Sample records for anticancer antibiotic daunomycin

  1. Distribution of anticancer antibiotic daunomycin in the rat heart and kidney revealed by immunocytochemistry using monoclonal antibodies

    DEFF Research Database (Denmark)

    Fujiwara, Kunio; Shin, Masashi; Hougaard, David M.


    Two monoclonal antibodies (ADM-1-11 and 79-31 mAbs) were raised against daunomycin (DM) conjugated to bovine serum albumin via the cross-linker N-(gamma-maleimidobutyryloxy)succinimide. The monoclonal antibodies (mAbs) specifically detected DM as well as its analogs doxorubicin and epirubicin......, but did not react with other anticancer antibiotics, including pepleomycin, mitomycin C, and actinomycin D. The mAbs reacted strongly with glutaraldehyde-conjugated DM in an enzyme linked immunosorbent assay (ELISA) used as a model system for immunocytochemistry as well as in appropriately pretreated...

  2. Affinity of anticancer drug, daunomycin, to core histones in solution:comparison of free and cross-linked proteins

    Institute of Scientific and Technical Information of China (English)



    Aim: The interaction of anthracyclinc anticancer drugs with chromatin, nuclco-somes and historic H1 has been extensively studied. In the present study, for the first time, we have investigated the binding of anthracycline antibiotic, daunomycin,to free and cross-linked thymus core histones (CL-core) in solution and in the absence of DNA. Methods: Fluorescence, UV/Vis spectroscopy and equilibrium dialysis techniques were used. Results: The UV spectroscopy results show that daunomycin induces hypochromicity in the absorption spectra of the core histones.Fluorescence emission intensity is decreased upon daunomycin binding and the process is concentration dependent. The equilibrium dialysis shows that the bind-ing is positive cooperative with the binding sites as Scatchard plot and Hill Coef-ficient confirm it. Conclusion: The results suggest that daunomycin shows much higher affinity to core histories free in solution than to CL-core, implying that the binding is most likely due to the accessibility of these proteins to the environment.It is suggested that daunomycin binds strongly to open state of histones, such as in tumor cells, rather than to their compact structure seen in normal chromatin.

  3. Anticancer, antioxidant and antibiotic activities of mushroom Ramaria flava. (United States)

    Liu, Kun; Wang, Junli; Zhao, Le; Wang, Qian


    Ramaria flava is a species of edible mushroom with some bioactivity. The anticancer, antioxidant and antibiotic activities and chemical composition of R. flava ethanol extract (EE) were evaluated. The present study exhibited that the EE displayed the strongest inhibitory activity against tumor cell MDA-MB-231 with an IC50 value of 66.54 μg/mL in three tested tumor cell lines, and the inhibition percent was 71.66% at the concentration of 200 μg/mL (MTT assay). The total phenolic compounds varied among four fractions of the EE from 6.66 to 61.01 mg gallic acid equivalent (GAE) per g dry weight. Water fraction exhibited high DPPH and OH radical-scavenging activities with low IC50 values of 5.86 and 18.08 μg/mL, respectively. Meanwhile, three phenolic compounds from water fraction were also identified by HPLC. The antibiotic activities of the EE were evaluated against three microorganisms and three fungi strains by means of the agar well diffusion method and the poisoned medium technique, respectively. The EE also showed moderate antibiotic activities. These results suggest that R. flava could hold a good potential source for human health.

  4. Daunomycin accumulation and induction of programmed cell death in rat hair follicles

    DEFF Research Database (Denmark)

    Shin, Masashi; Larsson, Lars-Inge; Hougaard, David M.


    The anthracycline antibiotic daunomycin (DM) is useful for the treatment of leukemia but has side-effects such as alopecia. Using immunocytochemistry, we show that, after a single i.v. injection, DM accumulates in the nuclei of matrix cells and in the outer root sheath of hair follicles. DM......-positive matrix cells are detectable up to 48 h after injection and exhibit a characteristic granular morphology, which is not observed in saline-injected controls. TUNEL-staining has revealed that DM injection induces programmed cell death (PCD) in rat hair follicles. Cells undergoing PCD are detectable as late...... (PCD type 2). Interestingly, little, if any, DM accumulation or apoptosis has been detected in the dermal hair papillae. This may have a bearing on potential regeneration of the hair follicles. Thus, DM accumulates in a characteristic pattern in hair follicles. This accumulation is associated...

  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


    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. Eradication of Biofilm-like Microcolony Structures of Borrelia burgdorferi by Daunomycin and Daptomycin but not Mitomycin C in Combination with Doxycycline and Cefuroxime

    Directory of Open Access Journals (Sweden)

    Jie eFeng


    Full Text Available Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. While the majority of Lyme disease patients can resolve their symptoms if treated promptly, 10-20% of patients suffer from prolonged symptoms called post-treatment Lyme disease syndrome (PTLDS. Although the cause for PTLDS is unclear, one possibility is the presence of bacterial persisters not effectively cleared by the current Lyme antibiotics. Recent studies identified several drug candidates including daptomycin, daunomycin, doxorubicin, and mitomycin C that had good activity against B. burgdorferi persisters. However, their relative activities against B. burgdorferi persisters have not been evaluated under the same conditions. In this study, we tested the anti-persister activities of these drugs against both 7-day and 15-day old stationary phase cultures of B. burgdorferi individually as well as in combination with Lyme antibiotics doxycycline and cefuroxime (Ceftin. Our findings demonstrate daunomycin and daptomycin were more active than mitomycin C in single drug comparison at 10 and 20 µM, as well as in drug combinations with doxycycline and cefuroxime. In addition, daunomycin was more active than doxorubicin which correlated with their ability to stain and accumulate in B. burgdorferi. The two drug combination of doxycycline and cefuroxime was unable to eradicate biofilm-like microcolonies of B. burgdorferi persisters. However, the addition of either daunomycin or daptomycin to the doxycycline + cefuroxime combination completely eradicated the biofilm-like structures and produced no visible bacterial regrowth after 7 days and 21 days, while the addition of doxorubicin was unable to prevent regrowth at either 7 day or 21 day subculture. Mitomycin C in combination with doxycycline and cefuroxime caused no regrowth at 7 days but visible spirochetal regrowth occurred after 21 day subculture. Furthermore, we found that

  7. Antibiotics (United States)

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

  8. Development of an Antigen-DNAzyme Based Probe for a Direct Antibody-Antigen Assay Using the Intrinsic DNAzyme Activity of a Daunomycin Aptamer

    Directory of Open Access Journals (Sweden)

    Noorsharmimi Omar


    Full Text Available G-Quadruplex (G-4 structures are formed when G-rich DNA sequences fold into intra- or intermolecular four-stranded structures in the presence of metal ions. G-4-hemin complexes are often effective peroxidase-mimicking DNAzymes that are applied in many detection systems. This work reports the application of a G-rich daunomycin-specific aptamer for the development of an antibody-antigen detection assay. We investigated the ability of the daunomycin aptamer to efficiently catalyze the hemin-dependent peroxidase activity independent of daunomycin. A reporter probe consisting of biotinylated antigen and daunomycin aptamer coupled to streptavidin gold nanoparticles was successfully used to generate a colorimetric readout. In conclusion, the daunomycin aptamer can function as a robust alternative DNAzyme for the development of colorimetric assays.

  9. Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work. (United States)

    Pang, Siu-Kwong


    Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to make a breakthrough, it was proposed that mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The mechanistically interpretable molecular descriptors used in this study include electrophilicity and the mathematical function in the London formula for dispersion interaction, and they were calculated using quantum chemical methods. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50, which were obtained by intraperitoneal injection into mice. The results reveal that the plots for electrophilicity, which can be interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represent the attraction between anthracyclines and biomolecules, can describe efflux from and influx into target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior. This structure-dependent toxicity behavior revealed in the plots can provide perspectives on design of anthracycline anticancer antibiotics.

  10. Synthesis of novel anthraquinones: Molecular structure, molecular chemical reactivity descriptors and interactions with DNA as antibiotic and anti-cancer drugs (United States)

    Al-Otaibi, Jamelah S.; EL Gogary, Tarek M.


    Anthraquinones are well-known anticancer drugs. Anthraquinones anticancer drugs carry out their cytotoxic activities through their interaction with DNA, and inhibition of topoisomerase II activity. Anthraquinones (AQ5 and AQ5H) were synthesized and studied with 1,5-DAAQ by computational and experimental tools. The purpose of this study is to shade more light on mechanism of interaction between anthraquinone DNA affinic agents and different types of DNA. This study will lead to gain of information useful for drug design and development. Molecular structures were optimized using DFT B3LYP/6-31 + G(d). Depending on intramolecular hydrogen bonding interactions four conformers of AQ5 were detected within the range of about 42 kcal/mol. Molecular reactivity of the anthraquinone compounds was explored using global and condensed descriptors (electrophilicity and Fukui functions). NMR and UV-VIS electronic absorption spectra of anthraquinones/DNA were investigated at the physiological pH. The interaction of the anthraquinones (AQ5 and AQ5H) were studied with different DNA namely, calf thymus DNA, (Poly[dA].Poly[dT]) and (Poly[dG].Poly[dC]). UV-VIS electronic absorption spectral data were employed to measure the affinity constants of drug/DNA binding using Scatchard analysis. NMR study confirms qualitatively the drug/DNA interaction in terms of peak shift and broadening.

  11. 2011~2013年南京市样本医院抗肿瘤抗生素应用现状和趋势分析%Status and Tendency of Anticancer Antibiotics from 2011 to 2013 in Nan-jing Sample Hospitals

    Institute of Scientific and Technical Information of China (English)

    彭苗苗; 方芸; 刘慧


    Objective: To comprehend the new therapeutic idea and way of using new drugs by estimating the using situation of anticancer antibiotics from 2011 to 2013 in 27 sample hospitals of Nanjing. Methods: With the method of defined daily dose (DDDs), the use of anticancer antibiotics was analyzed in respect of drug categories, consumption quantity, sales amount, DDDs and defined daily consumption (DDC), etc., from 2011 to 2013 in 27 sample hospitals. Results: The sales amount of anticancer antibiotics increased year by year, and the most commonly used drugs were antharcycline. The top four sales amounts were pharmorubicin, idarubicin, pirarubicin and adriamycin, the top four DDDs were pharmorubicin, pirarubicin, mitomycin and adriamycin. Most of the anticancer antibiotics sales amounts and the DDDs were concordant. Conclusion: The demand of anticancer antibiotics increased year by year. They have broad development prospects, especially antharcycline will become the leading anticancer antibiotics..%目的:评价南京地区27家样本医院2011~2013年抗肿瘤抗生素使用情况及特点,了解抗肿瘤抗生素治疗新理念和应用新药的新途径。方法:用限定日剂量法(DDDs)分析2011~2013年样本医院抗肿瘤抗生素应用的品种、数量、金额、日均用量数(DDDs)及日均费用(DDC)等情况。结果:抗肿瘤抗生素销售金额及销量逐年上升,最常用的是蒽环类抗肿瘤抗生素,已成为抗肿瘤抗生素的主体,销售金额排名前几位的药物主要是表柔比星、伊达比星、吡柔比星和阿霉素;DDDs排名前几位的药物主要是表柔比星、吡柔比星、丝裂霉素和阿霉素。大多数抗肿瘤抗生素的销量与使用同步性良好。结论:抗肿瘤抗生素的需求量逐年增加,尤其是蒽环类药物成为抗肿瘤抗生素的主流药物。

  12. A new daunomycin-peptide conjugate: synthesis, characterization and the effect on the protein expression profile of HL-60 cells in vitro. (United States)

    Orbán, Erika; Manea, Marilena; Marquadt, Andreas; Bánóczi, Zoltán; Csík, Gabriella; Fellinger, Erzsébet; Bosze, Szilvia; Hudecz, Ferenc


    Daunomycin (Dau) is a DNA-binding antineoplastic agent in the treatment of various types of cancer, such as osteosarcomas and acute myeloid leukemia. One approach to improve its selectivity and to decrease the side effects is the conjugation of Dau with oligopeptide carriers, which might alter the drug uptake and intracellular fate. Here, we report on the synthesis, characterization, and in vitro biological properties of a novel conjugate in which Dau is attached, via an oxime bond, to one of the cancer specific small peptides (LTVSPWY) selected from a random phage peptide library. The in vitro cytostatic effect and cellular uptake of Dau═Aoa-LTVSPWY-NH(2) conjugate were studied on various human cancer cell lines expressing different levels of ErbB2 receptor which could be targeted by the peptide. We found that the new daunomycin-peptide conjugate is highly cytostatic and could be taken up efficiently by the human cancer cells studied. However, the conjugate was less effective than the free drug itself. RP-HPLC data indicate that the conjugate is stable at least for 24 h in the pH 2.5-7.0 range of buffers, as well as in cell culture medium. The conjugate in the presence of rat liver lysosomal homogenate, as indicated by LC-MS analysis, could be degraded. The smallest, Dau-containing metabolite (Dau═Aoa-Leu-OH) identified and prepared expresses DNA-binding ability. In order to get insight on the potential mechanism of action, we compared the protein expression profile of HL-60 human leukemia cells after treatment with the free and peptide conjugated daunomycin. Proteomic analysis suggests that the expression of several proteins has been altered. This includes three proteins, whose expression was lower (tubulin β chain) or markedly higher (proliferating cell nuclear antigen and protein kinase C inhibitor protein 1) after administration of cells with Dau-conjugate vs free drug.

  13. Antibiotic Resistance (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 ...

  14. Antibiotic Safety (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 ...

  15. Antibiotics Quiz (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, ...

  16. Anticancer peptides from bacteria

    Directory of Open Access Journals (Sweden)

    Tomasz M. Karpiński


    Full Text Available Cancer is a leading cause of death in the world. The rapid development of medicine and pharmacology allows to create new and effective anticancer drugs. Among modern anticancer drugs are bacterial proteins. Until now has been shown anticancer activity among others azurin and exotoxin A from Pseudomonas aeruginosa, Pep27anal2 from Streptococcus pneumoniae, diphtheria toxin from Corynebacterium diphtheriae, and recently discovered Entap from Enterococcus sp. The study presents the current data regarding the properties, action and anticancer activity of listed peptides.

  17. Antibiotic Agents (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 ...

  18. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. (United States)

    Pommier, Yves; Leo, Elisabetta; Zhang, HongLiang; Marchand, Christophe


    DNA topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB topoisomerases (Top1), whereas human type IIA topoisomerases (Top2alpha and Top2beta) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors. We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes.

  19. Forgotten antibiotics

    DEFF Research Database (Denmark)

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


    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...

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

    Gewirtz, D A


    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. Anticancer properties of Monascus metabolites. (United States)

    Yang, Tao; Liu, Junwen; Luo, Feijun; Lin, Qinlu; Rosol, Thomas J; Deng, Xiyun


    This review provides up-to-date information on the anticancer properties of Monascus-fermented products. Topics covered include clinical evidence for the anticancer potential of Monascus metabolites, bioactive Monascus components with anticancer potential, mechanisms of the anticancer effects of Monascus metabolites, and existing problems as well as future perspectives. With the advancement of related fields, the development of novel anticancer Monascus food products and/or pharmaceuticals will be possible with the ultimate goal of decreasing the incidence and mortality of malignancies in humans.

  2. Antibiotic Resistance

    DEFF Research Database (Denmark)

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


    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....

  3. 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...

  4. Aerosolized Antibiotics. (United States)

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


    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.

  5. Engineer Novel Anticancer Bioagents (United States)


    selection (hence to create marker-free genetically modified organism – GMO as required by FDA regulations) have failed. The overall genetically modified organism – GMO , as required by FDA regulations). Key Research Status 1. Reconstitution of a complete FK228 biosynthetic...5 Food and Drug Administration (FDA) as a new class of anticancer drug for the treatment of 1 cutaneous T-cell lymphoma (CTCL) (1). FK228

  6. Sesterterpenoids with Anticancer Activity. (United States)

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert


    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review.

  7. Antibiotic-Associated Diarrhea (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 ...

  8. Geldanamycin and its anti-cancer activities. (United States)

    Fukuyo, Yayoi; Hunt, Clayton R; Horikoshi, Nobuo


    Geldanamycin is a benzoquinone ansamycin antibiotic that manifests anti-cancer activity through the inhibition of HSP90-chaperone function. The HSP90 molecular chaperone is expressed at high levels in a wide variety of human cancers including melanoma, leukemia, and cancers in colon, prostate, lung, and breast. In cancer cells dependent upon mutated and/or over-expressed oncogene proteins, HSP90 is thought to have a critical role in regulating the stability, folding, and activity of HSP90-associated proteins, so-called "client proteins". These client proteins include the growth-stimulating proteins and kinases that support malignant transformation. Recently, oncogenic activating BRAF mutants have been identified in variety of cancers where constitutive activation of the MEK/ERK MAPK signaling pathway is the key for tumorigenesis, and they have been shown to be client proteins for HSP90. Accordingly, HSP90 inhibition can suppress certain cancer-causing client proteins and therefore represents an important therapeutic target. The molecular mechanism underlying the anti-cancer effect of HSP90 inhibition is complicated. Geldanamycin and its derivatives have been shown to induce the depletion of mutationally-activated BRAF through several mechanisms. In this review, we will describe the HSP90-inhibitory mechanism, focusing on recent progress in understanding HSP90 chaperone structure-function relationships, the identification of new HSP90 client proteins and the development of HSP90 inhibitors for clinical applications.

  9. Melatonin Anticancer Effects: Review

    Directory of Open Access Journals (Sweden)

    Luigi Di Bella


    Full Text Available Melatonin (N-acetyl-5-methoxytryptamine, MLT, the main hormone produced by the pineal gland, not only regulates circadian rhythm, but also has antioxidant, anti-ageing and immunomodulatory properties. MLT plays an important role in blood composition, medullary dynamics, platelet genesis, vessel endothelia, and in platelet aggregation, leukocyte formula regulation and hemoglobin synthesis. Its significant atoxic, apoptotic, oncostatic, angiogenetic, differentiating and antiproliferative properties against all solid and liquid tumors have also been documented. Thanks, in fact, to its considerable functional versatility, MLT can exert both direct and indirect anticancer effects in factorial synergy with other differentiating, antiproliferative, immunomodulating and trophic molecules that form part of the anticancer treatment formulated by Luigi Di Bella (Di Bella Method, DBM: somatostatin, retinoids, ascorbic acid, vitamin D3, prolactin inhibitors, chondroitin-sulfate. The interaction between MLT and the DBM molecules counters the multiple processes that characterize the neoplastic phenotype (induction, promotion, progression and/or dissemination, tumoral mutation. All these particular characteristics suggest the use of MLT in oncological diseases.

  10. Facts about Antibiotic Resistance (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 ...

  11. Antibiotic / Antimicrobial Resistance Glossary (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. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T;


    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  13. Acupuncture as anticancer treatment? (United States)

    Kilian-Kita, Aneta; Püsküllüoglu, Mirosława; Krzemieniecki, Krzysztof


    The mystery of Traditional Chinese Medicine has been attracting people for years. Acupuncture, ranked among the most common services of Complementary and Alternative Medicine, has recently gained a lot of interest in the scientific world. Contemporary researchers have been continuously trying to shed light on its possible mechanism of action in human organism. Numerous studies pertaining to acupuncture’s application in cancer symptoms or treatment-related side effects management have already been published. Moreover, since the modern idea of acupuncture’s immunomodulating effect seems to be promising, scientists have propounded a concept of its potential application as part of direct anti-tumor therapy. In our previous study we summarized possible use of acupuncture in management of cancer symptoms and treatment-related ailments, such as chemotherapy-induced nausea and vomiting, pain, xerostomia, vasomotor symptoms, neutropenia, fatigue, anxiety, insomnia, lymphoedema after mastectomy and peripheral neuropathy. This article reviews the studies concerning acupuncture as a possible tool in modern anticancer treatment. PMID:28239282

  14. 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. (United States)

    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


    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.

  15. Anticancer Activity of Polyether Ionophore-Salinomycin. (United States)

    Antoszczak, Michał; Huczyński, Adam


    Since the discovery of unusual anti-tumor activity of natural polyether antibiotic - Salinomycin, this compound, along with its derivatives, has been intensively studied against different human cancer cells, both in vivo and in vitro. Salinomycin has shown strong inhibition activity against the proliferation process of many different cancer cells, including multi-drug resistance (MDR) cancer cells, as well as cancer stem cells (CSCs), i.e. leukemic stem cells, colon carcinoma stem cells, prostate cancer stem cells and many others. Additionally, the application of Salinomycin has been proved to enhance the anti-cancer effect of radio- and chemotherapy. Preliminary clinical studies have shown tumor regression and only transient acute side effects after application of Salinomycin. Up to now, major efforts have been devoted to elucidate the biological mechanisms of anti-tumor activity of Salinomycin and it is expected that the results may provide new therapeutic strategies based on biological modulation of Salinomycin activity. This review is focused on and describes the possible role of Salinomycin in cancer therapy and gives an overview of its properties.

  16. Anticancer activity of Amauroderma rude.

    Directory of Open Access Journals (Sweden)

    Chunwei Jiao

    Full Text Available More and more medicinal mushrooms have been widely used as a miraculous herb for health promotion, especially by cancer patients. Here we report screening thirteen mushrooms for anti-cancer cell activities in eleven different cell lines. Of the herbal products tested, we found that the extract of Amauroderma rude exerted the highest activity in killing most of these cancer cell lines. Amauroderma rude is a fungus belonging to the Ganodermataceae family. The Amauroderma genus contains approximately 30 species widespread throughout the tropical areas. Since the biological function of Amauroderma rude is unknown, we examined its anti-cancer effect on breast carcinoma cell lines. We compared the anti-cancer activity of Amauroderma rude and Ganoderma lucidum, the most well-known medicinal mushrooms with anti-cancer activity and found that Amauroderma rude had significantly higher activity in killing cancer cells than Ganoderma lucidum. We then examined the effect of Amauroderma rude on breast cancer cells and found that at low concentrations, Amauroderma rude could inhibit cancer cell survival and induce apoptosis. Treated cancer cells also formed fewer and smaller colonies than the untreated cells. When nude mice bearing tumors were injected with Amauroderma rude extract, the tumors grew at a slower rate than the control. Examination of these tumors revealed extensive cell death, decreased proliferation rate as stained by Ki67, and increased apoptosis as stained by TUNEL. Suppression of c-myc expression appeared to be associated with these effects. Taken together, Amauroderma rude represented a powerful medicinal mushroom with anti-cancer activities.

  17. Strengthening Control of Antibiotics

    Institute of Scientific and Technical Information of China (English)



    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,

  18. Know When Antibiotics Work

    Centers for Disease Control (CDC) Podcasts


    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.

  19. Systemic antibiotics in periodontics. (United States)

    Slots, Jørgen


    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.

  20. High Antibiotic Consumption

    DEFF Research Database (Denmark)

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


    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...

  1. Fungal metabolites with anticancer activity. (United States)

    Evidente, Antonio; Kornienko, Alexander; Cimmino, Alessio; Andolfi, Anna; Lefranc, Florence; Mathieu, Véronique; Kiss, Robert


    Covering: 1964 to 2013. Natural products from bacteria and plants have played a leading role in cancer drug discovery resulting in a large number of clinically useful agents. In contrast, the investigations of fungal metabolites and their derivatives have not led to a clinical cancer drug in spite of significant research efforts revealing a large number of fungi-derived natural products with promising anticancer activity. Many of these natural products have displayed notable in vitro growth-inhibitory properties in human cancer cell lines and select compounds have been demonstrated to provide therapeutic benefits in mouse models of human cancer. Many of these compounds are expected to enter human clinical trials in the near future. The present review discusses the reported sources, structures and biochemical studies aimed at the elucidation of the anticancer potential of these promising fungal metabolites.

  2. Anticancer molecular mechanisms of resveratrol

    Directory of Open Access Journals (Sweden)

    Elena Maria Varoni


    Full Text Available Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Despite it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to: extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin and developmental pathways; signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; immune-surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multi-drug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.

  3. Antibiotic resistance in Chlamydiae. (United States)

    Sandoz, Kelsi M; Rockey, Daniel D


    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.

  4. Anticancer and enhanced antimicrobial activity of biosynthesizd silver nanoparticles against clinical pathogens (United States)

    Rajeshkumar, Shanmugam; Malarkodi, Chelladurai; Vanaja, Mahendran; Annadurai, Gurusamy


    The present investigation shows the biosynthesis of eco-friendly silver nanoparticles using culture supernatant of Enterococcus sp. and study the effect of enhanced antimicrobial activity, anticancer activity against pathogenic bacteria, fungi and cancer cell lines. Silver nanoparticles was synthesized by adding 1 mM silver nitrate into the 100 ml of 24 h freshly prepared culture supernatant of Enterococcus sp. and were characterized by UV-vis spectroscopy, X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Selected Area Diffraction X-Ray (SAED), Energy Dispersive X Ray (EDX) and Fourier Transform Infra red Spectroscopy (FT-IR). The synthesized silver nanoparticles were impregnated with commercial antibiotics for evaluation of enhanced antimicrobial activity. Further these synthesized silver nanoparticles were assessed for its anticancer activity against cancer cell lines. In this study crystalline structured nanoparticles with spherical in the size ranges from 10 to 80 nm and it shows excellent enhanced antimicrobial activity than the commercial antibiotics. The in vitro assay of silver nanoparticles on anticancer have great potential to inhibit the cell viability. Amide linkages and carboxylate groups of proteins from Enterococcus sp. may bind with silver ions and convert into nanoparticles. The activities of commercial antibiotics were enhanced by coating silver nanoparticles shows significant improved antimicrobial activity. Silver nanoparticles have the great potential to inhibit the cell viability of liver cancer cells lines (HepG2) and lung cancer cell lines (A549).

  5. The Combination of Catechin and Epicatechin Gallate from Fructus Crataegi Potentiates β-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus (MRSA in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Jiang Zheng


    Full Text Available Fructus crataegi (hawthorn is the common name of all plant species in the genus Crataegus of the Rosaceae family. In the present study, three monomers of (+-catechin (C, (−-epicatechin gallate (ECg and (−-epigallocatechin (EGC were isolated from the hawthorn under the guide of antibacterial sensitization activity. The bioactivity of the composite fraction in enhancing the antibacterial effect of oxacillin against methicillin-resistant Staphylococcus aureus (MRSA was greater than that of the individual monomer of the hawthorn extract in vitro. Two-fold dilution and checkerboard methods were used to analyze antibacterial activity and screen for the combination and proportion of monomers with the best bioactivity. The result showed that C (128 mg/L combined with ECg (16 mg/L had the greatest effect and the combination also reduced the bacterial load in blood of septic mice challenged with a sublethal dose of MRSA, increased daunomycin accumulation within MRSA and down-regulated the mRNA expression of norA, norC and abcA, three important efflux pumps of MRSA. In summary, C and ECg enhanced the antibacterial effect of β-lactam antibiotics against MRSA in vitro and in vivo, which might be related to the increased accumulation of antibiotics within MRSA via suppression of important efflux pumps’ gene expression.

  6. Ribosomal Antibiotics: Contemporary Challenges

    Directory of Open Access Journals (Sweden)

    Tamar Auerbach-Nevo


    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.

  7. Heterocyclic chalcone analogues as potential anticancer agents. (United States)

    Sharma, Vikas; Kumar, Vipin; Kumar, Pradeep


    Chalcones, aromatic ketones and enones acting as the precursor for flavonoids such as Quercetin, are known for their anticancer effects. Although, parent chalcones consist of two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system, various synthetic compounds possessing heterocyclic rings like pyrazole, indole etc. are well known and proved to be effective anticancer agents. In addition to their use as anticancer agents in cancer cell lines, heterocyclic analogues are reported to be effective even against resistant cell lines. In this connection, we hereby highlight the potential of various heterocyclic chalcone analogues as anticancer agents with a brief summary about therapeutic potential of chalcones, mechanism of anticancer action of various chalcone analogues, and current and future prospects related to the chalcones-derived anticancer research. Furthermore, some key points regarding chalcone analogues have been reviewed by analyzing their medicinal properties.

  8. Antibiotics and Breastfeeding. (United States)

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


    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.

  9. Resistance to antibiotics



    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 ...

  10. Antibiotics: Miracle Drugs

    Centers for Disease Control (CDC) Podcasts


    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.

  11. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Steiner, Ulrich; Kollerova, Silvia; Jouvet, Lionel


    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....

  12. Saponins from Chinese Medicines as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Xiao-Huang Xu


    Full Text Available Saponins are glycosides with triterpenoid or spirostane aglycones that demonstrate various pharmacological effects against mammalian diseases. To promote the research and development of anticancer agents from saponins, this review focuses on the anticancer properties of several typical naturally derived triterpenoid saponins (ginsenosides and saikosaponins and steroid saponins (dioscin, polyphyllin, and timosaponin isolated from Chinese medicines. These saponins exhibit in vitro and in vivo anticancer effects, such as anti-proliferation, anti-metastasis, anti-angiogenesis, anti-multidrug resistance, and autophagy regulation actions. In addition, related signaling pathways and target proteins involved in the anticancer effects of saponins are also summarized in this work.

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

    NARCIS (Netherlands)

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


    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

  14. Replacement for antibiotics: Lysozyme (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 ...

  15. Antibiotic-Resistant Bacteria. (United States)

    Longenecker, Nevin E.; Oppenheimer, Dan


    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)

  16. Metagenomics and antibiotics. (United States)

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


    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.

  17. Antibiotic Resistance Questions and Answers (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 ...

  18. Advances in chalcones with anticancer activities. (United States)

    Karthikeyan, Chandrabose; Moorthy, Narayana S H Narayana; Ramasamy, Sakthivel; Vanam, Uma; Manivannan, Elangovan; Karunagaran, Devarajan; Trivedi, Piyush


    Chalcones are naturally occurring compounds exhibiting broad spectrum biological activities including anticancer activity through multiple mechanisms. Literature on anticancer chalcones highlights the employment of three pronged strategies, namely; structural manipulation of both aryl rings, replacement of aryl rings with heteroaryl scaffolds, molecular hybridization through conjugation with other pharmacologically interesting scaffolds for enhancement of anticancer properties. Methoxy substitutions on both the aryl rings (A and B) of the chalcones, depending upon their positions in the aryl rings appear to influence anticancer and other activities. Similarly, heterocyclic rings either as ring A or B in chalcones, also influence the anticancer activity shown by this class of compounds. Hybrid chalcones formulated by chemically linking chalcones to other prominent anticancer scaffolds such as pyrrol[2,1-c][1,4]benzodiazepines, benzothiazoles, imidazolones have demonstrated synergistic or additive pharmacological activities. The successful application of these three pronged strategies for discovering novel anticancer agents based on chalcone scaffold has resulted in many novel and chemically diverse chalcones with potential therapeutic application for many types of cancer. This review summarizes the concerted efforts expended on the design and development of anticancer chalcones recorded in recent literature and also provides an overview of the patents published in this area between 2007 and 2014 (WO2013022951, WO201201745 & US2012029489).

  19. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.


    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The major

  20. Antibiotic prophylaxis in otolaryngologic surgery

    Directory of Open Access Journals (Sweden)

    Ottoline, Ana Carolina Xavier


    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.

  1. Thiopeptide Antibiotics: Retrospective and Recent Advances

    Directory of Open Access Journals (Sweden)

    Xavier Just-Baringo


    Full Text Available Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.

  2. Anti-cancer Lead Molecule

    KAUST Repository

    Sagar, Sunil


    Derivatives of plumbagin can be selectively cytotoxic to breast cancer cells. Derivative `A` (Acetyl Plumbagin) has emerged as a lead molecule for testing against estrogen positive breast cancer and has shown low hepatotoxicity as well as overall lower toxicity in nude mice model. The toxicity of derivative `A` was determined to be even lower than vehicle control (ALT and AST markers). The possible mechanism of action identified based on the microarray experiments and pathway mapping shows that derivative `A` could be acting by altering the cholesterol-related mechanisms. The low toxicity profile of derivative `A` highlights its possible role\\'as future anti-cancer drug and/or as an adjuvant drug to reduce the toxicity of highly toxic chemotherapeutic\\'drugs

  3. The anticancer activity of propolis

    Directory of Open Access Journals (Sweden)

    Jacek Nikliński


    Full Text Available Propolis and its compounds have been the subject of many studies due to their antimicrobial and antiinflammatory activity; however, it is now known that they also possess antitumor properties. This review aims to summarize the results of studies on the mechanism of activity of propolis and its active compounds such as CAPE and chrysin in the apoptotic process, and their influence on the proliferation of cancer cells. Our review shows that propolis and its presented compounds induce apoptosis pathways in cancer cells. The antiproliferative effects of propolis, CAPE or chrysin in cancer cells are the result of the suppression of complexes of cyclins, as well as cell cycle arrest. The results of in vitro and in vivo studies suggest that propolis, CAPE and chrysin may inhibit tumor cell progression and may be useful as potential chemotherapeutic or chemopreventive anticancer drugs.

  4. [Anticancer propaganda: myth or reality?]. (United States)

    Demin, E V; Merabishvili, V M


    The authors raise a very important problem of anticancer propaganda aimed at the early detection of cancer to be solved nowadays by means of screening and constructive interaction between oncologists and the public. To increase the level of knowledge of the population in this area it is necessary to expand the range of its adequate awareness of tumor diseases. Only joint efforts can limit the destructive effect of cancer on people's minds, so that every person would be responsible for his own health, clearly understanding the advantages of early visit to a doctor. This once again highlights the need of educational work with the public, motivational nature of which allows strengthening the value of screening in the whole complex of measures to fight cancer.

  5. Bacteriocins as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Sukhraj eKaur


    Full Text Available Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have nonspecific toxicity towards normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity towards cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

  6. 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


    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

  7. In-vitro anticancer and antimicrobial activities of PLGA/silver nanofiber composites prepared by electrospinning. (United States)

    Almajhdi, Fahad N; Fouad, H; Khalil, Khalil Abdelrazek; Awad, Hanem M; Mohamed, Sahar H S; Elsarnagawy, T; Albarrag, Ahmed M; Al-Jassir, Fawzi F; Abdo, Hany S


    In the present work, a series of 0, 1 and 7 wt% silver nano-particles (Ag NPs) incorporated poly lactic-co-glycolic acid (PLGA) nano-fibers were synthesized by the electrospinning process. The PLGA/Ag nano-fibers sheets were characterized using SEM, TEM and DSC analyses. The three synthesized PLGA/silver nano-fiber composites were screened for anticancer activity against liver cancer cell line using MTT and LDH assays. The anticancer activity of PLGA nano-fibers showed a remarkable improvement due to increasing the concentration of the Ag NPs. In addition to the given result, PLGA nano-fibers did not show any cytotoxic effect. However, PLGA nano-fibers that contain 1 % nano silver showed anticancer activity of 8.8 %, through increasing the concentration of the nano silver to 7 % onto PLGA nano-fibers, the anticancer activity was enhanced to a 67.6 %. Furthermore, the antibacterial activities of these three nano-fibers, against the five bacteria strains namely; E.coli o157:H7 ATCC 51659, Staphylococcus aureus ATCC 13565, Bacillus cereus EMCC 1080, Listeria monocytogenes EMCC 1875 and Salmonella typhimurium ATCC25566 using the disc diffusion method, were evaluated. Sample with an enhanced inhibitory effect was PLGA/Ag NPs (7 %) which inhibited all strains (inhibition zone diameter 10 mm); PLGA/Ag NPs (1 %) sample inhibited only one strain (B. cereus) with zone diameter 8 mm. The PLGA nano-fiber sample has not shown any antimicrobial activity. Based on the anticancer as well as the antimicrobial results in this study, it can be postulated that: PLGA nanofibers containing 7 % nano silver are suitable as anticancer- and antibiotic-drug delivery systems, as they will increase the anticancer as well as the antibiotic drug potency without cytotoxicity effect on the normal cells. These findings also suggest that Ag NPs, of the size (5-10 nm) evaluated in the present study, are appropriate for therapeutic application from a safety standpoint.

  8. Fighting antibiotic resistance in the intensive care unit using antibiotics. (United States)

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


    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.

  9. Antibiotics for uncomplicated diverticulitis

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel M; Wille-Jørgensen, Peer


    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....

  10. Resistance-resistant antibiotics. (United States)

    Oldfield, Eric; Feng, Xinxin


    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.

  11. Plant antimicrobial peptides as potential anticancer agents. (United States)

    Guzmán-Rodríguez, Jaquelina Julia; Ochoa-Zarzosa, Alejandra; López-Gómez, Rodolfo; López-Meza, Joel E


    Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.

  12. Antibiotic Precautions in Athletes


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


    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...


    Directory of Open Access Journals (Sweden)

    Pandey Govind


    Full Text Available A great deal of pharmaceutical research has considerably improved the quality of herbal drugs used against various types of cancer. With the advanced knowledge of molecular science and the refinement in isolation and structure elucidation techniques, we are in a much better position now to identify various anticancer herbs. Scientists all over the world are concentrating on the use of herbs to boost immune system of the body against cancer. Scientists have contributed for a number of years to identify hundreds of anticancer herbs, and developed various herbal formulations from their active principles that inhibit growth and spread of cancer without any side effect. Such herbs possess anticancer, immunoenhancing, antiangiogenesis, antioxidant and antimutagenic properties. They inhibit growth and spread of cancer by modulating the activity of hormones, enzymes and other biological factors. The therapeutic effect of these herbs is executed by the complex synergistic interaction among their various active principles. Some important anticancer herbs have been discussed here.

  14. Novel anticancer agents from plant sources

    Institute of Scientific and Technical Information of China (English)

    Shah Unnati; Shah Ripal; Acharya Sanjeev; Acharya Niyati


    Plants remain an important source of new drugs,new drug leads and new chemical entities.Plant based drug discovery resulted mainly in the development of anticancer and anti-infectious agents,and continues to contribute to the new leads in clinical trials.Natural product drugs play a dominant role in pharmaceutical care.Several plant-derived compounds are currently successfully employed in cancer treatment.There are many classes of plant-derived cytotoxic natural products studied for further improvement and development of drugs.New anticancer drugs derived from research on plant antitumor agents will be continuously discovered.The basic aim of this review is to explore the potential of newly discovered anticancer compounds from medicinal plants,as a lead for anticancer drug development.It will be helpful to explore the medicinal value of plants and for new drug discovery from them for the researchers and scientists around the globe.

  15. Anticancer Properties of Capsaicin Against Human Cancer. (United States)

    Clark, Ruth; Lee, Seong-Ho


    There is persuasive epidemiological and experimental evidence that dietary phytochemicals have anticancer activity. Capsaicin is a bioactive phytochemical abundant in red and chili peppers. While the preponderance of the data strongly indicates significant anticancer benefits of capsaicin, more information to highlight molecular mechanisms of its action is required to improve our knowledge to be able to propose a potential therapeutic strategy for use of capsaicin against cancer. Capsaicin has been shown to alter the expression of several genes involved in cancer cell survival, growth arrest, angiogenesis and metastasis. Recently, many research groups, including ours, found that capsaicin targets multiple signaling pathways, oncogenes and tumor-suppressor genes in various types of cancer models. In this review article, we highlight multiple molecular targets responsible for the anticancer mechanism of capsaicin. In addition, we deal with the benefits of combinational use of capsaicin with other dietary or chemotherapeutic compounds, focusing on synergistic anticancer activities.

  16. Glutamic acid as anticancer agent: An overview. (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K


    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  17. Targeted anticancer therapy: overexpressed receptors and nanotechnology. (United States)

    Akhtar, Mohd Javed; Ahamed, Maqusood; Alhadlaq, Hisham A; Alrokayan, Salman A; Kumar, Sudhir


    Targeted delivery of anticancer drugs to cancer cells and tissues is a promising field due to its potential to spare unaffected cells and tissues, but it has been a major challenge to achieve success in these therapeutic approaches. Several innovative approaches to targeted drug delivery have been devised based on available knowledge in cancer biology and on technological advancements. To achieve the desired selectivity of drug delivery, nanotechnology has enabled researchers to design nanoparticles (NPs) to incorporate anticancer drugs and act as nanocarriers. Recently, many receptor molecules known to be overexpressed in cancer have been explored as docking sites for the targeting of anticancer drugs. In principle, anticancer drugs can be concentrated specifically in cancer cells and tissues by conjugating drug-containing nanocarriers with ligands against these receptors. Several mechanisms can be employed to induce triggered drug release in response to either endogenous trigger or exogenous trigger so that the anticancer drug is only released upon reaching and preferentially accumulating in the tumor tissue. This review focuses on overexpressed receptors exploited in targeting drugs to cancerous tissues and the tumor microenvironment. We briefly evaluate the structure and function of these receptor molecules, emphasizing the elegant mechanisms by which certain characteristics of cancer can be exploited in cancer treatment. After this discussion of receptors, we review their respective ligands and then the anticancer drugs delivered by nanotechnology in preclinical models of cancer. Ligand-functionalized nanocarriers have delivered significantly higher amounts of anticancer drugs in many in vitro and in vivo models of cancer compared to cancer models lacking such receptors or drug carrying nanocarriers devoid of ligand. This increased concentration of anticancer drug in the tumor site enabled by nanotechnology could have a major impact on the efficiency of cancer

  18. Modulation of anticancer drug toxicity by solcoseryl. (United States)

    Sołtysiak-Pawluczuk, D; Jedrych, A; Jastrzebski, Z; Czyzewska-Szafran, H; Danysz, A


    The studies of the effect of solcoseryl on toxicity of selected anticancer drugs were performed in mice. The observed differential influence of solcoseryl was dependent on the type of anticancer drug as well as on the schedule of solcoseryl administration. The protective effect of the biostimulator was noticed exclusively against 5-FU toxicity. The results of our studies could provide possible implications for therapeutic approach.

  19. Serendipity in anticancer drug discovery. (United States)

    Hargrave-Thomas, Emily; Yu, Bo; Reynisson, Jóhannes


    It was found that the discovery of 5.8% (84/1437) of all drugs on the market involved serendipity. Of these drugs, 31 (2.2%) were discovered following an incident in the laboratory and 53 (3.7%) were discovered in a clinical setting. In addition, 263 (18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1% (347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2% (31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind.

  20. Oncolytic viruses as anticancer vaccines

    Directory of Open Access Journals (Sweden)

    Norman eWoller


    Full Text Available Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

  1. Antibiotics after rattlesnake envenomation. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Saswati eSengupta


    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

  3. Cathelicidins: peptides with antimicrobial, immunomodulatory, anti-inflammatory, angiogenic, anticancer and procancer activities. (United States)

    Wong, Jack Ho; Ye, Xiu Juan; Ng, Tzi Bun


    The family of peptides designated as cathelicidins was identified over a decade ago. Cathelicidins have since gained increasing recognition, both as endogenous antibiotics and as effector molecules of the innate immune system. The human cathelicidin LL-37 is widely expressed in human tissues and plays diverse biological roles. It contributes substantially to host defense and impacts multiple aspects of immunity. In view of the escalating importance of cathelicidins, the activities of LL-37 with an emphasis on antimicrobial, immunomodulatory, anti-inflammatory, angiogenic, anticancer and procancer effects are discussed in this review article.

  4. Tetracycline Antibiotics and Resistance. (United States)

    Grossman, Trudy H


    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.

  5. Overdosing on Antibiotics

    Institute of Scientific and Technical Information of China (English)


    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.

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

  7. Suppression of antibiotic resistance acquisition by combined use of antibiotics. (United States)

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara


    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.

  8. Antibiotic resistance in Salmonella

    NARCIS (Netherlands)

    Vo, A.T.T.


    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

  9. Mission Critical: Preventing Antibiotic Resistance (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 ...

  10. Antibiotic-Resistant Gonorrhea (ARG) (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 ...

  11. Antibiotics and Pregnancy: What's Safe? (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: ...

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

    DEFF Research Database (Denmark)

    Leibovici, Leonard; Paul, Mical; Garner, Paul


    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...

  13. Antibiotic prevention of postcataract endophthalmitis

    DEFF Research Database (Denmark)

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


    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....

  14. Investigating the Antibiotic Resistance Problem. (United States)

    Lawson, Michael; Lawson, Amy L.


    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)

  15. Anticancer activity of Carica papaya: a review. (United States)

    Nguyen, Thao T T; Shaw, Paul N; Parat, Marie-Odile; Hewavitharana, Amitha K


    Carica papaya is widely cultivated in tropical and subtropical countries and is used as food as well as traditional medicine to treat a range of diseases. Increasing anecdotal reports of its effects in cancer treatment and prevention, with many successful cases, have warranted that these pharmacological properties be scientifically validated. A bibliographic search was conducted using the key words "papaya", "anticancer", and "antitumor" along with cross-referencing. No clinical or animal cancer studies were identified and only seven in vitro cell-culture-based studies were reported; these indicate that C. papaya extracts may alter the growth of several types of cancer cell lines. However, many studies focused on specific compounds in papaya and reported bioactivity including anticancer effects. This review summarizes the results of extract-based or specific compound-based investigations and emphasizes the aspects that warrant future research to explore the bioactives in C. papaya for their anticancer activities.

  16. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry). (United States)

    Zhao, Tiejun; Sun, Qiang; Marques, Maud; Witcher, Michael


    There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

  17. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry

    Directory of Open Access Journals (Sweden)

    Tiejun Zhao


    Full Text Available There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Phyllanthus emblica can account for some of the anticancer activity, but clearly other mechanisms are equally important. Herein, we provide a brief overview of the evidence supporting anticancer activity of Indian Gooseberry extracts, suggest possible mechanisms for these actions, and provide future directions that might be taken to translate these findings clinically.

  18. When and How to Take Antibiotics (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 ...

  19. Selection of antibiotic resistance at very low antibiotic concentrations. (United States)

    Sandegren, Linus


    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.

  20. 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)


    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.

  1. Studies with Myrtus communis L.: Anticancer properties. (United States)

    Ogur, Recai


    Myrtus communis (MC) L. is a well-known Mediterranean plant with important cultural significance in this region. In ancient times, MC was accepted as a symbol of immortality. Maybe due to this belief, it is used during cemetery visits in some regions. Although it is a well-known plant in cosmetics, and there is a lot of studies about its different medical properties, anticancer studies performed using its different extracts or oils are not so much, but increasing. We collected these anticancer property-related studies in this review.

  2. Magnetic polymer nanospheres for anticancer drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    JurIkova, A; Csach, K; Koneracka, M; Zavisova, V; Tomasovicova, N; Lancz, G; Kopcansky, P; Timko, M; Miskuf, J [Institute of Experimental Physics, Slovak Academy of Sciences, 040 01 Kosice (Slovakia); Muckova, M, E-mail: akasard@saske.s [Hameln rds a.s., 900 01 Modra (Slovakia)


    Poly(D,L-lactide-co-glycolide) polymer (PLGA) nanospheres loaded with biocom-patible magnetic fluid as a magnetic carrier and anticancer drug Taxol were prepared by the modified nanoprecipitation method with size of 200-250 nm in diameter. The PLGA polymer was utilized as a capsulation material due to its biodegradability and biocompatibility. Taxol as an important anticancer drug was chosen for its significant role against a wide range of tumours. Thermal properties of the drug-polymer system were characterized using thermal analysis methods. It was determined the solubility of Taxol in PLGA nanospheres. Magnetic properties investigated using SQUID magnetometry showed superparamagnetism of the prepared magnetic polymer nanospheres.

  3. Molecular mechanisms of antibiotic resistance. (United States)

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


    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.

  4. Synthesis of (-)-arctigenin derivatives and their anticancer activity. (United States)

    Gui-Rong, Chen; Li-Ping, Cai; De-Qiang, Dou; Ting-Guo, Kang; Hong-Fu, Li; Fu-Rui, Li; Ning, Jiang


    The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin, which was prepared from fructus arctii, showed obvious anticancer activity. The synthesis of four new (-)-arctigenin derivatives and their anticancer bioactivities were examined. The structures of the four new synthetic derivatives were elucidated.

  5. Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction. (United States)

    Chai, Feng; Abdelkarim, Mohamed; Laurent, Thomas; Tabary, Nicolas; Degoutin, Stephanie; Simon, Nicolas; Peters, Fabian; Blanchemain, Nicolas; Martel, Bernard; Hildebrand, Hartmut F


    The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).

  6. Reviving old antibiotics. (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


    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.

  7. 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...

  8. Methods for predicting anti-cancer response

    DEFF Research Database (Denmark)


    The present invention relates to methods for predicting response of a cancer in a subject to anti-cancer therapies based upon a determination and analysis of a chromosomal aberration score, such as the number of allelic imbalance or the number of telomeric allelic imbalance in the chromosomes...

  9. Cell death signaling and anticancer therapy

    Directory of Open Access Journals (Sweden)

    Lorenzo eGalluzzi


    Full Text Available For a long time, it was commonly believed that efficient anticancer regimens would either trigger the apoptotic demise of tumor cells or induce a permanent arrest in the G1 phase of the cell cycle, i.e., senescence. The recent discovery that necrosis can occur in a regulated fashion and the increasingly more precise characterization of the underlying molecular mechanisms have raised great interest, as non-apoptotic pathways might be instrumental to circumvent the resistance of cancer cells to conventional, pro-apoptotic therapeutic regimens. Moreover, it has been shown that some anticancer regimens engage lethal signaling cascades that can ignite multiple oncosuppressive mechanisms, including apoptosis, necrosis and senescence. Among these signaling pathways is mitotic catastrophe, whose role as a bona fide cell death mechanism has recently been reconsidered. Thus, anticancer regimens get ever more sophisticated, and often distinct strategies are combined to maximize efficacy and minimize side effects. In this review, we will discuss the importance of apoptosis, necrosis and mitotic catastrophe in the response of tumor cells to the most common clinically employed and experimental anticancer agents.

  10. Addressing resistance to antibiotics in systematic reviews of antibiotic interventions. (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


    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.

  11. Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo.

    Directory of Open Access Journals (Sweden)

    Yang Xu

    Full Text Available BACKGROUND: To mitigate the cardiotoxicity of anthracycline antibiotics without compromising their anticancer activities is still an issue to be solved. We previously demonstrated that schisandrin B (Sch B could protect against doxorubicin (Dox-induced acute cardiotoxicity via enhancing cardiomyocytic glutathione redox cycling that could attenuate oxidative stress generated from Dox. In this study, we attempted to prove if Sch B could also protect against Dox-induced chronic cardiotoxicity, a more clinically relevant issue, without compromising its anticancer activity. METHODOLOGY: Rat was given intragastrically either vehicle or Sch B (50 mg/kg two hours prior to i.p. Dox (2.5 mg/kg weekly over a 5-week period with a cumulative dose of Dox 12.5 mg/kg. At the 6th and 12th week after last dosing, rats were subjected to cardiac function measurement, and left ventricles were processed for histological and ultrastructural examination. Dox anticancer activity enhanced by Sch B was evaluated by growth inhibition of 4T1, a breast cancer cell line, and S180, a sarcoma cell line, in vitro and in vivo. PRINCIPAL FINDINGS: Pretreatment with Sch B significantly attenuated Dox-induced loss of cardiac function and damage of cardiomyocytic structure. Sch B substantially enhanced Dox cytotoxicities toward S180 in vitro and in vivo in mice, and increased Dox cytotoxcity against 4T1 in vitro. Although we did not observe this enhancement against the implanted 4T1 primary tumor, the spontaneous metastasis to lung was significantly reduced in combined treatment group than Dox alone group. CONCLUSION: Sch B is capable of protecting Dox-induced chronic cardiotoxicity and enhancing its anticancer activity. To the best of our knowledge, Sch B is the only molecule ever proved to function as a cardioprotective agent as well as a chemotherapeutic sensitizer, which is potentially applicable for cancer treatment.

  12. Antibiotics for acute maxillary sinusitis

    DEFF Research Database (Denmark)

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


    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


    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. Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans. (United States)

    Friedman, Mendel


    More than 2000 species of edible and/or medicinal mushrooms have been identified to date, many of which are widely consumed, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the mushrooms, including polysaccharides. Although β-glucans (homopolysaccharides) are believed to be the major bioactive polysaccharides of mushrooms, other types of mushroom polysaccharides (heteropolysaccharides) also possess biological properties. Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential. The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system. Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases.

  15. Mushroom polysaccharides: chemistry and antiobesity, antidiabetes, anticancer, and antibiotic properties in cells, rodents, and humans (United States)

    Mushrooms are widely consumed for their nutritional and health benefits. More than 2,000 species of edible and/or medicinal mushrooms have been identified to date, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the...

  16. Teratogens as anti-cancer drugs. (United States)

    Blagosklonny, Mikhail V


    Most anticancer drugs are teratogens, merely because they target vital cellular functions. Conversely, some plants produce agents that intentionally target embryonic signaling pathways, precisely to cause birth defects if pregnant animals eat such plants. Cyclopamine, a teratogen produced by a flowering plant, inhibits the Hh/Gli pathway, causing developmental defects such as cyclopia (one eye in the middle of the face). In theory, selective teratogens may suppress cancer cells that reactivate embryonic pathways, while sparing most normal cells. I discuss the potential (and limits) of teratogens in cancer therapy, linking diverse topics from morning sickness of pregnancy, embryonic pathways and poisonous plants to the mechanism of action of anticancer teratogens and their combinations with less selective cytotoxic agents.

  17. 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


    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

  18. Are isothiocyanates potential anti-cancer drugs?

    Institute of Scientific and Technical Information of China (English)

    Xiang WU; Qing-hua ZHOU; Ke XU


    Isothiocyanates are naturally occurring small molecules that are formed from glucosinolate precursors of cruciferous vegetables. Many isothiocyanates, both natural and synthetic, display anticarcinogenic activity because they reduce activation of carcinogens and increase their detoxification. Recent studies show that they exhibit anti-tumor activity by affecting multiple pathways including apoptosis, MAPK signaling, oxidative stress, and cell cycle progression. This review summarizes the current knowledge on isothiocyanates and focuses on their role as potential anti-cancer agents.

  19. Anticancer Properties of Phyllanthus emblica (Indian Gooseberry)


    Tiejun Zhao; Qiang Sun; Maud Marques; Michael Witcher


    There is a wealth of information emanating from both in vitro and in vivo studies indicating fruit extract of the Phyllanthus emblica tree, commonly referred to as Indian Gooseberries, has potent anticancer properties. The bioactivity in this extract is thought to be principally mediated by polyphenols, especially tannins and flavonoids. It remains unclear how polyphenols from Phyllanthus emblica can incorporate both cancer-preventative and antitumor properties. The antioxidant function of Ph...

  20. Recent Development of Anticancer Therapeutics Targeting Akt


    Morrow, John K.; Du-Cuny, Lei; Chen, Lu; Meuillet, Emmanuelle J.; Eugene A Mash; Powis, Garth; Zhang, Shuxing


    The serine/threonine kinase Akt has proven to be a significant signaling target, involved in various biological functions. Because of its cardinal role in numerous cellular responses, Akt has been implicated in many human diseases, particularly cancer. It has been established that Akt is a viable and feasible target for anticancer therapeutics. Analysis of all Akt kinases reveals conserved homology for an N-terminal regulatory domain, which contains a pleckstrin-homology (PH) domain for cellu...

  1. Antibiotics and antibiotic resistance: a bitter fight against evolution. (United States)

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


    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.

  2. Advances in cobalt complexes as anticancer agents. (United States)

    Munteanu, Catherine R; Suntharalingam, Kogularamanan


    The evolution of resistance to traditional platinum-based anticancer drugs has compelled researchers to investigate the cytostatic properties of alternative transition metal-based compounds. The anticancer potential of cobalt complexes has been extensively studied over the last three decades, and much time has been devoted to understanding their mechanisms of action. This perspective catalogues the development of antiproliferative cobalt complexes, and provides an in depth analysis of their mode of action. Early studies on simple cobalt coordination complexes, Schiff base complexes, and cobalt-carbonyl clusters will be documented. The physiologically relevant redox properties of cobalt will be highlighted and the role this plays in the preparation of hypoxia selective prodrugs and imaging agents will be discussed. The use of cobalt-containing cobalamin as a cancer specific delivery agent for cytotoxins will also be described. The work summarised in this perspective shows that the biochemical and biophysical properties of cobalt-containing compounds can be fine-tuned to produce new generations of anticancer agents with clinically relevant efficacies.

  3. Anticancer Drugs from Marine Flora: An Overview

    Directory of Open Access Journals (Sweden)

    N. Sithranga Boopathy


    Full Text Available Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. The chemicals have displayed an array of pharmacological properties especially antioxidant, immunostimulatory, and antitumour activities. The phytochemicals possibly activate macrophages, induce apoptosis, and prevent oxidative damage of DNA, thereby controlling carcinogenesis. In spite of vast resources enriched with chemicals, the marine floras are largely unexplored for anticancer lead compounds. Hence, this paper reviews the works so far conducted on this aspect with a view to provide a baseline information for promoting the marine flora-based anticancer research in the present context of increasing cancer incidence, deprived of the cheaper, safer, and potent medicines to challenge the dreadful human disease.

  4. The Antibiotic Resistance Problem Revisited (United States)

    Lawson, Michael A.


    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…

  5. Anticancer Efficacy of Polyphenols and Their Combinations

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki


    Full Text Available Polyphenols, found abundantly in plants, display many anticarcinogenic properties including their inhibitory effects on cancer cell proliferation, tumor growth, angiogenesis, metastasis, and inflammation as well as inducing apoptosis. In addition, they can modulate immune system response and protect normal cells against free radicals damage. Most investigations on anticancer mechanisms of polyphenols were conducted with individual compounds. However, several studies, including ours, have indicated that anti-cancer efficacy and scope of action can be further enhanced by combining them synergistically with chemically similar or different compounds. While most studies investigated the anti-cancer effects of combinations of two or three compounds, we used more comprehensive mixtures of specific polyphenols and mixtures of polyphenols with vitamins, amino acids and other micronutrients. The mixture containing quercetin, curcumin, green tea, cruciferex, and resveratrol (PB demonstrated significant inhibition of the growth of Fanconi anemia head and neck squamous cell carcinoma and dose-dependent inhibition of cell proliferation, matrix metalloproteinase (MMP-2 and -9 secretion, cell migration and invasion through Matrigel. PB was found effective in inhibition of fibrosarcoma HT-1080 and melanoma A2058 cell proliferation, MMP-2 and -9 expression, invasion through Matrigel and inducing apoptosis, important parameters for cancer prevention. A combination of polyphenols (quercetin and green tea extract with vitamin C, amino acids and other micronutrients (EPQ demonstrated significant suppression of ovarian cancer ES-2 xenograft tumor growth and suppression of ovarian tumor growth and lung metastasis from IP injection of ovarian cancer A-2780 cells. The EPQ mixture without quercetin (NM also has shown potent anticancer activity in vivo and in vitro in a few dozen cancer cell lines by inhibiting tumor growth and metastasis, MMP-2 and -9 secretion, invasion

  6. 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....

  7. What Can Be Done about Antibiotic Resistance? (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 ...

  8. In Silico Models for Designing and Discovering Novel Anticancer Peptides (United States)

    Tyagi, Atul; Kapoor, Pallavi; Kumar, Rahul; Chaudhary, Kumardeep; Gautam, Ankur; Raghava, G. P. S.


    Use of therapeutic peptides in cancer therapy has been receiving considerable attention in the recent years. Present study describes the development of computational models for predicting and discovering novel anticancer peptides. Preliminary analysis revealed that Cys, Gly, Ile, Lys, and Trp are dominated at various positions in anticancer peptides. Support vector machine models were developed using amino acid composition and binary profiles as input features on main dataset that contains experimentally validated anticancer peptides and random peptides derived from SwissProt database. In addition, models were developed on alternate dataset that contains antimicrobial peptides instead of random peptides. Binary profiles-based model achieved maximum accuracy 91.44% with MCC 0.83. We have developed a webserver, which would be helpful in: (i) predicting minimum mutations required for improving anticancer potency; (ii) virtual screening of peptides for discovering novel anticancer peptides, and (iii) scanning natural proteins for identification of anticancer peptides (

  9. A Systematic Review of Iran's Medicinal Plants With Anticancer Effects. (United States)

    Asadi-Samani, Majid; Kooti, Wesam; Aslani, Elahe; Shirzad, Hedayatollah


    Increase in cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. This study is a review of medicinal plants in Iran with already investigated anticancer effects on various cell lines. Thirty-six medicinal plants alongside their products with anticancer effects as well as the most important plant compounds responsible for the plants' anticancer effect were introduced. Phenolic and alkaloid compounds were demonstrated to have anticancer effects on various cancers in most studies. The plants and their active compounds exerted anticancer effects by removing free radicals and antioxidant effects, cell cycle arrest, induction of apoptosis, and inhibition of angiogenesis. The investigated plants in Iran contain the compounds that are able to contribute effectively to fighting cancer cells. Therefore, the extract and active compounds of the medicinal plants introduced in this review article could open a way to conduct clinical trials on cancer and greatly help researchers and pharmacists develop new anticancer drugs.

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

    Directory of Open Access Journals (Sweden)

    Justin M David


    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.

  11. Structures and Properties of Naturally Occurring Polyether Antibiotics

    Directory of Open Access Journals (Sweden)

    Jacek Rutkowski


    Full Text Available Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

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

    KAUST Repository

    Hong, Pei-Ying


    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.

  13. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes. (United States)

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


    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.

  14. 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


    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.

  15. Anticancer drug sensitivity by human tumor clonogenic assay.

    Directory of Open Access Journals (Sweden)



    Full Text Available The anticancer drug sensitivity of human cancers was tested by the human tumor clonogenic assay (HTCA. Of 152 human cancer specimens tested, 63 (41% formed more than 30 tumor cell colonies in control plates and could be used to evaluate the drug sensitivity of tumor cells. In 42 (93% of 45 clinical trials in 24 patients, a parallel correlation was observed between the in vitro anticancer drug sensitivity measured by the HTCA and the clinical response of tumors to anticancer drugs. These results suggest that the HTCA is a good technique for the in vitro test of the anticancer drug sensitivity of human cancers.

  16. CancerHSP: anticancer herbs database of systems pharmacology (United States)

    Tao, Weiyang; Li, Bohui; Gao, Shuo; Bai, Yaofei; Shar, Piar Ali; Zhang, Wenjuan; Guo, Zihu; Sun, Ke; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Mu, Jiexin; Pei, Tianli; Wang, Yuan; Li, Yan; Wang, Yonghua


    The numerous natural products and their bioactivity potentially afford an extraordinary resource for new drug discovery and have been employed in cancer treatment. However, the underlying pharmacological mechanisms of most natural anticancer compounds remain elusive, which has become one of the major obstacles in developing novel effective anticancer agents. Here, to address these unmet needs, we developed an anticancer herbs database of systems pharmacology (CancerHSP), which records anticancer herbs related information through manual curation. Currently, CancerHSP contains 2439 anticancer herbal medicines with 3575 anticancer ingredients. For each ingredient, the molecular structure and nine key ADME parameters are provided. Moreover, we also provide the anticancer activities of these compounds based on 492 different cancer cell lines. Further, the protein targets of the compounds are predicted by state-of-art methods or collected from literatures. CancerHSP will help reveal the molecular mechanisms of natural anticancer products and accelerate anticancer drug development, especially facilitate future investigations on drug repositioning and drug discovery. CancerHSP is freely available on the web at PMID:26074488

  17. Artemisinin–Second Career as Anticancer Drug?

    Directory of Open Access Journals (Sweden)

    Thomas Efferth


    Full Text Available Artemisinin represents a showcase example not only for the activity of medicinal herbs deriving from traditional chinese medicine, but for phytotherapy in general. Its isolation from Sweet Wormwood (qinhao, Artemisia annua L. represents the starting point for an unprecedent success story in the treatment of malaria worldwide. Beyond the therapeutic value against Plasmodium parasites, it turned out in recent years that the bioactivity of artemisinin is not restricted to malaria. We and others found that this sesquiterpenoid also exerts profound anticancer activity in vitro and in vivo. Artemisinin-type drugs exert multi-factorial cellular and molecular actions in cancer cells. Ferrous iron reacts with artemisinin, which leads to the formation of reactive oxygen species and ultimately to a plethora anticancer effects of artemisinins, e.g. expression of antioxidant response genes, cell cycle arrest (G1 as well as G2 phase arrests, DNA damage that is repaird by base excision repair, homogous recombination and non-homologous end-joining, as well as different modes of cell death (intrinsic and extrinsic apoptosis, autophagy, necrosis, necroptosis, oncosis, and ferroptosis. Furthermore, artemisinins inhibit neoangiogenesis in tumors. The signaling of major transcription factors (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc. and signaling pathways are affected by artemisinins (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, nitric oxide signaling, and others. Several case reports on the compassionate use of artemisinins as well as clinical Phase I/II pilot studies indicate the clinical activity of artemisinins in veterinary and human cancer patients. Larger scale of Phase II and III clinical studies are required now to further develop artemisinin-type compounds as novel anticancer drugs.

  18. Reactions and interactions in handling anticancer drugs. (United States)

    D'Arcy, P F


    The clinical toxicity of anticancer drugs has been well documented with regard to the adverse effects of treatment in patients. However, many of these drugs have a direct irritant effect on the skin, eyes, mucous membranes, and other tissues. Handled without due care, especially when being prepared for injection, most cytotoxic drugs can cause local toxic or allergic reactions; they also present hazards of carcinogenicity and mutagenicity. This spectrum of potential risk should be kept in mind by personnel administering or handling these drugs, especially in oncology units where just a few individuals may routinely and frequently reconstitute many doses of cytotoxic agents. This is work in which the hospital pharmacist should and must be involved; indeed, many of the techniques and skills required are identical with those used in standard aseptic procedures for preparing pharmaceutical products. Pharmacy departments should take the initiative in making hospital staff aware of the potential risks of handling neoplastic agents, and they should spearhead a multidisciplinary assessment for producing local guidelines for working with these drugs. This article warns practitioners about the inherent dangers of these practitioner-drug interactions and suggests ways in which they may be reduced. Information is given in tabular form regarding recommended procedures for reconstituting 24 anticancer drugs and precautions to protect the personnel handling them, especially when there is spillage of powdered or liquid drugs. Also, guidelines are given about incompatibilities with admixtures of such drugs, and the literature is reviewed relative to recent developments in hospital pharmacy departments where reconstitution of anticancer drugs has been incorporated into existing intravenous fluid preparation/admixture units. Not only has this been shown to be safer and more effective in terms of time and labor, but also it has cut the cost of injectable cytotoxic drugs by an

  19. Antibiotic prescribing for acute bronchitis

    DEFF Research Database (Denmark)

    Llor, Carl; Bjerrum, Lars


    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...

  20. Systemic antibiotic therapy in periodontics. (United States)

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


    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.

  1. Systemic antibiotic therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Anoop Kapoor


    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.

  2. Histone deacetylase inhibitors (HDACIs: multitargeted anticancer agents

    Directory of Open Access Journals (Sweden)

    Ververis K


    Full Text Available Katherine Ververis,1 Alison Hiong,1 Tom C Karagiannis,1,* Paul V Licciardi2,*1Epigenomic Medicine, Alfred Medical Research and Education Precinct, 2Allergy and Immune Disorders, Murdoch Childrens Research Institute, Melbourne, VIC, Australia*These authors contributed equally to this workAbstract: Histone deacetylase (HDAC inhibitors are an emerging class of therapeutics with potential as anticancer drugs. The rationale for developing HDAC inhibitors (and other chromatin-modifying agents as anticancer therapies arose from the understanding that in addition to genetic mutations, epigenetic changes such as dysregulation of HDAC enzymes can alter phenotype and gene expression, disturb homeostasis, and contribute to neoplastic growth. The family of HDAC inhibitors is large and diverse. It includes a range of naturally occurring and synthetic compounds that differ in terms of structure, function, and specificity. HDAC inhibitors have multiple cell type-specific effects in vitro and in vivo, such as growth arrest, cell differentiation, and apoptosis in malignant cells. HDAC inhibitors have the potential to be used as monotherapies or in combination with other anticancer therapies. Currently, there are two HDAC inhibitors that have received approval from the US FDA for the treatment of cutaneous T-cell lymphoma: vorinostat (suberoylanilide hydroxamic acid, Zolinza and depsipeptide (romidepsin, Istodax. More recently, depsipeptide has also gained FDA approval for the treatment of peripheral T-cell lymphoma. Many more clinical trials assessing the effects of various HDAC inhibitors on hematological and solid malignancies are currently being conducted. Despite the proven anticancer effects of particular HDAC inhibitors against certain cancers, many aspects of HDAC enzymes and HDAC inhibitors are still not fully understood. Increasing our understanding of the effects of HDAC inhibitors, their targets and mechanisms of action will be critical for the

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

    Directory of Open Access Journals (Sweden)

    Geoffrey Ivan Scott


    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 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

  4. Applying fluorescence lifetime imaging microscopy to evaluate the efficacy of anticancer drugs (United States)

    Kawanabe, Satoshi; Araki, Yoshie; Uchimura, Tomohiro; Imasaka, Totaro


    Fluorescence lifetime imaging microscopy was applied to evaluate the efficacy of anticancer drugs. A decrease in the fluorescence lifetime of the nucleus in apoptotic cancer cells stained by SYTO 13 dye was detected after treatment with antitumor antibiotics such as doxorubicin or epirubicin. It was confirmed that the change in fluorescence lifetime occurred earlier than morphological changes in the cells. We found that the fluorescence lifetime of the nucleus in the cells treated with epirubicin decreased more rapidly than that of the cells treated with doxorubicin. This implies that epirubicin was more efficacious than doxorubicin in the treatment of cancer cells. The change in fluorescence lifetime was, however, not indicated when the cells were treated with cyclophosphamide. The decrease in fluorescence lifetime was associated with the processes involving caspase activation and chromatin condensation. Therefore, this technique would provide useful information about apoptotic cells, particularly in the early stages.

  5. Prophylactic antibiotics versus post- operative antibiotics in herniorraphy

    Directory of Open Access Journals (Sweden)

    Abedulla Khan Kayamkani


    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.

  6. Repurposing the anticancer drug mitomycin C for the treatment of persistent Acinetobacter baumannii infections. (United States)

    Cruz-Muñiz, Martha Yumiko; López-Jacome, Luis Esau; Hernández-Durán, Melissa; Franco-Cendejas, Rafael; Licona-Limón, Paula; Ramos-Balderas, Jose Luis; Martinéz-Vázquez, Mariano; Belmont-Díaz, Javier A; Wood, Thomas K; García-Contreras, Rodolfo


    Acinetobacter baumannii is an emergent opportunistic bacterial pathogen responsible for recalcitrant infections owing to its high intrinsic tolerance to most antibiotics; therefore, suitable strategies to treat these infections are needed. One plausible approach is the repurposing of drugs that are already in use. Among them, anticancer drugs may be especially useful due their cytotoxic activities and ample similarities between bacterial infections and growing tumours. In this work, the effectiveness of four anticancer drugs on the growth of A. baumannii ATTC BAA-747 was evaluated, including the antimetabolite 5-fluorouracil and three DNA crosslinkers, namely cisplatin, mitomycin C (MMC) and merphalan. MMC was the most effective drug, having a minimum inhibitory concentration for 50% of growth in Luria-Bertani medium at ca. 7 µg/mL and completely inhibiting growth at 25 µg/mL. Hence, MMC was tested against a panel of 21 clinical isolates, including 18 multidrug-resistant (MDR) isolates, 3 of which were sensitive only to colistin. The minimum inhibitory concentrations and minimum bactericidal concentrations of MMC in all tested strains were found to be similar to those of A. baumannii ATCC BAA-747, and MMC also effectively killed stationary-phase, persister and biofilm cells. Moreover, MMC was able to increase survival of the insect larvae Galleria mellonella against an otherwise lethal A. baumannii infection from 0% to ≥53% for the antibiotic-sensitive A. baumannii ATCC BAA-747 strain and the MDR strains A560 and A578. Therefore, MMC is highly effective at killing the emergent opportunistic pathogen A. baumannii.

  7. A study of antibiotic prescribing

    DEFF Research Database (Denmark)

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


    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...

  8. Antibiotic resistance: An ethical challenge. (United States)

    Littmann, Jasper; Buyx, Alena; Cars, Otto


    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.

  9. Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm. (United States)

    Klich, Katarzyna; Pyta, Krystian; Kubicka, Marcelina M; Ruszkowski, Piotr; Celewicz, Lech; Gajecka, Marzena; Przybylski, Piotr


    Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. (1)H-(1)H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that the rebuilt C(5) arm is slightly differently oriented relative to the aglycone part if compared to that of spiramycin (1). Combined analysis of biological data together with experimentally determined lipophilicity (clogP) and solubility show the importance of the chemical nature of the newly introduced triazole C(5) arm in the presence of attractive antibacterial and anticancer potency. The most cytotoxic active triazole conjugates having a hydrophobic and bulky C(5) arm showed higher selectivity toward cancer cell lines (HeLa, KB, MCF-7, Hep-G2, and U87) relative to HDF normal cells than that of the parent spiramycin. Our studies have demonstrated that the aldehyde group is not crucial for the presence of interesting antibacterial [MIC(S. pneumoniae) ∼ 1.2 μM] and anticancer [IC50(HepG2) ∼ 6 μM] properties of 16-membered lactone macrolides based on spiramycin's aglycone.

  10. Assessment of probiotic potential and anticancer activity of newly isolated vaginal bacterium Lactobacillus plantarum 5BL. (United States)

    Nami, Yousef; Abdullah, Norhafizah; Haghshenas, Babak; Radiah, Dayang; Rosli, Rozita; Khosroushahi, Ahmad Yari


    Numerous bacteria in and on its external parts protect the human body from harmful threats. This study aimed to investigate the potential beneficial effects of the vaginal ecosystem microbiota. A type of bacteria was isolated from vaginal secretions of adolescent and young adult women, cultured on an appropriate specific culture medium, and then molecularly identified through 16S rDNA gene sequencing. Results of 16S rDNA sequencing revealed that the isolate belongs to the Lactobacillus plantarum species. The isolated strain exhibited probiotic properties such as low pH and high bile salt concentration tolerance, antibiotic susceptibility and antimicrobial activity against some pathogenic bacteria. The anticancer effects of the strain on human cancer cell lines (cervical, HeLa; gastric, AGS; colon, HT-29; breast, MCF-7) and on a human normal cell line (human umbilical vein endothelial cells [HUVEC]) were investigated. Toxic side effects were assessed by studying apoptosis in the treated cells. The strain exhibited desirable probiotic properties and remarkable anticancer activity against the tested human cancer cell lines (P ≤ 0.05) with no significant cytotoxic effects on HUVEC normal cells (P ≤ 0.05). Overall, the isolated strain showed favorable potential as a bioactive therapeutic agent. Therefore, this strain should be subjected to the other required tests to prove its suitability for clinical therapeutic application.

  11. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)


    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  12. PEGylated Silk Nanoparticles for Anticancer Drug Delivery. (United States)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew J; Seib, F Philipp


    Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential -56 ± 5.6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines.

  13. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang


    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  14. In vivo anticancer activity of vanillin semicarbazone

    Institute of Scientific and Technical Information of China (English)

    Shaikh M Mohsin Ali; M Abul Kalam Azad; Mele Jesmin; Shamim Ahsan; M Mijanur Rahman; Jahan Ara Khanam; M Nazrul Islam; Sha M Shahan Shahriar


    Objective:To evaluate the anticancer activity of vanillin semicarbazone (VSC) against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. Methods:The compound VSC at three doses (5, 7.5 and 10 mg/kg i.p.) was administered into the intraperitoneal cavity of the EAC inoculated mice to observe its efficiency by studying the cell growth inhibition, reduction of tumour weight, enhancement of survival time as well as the changes in depleted hematological parameters. All such parameters were also studied with a known standard drug bleomycin at the dose of 0.3 mg/kg (i.p.). Results:Among the doses studied, 10 mg/kg (i.p.) was found to be quite comparable in potency to that of bleomycin at the dose of 0.3 mg/kg (i.p.). The host toxic effects of VSC was found to be negligible. Conclusions: It can be concluded that VSC can therefore be considered as potent anticancer agent.

  15. Recent development of anticancer therapeutics targeting Akt. (United States)

    Morrow, John K; Du-Cuny, Lei; Chen, Lu; Meuillet, Emmanuelle J; Mash, Eugene A; Powis, Garth; Zhang, Shuxing


    The serine/threonine kinase Akt has proven to be a significant signaling target, involved in various biological functions. Because of its cardinal role in numerous cellular responses, Akt has been implicated in many human diseases, particularly cancer. It has been established that Akt is a viable and feasible target for anticancer therapeutics. Analysis of all Akt kinases reveals conserved homology for an N-terminal regulatory domain, which contains a pleckstrin-homology (PH) domain for cellular translocation, a kinase domain with serine/threonine specificity, and a C-terminal extension domain. These well defined regions have been targeted, and various approaches, including in silico methods, have been implemented to develop Akt inhibitors. In spite of unique techniques and a prolific body of knowledge surrounding Akt, no targeted Akt therapeutics have reached the market yet. Here we will highlight successes and challenges to date on the development of anticancer agents modulating the Akt pathway in recent patents as well as discuss the methods employed for this task. Special attention will be given to patents with focus on those discoveries using computer-aided drug design approaches.

  16. Antibiotics, the pill, and pregnancy.


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


    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 ...

  17. Prophylactic antibiotics in orthopaedic surgery. (United States)

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


    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.

  18. Expedient antibiotics production: Final report

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

  19. Antibiotic utilisation for hospitalised paediatric patients

    NARCIS (Netherlands)

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


    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

  20. Chalcone Scaffold in Anticancer Armamentarium: A Molecular Insight

    Directory of Open Access Journals (Sweden)

    Manik Das


    Full Text Available Cancer is an inevitable matter of concern in the medicinal chemistry era. Chalcone is the well exploited scaffold in the anticancer domain. The molecular mechanism of chalcone at cellular level was explored in past decades. This mini review provides the most recent updates on anticancer potential of chalcones.

  1. Polymeric micelles in anticancer therapy : Targeting, imaging and triggered release

    NARCIS (Netherlands)

    Oerlemans, Chris; Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J. Frank W.; Hennink, Wim E.


    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

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

    LENUS (Irish Health Repository)

    Murphy, D M


    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.

  3. 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)


    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)

  4. Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection. (United States)

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Zhang, Ying


    Lyme disease is the leading tick-borne disease in the USA. Whereas the majority of Lyme disease patients with early disease can be cured with standard treatment, some patients suffer from chronic fatigue and joint and muscular pain despite treatment, a syndrome called posttreatment Lyme disease syndrome. Although the cause is unclear, ineffective killing of Borrelia burgdorferi persisters by current Lyme disease antibiotics is one possible explanation. We took advantage of our recently developed high-throughput viability assay and screened the National Cancer Institute compound library collection consisting of 2526 compounds against stationary phase B. burgdorferi. We identified the top 30 new active hits, including the top six anthracycline antibiotics daunomycin 3-oxime, dimethyldaunomycin, daunomycin, NSC299187, NSC363998 and nogalamycin, along with other compounds, including prodigiosin, mitomycin, nanaomycin and dactinomycin, as having excellent activity against B. burgdorferi stationary phase culture. The anthracycline or anthraquinone compounds, which are known to have both anti-cancer and antibacterial activities, also had high activity against growing B. burgdorferi with low minimum inhibitory concentration. Future studies on the structure-activity relationship and mechanisms of action of anthracyclines/anthraquinones are warranted. In addition, drug combination studies with the anthracycline class of compounds and the current Lyme antibiotics to eradicate B. burgdorferi persisters in vitro and in animal models are needed to determine if they improve the treatment of Lyme disease.

  5. Synthesis and anticancer evaluation of spermatinamine analogues

    KAUST Repository

    Moosa, Basem


    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcystiene carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines i.e. cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5 - 10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines.

  6. System engineering approach to planning anticancer therapies

    CERN Document Server

    Świerniak, Andrzej; Smieja, Jaroslaw; Puszynski, Krzysztof; Psiuk-Maksymowicz, Krzysztof


    This book focuses on the analysis of cancer dynamics and the mathematically based synthesis of anticancer therapy. It summarizes the current state-of-the-art in this field and clarifies common misconceptions about mathematical modeling in cancer. Additionally, it encourages closer cooperation between engineers, physicians and mathematicians by showing the clear benefits of this without stating unrealistic goals. Development of therapy protocols is realized from an engineering point of view, such as the search for a solution to a specific control-optimization problem. Since in the case of cancer patients, consecutive measurements providing information about the current state of the disease are not available, the control laws are derived for an open loop structure. Different forms of therapy are incorporated into the models, from chemotherapy and antiangiogenic therapy to immunotherapy and gene therapy, but the class of models introduced is broad enough to incorporate other forms of therapy as well. The book be...

  7. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk


    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  8. Liposomal Drug Delivery of Anticancer Agents

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob

    In the first part of the thesis the work towards a new generation of liposomal drug delivery systems for anticancer agents is described. The drug delivery system takes advantage of the elevated level of secretory phospholipase A2 (sPLA2) IIA in many tumors and the enhanced permeability......-trans retinoic acid, α-tocopheryl succinate and calcitriol were examined for their ability to be incorporated into the investigated drug delivery system and syntheses of the phospholipid prodrugs are described. The majority of the phospholipid prodrugs were able to form particles with diameters close to 100 nm...... that upon sPLA2 triggering the formulated phospholipid prodrugs displayed IC50 values in range from 3–36 μM and complete cell death was observed when higher drug concentrations were applied. Promising for the drug delivery system the majority of the phospholipid prodrugs remain non-toxic in the absence...

  9. Liposomal anticancer therapy: pharmacokinetic and clinical aspects. (United States)

    Di Paolo, A


    Liposomes, which are vesicles composed of a phospholipid bilayer surrounding an aqueous milieu, represent a new strategy for anticancer drug delivery. Extravasation and accumulation of liposomal drugs within neoplastic tissues are possible because of the leaky vasculature and scarce lymphatic vessels of tumours (the enhanced permeability and retention effect). Furthermore, liposomal chemotherapeutic agents display distinctive pharmacokinetic characteristics, because they possess longer elimination half-lives, reduced clearance and smaller volume of distribution with respect to corresponding free drugs. Taken together, these features lead to highest levels of cytotoxic agents in tumours, as demonstrated in preclinical models and clinical trials, whereas healthy tissues are spared from toxicity. In fact, liposomal drugs (i.e., doxorubicin), alone or in combination with other cytotoxic agents, lead to improved clinical effectiveness and ameliorated toxicity profile with respect to corresponding free drugs when they are used for the treatment of metastatic breast and ovarian cancers, and Kaposi's sarcoma.

  10. Fenbendazole as a Potential Anticancer Drug (United States)



    Background/Aims To evaluate the anticancer activity of fenbendazole, a widely used antihelminth with mechanisms of action that overlap with those of the hypoxia-selective nitroheterocyclic cytotoxins/radiosensitizers and the taxanes. Materials and Methods We used EMT6 mouse mammary tumor cells in cell culture and as solid tumors in mice to examine the cytotoxic and antitumor effects of fenbendazole as a single agent and in combination regimens. Results Intensive treatments with fenbendazole were toxic to EMT6 cells in vitro; toxicity increased with incubation time and under conditions of severe hypoxia. Fenbendazole did not alter the dose-response curves for radiation or docetaxel; instead, the agents produced additive cytotoxicities. Febendazole in maximally-intensive regimens did not alter the growth of EMT6 tumors, or increase the antineoplastic effects of radiation. Conclusion These studies provided no evidence that fenbendazole would have value in cancer therapy, but suggested that this general class of compounds merits further investigation. PMID:23393324

  11. Chemical Biology of Microbial Anticancer Natural Products

    DEFF Research Database (Denmark)

    Bladt, Tanja Thorskov; Gotfredsen, Charlotte Held

    by cyanobacteria were discovered through target-guided isolation based on NMR. The micropeptins displayed inhibitory activity towards serine proteases: chymotrypsin and elastase with IC50 values between 5.9 and 28.0 μM. In conclusion, this PhD study adds to the knowledge of bioactive NPs produced by filamentous...... fungi, and in particular activity towards CLL cells. The results obtained here have been based on the use of a combined bio-guided and analytical dereplication approach. This PhD study also includes a review of 50 compounds or compound families with anticancer activity primarily produced by Aspergillus......-living cells in vivo. Fortunately viability of CLL cells can be maintained in vitro by co-cultivation with stromal cells mimicking in vivo conditions. This has led to the development of a co-culture assay that is ideally suited for screening of NPs. The main goal of this study has been to discover fungal NPs...

  12. PEGylated Silk Nanoparticles for Anticancer Drug Delivery

    DEFF Research Database (Denmark)

    Wongpinyochit, Thidarat; Uhlmann, Petra; Urquhart, Andrew


    .6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using...... clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines......Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of “stealth” design principals...

  13. Anticancer properties of distinct antimalarial drug classes.

    Directory of Open Access Journals (Sweden)

    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  14. Coumarin: a promising scaffold for anticancer agents. (United States)

    Kaur, Manjinder; Kohli, Swarandeep; Sandhu, Sonali; Bansal, Yogita; Bansal, Gulshan


    Coumarin enjoys an important place in drug discovery process due to its presence in diversity of biologically active compounds. Many compounds of plant origin are derivatives of coumarin. Taking these natural products as lead, research groups across the globe have designed and synthesized numerous coumarin analogues for treatment of varied diseases. Cancer is one of the dreadful chronic diseases, and many drugs are available for its treatment. However, due to heterogeneity of cancer, the search is still on to develop drugs for specific types of cancers. The present review is an attempt to study various coumarin derivatives of natural as well as synthetic origins, which are identified or developed for the treatment of different types of cancers. Herein, we have classified various anticancer coumarin derivatives on the basis of their origin as well as substitution around it. These are discussed under the headings of natural, semi-synthetic and synthetic coumarin derivatives. The synthetic coumarin derivatives are further classified as mono-, di- and poly-substituted and fused coumarin derivatives. Of the six positions available for substituents on coumarin nucleus, only three positions (C-3, C-4 and C-7) are exploited for the selection of functional groups appropriate for anticancer activity. The other positions (C-5, C-6 and C-8) are either unexplored or very less exploited. The present review is expected to provide the medicinal chemists a guide to choose new functional groups for substitution at different positions of coumarin nucleus for development of novel compounds for the treatment of a specific type of cancer.

  15. Peptides with Dual Antimicrobial and Anticancer Activities (United States)

    Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.


    In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting toward intracellular targets, which increases their success compartively to one-target specific drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials. PMID:28271058

  16. Background antibiotic resistance patterns in antibiotic-free pastured poultry production (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...

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

  18. Potency of Lobak Leaves (Raphanus sativus L. var. hortensis Back as Anticancer and Antimicrobial Candidates

    Directory of Open Access Journals (Sweden)



    Full Text Available One of vegetables can preventive cancer and have been used traditionally to cure infection, such as lobak (Raphanus sativus L.. Ineffectiveness antibiotics to against microbial infections was still problem until now. Types of antibiotics and anticancer agents from natural resources should be explored and developed. This study was aimed to know toxicity effect and antimicrobial activity of active fractions from lobak leaves. Toxicity study was conducted using Brine Shrimp Lethality Test (BST. Samples were prepared at the concentration of 100, 500, and 1000μg/mL. Antibacterial study against Staphylococcus aureus was conducted using agar-well diffusion method at concentration 30, 40, 50, 60, 70, 80, 100%. Ethyl acetate fraction from methanol extract is the most active that had larger clear zone in S. aureus culture (10,64 mm and insoluble ethyl acetate fraction from methanol extract is the most active against A. salina (84% death A. salina at 100 µg/mL. Bioactive compounds at active fraction were identified to contain polar compounds.

  19. Detection of antibiotic residues in poultry meat. (United States)

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


    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.

  20. Antibiotic drugs targeting bacterial RNAs

    Directory of Open Access Journals (Sweden)

    Weiling Hong


    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.

  1. Metabolomics-Driven Discovery of a Prenylated Isatin Antibiotic Produced by Streptomyces Species MBT28. (United States)

    Wu, Changsheng; Du, Chao; Gubbens, Jacob; Choi, Young Hae; van Wezel, Gilles P


    Actinomycetes are a major source of antimicrobials, anticancer compounds, and other medically important products, and their genomes harbor extensive biosynthetic potential. Major challenges in the screening of these microorganisms are to activate the expression of cryptic biosynthetic gene clusters and the development of technologies for efficient dereplication of known molecules. Here we report the identification of a previously unidentified isatin-type antibiotic produced by Streptomyces sp. MBT28, following a strategy based on NMR-based metabolomics combined with the introduction of streptomycin resistance in the producer strain. NMR-guided isolation by tracking the target proton signal resulted in the characterization of 7-prenylisatin (1) with antimicrobial activity against Bacillus subtilis. The metabolite-guided genome mining of Streptomyces sp. MBT28 combined with proteomics identified a gene cluster with an indole prenyltransferase that catalyzes the conversion of tryptophan into 7-prenylisatin. This study underlines the applicability of NMR-based metabolomics in facilitating the discovery of novel antibiotics.

  2. Nucleoside antibiotics: biosynthesis, regulation, and biotechnology. (United States)

    Niu, Guoqing; Tan, Huarong


    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.

  3. Antibiotic Policies in the Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Nese Saltoglu


    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

  4. Antibiotics and the resistant microbiome

    DEFF Research Database (Denmark)

    Sommer, Morten; Dantas, Gautam


    . 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....

  5. Antibiotic resistance of bacterial biofilms

    DEFF Research Database (Denmark)

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


    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...

  6. Hyaluronic acid for anticancer drug and nucleic acid delivery. (United States)

    Dosio, Franco; Arpicco, Silvia; Stella, Barbara; Fattal, Elias


    Hyaluronic acid (HA) is widely used in anticancer drug delivery, since it is biocompatible, biodegradable, non-toxic, and non-immunogenic; moreover, HA receptors are overexpressed on many tumor cells. Exploiting this ligand-receptor interaction, the use of HA is now a rapidly-growing platform for targeting CD44-overexpressing cells, to improve anticancer therapies. The rationale underlying approaches, chemical strategies, and recent advances in the use of HA to design drug carriers for delivering anticancer agents, are reviewed. Comprehensive descriptions are given of HA-based drug conjugates, particulate carriers (micelles, liposomes, nanoparticles, microparticles), inorganic nanostructures, and hydrogels, with particular emphasis on reports of preclinical/clinical results.

  7. Probiotic approach to prevent antibiotic resistance. (United States)

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


    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.

  8. Antibiotic associated diarrhoea: Infectious causes

    Directory of Open Access Journals (Sweden)

    Ayyagari A


    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.

  9. Use of antibiotics in children

    DEFF Research Database (Denmark)

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


    -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...

  10. Antibiotic resistance in probiotic bacteria

    Directory of Open Access Journals (Sweden)

    Miguel eGueimonde


    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.

  11. Origins and evolution of antibiotic resistance. (United States)

    Davies, Julian; Davies, Dorothy


    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.

  12. Antibiotic 'Report Card' Drills Guidelines into Dentists (United States)

    ... page: 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 ...

  13. Antibiotic Resistance in Human Chronic Periodontitis Microbiota

    NARCIS (Netherlands)

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


    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

  14. Nature's combinatorial biosynthesis and recently engineered production of nucleoside antibiotics in Streptomyces. (United States)

    Chen, Shawn; Kinney, William A; Van Lanen, Steven


    Modified nucleosides produced by Streptomyces and related actinomycetes are widely used in agriculture and medicine as antibacterial, antifungal, anticancer and antiviral agents. These specialized small-molecule metabolites are biosynthesized by complex enzymatic machineries encoded within gene clusters in the genome. The past decade has witnessed a burst of reports defining the key metabolic processes involved in the biosynthesis of several distinct families of nucleoside antibiotics. Furthermore, genome sequencing of various Streptomyces species has dramatically increased over recent years. Potential biosynthetic gene clusters for novel nucleoside antibiotics are now apparent by analysis of these genomes. Here we revisit strategies for production improvement of nucleoside antibiotics that have defined mechanisms of action, and are in clinical or agricultural use. We summarize the progress for genetically manipulating biosynthetic pathways for structural diversification of nucleoside antibiotics. Microorganism-based biosynthetic examples are provided and organized under genetic principles and metabolic engineering guidelines. We show perspectives on the future of combinatorial biosynthesis, and present a working model for discovery of novel nucleoside natural products in Streptomyces.

  15. Apigenin, an Anticancer Isolated from Macaranga gigantifolia Leaves

    Directory of Open Access Journals (Sweden)

    Sofa Fajriah


    Full Text Available Apigenin, a flavonoid compound has been isolated from the ethyl acetate fraction of methanol extract of Macaranga gigantifolia leaves. Isolation and purification of apigenin conducted using column and centrifugal chromatography and chemical structure characterized based on spectroscopic data. In vitro anticancer activity test against murine leukimia P-388 cell line showed potential activity as anticancer with IC50 14.13 µg/mL.

  16. Anticancer steroids: linking natural and semi-synthetic compounds. (United States)

    Salvador, Jorge A R; Carvalho, João F S; Neves, Marco A C; Silvestre, Samuel M; Leitão, Alcino J; Silva, M Manuel C; Sá e Melo, M Luisa


    Steroids, a widespread class of natural organic compounds occurring in animals, plants and fungi, have shown great therapeutic value for a broad array of pathologies. The present overview is focused on the anticancer activity of steroids, which is very representative of a rich structural molecular diversity and ability to interact with various biological targets and pathways. This review encompasses the most relevant discoveries on steroid anticancer drugs and leads through the last decade and comprises 668 references.

  17. The anti-cancer activity of noscapine: a review. (United States)

    Mahmoudian, Massoud; Rahimi-Moghaddam, Parvaneh


    Noscapine is an isoqiunoline alkaloid found in opium latex. Unlike most other alkaloids obtained from opium latex, noscapine is not sedative and has been used as antitussive drug in various countries. Recently, it has been introduced as an anti-mitotic agent. This drug can be used orally. When the resistance to other anti-cancer drugs such as paclitaxel manifests, noscapine might be effective. Therefore, noscapine and its analogs have great potential as novel anti-cancer agents.

  18. The Extraction, Anticancer Effect, Bioavailability, and Nanotechnology of Baicalin (United States)

    Moore, Ondrea A.; Gao, Ying; Chen, Allen Y.; Brittain, Ross; Chen, Yi Charlie


    The dried root of Baikal skullcap (Scutellaria baicalensis) has been historically and widely used in traditional Eastern medicine. Modern science proved that baicalin is the major bioactive responsible for the physiological activity of Baikal skullcap. Baicalin, a flavonoid found in several species in the genus Scutellaria, has been regarded as a potent anticancer agent. In this review, we present the main extraction methods, anticancer activity and bioavailability of baicalin. Besides, the utilization of nanotechnology to improve the bioavailability of baicalin is also mentioned.

  19. Apigenin, an Anticancer Isolated from Macaranga gigantifolia Leaves



    Apigenin, a flavonoid compound has been isolated from the ethyl acetate fraction of methanol extract of Macaranga gigantifolia leaves. Isolation and purification of apigenin conducted using column and centrifugal chromatography and chemical structure characterized based on spectroscopic data. In vitro anticancer activity test against murine leukimia P-388 cell line showed potential activity as anticancer with IC50 14.13 µg/mL.

  20. The antibiotics relo in bacteria resistance


    Santana, Vinicius Canato; CESUMAR


    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...

  1. Acquired antibiotic resistance genes: an overview.


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


    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...

  2. Squalamine: an aminosterol antibiotic from the shark.



    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...

  3. The determinants of the antibiotic resistance process

    Directory of Open Access Journals (Sweden)

    Beatriz Espinosa Franco


    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

  4. Macrocyclic trichothecenes as antifungal and anticancer compounds. (United States)

    de Carvalho, Maira Peres; Weich, Herbert; Abraham, Wolf-Rainer


    Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds. While many of these compounds are of concern in agriculture, the macrocyclic metabolites have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference with mitochondrial function, effects on cell division and membranes. These targets however have been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial importance regarding biological activity and selectivity. This review is focused on compounds belonging to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C- 15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR) are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying mechanisms may help to design highly specific drugs for cancer therapy.

  5. Anticancer Activity of Sea Cucumber Triterpene Glycosides

    Directory of Open Access Journals (Sweden)

    Dmitry L. Aminin


    Full Text Available Triterpene glycosides are characteristic secondary metabolites of sea cucumbers (Holothurioidea, Echinodermata. They have hemolytic, cytotoxic, antifungal, and other biological activities caused by membranotropic action. These natural products suppress the proliferation of various human tumor cell lines in vitro and, more importantly, intraperitoneal administration in rodents of solutions of some sea cucumber triterpene glycosides significantly reduces both tumor burden and metastasis. The anticancer molecular mechanisms include the induction of tumor cell apoptosis through the activation of intracellular caspase cell death pathways, arrest of the cell cycle at S or G2/M phases, influence on nuclear factors, NF-κB, and up-down regulation of certain cellular receptors and enzymes participating in cancerogenesis, such as EGFR (epidermal growth factor receptor, Akt (protein kinase B, ERK (extracellular signal-regulated kinases, FAK (focal adhesion kinase, MMP-9 (matrix metalloproteinase-9 and others. Administration of some glycosides leads to a reduction of cancer cell adhesion, suppression of cell migration and tube formation in those cells, suppression of angiogenesis, inhibition of cell proliferation, colony formation and tumor invasion. As a result, marked growth inhibition of tumors occurs in vitro and in vivo. Some holothurian triterpene glycosides have the potential to be used as P-gp mediated MDR reversal agents in combined therapy with standard cytostatics.

  6. NSAIDs: Old Drugs Reveal New Anticancer Targets

    Directory of Open Access Journals (Sweden)

    Gary A. Piazza


    Full Text Available There is compelling evidence that nonsteroidal anti-inflammatory drugs (NSAIDs and cyclooxygenase-2 selective inhibitors have antineoplastic activity, but toxicity from cyclooxygenase (COX inhibition and the suppression of physiologically important prostaglandins limits their use for cancer chemoprevention. Previous studies as reviewed here suggest that the mechanism for their anticancer properties does not require COX inhibition, but instead involves an off-target effect. In support of this possibility, recent molecular modeling studies have shown that the NSAID sulindac can be chemically modified to selectively design out its COX-1 and COX-2 inhibitory activity. Unexpectedly, certain derivatives that were synthesized based on in silico modeling displayed increased potency to inhibit tumor cell growth. Other experiments have shown that sulindac can inhibit phosphodiesterase to increase intracellular cyclic GMP levels and that this activity is closely associated with its ability to selectively induce apoptosis of tumor cells. Together, these studies suggest that COX-independent mechanisms can be targeted to develop safer and more efficacious drugs for cancer chemoprevention.

  7. Peptidomimetics and metalloprotease inhibitors as anticancer drugs

    Institute of Scientific and Technical Information of China (English)


    Peptidomimetics with three types, as the structural or functional mimetics of natural active peptides, can preserve the bioactivity and improve the bioavailability and the specificity towards the targets of the lead peptides. Peptidomimetics of high bioactivity can be designed through various ways including conformation restriction, modification and non-peptide design. Recently the concentration on the de-velopment of cancer chemotherapeutic drugs was transferred from cytotoxic drugs to target-based drugs, and many proteases and peptidases that play key roles in the process of tumor genesis and development was discovered, which means that peptidomimetics as potential cancer chemotherapeu-tic drugs should be paid close attention to. Our laboratory has focused on the development of small-molecule peptidomimetic inhibitors of APN, MMPs and HDACs as target-based anticancer agents. These three zinc-dependent metalloproteinases play very important roles in the process of tumor genesis, invasion, metastasis, angiogenesis and matrix degradation, so small-molecule peptidomimetic inhibitors based on them would be quite potential in the development of chemotherapeutic drugs with high selectivity.

  8. Calcium channel as a potential anticancer agent. (United States)

    Kriazhev, L


    Anticancer treatment in modern clinical practices includes chemotherapy and radiation therapy with or without surgical interventions. Efficiency of both methods varies greatly depending on cancer types and stages. Besides, chemo- and radiotherapy are toxic and damaging that causes serious side effects. This fact prompts the search for alternative methods of antitumor therapy. It is well known that prolonged or high increase of intracellular calcium concentration inevitably leads to the cell death via apoptosis or necrosis. However, stimulation of cell calcium level by chemical agents is hardly achievable because cells have very sophisticated machinery for maintaining intracellular calcium in physiological ranges. This obstacle can be overridden, nevertheless. It was found that calcium channels in so called calcium cells in land snails are directly regulated by extracellular calcium concentration. The higher the concentration the higher the calcium intake is through the channels. Bearing in mind that extracellular/intracellular calcium concentration ratio in human beings is 10,000-12,000 fold the insertion of the channel into cancer cells would lead to fast and uncontrollable by the cells calcium intake and cell death. Proteins composing the channel may be extracted from plasma membrane of calcium cells and sequenced by mass-spectrometry or N-terminal sequencing. Either proteins or corresponding genes could be used for targeted delivery into cancer cells.

  9. Indigofera suffruticosa: An Alternative Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Jeymesson Raphael Cardoso Vieira


    Full Text Available Indigofera suffruticosa Mill (Fabeceae occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53% and maceration (62.62% against sarcoma 180 in mice at a dose of 50 mg kg−1 (intraperitoneally, based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

  10. Potential Anticancer Properties of Grape Antioxidants

    Directory of Open Access Journals (Sweden)

    Kequan Zhou


    Full Text Available Dietary intake of foods rich in antioxidant properties is suggested to be cancer protective. Foods rich in antioxidant properties include grape (Vitis vinifera, one of the world’s largest fruit crops and most commonly consumed fruits in the world. The composition and cancer-protective effects of major phenolic antioxidants in grape skin and seed extracts are discussed in this review. Grape skin and seed extracts exert strong free radical scavenging and chelating activities and inhibit lipid oxidation in various food and cell models in vitro. The use of grape antioxidants are promising against a broad range of cancer cells by targeting epidermal growth factor receptor (EGFR and its downstream pathways, inhibiting over-expression of COX-2 and prostaglandin E2 receptors, or modifying estrogen receptor pathways, resulting in cell cycle arrest and apoptosis. Interestingly, some of these activities were also demonstrated in animal models. However, in vivo studies have demonstrated inconsistent antioxidant efficacy. Nonetheless, a growing body of evidence from human clinical trials has demonstrated that consumption of grape, wine and grape juice exerts many health-promoting and possible anti-cancer effects. Thus, grape skin and seed extracts have great potential in cancer prevention and further investigation into this exciting field is warranted.


    Directory of Open Access Journals (Sweden)

    Orel V. E.


    Full Text Available Mechanomagnetochemical activation can increase the concentration of paramagnetic centers (free radicals in the anticancer drug, for example, doxorubicin that enables to influence its magnetic properties under external electromagnetic field and improve its magnetic sensitivity and antitumor activity. The principles of design and operation of mechanomagnetic reactor for implementation of this technology which includes mechanomagnetochemical activation and electromagnetic radiation of the drug are described in the paper. The methods of vibration magnetometry, electron paramagnetic resonance spectroscopy and high-performance liquid chromatography were used for studying of doxorubicin mechanomagnetic activation effects. The studies have shown that a generator of sinusoidal electromagnetic wave, working chambers from caprolactam, fluoroplastic or organic materials with metal inserts and working bodies made from steel or agate depending on the required doxorubicin magnetic properties are expedient to use in the designed mechanomagnic reactor. Under influence of mechanomagnetochemical activation doxorubicin, which is diamagnetic, acquires the properties of paramagnetic without changing g-factors in the spectra of electron paramagnetic resonance. Mechanomagnetochemical activation of doxorubicin satisfies pharmacopoeia condi tions according to the results of liquid chromatography that points on perspective of this method using in technology of tumor therapy with nanosized structures and external electromagnetic radiation.

  12. Sensitization for Anticancer Drug-Induced Apoptosis by Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Simone Fulda


    Full Text Available We previously described that betulinic acid (BetA, a naturally occurring pentacyclic triterpenoid, induces apoptosis in tumor cells through the mitochondrial pathway. Here, for the first time, we provide evidence that BetA cooperated with anticancer drugs to induce apoptosis and to inhibit clonogenic survival of tumor cells. Combined treatment with BetA and anticancer drugs acted in concert to induce loss of mitochondrial membrane potential and the release of cytochrome c and Smac from mitochondria, resulting in activation of caspases and apoptosis. Overexpression of Bcl-2, which blocked mitochondrial perturbations, also inhibited the cooperative effect of BetA and anticancer drugs, indicating that cooperative interaction involved the mitochondrial pathway. Notably, cooperation of BetA and anticancer drugs was found for various cytotoxic compounds with different modes of action (e.g., doxorubicin, cisplatin, Taxol, VP16, or actinomycin D. Importantly, BetA and anticancer drugs cooperated to induce apoptosis in different tumor cell lines, including p53 mutant cells, and also in primary tumor cells, but not in human fibroblasts indicating some tumor specificity. These findings indicate that using BetA as sensitizer in chemotherapy-based combination regimens may be a novel strategy to enhance the efficacy of anticancer therapy, which warrants further investigation.

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

    NARCIS (Netherlands)

    Kimpen, JLL; van Houten, M.A.


    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. (United States)

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


    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.


    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


    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;


    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. (United States)

    So, Anthony D; Shah, Tejen A


    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


    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? (United States)

    Brown, David


    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. Surface modeling of soil antibiotics. (United States)

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


    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.

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


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


    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...

  3. Use of proteasome inhibitors in anticancer therapy

    Directory of Open Access Journals (Sweden)

    Sara M. Schmitt


    Full Text Available The importance of the ubiquitin-proteasome pathway to cellular function has brought it to the forefront in the search for new anticancer therapies. The ubiquitin-proteasome pathway has proven promising in targeting various human cancers. The approval of the proteasome inhibitor bortezomib for clinical treatment of relapsed/refractory multiple myeloma and mantle cell lymphoma has validated the ubiquitin-proteasome as a rational target. Bortezomib has shown positive results in clinical use but some toxicity and side effects, as well as resistance, have been observed, indicating that further development of novel, less toxic drugs is necessary. Because less toxic drugs are necessary and drug development can be expensive and time-consuming, using existing drugs that can target the ubiquitin-proteasome pathway in new applications, such as cancer therapy, may be effective in expediting the regulatory process and bringing new drugs to the clinic. Toward this goal, previously approved drugs, such as disulfiram, as well as natural compounds found in common foods, such as green tea polyphenol (--EGCG and the flavonoid apigenin, have been investigated for their possible proteasome inhibitory and cell death inducing abilities. These compounds proved quite promising in preclinical studies and have now moved into clinical trials, with preliminary results that are encouraging. In addition to targeting the catalytic activity of the proteasome pathway, upstream regulators, such as the 19S regulatory cap, as well as E1, E2, and E3, are now being investigated as potential drug targets. This review outlines the development of novel proteasome inhibitors from preclinical to clinical studies, highlighting their abilities to inhibit the tumor proteasome and induce apoptosis in several human cancers.

  4. Potential Anti-cancer Activity of Furanodiene

    Institute of Scientific and Technical Information of China (English)

    Zhen-zhen Ba; Yan-ping Zheng; Hui Zhang; Xiu-yan Sun; Dong-hai Lin


    Objective: To study the anti-tumor activities of furanodiene (C15H20O), a primary sesquiterpene compound isolated from the essential oil of the rhizome of Curcuma wenyujin YH Chen et C. Ling(Wen Ezhu), in vitro and in vivo.Methods: In vitro MTT assay was used to further study the effects of time and dosage on anti-proliferation of furanodiene against the sensitive Hela, Hep-2,HL-60, U251 cells, based on the cytotoxic effects of furanodiene on 12 human malignant tumor cell lines with the essential oil of Wen Ezhu as control., and the half-inhibitory concentration (IC50) was observed. In vivo uterine cervix (U14) tumor cell was selected and the conventional assay method of anti-tumor activity was employed. Furanodiene liposome was administered intraperitoneally, and tumor-inhibitory rate, thymus and spleen indexes were observed.Results: The inhibitive effects on cell proliferation were shown in all of the twelve cell lines and the cytotoxic effects of furanodiene against Hela, Hep-2, HL-60, U251 cells were observed after 12 h of administration, the effect could last for at least 48 h in a dose dependent manner, and the IC50 values were 0.6, 1.7, 1.8, 7.0 μg/ml, respectively. Furanodiene was also found to show inhibitive effects on the proliferation of uterine cervix (U14) tumor induced in mice. The tumor inhibition rates were 36.09% (40 mg/kg), 41.55% (60 mg/kg), 58.29% (80 mg/kg), respectively.Conclusion: Furanodiene is one of primary anti-cancer active components in the essential oil of Wen Ezhu, and also a very effective agent against uterine cervix cancer, and has protection effect on the immune function.

  5. From antimicrobial to anticancer peptides. A review.

    Directory of Open Access Journals (Sweden)

    Diana eGaspar


    Full Text Available Antimicrobial peptides (AMPs are part of the innate immune defense mechanism of many organisms. Although AMPs have been essentially studied and developed as potential alternatives for fighting infectious diseases, their use as anticancer peptides (ACPs in cancer therapy either alone or in combination with other conventional drugs has been regarded as a therapeutic strategy to explore. As human cancer remains a cause of high morbidity and mortality worldwide, an urgent need of new, selective and more efficient drugs is evident. Even though ACPs are expected to be selective towards tumor cells without impairing the normal body physiological functions, the development of a selective ACP has been a challenge. It is not yet possible to predict antitumor activity based on ACPs structures. ACPs are unique molecules when compared to the actual chemotherapeutic arsenal available for cancer treatment and display a variety of modes of action which in some types of cancer seem to co-exist. Regardless the debate surrounding the definition of structure-activity relationships for ACPs, great effort has been invested in ACP design and the challenge of improving effective killing of tumor cells remains. As detailed studies on ACPs mechanisms of action are crucial for optimizing drug development, in this review we provide an overview of the literature concerning peptides’ structure, modes of action, selectivity and efficacy and also summarize some of the many ACPs studied and/or developed for targeting different solid and hematologic malignancies with special emphasis on the first group. Strategies described for drug development and for increasing peptide selectivity towards specific cells while reducing toxicity are also discussed.

  6. Antibiotic resistance in cancer patients. (United States)

    Gudiol, Carlota; Carratalà, Jordi


    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.

  7. [Action of antibiotics as signalling molecules]. (United States)

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


    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.

  8. Bacterial vaccines and antibiotic resistance


    Henriques-Normark, Birgitta; Normark, Staffan


    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...

  9. Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds. (United States)

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


    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.

  10. In vivo evaluation on the effects of HemoHIM in promoting anticancer activities and reducing the side-effects of anticancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Sung Kee; Jung, U Hee; Park, Hae Ran; Ju, Eun Jin; Cho, Eun Hee


    In this project, we aimed to obtain the preclinical in vivo evaluation data for the development of the herbal composition (HemoHIM) as the auxiliary agent for the anticancer treatment that can reduce the side-effects of anticancer drugs and enhance their anticancer activities. Firstly, in vitro studies showed that HemoHIM did not show any effects on the tumor cell growth inhibition by 2 anticancer drugs (cisplatin, 5-FU), which indicated that at least HemoHIM does not exert any adverse effects on the activities of anticancer drugs. Next, the in vivo studies with mice implanted with tumor cells(B16F0, LLC1) showed that HemoHIM partially enhanced the anticancer activities of drugs (cisplatin, 5-FU), and improved endogenous anticancer immune activities. Furthermore, in the same animal models, HemoHIM effectively reduced the side-effects of anticancer drugs (liver and renal toxicities by cisplatin, immune and hematopoietic disorders by 5-FU). These results collectively showed that HemoHIM can enhance the activities of anticancer drugs and reduce their side-effects in vitro and in vivo and HemoHIM does not exert any adverse effects on the efficacy of anticancer drugs. The results of this project can be utilized as the basic preclinical data for the development and approval of HemoHIM as the auxiliary agent for the anticancer treatment

  11. Preclinical Evidence on the Anticancer Properties of Food Peptides. (United States)

    Rajendran, Subin R C K; Ejike, Chukwunonso E C C; Gong, Min; Hannah, William; Udenigwe, Chibuike C


    Natural, synthetic and analogues of peptides have shown prospects for application in cancer chemotherapy. Notably, some food protein-derived peptides are known to possess anticancer activities in cultured cancer cells, and also in animal cancer models via different mechanisms including induction of apoptosis, cell cycle arrest, cellular membrane disruption, inhibition of intracellular signalling, topoisomerases and proteases, and antiangiogenic activity. Although the mechanism of several anticancer food peptides is yet to be clearly elucidated, there is potential for practical applications of the peptides as functional food and nutraceutical ingredients, especially in adjuvant cancer therapy. This review describes the aetiological mechanisms of cancers and the production, structures, mechanisms of action, availability, and cellular and physiological anticancer activities of the food peptides.


    Directory of Open Access Journals (Sweden)

    Narah Merina


    Full Text Available Plants have been the beacon of therapeutic sources for curing diseases from times immemorial. Medicinal plants with their isolated lead molecules are also used as an alternative medicine for treating neoplastic cells. Neoplastic cells are the anomalous proliferation of cells in the body which cause cancer. Diverse efficient compounds derived from natural products have been isolated as anticancer agents. These chemical compounds are formulated with a view to create effective drugs against cancer. Some of the lead molecules isolated from different medicinal plants are already in use to treat cancer and chemotherapeutic side effects. These potential and successful anticancer molecules include Vincristine, Vinblastin, Taxol, Camptothecin and Podophyllotoxin. This paper deals with the selective medicinal plants having anticancer properties which could be further designed to produce cancer curing drugs.

  13. Alkaloids Isolated from Natural Herbs as the Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Jin-Jian Lu


    Full Text Available Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery. Several alkaloids isolated from natural herbs exhibit antiproliferation and antimetastasis effects on various types of cancers both in vitro and in vivo. Alkaloids, such as camptothecin and vinblastine, have already been successfully developed into anticancer drugs. This paper focuses on the naturally derived alkaloids with prospective anticancer properties, such as berberine, evodiamine, matrine, piperine, sanguinarine, and tetrandrine, and summarizes the mechanisms of action of these compounds. Based on the information in the literature that is summarized in this paper, the use of alkaloids as anticancer agents is very promising, but more research and clinical trials are necessary before final recommendations on specific alkaloids can be made.

  14. Autophagy modulation as a target for anticancer drug discovery

    Institute of Scientific and Technical Information of China (English)

    Xin LI; Huai-long XU; Yong-xi LIU; Na AN; Si ZHAO; Jin-ku BAO


    Autophagy,an evolutionarily conserved catabolic process involving the engulfment and degradation of non-essential or abnormal cellular organelles and proteins,is crucial for homeostatic maintenance in living cells.This highly regulated,multi-step process has been implicated in diverse diseases including cancer.Autophagy can function as either a promoter or a suppressor of cancer,which makes it a promising and challenging therapeutic target.Herein,we overview the regulatory mechanisms and dual roles of autophagy in cancer.We also describe some of the representative agents that exert their anticancer effects by regulating autophagy.Additionally,some emerging strategies aimed at modulating autophagy are discussed as having the potential for future anticancer drug discovery.In summary,these findings will provide valuable information to better utilize autophagy in the future development of anticancer therapeutics that meet clinical requirements.

  15. Anti-cancer natural products isolated from chinese medicinal herbs

    Directory of Open Access Journals (Sweden)

    Wu Guosheng


    Full Text Available Abstract In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin, alkaloids (berberine, terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid, quinones (shikonin and emodin and saponins (ginsenoside Rg3, which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed.

  16. Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy. (United States)

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


    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.

  17. Insights into antibiotic resistance through metagenomic approaches. (United States)

    Schmieder, Robert; Edwards, Robert


    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.

  18. Antibiotic Prescription in Danish General Practice

    DEFF Research Database (Denmark)

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


    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...

  19. New antibiotic therapies for acne and rosacea. (United States)

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


    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.

  20. Metal Complexes of Quinolone Antibiotics and Their Applications: An Update

    Directory of Open Access Journals (Sweden)

    Valentina Uivarosi


    Full Text Available Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle at the 7-position, and a carbonyl oxygen atom at the 4-position quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.

  1. Metal complexes of quinolone antibiotics and their applications: an update. (United States)

    Uivarosi, Valentina


    Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.

  2. Triterpenoids of Marine Origin as Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Yong-Xin Li


    Full Text Available Triterpenoids are the most abundant secondary metabolites present in marine organisms, such as marine sponges, sea cucumbers, marine algae and marine-derived fungi. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells, as well as anticancer efficacy in preclinical animal models. In this review efforts have been taken to review the structural features and the potential use of triterpenoids of marine origin to be used in the pharmaceutical industry as potential anti-cancer drug leads.

  3. Proteasome inhibitory activity of thiazole antibiotics


    Pandit, Bulbul; Bhat, Uppoor; Andrei L Gartel


    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...

  4. Priorities for antibiotic resistance surveillance in Europe

    DEFF Research Database (Denmark)

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


    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....

  5. Hydrofocusing Bioreactor Produces Anti-Cancer Alkaloids (United States)

    Gonda, Steve R.; Valluri, Jagan V.


    microgravitation of an HFB do not need to maintain the same surface forces as in normal Earth gravitation, they can divert more energy sources to growth and differentiation and, perhaps, to biosynthesis of greater quantities of desired medicinal compounds. Because one can adjust the HFB to vary effective gravitation, one can also test the effects of intermediate levels of gravitation on biosynthesis of various products. The potential utility of this methodology for producing drugs was demonstrated in experiments in which sandalwood and Madagascar periwinkle cells were grown in an HFB. The conditions in the HFB were chosen to induce the cells to form into aggregate cultures that produced anti-cancer indole alkaloids in amounts greater than do comparable numbers of cells of the same species cultured according to previously known methodologies. The observations made in these experiments were interpreted as suggesting that the aggregation of the cells might be responsible for the enhancement of production of alkaloids.

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

  7. Bactericidal antibiotics induce programmed metabolic toxicity

    Directory of Open Access Journals (Sweden)

    Aislinn D. Rowan


    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.

  8. Antibiotic treatments and microbes in the gut. (United States)

    Macfarlane, Sandra


    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.

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

  10. Helicobacter pylori Antibiotic Resistance: Trends Over Time

    Directory of Open Access Journals (Sweden)

    Raymond G Lahaie


    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.

  11. Anticancer effects of Chinese herbal medicine, science or myth?

    Institute of Scientific and Technical Information of China (English)

    RUAN Wen-jing; LAI Mao-de; ZHOU Jian-guang


    Currently there is considerable interest among oncologists to find anticancer drugs in Chinese herbal medicine (CHM).In the past, clinical data showed that some herbs possessed anticancer properties, but western scientists have doubted the scientific validity of CHM due to the lack of scientific evidence from their perspective. Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of CHM. Experiments showed that CHM played its anticancer role by inducing apoptosis and differentiation, enhancing the immune system, inhibiting angiogenesis, reversing multidrug resistance (MDR), etc. Clinical trials demonstrated that CHM could improve survival, increase tumor response, improve quality of life, or reduce chemotherapy toxicity, although much remained to be determined regarding the objective effects of CHM in human in the context of clinical trials. Interestingly, both laboratory experiments and clinical trials have demonstrated that when combined with chemotherapy, CHM could raise the efficacy level and lower toxic reactions. These facts raised the feasibility of the combination of herbal medicines and chemotherapy, although much remained to be investigated in this area.

  12. The anticancer properties of phytochemical extracts from Salvia plants

    Directory of Open Access Journals (Sweden)

    Jiang YY


    Full Text Available Yuanyuan Jiang,1,2 Li Zhang,2 HP Vasantha Rupasinghe1,3 1Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS, Canada; 2College of Science, Sichuan Agricultural University, Yaan, Sichuan, People's Republic of China; 3Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada Abstract: Salvia species have been used as traditional medicine in many countries for a long time for health benefits. More importantly, in recent decades, the extracts of Salvia species have been shown to exhibit significant anticancer effects in vitro and in vivo on a wide range of cancer types. Therefore, this review provides a systematic summary of the anticancer profile and the underlying mechanisms of the extracts from Salvia species, which reveals the potential of these species, especially Salvia miltiorrhiza and Salvia officinalis, to be used as natural anticancer agents or auxiliary agents and bring new insights for further research and development of the genus Salvia. Keywords: Salvia, chemoprevention, anticancer, phytochemicals, sage, Danshen

  13. Tanshinones: Sources, Pharmacokinetics and Anti-Cancer Activities

    Directory of Open Access Journals (Sweden)

    Sung-Hoon Kim


    Full Text Available Tanshinones are a class of abietane diterpene compound isolated from Salvia miltiorrhiza (Danshen or Tanshen in Chinese, a well-known herb in Traditional Chinese Medicine (TCM. Since they were first identified in the 1930s, more than 40 lipophilic tanshinones and structurally related compounds have been isolated from Danshen. In recent decades, numerous studies have been conducted to investigate the isolation, identification, synthesis and pharmacology of tanshinones. In addition to the well-studied cardiovascular activities, tanshinones have been investigated more recently for their anti-cancer activities in vitro and in vivo. In this review, we update the herbal and alternative sources of tanshinones, and the pharmacokinetics of selected tanshinones. We discuss anti-cancer properties and identify critical issues for future research. Whereas previous studies have suggested anti-cancer potential of tanshinones affecting multiple cellular processes and molecular targets in cell culture models, data from in vivo potency assessment experiments in preclinical models vary greatly due to lack of uniformity of solvent vehicles and routes of administration. Chemical modifications and novel formulations had been made to address the poor oral bioavailability of tanshinones. So far, human clinical trials have been far from ideal in their design and execution for the purpose of supporting an anti-cancer indication of tanshinones.

  14. Personalizing Anti-Cancer Treatment from Genetic and Pharmacokinetic Perspective

    NARCIS (Netherlands)

    S. Bins (Sander)


    markdownabstractOnly recently, systemic anti-cancer treatment consisted of little more than chemotherapy, targeting mitosis in rapidly dividing cells such as cancer cells. Increasing biological insight has led to the development of more biology driven treatments, e.g. tyrosine kinase inhibitors and

  15. Mitochondrial chaperones may be targets for anti-cancer drugs (United States)

    Scientists at NCI have found that a mitochondrial chaperone protein, TRAP1, may act indirectly as a tumor suppressor as well as a novel target for developing anti-cancer drugs. Chaperone proteins, such as TRAP1, help other proteins adapt to stress, but sc

  16. Electrolyte disorders associated with the use of anticancer drugs. (United States)

    Liamis, George; Filippatos, Theodosios D; Elisaf, Moses S


    The use of anticancer drugs is beneficial for patients with malignancies but is frequently associated with the occurrence of electrolyte disorders, which can be hazardous and in many cases fatal. The review presents the electrolyte abnormalities that can occur with the use of anticancer drugs and provides the related mechanisms. Platinum-containing anticancer drugs induce hypomagnesemia, hypokalemia and hypocalcemia. Moreover, platinum-containing drugs are associated with hyponatremia, especially when combined with large volumes of hypotonic fluids aiming to prevent nephrotoxicity. Alkylating agents have been linked with the occurrence of hyponatremia [due to syndrome of inappropriate antidiuretic hormone secretion (SIADH)] and Fanconi's syndrome (hypophosphatemia, aminoaciduria, hypouricemia and/or glucosuria). Vinca alkaloids are associated with hyponatremia due to SIADH. Epidermal growth factor receptor monoclonal antibody inhibitors induce hypomagnesemia, hypokalemia and hypocalcemia. Other, monoclonal antibodies, such as cixutumumab, cause hyponatremia due to SIADH. Tyrosine kinase inhibitors are linked to hyponatremia and hypophosphatemia. Mammalian target of rapamycin inhibitors induce hyponatremia (due to aldosterone resistance), hypokalemia and hypophosphatemia. Other drugs such as immunomodulators or methotrexate have been also associated with hyponatremia. The administration of estrogens at high doses, streptozocin, azacitidine and suramin may induce hypophosphatemia. Finally, the drug-related tumor lysis syndrome is associated with hyperphosphatemia, hyperkalemia and hypocalcemia. The prevention of electrolyte derangements may lead to reduction of adverse events during the administration of anticancer drugs.

  17. Preclinical and clinical pharmacology of oral anticancer drugs

    NARCIS (Netherlands)

    Oostendorp, R.L.


    Nowadays, more than 25% of all anticancer drugs are developed as oral formulations. Oral administration of drugs has several advantages over intravenous (i.v.) administration. It will on average be more convenient for patients, because they can take oral medication themselves, there is no need for f

  18. Anticancer Activity of Chamaejasmine: Effect on Tubulin Protein

    Directory of Open Access Journals (Sweden)

    Yingkun Nie


    Full Text Available In this work, the anticancer activity of chamaejasmine was studied by evaluating its in vitro cytotoxicity against several human cancer cell lines (MCF-7, A549, SGC-7901, HCT-8, HO-4980, Hela, HepG2, PC-3, LNCap, Vero and MDCK using the MTT assay. Results indicated chamaejasmine showed more notable anticancer activity than taxol against PC-3 cells, with IC50 values of 2.28 and 3.98 µM, respectively. Furthermore, Western blot analysis showed that chamaejasmine was able to increase the expression of β-tubulin, but not α-tubulin. In silico simulations indicated that chamaejasmine specifically interacts with the active site which is located at the top of β-tubulin, thanks to the presence of strong hydrophobic effects between the core templates and the hydrophobic surface of the TB active site. The binding energy (Einter was calculated to be −164.77 kcal·mol−1. Results presented here suggest that chamaejasmine possesses anti-cancer properties relating to β-tubulin depolymerization inhibition, and therefore is a potential source of anticancer leads for the pharmaceutical industry.

  19. Synergistic anti-cancer effect of phenformin and oxamate.

    Directory of Open Access Journals (Sweden)

    W Keith Miskimins

    Full Text Available Phenformin (phenethylbiguanide; an anti-diabetic agent plus oxamate [lactate dehydrogenase (LDH inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS. Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and (18F-fluorodeoxyglucose (FDG uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively.

  20. Exploring the anticancer potential of the bacterial protein azurin

    Directory of Open Access Journals (Sweden)

    Ananda M Chakrabarty


    Full Text Available Bacterial proteins and their derivative peptides have emerged as promising anticancer agents. Nowadays they represent a valuable set of candidate drugs with different origins and modes of action. Among these, monomeric cupredoxins, which are metalloproteins involved in the electron transport chain of prokaryotes, have been shown to possess potent anticancer activities. In particular, much attention has been focused on azurin produced by the pathogenic bacterium Pseudomonas aeruginosa. More recently, several in vitro and in vivo studies have reported the multi-targeting anticancer properties of azurin. Moreover, p28, a peptide derived from azurin, has completed two phase I clinical trials in cancer patients with promising results. In this updated review, we examine the current knowledge regarding azurin’s modes of action as an anticancer therapeutic protein. We also review the clinical trial results of p28 emphasizing findings that make it suited (alone or in combination as a therapeutic agent for cancer treatment. Finally we discuss and address the challenges of using the human microbiome to discover novel and unique therapeutic cupredoxin-like proteins.

  1. CNS Anticancer Drug Discovery and Development Conference White Paper. (United States)

    Levin, Victor A; Tonge, Peter J; Gallo, James M; Birtwistle, Marc R; Dar, Arvin C; Iavarone, Antonio; Paddison, Patrick J; Heffron, Timothy P; Elmquist, William F; Lachowicz, Jean E; Johnson, Ted W; White, Forest M; Sul, Joohee; Smith, Quentin R; Shen, Wang; Sarkaria, Jann N; Samala, Ramakrishna; Wen, Patrick Y; Berry, Donald A; Petter, Russell C


    Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. Following this concise review of the science and clinical aspects of new CNS anticancer drug discovery and development, we discuss, under the rubric "Accelerating Drug Discovery and Development for Brain Tumors," further reasons why the pharmaceutical industry and academia have failed to develop new anticancer drugs for CNS malignancies and what it will take to change the current status quo and develop the drugs so desperately needed by our patients with malignant CNS tumors. While this White Paper is not a formal roadmap to that end, it should be an educational guide to clinicians and scientists to help move a stagnant field forward.

  2. Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves

    Directory of Open Access Journals (Sweden)

    Aunyachulee Ganogpichayagrai


    Full Text Available Diabetes and cancer are a major global public health problem. Plant-derived agents with undesirable side-effects were required. This study aimed to evaluate antidiabetic and anticancer activities of the ethanolic leaf extract of Mangifera indica cv. Okrong and its active phytochemical compound, mangiferin. Antidiabetic activities against yeast α-glucosidase and rat intestinal α-glucosidase were determined using 1 mM of p-nitrophenyl-α-D-glucopyranoside as substrate. Inhibitory activity against porcine pancreatic α-amylase was performed using 1 mM of 2-chloro-4 nitrophenol-α-D-maltotroside-3 as substrate. Nitrophenol product was spectrophotometrically measured at 405 nm. Anticancer activity was evaluated against five human cancer cell lines compared to two human normal cell lines using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Mango leaf extract and mangiferin exhibited dose-dependent inhibition against yeast α-glucosidase with the IC 50 of 0.0503 and 0.5813 mg/ml, respectively, against rat α-glucosidase with the IC 50 of 1.4528 and 0.4333 mg/ml, respectively, compared to acarbose with the IC 50 of 11.9285 and 0.4493 mg/ml, respectively. For anticancer activity, mango leaf extract, at ≥200 μg/ml showed cytotoxic potential against all tested cancer cell lines. In conclusion, mango leaf possessed antidiabetic and anticancer potential in vitro.

  3. Synthesis of Some Benzimidazole Derivatives Bearing 1,3,4-Oxadiazole Moiety as Anticancer Agents. (United States)

    Mochona, Bereket; Mazzio, Elizabeth; Gangapurum, Madhavei; Mateeva, Nelly; Redda, K K


    In an effort to establish new benzimidazole related structural leads with improved anticancer activity, several new benzimidazole derivatives (5a-i) with 1,3,4-oxadiazole scaffold incorporated were synthesized and studied for their anticancer activity. The anticancer screening against MDA-MB-231 breast cancer cell lines showed that compound (5c) exhibited moderate cytotoxicity.

  4. In silico identification of anti-cancer compounds and plants from traditional Chinese medicine database (United States)

    Dai, Shao-Xing; Li, Wen-Xing; Han, Fei-Fei; Guo, Yi-Cheng; Zheng, Jun-Juan; Liu, Jia-Qian; Wang, Qian; Gao, Yue-Dong; Li, Gong-Hua; Huang, Jing-Fei


    There is a constant demand to develop new, effective, and affordable anti-cancer drugs. The traditional Chinese medicine (TCM) is a valuable and alternative resource for identifying novel anti-cancer agents. In this study, we aim to identify the anti-cancer compounds and plants from the TCM database by using cheminformatics. We first predicted 5278 anti-cancer compounds from TCM database. The top 346 compounds were highly potent active in the 60 cell lines test. Similarity analysis revealed that 75% of the 5278 compounds are highly similar to the approved anti-cancer drugs. Based on the predicted anti-cancer compounds, we identified 57 anti-cancer plants by activity enrichment. The identified plants are widely distributed in 46 genera and 28 families, which broadens the scope of the anti-cancer drug screening. Finally, we constructed a network of predicted anti-cancer plants and approved drugs based on the above results. The network highlighted the supportive role of the predicted plant in the development of anti-cancer drug and suggested different molecular anti-cancer mechanisms of the plants. Our study suggests that the predicted compounds and plants from TCM database offer an attractive starting point and a broader scope to mine for potential anti-cancer agents.

  5. 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. (United States)

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


    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.

  6. Anthracycline antibiotics non-covalently incorporated into the block copolymer micelles: in vivo evaluation of anti-cancer activity. (United States)

    Batrakova, E V; Dorodnych, T Y; Klinskii, E Y; Kliushnenkova, E N; Shemchukova, O B; Goncharova, O N; Arjakov, S A; Alakhov, V Y; Kabanov, A V


    The chemosensitising effects of poly(ethylene oxide)-poly(propylene oxide)-poly-(ethylene oxide) (PEO-PPO-PEO) block copolymers (Pluronic) in multidrug-resistant cancer cells has been described recently (Alakhov VY, Moskaleva EY, Batrakova EV, Kabanov AV 1996, Biocon. Chem., 7, 209). This paper presents initial studies on in vivo evaluation of Pluronic copolymers in the treatment of cancer. The anti-tumour activity of epirubicin (EPI) and doxorubicin (DOX), solubilised in micelles of Pluronic L61, P85 and F108, was investigated using murine leukaemia P388 and daunorubicin-sensitive Sp2/0 and -resistant Sp2/0(DNR) myeloma cells grown subcutaneously (s.c.). The study revealed that the lifespan of the animals and inhibition of tumour growth were considerably increased in mice treated with drug/copolymer compositions compared with animals treated with the free drugs. The anti-tumour activity of the drug/copolymer compositions depends on the concentration of the copolymer and its hydrophobicity, as determined by the ratio of the lengths of hydrophilic PEO and hydrophobic PPO segments. The data suggest that higher activity is associated with more hydrophobic copolymers. In particular, a significant increase in lifespan (T/C> 150%) and tumour growth inhibition (> 90%) was observed in animals with Sp2/0 tumours with EPI/P85 and DOX/L61 compositions. The effective doses of these compositions caused inhibition of Sp2/0 tumour growth and complete disappearance of tumour in 33-50% of animals. Future studies will focus on the evaluation of the activity of Pluronic-based compositions against human drug-resistant tumours.

  7. Acquired antibiotic resistance genes:an overview

    NARCIS (Netherlands)

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


    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,

  8. 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.


    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,

  9. Antibiotic resistance: a physicist’s view (United States)

    Allen, Rosalind; Waclaw, Bartłomiej


    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.

  10. Interplay between gut microbiota and antibiotics

    NARCIS (Netherlands)

    Jesus Bello Gonzalez, de Teresita


    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

  11. Optimising Antibiotic Usage to Treat Bacterial Infections (United States)

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


    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.

  12. Topical and oral antibiotics for acne vulgaris. (United States)

    Del Rosso, James Q


    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.

  13. 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.


    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

  14. 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.


    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

  15. Polyene antibiotic that inhibits membrane transport proteins

    NARCIS (Netherlands)

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


    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

  16. Repairing the broken market for antibiotic innovation. (United States)

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


    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.

  17. Analysis of antibiotic consumption in burn patients (United States)

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


    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

  18. Analysis of antibiotic consumption in burn patients

    Directory of Open Access Journals (Sweden)

    Soleymanzadeh-Moghadam, Somayeh


    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.

  19. Antibiotic RX in Hospitals: Proceed with Caution

    Centers for Disease Control (CDC) Podcasts


    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.

  20. 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.

  1. Antibiotic-Resistant Bacteria: There is Hope. (United States)

    Offner, Susan


    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)

  2. Snort Sniffle Sneeze: No Antibiotics Please

    Centers for Disease Control (CDC) Podcasts


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

  3. Antibiotics: Pharmacists Can Make the Difference

    Centers for Disease Control (CDC) Podcasts


    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.

  4. A functional perspective of nitazoxanide as a potential anticancer drug

    Energy Technology Data Exchange (ETDEWEB)

    Di Santo, Nicola, E-mail:; Ehrisman, Jessie, E-mail:


    Highlights: • Combination anti-cancer therapies are associated with increased toxicity and cross-resistance. • Some antiparasitic compounds may have anti-cancer potential. • Nitazoxanide interferes with metabolic and pro-death signaling. • Preclinical studies are needed to confirm anticancer ability of nitazoxanide. - Abstract: Cancer is a group of diseases characterized by uncontrolled cell proliferation, evasion of cell death and the ability to invade and disrupt vital tissue function. The classic model of carcinogenesis describes successive clonal expansion driven by the accumulation of mutations that eliminate restraints on proliferation and cell survival. It has been proposed that during cancer's development, the loose-knit colonies of only partially differentiated cells display some unicellular/prokaryotic behavior reminiscent of robust ancient life forms. The seeming “regression” of cancer cells involves changes within metabolic machinery and survival strategies. This atavist change in physiology enables cancer cells to behave as selfish “neo-endo-parasites” that exploit the tumor stromal cells in order to extract nutrients from the surrounding microenvironment. In this framework, it is conceivable that anti-parasitic compounds might serve as promising anticancer drugs. Nitazoxanide (NTZ), a thiazolide compound, has shown antimicrobial properties against anaerobic bacteria, as well as against helminths and protozoa. NTZ has also been successfully used to promote Hepatitis C virus (HCV) elimination by improving interferon signaling and promoting autophagy. More compelling however are the potential anti-cancer properties that have been observed. NTZ seems to be able to interfere with crucial metabolic and pro-death signaling such as drug detoxification, unfolded protein response (UPR), autophagy, anti-cytokine activities and c-Myc inhibition. In this article, we review the ability of NTZ to interfere with integrated survival mechanisms of

  5. Circadian rhythms and new options for novel anticancer therapies

    Directory of Open Access Journals (Sweden)

    Prosenc Zmrzljak U


    Full Text Available Ursula Prosenc ZmrzljakFaculty of Medicine, Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, University of Ljubljana, Ljubljana, SloveniaAbstract: The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.Keywords: circadian rhythms, cancer, chronotherapy, detoxification metabolism

  6. Aqueous extracts of microalgae exhibit antioxidant and anticancer activities

    Institute of Scientific and Technical Information of China (English)

    Sanaa MM Shanab; Soha SM Mostafa; Emad A Shalaby; Ghada I Mahmoud


    Objective: To investigate the antioxidant and anticancer activities of aqueous extracts of nine microalgal species. Methods: Variable percentages of major secondary metabolites (total phenolic content, terpenoids and alkaloids) as well as phycobiliprotein pigments (phycocyanin, allophycocyanin and phycoerythrin) in the aqueous algal extracts were recorded. Antioxidant activity of the algal extracts was performed using 2, 2 diphenyl-1-picrylhydrazyl (DPPH) test and 2,2'-azino-bis (ethylbenzthiazoline-6-sulfonic acid (ABTS.+) radical cation assay. Anticancer efficiency of the algal water extracts was investigated against Ehrlich Ascites Carcinoma cell (EACC) and Human hepatocellular cancer cell line (HepG2). Results: Antioxidant activity of the algal extracts was performed using DPPH test and ABTS.+ radical cation assays which revealed 30.1-72.4% and 32.0-75.9% respectively. Anticancer efficiency of the algal water extracts was investigated against Ehrlich Ascites Carcinoma Cell (EACC) and Human Hepatocellular cancer cell line (HepG2) with an activity ranged 87.25% and 89.4% respectively. Culturing the promising cyanobacteria species; Nostocmuscorum and Oscillatoria sp. under nitrogen stress conditions (increasing and decreasing nitrate content of the normal BG11 medium, 1.5 g/L), increased nitrate concentration (3, 6 and 9 g/L) led to a remarkable increase in phycobilin pigments followed by an increase in both antioxidant and anticancer activities in both cyanobacterial species. While the decreased nitrate concentration (0.75, 0.37 and 0.0 g/L) induced an obvious decrease in phycobilin pigments with complete absence of allophycocyanin in case of Oscillatoria sp. Conclusions: Nitrogen starvation (0.00 g/L nitrate) induced an increase and comparable antioxidant and anticancer activities to those cultured in the highest nitrate content.

  7. Advances in pneumococcal antibiotic resistance. (United States)

    Song, Jae-Hoon


    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.

  8. Retapamulin: A newer topical antibiotic

    Directory of Open Access Journals (Sweden)

    D Dhingra


    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.

  9. Antibiotic resistance pattern in uropathogens

    Directory of Open Access Journals (Sweden)

    Gupta V


    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.

  10. Engineering antibiotic production and overcoming bacterial resistance. (United States)

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


    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.

  11. Pneumonia in immunocompetent patients: combination antibiotic therapy. (United States)

    Salva, S; Borgatta, B; Rello, J


    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.

  12. Antibiotic Resistance in Pediatric Urinary Tract Infections. (United States)

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


    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.

  13. Antibiotic resistance: an editorial review with recommendations. (United States)

    Rosen, Ted


    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.

  14. Innovation of novel antibiotics: an economic perspective. (United States)

    McKellar, Michael R; Fendrick, A Mark


    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.

  15. [Allergy to beta-lactam antibiotics]. (United States)

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


    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.

  16. In vitro and in vivo Methods for Anticancer Activity Evaluation and Some Indian Medicinal Plants Possessing Anticancer Properties: An Overview

    Directory of Open Access Journals (Sweden)

    Sumitra Chanda


    Full Text Available Cancer is a major public health burden in both developed and developing countries. Anticancer activity is the effect of natural and synthetic or biological and chemical agents to reverse, suppress or prevent carcinogenic progression. Several synthetic agents are used to cure the disease but they have their toxicity and hence the research is going on to investigate the plant derived chemotherapeutic agents. Therefore an attempt has been made to review different in vitro and in vivo methods for estimating anticancer properties of natural products from medicinal plants. In this review, 50 anticancer medicinal plants of Indian origin belonging to 35 families are reported along with detailed information regarding part used, extract used, type of the model used, types of tested cancer cell lines, etc. These plants continue to be used against various types of tumours such as sarcoma, lymphoma, carcinoma and leukemia. All these plants are potential candidates for in vivo studies since they are showing good in vitro anticancer activity.

  17. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim


    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

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

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

  20. Get Smart: Know When Antibiotics Work - Symptom Relief (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 ...

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

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

  3. Get Smart: Know When Antibiotics Work - Ear Infections (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 ...

  4. Get Smart: Know When Antibiotics Work - Sore Throat (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 ...

  5. Systems, not pills: The options market for antibiotics seeks to rejuvenate the antibiotic pipeline. (United States)

    Brogan, David M; Mossialos, Elias


    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.

  6. Do antibiotics have environmental side-effects? Impact of synthetic antibiotics on biogeochemical processes. (United States)

    Roose-Amsaleg, Céline; Laverman, Anniet M


    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.

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

    Directory of Open Access Journals (Sweden)

    Tomson Göran


    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

  8. Persistence of antibiotic resistance in bacterial populations. (United States)

    Andersson, Dan I; Hughes, Diarmaid


    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.

  9. Molecular regulation of antibiotic biosynthesis in streptomyces. (United States)

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


    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.

  10. Fungal treatment for the removal of antibiotics and antibiotic resistance genes in veterinary hospital wastewater. (United States)

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


    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.

  11. Antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci. (United States)

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


    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.

  12. Inducing optimal substitution between antibiotics under open access to the resource of antibiotic susceptibility. (United States)

    Herrmann, Markus; Nkuiya, Bruno


    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.

  13. Bacteriocins - a viable alternative to antibiotics? (United States)

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


    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.

  14. Broad spectrum antibiotic compounds and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Koglin, Alexander; Strieker, Matthias


    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.

  15. Synthesis, cytotoxicity and antibacterial activity of new esters of polyether antibiotic - salinomycin. (United States)

    Antoszczak, Michał; Popiel, Katarzyna; Stefańska, Joanna; Wietrzyk, Joanna; Maj, Ewa; Janczak, Jan; Michalska, Greta; Brzezinski, Bogumil; Huczyński, Adam


    A series of 12 novel ester derivatives of naturally occurring polyether antibiotic - salinomycin were synthesized, characterised by spectroscopic method and evaluated for their in vitro antibacterial activity and cytotoxicity. The new esters were demonstrated to form complexes with monovalent and divalent metal cation of 1:1 stoichiometry in contrast to the salinomycin which forms only complexes with monovalent cations. All the obtained compounds show potent antiproliferative activity against human cancer cell lines and a good selectivity index for cancer versus mammalian cells. Additionally, 3 compounds showed higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity towards normal cells than those of unmodified salinomycin and standard anticancer drugs such as cisplatin and doxorubicin. Some of the synthesized compounds showed good inhibitory activity against Staphylococcus strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These studies show that salinomycin esters are interesting scaffolds for the development of novel anticancer and Gram-positive antibacterial agents.

  16. Anti-cancer activities of diospyrin, its derivatives and analogues

    KAUST Repository

    Sagar, Sunil


    Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

  17. The anticancer and antiobesity effects of Mediterranean diet. (United States)

    Kwan, Hiu Yee; Chao, Xiaojuan; Su, Tao; Fu, Xiuqiong; Tse, Anfernee Kai Wing; Fong, Wang Fun; Yu, Zhi-Ling


    Cancers have been the leading cause of death worldwide and the prevalence of obesity is also increasing in these few decades. Interestingly, there is a direct association between cancer and obesity. Each year, more than 90,000 cancer deaths are caused by obesity or overweight. The dietary pattern in Crete, referred as the traditional Mediterranean diet, is believed to confer Crete people the low mortality rates from cancers. Nevertheless, the antiobesity effect of the Mediterranean diet is less studied. Given the causal relationship between obesity and cancer, the antiobesity effect of traditional Mediterranean diet might contribute to its anticancer effects. In this regard, we will critically review the anticancer and antiobesity effects of this diet and its dietary factors. The possible mechanisms underlying these effects will also be discussed.

  18. Novel antimicrobial peptides with high anticancer activity and selectivity.

    Directory of Open Access Journals (Sweden)

    Hung-Lun Chu

    Full Text Available We describe a strategy to boost anticancer activity and reduce normal cell toxicity of short antimicrobial peptides by adding positive charge amino acids and non-nature bulky amino acid β-naphthylalanine residues to their termini. Among the designed peptides, K4R2-Nal2-S1 displayed better salt resistance and less toxicity to hRBCs and human fibroblast than Nal2-S1 and K6-Nal2-S1. Fluorescence microscopic studies indicated that the FITC-labeled K4R2-Nal2-S1 preferentially binds cancer cells and causes apoptotic cell death. Moreover, a significant inhibition in human lung tumor growth was observed in the xenograft mice treated with K4R2-Nal2-S1. Our strategy provides new opportunities in the development of highly effective and selective antimicrobial and anticancer peptide-based therapeutics.

  19. CEST theranostics: label-free MR imaging of anticancer drugs (United States)

    Xu, Jiadi; Yadav, Nirbhay N.; Chan, Kannie W. Y.; Luo, Liangping; McMahon, Michael T.; Vogelstein, Bert; van Zijl, Peter C.M.; Zhou, Shibin; Liu, Guanshu


    Image-guided drug delivery is of great clinical interest. Here, we explored a direct way, namely CEST theranostics, to detect diamagnetic anticancer drugs simply through their inherent Chemical Exchange Saturation Transfer (CEST) MRI signal, and demonstrated its application in image-guided drug delivery of nanoparticulate chemotherapeutics. We first screened 22 chemotherapeutic agents and characterized the CEST properties of representative agents and natural analogs in three major categories, i.e., pyrimidine analogs, purine analogs, and antifolates, with respect to chemical structures. Utilizing the inherent CEST MRI signal of gemcitabine, a widely used anticancer drug, the tumor uptake of the i.v.-injected, drug-loaded liposomes was successfully detected in CT26 mouse tumors. Such label-free CEST MRI theranostics provides a new imaging means, potentially with an immediate clinical impact, to monitor the drug delivery in cancer. PMID:26837220

  20. PEGylation in anti-cancer therapy: An overview

    Directory of Open Access Journals (Sweden)

    Prajna Mishra


    Full Text Available Advanced drug delivery systems using poly(ethylene glycol (PEG is an important development in anti-cancer therapy. PEGylation has the ability to enhance the retention time of the therapeutics like proteins, enzymes small molecular drugs, liposomes and nanoparticles by protecting them against various degrading mechanisms active inside a tissue or cell, which consequently improves their therapeutic potential. PEGylation effectively alters the pharmacokinetics (PK of a variety of drugs and dramatically improves the pharmaceutical values; recent development of which includes fabrication of stimuli-sensitive polymers/smart polymers and polymeric micelles to cope of with the pathophysiological environment of targeted site with less toxic effects and more effectiveness. This overview discusses PEGylation involving proteins, enzymes, low molecular weight drugs, liposomes and nanoparticles that has been developed, clinically tried for anti-cancer therapy during the last decade.

  1. Phytochemicals as Anticancer and Chemopreventive Topoisomerase II Poisons



    Phytochemicals are a rich source of anticancer drugs and chemopreventive agents. Several of these chemicals appear to exert at least some of their effects through interactions with topoisomerase II, an essential enzyme that regulates DNA supercoiling and removes knots and tangles from the genome. Topoisomerase II-active phytochemicals function by stabilizing covalent protein-cleaved DNA complexes that are intermediates in the catalytic cycle of the enzyme. As a result, these compounds convert...

  2. Synthesis and Anticancer Activity of Novel Thiazole-5-Carboxamide Derivatives

    Directory of Open Access Journals (Sweden)

    Wen-Xi Cai


    Full Text Available A series of novel 2-phenyl-4-trifluoromethyl thiazole-5-carboxamide derivatives have been synthesized and evaluated for their anticancer activity against A-549, Bel7402, and HCT-8 cell lines. Among the tested compounds, highest activity (48% was achieved with the 4-chloro-2-methylphenyl amido substituted thiazole containing the 2-chlorophenyl group on the two position of the heterocyclic ring. Other structurally similar compounds displayed moderate activity. The key intermediates have been fully characterized.

  3. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast


    Li, Yanran; Smolke, Christina D.


    Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides str...

  4. Metabolic monosaccharides altered cell responses to anticancer drugs. (United States)

    Chen, Long; Liang, Jun F


    Metabolic glycoengineering has been used to manipulate the glycochemistry of cell surfaces and thus the cell/cell interaction, cell adhesion, and cell migration. However, potential application of glycoengineering in pharmaceutical sciences has not been studied until recently. Here, we reported that Ac(4)ManNAc, an analog of N-acetyl-D-mannosamine (ManNAc), could affect cell responses to anticancer drugs. Although cells from different tissues and organs responded to Ac(4)ManNAc treatment differently, treated cells with increased sialic acid contents showed dramatically reduced sensitivity (up to 130 times) to anti-cancer drugs as tested on various drugs with distinct chemical structures and acting mechanisms. Neither increased P-glycoprotein activity nor decreased drug uptake was observed during the course of Ac(4)ManNAc treatment. However, greatly altered intracellular drug distributions were observed. Most intracellular daunorubicin was found in the perinuclear region, but not the expected nuclei in the Ac(4)ManNAc treated cells. Since sialoglycoproteins and gangliosides were synthesized in the Golgi, intracellular glycans affected intracellular signal transduction and drug distributions seem to be the main reason for Ac(4)ManNAc affected cell sensitivity to anticancer drugs. It was interesting to find that although Ac(4)ManNAc treated breast cancer cells (MDA-MB-231) maintained the same sensitivity to 5-Fluorouracil, the IC(50) value of 5-Fluorouracil to the same Ac(4)ManNAc treated normal cells (MCF-10A) was increased by more than 20 times. Thus, this Ac(4)ManNAc treatment enlarged drug response difference between normal and tumor cells provides a unique opportunity to further improve the selectivity and therapeutic efficiency of anticancer drugs.

  5. Assessing T-cell responses in anticancer immunotherapy (United States)

    Escors, David; Liechtenstein, Therese; Perez-Janices, Noemi; Schwarze, Julia; Dufait, Ines; Goyvaerts, Cleo; Lanna, Alessio; Arce, Frederick; Blanco-Luquin, Idoia; Kochan, Grazyna; Guerrero-Setas, David; Breckpot, Karine


    Since dendritic cells operate as professional antigen-presenting cells (APCs) and hence are capable of jumpstarting the immune system, they have been exploited to develop a variety of immunotherapeutic regimens against cancer. In the few past years, myeloid-derived suppressor cells (MDSCs) have been shown to mediate robust immunosuppressive functions, thereby inhibiting tumor-targeting immune responses. Thus, we propose that the immunomodulatory activity of MDSCs should be carefully considered for the development of efficient anticancer immunotherapies. PMID:24244902

  6. New trends for metal complexes with anticancer activity


    Bruijnincx, Pieter C A; Sadler, P. J.


    Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discuss...

  7. In silico prediction of anticancer peptides by TRAINER tool

    Directory of Open Access Journals (Sweden)

    Zohre Hajisharifi


    Full Text Available Cancer is one of the causes of death in the world. Several treatment methods exist against cancer cells such as radiotherapy and chemotherapy. Since traditional methods have side effects on normal cells and are expensive, identification and developing a new method to cancer therapy is very important. Antimicrobial peptides, present in a wide variety of organisms, such as plants, amphibians and mammals, are newly discovered agents. These peptides have various structures, sizes and molecular compositions; hence developing a computational method to predict these anticancer peptides is useful. In the present study, first, 2 databases with 138 and 206 anticancer and non-anticancer peptides were introduced, classified by TRAINER. TRAINER ( TRAINER/ is a new online tool designed for classification of any alphabet of sequences. TRAINER allows users to select from among several feature representation schemes and supervised machine learning methods with relevant parameters. In this study, Naive Bayes and radial basis were used in a support vector machine. The accuracy and specificity in combination of features by Naive Bayes were 83% and by radial basis 87% and 92% respectively. The results demonstrate that two methods are useful for classification of these peptides; however, the accuracy of Radial Basis is higher than Naive Bayes.

  8. Potential anti-cancer drugs commonly used for other indications. (United States)

    Hanusova, Veronika; Skalova, Lenka; Kralova, Vera; Matouskova, Petra


    An increasing resistance of mammalian tumor cells to chemotherapy along with the severe side effects of commonly used cytostatics has raised the urgency in the search for new anti-cancer agents. Several drugs originally approved for indications other than cancer treatment have recently been found to have a cytostatic effect on cancer cells. These drugs could be expediently repurposed as anti-cancer agents, since they have already been tested for toxicity in humans and animals. The groups of newly recognized potential cytostatics discussed in this review include benzimidazole anthelmintics (albendazole, mebendazole, flubendazole), anti-hypertensive drugs (doxazosin, propranolol), psychopharmaceuticals (chlorpromazine, clomipramine) and antidiabetic drugs (metformin, pioglitazone). All these drugs have a definite potential to be used especially in combinations with other cytostatics; the chemotherapy targeting of multiple sites now represents a promising approach in cancer treatment. The present review summarizes recent information about the anti-cancer effects of selected drugs commonly used for other medical indications. Our aim is not to collect all the reported results, but to present an overview of various possibilities. Advantages, disadvantages and further perspectives regarding individual drugs are discussed and evaluated.

  9. In silico prediction of anticancer peptides by TRAINER tool

    Directory of Open Access Journals (Sweden)

    Zohre Hajisharifi


    Full Text Available Cancer is one of the causes of death in the world. Several treatment methods exist against cancer cells such as radiotherapy and chemotherapy. Since traditional methods have side effects on normal cells and are expensive, identification and developing a new method to cancer therapy is very important. Antimicrobial peptides, present in a wide variety of organisms, such as plants, amphibians and mammals, are newly discovered agents. These peptides have various structures, sizes and molecular compositions; hence developing a computational method to predict these anticancer peptides is useful. In the present study, first, 2 databases with 138 and 206 anticancer and non-anticancer peptides were introduced, classified by TRAINER. TRAINER ( TRAINER/ is a new online tool designed for classification of any alphabet of sequences. TRAINER allows users to select from among several feature representation schemes and supervised machine learning methods with relevant parameters. In this study, Naive Bayes and radial basis were used in a support vector machine. The accuracy and specificity in combination of features by Naive Bayes were 83% and by radial basis 87% and 92% respectively. The results demonstrate that two methods are useful for classification of these peptides; however, the accuracy of Radial Basis is higher than Naive Bayes.

  10. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Neng [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Yin, Huabing, E-mail: [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Ji, Bozhi; Klauke, Norbert; Glidle, Andrew [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Zhang, Yongkui; Song, Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Cai, Lulu; Ma, Liang; Wang, Guangcheng [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Chen, Lijuan, E-mail: [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Wang, Wenwen [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)


    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: Black-Right-Pointing-Pointer BSA-doped calcium carbonate microspheres with porous structure were prepared. Black-Right-Pointing-Pointer Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. Black-Right-Pointing-Pointer The release of encapsulated camptothecin is pH dependent Black-Right-Pointing-Pointer In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  11. Anticancer effects and molecular mechanisms of epigallocatechin-3-gallate

    Directory of Open Access Journals (Sweden)

    Kyoung-jin Min


    Full Text Available Epigallocatechin-3-gallate (EGCG is a type of catechin found in green tea. EGCG exhibits a variety of activities, including anti-inflammatory, antidiabetes, antiobesity, and antitumor. In this review, we focus on the antitumor effects of EGCG. EGCG inhibits carcinogen activity, tumorigenesis, proliferation, and angiogenesis, and induces cell death. These effects are associated with modulation of reactive oxygen species (ROS production. Although EGCG has a dual function of antioxidant and pro-oxidant potential, EGCG-mediated modulation of ROS production is reported to be responsible for its anticancer effects. The EGCG-mediated inhibition of nuclear factor-κB signaling is also associated with inhibition of migration, angiogenesis, and cell viability. Activation of mitogen-activated protein kinases activity upregulates the anticancer effect of EGCG on migration, invasion, and apoptosis. In addition, EGCG could also induce epigenetic modification by inhibition of DNA methyltransferase activity and regulation of acetylation on histone, leading to an upregulation of apoptosis. Although EGCG promotes strong anticancer effects by multiple mechanisms, further studies are needed to define the use of EGCG in clinical treatment.

  12. Anticancer Effects of HESA-A:An Herbal Marine Compound

    Institute of Scientific and Technical Information of China (English)

    Amrollah Ahmadi; Gholamreza Habibi; Mehdi Farrokhnia


    @@ HESA-A,a natural biological compound,is a mixture of herbal-marine substances that includes Penaeus latisculatus (king prawn),Carum carvi and Apium graveolens with anticancer properties(1,2).Although the exact mechanism of action of HESA-A on tumor cells is not fully understood,it appears to have multiple pharmacological effects(2). The lack of selectivity for tumor cells,which is associated with conventional cancer chemotherapy,is the main cause of chemotherapy complications and failure of anticancer agents.Many complementary and alternative medicine (CAM) studies are focused on products obtained from plants,animals or other natural sources to find compounds with high therapeutic indices.HESA-A inhibits the growth of cancer cells selectively and in a dose dependent manner.At the highest concentration (5.4 mg/mL),HESA-A completely inhibits the growth of cells and this effect gradually decreases as the dose is reduced.HESA-A is not cytotoxic towards normal cell lines unlike cancer cells.A major concern in this selectivity effect is the possible interaction with the cell DNA.The apoptotic effects of HESA-A may also have a major role in its anticancer properties(3,4).

  13. Peptide-based proteasome inhibitors in anticancer drug design. (United States)

    Micale, Nicola; Scarbaci, Kety; Troiano, Valeria; Ettari, Roberta; Grasso, Silvana; Zappalà, Maria


    The identification of the key role of the eukaryotic 26S proteasome in regulated intracellular proteolysis and its importance as a target in many pathological conditions wherein the proteasomal activity is defective (e.g., malignancies, autoimmune diseases, neurodegenerative diseases, etc.) prompted several research groups to the development of specific inhibitors of this multicatalytic complex with the aim of obtaining valid drug candidates. In regard to the anticancer therapy, the peptide boronate bortezomib (Velcade®) represents the first molecule approved by FDA for the treatment of multiple myeloma in 2003 and mantle cell lymphoma in 2006. Since then, a plethora of molecules targeting the proteasome have been identified as potential anticancer agents and a few of them reached clinical trials or are already in the market (i.e., carfilzomib; Kyprolis®). In most cases, the design of new proteasome inhibitors (PIs) takes into account a proven peptide or pseudopeptide motif as a base structure and places other chemical entities throughout the peptide skeleton in such a way to create an efficacious network of interactions within the catalytic sites. The purpose of this review is to provide an in-depth look at the current state of the research in the field of peptide-based PIs, specifically those ones that might find an application as anticancer agents.

  14. Zirconium Phosphate Nanoplatelet Potential for Anticancer Drug Delivery Applications. (United States)

    González, Millie L; Ortiz, Mayra; Hernández, Carmen; Cabán, Jennifer; Rodríguez, Axel; Colón, Jorge L; Báez, Adriana


    Zirconium phosphate (ZrP) nanoplatelets can intercalate anticancer agents via an ion exchange reaction creating an inorganic delivery system with potential for cancer treatment. ZrP delivery of anticancer agents inside tumor cells was explored in vitro. Internalization and cytotoxicity of ZrP nanoplatelets were studied in MCF-7 and MCF-10A cells. DOX-loaded ZrP nanoplatelets (DOX@ZrP) uptake was assessed by confocal (CLSM) and transmission electron microscopy (TEM). Cytotoxicity to MCF-7 and MCF-10A cells was determined by the MTT assay. Reactive Oxy- gen Species (ROS) production was analyzed by fluorometric assay, and cell cycle alterations and induction of apoptosis were analyzed by flow cytometry. ZrP nanoplatelets were localized in the endosomes of MCF-7 cells. DOX and ZrP nanoplatelets were co-internalized into MCF-7 cells as detected by CLSM. While ZrP showed limited toxicity to MCF-7 cells, DOX@ZrP was cytotoxic at an IC₅₀ similar to that of free DOX. Meanwhile, DOX lC₅₀ was significantly lower than the equivalent concentration of DOX@ZrP in MCF-10A cells. ZrP did not induce apoptosis in both cell lines. DOX and DOX@ZrP induced significant oxidative stress in both cell models. Results suggest that ZrP nanoplatelets are promising as carriers of anticancer agents into cancer cells.

  15. Microfluidics: Emerging prospects for anti-cancer drug screening. (United States)

    Wlodkowic, Donald; Darzynkiewicz, Zbigniew


    Cancer constitutes a heterogenic cellular system with a high level of spatio-temporal complexity. Recent discoveries by systems biologists have provided emerging evidence that cellular responses to anti-cancer modalities are stochastic in nature. To uncover the intricacies of cell-to-cell variability and its relevance to cancer therapy, new analytical screening technologies are needed. The last decade has brought forth spectacular innovations in the field of cytometry and single cell cytomics, opening new avenues for systems oncology and high-throughput real-time drug screening routines. The up-and-coming microfluidic Lab-on-a-Chip (LOC) technology and micro-total analysis systems (μTAS) are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level. The vast miniaturization of LOC systems and multiplexing enables innovative strategies to reduce drug screening expenditures while increasing throughput and content of information from a given sample. Small cell numbers and operational reagent volumes are sufficient for microfluidic analyzers and, as such, they enable next generation high-throughput and high-content screening of anti-cancer drugs on patient-derived specimens. Herein we highlight the selected advancements in this emerging field of bioengineering, and provide a snapshot of developments with relevance to anti-cancer drug screening routines.

  16. Phenethyl isothiocyanate: a comprehensive review of anti-cancer mechanisms. (United States)

    Gupta, Parul; Wright, Stephen E; Kim, Sung-Hoon; Srivastava, Sanjay K


    The epidemiological evidence suggests a strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer. Among other constituents of cruciferous vegetables, isothiocyanates (ITC) are the main bioactive chemicals present. Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects. PEITC is known to not only prevent the initiation phase of carcinogenesis process but also to inhibit the progression of tumorigenesis. PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis. Pre-clinical evidence suggests that combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy. Based on accumulating evidence, PEITC appears to be a promising agent for cancer therapy and is already under clinical trials for leukemia and lung cancer. This is the first review which provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of PEITC as a future anti-cancer agent.

  17. Anticancer efficacy of unique pyridine-based tetraindoles. (United States)

    Fu, Chih-Wei; Hsieh, Yun-Jung; Chang, Tzu Ting; Chen, Chia-Ling; Yang, Cheng-Yu; Liao, Anne; Hsiao, Pei-Wen; Li, Wen-Shan


    Results of previous studies demonstrated that the tetraindole, SK228, which has a high lipid but low water solubility, displayed moderate anticancer efficacy in a xenograft model of breast cancer. This finding led to the proposal that new, pyridine based tetraindole (PBT) analogs of SK228, containing tetraindole moieties distributed about central protonated pyridine cores, would have enhanced bioavailabilities and anticancer efficacies. Among the PBTs prepared and subjected to biological studies, 3f (FCW81) was observed to display the highest antiproliferative activity against the two triple negative breast cancer (TNBCs) cell lines, MDA-MB-231 and BT549. In addition, its mode of action was shown to involve G2/M arrest of the cell cycle along with the promotion of increased levels of cyclin B1 and p-chk2 and a decreased level of p-cdc2. DNA damage and induction of apoptosis caused by FCW81 was found to be associated with a decrease in DNA repair. Significantly, FCW81 displays therapeutic efficacy in a xenograft model of human breast cancer by not only serving to inhibit markedly the growth of cancer cells but also to block effectively cancer cell metastasis. Collectively, the results of these studies have led to the identification of novel pyridine-tetraindole based anticancer agents with potential use in TNBC therapy.

  18. Green tea and anticancer perspectives: updates from last decade. (United States)

    Butt, Masood Sadiq; Ahmad, Rabia Shabir; Sultan, M Tauseef; Qayyum, Mir M Nasir; Naz, Ambreen


    Green tea is the most widely consumed beverage besides water and has attained significant attention owing to health benefits against array of maladies, e.g., obesity, diabetes mellitus, cardiovascular disorders, and cancer insurgence. The major bioactive molecules are epigallocatechin-3-gallate, epicatechin, epicatechin-3-gallate, epigallocatechin, etc. The anticarcinogenic and antimutagenic activities of green tea were highlighted some years ago. Several cohort studies and controlled randomized trials suggested the inverse association of green tea consumption and cancer prevalence. Cell culture and animal studies depicted the mechanisms of green tea to control cancer insurgence, i.e., induction of apoptosis to control cell growth arrest, altered expression of cell-cycle regulatory proteins, activation of killer caspases, and suppression of nuclear factor kappa-B activation. It acts as carcinoma blocker by modulating the signal transduction pathways involved in cell proliferation, transformation, inflammation, and metastasis. However, results generated from some research interventions conducted in different groups like smokers and nonsmokers, etc. contradicted with aforementioned anticancer perspectives. In this review paper, anticancer perspectives of green tea and its components have been described. Recent findings and literature have been surfed and arguments are presented to clarify the ambiguities regarding anticancer perspectives of green tea and its component especially against colon, skin, lung, prostate, and breast cancer. The heading of discussion and future trends is limelight of the manuscript. The compiled manuscript provides new avenues for researchers to be explored in relation to green tea and its bioactive components.

  19. Antibiotic inhibition of group I ribozyme function. (United States)

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


    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.

  20. Antibiotics as immunomodulant agents in COPD. (United States)

    Blasi, Francesco; Mantero, Marco; Aliberti, Stefano


    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.

  1. Mechanisms of antibiotic resistance in enterococci. (United States)

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


    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.

  2. The antibiotics in the chemical space. (United States)

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


    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.

  3. 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...

  4. Antibiotic stewardship in the intensive care unit. (United States)

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


    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.

  5. Alliance for the Prudent Use of Antibiotics (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 ...

  6. Controlling antibiotic resistance in the ICU

    NARCIS (Netherlands)

    Derde, L.P.G.


    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

  7. Prophylactic antibiotic regimens in tumour surgery (PARITY)

    DEFF Research Database (Denmark)

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


    -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...

  8. Get Smart: Know When Antibiotics Work

    Centers for Disease Control (CDC) Podcasts


    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.

  9. Structure-based design of a new bisintercalating anthracycline antibiotic. (United States)

    Chaires, J B; Leng, F; Przewloka, T; Fokt, I; Ling, Y H; Perez-Soler, R; Priebe, W


    A new bisintercalating anthracycline antibiotic, WP631, has been designed and synthesized. The rational design of the new compound was based upon the geometry of monomeric anthracyclines bound to DNA oligonucleotides observed in high-resolution crystal structures. Monomeric units of daunorubicin have been linked through their reactive 3' NH2 substituents on the daunosamine moieties to form the new bisanthracycline WP631. Viscosity studies confirmed that WP631 binds to DNA by bisintercalation. Differential scanning calorimetry and UV melting experiments were used to measure the ultratight binding of WP631 to DNA. The binding constant for the interaction of WP631 with herring sperm DNA was determined to be 2.7 x 10(11) M-1 at 20 degrees C. The large, favorable binding free energy of -15.3 kcal mol-1 was found to result from a large, negative enthalpic contribution of -30.2 kcal mol-1. A molecular model was generated that shows the favorable stereochemical fit of the linker in the DNA minor groove. The cytotoxicity of WP631 was compared to that of doxorubicin using MCF-7-sensitive and MCF-7/VP-16 MRP-mediated multidrug-resistant cell lines. These initial studies showed that while WP631 is slightly less cytotoxic than doxorubicin in the sensitive cell line, it appears to overcome MRP-mediated multidrug resistance and was much more cytotoxic against the MCF-7/VP-16 cell line than was doxorubicin. The design of new potential anticancer agents based on known structural principles was found to produce a compound with significantly increased DNA binding affinity and with interesting biological activity.

  10. Acquired Antibiotic Resistance Genes: An Overview


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


    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...

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



    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.

  12. The determinants of the antibiotic resistance process


    Espinosa, Beatriz


    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...

  13. Antibiotic stewardship in the intensive care unit


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


    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...

  14. Antibiotic tolerance and resistance in biofilms

    DEFF Research Database (Denmark)

    Ciofu, Oana; Tolker-Nielsen, Tim


    One of the most important features of microbial biofilms is their tolerance to antimicrobial agents and components of the host immune system. The difficulty of treating biofilm infections with antibiotics is a major clinical problem. Although antibiotics may decrease the number of bacteria...... in biofilms, they will not completely eradicate the bacteria in vivo which may have important clinical consequences in form of relapses of the infection....

  15. Direction of aminoacylated transfer RNAs into antibiotic synthesis and peptidoglycan-mediated antibiotic resistance. (United States)

    Shepherd, Jennifer; Ibba, Michael


    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.

  16. Assessing Antibiotic Resistance of Staphyloccocus: Students Use Their Own Microbial Flora To Explore Antibiotic Resistance. (United States)

    Omoto, Charlotte K.; Malm, Kirstin


    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)

  17. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents. (United States)

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


    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.

  18. 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


    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.

  19. Pharmacokinetic characteristics and anticancer effects of 5-Fluorouracil loaded nanoparticles

    Directory of Open Access Journals (Sweden)

    Jiang Wenqi


    Full Text Available Abstract Background It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU loaded block copolymers, with poly(γ-benzyl-L-glutamate (PBLG as the hydrophobic block and poly(ethylene glycol (PEG as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound. Methods 5-FU loaded PEG-PBLG (5-FU/PEG-PBLG nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM and transmission electron microscopy (TEM were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC. To study in vivo effects, LoVo cells (human colon cancer cell line or Tca8113 cells (human oral squamous cell carcinoma cell line were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres. Results 5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min, lower peak concentration (C, 4563.5 μg/L vs. 17047.3 μg/L, and greater distribution volume (VD, 0.114 L vs. 0.069 L. Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p 0.05. Conclusion In our model system, 5-FU/PEG-PBLG nanoparticles

  20. Selektion von Aptameren gegen Antibiotika und deren Einsatz in empflindlichen Assayformaten


    Wochner, Aniela


    Due to its toxicity, the use of daunomycin, an anthracycline antibiotic that is widely used in cancer therapy, poses a risk for everyone involved with the substance. Therefore, a strict surveillance of the working area of producers, pharmacists, and hospital staff is equally necessary as monitoring the actual dose of the drug in a patient's blood. Since a relevant proportion of administered daunomycin is excreted unmetabolised, contaminated waste water can also have an impact on the environme...

  1. DNA-Aptamers Binding Aminoglycoside Antibiotics

    Directory of Open Access Journals (Sweden)

    Nadia Nikolaus


    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


    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. (United States)

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


    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


    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.


    Directory of Open Access Journals (Sweden)



    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. (United States)

    Dane, Aaron


    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.


    Directory of Open Access Journals (Sweden)

    Ece Barça


    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 (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 (United States)

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


    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 (United States)

    Zhao, Yuyun; Jiang, Xingyu


    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)


    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. Tryptophan as a Probe to Study the Anticancer Mechanism of Action and Specificity of α-Helical Anticancer Peptides

    Directory of Open Access Journals (Sweden)

    Guirong Li


    Full Text Available In the present study, a single tryptophan, as a fluorescence probe, was shifted from the N-terminus to the middle and to the C-terminus of a 26-residue α-helical anticancer peptide sequence to study the mechanism of action and specificity. The hydrophobicity of peptides, as well as peptide helicity and self-associating ability, were slightly influenced by the position change of tryptophan in the peptide sequence, while the hemolytic activity and anticancer activity of the peptide analogs remained the same. The tryptophan fluorescence experiment demonstrated that peptide analogs were more selective against LUVs mimicking cancer cell membranes than LUVs mimicking normal cell membranes. During the interaction with target membranes, the N-terminus of an anticancer peptide may be inserted vertically or tilted into the hydrophobic components of the phospholipid bilayer first. The thermodynamic parameters of the peptides PNW and PCW, when interacting with zwitterionic DMPC or negatively charged DMPS, were determined by ITC. DSC experiments showed that peptide analogs significantly altered the phase transition profiles of DMPC, but did not dramatically modify the phase transition of DMPS. It is demonstrated that hydrophobic interactions are the main driving force for peptides interacting with normal cell membranes, whilst, electrostatic interactions dominate the interactions between peptides and cancer cell membranes. Utilizing tryptophan as a fluorescence probe molecule appears to be a practicable approach to determine the interaction of peptides with phospholipid bilayers.

  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:


    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. (United States)

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


    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


    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. Synthesis of ultrastable copper sulfide nanoclusters via trapping the reaction intermediate: potential anticancer and antibacterial applications. (United States)

    Wang, Hong-Yin; Hua, Xian-Wu; Wu, Fu-Gen; Li, Bolin; Liu, Peidang; Gu, Ning; Wang, Zhifei; Chen, Zhan


    Copper-based nanomaterials have broad applications in electronics, catalysts, solar energy conversion, antibiotics, tissue imaging, and photothermal cancer therapy. However, it is challenging to prepare ultrasmall and ultrastable CuS nanoclusters (NCs) at room temperature. In this article, a simple method to synthesize water-soluble, monodispersed CuS NCs is reported based on the strategy of trapping the reaction intermediate using thiol-terminated, alkyl-containing short-chain poly(ethylene glycol)s (HS-(CH2)11-(OCH2CH2)6-OH, abbreviated as MUH). The MUH-coated CuS NCs have superior stability in solutions with varied pH values and are stable in pure water for at least 10 months. The as-prepared CuS NCs were highly toxic to A549 cancer cells at a concentration of higher than 100 μM (9.6 μg/mL), making them be potentially applicable as anticancer drugs via intravenous administration by liposomal encapsulation or by direct intratumoral injection. Besides, for the first time, CuS NCs were used for antibacterial application, and 800 μM (76.8 μg/mL) CuS NCs could completely kill the E. coli cells through damaging the cell walls. Moreover, the NCs synthesized here have strong near-infrared (NIR) absorption and can be used as a candidate reagent for photothermal therapy and photoacoustic imaging. The method of trapping the reaction intermediate for simple and controlled synthesis of nanoclusters is generally applicable and can be widely used to synthesize many metal-based (such as Pt, Pd, Au, and Ag) nanoclusters and nanocrystals.

  17. 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


    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

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


    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.


    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...

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


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


    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 ...

  20. The interactions of anticancer agents with tea catechins: current evidence from preclinical studies. (United States)

    Shang, Weihu; Lu, Weidong; Han, Mei; Qiao, Jinping


    Tea catechins exhibit a broad range of pharmacological activities that impart beneficial effects on human health. Epigallocatechin-3-gallate (EGCG), one of the major tea catechins, has been widely associated with cancer prevention and treatment. In addition, tea catechins in combination with anticancer drugs are being evaluated as a new cancer treatment strategy. However, the interactions of anticancer drugs with tea catechins are largely unknown. Accumulated data indicate significant interactions between anticancer drugs and tea catechins, such as synergistic tumor inhibition or antagonist activity. Therefore, it is critical to understand comprehensively the effects of tea catechins on anticancer drugs. Focusing on evidence from preclinical studies, this paper will review the interactions between anticancer drugs and tea catechins, including pharmacodynamics and pharmacokinetics effects. We hope that by detailing the interactions between anticancer drugs and tea catechins, more attention will be directed to this important therapeutic combination in the future.

  1. 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


    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...

  2. RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance. (United States)

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


    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.

  3. 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.


    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

  4. Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture. (United States)

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


    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.

  5. 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.


    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.

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

    Directory of Open Access Journals (Sweden)

    Songhe Zhang


    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.

  7. Fighting urinary tract infections with antibiotic and non-antibiotic therapies. (United States)

    Peri, Lluis


    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.

  8. 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.


    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

  9. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption

    DEFF Research Database (Denmark)

    Megraud, Francis; Coenen, Samuel; Versporten, Ann


    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...

  10. 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.


    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

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

  12. Anticancer properties of polysaccharides isolated from fungi of the Basidiomycetes class. (United States)

    Lemieszek, Marta; Rzeski, Wojciech


    Basidiomycete mushrooms represent a valuable source of biologically active compounds with anticancer properties. This feature is primarily attributed to polysaccharides and their derivatives. The anticancer potential of polysaccharides is linked to their origin, composition and chemical structure, solubility and method of isolation. Moreover, their activity can be significantly increased by chemical modifications. Anticancer effects of polysaccharides can be expressed indirectly (immunostimulation) or directly (cell proliferation inhibition and/or apoptosis induction). Among the wide range of polysaccharides with documented anticancer properties, lentinan, polysaccharide-K (PSK) and schizophyllan deserve special attention. These polysaccharides for many years have been successfully applied in cancer treatment and their mechanism of action is the best known.

  13. Non-covalent carriage of anticancer agents by humanized antibody trastuzumab. (United States)

    Yadav, Arpita; Sharma, Sweta; Yadav, Veejendra Kumar


    This article explores the internalization and non-covalent carriage of small molecule anticancer agents like vinca alkaloids by humanized monoclonal antibody trastuzumab. Such carriage is marked by significant reduction in side effects and increased therapeutic value of these anticancer agents. This study is coherent with few clinical observations of enhanced efficiency of these anticancer agents when co-administered with therapeutic antibodies. This study will also serve as the foundation for screening a database of anticancer agents for possible compounds that may be co-delivered alongwith the antibody. Based on this study vincristine conformation inside antibody and its charge environment may be used as descriptors for screening purposes.

  14. [Acute otitis media and antibiotics. Evidence-based guidelines for antibiotic therapy?]. (United States)

    Thorøe, J; Lous, J


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  16. Mini profile of potential anticancer properties of propofol.

    Directory of Open Access Journals (Sweden)

    Jing Song

    Full Text Available BACKGROUND: Propofol (2, 6-diisopropylphenol is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to establish a profile to quantitatively and functionally evaluate the anticancer properties of propofol in three cancer cell lines: non-small cell lung carcinoma cell line A549, human colon carcinoma cell line LoVo, and human breast cancer cell line SK-BR-3. We demonstrated that the expression level of caspase-3, an apoptosis biomarker, significantly increased in a dose-dependent manner after 24-h stimulation with 100 µM propofol in A549 cells, and slightly increased in LoVo cells. However, there was no change in caspase-3 expression in SK-BR-3 cells. High caspase-3 expression in A549 cells may be modulated by the ERK1/2 pathway because phosphorylated ERK1/2 dramatically reduced after propofol treatment. BAX, a major protein that promotes apoptosis in the regulation phase, was highly expressed in A549 cells after treatment with 25 µM propofol. Apoptosis induced by propofol may be associated with cancer cells carrying Kras mutations. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the anti-cancer effects of propofol, which are consistent with those of previous studies, are likely associated with the Kras mutation status. Only Kras mutation in Codon 12 instead of other Kras status has been demonstrated to play an important role in sensitizing the propofol-induced apoptosis in cancer cell lines from our study. These findings may enable us a detailed investigation of propofol/Kras-mediated cancer cell apoptosis in the future.

  17. Anticancer activity of new compounds using benzimidazole as a scaffold. (United States)

    Rashid, Mohd; Husain, Asif; Shaharyar, Mohammad; Sarafroz, Mohd


    The design and synthesis of substituted 1-(1-ethy-1H-benzimidazol-2-yl) ethanone (3a-f) and substituted 1-(2-bromoethyl)-2- (1-hydrazinylidene or ethylidene)-1H-benzimidazole (3g-j) have been successfully achieved under microwave irradiation with an aim for finding promising anticancer agents. Among the synthetic compounds, those with potential activity were selected and evaluated in-vitro for anticancer activity at the National Cancer Institute (NCI), USA, against 60 cancer cell lines from nine types of human cancer. The title compound 3e (NSC: 765733/1) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10 µM) on all human cell lines of NCI. This compound was considered for further study at five dose levels (0.01, 0.1, 1, 10 and 100 µM) with GI50 values ranging from 0.19 to 92.7 µM. Compound 3e was found superior for Non-small cell lung cancer cell lines (HOP-92) and calculated end points (GI50 0.19, TGI 1.45, LC50 >100 and Log10GI50 -6.70, Log10TGI -5.84, Log10LC50 >-4.00). Docking study was performed using Maestro 9.0 to provide binding mode into binding sites of topoisomerase enzyme (PDB ID: 1SC7). Hopefully in the future, compound 3e could be used as novel template for the development of potential anticancer agents.

  18. Anticancer activity of Ficus religiosa engineered copper oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Sankar, Renu; Maheswari, Ramasamy; Karthik, Selvaraju [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India); Shivashangari, Kanchi Subramanian, E-mail: [Regional Forensic Science Laboratory, Tiruchirapalli, Tamilnadu (India); Ravikumar, Vilwanathan, E-mail: [Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu (India)


    The design, synthesis, characterization and application of biologically synthesized nanomaterials have become a vital branch of nanotechnology. There is a budding need to develop a method for environmentally benign metal nanoparticle synthesis, that do not use toxic chemicals in the synthesis protocols to avoid adverse effects in medical applications. Here, it is a report on an eco-friendly process for rapid synthesis of copper oxide nanoparticles using Ficus religiosa leaf extract as reducing and protecting agent. The synthesized copper oxide nanoparticles were confirmed by UV–vis spectrophotometer, absorbance peaks at 285 nm. The copper oxide nanoparticles were analyzed with field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, dynamic light scattering (DLS) and X-ray diffraction (XRD) spectrum. The FE-SEM and DLS analyses exposed that copper oxide nanoparticles are spherical in shape with an average particle size of 577 nm. FT-IR spectral analysis elucidates the occurrence of biomolecules required for the reduction of copper oxide ions. Zeta potential studies showed that the surface charge of the formed nanoparticles was highly negative. The XRD pattern revealed that synthesized nanoparticles are crystalline in nature. Further, biological activities of the synthesized nanoparticles were confirmed based on its stable anti-cancer effects. The apoptotic effect of copper oxide nanoparticles is mediated by the generation of reactive oxygen species (ROS) involving the disruption of mitochondrial membrane potential (Δψm) in A549 cells. The observed characteristics and results obtained in our in vitro assays suggest that the copper nanoparticles might be a potential anticancer agent. - Highlights: • Biogenic synthesis of copper oxide nanoparticles by leaf extract of Ficus religiosa • Characterized via UV–vis, FT-IR, DLS, FE-SEM with EDAX and XRD • Protein may act as an encapsulating, reducing and stabilizing

  19. Utilisation of antibiotic therapy in community practice.

    LENUS (Irish Health Repository)

    McGowan, B


    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.

  20. Intravenous desensitization to beta-lactam antibiotics. (United States)

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


    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.

  1. Multiple antibiotic sensitivity in a pediatric population. (United States)

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


    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.

  2. Antibiotic resistance: are we all doomed? (United States)

    Collignon, P


    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.

  3. 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.


    Directory of Open Access Journals (Sweden)

    V. V. Klochko


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

  5. Antibiotic prophylaxis in primary immune deficiency disorders. (United States)

    Kuruvilla, Merin; de la Morena, Maria Teresa


    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.

  6. (-)-Arctigenin as a lead compound for anticancer agent. (United States)

    Chen, Gui-Rong; Li, Hong-Fu; Dou, De-Qiang; Xu, Yu-Bin; Jiang, Hong-Shuai; Li, Fu-Rui; Kang, Ting-Guo


    (-)-Arctigenin, an important active constituent of the traditional Chinese herb Fructus Arctii, was found to exhibit various bioactivities, so it can be used as a good lead compound for further structure modification in order to find a safer and more potent medicine. (-)-Arctigenin derivatives 1-5 of (-)-arctingen were obtained by modifying with ammonolysis at the lactone ring and sulphonylation at C (6') and C (6″) and O-demethylation at CH3O-C (3'), CH3O-C (3″) and CH3O-C (4″), and their anticancer bioactivities were examined.

  7. Significance of Cancer Stem Cells in Anti-Cancer Therapies (United States)

    Botelho, Mónica; Alves, Helena


    Stem cells are the focus of cutting edge research interest because of their competence both to self-renew and proliferate, and to differentiate into a variety of tissues, offering enticing prospects of growing replacement organs in vitro, among other possible therapeutic implications. It is conceivable that cancer stem cells share a number of biological hallmarks that are different from their normal-tissue counterparts and that these might be taken advantage of for therapeutic benefits. In this review we discuss the significance of cancer stem cells in diagnosis and prognosis of cancer as well as in the development of new strategies for anti-cancer drug design.

  8. Synthesis and anticancer evaluation of alpha-lipoic acid derivatives. (United States)

    Zhang, Shi-Jie; Ge, Qiu-Fu; Guo, Dian-Wu; Hu, Wei-Xiao; Liu, Hua-Zhang


    alpha-Lipoic acid derivatives were synthesized and evaluated for their in vitro anticancer activities against NCI-460, HO-8910, KB, BEL-7402, and PC-3 cell lines. The results, for most compounds exhibited dose-dependent inhibitory property and several compounds had good inhibitions at the dose of 100 microg/mL. Compound 17 m was further selected for in vivo evaluation against S180 xenograft in ICR mice, which had 24.7% tumor-weight inhibition through intragastric administration of 200mg/kg of body weight. Moreover, the LD(50) in mice for 17 m through ig exceeded 1000 mg/kg of body weight.


    Institute of Scientific and Technical Information of China (English)


    Doxorubicin(ADM)-loaded magnetic anticancer nanoparticles,using Fe3O4 as core, doxorubicin as model drug and polyvinylpyrrolidone (PVP) as matrix, were prepared by inverse emulsion polymerization. The experimental results showed that the average diameter of Fe3O4 particles was 19.8nm. The X-ray diffraction indicated that the prepared Fe3O4 particle was pure cubic Fe3O4. The results obtained by SEM showed the magnetic nanoparticles under optimal operating condition had a smooth spherical surface , LLS showed an average size of 78.7nm. And IR results demonstrated that they consisted of ADM, PVP and Fe3O4.

  10. Discovery of Anticancer Agents of Diverse Natural Origin. (United States)

    Kinghorn, A Douglas; DE Blanco, Esperanza J Carcache; Lucas, David M; Rakotondraibe, H Liva; Orjala, Jimmy; Soejarto, D Doel; Oberlies, Nicholas H; Pearce, Cedric J; Wani, Mansukh C; Stockwell, Brent R; Burdette, Joanna E; Swanson, Steven M; Fuchs, James R; Phelps, Mitchell A; Xu, Lihui; Zhang, Xiaoli; Shen, Young Yongchun


    Recent progress is described in an ongoing collaborative multidisciplinary research project directed towards the purification, structural characterization, chemical modification, and biological evaluation of new potential natural product anticancer agents obtained from a diverse group of organisms, comprising tropical plants, aquatic and terrestrial cyanobacteria, and filamentous fungi. Information is provided on how these organisms are collected and processed. The types of bioassays are indicated in which initial extracts, chromatographic fractions, and purified isolated compounds of these acquisitions are tested. Several promising biologically active lead compounds from each major organism class investigated are described, and these may be seen to be representative of a very wide chemical diversity.

  11. [Anticancer properties of Trichoderma asperellum 302 from buried soils]. (United States)

    Tukhbatova, R I; Fattakhova, A N; Alimova, F K


    Melanoma is one of the most malignant tumors, which leaves no chance of survival in the case of the "bang". There are various ways to treat tumors, however, recently in the field of cancer research, there are studies in which fungal metabolites have been used as antitumor agents. In this study we examined the effect of the culture fluid of the fungus Trichoderma asperellum 302 on the growth and development of melanoma B 16. We have shown that these culture fluid has anticancer properties, causing destruction of tumor tissue. Obtained data open new possibilities and prospects for the use of active substances derived from fungi in the complex therapy of cancer.

  12. Medicinal organometallic chemistry: designing metal arene complexes as anticancer agents. (United States)

    Peacock, Anna F A; Sadler, Peter J


    The field of medicinal inorganic chemistry is rapidly advancing. In particular organometallic complexes have much potential as therapeutic and diagnostic agents. The carbon-bound and other ligands allow the thermodynamic and kinetic reactivity of the metal ion to be controlled and also provide a scaffold for functionalization. The establishment of structure-activity relationships and elucidation of the speciation of complexes under conditions relevant to drug testing and formulation are crucial for the further development of promising medicinal applications of organometallic complexes. Specific examples involving the design of ruthenium and osmium arene complexes as anticancer agents are discussed.


    Directory of Open Access Journals (Sweden)

    Madhuri S.


    Full Text Available Emblica officinalis (Amla is traditionally used for several diseases, and it is believed to increase the defense against diseases. It is particularly used for the treatment of cancer, diabetes, liver disorders, heart disease, ulcer, snake venom, haemorrhage, diarrhea, dysentery, anaemia and ophthalmic disorders. The antioxidant, immunomodulatory, anticancer, cytoprotective, analgesic, antimicrobial, antipyretic, antitussive and gastroprotective are the important properties of amla. Vitamin C, tannins and flavaniods present in amla have very powerful antioxidant activities. Due to rich vitamin C, amla is successfully used in the treatment of human scurvy.

  14. Targets of 3-bromopyruvate, a new, energy depleting, anticancer agent. (United States)

    Dell'Antone, Paolo


    3-bromopyruvate (3-BrPA), a pyruvate analog recently proposed as a possible anticancer drug, was investigated in relation to its capacity to inhibit energy production in fractions obtained from normal cells (rat hepatocytes) and in isolated rat thymocytes . Findings were that main targets of the drug were glyceraldehyde 3-phosphate dehydrogenase, and not hexokinase as suggested for hepatoma cells, and succinate -driven ATP synthesis. Consistently with the above findings, in the normal cells studied (thymocytes ) the drug elicited an important fall in ATP levels. The significance of the present findings in concern with a possible therapeutic usefulness of the drug is discussed.

  15. Isolated cell behavior drives the evolution of antibiotic resistance. (United States)

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


    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.

  16. An antibiotic's journey from marketing authorization to use, Norway. (United States)

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


    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.

  17. Spinal epidural abscess treated with antibiotics alone. (United States)

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


    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.

  18. Antibiotic tolerance facilitates the evolution of resistance. (United States)

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


    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.

  19. Antibiotic resistance genes in the environment

    Directory of Open Access Journals (Sweden)

    Jianqiang Su


    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.

  20. Antibiotics for acute otitis media in children. (United States)

    Nitsche, María Pía; Carreño, Monica


    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).

  1. Anticancer drug mithramycin interacts with core histones: An additional mode of action of the DNA groove binder

    Directory of Open Access Journals (Sweden)

    Amrita Banerjee


    Full Text Available Mithramycin (MTR is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin – histone proteins – as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode or both histones and chromosomal DNA (dual binding mode. The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR–DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg2+. As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.

  2. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink. (United States)

    Wilson, Maxwell Z; Wang, Rurun; Gitai, Zemer; Seyedsayamdost, Mohammad R


    While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed.

  3. Novel walnut peptide–selenium hybrids with enhanced anticancer synergism: facile synthesis and mechanistic investigation of anticancer activity

    Directory of Open Access Journals (Sweden)

    Liao W


    Full Text Available Wenzhen Liao,1 Rong Zhang,1 Chenbo Dong,2 Zhiqiang Yu,3 Jiaoyan Ren11College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 2Civil and Environmental Engineering, Rice University, Houston, TX, USA; 3School of Pharmaceutical Science, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaAbstract: This contribution reports a facile synthesis of degreased walnut peptides (WP1-functionalized selenium nanoparticles (SeNPs hybrids with enhanced anticancer activity and a detailed mechanistic evaluation of its superior anticancer activity. Structural and chemical characterizations proved that SeNPs are effectively capped with WP1 via physical absorption, resulting in a stable hybrid structure with an average diameter of 89.22 nm. A panel of selected human cancer cell lines demonstrated high susceptibility toward WP1-SeNPs and displayed significantly reduced proliferative behavior. The as-synthesized WP1-SeNPs exhibited excellent selectivity between cancer cells and normal cells. The targeted induction of apoptosis in human breast adenocarcinoma cells (MCF-7 was confirmed by the accumulation of arrested S-phase cells, nuclear condensation, and DNA breakage. Careful investigations revealed that an extrinsic apoptotic pathway can be attributed to the cell apoptosis and the same was confirmed by activation of the Fas-associated with death domain protein and caspases 3, 8, and 9. In addition, it was also understood that intrinsic apoptotic pathways including reactive oxygen species generation, as well as the reduction in mitochondrial membrane potential, are also involved in the WP1-SeNP-induced apoptosis. This suggested the involvement of multiple apoptosis pathways in the anticancer activity. Our results indicated that WP1-SeNP hybrids with Se core encapsulated in a WP1 shell could be a highly

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

    DEFF Research Database (Denmark)

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


    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...

  5. Antibiotics in dental implants: A review of literature (United States)

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


    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

  6. Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection (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.

  7. How to Fight Back Against Antibiotic Resistance

    DEFF Research Database (Denmark)

    Dantas, Gautam; Sommer, Morten


    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...

  8. Collateral sensitivity of antibiotic-resistant microbes. (United States)

    Pál, Csaba; Papp, Balázs; Lázár, Viktória


    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.

  9. Antibiotics, probiotics and prebiotics in IBD. (United States)

    Bernstein, Charles N


    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

  10. Chrysin-benzothiazole conjugates as antioxidant and anticancer agents. (United States)

    Mistry, Bhupendra M; Patel, Rahul V; Keum, Young-Soo; Kim, Doo Hwan


    7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS(+) scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.

  11. Metronomic Chemotherapy: Low Dose Less Toxicity Anticancer Strategy

    Directory of Open Access Journals (Sweden)

    Anjan Khadka


    Full Text Available Metronomic chemotherapy is the frequent administration of chemotherapy drugs at doses below the maximum tolerated dose and with no prolonged drug‑free break. It thus achieves a sustained low blood level of the drug without significant toxic side‑effects. Metronomic therapy leads to sustained plasma concentration of the drug without significant toxic side‑effects and hence there is reduced need for supportive therapy. However in case of conventional therapy toxicity is a concern. Metronomic chemotherapy exerts both direct and indirect effects on tumor cells and their microenvironment. It can inhibit tumor angiogenesis, stimulate anticancer immune response and also induces tumor dormancy. Optimizing a metronomic anticancer therapy is still a challenging task. New strategies are being developed to combine metronomic chemotherapy with conventional chemotherapy, radiotherapy and/or targeted therapy. An important disadvantage of this type of regimen is the empiricism in finding the optimal ‘low‑dose’ and in monitoring therapeutic efficacy during the course of treatment.

  12. "Ziziphus jujuba": A red fruit with promising anticancer activities

    Directory of Open Access Journals (Sweden)

    Zoya Tahergorabi


    Full Text Available Ziziphus jujuba Mill. (Z. jujuba is a traditional herb with a long history of use for nutrition and the treatment of a broad spectrum of diseases. It grows mostly in South and East Asia, as well as in Australia and Europe. Mounting evidence shows the health benefits of Z. jujuba, including anticancer, anti-inflammation, antiobesity, antioxidant, and hepato- and gastrointestinal protective properties, which are due to its bioactive compounds. Chemotherapy, such as with cis-diamminedichloroplatinium (CDDP, cisplatin and its derivatives, is widely used in cancer treatment. It is an effective treatment for human cancers,  including ovarian cancer; however, drug resistance is a major obstacle to successful treatment. A better understanding of the mechanisms and strategies for overcoming chemoresistance can greatly improve therapeutic outcomes for patients. In this review article, the bioactive compounds present in Z. jujuba are explained. The high prevalence of many different cancers worldwide has recently attracted the attention of many researchers. This is why our research group focused on studying the anticancer activity of Z. jujuba as well as its impact on chemoresistance both in vivo and in vitro. We hope that these studies can lead to a promising future for cancer patients.

  13. Reporter nanoparticle that monitors its anticancer efficacy in real time. (United States)

    Kulkarni, Ashish; Rao, Poornima; Natarajan, Siva; Goldman, Aaron; Sabbisetti, Venkata S; Khater, Yashika; Korimerla, Navya; Chandrasekar, Vineethkrishna; Mashelkar, Raghunath A; Sengupta, Shiladitya


    The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.

  14. Curcumin AntiCancer Studies in Pancreatic Cancer (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Leongito, Maddalena; Piccirillo, Mauro; Giudice, Aldo; Pivonello, Claudia; de Angelis, Cristina; Granata, Vincenza; Palaia, Raffaele; Izzo, Francesco


    Pancreatic cancer (PC) is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC. PMID:27438851

  15. Curcumin AntiCancer Studies in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte


    Full Text Available Pancreatic cancer (PC is one of the deadliest cancers worldwide. Surgical resection remains the only curative therapeutic treatment for this disease, although only the minority of patients can be resected due to late diagnosis. Systemic gemcitabine-based chemotherapy plus nab-paclitaxel are used as the gold-standard therapy for patients with advanced PC; although this treatment is associated with a better overall survival compared to the old treatment, many side effects and poor results are still present. Therefore, new alternative therapies have been considered for treatment of advanced PC. Several preclinical studies have demonstrated that curcumin, a naturally occurring polyphenolic compound, has anticancer effects against different types of cancer, including PC, by modulating many molecular targets. Regarding PC, in vitro studies have shown potent cytotoxic effects of curcumin on different PC cell lines including MiaPaCa-2, Panc-1, AsPC-1, and BxPC-3. In addition, in vivo studies on PC models have shown that the anti-proliferative effects of curcumin are caused by the inhibition of oxidative stress and angiogenesis and are due to the induction of apoptosis. On the basis of these results, several researchers tested the anticancer effects of curcumin in clinical trials, trying to overcome the poor bioavailability of this agent by developing new bioavailable forms of curcumin. In this article, we review the results of pre-clinical and clinical studies on the effects of curcumin in the treatment of PC.

  16. Anticancer activities of selected species of North American lichen extracts. (United States)

    Shrestha, Gajendra; El-Naggar, Atif M; St Clair, Larry L; O'Neill, Kim L


    Cancer is the second leading cause of human deaths in the USA. Despite continuous efforts to treat cancer over the past 50 years, human mortality rates have not decreased significantly. Natural products, such as lichens, have been good sources of anticancer drugs. This study reports the cytotoxic activity of crude extracts of 17 lichen species against Burkitt's lymphoma (Raji) cells. Out of the 17 lichen species, extracts from 14 species showed cytotoxicity against Raji cells. On the basis of IC50 values, we selected Xanthoparmelia chlorochroa and Tuckermannopsis ciliaris to study the mechanism of cell death. Viability of normal lymphocytes was not affected by the extracts of X. chlorochroa and T. ciliaris. We found that extracts from both lichens decreased proliferation, accumulated cells at the G0 /G1 stage, and caused apoptosis in a dose-dependent manner. Both lichen extracts also caused upregulation of p53. The T. ciliaris extract upregulated the expression of TK1 but X. chlorochroa did not. We also found that usnic, salazinic, constictic, and norstictic acids were present in the extract of X. chlorochroa, whereas protolichesterinic acid in T. ciliaris extracts. Our data demonstrate that lichen extracts merit further research as a potential source of anticancer drugs.

  17. Histone Methylation by Temozolomide; A Classic DNA Methylating Anticancer Drug (United States)

    Pickard, Amanda J.; Diaz, Anthony Joseph; Mura, Hugo; Nyuwen, Lila; Coello, Daniel; Sheva, Saif; Maria, Nava; Gallo, James M.; Wang, Tieli


    Background/Aim The alkylating agent, temozolomide (TMZ), is considered the standard-of-care for high-grade astrocytomas –known as glioblastoma multiforme (GBM)– an aggressive type of tumor with poor prognosis. The therapeutic benefit of TMZ is attributed to formation of DNA adducts involving the methylation of purine bases in DNA. We investigated the effects of TMZ on arginine and lysine amino acids, histone H3 peptides and histone H3 proteins. Materials and Methods Chemical modification of amino acids, histone H3 peptide and protein by TMZ was performed in phosphate buffer at physiological pH. The reaction products were examined by mass spectrometry and western blot analysis. Results Our results showed that TMZ following conversion to a methylating cation, can methylate histone H3 peptide and histone H3 protein, suggesting that TMZ exerts its anticancer activity not only through its interaction with DNA, but also through alterations of protein post-translational modifications. Conclusion The possibility that TMZ can methylate histones involved with epigenetic regulation of protein indicates a potentially unique mechanism of action. The study will contribute to the understanding the anticancer activity of TMZ in order to develop novel targeted molecular strategies to advance the cancer treatment. PMID:27354585

  18. The promising alliance of anti-cancer electrochemotherapy with immunotherapy. (United States)

    Calvet, Christophe Y; Mir, Lluis M


    Anti-tumor electrochemotherapy, which consists in increasing anti-cancer drug uptake by means of electroporation, is now implanted in about 140 cancer treatment centers in Europe. Its use is supported by the English National Institute for Health and Care Excellence for the palliative treatment of skin metastases, and about 13,000 cancer patients were treated by this technology by the end of 2015. Efforts are now focused on turning this local anti-tumor treatment into a systemic one. Electrogenetherapy, that is the electroporation-mediated transfer of therapeutic genes, is currently under clinical evaluation and has brought excitement to enlarge the anti-cancer armamentarium. Among the promising electrogenetherapy strategies, DNA vaccination and cytokine-based immunotherapy aim at stimulating anti-tumor immunity. We review here the interests and state of development of both electrochemotherapy and electrogenetherapy. We then emphasize the potent beneficial outcome of the combination of electrochemotherapy with immunotherapy, such as immune checkpoint inhibitors or strategies based on electrogenetherapy, to simultaneously achieve excellent local debulking anti-tumor responses and systemic anti-metastatic effects.

  19. pH-dependent anticancer drug release from silk nanoparticles. (United States)

    Seib, F Philipp; Jones, Gregory T; Rnjak-Kovacina, Jelena; Lin, Yinan; Kaplan, David L


    Silk has traditionally been used as a suture material because of its excellent mechanical properties and biocompatibility. These properties have led to the development of different silk-based material formats for tissue engineering and regenerative medicine. Although there have been a small number of studies about the use of silk particles for drug delivery, none of these studies have assessed the potential of silk to act as a stimulus-responsive anticancer nanomedicine. This report demonstrates that an acetone precipitation of silk allows the formation of uniform silk nanoparticles (98 nm diameter, polydispersity index 0.109), with an overall negative surface charge (-33.6 ± 5.8 mV), in a single step. Silk nanoparticles are readily loaded with doxorubicin (40 ng doxorubicin/μg silk) and show pH-dependent release (pH 4.5≫ 6.0 > 7.4). In vitro studies with human breast cancer cell lines demonstrates that the silk nanoparticles are not cytotoxic (IC50 > 120 μg mL(-1) ) and that doxorubicin-loaded silk nanoparticles are able to overcome drug resistance mechanisms. Live cell fluorescence microscopy studies show endocytic uptake and lysosomal accumulation of silk nanoparticles. In summary, the pH-dependent drug release and lysosomal accumulation of silk nanoparticles demonstrate the ability of drug-loaded silk nanoparticles to serve as a lysosomotropic anticancer nanomedicine.

  20. Anticancer Active Homoisoflavone from the Underground Bulbs of Ledebouria hyderabadensis

    Directory of Open Access Journals (Sweden)

    Yakaiah Chinthala


    Full Text Available Background: Ledebouria is a genus of deciduous or weakly evergreen bulbs in the Hyacinthaceae family. This is recognized as the first collection made of the new taxon Ledebouria hyderabadensis, exist in the Hyderabad city of Andhra Pradesh, India. Objective: The goal of this work was to investigate the phytochemical constituents present in the new specifies and also to evaluate the cytotoxic properties of the extracts and pure compounds against human cancer cell lines. Materials and Methods: The anticancer activity was evaluated in in vitro mode by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT test. Results: Phytochemical investigation of underground bulbs of indigenous, rare, and recently identified herb L. hyderabadensis yielded a bioactive homoisoflavanone, Scillascillin 1. The structure of the compound was established on the basis of various nuclear magnetic resonance and mass spectral data. The compound Scillascillin was isolated for the first time from L. hyderabadensis. In vitro anticancer activity, performed using MTT assay, showed compound 1 as significantly active against human cancer cell lines MCF-7 (breast cancer and DU-145 (prostate cancer with inhibitory concentration (IC 50 values 9.59 and 11.32 μg/ml respectively when compared with herb methanol extract (IC 50 values 36.21 and 44.86 μg/ml respectively.

  1. Paraptosis in the anti-cancer arsenal of natural products. (United States)

    Lee, Dongjoo; Kim, In Young; Saha, Sharmistha; Choi, Kyeong Sook


    Given the problems with malignant cancer cells showing innate and acquired resistance to apoptosis, we need alternative means to induce cell death in cancer. Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Although relatively little is known regarding the molecular basis of paraptosis, the underlying mechanism clearly differs from that of apoptosis. Recent studies have shown that various natural products, including curcumin, celastrol, 15d-PGJ2, ophiobolin A, and paclitaxel, demonstrate anti-cancer effects by inducing the paraptosis-associated cell death, which was commonly characterized by vacuolation derived from the ER. Perturbation of cellular proteostasis due to proteasomal inhibition and disruption of sulfhydryl homeostasis, generation of reactive oxygen species, and/or imbalanced homeostasis of ions (e.g., Ca(2+) and K(+)) appear to contribute to the accumulation of misfolded protein and proteotoxicity in this process. Given the pathophysiological importance of paraptosis and the debate regarding the importance of apoptosis in solid tumor, we need to collect the available knowledge regarding paraptosis and suggest future directions in the field. Here, we review the morphological and biochemical features of paraptosis, the natural products that induce paraptosis-associated cell death, their proposed mechanisms, and the significance of paraptosis as a potential anti-cancer strategy. Such work and future clarifications should enable the development of new strategies for preventing cancer and/or combating malignant cancer.

  2. "Ziziphus jujuba": A red fruit with promising anticancer activities. (United States)

    Tahergorabi, Zoya; Abedini, Mohammad Reza; Mitra, Moodi; Fard, Mohammad Hassanpour; Beydokhti, Hossein


    Ziziphus jujuba Mill. (Z. jujuba) is a traditional herb with a long history of use for nutrition and the treatment of a broad spectrum of diseases. It grows mostly in South and East Asia, as well as in Australia and Europe. Mounting evidence shows the health benefits of Z. jujuba, including anticancer, anti-inflammation, antiobesity, antioxidant, and hepato- and gastrointestinal protective properties, which are due to its bioactive compounds. Chemotherapy, such as with cis-diamminedichloroplatinium (CDDP, cisplatin) and its derivatives, is widely used in cancer treatment. It is an effective treatment for human cancers, including ovarian cancer; however, drug resistance is a major obstacle to successful treatment. A better understanding of the mechanisms and strategies for overcoming chemoresistance can greatly improve therapeutic outcomes for patients. In this review article, the bioactive compounds present in Z. jujuba are explained. The high prevalence of many different cancers worldwide has recently attracted the attention of many researchers. This is why our research group focused on studying the anticancer activity of Z. jujuba as well as its impact on chemoresistance both in vivo and in vitro. We hope that these studies can lead to a promising future for cancer patients.

  3. Genetic Interactions of STAT3 and Anticancer Drug Development

    Directory of Open Access Journals (Sweden)

    Bingliang Fang


    Full Text Available Signal transducer and activator of transcription 3 (STAT3 plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors.

  4. Genetic Interactions of STAT3 and Anticancer Drug Development

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Bingliang [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)


    Signal transducer and activator of transcription 3 (STAT3) plays critical roles in tumorigenesis and malignant evolution and has been intensively studied as a therapeutic target for cancer. A number of STAT3 inhibitors have been evaluated for their antitumor activity in vitro and in vivo in experimental tumor models and several approved therapeutic agents have been reported to function as STAT3 inhibitors. Nevertheless, most STAT3 inhibitors have yet to be translated to clinical evaluation for cancer treatment, presumably because of pharmacokinetic, efficacy, and safety issues. In fact, a major cause of failure of anticancer drug development is lack of efficacy. Genetic interactions among various cancer-related pathways often provide redundant input from parallel and/or cooperative pathways that drives and maintains survival environments for cancer cells, leading to low efficacy of single-target agents. Exploiting genetic interactions of STAT3 with other cancer-related pathways may provide molecular insight into mechanisms of cancer resistance to pathway-targeted therapies and strategies for development of more effective anticancer agents and treatment regimens. This review focuses on functional regulation of STAT3 activity; possible interactions of the STAT3, RAS, epidermal growth factor receptor, and reduction-oxidation pathways; and molecular mechanisms that modulate therapeutic efficacies of STAT3 inhibitors.

  5. Anti-cancer chalcones: Structural and molecular target perspectives. (United States)

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek


    Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold remained a fascination among researchers in the 21st century due to its simple chemistry, ease of synthesis and a wide variety of promising biological activities. Several natural and (semi) synthetic chalcones have shown anti-cancer activity due to their inhibitory potential against various targets namely ABCG2/P-gp/BCRP, 5α-reductase, aromatase, 17-β-hydroxysteroid dehydrogenase, HDAC/Situin-1, proteasome, VEGF, VEGFR-2 kinase, MMP-2/9, JAK/STAT signaling pathways, CDC25B, tubulin, cathepsin-K, topoisomerase-II, Wnt, NF-κB, B-Raf and mTOR etc. In this review, a comprehensive study on molecular targets/pathways involved in carcinogenesis, mechanism of actions (MOAs), structure activity relationships (SARs) and patents granted have been highlighted. With the knowledge of molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-cancer chalcones.

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

    Directory of Open Access Journals (Sweden)

    Sharma Savitri


    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.

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


    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.

  8. Sensitivity of antibiotic resistant and antibiotic susceptible Escherichia coli, Enterococcus and Staphylococcus strains against ozone. (United States)

    Heß, Stefanie; Gallert, Claudia


    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.

  9. Antibiotics in Drinking Water in Shanghai and Their Contribution to Antibiotic Exposure of School Children. (United States)

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


    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.

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

    Kamal, Fatima; Dennis, Jonathan J


    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.

  11. Relationships between antibiotics and antibiotic resistance gene levels in municipal solid waste leachates in Shanghai, China. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    Suresh Jaiswal et al.


    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.

  13. Emerging antibiotic resistance in bacteria with special reference to India. (United States)

    Raghunath, D


    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.

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

    Indian Academy of Sciences (India)

    D Raghunath


    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.

  15. 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)



    Full Text Available On 27 Feb., 2017, the World Health Organization (WHO announced the first list of important antibiotic-resistant bacteria (, 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.

  16. Comparative investigation of the free radical scavenging potential and anticancer property of Diospyros blancoi (Ebenaceae

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan


    Conclusions: Our results indicate that Diospyros blancoi stem bark had the significant highest antioxidant and free radical scavenging properties as well as moderate anticancer activity. Hence, we assume that the anticancer activity of this plant can be, at least in part, attributed to its content in phenolic compounds as well as its significant free radical scavenging properties.

  17. Design, synthesis, and anticancer activity of novel berberine derivatives prepared via CuAAC "click" chemistry as potential anticancer agents. (United States)

    Jin, Xin; Yan, Tian-Hua; Yan, Lan; Li, Qian; Wang, Rui-Lian; Hu, Zhen-Lin; Jiang, Yuan-Ying; Sun, Qing-Yan; Cao, Yong-Bing


    A series of novel derivatives of phenyl-substituted berberine triazolyls has been designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click chemistry in an attempt to develop antitumor agents. All of the compounds were evaluated for anticancer activity against a panel of three human cancer cell lines, including MCF-7 (breast), SW-1990 (pancreatic), and SMMC-7721 (liver) and the noncancerous human umbilical vein endothelial cell (HUVEC) cell lines. The results indicated that most of the compounds displayed notable anticancer activities against the MCF-7 cells compared with berberine. Among these derivatives, compound 16 showed the most potent inhibitory activity against the SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration (IC50) values of 8.54±1.97 μM and 11.87±1.83 μM, respectively. Compound 36 exhibited the most potent inhibitory activity against the MCF-7 cell line, with an IC50 value of 12.57±1.96 μM. Compound 16 and compound 36 exhibited low cytotoxicity in the HUVEC cell line, with IC50 values of 25.49±3.24 μM and 30.47±3.47 μM. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited much better selectivity than berberine toward the normal cell line HUVEC.


    Institute of Scientific and Technical Information of China (English)

    江涛; 于少卿; 薛学温


    Taurolidine is a broad-spectrum antibiotic and has been used to treat infectious diseases in clinics. In recent years, it is reported that Taurolidine has the anticancer activities.Although the mechanism has not completely known, the present research results show that Taurolidine's anti-tumor effects may be achieved by enhancing apoptosis, inhibiting angiogenesis and tumor adherence, down-regulating pro-inflammatory cytokine levels, and stimulating the immune system in response to surgically.%滔罗定(Taurolidine)是1种广谱抗菌药,临床上可用于多种感染疾病的治疗.近年来大量研究表明Taurolidine具有良好的抗肿瘤活性.Taurolidine的抗肿瘤机制尚未完全明确,已有的研究证明其通过促进细胞凋亡、抑制血管生成、减少肿瘤黏附、下调促炎细胞因子释放水平和刺激外科手术后抗肿瘤免疫调节等多种途径发挥抗肿瘤作用.本文综述Tauro1idine在抗肿瘤方面的研究进展.

  19. Advancement in research of anti-cancer effects of toad venom (ChanSu) and perspectives

    Institute of Scientific and Technical Information of China (English)

    Miao Liu; Li-Xing Feng; Li-Hong Hu; Xuan Liu; De-An Guo


    Toad venom, called as ChanSu in China, is a widely used traditional Chinese medicine (TCM) whose active components are mainly bufadienolides. ChanSu could exhibit cardiotonic, anti-microbial, anti-inflammatory and, most importantly, anti-cancer effects. In the present review, reports about the in vitro, in vivo and clinical anti-cancer effects of ChanSu or its representative component, bufalin, were summarized. And, reported anti-cancer mechanisms of cardenolides, structure analogues of bufadienolides, were also introduced. Based on the results got from research of ChanSu/bufalin and the results from cardenolides, possible signal network related to the anti-cancer effects of ChanSu/bufalin was predicted. Furthermore, future potential use of ChanSu in anti-cancer therapy was discussed.

  20. In vitro evaluation of anticancer effect and neurotoxicity of Styrylpyrone derivative (SPD) (United States)

    Yip, Chee-Wai; Nagaoka, Yasuo; Nor, Norefrina Shafinaz Md.; Ibrahim, Nazlina


    The increasing number of death due to cancer emphasizes the need of novel anticancer agents. Styrylpyrone derivative (SPD) was previously found to have potential anticancer action towards many types of cancer. Some of the SPD-anticancer mechanisms were elucidated as induction of cancer cell apoptosis. However, more understanding on cancer cell type specific action of SPD-anticancer effects needs to be evaluated. HCT-116 cell line, a type of human colon carcinoma, was used to study SPD-anticancer effect. It was found that SPD concentration as low as 0.25 µM was able to inhibit 80% growth of cancer cells. IC50 value of SPD for HCT-116 was found to be 0.038 µM. Neurotoxicity test, carried out to determine the adverse effect of SPD towards nerve cells, gives CC50 value as 4.88 µM, thus concluded it to be a neurotoxic compound.

  1. Current developments of coumarin-based anti-cancer agents in medicinal chemistry. (United States)

    Emami, Saeed; Dadashpour, Sakineh


    Cancer is one of the leading health hazards and the prominent cause of death in the world. A number of anticancer agents are currently in clinical practice and used for treatment of various kinds of cancers. There is no doubt that the existing arsenal of anticancer agents is insufficient due to the high incidence of side effects and multidrug resistance. In the efforts to develop suitable anticancer drugs, medicinal chemists have focused on coumarin derivatives. Coumarin is a naturally occurring compound and a versatile synthetic scaffold possessing wide spectrum of biological effects including potential anticancer activity. This review article covers the current developments of coumarin-based anticancer agents and also discusses the structure-activity relationship of the most potent compounds.

  2. Aminoglycoside antibiotics and autism: a speculative hypothesis

    Directory of Open Access Journals (Sweden)

    Manev Hari


    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.

  3. Respiratory infection and antibiotic prescription rates.

    NARCIS (Netherlands)

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


    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.

  4. Prophylactic antibiotics and anticonvulsants in neurosurgery. (United States)

    Ratilal, B; Sampaio, C


    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.

  5. Antibiotics: neuropsychiatric effects and psychotropic interactions. (United States)

    Sternbach, H; State, R


    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.

  6. Inhalation of antibiotics in cystic fibrosis

    NARCIS (Netherlands)

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


    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

  7. The genomic enzymology of antibiotic resistance. (United States)

    Morar, Mariya; Wright, Gerard D


    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.

  8. Antibiotic production by bacterial biocontrol agents

    NARCIS (Netherlands)

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


    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

  9. Physics and the Production of Antibiotics: 2 (United States)

    Fairbrother, Robert; Riddle, Wendy; Fairbrother, Neil


    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…

  10. Towards new β-lactam antibiotics

    NARCIS (Netherlands)

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


    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,

  11. Proteome studies of bacterial antibiotic resistance mechanisms. (United States)

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


    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.

  12. Selective decontamination and antibiotic resistance in ICUs

    NARCIS (Netherlands)

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


    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

  13. The negative impact of antibiotic resistance. (United States)

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


    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.

  14. 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.


    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

  15. Non-absorbed Antibiotics for IBS (United States)


    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

  16. 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.


    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

  17. Proficiency test for antibiotics in beef

    NARCIS (Netherlands)

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


    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

  18. Proficiency test for antibiotics in bovine muscle

    NARCIS (Netherlands)

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


    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

  19. 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: [Department of Medicine, Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43614 (United States)


    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.

  20. 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

  1. Antibiotic resistance: from Darwin to Lederberg to Keynes. (United States)

    Amábile-Cuevas, Carlos F


    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.

  2. Antibiotic Resistance Threats in the U.S. (United States)

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

  3. 'Superbug' Resistant to All Antibiotics Killed Nevada Woman (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 ...

  4. Skip the Antibiotics for Mild Eczema in Kids (United States)

    ... 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 ...

  5. Treating Sinusitis: Don't Rush to Antibiotics (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 ...

  6. Dilemmas in primary care: antibiotic treatment of acute otitis media. (United States)

    True, B L; Helling, D K


    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.


    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...

  8. Doctors' Decision-Making Tool Could Cut Unnecessary Antibiotic Use (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, ...

  9. 2nd Antibiotic Halves C-Section Infection Rate (United States)

    ... 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 ...

  10. 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.


    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

  11. 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.


    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

  12. Antibiotic-Resistant Bacteria Detected in Sewage Spill (United States)

    ... 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 ...

  13. Antibiotic stewardship through the EU project "ABS International". (United States)

    Allerberger, Franz; Frank, Annegret; Gareis, Roland


    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.

  14. Challenging the concept of bacteria subsisting on antibiotics. (United States)

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


    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.

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

    DEFF Research Database (Denmark)

    Stokholm, Jakob; Schjørring, Susanne; Pedersen, Louise


    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....

  16. Anti-Cancer Effects of Xanthones from Pericarps of Mangosteen

    Directory of Open Access Journals (Sweden)

    Yoshinori Nozawa


    Full Text Available Mangosteen, Garcinia mangostana Linn, is a tree found in South East Asia, and its pericarps have been used as traditional medicine. Phytochemical studies have shown that they contain a variety of secondary metabolites, such as oxygenated and prenylated xanthones. Recent studies revealed that these xanthones exhibited a variety of biological activities containing anti-inflammatory, anti-bacterial, and anti-cancer effects. We previously investigated the anti-proliferative effects of four prenylated xanthones from the pericarps; α-mangostin, β-mangostin, γ-mangostin, and methoxy-β-mangostin in various human cancer cells. These xanthones are different in the number of hydroxyl and methoxy groups. Except for methoxy-β-mangostin, the other three xanthones strongly inhibited cell growth at low concentrations from 5 to 20 μM in human colon cancer DLD-1 cells. Our recent study focused on the mechanism of α-mangostin-induced growth inhibition in DLD-1 cells. It was shown that the anti-proliferative effects of the xanthones were associated with cell-cycle arrest by affecting the expression of cyclins, cdc2, and p27; G1 arrest by α- mangostin and β-mangostin, and S arrest by γ-mangostin. α-Mangostin found to induce apoptosis through the activation of intrinsic pathway following the down-regulation of signaling cascades involving MAP kinases and the serine/threonine kinase Akt. Synergistic effects by the combined treatment of α-mangostin and anti-cancer drug 5-FU was to be noted. α-Mangostin was found to have a cancer preventive effect in rat carcinogenesis bioassay and the extract from pericarps, which contains mainly α-mangostin and γ- mangostin, exhibited an enhancement of NK cell activity in a mouse model. These findings could provide a relevant basis for the development of xanthones as an agent for cancer prevention and the combination therapy with

  17. 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


    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

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


    Raghunath, D.


    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...

  19. The world alliance against antibiotic resistance: consensus for a declaration. (United States)

    Carlet, Jean


    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.

  20. Evolutionary Rationale for Phages as Complements of Antibiotics. (United States)

    Torres-Barceló, Clara; Hochberg, Michael E


    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.