    Science.gov (United States)

    Song, Jae-Hoon

    2013-10-01

    Antimicrobial resistance and serotypes in Streptococcus pneumoniae have been evolving with the widespread use of antibiotics and the introduction of pneumococcal conjugate vaccines (PCV). Particularly, among various types of antimicrobial resistance, macrolide resistance has most remarkably increased in many parts of the world, which has been reported to be >70% among clinical isolates from Asian countries. Penicillin resistance has dramatically decreased among nonmeningeal isolates due to the changes in resistance breakpoints, although resistance to other β-lactams such as cefuroxime has increased. Multidrug resistance became a serious concern in the treatment of invasive pneumococcal diseases, especially in Asian countries. After PCV7 vaccination, serotype 19A has emerged as an important cause of invasive pneumococcal diseases which was also associated with increasing prevalence of multidrug resistance in pneumococci. Widespread use of PCV13, which covers additional serotypes 3, 6A and 19A, may contribute to reduce the clonal spread of drug-resistant 19A pneumococci.

  3. Retapamulin: A newer topical antibiotic

    Directory of Open Access Journals (Sweden)

    D Dhingra

    2013-01-01

    Full Text Available Impetigo is a common childhood skin infection. There are reports of increasing drug resistance to the currently used topical antibiotics including fusidic acid and mupirocin. Retapamulin is a newer topical agent of pleuromutilin class approved by the Food and Drug Administration for treatment of impetigo in children and has been recently made available in the Indian market. It has been demonstrated to have low potential for the development of antibacterial resistance and a high degree of potency against poly drug resistant Gram-positive bacteria found in skin infections including Staphylococcus aureus strains. The drug is safe owing to low systemic absorption and has only minimal side-effect of local irritation at the site of application.

  4. 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.

  5. Engineering antibiotic production and overcoming bacterial resistance.

    Science.gov (United States)

    Planson, Anne-Gaëlle; Carbonell, Pablo; Grigoras, Ioana; Faulon, Jean-Loup

    2011-07-01

    Progress in DNA technology, analytical methods and computational tools is leading to new developments in synthetic biology and metabolic engineering, enabling new ways to produce molecules of industrial and therapeutic interest. Here, we review recent progress in both antibiotic production and strategies to counteract bacterial resistance to antibiotics. Advances in sequencing and cloning are increasingly enabling the characterization of antibiotic biosynthesis pathways, and new systematic methods for de novo biosynthetic pathway prediction are allowing the exploration of the metabolic chemical space beyond metabolic engineering. Moreover, we survey the computer-assisted design of modular assembly lines in polyketide synthases and non-ribosomal peptide synthases for the development of tailor-made antibiotics. Nowadays, production of novel antibiotic can be tranferred into any chosen chassis by optimizing a host factory through specific strain modifications. These advances in metabolic engineering and synthetic biology are leading to novel strategies for engineering antimicrobial agents with desired specificities.

  6. Pneumonia in immunocompetent patients: combination antibiotic therapy.

    Science.gov (United States)

    Salva, S; Borgatta, B; Rello, J

    2014-04-01

    Pneumonia's burden is still important worldwide not only because of its high incidence and mortality, but also for the elevated costs related to it. Despite the concerted efforts to reduce the incidence of sepsis-related complications, they continue to represent a major human and economic burden. The cornerstone of sepsis management is early appropriate empiric broad spectrum antibiotics, resuscitation, and source control. The association between inappropriate use of antibiotics and increased mortality is the rationale for the use of empiric antibiotic combination therapy in critically ill patients. The aim of this manuscript was to discuss recent literature regarding the management of severe pneumonia, both community-acquired and hospital-acquired/ventilator-associated, in critically ill patients. Use of combination therapy is warranted in severe infections with shock; considerations should be made on the importance of optimal antibiotic administration and adverse reactions, thus providing guidance for a rational use of antibiotics.

  7. Antibiotic Resistance in Pediatric Urinary Tract Infections.

    Science.gov (United States)

    Stultz, Jeremy S; Doern, Christopher D; Godbout, Emily

    2016-12-01

    Urinary tract infections (UTIs) are a common problem in pediatric patients. Resistance to common antibiotic agents appears to be increasing over time, although resistance rates may vary based on geographic region or country. Prior antibiotic exposure is a pertinent risk factor for acquiring resistant organisms during a first UTI and recurrent UTI. Judicious prescribing of antibiotics for common pediatric conditions is needed to prevent additional resistance from occurring. Complex pediatric patients with histories of hospitalizations, prior antibiotic exposure, and recurrent UTIs are also at high risk for acquiring UTIs due to extended spectrum beta-lactamase-producing organisms. Data regarding the impact of in vitro antibiotic susceptibility testing interpretation on UTI treatment outcomes is lacking.

  8. Antibiotic resistance: an editorial review with recommendations.

    Science.gov (United States)

    Rosen, Ted

    2011-07-01

    Within a relatively short period of time after the first antimicrobial drugs were introduced, bacteria began exhibiting varying degrees of resistance. The excessive use (and abuse) of antibiotics in agriculture, and in both human and veterinary medicine, has played a critical causative role in the development of antibiotic resistance, which is now recognized as a global public health threat. Increasing concern over this issue should impact the practice of cutaneous medicine and surgery, as dermatologists can easily adopt new healthcare delivery patterns that might reduce the development of antibiotic resistance and still achieve acceptable treatment outcomes. Dermatologists should seriously consider any and all alternative therapies before committing to an extended course of antibiotic therapy for disease entities that are almost certainly not infectious. Conversely, dermatologists should carefully and closely adhere to dosage and duration recommendations when using antibiotics to treat a bona fide infectious disorder.

  9. Innovation of novel antibiotics: an economic perspective.

    Science.gov (United States)

    McKellar, Michael R; Fendrick, A Mark

    2014-10-15

    Despite the public attention to antibiotic overuse and the specter of antimicrobial-resistant pathogens, current infections necessitate the use of antibiotics. Yet, patients and providers may not fully consider the societal cost associated with inappropriate antimicrobial use and subsequent resistance. Policies intended to limit use to minimize resistance must be balanced with the competing concern of underutilization. It is difficult to determine whether research and development incentives or reducing the costs of bringing new antibiotics through expedited review will be sufficient. Likely, the most effective method would be allowing higher prices for use deemed to be clinically appropriate. The ultimate policy goal is to ensure that antibiotics are used appropriately, with the right patients receiving the right medication at the right time, and that the world has a steady stream of future antibiotics to effectively treat the resistant organisms that will inevitably emerge.

  10. [Allergy to beta-lactam antibiotics].

    Science.gov (United States)

    Comte, D; Petitpierre, S; Spertini, F; Bart, P-A

    2012-04-18

    Beta-lactam antibiotics allergies are common. Up to 10% of the population describe a former allergy to penicillins. However only 10 to 15% of these individuals are actually allergic. In most cases, beta-lactam antibiotics will be avoided and replaced by other antibiotics such as quinolones. This fear of a serious allergic reaction has an economic impact and may lead to the emergence of antibiotic resistance. A thorough allergic work-up can accurately determine true allergic patients. Most of the patients with a proven allergy will be able to tolerate other antibiotics belonging to the beta-lactam family. This article focuses on the management of beta-lactam allergic patients.

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

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

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

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

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

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

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

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

  15. Get Smart: Know When Antibiotics Work - Bronchitis (Chest Cold)

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

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

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

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

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

  18. 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.

  19. Do antibiotics have environmental side-effects? Impact of synthetic antibiotics on biogeochemical processes.

    Science.gov (United States)

    Roose-Amsaleg, Céline; Laverman, Anniet M

    2016-03-01

    Antibiotic use in the early 1900 vastly improved human health but at the same time started an arms race of antibiotic resistance. The widespread use of antibiotics has resulted in ubiquitous trace concentrations of many antibiotics in most environments. Little is known about the impact of these antibiotics on microbial processes or "non-target" organisms. This mini-review summarizes our knowledge of the effect of synthetically produced antibiotics on microorganisms involved in biogeochemical cycling. We found only 31 articles that dealt with the effects of antibiotics on such processes in soil, sediment, or freshwater. We compare the processes, antibiotics, concentration range, source, environment, and experimental approach of these studies. Examining the effects of antibiotics on biogeochemical processes should involve environmentally relevant concentrations (instead of therapeutic), chronic exposure (versus acute), and monitoring of the administered antibiotics. Furthermore, the lack of standardized tests hinders generalizations regarding the effects of antibiotics on biogeochemical processes. We investigated the effects of antibiotics on biogeochemical N cycling, specifically nitrification, denitrification, and anammox. We found that environmentally relevant concentrations of fluoroquinolones and sulfonamides could partially inhibit denitrification. So far, the only documented effects of antibiotic inhibitions were at therapeutic doses on anammox activities. The most studied and inhibited was nitrification (25-100 %) mainly at therapeutic doses and rarely environmentally relevant. We recommend that firm conclusions regarding inhibition of antibiotics at environmentally relevant concentrations remain difficult due to the lack of studies testing low concentrations at chronic exposure. There is thus a need to test the effects of these environmental concentrations on biogeochemical processes to further establish the possible effects on ecosystem functioning.

  20. 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.

  1. IL-12 induces T helper 1-directed antitumor response.

    Science.gov (United States)

    Tsung, K; Meko, J B; Peplinski, G R; Tsung, Y L; Norton, J A

    1997-04-01

    Although IL-12 possesses the most potent single-cytokine antitumor efficacy, the mechanism by which IL-12 exerts its antitumor activities remains unclear. Using a complete tumor regression model induced by IL-12 treatment, we demonstrate that the antitumor response induced by IL-12 is mediated by a Th1 cell-directed process, with the macrophage as the effector cell and nitric oxide produced by the activated macrophage as the effector molecule. The induction of the Th1 response by IL-12 depends on the existence of a host T cell response to the tumor before IL-12 administration. IL-12 treatment causes the complete regression of 10-day established s.c. tumors (4-8 mm). Associated with the induction of tumor necrosis, activated macrophages expressing high levels of inducible nitric oxide synthase were found surrounding the tumor. The importance of nitric oxide as the effector molecule was further confirmed by the delay and loss of tumor regression in the presence of a nitric oxide synthase inhibitor in vivo. Examination of tumor-associated T cells indicates that IL-12 induces production of the Th1 cytokine IFN-gamma and suppresses production of IL-2, IL-4, and IL-10 at the tumor site, where these are found to be the predominant cytokines produced by tumor-associated T cells before IL-12 treatment. These findings demonstrate that IL-12 plays an essential role in the induction of an effective Th1 type of cell-mediated immune response against established tumors.

  2. In vivo toxicity and antitumor activity of mangosteen extract.

    Science.gov (United States)

    Kosem, Nuttavut; Ichikawa, Kazuhiro; Utsumi, Hideo; Moongkarndi, Primchanien

    2013-04-01

    Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine of Thailand to treat various ailments, especially diseases of the digestive system and infections. Many reports show antiproliferation of crude extracts and active constituents from mangosteen against many cancer cell lines. Therefore, the current study is proposed to demonstrate in vivo evidence on the antitumor activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp including 25.19 % α-mangostin as an active xanthone was used in this study. The inhibition on tumor cell proliferation of CME was preliminarily evaluated against the murine colon cancer cell line NL-17 with an IC50 value of 17 and 84 μg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal application was assessed by in vivo toxicity studies using female BALB/c mice. Acute toxicity showed an LD50 value and approximate lethal dose at 1,000 mg/kg, whereas the suitable dose for short-term study should be ≤200 mg/kg. The effective dose for antitumor activity of CME was found to be between 100 and 200 mg/kg, with a tumor size reduction of 50-70 %. Histological staining clearly illustrated a decrease of tumor cell density in the footpad in a dose-dependent manner. The median survival time and life span significantly increased in tumor-bearing mice with CME treatment. This study suggests that CME possesses a powerful antitumor activity. Therefore, it is worth undertaking further investigation to identify active compounds and obtain a deeper understanding of their mechanism, in order to acquire novel effective anticancer drugs.

  3. 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.

  4. Arginine Deiminase Enzyme Evolving As A Potential Antitumor Agent.

    Science.gov (United States)

    Somani, Rakesh; Chaskar, Pratip K

    2016-08-17

    Some melanomas and hepatocellular carcinomas have been shown to be auxotrophic for arginine. Arginine deiminase (ADI), an arginine degrading enzyme isolated from Mycoplasma, can inhibit the growth of these tumors. It is a catabolizing enzyme which catabolizes arginine to citrulline. Tumor cells do not express an enzyme called arginosuccinate synthetase (ASS) and hence, these cells becomes auxotrophic for arginine. It is found that ADI is specific for arginine and did not degrade other amino acid. This review covers various aspects of ADIs like origin, properties and chemical modifications for better antitumor activity.

  5. 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.

  6. "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

  7. Persistence of antibiotic resistance in bacterial populations.

    Science.gov (United States)

    Andersson, Dan I; Hughes, Diarmaid

    2011-09-01

    Unfortunately for mankind, it is very likely that the antibiotic resistance problem we have generated during the last 60 years due to the extensive use and misuse of antibiotics is here to stay for the foreseeable future. This view is based on theoretical arguments, mathematical modeling, experiments and clinical interventions, suggesting that even if we could reduce antibiotic use, resistant clones would remain persistent and only slowly (if at all) be outcompeted by their susceptible relatives. In this review, we discuss the multitude of mechanisms and processes that are involved in causing the persistence of chromosomal and plasmid-borne resistance determinants and how we might use them to our advantage to increase the likelihood of reversing the problem. Of particular interest is the recent demonstration that a very low antibiotic concentration can be enriching for resistant bacteria and the implication that antibiotic release into the environment could contribute to the selection for resistance. Several mechanisms are contributing to the stability of antibiotic resistance in bacterial populations and even if antibiotic use is reduced it is likely that most resistance mechanisms will persist for considerable times.

  8. Molecular regulation of antibiotic biosynthesis in streptomyces.

    Science.gov (United States)

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

    2013-03-01

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

  9. 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.

  10. Antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci.

    Science.gov (United States)

    McMurray, Claire L; Hardy, Katherine J; Verlander, Neville Q; Hawkey, Peter M

    2015-12-01

    Staphylococci are a significant cause of hospital-acquired infection. Nasal carriage of Staphylococcus aureus is an important risk factor for infection in surgical patients and coagulase-negative staphylococci (CNS) are a major cause of prosthetic joint infections. The impact that antibiotic surgical prophylaxis has on the nasal carriage of staphylococci has not been studied. Daily nasal swabs were taken from 63 patients who received antibiotic surgical prophylaxis and 16 patients who received no antibiotics. Total aerobic bacterial count, S. aureus and CNS were enumerated by culture from nasal swabs. Representative isolates were typed by staphylococcal interspersed repeat units (SIRU) typing and PFGE, and MICs to nine antibiotics were determined. After antibiotic administration, there was a reduction in S. aureus counts (median - 2.3 log(10)c.f.u. ml(- 1)) in 64.0 % of S. aureus carriers, compared with only a 0.89 log(10)c.f.u. ml(- 1) reduction in 75.0 % of S. aureus carriers who did not receive antibiotics. A greater increase in the nasal carriage rate of meticillin-resistant CNS was observed after antibiotic surgical prophylaxis compared with hospitalization alone, with increases of 16.4 and 4.6 %, respectively. Antibiotic-resistant S. epidermidis carriage rate increased by 16.6 % after antibiotic administration compared with 7.5 % with hospitalization alone. Antibiotic surgical prophylaxis impacts the nasal carriage of both S. aureus and CNS.

  11. Inducing optimal substitution between antibiotics under open access to the resource of antibiotic susceptibility.

    Science.gov (United States)

    Herrmann, Markus; Nkuiya, Bruno

    2016-05-15

    This paper designs a bio-economic model to examine the use of substitute antibiotic drugs (analogs) sold by an industry that has open access to the resource of the antibiotic class's susceptibility (treatment effectiveness). Antibiotics are characterized by different expected recovery rates and production costs, which in conjunction with the class's treatment susceptibility determines their relative effectiveness. Our analysis reveals that the high-quality antibiotic drug loses its comparative advantage over time making the low-quality drug the treatment of last resort in the market equilibrium and the social optimum when antibiotic susceptibility cannot replenish. However, when antibiotic susceptibility is renewable, both antibiotics may be used in the long run, and the comparative advantage of the high-quality drug may be restored in the social optimum that allows lowering infection in the long run. We develop the optimal tax/subsidy scheme that would induce antibiotic producers under open access to behave optimally and account for the social cost of infection and value of antibiotic susceptibility. We show that the welfare loss associated with the uncorrected open-access allocation is highest; when the resource of antibiotic susceptibility is non-renewable, high morbidity costs are incurred by individuals, and low social discount rates apply. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Purification and Crystallization of Flammulin, a Basic Protein with Anti-tumor Activities from Flammulina Velutipes

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Flammulin, an anti-tumor protein, was purified from the aqueous extract of basidiomes of Flammulina Velutipes to electrophoretic homogeneity and crystallized by microdialysis against a polyethylene glycol- sodium phosphate buffer. The purified product was found to have marked antitumor effects and be able to affect the tumor cells directly.

  13. 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.

  14. Bacteriocins - a viable alternative to antibiotics?

    Science.gov (United States)

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

    2013-02-01

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

  15. 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.

  16. Antitumor activities of D-glucosamine and its derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li; LIU Wan-shun; HAN Bao-qin; PENG Yan-fei; WANG Dong-feng

    2006-01-01

    The growth inhibitory effects of D-glucosamine hydrochloride (GlcNH2·HCl), D-glucosamine (GlcNH2) and N-acetyl glucosamine (NAG) on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH2·HCl and GlcNH2 resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH2·HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells.GlcNH2·HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125~500 mg/kg, dose of 250 mg/kg being the best. GlcNH2·HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH2·HCl is probably host-mediated and cytocidal.

  17. 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.

  18. [Immunomodulatory and antitumor properties of polysaccharide peptide (PSP)].

    Science.gov (United States)

    Piotrowski, Jakub; Jędrzejewski, Tomasz; Kozak, Wiesław

    2015-01-21

    Modern medicine successfully uses multiple immunomodulators of natural origin, that can affect biological reactions and support body's natural defense mechanisms including antitumor activities. Among them is a group of products derived from fungi, including schizophyllan, lentinan, polysaccharide Krestin (PSK), and polysaccharidepeptide (PSP). Present paper is focused on polysaccharidepeptide, which due to the negligible toxicity and numerous benefits for health, is increasingly used in China and Japan as an adjuvant in the treatment of cancer. PSP is a protein-polisaccharide complex with a molecular weight 100 kDa derived from Coriolus versicolor mushroom. The results of numerous studies and clinical trials confirm that it inhibits the growth of cancer cells in in vitro and in vivo settings as well as decreases cancer treatment-related adverse side effects such as fatigue, loss of appetite, nausea, vomiting, and pain. PSP is able to restore weakened immune response observed in patients with cancer during chemotherapy. Its anti-tumor effects seemed to be mediated through immunomodulatory regulation. PSP stimulates cells of the immune system, induces synthesis of cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), eicosanoids including prostaglandin E2 (PGE2), histamine, reactive oxygen species and nitrogen mediators. There is a growing interest in understanding the mechanisms of PSP action. Because of its unique properties and safety, PSP may become a widely used therapeutic agent in the near future.

  19. 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.

  20. Proteomic Study to Survey the CIGB-552 Antitumor Effect

    Directory of Open Access Journals (Sweden)

    Arielis Rodríguez-Ulloa

    2015-01-01

    Full Text Available CIGB-552 is a cell-penetrating peptide that exerts in vitro and in vivo antitumor effect on cancer cells. In the present work, the mechanism involved in such anticancer activity was studied using chemical proteomics and expression-based proteomics in culture cancer cell lines. CIGB-552 interacts with at least 55 proteins, as determined by chemical proteomics. A temporal differential proteomics based on iTRAQ quantification method was performed to identify CIGB-552 modulated proteins. The proteomic profile includes 72 differentially expressed proteins in response to CIGB-552 treatment. Proteins related to cell proliferation and apoptosis were identified by both approaches. In line with previous findings, proteomic data revealed that CIGB-552 triggers the inhibition of NF-κB signaling pathway. Furthermore, proteins related to cell invasion were differentially modulated by CIGB-552 treatment suggesting new potentialities of CIGB-552 as anticancer agent. Overall, the current study contributes to a better understanding of the antitumor action mechanism of CIGB-552.

  1. 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.

  2. Antibiotic inhibition of group I ribozyme function.

    Science.gov (United States)

    von Ahsen, U; Davies, J; Schroeder, R

    1991-09-26

    The discovery of catalytically active RNA has provided the basis for the evolutionary concept of an RNA world. It has been proposed that during evolution the functions of ancient catalytic RNA were modulated by low molecular weight effectors, related to antibiotics, present in the primordial soup. Antibiotics and RNA may have coevolved in the formation of the modern ribosome. Here we report that a set of aminoglycoside antibiotics, which are known to interact with the decoding region of the 16S ribosomal RNA of Escherichia coli, inhibit the second step of splicing of the T4 phage-derived td intron. Thus catalytic RNA seems to interact not only with a mononucleotide and an amino acid, but also with another class of biomolecules, the sugars. Splicing of other group I introns but not group II introns was inhibited. The similarity in affinity and specificity of these antibiotics for group I introns and rRNAs may result from recognition of evolutionarily conserved structures.

  3. Antibiotics as immunomodulant agents in COPD.

    Science.gov (United States)

    Blasi, Francesco; Mantero, Marco; Aliberti, Stefano

    2012-06-01

    It is widely accepted that some antibiotics have activities beyond their direct antibacterial effects. Macrolide is the antibiotic class with more convincing studies and evidence on its immunomodulatory and anti-inflammatory activities. Different clinical studies have shown that macrolide prophylaxis in patients with moderate-severe chronic obstructive pulmonary disease (COPD) can have a significant impact on the exacerbation rate reducing morbidity and, potentially, mortality of the disease. Other antibiotics, such as fluoroquinolones, demonstrate a variety of immunomodulatory effects but only few clinical data are available in COPD. New macrolide derivatives devoid of antibacterial activity have been synthetized. This review analyses the relevance of immunomodulatory and anti-inflammatory effects of antibiotics in the management of COPD.

  4. Mechanisms of antibiotic resistance in enterococci.

    Science.gov (United States)

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2014-10-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches.

  5. The antibiotics in the chemical space.

    Science.gov (United States)

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

    2009-01-01

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

  6. The effect of antibiotics on diatom communities

    Digital Repository Service at National Institute of Oceanography (India)

    DeCosta, P.M.; Anil, A.C.

    –100% and favoured emergence of yeast, probably due to high concentrations and synergistic effects. Changes in diatom communities in the individual antibiotic treatments were either direct (chloramphenicol and potentially streptomycin) or bacteria...

  7. Antibiotic stewardship in the intensive care unit.

    Science.gov (United States)

    Luyt, Charles-Edouard; Bréchot, Nicolas; Trouillet, Jean-Louis; Chastre, Jean

    2014-01-01

    The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Appropriate antibiotic stewardship in ICUs includes not only rapid identification and optimal treatment of bacterial infections in these critically ill patients, based on pharmacokinetic-pharmacodynamic characteristics, but also improving our ability to avoid administering unnecessary broad-spectrum antibiotics, shortening the duration of their administration, and reducing the numbers of patients receiving undue antibiotic therapy. Either we will be able to implement such a policy or we and our patients will face an uncontrollable surge of very difficult-to-treat pathogens.

  8. Alliance for the Prudent Use of Antibiotics

    Science.gov (United States)

    ... costs Concerns arise over 2016 Olympic water quality Poverty breeds antimicrobial resistance Fast food companies urged to ... the Prudent Use of Antibiotics. Launched at the World Economic Forum in Davos, Switzerland, this declaration formally ...

  9. 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

  10. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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......% 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 post-operative...... to 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...

  11. 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.

  12. Acquired Antibiotic Resistance Genes: An Overview

    OpenAIRE

    Hoek, Angela H.A.M. van; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants betw...

  13. The trouble with antibiotics and pesticides is...

    OpenAIRE

    1996-01-01

    The paper discusses the output of the meeting on the use of chemicals in aquaculture in Asia. The effects of chemical use on cultured stocks in the farm, the immediate environment through discharges and effluents, surrounding areas, farm staff, consumers and drug resistance organisms are also discussed. It also shows how an antibiotic-resistant microorganism develops as the result of indiscriminate use of antibiotics.

  14. The determinants of the antibiotic resistance process

    OpenAIRE

    Espinosa, Beatriz

    2009-01-01

    Beatriz Espinosa Franco1, Marina Altagracia Martínez2, Martha A Sánchez Rodríguez1, Albert I Wertheimer31Facultad de Estudios Superiores Zaragoza (UNAM), Mexico; 2Universidad Autónoma Metropolitana Unidad Xochimilco, Mexico; 3Temple University, Philadelphia, Pennsylvania, USABackground: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a se...

  15. Antibiotic stewardship in the intensive care unit

    OpenAIRE

    Luyt, Charles-Edouard; Bréchot, Nicolas; Trouillet, Jean-Louis; Chastre, Jean

    2014-01-01

    International audience; The rapid emergence and dissemination of antimicrobial-resistant microorganisms in ICUs worldwide constitute a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antibiotic resistance is highly correlated with selective pressure resulting from inappropriate use of these drugs. Appropriate antibiotic stewardship in ICUs includes not only rapid identification and optimal treatment of bacterial...

  16. Antibiotic tolerance and resistance in biofilms

    DEFF Research Database (Denmark)

    Ciofu, Oana; Tolker-Nielsen, Tim

    2010-01-01

    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 biofilms, they will not completely eradicate the bacteria in vivo which may have important clinical consequences in form of relapses of the infection....

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

    Science.gov (United States)

    Shepherd, Jennifer; Ibba, Michael

    2013-09-17

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

  18. Assessing Antibiotic Resistance of Staphyloccocus: Students Use Their Own Microbial Flora To Explore Antibiotic Resistance.

    Science.gov (United States)

    Omoto, Charlotte K.; Malm, Kirstin

    2003-01-01

    Describes a microbiology laboratory experiment in which students test their own microbial flora of Staphylococcus for antibiotic resistance. Provides directions on how to conduct the experiment. (YDS)

  19. 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.

  20. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance$

    Institute of Scientific and Technical Information of China (English)

    Nishant A. Dafale n; Uttam P. Semwal; Rupak K. Rajput; G.N. Singh

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Re-sistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the potency of antibiotics. HPLC method is commonly used for the quantification of potency of antibiotics, but unable to determine the bioactivity; whereas microbiological assay estimates both potency and bioactivity of antibiotics. Additionally, bioassay is used to estimate the effective dose against antibiotic resistant microbes. Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutation prevention concentration (MPC) and critical concentration (Ccr) which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

  1. 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.

  2. 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.

  3. 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.

  4. Microfluidics for Antibiotic Susceptibility and Toxicity Testing

    Directory of Open Access Journals (Sweden)

    Jing Dai

    2016-10-01

    Full Text Available The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing.

  5. 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.

  6. Active controlled studies in antibiotic drug development.

    Science.gov (United States)

    Dane, Aaron

    2011-01-01

    The increasing concern of antibacterial resistance has been well documented, as has the relative lack of antibiotic development. This paradox is in part due to challenges with clinical development of antibiotics. Because of their rapid progression, untreated bacterial infections are associated with significant morbidity and mortality. As a consequence, placebo-controlled studies of new agents are unethical. Rather, pivotal development studies are mostly conducted using non-inferiority designs versus an active comparator. Further, infections because of comparator-resistant isolates must usually be excluded from the trial programme. Unfortunately, the placebo-controlled data classically used in support of non-inferiority designs are largely unavailable for antibiotics. The only available data are from the 1930s and 1940s and their use is associated with significant concerns regarding constancy and assay sensitivity. Extended public debate on this challenge has led to proposed solutions by some in which these concerns are addressed by using very conservative approaches to trial design, endpoints and non-inferiority margins, in some cases leading to potentially impractical studies. To compound this challenge, different Regulatory Authorities seem to be taking different approaches to these key issues. If harmonisation does not occur, antibiotic development will become increasingly challenging, with the risk of further decreases in the amount of antibiotic drug development. However with clarity on Regulatory requirements and an ability to feasibly conduct global development programmes, it should be possible to bring much needed additional antibiotics to patients.

  7. 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.

  8. Antibiotics in agroecosystems: Introduction to the special section

    Science.gov (United States)

    The presence of antibiotic drug residues, antibiotic resistant bacteria, and antibiotic resistance genes in agroecosystems has become a significant area of research in recent years, and is a growing public health concern. While antibiotics are utilized for human medicine and agricultural practices, ...

  9. 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…

  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. Trends in Antibiotic Prescribing in Adults in Dutch General Practice

    NARCIS (Netherlands)

    M.B. Haeseker (Michiel); N.H.T.M. Dukers-Muijrers (Nicole); C.J.P.A. Hoebe (Christian); C.A. Bruggeman (Cathrien); J.W.L. Cals (Jochen); A. Verbon (Annelies)

    2012-01-01

    textabstractBackground: Antibiotic consumption is associated with adverse drug events (ADE) and increasing antibiotic resistance. Detailed information of antibiotic prescribing in different age categories is scarce, but necessary to develop strategies for prudent antibiotic use. The aim of this stud

  12. 脂肽类抗生素及其作用机制%Lipopeptide Antibiotics & Its Action Mechanism

    Institute of Scientific and Technical Information of China (English)

    陈萍; 冯芬; 杨恬然; 辛明秀

    2015-01-01

    脂肽类抗生素是由微生物代谢产生的一类具有很强表面活性的生物活性物质,含有由亲水性氨基酸和疏水性脂肪酸链组成的特殊分子结构,表现出亲水、亲脂两亲性的特性,具有抗菌、抗肿瘤和抗病毒等多种生物学活性,作为抗菌药物和肿瘤抑制剂在医药和临床应用领域具有良好的应用潜力和前景。本文对脂肽类抗生素的结构、生物学功能和作用机制等最新研究进展进行综述。%Lipopeptideantibioticsarekindsofimportantantibacterialmaterialwithstrongsurfaceactivitytypically synthesized by microorganisms,especially by Bacillus. It contains special molecular structure composed of hydrophilic amino acids and hydrophobic fatty acid chains that shows amphipathic features. Lipopeptide antibiotics possesse anti-bacterial,antifungal,antiviral and antitumor activities,and other multiple bio-activities. As antibiotic medicine and tumor inhibition preparations lipopeptide antibiotics have potential application and outlook in the fields of medicines and clinics. Advances in the structure characteristics,biological function and action mechanism were reviewed in this paper.

  13. 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.

  14. 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.

  15. Predation and selection for antibiotic resistance in natural environments

    DEFF Research Database (Denmark)

    Leisner, Jørgen; Jørgensen, Niels O. G.; Middelboe, Mathias

    2016-01-01

    Genes encoding resistance to antibiotics appear, like the antibiotics themselves, to be ancient, originating long before the rise of the era of anthropogenic antibiotics. However, detailed understanding of the specific biological advantages of antibiotic resistance in natural environments is still...... lacking, thus limiting our efforts to prevent environmental influx of resistance genes. Here, we propose that antibiotic-resistant cells not only evade predation from antibiotic producers but also take advantage of nutrients released from cells that are killed by the antibiotic-producing bacteria. Thus......, predation is potentially an important mechanism for driving antibiotic resistance during slow or stationary phase of growth when nutrients are deprived. This adds to explain the ancient nature and widespread occurrence of antibiotic resistance in natural environments unaffected by anthropogenic antibiotics...

  16. Epidemiology of antibiotic resistance in Burkina Faso

    Institute of Scientific and Technical Information of China (English)

    Simpore J; Zeba B; Karou D; Ilboudo D; Pignatelli S; Nacoulma OG; Musumeci S

    2008-01-01

    Burkina Faso (West Africa)is a tropical country with a high incidence of infectious diseases.The uncontrolled use of antibiotics against bacterial pathogens has given rise to the emergence of antibiotic resistance in this country.The aims of this study were.i)to determine the prevalences of the most important pathogenic bacteri-a,isolated in the town of Ouagadougou.ii)to identify the bacterial species which have acquired resistance as a result of antibiotic selection.iii)to compare antibiotic-resistances ofEscherichia coli isolated from stool cul-ture in the present study,with results obtained in 2002 from strains collected in the same structure in Burkina Faso.iv)to determine the trend of antibiotic resistance in Burkina Faso in order to give local advice on the most appropriate empiric antibiotic therapy.Six thousand two hundred and sixty four samples of blood,stools, urine,sputum,pus and vaginal secretion were collected and analyzed in Saint Camille Medical Center (SC-MC)laboratory from May 2001 to May 2006.Out of the 6264 samples tested no pathogen was identified in 1583 (25.31%),whilst 4681 (74.73%)were positive,with the incidence of the microrganisms isolated be-ing as follows:Escherichia coli 1291 (27.6%),Staphylococcus aureus 922 (19.7%),Salmonella spp 561 (12.0%),Streptococcus spp 499 (10.7%),Klebsiella spp 359 (7.7%),Shigella spp (6.3%),Acineto-bacter spp 266 (5.7%)and others 783 (16.7%).Among the isolated pathogens,the highest resistance was found to Amoxycillin:Proteus spp 95.6%,Escherichia coli 78.2%,Salmonella spp 62.2%,Shigella spp 73. 4% and Klebsiella spp 89.9%,followed by resistance to Ampicillin and cotrimoxazole.Comparing the preva-lence of antibiotic resistance of Escherichia coli from stool cultures isolated during 1999-2000 to that of 2001-2006,a significant reduction was found,which could be due to the improved use of antibiotics in recent years. The reduced antibiotic-resistance observed in pathogens isolated in Burkina Faso during this

  17. Antibiotic use and resistance in long term care facilities.

    OpenAIRE

    Buul, L.W. van; Steen, J.T. van der; Veenhuizen, R.B.; Achterberg, W.P.; Schellevis, F G; Essink, R.T.G.M.; VAN BENTHEM, B. H B; Natsch, S. (Stefan); Hertogh, C. M. P. M.

    2012-01-01

    Introduction: The common occurrence of infectious diseases in nursing homes and residential care facilities may result in substantial antibiotic use, and consequently antibiotic resistance. Focusing on these settings, this article aims to provide a comprehensive overview of the literature available on antibiotic use, antibiotic resistance, and strategies to reduce antibiotic resistance. Methods: Relevant literature was identified by conducting a systematic search in the MEDLINE and EMBASE dat...

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

    OpenAIRE

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

    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 ...

  19. Toward the definition of immunosuppressive regimens with antitumor activity.

    Science.gov (United States)

    Casadio, F; Croci, S; D'Errico Grigioni, A; Corti, B; Grigioni, W F; Landuzzi, L; Lollini, P-L

    2005-06-01

    Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors.

  20. 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.

  1. 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.

  2. 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.

  3. Expression, Purification and Anti-tumor Activity of Curcin

    Institute of Scientific and Technical Information of China (English)

    Meng-Jun LUO; Xin-Yu YANG; Wei-Xin LIU; Ying XU; Ping HUANG; Fang YAN; Fang CHEN

    2006-01-01

    Curcin, purified from the seeds of Jatropha curcas, can be used as a cell-killing agent. Understanding the anti-tumor activity of the recombinant protein of curcin is important for its application in clinical medicine.The segment encoding the mature protein of curcin was inserted into Escherichia coli strain M15, and the recombinant strain was induced to express by isopropyl-β-D-thiogalactopyranoside at concentration of 0.5 mM. The recombinant protein was expressed in the form of inclusion bodies and purified by Ni-NTA affinity chromatography. The target protein was incubated with the tumor cells at different concentrations for different times and the results demonstrated that the target protein could inhibit the growth of tumor cells (NCL-H446, SGC-7901 and S180) at 5 μg/ml.

  4. Antitumor Effects of Laminaria Extract Fucoxanthin on Lung Cancer

    Directory of Open Access Journals (Sweden)

    ChengHan Mei

    2017-02-01

    Full Text Available Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX, a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time. Flow cytometry, real-time PCR, western blotting and immunohistochemistry revealed that FX arrested cell cycle and induced apoptosis by modulating expression of p53, p21, Fas, PUMA, Bcl-2 and caspase-3/8. These results show that FX is a potent marine drug for human non-small-cell lung cancer treatment.

  5. 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.

  6. OFFICIAL MEDICATIONS FOR ANTI-TUMOR GENE THERAPY

    Directory of Open Access Journals (Sweden)

    E. R. Nemtsova

    2016-01-01

    Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in  replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the  recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of  melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.

  7. Cancer vaccines: harnessing the potential of anti-tumor immunity.

    Science.gov (United States)

    Suckow, Mark A

    2013-10-01

    Although the presence of cancer suggests failure of the immune system to protect against development of tumors, the possibility that immunity can be redirected and focused to generate an anti-tumor response offers great translational possibility. The key to this is identifying antigens likely to be present in any given tumor and functionally critical to tumor survival and growth. Such tumor-associated antigens (TAAs) are varied and optimally should be absent from normal tissue. Of particular interest are TAAs associated with the tumor stroma, as immunity directed against the stroma may restrict the ability of the tumor to grow and metastasize. Important to directing the immune system toward an effect anti-tumor response is the understanding of how TAAs are processed and how the tumor is able to evade immune elimination. The process of immunoediting happens in response to the selective pressure that the immune system places upon tumor cell populations and allows for emergence of tumor cells capable of escaping immune destruction. Efforts to harness the immune system for clinical application has been aided by vaccines based on purified recombinant protein or nucleic acid TAAs. For example, a vaccine for canine melanoma has been developed and approved based on immunization with DNA components of tyrosinase, a glycoprotein essential to melanin synthesis. The performance of cancer vaccines has been aided in some cases when supplemented with immunostimulatory molecules such as interleukin 2 or a novel extracellular matrix vaccine adjuvant. Vaccines with the broadest menu of antigenic targets may be those most likely to succeed against cancer. For this reason, tissue vaccines produced from harvested tumor material may offer significant benefit. With several cancer vaccines on the veterinary and human markets, efforts to understand basic tumor immunology are soon to yield great dividends.

  8. 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 (n=12 per group) were dosed by oral gavage with either amoxicillin...

  9. 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.

  10. Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy

    NARCIS (Netherlands)

    Stigter, M.; Bezemer, J.; Groot, de K.; Layrolle, P.

    2004-01-01

    Carbonated hydroxyapatite (CHA) coatings were applied onto titanium implants by using a biomimetic precipitation method. Different antibiotics were incorporated into the CHA coatings and their release and efficacy against bacteria growth were studied in vitro. The following antibiotics were used wit

  11. 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.

  12. Effects of combination of antibiotic-resistant bifidobacteria and corresponding antibiotics on survival of irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Korshunov, V.M.; Pinegin, B.V.; Ivanova, N.P.; Mal' tsev, V.N.

    1982-05-01

    Broad-spectrum antibiotics are used to treat intestinal dysbacteriosis of diverse etiology, including postradiation dysbacteriosis. Antibiotic therapy is instrumental in decontaminating the intestine. In addition to pathogenic microorganisms, there is disappearance of lactobacilli and bifidobacteria which perform several important and useful functions. For this reason, in addition to antibiotics, bifidobacterial preparations are used to restore the microbial cenosis and administration thereof is started after antibiotics are discontinued. There are some flaws to deferred administration of bifidobacteria, since the process of colonization of the intestine with commercial bifidobacterial preparations is rather lengthy, and there is slow elevation of bididobacterium level in the intestinal tract, whereas exogenous recontamination of the intestine by conditionally pathogenic bacteria is possible after antibiotic therapy is discontinued. On the other hand, use of antibiotics alone could, in turn, be the cause of intestinal dysbacteriosis. Our objective was to eliminate intestinal dysbacteriosis in irradiated animals by means of combining antibiotics and preparations of bifidobacteria resistant to these antibiotics, and thus prolong the life of these animals.

  13. 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.

  14. Fighting urinary tract infections with antibiotic and non-antibiotic therapies.

    Science.gov (United States)

    Peri, Lluis

    2016-06-25

    Urinary tract infections (UTIs) place a considerable burden on the patient and are associated with substantial economic cost. Treatment of UTIs is mainly achieved using antibiotics, however, the rise in antibiotic resistance is concerning and the use of non-antimicrobial prophylaxis offers alternative treatment methods.

  15. 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

  16. 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

    OBJECTIVE: Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori infection. A study was conducted to assess prospectively the antibacterial resistance rates of H pylori in Europe and to study the link between outpatient antibiotic use and resistance levels in di...

  17. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance.

    NARCIS (Netherlands)

    Bell, B.G.; Schellevis, F.; Stobberingh, E.; Goossen, H.; Pringle, M.

    2014-01-01

    Background: Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substant

  18. 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...

  19. 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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Ali Moghadam

    Full Text Available 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.

  2. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    Science.gov (United States)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  3. Synthesis and Biological Evaluation of Novel Tricyclic Oximino Derivatives as Antitumor Agents

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A series of novel alkylthio/sulfinyl-8H-thieno[2,3-b]pyrrolizin-8-oximino derivatives Ⅴ1-Ⅷ15 were designed and synthesized as antitumor agents. Their structures were confirmed using IR, 1H NMR, elemental analysis,and MS. The antitumor activities of all the target compounds were tested by the MTT method in vitro against Bel-7402,HT-1080, SGC-7901, and A549 Cell Lines. Among them, compound Ⅵ9 displayed a promising antitumor activity superior to that of Cisplatin.

  4. [Acute otitis media and antibiotics. Evidence-based guidelines for antibiotic therapy?].

    Science.gov (United States)

    Thorøe, J; Lous, J

    1999-09-27

    Antibiotic treatment of acute otitis media is controversial. The questions are when to treat, with which antibiotic, and for how long? Within the last years three reviews attempting to discuss these questions have been published. All three found only a marginal effect of antibiotic treatment. The effect was less earache after the first day. The meta-analyses showed that between eight and 22 children had to be treated before one had any benefit of the treatment. The randomized studies did not find a greater effect of amoxicillin than of penicillin. The marginal effect of antibiotics on acute otitis media supports watchful waiting and individualized care and follow-up. There is a need for well-organized, randomized, placebo-controlled trials including the youngest children and the more severe cases of acute otitis media where the effect of antibiotic treatment may turn out to be most beneficial.

  5. 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...

  6. 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.

  7. Intravenous desensitization to beta-lactam antibiotics.

    Science.gov (United States)

    Borish, L; Tamir, R; Rosenwasser, L J

    1987-09-01

    Patients allergic to penicillin (PCN) often require treatment with beta-lactam antibiotics for life-threatening bacterial infections. In this article, we review our experience with rapid intravenous desensitization for patients who gave a history of PCN allergy and who had hypersensitivity demonstrated by skin tests. Skin testing was performed with both prick and intradermal techniques and with the recommended antibiotic as well as PCN G, penicilloyl polylysine, and a minor determinant mixture. Patients were transferred to the intensive care unit, and desensitization was performed with a buret technique that required minimal preparation and was easily applied to any antibiotic. Fifteen desensitizations in 12 patients were associated with no immediate reactions. One patient developed a delayed reaction consisting of a pruritic rash and angioedema. A second patient developed a more serious delayed serum sickness-like illness with fever, rash, eosinophilia, abnormal liver function tests, and urinary abnormalities. These reactions did not necessitate stopping the antibiotic, although the latter patient required corticosteroids to suppress his symptoms. Rapid intravenous desensitization is a rapid, safe, and effective technique for patients demonstrating hypersensitivity to beta-lactam antibiotics who require therapy with these medications.

  8. Multiple antibiotic sensitivity in a pediatric population.

    Science.gov (United States)

    Kamada, M M; Twarog, F; Leung, D Y

    1991-01-01

    Multiple antibiotic sensitivity (MAS), a common but complex clinical problem, has not been reviewed in the pediatric population. We evaluated 120 children with a history of MAS. The offending antibiotics were beta lactam (186 adverse reactions), sulfonamide (86 adverse reactions), macrolide (32 adverse reactions), erythromycin/sulfisoxazole (26 adverse reactions), aminoglycoside (2 adverse reactions), and tetracycline (2 adverse reactions). Urticaria occurred in 183 reactions, followed by polymorphous rash (n = 71), angioedema (n = 19), erythema multiform (n = 9), bronchospasm (n = 8), arthralgia (n = 7), serum sickness (n = 4), and laryngeal edema (n = 3), the mean age for the first reaction was 3 years (range 1 month to 13 years). Adverse reaction to three classes of antibiotics were noted in 22 patients, and two patients were noted to have adverse reactions to four or more antibiotic classes. Skin tests (ST) were performed in 98 children using penicillin G, a commercial benzyl penicilloyl polylysine, a minor determinant mixture, and a beta lactam analog. Positive ST were noted in 26% (31/120) of the MAS patients. Children with a history of MAS are likely to have true IgE-mediated reactions as documented by positive immediate hypersensitivity reactions to penicillin and/or its minor determinants. Therefore, MAS patients should be carefully evaluated for antibiotic sensitivity and not be assumed to have sensitivity to drug formulation as a basis for MAS.

  9. 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.

  10. The Biogeography of Putative Microbial Antibiotic Production.

    Directory of Open Access Journals (Sweden)

    Hélène Morlon

    Full Text Available Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics.

  11. 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.

  12. Antibiotic prophylaxis in primary immune deficiency disorders.

    Science.gov (United States)

    Kuruvilla, Merin; de la Morena, Maria Teresa

    2013-01-01

    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

  13. Isolated cell behavior drives the evolution of antibiotic resistance.

    Science.gov (United States)

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

    2015-07-29

    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 relationship between MIC and bacterial fitness in the antibiotic is not well defined. Here, we demonstrate that the resistance of a single, isolated cell-which we call the single-cell MIC (scMIC)-provides a superior metric for quantifying antibiotic resistance. Unlike the MIC, we find that the scMIC predicts the direction of selection and also specifies the antibiotic concentration at which selection begins to favor new mutants. Understanding the cooperative nature of bacterial growth in antibiotics is therefore essential in predicting the evolution of antibiotic resistance.

  14. An antibiotic's journey from marketing authorization to use, Norway.

    Science.gov (United States)

    Årdal, Christine; Blix, Hege Salvesen; Plahte, Jens; Røttingen, John-Arne

    2017-03-01

    Here we describe in detail marketing authorization and reimbursement procedures for medicinal products in Norway, with particular reference to nine novel antibiotics that received marketing authorization between 2005 and 2015. The description illustrates that, in places like Norway, with effective antibiotic stewardship policies and an associated low prevalence of antibiotic-resistant bacterial infection, there is little need for newer, more expensive antibiotics whose therapeutic superiority to existing compounds has not been demonstrated. Since resistance begins to emerge as soon as an antibiotic is used, Norway's practice of leaving newer antibiotics on the shelf is consistent with the goal of prolonging the effectiveness of newer antibiotics. An unintended consequence is that the country has signalled to the private sector that there is little commercial value in novel antibiotics, which may nevertheless still be needed to treat rare or emerging infections. Every country aims to improve infection control and to promote responsible antibiotic use. However, as progress is made, antibiotic-resistant bacteria should become less common and, consequently, the need for, and the commercial value of, novel antibiotics will probably be reduced. Nevertheless, antibiotic innovation continues to be essential. This dilemma will have to be resolved through the introduction of alternative reward systems for antibiotic innovation. The DRIVE-AB (Driving re-investment in research and development and responsible antibiotic use) research consortium in Europe has been tasked with identifying ways of meeting this challenge.

  15. Spinal epidural abscess treated with antibiotics alone.

    Science.gov (United States)

    Pathak, Ashish; Singh, Poonam; Gehlot, Prateek; Dhaneria, Mamta

    2013-04-30

    Spinal epidural abscess (SEA) is a rare clinical condition among children. Most patients do not present with classical signs. A 13-year-old boy without any predisposing factors presented with paraparesis, bladder and bowel involvement. MRI spine demonstrated an SEA at the C7 and D1 levels on both sides of the midline with cord oedema at the C2-3 to C6 level with minimal marrow oedema in the C6 vertebral body. We treated the patient with antibiotics (ceftriaxone and vancomycin) alone. The patient showed excellent response with only minimal residual gait disturbance at the end of 6 weeks of antibiotic therapy. This is the first paediatric report of complete recovery of a patient at clinical stage 4 following antibiotic treatment alone from India. However, caution should be exercised to closely monitor the patient's recovery as any progression in the neurological state warrants surgery.

  16. Antibiotic tolerance facilitates the evolution of resistance.

    Science.gov (United States)

    Levin-Reisman, Irit; Ronin, Irine; Gefen, Orit; Braniss, Ilan; Shoresh, Noam; Balaban, Nathalie Q

    2017-02-24

    Controlled experimental evolution during antibiotic treatment can help to explain the processes leading to antibiotic resistance in bacteria. Recently, intermittent antibiotic exposures have been shown to lead rapidly to the evolution of tolerance-that is, the ability to survive under treatment without developing resistance. However, whether tolerance delays or promotes the eventual emergence of resistance is unclear. Here we used in vitro evolution experiments to explore this question. We found that in all cases, tolerance preceded resistance. A mathematical population-genetics model showed how tolerance boosts the chances for resistance mutations to spread in the population. Thus, tolerance mutations pave the way for the rapid subsequent evolution of resistance. Preventing the evolution of tolerance may offer a new strategy for delaying the emergence of resistance.

  17. Antibiotic resistance genes in the environment

    Directory of Open Access Journals (Sweden)

    Jianqiang Su

    2013-07-01

    Full Text Available Antibiotic resistance and its spread in bacteria are topics of great importance in global research. In this paper, we review recent progress in understanding sources, dissemination, distribution and discovery of novel antibiotics resistance genes (ARGs in the environment. Bacteria exhibiting intrinsic resistance and antibiotic resistant bacteria in feces from humans and animals are the major sources of ARGs occurring in the environment. A variety of novel ARGs have been discovered using functional metagenomics. Recently, the long-term overuse of antibotics in drug therapy and animal husbandry has led to an increase in diversity and abundance of ARGs, causing the environmental dissemination of ARGs in aquatic water, sewage treatmentplants, rivers, sediment and soil. Future research should focus on dissemination mechanisms of ARGs, the discovery of novel ARGs and their resistant mechanisms, and the establishment of environmental risk assessment systems for ARGs.

  18. Antibiotics for acute otitis media in children.

    Science.gov (United States)

    Nitsche, María Pía; Carreño, Monica

    2015-10-29

    Acute otitis media is one of the most common infectious diseases diagnosed in children. Antibiotic treatment use remains controversial. This summary aims to evaluate the effectiveness and safety of antibiotics in children with acute otitis media. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including 18 randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded antibiotics reduce pain at 48-72 hours and reduce the risk of tympanic perforations in children with acute otitis media, but they do not reduce late recurrences and increase the risk of side effects (rash, vomiting and diarrhea).

  19. Synthesis and in vitro antitumor activities of lupeol dicarboxylic acid monoester derivatives.

    Science.gov (United States)

    Li, Weijie; Hao, Jing; Xiao, Yeyu

    2013-12-01

    Ten lupeol dicarboxylic acid monoester derivatives as new potent antitumor agents were synthesized and evaluated for in vitro antitumor activities against A549, LAC, HepG2 and HeLa cell lines. Among them, compounds 1-5 showed excellent antitumor activities against all tested tumor cell lines and compounds 6-10 exhibited high activities against A549, HepG2 and HeLa cells, exceeded lupeol, lupanol and doxorubicin. Compound 2 displayed the highest potent antitumor activities with IC50 values of 5.78 μM against A549 cell, 2.38 μM against LAC cell, 6.14 μM against HepG2 cell and 0.00842 μM against HeLa cell.

  20. 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.

  1. [Antitumor Activity of Polysaccharides from Ganoderma lucidum Mycelium: in vivo Comparative Study].

    Science.gov (United States)

    Krasnopolskaya, L M; Yarina, M S; Avtonomova, A V; Usov, A I; Isakova, E B; Bukchman, V M

    2015-01-01

    Fractions of water soluble and alkali soluble polysaccharides, as well as fucogalactan, a water soluble polysaccharide, and xylomannan, an alkali soluble polysaccharide, were isolated from the Ganoderma lucidum submerged mycelium. When administered orally, the polysaccharides showed antitumor activity in vivo on murine models of solid tumors. Xylomannan and fucogalactan showed the highest antitumor activity. Sensitivity to xylomannan was more pronounced in adenocarcinoma Ca755 as compared to the T-cell lymphocytic leukemia P388. The antitumor activity of the water soluble polysaccharides total fractions from the mycelium and fruiting bodies of the G. lucidum strain was almost identical. The maximum antitumor effect of the mycelium water soluble polysaccharides total fraction was observed with the use of the daily dose of 2 mg/kg.

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

    Institute of Scientific and Technical Information of China (English)

    Zhi-binLIN; Hui-naZHANG

    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.

  3. Carboxylate groups play a major role in antitumor activity of Ganoderma applanatum polysaccharide.

    Science.gov (United States)

    Sun, Xiaobo; Zhao, Chen; Pan, Wei; Wang, Jinping; Wang, Weijun

    2015-06-05

    In this paper, the structure difference between the polysaccharides isolated from fruit bodies (FGAP) and submerged fermentation system (SGAP) of Ganoderma applanatum was investigated by means of GPC, HPLC and IR, respectively. And their antitumor activities were evaluated against Sarcoma 180 in vivo. The results showed that FGAP and SGAP were typical polysaccharides with different molecular weights, monosaccharide components, and functional groups. Closely related to the distinct structures, FGAP exhibited a better antitumor activity than SGAP. Moreover, since FGAP contained carboxylate groups rather than SGAP, such groups were chemically introduced into SGAP (CSGAP) by carboxymethylation in order to identify their contribution to antitumor activity. The results demonstrated that the inhibition of CSGAP against Sarcoma 180 in vivo was significantly enhanced by comparison to the native SGAP and even higher than that of FGAP, suggesting that the carboxylate groups played a major role in antitumor activity of G. applanatum polysaccharide.

  4. 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.

  5. Similar outcomes for anti-tumor necrosis factor-α antibody and immunosuppressant following seton drainage in patients with Crohn's disease-related anal fistula.

    Science.gov (United States)

    Lin, Xutao; Fan, Dejun; Cai, Zerong; Lian, Lei; He, Xiaowen; Zhi, Min; Wu, Xiaojian; He, Xiaosheng; Lan, Ping

    2016-09-01

    Anal fistula is common in patients with Crohn's disease (CD) and leads to significant morbidity. The efficacy of seton drainage combined with anti-tumor necrosis factor-α monoclonal antibody (anti-TNF-α) or immunosuppressant in the treatment of CD-related anal fistula remains unclear. The aim of the present study was to compare the efficacy between seton drainage combined with anti-TNF-α and seton drainage combined with immunosuppressant postoperatively on the treatment of CD-related anal fistula. A total of 65 patients with CD-related anal fistula who had received seton drainage combined with postoperative medication were divided into an antibiotics only group, anti-TNF-α group and immunosuppressant group; all patients were treated with antibiotics. Fistula closure, external orifice exudation rate and recurrence rate were assessed among these patients. The duration of follow-up ranged from 3 to 84 months with an average of 25.3 months. There were 11 (16.9%) cases of recurrence after seton drainage, 9 of which underwent a second seton drainage. In the total study group, 34 (52.3%) cases achieved complete fistula closure, and 10 (15.4%) cases showed external orifice exudation. No significant difference was found among these three groups, regarding fistula closure rate, closure time of fistula and recurrence rate. The external orifice exudation rate was significantly higher in the anti-TNF-α group compared with the antibiotics only group and immunosuppressant group (P=0.004 and P=0.026, respectively). Seton drainage is an effective treatment for CD-related anal fistula. The efficacy is similar whether combined with anti-TNF-α or immunosuppressant.

  6. 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...... protocol to assemble short-read sequence data after antibiotic selection experiments, using 12 different drugs in all antibiotic classes, and compared antibiotic resistance gene sequences between soil bacteria and clinically occurring pathogens. Sixteen sequences, representing seven gene products, were...

  7. Antibiotics in dental implants: A review of literature

    Science.gov (United States)

    Surapaneni, Hemchand; Yalamanchili, Pallavi Samatha; Basha, Md. Hafeez; Potluri, Sushma; Elisetti, Nirupa; Kiran Kumar, M. V.

    2016-01-01

    The routine use of antibiotics in oral implant treatment seems to be widespread. The pre- or post-operative use of antibiotics in conjunction with implant surgery and its correlation with failure and success rates are poorly documented in the literature. The debate regarding overprescription of antibiotics raises the need for a critical evaluation of proper antibiotic coverage in association with implant treatment. The benefits of prophylactic antibiotics are well-recognized in dentistry. However, their routine use in the placement of endosseous dental implants remains controversial. The purpose of this review is to know the efficacy of antibiotic prophylaxis in implant dentistry. PMID:27829741

  8. 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.

  9. 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...

  10. Collateral sensitivity of antibiotic-resistant microbes.

    Science.gov (United States)

    Pál, Csaba; Papp, Balázs; Lázár, Viktória

    2015-07-01

    Understanding how evolution of microbial resistance towards a given antibiotic influences susceptibility to other drugs is a challenge of profound importance. By combining laboratory evolution, genome sequencing, and functional analyses, recent works have charted the map of evolutionary trade-offs between antibiotics and have explored the underlying molecular mechanisms. Strikingly, mutations that caused multidrug resistance in bacteria simultaneously enhanced sensitivity to many other unrelated drugs (collateral sensitivity). Here, we explore how this emerging research sheds new light on resistance mechanisms and the way it could be exploited for the development of alternative antimicrobial strategies.

  11. 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

  12. Trends in antibiotic resistance of corneal pathogens: Part I. An analysis of commonly used ocular antibiotics

    Directory of Open Access Journals (Sweden)

    Sharma Savitri

    1999-01-01

    Full Text Available Purpose: To analyse commonly used ocular antibiotics and determine their in-vitro efficacies against bacterial keratitis pathogens. Methods: A retrospective review of microbiology records at the LV Prasad Eye Institute in Hyderabad, India identified 1,633 bacterial keratitis isolates. Antibiotic susceptibility of corneal isolates was determined for various ocular antibiotics using the Kirby-Bauer disc-diffusion method. Results: Cefazolin had coverage against 1,296 (83.0% of 1,562 isolates tested; chloramphenicol against 1,136 (71.7% of 1,585 isolates; ciprofloxacin against 1,080 (69.3% of 1,558 isolates; gentamicin against 1,106 (70.6% of 1,567 isolates; norfloxacin against 1,057 (67.7% of 1,561 isolates; vancomycin against 463 (84.3% of 549 isolates; and framycetin against 105 (36.2% of 290 isolates. Also included is a breakdown by species, and sensitivity profiles for resistant isolates.Conclusion: This study provides information on the efficacies of ocular antibiotics commonly used against bacterial keratitis pathogens. It also examines the antibiotic susceptibility profiles for corneal pathogens that are resistant to an ocular antibiotic but sensitive to other selected antibiotics. It is hoped that this information will aid in the decision-making of empiric initial treatment of bacterial keratitis.

  13. Removal of antibiotics and antibiotic resistance genes in rural wastewater by an integrated constructed wetland.

    Science.gov (United States)

    Chen, Jun; Liu, You-Sheng; Su, Hao-Chang; Ying, Guang-Guo; Liu, Feng; Liu, Shuang-Shuang; He, Liang-Ying; Chen, Zhi-Feng; Yang, Yong-Qiang; Chen, Fan-Rong

    2015-02-01

    Integrated constructed wetlands (ICWs) are regarded as one of the most important removal technology for pollutants in rural domestic wastewaters. This study investigated the efficiency of an ICW consisting of a regulating pool, four surface and subsurface flow-constructed wetlands, and a stabilization unit for removing antibiotics and antibiotic resistance genes (ARGs) from rural domestic wastewaters. The results showed that antibiotics leucomycin, ofloxacin, lincomycin, and sulfamethazine, and ARGs sul1, sul2, tetM, and tetO were the predominant antibiotics and ARGs in the influent, respectively. The ICW system could significantly reduce most of the detected antibiotics and ARGs with their aqueous removal rates of 78 to 100 % and >99 %, respectively. Based on the measured concentrations, the total pollution loadings of antibiotics were 3,479 μg/day in the influent and 199 μg/day in the final effluent. Therefore, constructed wetlands could be a promising technology for rural wastewater in removing contaminants such as antibiotics and ARGs.

  14. 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.

  15. 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.

  16. Synthesis and Antitumor Activities of 26-O-tert-Butyldimethylsiliyl Protodisogenyl β-D-Glucopyranoside

    Institute of Scientific and Technical Information of China (English)

    Liang ZHOU; Shu Jie HOU; Peng XU; De Quan YU; Ping Sheng LEI; Chuan Chun ZOU

    2006-01-01

    New saponin 26-O-tert-butyldimethylsiliyl protodiosgenyl β-D-glucopyranoside 1 was synthesized and its cytotoxicity activity in vitro was evaluated by MTT. It showed potent antitumor activity to human cancer cells. E ring and C22-OH play important roles in the antitumor activity of 1. A method to selective removal of acetyl group in the presence of benzoyl group was reported.

  17. Antibiotics in Drinking Water in Shanghai and Their Contribution to Antibiotic Exposure of School Children.

    Science.gov (United States)

    Wang, Hexing; Wang, Na; Wang, Bin; Zhao, Qi; Fang, Hong; Fu, Chaowei; Tang, Chuanxi; Jiang, Feng; Zhou, Ying; Chen, Yue; Jiang, Qingwu

    2016-03-01

    A variety of antibiotics have been found in aquatic environments, but antibiotics in drinking water and their contribution to antibiotic exposure in human are not well-explored. For this, representative drinking water samples and 530 urine samples from schoolchildren were selected in Shanghai, and 21 common antibiotics (five macrolides, two β-lactams, three tetracyclines, four fluoquinolones, four sulfonamides, and three phenicols) were measured in water samples and urines by isotope dilution two-dimensional ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. Drinking water included 46 terminal tap water samples from different spots in the distribution system of the city, 45 bottled water samples from 14 common brands, and eight barreled water samples of different brands. Of 21 antibiotics, only florfenicol and thiamphenicol were found in tap water, with the median concentrations of 0.0089 ng/mL and 0.0064 ng/mL, respectively; only florfenicol was found in three bottled water samples from a same brand, with the concentrations ranging from 0.00060 to 0.0010 ng/mL; no antibiotics were found in barreled water. In contrast, besides florfenicol and thiamphenicol, an additional 17 antibiotics were detected in urine samples, and the total daily exposure doses and detection frequencies of florfenicol and thiamphenicol based on urine samples were significantly and substantially higher than their predicted daily exposure doses and detection frequencies from drinking water by Monte Carlo Simulation. These data indicated that drinking water was contaminated by some antibiotics in Shanghai, but played a limited role in antibiotic exposure of children.

  18. Burkholderia cepacia complex Phage-Antibiotic Synergy (PAS): antibiotics stimulate lytic phage activity.

    Science.gov (United States)

    Kamal, Fatima; Dennis, Jonathan J

    2015-02-01

    The Burkholderia cepacia complex (Bcc) is a group of at least 18 species of Gram-negative opportunistic pathogens that can cause chronic lung infection in cystic fibrosis (CF) patients. Bcc organisms possess high levels of innate antimicrobial resistance, and alternative therapeutic strategies are urgently needed. One proposed alternative treatment is phage therapy, the therapeutic application of bacterial viruses (or bacteriophages). Recently, some phages have been observed to form larger plaques in the presence of sublethal concentrations of certain antibiotics; this effect has been termed phage-antibiotic synergy (PAS). Those reports suggest that some antibiotics stimulate increased production of phages under certain conditions. The aim of this study is to examine PAS in phages that infect Burkholderia cenocepacia strains C6433 and K56-2. Bcc phages KS12 and KS14 were tested for PAS, using 6 antibiotics representing 4 different drug classes. Of the antibiotics tested, the most pronounced effects were observed for meropenem, ciprofloxacin, and tetracycline. When grown with subinhibitory concentrations of these three antibiotics, cells developed a chain-like arrangement, an elongated morphology, and a clustered arrangement, respectively. When treated with progressively higher antibiotic concentrations, both the sizes of plaques and phage titers increased, up to a maximum. B. cenocepacia K56-2-infected Galleria mellonella larvae treated with phage KS12 and low-dose meropenem demonstrated increased survival over controls treated with KS12 or antibiotic alone. These results suggest that antibiotics can be combined with phages to stimulate increased phage production and/or activity and thus improve the efficacy of bacterial killing.

  19. 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 antibiotics can prevail in MSW leachates and landfills may be an underappreciated as a source of antibiotics and ARGs to the environment.

  20. Synthesis and Primary Research on Antitumor Activity of Three New Panaxadiol Fatty Acid Esters

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    For making use of Ginseng resources that exhibit an antitumor activity and for finding new anticancer drugs,three new fatty acid ester compounds: 3β-acetoxy panaxadiol ( Ⅰ ), 3β-palmitic acid aceloxy panaxadiol ( Ⅱ ), and 3β-octadecanoic acid aceloxy panaxadiol( Ⅰ , Ⅱ , and Ⅲ ) were synthesized with panaxadiol, diacetyl oxide, palmityl chloride and stearyl chloride, and their structures were determined via MS, 13C NMR, IR, TLC, and so on. The molar yields of the three compounds are 75.14%, 79. 08%, and 72. 57%, respectively. Meanwhile, the antitumor activity of the three new panaxadiol fatty acid ester derivatives and panaxadiol was compared by using the method of MTT. Tumor cell used was Vero cell line. Positive control was 5-FU, blank was an RPMI1640 culture medium, negative control was an RPMI1640 culture medium and the solvent for drugs to be tested. Compound Ⅰ has the strongest antitumor activity followed by panaxadiol; compounds Ⅱ and Ⅲ have similar and weakest antitumor activities.Furthermore, the antitumor activities of the panaxadiol fatty acid ester derivatives show positive correlation with the concentration of the test group, but show no relationship with the molecular weight of fatty acid. The methods that are used to synthesize the three compounds with high yields and strong antitumor activities are simple and show a great potential for meeting the needs of industrial manufacture of these drugs.

  1. Synthesis and docking studies of novel antitumor benzimidazoles.

    Science.gov (United States)

    Omar, Mohamed A; Shaker, Yasser M; Galal, Shadia A; Ali, Mamdouh M; Kerwin, Sean M; Li, Jing; Tokuda, Harukuni; Ramadan, Raghda A; El Diwani, Hoda I

    2012-12-15

    In this work, the benzimidazole-pyrrole conjugates 6a-h and benzimidazole-tetracycles conjugates 12-14 were prepared. The cytotoxicity of the compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 was tested against lung cancer cell line A549. Compound 6b exhibited higher activity than the bis-benzoxazole natural product (UK-1), the standard. The tested 4g,h, 6a-h, 10 and 12-14 exhibited remarkable cytotoxicity activity against breast cancer cell line MCF-7 with higher activity than tamoxifen. Furthermore, compound 4h was found to be also more potent than doxurubicin. The antitumor promotion activity of synthesized compounds 4g,h, 6a-h, 10 and 12-14 has been estimated by studying their possible inhibitory effects on EBV-EA activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds, the inhibitory activities of compounds 8, 13 and 14 demonstrated strong inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation without showing any cytotoxicity on the Raji cells and their effects being stronger than that of a representative control, oleanolic acid. Moreover, the molecular docking of the new compounds into plasminogen activator (uPA) receptor has been in correlation with the antitumor activity. All synthesized compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 were docked into same groove of the binding site of the native co-crystalized (4-iodobenzo[b]thiophene-2-carboxamidine) ligand (PDB code:1c5x) for activity explaination. Compounds 4h, 6b and 13, giving the best docking results, were further studied to estimate their effect on the level of uPA using AssayMax human urokinase (uPA) ELISA kit. In case of A549 cell line, compound 6 exhibited similar activity to MMC, and for MCF-7 cell line, compound 4h exhibited similar activity to doxorubicin, in inhibiting the expression of uPA.

  2. 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.

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

    Science.gov (United States)

    Raghunath, D

    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.

  4. 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.

  5. Countermeasures to Antibiotics Crisis: a Global Priority List of Antibiotic-Resistant Bacteria for Research and Development of New Antibiotics

    Directory of Open Access Journals (Sweden)

    Editorial

    2017-03-01

    Full Text Available On 27 Feb., 2017, the World Health Organization (WHO announced the first list of important antibiotic-resistant bacteria (http://www.who.int/mediacentre/news/releases/2017/bacteria-antibiotics-needed/en/, which tremendously threat human-being’s health. This list included 12 kinds of bacteria that were categorized into three priority tiers: Critical, High and Medium. In the first tier, Critical, three Gram negative bacteria were included: Acinetobacter baumannii with carbapenem-resistant, Pseudomonas aeruginosa with carbapenem-resistant; and Enterobacteriaceae with carbapenem-resistant, the third generation cephalosporin-resistant. In the second tier, High, six bacteria were suggested: Enterococcus faecium with vancomycin-resistant, Staphylococcus aureus with methicillin-resistant, vancomycin intermediate and resistant, Helicobacter pylori with clarithromycin-resistant, Campylobacter with fluoroquinolone-resistant, Salmonella spp. with fluoroquinolone-resistant, Neisseria gonorrhoeae with the third generation cephalosporin-resistant, fluoroquinolone-resistant. In the third tier, Medium, three bacteria were listed: Streptococcus pneumonia with penicillin-non-susceptible, Haemophilus influenza with ampicillin-resistant, and Shigella spp. with fluoroquinolone-resistant. This list was proposed by an expert panel, chaired by Dr. E. Tacconelli from Infectious Diseases, DZIF Center, Tübingen University, Germany and Dr. N. Magrini from EMP Department of WHO. This proposal recommended some key steps to countermeasure the challenges posed by multi-drug- and extensively drug-resistant bacteria, including research and development of new classes of antibiotics for the paediatric population, for preventing cross- and co-resistance to existing classes of antibiotics, and for oral formulations for community-acquired diseases with a high morbidity burden. This list will guide our future research and development of new antibiotics in future.

  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. Respiratory infection and antibiotic prescription rates.

    NARCIS (Netherlands)

    Otters, H.; Wouden, J. van der; Schellevis, F.

    2004-01-01

    In the October issue of the BJGP, Fleming et al showed that a decrease in antibiotic prescription rates is directly related to a decrease in respiratory infections presented in general practice. We compliment the authors for their interesting study and the clear presentation of their results.

  8. Prophylactic antibiotics and anticonvulsants in neurosurgery.

    Science.gov (United States)

    Ratilal, B; Sampaio, C

    2011-01-01

    The prophylactic administration of antibiotics to prevent infection and the prophylactic administration of anticonvulsants to prevent first seizure episodes are common practice in neurosurgery. If prophylactic medication therapy is not indicated, the patient not only incurs the discomfort and the inconvenience resulting from drug treatment but is also unnecessarily exposed to adverse drug reactions, and incurs extra costs. The main situations in which prophylactic anticonvulsants and antibiotics are used are described and those situations we found controversial in the literature and lack further investigation are identified: anticonvulsants for preventing seizures in patients with chronic subdural hematomas, antiepileptic drugs for preventing seizures in those suffering from brain tumors, antibiotic prophylaxis for preventing meningitis in patients with basilar skull fractures, and antibiotic prophylaxis for the surgical introduction of intracranial ventricular shunts.In the following we present systematic reviews of the literature in accordance with the standard protocol of The Cochrane Collaboration to evaluate the effectiveness of the use of these prophylactic medications in the situations mentioned. Our goal was to efficiently integrate valid information and provide a basis for rational decision-making.

  9. Antibiotics: neuropsychiatric effects and psychotropic interactions.

    Science.gov (United States)

    Sternbach, H; State, R

    1997-01-01

    Antibiotics are the second most commonly prescribed class of medication in the United States. An awareness and understanding of their potential effects on the central nervous system and their interactions with psychotropic agents is important in the evaluation of neuropsychiatric signs and symptoms in patients. Since the introduction of antibiotic agents in the 1930s, numerous (primarily anecdotal) reports have appeared describing psychiatric side effects ranging from anxiety and panic to major depression, psychosis, and delirium in patients with and without a premorbid psychiatric history. Risk factors have included prior psychopathology, coexisting medical conditions, slow acetylator status, advanced age, concomitant medications, and increased permeability of the blood-brain barrier, as well as high antibiotic dosage and intrathecal or intravenous administration. Psychiatric toxicity may result from various mechanisms of action, including antagonism of gamma-aminobutyric acid or pyridoxine, adverse interactions with alcohol, or inhibition of protein synthesis. Adverse pharmacokinetic and pharmacodynamic interactions between antibiotics and concomitant medications including lithium, benzodiazepines, carbamazepine, valproate, neuroleptics, antidepressants, methadone, and disulfiram have also been reported. Because such effects are often not recognized by clinicians, accurate epidemiologic data on their incidence are not available.

  10. 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

  11. The genomic enzymology of antibiotic resistance.

    Science.gov (United States)

    Morar, Mariya; Wright, Gerard D

    2010-01-01

    The need for new antibiotic therapies is acute and growing in large part because of the emergence of drug-resistant pathogens. A vast number of resistance determinants are, however, found in nonpathogenic micro-organisms. The resistance totality in the global microbiota is the antibiotic resistome and includes not only established resistance genes but also genes that have the potential to evolve into resistance elements. We term these proto-resistance genes and hypothesize that they share common ancestry with other functional units known as housekeeping genes. Genomic enzymology is the study of protein structure-function in light of genetic context and evolution of protein superfamilies. This concept is highly applicable to study of antibiotic resistance evolution from proto-resistance elements. In this review, we summarize some of the genomic enzymology evidence for resistance enzymes pointing to common ancestry with genes of other metabolic functions. Genomic enzymology plays a key role in understanding the origins of antibiotic resistance and aids in designing strategies for diagnosis and prevention thereof.

  12. Antibiotic production by bacterial biocontrol agents

    NARCIS (Netherlands)

    Raaijmakers, J.M.; Vlami, M.; Souza, de J.T.

    2002-01-01

    Interest in biological control of plant pathogens has been stimulated in recent years by trends in agriculture towards greater sustainability and public concern about the use of hazardous pesticides. There is now unequivocal evidence that antibiotics play a key role in the suppression of various soi

  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. Towards new β-lactam antibiotics

    NARCIS (Netherlands)

    Andersson, I.; Terwisscha van Scheltinga, A.C.; Valegård, K.

    2001-01-01

    Antibiotics have had a profound impact on human health and belong to one of the largest-selling classes of drugs worldwide. Introduced into industrial production only some half century ago, these miracle drugs have been the main contributors to the recent increase in human life expectancy. However,

  15. Proteome studies of bacterial antibiotic resistance mechanisms.

    Science.gov (United States)

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

    2014-01-31

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

  16. Selective decontamination and antibiotic resistance in ICUs

    NARCIS (Netherlands)

    Plantinga, Nienke L.; Bonten, Marc J. M.

    2015-01-01

    Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) have been associated with reduced mortality and lower ICU-acquired bacteremia and ventilator-associated pneumonia rates in areas with low levels of antibiotic resistance. However, the effect of selective deco

  17. The negative impact of antibiotic resistance.

    Science.gov (United States)

    Friedman, N D; Temkin, E; Carmeli, Y

    2016-05-01

    Antibacterial therapy is one of the most important medical developments of the twentieth century; however, the spread of resistance in healthcare settings and in the community threatens the enormous gains made by the availability of antibiotic therapy. Infections caused by resistant bacteria lead to up to two-fold higher rates of adverse outcomes compared with similar infections caused by susceptible strains. These adverse outcomes may be clinical or economic and reflect primarily the failure or delay of antibiotic treatment. The magnitude of these adverse outcomes will be more pronounced as disease severity, strain virulence, or host vulnerability increases. The negative impacts of antibacterial resistance can be measured at the patient level by increased morbidity and mortality, at the healthcare level by increased resource utilization, higher costs and reduced hospital activity and at the society level by antibiotic treatment guidelines favouring increasingly broad-spectrum empiric therapy. In this review we will discuss the negative impact of antibiotic resistance on patients, the healthcare system and society.

  18. 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

  19. Non-absorbed Antibiotics for IBS

    Science.gov (United States)

    2012-03-16

    physiologic, rather than clinical, endpoints. Over the last decade, the Food and Drug Administration has favored a global IBS endpoint for Phase 3...question surrounding the use of antibiotics such as rifaximin, as well as agents such as probiotics , as IBS therapies is exactly how they are exert- ing

  20. 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

  1. Proficiency test for antibiotics in beef

    NARCIS (Netherlands)

    Berendsen, B.J.A.; Stolker, A.A.M.

    2009-01-01

    The aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of antibiotics in bovine tissues, including the screening analysis. This study also provided an evaluation of the methods applied for screening and quantitative and

  2. Proficiency test for antibiotics in bovine muscle

    NARCIS (Netherlands)

    Elbers, I.J.W.; Berendsen, B.J.A.; Pikkemaat, M.G.; Stolker, A.A.M.

    2010-01-01

    The aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of antibiotics in bovine muscle, including the screening analysis. This study also provided an evaluation of the methods applied for screening and quantitative conf

  3. 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.

  4. 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

  5. Antibiotic resistance: from Darwin to Lederberg to Keynes.

    Science.gov (United States)

    Amábile-Cuevas, Carlos F

    2013-04-01

    The emergence and spread of antibiotic-resistant bacteria reflects both, a gradual, completely Darwinian evolution, which mostly yields slight decreases in antibiotic susceptibility, along with phenotypes that are not precisely characterized as "resistance"; and sudden changes, from full susceptibility to full resistance, which are driven by a vast array of horizontal gene transfer mechanisms. Antibiotics select for more than just antibiotic resistance (i.e., increased virulence and enhanced gene exchange abilities); and many non-antibiotic agents or conditions select for or maintain antibiotic resistance traits as a result of a complex network of underlying and often overlapping mechanisms. Thus, the development of new antibiotics and thoughtful, integrated anti-infective strategies is needed to address the immediate and long-term threat of antibiotic resistance. Since the biology of resistance is complex, these new drugs and strategies will not come from free-market forces, or from "incentives" for pharmaceutical companies.

  6. 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, ...

  7. 'Superbug' Resistant to All Antibiotics Killed Nevada Woman

    Science.gov (United States)

    ... news/fullstory_163038.html 'Superbug' Resistant to All Antibiotics Killed Nevada Woman She died after possibly picking ... September from a "superbug" infection that resisted all antibiotics, according to a report released Friday. The case ...

  8. Skip the Antibiotics for Mild Eczema in Kids

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_164083.html Skip the Antibiotics for Mild Eczema in Kids Skin condition cleared ... March 14, 2017 (HealthDay News) -- Despite widespread use, antibiotics are not an effective treatment for milder cases ...

  9. Treating Sinusitis: Don't Rush to Antibiotics

    Science.gov (United States)

    ... AAAAI) Treating Sinusitis (AAAAI) Don’t rush to antibiotics DOWNLOAD PDF The sinuses are small, hollow spaces ... or teeth. Each year, millions of people use antibiotic drugs to treat sinus problems. However, they usually ...

  10. Dilemmas in primary care: antibiotic treatment of acute otitis media.

    Science.gov (United States)

    True, B L; Helling, D K

    1986-09-01

    Antibiotic treatment of acute otitis media (AOM) accounts for a significant number of all antibiotic prescriptions each year. In the primary care setting, initial antibiotic selection is rarely based on direct evidence, such as cultures of middle ear fluid. Initial antibiotic therapy by the primary care practitioner involves the evaluation and application of information related to prevalence of infecting organisms; in vitro antibiotic spectrum and penetration into middle ear fluid; initial cure rate, relapse and recurrence rates; and antibiotic cost, safety, and convenience. The influence of these factors on the initial antibiotic choice for AOM is reviewed. Several therapeutic dilemmas confronting the prescriber are discussed and a rational approach to initial antibiotic therapy is presented.

  11. CURRENT ISSUES REGARDING ENDOCRINE DISRUPTING CHEMICALS AND ANTIBIOTIC RESISTANCE

    Science.gov (United States)

    Recently public concern has increased regarding industrial and environmental substances that may have adverse hormonal effects in human and wildlife populations. This concern has also been expanded to include antibiotic-resistant bacteria and the presence of various antibiotics a...

  12. Doctors' Decision-Making Tool Could Cut Unnecessary Antibiotic Use

    Science.gov (United States)

    ... html Doctors' Decision-Making Tool Could Cut Unnecessary Antibiotic Use A drop of about 10 percent is ... for doctors may help reduce unnecessary use of antibiotics in children with respiratory tract infections and cough, ...

  13. 2nd Antibiotic Halves C-Section Infection Rate

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_161230.html 2nd Antibiotic Halves C-Section Infection Rate: Study Two medications ... 29, 2016 (HealthDay News) -- Doctors routinely give an antibiotic before a cesarean-section, the surgical delivery of ...

  14. Antibiotic use and resistance in long term care facilities

    NARCIS (Netherlands)

    Buul, L.W. van; Steen, J.T. van der; Veenhuizen, R.B.; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.G.M.; Benthem, B.H. van; Natsch, S.S.; Hertogh, C.M.P.M.

    2012-01-01

    INTRODUCTION: The common occurrence of infectious diseases in nursing homes and residential care facilities may result in substantial antibiotic use, and consequently antibiotic resistance. Focusing on these settings, this article aims to provide a comprehensive overview of the literature available

  15. Antibiotic use and resistance in long term care facilities.

    NARCIS (Netherlands)

    Buul, L.W. van; Steen, J.T. van der; Veenhuizen, R.B.; Achterberg, W.P.; Schellevis, F.G.; Essink, R.T.G.M.; Benthem, B.H.B. van; Natsch, S.; Hertogh, C.M.P.M.

    2012-01-01

    Introduction: The common occurrence of infectious diseases in nursing homes and residential care facilities may result in substantial antibiotic use, and consequently antibiotic resistance. Focusing on these settings, this article aims to provide a comprehensive overview of the literature available

  16. 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 ...

  17. Antibiotic stewardship through the EU project "ABS International".

    Science.gov (United States)

    Allerberger, Franz; Frank, Annegret; Gareis, Roland

    2008-01-01

    The increasing problem of antimicrobial resistance requires implementation of antibiotic stewardship (ABS) programs. The project "ABS International--implementing antibiotic strategies for appropriate use of antibiotics in hospitals in member states of the European Union" was started in September 2006 in Austria, Belgium, the Czech Republic, Germany, Hungary, Italy, Poland, Slovenia and Slovakia. A training program for national ABS trainers was prepared and standard templates for ABS tools (antibiotic list, guides for antibiotic treatment and surgical prophylaxis, antibiotic-related organization) and valid process measures, as well as quality indicators for antibiotic use were developed. Specific ABS tools are being implemented in up to five healthcare facilities in each country. Although ABS International clearly focuses on healthcare institutions, future antimicrobial stewardship programs must also cover public education and antibiotic prescribing in primary care.

  18. Challenging the concept of bacteria subsisting on antibiotics.

    Science.gov (United States)

    Walsh, Fiona; Amyes, Sebastian G B; Duffy, Brion

    2013-06-01

    Antibiotic resistance concerns have been compounded by a report that soil bacteria can catabolise antibiotics, i.e. break down and use them as a sole carbon source. To date this has not been verified or reproduced, therefore in this study soil bacteria were screened to verify and reproduce this hypothesis. Survival in high concentrations of antibiotics was initially observed; however, on further analysis these bacteria either did not degrade the antibiotics or they used an intrinsic resistance mechanism (β-lactamases) to degrade the β-lactams, as demonstrated by high-performance liquid chromatography. These results did not verify or reproduce the hypothesis that bacteria subsist on antibiotics or catabolise antibiotics as previously reported. This study identified that bacteria with a catabolising phenotype did not degrade streptomycin or trimethoprim and therefore could not utilise the antibiotics as a nutrient source. Therefore, we conclude that soil bacteria do not catabolise antibiotics.

  19. 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....

  20. Antitumor effects of the combination of cholesterol reducing drugs.

    Science.gov (United States)

    Issat, Tadeusz; Nowis, Dominika; Bil, Jacek; Winiarska, Magdalena; Jakobisiak, Marek; Golab, Jakub

    2011-07-01

    There are a number of potential mechanisms linking cholesterol homeostasis to processes that are tightly linked with carcinogenesis. Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), the rate-limiting enzyme in the mevalonic acid synthesis pathway, exert cytostatic and cytotoxic effects towards tumor cells. It seems that the cytostatic and cytotoxic effects of statins result from blocking protein prenylation, leading to inhibition of isoprenoid compound synthesis. Another compound which affects cholesterol metabolism is the plant alkaloid berberine. The aim of this study was to investigate potential antitumor effects of lovastatin combined with berberine. Combined with berberine, lovastatin appeared to exert potentiated cytostatic and/or cytotoxic effects against human MDA-MB231 breast cancer and murine Panc 02 pancreatic cancer cells. The obtained results indicated that the effect of berberine is not dependent on blocking protein prenylation in cells, and the toxic effect of lovastatin combined with berberine is reversed by addition of the substrates of this pathway to the level brought out by lovastatin alone. Lovastatin-berberine combination caused cell cycle inhibition in G1 phase after 48 h of incubation with drugs. In a Panc 02 pancreatic cancer model in mice, lovastatin-berberine combination slightly, but significantly, slowed down tumor growth. Taking into account the number of patients treated with the investigated drugs one may suppose that the described interactions may be of clinical value.

  1. Pharmacokinetic evaluation and antitumor activity of 2-methoxyestradiol nanosuspension.

    Science.gov (United States)

    Du, Shuzhang; Zhu, Ling; Du, Bin; Shi, Xiufang; Zhang, Zhenzhong; Wang, Shuyu; Zhang, Chaofeng

    2012-04-01

    The aim of the present study was to evaluate the pharmacokinetic and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension relative to 2-ME solution both in vitro and in vivo. The pharmacokinetics of 2-ME administered either as a nanosuspension or as a solution were compared after I.V. administration to rats. In plasma, 2-ME nanosuspension exhibited a significantly (p nanosuspension could significantly enhance the cytotoxicity of 2-ME on EC9706 cells in vitro. After 72 h exposure, the IC(50) value of 2-ME nanosuspension was much lower than that of 2-ME solution (1.81 ± 0.15 μmol/L versus 4.14 ± 0.30 μmol/L). Studies on BALB/c mice with EC9706 solid tumors demonstrated significantly greater inhibition of tumor growth following treatment with 2-ME nanosuspension than 2-ME solution at the same dosage. These results suggest that the delivery of 2-ME nanosuspension is a promising approach for the treatment of tumors.

  2. In vitro and in vivo antitumor activity of oridonin nanosuspension.

    Science.gov (United States)

    Lou, Haiyan; Zhang, Xiumei; Gao, Lei; Feng, Feifei; Wang, Juying; Wei, Xinbing; Yu, Zongqin; Zhang, Dianrui; Zhang, Qiang

    2009-09-08

    The aim of the present study was to evaluate the antitumor activity of an oridonin (ORI) nanosuspension relative to ORI solution both in vitro and in vivo. ORI nanosuspension with a particle size of 897.2+/-14.2 nm was prepared by the high pressure homogenization method (HPH). MTT assay showed that ORI nanosuspension could significantly enhance the in vitro cytotoxicity against K562 cells compared to the ORI solution, the IC(50) value at 36 h was reduced from 12.85 micromol/L for ORI solution to 8.11 micromol/L for ORI nanosuspension. Flow cytometric analysis demonstrated that the ORI nanosuspension also induced a higher apoptotic rate in K562 cells compared to ORI solution. In vivo studies in a mouse model of sarcoma-180 solid tumors demonstrated significantly greater inhibition of tumor growth following treatment with ORI nanosuspension than ORI solution at the same dosage. The mice injected with ORI nanosuspension showed a higher reduction in tumor volume and tumor weight at the dose of 20mg/kg compared to the ORI solution (Pnanosuspension. Taken together, these results suggest that the delivery of ORI in nanosuspension is a promising approach for the treatment of the tumor.

  3. Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts

    Directory of Open Access Journals (Sweden)

    Betancur-Galvis LA

    1999-01-01

    Full Text Available Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity and antiherpetic activity. MTT (Tetrazolium blue and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2. The 50% cytotoxic concentration (CC50 and the 50% inhibitory concentration of the viral effect (EC50 for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x103mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50. These species are good candidates for further activity-monitored fractionation to identify active principles.

  4. [Procedure for determination of individual sensitivity to antitumor drugs].

    Science.gov (United States)

    Abduvaliev, A A; Gil'dieva, M S; Tatarskiĭ, V P

    2006-05-01

    The present paper proposes to employ the cultured tumor cells of the breast and chick fibroblasts after long-term cultivation (for above 24 days) to determine their individual drug sensitivity and, as a criterion of cell damage, to use the percent of destruction of the cell layer formed in the wells 24 hours after drug insertion. It also presents the comparative results of tests of 2 cellular models that have been used to determine the in vitro sensitivity of the cells of breast cancer and chick fibroblasts to melfalan and its complex compound with copper acetylacetonate - MOK*M. At the same time, the cytotoxic activity of MOK*M and melfalan against tumor cells has been not shown to differ greatly (16.02+/-1.85 and 15.71+/-0.65% cell layer destruction, respectively), but the same activity of MOK*M against the model of intact cells (chick fibroblasts) was much less (15.23+/-1.97%) than that of melfalan (95.39+/-1.11%). The test system proposed by the authors is of certain informative value and it may be used for the determination of the individual sensitivity of tumor cells to antitumor drugs.

  5. [Progress of anti-tumor study based on BRAF].

    Science.gov (United States)

    Yan, Gui-Rui; Xu, Zhi-Jian; Wang, He-Yao; Zhu, Wei-Liang

    2012-12-01

    BRAF is one of the most important pro-oncogenes, which is mutated in approximately 8% of human tumors. The most common BRAF mutation is a valine-to-glutamate transition (V600E) that is expressed primarily in melanoma, colorectal cancer and thyroid carcinoma. MEK/ERK is constitutively activated in the cells expressing BRAFV600E, leading to tumor development, invasion, and metastasis. Therefore, BRAFV600E is a therapeutic target for melanoma and some other BRAFV600E tumors. Vemurafenib, a BRAFV600E inhibitor, which was approved by FDA for the treatment of late-stage melanoma in 2011, produces improved rates of overall and progression-free survival in patients with the BRAFV600E mutation, making a dramatic breakthrough in melanoma treatment. Vemurafenib is also an individual target drug based on genetic diagnosis. However, its therapeutic success is limited by the emergence of drug resistance. Therefore, it is important to explore the mechanisms underlying the resistance for developing new inhibitor drugs and for preventing or delaying the resistance evolution to BRAF inhibitor drugs. In this review, we described the role of BRAFV600E as an anti-tumor drug target and the development of BRAF inhibitors. We also discussed the mechanisms leading to resistance of BRAFV600E inhibitors. Furthermore, therapeutic strategies that might be employed to overcome acquired resistance were proposed.

  6. Antitumor Lipids--Structure, Functions, and Medical Applications.

    Science.gov (United States)

    Kostadinova, Aneliya; Topouzova-Hristova, Tanya; Momchilova, Albena; Tzoneva, Rumiana; Berger, Martin R

    2015-01-01

    Cell proliferation and metastasis are considered hallmarks of tumor progression. Therefore, efforts have been made to develop novel anticancer drugs that inhibit both the proliferation and the motility of tumor cells. Synthetic antitumor lipids (ATLs), which are chemically divided into two main classes, comprise (i) alkylphospholipids (APLs) and (ii) alkylphosphocholines (APCs). They represent a new entity of drugs with distinct antiproliferative properties in tumor cells. These compounds do not interfere with the DNA or mitotic spindle apparatus of the cell, instead, they incorporate into cell membranes, where they accumulate and interfere with lipid metabolism and lipid-dependent signaling pathways. Recently, it has been shown that the most commonly studied APLs inhibit proliferation by inducing apoptosis in malignant cells while leaving normal cells unaffected and are potent sensitizers of conventional chemo- and radiotherapy, as well as of electrical field therapy. APLs resist catabolic degradation to a large extent, therefore accumulate in the cell and interfere with lipid-dependent survival signaling pathways, notably PI3K-Akt and Raf-Erk1/2, and de novo phospholipid biosynthesis. They are internalized in the cell membrane via raft domains and cause downstream reactions as inhibition of cell growth and migration, cell cycle arrest, actin stress fibers collapse, and apoptosis. This review summarizes the in vitro, in vivo, and clinical trials of most common ATLs and their mode of action at molecular and biochemical levels.

  7. Organo-platinum complexes as antitumor agents (review).

    Science.gov (United States)

    Hill, J M; Speer, R J

    1982-01-01

    Rosenberg et al discovered in the coordination complexes of platinum a new, novel type of potential antitumor agent. Cisplatin [cis-dichlorodiammine platinum (II)4 proved active against a variety of rodent tumors and acted synergistically when combined with other chemotherapeutic agents. Initial clinical tests by Hill et al in 1971, showed cisplatin to be active against malignant lymphoma, Hodgkin's disease, and certain other malignancies. Significant nephrotoxicity, nausea, and vomiting were noted. Since then, cisplatin has been tested alone and in combination chemotherapy and has proven an efficacious anticancer agent in squamous cell carcinoma of head and neck, ovarian carcinoma, disseminated testicular cancer, and others. Its therapeutic value was acknowledged when approved in 1978 by the U.S. FDA for treatment of the latter cancer. The current clinical literature indicates clearly that the full potential of this drug has not yet been realized. Hydration and diuresis have served to mitigate much of the nephrotoxicity, while significant strides toward amelioration of the nausea and vomiting have also been achieved. Literally, thousands of chemically-related congeners have been synthesized, and many have shown marked potency against rodent tumors. Very few, however, have been evaluated clinically, vis-a-vis malonato trans(-)-1,2-diaminocyclohexane platinum(II); this appears a most promising and fertile area of future investigation.

  8. 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.

  9. Mechanisms of selective antitumor action of cold atmospheric plasma

    Science.gov (United States)

    Graves, David; Bauer, Georg

    2016-09-01

    Transformed (precancerous) cells are known to be subject to elimination through intercellular RONS-dependent apoptosis-inducing signaling. It is a remarkable fact that the chemical species utilized by apoptosis induction in transformed cells are essentially identical to chemical species created by cold atmospheric plasma (CAP) in aqueous solutions. The association between CAP-induced biochemistry and natural cell anti-tumor mechanisms offers the opportunity to establish a rationale for the observed successes of CAP in selectively eliminating tumor cells in vitro and in vivo. In particular, 1O2 appears to act to selectively induce apoptosis in tumor cells, and can also result in self-perpetuating, cell-to-cell apoptotic signaling. Various CAP-generated liquid phase species can react to form 1O2, thus providing a hypothetical mechanism to explain how CAP can trigger therapeutic apoptosis in tumors. The analysis of model experiments performed with defined RONS in vitro implies that CAP-derived 1O2 induces the mechanism through which CAP acts selectively against cancer cells in vitro and tumors in vivo. This hypothesis needs to be tested experimentally in order to establish its validity.

  10. 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.

  11. Design and synthesis of modified quinolones as antitumoral acridones.

    Science.gov (United States)

    Tabarrini, O; Cecchetti, V; Fravolini, A; Nocentini, G; Barzi, A; Sabatini, S; Miao, H; Sissi, C

    1999-06-17

    The bacterial topoisomerase II (DNA gyrase) and the mammalian topoisomerase II represent the cellular targets for quinolone antibacterials and a wide variety of anticancer drugs, respectively. In view of the mechanistic similarities and sequence homologies exhibited by the two enzymes, tentative efforts to selectively shift from an antibacterial to an antitumoral activity was made by synthesizing a series of modified tricyclic quinolones, in which the essential 3-carboxylic function is surrogated by phenolic OH and the classic C-6 fluorine atom is replaced by a NH2 group. The resulting 7-amino-9-acridone derivatives were assayed for their antibacterial as well as cytotoxic activities. No antibacterial activity was found. On the other hand, many derivatives showed significant cytotoxic activity against both HL-60 and P388 leukemias and a wide panel of human and rodent solid tumor cells, derivatives 25 and 26 displaying the best overall antiproliferative activity. Against the LoVo cell line, derivative 25 exhibited higher cytotoxic effects than etoposide.

  12. 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

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

    OpenAIRE

    Raghunath, D.

    2008-01-01

    The antibiotic era started in the 1940s and changed the profi le 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 s...

  14. The world alliance against antibiotic resistance: consensus for a declaration.

    Science.gov (United States)

    Carlet, Jean

    2015-06-15

    Antibiotic resistance is increasing worldwide and has become a very important threat to public health. The overconsumption of antibiotics is the most important cause of this problem. We created a World Alliance Against Antibiotic Resistance (WAAAR), which now includes 720 people from 55 different countries and is supported by 145 medical societies or various groups. In June 2014, WAAAR launched a declaration against antibiotic resistance. This article describes the process and the content of this declaration.

  15. Evolutionary Rationale for Phages as Complements of Antibiotics.

    Science.gov (United States)

    Torres-Barceló, Clara; Hochberg, Michael E

    2016-04-01

    Antibiotic-resistant bacterial infections are a major concern to public health. Phage therapy has been proposed as a promising alternative to antibiotics, but an increasing number of studies suggest that both of these antimicrobial agents in combination are more effective in controlling pathogenic bacteria than either alone. We advocate the use of phages in combination with antibiotics and present the evolutionary basis for our claim. In addition, we identify compelling challenges for the realistic application of phage-antibiotic combined therapy.

  16. The role of aquatic ecosystems as reservoirs of antibiotic resistance.

    Science.gov (United States)

    Marti, Elisabet; Variatza, Eleni; Balcazar, Jose Luis

    2014-01-01

    Although antibiotic resistance has become a major threat to human health worldwide, this phenomenon has been largely overlooked in studies in environmental settings. Aquatic environments may provide an ideal setting for the acquisition and dissemination of antibiotic resistance, because they are frequently impacted by anthropogenic activities. This review focuses primarily on the emergence and dissemination of antibiotic resistance in the aquatic environment, with a special emphasis on the role of antibiotic resistance genes.

  17. REDUCTION OF ANTIBIOTIC RESISTANCE IN BACTERIA: A REVIEW

    OpenAIRE

    Suresh Jaiswal et al.

    2012-01-01

    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 resi...

  18. Persistence and resistance as complementary bacterial adaptations to antibiotics

    OpenAIRE

    Vogwill, T.; Comfort, A. C.; Furió, V.; MacLean, R. C.

    2016-01-01

    Abstract Bacterial persistence represents a simple of phenotypic heterogeneity, whereby a proportion of cells in an isogenic bacterial population can survive exposure to lethal stresses such as antibiotics. In contrast, genetically based antibiotic resistance allows for continued growth in the presence of antibiotics. It is unclear, however, whether resistance and persistence are complementary or alternative evolutionary adaptations to antibiotics. Here, we investigate the co‐evolution of res...

  19. [Sputum purulence: practical guide to introduce antibiotic therapy].

    Science.gov (United States)

    Egger, Micaela; Raetzo, Marc-Andrédre; Kherad, Omar

    2016-02-03

    In the collective unconscious of doctors and patients, purulent sputum is correlated with bacterial infection requiring antibiotics. The introduction of antibiotic therapy in a patient with purulent sputum is legitimate only in certain situations. The presence of purulent sputum during a mild infection of the upper airways does not generally justify the introduction of antibiotic treatment. In patients with chronic respiratory diseases, studies have shown that purulent sputum is often associated with a secondary bacterial infection and antibiotic therapy may provide clinical benefit.

  20. [Documentation of Antibiotic Stewardship (ABS)-interventions during proactive audit of antibiotic use].

    Science.gov (United States)

    Wilke, Katja; de With, Katja

    2015-01-01

    Proactive audit of antibiotic use ensures quality of prescribing and can improve outcome in patients with infections. A rational, individualized therapy is being defined in interdisciplinary cooperation on the basis of clinical, laboratory, radiological and microbiological examination findings. By fostering targeted antibiotic therapy proactive audit reduces adverse effects and contributes to drug therapy safety and subsequently to patient safety. A proactive audit of antibiotic use is performed weekly on four intensive care units at the University Hospital Dresden by a infectious disease specialist a pharmacist and the attending physicians. Patient-related therapy adjustments were systematically documented over a 4-month period; antibiotic use before and after audit as well as ABS strategies (de-escalation, oral switch, duration of treatment, dose and administration optimization) were analyzed. Both targeted therapy and interventions regarding the duration of treatment led to a reduction in the prescribing of broad spectrum antibiotics by 20%. Routine interdisciplinary proactive audit of antibiotic use with intervention and feedback increases guideline-adherent therapy and process quality.

  1. 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 pap...

  2. 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

  3. Addressing the Natural Antibiotic Resistome in Studies of Soil Resistance

    Science.gov (United States)

    The environment is recognized as a source and a reservoir of antibiotic resistance (AR). Many antibiotic compounds are derived from bacteria and fungi that are naturally present in the environment. These microbes carry genes encoding resistance to the antibiotic that they produce and their resistanc...

  4. 9 CFR 114.10 - Antibiotics as preservatives.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Antibiotics as preservatives. 114.10... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.10 Antibiotics as preservatives. Antibiotics are authorized for use...

  5. 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

  6. Quality indicators to measure appropriate antibiotic use in hospitalized adults

    NARCIS (Netherlands)

    Bosch, C.M.A. van den; Geerlings, S.E.; Natsch, S.S.; Prins, J.M.; Hulscher, M.

    2015-01-01

    BACKGROUND: An important requirement for an effective antibiotic stewardship program is the ability to measure appropriateness of antibiotic use. The aim of this study was to develop quality indicators (QIs) that can be used to measure appropriateness of antibiotic use in the treatment of all bacter

  7. Improving antibiotic use for complicated urinary tract infections

    NARCIS (Netherlands)

    V. Spoorenberg

    2014-01-01

    Guidelines for antimicrobial treatment are important in the process of improving antibiotic use, because they describe appropriate antibiotic use. In this thesis, we demonstrated the value of appropriate antibiotic use (i.e. guideline adherence) in patients with a complicated urinary tract infection

  8. Occurrence and reservoirs of antibiotic resistance genes in the environment

    NARCIS (Netherlands)

    Seveno, N.; Kallifidas, D.; Smalla, K.; Elsas, van J.D.; Collard, J.M.; Karagouni, A.; Wellington, E.M.H.

    2002-01-01

    Antibiotic resistance genes have become highly mobile since the development of antibiotic chemotherapy. A considerable body of evidence exists proving the link between antibiotic use and the significant increase in drug-resistant human bacterial pathogens. The application of molecular detection and

  9. Demonstrating Effectiveness of Antibiotics Against Known Bacteria Strains

    Science.gov (United States)

    Keefe, Lois M.

    1977-01-01

    Procedures are described for showing the effectiveness of antibiotics (penicillin, ampicillin, and tetracycline) against a nonpathogenic bacteria strain (Bacillus cereus). Methods are outlined for preparing nutrient agar, sterilizing tubes, pouring agar plates, preparing antibiotic discs, and transferring antibiotic discs to agar plates. (CS)

  10. 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

  11. Antibiotic resistance shaping multi-level population biology of bacteria.

    Science.gov (United States)

    Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

  12. 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...... 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....

  13. Bacteriocins - exploring alternatives to antibiotics in mastitis treatment.

    Science.gov (United States)

    Pieterse, Reneé; Todorov, Svetoslav D

    2010-07-01

    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.

  14. 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.

  15. Fate and effects of veterinary antibiotics in soil.

    Science.gov (United States)

    Jechalke, Sven; Heuer, Holger; Siemens, Jan; Amelung, Wulf; Smalla, Kornelia

    2014-09-01

    Large amounts of veterinary antibiotics are applied worldwide to farm animals and reach agricultural fields by manure fertilization, where they might lead to an increased abundance and transferability of antibiotic-resistance determinants. In this review we discuss recent advances, limitations, and research needs in determining the fate of veterinary antibiotics and resistant bacteria applied with manure to soil, and their effects on the structure and function of soil microbial communities in bulk soils and the rhizosphere. The increased abundance and mobilization of antibiotic-resistance genes (ARGs) might contribute to the emergence of multi-resistant human pathogens that increasingly threaten the successful antibiotic treatment of bacterial infections.

  16. The Synthesis and Antitumor Activity of Twelve Galloyl Glucosides

    Directory of Open Access Journals (Sweden)

    Chang-Wei Li

    2015-01-01

    Full Text Available Twelve galloyl glucosides 1–12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9, ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11 and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12, are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1, 1,4,6-tri-O-galloyl-β-D-glucopyranose (2, 1,2-di-O-galloyl-β-D-glucopyranose (3, 1,3-di-O-galloyl-β-D-glucopyranose (4, 1,2,3-tri-O-galloyl-α-D-glucopyranose (6 and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10, were synthesized for the first time in the present study. In in vitro MTT assay, 1–12 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50 values were determined to be varied in 17.2–124.7 μM on the tested three human cancer cell lines. In addition, compounds 1–12 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control.

  17. Potent and specific antitumor effect of CEA-targeted photoimmunotherapy.

    Science.gov (United States)

    Shirasu, Naoto; Yamada, Hiromi; Shibaguchi, Hirotomo; Kuroki, Motomu; Kuroki, Masahide

    2014-12-01

    Conventional photodynamic therapy (PDT) for cancer is limited by the insufficient efficacy and specificity of photosensitizers. We herein describe a highly effective and selective tumor-targeted PDT using a near-infrared (NIR) photosensitizer, IRDye700DX, conjugated to a human monoclonal antibody (Ab) specific for carcinoembryonic antigen (CEA). The antitumor effects of this Ab-assisted PDT, called photoimmunotherapy (PIT), were investigated in vitro and in vivo. The Ab-IRDye conjugate induced potent cytotoxicity against CEA-positive tumor cells after NIR-irradiation, whereas CEA-negative cells were not affected at all, even in the presence of excess photoimmunoconjugate. We found an equivalent phototoxicity and a predominant plasma membrane localization of Ab-IRDye after both one and six hours of incubation. Either no or little caspase activation and membrane peroxidation were observed in PIT-treated cells and a panel of scavengers for reactive oxygen species showed only partial inhibition of the phototoxic effect. Strikingly, Ab-IRDye retained significant phototoxicity even under hypoxia. We established a xenograft model, which allowed us to sensitively investigate the therapeutic efficacy of PIT by non-invasive bioluminescence imaging. Luciferase-expressing MKN-45-luc human gastric carcinoma cells were subcutaneously implanted into both flanks of nude mice. NIR-irradiation was performed for only the tumor on one side. In vivo imaging and measurement of the tumor size revealed that a single PIT treatment, with intraperitoneal administration of Ab-IRDye and subsequent NIR-irradiation, caused rapid cell death and significant inhibition of tumor growth, but only on the irradiated side. Together, these data suggest that Ab-IRDye-mediated PIT has great potential as an anticancer therapeutics targeting CEA-positive tumors.

  18. 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.

  19. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

    Science.gov (United States)

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy; Wang, Hua H

    2013-08-01

    This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

  20. [Review and categorization of quinolone antibiotics].

    Science.gov (United States)

    Benes, Jirí

    2005-02-01

    No standard categorization of quinolone antibiotics into generations may be found in either Czech or world literature. The author recommends a categorization into four groups defined according to their spectrum of action and utilization: 1) preparations for the treatment of urinary tract infections; 2) systemically acting quinolones chiefly efficacious against Gram-negative bacteria; 3) so-called respiratory quinolones; and 4) quinolones with a very broad spectrum of action suitable for the treatment of very complicated infections. The author describes the chief characteristics of the most important quinolone antibiotics, including preparations either in their development stage or whose development has been prematurely interrupted because of adverse side-effects. The list includes all preparations that are or were temporarily registered in the Czech Republic.

  1. [A case of pseudothrombocytopenia during antibiotic administration].

    Science.gov (United States)

    Kinoshita, Yoshimitsu; Yamane, Takahisa; Kamimoto, Akio; Oku, Hiroko; Iwata, Yasuhiro; Kobayashi, Toru; Hino, Masayuki

    2004-02-01

    A 70 year-old woman was prescribed of levofloxacin and ceftriaxone for acute bronchitis. On the seventh day of administration she was hospitalized with a dry cough and a decreased platelet count(2.1 x 10(4)/microliter). However, bleeding tendency was not seen. So, we changed anticoagulants with citric acid and heparin from EDTA, and measured platelet count because we suspected pseudothrombocytopenia(PTCP), then platelet count became elevated (respectively, 12.5 x 10(4)/microliter and 15.0 x 10(4)/microliter). In addition, platelet associated IgG increased to 309.3 ng/10(7) cells. Based on drug lymphocyte stimulation test, she was diagnosed as having antibiotic-induced PTCP, especially as she had no history of thrombocytopenia. PTCP should be considered when thrombocytopenia occurs during antibiotic treatment.

  2. [Antibiotic prophylaxis with cephalosporins in heart surgery].

    Science.gov (United States)

    Reichart, B; Klinner, W; Adam, D

    1981-08-13

    60 minutes after i.v. injection tissue levels of 7 different cephalosporins were obtained using biological assay. The following concentrations were measured: cephalothn 1.4 micrograms/g; cepharin 4.7 micrograms/g; cephacetrile 11.2 micrograms/g; cephradine 15.4 micrograms/g; cefazedone 26.9 micrograms/g; cefamandole 40.3 micrograms/g, and finally cefoxitin 43 micrograms/g. The high tissue levels of cefamandole and cefoxitin are especially remarkable as i.v. doses of both antibiotics had been 50 mg/kg body weight ( doses of all other cephalosporins 100 mg/kg body weight). Except cephalothin, all cephalosporins tested were suitable for antibiotic prophylaxis in cardiac surgery.

  3. [Macrotetrolide antibiotics from mycelia of Streptomyces chrysomallus].

    Science.gov (United States)

    Nefelova, M V; Sverdlova, A N; Egorov, N S

    1985-03-01

    White crystalline antibiotically active substances identified as macrotetrolides were isolated from the mycelium of four actinomycetous strains, i.e. S. chrysomallus var. I, S. chrysomallus var. III, S. chrysomallus var. carotenoides and S. chrysomallus var. macrotetrolidi. The component composition of the macrotetrolide antibiotics of all four strains was identical. It was characterized by predominance of nonactin, a lower homologue. The composition ratio was the following: 69-79 per cent of nonactin, 19-29 per cent of monactin, 1-3 per cent of dinactin and the traces of trinactin and tetranactin. The strains differed in the intensity of production of the macrotetrolides and the ability to synthesize other biologically active substances.

  4. Vancomycin Molecular Interactions: Antibiotic and Enantioselective Mechanisms

    Science.gov (United States)

    Ward, Timothy J.; Gilmore, Aprile; Ward, Karen; Vowell, Courtney

    Medical studies established that vancomycin and other related macrocyclic antibiotics have an enhanced antimicrobial activity when they are associated as dimers. The carbohydrate units attached to the vancomycin basket have an essential role in the dimerization reaction. Covalently synthesized dimers were found active against vancomycin-resistant bacterial strains. A great similarity between antibiotic potential and enantioselectivity was established. A covalent vancomycin dimer was studied in capillary electrophoresis producing excellent chiral separation of dansyl amino acids. Balhimycin is a macrocyclic glycopeptide structurally similar to vancomycin. The small differences are, however, responsible for drastic differences in enantioselectivity in the same experimental conditions. Contributions from studies examining vancomycin's mechanism for antimicrobial activity have substantially aided our understanding of its mechanism in chiral recognition.

  5. Improving shared decision-making in adolescents through antibiotic education.

    Science.gov (United States)

    Ngadimon, I W; Islahudin, F; Mohamed Shah, N; Md Hatah, E; Makmor-Bakry, M

    2017-02-01

    Background Shared decision-making is vital in achieving desired drug therapy goals, especially with antibiotics, in view of the potential long-term reduction in drug resistance. However, shared decision-making is rarely practiced with adolescent patients. Objectives The aim of the study was to identify the effect antibiotic education has on willingness to engage in shared decision-making among adolescents in Malaysia. Setting Participants from secondary schools in Malaysia were enrolled with ethical approval. Method The adolescents answered a validated questionnaire, which included demographics, antibiotic knowledge, attitude towards antibiotic use, and the Control Preference Scale, which measures willingness to engage in shared decision-making. Afterwards, antibiotic education was delivered to participating students. Main outcome measure Knowledge about and attitude toward antibiotics were investigated. Results A total of 510 adolescents participated in the study. Knowledge of antibiotics significantly increased post education (pre 3.2 ± 1.8 vs. post 6.8 ± 2.1, p decision-making post education (χ = 36.9, df = 2, p decision-making had a significantly higher total antibiotics knowledge and attitude scores compared to those who were not collaborative (p = 0.003). Conclusion The present work demonstrates that antibiotic education improves knowledge, attitude, and willingness to engage in shared decision-making among adolescents. Antibiotic education can therefore be introduced as a strategy to reduce inappropriate antibiotic use.

  6. Antibiotic resistance in bacteria from shrimp farming in mangrove areas.

    Science.gov (United States)

    Le, Tuan Xuan; Munekage, Yukihiro; Kato, Shin-ichiro

    2005-10-15

    Shrimp farming is a sufficiently large and mature industry to have an effective range of antimicrobial agents for most bacterial diseases in shrimp culture. However, at present, there exists great concern over the widespread use of antibiotics in aquaculture, which may result in residue of antibiotics in water and mud, and subsequently, the development of antibiotic resistance in bacteria in the environment. There is limited understanding about the effect of antibiotic residues on bacteria resistance in shrimp farming environment. Therefore, a study was conducted to investigate bacterial resistance to Norfloxacin (NFXC), Oxolinic Acid (OXLA), Trimethoprim (TMP) and Sulfamethoxazole (SMX), which were found in four shrimp farming locations in mangrove areas in Vietnam. Findings indicate that there is a relatively high incidence of bacteria resistance to these antibiotics observed in most of the studied sites, particularly to antibiotics with concentration of 0.1 microg/ml. Yet the relation between concentration of antibiotic residues and incidence of antibiotic resistance is not clearly defined. Among individual antibiotics, the incidence of resistance to TMP and SMX was higher than the others. Identification of bacteria isolated from mud samples by DNA analyzer shows that Bacillus and Vibrio are predominant among bacteria resistant to the antibiotics. The result of the study also indicates that these antibiotics in media degraded more rapidly due to the presence of resistant bacteria.

  7. Comparative antitumor and anti-proliferative activities ofHippophae rhamnoidesL. leaves extracts

    Institute of Scientific and Technical Information of China (English)

    Javid Ali; Bashir Ahmad

    2015-01-01

    Objective:To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform andn-hexane extracts ofHippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens) with three different concentrations of test samples (10, 100 and 1 000 mg/L). Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8%) was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated inn-hexane extract. The difference in tumor and cell inhibition (%) may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions:Our finding showed thatHippophae rhamnoidesleaves are a potent natural source of antitumor and antiproliferative agent.

  8. Paracetamol Supplementation Does Not Alter The Antitumor Activity and Lung Toxicity of Bleomycin

    Directory of Open Access Journals (Sweden)

    Ghada M. Suddek

    2014-01-01

    Full Text Available Bleomycin (BLM is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Hyperpyrexia following injection of BLM was reported thus, paracetamol is sometimes administered with BLM as antipyretic drug. Actually, paracetamol was found to interfere with cytotoxicity of some drugs. This study was conducted to investigate the effect of paracetamol administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma (EAC cells. Paracetamol did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-hydroxytryptamine (5-HT and increase in the contractility of tracheal smooth muscles induced by acetylcholine (ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in reduced glutathione (GSH level. Pretreatment with paracetamol did not significantly change lipid peroxidation, GSH level, percent survival of rats or the response of pulmonary arterial rings and tracheal smooth muscles to 5-HT and ACh respectively. The results of the present study indicated that paracetamol neither modified the antitumor effect of BLM nor changed drug-induced lung toxicity.

  9. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Zong Sheng eGuo

    2014-04-01

    Full Text Available Oncolytic viruses (OVs are novel immunotherapeutic agents whose anticancer effects come from both oncolysis and elicited antitumor immunity. OVs induce mostly immunogenic cancer cell death (ICD, including immunogenic apoptosis, necrosis/necroptosis, pyroptosis and autophagic cell death, leading to exposure of calreticulin and heat-shock proteins to the cell surface, and/or released ATP, high mobility group box-1 [HMGB1], uric acid, and other DAMPs as well as PAMPs as danger signals, along with tumor-associated antigens, to activate dendritic cells (DCs and elicit adaptive antitumor immunity. Dying the right way may greatly potentiate adaptive antitumor immunity. The mode of cancer cell death may be modulated by individual OVs and cancer cells as they often encode and express genes that inhibit/promote apoptosis, necroptosis or autophagic cell death. We can genetically engineer OVs with death-pathway-modulating genes and thus skew the infected cancer cells towards certain death pathways for the enhanced immunogenicity. Strategies combining with some standard therapeutic regimens may also change the immunological consequence of cancer cell death. In this review, we discuss recent advances in our understanding of danger signals, modes of cancer cell death induced by OVs, the induced danger signals and functions in eliciting subsequent antitumor immunity. We also discuss potential combination strategies to target cells into specific modes of ICD and enhance cancer immunogenicity, including blockade of immune checkpoints, in order to break immune tolerance, improve antitumor immunity and thus the overall therapeutic efficacy.

  10. 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.

  11. Lead optimization through VLAK protocol: new annelated pyrrolo-pyrimidine derivatives as antitumor agents.

    Science.gov (United States)

    Lauria, Antonino; Patella, Chiara; Abbate, Ilenia; Martorana, Annamaria; Almerico, Anna Maria

    2012-09-01

    The chemometric protocol VLAK was applied to predict improvement of the biological activity of pyrrolo-pyrimidine derivatives as anticancer agents, by using the NCI ACAM Database as depository of antitumor drugs with a known mechanism of action. Among the selected compounds two of these showed a good increase in the antitumor activity. These new pyrrolo-pyrimidine compounds were demonstrated effective against the full panels of NCI DTP tumour human cell lines. The derivative 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one reveled efficacious against the leukemia subpanel, in particular the RPMI cell line resulted the most sensitive (pGI(50) = 6.68). Moreover the derivative 7-(3-Chloropropyl)-9-methyl-5-(methylsulfanyl)-8-phenyl-3H-imidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-2(7H)-one showed a good antitumor activity against the leukemia subpanel with a low cytotoxic activity, above all against the HCT11 human tumour cell line. The VLAK protocol revealed a good method to design new molecules with good antitumor activity, starting from low active compounds. Moreover this protocol focused on the pyrrolo-pyrimidine derivatives as useful starting point for further development to obtain more potent antitumor agents.

  12. 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.

  13. 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.

  14. 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.

  15. Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

    Directory of Open Access Journals (Sweden)

    M Venkatesh

    2011-01-01

    Full Text Available Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20 th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.

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

    Science.gov (United States)

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

    2014-09-23

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

  17. Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives.

    Science.gov (United States)

    Venkatesh, M; Bairavi, V G; Sasikumar, K C

    2011-01-01

    Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20(th) century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today..

  18. 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.

  19. Sulfated fucan as support for antibiotic immobilization.

    Science.gov (United States)

    Araújo, P M; Oliveira, G B; Córdula, C R; Leite, E L; Carvalho Jr, L B; Silva, M P C

    2004-03-01

    Xylofucoglucuronan from Spatoglossum schröederi algae was tested as a support for antibiotic immobilization. The polysaccharide (20 mg in 6 ml) was first activated using carbodiimide, 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide methiodide (20 mg in 2 ml), under stirring for 1 h at 25 masculine C and pH from 4.5 to 5.0. After adjusting the pH to 8.0, either gentamicin or amikacin (62.5 mg in 1.25 ml) was then immobilized on this chemically modified polysaccharide with shaking for 24 h in a cold room. Infrared spectra of the activated carbodiimide xylofucoglucuronan showed two bands to carbonyl (C=O at 1647.9 and 1700.7 cm(-1)) and to amide (C-NH2) groups (1662.8 and 1714.0 cm(-1)). Microbial characterization of the derivatives was carried out by the disk diffusion method using Staphylococcus aureus or Klebsiella pneumoniae incorporated in Müller Hinton medium. Inhibition halos of bacterial growth were observed for the antibiotics immobilized on this sulfated heteropolysaccharide before and after dialysis. However, the halos resulting from the samples after dialysis were much smaller, suggesting that dialysis removed either non-covalently bound antibiotic or other small molecules. In contrast, bacterial growth was not inhibited by either xylofucoglucuronan or its activated form or by gentamicin or amikacin after dialysis. An additional experiment was carried out which demonstrated that the sulfated heteropolysaccharide was hydrolyzed by the microorganism. Therefore, the antibiotic immobilized on xylofucoglucuronan can be proposed as a controlled drug delivery system. Furthermore, this sulfated heteropolysaccharide can be extracted easily from sea algae Spatoglossum schröederi.

  20. 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.

  1. 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...

  2. Sulfated fucan as support for antibiotic immobilization

    Directory of Open Access Journals (Sweden)

    Araújo P.M.

    2004-01-01

    Full Text Available Xylofucoglucuronan from Spatoglossum schröederi algae was tested as a support for antibiotic immobilization. The polysaccharide (20 mg in 6 ml was first activated using carbodiimide, 1-ethyl-3-(3-dimethylamino-propylcarbodiimide methiodide (20 mg in 2 ml, under stirring for 1 h at 25ºC and pH from 4.5 to 5.0. After adjusting the pH to 8.0, either gentamicin or amikacin (62.5 mg in 1.25 ml was then immobilized on this chemically modified polysaccharide with shaking for 24 h in a cold room. Infrared spectra of the activated carbodiimide xylofucoglucuronan showed two bands to carbonyl (C = O at 1647.9 and 1700.7 cm-1 and to amide (CÝ-NH2 groups (1662.8 and 1714.0 cm-1. Microbial characterization of the derivatives was carried out by the disk diffusion method using Staphylococcus aureus or Klebsiella pneumoniae incorporated in Müller Hinton medium. Inhibition halos of bacterial growth were observed for the antibiotics immobilized on this sulfated heteropolysaccharide before and after dialysis. However, the halos resulting from the samples after dialysis were much smaller, suggesting that dialysis removed either non-covalently bound antibiotic or other small molecules. In contrast, bacterial growth was not inhibited by either xylofucoglucuronan or its activated form or by gentamicin or amikacin after dialysis. An additional experiment was carried out which demonstrated that the sulfated heteropolysaccharide was hydrolyzed by the microorganism. Therefore, the antibiotic immobilized on xylofucoglucuronan can be proposed as a controlled drug delivery system. Furthermore, this sulfated heteropolysaccharide can be extracted easily from sea algae Spatoglossum schröederi.

  3. 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

  4. New Capoamycin-Type Antibiotics and Polyene Acids from Marine Streptomyces fradiae PTZ0025

    Directory of Open Access Journals (Sweden)

    Zhizhen Zhang

    2012-10-01

    Full Text Available Capoamycin-type antibiotics (2–5 and polyene acids (6, 7 were isolated from marine Streptomyces fradiae strain PTZ0025. Their structures were established by extensive nuclear magnetic resonance (NMR and high resolution electron spray ionization mass spectroscopy (HRESIMS analyses and chemical degradation. Compounds 3, 4, 6, 7 were found to be new and named as fradimycins A (3 and B (4, and fradic acids A (6 and B (7. Compounds 3–5 showed in vitro antimicrobial activity against Staphylococcus aureus with a minimal inhibitory concentration (MIC of 2.0 to 6.0 μg/mL. Interestingly, Compounds 3–5 also significantly inhibited cell growth of colon cancer and glioma with IC50 values ranging from 0.13 to 6.46 μM. Fradimycin B (4, the most active compound, was further determined to arrest cell cycle and induce apoptosis in tumor cells. The results indicated that fradimycin B (4 arrested the cell cycle at the G0/G1 phase and induced apoptosis and necrosis in colon cancer and glioma cells. Taken together, the results demonstrated that the marine natural products 3–5, particularly fradimycin B (4, possessed potent antimicrobial and antitumor activities.

  5. Antibiotic therapy in impacted third molar surgery.

    Science.gov (United States)

    Monaco, G; Staffolani, C; Gatto, M R; Checchi, L

    1999-12-01

    The use of routine antibiotic therapy in patients undergoing surgical third molar extraction is controversial. The efficacy of antibiotic therapy in preventing postoperative complications following surgical third molar extractions was evaluated in 141 patients. In the test group (66 patients), the protocol utilized a regimen of 2 g of amoxicillin orally daily for 5 d postoperatively, starting at the completion of surgery. In the control group (75 patients), no antibiotic therapy was given. No significant difference was found between the test group and the control group in the incidence of postoperative sequelae, i.e. fever, pain, swelling and alveolar osteitis. A statistically significant association between smoking, habitual drinking and increased postoperative pain and fever was found. Patient age > or = 18 yr was positively correlated with an increased incidence of alveolar osteitis. Swelling was found to be gender-related, in that female patients experienced more swelling than male patients. No correlation was found between the time required for surgery or difficulty of extraction and post-operative pain. In conclusion, no difference was found between patients receiving postoperative amoxicillin and the control group in the incidence of postoperative sequelae.

  6. Ceftobiprole: a new beta-lactam antibiotic.

    Science.gov (United States)

    Stein, R A; Goetz, R M; Ganea, G M

    2009-06-01

    The increasing threat of antimicrobial resistance in general, and that of methicillin-resistant Staphylococcus aureus (MRSA) in particular, is raising significant medical, economical and public health challenges worldwide, both within hospitals and throughout the community. These considerations, along with the extensive time and costs associated with the development and approval of new therapeutic agents, represent some of the major reasons why understanding the advantages and limitations of new antibiotics, ensuring their judicious use and maximising their active shelf life should become global priorities. On March 18, 2008, the Food and Drug Administration issued an approvable letter for ceftobiprole, a broad-spectrum beta-lactam antibiotic active against MRSA and other clinically relevant Gram-positive and Gram-negative pathogens. Ceftobiprole is currently available only for parenteral administration, and besides its remarkable antimicrobial spectrum, this antibiotic possesses additional desirable characteristics, such as low propensity to select for resistance, efficacy in animal models of disease and good safety profile. Furthermore, in recently completed clinical trials, ceftobiprole demonstrated non-inferiority to comparator compounds such as vancomycin, and emerged as a promising clinical option of monotherapy for the treatment of complicated skin and skin structure infections and community-acquired pneumonia. Here, we discuss some of the most important clinically relevant findings on ceftobiprole obtained from in vitro studies, animal models of disease and recently completed phase III clinical trials.

  7. Synergism between maggot excretions and antibiotics.

    Science.gov (United States)

    Cazander, Gwendolyn; Pawiroredjo, Janity S; Vandenbroucke-Grauls, Christina M J E; Schreurs, Marco W J; Jukema, Gerrolt N

    2010-01-01

    Maggots are successfully used to treat severe, infected wounds. This study investigated whether maggot excretions/secretions influence the antibacterial activity of different antibiotics. Minimal inhibitory concentrations and minimal bactericidal concentrations (MBC) were determined of gentamicin and flucloxacillin for Staphylococcus aureus, of penicillin for Streptococcus pyogenes, of amoxicillin and vancomycin for Enterococcus faecalis, of gentamicin for Enterobacter cloacae, and of gentamicin, tobramycin, and ciprofloxacin for Pseudomonas aeruginosa by checkerboard titration. A range of concentrations of antibiotics in combination with excretions/secretions was examined to investigate the potential of maggot excretions/secretions to affect antibacterial activity. The results showed a dose-dependent increase of the antibacterial effect of gentamicin in the presence of excretions/secretions on S. aureus. Minimal concentrations and MBC of gentamicin decreased, respectively, 64- and 32-fold. The MBC of flucloxacillin and excretions/secretions against S. aureus were also decreased. The other antibiotic and excretions/secretions combinations exerted an indifferent effect. Excretions/secretions alone did not have any antibacterial effect. The synergism between gentamicin and maggot excretions/secretions could be of direct importance in clinical practice, because it could allow the use of lower doses of gentamicin and thus minimize the risk of gentamicin-related side effects.

  8. [Regulation of antibiotic biosynthesis in Streptomycetes].

    Science.gov (United States)

    Matseliukh, B P

    2006-01-01

    The review of literature presents the modern data about cascade regulation of antibiotic biosynthesis in Streptomycetes including basal and global levels. The first regulatory level is presented by related proteins of SARP family playing the role of positive transcription factors of pathway-specific genes of clusters of antibiotic biosynthesis. In their turn these regulatory genes are under the control of higher regulatory level represented by bldA- and A-factor-dependent cascade regulation and two-component signal transduction system (AfsK-AfsR, AbsAl-AbsA2, AfsQ1-AfsQ2 and others), consisting of sensor protein kinase and response regulator protein.Streptomycetes, in contrast to other microorganisms, have dozens of protein kinases and related regulator proteins that testifies to the great importance of protein phosphorylation in regulation of secondary metabolism and morphogenesis in cell response to internal and external signals. The role of camp, ppGpp and other proteins in regulation of antibiotic biosynthesis was also considered in this review.

  9. 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.

  10. Use of commercial organic fertilizer increases the abundance of antibiotic resistance genes and antibiotics in soil.

    Science.gov (United States)

    Zhou, Xue; Qiao, Min; Wang, Feng-Hua; Zhu, Yong-Guan

    2017-01-01

    The application of manure-based commercial organic fertilizers (COFs) is becoming increasingly extensive because of the expanding market for organic food. The present study examined the effects of repeated applications of chicken or swine manure-based COFs on the fate of antibiotics and antibiotic resistance genes (ARGs) in soil by conducting a soil microcosm experiment. Application of COFs significantly increased antibiotics residues, as well as the relative abundance of ARGs and the integrase gene of class 1 integrons (intΙ1) in soil. Two months after each application, antibiotics and ARGs dissipated in amended soils, but they still remained at an elevated level, compared with the control. And, the accumulation of antibiotics was found due to repeated COF applications. However, the relative abundance of ARGs in most COF-amended soils did not differ significantly between the first application and the repeated application. The results imply that 2 months are not sufficient for ARGs to approach background levels, and that animal manure must be treated more effectively prior to using it in agriculture ecosystems.

  11. Sensitivity and resistance of Legionella pneumophila to some antibiotics and combinations of antibiotics.

    Science.gov (United States)

    Moffie, B G; Mouton, R P

    1988-10-01

    For the treatment of Legionella pneumophila infections erythromycin and rifampicin are the antibiotics of choice. In view of reported therapy failures other antibiotics, e.g. the quinolones, are currently under investigation. The sensitivity of L. pneumophila to four antibiotics and to combinations of antibiotics was investigated and the rate of mutations was calculated. For 20 L. pneumophila strains we determined the MIC of rifampicin (0.002-0.004 mg/l), erythromycin (0.063-0.125 mg/l), norfloxacin (0.125 mg/l) and ciprofloxacin (0.016-0.032 mg/l). Mutation rates ranged from 1 x 10(-8) for ciprofloxacin to greater than 1 x 10(-7) for erythromycin, resulting in high-level resistance to rifampicin in most strains and erythromycin resistance in one strain, but not in resistance to the quinolones. The combination of erythromycin and rifampicin was synergistic (FIC index less than 0.5) against four of the L. pneumophila strains and showed indifference (FIC index 0.5-2.0) for the remainder (mean FIC index 0.79). Combinations of ciprofloxacin and erythromycin and of rifampicin and ciprofloxacin showed only indifference (mean FIC index respectively 1.05 and 1.21). Combining rifampicin with ciprofloxacin was not effective in reducing the number of mutants for either of these antibiotics, whereas the other combinations did prevent this.

  12. Antibiotic resistance: current issues and future strategies

    Directory of Open Access Journals (Sweden)

    Giancarlo Scarafile

    2016-09-01

    Full Text Available The antibiotic resistance (antimicrobial resistance – AMR and the particular emergence of multi-resistant bacterial strains, is a problem of clinical relevance involving serious threats to public health worldwide. From early this decade, a lot of studies have demonstrated a significant increase in the rates of antibiotic resistance by bacterial pathogens responsible for nosocomial and community infections all over the world. The AMR leads to a reduced drug efficacy in the treatment options available and therefore, to an increase in mortality rates. The original causes of the phenomenon are: environmental factors which favor a mutation of the genetic bacterial inheritance, thereby inhibiting the active ingredient of the antibiotics; unsuitable administering of antibiotics in veterinary, incorrect taking both in hospitals and at home and, lately, lack of investments in the development of new drugs. The alarming epidemiological data prompted the World Health Organization (WHO in 2011 to coin the slogan "No action today, no cure tomorrow" in order to immediately implement a new strategy to improve the use of available drugs and to accelerate the introduction of new ones through a new phase of research involving private and public institutions. The European Union has stressed that the surveillance is considered an essential factor for an effective response to this problem but it has also highlighted that the results produced have been lower than expectations because of serious shortcomings such as lack of methodological standards, insufficient data sharing and no coordination among European countries. In Italy the situation is much more troubling; in fact, according to the Ministry of Health, 5000-7000 yearly deaths are deemed due to nosocomial infections, with an annual cost of more than 100 million €.These figures explain how the fight against infections is far from being won. The purpose of this review is to analyze the basic causes of the

  13. 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

  14. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice

    Science.gov (United States)

    Barakat, Waleed; Elshazly, Shimaa M.; Mahmoud, Amr A. A.

    2015-01-01

    Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive. PMID:26366170

  15. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice

    Directory of Open Access Journals (Sweden)

    Waleed Barakat

    2015-01-01

    Full Text Available Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg. Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive.

  16. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice.

    Science.gov (United States)

    Barakat, Waleed; Elshazly, Shimaa M; Mahmoud, Amr A A

    2015-01-01

    Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive.

  17. ANTITUMOR AQCTIVITY OF REGIONAL ADMINISTRATION OF A-NK CELLS IN VIVO

    Institute of Scientific and Technical Information of China (English)

    GAO Jun; WANG Zhi-hua; ZHANG Zhi-bin; YANG Hong

    2006-01-01

    Objective: To observe the proliferation of A-NK in vitro and antitumor activity in vivo. Methods: The growth curve of A-NK and NA-NK cells was drawn in vitro. In the rat model, we compared the regional administration of A-NK-/IL-2 with the systemic administration. Results: The expansion of A-NK cells reached to climax on day 10 in the culture, increased 16.08 folds compared with the only 3.36 folds for NA-NK cells. In the rat model, we found that the regional administration of A-NK/IL-2 was better than systemic administration or administration of NA-NK/IL-2 not only in tumor infiltration and antitumor response, but also in the survival rate of rats (P<0.05). Conclusion: A-NK cells is a new immune effecter cells with high expansibility and high antitumor activity in vivo and in vitro.

  18. Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates.

    Science.gov (United States)

    Chudzinski-Tavassi, Ana Marisa; Morais, Katia L P; Pacheco, Mário Thiego Fernandes; Pasqualoto, Kerly Fernanda Mesquita; de Souza, Jean Gabriel

    2016-02-01

    Nowadays, the relationship between cancer blood coagulation is well established. Regarding biodiversity and bioprospection, the tick biology has become quite attractive natural source for coagulation inhibitors, since its saliva has a very rich variety of bioactive molecules. For instance, a Kunitz-type FXa inhibitor, named Amblyomin-X, was found through transcriptome of the salivary gland of the Amblyomma cajennense. tick. This TFPI-like inhibitor, after obtained as recombinant protein, has presented anticoagulant, antigionenic, and antitumor properties. Although its effects on blood coagulation could be relevant for antitumor effect, Amblyomin-X acts by non-hemostatic mechanisms, such as proteasome inhibition and autophagy inhibition. Notably, cytotoxicity was not observed on non-tumor cells treated with this protein, suggesting some selectivity for tumor cells. Considering the current efforts in order to develop effective anticancer therapies, the findings presented in this review strongly suggest Amblyomin-X as a promising novel antitumor drug candidate.

  19. Antitumor Effect of Water Decoctions of Taxus Cuspidate on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Chao Qu

    2014-01-01

    Full Text Available The Taxus cuspidate has been used as a traditional Chinese medicinal herb and considered to affect various physiological functions in the body for thousands of years. As we know that taxol isolated from the Taxus cuspidate has been approved for the treatment of ovarian cancer, it has also shown its antitumor abilities against other kinds of cancers. But the antitumor activity of other components which are free of paclitaxel and hydrophilic paclitaxel derivatives from Taxus cuspidate has not been fully understood. In this study, we investigated the effect of the water decoctions from the leaves of Taxus cuspidate on pancreatic cancer cell proliferation and the potential mechanism(s; though its antitumor activity and mechanism in vitro remain to be elucidated, the water soluble constituents from Taxus cuspidate could be used in clinical for cancer patients.

  20. Novel natural-product-like caged xanthones with improved druglike properties and in vivo antitumor potency.

    Science.gov (United States)

    Wu, Yue; Hu, Mingyang; Yang, Li; Li, Xiang; Bian, Jinlei; Jiang, Fen; Sun, Haopeng; You, Qidong; Zhang, Xiaojin

    2015-06-15

    DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo cytotoxic potency, a novel series of 19 prenyl group-modified derivatives of DDO-6101 was synthesized and evaluated for their in vitro antitumor activity and druglike properties. The SAR and SPR information of these compounds was also obtained. In the light of the in vitro antitumor activity and druglike properties such as aqueous solubility and permeability, compound 6f (named as DDO-6306) was advanced into in vivo efficacy experiment. The results showed that DDO-6306 is more potent than DDO-6101 in vivo and is a promising antitumor candidate for further evaluation.

  1. Design, synthesis and biological evaluation of new rhodacyanine analogues as potential antitumor agents

    Institute of Scientific and Technical Information of China (English)

    Yang Xiong Li; Xin Zhai; Wei Ke Liao; Wu Fu Zhu; Ying He; Ping Gong

    2012-01-01

    In an attempt to develop potent antitumor agents,new rhodacyanine analogues containing the pyridinium ring (5a-5h),the isoquinolinium ring (6a-6c) and the quinolinium ring (7a-7e) linked to the rhodanine ring via N-N covalent bond were designed,synthesized and evaluated for antitumor activity against human lung cancer cell line (H460) by MTT assay in vitro.Most of the tested compounds showed enhanced antitumor activity with IC50 values ranging from 0.006 to 9.2 μmol/L as compared to the lead compound MKT-077.Among them,the most promising compound 7d (IC50 =0.006 μmol/L) was 216.7 times more active than MKT-077 (IC50 =1.3 μmol/L).The preliminary structure-activity relationship of the target compounds was discussed.

  2. Enhancement of Antitumor Effect of Tegafur/Uracil (UFT) plus Leucovorin by Combined Treatment with Protein-Bound Polysaccharide, PSK, in Mouse Models

    Institute of Scientific and Technical Information of China (English)

    Ryoji Katoh; Mitsuru Ooshiro

    2007-01-01

    We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV)and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly.UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

  3. Use of the Malthus Microbial Growth Analyser to study the post antibiotic effect of antibiotics.

    Science.gov (United States)

    Gould, I M; Jason, A C; Milne, K

    1989-10-01

    The post antibiotic effect (PAE) of ceftazidime, ciprofloxacin, mecillinam and imipenem alone and in combination against Gram-negative bacteria was assessed by a new technique using a Malthus Microbial Growth Analyser. Ciprofloxacin gave the most prolonged and consistent PAE (1.3-2.9 h) and imipenem also gave a significant PAE against some bacterial strains (up to 1.3 h). The PAE of both antibiotics was dependent on concentration. The PAE of combinations of ciprofloxacin and imipenem often showed less PAE than was present with either agent alone. Ceftazidime gave no significant PAE (-1.5-0.4 h), though mecillinam consistently gave a short PAE (approximately 0.5 h) against Escherichia coli. The new method allows for the rapid and labour saving evaluation of PAE. We believe that further studies on PAE of antibiotic combinations are desirable.

  4. Antibiotic resistance in Enterobacteriaceae: what impact on the efficacy of antibiotic prophylaxis in colorectal surgery?

    Science.gov (United States)

    Kirby, A; Santoni, N

    2015-04-01

    Antibiotic prophylaxis, introduced in the 1940s, brought in an era of relatively safe colorectal surgery. This was achieved in part due to the prevention of surgical site infections (SSIs) caused by Enterobacteriaceae. Since then, Enterobacteriaceae have become increasingly resistant to the antibiotics commonly used for prophylaxis. The impact of being colonized preoperatively with resistant Enterobacteriaceae on the efficacy of colorectal SSI prophylaxis, if any, is unknown. It is also difficult to predict the likely impact of resistance as the exposure‒response relationships have not been determined for antibiotic surgical prophylaxis. Neither is it known which test for resistance to use; the importance of the concentration of Enterobacteriaceae in the colon, the ability of different species of Enterobacteriaceae to cause SSIs, and the comparative ability of minimum inhibitory concentration or presence of a resistance mechanism in predicting SSI risk have yet to be established. Clinical research is urgently needed to answer these questions.

  5. Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment

    DEFF Research Database (Denmark)

    Pruden, Amy; Larsson, D.G. Joakim; Amézquita, Alejandro

    2013-01-01

    determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial...... wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness...... of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little...

  6. Intermittent Metronomic Drug Schedule Is Essential for Activating Antitumor Innate Immunity and Tumor Xenograft Regression

    Directory of Open Access Journals (Sweden)

    Chong-Sheng Chen

    2014-01-01

    Full Text Available Metronomic chemotherapy using cyclophosphamide (CPA is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25% reduction in CPA dose. Moreover, an ~20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.

  7. Silencing invariant chains of dendritic cells enhances anti-tumor immunity using small-interfering RNA

    Institute of Scientific and Technical Information of China (English)

    KE Shan; CHEN Xue-hua; ZHU Zheng-gang; LI Jian-fang; YU Bei-qin; GU Qin-long; LIU Bing-ya

    2010-01-01

    Background Genetic modification of dendritic cells (DCs) has been used as an effective approach to enhance anti-tumor immunity. RNA interference (RNAi), which can cause the degradation of any RNA in a sequence-specific manner, is a post-transcriptional gene silencing mechanism. In this study, small-interfering RNA (siRNA) specific for the Ii gene was transfected into DCs, and the anti-tumor immunity of Ii-silenced DCs was assessed.Methods The silencing effect of siRNA was evaluated by Western blotting and real-time PCR analyses. In vitro cytotoxic activity of T cells was evaluated using a Cytotox 96(R) non-radioactive cytotoxicity assay kit. The time to tumor onset and the tumor volumes were used as reliable indices to assess the anti-tumor immunity in vivo. To further examine the mechanisms underlying the anti-tumor immunity, flow cytometry analysis was used.Results The Ii expression of DCs was significantly reduced after Ii siRNA transfection. Significant in vitro anti-tumor ability was exhibited when DCs were co-transfected with Ii siRNA plus endogenous tumor antigen (P <0.05). Furthermore,tumor growth was greatly inhibited when mice were immunized with DCs transfected with Ii siRNA plus tumor antigen prior to or subsequent to tumor implantation. Flow cytometry analysis in vitro and in vivo indicated that both CD4+ and CD8+ T cells were significantly activated in the Ii siRNA group (P <0.05).Conclusion Silencing of the Ii gene of DCs may offer a potential approach to enhance DC-based anti-tumor immunity.

  8. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

    Science.gov (United States)

    Demaria, Olivier; De Gassart, Aude; Coso, Sanja; Gestermann, Nicolas; Di Domizio, Jeremy; Flatz, Lukas; Gaide, Olivier; Michielin, Olivier; Hwu, Patrick; Petrova, Tatiana V; Martinon, Fabio; Modlin, Robert L; Speiser, Daniel E; Gilliet, Michel

    2015-12-15

    Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma.

  9. Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

    Science.gov (United States)

    Qi, Quan; Li, Rui; Li, Hui-ying; Cao, Yu-bing; Bai, Ming; Fan, Xiao-jing; Wang, Shu-yan; Zhang, Bo; Li, Shao

    2016-01-01

    Aim: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The anti-tumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results: The nuciferine target profile was enriched with signaling pathways and biological functions, including “regulation of lipase activity”, “response to nicotine” and “regulation of cell proliferation”. Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels. PMID:27180984

  10. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  11. Evaluation of cytotoxic and anti-tumor activity of partially purified serine protease isolate from the Indian earthworm Pheretima posthuma

    Directory of Open Access Journals (Sweden)

    Mahendra Kumar Verma

    2013-11-01

    Conclusions: Exact molecular mechanism of the cytotoxic and antitumor activities is yet to be explored and currently we are working on ultra-purification and biophysical characterization of this fraction. Further investigation into the mechanism(s of cytotoxic and antitumor activities at molecular level would be useful in treatment of various classes of cancer and viral infections in future.

  12. The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa Abdul-Hussein H; Krag, Aleksander; Olaison, Gunnar

    2013-01-01

    Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.......Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications....

  13. 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.

  14. [Use of antibiotics in a general hospital (author's transl)].

    Science.gov (United States)

    Escolar, A; Gómez, J; Andreo, J; García-Estany, J; Espi, F; Amorós, T

    1980-10-25

    The utilization of antibiotics at a general hospital has been assessed by retrospectively studying the clinical histories of all patients admitted during the month of April 1978 to the Residencia General de la Ciudad Sanitaria Virgen de la Arrixaca (Murcia, Spain). Medical records were reviewed according to a preestablished protocol. Out of 1.057 patients admitted antibiotics were used in 419 (46%), of whom 189 belonged to the medical services and 302 to the surgical ones. Overall, the surgical services utilized more antibiotics and had less bacteriologic data on their patients. Antibiotics more utilized were ampicillin, which use was generally correct, followed by gentamicin, the G-penicillins, and trimethoprim-sulfamethoxazol. Undesirable side-effects of antibiotic treatment were found in 13 cases (2,6%). Infectious disease of bacterial origin was correctly diagnosed in 40% of the cases, while the diagnosis was doubtful or incorrect in the remaining 60% of cases treated with antibiotics. Appropriate bacteriological data were obtained only in 164 cases (33,4%), with positive results in 75 (49,9%). Independent antibiotics were given in association in 157 cases (31,9%). From this study it can be concluded that the more frequent causes of improper antibiotic utilization were the incorrect clinical diagnosis of bacterial infectious disease, the prophylactic use of antibiotics and the scarcity of bacteriological data. It is therefore suggested that systems of supervision of in-hospital antibiotic prescription be updated and continuous education programs for hospital staff be instituted.

  15. Using Chemical Reaction Kinetics to Predict Optimal Antibiotic Treatment Strategies

    Science.gov (United States)

    Abel zur Wiesch, Pia; Cohen, Ted

    2017-01-01

    Identifying optimal dosing of antibiotics has proven challenging—some antibiotics are most effective when they are administered periodically at high doses, while others work best when minimizing concentration fluctuations. Mechanistic explanations for why antibiotics differ in their optimal dosing are lacking, limiting our ability to predict optimal therapy and leading to long and costly experiments. We use mathematical models that describe both bacterial growth and intracellular antibiotic-target binding to investigate the effects of fluctuating antibiotic concentrations on individual bacterial cells and bacterial populations. We show that physicochemical parameters, e.g. the rate of drug transmembrane diffusion and the antibiotic-target complex half-life are sufficient to explain which treatment strategy is most effective. If the drug-target complex dissociates rapidly, the antibiotic must be kept constantly at a concentration that prevents bacterial replication. If antibiotics cross bacterial cell envelopes slowly to reach their target, there is a delay in the onset of action that may be reduced by increasing initial antibiotic concentration. Finally, slow drug-target dissociation and slow diffusion out of cells act to prolong antibiotic effects, thereby allowing for less frequent dosing. Our model can be used as a tool in the rational design of treatment for bacterial infections. It is easily adaptable to other biological systems, e.g. HIV, malaria and cancer, where the effects of physiological fluctuations of drug concentration are also poorly understood. PMID:28060813

  16. Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized w...

  17. The application of antitumor drug-targeting models on liver cancer.

    Science.gov (United States)

    Yan, Yan; Chen, Ningbo; Wang, Yunbing; Wang, Ke

    2016-06-01

    Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.

  18. [Research advances of anti-tumor immune response induced by pulse electric field ablation].

    Science.gov (United States)

    Cui, Guang-ying; Diao, Hong-yan

    2015-11-01

    As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies.

  19. Purification, Characterization and Antitumor Activities of a New Protein from Syngnathus acus, an Officinal Marine Fish

    OpenAIRE

    Ying Peng; Fen He; Mengyue Wang; Chunfu Wu; Jingyu Yang; Yuxiao Nie; Xiaobo Li

    2011-01-01

    Discovery and development of new antitumor agents from abundant marine fish are attracting an increasing interest. In the present study, we extracted and purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus acus L., a precious marine fish traditionally used for tumors. Syngnathusin was comprised of 16 kinds of amino acids, mainly acidic amino acids. Its molecular weight was 67.3 kDa and its isoelectric point was 4.57. The N-terminal amino acid sequence of Syngnath...

  20. Antitumoral effects of vasoactive intestinal peptide in human renal cell carcinoma xenografts in athymic nude mice.

    Science.gov (United States)

    Vacas, Eva; Arenas, M Isabel; Muñoz-Moreno, Laura; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2013-08-01

    We studied antitumor effect of VIP in human renal cell carcinoma (RCC) (A498 cells xenografted in immunosuppressed mice). VIP-treated cells gave resulted in p53 upregulation and decreased nuclear β-catenin translocation and NFκB expression, MMP-2 and MMP-9 activities, VEGF levels and CD-34 expression. VIP led to a more differentiated tubular organization in tumours and less metastatic areas. Thus, VIP inhibits growth of A498-cell tumours acting on the major issues involved in RCC progression such as cell proliferation, microenvironment remodelling, tumour invasion, angiogenesis and metastatic ability. These antitumoral effects of VIP offer new therapeutical possibilities in RCC treatment.